bluuebunny/crossref_metadata_2025 huggingface dataset:
Conserved supersecondary structural motif in NAD‐dependent dehydrogenases
Authors: Kutzenko Alexey S , Lamzin Victor S , Popov Vladimir O
Published: July 2002

l‐ and d‐specific nicotinamide adenine dinucleotide (NAD)‐dependent dehydrogenases map to the same structural protein superfamily as defined by the Structural Classification of Proteins (SCOP) and are based on the Rossmann fold type domains. A detailed classification of these domains is proposed using a novel diagnostic parameter of the rms per aligned pair. The catalytic domain in d‐specific dehydrogenases shows a strong structural homology to the coenzyme binding domain. A topologically conserved part within the dehydrogenase superfamily reveals a supersecondary structural motif comprising the 5‐stranded left‐handedly twisted parallel β‐sheet with one complete and one partial Rossmann fold units and two α‐helices, the long helix, adjacent to and running roughly parallel with the β‐sheet plane and the helix connecting two Rossmann folds.
Heterologously overexpressed, affinity‐purified human meprin α is functionally active and cleaves components of the basement membrane in vitro
Authors: Köhler Danny , Kruse Markus-N. , Stöcker Walter , Sterchi Erwin E.
Published: July 2002

Meprins are astacin‐like metalloproteases of renal and intestinal epithelia and embryonic neuroepithelial cells. The full length cDNA of the human meprin α subunit has been overexpressed in baculovirus‐infected insect cells yielding the tetrameric proprotein which could be proteolytically activated and affinity‐purified to homogeneity. Recombinant meprin α hydrolyzes the synthetic substrate N‐benzoyl‐tyrosyl‐p‐aminobenzoic acid (PABA‐peptide) and cleaves by limited proteolysis the basement membrane constituents laminin 1 and laminin 5. This supports a concept that meprin α, when basolaterally secreted by human colon carcinoma epithelial cells, increases the proteolytic capacity for tumor progression in the stroma.
The potential of midwives providing primary obstetric care to reduce perinatal deaths in a rural region
Authors: Theron G.B
Published: July 2002

Objective: To determine the proportion of perinatal deaths that could be reduced by midwives providing primary obstetric services. Method: The study was conducted in a rural region of the Eastern Cape, South Africa. The primary obstetric and final causes of perinatal deaths and avoidable factors related to these deaths were determined in a large town and two small towns. Results: In the three towns 52 (48.6%) of the 107 avoidable factors were related to medical care while 20 (38.5%) of these had the potential to be prevented at the level of care rendered by midwives. In the large town 21 (20.6%) of 102 and in the smaller towns 15 (24.6%) of 61 perinatal deaths had potential for intervention by midwives. Conclusion: The 22.1% of perinatal deaths potentially preventable by midwives presupposes complete patient cooperation within an optimally functioning health system.
Endometrial histologic changes in post‐menopausal breast cancer patients using tamoxifen
Authors: Marchesoni D. , Driul L. , Fabiani G. , Di Loreto C. , Cataldi P. , Mozzanega B.
Published: July 2002

Objective: The aim of this study was to evaluate the effect of tamoxifen on the endometrium of post‐menopausal women with breast cancer and to examine the relationship between ultrasonography, hysteroscopy and histopathologic changes. Method: Included in this longitudinal study were 303 post‐menopausal women taking 20 mg daily of tamoxifen. Hysteroscopy was performed in 83 patients with an endometrial thickness of only ≥5 mm and 34 with vaginal bleeding also. Forty‐five asymptomatic patients (control group) underwent hysteroscopies. Result: The most frequent outcome in patients with endometrial thickness of only ≥5 mm was an atrophic endometrium in an empty cavity (79.5%) whereas simple hyperplasia (35.3%) was found in women with vaginal bleeding. Carcinoma was diagnosed in seven cases (5.9%). In the control group, no endometrial cancer was found. Conclusion: This study suggests that patients with a thickness >5 mm should be offered a whole hysteroscopic evaluation, whenever bleeding is reported.
Recommendations for renovating an operating theater at an emergency obstetric care facility
Authors: Abreu E , Potter D
Published: July 2002

The importance of emergency obstetric care (EmOC) in reducing maternal mortality has focused attention on both the skills of the clinicians to provide high quality care and on the health facilities in which the care is provided. Essential elements of EmOC include the capacity to perform cesarean sections for which an operating theater is needed. This article focuses on renovation of existing operating theaters to meet the necessary standards. While building, adding to, or renovating operating theaters can be expensive, this article emphasizes appropriate materials that are likely to be locally available and relatively inexpensive. The importance of proper maintenance is discussed.
China's inter-provincial disparities An explanation
Authors: Duncan Ron , Tian Xiaowen
Published: July 2002

China's inter-provincial output and livelihood disparities moved in different directions in the pre-reform and the reform periods. This paper sets out to identify the driving forces behind these developments. It suggests that in the transition to a market system, China has succeeded in narrowing inter-provincial output disparities by pursuing outward-looking and de-nationalisation oriented industrialisation, but has failed to prevent a widening of inter-provincial livelihood disparities owing to the weakening of government intervention in the form of regional income redistribution.
Manipulating the Local Electronic Structure in Li‐Rich Layered Cathode Towards Superior Electrochemical Performance
Authors: Zheng Hongfei , Zhang Chenying , Zhang Yinggan , Lin Liang , Liu Pengfei , Wang Laisen , Wei Qiulong , Lin Jie , Sa Baisheng , Xie Qingshui , Peng Dong‐Liang
Published: May 2021

