bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐Throughput Single‐Cell Mass Spectrometry Reveals Abnormal Lipid Metabolism in Pancreatic Ductal Adenocarcinoma
Authors: Liu Qinlei , Ge Wenjie , Wang Tongtong , Lan Jiayi , Martínez‐Jarquín Sandra , Wolfrum Christian , Stoffel Markus , Zenobi Renato
Published: September 2021

Even populations of clonal cells are heterogeneous, which requires high‐throughput analysis methods with single‐cell sensitivity. Here, we propose a rapid, label‐free single‐cell analytical method based on active capillary dielectric barrier discharge ionization mass spectrometry, which can analyze multiple metabolites in single cells at a rate of 38 cells/minute. Multiple cell types (HEK‐293T, PANC‐1, CFPAC‐1, H6c7, HeLa and iBAs) were discriminated successfully. We found evidence for abnormal lipid metabolism in pancreatic cancer cells. We also analyzed gene expression in a cancer genome atlas dataset and found that the mRNA level of a critical enzyme of lipid synthesis (ATP citrate lyase, ACLY) was upregulated in human pancreatic ductal adenocarcinoma (PDAC). Moreover, both an ACLY chemical inhibitor and a siRNA approach targeting ACLY could suppress the viability of PDAC cells. A significant reduction in lipid content in treated cells indicates that ACLY could be a potential target for treating pancreatic cancer.
Surrogate model to screen for inactivation‐based clearance of enveloped viruses during biotherapeutics process development
Authors: Feroz Hasin , Cetnar Daniel , Hewlett Robert , Sharma Satish , Holstein Melissa , Ghose Sanchayita , Li Zheng Jian
Published: September 2021

Viral surrogates to screen for virus inactivation (VI) can be a faster, cheaper and safer alternative to third‐party testing of pathogenic BSL2 (Biosafety level 2) model viruses. Although the bacteriophage surrogate, Ø6, has been used to assess low pH BSL2 VI, it has not been used for evaluation of detergent‐mediated VI. Furthermore, Ø6 is typically assayed through host cell infectivity which introduces the risk of cross‐contaminating other cell lines in the facility. To circumvent contamination, we developed an in‐house RT‐qPCR (Reverse transcriptase quantitative polymerase chain reaction) assay for selective detection of active Ø6 from a population of live and dead phage. The RT‐qPCR assay was used to evaluate Ø6 inactivation in cell culture fluid of monoclonal antibody and fusion protein. Complementary Ø6 infectivity was also conducted at a third‐party testing facility. The Ø6 RT‐qPCR and infectivity data was modeled against VI of three BSL2 viruses, X‐ MuLV, A‐ MuLV and HSV‐1 in corresponding therapeutics. Both Ø6 methods demonstrate that any VI agent showing Ø6 clearance of a minimum of 2.5 logs would demonstrate complete BSL2 VI of ≥ 4.0 logs. Compared to BSL2 virus testing, this in‐house Ø6 RT‐qPCR tool can screen VI agents at 5% the cost and a turnaround time of 2 to 3 days vs. 4 to 7 months.
CRISPR‐Cas enzymes: The toolkit revolutionizing diagnostics
Authors: Verosloff Matthew S. , Shapiro Sarah J. , Hawkins Elizabeth M. , Alpay Emel , Verma Deepika , Stanfield Emma G. , Kreindler Lior , Jain Sonal , McKay Bridget , Hubbell Shae A. , Hendriks Carley G. , Blizard Benjamin A. , Broughton James P. , Chen Janice S.
Published: September 2021

The programmable nature of sequence‐specific targeting by CRISPR‐Cas nucleases has revolutionized a wide range of genomic applications and is now emerging as a method for nucleic acid detection. We explore how the diversity of CRISPR systems and their fundamental mechanisms have given rise to a wave of new methods for target recognition and readout. These cross‐disciplinary advances found at the intersection of CRISPR biology and engineering have led to the ability to rapidly generate solutions for emerging global challenges like the COVID‐19 pandemic. We further discuss the advances and potential for CRISPR‐based detection to have an impact across a continuum of diagnostic applications.
Pseudomonas putida KT2440 endures temporary oxygen limitations
Authors: Demling Philipp , Ankenbauer Andreas , Klein Bianca , Noack Stephan , Tiso Till , Takors Ralf , Blank Lars M.
Published: September 2021

The obligate aerobic nature of Pseudomonas putida, one of the most prominent whole‐cell biocatalysts emerging for industrial bioprocesses, questions its ability to be cultivated in large‐scale bioreactors, which exhibit zones of low dissolved oxygen tension. P. putida KT2440 was repeatedly subjected to temporary oxygen limitations in scale‐down approaches to assess the effect on growth and an exemplary production of rhamnolipids. At those conditions, the growth and production of P. putida KT2440 were decelerated compared to well‐aerated reference cultivations, but remarkably, final biomass and rhamnolipid titers were similar. The robust growth behavior was confirmed across different cultivation systems, media compositions, and laboratories, even when P. putida KT2440 was repeatedly exposed to dual carbon and oxygen starvation. Quantification of the nucleotides ATP, ADP, and AMP revealed a decrease of intracellular ATP concentrations with increasing duration of oxygen starvation, which can, however, be restored when re‐supplied with oxygen. Only small changes in the proteome were detected when cells encountered oscillations in dissolved oxygen tensions. Concluding, P. putida KT2440 appears to be able to cope with repeated oxygen limitations as they occur in large‐scale bioreactors, affirming its outstanding suitability as a whole‐cell biocatalyst for industrial‐scale bioprocesses.
Catalytic Hydrodeoxygenation of Model Bio‐oils Using HZSM‐5 and Ni2P/HZM‐5 Catalysts: Comprehension of Interaction
Authors: Wang Jundong , Abdelouahed Lokmane , Xu Jie , Brodu Nicolas , Taouk Bechara
Published: September 2021

