bluuebunny/crossref_metadata_2025 huggingface dataset:
Promoting firm innovativeness through servant leadership and corporate social responsibility to employees
Authors: Mallén Broch Francisco Fermín , Domínguez Escrig Emilio , Chiva Gómez Ricardo , Lapiedra Alcamí Rafael
Published: May 2020

Purpose

Based on the upper echelons and organisational identification theories, this paper focuses on the relationship between servant leadership and firm innovativeness, as well as the underlying mechanisms that explain this relationship. More specifically, we analyse the relationship between servant leadership, firm innovativeness and corporate social responsibility to employees (CSRE).

Design/methodology/approach

A total of 285 Spanish firms took part in the study, and 570 questionnaires were gathered. Structural equation modelling was used to validate the proposed hypotheses.

Findings

Results suggest that servant leadership has a positive relationship with firm innovativeness, and this relationship is fully mediated by CSRE.

Research limitations/implications

HR managers have an overall view of their company and of the behaviour of other leaders. However, future research should also consider employees perceptions. The present study is cross-sectional, and it would be interesting to study the development of the interaction between leaders and followers, which calls for longitudinal and multilevel studies.

Practical implications

According to our results, managers could foster firm innovativeness if they select and promote leaders who display the different leadership behaviours related to servant leadership: empowerment, servitude, accountability, courage, authenticity, humility and stewardship. Moreover, training programmes should also foster these behaviours.

Originality/value

Few empirical studies analyse the relationship between servant leadership and innovation. The main contribution of the present research is to further the current knowledge of this relationship by disentangling the mediating role of corporate social responsibility to employees.
Dermoscopic features and differential diagnosis of sebaceous carcinoma
Authors: Cheng Chun‐Yu , Su Hsing‐Jou , Kuo Tseng‐Tong
Published: May 2020

Sebaceous carcinoma is a rare malignant skin neoplasm arising from sebaceous glands. Its clinical diagnosis is difficult and reports of dermoscopic findings have been limited. This study aims to analyze its dermoscopic features and differential diagnosis in dermoscopic examination. The study included patients diagnosed with histologically proven sebaceous carcinomas as well as diagnosed cases of sebaceous hyperplasia, sebaceoma, squamous cell carcinoma and basal cell carcinoma for comparison of dermoscopic findings. The dermoscopic criterion of presence of sebaceous carcinoma was scored only if the two evaluators reached a consensus. Fifteen cases of histologically diagnosed sebaceous carcinoma were included in our study. All cases were extraocular sebaceous carcinoma. A total of 60 (15 basal cell carcinomas, 15 squamous cell carcinomas, 15 sebaceous hyperplasias and 15 sebaceomas) cases were collected for comparing dermoscopic features with sebaceous carcinoma. In dermoscopic analysis of sebaceous carcinoma, the majority of tumors (66.67%) presented polymorphic vessel pattern. Other features included whitish‐pink areas (80%), yellowish structures (73.33%) and yellowish structureless areas (60%). Yellowish structures in sebaceous carcinomas are the main dermoscopic findings to differentiate squamous cell and basal cell carcinomas (P < 0.001), whereas purplish globules, shiny white blotches and strands and whitish‐pink area distinguish sebaceous carcinomas from other sebaceous tumors (P < 0.05).
Kampo medicines suppress the production of exfoliative toxins causing impetigo in Staphylococcus aureus
Authors: Katayama Ibu , Nakaminami Hidemasa , Yamada Tetsuya , Ikoshi Hideaki , Noguchi Norihisa
Published: May 2020

An alternative approach, such as antivirulence therapy that modulates the production of bacterial toxins or virulence factors, is necessary to tackle the emergence of antimicrobial‐resistant strains. Here, we investigated the potential antivirulence effects of seven Kampo medicines (Jumihaidokuto, Eppikajutsuto, Jizusoippo, Shomakakkonto, Sammotsuogonto, Hainosankyuto and Inchinkoto) against exfoliative toxin (ET)‐positive Staphylococcus aureus, which is the major causative agent of impetigo. A growth inhibition assay showed that all of the selected Kampo medicines inhibited the growth of S. aureus at 1/5 (2.5 mg/mL) or less of the conventionally used concentrations. Among these, Jizusoippo and Inchinkoto (0.25–1 mg/mL) suppressed the production of ET without inhibiting the bacterial growth. Furthermore, Jizusoippo and Inchinkoto significantly suppressed the expression of ET genes in a concentration‐dependent manner. Our findings strongly suggest, for the first time, that Kampo medicines, especially Jizusoippo and Inchinkoto, have the potential to serve as antivirulence agents against skin infections caused by S. aureus by suppressing the production of ET.
The anti‐tumourigenic effect of ellagic acid in SKOV‐3 ovarian cancer cells entails activation of autophagy mediated by inhibiting Akt and activating AMPK
Authors: Elsaid Fahmy G. , Alshehri Mohamed A. , Shati Ali A. , Al‐Kahtani Mohamed A. , Alsheri Ali S. , Massoud Ehab E. , El‐kott Attalla F. , El‐Mekkawy Haitham I. , Al‐Ramlawy Amira M. , Abdraboh Mohamed E.
Published: May 2020

