bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein with negative surface charge distribution, Bnr1, shows characteristics of a DNA‐mimic protein and may be involved in the adaptation of Burkholderia cenocepacia
Authors: Dennehy Ruth , Duggan Niamh , Dignam Simon , McCormack Sarah , Dillon Eugene , Molony Jessica , Romano Maria , Hou Yueran , Ardill Laura , Whelan Matthew V. X. , Drulis‐Kawa Zuzanna , Ó'Cróinín Tadhg , Valvano Miguel A. , Berisio Rita , McClean Siobhán
Published: February 2022

Adaptation of opportunistic pathogens to their host environment requires reprogramming of a vast array of genes to facilitate survival in the host. Burkholderia cenocepacia, a Gram‐negative bacterium with a large genome of ∼8 Mb that colonizes environmental niches, is exquisitely adaptable to the hypoxic environment of the cystic fibrosis lung and survives in macrophages. We previously identified an immunoreactive acidic protein encoded on replicon 3, BCAS0292. Deletion of the BCAS0292 gene significantly altered the abundance of 979 proteins by 1.5‐fold or more; 19 proteins became undetectable while 545 proteins showed ≥1.5‐fold reduced abundance, suggesting the BCAS0292 protein is a global regulator. Moreover, the ∆BCAS0292 mutant showed a range of pleiotropic effects: virulence and host‐cell attachment were reduced, antibiotic susceptibility was altered, and biofilm formation enhanced. Its growth and survival were impaired in 6% oxygen. In silico prediction of its three‐dimensional structure revealed BCAS0292 presents a dimeric β‐structure with a negative surface charge. The ΔBCAS0292 mutant displayed altered DNA supercoiling, implicated in global regulation of gene expression. Three proteins were identified in pull‐downs with FLAG‐tagged BCAS0292, including the Histone H1‐like protein, HctB, which is recognized as a global transcriptional regulator. We propose that BCAS0292 protein, which we have named Burkholderia negatively surface‐charged regulatory protein 1 (Bnr1), acts as a DNA‐mimic and binds to DNA‐binding proteins, altering DNA topology and regulating the expression of multiple genes, thereby enabling the adaptation of B. cenocepacia to highly diverse environments.
Increased Transferrin Sialylation Predicts Phenoconversion in IsolatedREMSleep Behavior Disorder
Authors: Ganapathy S. Ranjani , Levová Kateřina , Kotačková Lenka , Trnka Jiří , Zogala David , Rusz Jan , Zima Tomáš , Devos David , Šonka Karel , Růžička Evžen , Kalousová Marta , Dušek Petr
Published: February 2022

Background

Sialic acid–protein interactions are involved in regulating central nervous system immunity; therefore, derangements in sialylation could be involved in neurodegeneration.

Objectives

We evaluate the differences in serum transferrin sialylation in prodromal and early‐stage Parkinson's disease (PD), its relation to substantia nigra degeneration, and the risk of phenoconversion to manifest disease.

Methods

Sixty treatment‐naive PD patients; 72 polysomnography‐confirmed isolated rapid eye movement sleep behavior disorder (iRBD) patients, that is, patients with prodromal synucleinopathy; and 46 healthy volunteers aged ≥45 years and drinking ≤60 standard drinks per month were included. The proportion of serum low‐sialylated, carbohydrate‐deficient transferrin (CDT) isoforms was assessed using high‐performance liquid chromatography, and the values were adjusted for alcohol intake (CDTadj). Dopamine transporter single‐photon emission computed tomography (DaT‐SPECT) imaging was performed. In iRBD, phenoconversion risk of DaT‐SPECT and CDTadjwas evaluated using Cox regression adjusted for age and sex.

Results

Median CDTadjwas lower in PD (1.1 [interquartile range: 1.0–1.3]%) compared to controls (1.2 [1.1–1.6]%) (P = 0.001). In iRBD, median CDTadjwas lower in subjects with abnormal (1.1 [0.9–1.3]%) than normal (1.3 [1.2–1.6]%) DaT‐SPECT (P = 0.005). After a median 44‐month follow‐up, 20% of iRBD patients progressed to a manifest disease. Although iRBD converters and nonconverters did not significantly differ in CDTadjlevels (P = 0.189), low CDTadjincreased the risk of phenoconversion with hazard ratio 3.2 (P = 0.045) but did not refine the phenoconversion risk associated with abnormal DaT‐SPECT yielding hazard ratio 15.8 (P < 0.001).

Conclusions

Decreased serum CDTadjis associated with substantia nigra degeneration in synucleinopathies. iRBD patients with low CDTadjare more likely to phenoconvert to manifest disease. © 2022 The Authors.Movement Disorderspublished by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.
A 65‐nm 28‐GHz CMOS Wilkinson power divider with improved isolation
Authors: Song Jae‐Hyeok , Oh Hyun‐Myung , Kim Choul‐Young
Published: February 2022

