bluuebunny/crossref_metadata_2025 huggingface dataset:
Translation and psychometric properties of the Persian version of the position on nursing diagnosis scale
Authors: Ramezanian Tayebeh , Mohammadipour Fatemeh , Mohammadi Rasool , Kordestani‐Moghaddam Parastou
Published: February 2021

Aim

To validate the Positions on Nursing Diagnosis scale developed by Lunney and Krenz (1992) in Persian language.

Design

Cross‐sectional survey.

Methods

A methodological study conducted in two stages of translation (by applying the forward and back‐translation method) and psychometric assessment was conducted in a western area of Iran. The scale was completed by 600 nurses selected by quota method from different wards of four provinces. Date of data collection is 1‐April‐2019 to 1‐Dec‐2019.

Results

The Positions on Nursing Diagnosis scale showed acceptable content validity with index of 0.97. The 20 items of the Positions on Nursing Diagnosis scale load on four factors. The confirmatory factor analysis demonstrated the good fit of the model's indicators. Cronbach's alpha coefficient for the whole instrument was 0.85. The intraclass correlation coefficient was 0.86.
Measuring Ovarian Escape in Premenopausal Estrogen Receptor-Positive Breast Cancer Patients on Ovarian Suppression Therapy
Authors: Burns Ethan , Koca Emre , Xu Jiaqiong , McLean Edward , Lee Rosetta , Patel Tejal , Chang Jenny , Niravath Polly
Published: February 2021

Purpose

This study evaluated the proportion of premenopausal women who experience persistent ovarian escape (OE) while receiving ovarian suppression (OS) therapy for estrogen receptor-positive (ER+) breast cancer treatment. The study also examined clinical factors that may predispose to higher risk of persistent OE.

Materials and Methods

This was a retrospective, “real-world” study to evaluate premenopausal women receiving adjuvant endocrine OS therapy. The primary objective was to measure the percentage of persistent OE within the first 3 months of OS injections (using either leuprolide or goserelin). The secondary objective was to associate baseline clinical data (age, body mass index [BMI], and previous chemotherapy) with the probability of OE.

Results

Of the 46 patients included in this analysis, 11 (23.9%) women did not achieve OS within 3 months. Three women (6.5%) remained in OE at 12 months. Older age (odds ratio, 0.86; confidence interval, 0.76–0.98, p = .024) was associated with lower chance of developing OE. BMI, previous chemotherapy, and drug used (tamoxifen versus aromatase inhibitor) did not correlate with the likelihood of OE in this patient cohort.

Conclusion

Among the premenopausal women who did not attain complete ovarian suppression, young age was a significant risk factor for likelihood of OE. Although the clinical relevance of this finding is not yet known, it should prompt further studies to determine whether inadequate OS is associated with higher recurrence risk for patients with ER+ breast cancer.

Implications for Practice

Because up to a quarter of premenopausal women do not attain adequate ovarian suppression within the first 3 months of gonadotropin-releasing hormone (GnRH) agonist therapy, bloodwork should be checked to ascertain hormone levels prior to starting aromatase inhibitor therapy, and at regular intervals, for these women.
The outbreak of COVID‐19 pandemic and its impact on stock market volatility: Evidence from a worst‐affected economy
Authors: Bora Debakshi , Basistha Daisy
Published: February 2021

This paper empirically investigates the impact of COVID‐19 on the volatility of stock prices in India with the help of a generalized autoregressive conditional heteroscedasticity model. Daily closing prices of stock indices, Nifty and Sensex from September 3, 2019 to July 10, 2020 has been used for the analysis. Further, the study has been attempted to make a comparison of stock price return in pre‐COVID‐19 and during COVID‐19 situation. Findings reveal that the stock market in India has experienced volatility during the pandemic period. While comparing the result during COVID period with that of the pre‐COVID, we found that the return on the indices is higher in the pre‐COVID‐19 period than during COVID‐19.
Effects of Access to Legal Same‐Sex Marriage on Marriage and Health
Authors: Carpenter Christopher S. , Eppink Samuel T. , Gonzales Gilbert , McKay Tara
Published: February 2021

We provide the first comprehensive evidence on the effects of access to legal same‐sex marriage (SSM) on marriage and adult health using the full rollout of marriage equality across the United States. Using data from the CDC BRFSS from 2000 to 2017, we relate changes in outcomes for individuals in same‐sex households (SSH) coincident with adoption of legal SSM in two‐way fixed effects models. A substantial share of these households includes gay and lesbian couples. For men in SSH, we find robust evidence that access to legal SSM significantly increased marriage take‐up, health insurance coverage, access to care, and healthcare utilization. Results for women in SSH are inconclusive apart from a clear increase in marriage take‐up. Our results provide the first evidence that legal access to SSM significantly improved health for adult gay men.
Novel treatments for hemophilia through rebalancing of the coagulation cascade
Authors: Zhao Yakun , Weyand Angela C. , Shavit Jordan A.
Published: February 2021

