bluuebunny/crossref_metadata_2025 huggingface dataset:
Constitutive protein kinase G activation exacerbates stress‐induced cardiomyopathy
Authors: Schwaerzer Gerburg K. , Casteel Darren E. , Cividini Federico , Kalyanaraman Hema , Zhuang Shunhui , Gu Yusu , Dalton Nancy D. , Peterson Kirk L. , Dillmann Wolfgang H. , Boss Gerry R. , Pilz Renate B.
Published: May 2021

Background and Purpose

Heart failure is associated with high morbidity and mortality, and new therapeutic targets are needed. Preclinical data suggest that pharmacological activation of protein kinase G (PKG) can reduce maladaptive ventricular remodelling and cardiac dysfunction in the stressed heart. However, clinical trial results have been mixed and the effects of long‐term PKG activation in the heart are unknown.

Experimental Approach

We characterized the cardiac phenotype of mice carrying a heterozygous knock‐in mutation of PKG1 (Prkg1R177Q/+), which causes constitutive, cGMP‐independent activation of the kinase. We examined isolated cardiac myocytes and intact mice, the latter after stress induced by surgical transaortic constriction or angiotensin II (Ang II) infusion.

Key Results

Cardiac myocytes from Prkg1R177Q/+ mice showed altered phosphorylation of sarcomeric proteins and reduced contractility in response to electrical stimulation, compared to cells from wild type mice. Under basal conditions, young PKG1R177Q/+ mice exhibited no obvious cardiac abnormalities, but aging animals developed mild increases in cardiac fibrosis. In response to angiotensin II infusion or fixed pressure overload induced by transaortic constriction, young PKGR177Q/+ mice exhibited excessive hypertrophic remodelling with increased fibrosis and myocyte apoptosis, leading to increased left ventricular dilation and dysfunction compared to wild type litter mates.

Conclusion and Implications

Long‐term PKG1 activation in mice may be harmful to the heart, especially in the presence of pressure overload and neurohumoral stress.

LINKED ARTICLES

This article is part of a themed issue on cGMP Signalling in Cell Growth and Survival. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.11/issuetoc
Halokinetic modulation of sedimentary thickness and architecture: A numerical modelling approach
Authors: Cumberpatch Zoë A. , Finch Emma , Kane Ian A. , Pichel Leonardo M. , Jackson Christopher A.‐L. , Kilhams Ben A. , Hodgson David M. , Huuse Mads
Published: May 2021

Subsurface salt flow can deform overlying strata and influence contemporaneous sedimentary systems. Studying salt‐sediment interactions is challenging in the subsurface due to poor imaging adjacent to salt, and in the field due to the dissolution of halite. Discrete Element Modelling provides an efficient and inexpensive tool to model stratigraphy and deformation around salt structures, which is advantageous over other modelling techniques as it realistically recreates brittle processes such as faulting. Six 2D experiments were run representing 4.6 Myr to determine the effect of salt growth on syn‐kinematic stratigraphy. Halokinetic deformation of stratigraphic architecture was assessed by varying sediment input rates through time. Results show the realistic formation and evolution of salt‐related faults which define a zone of halokinetic influence ca. 3 times the width of the initial diapir. Outside of this, early diapiric and syn‐kinematic stratigraphy are undeformed. Within this zone, syn‐kinematic strata are initially isolated into primary salt withdrawal basins, onlapping and thinning towards the salt‐cored high. In most models, syn‐kinematic strata eventually thin across and cover the diapir roof. Thinning rates are up to six times greater within 350 m of the diapir, compared to further afield, and typically decrease upwards (with time) and laterally (with distance) from the diapir. Outputs are compared to a subsurface example from the Pierce field, UK North Sea, which highlights the importance of considering local fluctuations in diapir rise rate. These can create stratigraphic architectures that may erroneously be interpreted to represent increases/decreases in sedimentation rate. Exposed examples, such as the Bakio diapir, northern Spain, can be used to make inferences of the expected depositional facies, below model resolution. Our models aid the prediction of sedimentary unit thickness and thinning rates and can be used to test interpretations arising from incomplete or low‐resolution subsurface and outcrop data when building geological models for subsurface energy.
Substance P‐induced lung inflammation in mice is mast cell dependent
Authors: Wang Nan , Wang Jue , Zhang Yongjing , Hu Shiling , Zhang Tianxiao , Wu Yuanyuan , Sun Xiuzhen , Zhang Tao , Yang Shuanying , He Langchong
Published: May 2021

Background

Allergic asthma is a common inflammatory lung disease and a major health problem worldwide. Mast cells (MCs) play a key role in the early‐stage pathophysiology of allergic asthma. Substance P (SP) functions in neurogenic inflammation by activating MCs, and therefore, it may to participate in the occurrence and development of asthma.

Objective

We examined the relationship between SP and lung inflammation, and also whether SP can directly trigger asthma.

Methods

We measured the number of peripheral blood eosinophils, neutrophils and basophils and evaluated the levels of IgE and SP in blood samples of 86 individuals with allergic asthma. Serum IgE and SP levels were also determined in 29 healthy individuals. C57BL/6 mice were subjected to different doses of SP, and bronchoalveolar lavage fluid (BALF) was collected to count the inflammatory cells. Lung tissues were analysed using histopathological methods to evaluate lung peribronchial inflammation, fibrosis and glycogen deposition. Levels of IgE, interleukin (IL)‐1, IL‐2, IL‐4, IL‐5, IL‐13, IL‐17 and IFN‐γ were determined in mouse serum.

