bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient secretory production of large‐size heterologous enzymes in Bacillus subtilis: A secretory partner and directed evolution
Authors: Liu Shan , Wang Juan , Zhu Zhiguang , Shi Ting , Zhang Yi‐Heng P. Job
Published: June 2020

Secretory production of recombinant proteins provides a simple approach to the production and purification of target proteins in the enzyme industry. We developed a combined strategy for the secretory production of three large‐size heterologous enzymes with a special focus on 83‐kDa isoamylase (IA) from an archaeon Sulfolobus tokodaii in a bacterium Bacillus subtilis. First, a secretory protein of the B. subtilis family 5 glycoside hydrolase endoglucanase (Cel5) was used as a fusion partner, along with the NprB signal peptide, to facilitate secretory production of IA. This secretory partner strategy was effective for the secretion of two other large enzymes: family 9 glycoside hydrolase from Clostridium phytofermentas and cellodextrin phosphorylase from Clostridium thermocellum. Second, the secretion of Cel5‐IA was improved by directed evolution with two novel double‐layer Petri‐dish‐based high‐throughput screening (HTS) methods. The high‐sensitivity HTS relied on the detection of high‐activity Cel5 on the carboxymethylcellulose/Congo‐red assay. The second modest‐sensitivity HTS focused on the detection of low‐activity IA on the amylodextrin‐I2 assay. After six rounds of HTS, a secretory Cel5‐IA level was increased to 234 mg/L, 155 times the wild‐type IA with the NprB signal peptide only. This combinatory strategy could be useful to enhance the secretory production of large‐size heterologous proteins in B. subtilis.
Modelling centralization of pancreatic surgery in a nationwide analysis
Authors: Balzano G , Guarneri G , Pecorelli N , Paiella S , Rancoita P M V , Bassi C , Falconi M
Published: June 2020

Background

The benefits of centralization of pancreatic surgery have been documented, but policy differs between countries. This study aimed to model various centralization criteria for their effect on a nationwide cohort.

Methods

Data on all pancreatic resections performed between 2014 and 2016 were obtained from the Italian Ministry of Health. Mortality was assessed for different hospital volume categories and for each individual facility. Observed mortality and risk-standardized mortality rate (RSMR) were calculated. Various models of centralization were tested by applying volume criteria alone or in combination with mortality thresholds.

Results

A total of 395 hospitals performed 12 662 resections; 305 hospitals were in the very low-volume category (mean 2·6 resections per year). The nationwide mortality rate was 6·2 per cent, increasing progressively from 3·1 per cent in very high-volume to 10·6 per cent in very low-volume hospitals. For the purposes of centralization, applying a minimum volume threshold of at least ten resections per year would lead to selection of 92 facilities, with an overall mortality rate of 5·3 per cent. However, the mortality rate would exceed 5 per cent in 48 hospitals and be greater than 10 per cent in 17. If the minimum volume were 25 resections per year, the overall mortality rate would be 4·7 per cent in 38 facilities, but still over 5 per cent in 17 centres and more than 10 per cent in five. The combination of a volume requirement (at least 10 resections per year) with a mortality threshold (maximum RSMR 5 or 10 per cent) would allow exclusion of facilities with unacceptable results, yielding a lower overall mortality rate (2·7 per cent in 45 hospitals or 4·2 per cent in 76 respectively).

Conclusion

The best performance model for centralization involved a threshold for volume combined with a mortality threshold.
Relationship between insecure attachment and physical symptom severity is mediated by sensory sensitivity
Authors: Le Thao Lan , Geist Rose , Hunter Jon , Maunder Robert G.
Published: June 2020

Objective

Various models have been used to explain somatization, including attachment theory, which describes how formative experiences influence perceptions of vulnerability and threat. Although attachment insecurity is associated with greater physical symptoms, the mechanisms by which attachment insecurity influences the experience of physical symptoms are not clear. Sensory processing sensitivity (SPS) describes a low threshold to responding to stimuli and high emotional reactivity. It is associated with both attachment insecurity and physical symptoms. The purpose of this study is to test a model in which attachment insecurity, depression, and SPS interact to influence physical symptoms.

Methods

Cross‐sectional data from the online Self‐Assessment Kiosk were used (N = 186). Participants were surveyed regarding attachment insecurity (ECR‐M16), physical symptom severity (PHQ‐15), sensory processing sensitivity (HSPS), and depression (PHQ‐9). A path analysis was used to analyze the data.

Results

Modal participants were white (74%) single (45%) women (80%) with university education (79%). Attachment anxiety, attachment avoidance, and sensitivity were correlated with physical symptom severity. The data suggested that sensitivity mediates between attachment anxiety and physical symptoms (βindirect = 0.070, p = .003 and βdirect = −0.030, p> .05) and this relationship remains significant when controlling for depression.

Conclusions

This study extends our understanding of the potential pathways that lead individuals with attachment insecurity to experience burdensome physical symptoms by supporting a mediating role for SPS.
Robot‐assisted therapy for upper‐limb rehabilitation in subacute stroke patients: A systematic review and meta‐analysis
Authors: Chien Wai‐tong , Chong Yuen‐yu , Tse Man‐kei , Chien Cheuk‐woon , Cheng Ho‐yu
Published: June 2020

Background

Stroke survivors often experience upper‐limb motor deficits and achieve limited motor recovery within six months after the onset of stroke. We aimed to systematically review the effects of robot‐assisted therapy (RT) in comparison to usual care on the functional and health outcomes of subacute stroke survivors.