Hydrodeoxygenation (HDO) of Mixture 1 (acetic acid and phenol) and Mixture 2 (acetone, acetic acid, phenol, 4‐ethylguaiacolis, furfural, and water) as model bio‐oils was performed to investigate the interactions. Ni2P/HZSM‐5 catalysts exhibited higher activity than blank HZSM‐5. The conversion rate of acetic acid enhanced with the increase of temperature, contrary to the value of phenol due to the differential adsorption capacity on active phases. Acetone can be formed by self‐ketonization of acetic acid. Low temperatures favored esterification, while high temperatures promoted the synthesis of alkyl‐substituted phenols and aromatic hydrocarbons via mainly alkyl substitution of phenol and benzene, respectively. Two reaction networks of model bio‐oil HDO with the main reactions were proposed.
Electrochemical Studies of CO2‐Reducing Metalloenzymes
Authors: Meneghello Marta , Léger Christophe , Fourmond Vincent
Published: September 2021

Only two enzymes are capable of directly reducing CO2: CO dehydrogenase, which produces CO at a [NiFe4S4] active site, and formate dehydrogenase, which produces formate at a mononuclear W or Mo active site. Both metalloenzymes are very rapid, energy‐efficient and specific in terms of product. They have been connected to electrodes with two different objectives. A series of studies used protein film electrochemistry to learn about different aspects of the mechanism of these enzymes (reactivity with substrates, inhibitors…). Another series focused on taking advantage of the catalytic performance of these enzymes to build biotechnological devices, from CO2‐reducing electrodes to full photochemical devices performing artificial photosynthesis. Here, we review all these works.
Development and Application of a Complete Active Space Spin‐Orbit Configuration Interaction Program Designed for Single Molecule Magnets
Authors: Bodenstein Tilmann , Heimermann Andreas , Fink Karin , van Wüllen Christoph
Published: September 2021

We present a spin‐orbit configuration interaction program which has been tailored for the description of the magnetic properties of polynuclear metal complexes with partially filled d‐ and f‐shells. The spin‐orbit operators are directly included in the configuration interaction program based on Slater‐determinants. The lowest states are obtained by a Block‐Davidson‐type diagonalisation. The usage of localised active orbitals enables the construction of start vectors from tensor products of single‐center wave functions that already include spin‐orbit interaction. This allows for an analysis of the role and the interplay of the different metal centres. Furthermore, in case of weak coupling of the metal centres these tensor products are already close to the final wave functions ensuring fast convergence. In combination with a two‐layer hybrid parallelisation, this makes the program highly efficient. Based on the spin‐orbit coupled wave functions, magnetic D‐tensors, g‐tensors and temperature‐dependent susceptibilities can be calculated. The applicability and performance of the program is shown exemplarily on a trinuclear transition metal (CoIIVIICoII) complex.
Cytological features of ovarian or tubal high‐grade serous carcinoma: A retrospective study of 12 cases with abnormal cervical liquid‐based smear
Authors: Xu Yanning , Liu Bingbing , Zhang Xiaojing , Chen Ling
Published: September 2021

Background

High‐grade serous carcinoma (HGSC) is the most common epithelial carcinoma of the tubo‐ovarian region, with a poor prognosis, which presents with an advanced stage at the time of diagnosis. This study summarizes the cytological features of cervical liquid‐based cytological examination in order to diagnose ovarian or tubal HGSC at an early stage by cervical cytology smear.

Methods

A total of 12 patients who were diagnosed with atypical glandular cell (AGC) and above lesions by cervical cytological examination and ovarian or tubal HGSC by histopathology were enrolled in this study. The cytological characteristics, including the arrangement and shape of the neoplastic cells, nuclear and cytoplasmic features, and the presence of tumor diathesis were reviewed.

Results

Nine cases were determined to be AGC, and three cases were determined to be AGC favor neoplastic (AGC‐FN) in the 12 cervical cytological diagnoses. The glandular cells showed significant atypia and proliferated actively with a three‐dimensional structure. Increased nuclear‐to‐cytoplasmic ratios, prominent nucleoli, and hyperchromasia were common. Vacuole‐like changes were observed in the cytoplasm. Tumor diathesis was observed in only one case (1/12, 8.30%).