In this study, we implemented a Wilkinson power divider/combiner composed of lumped elements suitable for 28‐GHz of fifth‐generation mobile communication technology. To improve the isolation of the system, signal perfect cancellation analysis is used with optimized values of the lumped elements of the Wilkinson power divider, which is fabricated using bulk complementary metal–oxide–semiconductor (CMOS) 1P9M 65‐nm process and the fabricated circuit area was 0.046 mm2. The measured insertion loss of this system is less than 0.62 dB, input/output matching exceeds 16.9 dB, and isolation between the output ports exceeds 19.6 dB in the operating frequency range of 25.5–29.5 GHz. The circuit thus has low insertion loss and good isolation compared to conventional Wilkinson power dividers manufactured for use in the similar frequency bands.
Carboplatin‐induced renal salt‐wasting syndrome in pediatric patients with intracranial germ cell tumors and concomitant diabetes insipidus
Authors: Wan Tania , Yuet‐Ling Tung Joanna , Ma Alison , Lai‐Ka Lee Samantha , Pak‐Yin Liu Anthony , Tak‐Loi Ku Dennis , Yau Ping‐Wa , Ming‐Kong Shing Matthew
Published: February 2022

We report a case series of 14 children with intracranial germ cell tumor and concomitant central diabetes insipidus, who developed hyponatremia secondary to renal salt‐wasting syndrome (RSWS) following the administration of carboplatin. Clinicians prescribing platinum‐based chemotherapy for this group of patients should be alert to the risk of RSWS. Regular monitoring should be performed as hyponatremia can be asymptomatic until it is severe.
Optimization of high‐quality carbon fiber production from electrospun aligned lignin fibers
Authors: Chen Jiawei , Ghosh Tanushree , Tang Tian , Ayranci Cagri
Published: February 2022

In recent years, investigating lignin as an alternative carbon fiber precursor has received immense research attention as a way to reduce the cost and replace the unsustainable conventional petroleum‐based precursors for carbon fiber production. The predominant challenge for lignin‐based carbon fibers is its low mechanical performance compared to conventional ones. In this work, mechanical properties of electrospun lignin carbon fiber mats were shown to be considerably enhanced via alignment of the submicron fibers. Over 60% of the fibers were aligned via a rotating drum collector utilized during fiber production. The main electrospinning parameters, namely electric field, rotating speed, and flow rate were optimized with the Box–Behnken method to enhance mechanical properties with reduced fiber diameter and improved fiber alignment. The optimal electrospinning process parameter was achieved at 2000 rpm collection speed, 80 kV/m electric field, and 440 nl/s flow rate. The lignin carbon fibers produced under the optimized condition exhibited elastic modulus of 3145.47 ± 917.75 MPa, tensile strength of 18.78 ± 6.11 MPa, and average fiber diameter of 697.07 ± 96.41 nm. The analysis on the interactions between electrospinning parameters has laid a solid foundation for the production of high‐quality carbon fibers from lignin precursor.
Catalyzed Michael addition, polycondensation, and the related performance of Diels–Alder self‐healing crosslinked polyamides
Authors: Chen Shuo , Feng Yu , Zhang Zhi‐Yuan , Li Xiang‐Yuan , Zhang Jun‐Ying , Zhao Jing‐Bo
Published: February 2022

Diels–Alder (DA) addition is an efficient method to repair damages at mild conditions. It is often used in self‐healing polyurethanes and epoxy resins and seldom used in cross‐linked polyamides (cPAs). Michael addition becomes a useful method to synthesize cPAs. However, no efficient way has been established to conduct double‐addition of primary amines. In this work, organic catalyzed Michael addition and polycondensation were established to prepare polyamide oligomers with furan pendent groups (pFU‐PAs), and a DA addition was adopted to prepare self‐healing cross‐linked polyamides (SH‐cPAs). A bulk double Michael addition of furfurylamine and methyl acrylate was performed at 30–70°C in the presence of 1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene (TBD), 7‐methyl‐1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene (MTBD), or 4‐(N,N‐dimethylamino) pyridine (DMAP), and a high yield of furfurylamine‐N,N‐bis(methyl propionate) (FA‐BMP) was prepared. The catalytic activity order is MTBD>TBD >>DMAP in Michael addition. Melt polycondensation of FA‐BMP with bis(2‐aminopropyl) polypropyleneglycol and hexamethylene diamine was catalyzed by MTBD and N,N′‐diphenylthiourea. The DA addition of 1,5‐bismaleimido‐2‐methylpentane and pFU‐PAs was monitored by FT‐IR,1H NMR, DSC, polarizing optical microscopy, and gel content. In these catalyzed processes, the structures of FA‐BMP, pFU‐PAs, and SH‐cPAs were controlled easily, and the SH‐cPAs showed good mechanical property and excellent self‐healing performance of 88%–98%.
PP‐GF‐EPP sandwich structures as housing materials for rechargeable energy storage system of electric vehicles: Investigations into flame retardancy
Authors: Höhne Carl‐Christoph , Gettwert Volker , Kilian Sascha , Tillner Benjamin , Jahn Ivonne , Menrath Andreas
Published: February 2022

The growing importance of electric mobility has led to an increased demand for safety technologies in the automotive sector, such as the flame retardancy of materials used for electric vehicles. The fire protection of a fully equipped rechargeable energy storage system (REESS), including battery, housing, control electronics, etc., against a fuel fire must be tested according to UNECE Regulation No. 100 Annex 8E ‐ Fire Resistance (UNECE‐R100‐8E). To pass this fire retardancy requirement, the flame retardancy of the housing materials is of great importance. In this study, the flame retardancy of glass‐fiber‐reinforced polypropylene (PP‐GF) tape laminates containing the flame retardant magnesium hydroxide and different GF amounts, as well as sandwich structures of these PP‐GF tape laminates with a polypropylene bead foam (EPP) core, are investigated by a limiting oxygen index test, a UL94 test and a cone calorimeter test. Furthermore, a newly developed approach of a bench‐scale fuel fire test which simulates the fire treatment of the UNECE‐R100‐8E on component level is used.
“Communicating Lily’s Pain”: A reflective narrative commentary about co‐creating a resource to provoke thinking and change about assessing and managing the pain of children with profound cognitive impairment
Authors: Carter Bernie , Young Rob , Munro James
Published: February 2022