This study investigated the effect of ellagic acid (EA) on SKOV‐3 cell growth and invasiveness and tested if the underlying mechanism involves modulating autophagy. Cells were treated with EA in the presence or absence of chloroquine (CQ), an autophagy inhibitor, compound C (CC), an AMPK inhibitor, or an insulin‐like growth factor‐1 (IGF‐1), a PI3K/Akt activator. EA, at an IC50 of 36.6 µmol/L, inhibited cell proliferation, migration, and invasion and induced cell apoptosis in SKOV‐3 cells. These events were prevented by CQ. Also, EA increased levels of Beclin‐1, ATG‐5, LC3I/II, Bax, cleaved caspase‐3/8 and reduced those of p62 and Bcl‐2 in these cancer cells. Mechanistically, EA decreased levels of p‐S6K1 (Thr389) and 4EBP‐1 (Thr37/46), two downstream targets of mTORC1, and p‐Akt (Thr308) but increased levels of AMPK (Thr172) and p‐raptor (Ser792), a natural inhibitor of mTORC1. CC or IGF‐1 alone partially prevented the effect of EA on cell survival, cell invasions, and levels of LDH, Beclin‐1, and cleaved caspase‐3. In conclusion, EA can inhibit SKOV‐3 growth, migration, and invasion by activating cytotoxic autophagy mediated by inhibition of mTORC1 and Akt and activation of AMPK.
Biochemical investigation of rs1801282 variations in PPAR‐γ gene and its correlation with risk factors of diabetes mellitus in coronary artery disease
Authors: Rehman Kanwal , Jabeen Komal , Awan Fazli Rabbi , Hussain Misbah , Saddique Muhammad Asim , Akash Muhammad Sajid Hamid
Published: May 2020

We aimed to investigate the association of single nucleotide polymorphism of Pro/Ala (rs1801282) in peroxisome proliferator‐activated receptor‐gamma (PPAR‐γ) gene with risk factors of diabetes mellitus (DM) in cardiovascular disease (CVD) patients. We recruited 244 participants from Faisalabad Institute of Cardiology and Department of Cardiology, Sargodha District Head Quarter Teaching Hospital, Pakistan. Out of 244 participants, 144 cases were CVD patients and 100 were healthy controls. CVD patients were further divided into 111 coronary artery disease (CAD) and 33 cardiomyopathy (CMP) patients. Assessment of variant specific polymorphism/mutation of Pro/Pro and Pro/Ala genotypes was done through amplification refractory mutation system polymerase chain reaction (ARMS‐PCR). Further, serum biomarkers were measured to investigate the association among risk factors of DM and Pro/Ala polymorphism in PPAR‐γ gene. About 31.5% Pro/Ala genotype was found in CVD patients out of which 22.5% were CAD patients and 9% were CMP patients. As a result, obesity, hypertension and smoking (35%, 23%, 21%, respectively) were observed to be the most critical risk factors accompanying Pro/Ala mutation in PPAR‐γ particularly in CAD patients as compared to that in CMP patients. A similar pattern of association was observed among the elevated levels of glucose, cholesterol, triglyceride and ALT with Pro/Ala mutation in CAD patients. Further, CAD patients using ACE inhibitors (18%) and β‐blockers (13%) were found to be the carriers of Pro/Ala genotype and also showed significant increase in glucose level. This study suggests that hyperglycaemia in CAD patients particularly obese, smokers and hypertensives having Pro/Ala polymorphism in PPAR‐γ gene are at high risk of developing DM as clearly observed by hyperglycaemia in CAD patients.
Commodity or Propriety? Unauthorised Transfer of Intangible Entitlements in the EU Emissions Trading System
Authors: Holligan Bonnie
Published: May 2020

