bluuebunny/crossref_metadata_2025 huggingface dataset:
Autocrine regulation of airway smooth muscle contraction by diacylglycerol kinase
Authors: Yadav Santosh K. , Sharma Pawan , Shah Sushrut D. , Panettieri Reynold A. , Kambayashi Taku , Penn Raymond B. , Deshpande Deepak A.
Published: July 2021

Diacylglycerol kinase (DGK), a lipid kinase, catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid, thereby terminating DAG‐mediated signaling by Gq‐coupled receptors that regulate contraction of airway smooth muscle (ASM). A previous study from our laboratory demonstrated that DGK inhibition or genetic ablation leads to reduced ASM contraction and provides protection for allergen‐induced airway hyperresponsiveness. However, the mechanism by which DGK regulates contractile signaling in ASM is not well established. Herein, we investigated the role of prorelaxant cAMP‐protein kinase A (PKA) signaling in DGK‐mediated regulation of ASM contraction. Pretreatment of human ASM cells with DGK inhibitor I activated PKA as demonstrated by the phosphorylation of PKA substrates, VASP, Hsp20, and CREB, which was abrogated when PKA was inhibited pharmacologically or molecularly using overexpression of the PKA inhibitor peptide, PKI. Furthermore, inhibition of DGK resulted in induction of cyclooxygenase (COX) and generation of prostaglandin E2 (PGE2) with concomitant activation of Gs‐cAMP‐PKA signaling in ASM cells in an autocrine/paracrine fashion. Inhibition of protein kinase C (PKC) or extracellular‐signal‐regulated kinase (ERK) attenuated DGK‐mediated production of PGE2 and activation of cAMP‐PKA signaling in human ASM cells, suggesting that inhibition of DGK activates the COX‐PGE2 pathway in a PKC‐ERK‐dependent manner. Finally, DGK inhibition‐mediated attenuation of contractile agonist‐induced phosphorylation of myosin light chain 20 (MLC‐20), a marker of ASM contraction, involves COX‐mediated cAMP production and PKA activation in ASM cells. Collectively these findings establish a novel mechanism by which DGK regulates ASM contraction and further advances DGK as a potential therapeutic target to provide effective bronchoprotection in asthma.
TGF‐β signaling: A recap of SMAD‐independent and SMAD‐dependent pathways
Authors: Aashaq Sabreena , Batool Asiya , Mir Shabir Ahmad , Beigh Mushtaq Ahmad , Andrabi Khurshid Iqbal , Shah Zaffar Amin
Published: July 2021

Transforming growth factor‐β (TGF‐β) is a proinflammatory cytokine known to control a diverse array of pathological and physiological conditions during normal development and tumorigenesis. TGF‐β‐mediated physiological effects are heterogeneous and vary among different types of cells and environmental conditions. TGF‐β serves as an antiproliferative agent and inhibits tumor development during primary stages of tumor progression; however, during the later stages, it encourages tumor development and mediates metastatic progression and chemoresistance. The fundamental elements of TGF‐β signaling have been divulged more than a decade ago; however, the process by which the signals are relayed from cell surface to nucleus is very complex with additional layers added in tumor cell niches. Although the intricate understanding of TGF‐β‐mediated signaling pathways and their regulation are still evolving, we tried to make an attempt to summarize the TGF‐β‐mediated SMAD‐dependent andSMAD‐independent pathways. This manuscript emphasizes the functions of TGF‐β as a metastatic promoter and tumor suppressor during the later and initial phases of tumor progression respectively.
Genetic counseling practice for inherited eye diseases in an Israeli medical center during the COVID‐19 pandemic
Authors: Macarov Michal , Schneider Nina , Eilat Avital , Yahalom Claudia
Published: July 2021

Inherited eye diseases (IED) are among the most common causes for childhood and young adulthood blindness in developed countries. Genetic counseling and testing have become an essential part of caregiving for families affected by one of these severe ocular pathologies. The objective of our study is to describe our experience during the 2020 (COVID‐19) pandemic, following a practice protocol of safe genetic counseling for inherited ophthalmic diseases. We conducted a review of the genetic counseling practices from January until December 2020 in a multidisciplinary clinic for patients with visual impairment, in a tertiary hospital. The new protocol covered patient screening, required personal protective equipment, and the implementation of telemedicine.

One hundred and eighty‐three counseling sessions were done in this period of time; 33/183 were telemedicine counseling. The results of this study indicate that the practice of genetic counseling in regard to inherited eye diseases in the era of COVID‐19 is effective and safe. Despite the high risk of infectivity that threatened healthcare professionals, safety measures adopted to reduce the risk of infection allowed us to prevent the cancelation of routine counseling, while keeping patient care our priority. The use of telemedicine was a very useful tool for providing counseling during lockdown periods in 2020.
Examining disease boundaries: Genetics of myelodysplastic/myeloproliferative neoplasms
Authors: Hochman Michael J. , Savani Bipin N. , Jain Tania
Published: July 2021

Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are clonal myeloid malignancies that are characterized by dysplasia resulting in cytopenias as well as proliferative features such as thrombocytosis or splenomegaly. Recent studies have better defined the genetics underlying this diverse group of disorders. Trisomy 8, monosomy 7, and loss of Y chromosome are the most common cytogenetic abnormalities seen. Chronic myelomonocytic leukemia (CMML) likely develops from early clones with TET2 mutations that drive granulomonocytic differentiation. Mutations in SRSF2 are common and those in the RAS‐MAPK pathway are typically implicated in disease with a proliferative phenotype. Several prognostic systems have incorporated genetic features, with ASXL1 most consistently demonstrating worse prognosis. Atypical chronic myeloid leukemia (aCML) is most known for granulocytosis with marked dysplasia and often harbors ASXL1 mutations, but SETBP1 and ETNK1 are more specific to this disease. MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN‐RS‐T) most commonly involves spliceosome mutations (namely SF3B1) and mutations in the JAK‐STAT pathway. Finally, MDS/MPN‐unclassifiable (MDS/MPN‐U) is least characterized but a significant fraction carries mutations in TP53. The remaining patients have clinical and/or genetic features similar to the other MDS/MPNs, suggesting there is room to better characterize this entity. Evolution from age‐related clonal hematopoiesis to MDS/MPN likely depends on the order of mutation acquisition and interactions between various biologic factors. Genetics will continue to play a critical role in our understanding of these illnesses and advancing patient care.
Cardiac involvement in Wilson disease: Review of the literature and description of three cases of sudden death
Authors: Chevalier Kevin , Benyounes Nadia , Obadia Michaël Alexandre , Van Der Vynckt Clélie , Morvan Erwan , Tibi Thierry , Poujois Aurélia
Published: July 2021

Wilson disease (WD) is a rare genetic condition that results from a build‐up of copper in the body. It requires life‐long treatment and is mainly characterized by hepatic and neurological features. Copper accumulation has been reported to be related to the occurrence of heart disease, although little is known regarding this association. We have conducted a systematic review of the literature to document the association between WD and cardiac involvement. Thirty‐two articles were retained. We also described three cases of sudden death. Cardiac manifestations in WD include cardiomyopathy (mainly left ventricular (LV) remodeling, hypertrophy, and LV diastolic dysfunction, and less frequently LV systolic dysfunction), increased levels of troponin, and/or brain natriuretic peptide, electrocardiogram (ECG) abnormalities, and rhythm or conduction abnormalities, which can be life‐threatening. Dysautonomia has also been reported. The mechanism of cardiac damage in WD has not been elucidated. It may be the result of copper accumulation in the heart, and/or it could be due to a toxic effect of copper, resulting in the release of free oxygen radicals. Patients with signs and/or symptoms of cardiac involvement or who have cardiovascular risk factors should be examined by a cardiologist in addition to being assessed by their interdisciplinary treating team. Furthermore, ECG, cardiac biomarkers, echocardiography, and 24‐hours or more of Holter monitoring at the diagnosis and/or during the follow‐up of patients with WD need to be evaluated. Cardiac magnetic resonance imaging, although not always available, could also be a useful diagnostic tool, allowing assessment of the risk of ventricular arrhythmias and further guidance of the cardiac workup.
A role for T‐cell exhaustion in Long COVID‐19 and severe outcomes for several categories of COVID‐19 patients
Authors: Roe Kevin
Published: July 2021

Unusual mortality rate differences and symptoms have been experienced by COVID‐19 patients, and the postinfection symptoms called Long COVID‐19 have also been widely experienced. A substantial percentage of COVID‐19‐infected individuals in specific health categories have been virtually asymptomatic, several other individuals in the same health categories have exhibited several unusual symptoms, and yet other individuals in the same health categories have fatal outcomes. It is now hypothesized that these differences in mortality rates and symptoms could be caused by a SARS‐CoV‐2 virus infection acting together with one or more latent pathogen infections in certain patients, through mutually beneficial induced immune cell dysfunctions, including T‐cell exhaustion. A latent pathogen infection likely to be involved is the protozoan parasite Toxoplasma gondii, which infects approximately one third of the global human population. Furthermore, certain infections and cancers that cause T‐cell exhaustion can also explain the more severe outcomes of other COVID‐19 patients having several disease and cancer comorbidities.
Erbium‐doped: yttrium‐aluminum‐garnet (Er:YAG) versus scaling and root planing for the treatment of periodontal disease: A single‐blinded split‐mouth randomized clinical trial
Authors: Gurpegui Abud Daniela , Shariff Jaffer A. , Linden Eric , Kang Philip Y.
Published: July 2021

Background

This randomized, controlled clinical trial aimed to compare the differences in periodontal clinical outcomes, duration of the procedure, and patient's experience between conventional scaling and root planing and erbium‐doped: yttrium‐aluminum‐garnet (Er:YAG) in the treatment of generalized moderate to severe chronic periodontitis or generalized Stages II or III, and Grade B periodontitis based on the Centers for Disease Control (CDC), American Academy of Periodontology (AAP), and European Federation of Periodontology (EFP) definitions.

Methods

Thirty subjects were initially recruited. In a split‐mouth fashion, right and left sides were randomly allocated into two treatment arms: conventional scaling and root planing (C‐SRP) versus laser‐assisted scaling and root planing (L‐SRP). A blinded examiner recorded clinical measurements at baseline and 3 months. Duration of the procedure was also recorded for each visit, and the patient's experience was assessed with a questionnaire at baseline, 1, and 3 months.

Results

The final sample consisted of 26 subjects. Both treatments resulted in overall improvement, but no significant differences were found between modalities for clinical attachment gain or probing depth reduction. The duration of the procedure was approximately half for L‐SRP, and postoperative sensitivity was greater in C‐SRP.

