bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational Study Into the Oxidative Ring‐Closure Mechanism During the Biosynthesis of Deoxypodophyllotoxin
Authors: Hardy Fintan G. , Wong Henrik P. H. , de Visser Sam P.
Published: February 2024

The nonheme iron dioxygenase deoxypodophyllotoxin synthase performs an oxidative ring‐closure reaction as part of natural product synthesis in plants. How the enzyme enables the oxidative ring‐closure reaction of (−)‐yatein and avoids substrate hydroxylation remains unknown. To gain insight into the reaction mechanism and understand the details of the pathways leading to products and by‐products we performed a comprehensive computational study. The work shows that substrate is bound tightly into the substrate binding pocket with the C7’−H bond closest to the iron(IV)‐oxo species. The reaction proceeds through a radical mechanism starting with hydrogen atom abstraction from the C7’−H position followed by ring‐closure and a final hydrogen transfer to form iron(II)‐water and deoxypodophyllotoxin. Alternative mechanisms including substrate hydroxylation and an electron transfer pathway were explored but found to be higher in energy. The mechanism is guided by electrostatic perturbations of charged residues in the second‐coordination sphere that prevent alternative pathways.
Ist der Zug schon abgefahren?
Authors: Gandert Etwina
Published: February 2024

Das Streichen von 155 Mio. EUR Fördermittel für die Batterieforschung, die das Bundesforschungsministerium (BMBF) kürzlich offiziell bestätigte, sendet ein fatales Signal in die Batteriebranche. Nach einem intensiven Wettlauf haben sich in Deutschland einige Leuchttürme eine beachtliche Position in der weltweiten Batterieforschung erarbeitet. Dieser technologische Vorsprung ist eine Säule, um im globalen industriellen Wettbewerb um die Batterieproduktion weiter aufzuholen. Denn Was uns derzeit fehlt, ist die Erfahrung mit der Massenproduktion ‐ es ist die zentrale Aufgabe der kommenden Jahre, durch die ausgezeichnete Forschungslandschaft und Fachkräfteausbildung auch hierin industrielle Maßstäbe zu setzen, wie Prof. Arno Kwade im CITplus‐Interview (S. 16) unterstreicht.
Vollständige Charakterisierung der Batteriematerialien
Authors: Chalou Anthony
Published: February 2024

Das 1922 in Graz (österreich) gegründete Unternehmen Anton Paar ist Weltmarktführer in der Messung von Dichte & Konzentration, der Bestimmung von gelöstem Kohlendioxid sowie in den Bereichen Rheometrie und Viskosimetrie. Zum Kundenkreis gehören große Bier‐ und Softdrinkhersteller weltweit, Unternehmen aus der Lebensmittel‐, Chemie‐, Erdöl‐ und Pharmaindustrie sowie führende akademische Gruppen. Die Anton Paar Gruppe ist in mehr als 110 Ländern tätig und verfügt über 37 Vertriebsgesellschaften und neun Produktionsbetriebe in Europa und den USA. Mehr als 4.200 Mitarbeitende sind in einem weltweiten Netzwerk, das Forschung & Entwicklung, Produktion, Vertrieb und Support umfasst, für die Qualität, die Zuverlässigkeit und den Service der Produkte verantwortlich. Seit 2003 ist die gemeinnützige Santner Privatstiftung Eigentümerin von Anton Paar. Sie ist ausschließlich und unmittelbar gemeinnützigen Zwecken gewidmet.
Ein neues Energiespeicherprinzip für Elektrizität und Wasserstoff
Authors: Hahn Robert , Schamel Andreas
Published: February 2024

Grüner Wasserstoff soll als Energiespeicher in zukünftigen erneuerbaren Energiesystemen eingesetzt werden. Erfolgsbestimmende Faktoren sind hierfür der Wirkungsgrad und die Kosten. Eine elektrochemische Zelle, die elektrische Energie in Form von abgeschiedenem Zink speichert und bei Bedarf Energie in Form von Wasserstoff und Strom freisetzt kann
Effizienzsteigerung für Rotating Equipment
Authors: Döring Marco
Published: February 2024

Die Prozessindustrie setzt auf Innovation, Effizienz, Nachhaltigkeit und Anpassungsfähigkeit, unterstützt durch Technologien wie künstliche Intelligenz, maschinelles Lernen und fortschrittliche Analysetools, um die Prozesse nachhaltiger zu gestalten. Mit einer Analysesoftware lassen sich die wirtschaftliche Rentabilität von Rotating Equipment bewerten und Energieeinsparungen erzielen.
Druckluft und Wärme statt Strom und Wärme erzeugen
Authors: Schlüter Christian
Published: February 2024

In einem Gasmotor‐Kompressormodul (GK‐Modul) werden die Hauptkomponenten eines Blockheizkraftwerkes (BHKW) mit einem Schrauben‐Kompressor gekoppelt. Dabei wird anstatt eines Stromgenerators die Verdichterstufe des Kompressors direkt an den Gasmotor angebunden. Mit den neuen Gasmotor‐Kompressormodulen sind 90 % der eingesetzten Energie in Form von Wärme nutzbar und Druckluft steht ebenfalls zur Verfügung
Hole‐Transporting Materials with Rational Combination of Pyridine and Dibenzo[a,c]phenazine as Electron Acceptor for Dopant‐Free Perovskite Solar Cells†
Authors: Ling Weidong , Wu Fei , Yuan Wentao , Zhu Linna , Li Qianqian , Li Zhen
Published: February 2024