Results

Substance P levels were increased in the serum samples of patients with asthma. SP induced mouse lung peribronchial inflammation, fibrosis and glycogen deposition, with high levels of Th2‐related cytokines such as IL‐4, IL‐5 and IL‐13 observed in the BALF. Furthermore, low level of total IgE was noted in the serum, and SP had little effect on MC‐deficient kitW‐sh/W‐sh mice.

Conclusions & clinical relevance

Substance P levels increased significantly in serum of asthmatic patients and independently associated with the risk of asthma. Furthermore, SP induced Th2 lung inflammation in mice, which was dependent on MCs.
The prevalence of anti-neurofascin-155 antibodies in patients with neuromyelitis optica spectrum disorders
Authors: Chang Sheng-Hui , Wang Jing , Zhang Xu , Zhao Ning , Jia Kun , Yi Ming , Zhang Qiu-Xia , Zhai Hui , Li Xiao-Wen , Yang Chun-Sheng , Yang Li , Zhang Lin-Jie
Published: May 2021

Anti-neurofascin-155 (NF155) antibodies have been observed in two cases with neuromyelitis optica spectrum disorders (NMOSD). This study investigated the prevalence of anti-NF155 antibodies in patients with NMOSD and the clinical features of anti-NF155 antibody-positive patients. Sera from 129 patients with NMOSD were screened with anti-NF155 antibodies by cell-based assay (CBA) and re-examined using immunostaining of teased mouse sciatic nerve fibres. Fifty-six patients with multiple sclerosis (MS) and 50 healthy controls (HC) were also enrolled for detecting anti-NF155 antibodies. A total of 12.40% (16 of 129) of patients with NMOSD were positive for anti-NF155 antibodies confirmed by both CBA and immunostaining. Immunoglobulin (Ig) G1 was the predominant subclass. However, none of 56 MS patients or 50 HC were positive for anti-NF155 antibodies. Anti-NF155 antibody-positive NMOSD patients had a higher proportion of co-existing with autoimmune diseases (p < 0.001) and higher positive rates of serum non-organ-specific autoantibodies, including anti-SSA antibodies (p < 0.001), anti-SSB antibodies (p = 0.008), anti-Ro-52 antibodies (p < 0.001) and rheumatoid factor (p < 0.001). Five anti-NF155 antibody-positive NMOSD patients who took part in the nerve conduction study showed mildly abnormal results. Differences in some nerve conduction study parameters were observed between anti-NF155 antibody-positive and negative patients. Anti-NF155 antibodies occurred in a small proportion of NMOSD patients. Anti-NF155 antibody-positive NMOSD patients tended to co-exist with autoimmune diseases.
The importance of precision medicine in modern molecular oncology
Authors: Wang Yuanli , Zheng Dawu
Published: May 2021

With the rapid development of modern medical technology, information data modeling has been gradually applied to clinical diagnosis and treatment. Precision medicine is an important approach that focuses on individual patients in terms of their own characteristics, genomic information, proteomics and even social environments. Genome‐wide high‐throughput technologies, including DNA‐seq, RNA‐seq, exosome‐seq…, contribute enormous amounts of molecular data to aid in diagnosis and analysis. Here, we review the developmental history of different next‐generation sequencing platforms, introduce their applications in different tumor diagnosis and therapy, and further discuss the remaining challenges in precision medicine.
Where have all the young wolves gone? Traffic and cryptic mortality create a wolf population sink in Denmark and northernmost Germany
Authors: Sunde Peter , Collet Sebastian , Nowak Carsten , Thomsen Philip Francis , Hansen Michael Møller , Schulz Björn , Matzen Jens , Michler Frank‐Uwe , Vedel‐Smith Christina , Olsen Kent
Published: May 2021

Large carnivores are currently recolonizing Europe following legal protection, but increased mortality in landscapes highly impacted by humans may limit further population expansion. We analyzed mortality and disappearance rates of 35 wolves (of which three emigrated, nine died and 14 disappeared by 1 January 2020) by genetic monitoring in the heavily cultivated and densely populated Jutland peninsula (Denmark and Schleswig‐Holstein, Germany). Annual traffic kill rate estimates ranged from 0.37 (95% CI: 0.11–0.85) to 0.78 (0.51–0.96) in the German part, equivalent to 0.08 (0.02–0.29)–0.25 (0.13–0.46) for the entire region, in the absence of any registered Danish roadkills. In Denmark, annual mortality rate estimates ranged from 0.46 (0.29–0.67) to 0.52 (0.35–0.71), predominantly from cryptic mortality. Despite successful reproductions, we conclude the region is a wolf population sink, primarily driven by cryptic mortality, most likely illegal killing. We hypothesize that frequent encounters between wolves and wolf‐averse persecutors in cultivated landscapes may cause unsustainably high mortality rates despite the majority of hunters respecting protection laws.
Effects of water‐based Liuzijue exercise on peak exercise capacity, functional exercise capacity, and quality of life in people with COPD
Authors: Liu Xiaodan , Wu Weibing , Li Ning , Li Peijun , Wang Zhenwei , Shan Chunlei
Published: May 2021

Objectives

This study was conducted to investigate the effect of water‐based Liuzijue exercise on peak exercise capacity, functional exercise capacity, and quality of life in people with COPD.

