bluuebunny/crossref_metadata_2025 huggingface dataset:
A new variety of chondrocoracoideus muscle, or an additional head of pectoralis major muscle
Authors: Zielinska Nicol , Ruzik Kacper , Georgiev Georgi P. , Dimitrova Iva N. , Tubbs R. Shane , Olewnik Łukasz
Published: January 2022

The pectoralis major and pectoralis minor muscles are located in the anterior chest wall. This region is characterized by high morphological variability. During dissection an additional muscle was found, originating from the lateral border of the pectoralis major muscle. After fusion it passed into the tendinous part coursing under the insertion of the pectoralis major muscle, then formed a common junction with the short head of the biceps brachii muscle, the distal attachment of which is on the coracoid process. Such an accessory structure could lead to neurovascular compression and cause thoracic outlet syndrome, of which pain is usually the first symptom. This muscle has not been described in the literature so far and for that reason we can name the present case as an unique structure.
Immune checkpoint inhibitors: immune-related adverse events, healthcare utilization, and costs among commercial and Medicare Advantage patients
Authors: Gunturu Krishna S. , Pham Timothy T. , Shambhu Sonali , Fisch Michael J. , Barron John J. , Debono David
Published: January 2022

Background

Immune checkpoint inhibitors (ICI) are increasingly used across multiple cancer types and stages and little is known about real-world outcomes. This study sought to determine healthcare utilization, costs, immune-related adverse events (irAEs), and all-cause mortality of single-agent versus combination ICI in the USA.

Materials and methods

This is a retrospective study conducted with 2016–2018 data from the HealthCore Integrated Research Database, consisting of commercial and Medicare-insured adult patients with a cancer diagnosis using ICI in the USA. Outcomes were healthcare utilization, costs, and irAEs (FDA-recognized and others) up to 1-year post-index between patients using ICI monotherapy (mono, PD-1/PD-L1 inhibitor) and combination therapy (combo, PD-1/PD-L1 with CTLA-4 inhibitors).

Results

In total, 9084 patients received monotherapy and 904 patients received combo therapy. Mean age 65 years for mono and 58 years for combo. Overall, the combo arm had higher rates of FDA-recognized irAEs (67.4% vs. 45.9%), especially endocrinopathies (27.7% vs 14.7%) and dermatitis (25.9% vs. 12.4%). All-cause mortality over 1-year follow-up was similar, 30.7% in mono vs 30.8% in combo arms. The combo group had higher rates of all-cause inpatient hospitalizations (55.4% mono vs 65.6% combo) and emergency department (ED) visits (33.7% mono vs 41.4% combo). IrAE-related hospitalizations were higher in combo (55.2% vs 42.1%). IrAE-related ED visits were 15.7% mono vs 22.7% combo. This increased toxicity and health care utilization was reflected in significant differences in healthcare costs. Stark differences were seen in all-cause medical costs as well as costs related to inpatient and ED utilization and costs attributed to irAEs.

Conclusions

Higher rates of irAEs, healthcare utilization, and costs occur with combination immunotherapy. As further indications are approved for combination ICI, our study highlights the real-world tradeoffs involved with combination therapy regarding burdens of toxicity and increased healthcare utilization.
Am Limit? – Einschätzungen zur Grundwasserbewirtschaftung im Großraum Grünstadt (Rheinland-Pfalz)
Authors: Bitzer Frank , Baumeister Christoph , Kampf Jochen , Schykowski Martin
Published: January 2022

Im Großraum Grünstadt erfolgt die Wasserversorgung weitgehend dezentral aus Grundwasserleitern des Buntsandsteins. Dieser ist aufgrund der geologisch-tektonischen Verhältnisse räumlich komplex gegliedert. In Verbindung mit Abschätzungen zu Grundwasserfließrichtungen und Altersdatierungen ist eine Gliederung in bilanzierbare Teilräume möglich.

Daten zu Grundwasserständen und zur Grundwasserbeschaffenheit weisen auf mitunter erhebliche Veränderungen seit etwa 1960 hin. Daten zu den Grundwasserentnahmen liegen erst ab 2013 vor. Die annähernd konstanten Absenkungsraten können als Entwicklung in der späten instationären Phase langfristiger, gering schwankender Grundwasserentnahmen interpretiert werden.

Auf Basis der Wasserbilanz für den zentralen Bilanzraum wurde die dort zur Bilanzdeckung notwendige Grundwasserneubildung abgeschätzt. Sie wurde den Ergebnissen zweier methodisch unterschiedlicher Grundwasserneubildungsmodelle gegenübergestellt. Die dokumentierten Absenkungen lassen sich mit dem Neubildungsmodell auf Basis des flächendifferenzierten Bodenwasserhaushaltsmodells GWN-BW in Einklang bringen. Für den zentralen bilanzierten Teilraum ist von einer langfristig über der Grundwasserneubildung liegenden Grundwasserentnahme auszugehen.
A macroscopic approach for stress-driven anisotropic growth in bioengineered soft tissues
Authors: Lamm L. , Holthusen H. , Brepols T. , Jockenhövel S. , Reese S.
Published: January 2022