Comprehensive Summary

Perovskite solar cells (PSCs) have been proven to be a promising option for photovoltaic conversion. With the aim to achieve efficient and stable PSCs, it is essential to explore dopant‐free hole‐transporting materials (HTMs) with high hole mobility. Herein, HTMs bearing electron donor (D)‐electron acceptor (A)‐electron donor (D) structures have been constructed with strong intramolecular charge transfer (ICT) effect, based on rational combination of dibenzo[a,c]phenazine and pyridine as electronic acceptors and anchoring groups to perovskite layer. Accordingly, high hole mobility (7.31 × 10–5 cm2·V–1·s–1) and photoelectric conversion efficiency (20.45%) have been achieved by dopant‐free DPyP‐based PSC. It afforded an efficient way to design HTMs with high hole mobility by adjustment of molecular configurations and electronic property of conjugated systems.
Pets, furry animal allergen components, and asthma in childhood
Authors: Lajunen Katariina , Määttä Anette M. , Malmström Kristiina , Kalliola Satu , Knihtilä Hanna , Savinko Terhi , Malmberg L. Pekka , Pelkonen Anna S. , Mäkelä Mika J.
Published: February 2024

Background

The use of component‐resolved allergy diagnostics has provided a clearer understanding of the species‐specific sensitization and severity of potential allergic reactions. This cross‐sectional study aimed to determine whether sensitization to allergen components in furry animals is indicative of blood eosinophilia, a positive fractional exhaled nitric oxide (FeNO) test, abnormal lung function, and asthma symptoms in children. Additionally, we investigated whether having pets during childhood affects the development of asthma or allergic sensitization to furry animals.

Methods

We recruited 203 children aged 4–17 years with asthma diagnosis based on abnormal lung function and 33 controls. IgE‐sensitization to allergen components for dogs, cats, and horses was analyzed using a multiplex microarray. Children were tested with FeNO, impulse oscillometry, spirometry, methacholine challenge, and skin prick test. A questionnaire was used to investigate pet ownership and symptom profile.

Results

FeNO results and blood eosinophilia revealed a correlation with sensitization to all furry animal allergens, particularly lipocalins (r = 0.203–0.560 and 0.206–0.560, respectively). Can f 3 was found to correlate with baseline R5 (r = 0.298). No association between methacholine challenge results and sensitization to furry animal allergens was found. Children with asthma who were sensitized to Can f 1, Can f 6, or both frequently reported asthma symptoms. Dog ownership was associated with a lower level of IgE‐sensitization to lipocalins, fewer asthma symptoms, and less blood eosinophilia.

Conclusion

Furry animal allergen component IgE‐sensitization is a risk factor for type 2‐inflammation and asthma symptoms.
Cell block practices in European cytopathology laboratories
Authors: Srebotnik Kirbis Irena , Kholova Ivana , Huhtala Heini , Bongiovanni Massimo , Strojan Flezar Margareta , Hodgson Chantell , Cochand‐Priollet Beatrix
Published: February 2024

Background

There are numerous methods and procedures described for the preparation of cell blocks (CBs) from cytological samples. The objective of this study was to determine current practices and issues with CBs in European laboratories.

Methods

A link to an online survey, with 11 questions about CB practices, was distributed to cytology laboratories via participants of United Kingdom National External Quality Assurance Service for Cellular Pathology Techniques and national representatives in the European Federation of Cytology Societies.

Results

A total of 402 laboratories responded completely (337/402, 84%) or partially (65/402, 16%) to the survey by February 4, 2022. The most common CB practice is embedding cell pellets using plasma and thrombin (23.3%), agar (17.1%), Shandon/Epredia Cytoblock (11.4%), HistoGel (7.9%), and Cellient (3.5%). Other methods such as CytoFoam, albumin, gelatin, Cytomatrix, and collodion bags are rarely used (1.0%, 0.7%, 0.7%, 0.3%, and 0.2%, respectively). CBs are also prepared from naturally occurring clots or tissue fragments (29.5%) and cells scraped from unstained or prestained smears (4.4%). The most frequent issues with the CBs in a daily cytology practice are low cellularity (248/402, 62%) and dispersed cells (89/402, 22%), regardless of the CBs preparation method or how the samples for embedding were selected.

Conclusions

There is a great variability in CB practices in European laboratories with low cellular CBs as the main issue. Additional studies are mandatory to evaluate and improve performance and cellular yield of CBs.
LoHDP: Adaptive local differential privacy for high‐dimensional data publishing
Authors: Shen Guohua , Cai Mengnan , Huang Zhiqiu , Yang Yang , Guo Feifei , Wei Linlin
Published: February 2024

The increasing availability of high‐dimensional data collected from numerous users has led to the need for multi‐dimensional data publishing methods that protect individual privacy. In this paper, we investigate the use of local differential privacy for such purposes. Existing solutions calculate pairwise attribute marginals to construct probabilistic graphical models for generating attribute clusters. These models are then used to derive low‐dimensional marginals of these clusters, allowing for an approximation of the distribution of the original dataset and the generation of synthetic datasets. Existing solutions have limitations in computing the marginals of pairwise attributes and multi‐dimensional distribution on attribute clusters, as well as constructing relational dependency graphs that contain large clusters. To address these problems, we propose LoHDP, a high‐dimensional data publishing method composed of adaptive marginal computing and an effective attribute clustering method. The adaptive local marginal calculates anyk‐dimensional marginals required in the algorithm. In particular, methods such as sampling‐based randomized response are used instead of privacy budget splits to perturb user data. The attribute clustering method measures the correlation between pairwise attributes using an effective method, reduces the search space during the construction of the dependency graph using high‐pass filtering technology, and realizes dimensionality reduction by combining sufficient triangulation operation. We demonstrate through extensive experiments on real datasets that our LoHDP method outperforms existing methods in terms of synthetic dataset quality.
Resolving the heterogeneous tumour microenvironment in cardiac myxoma through single‐cell and spatial transcriptomics
Authors: Liu Xuanyu , Shen Huayan , Yu Jinxing , Luo Fengming , Li Tianjiao , Li Qi , Yuan Xin , Sun Yang , Zhou Zhou
Published: February 2024