Methods

The study included 50 participants randomly divided into three groups: a control group (CG = 17), a land‐based Liuzijue exercise group (LG = 17), and a water‐based Liuzijue exercise group (WG = 16). The LG and WG performed Liuzijue exercise in different environments, and the CG had no exercise intervention. All participants received prescribed medical treatment. Liuzijue exercise was performed according to the description of Health Qigong Liuzijue compiled by Chinese Health Qigong Association for 60 minutes, two times per week, for 12 weeks.

Results

After intervention, peak oxygen uptake and peak working rate were significantly improved in WG (P = .02). The results of the 6 minutes walking test (6MWT) and 30 seconds sit‐to‐stand test were significantly improved in both WG and LG (P < .05), and significant difference was found between WG and CG in 6MWT (P = .03). The St. George's Respiratory Questionnaire (SGRQ) activity score increased significantly in the CG (P = .03), while all domains of SGRQ significantly decreased in both training groups (P < .01). All SGRQ scores showed a significant difference between LG and CG (P < .05) and, except for the activity score, between WG and CG (P < .05).

Conclusions

Water‐based Liuzijue exercise can effectively improve peak exercise capacity, functional exercise capacity, and quality of life in people with COPD, especially with respect to increasing peak VO2 and 6MWD.
Folic acid supplementation rescues valproic acid‐induced developmental neurotoxicity and behavioral alterations in zebrafish embryos
Authors: Muhsen Maram , Youngs Jaclyn , Riu Anne , Gustafsson Jan‐Åke , Kondamadugu Vijay Sai , Garyfalidis Elefterios , Bondesson Maria
Published: May 2021

Objective

Fetal exposure to the anticonvulsant drug valproic acid (VPA), used to treat certain types of epilepsy, increases the risk for birth defects, including neural tube defects, as well as learning difficulties and behavioral problems. Here, we investigated neurotoxic effects of VPA exposure using zebrafish as a model organism. The capacity of folic acid (FA) supplementation to rescue the VPA‐induced neuronal and behavioral perturbations was also examined.

Methods

Zebrafish embryos of different transgenic lines with neuronal green fluorescent protein expression were exposed to increasing concentrations of VPA with or without FA supplementation. Fluorescence microscopy was used to visualize alterations in brain structures and neural progenitor cells, as well as motor neurons and neurite sprouting. A twitching behavioral assay was used to examine the functional consequences of VPA and FA treatment.

Results

In zebrafish embryos, VPA exposure caused a decrease in the midbrain size, an increase in the midline gap of the hindbrain, and perturbed neurite sprouting of secondary motor neurons, in a concentration‐dependent manner. VPA exposure also decreased the fluorescence intensity of neuronal progenitor cells in early developmental stages, indicating fewer cells. Furthermore, VPA exposure significantly altered embryonic twitching activity, causing hyperactivity in dark and hypoactivity in light. Supplementation of FA rescued the VPA‐induced smaller midbrain size and hindbrain midline gap defects. FA treatment also increased the number of neuronal progenitor cells in VPA‐treated embryos and salvaged neurite sprouting of the secondary motor neurons. FA rescued the VPA‐induced alterations in twitching activity in light but not in dark.

Significance

We conclude that VPA exposure induces specific neurotoxic perturbations in developing zebrafish embryos, and that FA reversed most of the identified defects. The results demonstrate that zebrafish is a promising model to study VPA‐induced teratogenesis and to screen for countermeasures.
TRAF3 and NBR1 both influence the effect of the disease‐causing CYLD(Arg936X) mutation on NF‐κB activity
Authors: Danis Judit , Kelemen Evelyn , Rajan Neil , Nagy Nikoletta , Széll Márta , Ádám Éva
Published: May 2021

Recently described Hungarian and Anglo‐Saxon pedigrees that are affected by CYLD cutaneous syndrome (syn: Brooke‐Spiegler syndrome (BSS)) carry the same disease‐causing mutation (c.2806C>T, p.Arg936X) of the cylindromatosis (CYLD) gene but exhibit striking phenotypic differences. Using whole exome sequencing, missense genetic variants of the TRAF3 and NBR1 genes were identified in the affected family members of the Hungarian pedigree that are not present in the Anglo‐Saxon pedigree. This suggested that the affected proteins (TRAF3 and NBR1) are putative phenotype‐modifying factors. An in vitro experimental system was set up to clarify how wild type and mutant TRAF3 and NBR1 modify the effect of CYLD on the NF‐κB signal transduction pathway. Our study revealed that the combined expression of mutant CYLD(Arg936X) with TRAF3 and NBR1 caused increased NF‐κB activity, regardless of the presence or absence of mutations in TRAF3 and NBR1. We concluded that increased expression levels of these proteins further strengthen the effect of the CYLD(Arg936X) mutation on NF‐κB activity in HEK293 cells and may explain the phenotype‐modifying effect of these genes in CYLD cutaneous syndrome. These results raise the potential that detecting the levels of TRAF3 and NBR1 might help explaining phenotypic differences and prognosis of CCS.
Topical application of an amygdalin analogue reduces inflammation and keratinocyte proliferation in a psoriasis mouse model
Authors: Gago‐López Nuria , Lagunas Arnal Carmen , Perez Juan J. , Wagner Erwin F.
Published: May 2021