Conclusion

Ovarian or tubal HGSC can occasionally be detected using cervical liquid‐based cytology. It has distinct cytological characteristics. Primary ovarian or tubal HGSC with positive cervical cytology was accompanied by tumor cells in ascites, which suggested that the patient had progressed to an advanced stage.
The dominant left ventricular assist device: lessons from an era
Authors: Alam Amit , Milligan Gregory P. , Gong Timothy
Published: September 2021

The production and distribution of the HeartWare ventricular assist device has come to an abrupt end, but with this end comes the opportunity to reflect upon lessons learned from its lifespan. Running counter to the standard of evidence‐based practice, the era of the HeartWare ventricular assist device was marred with fragmented data in relation to its primary counterpart, the HeartMate III. This created an incomplete understanding of devices, limited individualized patient care, and effectively positioned providers to make inferences regarding device superiority. We briefly review pertinent literature on this topic among the most commonly implanted durable devices from the era, detail the inherent limitations of this data, and argue the necessity of randomized clinical trials among novel devices towards the optimization of patient care.
Temperature and Counterion Dependent Spin Crossover in a Hexaamineiron(II) Complex
Authors: Connolly Blake J. P. , Brosius Victor , Mertes Nicole , Demidova Caroline , Bilyj Jessica K. , Riley Mark J. , Bernhardt Paul V.
Published: September 2021

Based on previous results with [Fe(tame)2]Cl2.MeOH (tame=1,1,1‐tris(aminomethyl)ethane), which exhibits temperature dependent spin crossover, we report a series of isostructural rhombohedral salts [Fe(tame)2]X2.MeOH (X=Br−, ClO4−, BF4−) and examine their temperature dependent structures. In the case of [Fe(tame)2]Br2.MeOH, temperature dependent single crystal Vis‐NIR spectroscopy is reported as a complement to single crystal X‐ray diffraction results. The [Fe(tame)2]Br2.MeOH compound does show spin crossover behaviour but at very low temperatures (<100 K) and the spin active complex cation could not be converted exclusively to its low spin form even at 12 K. This is significantly different to its relative [Fe(tame)2]Cl2.MeOH which is entirely low spin at 60 K. The isostructural [Fe(tame)2]X2.nMeOH (X=ClO4− (n=0.5) and BF4− (n=1)) compounds show no spin crossover at the temperatures examined and remain exclusively in their high spin form. Removal of the MeOH solvent leads to another isostructural compound [Fe(tame)2](ClO4)2, which shows a remarkable reversible loss of crystallinity below 200 K that could be restored by warming to temperatures above 200 K. The fluoride and trifluoromethanesulfonate salts of [Fe(tame)2]2+ crystallise in monoclinic lattices and show no spin crossover behaviour.
Stereoselective Mannich Reaction of α‐Acetoxy‐β‐keto Esters with Isatin Imine: An Efficient Access to Vicinal Tetra‐Substituted Stereocenters
Authors: Kaur Jasneet , Preet Kaur Banni , Islam Nasarul , Chauhan Pankaj , Singh Chimni Swapandeep
Published: September 2021

A highly diastereo‐ and enantioselective Mannich reaction of α‐acetoxy‐β‐keto esters with isatin imine was developed. The quinine thiourea organocatalyst smoothly promoted the asymmetric Mannich reaction to furnish various 3‐substituted‐3‐aminooxindole derivatives bearing two adjacent tetra‐substituted stereocenters in up to 93 % yield, up to 98 % ee with >20 : 1 dr. The transition state structure and absolute configuration of the obtained product were predicted using DFT calculations, and results from single crystal X‐ray analysis are in agreement with the DFT studies.
An Efficient Novel Electrochemical Sensor for Simultaneous Determination of Vitamin C and Aspirin Based on a PMR/Zn‐Al LDH/GCE
Authors: Abo‐bakr A. M. , Abd‐Elsabour M. , Abou‐Krisha M. M.
Published: September 2021

A sensitive, low‐cost, and simple electrochemical sensor based on Zn−Al layered double hydroxide (Zn−Al LDH) combined with a polymer film of methyl red (PMR) to modify a GCE has been created for the first time. Using cyclic voltammetry (CV), the electrochemical characteristics of the newly fabricated sensor were investigated. The characterised PMR/Zn−Al LDH/GCE shows high electro‐catalytic activity towards the vitamin C (AA) and aspirin (ASA) oxidation. Schematic fabrication of PMR/Zn−Al LDH/GCE for the determination of AA or ASA was presented. The new sensor demonstrated superior analytical efficiency for the simultaneous identification of AA and ASA traces in well‐spaced anodic peaks, even in the presence of certain intervening species. According to experimental results, the fabricated sensor represented two well‐separated oxidation peaks for AA and ASA oxidation with potential difference of 799 mV (vs. Ag/AgCl). The linear dependences of the anodic peak currents of AA and ASA on their concentrations in the ranges of 0.10–53.17 μM are good. The detection limits of AA and ASA at the PMR/Zn−Al LDH/GCE were found to be 1.26 and 1.27 μM, respectively. Meanwhile, the quantification limits of AA and ASA were calculated as 4.21 and 4.25 μM, respectively. On other hand, the limit of detection (LODs) of AA and ASA oxidation were determined to be 0.47 and 0.21 μM, respectively, according to DPV method. The effect of scan rate (100 to 800 mV/s) on the anodic peak currents of AA and ASA was examined. A sensing model mechanism has been suggested and discussed in detail. Finally, the proposed sensor displayed a good reproducibility, stability and selectivity. The developed sensor was eventually used to successfully detect AA and ASA in urine samples.
A dengue fever model with free boundary incorporating the time‐periodicity and spatial‐heterogeneity
Authors: Zhu Min , Xu Yong , Zhang Lai , Cao Jinde
Published: September 2021