Background

Cardiac myxoma (CM) is the most common (58%–80%) type of primary cardiac tumours. Currently, there is a need to develop medical therapies, especially for patients not physically suitable for surgeries. However, the mechanisms that shape the tumour microenvironment (TME) in CM remain largely unknown, which impedes the development of targeted therapies. Here, we aimed to dissect the TME in CM at single‐cell and spatial resolution.

Methods

We performed single‐cell transcriptomic sequencing and Visium CytAssist spatial transcriptomic (ST) assays on tumour samples from patients with CM. A comprehensive analysis was performed, including unsupervised clustering, RNA velocity, clonal substructure inference of tumour cells and cell–cell communication.

Results

Unsupervised clustering of 34 759 cells identified 12 clusters, which were assigned to endothelial cells (ECs), mesenchymal stroma cells (MSCs), and tumour‐infiltrating immune cells. Myxoma tumour cells were found to encompass two closely related phenotypic states, namely, EC‐like tumour cells (ETCs) and MSC‐like tumour cells (MTCs). According to RNA velocity, our findings suggest that ETCs may be directly differentiated from MTCs. The immune microenvironment of CM was found to contain multiple factors that promote immune suppression and evasion, underscoring the potential of using immunotherapies as a treatment option. Hyperactive signals sent primarily by tumour cells were identified, such as MDK, HGF, chemerin, and GDF15 signalling. Finally, the ST assay uncovered spatial features of the subclusters, proximal cell–cell communication, and clonal evolution of myxoma tumour cells.

Conclusions

Our study presents the first comprehensive characterisation of the TME in CM at both single‐cell and spatial resolution. Our study provides novel insight into the differentiation of myxoma tumour cells and advance our understanding of the TME in CM. Given the rarity of cardiac tumours, our study provides invaluable datasets and promotes the development of medical therapies for CM.
Type 1 diabetes: A new vision of the disease based on endotypes
Authors: Weston Craig Sinclair , Boehm Bernhard O. , Pozzilli Paolo
Published: February 2024

Diagnosis and management of type 1 diabetes (T1D) have remained largely unchanged for the last several years. The management of the disease remains primarily focused on its phenotypical presentation and less on endotypes, namely the specific biological mechanisms behind the development of the disease. Furthermore, the treatment of T1D is essentially universal and indiscriminate—with patients administering insulin at varying dosages and frequencies to maintain adequate glycaemic control. However, it is now well understood that T1D is a heterogeneous disease with many different biological mechanisms (i.e. endotypes) behind its complex pathophysiology. A range of factors, including age of onset, immune system regulation, rate of β‐cell destruction, autoantibodies, body weight, genetics and the exposome are recognised to play a role in the development of the condition. Patients can be classified into distinct diabetic subtypes based on these factors, which can be used to categorise patients into specific endotypes. The classification of patients into endotypes allows for a greater understanding of the natural progression of the disease, giving rise to more accurate and patient‐centred therapies and follow‐up monitoring, specifically for other autoimmune diseases. This review proposes 6 unique endotypes of T1D based on the current literature. The recognition of these endotypes could then be used to direct therapeutic modalities based on patients' individual pathophysiology.
Evaluation of a single Eporatio® micro‐dose in urine and dried blood spots
Authors: Heiland Carmel E. , Lehtihet Mikael , Börjesson Annica , Ekström Lena
Published: February 2024

Recombinant human erythropoietin (rhEPO) has been abused as a performance enhancer in sports for several years, but with advancements in detection methods, even micro‐doses can be detected in dried blood spot (DBS) samples. Here, we present the results from an Eporatio® (epoetin theta) micro‐dose administration study to detect rhEPO in DBS samples. Five healthy male volunteers received a 15 IU/kg subcutaneous dose of Eporatio®. Urine and DBS samples (Mitra® VAMS and Capitainer® B50) were collected 1, 10, 24, 36, 48 and 72 h after drug administration. After 1 h, all urine samples were negative for rhEPO, whereas 40% of DBS samples were considered suspicious. All samples between 10 and 48 h were suspicious for the presence of Eporatio®, except one urine sample that was negative at 48 h. After 72 h, 40% of urine samples and 60% of DBS samples were suspicious and would have proceeded to a confirmation analysis. DBS is an efficient complementary matrix to urine for detection of rhEPO micro‐doses.
Heart failure outcomes by left ventricular ejection fraction in a contemporary region‐wide patient cohort
Authors: Sundström Johan , Ärnlöv Johan , Karayiannides Stelios , Bodegard Johan , Ersmark Karolina , Gustafsson Stefan , Cars Thomas , Svensson Maria K. , Norhammar Anna
Published: February 2024

Aims

This study aimed to characterize a contemporary population with subtypes of incident or prevalent heart failure (HF) based on reduced (HFrEF), mildly reduced, or preserved (HFpEF) left ventricular ejection fraction (LVEF) and to assess how outcomes, healthcare, treatments, and healthcare costs vary between each subtype of incident HF.