Hemophilia A and B are inherited hemorrhagic disorders that result from alterations in the coagulation cascade. Aside from spontaneous bleeding, the main complication of hemophilia is hemarthrosis. Progress over the last three decades, specifically prophylaxis using recombinant factor, has prevented hemarthrosis and lengthened patient life expectancies. However, many treatments require frequent dosing up to three times a week, and alloantibodies (inhibitors) against replacement factor continues to be an issue. These problems call for novel treatments for patients with hemophilia. Although there has been progress in extended half‐life factors and mimetics of factor VIII, an alternative treatment methodology is to rebalance the activities of pro‐ and anticoagulant factors through inhibition of the natural anticoagulants: antithrombin, tissue factor pathway inhibitor, protein C, and protein S. This review will explore the efficacy of targeting these inhibitory pathways from preclinical development through clinical trials, and delve into concerns of thrombotic risk.
Severe adverse events during sirolimus “off‐label” therapy for vascular anomalies
Authors: Rössler Jochen , Baselga Eulalia , Davila Victoria , Celis Veronica , Diociaiuti Andrea , El Hachem Maya , Mestre Sandrine , Haeberli Dario , Prokop Aram , Hanke Christof , Loichinger Wolfgang , Quéré Isabelle , Baumgartner Iris , Niemeyer Charlotte M. , Kapp Friedrich G.
Published: February 2021

Objectives

Clinical studies have shown low toxicity and a favorable safety profile for sirolimus in vascular anomalies. Here, we describe severe adverse events (SAEs) observed during “off‐label use” for vascular anomalies.

Methods

We performed a retrospective, multicenter chart review for SAEs during “off‐label” sirolimus therapy for vascular anomalies and analyzed these cases by a predesigned workflow.

Results

We identified 17 SAEs in 14 patients diagnosed with generalized lymphatic anomaly (n = 4), Gorham–Stout disease (n = 2), central conducting lymphatic anomaly (n = 1), lymphatic malformation (n = 4), tufted angioma (n = 1), kaposiform hemangioendothelioma (n = 1), and venous malformation in a patient with CLOVES syndrome (n = 1). Three patients presented two SAEs each. The age at initiation of sirolimus therapy was under 2 years (n = 5), 2–6 years (n = 5), and older than 12 years (n = 4). SAEs occurred during the first 3 months of sirolimus therapy (n = 7), between 3 and 12 months (n = 7) and after 1 year of therapy (n = 3). The most frequent SAE was viral pneumonia (n = 8) resulting in one death due to a metapneumovirus infection in a 3 months old and a generalized adenovirus infection in a 28‐month‐old child. Sirolimus blood level at the time of SAEs ranged between 2.7 and 21 ng/L. Five patients were on antibiotic prophylaxis.

Conclusions

Most SAEs are observed in the first year of sirolimus therapy; however, SAEs can also occur after a longer treatment period. SAEs are potentially life threatening, especially in early infancy. Presence of other risk factors, that is, underlying vascular anomaly or immune status, may contribute to the risk of SAEs. Sirolimus is an important therapeutic option for vascular anomalies, but patients and physicians need to be aware that adequate monitoring is necessary, especially in patients with complex lymphatic anomalies that are overrepresented in our cohort of SAEs.
The influence of processing conditions on tensile properties of wholly thermoplastic composites reinforced with nanotubes
Authors: Han Jier Y. , Baird Donald G.
Published: February 2021

This paper is concerned with novel wholly thermoplastic composites (WTCs) reinforced with supercritical carbon dioxide‐aided exfoliated multi‐walled carbon nanotubes (MWCNTs) and the enhancement of mechanical properties. The bicomponent in situ injection molded plaques consist of polyamide 6 (PA6) and microfibers of thermotropic liquid crystalline polymer (TLCP) with miss‐matched melting temperature. Multiple mixing histories with MWCNTs and processing temperatures were studied and tested for minimizing matrix thermal degradation and maximizing tensile properties of the multi‐scale WTCs. The optimum in situ injection molding temperature was found at 300°C with melt blending nylon 6 matrix and exfoliated MWCNTs in advance. Exfoliated MWCNTs acted as bridging elements between the TLCP and the nylon 6 matrix, which lead to effective stress transfer from the nylon 6 matrix to the TLCP fibrils. Compared to the WTCs without MWCNTs reinforcement, tensile modulus and tensile strength in longitudinal and latitudinal directions were both improved. Furthermore, with the reinforcement of TLCP and exfoliated MWCNTs, the tensile modulus and tensile strength of nylon 6 were enhanced by 173% and 35% in the fluid flow direction, respectively. These experimental results for 20 wt% TLCP/PA6 were even better than the mechanical properties of 20 wt% carbon fiber (CF)/PA6 reported in the literature.
Characterization of hybrid composites reinforced with metal and ceramic nanoparticles
Authors: Jeong Ji Won , Song Young Seok
Published: February 2021

In this study, we prepared a hybrid composite by incorporating metal and ceramic nanoparticles into aliphatic polyketone. Aliphatic polyketone, a copolymer composed of olefin and carbon monoxide has relatively high crystallinity, impact resistance, tribological properties, good resistance to strong acid, and high gas barrier properties. Aluminum and sepiolite powders were compounded with the polymer. The process was carried out using a twin‐screw extruder, and dog‐bone specimens were prepared via injection molding. The thermal, mechanical, and rheological properties of the composites were analyzed experimentally. In addition, morphological characterization was carried out. When the microflake and nanoparticles were embedded into the composites, the initial pyrolysis temperature were increased. The effect of the nanoparticle addition was more significant than that of the microsized particle addition, and the heat treated sepiolite nanocomposite was found to have the highest viscosity, storage modulus, and loss modulus.
Exposure to phthalates: germline dysfunction and aneuploidy
Authors: Henderson Ayana L. , Colaiácovo Monica P.
Published: February 2021

