bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using economics in conservation practice: Insights from a global environmental organization
Authors: Springer Nathaniel , Musengezi Jessica , Hunter Eric O. , Kaiser Charlotte , Shyamsundar Priya 
Published: February 2021

AbstractIdentifying and implementing successful strategies to conserve nature is a central goal of environmental practitioners. Conservation tools increasingly have an economic rationale to them, expanding the array of means available to trigger environmental actions. Missing is a comprehensive list of economic and financial instruments for conservation practitioners that highlights their current applicability, context, and relative success. To address this gap, we assembled such a list and surveyed units of The Nature Conservancy, a global conservation organization, to understand how these instruments are being used in varied contexts. We find that the majority of respondents have used economic or financial instruments, with the most common types being markets and price premiums, investments and funds, and payments for ecosystem services. A variety of factors influence the choice of instruments, including stakeholder interests, experience, and replication possibilities. Institutional constraints act as a significant barrier to implementation. These findings identify and offer insights on an expanded set of instruments that the non‐profit conservation sector can use, replicate, and develop to meet conservation goals.
Benefits, safety and side effects of tumescent local anesthesia in dermatologic surgery in infants
Authors: Roerden Alisa , Neunhoeffer Felix , Götz Angelika , Häfner Hans‐Martin , Kofler Lukas 
Published: February 2021

SummaryTumescent local anesthesia (TLA) plays an important role in dermatosurgical procedures. TLA has several benefits such as long‐lasting anesthesia, reduced bleeding during surgery and the avoidance of general anesthesia‐associated complications. Convenience and a favorable risk profile along with a broad spectrum of indications are further reasons why TLA is increasingly applied in infants as well. There are not only a variety of indications for surgical excisions in infancy, such as congenital nevi, but also substantial benefits when performing these excisions at an early age. These include the smaller size of the lesions as well as the unproblematic wound healing and tissue regeneration in infancy. Nevertheless, several aspects need to be considered when applying TLA in infants including dosing, altered plasma protein binding and the need for adequate and long‐lasting pain control.
Importance of diagnostics and risk of secondary malignancies in primary cutaneous lymphomas
Authors: Scheu Alexander , Schnabl Saskia Maria , Steiner Daniel Patric , Fend Falko , Berneburg Mark , Yazdi Amir Sadegh 
Published: February 2021

SummaryBackground and ObjectivesPrimary cutaneous lymphomas (PCL) often strongly differ in clinical behavior and prognosis from systemic lymphomas of the same histopathologic type. The aim of the study was to investigate the distribution of PCL subtypes, the average time from disease manifestation to diagnosis, the importance of diagnostic procedures, the occurrence of secondary malignancies and the different treatment modalities.Patients and MethodsRetrospective analysis of 152 patients with PCL examined at the Department of Dermatology of the University Hospital Tübingen from 2010–2012.Results105 patients with CTCL (69.1 %) and 47 patients with CBCL (30.9 %) were included. The average time from disease manifestation to diagnosis was four years. The most common diagnosed lymphoma was mycosis fungoides (MF) (47.4 %). First‐line therapies here include phototherapy only (psoralen‐UV‐A [PUVA], n = 48; UVB 311 nm, n = 7) or combination therapies primarily phototherapy with systemic retinoids (n = 18). Most frequent second‐line therapy was interferon (INF)‐α plus PUVA (n = 15). The outcome was favorable (45.2 % remission, 28.6 % stable disease, 22.6 % progressive disease). Malignant comorbidities were observed more frequently compared to a healthy control group.ConclusionsThe diagnosis of lymphoma often takes several years. The value of staging procedures is still low and the treatment modalities for MF in earlier stages are mainly based on phototherapy.
Pluripotent stem cells in the research for extraembryonic cell differentiation
Authors: Toyooka Yayoi 
Published: February 2021