The simulation of growth processes within soft biological tissues is of utmost importance for many applications in the medical sector. Within this contribution, we propose a new macroscopic approach for modelling stress-driven volumetric growth occurring in soft tissues. Instead of using the standard approach of a-priori defining the structure of the growth tensor, we postulate the existence of a general growth potential. Such a potential describes all eligible homeostatic stress states that can ultimately be reached as a result of the growth process. Making use of well-established methods from visco-plasticity, the evolution of the growth-related right Cauchy–Green tensor is subsequently defined as a time-dependent associative evolution law with respect to the introduced potential. This approach naturally leads to a formulation that is able to cover both, isotropic and anisotropic growth-related changes in geometry. It furthermore allows the model to flexibly adapt to changing boundary and loading conditions. Besides the theoretical development, we also describe the algorithmic implementation and furthermore compare the newly derived model with a standard formulation of isotropic growth.
A mathematical model and mesh-free numerical method for contact-line motion in lubrication theory
Authors: Pang Khang Ee , Ó Náraigh Lennon
Published: January 2022

We introduce a mathematical model with a mesh-free numerical method to describe contact-line motion in lubrication theory. We show how the model resolves the singularity at the contact line, and generates smooth profiles for an evolving, spreading droplet. The model describes well the physics of droplet spreading–including Tanner’s Law for the evolution of the contact line. The model can be configured to describe complete wetting or partial wetting, and we explore both cases numerically. In the case of partial wetting, the model also admits analytical solutions for the droplet profile, which we present here.

Article highlights

We formulate a mathematical model to regularize the contact-line singularity for droplet spreading.

The model can be solved using a fast, accurate mesh-free numerical method.

Numerical simulations confirm that the model describes the quantitative aspects of droplet spreading well.
Uniform and scalable sampling of highly configurable systems
Authors: Heradio Ruben , Fernandez-Amoros David , Galindo José A. , Benavides David , Batory Don
Published: January 2022

Many analyses on configurable software systems are intractable when confronted with colossal and highly-constrained configuration spaces. These analyses could instead use statistical inference, where a tractable sample accurately predicts results for the entire space. To do so, the laws of statistical inference requires each member of the population to be equally likely to be included in the sample, i.e., the sampling process needs to be “uniform”. SAT-samplers have been developed to generate uniform random samples at a reasonable computational cost. However, there is a lack of experimental validation over colossal spaces to show whether the samplers indeed produce uniform samples or not. This paper (i) proposes a new sampler named , (ii) presents a new statistical test to verify sampler uniformity, and (iii) reports the evaluation of and five other state-of-the-art samplers: , , , , and . Our experimental results show only satisfies both scalability and uniformity.
A prioritised inventory of crop wild relatives and wild harvested plants of Tunisia
Authors: El Mokni Ridha , Barone Giulio , Maxted Nigel , Kell Shelagh , Domina Gianniantonio
Published: January 2022

An inventory of crop wild relatives (CWR) and wild harvested plants (WHP) occurring in Tunisia, based on the integration of the last available floristic checklists, is presented. The taxa were prioritised according to economic value of the related crop, potential for crop improvement, threat status, endemism, inclusion in the ITPGRFA (Annex I) and average annual contributions to dietary energy (kilocalories) per capita per day by applying a scoring system based on 4 priority levels. Of a total of 2912 taxa belonging to the Tunisian Flora, 2504 CWR and/or WHP (86% of the total), from 143 families and 686 genera, were identified, 2445 of which are CWR and 847 are WHP. In detail, 1654 are solely CWR and 59 are WHP only, whereas 788 are both CWR and WHP. The final priority list for active conservation includes 1036 CWR (43% of the total CWR taxa), with 139 taxa rated as high priority, 660 medium priority and 237 low priority. The final priority list for WHP is composed of 344 taxa and includes eight high priority, 254 medium priority and 82 low priority taxa. Our results confirm Tunisia as a hotspot of CWR and WHP diversity in the Mediterranean area. The inventory here proposed provides the basis for the development and implementation of a more targeted national CWR/WHP conservation strategy for Tunisia.
A Spatial Connectivity Approach to Landscapes of Conflict: Julius Caesar and the Assault to Puig Ciutat (NE Iberian Peninsula)
Authors: Rubio-Campillo Xavier , Ble Eduard , Pujol Àngels , Sala Roger , Tamba Robert
Published: January 2022

Landscape plays a vital role in the development of military campaigns through the definition of geostrategic landmarks that structure the control of the territory, the imposition of constraints to the movement of armies and the identification of features that facilitate defence against attackers. These factors are linked to the study of past spatial mobility which is typically done by finding optimal pathways between pairs of points using Least-Cost Path analysis. This emphasis on optimality may not be ideal for case studies that need a general approach to spatial connectivity such as the study of conflict-related dynamics. Connectivity modelling based on Circuit Theory (CT) is an alternative approach to spatial mobility that captures the connectivity of an entire region identifying not only optimal paths but also bottlenecks, dead-ends and any other spatial feature that may impact movement. We present here a framework to study landscapes of conflict using connectivity modelling; the framework combines CT, visibility analysis and statistical hypothesis testing to understand the reasons behind the assault and destruction of Puig Ciutat (NE Iberian Peninsula) during Julius Caesar’s civil war. Results suggest that the site exerted decisive control over a highly connected area linking two possible logistical bases (Emporion and Massalia) to the armies fighting at Ilerda (49 BC).
Dedekind and Wolffian Deductive Method
Authors: Ferreirós José , Lassalle-Casanave Abel
Published: January 2022