Epidemiological studies continue to reveal the enduring impact of exposures to environmental chemicals on human physiology, including our reproductive health. Phthalates, a well characterized class of endocrine disrupting chemicals and commonly utilized plasticizers, are among one of the many toxicants ubiquitously present in our environment. Phthalate exposure has been linked to increases in the rate of human aneuploidy, a phenomenon that is detected in 0.3% of livebirths resulting in genetic disorders including trisomy 21, approximately 4% of stillbirths, and over 35% of miscarriages. Here we review recent epidemiological and experimental studies that have examined the role that phthalates play in germline dysfunction, including increases in apoptosis, oxidative stress, DNA damage, and impaired genomic integrity, resulting in aneuploidy. We will further discuss subject variability, as it relates to diet and polymorphisms, and the sexual dimorphic effects of phthalate exposure, as it relates to sex‐specific targets. Lastly, we discuss some of the conserved effects of phthalate exposure across humans, mammalian models and nonmammalian model organisms, highlighting the importance of using model organisms to our advantage for chemical risk assessment and unveiling potential mechanisms that underlie phthalate‐induced reproductive health issues across species.
Statins and risk of diverticular disease: Nested case–control study
Authors: Skajaa Nils , Schønfeldt Troelsen Frederikke , Pedersen Lars , Ekholm Ola , Strate Lisa L. , Erichsen Rune , Sørensen Henrik Toft
Published: February 2021

Background

Statins exert pleiotropic anti‐inflammatory effects and may prevent diverticular disease. However, the association remains poorly understood with previous studies obtaining conflicting results.

Aims

To examine the effect of statin on the subsequent risk of diverticular disease.

Methods

We conducted a nested case–control study in Denmark among respondents (>18 years) of the 2010 or the 2013 Danish National Health Survey. Among these, we identified 8809 cases of hospital‐diagnosed diverticular disease and risk‐set sampled population controls without diverticular disease. Using complete prescription and hospital records, we used conditional logistic regression to compute odds ratios (ORs) associating statin use with diverticular disease. In adjusted analyses, we controlled for hospital‐based diagnoses, medication use other than statins, and lifestyle and socioeconomic factors.

Results

The fully adjusted OR for diverticular disease associated with ever use (≥1 statin prescription filling) was 1.19 (95% CI: 1.12–1.27) compared with never use. However, we observed no dose–response relation. For example, among short‐term users (<5 years), the OR was 1.18 (95% CI: 1.04–1.35) for low intensity users and 1.13 (95% CI: 1.01–1.26) for high intensity users. Among long‐term users (≥5 years), the respective ORs were 1.25 (95% CI: 1.13–1.38) and 1.11 (95% CI: 0.98–1.24). In analyses restricting to cases and controls with a previous colonoscopy, associations were null (OR: 1.01 [95% CI: 0.85–1.20]).

Conclusions

The observed association of a higher risk of diverticular disease associated with statins could be explained by diagnostic bias. Our study did not support a protective nor harmful effect of statins on the risk of diverticular disease.
Phenol‐enriched hydroxy depolymerized lignin by microwave alkali catalysis to prepare high‐adhesive biomass composites
Authors: Di Bing , Li Zheng , Lei Yin , Wang Xiaofeng , Zhu Yanchao , Qi Wei , Tian Yumei
Published: February 2021

Lignin, a by‐product produced during pulping and papermaking, is a phenol‐rich compound with excellent prospect to be used as a substitute for phenol in phenolic resin adhesive. Phenol‐enriched hydroxy depolymerized lignin by microwave alkali catalysis is an effective method to prepare high‐adhesive biomass composite. This study investigated the microwave digestion of lignin under different conditions of the alkali catalysis (sodium hydroxide) concentration, power, reaction time, and reaction temperature. The results show that on the condition of sodium hydroxide concentration of 0.3 mol/L, temperature of 170 °C, and time of 20 min, the highest phenolic hydroxy content obtained by depolymerization of lignin is 21.68%. SEM shows that the depolymerized lignin has no original basic constituent units and lignin‐based phenolic resin has dense uniform pine needle units. Therefore, it has a high bonding strength of 1.934 MPa. The bonding strength and phenol content obtained by the microwave depolymerization method are much higher than those of other modification methods.
A pilot study of the efficacy of an adventure therapy programme on borderline personality disorder: A pragmatic controlled clinical trial
Authors: Mendo‐Cullell Mariona , Arenas‐Pijoan Laura , Forné Carles , Fernández‐Oñate David , Ruiz de Cortázar‐Gracia Natalia , Facal Carmen , Torrent Aurora , Palacios Roberto , Pifarré Josep , Batalla Iolanda
Published: February 2021