Conclusions

The low‐energy protocol with Er:YAG (50 mJ) used for the non‐surgical treatment of moderate‐severe chronic or Stage II‐III, Grade B periodontitis performed in this study population was a treatment modality that yielded similar clinical improvements when compared to conventional scaling and root planing.
The bacterial and fungal community composition in time and space in the nest mounds of the antFormicaexsecta(Hymenoptera: Formicidae)
Authors: Lindström Stafva , Timonen Sari , Sundström Liselotte
Published: July 2021

In a subarctic climate, the seasonal shifts in temperature, precipitation, and plant cover drive the temporal changes in the microbial communities in the topsoil, forcing soil microbes to adapt or decline. Many organisms, such as mound‐building ants, survive the cold winter owing to the favorable microclimate in their nest mounds. We have previously shown that the microbial communities in the nest of the antFormicaexsectaare significantly different from those in the surrounding bulk soil. In the current study, we identified taxa, which were consistently present in the nests over a study period of three years. Some taxa were also significantly enriched in the nest samples compared with spatially corresponding reference soils. We show that the bacterial communities in ant nests are temporally stable across years, whereas the fungal communities show greater variation. It seems that the activities of the ants contribute to unique biochemical processes in the secluded nest environment, and create opportunities for symbiotic interactions between the ants and the microbes. Over time, the microbial communities may come to diverge, due to drift and selection, especially given the long lifespan (up to 30 years) of the ant colonies.
Corporate social responsibility spending as a building block for sustainable corporate ethical identity: Lessons from Indian business groups
Authors: Dutta Shantanu , Katti Supriya , Phani B. V. , Zhu Pengcheng
Published: July 2021

We examine the cost implications of using corporate social responsibility (CSR) as a vehicle to build sustainable corporate ethical identity (CEI). CSR investment is recognized as one of the effective channels to promote a firm's CEI. However, excessive CSR could divert resources from other strategic projects, and shareholder may not favor such initiatives. We address this managerial dilemma with a unique Indian CSR regulatory environment. Our results show that firms with greater reputational concerns have a higher proclivity to meet the mandatory CSR investment level but are reluctant to exceed the mandatory CSR limit due to absence of incremental financial benefits.
Novel and very rare causative variants in the COL7A1 gene of Vietnamese patients with recessive dystrophic epidermolysis bullosa revealed by whole‐exome sequencing
Authors: Ma Thi Huyen Thuong , Luong Thi Lan Anh , Hoang Thu Lan , Nguyen Thi Thanh Hoa , Vu Thi Ha , Tran Van Khoa , Nguyen Duy Bac , Trieu Tien Sang , Nguyen Hai Ha , Nong Van Hai , Nguyen Dang Ton
Published: July 2021

Background

Dystrophic epidermolysis bullosa (DEB) is a rare inherited disorder characterized by skin fragility leading to trauma‐induced subepidermal blisters and healing with scarring. DEB is caused by mutations in COL7A1, the gene encoding for type VII collagen (COLVII). The DEB inheritance trait is divided into dominant dystrophic epidermolysis bullosa (DDEB) and recessive dystrophic epidermolysis bullosa (RDEB).

Methods

Whole‐exome sequencing (WES) was performed for identifying mutations in six affected individuals of five Vietnamese families.

Results

Three novel variants in total of eight variants were found in five families. The first novel variant causing glycine substitution (c.8279G>A, p.G2760E), the remaining two novel variants resulted in splice site affecting (c.4518+2delT and c.5821‐2A>G). Functional analysis indicated that the splice site at c.4518+2delT resulted in a skipping of exon 43, leading to an in‐frame deletion of 12 amino acids.

Conclusion

Our finding expands the spectrum of COL7A1 mutations and reports altered splicing at c.4518+2delT during the processing of the pre‐mRNA. This study provides an additional scientific basis for diagnosis, genetic counseling, and prognosis purposes of EB patients.
Compact, broadband, wide angular stable circuit analog absorber at sub‐6 GHz for radar cross section reduction
Authors: Shukoor Mohammad Abdul , Dey Sukomal
Published: July 2021

This work presents a compact broadband wide angular stable polarization‐insensitive circuit analog absorber at sub 6 GHz. It shows almost 95% absorption from 2.26 to 5.76 GHz over the entire operating range. A transmission line equivalent circuit is modeled, and the response is validated. The design is obliquely stable up to 45° for both transverse electric and transverse magnetic incidences. The analysis of surface current distributions at two resonant frequencies confirming magnetic resonances' role in near‐unity absorption. It is compact with a periodicity of 0.1 λL and thickness of 0.08 λL. Finally, bistatic radar cross section reduction of the proposed absorber attached with an antenna is measured.
Interventional cardiac MRI using an add‐on parallel transmit MR system: In vivo experience in sheep
Authors: Godinez Felipe , Tomi‐Tricot Raphael , Delcey Marylène , Williams Steven E. , Mooiweer Ronald , Quesson Bruno , Razavi Reza , Hajnal Joseph V. , Malik Shaihan J.
Published: July 2021

Purpose

We present in vivo testing of a parallel transmit system intended for interventional MR‐guided cardiac procedures.

Methods

The parallel transmit system was connected in‐line with a conventional 1.5 Tesla MRI system to transmit and receive on an 8‐coil array. The system used a current sensor for real‐time feedback to achieve real‐time current control by determining coupling and null modes. Experiments were conducted on 4 Charmoise sheep weighing 33.9‐45.0 kg with nitinol guidewires placed under X‐ray fluoroscopy in the atrium or ventricle of the heart via the femoral vein. Heating tests were done in vivo and post‐mortem with a high RF power imaging sequence using the coupling mode. Anatomical imaging was done using a combination of null modes optimized to produce a useable B1 field in the heart.