Methods

Randomized controlled trials (RCTs) published between January 1, 2000 and December 31, 2019 were identified from six electronic databases. Pooled estimates of standardized mean differences for five outcomes, including motor control (primary outcome), functional independence, upper extremity performance, muscle tone, and quality of life were derived by random effects meta‐analyses. Assessments of risk of bias in the included RCTs and the quality of evidence for every individual outcomes were conducted following the guidelines of the Cochrane Collaboration.

Results

Eleven RCTs involving 493 participants were included for review. At post‐treatment, the effects of RT when compared to usual care on motor control, functional independence, upper extremity performance, muscle tone, and quality of life were nonsignificant (all ps ranged .16 to .86). The quality of this evidence was generally rated as low‐to‐moderate. Less than three RCTs assessed the treatment effects beyond post‐treatment and the results remained nonsignificant.

Conclusion

Robot‐assisted therapy produced benefits similar, but not significantly superior, to those from usual care for improving functioning and disability in patients diagnosed with stroke within six months. Apart from using head‐to‐head comparison to determine the effects of RT in subacute stroke survivors, future studies may explore the possibility of conducting noninferiority or equivalence trials, given that the less labor‐intensive RT may offer important advantages over currently available standard care, in terms of improved convenience, better adherence, and lower manpower cost.
External validation of life expectancy prognostic models in patients evaluated for palliative radiotherapy at the end‐of‐life
Authors: Mojica‐Márquez Adrianna E. , Rodríguez‐López Joshua L. , Patel Ankur K. , Ling Diane C. , Rajagopalan Malolan S. , Beriwal Sushil
Published: June 2020

Background

The TEACHH and Chow models were developed to predict life expectancy (LE) in patients evaluated for palliative radiotherapy (PRT). We sought to validate the TEACHH and Chow models in patients who died within 90 days of PRT consultation.

Methods

A retrospective review was conducted on patients evaluated for PRT from 2017 to 2019 who died within 90 days of consultation. Data were collected for the TEACHH and Chow models; one point was assigned for each adverse factor. TEACHH model included: primary site of disease, ECOG performance status, age, prior palliative chemotherapy courses, hospitalization within the last 3 months, and presence of hepatic metastases; patients with 0‐1, 2‐4, and 5‐6 adverse factors were categorized into groups (A, B, and C). The Chow model included non‐breast primary, site of metastases other than bone only, and KPS; patients with 0‐1, 2, or 3 adverse factors were categorized into groups (I, II, and III).

Results

A total of 505 patients with a median overall survival of 2.1 months (IQR: 0.7‐2.6) were identified. Based on the TEACHH model, 10 (2.0%), 387 (76.6%), and 108 (21.4%) patients were predicted to live >1 year, >3 months to ≤1 year, and ≤3 months, respectively. Utilizing the Chow model, 108 (21.4%), 250 (49.5%), and 147 (29.1%) patients were expected to live 15.0, 6.5, and 2.3 months, respectively.

Conclusion

Neither the TEACHH nor Chow model correctly predict prognosis in a patient population with a survival <3 months. A better predictive tool is required to identify patients with short LE.
Prioritizing elective cardiovascular procedures during the COVID‐19 pandemic: The cardiovascular medically necessary, time‐sensitive procedure scorecard
Authors: Waxman Sergio , Garg Aakash , Torre Sabino , Wasty Najam , Roelke Marc , Cohen Marc , Salemi Arash
Published: June 2020

Background

Following the surge of the coronavirus disease 2019 (COVID‐19) pandemic, government regulations, and recommendations from professional societies have conditioned the resumption of elective surgical and cardiovascular (CV) procedures on having strategies to prioritize cases because of concerns regarding the availability of sufficient resources and the risk of COVID‐19 transmission.

Objectives

We evaluated the use of a scoring system for standardized triage of elective CV procedures.

Methods

We retrospectively reviewed records of patients scheduled for elective CV procedures that were prioritized ad hoc to be either performed or deferred when New Jersey state orders limited the performance of elective procedures due to the COVID‐19 pandemic. Patients in both groups were scored using our proposed CV medically necessary, time‐sensitive (MeNTS) procedure scorecard, designed to stratify procedures based on a composite measure of hospital resource utilization, risk of COVID‐19 exposure, and time sensitivity.

Results

A total of 109 scheduled elective procedures were either deferred (n = 58) or performed (n = 51). The median and mean cumulative CV MeNTS scores for the group of performed cases were significantly lower than for the deferred group (26 (interquartile range (IQR) 22–31) vs. 33 (IQR 28–39), p < .001, and 26.4 (SE 0.34) vs. 32.9 (SE 0.35), p < .001, respectively).

Conclusions

The CV MeNTS procedure score was able to stratify elective cases that were either performed or deferred using an ad hoc strategy. Our findings suggest that the CV MeNTS procedure scorecard may be useful for the fair triage of elective CV cases during the time when available capacity may be limited due to the COVID‐19 pandemic.
Access site related vascular complications with third generation transcatheter heart valve systems
Authors: Ruge Hendrik , Burri Melchior , Erlebach Magdalena , Lange Ruediger
Published: June 2020

Objectives

This study examines the impact of anatomical and procedural factors on Valve Academic Research Consortium‐2‐defined vascular complications at the femoral access site in transcatheter aortic valve replacement (TAVR) with third generation transcatheter heart valve (THV)‐systems.

Background

Randomized clinical trials reported on vascular complications with current THV‐systems. However, clinical presentation and consequences of these events are not well studied.