Adventure therapy (AT) is a therapeutic intervention that has demonstrated effectiveness in different populations, but there are no studies on this therapy in borderline personality disorder (BPD). The objective of this study was to assess the response to AT in comparison with treatment as usual (based on cognitive‐behavioural therapy) in patients with BPD. Regarding the comparison of the differences post‐therapy–pre‐therapy between both groups, some metabolic variables improved more in the AT group, with medium–large effect sizes. Almost all psychometric variables evolved better in the AT group, with negligible effects. AT could be considered in BPD treatment because it results in healthier lifestyle habits and increases functionality and quality of life in patients who are prone to self‐destruction. © 2021 John Wiley & Sons, Ltd.
Human myeloma cell‐ and plasma‐derived extracellular vesicles contribute to functional regulation of stromal cells
Authors: Reale Antonia , Carmichael Irena , Xu Rong , Mithraprabhu Sridurga , Khong Tiffany , Chen Maoshan , Fang Haoyun , Savvidou Ioanna , Ramachandran Malarmathy , Bingham Nicholas , Simpson Richard J. , Greening David W. , Spencer Andrew
Published: February 2021

Circulating small extracellular vesicles (sEV) represent promising non‐invasive biomarkers that may aid in the diagnosis and risk‐stratification of multiple myeloma (MM), an incurable blood cancer. Here, we comprehensively isolated and characterized sEV from human MM cell lines (HMCL) and patient‐derived plasma (psEV) by specific EV‐marker enrichment and morphology. Importantly, we demonstrate that HMCL‐sEV are readily internalised by stromal cells to functionally modulate proliferation. psEV were isolated using various commercial approaches and pre‐analytical conditions (collection tube types, storage conditions) assessed for sEV yield and marker enrichment. Functionally, MM‐psEV was shown to regulate stromal cell proliferation and migration. In turn, pre‐educated stromal cells favour HMCL adhesion. psEV isolated from patients with both pre‐malignant plasma cell disorders (monoclonal gammopathy of undetermined significance [MGUS]; smouldering MM [SMM]) and MM have a similar ability to promote cell migration and adhesion, suggesting a role for both malignant and pre‐malignant sEV in disease progression. Proteomic profiling of MM‐psEV (305 proteins) revealed enrichment of oncogenic factors implicated in cell migration and adhesion, in comparison to non‐disease psEV. This study describes a protocol to generate morphologically‐intact and biologically functional sEV capable of mediating the regulation of stromal cells, and a model for the characterization of tumour‐stromal cross‐talk by sEV in MM.
Recovery in glioblastoma multiforme during inpatient rehabilitation is equivalent in first versus repeat resection: A 10‐year retrospective analysis
Authors: Chowdhury Nasim , Scott Charles , O'Dell Michael W.
Published: February 2021

Background

Inpatient rehabilitation improves function in people with brain tumors, including glioblastoma multiforme (GBM) but there are limited data on the impact of multiple resections on outcomes. We hypothesize that outcomes will be more favorable for those patients with a single resection when compared to those with more than one resection.

Objective

To examine functional outcomes in inpatient rehabilitation for people with GBM who underwent one or more resections prior to admission.

Design

Retrospective analysis.

Setting

Inpatient rehabilitation unit within a large, urban, academic medical center.

Participants

Patients who were admitted to our institution for the treatment of initial GBM or GBM recurrence necessitating surgical resection or repeat resection.

Interventions

Not applicable.

Main Outcome Measure(s)

Total FIM Change, Total Functional Independence Measure (FIM) Efficiency, Motor and Cognitive FIM efficiency, and proportion discharged home.

Results

From 2006 to 2016, 94 persons with GBM were admitted. Eight were readmissions classified as “repeat” and another seven transferred to the medical floor and excluded. Of the 79 patients included, 56 were first and 23 second resections, with a group mean age of 62.7 + 12.2 years and were 51% male. On analysis of covariance, change in FIM score from admission to discharge was insignificant between groups, adjusted for age and acute care length of stay (17.1 vs. 17.4, F[1, 75] = 0.027, P = .871). Likewise, the proportion of home discharge was not significant between groups (chi‐square, 75.0% vs. 78.3%, P = .758).

Conclusions

Patients who have undergone second resections for GBM are reasonable candidates for admission to the inpatient rehabilitation units despite carrying a poor prognosis and having multiple exposures to surgical morbidity. Factors to take into account are that candidates considered for a second resection may be relatively younger or healthier and therefore may perform better from a functional standpoint. In addition, postoperative steroid administration may play a role in the similarities the authors noted. A larger, multicenter study should validate our findings (limited by sample size and a single location) and identify factors predicting a successful outcome.
ECT and somatoform disorder: case report and literature review
Authors: Lau Jennie , Burlingham Amy , Quraishi Shahid
Published: February 2021

Patients with somatoform disorders can be significantly impacted by the condition and there is often comorbid depression and anxiety. In cases that are treatment resistant, with the disorder persisting despite intensive psychological input and numerous psychotropic medications, the use of electroconvulsive therapy (ECT) has been considered a possible treatment option. Here, the authors report the case of such a patient who responded to ECT treatment and present a literature review exploring the topic.
Strain‐induced post‐curing of acrylate networks
Authors: Maassen Eveline E. L. , Anastasio Rosaria , Poto Serena , Cardinaels Ruth , Sijbesma Rint P. , van Breemen Lambèrt C. A. , Heuts Johan P. A.
Published: February 2021