This paper draws together about 20 years of research work and discovery and the development of a resource about pain assessment and management in children with profound cognitive impairment. The animation tells the story of an imagined child called Lily and the skills her mother uses and the challenges that her mother faces in assessing and managing Lily's pain. The animation is built on stories drawn from qualitative research findings, conversations while in clinical practice and with members of the general public, parent advisers and other sources. Most of the “evidence” came from stories shared by parents and healthcare professionals. This paper draws on some elements of socio‐narratology and is predicated on the basis that stories are important and they can act on and with us. By using an animation to tell Lily's story, the intention was to communicate research findings to a wider and more diverse audience than the typical readership of an academic journal. The intention was to act in and on people's consciousness about children's pain and to strengthen relationships and create bonds between clinicians, parents, and children in pain to make their dialog more social, connected, and meaningful. All three of us—the researcher, the writer, and the animator—have been marked and “re‐shaped” by our work related to creating Lily; we have learned more about children like Lily and their mothers, and we have learned more about ourselves and our humanity. This animation is still a story in progress, a story ‘in the wild’, a story (and a resource) we would like you to re‐tell and share. The story of Lily's pain aimed to change the lives of parents and children and professionals. Our hope is that you can be part of that change.
Investigating Growth of Gold Nanorods by Simultaneous Small‐Angle X‐Ray and Neutron Scattering
Authors: Zech Tobias , Metwalli Ezzeldin , Götz Klaus , Schuldes Isabel , Porcar Lionel , Unruh Tobias
Published: February 2022

Increased usage of gold nanorods (AuNRs) in various biosensing and medical applications requires tight size and morphology control. This is often achieved by tuning the aggregation behavior of the stabilizing ligand cetrimonium bromide (CTAB). Because the role of CTAB during AuNR growth is still a matter of debate, simultaneous small‐angle X‐ray and neutron scattering experiments (SAXS/SANS) and measurements are performed. The SAXS/SANS measurements have enabled an instantaneous correlation between the size of evolving AuNR and the nanostructure of guiding CTAB moieties. Upon modifying the aggregation behavior of CTAB micelles by adding hexanol or pentanol as inert additives in the precursor solution, a marked change in reaction kinetics is observed. Alcohol‐modified CTAB nanostructures have improved AuNR size uniformity compared to those prepared in alcohol‐free CTAB solutions, which are attributed to different growth modes. The change in reaction kinetics is linked to a changed stabilization mechanism of reactants and nascent AuNR facilitated by CTAB micelles.
Incorporating historical controls in clinical trials with longitudinal outcomes using the modified power prior
Authors: Qi Hongchao , Rizopoulos Dimitris , Lesaffre Emmanuel , van Rosmalen Joost
Published: February 2022

Several dynamic borrowing methods, such as the modified power prior (MPP), the commensurate prior, have been proposed to increase statistical power and reduce the required sample size in clinical trials where comparable historical controls are available. Most methods have focused on cross‐sectional endpoints, and appropriate methodology for longitudinal outcomes is lacking. In this study, we extend the MPP to the linear mixed model (LMM). An important question is whether the MPP should use the conditional version of the LMM (given the random effects) or the marginal version (averaged over the distribution of the random effects), which we refer to as the conditional MPP and the marginal MPP, respectively. We evaluated the MPP for one historical control arm via a simulation study and an analysis of the data of Alzheimer's Disease Cooperative Study (ADCS) with the commensurate prior as the comparator. The conditional MPP led to inflated type I error rate when there existed moderate or high between‐study heterogeneity. The marginal MPP and the commensurate prior yielded a power gain (3.6%–10.4% vs. 0.6%–4.6%) with the type I error rates close to 5% (5.2%–6.2% vs. 3.8%–6.2%) when the between‐study heterogeneity is not excessively high. For the ADCS data, all the borrowing methods improved the precision of estimates and provided the same clinical conclusions. The marginal MPP and the commensurate prior are useful for borrowing historical controls in longitudinal data analysis, while the conditional MPP is not recommended due to inflated type I error rates.
Morus alba L. water extract changes gut microbiota and fecal metabolome in mice induced by high‐fat and high‐sucrose diet plus low‐dose streptozotocin
Authors: Du Yan , Li Ding‐xiang , Lu Dong‐yu , Zhang Ran , Zheng Xiao‐xiao , Xu Bing‐ju , Zhao Yan‐lin , Ji Shuai , Guo Meng‐zhe , Wang Liang , Tang Dao‐quan
Published: February 2022