Methods

All patients who underwent a transfemoral TAVR using an Edwards Sapien3®/Sapien3ultra® or a Medtronic Evolut‐R®/Evolut‐PRO® have been identified from our institutional database. Only procedures utilizing the PerClose‐ProGlide® vascular closure device were included. Risk factors for vascular complications were analyzed with a logistic regression model. Preoperative and procedural data were collected. The postoperative course of patients with and without vascular complications was compared.

Results

A total of 878 patients met the inclusion criteria. Of these, 152 patients (17.3%) had an access‐site related vascular complication (87 major complications, 9.9%). Sheath‐to‐femoral‐artery‐ratio (SFAR) (OR per 0.1 increase = 1.35, p < .001) and more than 2 vessel entries with large bore sheaths (OR = 1.76, p = .029) were independent risk factors for vascular complications. Female gender (OR = 1.44, p = .07) and two vessel entries with large bore sheaths (OR = 1.2, p = .53) increased the risk, although no statistical significance was shown.

Age (OR = 1.07, p = .62), body mass index (OR = 1.1 per 5 points, p = .32) and vessel wall calcification at puncture site (OR = 0.93, p = .7) had no influence on vascular complications. Patients with vascular complications had a higher need for blood transfusion (p < .001) and a higher in‐hospital mortality (2.6 vs. 0.4%, p = .019).

Conclusions

Procedural risk assessment should include SFAR calculation and consider the need for large bore sheath exchange. This might reduce the vascular trauma, lower vascular complication rates and improve the clinical outcome after TAVR.
Drug‐Coated balloons vs drug‐eluting stents for the treatment of small coronary artery disease: A meta‐analysis of randomized trials
Authors: Sanz Sánchez Jorge , Chiarito Mauro , Cortese Bernardo , Moretti Andrea , Pagnotta Paolo , Reimers Bernhard , Stefanini Giulio G. , Ferrante Giuseppe
Published: June 2020

Objectives and background

There is conflicting evidence about the effects of drug‐coated balloons (DCB) compared with drug‐eluting stents (DES) in patients with native small vessel coronary artery disease (CAD).

Methods

The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases and main international conference proceedings were searched for randomized controlled trials (RCT) comparing DCB versus DES in patients with native small vessel CAD. Data were pooled by meta‐analysis using a random‐effects model. The primary endpoint was target vessel revascularization (TVR). Secondary clinical endpoints were: myocardial infarction (MI), target lesion revascularization (TLR), all‐cause death, cardiac death, and stent thrombosis or target vessel thrombosis. Secondary angiographic outcomes were: in‐segment restenosis, in‐segment percentage‐diameter stenosis, in‐segment late lumen loss, in‐segment net luminal gain, and in‐segment minimal lumen diameter.

Results

Five trials enrolling 1,459 patients were included. Mean clinical follow‐up was 10.2 months. The use of DCB, compared with DES, was associated with similar risk of TVR (odds ratio [OR]: 0.97; 95% confidence interval [CI] 0.56 to 1.68; p = .92), TLR (OR: 1.74; 95% CI: 0.57 to 5.28; p = .33), all‐cause death (OR: 1.03; 95% CI: 0.14 to 7.48; p = .98), with a trend toward a lower risk of MI (OR: 0.49; 95% CI: 0.23 to 1.03; p = .06), and with significant lower risk of vessel thrombosis (OR: 0.12; 95% CI: 0.01 to 0.94; p = .04). DCB use was associated with similar risk of angiographic restenosis (OR: 1.12; 95% CI 0.69 to 1.84; p = .64), comparable late luminal loss (standardized mean difference (SMD): –0.18; 95% CI: −0.39 to 0.03; p = .09), while leading to significant higher percentage diameter stenosis (SMD: 0.27; 95% CI 0.12 to 0.41; p < .01) and smaller minimal luminal diameter (SMD: ‐0.52; 95% CI: −0.86 to −0.18; p = .003).

Conclusion

Compared with DES, the use of DCB for the treatment of native small vessel CAD is associated with similar TVR and restenosis and reduces the risk of vessel thrombosis, although DES implantation yields slightly better angiographic surrogate endpoints.
Neurosyphilis in AIDS patient presenting as isolated cranial nerve 6 palsy
Authors: Singh Sanjay , Puranik Priyangi , Lin Ethan , Marti Miriam , Liu Antonio
Published: June 2020

Early neurosyphilis can occur in an immunocompromised host. It has a widely varied presentation. Isolated CN6 as presenting symptom has not been described.
An asymptomatic mediastinal cyst in a young child: Case report and summary of the literature
Authors: Votto Martina , Castagnoli Riccardo , Prevedoni Gorone Maria Sole , Marseglia Gian Luigi , Licari Amelia
Published: June 2020

Bronchogenic cyst is a rare congenital chest malformation that mainly presents with wheeze and feeding issues in early life. A multidisciplinary approach and follow‐up are pivotal for the improvement of lung function, mostly in cases of mediastinal complications.
Effects of imatinib mesylate on cutaneous neurofibromas associated with neurofibromatosis type 1
Authors: Yasuda Ken‐ichi , Nobeyama Yoshimasa , Ishiji Takaoki , Ota Arihito , Asahina Akihiko
Published: June 2020

Imatinib mesylate seemed to inhibit development of cutaneous neurofibromas (c‐NFs) and promote growth of pre‐existing c‐NFs in our neurofibromatosis type 1 case. This report potentially provides new findings in the effects of imatinib mesylate.
Enzyme Dynamics: Looking Beyond a Single Structure
Authors: Agarwal Pratul K. , Bernard David N. , Bafna Khushboo , Doucet Nicolas
Published: June 2020