Psoriasis is a chronic inflammatory skin disease without cure. Systemic and biological therapies are the most effective treatments for patients with severe psoriasis. However, these drugs can cause serious side effects from extended use. Safe and effective topical drugs are needed to decrease psoriatic plaques and reduce the risk of adverse effects. Amygdalin analogues are stable small molecules that showed benefits in psoriasis xenografts to immune‐deficient mice by systemic application. However, whether topical application of these amygdalin analogues could reduce the progression of the psoriatic phenotype in an immune‐competent organism is unknown. Here, we analyse the efficiency of topical application of an amygdalin analogue cream on a well‐established genetic and immune‐competent mouse model of psoriasis. Topical application of an amygdalin analogue cream ameliorates psoriasis‐like disease in mice, reduces epidermal hyperplasia and skin inflammation. Amygdalin analogue treatment leads to reduced expression of local pro‐inflammatory cytokines, but systemic pro‐inflammatory cytokines that are highly expressed in psoriasis patients such as IL‐17A, IL6 or G‐CSF are also decreased. Furthermore, expression of important mediators of psoriasis initiation and epidermal hyperplasia, such as TNFa, S100A9 and TSLP, is decreased in lesional epidermis after amygdalin analogue treatment. In conclusion, we show that amygdalin analogue reduces the proliferative capacity of psoriasis‐like stimulated keratinocytes and their inflammatory response in vivo and in vitro. These results suggest that topical application of amygdalin analogues may represent a safe and effective treatment for psoriasis.
Cysteine 159 delineates a hinge region of the alternating access monocarboxylate transporter 1 and is targeted by cysteine‐modifying inhibitors
Authors: Köpnick Anna‐Lena , Geistlinger Katharina , Beitz Eric
Published: May 2021

Monocarboxylate transporter isoforms 1–4, MCT, of the solute carrier SLC16A family facilitate proton‐coupled transport of l‐lactate. Growth of tumors that exhibit the Warburg effect, that is, high rates of anaerobic glycolysis despite availability of oxygen, relies on swift l‐lactate export, whereas oxygenic cancer cells import circulating l‐lactate as a fuel. Currently, MCTs are viewed as promising anticancer targets. Small‐molecule inhibitors have been found, and, recently, high‐resolution protein structures have been obtained. Key questions, however, regarding the exact binding sites of cysteine‐modifying inhibitors and the substrate translocation cycle lack a conclusive experimental basis. Here, we report Cys159 of the ubiquitous human MCT1 to reside in a critical hinge region of the alternating access‐type transporter. We identified Cys159 as the binding site of the organomercurial pCMBS. The inhibitory effect of pCMBS was proposed to be indirect via modification of the chaperone basigin. We provide evidence that pCMBS locks MCT1 in its outward open conformation in a wedge‐like fashion. We corroborated this finding using smaller cysteine‐modifying reagents that size‐dependently inhibited l‐lactate transport. The smallest modifiers targeted additional cysteines as shown by a C159S mutant. We found a Cys399/Cys400 pair to constitute the second hinge of the transporter that tolerated only individual replacement by serine. The hinge cysteines, in particular the selectively addressable Cys159, provide natural anchors for placing probes into MCTs to report, for instance, on the electrostatics or hydration upon binding of the transported l‐lactate substrate and the proton cosubstrate.
APOBEC3G rescues cells from the deleterious effects of DNA damage
Authors: Botvinnik Alexander , Shivam Pushkar , Smith Yoav , Sharma Gunjan , Olshevsky Udy , Moshel Ofra , Manevitch Zakhariya , Climent Nuria , Oliva Harold , Britan‐Rosich Elena , Kotler Moshe
Published: May 2021

Human apolipoprotein B mRNA editing enzyme, catalytic polypeptide‐like 3G (hA3G), a member of the APOBEC family, was described as an anti‐HIV‐1 restriction factor, deaminating reverse transcripts of the HIV‐1 genome. Several types of cancer cells that express high levels of A3G, such as diffuse large B‐cell lymphoma cells and glioblastomas, show enhanced cell survival after ionizing radiation and chemotherapy treatments. Previously, we showed that hA3G promotes (DNA) double‐strand breaks repair in cultured cells and rescues transgenic mice from a lethal dose of ionizing radiation. Here, we show that A3G rescues cells from the detrimental effects of DNA damage induced by ultraviolet irradiation and by combined bromodeoxyuridine and ultraviolet treatments. The combined treatments stimulate the synthesis of cellular proteins, which are exclusively associated with A3G expression. These proteins participate mainly in nucleotide excision repair and homologous recombination DNA repair pathways. Our results implicate A3G inhibition as a potential strategy for increasing tumor cell sensitivity to genotoxic treatments.
Large potential for crop production adaptation depends on available future varieties
Authors: Zabel Florian , Müller Christoph , Elliott Joshua , Minoli Sara , Jägermeyr Jonas , Schneider Julia M. , Franke James A. , Moyer Elisabeth , Dury Marie , Francois Louis , Folberth Christian , Liu Wenfeng , Pugh Thomas A.M. , Olin Stefan , Rabin Sam S. , Mauser Wolfram , Hank Tobias , Ruane Alex C. , Asseng Senthold
Published: May 2021