Results

Anatomical imaging produced cine images of the heart comparable in quality to imaging with the quad mode (all channels with the same amplitude and phase). Maximum observed temperature increases occurred when insulation was stripped from the wire tip. These were 4.1℃ and 0.4℃ for the coupling mode and null modes, respectively for the in vivo case; increasing to 6.0℃ and 1.3℃, respectively for the ex vivo case, because cooling from blood flow is removed. Heating < 0.1℃ was observed when insulation was not stripped from guidewire tips. In all tests, the parallel transmit system managed to reduce the temperature at the guidewire tip.

Conclusion

We have demonstrated the first in vivo usage of an auxiliary parallel transmit system employing active feedback‐based current control for interventional MRI with a conventional MRI scanner.
Augmented and Mixed Reality Optical See‐Through Combiners Based on Plastic Optics
Authors: Park Soon‐gi
Published: July 2021

Smart glasses contain an optical combiner, which is one of the main components in AR/MR devices and the key to overcoming many hurdles.
TriLite Addresses Challenges with Projection Display Technologies for AR Glasses
Authors: Noui Louahab , Reitterer Jörg
Published: July 2021

While AR deployment in enterprise applications is accepted by trading off size, weight, and power consumption, this trade‐off is not accepted in the consumer market.
Applications for Flexible TFT Arrays Emerge in the Biomedical Domain
Authors: Kronemeijer Auke Jisk , Gelinck Gerwin H.
Published: July 2021

As flexible TFT backplane technology increases in utility, can display manufacturing technology make the leap into the biomedical domain?
A facile method for synthesizing polymeric nanofiber‐fragments
Authors: Banerjee Aihik , Jariwala Tanvi , Kim Sanggon , Tai Youyi , Chiang Sharon , Park Honghyun , Myung Nosang V. , Nam Jin
Published: July 2021

Electrospinning is a versatile method for synthesizing nanofibrous structures from nearly all polymers, offering a solution for the industrial‐scale mass production of nanomaterials in a wide range of applications. However, the continuous non‐woven structure intrinsic to electrospun fibers limits their applications, where a smaller length scale is desired. Here, we present a novel method to synthesize polymeric nanofiber‐fragments based on colloid electrospinning of polymer and sacrificial silica nanoparticles, followed by mechanical fracturing with ultrasonication. The size and hydrophobicity of silica nanoparticles are optimized for their improved integration within the polymer matrix, and the controllability of nanofiber‐fragment length by the amount of silica nanoparticle loading, down to 2 µm in length for poly(vinylidene fluoride‐trifluoroethylene) nanofibers with an average fiber diameter of approximately 100 nm, is shown. The resultant nanofiber‐fragments are shown to maintain their material properties including piezoelectric coefficients and their enhanced injectability for drug delivery application is demonstrated with an animal model.
Transition care continuity promotes long‐term retention in adult care among young adults with sickle cell disease
Authors: Howell Kristen E. , Saulsberry‐Abate Anjelica C. , Mathias Joacy G. , Porter Jerlym S. , Hodges Jason R. , Ataga Kenneth I. , Anderson Sheila , Nolan Vikki , Hankins Jane S.
Published: July 2021

Background/objectives

Care continuity prevents increased health care utilization and mortality during transition from pediatric to adult care. Our program employs a co‐located care delivery model, in which pediatric provider involvement continues during young adulthood. We tested the hypothesis that individuals who participated in the co‐located model have greater retention in adult care compared to those who only received pediatric transition services.

Methods

This study consisted of 311 youth with SCD (51.4% male; 63.0% HbSS/HbSβ0‐thalassemia) who transferred to adult care from 2007 to 2017. Retention was defined as continuation with an adult provider for ≥12 or ≥24 months post‐pediatric care. Logistic regression estimated the association between co‐location status and retention at 12 and 24 months. Logistic regression and t‐tests were used to evaluate potential predictors of retention in adult care.

Results

Individuals who participated in the co‐location model were 1.9 times more likely to remain in adult care 12 (95% CI: 1.01, 3.47) and 24 (95% CI: 1.01, 3.70) months post‐pediatric care compared to those who did not participate. Individuals with HbSS/HbSβ0‐thalassemia were 1.9 times more likely to be retained at 12 months compared to those with HbSC/HbSβ+‐thalassemia/HbS/HPFH (95% CI: 1.12, 3.09). For every clinic encounter in the last 2 years of pediatric care, the odds of being retained at least 24 months after initiating adult care increased 1.1 times (95% CI: 1.02, 1.13).

Conclusions

Continuity of providers from pediatric to adult care may increase long‐term retention in adult care. Longitudinal monitoring of adult outcomes is critical to identifying the efficacy of transition services.
Statins – the medicines people love to hate!
Authors: Thompson Angus
Published: July 2021

Statins seem to attract more controversy than any other drug class. Angus Thompson considers why this might be, and suggests how to approach discussions with patients who may have concerns.
Microstructure‐Dependent Charge/Discharge Behaviors of Hollow Carbon Spheres and its Implication for Sodium Storage Mechanism on Hard Carbon Anodes
Authors: Chen Xiaoyang , Fang Youlong , Lu Haiyan , Li Hui , Feng Xiangming , Chen Weihua , Ai Xinping , Yang Hanxi , Cao Yuliang
Published: July 2021