Dedekind’s methodology, in his classic booklet on the foundations of arithmetic, has been the topic of some debate. While some authors make it closely analogue to Hilbert’s early axiomatics, others emphasize its idiosyncratic features, most importantly the fact that no axioms are stated and its careful deductive structure apparently rests on definitions alone. In particular, the so-called Dedekind “axioms” of arithmetic are presented by him as “characteristic conditions” in thedefinitionof the complex concept of asimply infinitesystem. Making sense of Dedekind’s method may be dependent on an analysis of the classical model of deductive science, as presented by authors from the eighteenth and early nineteenth centuries. Studying the modern reconstructions of Euclidean geometry, we show that they did not presuppose deductive independence of the axioms from the definitions. Authors like Wolff elaborated a mathematicsbased on definitions, and the Wolffian model of deductive science shows significant coincidences with Dedekind’s method, despite the great differences in content and approach. Wolff had a conception of definitions asgenetic, which bears some similarities with Kant’s idea of synthetic definitions: they are understood as positing the content of mathematical concepts and introducing thought objects (Gedankendinge) that are the objects of mathematics. The emphasis on the spontaneity of the understanding, which can be found in this philosophical tradition, can also be fruitfully related with Dedekind’s idea of the “free creation” of mathematical objects.
The role of microRNA-155 in glomerular endothelial cell injury induced by high glucose
Authors: He Kaiying , Chen Zhan , Zhao Jing , He Yang , Deng Rongrong , Fan Xin , Wang Jianqin , Zhou Xiaochun
Published: January 2022

Objective

To investigate the role of microRNA-155-5p on apoptosis and inflammatory response in human renal glomerular endothelial cells (HRGEC) cultured with high glucose.

Methods

The primary HRGEC were mainly studied, light microscopy was used to detect changes in cell morphology. Quantitative Real Time-Polymerase Chain Reaction, Western Blot, immunofluorescence were aimed to observe the mRNA and protein expression levels of target gene ETS-1, downstream factors VCAM-1, MCP-1 and cleaved caspase-3 in each group after high glucose treatment as well as transfection with miR-155 mimics or inhibitor.

Results

The expression of inflammatory factors and apoptosis of HRGEC cells increased under high glucose treatment. Compared with normal-glucose treatment, the expression of microRNA-155 markedly increased in HRGECs treated with high-glucose, as well as the mRNA and protein levels of ETS-1, VCAM-1, MCP-1 and cleaved caspase-3. Overexpression of microRNA-155 remarkably downregulated mRNA and protein levels of ETS-1, VCAM-1, MCP-1 and cleaved caspase-3, whereas miRNA-155 knockdown upregulated their levels. In addition, HRGEC cells were transfected with miR-155 mimics and ETS-1 siRNA with high glucose stimulation. The expression of ETS-1 was positively correlated with the expression of downstream factors VCAM-1 and MCP-1. These results suggest that ETS-1 can mediate endothelial cell inflammation by regulating VCAM-1 and MCP-1.

Conclusion

MiR-155 can negatively regulate the expression of target gene ETS-1 and its downstream factors VCAM-1, MCP-1 and cleaved caspase-3, thus mediating the inflammatory response and apoptosis of HRGEC.
Exogenous Melatonin Alleviates Skeletal Muscle Wasting by Regulating Hypothalamic Neuropeptides Expression in Endotoxemia Rats
Authors: Duan Jianfeng , Cheng Minhua , Xu Yali , Chen Yan , Gao Tao , Gu Qin , Yu Wenkui
Published: January 2022

To investigate whether exogenous melatonin (MLT) could alleviate skeletal muscle wasting by regulating hypothalamic neuropeptides expression. Adult male Sprague Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS) (10 mg/kg), followed by MLT (30 mg/kg/day) or saline for 3 days. Hypothalamic tissues and skeletal muscle were obtained on day 3. Skeletal muscle wasting was measured by the mRNA expression of two E3 ubiquitin ligases, muscle atrophy F-box and muscle ring finger 1 as well as 3-methylhistidine (3-MH) and tyrosine release. Three hypothalamic neuropeptides (POMC, AgRP, CART) expression were detected in all groups. POMC expression knockdown was achieved by ARC injection of lentiviruses containing shRNA against POMC. Two weeks after ARC viruses injection, rats were i.p. injected with LPS (10 mg/kg) followed by MLT (30 mg/kg/day) or saline for 3 days. Brain tissues were harvested for immunostaining. In septic rats, 3-MH, tyrosine release and muscle atrophic gene expression were significantly decreased in MLT treated group. POMC and CART expression were lower while AgRP expression was higher in MLT treated group. Furthermore, in septic rats treated with MLT, muscle wasting in those with lower expression of neuropeptide POMC did not differ from those with normal POMC expression. Exogenous MLT could alleviate skeletal muscle wasting in septic rats by regulating hypothalamic neuropeptides.
Isolated Psychiatric Ward Patients in Southern Israel with Severe Mental Illnesses Describe Their Sexual Needs: A Qualitative Study
Authors: Kaplan Michal , Peleg-Sagy Tal , Guez Jonathan , Sagy Iftach
Published: January 2022