Climate change affects global agricultural production and threatens food security. Faster phenological development of crops due to climate warming is one of the main drivers for potential future yield reductions. To counter the effect of faster maturity, adapted varieties would require more heat units to regain the previous growing period length. In this study, we investigate the effects of variety adaptation on global caloric production under four different future climate change scenarios for maize, rice, soybean, and wheat. Thereby, we empirically identify areas that could require new varieties and areas where variety adaptation could be achieved by shifting existing varieties into new regions. The study uses an ensemble of seven global gridded crop models and five CMIP6 climate models. We found that 39% (SSP5‐8.5) of global cropland could require new crop varieties to avoid yield loss from climate change by the end of the century. At low levels of warming (SSP1‐2.6), 85% of currently cultivated land can draw from existing varieties to shift within an agro‐ecological zone for adaptation. The assumptions on available varieties for adaptation have major impacts on the effectiveness of variety adaptation, which could more than half in SSP5‐8.5. The results highlight that region‐specific breeding efforts are required to allow for a successful adaptation to climate change.
Island sternocleidomastoid myocutaneous flap for posterior pharyngeal wall defect repair after anterior cervical spine surgery
Authors: Zhang Xinling , Zhao Runlei , Wang Guanhuier , Chen Yujie , Ding Pengbing , Yang Xin , Zhao Zhenmin , Zhang Yuan
Published: May 2021

Injuries and tumours of the cervical spine represent therapeutic challenges to the treating surgeon due to the complex anatomical relationships and biomechanical features. The anterior cervical midline (ACM) and anterior cervical retropharyngeal (ACR) approaches are effective and safe surgical approaches for certain cervical spine lesions, such as cervical spine neoplasms, atlantoaxial subluxation, and certain odontoid fractures. Posterior pharyngeal wall defects (PPWDs) is one of the most frequently encountered surgical morbidities after anterior cervical spine surgery (ACSS). However, limited information has been published concerning effective approaches for PPWD reconstruction after ACSS. The manuscript aimed to describe a novel application of the island sternocleidomastoid myocutaneous flap (ISMF) in the management of PPWDs after ACSS, including surgery with the ACM approach and ACR approach. From April 2015 to November 2019, the clinical data of three patients with PPWDs repaired using the ISMF in Peking university third hospital were retrospectively analysed. The observational indexes are as follows: postoperative survival of the flap, wound healing 2 weeks after surgery, eating and pronunciation function 2 months after surgery. The above indexes of these three cases recovered well. Three patients did not have any persistent PPWD after repair with the ISMF and did not require any further surgical procedures related to the cervical spine.
Effect of orthodontic therapy in periodontitis and non‐periodontitis patients: a systematic review with meta‐analysis
Authors: Martin Conchita , Celis Beatriz , Ambrosio Nagore , Bollain Juan , Antonoglou Georgios N. , Figuero Elena
Published: May 2021

Aim

To answer these PICO questions:

#1: In adult patients with malocclusion, what are the effects of orthodontic tooth movement (OTM) on clinical attachment level (CAL) changes in treated periodontitis patients with a healthy but reduced periodontium compared to non‐periodontitis patients?

#2: In adult patients with treated periodontitis and malocclusion, which is the efficacy of skeletal anchorage devices compared to conventional systems in terms of orthodontic treatment outcomes?

Material and methods

Seven databases were searched until June 2020 looking for randomized, non‐randomized trials and case series. Mean effects (ME) and 95% confidence intervals (CIs) were calculated.

Results

Twenty‐six studies with high risk of bias were included.

PICO#1: In 26 patients without periodontitis and in 69 treated periodontitis patients, minimal changes in periodontal outcomes were reported after orthodontic therapy (p > 0.05). A significant CAL gain (mm) (ME = 3.523; 95% CI [2.353; 4.693]; p < 0.001) was observed in 214 patients when periodontal outcomes were retrieved before a combined periodontal and orthodontic therapy.

PICO#2: Orthodontic variables were scarcely reported, and objective assessment of the results on orthodontic therapy was missing.

Conclusions

Based on a small number of low‐quality studies, in non‐periodontitis and in stable treated periodontitis patients, OTM had no significant impact on periodontal outcomes.
Lentigo maligna: defining margins and predictors of recurrence utilizing clinical, dermoscopic, confocal microscopy and histopathology features
Authors: Star P. , Rawson R.V. , Drummond M. , Lo S. , Scolyer R.A. , Guitera P.
Published: May 2021

Background

Lentigo maligna (LM) is a subtype of melanoma in situ with poorly defined margins and a high recurrence rate. The biological behaviour of LM appears to differ widely between cases, from biologically indolent to biologically active variants, with some patients experiencing multiple recurrences. It is not known whether this is secondary to inadequate margins, field cancerization or the innate biology of the lesion itself.

Objectives

(a) Describe the margins of LM in detail by analysing LM in three zones, that is centre, edge and surround using reflectance confocal microscopy (RCM) and histopathology; (b) ascertain association of histological distance of LM and atypical melanocytic hyperplasia from the surgical margin with multi‐recurrent (MR) disease and (c) identify features (clinical, dermoscopy, RCM and histopathology) associated with MR LM.

Methods

(1) Descriptive observational study comparing the centre, edge and surround of LM on histopathology and RCM; (2) retrospective cohort study comparing parameters associated with MR and non‐recurrent (NR) LM.

Results

30 patients (median follow‐up time 6.2 years) were included. On histopathology, confluent or near confluent lentiginous proliferation, melanocyte density >15 per 0.5 mm and adnexal spread were best for distinguishing surround from edge of LM. On RCM, predominant melanocytes, lentiginous proliferation and pleomorphism distinguished surround from centre/edge. MR patients had a median histological distance of LM from the surgical margin of 2mm (versus NR patients with an average distance of 4mm). MR patients had a greater proportion of more florid features, compared with NR on histopathology at both the centre and the edge but were similar in the surround.