Manipulating the local electronic structure is employed to address the capacity/voltage decay and poor rate capability of Li‐rich layered cathodes (LLOs) via the dual‐doping of Na+ and F− ions, as well as the regulation of Li+/Ni2+ intermixing and the content of “LiOLi” configuration. The designed cathode exhibits a high initial Coulombic efficiency of about 90%, large specific capacity of 296 mAh g−1 and energy density of 1047 Wh kg−1 at 0.2 C, and a superior rate capability of 222 mAh g−1 at 5 C with a good capacity retention of 85.7% even after 500 cycles. And the operating voltage is increased without compromising the high‐capacity advantage. Such improved electrochemical performances primarily result from the band shift of the TM 3d‐O 2p and non‐bonding O‐2p to lower energy, which would decrease Li+ diffusion activation energy and increase oxygen vacancy forming energy, finally improving the Li+ diffusion kinetics and stabilizing lattice oxygen. Moreover, the increased “LiOLi” configuration in the Li2MnO3 phase via increasing the Mn concentration can increase the reversible capacity to offset the negative effect of inactive doping and Li+/Ni2+ intermixing. This strategy of modulating the local electronic structure of LLOs provides great potential to design high‐energy‐density Li‐ion batteries.
Mechanically Robust and UV‐Curable Shape‐Memory Polymers for Digital Light Processing Based 4D Printing
Authors: Zhang Biao , Li Honggeng , Cheng Jianxiang , Ye Haitao , Sakhaei Amir Hosein , Yuan Chao , Rao Ping , Zhang Yuan‐Fang , Chen Zhe , Wang Rong , He Xiangnan , Liu Ji , Xiao Rui , Qu Shaoxing , Ge Qi
Published: May 2021

4D printing is an emerging fabrication technology that enables 3D printed structures to change configuration over “time” in response to an environmental stimulus. Compared with other soft active materials used for 4D printing, shape‐memory polymers (SMPs) have higher stiffness, and are compatible with various 3D printing technologies. Among them, ultraviolet (UV)‐curable SMPs are compatible with Digital Light Processing (DLP)‐based 3D printing to fabricate SMP‐based structures with complex geometry and high‐resolution. However, UV‐curable SMPs have limitations in terms of mechanical performance, which significantly constrains their application ranges. Here, a mechanically robust and UV‐curable SMP system is reported, which is highly deformable, fatigue resistant, and compatible with DLP‐based 3D printing, to fabricate high‐resolution (up to 2 µm), highly complex 3D structures that exhibit large shape change (up to 1240%) upon heating. More importantly, the developed SMP system exhibits excellent fatigue resistance and can be repeatedly loaded more than 10 000 times. The development of the mechanically robust and UV‐curable SMPs significantly improves the mechanical performance of the SMP‐based 4D printing structures, which allows them to be applied to engineering applications such as aerospace, smart furniture, and soft robots.
Designing Ion‐Selective Membranes for Vanadium Redox Flow Batteries
Authors: Amiri Hamid , Khosravi Mohsen , Ejeian Mojtaba , Razmjou Amir
Published: May 2021

It is predicted that the future of energy will mainly rely on batteries such as vanadium redox flow batteries (VRFBs), and its related research has already attracted significant attention. The primary function of a membrane in VRFBs is to control proton transport between the half‐cells and to hinder admixing the anolyte and catholyte at the same time. However, to develop a low‐cost and energy‐efficient VRFB, other membrane roles are crucial. The combination of a highly stable backbone of polytetrafluoroethylene with hydrophilic perfluorinated‐vinyl‐polyether side chains equipped with sulfonic acid groups (Nafion membranes) has led to a breakthrough in the field. However, suffering from high cost and low selectivity, these perflurinated membranes are not properly qualified for VRFBs. Sulfonation of aromatic hydrocarbon polymers is suggested as cost‐effective alternative chemistry for VRFBs’ membrane design. Further tunning the performance of the membrane and VRFB is obtained through designing their microstructure by different tools, especially adjusting the degree of sulfonation and degree of branching, utilizing additional membrane layers, and incorporation of particles in the polymer matrix. In this review, the studies performed to develop membranes for VRFBs are discussed as a road map for the development of advanced membranes qualified for VRFBs.
Emerging Biomedical Applications of Organic Light‐Emitting Diodes
Authors: Murawski Caroline , Gather Malte C.
Published: May 2021

As solid‐state light sources based on amorphous organic semiconductors, organic light‐emitting diodes (OLEDs) are widely used in modern smartphone displays and TVs. Due to the dramatic improvements in stability, efficiency, and brightness achieved over the last three decades, OLEDs have also become attractive light sources for compact and “imperceptible” biomedical devices that use light to probe, image, manipulate, or treat biological matter. The inherent mechanical flexibility of OLEDs and their compatibility with a wide range of substrates and geometries are of particular benefit in this context. Here, recent progress in the development and use of OLEDs for biomedical applications is reviewed. The specific requirements that this poses are described and compared to the current state of the art, in particular in terms of the brightness, patterning, stability, and encapsulation of OLEDs. Examples from several main areas are then discussed in some detail: on‐chip sensing and integration with microfluidics, wearable devices for optical monitoring, therapeutic devices, and the emerging use in neuroscience for targeted photostimulation via optogenetics. The review closes with a brief outlook on future avenues to scale the manufacturing of OLED‐based devices for biomedical use.
The antidiabetic potential of endophytic fungi: Future prospects as therapeutic agents
Authors: Agrawal Shivankar , Samanta Sreeparna , Deshmukh Sunil Kumar
Published: May 2021