Methods and results

Using Swedish data from the CardioRenal and Metabolic disease Heart Failure (CaReMe HF) study, updated to cover a more recent time period, this population‐based study characterized patients from Stockholm County, Sweden, with incident HF (patients with a first HF diagnosis between 1 January 2015 and 31 December 2019) or prevalent HF (patients with a first HF diagnosis before 1 January 2020). Patients with incident HF had LVEF measured by echocardiography within ±90 days of their first HF diagnosis, and patients with prevalent HF within 5 years prior to the index date. The 13 375 patients with prevalent HF (39.2% women, mean age 73.9 years) had multiple comorbidities (cardiovascular diseases, chronic kidney disease, diabetes, and cancer). These were already highly prevalent at the time of the first HF diagnosis in the 8042 patients with incident HF (40.5% women, mean age 72.3 years). Patients with incident HFpEF received less specialist HF care at outpatient secondary care facilities following their first HF diagnosis than those with incident HFrEF. Patients with HFrEF had higher risks of complications and exerted a higher burden, in terms of care for and costs of HF, on the healthcare system.

Conclusions

This study of contemporary patients with incident HF demonstrates that those with HFpEF and HFrEF differ considerably in terms of clinical presentation, prognosis, and care, highlighting a potential to improve HF outcomes.
Investigating the relationship between FRailty And Quality of LIfe in patients with heart faiLure and CKD (FRAIL study)
Authors: McNally Thomas , Tumelty Ella , Chung Isaac , Hussain Sabba , Mookerjee Souradip , Ali Mahrukh Ayesha , Anderson Lisa , Rosano Giuseppe , Banerjee Debasish
Published: February 2024

Aims

Patients with chronic kidney disease (CKD) or heart failure (HF) are disproportionally affected by frailty, an independent predictor of morbidity. The prevalence of frailty and its impact on quality of life (QoL) in a unique population of patients with both CKD and HF (CKD‐HF) is unclear. The aim of this study was to investigate the association between frailty and QoL in patients with CKD‐HF.

Methods and results

Patients were identified from a tertiary care cardiorenal clinic. Eligible patients had CKD‐HF with a stable estimated glomerular filtration rate of <60 mL/min/1.732. Data were collected from each participant at one point in time using surveys delivered by study personnel between 14 July 2022 and 31 March 2023. Frailty was defined as Modified Frailty Phenotype (MFP) score ≥3. The Medical Outcomes Study 36‐item Short Form Health Survey (SF‐36) was used to assess QoL. Demographic data were retrospectively collected from electronic patient records. Demographics and QoL were compared between frail and non‐frail cohorts using Pearson's R and Student's t‐test (two‐tailed, alpha‐priori = 0.05). One hundred five participants consented, and 103 completed the questionnaires in full. Amongst the 103 participants, 49.5% (n = 51) were frail. Frailty was related to sex (P = 0.021) and medication count (P = 0.007), however not to other clinical measures, including estimated glomerular filtration rate (P = 0.437) and ejection fraction (P = 0.911). Frail patients reported poorer QoL across physical functioning (P < 0.001), general health (P < 0.001), bodily pain (P = 0.004), social functioning (P < 0.001), and energy levels (P < 0.001), however not emotional wellbeing (P = 0.058); 51.5% cited ‘better quality of life’ as their healthcare priority, over longer survival (23.3%) or avoiding hospital admissions (22.3%). This was consistent across frail and non‐frail groups.

Conclusions

A large proportion of CKD‐HF patients are frail, regardless of disease severity, and more susceptible to significantly poorer QoL across physical and social domains. Improving QoL is the priority of patients across both frail and non‐frail cohorts, further emphasizing the need for prompt recognition of frailty as well as possible intervention and prevention.
Prognostic models for patients suffering a heart failure with a preserved ejection fraction: a systematic review
Authors: Jia Ying‐Ying , Cui Nian‐Qi , Jia Ting‐Ting , Song Jian‐Ping
Published: February 2024

The purpose of this study was to systematically review the development, performance, and applicability of prognostic models developed for predicting poor events in patients with heart failure with preserved ejection fraction (HFpEF). Databases including Embase, PubMed, Web of Science Core Collection, the Cochrane Library, China National Knowledge Infrastructure, Wan Fang, Wei Pu, and China Biological Medicine were queried from their respective dates of inception to 1 June 2023, to examine multivariate models for prognostic prediction in HFpEF. Both forward and backward citations of all studies were included in our analysis. Two researchers individually used the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) checklist to extract data and assess the quality of the models using the Predictive Mode Bias Risk Assessment Tool (PROBAST). Among the 6897 studies screened, 16 studies derived and/or validated a total of 39 prognostic models. The sample size ranges for model development, internal validation, and external validation are 119 to 5988, 152 to 1000, and 30 to 5957, respectively. The most frequently employed modelling technique was Cox proportional hazards regression. Six studies (37.50%) conducted internal validation of models; bootstrap and k‐fold cross‐validation were the commonly used methods for internal validation of models. Ten of these models (25.64%) were validated externally, with reported the c‐statistic in the external validation set ranging from 0.70 to 0.96, while the remaining models await external validation. The MEDIA echo score and I‐PRESERVE‐sudden cardiac death prediction mode have been externally validated using multiple cohorts, and the results consistently show good predictive performance. The most frequently used predictors identified among the models were age, n‐terminal pro‐brain natriuretic peptide, ejection fraction, albumin, and hospital stay in the last 5 months owing to heart failure. All study predictor domains and outcome domains were at low risk of bias, high or unclear risk of bias of all prognostic models due to underreporting in the area of analysis. All studies did not evaluate the clinical utility of the prognostic models. Predictive models for predicting prognostic outcomes in patients with HFpEF showed good discriminatory ability but their utility and generalization remain uncertain due to the risk of bias, differences in predictors between models, and the lack of clinical application studies. Future studies should improve the methodological quality of model development and conduct external validation of models.
Narrative synthesis of the effectiveness and characteristics of heart failure disease self‐management support programmes
Authors: Koontalay Apinya , Botti Mari , Hutchinson Anastasia
Published: February 2024