Intimacy and sexuality are fundamental issues in human nature, but have been neglected in the rehabilitation of mental health patients, particularly those admitted into psychiatric wards. Patients’ sexuality is excluded from the discourse; yet it exists in the daily lives of the patients. The study examines the sexual needs and challenges of people with severe mental illnesses admitted to an isolated psychiatric ward. 13 men were interviewed in a semi-structured interview regarding their sexuality and the challenges they meet when experiencing and expressing their sexuality as patients in an isolated ward. A thematic analysis was conducted. Two principal themes were identified: 1. Challenges in realizing sexuality within the isolated ward. This theme included sub themes: performing sexual acts and exposure to sexuality within the ward; medications' side effects; dialogue with the staff; sexuality in the ward presented as crossing limits; and absence of a space to fulfill sexuality. 2. Suggestions for improvements in the hospital, stemming from the patients' experiences and ideas, such as starting an open dialogue with the staff, supplying patients with measures for protected sex, and more. The findings highlight the lack of healthy expression of sexuality inside the wards, despite its importance for improving patients’ well-being during their rehabilitation. Medical staff and policymakers should be aware of the sexual aspects of hospitalization in a psychiatric ward. The study also indicates the need for national policy that will address patients' sexual needs, including clear instructions that consider the uniqueness of the target population.
Many are the ways to learn identifying multi-modal behavioral profiles of collaborative learning in constructivist activities
Authors: Nasir Jauwairia , Kothiyal Aditi , Bruno Barbara , Dillenbourg Pierre
Published: January 2022

Understanding the way learners engage with learning technologies, and its relation with their learning, is crucial for motivating design of effective learning interventions. Assessing the learners’ state of engagement, however, is non-trivial. Research suggests that performance is not always a good indicator of learning, especially with open-ended constructivist activities. In this paper, we describe a combined multi-modal learning analytics and interaction analysis method that uses video, audio and log data to identify multi-modal collaborative learning behavioral profiles of 32 dyads as they work on an open-ended task around interactive tabletops with a robot mediator. These profiles, which we name Expressive Explorers, Calm Tinkerers, and Silent Wanderers, confirm previous collaborative learning findings. In particular, the amount of speech interaction and the overlap of speech between a pair of learners are behavior patterns that strongly distinguish between learning and non-learning pairs. Delving deeper, findings suggest that overlapping speech between learners can indicate engagement that is conducive to learning. When we more broadly consider learner affect and actions during the task, we are better able to characterize the range of behavioral profiles exhibited among those who learn. Specifically, we discover two behavioral dimensions along which those who learn vary, namely, problem solving strategy (actions) and emotional expressivity (affect). This finding suggests a relation between problem solving strategy and emotional behavior; one strategy leads to more frustration compared to another. These findings have implications for the design of real-time learning interventions that support productive collaborative learning in open-ended tasks.
Patients’ Experiences of Weight Regain After Bariatric Surgery
Authors: Tolvanen Liisa , Christenson Anne , Surkan Pamela J. , Lagerros Ylva Trolle
Published: January 2022

Purpose

Bariatric surgery is a successful obesity treatment; however, an estimated 1/5 of patients have regained more than 15% of their body weight 5 years post-surgery. To increase the understanding of patients who experienced weight regain after bariatric surgery, we conducted a qualitative study.

Materials and Methods

We recruited 16 adult participants (4 men, 12 women) at an obesity clinic in Stockholm, Sweden, 2018 to 2019, and performed semi-structured individual interviews. The transcribed recorded interview data was analyzed with thematic analysis.

Results

Participants had undergone gastric bypass surgery on average 10 years prior to study and regained 36% (range 12 to 71%) of their weight from their nadir. Participants experienced challenges such as eating in social settings, loneliness, family difficulties, increases in appetite, and physical and mental health problems, which distracted them from weight management. Participants responded to weight regain with emotional distress, particularly with hopelessness, discouragement, shame, and frustration (theme: loss of control and focus). Nonetheless, participants experienced remaining benefits from the surgery, despite weight regain. Social support, self-care, and behavioral strategies were perceived as facilitators for weight management (theme: reducing the burden of weight management).

Conclusions

Weight regain after bariatric surgery was perceived to be an unexpected and difficult experience that induced hopelessness, discouragement, shame, and frustration. Results indicate that internal and external circumstances such as psychosocial factors, changes in appetite, and physical and mental health problems may contribute to loss of control over weight. Social support, self-care, and behavioral strategies might facilitate long-term post-surgical weight management.

Graphical abstract
The Role of Single Nucleotide Polymorphisms of Monoamine Oxidase B, Dopamine D2 Receptor, and DOPA Decarboxylase Receptors Among Patients Treated for Parkinson’s Disease
Authors: Zapała Barbara , Stefura Tomasz , Piwowar Monika , Czekalska Sylwia , Zawada Magdalena , Hadasik Maria , Solnica Bogdan , Rudzińska-Bar Monika
Published: January 2022