Diabetes mellitus is one of the most common systemic diseases in the world, and it occurs when the body becomes resistant to insulin or does not make enough insulin. As described by the World Health Organization, diabetes mellitus of all types has exponentially grown in the past decades across the globe and it is estimated to be 629 million by 2045. Despite this alarming prevalence of diabetes mellitus, there is still the lack of harmless preventive medicines. Natural products and compounds obtained from plants, fungi, bacteria, and other living organisms have been used for many decades in folklore medicine to prepare a varied range of natural formulations to treat multiple diseases and illnesses. Endophytic fungi reside inside the plant while causing no harm to the host plant and are relatively less explored as the primary source for the bioactive metabolites such as anticancer, antioxidant, antimicrobial, antidiabetic, and industrial enzymes. This mini‐review summarizes the potential of compounds and extracts from endophytic fungi against diabetes mellitus. Not much research has been dedicated in‐depth understanding of the role of extracts of endophytic fungi and their effect on diabetes mellitus. Therefore, this article will focus on recent work and warrant further commentaries on the published articles.
Candesartan and carvedilol for primary prevention of subclinical cardiotoxicity in breast cancer patients without a cardiovascular risk treated with doxorubicin
Authors: Lee Myunhee , Chung Woo‐Baek , Lee Ji‐eun , Park Chan‐Seok , Park Woo‐Chan , Song Byung‐Joo , Youn Ho‐Joong
Published: May 2021

Background

There is no proven primary preventive strategy for doxorubicin‐induced subclinical cardiotoxicity (DISC), especially among patients without a cardiovascular (CV) risk. We investigated the primary preventive effect on DISC of the concomitant use of angiotensin receptor blockers (ARBs) or beta‐blockers (BBs), especially among breast cancer patients without a CV risk.

Methods

A total of 385 patients who were scheduled for doxorubicin chemotherapy were screened. Among them, 195 patients of the study populations were included and were randomly divided into two groups [candesartan 4 mg q.d. vs. carvedilol 3.125 mg q.d.] and patients who were unwilling to take one of the medications were evaluated as controls. The primary outcomes were the incidence of early DISC (DISC developing within 6 months after chemotherapy), and late DISC (DISC developing only at least 12 months after chemotherapy).

Result

Compared with the control group (8 out of 43 patients (18.6%)), only the candesartan group (4 out of 82 patients (4.9%)) showed a significantly lower incidence of early DISC (p = 0.022). Compared with the control group, the candesartan group demonstrated a significantly reduced decrease in left ventricular ejection fraction (LVEF) throughout the study period [−1.0% vs. −3.00 (p < 0.001) at the first follow‐up, −1.10% vs. −3.40(p = 0.009) at the second follow‐up].

Conclusions

Among breast cancer patients without a CV risk treated with doxorubicin‐containing chemotherapy, subclinical cardiotoxicity is prevalent and concomitant administration of low‐dose candesartan might be effective to prevent an early decrease in LVEF. Further large‐scale, randomized controlled trials will be needed to confirm our findings.
Effects of Oxygen Vacancy and Pt Doping on the Catalytic Performance of CeO2 in Propane Dehydrogenation: A First‐Principles Study
Authors: Zeeshan Muhammad , Chang Qing‐Yu , Zhang Jun , Hu Ping , Sui Zhi‐Jun , Zhou Xing‐Gui , Chen De , Zhu Yi‐An
Published: May 2021

Main observation and conclusion

The catalytic properties of the CeO2 catalyst for propane dehydrogenation (PDH) are examined by employing the density functional theory calculations. Surface modifications and their effects on the surface reactivity are explored by creating the oxygen vacancy and single Pt atom doping. A comparative study between the binding energies of the different PDH reaction species reveals a considerable Lewis acid‐base interaction over the pristine and defective surfaces, which dominantly strengthens the bond formation between the adsorbates and the catalyst surface, resulting in the enhancement of surface reactivity. The creation of oxygen vacancy and doping the CeO2(111) surface with single Pt atoms changes the charge distribution over the surface on account of excess 4f electrons. This electronic change increases the bond formation abilities of the inactive Ce atom and hence increases the adsorption strength. Oxygen vacancy in the defective CeO2(111) surface migrates over the surface with the addition of an appropriate adsorbate. Moreover, it is revealed that the propylene is more strongly adsorbed on the single‐Pt‐atom‐doped CeO2(111) surface than the pristine and defective surfaces, which decreases the deep dehydrogenation energy barrier and ultimately results in the lowering of the selectivity.
Co‐MOF Nanosheet Arrays for Efficient Alkaline Oxygen Evolution Electrocatalysis
Authors: Yu Jin , Cao Yang , Liu Qian , Luo Yonglan , Liu Yang , Shi Xifeng , Asiri Abdullah M. , Li Tingshuai , Sun Xuping
Published: May 2021