A deeper understanding of the key elements that should be included in heart failure (HF) disease self‐management support (DSMS) programmes is crucial to enhance programme effectiveness and applicability to diverse settings. We investigated the characteristics and effectiveness of DSMS programmes designed to improve survival and decrease acute care readmissions for people with HF and determine the generalizability and applicability of the evidence to low‐ and middle‐income countries (LMICs). A narrative meta‐synthesis approach was used, and systematic reviews of randomized controlled trials (RCTs) of DSMS programmes were included. The Cochrane Database of Systematic Reviews, MEDLINE, and Embase were searched without language restriction and guided by the adapted Preferred Reporting Items for Systematic Reviews and Meta‐Analyses. Eight high‐quality systematic reviews were identified representing 250 studies, of which 138 were unique RCTs measuring the outcomes of interest. The findings revealed statistically significant reductions in HF readmissions [relative risk (RR) range 0.64–0.85, P < 0.5, five out of six reviews], all‐cause readmissions (RR range 0.85–0.95, P < 0.5, five out of six reviews), and all‐cause mortality (RR range 0.67–0.87, P < 0.5, five out of five reviews). Overall, 44.2% (n = 61) of RCTs reduced acute care readmission and improved survival. Studies were categorized according to intensity (low, moderate, moderate+, and high) based on the opportunity for immediate treatment of HF instability; 29.2% (14/48) of low‐intensity, 63.6% (21/33) of moderate‐intensity, 40% (6/15) of moderate+‐intensity, and 47.6% (20/42) of high‐intensity interventions were effective. Most effective programmes used moderate‐intensity (39.4%, 48%, or 50%, respectively) or high‐intensity (33.3%, 36%, and 43.7%, respectively) interventions. The majority of studies (90.6%) were conducted in high‐income countries. Programmes that provided opportunities for early recognition and response to HF instability were more likely to reduce acute care readmission and enhance survival. Generalizability and applicability to LMICs are clearly limited. Tailoring HF DSMS programmes to accommodate cultural, resource, and environmental challenges requires careful consideration of intervention intensity, duration of follow‐up, and feasibility in low‐resource settings.
The role of temporal analogies in collective movements
Authors: Coenen Ann‐Cathrin , Jüttemeier Marilena , Obaidi Milan , Power Séamus A. , Kunst Jonas R.
Published: February 2024

Although the importance of temporal perspectives for understanding collective movements has been theoretically emphasised, they are rarely considered in research. Focusing on the mass protests against COVID‐19 policies in Germany, we investigated how protesters make use of temporal references in their protest narratives. Results from 11 multi‐site protest observations and 31 interviews showed that participants (a) drew historical perpetrator and victim analogies and imagined a dystopian future, bolstering perceptions of injustice, (b) drew on resistance narratives and imagined the ideal, utopian future society, increasing their perceived efficacy and (c) countered feelings of insignificance by identifying with past heroes. Protesters living in the East of Germany drew comparatively more resistance analogies than those living in the West, who often likened those complying with the COVID‐19 policies to the perpetrators of the past national‐socialist and communist dictatorships. The findings empirically underline the importance of integrating historical–cultural–future perspectives into models of collective action.
Study of active components and mechanisms mediating the hypolipidemic effect of Inonotus obliquus polysaccharides
Authors: Ding Guanwen , Guo Xiao , Li Xiao , An Liping , Shi Huawen
Published: February 2024

Hyperlipidemia is a multifaceted metabolic disease, which is the major risk factor for atherosclerosis and cardiovascular diseases. Traditional Chinese medicine provides valuable therapeutic strategies in the treatment of hyperlipidemia. Inonotus obliquus has been used in traditional medicine to treat numerous diseases for a long time. To screen and isolate the fractions of I. obliquus polysaccharides (IOP) that can reduce blood lipid in the hyperlipemia animals and cell models, and investigate its mechanisms. The active component IOP‐A2 was isolated, purified, and identified. In vivo, rats were randomly divided into blank control group (NG), the high‐fat treatment group (MG), lovastatin group (PG), and IOP‐A group. Compared with MG, the hyperlipidemic rats treated with IOP‐A2 had decreased body weight and organ indexes, with the level of serum total cholesterol (TC), triglyceride (TG), and low‐density lipoprotein cholesterol (LDL‐C) significantly decreased (p < .05), and level of serum high‐density lipoprotein cholesterol (HDL‐C) significantly increased (p < .05). Hepatocyte steatosis in hepatic lobules was significantly reduced. In vitro, the accumulation of lipid droplets in the model of fatty degeneration of HepG2 cells was significantly alleviated, and cellular TC and TG content was significantly decreased (p < .01). Moreover, the expression of recombinant cytochrome P450 7A1 (CYP7A1) and Liver X Receptor α (LXRα) were up‐regulated (p < .05) both in vivo and in vitro. The results showed that IOP‐A2 may exert its hypolipidemic activity by promoting cholesterol metabolism and regulating the expression of the cholesterol metabolism‐related proteins CYP7A1, LXRα, SR‐B1, and ABCA1.
Genome Engineering as a Therapeutic Approach in Cancer Therapy: A Comprehensive Review
Authors: Gemayel Jack , Chebly Alain , Kourie Hampig , Hanna Colette , Mheidly Kayane , Mhanna Melissa , Karam Farah , Ghoussaini Daniel , Najjar Paula El , Khalil Charbel
Published: February 2024