Hard carbons are actively developed as a promising anode material for sodium ion batteries (SIBs). However, their sodium storage mechanism is poorly understood, leading to difficulties in design and development of high‐performance hard carbon anode materials. In this work, hollow carbon spheres (HCSs) with different shell thickness as a model material to investigate the correlation between the microstructural change and resulting Na+ storage behavior during charge/discharge cycles are designed and synthesized. Ex situ X‐ray diffraction and Raman evidences reveal that an interlayer spacing change of the graphitic nanodomains occurs in HCS electrode, leading to a shift of the reversible capacity from the high‐potential sloping (HPS) region to the low‐potential plateau (LPP) region. This unusual capacity shift suggests a microstructure‐dependent Na+ storage reaction on the HCS electrode and can be well explained by “adsorption‐intercalation” mechanism for these HCS materials. This work strengthens the understanding of the sodium storage behavior and provides a new perspective for the morphological and structural design of hard carbon anode materials for high‐performance SIBs.
Effect of Soy Waste/Cellulose on Mechanical, Water Sorption, and Biodegradation Properties of Thermoplastic Starch Composites
Authors: Behera Ajaya Kumar , Manna Suvendu , Das Nigamananda
Published: July 2021

Thermoplastic starch (TPS)/soy pulp (soy waste) composites (TSS) with varying compositions are successfully prepared in an internal mixer followed by compression molding. The mechanical, water absorption, and biodegradable properties of the developed composites are studied and compared with virgin TPS and cellulose reinforced TPS composites (TSC). Optimum tensile and flexural strength is observed for TSS and TSC composites with 10 wt.% soy waste and cellulose. Fourier Transform Infrared Spectroscopy (FT‐IR) and Scanning Electron Microscope (SEM) analyses indicated the interaction occurred between soy pulp/cellulose and TPS. Water absorptivity is found to increase from 6.2% to as high as 42.3% with the addition of 0 to 25 wt.% cellulose filler to the TPS matrix. Moreover, the soil burial degradation study shows higher degradability of the composites with a higher amount of soy pulp/cellulose. The developed composites show moderate mechanical properties with a hydrophobic and biodegradable nature. Therefore, there is a great possibility for these biocomposites to be utilized in applications such as disposable items, packaging materials, office cuboids, and transport sectors.
Attenuation of chloroquine and hydroxychloroquine on the invasive potential of bladder cancer through targeting matrix metalloproteinase 2 expression
Authors: Chou Kuang‐Yu , Chen Po‐Chun , Chang An‐Chen , Tsai Te‐Fu , Chen Hung‐En , Ho Chao‐Yen , Hwang Thomas I‐Sheng
Published: July 2021

Bladder cancer (BC), one of the most common urological neoplastic disorders in men, has an extremely low survival rate because of its tendency to metastasize. The anticancer drugs chloroquine (CQ) and hydroxy CQ (HCQ) might inhibit tumor progression and invasiveness. However, the mechanism by which CQ and HCQ influence BC is undetermined. In this study, CQ and HCQ treatments inhibited the migration and invasion of two BC cell types (5637 and T24) through expression modulation of matrix metalloproteinase‐2 (MMP‐2), which belongs to the matrix MMP family and is a key mediator of cancer progression. Moreover, additional data revealed that the migrative and invasive effects of BC cells treated with CQ or HCQ were abolished after treatment with rapamycin, which induces autophagy, demonstrating that CQ and HCQ functions in BC are based on autophagy inhibition. In conclusion, our research demonstrated that CQ and HCQ regulated cell motility in BC through MMP‐2 downregulation by targeting autophagy functions, providing a novel therapeutic strategy for BC treatment.
Speaking of Transition
Authors: Jonker Jan , Faber Niels
Published: July 2021

We are confronted with increasingly pressing questions about economic and social transition. Things have to change, but how? We believe that this change is concerned with three closely related challenges, which we call the triple transition—climate, energy, and circularity. These challenges combined result in a call for radical and major changes in the configuration of our economies and for the reconsideration and redesign of our systems. The fact remains that we live in organized societies and economies in which together we need to shape these transitions. Central to this book stands the premise that transition requires new forms of value creation materialized in the new generation of sustainable and circular business models. To make this possible the Business Model Template (BMT) was developed. The purpose of this chapter is to introduce you to the structure and style of this book and how the BMT is presented in the various chapters.
External Test
Authors: Jonker Jan , Faber Niels
Published: July 2021

The external test is the tenth and final building block of the first and second stage of the Business Model Template (BMT). You will test the viability of the business model concept you have developed so far. You can test your business model idea against all kinds of criteria. If you do not have much time, perform your check on the basis of the very concise set of seven questions we provide. But we also provide many other tools in this chapter. Please bear in mind that you must be well-prepared when looking for feedback. Look for people you know or hope will respond critically and constructively. Going through the External Test steps may mean that you need to partially adjust some elements of your business model before you move on. So be it. Remember that every version of your business model in this stage is a beta version and that feedback will help to make it better.
The Dream
Authors: Jonker Jan , Faber Niels
Published: July 2021

Looking for your Dream provides a second tool to help you build your business model in this first stage of the Business Model Template (BMT). You have previously indicated which major social and/or ecological issues you want to solve. Now you will determine what the result of that solution could be. Look for a solution that goes beyond just tackling one issue. The Dream building block demands thinking big: it is a Big, Hairy, Audacious Goal (BHAG) on which you are going to work. How and why will your business model idea really make a difference? In order to not get lost in thinking about dreams, you could make use of various tools such as scenarios, metaphors or framing, all of which are addressed in this chapter. Putting all the steps in this chapter together, you will have dreamed up something big that you want to go for.
The Value Proposition
Authors: Jonker Jan , Faber Niels
Published: July 2021