It's highly desirable to devise and develop non‐precious metal catalysts for efficient water oxidation catalysis in alkaline solution. Herein, we report Co‐MOF nanosheet arrays grown on the three dimensional conductive nickel foam (Co‐MOF/NF) through a hydro‐thermal process for efficient alkaline oxygen evolution electrocatalysis. Such catalyst displays an excellent electrochemical performance by achieving an overpotential of 290 mV at 20 mA cm−2 in 1.0 M KOH. Besides, it possesses both a good electrochemical stability and a high turnover frequency of 0.14 s−1 at the overpotential of 400 mV.
A 3D‐Printed Open Access Photoreactor Designed for Versatile Applications in Photoredox‐ and Photoelectrochemical Synthesis
Authors: Schiel Florian , Peinsipp Christoph , Kornigg Stefan , Böse Dietrich
Published: May 2021

The front cover artwork is provided by the medicinal chemistry department at Boehringer Ingelheim RCV (Austria). The image shows the 3D‐printed photoreactor, which releases the product of an sp2–sp3 cross‐electrophile coupling reaction. Read the full text of the Article at 10.1002/cptc.2020000291.
Dynamics of antibodies to SARS‐CoV‐2 in convalescent plasma donors
Authors: Steenhuis Maurice , van Mierlo Gerard , Derksen Ninotska IL , Ooijevaar‐de Heer Pleuni , Kruithof Simone , Loeff Floris L , Berkhout Lea C , Linty Federica , Reusken Chantal , Reimerink Johan , Hogema Boris , Zaaijer Hans , van de Watering Leo , Swaneveld Francis , van Gils Marit J , Bosch Berend Jan , van Ham S Marieke , ten Brinke Anja , Vidarsson Gestur , van der Schoot Ellen C , Rispens Theo
Published: May 2021

Objectives

Characterisation of the human antibody response to SARS‐CoV‐2 infection is vital for serosurveillance purposes and for treatment options such as transfusion with convalescent plasma or immunoglobulin products derived from convalescent plasma. In this study, we longitudinally and quantitatively analysed antibody responses in RT‐PCR‐positive SARS‐CoV‐2 convalescent adults during the first 250 days after onset of symptoms.

Methods

We measured antibody responses to the receptor‐binding domain (RBD) of the SARS‐CoV‐2 spike protein and the nucleocapsid protein in 844 longitudinal samples from 151 RT‐PCR‐positive SARS‐CoV‐2 convalescent adults. With a median of 5 (range 2–18) samples per individual, this allowed quantitative analysis of individual longitudinal antibody profiles. Kinetic profiles were analysed by mixed‐effects modelling.

Results

All donors were seropositive at the first sampling moment, and only one donor seroreverted during follow‐up analysis. Anti‐RBD IgG and anti‐nucleocapsid IgG levels declined with median half‐lives of 62 and 59 days, respectively, 2–5 months after symptom onset, and several‐fold variation in half‐lives of individuals was observed. The rate of decline of antibody levels diminished during extended follow‐up, which points towards long‐term immunological memory. The magnitude of the anti‐RBD IgG response correlated well with neutralisation capacity measured in a classic plaque reduction assay and in an in‐house developed competitive assay.

Conclusion

The result of this study gives valuable insight into the long‐term longitudinal response of antibodies to SARS‐CoV‐2.
College student attitudes and strategies for intervention with a hypothetical peer exhibiting disordered eating
Authors: Sangiorgio Celeste , Blackstone Sarah R. , Herrmann Lynn K.
Published: May 2021

Objective

The present study assesses stigma, attitudes, and strategies of college students in intervening with peers demonstrating disordered eating behaviors.

Method

Four hundred and eighty nine college students (384 women) completed questionnaires that assessed eating disorder symptoms and bystander attitudes adapted for disordered eating. Participants read one of three vignettes of a 20‐year‐old hypothetical peer displaying symptoms of disordered eating aligned with bulimia nervosa, anorexia nervosa, or binge‐eating disorder; participants then described whether the vignette subject had a problem, what the problem was, and strategies for intervention. Relationships among eating disorder history, bystander attitudes, demographics, and intention to intervene in disordered eating were assessed using descriptive and regressive analyses; peer intervention strategies were organized and evaluated for frequencies of responses.

Results

Demographics (female‐identification) and familiarity with disordered eating were associated with likelihood to intervene in disordered eating. Most students recognized that the peer had a problem, but fewer than half believed the problem was disordered eating; nearly a quarter (22%) of the students stated that they would be uncomfortable talking to a peer about disordered eating. The majority of students cited vague or nonproblem‐related intervention strategies (62%), followed by emotion‐focused strategies (22.5%), or body and behavior‐focused strategies (15%).

Discussion

College students, particularly women and those with previous exposure to eating disorders, are likely to intervene peers disordered eating. However, students tend to use vague or body‐focused intervention strategies. Bystander intervention training that provides rationale and rehearsal for supportive communication strategies is needed to address students' lack of intervention skills, particularly among men.
Elevational gradients strongly mediate habitat selection patterns in a nocturnal predator
Authors: Kramer H. Anu , Jones Gavin M. , Kane Van R. , Bartl‐Geller Bryce , Kane Jonathan T. , Whitmore Sheila A. , Berigan William J. , Dotters Brian P. , Roberts Kevin N. , Sawyer Sarah C. , Keane John J. , North Malcolm P. , GutiÉrrez R. J. , Peery M. Zachariah
Published: May 2021