Conclusion

These data may help pathologists and confocalists better define margins of LM. More florid features in MR patients, despite a similar background of sun‐damaged skin, suggest the innate biology of the lesion rather than the field of cancerization may explain MR LM.
Evaluation of the environmental sustainability of the inshore great scallop (Pecten maximus) fishery in Galicia
Authors: Cortés Antonio , González‐García Sara , Franco‐Uría Amaya , Moreira Maria Teresa , Feijoo Gumersindo
Published: May 2021

Great scallop (Pecten maximus) is a bivalve species belonging to the Pectinidae family that is deeply linked to the well‐known network of pilgrimages in Spain (The Way of Saint James), becoming a gourmet product of the Galician cuisine. The goal of this study was to fill the gaps that currently exist in a specific inventory dedicated to the capture and processing of great scallop, as well as to assess the environmental burdens derived from this system. The construction of a comprehensive life cycle inventory was one of the fundamental stages, gathering primary information from questionnaires filled out by 14 skippers and the manager of the evisceration plant in the port of Cambados. Diesel consumption of the fishing boats was identified as the major contributor to the environmental burdens. Furthermore, electricity consumption in the evisceration plant also stood out as a determinant element in the environmental profile of the product. The integrated GHG emission/protein content correlation placed the scallop in the quadrant of high‐protein content (the highest of the fisheries), but also high environmental impact (mainly due to the high fuel use intensity and low edible yield). It is important to highlight that to date and according to our knowledge, this is the first study that aims to analyze the environmental impacts of the great scallop fishery.
2010 versus the 2000 consensus criteria in patients with normalised insulin‐like growth factor 1 after transsphenoidal surgery has high predictive values for long‐term recurrence‐free survival in acromegaly
Authors: Shen Ming , Chen Zhengyuan , Shou Xuefei , He Wenqiang , Qiao Nidan , Ma Zengyi , Ye Zhao , Zhang Yichao , Zhang Qilin , Zhou Xiang , Cao Xiaoyun , Zhang Zhaoyun , Ye Hongying , Li Yiming , Zhao Yao , Li Shiqi , He Min , Wang Yongfei
Published: May 2021

The present study investigated the factors associated with recurrence during long‐term follow‐up in acromegaly and compared the recurrence rate between patients in remission with 2010 vs 2000 consensus criteria. We retrospectively recruited 133 adult acromegalic patients who had undergone transsphenoidal surgery (TSS) from January 2013 to December 2014 and assessed their clinical characteristics, surgical outcomes and recurrence. Surgical remission was defined as normalised insulin‐like growth factor 1 (IGF‐1) with nadir growth hormone (GH) during an oral glucose tolerance test (OGTT) < 1 μg/ L no less than 3 months after TSS without adjuvant therapy. Recurrence was defined as persistently reelevated IGF‐1 after surgical remission. Cox regression analysis and Kaplan‐Meier survival analysis were performed to evaluate the factors associated with recurrence. Remission was achieved in 77 cases (57.9%) after TSS alone. Recurrence was seen in five cases (6.5%) at 12, 12, 12, 36 and 54 months, respectively, after surgery. Cox regression analysis showed that a nadir GH < 0.4 μg /L (vs 0.4‐1.0 μg /L) at surgical remission (odds ratio [OR] = 0.106; 95% confidence interval [CI] = 0.017‐0.645; P = 0.015) and Ki‐67 index (OR = 2.636; 95% CI = 1.023‐6.791; P = 0.045) were independent factors influencing recurrence. Kaplan‐Meier survival analysis showed that the median recurrence‐free survival was 36 months (95% CI = 20‐52) for patients with nadir GH 0.4‐1.0 μg /L at surgical remission. The median recurrence‐free survival for patients with nadir GH < 0.4 μg /L at surgical remission was much longer (ie, required further follow‐up to estimate). A failure of GH suppression under 0.4 μg /L during an OGTT in patients with normalised IGF‐1 and a higher Ki‐67 index are independent predictors of recurrence after surgical remission in GH‐secreting pituitary adenomas. Compared to patients with nadir GH < 0.4 μg /L, those with nadir GH 0.4‐1.0 μg /L appear to have a significantly higher risk of recurrence.
Understanding Women’s Cardiovascular Health Using MyStrengths+MyHealth: A Patient‐Generated Data Visualization Study of Strengths, Challenges, and Needs Differences
Authors: Austin Robin R. , Mathiason Michelle A. , Lindquist Ruth A. , McMahon Siobhan K. , Pieczkiewicz David S. , Monsen Karen A.
Published: May 2021

Purpose

The purpose of this data visualization study was to identify patterns in patient‐generated health data (PGHD) of women with and without Circulation signs or symptoms. Specific aims were to (a) visualize and interpret relationships among strengths, challenges, and needs of women with and without Circulation signs or symptoms; (b) generate hypotheses based on these patterns; and (c) test hypotheses generated in Aim 2.

Design

The design of this visualization study was retrospective, observational, case controlled, and exploratory.

Methods

We used existing de‐identified PGHD from a mobile health application, MyStrengths+MyHealth (N= 383). From the data, women identified with Circulation signs or symptoms (n= 80) were matched to an equal number of women without Circulation signs or symptoms. Data were analyzed using data visualization techniques and descriptive and inferential statistics.

Findings

Based on the patterns, we generated nine hypotheses, of which four were supported. Visualization and interpretation of relationships revealed that women without Circulation signs or symptoms compared to women with Circulation signs or symptoms had more strengths, challenges, and needs—specifically, strengths in connecting; challenges in emotions, vision, and health care; and needs related to info and guidance.