A business model is a description of how value creation is organized, underpinned by a value proposition. Such a proposition solves a problem or appeals to new, often yet undiscovered needs. Value creation has several facets. This building block offers a framework of five positions of value creation from which to choose and links it to strategies you can use. This in turn is then linked to the possibility of creating change with your business model-to-be. The more precisely you align the nature of those values and the change you would like to create, the better you will be able to design an appropriate (organizational) logic at a later stage. Formulating a clear and compelling value proposition is crucial in the development of a business model. It gives direction to the strategy, to the stakeholders with whom you could take these steps, and to what impact you expect to realize.
Parties Involved
Authors: Jonker Jan , Faber Niels
Published: July 2021

The central question in this building block of the Business Model Template (BMT) is identifying what stakeholders and other parties are pivotal for your success. Here you make an overview of them, not only determining who they are but also what interests they have in relation to your business model. Numerous tools have been developed to identify stakeholders. We will provide you with various tools to make a balanced identification. Defining the interests, influence and interrelationships between the stakeholders in your network helps to determine the connections that must be reinforced or made in order for your business model to function. In addition it helps in understanding who can play a crucial role in helping to create a fit between your business model and its environment. Finally, reflection on the key stakeholders and their roles is vital because of the input for the choice of strategy underpinning your business model.
Core Activities
Authors: Jonker Jan , Faber Niels
Published: July 2021

In this chapter, the central question is which core activities you will undertake in order to achieve your goal, organizing your value proposition with success. Because you are working towards a specific goal, and with selected strategies, it is useful to state which (core) activities are necessary to realize your sustainable business model. The idea of a core activity is that a specific part of the organizational activities can be seen as the speciality of a company, a network, or a community: it tells what they are really good at. Core activities should contribute to operationalizing the chosen strategy, thus contributing to the realization of the overall goal, coherent with the value proposition. We offer a core activities framework based on the conventional sustainability trio: reduce, reuse, recycle. This has evolved over the years into a whole family—commonly referred to as the RE-strategies and presented here as the 13 REs.
„Der Andere“ und zugleich „der Gleiche“ sein: Vom Umgang männlicher Kinderbetreuer mit Identitätsdissonanz
Authors: Nentwich Julia C. , Tennhoff Wiebke
Published: July 2021

Männer in der Kita sehen sich mit widersprüchlichen „Anrufungen“ konfrontiert. Zum einen müssen sie Erwartungen an die Männlichkeit ihrer Person gerecht werden, zum anderen aber auch als „Gleiche“ handeln, wollen sie das weiblich konnotierte Ideal der guten Kinderbetreuerin erfüllen. Mit der entstehenden Identitätsdissonanz umgehen zu können wird zu einer grundlegenden Anforderung an Männer in einem Frauenberuf. Mit einer diskurspsychologischen Analyse arbeiten wir insgesamt sechs diskursive Praktiken heraus, mittels derer es den zehn von uns interviewten männlichen Kinderbetreuern gelingt, im Interview trotz erlebter Identitätsdissonanz verschiedene legitime Subjektpositionen zu etablieren.
(Un)doing gender empirisch: Konzeptionelle, methodische und praktische Schlussfolgerungen
Authors: Nentwich Julia C. , Vogt Franziska
Published: July 2021

Im Forschungsprojekt „(Un)doing gender in der Kita“ haben wir vielfältige theoretische Konzeptionen von doing und undoing gender empirisch untersucht. Im folgenden Kapitel stellen wir die hierfür entwickelte Methodologie des Explizierens, Reflektierens und Kontrastierens sowie den Zugang einer multimethodischen und mehrperspektivischen Ethnografie dar. Die so erzielten Ergebnisse sind auch für die Praxis relevant. Führung und Zusammenarbeit, die Inklusion von Männern in das Team wie auch eine geschlechtergerechte Pädagogik profitieren von im Rahmen von Organisationsentwicklungsprozessen gemachten Reflexionen.
Exact-WKB, complete resurgent structure, and mixed anomaly in quantum mechanics on S1
Authors: Sueishi Naohisa , Kamata Syo , Misumi Tatsuhiro , Ünsal Mithat
Published: July 2021

Abstract

We investigate the exact-WKB analysis for quantum mechanics in a periodic potential, with N minima on S1. We describe the Stokes graphs of a general potential problem as a network of Airy-type or degenerate Weber-type building blocks, and provide a dictionary between the two. The two formulations are equivalent, but with their own pros and cons. Exact-WKB produces the quantization condition consistent with the known conjectures and mixed anomaly. The quantization condition for the case of N-minima on the circle factorizes over the Hilbert sub-spaces labeled by discrete theta angle (or Bloch momenta), and is consistent with ’t Hooft anomaly for even N and global inconsistency for odd N. By using Delabaere-Dillinger-Pham formula, we prove that the resurgent structure is closed in these Hilbert subspaces, built on discrete theta vacua, and by a transformation, this implies that fixed topological sectors (columns of resurgence triangle) are also closed under resurgence.
K → μ+μ− as a clean probe of short-distance physics
Authors: Dery Avital , Ghosh Mitrajyoti , Grossman Yuval , Schacht Stefan
Published: July 2021