Propagation of dengue fever is characterized by periodicity and seasonality and further influenced by geographic heterogeneity. To account for these characteristics, we formulate a dengue model in a spatial‐heterogeneous and time‐periodic environment. Moreover, the free boundary is additionally incorporated into our model to reflect the boundary change of region where dengue virus spreads. Employing the properties of the contagion risk threshold, that is the spatial‐temporal basic reproduction ratio, we derive some sufficient conditions regarding the vanishing and spreading of virus. Importantly, the long‐time asymptotic behavior of solution is studied in depth when spreading happens. Our findings manifest that as time goes on, dengue virus will behave periodically when spreading. Finally, these phenomena are numerically simulated and epidemiologically explained.
Pain in acute motor axonal neuropathy
Authors: Zhao Fei , Wang Juan , Zhang Jing , Pang Xiaomin , Huang Shan , Chang Xueli , Guo Junhong , Zhang Wei
Published: September 2021

Introduction/Aims

Patients with acute motor axonal neuropathy (AMAN) generally have pure motor neuropathy and clinicians usually do not link pain with AMAN. The aim of this retrospective study was to describe the character, location, and intensity of pain in AMAN and acute inflammatory demyelinating polyneuropathy (AIDP) in the acute phase.

Methods

This was a retrospective study in 44 patients with Guillain‐Barré syndrome (GBS) having progressive weakness of more than one limb. The information, including the demographic characteristics, preceding infections, clinical symptoms and signs, severity at nadir, the characteristics of pain, use of analgesics, laboratory and electrophysiological data, and the medical treatment for GBS, were collected from the medical records.

Results

In 44 patients, 40.9% were diagnosed as AMAN, and 34.1% as AIDP. Pain was more prevalent in AMAN (76.5%) than in AIDP (26.7%, P = .02). Low back and extremities were the most common locations of pain in AMAN (7/13 and 7/13, respectively) and AIDP (2/4 and 2/4, respectively).

Discussion

Pain was a common symptom in AMAN in the acute stage. The presence or absence of pain is not useful for distinguishing AIDP from AMAN.
Artificial intelligence strategy integrating morphologic and architectural biomarkers provides robust diagnostic accuracy for disease progression in chronic lymphocytic leukemia
Authors: El Hussein Siba , Chen Pingjun , Medeiros L Jeffrey , Wistuba Ignacio I , Jaffray David , Wu Jia , Khoury Joseph D
Published: September 2021

Artificial intelligence‐based tools designed to assist in the diagnosis of lymphoid neoplasms remain limited. The development of such tools can add value as a diagnostic aid in the evaluation of tissue samples involved by lymphoma. A common diagnostic question is the determination of chronic lymphocytic leukemia (CLL) progression to accelerated CLL (aCLL) or transformation to diffuse large B‐cell lymphoma (Richter transformation; RT) in patients who develop progressive disease. The morphologic assessment of CLL, aCLL, and RT can be diagnostically challenging. Using established diagnostic criteria of CLL progression/transformation, we designed four artificial intelligence‐constructed biomarkers based on cytologic (nuclear size and nuclear intensity) and architectural (cellular density and cell to nearest‐neighbor distance) features. We analyzed the predictive value of implementing these biomarkers individually and then in an iterative sequential manner to distinguish tissue samples with CLL, aCLL, and RT. Our model, based on these four morphologic biomarker attributes, achieved a robust analytic accuracy. This study suggests that biomarkers identified using artificial intelligence‐based tools can be used to assist in the diagnostic evaluation of tissue samples from patients with CLL who develop aggressive disease features. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Synthesis, characterization and biological activity of bifunctional ionic liquids based on dodine ion
Authors: Kukawka Rafal , Spychalski Maciej , Stróżyk Ewa , Byzia Ewa , Zajac Adrian , Kaczyński Piotr , Łozowicka Bożena , Pospieszny Henryk , Smiglak Marcin
Published: September 2021

BACKGROUND

Development of new plant protection strategies has become an urgent matter in modern agriculture, in view of the evidently proved negative effect of currently used active ingredients of pesticides. In recent years, much effort has been made to eliminate the use of pesticides established to be toxic to pollinators.

RESULTS

In this study, we present a group of new bifunctional ionic liquids based on dodine (N‐dodecylguanidine) cation whose physical and biological properties have been modified relative to those of the commercially available N‐dodecylguanidine acetate. The decreased level of residue of active substances in plant tissues reduces their availability to pollinators, which increases the safety of their use. Moreover, lower environmental impact in combination with high antifungal activity and an additional biological function, that is the systemic acquired resistance induction, are in line with the goals of sustainable agriculture.

CONCLUSION

The presented approach shows the possibility of derivatization of commonly used fungicide into the form of bifunctional salts whose physical and biological properties can be easily modified. The paper reports successful design and synthesis of new sustainable and green chemicals for the modern agriculture, being less toxic to the environment and human health but still effective against pathogens. © 2021 Society of Chemical Industry.
Safety‐catch linkers for Fmoc solid‐phase synthesis of peptide thioesters and hydrazides by amide‐to‐imide activation
Authors: Paprocki Maciej P. , Rasmussen Jakob E. , Sørensen Kasper K. , Jensen Knud J.
Published: September 2021