Mountain ecosystems contain strong elevational gradients in climate and vegetation that shape species distributions and the structure of animal communities. Nevertheless, studies of habitat selection for individual species rarely account for such gradients that often result in species being managed uniformly across their range, which may not improve conservation as intended. Therefore, we characterized variation in nocturnal habitat selection by 18 GPS‐tagged California spotted owls (Strix occidentalis occidentalis) along a 1400‐m elevational gradient in the Sierra Nevada, California. We characterized three‐dimensional forest structure with light detection and ranging data that we used in mixed‐effects resource‐ and step‐selection analyses of owl habitat selection. At lower elevations, owls selected stands with shorter trees, sites closer to hard edges between tall forests and open areas, sites with less diversity in forest seral types and sites with more ridge and southwest aspects. In contrast, owls at higher elevations selected the opposite. Within public forests that had taller trees and within their home range core (45% kernel density estimate of GPS points) areas, owls selected forests with less and more canopy cover at low and high elevations, respectively. Outside of their core areas, owls selected areas with fewer and more tall trees at low and high elevations, respectively. These findings may be explained by elevational gradients in prey distribution and variation in owl diet because owls consume more woodrats (Neotoma spp; earlier seral species) at lower elevations and more flying squirrels (Glaucomys sabrinus; older forest species) at higher elevations. Thus, at low elevations and in areas unlikely to support nesting, spotted owls could benefit from management that promotes woodrat habitat by encouraging oak regeneration and creating small brushy openings within forests with shorter (younger) trees. Conversely, at higher elevations, (1) enhancing flying squirrel habitat by promoting large trees and denser canopy on mesic sites and (2) managing for greater cover type diversity on southwest‐facing slopes and ridgetops is more likely to improve foraging habitat quality for spotted owls. The patterns of owl selection over elevational gradients has not been explicitly considered in most habitat management plans but clearly would improve management throughout mountain ecosystems.
Association between up‐titration of medical therapy and total hospitalizations and mortality in patients with recent worsening heart failure across the ejection fraction spectrum
Authors: Bistola Vasiliki , Simitsis Panagiotis , Parissis John , Ouwerkerk Wouter , van Veldhuisen Dirk J. , Cleland John G. , Anker Stefan D. , Samani Nilesh J. , Metra Marco , Zannad Faiez , Polyzogopoulou Eftihia , Keramida Kalliopi , Farmakis Dimitrios , Voors Adriaan A. , Filippatos Gerasimos
Published: May 2021

Background

The role of neurohormonal inhibition in chronic heart failure (HF) is well established. There are limited data on the effect of up‐titration of renin–angiotensin inhibitors (RASi) and beta‐blockers (BBs) on clinical outcomes of patients with worsening HF across the left ventricular ejection fraction (LVEF) spectrum.

Methods and results

We analysed data from 2345 patients from BIOSTAT‐CHF (80.9% LVEF <40%), who completed a 3‐month up‐titration period after recent worsening of HF. Patients were classified by achieved dose (% of recommended): ≥100%, 50–99%, 1–49%, and none. Recurrent event analysis using joint and shared frailty models was used to examine the association between RASi/BB dose and all‐cause and HF hospitalizations. In the 21 months following up‐titration, 512 patients died and 879 (37.5%) had ≥1 hospitalization. RASi up‐titration was associated, incrementally, with reduced risk of all‐cause hospitalization at all achieved dose levels compared to no treatment [hazard ratio (95% confidence interval): ≥100%: 0.60 (0.49–0.74), P < 0.001; 50–99%: 0.56 (0.46–0.68), P < 0.001; 1–49%: 0.71 (0.59–0.86), P < 0.001]. This association was consistent up to an LVEF of 49% (P < 0.001), and when considering only HF hospitalizations. Up‐titration of BBs was associated with fewer all‐cause hospitalizations only when LVEF was <40% (overall P < 0.001), but with more HF hospitalizations when LVEF was ≥50%. Up‐titration of both RASi/BBs was associated with lower mortality in LVEF up to 49%.

Conclusion

After recent worsening of HF, up‐titration of RASi and BBs was associated with a better prognosis in patients with LVEF ≤49%. Up‐titration of BBs was associated with a greater risk of HF hospitalization when LVEF was ≥50%.
Renal function and the effects of vericiguat in patients with worsening heart failure with reduced ejection fraction: insights from the VICTORIA (Vericiguat Global Study in Subjects with HFrEF) trial
Authors: Voors Adriaan A. , Mulder Hillary , Reyes Eugene , Cowie Martin R. , Lassus Johan , Hernandez Adrian F. , Ezekowitz Justin A. , Butler Javed , O'Connor Christopher M. , Koglin Joerg , Lam Carolyn S.P. , Pieske Burkert , Roessig Lothar , Ponikowski Piotr , Anstrom Kevin J. , Armstrong Paul W. ,   for the VICTORIA Study Group
Published: May 2021

Aims

Vericiguat reduced the primary composite outcome of cardiovascular death or heart failure (HF) hospitalization in patients with worsening HF with reduced ejection fraction (HFrEF) and a lower limit of baseline estimated glomerular filtration rate (eGFR) of 15 mL/min/1.73 m2. We evaluated the relationship between the efficacy of vericiguat and baseline and subsequent changes in renal function.