The mechanical properties and network structure of photocurable polymers are strongly dependent on processing conditions. Here it is reported that highly crosslinked acrylate systems undergo unexpected additional post‐curing during DMTA measurements, resulting in an increase in glass‐transition temperature (Tg). A detailed study of the conditions under which this increase in Tg takes place unequivocally shows that a small (0.1%) oscillatory strain applied above Tg is responsible for additional cross‐linking reactions. The effect of strain‐induced post‐curing is confirmed by applying post‐curing treatments under oscillatory shear strain in rheological tests. Different acrylate systems were characterized and the results show that the strain induced post‐curing depends on the network structure of the polymer. In polymer networks with an initial high crosslink density the effect is pronounced while in polymers with an initial lower crosslink density no shift in Tg is observed.
Study of the anticancer effects of a helium plasma jet combined with four anticancer drugs on 3D bladder tumour spheroids
Authors: Zhang Jishen , Li Bing , Xu Shengduo , Liu Dingxin , Zhang Hao , Xu Dehui , Guo Li , Kong Michael G.
Published: February 2021

Current studies of cold atmospheric plasma cancer therapy mainly focus on the application of plasma alone and neglect the application of plasma combined with traditional therapeutic techniques. In this paper, the anticancer effects of a plasma jet combined with four clinical anticancer drugs (cisplatin, methotrexate, adriamycin and paclitaxel) on three‐dimensional bladder tumour spheroids (T24 cells) were studied. The results show that all four drugs had little impact on the liquid‐phase oxidative pressure induced by the plasma jet, and anticancer effects from strong to weak were as follows: Plasma jet + paclitaxel, plasma jet + adriamycin, plasma jet + cisplatin, plasma jet and plasma jet + methotrexate. Our research indicates that plasma exhibits selectivity in combination with particular anticancer drugs.
Visualising an invisible symbiosis
Authors: McGaley Jennifer , Paszkowski Uta
Published: February 2021

Societal Impact Statement

Despite the vast abundance and global importance of plant and microbial species, the large majority go unnoticed and unappreciated by humans, contributing to pressing issues including the neglect of study and research of these organisms, the lack of interest and support for their protection and conservation, low microbial and botanical literacy in society, and a growing disconnect between people and nature. The invisibility of many of these organisms is a key factor in their oversight by society, but also points to a solution: sharing the wealth of visual data produced during scientific research with a broader audience. Here, we discuss how the invisible can be visualised for a public audience, and the benefits it can bring.

Whether too small, slow or concealed, the majority of species on Earth go unseen by humans. One such rather unobservable group of organisms are the arbuscular mycorrhizal (AM) fungi, who form beneficial symbioses with plants. AM symbiosis is ubiquitous and vitally important globally in ecosystem functioning, but partly as a consequence of its invisibility, it receives disproportionally little attention and appreciation. Yet AM fungi, and other unseen organisms, need not remain overlooked: from decades of scientific research there exists a goldmine of visual data, which if shared effectively we believe can alleviate the issues of low awareness. Here, we use examples from our experience of public engagement with AM symbiosis as well as evidence from the literature to outline the diverse ways in which invisible organisms can be visualised for a broad audience. We highlight outcomes and knock‐on consequences of this visualisation, ranging from improved human mental health to environmental protection, making the case for researchers to share their images more widely for the benefit of plants (and fungi and other overlooked organisms), people and planet.
Artificial intelligence as ally in hazard analysis
Authors: Garvin Thomas , Kimbleton Scott
Published: February 2021

Hazard analysis techniques have been around for many years, and have proven effective in the prevention of incidents and no doubt the saving of lives. Process hazard analysis (PHA) is now fairly robust and regulated, focused on overarching risks associated with the safe handling of hazardous materials and approaches to engineer‐out such risks. Occupational hazard analysis (OHA) is keenly focused on human activity, and personal protection in hazardous working conditions. Both approaches are critical ‐ but are often carried out separately, by different parts of an organization, which could result in an incomplete picture of the full set of operational risks in the field. Developing a holistic picture of both past and present dangers calls for a deep exploration of evidence. HAZOPs, PHA's, incident records and investigations provide expert analysis of hazards and mitigating strategies. Near‐miss reports and safety observations add a large amount of information as well; the reporting frequency of these “leading indicators” can be both a blessing and a curse, as time and available resources constrain the ability to analyze and detect hazard signals within. As important as analyzing the historical record is for lessons learned, the more recent observations could indicate new hazards or highlight concerning trends. These could feed valuable “real time” information back to operations and maintenance teams to improve risk assessments and task planning. Enter artificial intelligence (AI) as a means to analyze the large amount of written hazard analyses, reports and observations to quickly extract insights around hazardous conditions, activities, incident causes and risk mitigation measures. Trained to understand concepts and contexts in both process and personal safety, AI can provide a natural‐language information exploration environment for scanning thousands of documents in seconds and present common themes and related records. Not unlike us humans, AI learns from the past, informs the present and can help reduce risks in the future.
The effects of resveratrol supplementation on PPARα, p16, p53, p21 gene expressions, and sCD163/sTWEAK ratio in patients with type 2 diabetes mellitus: A double‐blind controlled randomized trial
Authors: Toupchian Omid , Abdollahi Shima , Salehi‐Abargouei Amin , Heshmati Javad , Clark Cain C. T. , Sheikhha Mohammad Hasan , Fallahzadeh Hossein , Mozaffari‐Khosravi Hassan
Published: February 2021