AbstractMouse embryonic stem cells (mESCs) are pluripotent stem cell populations derived from the preimplantation embryo and are used to study the differentiation of many types of somatic and germ cells in developing embryos. They are also used to study cell lineages of extraembryonic tissues, such as the trophectoderm (TE) and the primitive endoderm (PrE). mESC cultures are suitable systems for reproducing cellular and molecular events occurring during the differentiation of these cell types, such as changes in gene expression patterns, signaling events, and genome rearrangements although the consistency between the results obtained using mESCs and those of in vivo studies on embryos should be carefully taken into account. Since TE and PrE cells can be induced from mESCs in vitro, mESC cultures are useful systems to study differentiation of these cell lineages during development, if used appropriately. In addition, human pluripotent stem cells (hPSCs), such as human embryonic stem cells (hESCs) and human‐induced pluripotent stem cells (hiPSCs), are capable of generating extraembryonic lineages in vitro and are promising tools to study the differentiation of these lineages in the human embryo.
Evaluation of left ventricular functions by speckle‐tracking echocardiography in coarctation patients
Authors: Demircan Tülay , Kizilca Özgür , Yilmaz Nuh , Zihni Cüneyt , Kir Mustafa , Ünal Nurettin 
Published: February 2021

AbstractBackground/AimTwo‐dimensional speckle‐tracking echocardiography (2D‐STE) is a novel method that allows the assessment of regional myocardial function. The aim of our study was to use 2D‐STE to assess left ventricular deformation in patients with coarctation of the aorta (CoA).MethodsIn this prospective study, patients with CoA (n = 42) and healthy controls (n = 39) were recruited. Children with CoA who visited the outpatient clinic between 2013 and 2014 were included. The data were compared with those obtained from the sex‐ and age‐matched controls.ResultsThe mean age of the patients was 5.8 ± 4.5 years. Global longitudinal strain based on all three apical views and total global strain values did not appear to be different between the patient and the control groups (P = .59, P = .51, P = .15, P = .38). Hypertension was detected in 14 (33.3%) patients with CoA. There were significant differences between the global longitudinal strain values of the normotensive CoA subgroup and the hypertensive CoA subgroup (P < .05).ConclusionsIn our study, we found that 2D‐STE total strain analysis of patients with CoA was not different from comparative healthy controls. However, we determined that 2D‐STE parameters were lower in the hypertensive CoA subgroup compared to the normotensive CoA subgroup.
Characteristics of pediatric maxillofacial fractures in Kuwait: A single‐center retrospective study
Authors: AlAli Ahmad M. , Ibrahim Hussein H. H. , Algharib Abdullah , Alsaad Fahad , Rajab Bashar 
Published: February 2021

AbstractBackgroundPediatric maxillofacial fractures always present a challenge due to the unique nature of the facial skeleton anatomy and development. The aim of this study was to investigate the incidence, etiology, site of fracture, and management modalities of pediatric maxillofacial fractures in Kuwait.MethodsA retrospective cross‐sectional study was conducted. The records of all pediatric patients who were diagnosed with maxillofacial fractures and admitted to one of the major hospitals in Kuwait between January 2007 and March 2020 were reviewed.ResultsA total of 186 patients aged between 0 and 13 years old were included. An average of 13 patients was seen each year between 2007 and 2020. The leading cause of the pediatric maxillofacial trauma was road traffic accidents (RTA) that accounted for 38.2% of the patients followed by 22% falls from height (FFH). Male patients were more affected than females, with a ratio of 2.3:1. More than half of the children had mid‐face fractures, of which 57% were in multiple sites. Conservative management was the main approach for 52.2% of the patients.ConclusionsPediatric maxillofacial fractures were mainly attributed to road traffic accidents in Kuwait. Mid‐face bone fractures were reported more than mandibular fractures and were mostly managed conservatively.
The ups and downs of alkyl‐carbamates in epilepsy therapy: How does cenobamate differ?
Authors: Löscher Wolfgang , Sills Graeme J. , White H. Steve 
Published: February 2021