Methods and results

In VICTORIA, core laboratory serum creatinine was measured at baseline (n = 4956) and weeks 16, 32, and 48. Worsening renal function (WRF), defined as an increase ≥0.3 mg/dL in creatinine from baseline to week 16, was assessed via a Cox model with respect to subsequent primary events. Mean age was 69 years, 24% were female, and mean baseline eGFR was 61 mL/min/1.73 m2. During 48 weeks of treatment, the trajectories in eGFR and creatinine with vericiguat were similar to placebo (P = 0.50 and 0.18). The beneficial effects of vericiguat on the primary outcome were not influenced by baseline eGFR (interaction P = 0.48). WRF occurred in 15% of patients and was associated with worse outcomes (adjusted hazard ratio 1.28, 95% confidence interval 1.11–1.47; P < 0.001), but the beneficial effects of vericiguat on the primary outcome were similar in patients with or without WRF (interaction P = 0.76).

Conclusion

Renal function trajectories were similar between vericiguat‐ and placebo‐treated patients and the beneficial effects of vericiguat on the primary outcome were consistent across the full range of eGFR and irrespective of WRF.
Combining Organocatalyzed Aldolization and Reductive Amination: An Efficient Reaction Sequence for the Synthesis of Iminosugars
Authors: Ferjancic Zorana , Saicic Radomir N.
Published: May 2021

Over the past two decades, organocatalytic aldol reaction emerged as a powerful method for the enantioselective carbon–carbon bond formation, often offering more efficient, economical and environmentally friendly synthesis of chiral molecules. On the other hand, reductive amination is one of the most important reactions in synthesis of biologically active compounds and drug candidates. Coupling these two reactions results in a powerful combination that allows for a rapid, stereoselective access to substituted, highly functionalized five‐ and six‐membered N‐heterocycles. This minireview illustrates the applicability of this approach as the key feature in syntheses of various iminosugars – a class of polyhydroxylated alkaloids with a range of interesting biological activities and high pharmacological potential.
Recent Visible Light and Metal Free Strategies in [2+2] and [4+2] Photocycloadditions
Authors: Sicignano Marina , Rodríguez Ricardo I. , Alemán José
Published: May 2021

When aiming to synthesize molecules with elevated molecular complexity starting from relatively simple starting materials, photochemical transformations represent an open avenue to circumvent analogous multistep procedures. Specifically, light‐mediated cycloadditions remain as powerful tools to generate new bonds begotten from non‐very intuitive disconnections, that alternative thermal protocols would not offer. In response to the current trend in both industrial and academic research pointing towards green and sustainable processes, several strategies that meet these requirements are currently available in the literature. This Minireview summarizes [2+2] and [4+2] photocycloadditions that do not require the use of metal photocatalysts by means of alternative strategies. It is segmented according to the cycloaddition type in order to give the reader a friendly approach and we primarily focus on the most recent developments in the field carried out using visible light, a general overview of the mechanism in each case is offered as well.
Financial hedging and operational flexibility as instruments to manage exchange‐rate uncertainty in multinational corporations
Authors: Fisch Jan Hendrik , Puhr Harald
Published: May 2021

Research Summary

Literature that compares the advantages of financial hedging and operational flexibility as instruments to manage exchange‐rate uncertainty presents inconsistent results. This study addresses such inconsistencies in two ways. First, it clarifies that the effects of financial hedging and operational flexibility are asymmetric. Financial hedging helps an MNC to reduce a negative effect of exchange‐rate uncertainty on firm value, whereas operational flexibility allows an MNC to enhance a positive effect of exchange‐rate uncertainty on firm value. Second, the study demonstrates that these effects are contextual to the MNC's subsidiary network. Depending on whether exchange‐rate correlation in the subsidiary network is positive or negative, either financial hedging or operational flexibility is more effective than the other. Regressions on a sample of U.S. manufacturing firms support the predictions.

Managerial Summary

Multinational corporations face exchange‐rate fluctuations in their subsidiary networks as a source of substantial uncertainty. MNCs can manage this uncertainty using financial hedging and operational flexibility. However, the literature is inconclusive on whether MNCs can use both instruments in equal measure. This study clarifies that financial hedging allows MNCs to limit negative consequences of exchange‐rate uncertainty on their stock‐market valuations. Operational flexibility, by contrast, gives MNCs the opportunity to exploit exchange‐rate uncertainty and thereby to enhance their firm value. In addition, the study proposes that the effectiveness of financial hedging and operational flexibility depends on the individual MNC's subsidiary network configuration. Based on these findings, MNCs can identify the effective instrument for managing exchange‐rate uncertainty.
Does women's board representation affect non‐managerial gender inequality?
Authors: Biswas Pallab Kumar , Roberts Helen , Stainback Kevin
Published: May 2021

Research examining gender and corporate boards has explored how women's representation impacts firm strategy and policy, particularly around corporate social responsibility (CSR) issues related to communities and other relevant stakeholders, the environment, and diversity and equity initiatives. However, fewer studies have examined how women's representation on boards affects gender inequality in firms. The studies that have been conducted generally focus on gender board diversity and the appointment of women executives. Yet, prior research has not sufficiently examined women's board representation and gender equality below executive level. Does women's representation have broader effects on gender equity beyond top leadership? And if so, is there a critical mass effect? In this article, we examine the relationship between women's board representation and non‐managerial gender segregation. Gender segregation is an ideal measure of gender equality given that it captures the evenness of the distribution of women and men across jobs within workplaces and its well‐known relationship to gender disparities in earnings and other job rewards. Drawing on Australian organization data (2014–2019) we find that the contemporaneous relationship between women's board representation and gender segregation is nonsignificant, but becomes significant and increases in magnitude with 1, 2, and 3‐year lags. Our critical mass analysis suggests that having one woman on a board may not be enough to promote change but rather two or more women directors, or holding 20% or more board seats, appears to be more effective in reducing gender segregation. These findings demonstrate that the appointment of more women to corporate boards has broader effects on workplace gender equity beyond top leadership teams.
Cyclization Strategies for the Concurrent Installation of Multiple Quaternary Stereogenic Centers
Authors: Alachouzos Georgios , Frontier Alison J.
Published: May 2021