Cancer is one of the foremost causes of mortality. The human genome remains stable over time. However, human activities and environmental factors have the power to influence the prevalence of certain types of mutations. This goes to the excessive progress of xenobiotics and industrial development that is expanding the territory for cancers to develop. The mechanisms involved in immune responses against cancer are widely studied. Genome editing has changed the genome‐based immunotherapy process in the human body and has opened a new era for cancer treatment. In this review, recent cancer immunotherapies and the use of genome engineering technology are largely focused on.
Assessment of growth monitoring among children younger than 5 years at early childhood development centres in Nelson Mandela Bay, South Africa
Authors: McLaren Shawn W. , Steenkamp Liana , Ronaasen Jessica
Published: February 2024

Introduction

Early childhood development (ECD) centres are important community hubs in South Africa and act as sites for community detection of childhood nutrition problems. This study aimed to assess the ability of trained ECD practitioners with optimal support to correctly classify the nutritional status of infants and young children at ECD centres in the Nelson Mandela Bay.

Methods

A descriptive, cross‐sectional study was used to collect data from 1645 infants and children at 88 ECD centres. Anthropometric measurements were taken by trained fieldworkers and growth monitoring and promotion infrastructure was audited at ECD centres.

Results

Of the sample, 4.4% (n = 72) were underweight by weight for age Z‐score (WAZ < −2) and 0.8% (n = 13) were severely underweight (WAZ < −3). Results showed that 13.1% (n = 214) were stunted by height for age Z‐score (HAZ < −2) and 4.5% (n = 74) were severely stunted (HAZ < −3). The prevalence of moderate acute malnutrition was 1.2% and severe acute malnutrition was 0.5%, while the prevalence of overweight was 9.2% and the prevalence of obesity was 4%. A significant level of agreement between the correct interpretation and the ECD practitioners' interpretation was observed across all the anthropometric indicators investigated. The true positive wasting cases had a mean mid‐upper arm circumference (MUAC) of 14.6 cm, which may explain the high false negative rate found in terms of children identified with wasting, where ECD practitioners fail to use the weight for height Z‐score (WHZ) interpretation for screening.

Conclusion

By using ECD centres as hub to screen for malnutrition, it may contribute to the early identification of failure to thrive among young children. Although it was concerning that trained ECD practitioners are missing some children with an unacceptably high false negative rate, it may have been due to the fact that wasting in older children cannot be identified with MUAC alone and that accurate WFH plotting is needed. Onsite mentorship by governmental health workers may provide ECD practitioners with more confidence to screen children for growth failure based on regular WFH measurements. Moreover, ECD practitioners will be more confident to monitor the Road to Health booklets for missed vaccinations, vitamin A and deworming opportunities.
Parameterization of the Ångström–Prescott formula based on machine learning benefit estimation of reference crop evapotranspiration with missing solar radiation data
Authors: Chen Shang , Feng Wenzhe , He Liang , Xiao Wei , Feng Hao , Yu Qiang , Liu Jiandong , He Jianqiang
Published: February 2024

Accurately estimated reference evapotranspiration (ET0) is essential to regional water management. The FAO recommends coupling the Penman–Monteith (P‐M) model with the Ångström–Prescott (A‐P) formula as the standard method for ET0 estimation with missing Rs measurements. However, its application is usually restricted by the two fundamental coefficients (a and b) of the A‐P formula. This paper proposes a new method for estimating ET0 with missing Rs by combining machine learning with physical‐based P‐M models (PM‐ET0). The benchmark values of the A‐P coefficients were first determined at the daily, monthly, and yearly scales, and further evaluated in Rs and ET0 estimates at 80 national Rs measuring stations. Then, three empirical models and four machine‐learning methods were evaluated in estimating the A‐P coefficients. Machine learning methods were also used to estimate ET0 (ML‐ET0) to compare with the PM‐ET0. Finally, the optimal estimation method was used to estimate the A‐P coefficients for the 839 regular weather stations for ET0 estimation without Rs measurement for China. The results demonstrated a descending trend for coefficient a from northwest to southeast China, with larger values in cold seasons. However, coefficient b showed the opposite distribution as the coefficient a. The FAO has recommended a larger a but a smaller b for southeast China, which produced the region's largest Rs and ET0 estimation errors. Additionally, the A‐P coefficients calibrated at the daily scale obtained the best estimation accuracy for both Rs and ET0, and slightly outperformed the monthly and yearly coefficients without significant difference in most cases. The machine learning methods outperformed the empirical methods for estimating the A‐P coefficients, especially for the sites with extreme values. Further, ML‐ET0 outperformed the PM‐ET0 with yearly A‐P coefficients but underperformed those with daily and monthly ones. This study indicates an exciting potential for combining machine learning with physical models for estimating ET0. However, we found that using the A‐P coefficients with finer time scales is unnecessary to deal with the missing Rs measurements.
On stakeholder theory and corporate investment under financial frictions
Authors: Mykhayliv Dariya , Zauner Klaus G.
Published: February 2024