Conventional understanding of how enzymes function strongly emphasizes the role of structure. However, increasing evidence clearly indicates that enzymes do not remain fixed or operate exclusively in or close to their native structure. Different parts of the enzyme (from individual residues to full domains) undergo concerted motions on a wide range of time‐scales, including that of the catalyzed reaction. Information obtained on these internal motions and conformational fluctuations has so far uncovered and explained many aspects of enzyme mechanisms, which could not have been understood from a single structure alone. Although there is wide interest in understanding enzyme dynamics and its role in catalysis, several challenges remain. In addition to technical difficulties, the vast majority of investigations are performed in dilute aqueous solutions, where conditions are significantly different than the cellular milieu where a large number of enzymes operate. In this review, we discuss recent developments, several challenges as well as opportunities related to this topic. The benefits of considering dynamics as an integral part of the enzyme function can also enable new means of biocatalysis, engineering enzymes for industrial and medicinal applications.
Embedding Silicon in Pinecone‐Derived Porous Carbon as a High‐Performance Anode for Lithium‐Ion Batteries
Authors: Xu Changhaoyue , Wang Boya , Luo Hang , Jing Peng , Zhang Xuemei , Wang Qian , Zhang Yun , Wu Hao
Published: June 2020

Silicon with the advantages of ultra‐high theoretical specific capacity (4200 mAh g−1) and low potential is regarded as a promising anode material. However, its commercial application is still impeded by the poor rate capability and bad cycling durability caused by its low electrical/ionic conductivities and exaggerated volume change. Herein, an eco‐friendly pinecone‐derived porous carbon (PPC) is rationally prepared as a promising host material for Si/carbon composite anodes. Benefiting from the natural porous structure of pinecones, Si nanoparticles are successfully enclosed in the PPC substrate, forming the final PPC/Si composite. In this composite, the electroconductive PPC network combined with ultrafine Si nanoparticles enhances both rapid electron transfer and ion transport, and the porous structures not only ensure the effective infiltration of electrolyte but also accommodate the volume expansion of Si during cycling. As a result, the optimized PPC/Si composite exhibits remarkable rate performance (478.4 mAh g−1 at 2 A g−1) as well as prolonged cyclic stability (720.6 mAh g−1 at 0.2 A g−1 after 300 cycles). With a view to the eco‐friendly method and desirable lithium storage ability, our strategy may offer a new sight for the facile synthesis of Si‐based anode materials with great electrochemical performance.
Fracture behavior of metakaolin‐based geopolymer reinforced with carbon nanofibers
Authors: Akono Ange‐Therese
Published: June 2020

We investigate the fracture response of metakaolin‐based geopolymer reinforced with 0.1 wt%, 0.2 wt%, and 0.5 wt% carbon nanofibers. We measure the elastoplastic response using microindentation tests. We note an increase in indentation modulus of 5%, 13%, and 21%, and an increase in indentation hardness of 9%, 18%, and 25%, respectively. We measure the fracture energy using cutting‐edge microscopic fracture tests. In our tests, a sphero‐conical diamond indenter pushes across the specimen's surface under a prescribed vertical force. We analyze the recorded penetration depth and horizontal force using nonlinear fracture mechanics and extract the fracture parameters. We find that carbon nanofibers enhance fracture resistance. The fracture toughness increases by, respectively, 38%, 40%, and 45%; meanwhile, the fracture energy increases by, respectively, 83%, 72%, and 74%. We find that carbon nanofibers lead to a densification of the microstructure. Moreover, we observe crack‐bridging mechanisms in geopolymer nanocomposites. This study is important to pave the way for novel enhanced‐performance and multifunctional structural materials.
A Colorimetric Assay to Enable High‐Throughput Identification of Biofilm Exopolysaccharide‐Hydrolyzing Enzymes
Authors: Wang Shaochi , Breslawec Alexandra P. , Li Crystal , Poulin Myles B.
Published: June 2020

Glycosidase enzymes that hydrolyze the biofilm exopolysaccharide poly‐β‐(1→6)‐N‐acetylglucosamine (PNAG) are critical tools to study biofilm and potential therapeutic biofilm dispersal agents. Function‐driven metagenomic screening is a powerful approach for the discovery of new glycosidase but requires sensitive assays capable of distinguishing between the desired enzyme and functionally related enzymes. Herein, we report the synthesis of a colorimetric PNAG disaccharide analogue whose hydrolysis by PNAG glycosidases results in production of para‐nitroaniline that can be continuously monitored at 410 nm. The assay is specific for enzymes capable of hydrolyzing PNAG and not related β‐hexosaminidase enzymes with alternative glycosidic linkage specificities. This analogue enabled development of a continuous colorimetric assay for detection of PNAG hydrolyzing enzyme activity in crude E. coli cell lysates and suggests that this disaccharide probe will be critical for establishing the functional screening of metagenomic DNA libraries.
Concise Approach to T‐Shaped NBN‐Phenalene Cored Luminogens as Intensive Blue Light Emitters
Authors: Wang Xiaofeng , Sun Zuobang , Ding Kuangyu , Qiang Peirong , Zhu Wenqing , Han Sheng , Zhang Fan
Published: June 2020

Small organic molecules with finely tunable physical properties are highly desired for the fabrication of low‐cost and high‐performance organic electronic devices. In this work, the syntheses of a series of T‐shaped NBN‐embedded dibenzophenalene derivatives through the formation of a key brominated intermediate in a stoichiometrically controlled reaction are presented. The geometric and electronic structures of these T‐shaped molecules can be simply tailored by attaching substituents along the direction perpendicular to the molecular main backbones, resulting in desirable physical properties, such as high thermal stability with a decomposition temperature of more than 350 °C, and intensive blue luminescence with a quantum yield up to 0.62. Organic light‐emitting diode devices fabricated with such molecules as the emitting layer release pure blue light with CIE (0.16, 0.12).
Fluorine‐InducedPseudo‐Anomeric Effects in Methoxycyclohexanes through Electrostatic 1,3‐Diaxial Interactions
Authors: Piscelli Bruno A. , Sanders William , Yu Cihang , Al Maharik Nawaf , Lebl Thomas , Cormanich Rodrigo A. , O'Hagan David
Published: June 2020