Gut microbiota plays a key role in the pathophysiology of type 2 diabetes mellitus (T2D). Mulberry leaf has a hypoglycemic effect, but the potential mechanism is not fully understood. This study aimed to explore the influences and potential mechanisms of mulberry leaf water extract (MLWE) intervention on mice with T2D induced through a high‐fat and high‐sucrose diet combined with streptozotocin by the combination of fecal metabolomics and gut microbiota analysis. Results showed that MLWE could decrease fasting blood glucose and body weight while ameliorating lipid profiles, insulin resistance, liver inflammation, and the accumulation of lipid droplets in T2D mice. MLWE could reverse the abundances of the phyla Actinobacteria and Bacteroidetes and the ratio of Firmicutes/Bacteroidetes, and increase the abundances of the phyla Cyanobacteria and Epsilonbacteraeota in the feces of T2D mice. The abundances of genera Alloprevotella, Parabacteroides, Muribaculaceae, and Romboutsia in the feces of T2D mice could be reversed, while Oscillatoriales_cyanobacterium and Gastranaerophilales could be reinforced by MLWE supplementation. The levels of nine metabolites in the feces of T2D mice were improved, among which glycine, Phe‐Pro, urocanic acid, phylloquinone, and lactate were correlated with Romboutsia and Gastranaerophilales. Taken together, we conclude that MLWE can effectively alleviate T2D by mediating the host–microbial metabolic axis.
Anhydrous Nucleic Acid Nanoparticles for Storage and Handling at Broad Range of Temperatures
Authors: Tran Allison N. , Chandler Morgan , Halman Justin , Beasock Damian , Fessler Adam , McKeough Riley Q. , Lam Phuong Anh , Furr Daniel P. , Wang Jian , Cedrone Edward , Dobrovolskaia Marina A. , Dokholyan Nikolay V. , Trammell Susan R. , Afonin Kirill A.
Published: February 2022

Recent advances in nanotechnology now allow for the methodical implementation of therapeutic nucleic acids (TNAs) into modular nucleic acid nanoparticles (NANPs) with tunable physicochemical properties which can match the desired biological effects, provide uniformity, and regulate the delivery of multiple TNAs for combinatorial therapy. Despite the potential of novel NANPs, the maintenance of their structural integrity during storage and shipping remains a vital issue that impedes their broader applications. Cold chain storage is required to maintain the potency of NANPs in the liquid phase, which greatly increases transportation costs. To promote long‐term storage and retention of biological activities at higher temperatures (e.g., +50 °C), a panel of representative NANPs is first exposed to three different drying mechanisms—vacuum concentration (SpeedVac), lyophilization (Lyo), and light‐assisted drying (LAD)—and then rehydrated and analyzed. While SpeedVac primarily operates using heat, Lyo avoids temperature increases by taking advantage of pressure reduction and LAD involves a near‐infrared laser for uniform drying in the presence of trehalose. This work compares and defines refinements crucial in formulating an optimal strategy for producing stable, fully functional NANPs and presents a forward advancement in their development for clinical applications.
Field‐assisted thermionic emission toward quantitative modeling of charge‐transfer mechanisms in contact electrification
Authors: Xia Xin , Wang Haoyu , Zi Yunlong
Published: February 2022

Charge transfer mechanisms of contact electrification (CE) are essential for widening applications of the triboelectric nanogenerator, and thus are widely studied by scientists around the world. However, the quantitative modeling of CE, especially that between polymers, is still lacking. Herein, a model was proposed to describe the contributions from different mechanisms, including electron transfer and mass transfer in polymer/polymer CE through the field‐assisted thermionic emission, where three groups of charge transfer mechanisms were distinguished by the polarity of the charge transfer and the corresponding electric field. The results indicated that the total generated charge in CE is actually much larger than the measured net surface charge, confirming the bidirectional material‐dependent charge transfer mechanisms between two surfaces, which is meaningful for understanding the millennium puzzle in triboelectrification and provides a new perspective for promoting the applications to tailor surface charge generation.
Paediatric Acute Lymphoblastic Leukaemia (ALL)
Authors: Bader Peter , Locatelli Franco , Peters Christina
Published: February 2022

Acute lymphoblastic leukaemia (ALL) is the most frequent malignant disease in childhood and adolescence, with an annual incidence of approximately 3–4 cases per 100,000 children under 15 years of age. Multimodal chemotherapy forms the base of current ALL treatment. Based on excellent national and international collaboration in consecutive prospective, randomized clinical trials, the prognosis of childhood ALL has significantly improved over time. Currently, up to 90% of all paediatric patients with ALL will survive.
Diffuse Large B Cell Lymphoma and Primary Mediastinal Lymphoma
Authors: Glass Bertram , Kersten Marie José
Published: February 2022

The outcome of patients with large B cell lymphoma (LBCL) who did not respond to a classical immunochemotherapy regimen at any time or relapsed within 1 year following chemoimmunotherapy is poor. The Scholar-One-Study showed long-term event-free survival for less than 20% of these patients (Crump et al. 2017). The introduction of chimeric antigen receptor T cell therapy (CAR-T) is a substantial advancement for these patients, offering long-term remission and a curative prospect for 30 to 40% of patients (summarized in Table 12.1), (Abramson et al. 2020; Neelapu et al. 2017; Schuster et al. 2019b). To date, in Europe, two products (axicabtagene ciloleucel and tisagenlecleucel) have been licenced by the European Medical Agency, and a third product (lisocabtagene maraleucel) will become available in 2021. All these products are licenced for patients who have failed at least two prior lines of systemic therapy. This initially defines, however broad, a range of possible situations in which the application of CART is indicated. The following considerations may help to further define the patient population that should be offered CAR-T cells as the next line of treatment. Studies addressing the potential benefit of CAR-T cells compared to high-dose chemotherapy and autologous stem cell transplantation for second-line treatment of LBCL have been fully recruited, but the results are still pending.
Developments in Solid Tumours
Authors: Pedrazzoli Paolo , Haanen John B. A. G.
Published: February 2022