The view that corporations have a wider focus than just maximising shareholder value has received considerable attention from practitioners, managers, and academics alike. We investigate the Q theory of corporate investment with financial frictions when management maximises stakeholder value instead of shareholder value. Different objective functions are investigated. We characterise the optimal investment and financial policy of the firm. The results show that stakeholder firms invest more than shareholder firms, that is, over invest, and an increase of stakeholder shares increases investment, except when equity issuing firms face severe informational asymmetries or severe cost of external equity. We also discuss different approaches to model investment of stakeholder firms and their implications for empirical analysis.
Secretory Component and Serum Immunoglobulin A Deficiencies with Intestinal Autoantibody Formation and Autoimmune Disease
Authors: Fisher Stanley E. , Smith William I. , Rabin Bruce S. , Tomasi Thomas B. , Lester Roger , Van Thiel David H.
Published: February 2024

A teenage boy with both secretory component deficiency and selective serum immunoglobulin A deficiency also developed pernicious anemia, insulin‐dependent diabetes mellitus, pancreatic insufficiency, lymphopenia, intestinal candidiasis, and anti‐intestinal antibody. The patient's father had pernicious anemia and diabetes mellitus while the paternal grandfather also had pernicious anemia. Because the patient had inherited the paternal grandmother's human leukocyte antigen complex, there was no direct association between pernicious anemia and the genetic markers. The presence of multiple immunologic abnormalities in a single patient supports the concept of an underlying defect in immune regulation as a central factor in the pathogenesis of these disorders.
Clotted Feeding Tubes Associated with Transpyloric Feeding of Premature Infant Formula
Authors: Moyer Laurie , Chan Gary M.
Published: February 2024

Use of a constant infusion of formula via transpyloric (TP) administration has been utilized as a means of supplying nutrition to the smaller (< 1,200 g) premature infant. We have noticed that many of our infants being fed with a “reformulated” premature infant formula (Enfamil®) by TP route have experienced clotted feeding tubes in spite of regular irrigation with sterile water. A retrospective study was conducted over a 9‐month period comparing all infants fed via TP tube (5 French polyvinyl) and receiving either premature formula or their own mother's milk. An in vitro study was also conducted comparing the premature infant formula and a standard formula with human milk placed in TP tubes at the milk's own original pH and an alkaline pH. A total of 59 infants received feedings via TP infusion. Thirty‐nine were fed premature formula and 20 infants received human milk. There were no differences in birth weight and gestational age between the two groups. No infant receiving human milk developed a clotted feeding tube. However, of infants receiving premature formula, 15 of the 39 (389?) developed at least one clotted feeding tube. The clotted group was smaller in birth weight (mean of 1,044 vs. 1,418 g, p < 0.001) and younger in gestational age (mean of 29 vs. 32 weeks, p < 0.05) than the nonclotted group. There were no differences between the two groups in age of initial feeding or rate of infusion. The in vitro study showed that feeding tubes were completely occluded consistently after 24 h for the premature formula at both original pH (6.70) and alkaline pH (8.0). Neither the human milk nor standard formula developed any clot. We believe that premature infant formulas should be used with caution when administered via a TP route.
Immunocompetence and Dietary Protein Intake in Early Infancy
Authors: Zoppi Giuseppe , Gerosa Franca , Pezzini Angela , Bassani Nilo , Rizzotti Paolo , Bellini Pierantonio , Todeschini Gianna , Zamboni Giorgio , Vazzoler Gianfranco , Tridente Giuseppe
Published: February 2024

Forty‐one normal full‐term infants were fed from birth, during the first 4.5 months of life, different diets based on two formulas similar in rough composition but basically different, the one being constituted only of cow milk protein and the other of soy protein. From each of the two formulas two different dilutions were prepared so that all diets supplied about 100 kcal/kg/day, but, respectively. 2.0 and 4.0 g/kg/day of cow milk protein and 2.0 and 5.0 g/kg/day of soy protein. After 4.5 months, growth in weight, length, and head circumference was normal and very similar in all infants. Gammaglobulin, immunoglobulin, transferrin, and some complement fractions (particularly C'3, C'1 INA, C'3 PA) were lower in infants receiving soy protein diets than in those receiving cow milk protein diets, and, within each type of diet, in those infants receiving lower amounts of protein. In particular, values of infants receiving 5.0 g/kg/day of soy protein were roughly comparable to those of infants receiving 2.0 g/kg/day of cow milk protein. B lymphocyte markers and reactivity did not show significant differences among the various groups. T lymphocyte markers and reactivity showed an impairment in soy protein diets (and in particular in 2.0 g/kg/day protein diets) with respect to cow milk diets. It was also observed that morbidity (mainly infections of upper respiratory tract) was higher in those infants who took soybean protein and in those who took lesser amount of protein.
Relationship of Iron Status to Urinary Norepinephrine Excretion in Children 7–12 Years of Age
Authors: Webb Thomas E. , Krill Carl E. , Oski Frank A. , Kwan‐Chung Tsou
Published: February 2024