This study aimed to investigate the association between selected variants of genes related to dopamine metabolism pathways and the risk of and progression of Parkinson’s disease (PD). This prospective cohort study was conducted in one academic teaching hospital. The study was conducted on 126 patients diagnosed with idiopathic Parkinson’s disease. Blood samples were collected to conduct a genotyping of MAOB, DRD1, DRD2, and DDC genes. Genotype and allele frequencies of MAOB (rs1799836) variants were not associated with the course of PD. Genotype and allele frequencies of DRD2 (rs2283265) variants were associated with risk of dementia (p = 0.001) and resulted in parts II and III of the UPDRS scale (p = 0.001). Genotype and allele frequencies of DRD2 (rs1076560) variants were associated with risk of dementia (p = 0.001) and resulted in parts II and III of the UPDRS scale (p = 0.001). Genotype and allele frequencies of DDC (rs921451) variants were not associated with the course of PD.
NEO E-vita—NEO era!
Authors: Jakob Heinz , Mourad Fanar
Published: January 2022

In this review article, the history of the first commercially available thoracic aortic hybrid graft, the E-vita Open, later modified to the blood-impermeable E-vita Open Plus, is reported from its beginning in 2005 until its newest variation, the E-vita Open NEO, European conformity (CE) marked in 2020. Besides the background of its design and clinical experience in Essen, concomitant evolutionary steps in surgery as well as in strategic approaches like the hybrid operating room concept are displayed, finally leading to a well-rounded surgical package with a device that can be applied in all elective as well as emergency situations with complex arch involving aortic pathologies. With the E-vita Open NEO, now, surgery has been facilitated to convenient anastomosing in any of the arch zones, with the opportunity to use the island technique with a straight graft variation as well as individual head vessel anastomosing with either a trifurcated graft for zone 0 or the branched graft for zone 2 or 3 implantation. With its proven long-term stability, the surgical armamentarium to cope with complex multisegmental thoracic aortic pathologies has been significantly improved.
Connectivity Shapes Functional Diversity and Maintains Complementarity in Surf Zones on Exposed Coasts
Authors: Henderson Christopher J. , Gilby Ben L. , Olds Andrew D. , Mosman Jesse , Connolly Rod M. , Hyndes Glenn , Kelaher Brendan , Maslo Brooke , Williams Alan , Schlacher Thomas A.
Published: January 2022

Habitat complexity and connectivity can influence the number of species and their diversity across a landscape. For the surf zones of ocean-exposed beaches, globally one of the longest habitat interfaces, the assumed low structural complexity, and apparent homogeneity, of the sandy seafloor habitats predicts low taxonomic and functional diversity. Here, we assessed how the configuration of the seascape and the context of different beach structure functional diversity and functional niche space of fish assemblages in surf zones. We expected that beaches that were well connected with highly productive and complex estuarine and reef habitats would support a greater level of functional diversity, and a greater degree of functional complementarity within different niches. We sampled surf zones at twenty-five beaches along 50 km of coastline in southeast Queensland, Australia. We calculated functional diversity and functional niche space using variation in the functional traits of fish assemblages. We found that increased proximity with nearby subtidal rocky reefs was the key feature of the coastline shaping functional diversity and functional niche space in surf zone fishes. These effects resulted in increased functional complementarity within a number of fish functional group niches when rocky reefs were nearby. We provide empirical evidence that habitat proximity can structure functional diversity and complementarity in the surf zones of ocean beaches, a system traditionally viewed as having low habitat heterogeneity. Our results highlight the focus management must take in conserving these highly connected ecosystems to avoid negative functional consequences.
Tracking mutation and drug-driven alterations of oncokinase conformations
Authors: Feichtner Andreas , Kugler Valentina , Schwaighofer Selina , Nuener Thomas , Fleischmann Jakob , Stefan Eduard
Published: January 2022

Numerous kinases act as central nodes of cellular signaling networks. As such, many of these enzymes function as molecular switches for coordinating spatiotemporal signal transmission. Typically, it is the compartmentalized phosphorylation of protein substrates which relays the transient input signal to determine decisive physiological cell responses. Genomic alterations affect kinase abundance and/or their activities which contribute to the malignant transformation, progression, and metastasis of human cancers. Thus, major drug discovery efforts have been made to identify lead molecules targeting clinically relevant oncokinases. The concept of personalized medicine aims to apply the therapeutic agent with the highest efficacy towards a patient-specific mutation. Here, we discuss the implementation of a cell-based reporter system which may foster the decision-making process to identify the most promising lead-molecules. We present a modular kinase conformation (KinCon) biosensor platform for live-cell analyses of kinase activity states. This biosensor facilitates the recording of kinase activity conformations of the wild-type and the respective mutated kinase upon lead molecule exposure. We reflect proof-of-principle studies demonstrating how this technology has been extended to profile drug properties of the full-length kinases BRAF and MEK1 in intact cells. Further, we pinpoint how this technology may open new avenues for systematic and patient-tailored drug discovery efforts. Overall, this precision-medicine-oriented biosensor concept aims to determine kinase inhibitor specificity and anticipate their drug efficacies.
A risk scoring system based on tumor microenvironment cells to predict prognosis and immune activity in triple-negative breast cancer
Authors: Yang Anli , Wu Minqing , Ni Mengqian , Zhang Lijuan , Li Mingyue , Wei Peijun , Yang Yonggang , Xiao Weikai , An Xin
Published: January 2022