We report counter‐intuitive axial preferences in non‐stereochemically biased, selectively fluorinated methoxycyclohexanes. These pseudo‐anomeric effects are apparent when electronegative CF2groups are placed at the C‐2, C‐4 and C‐6 positions of the cyclohexane ring to render the C‐3/5 axial hydrogen atoms electropositive. The electrostatic interaction between these axial hydrogen atoms and the ‐OMe oxygen is stabilising. The effect is explored using high‐level ab initio and DFT calculations in the framework of NBO, QTAIM and NCI analysis across a range of derivatives, and experimentally (19F{1H}‐NMR at −80 °C) for some illustrative examples. The effect is significant in energy terms for a weak interaction, and illustrates a new stereoelectronic aspect attributed to selective fluorine substitution in organic chemistry.
Light adaptation mechanisms in the eye of the fiddler crab Afruca tangeri
Authors: Brodrick Emelie A. , Roberts Nicholas W. , Sumner‐Rooney Lauren , Schlepütz Christian M. , How Martin J.
Published: June 2020

A great diversity of adaptations is found among animals with compound eyes and even closely related taxa can show variation in their light‐adaptation strategies. A prime example of a visual system evolved to function in specific light environments is the fiddler crab, used widely as a model to research aspects of crustacean vision and neural pathways. However, questions remain regarding how their eyes respond to the changes in brightness spanning many orders of magnitude, associated with their habitat and ecology. The fiddler crab Afruca tangeri forages at low tide on tropical and semi‐tropical mudflats, under bright sunlight and on moonless nights, suggesting that their eyes undergo effective light adaptation. Using synchrotron X‐ray tomography, light and transmission electron microscopy and in vivo ophthalmoscopy, we describe the ultrastructural changes in the eye between day and night. Dark adaptation at dusk triggered extensive widening of the rhabdoms and crystalline cone tips. This doubled the ommatidial acceptance angles and increased microvillar surface area for light capture in the rhabdom, theoretically boosting optical sensitivity 7.4 times. During daytime, only partial dark‐adaptation was achieved and rhabdoms remained narrow, indicating strong circadian control on the process. Bright light did not evoke changes in screening pigment distributions, suggesting a structural inability to adapt rapidly to the light level fluctuations frequently experienced when entering their burrow to escape predators. This should enable fiddler crabs to shelter for several minutes without undergoing significant dark‐adaptation, their vision remaining effectively adapted for predator detection when surfacing again in bright light.
Elucidating the Relationship between Multiradical Character and Predicted Singlet Fission Activity
Authors: Omar Ömer H. , Padula Daniele , Troisi Alessandro
Published: June 2020

The diradical and multiradical characters of a large and diverse set of 241 predicted singlet fission candidates are determined by multiconfigurational wavefunction methods, specifically natural orbital occupation number (NOON) analysis using the CASSCF method. The ascertained multiradical character strongly supports the current prediction that a good singlet fission candidate, independent of its structure, will tend to be of the weak biradicaloid class as well as having very little tetraradical character. Although the rule remains robust, it is not absolute as a small portion of our potential candidates are predicted to be closed shell. Additionally, a smaller handful of outliers with apparent tetraradical characters are identified, suggesting there may be the possibility, albeit rare, of singlet fission amongst weak tetraradicaloids.
Interfirm collaboration and corporate social responsibility expenditure in turbulent environments: The moderating role of entrepreneurial orientation
Authors: Adomako Samuel , Nguyen Nguyen Phong
Published: June 2020

This paper draws on the resource dependency theory to examine the impact of interfirm collaboration on corporate social responsibility (CSR) expenditure. In addition, we examine entrepreneurial orientation as a moderator of the relationship between interfirm collaboration and CSR expenditure. We test our research model using survey data from 230 small‐ and medium‐sized enterprises (SMEs) in Ghana. Results from our empirical analyses reveal that interfirm collaboration positively impacts CSR expenditure and this relationship is strengthened when entrepreneurial orientation is greater in turbulent environments. Implications for theory and practice are discussed.
MODY patients exhibit shorter telomere length than non‐diabetic subjects
Authors: Millan Andrea L. , Trobo Sofía I. , de Dios Alejandro , Cerrato García Martina , Pérez María S. , Cerrone Gloria E. , Frechtel Gustavo D. , López Ariel P.
Published: June 2020

Background

Given the increasing evidence supporting the association between telomere shortening and diabetes, the aim of the present work was to establish whether MODY patients suffer a reduction in telomere lenght (TL) due to oxidative stress produced by chronic hyperglycemia, despite not presenting insulin resistance or inflammation.

Methods

We analysed clinical and biochemical parameters in 35 MODY2 and 12 MODY3 patients compared with 48 control subjects. The absolute telomere length (aTL) of peripheral blood leukocytes was measured using the quantitative polymerase chain reaction (qPCR).

Results

A significant negative correlation was observed between aTL and age in the whole population, among MODY patients and in each subtype studied, MODY2 and MODY3, which allowed us to validate the method. We found, for the first time, that MODY patients have shorter aTL with respect to non‐diabetic controls (6.49 ± 3.31 kbp vs 11.13 ± 7.82 kbp, p = .006). However, no differences were found between MODY2 and MODY3. In addition, aTL showed a negative correlation with duration of the disease and fasting plasma glucose (FPG) levels in MODY patients in general and also with HbA1c in MODY2 patients in particular.