The use of C‐terminal peptide thioesters and hydrazides in synthetic protein chemistry has inspired the search for optimal solid‐phase peptide synthesis (SPPS) strategies for their assembly. However, peptide thioesters are not directly accessible by conventional Fmoc‐SPPS owing to the nucleophilicity of the secondary amine required for Fmoc removal. Here, we report the mild and effective activation of the pGlu linker and a new safety‐catch linker that was used for the convenient synthesis of peptide thioesters and hydrazides via efficient amide‐to‐imide activation followed by nucleophilic displacement.
Horace Cecil Menear
Authors: Barlow Alex , Mitchell Cliff , Sirl Christa
Published: September 2021

A vet with a strong character and a keen mind, who was never happier than when on a beach with his family.
Hugh Charles Brent Reed
Authors: Logue David , Reed John
Published: September 2021

A vet who was well known in the field of artificial insemination of pigs.
Hyperbaric oxygen therapy for extensive wounds in a Bengal kitten
Authors: Milich Kelsey , Dong Charli
Published: September 2021

A five‐month‐old Bengal kitten was presented for symmetric extensive wounds of unknown origin on the caudomedial thighs. The location of the wounds plus the patient's age and temperament made bandaging for open wound management challenging. Cutaneous wounds in cats have been shown to heal slower than dogs. The kitten completed 17 hyperbaric oxygen therapy sessions, with full closure of wounds by day 31. Hyperbaric oxygen therapy has long been used in human medicine for both acute and chronic wounds, and many publications are available on its mechanisms of action. This case emphasizes the potential benefits of hyperbaric oxygen therapy in wound healing in cats.
The growing field of digital psychiatry: current evidence and the future of apps, social media, chatbots, and virtual reality
Authors: Torous John , Bucci Sandra , Bell Imogen H. , Kessing Lars V. , Faurholt‐Jepsen Maria , Whelan Pauline , Carvalho Andre F. , Keshavan Matcheri , Linardon Jake , Firth Joseph
Published: September 2021

As the COVID‐19 pandemic has largely increased the utilization of telehealth, mobile mental health technologies – such as smartphone apps, vir­tual reality, chatbots, and social media – have also gained attention. These digital health technologies offer the potential of accessible and scalable interventions that can augment traditional care. In this paper, we provide a comprehensive update on the overall field of digital psychiatry, covering three areas. First, we outline the relevance of recent technological advances to mental health research and care, by detailing how smartphones, social media, artificial intelligence and virtual reality present new opportunities for “digital phenotyping” and remote intervention. Second, we review the current evidence for the use of these new technological approaches across different mental health contexts, covering their emerging efficacy in self‐management of psychological well‐being and early intervention, along with more nascent research supporting their use in clinical management of long‐term psychiatric conditions – including major depression; anxiety, bipolar and psychotic disorders; and eating and substance use disorders – as well as in child and adolescent mental health care. Third, we discuss the most pressing challenges and opportunities towards real‐world implementation, using the Integrated Promoting Action on Research Implementation in Health Services (i‐PARIHS) framework to explain how the innovations themselves, the recipients of these innovations, and the context surrounding innovations all must be considered to facilitate their adoption and use in mental health care systems. We conclude that the new technological capabilities of smartphones, artificial intelligence, social media and virtual reality are already changing mental health care in unforeseen and exciting ways, each accompanied by an early but promising evidence base. We point out that further efforts towards strengthening implementation are needed, and detail the key issues at the patient, provider and policy levels which must now be addressed for digital health technologies to truly improve mental health research and treatment in the future.
The clinical characterization of the adult patient with an anxiety or related disorder aimed at personalization of management
Authors: Stein Dan J. , Craske Michelle G. , Rothbaum Barbara O. , Chamberlain Samuel R. , Fineberg Naomi A. , Choi Karmel W. , de Jonge Peter , Baldwin David S. , Maj Mario
Published: September 2021

The clinical construct of “anxiety neurosis” was broad and poorly defined, so that the delineation of specific anxiety disorders in the DSM‐III was an important advance. However, anxiety and related disorders are not only frequently comorbid, but each is also quite heterogeneous; thus diagnostic manuals provide only a first step towards formulating a management plan, and the development of additional decision support tools for the treatment of anxiety conditions is needed. This paper aims to describe systematically important domains that are relevant to the personalization of management of anxiety and related disorders in adults. For each domain, we summarize the available research evidence and review the relevant assessment instruments, paying special attention to their suitability for use in routine clinical practice. We emphasize areas where the available evidence allows the clinician to personalize the management of anxiety conditions, and we point out key unmet needs. Overall, the evidence suggests that we are becoming able to move from simply recommending that anxiety and related disorders be treated with selective serotonin reuptake inhibitors, cognitive‐behavioral therapy, or their combination, to a more complex approach which emphasizes that the clinician has a broadening array of management modalities available, and that the treatment of anxiety and related disorders can already be personalized in a number of important respects.
Overview of Nutrition Care in Geriatrics and Orthogeriatrics
Authors: Geirsdóttir Ólöf G. , Hertz Karen , Santy-Tomlinson Julie , Johansen Antony , Bell Jack J.
Published: September 2021

Engaging older adults, and all those who care for them, is pivotal to providing high-value nutrition care for older adults. Nurses and other interdisciplinary team members are essential to this process. The aim of this chapter is to provide an overview of the rationale and evidence for interdisciplinary and systematised nutrition care as an effective nutrition care approach for older adults with or at risk of malnutrition. This chapter also serves as a guide to detailed chapters across this book to provide focal points on different aspects of nutrition care that should be considered across primary prevention, acute care, rehabilitation, secondary prevention and community settings (Dreinhöfer et al., Injury 49(8):1393–1397, 2018).
Delivering Interprofessional Education to Embed Interdisciplinary Collaboration in Effective Nutritional Care
Authors: Santy-Tomlinson Julie , Laur Celia V. , Ray Sumantra
Published: September 2021