In a group of 7− to 12‐year‐old children without manifest clinical iron deficiency, urinary excretion of free norepinephrine was found to have substantial positive correlation with measure of total iron‐binding capacity and negative correlation with serum ferritin. Results support earlier reports of an inverse contingency between iron status and urinary norepinephrine level as observed with severe iron lack, findings consistent with speculation that monoamine oxidase activity may be modified by iron availability.
Permeability of Adolescent Rat Intestine to Pancreatic Ribonuclease
Authors: Urban Ernest , Zingery Amy Ahrens , Bundrant Teril , Weser Elliot , Ziegler Daniel M.
Published: February 2024

There are indications that exocrine pancreatic enzymes may undergo an enteric recirculation. Ribonuclease (RNase) is present in considerable quantities in pancreatic exocrine secretions. Therefore we studied the intestinal transport of pancreatic RNase using everted gut sacs from duodenum, midgut, and ileum of young rats. Gut sacs were incubated aerobically at 37°C, 22°C, and 0°C, and anaerobically at 37°C. Measurable amounts of RNase crossed the intestinal barrier, but neither duodenum, midgut nor ileum absorbed RNase preferentially. The experimental data favor simple diffusion of RNase across rat small bowel. However, the amounts of pancreatic RNase absorbed were small. Thus, while our data do not negate the concept of an enteropancreatic recirculation in the rat, only a minor quantity of luminal, pancreatic RNase could recirculate.
Does Mixing Pancreatic Enzyme Microspheres (Pancreaser) with Food Damage the Enteric Coating?
Authors: Sackman Jeffrey W. , Smith Kathleen E. , Graham David Y.
Published: February 2024

Supplemental pancreatic enzymes are required for the treatment of malabsorption associated with cystic fibrosis. It is a general practice for enzymes to be sprinkled on, or administered in, food given to infants or children who require pancreatic enzyme replacement. We tested the effect of in vitro incubation of enteric‐coated pancreatic enzyme microspheres with infant foods on total recoverable enzyme activity and on the enteric coating. Incubation of enzyme beads with foods with pH 5 (i.e., chicken pH 6.5, veal pH 6.3, and green beans pH 5.6) was without significant effect on either parameter. There was a statistically significant, albeit minor, reduction in maximum enzyme activity recovered following incubation with applesauce (pH 3.5). In addition, the thickness of the enteric coating was significantly reduced. Whether changes in the enzyme beads results in improved or diminished efficiency of therapy remains to be determined. Lipase, unprotected by enteric coating, was rapidly inactivated in applesauce, emphasizing the need to instruct parents about which foods to avoid when administering pancreatic enzymes without enteric coating.
Increased [125I]Trypsin‐Binding in Serum from Cystic Fibrosis Patients
Authors: Cox Kenneth L. , Frates Ralph C. , Sheikholislam Bagher M. , Iwahashi‐Hosoda Christine K.
Published: February 2024

The capacities of normal and cystic fibrosis (CF) sera to bind to exogenous human [125I]trypsin were compared. Sera from eight older CF patients bound significantly more exogenous human [125I]trypsin than did sera from eight normal subjects (p < 0.001). Disregarding the increased trypsinbinding (TB) of CF sera, serum immunoreactive trypsinogen (SIRT) levels were not detectable in these eight older CF patients. However, when SIRT levels were corrected for TB, four CF patients had normal SIRT concentrations and four had low but detectable SIRT levels. As compared to five normal newborns' sera, serum from a newborn with CF had normal TB and the SIRT levels were very high. In conclusion, increased TB in CF serum lowers results of SIRT assays. Therefore, unless SIRT levels are corrected for TB, results obtained from currently available SIRT kits may be invalid.
Effect of Human Growth Hormone on Gastrin Secretion in Children with Hyposomatotropism
Authors: Root Allen W. , Auritt Aileen , Livingston Catherine
Published: February 2024

The effect of human growth hormone (hGH) on gastrin secretion was evaluated in 13 hyposomatotropic children and two subjects with bioinactive growth hormone (GH). Serum concentrations of gastrin were quantitated by radioimmunoassay after ingestion of a standard meal and following intravenous infusion of arginine. prior to and after ft and 12 months of hGH administration. Although the meal provoked a significant increment in gastrin values at each point, hGH did not alter basal concentrations or meal‐evoked secretion of gastrin in these subjects. Arginine had no effect on gastrin levels. Serum im‐munoreaetive insulin concentrations increased in response to eating and arginine. but hGH did not alter the insulin secretory response to either stimulus. It is concluded that hGH did not affect the secretion of gastrin or insulin under the conditions of this study.
Effect of Short‐Term Cimetidine Administration on Fecal Bile Acid Losses in Cystic Fibrosis
Authors: Isenberg Nevin J. , Hendrix Pamela Y. , Cox Kenneth L.
Published: February 2024

Eight children with cystic fibrosis and exocrine pancreatic insufficiency were voluntarily hospitalized in a clinical research setting so that diet and enzyme supplements could be well controlled for consecutive 72‐h balance studies. We previously reported on these patients, as part of a larger study group, because they showed significantly reduced fecal losses of fat and nitrogen at the highest dose of cimetidine added to the otherwise constant regimen. Analysis of specimens from this same study shows a cimetidine‐related reduction in fecal bile acid loss. Numerous variables thought to influence fecal bile acid loss were closely controlled and/or measured in this clinical study setting. In order to potentially learn more about this complex phenomenon, we carried out a stepwise regression analysis of the data which indicated that half of the variance in fecal bile acid loss is still unaccounted for by the five “independent” variables tested in the regression. However, in this variance analysis system cimetidine assumes a larger relative role in modulating bile acid loss than it does in fecal losses of fat and nitrogen.