Conclusions

Both MODY2 and MODY3 types present telomere shortening, which, at least partly, responds to HbA1c and FPG levels. These findings suggest comparable mechanisms underlying the attrition of TL. Taken together, our results on aTL in MODY patients may provide a parameter relatively easy and inexpensive to quantify in order to measure the impact of high glucose levels and potentially carry out antidiabetic treatment with stricter targets.
The body size and temperature dependence of organismal locomotion
Authors: Cloyed Carl S. , Dell Anthony I.
Published: June 2020

The speed and maneuverability of organisms are central to their fitness, determining the strength and outcome of many species interactions that drive population and community‐level processes. While locomotion is influenced by many internal and external factors, body size and temperature are two key factors governing organismal locomotion. Biologists have been measuring locomotor performance, particularly maximum speed, for over a century. Studies have tended to focus on single species or groups of species that are either phylogenetically related, functionally similar, or use the same habitat. Few studies compare locomotor performance across a diverse range of taxa or locomotor modes, very few have incorporated locomotor traits other than maximum speed, and the data are not accessible in a single database with standardized units. Here, we present a data set we compiled from the literature that contains 2,951 measurements of locomotor performance for five traits (exploratory speed, maximum speed, maximum acceleration, minimum powered turn radius, and maximum angular speed) that are important in the daily lives of many organisms. This represents the most diverse and comprehensive database on animal locomotion yet published and includes 884 species spanning 23 orders of magnitude of body size. Together with body size (mass and length) and temperature (body and ambient), we also provide data on trophic group and habitat (aerial, terrestrial, aquatic). In publishing our data set, we hope to encourage others to contribute to a continued effort to build this locomotion database and to analyze these data for underlying patterns. Interspecific analyses can help elucidate how organismal locomotion varies with important morphological and physiological traits and environmental conditions, revealing generalities and deviations in organismal locomotion. Additionally, intraspecific analyses, which are possible for a number of species in our data set, can help corroborate these patterns and deviations and explore potential mechanisms that could underlie these patterns. Insights from these analyses should uncover drivers of locomotor performance and contribute to an understanding about how locomotion shapes ecological processes across scales. There are no copyright or proprietary restrictions, except this data paper should be cited when data are used for publication. In addition, we would appreciate hearing for which research projects or teaching exercises these data are used.
Can environmental DNA be used to detect first arrivals of the cane toad, Rhinella marina, into novel locations?
Authors: Villacorta‐Rath Cecilia , Adekunle Adeshina I. , Edmunds Richard C. , Strugnell Jan M. , Schwarzkopf Lin , Burrows Damien
Published: June 2020

Eradicating invasive species is difficult, but success is more likely when populations are small after arrival. The cane toad, Rhinella marina, is an invasive pest species that threatens native fauna worldwide. Increasingly, environmental DNA (eDNA) is used as a technique to monitor the presence of invasive species given its power to detect low numbers of individuals. We aimed to investigate eDNA persistence in freshwater at three different temperatures (25, 30 and 35°C) and eDNA detection thresholds for R. marina using controlled experiments in aquaria. For the latter, two water volumes and two cane toad exposure times were used (800 or 200 L volume with 5 or 30 min exposure). A 15‐ml water sample was collected from each replicated aquaria and preserved with 5 ml Longmire's buffer. Environmental DNA was extracted and four technical quantitative PCR replicates were analyzed targeting the cane toad 16S rDNA mitochondrial gene. Environmental DNA decayed rapidly in water and was reliably detected for up to 3 days after cane toad removal, regardless of the temperature treatment. Also, cane toad eDNA was detected in the water after a 5‐min initial exposure of a single individual in 800 L of water. Under the physical parameters tested here, a positive detection means that a cane toad has been in contact with the water body between 1 and 3 days prior to the sampling event. The results of the present study show the importance of eDNA for determining the presence of a species that occurs at low abundance in a small water body, such as at the onset of a cane toad invasion.
Prognostic nutritional index in elderly patients hospitalized for acute heart failure
Authors: Candeloro Matteo , Di Nisio Marcello , Balducci Martina , Genova Stefano , Valeriani Emanuele , Pierdomenico Sante Donato , Porreca Ettore
Published: June 2020

Aims

Acute heart failure (AHF) represents a frequent cause of hospitalization and is associated with significant mortality among elderly patients. Risk assessment models like the prognostic nutritional index (PNI) have been proposed to stratify the risk of death and identify patients requiring more intensive levels of care. We evaluated the predictive value of PNI for in‐hospital and overall mortality in a cohort of consecutive elderly patients hospitalized for AHF.

Methods and results

Prognostic nutritional index, laboratory, and clinical parameters were collected upon admission. PNI values were calculated from albumin concentration and lymphocyte count and reported on a continuous scale with lower values indicating worse prognosis. The primary outcome was overall all‐cause mortality defined as death from any cause occurring during hospitalization up to 6 months after discharge. Cox proportional regression analysis was used to calculate hazard ratios (HRs) and the relative 95% confidence intervals (CIs). The study population included 344 patients (median age 84 years, range 65 to 101). During a median follow‐up of 158 days (range 2 to 180 days), 75 patients (21.8%) died of whom 28 (8.1%) died during hospitalization. The median PNI was 34 (range 17 to 55). In univariable analysis, PNI was inversely associated with overall mortality (HR 0.90; 95% CI, 0.87 to 0.94) and in‐hospital mortality (HR 0.91; 95% CI, 0.85 to 0.98). In multivariable analysis, PNI remained a significant predictor of overall mortality (HR 0.93; 95% CI, 0.89 to 0.98) after adjustment for age, anaemia, NT‐proBNP values, and bedridden status. PNI values ≤34 were associated with a two‐fold higher risk of overall mortality (HR 2.54; 95% CI, 1.52 to 4.24) and three‐fold higher risk of in‐hospital mortality (HR 3.37; 95% CI, 1.14 to 9.95).