The tumor microenvironment (TME) interacting with the malignant cells plays a vital role in cancer development. Herein, we aim to establish and verify a scoring system based on the characteristics of TME cells for prognosis prediction and personalized treatment guidance in patients with triple-negative breast cancer (TNBC). 158 TNBC samples from The Cancer Genome Atlas (TCGA) were included as the training cohort, and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (N = 297), as well as GSE58812 (N = 107), were included as the validation cohort. The enrichment scores of 64 immune and stromal cells were estimated by the xCell algorithm. In the training cohort, cells with prognostic significance were found out using univariate Cox regression analysis and further applied to the random survival forest (RSF) model. Based on the scores of M2 macrophages, CD8+ T cells, and CD4+ memory T cells, a risk scoring system was constructed, which divided TNBC patients into 4 phenotypes (M2low, M2highCD8+ThighCD4+Thigh, M2highCD8+ThighCD4+Tlow, and M2highCD8+Tlow). Furthermore, types 1 and 2 patients were merged into the low-risk group, while types 3 and 4 patients were in the high-risk group. The low-risk group had superior survival outcomes than the high-risk one, which was further confirmed in the validation cohort. Moreover, in the low-risk group, immune-related pathways were significantly enriched, and a higher level of antitumoral immune cells and immune checkpoint molecules, including PD-L1, PD-1, and CTLA-4, could be observed. Additionally, consistent results were achieved in the SYSUCC cohort when the scoring system was applied. In summary, this novel scoring system might predict the survival and immune activity of patients and might serve as a potential index for immunotherapy.
Onderzoeksopzet evaluatie Gezonde School: onder welke condities doet het ertoe?
Authors: Vennegoor Gerjanne , Vonk Lisanne , van Assema Patricia , Huijts Tim , Eekhout Iris , Molleman Gerard R. M. , Levels Mark , Jansen Maria W. J.
Published: January 2022

Samenvatting

Hoewel steeds meer scholen het vignet Gezonde School hebben behaald, is weinig bekend over de factoren, kenmerken en processen, ofwel condities, die de effectiviteit van het programma Gezonde School beïnvloeden. Daarom wordt een evaluatieonderzoek uitgevoerd op drie niveaus: de leerling, de school en de regio. De drie centrale onderzoeksvragen zijn gericht op: 1) condities voor leerlinguitkomsten, 2) condities voor implementatie op school, en 3) condities voor regionale ondersteuning. Daarbij worden de school en de regio beschouwd als complexe adaptieve systemen. Condities voor beoogde uitkomsten op leefstijl, gezondheid en schoolprestaties van leerlingen worden onderzocht met een combinatie van bestaande databronnen waaraan schoolcodes kunnen worden toegevoegd. Goed en minder goed presterende scholen worden geselecteerd voor een overwegend kwalitatieve vervolganalyse om verschillen in uitkomsten verder te verklaren. Om inzicht te krijgen in condities voor implementatie op school en de regionale ondersteuning in negen GGD-regio’s wordt met een vragenlijst de implementatiegraad bepaald, om daarna scholen te selecteren voor overwegend kwalitatief vervolgonderzoek. Dit onderzoek biedt niet alleen inzicht in de huidige stand van zaken op de drie niveaus, maar kan ook verschillen in uitkomsten tussen leerlingen, scholen en regio’s verklaren. Zo kunnen concrete aangrijpingspunten worden gegeven om de implementatie van Gezonde School verder te versterken.
Gosha-Jinki-Gan Improved Erectile Dysfunction Caused by Anti-Cancer Agent Oxaliplatin by Decreasing Transcriptional Expression of Phosphodiesterase-5 in Rats
Authors: Kataoka Tomoya , Kawaki Yuto , Kito Yohei , Suzuki Jun , Mori Taiki , Hotta Yuji , Sanagawa Akimasa , Kawade Yoshihiro , Maeda Yasuhiro , Furukawa-Hibi Yoko , Kimura Kazunori
Published: January 2022

Background

A platinum-containing anti-cancer agent, oxaliplatin (L-OHP), is known to induce peripheral neuropathy, including erectile dysfunction (ED) as a side effect, while Gosha-jinki-gan (GJG) is a traditional Japanese herbal medicine mainly used for peripheral neuropathy.

Aim

To investigate the effect of GJG on L-OHP-induced ED in rats.

Methods

Twelve-week-old male Wister/ST rats were categorized into the following groups: Sham, Sham+GJG, L-OHP, and L-OHP+GJG (each n = 10). The L-OHP and L-OHP+GJG groups were injected intravenously with L-OHP (4 mg/kg) for 2 consecutive days in the first week. Statistical significance was determined using Bonferroni's multiple comparison test.

Outcomes

At the end of the study period, erectile function was evaluated by measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP) after cavernous nerve stimulation. Western blot analysis was used to assess the neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) levels, and quantitative polymerase chain reaction was used to assess the expression of phosphodiesterase-5 (PDE-5) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-1.

Results

The ICP/MAP ratio of L-OHP rats (0.34 ± 0.06) was significantly lower than that of Sham rats (0.67 ± 0.03, P < .01), however, the ICP/MAP ratio of L-OHP+GJG rats (0.55 ± 0.01) was significantly higher than that of L-OHP rats (P < .01). There were no significant differences in the nNOS and eNOS protein expression between both groups (P > .05). GJG administration significantly decreased PDE-5 and NADPH oxidase-1 messenger RNA expressions in the L-OHP+GJG group.

Clinical Translation

This animal model study suggests that GJG might be effective for erectile function in cancer survivors.