The present study sought to evaluate the effect of resveratrol supplementation on mRNA expression levels of peroxisome proliferator‐activated receptor alpha (PPARα), p53, p21, p16, and serum levels of cluster of differentiation 163 (CD163) to TNF‐like weak inducer of apoptosis (TWEAK) ratio in patients with type 2 diabetes. In this double‐blind randomized controlled trial, 71 patients were randomly assigned to receive either 1,000 mg of trans‐resveratrol or placebo (methyl cellulose) for 8 weeks. Expression levels of genes of interest, and serum levels of sCD163 and sTWEAK were assessed at baseline and at the end of the study. Resveratrol supplementation significantly increased mRNA expression levels of p53 and p21 genes, compared with the placebo group (fold change of p53 = 1.29, p = .04; fold change of p21 = 1.46, p = .006). However, no significant effect on expression levels of PPARα and p16 genes was observed after supplementation. In addition, resveratrol significantly reduced serum levels of sCD163/sTWEAK ratio compared with the placebo group (p = .003). Resveratrol supplementation resulted in significant changes in p53 and p21 genes expression, while serum levels of sCD163/sTWEAK ratio also improved in the resveratrol group, without any significant change in adjusted sCD163 levels. More research is needed to confirm the beneficial effects of resveratrol for patients with diabetes.
Antihypertensive and pleiotropic effects of Phyllanthus emblica extract as an add‐on therapy in patients with essential hypertension—A randomized double‐blind placebo‐controlled trial
Authors: Shanmugarajan Dayanidhi , Girish Chandrashekaran , Harivenkatesh Natarajan , Chanaveerappa Bammigatti , Prasanna Lakshmi Nakka Chandrasekar
Published: February 2021

Essential hypertension is an important cause of cardiovascular morbidity and mortality that is compounded by concomitant risk factors like diabetes mellitus and dyslipidemia. Phyllanthus emblica is a rich source of antioxidants, tannins, and vitamin C and is used in treating various ailments in traditional medicine. This study aimed to elucidate the effects of aqueous extract of Phyllanthus emblica on essential hypertension and other protective actions. This randomized controlled trial was conducted on 150 patients with essential hypertension. Participants were randomly assigned to receive Phyllanthus emblica capsule (500 mg) or placebo twice daily, added to their routine medications for 12 weeks. Blood pressure was assessed at baseline, 2, 4, 8, and 12 weeks after beginning treatment or placebo. Other investigations like lipid parameters, oxidant and antioxidant enzyme levels, hs‐CRP levels, HbA1C, LFT, RFT, uric acid, and endothelial function were measured at baseline and 12 weeks. Both Phyllanthus emblica and placebo groups were comparable at baseline. Phyllanthus emblica had a good safety profile in patients with essential hypertension. However, the treatment with Phyllanthus emblica failed to produce any additional reduction in systolic and/or diastolic blood pressure levels and did not exhibit improvement in oxidant status, antioxidant capacity, lipid profile, HbA1C, arterial stiffness parameters, or hs‐CRP levels.
Theoretical mechanistic study of nickel‐catalyzed anti‐Markovnikov hydroarylation of alkenes
Authors: Li Jing , Guan Wei
Published: February 2021

Transition metal‐catalyzed hydroarylation of alkenes can provide various Markovnikov products, but so‐called anti‐Markovnikov additions to alkenes are rarely reported. Here, a divalent nickel hydride complex catalyzed anti‐Markovnikov reductive cross‐coupling of styrene and aryl iodide has been investigated using density functional theory. The reaction occurs via the regio‐determining hydronickelation, the oxidative addition of the CI bond to Ni(II) center, and the rate‐determining reductive elimination of hydroarylation product. The electronic processes were investigated with a fragment molecular orbital analysis to understand the origin of anti‐Markovnikov selectivity and successive oxidative addition and reductive elimination steps.
Effect of transdermal estrogen dose regimen for endometrial preparation of frozen‐thawed embryo transfer on reproductive and obstetric outcomes
Authors: Ogawa Tatsuyuki , Kasai Tsuyoshi , Ogi Maki , Fukushima Jiro , Hirata Shuji
Published: February 2021

Purpose

Previous studies have reported different methods of estrogen administration during endometrial preparation for frozen‐thawed embryo transfer (FET). This study aimed to investigate a beneficial regimen of transdermal estrogen administration for FET.

Methods

We investigated the reproductive and obstetric outcomes of FET by comparing the increasing dose (ID) group that mimics changes in serum estradiol during the menstrual cycle and the constant dose (CD) group. Transdermal patches were used for estrogen administration in both groups. In our hospital, we targeted 315 cycles of the ID group in which FET was performed in 2017 and 324 cycles of the CD group in which FET was performed in 2018. In all cases, single embryo transfer was performed.

Results

All were singleton pregnancies. There was no difference in clinical pregnancy rate (28.9% vs 28.2%, P =.837) and live birth rate (17.3% vs 21.4%, P =.201) between the ID and CD groups. Spontaneous abortion rate was significantly lower in the CD group than in the ID group (37.2% vs 23.0%, P =.041). There was no difference in obstetrical outcomes.