Conclusions

Low PNI values are associated with short‐term and long‐term mortality among elderly patients hospitalized for acute decompensated heart failure. Future studies are warranted to confirm these findings and evaluate the use of PNI to guide therapeutic decisions.
Circulating troponin and further left ventricular ejection fraction improvement in patients with previously recovered left ventricular ejection fraction
Authors: Howlett Jonathan G. , Sharma Nakul , Alemayehu Wendimagegn G. , Dyck Jason R.B. , Anderson Todd , Fine Nowell , Becker Harald , White James A. , Paterson D. Ian , Thompson Richard B. , Oudit Gavin Y. , Haykowsky Mark J. , Ezekowitz Justin A.
Published: June 2020

Aims

The aim of this study is to determine factors associated with long‐term recovery of left ventricular ejection fraction (LVEF) in patients with heart failure with reduced EF (HFrEF) and if further recovery also occurs in this group.

Methods and results

Among 621 participants enrolled in the Alberta Heart Failure Etiology and Analysis Team (HEART) Study, 316 with Stage C HF underwent comprehensive imaging and biomarker testing at enrolment and at 1‐year follow up. Using pre‐enrolment data, HF with recovered EF (HFrecEF) was defined as an absolute improvement ≥5% in LVEF from the prior lowest LVEF value, with a final LVEF value > 35% at or prior to study baseline. Participants with all LVEF > 40% were included for comparison. Hospitalization‐free survival to 5 years was performed.

The median cohort age was 66 years, and time from diagnosis was 4 years; 82% were male patients. Of the 316 patients, 95 (30%) patients had HFrecEF and 56 (18%) patients pHFrEF. On multivariate analysis, only shorter duration of HF was predictive of HFrecEF status. Over 1 year, LVEF increased in the HFrecEF group 4.0% (0.15–7.90, P = 0.042) as compared with persistent HFrEF, who in turn demonstrated higher baseline serum high sensitivity Troponin‐T with further increase at follow up 0.55(0.33–0.86, P = 0.011). No change in any parameter in the HFpEF/HFmrEF group at follow up was observed.

Conclusions

Patients with HFrecEF demonstrate evidence of additional late improvement in LVEF and unchanged troponin levels, in contrast to those with persistent HFrEF, where LVEF does not improve and serum troponin rises over time. These data help to inform mechanisms relating to late LV remodelling.
Pulmonary artery pressure‐guided therapy in ambulatory patients with symptomatic heart failure: the CardioMEMS European Monitoring Study for Heart Failure (MEMS‐HF)
Authors: Angermann Christiane E. , Assmus Birgit , Anker Stefan D. , Asselbergs Folkert W. , Brachmann Johannes , Brett Marie‐Elena , Brugts Jasper J. , Ertl Georg , Ginn Greg , Hilker Lutz , Koehler Friedrich , Rosenkranz Stephan , Zhou Qian , Adamson Philip B. , Böhm Michael ,   for the MEMS‐HF Investigators
Published: June 2020

Aims

Heart failure (HF) leads to repeat hospitalisations and reduces the duration and quality of life. Pulmonary artery pressure (PAP)‐guided HF management using the CardioMEMS™ HF system was shown to be safe and reduce HF hospitalisation (HFH) rates in New York Heart Association (NYHA) class III patients. However, these findings have not been replicated in health systems outside the United States. Therefore, the CardioMEMS European Monitoring Study for Heart Failure (MEMS‐HF) evaluated the safety, feasibility, and performance of this device in Germany, The Netherlands, and Ireland.

Methods and results

A total of 234 NYHA class III patients (68 ± 11 years, 22% female, ≥1 HFH in the preceding year) from 31 centres were implanted with a CardioMEMS sensor and underwent PAP‐guided HF management. One‐year rates of freedom from device‐ or system‐related complications and from sensor failure (co‐primary outcomes) were 98.3% [95% confidence interval (CI) 95.8–100.0] and 99.6% (95% CI 97.6–100.0), respectively. Survival rate was 86.2%. For the 12 months post‐ vs. pre‐implant, HFHs decreased by 62% (0.60 vs. 1.55 events/patient‐year; hazard ratio 0.38, 95% CI 0.31–0.48; P < 0.0001). After 12 months, mean PAP decreased by 5.1 ± 7.4 mmHg, Kansas City Cardiomyopathy Questionnaire (KCCQ) overall/clinical summary scores increased from 47.0 ± 24.0/51.2 ± 24.8 to 60.5 ± 24.3/62.4 ± 24.1 (P < 0.0001), and the 9‐item Patient Health Questionnaire sum score improved from 8.7 ± 5.9 to 6.3 ± 5.1 (P < 0.0001).