In this review we highlight the general cyclization strategies currently available to organic chemists for the concurrent and stereoselective installation of multiple Quaternary Stereogenic Centers (QSC) atoms in cyclic or polycyclic architectures. QSCs embedded in rigid cyclic architectures are motifs found in many blockbuster drugs and important bioactive natural product classes, and yet, direct access to these structures stereoselectively from simple precursors remains a significant challenge. Underscoring the difficulty associated with their synthesis, such topologically three‐dimensional molecules are underrepresented in existing small molecule compound libraries, which are instead dominated by linear or flat molecules. This review focuses on methods disclosed in both natural product synthesis and methodology studies since the turn of the 21st century. The cases to be examined successfully achieve these challenging transformations: (1) one‐step assembly of the cyclized architecture; and (2) concurrent stereoselective installation of multiple (≥2) new QSCs. These cyclization strategies, which address the aforementioned fundamental challenges in complex molecule synthesis, have been categorized into five broad groups: i) Biomimetic Polyene Cyclization Cascades; ii) Cyclization Cascades of Prochiral Alkenes; iii) Cycloadditions; iv) Dearomatizations; v) Electrocyclizations.
Effect of ranolazine on Tp‐e interval, Tp‐e/QTc, and P‐wave dispersion in patients with stable coronary artery disease
Authors: Akcay Murat , Coksevim Metin , Yenercag Mustafa
Published: May 2021

Introduction

Ranolazine is an antianginal drug and also exhibits antiarrhythmic effect by affecting action potential time, refractory period, and repolarization reserve. We evaluated the effect of ranolazine therapy on myocardial repolarization parameters (Tp‐e, QT, QTc intervals, Tp‐e/QT, and Tp‐e/QTc ratios), index of cardiac electrophysiological balance (iCEB) (QT/QRS, QTc/QRS) and P‐wave dispersion (PWD) in patients with stable coronary artery disease (CAD).

Methods

This study included 175 patients, aged between 35 and 90 years who were followed with stable CAD for at least 3 months. Ninety patients had been receiving ranolazine for at least 1 month, and 85 patients had never received ranolazine. All patients' basic demographic data, risk factors, medications, and echocardiographic parameters recorded. Myocardial repolarization parameters, P‐wave times, and PWD were analyzed from 12 lead electrodes.

Results

There was no variation between the groups in terms of basic demographic parameters and CAD risk factors. Tp‐e interval (87.3 ± 14.4 vs. 90.8 ± 12.4 msn, P < .001), Tp‐e/QT (0.22 ± 0.04 vs. 0.23 ± 0.03; P = .03), Tp‐e/QTc (0.21 ± 0.04 vs. 0.22 ± 0.04 P = .001), and PWD (39.2 ± 13.7 vs. 43.5 ± 12.9 P = .028) were significantly lower in the ranolazine group. But iCEB was similar in both groups. In multivariate analysis after adjusted confounding factors such as age and BMI, Tp‐e/QTc ratio, QTc, Pmax, and PWD were found significantly in ranolazine group again.

Conclusion

Tp‐e/QTc ratio, QTc, Pmax, and PWD were significantly lower in stable CAD patients under ranolazine therapy. In stable CAD patients, the prognostic significance of ranolazine for arrhythmic events requires further evaluation of these parameters through long‐term follow‐up and large‐scale prospective studies.
Contribution to determination of extracellular DNA origin in the biofilm matrix
Authors: Svarcova Viviana , Zdenkova Kamila , Sulakova Martina , Demnerova Katerina , Pazlarova Jarmila
Published: May 2021

This study is focused on the analysis of extracellular DNA (eDNA) from a biofilm matrix formed by Staphylococcus aureus, Listeria monocytogenes, and Salmonella enterica. The presence of eDNA in the biofilm of all the studied strains was confirmed by confocal laser scanning microscopy using fluorescent dyes with high affinity to nucleic acid. The protocol for eDNA isolation from the biofilm matrix was established, and subsequent characterization of the eDNA was performed. The purified eDNA obtained from the biofilm matrix of all three microorganisms was compared to the genomic DNA (gDNA) isolated from relevant planktonic grown cells. The process of eDNA isolation consisted of biofilm cultivation, its collection, sonication, membrane filtration, dialysis, lyophilisation, and extraction of DNA separated from the biofilm matrix with cetyltrimethylammonium bromide. An amplified fragment length polymorphism (AFLP) was used for comparing eDNA and gDNA. AFLP profiles showed a significant similarity between eDNA and gDNA at the strain level. The highest similarity, with a profile concordance rate of 94.7% per strain, was observed for S. aureus, L. monocytogenes, and S. enterica exhibited lower profiles similarity (78% and 60%, respectively). The obtained results support the hypothesis that the eDNA of studied bacterial species has its origin in the gDNA.
Patients’ illness perception before and after non‐surgical periodontal therapy: A pre‐post quasi‐experimental study
Authors: Discepoli Nicola , Marruganti Crystal , Mirra Raffaele , Pettinari Gessica , Ferrari Cagidiaco Edoardo , Ferrari Marco
Published: May 2021