Conclusions

It was considered that the simple CD regimen may be more beneficial than the complicated ID regimen.
The role of pituitary gonadotropins and intraovarian regulators in follicle development: A mini‐review
Authors: Orisaka Makoto , Miyazaki Yumiko , Shirafuji Aya , Tamamura Chiyo , Tsuyoshi Hideaki , Tsang Benjamin K. , Yoshida Yoshio
Published: February 2021

Background

The process of follicle development is tightly regulated by pituitary gonadotropins (follicle‐stimulating hormone [FSH] and luteinizing hormone [LH]) and intraovarian regulators (eg, steroids, growth factors, and cytokines).

Methods

This review outlines recent findings on the mechanisms of human follicle development, based on the research on animal models such as mice, rats, cows, and sheep.

Main findings

Phosphatidylinositol 3‐kinase/protein kinase B signaling pathway and anti‐Müllerian hormone are involved in primordial follicle activation during the gonadotropin‐independent phase. The intraovarian regulators, such as androgen, insulin‐like growth factor system, activin, oocyte‐derived factors (growth differentiation factor‐9 and bone morphogenetic protein 15), and gap junction membrane channel protein (connexin), play a central role in the acquisition of FSH dependence in preantral follicles during the gonadotropin‐responsive phase. Antral follicle development can be divided into FSH‐dependent growth and LH‐dependent maturation. The indispensable tetralogy for follicle selection and final maturation of antral follicles involves (a) acquisition of LH dependence, (b) greater capacity for E2 production, (c) activation of the IGF system, and (d) an antiapoptotic follicular microenvironment.

Conclusion

We reproductive endocrinologists should accumulate further knowledge from animal model studies to develop methods that promote early folliculogenesis and connect to subsequent gonadotropin therapy in infertile women.
Finite horizon robust synthesis using integral quadratic constraints
Authors: Buch Jyot , Seiler Peter
Published: February 2021

We present a robust synthesis algorithm for uncertain linear time‐varying (LTV) systems on finite horizons. The uncertain system is described as an interconnection of a known LTV system and a perturbation. The input–output behavior of the perturbation is specified by time‐domain Integral Quadratic Constraints (IQCs). The objective is to synthesize a controller to minimize the worst‐case performance. This leads to a nonconvex optimization. The proposed approach alternates between an LTV synthesis step and an IQC analysis step. Both inducedand terminal Euclidean norm penalties on output are considered for finite horizon performance. The proposed algorithm ensures that the robust performance is nonincreasing at each iteration step. The effectiveness of this method is demonstrated using numerical examples.
Remote sensing liana infestation in an aseasonal tropical forest: addressing mismatch in spatial units of analyses
Authors: Chandler Chris J. , van der Heijden Geertje M. F. , Boyd Doreen S. , Cutler Mark E. J. , Costa Hugo , Nilus Reuben , Foody Giles M.
Published: February 2021

The ability to accurately assess liana (woody vine) infestation at the landscape level is essential to quantify their impact on carbon dynamics and help inform targeted forest management and conservation action. Remote sensing techniques provide potential solutions for assessing liana infestation at broader spatial scales. However, their use so far has been limited to seasonal forests, where there is a high spectral contrast between lianas and trees. Additionally, the ability to align the spatial units of remotely sensed data with canopy observations of liana infestation requires further attention. We combined airborne hyperspectral and LiDAR data with a neural network machine learning classification to assess the distribution of liana infestation at the landscape‐level across an aseasonal primary forest in Sabah, Malaysia. We tested whether an object‐based classification was more effective at predicting liana infestation when compared to a pixel‐based classification. We found a stronger relationship between predicted and observed liana infestation when using a pixel‐based approach (RMSD = 27.0% ± 0.80) in comparison to an object‐based approach (RMSD = 32.6% ± 4.84). However, there was no significant difference in accuracy for object‐ versus pixel‐based classifications when liana infestation was grouped into three classes; Low [0–30%], Medium [31–69%] and High [70–100%] (McNemar’s χ2 = 0.211, P = 0.65). We demonstrate, for the first time, that remote sensing approaches are effective in accurately assessing liana infestation at a landscape scale in an aseasonal tropical forest. Our results indicate potential limitations in object‐based approaches which require refinement in order to accurately segment imagery across contiguous closed‐canopy forests. We conclude that the decision on whether to use a pixel‐ or object‐based approach may depend on the structure of the forest and the ultimate application of the resulting output. Both approaches will provide a valuable tool to inform effective conservation and forest management.
Development of an optimized and scalable method for isolation of umbilical cord blood-derived small extracellular vesicles for future clinical use
Authors: Cardoso Renato M. S. , Rodrigues Silvia C. , Gomes Claudia F. , Duarte Filipe V. , Romao Maryse , Leal Ermelindo C. , Freire Patricia C. , Neves Ricardo , Simões-Correia Joana
Published: February 2021