This article argues that the law governing transfer of allowances within the EU Emissions Trading System (EU ETS) should place greater weight upon transactional (and environmental) integrity, even over market liquidity. More broadly, it reflects on the role played by registries in sharing or concealing information about the material world. Although property rules enable market activity through the creation of an abstract carbon commodity, they must also link past to future entitlements in a just way. In emissions trading markets, justice in private transactions is intimately connected to public questions of environmental justice. The relevant EU Regulation prioritises facility of transfer over protection of existing holders, insulating registered entitlements from prior proprietary claims. This approach ignores the important connections between history, integrity and responsibility in both public and private spheres. A preferable response would be to distinguish between transactional and register error, protecting against register mistakes, but not transactional defects.
Impact of different prenatal management strategies in short‐ and long‐term outcomes in monochorionic twin pregnancies with selective intrauterine growth restriction and abnormal flow velocity waveforms in the umbilical artery Doppler: a retrospective observational study of 108 cases
Authors: Colmant C , Lapillonne A , Stirnemann J , Belaroussi I , Leroy‐Terquem E , Kermovant‐Duchemin E , Bussieres L , Ville Y
Published: May 2020

Objectives

To review perinatal and neurodevelopmental outcome (NDO) following selective fetoscopic laser coagulation (SFLC), cord coagulation (CC) or expectant management of monochorionic diamniotic twin pregnancies complicated with selective intrauterine growth restriction (sIUGR) and absent or reverse end‐diastolic flow (AREDF) in the umbilical arteries (UA).

Design and setting

Single‐centre retrospective observational study.

Population

108 cases of sIUGR diagnosed before 26+6 weeks’ gestation with AREDF in the UA.

Methods

Survival rate and potential risk factors were analysed. NDO was assessed using parental questionnaires.

Main outcomes measures

Survival, gestational age at delivery and NDO.

Results

SFLC, CC and EM were performed in 13, 50 and 45 cases, respectively, with an overall survival of 23.1, 40 and 77.8% and intrauterine demise of the co‐twin of 30.8, 10 and 6.7% respectively. Intrauterine demise of the sIUGR twin occurred in 76.9 and 17.8% following SFLC and EM, respectively. The discordance in EFW at diagnosis was higher and absent/negative a‐wave in the ductus venosus (DV) was more prevalent in the surgical groups. NDO in survivors at follow up was abnormal in 0 and 18% in the smaller twin following SFLC and EM, respectively, and in 25, 24 and 21% in the larger twin following SFLC, CC and EM, respectively.

Conclusion

SFLC yielded a poor result. EM seems a valid option when EFW discordance is <30% and a‐wave in DV is positive. Otherwise, CC should be considered to protect the AGA co‐twin. The long‐term outcome of both small and large twins seems unaffected by the choice in primary prenatal management strategy.

Tweetable abstract

In type II sIUGR in MC twins, long‐term neurodevelopment is normal in over 80% of the survivors.
Integrating genomics into conservation management
Authors: Latch Emily K.
Published: May 2020

Captive populations play a vital role in conservation, supporting both in situ and ex situ conservation projects. A healthy, self‐sustaining captive population serves as valuable insurance against extinctions and a source of individuals for reintroduction into the wild. Genetic and genomic data can advance conservation and management across a range of scenarios. Although expanding, genomic data do not exist for most captive populations and there remain few examples of how these data can be integrated directly into conservation efforts. In this issue of Molecular Ecology Resources, Humble et al. (2020) present a chromosomal‐level genome assembly for the extinct‐in‐the‐wild scimitar‐horned oryx (Oryx dammah), and resequencing data to survey genetic variation across captive populations. These data are exciting for reintroduction planning by offering guidance for selecting source populations to maximize global genetic variation and valuable resources for effective post‐release monitoring. The genomic resources generated also are valuable tools with the power to yield novel and important insights into the evolution of scimitar‐horned oryx and other antelope species.
Impact ofTP53mutations in breast cancer: Clinicopathological features and prognosisImpact ofTP53mutations in breast CA
Authors: Li Xuerui , Chen Xiaoqing , Wen Lingzhu , Wang Yulei , Chen Bo , Xue Yunlian , Guo Liping , Liao Ning
Published: May 2020

Background

TP53is a crucial tumor suppressor gene. However, the mutation pattern ofTP53in Chinese patients with breast cancer has not yet been determined.

Methods

A total of 411 untreated patients with invasive breast cancer diagnosed at Guangdong Provincial People's Hospital (GDPH) between June 2017 to September 2018 were recruited into the study. Mutational alterations inTP53were detected and correlations betweenTP53mutations and clinicopathological features analyzed. Comparative analysis of the data in the GDPH cohort with those in the METABRIC cohort were carried out.