AbstractSince 1955, several alkyl‐carbamates have been developed for the treatment of anxiety and epilepsy, including meprobamate, flupirtine, felbamate, retigabine, carisbamate, and cenobamate. They have each enjoyed varying levels of success as antiseizure drugs; however, they have all been plagued by the emergence of serious and sometimes life‐threatening adverse events. In this review, we compare and contrast their predominant molecular mechanisms of action, their antiseizure profile, and where possible, their clinical efficacy. The preclinical, clinical, and mechanistic profile of the prototypical γ‐aminobutyric acidergic (GABAergic) modulator phenobarbital is included for comparison. Like phenobarbital, all of the clinically approved alkyl‐carbamates share an ability to enhance inhibitory neurotransmission through modulation of the GABAA receptor, although the specific mechanism of interaction differs among the different drugs discussed. In addition, several alkyl‐carbamates have been shown to interact with voltage‐gated ion channels. Flupirtine and retigabine share an ability to activate K+ currents mediated by KCNQ (Kv7) K+ channels, and felbamate, carisbamate, and cenobamate have been shown to block Na+ channels. In contrast to other alkyl‐carbamates, cenobamate seems to be unique in its ability to preferentially attenuate the persistent rather than transient Na+ current. Results from recent randomized controlled clinical trials with cenobamate suggest that this newest antiseizure alkyl‐carbamate possesses a degree of efficacy not witnessed since felbamate was approved in 1993. Given that ceno‐bamate's mechanistic profile is unique among the alkyl‐carbamates, it is not clear whether this impressive efficacy reflects an as yet undescribed mechanism of action or whether it possesses a unique synergy between its actions at the GABAA receptor and on persistent Na+ currents. The high efficacy of cenobamate is, however, tempered by the risk of serious rash and low tolerability at higher doses, meaning that further safety studies and clinical experience are needed to determine the true clinical value of cenobamate.
Long‐term chemogenetic suppression of seizures in a multifocal rat model of temporal lobe epilepsy
Authors: Goossens Marie‐Gabrielle , Boon Paul , Wadman Wytse , Van den Haute Chris , Baekelandt Veerle , Verstraete Alain G. , Vonck Kristl , Larsen Lars E. , Sprengers Mathieu , Carrette Evelien , Desloovere Jana , Meurs Alfred , Delbeke Jean , Vanhove Christian , Raedt Robrecht 
Published: February 2021

SummaryObjectiveOne third of epilepsy patients do not become seizure‐free using conventional medication. Therefore, there is a need for alternative treatments. Preclinical research using designer receptors exclusively activated by designer drugs (DREADDs) has demonstrated initial success in suppressing epileptic activity. Here, we evaluated whether long‐term chemogenetic seizure suppression could be obtained in the intraperitoneal kainic acid rat model of temporal lobe epilepsy, when DREADDs were selectively expressed in excitatory hippocampal neurons.MethodsEpileptic male Sprague Dawley rats received unilateral hippocampal injections of adeno‐associated viral vector encoding the inhibitory DREADD hM4D(Gi), preceded by a cell‐specific promotor targeting excitatory neurons. The effect of clozapine‐mediated DREADD activation on dentate gyrus evoked potentials and spontaneous electrographic seizures was evaluated. Animals were systemically treated with single (.1 mg/kg/24 h) or repeated (.1 mg/kg/6 h) injections of clozapine. In addition, long‐term continuous release of clozapine and olanzapine (2.8 mg/kg/7 days) using implantable minipumps was evaluated. All treatments were administered during the chronic epileptic phase and between 1.5 and 13.5 months after viral transduction.ResultsIn the DREADD group, dentate gyrus evoked potentials were inhibited after clozapine treatment. Only in DREADD‐expressing animals, clozapine reduced seizure frequency during the first 6 h postinjection. When administered repeatedly, seizures were suppressed during the entire day. Long‐term treatment with clozapine and olanzapine both resulted in significant seizure‐suppressing effects for multiple days. Histological analysis revealed DREADD expression in both hippocampi and some cortical regions. However, lesions were also detected at the site of vector injection.SignificanceThis study shows that inhibition of the hippocampus using chemogenetics results in potent seizure‐suppressing effects in the intraperitoneal kainic acid rat model, even 1 year after viral transduction. Despite a need for further optimization, chemogenetic neuromodulation represents a promising treatment prospect for temporal lobe epilepsy.
The HSP90 inhibitor RGRN‐305 exhibits strong immunomodulatory effects in human keratinocytes
Authors: Hansen Rikke S , Thuesen Katrine K. H. , Bregnhøj Anne , Moldovan Liviu I. , Kristensen Lasse S. , Grek Christina L. , Ghatnekar Gautam S. , Iversen Lars , Johansen Claus 
Published: February 2021