Conclusions

This study suggests that visualization of whole‐person health including strengths, challenges, and needs enabled detection and testing of new health patterns. Some findings were unexpected, and perspectives of the patient would not have been detected without PGHD, which should be valued and sought. Such data may support improved clinical interactions as well as policies for standardization of PGHD as sharable and comparable data across clinical and community settings.

Clinical Relevance

Standardization of patient‐generated whole‐person health data enabled clinically relevant research that included the patients’ perspective.
Genome medicine in male infertility: From karyotyping to single‐cell analysis
Authors: Shiraishi Koji
Published: May 2021

Male infertility is a multifactorial pathological condition that affects half of infertile couples. The majority of cases are categorized as idiopathic, especially in cases of nonobstructive azoospermia (NOA). An increasing number of genetic abnormalities have been shown to cause spermatogenic impairment with the development of microarray technologies and next‐generation sequencing (NGS), moving beyond classical karyotype and polymerase chain reaction analyses of targeted genes. However, the majority of gene mutations, such as Klinefelter syndrome, azoospermia factor microdeletion, or congenital bilateral absence of the vas deferens, fail to function in a one gene‐one phenotype manner. Single‐cell transcriptome analysis performed using human testicular samples has begun to be published, which has brought about a more comprehensive understanding of testicular pathology. NGS also enables omics approaches, which provide more powerful tools to interrogate the genome, epigenome, transcriptome, and proteome. Simultaneously, the involvement of environmental factors and comorbidities, which may potentially regulate epigenetic factors, has been shown, resulting in a more complex understanding of the pathophysiology of spermatic disorders, especially NOA. The combination of phenotypic data and large amounts of bioinformatical data obtained by NGS may provide a more comprehensive understanding of the pathophysiology of male infertility, which will contribute not only to a diagnosis but also to the proper selection of infertility treatment and the development of new treatment modalities for male infertility.
Treatment failure in hyperthyroid cats after radioiodine (I‐131) injection
Authors: Mullowney Deirdre , Chang Yu‐Mei , Glanemann Barbara , Syme Harriet M.
Published: May 2021

Background

There is limited published information on the outcome for cats where total thyroxine concentration (TT4) remains elevated after treatment with radioactive iodine (RAI).

Objective

To determine the frequency of, and predictors for, subsequent treatment failure in cats for which TT4 remains elevated at hospital discharge, and to report clinical outcomes for cats requiring repeat treatment.

Animals

One hundred twenty‐one cats with TT4 ≥40 nmol/L after treatment with RAI (out of an original, treated study sample of 959 cats).

Methods

Retrospective study. Data regarding signalment, weight, TT4 concentration (before RAI treatment, at discharge, and percentage change), day of sampling, and I‐131 dose were acquired. Logistic regression was performed to evaluate predictors of treatment failure.

Results

In the 87 cats for which classification was possible, 35 (40%) became euthyroid without further treatment. All TT4 variables and weight normalized RAI dose were independently predictive of subsequent treatment failure. In multivariate analysis, TT4 concentration at discharge (P < .001) and weight normalized RAI dose (P = .04) remained in the final model. All 28 cats with TT4 concentration ≥150 nmol/L at discharge ultimately failed treatment, compared with 13/40 (32.5%) and 11/19 (57.9%) cats with TT4 concentrations of 40‐100 nmol/L and 100‐150 nmol/L, respectively. Of the 52 cats that failed treatment, 14 were subsequently managed medically, 12 underwent thyroidectomy (4 with carcinoma), 14 had repeat RAI treatment which was successful in 12/14 (86%) cats, and 13 had no further treatment.

Conclusions and Clinical Importance

Cats with TT4 >150 nmol/L at discharge after RAI might be candidates for immediate repeat treatment.
Ancestral transoceanic colonization and recent population reduction in a nonannual killifish from the Seychelles archipelago
Authors: Cui Rongfeng , Tyers Alexandra M. , Malubhoy Zahabiya Juzar , Wisotsky Sadie , Valdesalici Stefano , Henriette Elvina , Kosakovsky Pond Sergei L. , Valenzano Dario Riccardo
Published: May 2021

Whether freshwater fish colonize remote islands following tectonic or transoceanic dispersal remains an evolutionary puzzle. Integrating dating of known tectonic events with phylogenomics and current species distribution, we find that killifish species distribution is not explained by species dispersal by tectonic drift only. Investigating the colonization of a nonannual killifish (golden panchax, Pachypanchax playfairii) on the Seychelle islands, we found genetic support for transoceanic dispersal and experimentally discovered an adaptation to complete tolerance to seawater. At the macroevolutionary scale, despite their long‐lasting isolation, nonannual golden panchax show stronger genome‐wide purifying selection than annual killifishes from continental Africa. However, progressive decline in effective population size over a more recent timescale has probably led to the segregation of slightly deleterious mutations across golden panchax populations, which represents a potential threat for species preservation in the long term.
Host population structure for tolerance determines the evolution of plant–virus interactions
Authors: Montes Nuria , Vijayan Viji , Pagán Israel
Published: May 2021

Heterogeneity for plant defences determines both the capacity of host populations to buffer the effect of infection and the pathogen´s fitness. However, little information is known on how host population structure for tolerance, a major plant defence, impacts the evolution of plant–pathogen interactions.

By performing 10 serial passages of Turnip mosaic virus (TuMV) in Arabidopsis thaliana populations with varying proportion of tolerant genotypes simulating different structures for this trait, we analysed how host heterogeneity for this defence shapes the evolution of both virus multiplication, the effect of infection on plant fecundity and mortality, and plant tolerance and resistance.