Results

A significantly higher rate ofTP53mutations was detected in the GDPH cohort (51.3%) compared with the METABRIC cohort (34.4%) (P < 0.01). In the GDPH cohort, 77.8% of the mutations were located in the conserved areas across exons 5–8 ofTP53; among these, 112 were identified as missense mutations and mainly clustered in the DNA‐binding region. R273C/H (n= 11) and R248Q/W (n= 10) were two of the most common mutation sites ofTP53detected in the cohort of GDPH patients. Logistic regression multivariate analysis showed that histological grade III, ki‐67 > = 25%, HR‐ and Her2+ in breast cancer had higher mutation probability ofTP53(P< 0.001 in the GDPH cohort). Furthermore, receiver operating characteristic (ROC) model combining molecular typing and Ki‐67 was established to predict the mutation ofTP53, and the AUC was 0.846.

Conclusions

A significantly higher rate ofTP53mutation was detected in the Chinese cohort compared with the METABRIC. Correlation analysis revealed a significant association ofTP53mutation with HR‐ and HER2+, higher Ki‐67 and histological grade in breast cancer patients.
The omnistat: A flexible continuous‐culture system for prolonged experimental evolution
Authors: Ekkers David M. , Branco dos Santos Filipe , Mallon Cyrus A. , Bruggeman Frank , van Doorn G. Sander
Published: May 2020

Microbial evolution experiments provide a powerful tool to unravel the molecular basis of adaptive evolution but their outcomes can be difficult to interpret, unless the selective forces that are applied during the experiment are carefully controlled. In this respect, experimental evolution in continuous cultures provides advantages over commonly used sequential batch‐culture protocols because continuous cultures allow for more accurate control over the induced selective environment. However, commercial continuous‐culture systems are large and expensive, while available DIY continuous‐culture systems are not versatile enough to allow for multiple sensors and rigorous stirring.

We present a modular continuous‐culture system that adopts the commonly used GL45 glass laboratory bottle as a bioreactor vessel. Our design offers three advantages: first, it is equipped with a large head plate, fitting two sensors and seven input/output ports, enabling the customization of the system for many running modes (chemostat, auxostat, etc.). Second, the bioreactor is small (25–250 ml), which makes it feasible to run many replicates in parallel. Third, bioreactor modules can be coupled by uni‐ or bi‐directional flows to induce spatiotemporal variation in selection. These features result in a particularly flexible culturing platform that facilitates the investigation of a broad range of evolutionary and ecological questions.

To illustrate the versatility of our culturing system, we outline two evolution experiments that impose a temporally or spatially variable regime of selection. The first experiment illustrates how controlled temporal variation in resource availability can be utilized to select for anticipatory switching. The second experiment illustrates a spatially structured morbidostat setup that is designed to probe epistatic interactions between adaptive mutations. Furthermore, we demonstrate how sensor data can be used to stabilize selection pressures or track evolutionary adaptation.

Evolution experiments in which populations are exposed to controlled spatiotemporal variation, are essential to gain insight into the process of adaptation and the mechanisms that constrain evolution. Continuous‐culture systems, like the one presented here, offer control over key environmental parameters and establish a well‐defined regime of selection. As such, they create the opportunity to expose evolutionary constraints in the form of phenotypic trade‐offs, contributing to a mechanistic understanding of adaptive evolution.
Survival after primary breast cancer surgery following propofol or sevoflurane general anesthesia—A retrospective, multicenter, database analysis of 6305 Swedish patients
Authors: Enlund Mats , Berglund Anders , Ahlstrand Rebecca , Walldén Jakob , Lundberg Johan , Wärnberg Fredrik , Ekman Andreas , Sjöblom Widfeldt Nina , Enlund Anna , Bergkvist Leif
Published: May 2020

Background

Retrospective studies indicate that the choice of anesthetic can affect long‐term cancer survival. Propofol seems to have an advantage over sevoflurane. However, this is questioned for breast cancer. We gathered a large cohort of breast cancer surgery patients from seven Swedish hospitals and hypothesized that general anesthesia with propofol would be superior to sevoflurane anesthesia regarding long‐term breast cancer survival.

Methods

We identified all patients who were anaesthetized for breast cancer surgery between 2006 and 2012. The patients were matched to the Swedish Breast Cancer Quality Register, to retrieve tumor characteristics, prognostic factors, and adjuvant treatment as well as date of death. Overall survival between patients undergoing sevoflurane and propofol anesthesia was analyzed with different statistical approaches: (a) multiple Cox regression models adjusted for demographic, oncological, and multiple control variables, (b) propensity score matching on the same variables, but also including the participating centers as a cofactor in a separate analysis.