AbstractKeratinocytes are the key cellular target for IL‐17A‐mediated effects in psoriasis and HSP90 is important for IL‐17A‐mediated signalling. RGRN‐305 is a novel HSP90 inhibitor reported to reduce psoriatic phenotypes in preclinical animal models. The aim of this study was to investigate the effect of RGRN‐305 on a psoriasis‐like inflammatory response in human keratinocytes in vitro. Using RT‐qPCR, we demonstrated a significantly increased expression of the HSP90 isoforms HSP90AB1, HSP90B1 and TRAP1 in lesional compared with non‐lesional psoriatic skin. In a psoriasis‐like setting where keratinocytes were stimulated with TNFα and/or IL‐17A, we analysed the mRNA expression using the NanoString nCounter technology and demonstrated that the HSP90 inhibitor RGRN‐305 significantly reduced the IL‐17A‐ and TNFα‐induced gene expression of a number of proinflammatory genes, including the psoriasis‐associated genes CCL20, NFKBIZ, IL36G and IL23A. In agreement with the mRNA data, the protein level of CCL20, IκBζ and IL‐36γ were inhibited by RGRN‐305 as demonstrated by western blotting and ELISA. Interestingly, when keratinocytes were stimulated with a TLR3 agonist, RGRN‐305 also demonstrated potent immunomodulatory effects, significantly inhibiting poly(I:C)‐induced expression of the proinflammatory genes TNFα, IL1B, IL6 and IL23A. Taken together, our data support a role for HSP90 not only in the pathogenesis of psoriasis, but also in broader immune responses. Therefore, HSP90 provides an attractive target for the treatment of psoriasis and other diseases where the innate immune system plays an important role.
Efficacy of PARP inhibition combined with EZH2 inhibition depends on BRCA mutation status and microenvironment in breast cancer
Authors: Chen Mei‐Kuang 
Published: February 2021

The efficacy of the combination of a PARP inhibitor (PARPi) and an EZH2 inhibitor has been investigated in breast cancer cells with either BRCA1 mutation or BRCA2 mutation. However, earlier studies focused on the efficacy of this combination against BRCA‐mutated but not BRCA‐proficient breast cancer. Yang et al. observed that PARP1 depletion combined with EZH2 depletion via PRC2 depletion did not affect the growth of BRCA1/2 wild‐type breast cancer cells in vitro. Moreover, Yang et al. reported that this combination stimulated synthetic viability of BRCA1/2‐proficient breast cancer cells in vivo by regulating the tumor microenvironment to induce angiogenesis and differentiation of M2‐type macrophages. The findings of Yang et al. provided evidence that both in vitro and animal models should be employed in the studies of PARPi combination therapies in order to involve the alteration of the tumor microenvironment in these investigations. These studies of PARP inhibition combined with EZH2 inhibition in breast cancer showed that this combination may benefit breast cancer patients carrying BRCA1‐mutated tumor, but the combination may also enhance recurrence of BRCA2‐mutated tumor and may even promote BRCA‐proficient cancer cell survival. Therefore, BRCA1 mutation status should be used to select breast cancer patients for PARPi and EZH2 inhibitor combination treatment in clinical trials in the future.
Differential lysine‐mediated allosteric regulation of plant dihydrodipicolinate synthase isoforms
Authors: Hall Cody J. , Lee Mihwa , Boarder Matthew P. , Mangion Alexandra M. , Gendall Anthony R. , Panjikar Santosh , Perugini Matthew A. , Soares da Costa Tatiana P. 
Published: February 2021