Chimeric antigen receptor (CAR) T cells have emerged as breakthrough therapies in patients with refractory haematologic malignancies, and the highly encouraging clinical results have fuelled expectations of implementing these strategies in other cancer types. However, a similar success of CAR-T cell treatment has not yet been observed in solid tumours. Various factors, including the immunosuppressive nature of the tumour microenvironment, hinder CAR-T cell trafficking and infiltration into scarcely accessible tumour sites, and difficulties in identifying targetable antigens with optimal expression and a good toxicity profile, limiting CAR-T dose escalation, must be overcome to achieve success in the treatment of solid cancers (Comoli et al. 2019).
Bridging to CAR-T Cells in Children, Adolescents, and Young Adults with ALL
Authors: Baruchel André
Published: February 2022

Leukapheresis can be performed in most patients, including infants, but not all patients will receive autologous CAR-T cells. The ELIANA trial can be taken as an example to help understand the issues: 97 patients were successfully screened and enrolled, but only 79 of them finally made it to the infusion. Of the remaining 18 patients, 10 died or experienced an AE during the manufacturing time, and 8 patients had issues with the manufacturing process (Grupp et al. 2018).
Bridging Chemotherapy: Multiple Myeloma
Authors: Manier Salomon , Jurczyszyn Artur , Vesole David H.
Published: February 2022

In the phase 2 KarMMa study, 88% of the patients received bridging therapy with only a 5% response (Munshi et al. 2021). In the CARTITUDE 1 trial, 75% of the patients received bridging therapy, with a reduction in tumour burden observed in 34% of the patients prior to cilta-cel infusion, but no patients achieved a CR or better while on bridging therapy (Madduri et al. 2019). Bridging therapy is recommended for virtually all patients. An exception can be discussed for patients with slowly progressive disease, who may not need to receive bridging therapy after leukapheresis; however, this strategy exposes them to a risk of rapid progression later during the manufacturing period. In the future, with allogeneic CAR-T cells, bridging therapy will likely not be necessary because the time between patient inclusion and CAR-T cell infusion is much reduced.
The Regulatory Framework for CAR-T Cells in Europe: Current Status and Foreseeable Changes AND Centre Qualification by Competent Authorities and Manufacturers
Authors: McGrath Eoin , Machalik Petr
Published: February 2022

Under current European Union regulations, CAR-T cell therapies fall under the advanced therapy medicinal products (ATMPs) framework. ATMPs represent a category of medicinal products defined in EU Regulation 1394/2007 and subdivided into four categories, of which autologous or allogeneic CAR-T cells, among other therapies, are considered gene therapy medicinal products (GTMPs). ATMPs are subject to a centralized evaluation framework whereby one authorization is valid for all countries in the EU led by the European Medicines Agency’s Committee for Advanced Therapies (CAT). The framework includes different regulatory pathways for bringing ATMPs from clinical trials to market authorization, and the regulatory pathway taken will depend on a product’s characteristics and the target patient population. In 2018, two chimeric antigen receptor (CAR) T cell therapies, Yescarta and Kymriah, completed their authorization process via the priority medicines PRIME scheme to Marketing Authorization (Detela and Lodge 2019).
Educational Needs for Cell Processing Facility Personnel
Authors: Calmels Boris
Published: February 2022

Training on ATMP processes and procedures is systematically provided by the sponsor after site certification/accreditation.
Patient Referral
Authors: Snowden John , Duarte Rafael F.
Published: February 2022

Early and efficient patient referral is a critical step in the ability of potential candidates to access CAR-T therapy. Despite improvements in centre qualification and availability, regulatory and reimbursement frameworks, and addressing the educational needs of the various members of the health care team, referring haematologists and oncologists identify major barriers to prescribing CAR-T therapy, including cumbersome logistics, high cost and toxicity, and clinical challenges, such as deterioration of the patient prior to CAR-T administration and the need for bridging chemotherapy while awaiting manufacturing.
The relationship between bending and tension strength of Irish and UK spruce and pine
Authors: Gil-Moreno David , Ridley-Ellis Dan , O’Ceallaigh Conan , Harte Annette M.
Published: February 2022

The correct characterisation of wood properties is fundamental for the best utilisation of resources. In Europe, grading is defined by strength classes that are determined based on either bending or tension tests. The European standards give equations to estimate characteristic strength in tension from characteristic strength in bending, and vice versa depending on which was tested. These equations are applied to all softwoods. The aim of this paper is to empirically determine the relationship between bending and tension strength properties using two conifer species grown in Ireland and the UK. The results show that the relationships change with species. The standard conversion underestimates, importantly, the performance of spruce for tension loads calculated for the most common bending strength class for Ireland and the UK, C16. The opposite occurs on the reverse conversion. Additionally, the study includes published data from continental Europe, to establish a new conversion that uses timber from a broader range of grades, and that adjusts the tension performance of Irish and UK spruce obtained from bending strength classes, ensuring safe values for design.
Chancen und Risiken der Telemedizin in der Urologie
Authors: Wülfing Christian
Published: February 2022