Strengths & limitations

Our study identified that GJG had no notable side effects in the treated group. Further investigation of the cavernous nerve would also help elucidate the mechanism of GJG effect, which is a limitation of this study.

Conclusion

We found that GJG administration improved L-OHP-induced ED by improving transcriptional PDE-5 expression.
A pilot model of a public–private partnership for implementation of a coronavirus disease 2019 (COVID-19) diagnostic testing program to facilitate a safe school reopening
Authors: Branch-Elliman Westyn , van den Berg Polly , Dong Sara W. , Kapoor Andrew K. , Merchant Elisabeth A. , Schechter-Perkins Elissa M.
Published: January 2022

Objective:

We developed an implementation plan to integrate diagnostic testing for coronavirus disease 2019 (COVID-19) into a public school system. Implementation barriers were identified and strategies were mapped to overcome them.

Design:

A COVID-19 diagnostic testing program leveraging a public–private partnership was developed for a public school system.

Setting:

A suburban school district and a local hospital during the 2020–2021 academic year.

Methods:

Using Consolidated Framework for Implementation Research (CFIR) constructs and evidenced-based implementation strategies, the program was designed as a “closed system” and was adapted based on stakeholder feedback. Implementation barriers and facilitators were identified and mapped to CFIR constructs to provide insights into factors influencing program adoption.

Results:

Preimplementation stages of engagement, feasibility, and readiness planning were completed. The program did not progress to implementation due to multiple factors, including changes in school leadership (inner setting and process-level constructs), improved access to outside testing, and lack of an existing paradigm for in-school testing (external constructs). Limited support from key stakeholders and opinion leaders was also a barrier (process-level construct).

Conclusions:

Although this locally initiated program did not progress beyond the preimplementation stage, the processes developed and barriers identified may be useful to inform planning efforts in other testing programs within public school systems. Future programs may consider incorporating multiplex diagnostic testing for influenza in addition to COVID-19. With relaxation of infection control measures, the prevalence of other respiratory viruses will increase. Actionable results will be needed to inform decisions about closures and quarantines.
A hierarchical decomposition of internal wave fields
Authors: Dobra Thomas E. , Lawrie Andrew G.W. , Dalziel Stuart B.
Published: January 2022

Internal gravity wave fields are decomposed into temporal modes revealing the hierarchical structure of nonlinear wave–wave interactions. We present a novel fusion of Green's functions for solving the forced internal wave equation with a weakly nonlinear perturbation expansion. Our approach is semi-analytical, based on integration over finite elements with the perturbation expansion ensuring source terms at each order are only dependent on the solutions at lower orders. Thus, the procedure is purely inductive and efficient to compute. To perform a thorough validation of our new method, we diagnose experiments using synthetic Schlieren and apply sophisticated post-processing techniques, including dynamic mode decomposition, to obtain these temporal modes for systems with discrete input frequencies. By decomposing the experimental field and comparing individual constituents against equivalents synthesised by our model, we are able to present the first truly comprehensive, validated, mechanistic picture of wave–wave interactions to arbitrary order. This synergy enables us to identify non-wave oscillatory behaviour at frequencies shared by waves in the hierarchy and leads us to discover an important open question regarding transmission efficiency within individual wave–wave interactions. Although our experiments are generated by boundary displacements, we present equivalences between source terms and boundary displacements so that the class of applicable systems may be broadened. Our technique also generalises to aperiodic and unbounded configurations and to any weakly nonlinear wave-governed system for which there is an available Green's function.
Monitoring of COVID-19 pandemic-related psychopathology using machine learning
Authors: Enevoldsen Kenneth C. , Danielsen Andreas A. , Rohde Christopher , Jefsen Oskar H. , Nielbo Kristoffer L. , Østergaard Søren D.
Published: January 2022

The COVID-19 pandemic is believed to have a major negative impact on global mental health due to the viral disease itself as well as the associated lockdowns, social distancing, isolation, fear, and increased uncertainty. Individuals with preexisting mental illness are likely to be particularly vulnerable to these conditions and may develop outright ‘COVID-19-related psychopathology’. Here, we trained a machine learning model on structured and natural text data from electronic health records to identify COVID-19 pandemic-related psychopathology among patients receiving care in the Psychiatric Services of the Central Denmark Region. Subsequently, applying this model, we found that pandemic-related psychopathology covaries with the pandemic pressure over time. These findings may aid psychiatric services in their planning during the ongoing and future pandemics. Furthermore, the results are a testament to the potential of applying machine learning to data from electronic health records.
Vitamins, microelements and the immune system: current standpoint in the fight against coronavirus disease 2019
Authors: Djordjevic Branka , Milenkovic Jelena , Stojanovic Dijana , Velickov Aleksandra , Djindjic Boris , Jevtovic Stoimenov Tatjana
Published: January 2022