Previous and forthcoming chapters describe how to improve nutrition care with an emphasis on interdisciplinary approaches. Developing and improving the skills and knowledge of the interdisciplinary team through interprofessional education are essential for embedding evidence-based, collaborative, nutritional care. This capacity building in turn supports delivery of effective nutritional care for older adults.
Nutrition and Delirium
Authors: Mudge Alison , Young Adrienne , Cahill Margaret , Treleaven Elise , Spirgienė Lina
Published: September 2021

Delirium is a common and serious complication in hospitalised older people. Poor nutrition and hydration are both risk factors for, and consequences of, delirium. This chapter will discuss the phenomenology of delirium and the role of nurses in recognising, preventing and managing this serious complication. It will also provide practical strategies to support nutrition and hydration in patients with, or at risk of, delirium.
Nutritional Assessment, Diagnosis, and Treatment in Geriatrics
Authors: Holst Mette , Beck Anne Marie
Published: September 2021

The purpose of this chapter is to share knowledge about terminology and best practice approaches for the nutrition care process, including nutritional screening, assessment, diagnosis, intervention, and monitoring. This will focus on nutrition care for older adults with or at risk of malnutrition, in their own home, hospital, or caring facilities.
Supporting Nutrition Care in Older Adults: An Essential Component of ‘Best Practice’ Nursing
Authors: Spirgienė Lina , Damulevičienė Gytė , Bales Gabriele , Bell Jack J.
Published: September 2021

Evidence-based guidelines, recommendations and standards are considered the cornerstone of ‘best practice’ in nursing care. However, what optimal nutrition care of older adults actually looks like in real-world settings is also dependent on age, disease and care contexts and, perhaps most importantly, what matters to the older adult.
Theoretical and Methodological Validation of the Action Research: Methodology of the Scientific Study
Authors: Monkevičienė Ona , Galkienė Alvyra
Published: September 2021

This chapter presents the theoretical and methodological substantiation of the action research, which was used by collaborating research teams from Poland, Lithuania, Finland and Austria for the study “Improving Inclusive Education Through Universal Design for Learning”. The chapter discusses different sociocultural contexts in the participating countries and what led to the research question, which asks “How does the implementation of universal design for learning enrich the practice of inclusive education in different educational contexts”. This question was looked at in terms of its relevance to the four above-mentioned countries. It can be argued that the action research is favourable for the development of theory and that inclusive education can be changed and reflected by it. The types of action research chosen by the research teams are discussed, those being collaborative, and critical participatory. The cycles of action research and their goals are also presented. Seeking to substantiate the choices of research teams regarding the process and methods of action research, this chapter elaborates on the aspects of action research organisation that are interpreted differently by the researchers: Can the action research be conducted only by the researcher–teachers or can it be carried out by teachers in cooperation with researchers? Is it possible to use a combination of qualitative and quantitative research? The problem with quality and validity of action research is discussed.
Development of Knowledgeable and Resourceful Learners
Authors: Galkienė Alvyra , Monkevičienė Ona
Published: September 2021

This chapter introduces a study carried out in the context of the transformation of the Lithuanian education system towards inclusive education, with the aim of revealing the educational factors that contribute to students becoming knowledgeable and resourceful expert learners in the universal design for learning (UDL) approach. The UDL framework was chosen as a systematic reasoning instrument for the teacher and the school, aiding in achieving the development of expert learner qualities in every student in the general education context and ensuring the quality of inclusive education. The chapter briefly introduces the theoretical approach of the research, the context of Lithuanian education and the school where the research took place, which is relevant for the interpretation of the results, and other important methodological aspects. The research data show that applying the UDL approach helped the teachers to modify the educational process in order to develop in students the qualities of knowledgeable and resourceful expert learners. The results, presented in a structured manner in the chapter, reveal the process and contributing educational factors to students’ becoming actively perceiving, self-directed, knowledge-creating and co-creating learners and learners constructing their own deep comprehension. The research data reveal the methods used by the teachers to recognise and overcome the barriers in cultivating these qualities in their students. We also identified the emerging changes in teachers’ dispositions when applying the UDL approach and designing lessons aimed at promoting the qualities of knowledgeable and resourceful expert learners.
Implementing UDL: Development of Purposeful and Motivated Students
Authors: Stasiūnaitienė Eglė , Navaitienė Julita
Published: September 2021

The assurance of purposeful and motivated learning activities in educational practice has been explored for many years. The essence of purposeful learning, which combines the goals of both teachers and learners, is to focus the participants of the pedagogical process on positive pedagogical interactions and mutual progress. The learner receives a package of knowledge, skills, behaviour and values important for socialisation from the teacher, whereas the teacher ensures confirmation of the quality of their own activity through pedagogical interactions. This chapter presents the results of a study aiming to answer two research questions: (1) What qualities and abilities of a purposeful and motivated expert learner are developed by applying the universal design for learning (UDL) approach? (2) How do educational factors facilitate the development of a purposeful and motivated expert learner by applying the UDL approach? In answering these questions, the processes occurring in the context of Lithuanian education were studied.
Spatial Justice Models: An Exploratory Analysis on Fair Distribution of Opportunities
Authors: Feitosa Fillipe Oliveira , Wolf Jan-Hendrik , Marques João Lourenço
Published: September 2021