Conclusion

Haemodynamic‐guided HF management proved feasible and safe in the health systems of Germany, The Netherlands, and Ireland. Physician‐directed treatment modifications based on remotely obtained PAP values were associated with fewer HFH, sustainable PAP decreases, marked KCCQ improvements, and remission of depressive symptoms.
Risk of bias in studies investigating novel diagnostic biomarkers for heart failure with preserved ejection fraction. A systematic review
Authors: Henkens Michiel T.H.M. , Remmelzwaal Sharon , Robinson Emma L. , van Ballegooijen Adriana J. , Barandiarán Aizpurua Arantxa , Verdonschot Job A.J. , Raafs Anne G. , Weerts Jerremy , Hazebroek Mark R. , Sanders‐van Wijk Sandra , Handoko M. Louis , den Ruijter Hester M. , Lam Carolyn S.P. , de Boer Rudolf A. , Paulus Walter J. , van Empel Vanessa P.M. , Vos Rein , Brunner‐La Rocca Hans‐Peter , Beulens Joline W.J. , Heymans Stephane R.B.
Published: June 2020

Aim

Diagnosing heart failure with preserved ejection fraction (HFpEF) in the non‐acute setting remains challenging. Natriuretic peptides have limited value for this purpose, and a multitude of studies investigating novel diagnostic circulating biomarkers have not resulted in their implementation. This review aims to provide an overview of studies investigating novel circulating biomarkers for the diagnosis of HFpEF and determine their risk of bias (ROB).

Methods and results

A systematic literature search for studies investigating novel diagnostic HFpEF circulating biomarkers in humans was performed up until 21 April 2020. Those without diagnostic performance measures reported, or performed in an acute heart failure population were excluded, leading to a total of 28 studies. For each study, four reviewers determined the ROB within the QUADAS‐2 domains: patient selection, index test, reference standard, and flow and timing. At least one domain with a high ROB was present in all studies. Use of case‐control/two‐gated designs, exclusion of difficult‐to‐diagnose patients, absence of a pre‐specified cut‐off value for the index test without the performance of external validation, the use of inappropriate reference standards and unclear timing of the index test and/or reference standard were the main bias determinants. Due to the high ROB and different patient populations, no meta‐analysis was performed.

Conclusion

The majority of current diagnostic HFpEF biomarker studies have a high ROB, reducing the reproducibility and the potential for clinical care. Methodological well‐designed studies with a uniform reference diagnosis are urgently needed to determine the incremental value of circulating biomarkers for the diagnosis of HFpEF.
Synthesis, Crystal Structure, and DFT Study of Two New Dinuclear Copper(I) Complexes Bearing Ar‐BIAN Ligands Functionalized with NO2 Groups
Authors: Outis Mani , Rosa Vitor , Laia César A. T. , Lima João Carlos , Barroso Sónia , Carvalho Ana Luísa , Calhorda Maria José , Avilés Teresa
Published: June 2020

Two new bis(aryl‐imino)‐acenaphthene, Ar‐BIAN (Ar = 2,4,6‐trimethylphenyl = mes) ligands, bearing the NO2 group in the naphthalene moiety of the iminoacenaphthene at para‐ (5‐NO2) and meta‐ (4‐NO2) position, of formulations 1,2‐bis(mes‐imino)‐5‐nitroacenaphthene, 1, and 1,2‐bis(mes‐imino)‐4‐nitroacenaphthene, 2, were synthesized. Their respective dinuclear iodide bridged copper(I) complexes [Cu2(µ‐I)2(mes‐BIAN‐5‐NO2)2], 3 and [Cu2(µ‐I)2(mes‐BIAN‐4‐NO2)2], 4, were obtained in good yields by treatment with an equimolar amount of CuI. All compounds were characterized by elemental analysis, single‐crystal X‐ray diffraction, 1H‐NMR, 13C‐NMR, FTIR, UV/Vis spectroscopy. DFT calculations helped to understand the different molecular structure observed in the crystals of 3 and 4 and the determining role of packing forces. TDDFT revealed that the absorption bands in the visible were essentially MLCT (Metal to Ligand Charge Transfer), with some n→π* character (intra ligand). The shift to the red compared to the spectrum of the Cu(I) complex analogue without the NO2 group, [Cu2(µ‐I)2](mes‐BIAN)2], 6, could be explained by the stabilization of the ligand unoccupied π* orbitals in the presence of NO2.
Biometal Corrole Active Esters and Their Amino Acid and Peptide Conjugates
Authors: Oelmann Julian , Miller Reece G. , Baabe Dirk , Metzler‐Nolte Nils , Bröring Martin
Published: June 2020

The synthesis of a series of A2B‐corroles with 4‐carboxyphenyl substituent is described. The macrocycles are prepared from dipyrromethanes and 4‐formylbenzoic acid under Gryko conditions. Redox active biometal complexes are formed from the corrole carboxylic acids with the metal ions of cobalt, iron, and manganese, but not with copper. From all free corrole bases and metal complexes, the respective active esters are obtained in good yields by condensation with NHS (N‐hydroxysuccinimide) and EDC (1‐ethyl‐3‐dimethylaminopropyl‐carbodiimide). Starting from the active esters of the free corrole bases, the copper corroles are accessible in acceptable yields. Oxidation‐ and spin states of the biometal corroles correspond to those of simple corroles and are confirmed spectroscopically and magnetically. Ethylenediamine is efficiently coupled with the corrole carboxylic acids by EDC, whereby selective two‐fold coupling is observed. For the coupling to NαBoc‐lysine as well as NαFmoc‐lysine the use of corrole active esters is advantageous. The metalation of corroles carrying N‐protected lysine side chains turns out to proceed only with loss of most of the material. Here, the coupling of the amino acid building block with the metal corrole active ester proved to be the synthetically more applicable variant. The resulting NαFmoc‐lysine conjugates of both a free base corrole and a manganese corrole complex are shown to be suitable for use in Merrifield solid phase peptide synthesis.