Background

Patient's illness perception, assessed through the Brief‐Illness Perception Questionnaire (Brief‐IPQ), plays a decisive role in the treatment effectiveness of a wide range of chronic diseases; nonetheless, evidence is still lacking regarding periodontitis. The aim of the present pre‐post quasi‐experimental study was to evaluate the change in the Brief‐IPQ before and after non‐surgical periodontal treatment (NST) and to evaluate its ability to foresee the efficacy of NST.

Methods

A total of 126 periodontitis participants starting NST were asked to participate in the study. The nine‐item Brief‐IPQ together with a full periodontal chart were recorded at baseline and at the 3‐month follow up (reevaluation) after NST. Pre‐post comparisons of psychometric and periodontal variables were carried out through the Wilcoxon signed‐rank test (α = 0.05). A predictive model was built to test the ability of the Brief‐IPQ items to foresee the efficacy of NST.

Results

NST led to a significant reduction in all periodontal parameters (P < 0.001); the proportion of pockets closed was 64.18%. Although the overall sum score of the Brief‐IPQ remained fairly stable (P = 0.0673), significant changes occurred for items seven (“understanding”) (P < 0.001) and 8 (“emotional response”) (P < 0.05). The best model (R2 = 0.068, F = 2.15, P = 0.033) obtained from the multivariate linear regression analysis demonstrated that item five (“identity”) (β = 2.340, P = 0.017) and item eight (“emotional response”) (β = ‐2.569, P = 0.008) significantly predict the efficacy of NST (i.e., the proportion of pockets closed at reevaluation).

Conclusions

NST significantly ameliorates patient's understanding and emotional burden related to periodontitis. Baseline values of perceived symptoms and emotional response are predictive for the short‐term efficacy of NST.
Enabling rapid identification of biotherapeutic protein products using handheld Raman spectrometers and principal component analysis
Authors: Soto Robert J. , Meriage David S. , Wagner Robin L. , Wang Ting , Semin David J.
Published: May 2021

Herein, the utility of Raman spectroscopy for rapid identity (ID) verification of biotherapeutic protein products in solution is demonstrated. The success of this approach hinges on the unique combination of Raman features associated with both the therapeutic agent and excipients as the basis for product differentiation. Product ID method development subjects Raman spectra of the target product(s) to dimension reduction using principal component analysis (PCA) to define product‐specific models which serve as the basis for the ID method decision algorithm. In the initial stages of this work, instrumental sources of variance such as intensity‐axis multiplicative scaling and wavenumber‐axis alignment lead to high rates of erroneous false‐negatives when the methods were executed on other instruments that were not used for model development. To overcome these issues, the PCA‐based spectral models were systematically studied and iteratively adjusted to elucidate key design requirements for transferable models. The use of specific spectral preprocessing algorithms was implemented to compensate for instrumental variance, which reduced false‐negative rates without sacrificing method specificity. Five different methods, along with the associated product samples, were evaluated on 15 Raman instruments that had not been used for method development. No false‐positive analyses occurred for any of the five methods. A small number of false negatives (~2%) were observed on analyzers that performed outside of the instrument manufacturer's specifications and thus would have been identified during preventive maintenance. Taken together, this paper lays the groundwork for developing and implementing Raman ID methods for solution‐based protein products in the biopharmaceutical industry.
Comparison of urinary incontinence, based on pelvic floor and abdominal muscle strength, between nulliparous female athletes and non‐athletes: A secondary analysis
Authors: Arbieto Eliane Regina Mendoza , dos Santos Keyla Mara , da Luz Soraia Cristina Tonon , Da Roza Thuane
Published: May 2021

Aims

To compare the strength of abdominal and pelvic floor muscles (PFM) between nulliparous female athletes (FAs) and non‐athletes (FNAs), to determine the frequency of urinary incontinence (UI) in these groups.

Methods

This cross‐sectional comparative study of nulliparous women included 39 professional FAs, who competed at the district level or above, and 34 FNAs. Participants underwent pelvic floor and abdominal muscle assessments. PFM function and strength were assessed using the modified Oxford scale and a manometer (PERINA 996‐2 QUARK). Abdominal muscle function and strength were assessed using a 4‐Pro isokinetic dynamometer. The International Consultation on Incontinence Questionnaire‐Short Form was used to assess UI symptoms among the athletes, and the International Physical Activity Questionnaire‐Short Form was used to establish the level of physical activity among the non‐athletes.

Results

The prevalence of UIs in the FAs was 53.8%, while that for FNAs was 35.3%. There was no association between being an athlete and having UI (p = 0.112). FAs were found to weigh more (p = 0.012) and have increased abdominal muscle strength (p = 0.014) and maximum voluntary PFM contraction as recorded by the manometer (p = 0.035), as well as a decreased PFM contraction endurance time (p = 0.025) than FNAs.

Conclusion

FAs had stronger abdominal muscles and PFM contraction, as assessed by a manometer, but less PFM endurance when compared to FNAs. Despite these differences, the prevalence of UI was similar between groups.