Lysine biosynthesis in plants occurs via the diaminopimelate pathway. The first committed and rate‐limiting step of this pathway is catalysed by dihydrodipicolinate synthase (DHDPS), which is allosterically regulated by the end product,l‐lysine (lysine). Given that lysine is a common nutritionally limiting amino acid in cereal crops, there has been much interest in probing the regulation of DHDPS. Interestingly, knockouts inArabidopsis thalianaof each isoform (AtDHDPS1 and AtDHDPS2) result in different phenotypes, despite the enzymes sharing > 85% protein sequence identity. Accordingly, in this study, we compared the catalytic activity, lysine‐mediated inhibition and structures of bothA. thalianaDHDPS isoforms. We found that although the recombinantly produced enzymes have similar kinetic properties, AtDHDPS1 is 10‐fold more sensitive to lysine. We subsequently used X‐ray crystallography to probe for structural differences between the apo‐ and lysine‐bound isoforms that could account for the differential allosteric inhibition. Despite no significant changes in the overall structures of the active or allosteric sites, we noted differences in the rotamer conformation of a key allosteric site residue (Trp116) and proposed that this could result in differences in lysine dissociation. Microscale thermophoresis studies supported our hypothesis, with AtDHDPS1 having a ~ 6‐fold tighter lysine dissociation constant compared to AtDHDPS2, which agrees with the lower half minimal inhibitory concentration for lysine observed. Thus, we highlight that subtle differences in protein structures, which could not have been predicted from the primary sequences, can have profound effects on the allostery of a key enzyme involved in lysine biosynthesis in plants.DatabasesStructures described are available in the Protein Data Bank under the accession numbers6VVHand6VVI.
Was historical cisco Coregonus artedi yield consistent with contemporary recruitment and abundance in Lake Superior?
Authors: Rook Benjamin J. , Hansen Michael J. , Goldsworthy Cory A. , Ray Bradley A. , Gorman Owen T. , Yule Daniel L. , Bronte Charles R. 
Published: February 2021

AbstractHistorically, cisco Coregonus artedi Lesueur was the predominant prey fish and target of commercial fisheries throughout Lake Superior, but most spawning stocks collapsed by the mid‐1900s. Stocks partially recovered by the early 1990s, but contemporary abundance is considered to be below historical levels and driven by intermittent recruitment. Stochastic, age‐structured simulation models were used to determine whether historical (pre‐1955) cisco yield in Lake Superior was consistent with contemporary (1992–2015) abundance, life‐history characteristics and recruitment dynamics. When compared to contemporary stocks, the findings suggest historical stocks had: (1) similar recruits per spawner at low spawning stock sizes; (2) lower rates of compensatory density dependence; (3) similar or lower recruitment variation depending on the area and (4) higher median adult and age‐1 density. These findings are consistent with the hypothesis that eutrophication during the historical period supported greater recruitment and adult abundance and that re‐oligotrophication during the contemporary period may be limiting full recovery.
Urbanisation and eutrophication as drivers of morphological and physiological divergence among riverine fish populations
Authors: Côte Jessica , Morisseau Océane , Pilisi Camille , Veyssière Charlotte , Perrault Annie , Jezequel Céline , Loot Géraldine , Blanchet Simon , Jean Séverine , Jacquin Lisa 
Published: February 2021

Abstract

Freshwater ecosystems are highly impacted by human activities, but the effects of human‐induced perturbations on fish phenotypic divergence remain poorly understood, especially in riverine systems.

In this study, we tested the effects of urbanisation and eutrophication on several morphological and physiological traits in 17 gudgeon populations of Gobio occitaniae from South of France.

We first demonstrated that eutrophication gradient was associated with changes in morphology and energy reserves, while urbanisation was associated with changes in body condition. More specifically, fish from highly eutrophic sites had deeper bodies and larger jaws, and a higher lipid content in their muscles.

Urban fish had a higher body condition compared to their rural counterparts. The phenotypic divergence (Pst) among sites was significantly higher than the neutral genetic differentiation (Fst), suggesting that these morphological and physiological differences cannot be explained by neutral genetic drift alone.

This study thus suggests that eutrophication and urbanisation are major drivers of phenotypic divergence in riverine fish populations, and calls for further experimental studies investigating the ecological and evolutionary effects of human activities on riverine fish populations.