Die Telemedizin in Deutschland ist auf dem Vormarsch. Die gesetzlichen Rahmenbedingungen für die Telemedizin sind seit 2018 sehr vorangetrieben worden. Neben dem Terminservice- und Versorgungsgesetz (TSVG) traten das Digitale-Versorgung-Gesetz (DVG) und das Patientendaten-Schutz-Gesetz (PDSG) sowie das Krankenhauszukunftsgesetz (KHZG) in Kraft. Auf der Anbieterseite kommen nun besonders die digitalen Gesundheitsanwendungen (DiGA), die zukünftig als „App auf Rezept“ verfügbar und von den Kostenträgern erstattbar sein werden, in den Markt (inklusive urologischer Anwendungen). Ebenso ist die Videosprechstunde nicht zuletzt durch die Coronapandemie sehr vorangekommen und dabei, sich weiter zu etablieren. Auch die elektronische Patientenakte (ePA) wird hoffentlich in hoher Geschwindigkeit umfassend verfügbar sein und genutzt werden, weil hierdurch ein starker Effizienzschub in der täglichen Arbeit eintreten wird. Dieses wird ergänzt durch das E‑Rezept und weitere Innovationen im Bereich der Medikamentenversorgung und -zustellung, die diese Entwicklung unterstützen werden. Als Herausforderungen im Umsetzungsprozess der Telemedizin bleiben v. a. die sehr wichtigen Aspekte des Datenschutzes, der Datensicherheit und die Problematik der Interoperabilität erhalten, werden hoffentlich aber den Fortschritt, der dringend benötigt wird, nicht sonderlich abbremsen. Urologinnen und Urologen werden durch die Fortschritte in der Digitalisierung der Medizin und der Urologie einen erheblichen Effizienzgewinn in der täglichen Arbeit erreichen.
Improved high-throughput screening technique to rapidly isolate Chlamydomonas transformants expressing recombinant proteins
Authors: Sproles Ashley E. , Berndt Anthony , Fields Francis J. , Mayfield Stephen P.
Published: February 2022

The single-celled eukaryotic green alga Chlamydomonas reinhardtii has long been a model system for developing genetic tools for algae, and is also considered a potential platform for the production of high-value recombinant proteins. Identifying transformants with high levels of recombinant protein expression has been a challenge in this organism, as random integration of transgenes into the nuclear genome leads to low frequency of cell lines with high gene expression. Here, we describe the design of an optimized vector for the expression of recombinant proteins in Chlamydomonas, that when transformed and screened using a dual antibiotic selection, followed by screening using fluorescence activated cell sorting (FACS), permits rapid identification and isolation of microalgal transformants with high expression of a recombinant protein. This process greatly reduces the time required for the screening process, and can produce large populations of recombinant algae transformants with between 60 and 100% of cells producing the recombinant protein of interest, in as little as 3 weeks, that can then be used for whole population sequencing or individual clone analysis. Utilizing this new vector and high-throughput screening (HTS) process resulted in an order of magnitude improvement over existing methods, which normally produced under 1% of algae transformants expressing the protein of interest. This process can be applied to other algal strains and recombinant proteins to enhance screening efficiency, thereby speeding up the discovery and development of algal-derived recombinant protein products.

Key points

• A protein expression vector using double-antibiotic resistance genes was designed

• Double antibiotic selection causes fewer colonies with more positive for phenotype

• Coupling the new vector with FACS improves microalgal screening efficiency > 60%
Volume minimising unit vector fields on three dimensional space forms of positive curvature
Authors: Gil-Medrano Olga
Published: February 2022

We prove that on a closed 3-manifold of constant positive curvature the unit vector fields of minimum volume are exactly the Hopf vector fields.
Concerns About Psychiatric Neurosurgery and How They Can Be Overcome: Recommendations for Responsible Research
Authors: Müller Sabine , van Oosterhout Ansel , Bervoets Chris , Christen Markus , Martínez-Álvarez Roberto , Bittlinger Merlin
Published: February 2022

Background

Psychiatric neurosurgery is experiencing a revival. Beside deep brain stimulation (DBS), several ablative neurosurgical procedures are currently in use. Each approach has a different profile of advantages and disadvantages. However, many psychiatrists, ethicists, and laypeople are sceptical about psychiatric neurosurgery.

Methods

We identify the main concerns against psychiatric neurosurgery, and discuss the extent to which they are justified and how they might be overcome. We review the evidence for the effectiveness, efficacy and safety of each approach, and discuss how this could be improved. We analyse whether and, if so, how randomised controlled trials (RCTs) can be used in the different approaches, and what alternatives are available if conducting RCTs is impossible for practical or ethical reasons. Specifically, we analyse the problem of failed RCTs after promising open-label studies.

Results

The main concerns are: (i) reservations based on historical psychosurgery, (ii) concerns about personality changes, (iii) concerns regarding localised interventions, and (iv) scepticism due to the lack of scientific evidence. Given the need for effective therapies for treatment-refractory psychiatric disorders and preliminary evidence for the effectiveness of psychiatric neurosurgery, further research is warranted and necessary. Since psychiatric neurosurgery has the potential to modify personality traits, it should be held to the highest ethical and scientific standards.