Extracellular vesicles (EV) are a promising therapeutic tool in regenerative medicine. These particles were shown to accelerate wound healing, through delivery of regenerative mediators, such as microRNAs. Herein we describe an optimized and upscalable process for the isolation of EV smaller than 200 nm (sEV), secreted by umbilical cord blood mononuclear cells (UCB-MNC) under ischemic conditions and propose quality control thresholds for the isolated vesicles, based on the thorough characterization of their protein, lipid and RNA content. Ultrafiltration and size exclusion chromatography (UF/SEC) optimized methodology proved superior to traditional ultracentrifugation (UC), regarding production time, standardization, scalability, and vesicle yield. Using UF/SEC, we were able to recover approximately 400 times more sEV per mL of media than with UC, and upscaling this process further increases EV yield by about 3-fold. UF/SEC-isolated sEV display many of the sEV/exosomes classical markers and are enriched in molecules with anti-inflammatory and regenerative capacity, such as hemopexin and miR-150. Accordingly, treatment with sEV promotes angiogenesis and extracellular matrix remodeling, in vitro. In vivo, UCB-MNC-sEV significantly accelerate skin regeneration in a mouse model of delayed wound healing. The proposed isolation protocol constitutes a significant improvement compared to UC, the gold-standard in the field. Isolated sEV maintain their regenerative properties, whereas downstream contaminants are minimized. The use of UF/SEC allows for the standardization and upscalability required for mass production of sEV to be used in a clinical setting.
Closing the sustainable development gap: A global study of goal interactions
Authors: Linnerud Kristin , Holden Erling , Simonsen Morten
Published: February 2021

Meeting one sustainable development goal on human needs, social justice, or environmental limits can make it harder (or easier) to meet others. The extent to which countries succeed in reconciling these goals is context specific but depends largely on how we organize society and on what policy options and strategies we use. We present a model for sustainable development consisting of six indicators and assign thresholds that define a sustainable development space. The distances between the indicator values and their corresponding thresholds constitute the sustainable development gap. We then apply a cluster analysis technique to group 117 countries into six clusters that face similar challenges in closing this gap. Finally, we use illustrative spider web diagrams to assess the performance of these clusters at two points in time. We show that some countries have clearly been better than others at reconciling these goals, and many have reduced their sustainable development gap over time.
Relationship between human capital, new venture ideas, and opportunity beliefs: A meta‐analysis
Authors: Canavati Sergio , Libaers Dirk , Wang Tang , Hooshangi Soheil , Sarooghi Hessam
Published: February 2021

Research summary

We meta‐analyze the structural relationship between human capital, the ability to generate new venture ideas, and the favorability of opportunity beliefs to address divergent theoretical predictions and inconsistent empirical findings. We test a two‐stage process model of entrepreneurial opportunity identification, distinguishing between the ability to generate new venture ideas and the favorability of third and first‐person opportunity beliefs. We also distinguish between two categories of human capital: general and specific human capital. Our results suggest that general and specific human capital are positively associated with the ability to generate new venture ideas. Furthermore, only specific human capital matters in influencing the favorability of opportunity beliefs, yet the ability to generate new venture ideas is far more important than human capital for the favorability of opportunity beliefs.

Managerial summary

How does an individual's human capital relate to the attractiveness of opportunities identified? In this study, we review the body of literature on this topic and analyze the relationships between two types of human capital—general and specific human capital, the ability to generate new venture ideas, and the attractiveness of opportunities. We find that both general human capital—primarily education and work experience—and specific human capital—industry and entrepreneurial experience—are useful for generating new venture ideas. However, only specific human capital is useful when assessing which new venture ideas can turn into attractive opportunities. We also find that the ability to generate new venture ideas is more strongly associated with the attractiveness of opportunities than either type of human capital.
Qualifying drug dosing regimens in pediatrics using Gaussian processes
Authors: Siivola Eero , Weber Sebastian , Vehtari Aki
Published: February 2021

Drug development commonly studies an adult population first and then the pediatric population. The knowledge from the adult population is taken advantage of for the design of the pediatric trials. Adjusted drug doses for these are often derived from adult pharmacokinetic (PK) models which are extrapolated to patients with smaller body size. This extrapolation is based on scaling physiologic model parameters with a body size measure accounting for organ size differences. The inherent assumption is that children are merely small adults. However, children can be subject to additional effects such as organ maturation. These effects are not present in the adult population and are possibly overlooked at the design stage of the pediatric trials. It is thus crucial to qualify the extrapolation assumptions once the pediatric trial data are available. In this work, we propose a model based on a non‐parametric regression method called Gaussian process (GP) to detect deviations from the made extrapolation assumptions. We introduce the theoretical background of this model and compare its performance to a parametric expansion of the adult model. The comparison includes simulations and a clinical study data example. The results show that the GP approach can reliably detect maturation trends from sparse pediatric data.
Predicting study duration in clinical trials with a time‐to‐event endpoint
Authors: Machida Ryunosuke , Fujii Yosuke , Sozu Takashi
Published: February 2021

In event‐driven clinical trials comparing the survival functions of two groups, the number of events required to achieve the desired power is usually calculated using the Freedman formula or the Schoenfeld formula. Then, the sample size and the study duration derived from the required number of events are considered; however, their combination is not uniquely determined. In practice, various combinations are examined considering the enrollment speed, study duration, and the cost of enrollment. However, effective methods for visually representing their relationships and evaluating the uncertainty in study duration are insufficient. We developed a graphical approach for examining the relationship between sample size and study duration. To evaluate the uncertainty in study duration under a given sample size, we also derived the probability density function of the study duration and a method for updating the probability density function according to the observed number of events (ie, information time). The proposed methods are expected to improve the operation and management of clinical trials with a time‐to‐event endpoint.