Abstract

TheK→μ+μ−decay is often considered to be uninformative of fundamental theory parameters since the decay is polluted by long-distance hadronic effects. We demonstrate that, using very mild assumptions and utilizing time-dependent interference effects, ℬ(KS→μ+μ−)ℓ=0can be experimentally determined without the need to separate theℓ= 0 andℓ= 1 final states. This quantity is very clean theoretically and can be used to test the Standard Model. In particular, it can be used to extract the CKM matrix element combination$$ \mid {V}_{ts}{V}_{td}\sin \left(\beta +{\beta}_s\right)\mid \approx \mid {A}^2{\lambda}^5\overline{\eta}\mid $$∣VtsVtdsinβ+βs∣≈∣A2λ5η¯∣with hadronic uncertainties below 1%.
History and evolution of the afroalpine flora: in the footsteps of Olov Hedberg
Authors: Brochmann Christian , Gizaw Abel , Chala Desalegn , Kandziora Martha , Eilu Gerald , Popp Magnus , Pirie Michael D. , Gehrke Berit
Published: July 2021

The monumental work of Olov Hedberg provided deep insights into the spectacular and fragmented tropical alpine flora of the African sky islands. Here we review recent molecular and niche modelling studies and re-examine Hedberg’s hypotheses and conclusions. Colonisation started when mountain uplift established the harsh diurnal climate with nightly frosts, accelerated throughout the last 5 Myr (Plio-Pleistocene), and resulted in a flora rich in local endemics. Recruitment was dominated by long-distance dispersals (LDDs) from seasonally cold, remote areas, mainly in Eurasia. Colonisation was only rarely followed by substantial diversification. Instead, most of the larger genera and even species colonised the afroalpine habitat multiple times independently. Conspicuous parallel evolution occurred among mountains, e.g., of gigantism inLobeliaandDendrosenecioand dwarf shrubs inAlchemilla. Although the alpine habitat was ~ 8 times larger and the treeline was ~ 1000 m lower than today during the Last Glacial Maximum, genetic data suggest that the flora was shaped by strong intermountain isolation interrupted by rare LDDs rather than ecological connectivity. The new evidence points to a much younger and more dynamic island scenario than envisioned by Hedberg: the afroalpine flora is unsaturated and fragile, it was repeatedly disrupted by the Pleistocene climate oscillations, and it harbours taxonomic and genetic diversity that is unique but severely depauperated by frequent bottlenecks and cycles of colonisation, extinction, and recolonisation. The level of intrapopulation genetic variation is alarmingly low, and many afroalpine species may be vulnerable to extinction because of climate warming and increasing human impact.
Long-term sensibility outcomes of secondary digital nerve reconstruction with sural nerve autografts: a retrospective study
Authors: Dębski Tomasz , Złotorowicz Marcin , Noszczyk Bartłomiej Henryk
Published: July 2021

Background

Recovery of sensibility after digital nerve injury is crucial for restoring normal hand function. We evaluated long-term outcomes of digital nerve reconstruction with autografts.

Methods

This retrospective study included patients who underwent secondary reconstruction of digital nerves with nerve autografting. Recovery of sensibility was evaluated based on the following: patient self-assessment, two-point discrimination (2PD), and a total sensation score (sum of proprioception, temperature sensation, and sharp/dull discrimination). Mixed models regression was used to study predictors of sensibility outcomes. The predictors analyzed were age, sex, smoking status, number of fingers involved in a patient (as a measure of injury severity), time to reconstruction, and time to follow-up.

Results

In 61 patients, 174 digital nerves in 126 fingers were reconstructed after an average of 33.1 weeks from injury. The mean follow-up was 6.4 years from reconstruction. The mean graft length was 3.6 cm. Self-rated sensibility in the affected area was very good in 13% of patients, good in 33%, satisfactory in 40%, and poor in 24%. 2PD at 6 mm was present in 17% of patients, at 10 mm in 12%, and at 15 mm in 18% (mean 2PD was 10.8). Proprioception was preserved in 107 (85%) fingers, sensation of temperature was preserved in 99 (75%) of fingers, and sharp/dull discrimination in 88 (70%) fingers. Time from injury to reconstruction was the only significant predictor of the total sensation score.

Conclusion

Our data indicate that earlier reconstruction is associated with a favorable outcome.
Reversible parallel communicating finite automata systems
Authors: Bordihn Henning , Vaszil György
Published: July 2021

We study the concept of reversibility in connection with parallel communicating systems of finite automata (PCFA in short). We define the notion of reversibility in the case of PCFA (also covering the non-deterministic case) and discuss the relationship of the reversibility of the systems and the reversibility of its components. We show that a system can be reversible with non-reversible components, and the other way around, the reversibility of the components does not necessarily imply the reversibility of the system as a whole. We also investigate the computational power of deterministic centralized reversible PCFA. We show that these very simple types of PCFA (returning or non-returning) can recognize regular languages which cannot be accepted by reversible (deterministic) finite automata, and that they can even accept languages that are not context-free. We also separate the deterministic and non-deterministic variants in the case of systems with non-returning communication. We show that there are languages accepted by non-deterministic centralized PCFA, which cannot be recognized by any deterministic variant of the same type.
Natural language guided object retrieval in images
Authors: Ostovar Ahmad , Bensch Suna , Hellström Thomas
Published: July 2021