Conclusions

Psychiatric neurosurgery procedures with preliminary evidence for efficacy and an acceptable risk–benefit profile include DBS and micro- or radiosurgical anterior capsulotomy for intractable obsessive–compulsive disorder. These methods may be considered for individual treatment attempts, but multi-centre RCTs are necessary to provide reliable evidence.
Geographic latitude and human height - Statistical analysis and case studies from China
Authors: Lu Guoguang , Hu Yi , Yang Zhihui , Zhang Yan , Lu Shengxu , Gong Siyuan , Li Tingting , Shen Yijie , Zhang Sihan , Zhuang Hanya
Published: February 2022

Based on Chinese General Social Survey(CGSS) data, this paper selects ten variables, including height, gender, household registration, and age. Through the statistical analysis of 57,574 survey samples, this study finds that the average height of China’s population has increased by more than 10 cm in the past 100 years. Among the findings, the data indicate the average height of men born after the 1990s is 11 cm taller than that of men born after the 1920s, which has now reached 173 cm, and that the height of women is 10.93 cm taller, averaging 163 cm. The average height of the Chinese population reflects significant differences in gender, region or province, urbanity and rurality, and nationality, among other variables. The average height of men and women gradually increases with the increase of geographical latitude. Some economically developed southern provinces approach the average height of the North. This paper predicts that the average height of the newborn population will continue to have inertial growth in the next 20 years, and the newborn male population will reach the World Health Organization’s ideal height standard of 176.5 cm by 2030. The analysis suggests that geographic latitude and heredity are the determinants of body development. Geographical latitude difference is a super-variable for human mitochondria to regulate the proportion of heat outflow and ATP transformation. Historically, the population living in high-latitude areas of China migrates to economically developed low-latitude provinces such as Shanghai, Jiangsu, Zhejiang, and Guangdong, which is the main reason why the per capita height in these areas is significantly taller than that in other southern provinces.
Groundwater exploration by magnetotelluric method within the birimian rocks of mankessim, Ghana
Authors: Agyemang Victor Ofori
Published: February 2022

The Magnetotelluric (MT) geophysical method has successfully been applied in groundwater exploration within the Birimian rocks of Mankessim. The technique has provided information on the rocks and structural relationships within the investigative depth of up to 300 m for hydrogeological purposes. The method provides information on the aquiferous zone and the general depth of burial. The study revealed that the resistivity of the subsurface materials within the study area ranges from 0.1 Ωm to 4.0 Ωm. The study shows that the groundwater occurrence in the area is mainly controlled by fractured and weathered zones. It is highly possible to encounter groundwater at the saprock zone. This zone is fractured and weathered zones sandwiched by the overburden and the bedrock. The static water level of the study area is about 25 m. This shallow depth makes the groundwater resource prone to contamination through anthropogenic activities such as the application of agrochemicals and the use of pit latrine which are common practices in the study area. The MT method is effective in the exploration of groundwater within the sedimentary environment.
Prospect evaluation based on integrated petroleum system analysis: Block E case study, south-eastern edge of Precaspian Basin (Kazakhstan)
Authors: Zhanserkeyeva A. A. , Kassenov A. K.
Published: February 2022

Generative potential and thermal maturity for Upper Palaeozoic source rocks from the south-eastern edge of Precaspian Basin were determined using Rock–Eval. A high hydrocarbon source rock generative potential and high degree of thermal maturity for the Lower Permian, Mid-Carboniferous strata have been revealed based on 39 rock samples. TOC values of 0.4–5.5% have been obtained for mature source rocks. Integrated geochemical analysis determined from Rock–Eval studies combined with 1D basin modelling was utilized in order to reconstruct thermal evolution for the Upper Palaeozoic source rocks. Calibrated 1D models for three wells had been constructed to understand petroleum system. For two deep exploration wells (Nur-1 and Tassym SE-1), which penetrated pre-salt strata at the depths of 5.7 and 7 km, respectively, the impact of salt diapirism on timing of maturation was modelled. Type II kerogen was used, which is based on previous palaeogeographic studies. The stratigraphic framework and major stages of geodynamic evolution were analysed. Salt-related structural traps in post-salt strata have been described based on 3D seismic data, and additional intra-salt sediment packages have been delineated. Discovered producing oil fields in the Upper Triassic and Jurassic–Cretaceous stratigraphic sections are mainly confined to the four-way dip structural closures above the steep flanks of salt structures. Based on burial and thermal modelling, the maturation and generation behaviour of kerogen Type II below salt-related minibasins and close to thick salt diapirs were inferred. For Lower Permian SR with type II kerogen, the generation peak (maturity over 50%) occurs in Middle to Late Jurassic. For predominantly carbonate and terrigenous-carbonate Mid-Carboniferous marine SR, generation peak occurs earlier below salt withdrawal minibasins. Implications for deeper hydrocarbon prospectivity were made for the study area, and methodology for evaluating hydrocarbon potential adopting 1D basin modelling technique and geochemical data is presented.
Fathering a child after childhood cancer treatments
Authors: Serrano Joana B. , Meißner Andreas , van Pelt Ans M. M. , Mulder Callista L.
Published: February 2022

Among many deleterious ramifications of oncological treatments, there is permanent male infertility due to the damage to spermatogonial stem cells (SSC) in the testes after chemotherapy or irradiation. For those patients that cannot produce sperm before cancer treatment, because of prepubertal age, there are no clinical options available to father a child. To preserve fertility in childhood cancer patients, freezing of a testis biopsy is already offered before cancer treatment, while fertility treatment options using this biopsy are still under development, including spermatogonial stem cell transplantation (SSCT). SSCT requires isolation and in vitro propagation of spermatogonial stem cells from the cryopreserved biopsy, followed by autologous transplantation back to the adult cancer survivor. Given the implications of this potential stem cell therapy to recipients, their partners, and future offspring, we here aim to thoroughly appraise the state-of-the-art of SSCT focussing on safety for both patient and his future children.
On Eisenstein series, color partition and divisor function
Authors: Pushpa K. , Vasuki K. R.
Published: February 2022