Equity, fairness, and justice are related concepts widely discussed in several areas of study but remain an open field in terms of spatial justice and support decision systems application. Uneven spatial development have shown a tendency to amplify social inequalities alongside territories. To better understand the spatial configuration and spatial distribution of resources for different social groups, multiple objective criteria can be used to formulate optimal resource allocation. This work discusses spatial justice by utilitarianism and Rawlsian difference principle perspectives to formulate two models based on facility location problem (FLP) framework. Assuming the proximity to a desired opportunity (service or resource) as a measure of wellbeing and satisfaction, we weight the distances to the nearest facility by a social factor based on exponential function. Optimization results tend to favor outliers for weighted FLP, while the regular distances FLP formulation tend to favor heavy urban areas. We found that results are heavy context based, as the distribution of social groups are determinant in optimization process.
Spatial Automated Valuation Model (sAVM) – From the Notion of Space to the Design of an Evaluation Tool
Authors: Marques João Lourenço , Batista Paulo , Castro Eduardo Anselmo , Bhattacharjee Arnab
Published: September 2021

Assuming that it is not possible to detach a dwelling from its location, this article highlights the relevance of space in the context of housing market analysis and the challenge of capturing the key elements of spatial structure in an automated valuation model: location attributes, heterogeneity, dependence and scale. Thus, the aim is to present a spatial automated valuation model (sAVM) prototype, which uses spatial econometric models to determine the value of a residential property, based on identification of eight housing characteristics (seven are physical attributes of a dwelling, and one is its location; once this spatial data is known, dozens of new variables are automatically associated with the model, producing new and valuable information to estimate the price of a housing unit). This prototype was developed in a successful cooperation between an academic institution (University of Aveiro) and a business company (PrimeYield SA), resulting the Prime AVM & Analytics product/service. This collaboration has provided an opportunity to materialize some of fundamental knowledge and research produced in the field of spatial econometric models over the last 15 years into decision support tools.
RGD-functionalised melanin nanoparticles for intraoperative photoacoustic imaging-guided breast cancer surgery
Authors: Liu Jing-Jing , Wang Zun , Nie Li-Ming , Zhu Yuan-Yuan , Li Ge , Lin Lin-Ling , Chen Min , Zhang Guo-Jun
Published: September 2021

Purpose

Obtaining tumour-free margins is critical for avoiding re-excision and reducing local recurrence following breast-conserving surgery; however, it remains challenging. Imaging-guided surgery provides precise detection of residual lesions and assists surgical resection. Herein, we described water-soluble melanin nanoparticles (MNPs) conjugated with cyclic Arg-Gly-Asp (cRGD) peptides for breast cancer photoacoustic imaging (PAI) and surgical navigation.

Methods

The cRGD-MNPs were synthesised and characterized for morphology, photoacoustic characteristics and stability. Tumour targeting and toxicity of cRGD-MNPs were determined by using either breast cancer cells, MDA-MB-231 tumour-bearing mice or the FVB/N-Tg (MMTV-PyVT) 634Mul/J mice model. PAI was used to locate the tumour and guide surgical resection in MDA-MB-231 tumour-bearing mice.

Results

The cRGD-MNPs exhibited excellent in vitro and in vivo tumour targeting with low toxicity. Intravenous administration of cRGD-MNPs to MDA-MB-231 tumour-bearing mice showed an approximately 2.1-fold enhancement in photoacoustic (PA) intensity at 2 h, and the ratio of the PA intensity at the tumour site to that in the surrounding normal tissue was 3.2 ± 0.1, which was higher than that using MNPs (1.7 ± 0.3). Similarly, the PA signal in the spontaneous breast cancer increased ~ 2.5-fold at 2 h post-injection of cRGD-MNPs in MMTV-PyVT transgenic mice. Preoperative PAI assessed tumour volume and offered three-dimensional (3D) reconstruction images for accurate surgical planning. Surgical resection following real-time PAI showed high consistency with histopathological analysis.

Conclusion

These results highlight that cRGD-MNP-mediated PAI provide a powerful tool for breast cancer imaging and precise tumour resection. cRGD-MNPs with fine PA properties have great potential for clinical translation.
Cooperatively breeding banded mongooses do not avoid inbreeding through familiarity-based kin recognition
Authors: Khera Monil , Arbuckle Kevin , Hoffman Joseph I. , Sanderson Jennifer L. , Cant Michael A. , Nichols Hazel J.
Published: September 2021

In species that live in family groups, such as cooperative breeders, inbreeding is usually avoided through the recognition of familiar kin. For example, individuals may avoid mating with conspecifics encountered regularly in infancy, as these likely include parents, siblings, and closely related alloparents. Other mechanisms have also been reported, albeit rarely; for example, individuals may compare their own phenotype to that of others, with close matches representing likely relatives (“phenotype matching”). However, determinants of the primary inbreeding avoidance mechanisms used by a given species remain poorly understood. We use 24 years of life history and genetic data to investigate inbreeding avoidance in wild cooperatively breeding banded mongooses (Mungos mungo). We find that inbreeding avoidance occurs within social groups but is far from maximised (mean pedigree relatedness between 351 breeding pairs = 0.144). Unusually for a group-living vertebrate, we find no evidence that females avoid breeding with males with which they are familiar in early life. This is probably explained by communal breeding; females give birth in tight synchrony and pups are cared for communally, thus reducing the reliability of familiarity-based proxies of relatedness. We also found little evidence that inbreeding is avoided by preferentially breeding with males of specific age classes. Instead, females may exploit as-yet unknown proxies of relatedness, for example, through phenotype matching, or may employ postcopulatory inbreeding avoidance mechanisms. Investigation of species with unusual breeding systems helps to identify constraints against inbreeding avoidance and contributes to our understanding of the distribution of inbreeding across species.