Coronavirus disease 2019 (COVID-19) is an acute respiratory disease associated with severe systemic inflammation. The optimal status of vitamins and microelements is considered crucial for the proper functioning of the immune system and necessary for successful recovery. Most patients with respiratory distress in COVID-19 are vitamin and microelement deficient, with vitamin D and Se deficiency being the most common. Anyway, various micronutrient supplements are widely and arbitrarily used for prevention or in the treatment of COVID-19. We aimed to summarise current knowledge about molecular and physiological mechanisms of vitamins (D, A, C, B6, B9and B12) and microelements (Se, Zn, Cu and Fe) involved in the immune system regulation in consideration with COVID-19 pathogenesis, as well as recent findings related to their usage and effects in the prevention and treatment of COVID-19. In the early course of the pandemic, several, mainly observational, studies reported an association of some micronutrients, such as vitamin C, D and Zn, with severity reduction and survival improvement. Still, emerging randomised controlled trials showed no effect of vitamin D on hospitalisation length and no effect of vitamin C and Zn on symptom reduction. Up to date, there is evidence neither for nor against the use of micronutrients in the treatment of COVID-19. The doses that exceed the recommended for the general population and age group should not be used, except in clinical trials. Benefits of supplementation are primarily expected in populations prone to micronutrient deficiencies, who are, as well, at a higher risk of worse outcomes in COVID-19.
Considering escaping hell
Authors: Ani Emmanuel Ifeanyi
Published: January 2022

Adams argues that the traditional doctrine of eternal hellish experience stretches the Problem of Evil beyond any reasonable solution, as hell is stubbornly incompatible with God's omnipotence, omniscience, and perfect goodness. Buckareff and Plug argue that people could leave hell. Matheson responds that if people could leave hell, people could leave heaven. But Matheson provides reasons to think that this is not possible. Luck attempts to refute Matheson's argument. I show that Luck's attempt contains analogies that lack features that crucially depict the asymmetrical relationship between heaven and hell. I advance some other analogies that I think contain such features.
SOME HOMOLOGICAL PROPERTIES OF CATEGORY FOR LIE SUPERALGEBRAS
Authors: CHEN CHIH-WHI , MAZORCHUK VOLODYMYR
Published: January 2022

For classical Lie superalgebras of type I, we provide necessary and sufficient conditions for a Verma supermodule
$\Delta (\lambda )$
to be such that every nonzero homomorphism from another Verma supermodule to
$\Delta (\lambda )$
is injective. This is applied to describe the socle of the cokernel of an inclusion of Verma supermodules over the periplectic Lie superalgebras
$\mathfrak {pe} (n)$
and, furthermore, to reduce the problem of description of
$\mathrm {Ext}^1_{\mathcal O}(L(\mu ),\Delta (\lambda ))$
for
$\mathfrak {pe} (n)$
to the similar problem for the Lie algebra
$\mathfrak {gl}(n)$
. Additionally, we study the projective and injective dimensions of structural supermodules in parabolic category
$\mathcal O^{\mathfrak {p}}$
for classical Lie superalgebras. In particular, we completely determine these dimensions for structural supermodules over the periplectic Lie superalgebra
$\mathfrak {pe} (n)$
and the orthosymplectic Lie superalgebra
$\mathfrak {osp}(2|2n)$
.
A compact dual band MIMO antenna for 5G/WLAN applications
Authors: Liu Gui , Zhang Chuanba , Chen Zhuoni , Chen Bo
Published: January 2022

To satisfy the increasing requirements of wireless communication, a compact dual band MIMO antenna is presented in this paper. The presented antenna consists of two symmetric radiating elements operating at both 3.5 and 4.5 GHz bands. To enhance the isolation between the two radiating elements, an I-shaped decoupling structure is introduced. The measured −10 dB reflection coefficients frequency bands are 3.3–3.8 and 4.3–5.8 GHz. The measured isolation S21 between the two radiating elements are better than 15 and 17 dB at the lower and higher frequency band, respectively. The overall dimension of the proposed antenna is 50 × 22 × 1.59 mm3. The measured result indicates that the proposed antenna can be a good candidate for 5 G/WLAN wireless communication.
Prokrastination - Extremes Aufschieben
Authors: Höcker Anna , Engberding Margarita , Rist Fred
Published: January 2022

Psychotherapeutinnen und Psychotherapeuten werden in der Praxis immer häufiger mit dem Anliegen Prokrastination, also dem chronischen exzessiven Aufschieben, oder mit milderen Formen des Aufschiebens konfrontiert, die zwar nicht „pathologisch“ sind, aber dennoch als störend oder belastend empfunden werden. Das Buch liefert einen praxisorientierten Leitfaden für die Diagnostik und Behandlung von Prokrastination.
Chronisch-exzessives Aufschieben ist ein Problem der Selbststeuerung. Es hat gravierende Folgen sowohl für die Leistungs- und Arbeitsfähigkeit als auch für die allgemeine Lebensführung und das psychische Wohlbefinden. Prokrastination kann Ursache psychischer Symptome und Störungen sein, als Symptom im Rahmen psychischer Störungen auftreten oder selbst eine klinisch relevante Symptomatik darstellen. Der Band liefert neben einer Beschreibung der speziellen Arbeitsstörung ein kognitiv-behaviorales Erklärungsmodell und eine Anleitung für das diagnostische Vorgehen. Weiterhin werden Behandlungsmodule vorgestellt, die je nach individueller Problemlage und nach zeitlichen Rahmenbedingungen unterschiedlich kombiniert werden können. Die Module sind einzeln durchführbar oder können in eine bestehende umfassendere Behandlung oder Beratung integriert werden. Lösungen für die Bewältigung problemtypischer Schwierigkeiten in der Behandlung werden erörtert. Arbeitsmaterialien erleichtern die Umsetzung des Vorgehens in die Praxis.