Ramanujan recorded Eisenstein series identities of level 5 of weight 2. The objective of this article is to prove these identities by classical method and also we find some new Eisenstein series identities for level 7. Finally we make use of these results to obtain convolution sums of divisor functions. We will also be introducing certain restricted color partition functions which helps us to represent the convolution sums in a much elegant form than the existing ones.
A Genealogical Study of Facemasks in China: From Hygienic Modernity to Care
Authors: Gong Buyun
Published: February 2022

Despite the omnipresence of facemasks in the ongoing COVID-19 pandemic, recent studies on their sociopolitical aspects remain insufficient. This article conducts a genealogical study that investigates the emergence of two differing masking strategies in two epidemic events in Chinese history. First, during the Manchurian plague 1910/11, it shows how the germ theory and historical anecdotes made anti-plague masks thinkable and practicable as a solution not only for airborne contagion but also for the biopolitical problem of ‘unhygienic’ population. In the second part, the analytical focus is shifted to the emergence of collective mask-wearing practices during SARS 2002/03 from the vantage point of subjectification. Facemasks then became a symbol of care in the neoliberal regime of responsibilization. This article concludes by arguing for a rethinking of facemasks as actants who actively participate in the constitution of the world we share.
Die innere Dynamik von selbst- und umweltbezogenen Tugenden im tugendhaften Akteur.
Authors: Runge Richard Friedrich
Published: February 2022

Die eudaimonistische Tugendethik sieht sich, was ihre innere Struktur anbelangt, standardmäßig mit den Vorwürfen des Egoismus und Anthropozentrismus konfrontiert, was auch das Projekt einer ökologischen Tugendethik zu gefährden scheint. Der vorliegende Artikel versucht, ausgehend von der Tugendethik Erich Fromms, eine neue Perspektive auf diese Standardvorwürfe zu entwickeln, indem er den theoretischen Implikationen nachgeht, die die Anerkennung der Biophilie – der Liebe zum Leben – als eine der Tugenden des Menschen für den Frommschen Ansatz hat. Die zunächst noch exegetisch ausgerichtete Diskussion der werkinternen Relation von humanistischer und biophiler Ethik bei Erich Fromm leitet schließlich zu einer stärker systematisch ausgerichteten Diskussion der inneren Dynamik von selbst- und umweltbezogenen Tugenden im tugendhaften Akteur über. In diesem Zuge wird deutlich gemacht, dass das selbstbezogene Streben nach eigener Eudaimonie und das umweltbezogene Streben nach der Förderung des Objekts der eigenen Liebe zwar durchaus miteinander in einen Konflikt geraten können, dass dieser Konflikt aber nicht zur Selbstauslöschung der Tugendethik führt, sondern stattdessen im tugendhaften Akteur eine produktive Dynamik entfaltet. Die klassische Gegenüberstellung von Anthropozentrismus und Biozentrismus innerhalb der Ethik lässt sich auf diese Weise unterlaufen.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody prevalence in a healthcare worker population exceeded self-reported infection rates, 2020
Authors: Hoover Susan E. , Reed Valerie
Published: February 2022

A study of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) seroprevalence at a healthcare institution prior to the availability of vaccine showed that seroprevalence in the cohort increased over 6 months from 25% to 55%. The number of employees with antibodies was higher than the number who reported an exposure or diagnosis at each time point.
The clinical and neuroimaging features of sporadic adult-onset neuronal intranuclear inclusion disease
Authors: Ni You , Yang Zhao , Zhou Qinming , Liu Jun , Zhou Haiyan , Chen Sheng
Published: February 2022

Background:

Neuronal intranuclear inclusion disease (NIID) is a rare slowly progressive neurodegenerative disorder that is characterized pathologically by the presence of eosinophilic intranuclear inclusions. NIID is a heterogeneous disease with diverse clinical manifestations, making diagnosis difficult. Here, we analyzed the clinical, pathological, and radiological features of Chinese NIID patients to improve our understanding of NIID.

Methods:

A total of 17 patients with sporadic NIID were recruited from the Ruijin Hospital Database between 2014 and 2021. Clinical patient information and brain MRI data were collected. All of the patients underwent standard skin biopsy procedures.

Results:

The average age of onset for symptoms was 60.18 years, and the average duration of illness was 4.06 years. All patients were diagnosed with NIID due to the presence of intranuclear inclusions confirmed by skin biopsy. Tremor was the most common initial symptom. The average ages at onset and at diagnosis were both lower in patients with tremor than in patients without tremor. NIID may be a systemic disease that affects multiple organs, for one patient had a history of chronic renal insufficiency for more than 10 years. In addition to high-intensity U-fibers signals on diffusion-weighted imaging, there were several other MRI findings, such as focal leukoencephalopathy and cortical swelling. Encephalitic episodes followed by reversible leukoencephalopathy was another important imaging feature of NIID.

Conclusion:

The clinical manifestations of NIID are highly variable. Tremor may be the most common initial symptom in certain cohorts. Encephalitic episodes followed by reversible asymmetric leukoencephalopathy may also indicate this disease.