Significance statement

Choosing the right mate is never easy, but it may be particularly difficult for banded mongooses. In most social animals, individuals avoid mating with those that were familiar to them as infants, as these are likely to be relatives. However, we show that this rule does not work in banded mongooses. Here, the offspring of several mothers are raised in large communal litters by their social group, and parents seem unable to identify or direct care towards their own pups. This may make it difficult to recognise relatives based on their level of familiarity and is likely to explain why banded mongooses frequently inbreed. Nevertheless, inbreeding is lower than expected if mates are chosen at random, suggesting that alternative pre- or post-copulatory inbreeding avoidance mechanisms are used.
Human placental extract ameliorates methotrexate-induced hepatotoxicity in rats via regulating antioxidative and anti-inflammatory responses
Authors: Ghoneum Mamdooh , El-Gerbed Mohamed S. A.
Published: September 2021

Purpose

Methotrexate (MTX) induces hepatotoxicity, limiting its clinical efficacy as a widely known chemotherapy drug. In the current study, we examined the protective effect of human placenta extract (HPE) against MTX-induced liver damage in rats, as well as its ability to regulate antioxidative and anti-inflammatory liver responses.

Methods

Male rats were orally administered MTX at a daily dose of 5 mg/kg-body-weight in the presence or absence of HPE (10.08 mg/kg) for 2 weeks. We measured the biological effects of MTX and HPE on the levels of liver enzymes, lipid profile, lipid peroxidation, oxidative stress biomarkers, and cytokines [tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10)]. In addition, histological examination and histopathological scoring of liver tissues were performed.

Results

MTX-treated rats showed significantly increased (p < 0.001) liver enzyme levels for aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, total cholesterol, and triglyceride levels. However, HPE supplementation in MTX-treated rats significantly decreased (p < 0.001) these elevated levels. HPE supplementation also significantly reduced the oxidative stress biomarker malondialdehyde (MDA), reversed the reduction in glutathione (GSH), and markedly increased the antioxidant enzyme activities of catalase (CAT) and superoxide dismutase (SOD) in the livers of MTX-treated rats. Furthermore, HPE supplementation significantly decreased the MTX-elevated levels of the pro-inflammatory cytokines TNF-α, IL-6, and IL-10. Histopathological examinations showed that MTX produced severe cellular damage and inflammatory lesions in liver tissues, while treatment with HPE improved hepatic histologic architecture.

Conclusion

HPE has the ability to ameliorate methotrexate-induced liver injury in rats by mechanisms that include boosting antioxidative responses and down-regulating MDA and pro-inflammatory cytokine production.
Ruxolitinib exposure in patients with acute and chronic graft versus host disease in routine clinical practice—a prospective single-center trial
Authors: Isberner Nora , Kraus Sabrina , Grigoleit Götz Ulrich , Aghai Fatemeh , Kurlbaum Max , Zimmermann Sebastian , Klinker Hartwig , Scherf-Clavel Oliver
Published: September 2021

Purpose

Knowledge on Ruxolitinib exposure in patients with graft versus host disease (GvHD) is scarce. The purpose of this prospective study was to analyze Ruxolitinib concentrations of GvHD patients and to investigate effects of CYP3A4 and CYP2C9 inhibitors and other covariates as well as concentration-dependent effects.

Methods

262 blood samples of 29 patients with acute or chronic GvHD who were administered Ruxolitinib during clinical routine were analyzed. A population pharmacokinetic model obtained from myelofibrosis patients was adapted to our population and was used to identify relevant pharmacokinetic properties and covariates on drug exposure. Relationships between Ruxolitinib exposure and adverse events were assessed.

Results

Median of individual mean trough serum concentrations was 39.9 ng/mL at 10 mg twice daily (IQR 27.1 ng/mL, range 5.6–99.8 ng/mL). Applying a population pharmacokinetic model revealed that concentrations in our cohort were significantly higher compared to myelofibrosis patients receiving the same daily dose (p < 0.001). Increased Ruxolitinib exposure was caused by a significant reduction in Ruxolitinib clearance by approximately 50%. Additional comedication with at least one strong CYP3A4 or CYP2C9 inhibitor led to a further reduction by 15% (p < 0.05). No other covariate affected pharmacokinetics significantly. Mean trough concentrations of patients requiring dose reduction related to adverse events were significantly elevated (p < 0.05).

Conclusion

Ruxolitinib exposure is increased in GvHD patients in comparison to myelofibrosis patients due to reduced clearance and comedication with CYP3A4 or CYP2C9 inhibitors. Elevated Ruxolitinib trough concentrations might be a surrogate for toxicity.