The ability to understand the surrounding environment and being able to communicate with interacting humans are important functionalities for many automated systems where visual input (e.g., images, video) and natural language input (speech or text) have to be related to each other. Possible applications are automatic image caption generation, interactive surveillance systems, or human robot interaction. In this paper, we propose algorithms for automatic responses to natural language queries about an image. Our approach uses a predefined neural net for detection of bounding boxes and objects in images, spatial relations between bounding boxes are modeled with a neural net, the queries are analyzed with a syntactic parser, and algorithms to map natural language to properties in the images are introduced. The algorithms make use of semantic similarity and antonyms. We evaluate the performance of our approach with test users assessing the quality of our system’s generated answers.
Placebo and Side Effects Confound Clinical Trials on New Antitussives
Authors: Eccles Ronald
Published: July 2021

This review discusses how the placebo effect related to treatment side effects may confound clinical trials on antitussives and specifically looks at the implications for trials on ATP antagonists. These new antitussives have distinctive side effects on the sensation of taste, and investigators have expressed concerns that this may unblind the clinical trials. Blinding is an essential component of trial design, but the degree of blinding in trials is rarely assessed. The assumptions of additivity and balance in clinical trials are discussed as important factors that allow assessment of the pharmacological activity of an antitussive. How side effects unbalance a clinical trial by amplifying the placebo effect of active treatments is discussed. The point is made that unblinding of trials invalidates any assessment of efficacy but that there is little interest or discussion about this fundamental aspect of trials. Proposals are discussed which may improve the blinding of trials and control placebo effects by changes to participant information, trial design, patient selection and use of active placebos. The issue of unblinding of clinical trials is not a new issue, but if real progress is to be made in developing new antitussives, then it is an issue that needs to be urgently addressed.
Simultaneous pancreas and kidney transplantation for end-stage kidney disease patients with type 2 diabetes mellitus: a systematic review and meta-analysis
Authors: Cao Yu , Liu Xiaoli , Lan Xiangyu , Ni Kaiwen , Li Lin , Fu Yingxin
Published: July 2021

Purpose

The indications for patients with type 2 diabetes mellitus (T2DM) combined with end-stage kidney disease (ESKD) undertaking simultaneous pancreas and kidney transplantation (SPK) remain an unresolved issue. This study aimed to systematically review the survival outcomes of SPK among T2DM-ESKD patients.

Methods

Online databases including PubMed, MEDLINE, EMBASE, and the CENTRAL Library, CNKI, Chinese Biomedical Literature Database, and Wan-Fang database were used to locate the studies of ESKD patients with T2DM undertaking SPK up to May 2021. A third reviewer was consulted if there were disagreements. Data were analyzed with STATA (15.0).

Results

Nine cohort studies were identified. The pooled 1-year, 3-year, and 5-year patient survival rates of patients with T2DM and ESKD after SPK were 98%, 95%, and 91% respectively. Comparing the treatment effect of SPK between type 1 diabetes mellitus (T1DM) and T2DM, the survival estimates were comparable. For T2DM patients, SPK had a survival advantage compared with KTA.

Conclusions

The synthesized clinical outcomes of T2DM patients with ESKD after SPK were relatively better than KTA, but a subset of T2DM-ESKD patients who would benefit the most from SPK was to be defined.

PROSPERO registration number

CRD42019118321. Date of registration: 14 Jan 2019 (retrospectively registered)
Oral health-related quality of life in patients with early rheumatoid arthritis is associated with periodontal inflammation and painful temporomandibular disorders: a cross-sectional study
Authors: Kroese Johanna M. , Volgenant Catherine M. C. , van Schaardenburg Dirkjan , van Boheemen Laurette , van Selms Maurits K. A. , Visscher Corine M. , Crielaard Wim , Loos Bruno G. , Lobbezoo Frank
Published: July 2021

Objectives

To evaluate oral health-related quality of life (OHRQoL) in early rheumatoid arthritis (ERA) patients and individuals at risk of rheumatoid arthritis (RA) compared to healthy controls, and to explore possible associated factors.

Materials and methods

Fifty ERA patients, 50 at-risk individuals, and 50 age and gender matched healthy controls were recruited. OHRQoL (Oral Health Impact Profile-14 (OHIP-14)); number of decayed, missing, and filled teeth (DMFT); denture use; periodontal inflamed surface area (PISA); xerostomia (xerostomia inventory (XI)); and possible TMD (-pain) diagnoses were recorded. The groups were compared on these variables. Subsequently, backward multiple regression analyses were performed for the ERA and at-risk groups, with OHRQoL as the dependent variable and gender, age, DMFT, denture use, PISA, XI, non-painful TMD, and TMD pain as independent variables.

Results

At-risk individuals had higher XI scores (U = 789.5, z = -3.181, p = 0.001, r = -0.32) and higher prevalence of TMD pain (p = 0.046, OR = 4.57; 95% CI 0.92–22.73) than healthy controls and higher OHIP-14 scores than the ERA group (U = 894.5, z = -2.418, p = 0.016, r = -0.24), while no difference in OHIP-14 was found between the control group and both other groups. For ERA patients, OHRQoL was associated with PISA and TMD pain (R2 = 0.498, p < 0.001). For at-risk individuals, OHRQoL was associated with XI score (R2 = 0.410, p < 0.001).

Conclusions

Alertness of health professionals to TMD pain and periodontal inflammation in ERA patients and to xerostomia and TMD pain in at-risk individuals is recommended.

Clinical relevance

The results of this study address orofacial aspects that require attention of health professionals in the timeframe around RA onset.

Trial registration: Dutch National Trial Register (NTR, NTR6362)