Results indicated that a higher proportion of tolerant genotypes in the host population promotes virus multiplication and reduces the effect of infection on plant mortality, but not on plant fecundity. These changes resulted in more effective plant tolerance to virus infection. Conversely, a lower proportion of tolerant genotypes reduced virus multiplication, boosting plant resistance.

Our work for the first time provides evidence of the main role of host population structure for tolerance on pathogen evolution and on the subsequent feedback loops on plant defences.
How efficient is customized lingual orthodontics? An assessment of treatment outcome
Authors: Fontinha Clara , Cattaneo Paolo M. , Cornelis Marie A.
Published: May 2021

Objective

To assess the efficacy of lingual orthodontics by comparing setups and post‐treatment casts.

Setting and sample population

Thirty‐two consecutive patients treated with a customized lingual orthodontic appliance were included in this retrospective study.

Materials and methods

Initial casts, post‐treatment casts and setups were scanned, and the digital models produced were analysed in terms of overjet; overbite; molar and canine relationships; intercanine, interpremolar and intermolar distances; upper and lower arch lengths; midline deviation; bucco‐lingual angulation of all teeth and mesio‐distal angulation of anterior teeth. Comparisons between setups and post‐treatment casts were performed via paired t tests. Relationships between the planned and actual correction were studied using regression analysis.

Results

Statistically significant differences in bucco‐lingual torque between setups and post‐treatment casts were found for all upper teeth, except for central incisors. In the lower jaw, statistically significant differences in bucco‐lingual torque were found between setups and post‐treatment casts for the lower incisors and molars. No statistically significant differences in mesio‐distal angulation of anterior teeth were found between setups and post‐treatment casts. Upper and lower arch widths did not vary significantly between setups and final casts, except upper inter‐second premolar and intermolar distances.

Conclusion

Customized lingual appliances offer efficient control of mesio‐distal angulation of all anterior teeth. Significant differences in torque between setups and post‐treatment casts were observed for upper lateral incisors, canines, premolars and molars, as well as lower incisors and molars. However, the torque difference was clinically significant (over three degrees) for upper second premolars and molars only.
Corneal asphericity and related factors in the geriatric population: A population‐based study
Authors: Hashemi Hassan , Nabovati Payam , Aghamirsalim Mohamadreza , Mahboubipour Hassan , Yekta Abbasali , Khabazkhoob Mehdi
Published: May 2021

Purpose

To determine the distribution of the corneal asphericity coefficient (Q value) and related factors in an Iranian geriatric population.

Methods

This population‐based study was conducted in 2019 in Tehran, using stratified multistage random cluster sampling. The study population was ≥60 years of age. Participants underwent corneal imaging using a Pentacam HR. Mean keratometry, corneal astigmatism, central corneal thickness, anterior chamber depth and the overall anterior and posterior Q values (for 8 mm chord diameter) were recorded. Axial length measurements were performed using the IOL Master 500.

Results

2457 eyes of 2457 individuals were analysed. The mean age was 67.3 ± 5.82 years and 1479 (60.2%) were female. The mean Q value for the anterior corneal surface was −0.35 ± 0.17 (95% CI: −0.35 to −0.34). The anterior Q value showed a statistically significant inverse relationship with axial length and mean keratometry, and a significant direct association with anterior chamber depth and corneal astigmatism. The mean posterior Q value was −0.41 ± 0.15 (95% CI: −0.42 to −0.40). The posterior Q value had a significant direct relationship with age, anterior chamber depth, mean keratometry and corneal astigmatism.

Conclusion

The corneal Q values in this geriatric Iranian population were more negative than the values reported in most previous studies. Corneal asphericity was greater affected by ocular biometry and corneal curvature than demographic factors and refractive status.
What does it take to facilitate the integration of clinical practice guidelines for the management of low back pain into practice? Part 1: A synthesis of recommendation
Authors: Longtin Christian , Décary Simon , Cook Chad E. , Tousignant‐Laflamme Yannick
Published: May 2021

Background

Despite the emergence of multiple clinical practice guidelines (CPGs) for the rehabilitation of low back pain (LBP) over the last decade, self‐reported levels of disability in this population have not improved. This may be explained by the numerous implementation barriers, such as the complexity of information and sheer volumes of CPGs.

Objectives

The purpose of this study was to summarize the evidence and recommendations from the most recent and high‐quality CPGs on the rehabilitation management of LBP by developing an infographic summarizing the recommendations to facilitate dissemination into clinical practice.

Methods

We performed a systematic review of high‐quality CPGs with an emphasis on rehabilitation approaches. We searched major health‐related research databases (e.g., PubMed, CINAHL, and PEDro). We performed quality assessment via the AGREE‐II instrument. Contents of the CPGs were synthesized by extracting recommendations, which were then compared to one another to identify consistencies based on an iterative evaluation process.

Results

We identified and assessed 5 recent high‐quality CPGs. We synthesized 13 recommendations on the rehabilitation management of LBP (2 for screening procedures, 3 for assessment procedures, and 8 involving treatment approaches) and 2 underlying principles were highlighted. These results were then synthetized and illustrated in a concise infographic that serves as a conceptual roadmap that identifies the specific behavior changes (i.e., adoption of CPGs’ recommendations) rehabilitation professionals should adopt in order to integrate an evidenced‐based approach for the management of LBP.

Conclusions

We systematically reviewed the literature for CPGs’ recommendations for the physical rehabilitation management of LBP and synthesized the information through an infographic.