Results

The database analysis identified 6305 patients. The 5‐year survival rates were 91.0% and 81.8% for the propofol and sevoflurane group, respectively, in the final model (P = .126). Depending on the statistical adjustment method used, different results were obtained, from a non‐significant to a "proposed" and even a "determined" difference in survival that favored propofol, with a maximum of 9.2 percentage points higher survival rate at 5 years (hazard ratio 1.46, 95% CI 1.10‐1.95).

Conclusions

It seems that propofol may have a survival advantage compared with sevoflurane among breast cancer patients, but the inherent weaknesses of retrospective analyses were made apparent.
Whinchat survival estimates across Europe: can excessive adult mortality explain population declines?
Authors: Fay R. , Schaub M. , Banik M. V. , Border J. A. , Henderson I. G. , Fahl G. , Feulner J. , Horch P. , Korner F. , Müller M. , Michel V. , Rebstock H. , Shitikov D. , Tome D. , Vögeli M. , Grüebler M. U.
Published: May 2020

European farmland birds show massive large‐scale population declines due to agricultural intensification. Long‐distance migrants are particularly affected as their populations appear to undergo larger declines than those of residents and short‐distance migrants, raising the question about the impact of non‐breeding environmental conditions and their potential impact on annual survival. The whinchatSaxicola rubetra,an Afro‐Palaearctic migrant inhabiting open habitats, has strongly declined over the last decades. Most of the conservation effort for this species has focused on improving the breeding success in Europe, but it remains unclear whether habitat changes in non‐breeding areas may also have contributed to the population declines through a decrease in adult survival. We studied survival of whinchats from eight breeding populations across Europe by analysing capture–recapture data. We found that apparent survival was consistently higher in males than in females and higher in successful than in failed breeders independently of the sex. True adult survival may, however, hardly differ between sexes being about 0.5 and 0.6 and a simple population model suggests true juvenile survival to be between 0.2 and 0.35. Adult survival was unrelated to population trends suggesting that the main demographic problem of the whinchats is likely insufficient reproduction, a feature that is shared with other declining grassland specialists. Finally, in line with results on other migratory farmland species, our study suggests that conservation activities for whinchats should in first place focus on Europe.
Effect of screening, brief intervention and referral to treatment for unhealthy alcohol and other drug use in mental health treatment settings: a randomized controlled trial
Authors: Karno Mitchell P. , Rawson Richard , Rogers Benjamin , Spear Suzanne , Grella Christine , Mooney Larissa J. , Saitz Richard , Kagan Bruce , Glasner Suzette
Published: May 2020

Aims

To test the efficacy of a brief intervention to reduce alcohol or drug use and to promote use of addiction services among patients seeking mental health treatment.

Design and setting

A multi‐centre, longitudinal, two‐group randomized controlled trial with randomization within each of two mental health treatment systems located in Ventura County and Los Angeles County in California, USA.

Participants

A total of 718 patients (49.2% female) aged 18 and older with a mental health diagnosis and either a heavy drinking day or any use of cannabis or stimulants in the past 90 days.

Intervention and comparator

A motivation‐based brief intervention with personalized feedback (screening, brief intervention and referral to treatment (SBIRT) condition) (n = 354) or a health education session (control condition) (n = 364).

Measurements

Primary outcomes included frequency of heavy drinking days, days of cannabis use and days of stimulant use at the primary end‐point 3 months post‐baseline. Secondary outcomes included frequency and abstinence from substance use out to a 12‐month follow‐up and the use of addiction treatment services.

Findings

Participants in the SBIRT condition had fewer heavy drinking days [odds ratio (OR) = 0.53; 95% credible interval (CrI) = 0.48–0.6] and fewer days of stimulant use (OR = 0.58; 95% CrI = 0.50–0.66) at the 3‐month follow‐up compared with participants in the health education condition. Participants in the SBIRT condition did not comparatively reduce days of cannabis use at the 3‐month follow‐up (OR = 0.93; 95% CrI = 0.85–1.01). Secondary outcomes indicated sustained effects of SBIRT on reducing the frequency of heavy drinking days and days of stimulant use. No effects were observed on abstinence rates or use of addiction treatment services.

Conclusions

Screening and brief intervention for unhealthy alcohol and drug use in mental health treatment settings were effective at reducing the frequency of heavy drinking and stimulant use.
DNA fragmentation of human spermatozoa: Simple assessment of single‐ and double‐strand DNA breaks and their respective dynamic behavioral response
Authors: Tímermans Ana , Vázquez Rosana , Otero Fátima , Gosálvez Jaime , Johnston Stephen , Fernández José Luis
Published: May 2020

Background

Procedures to detect sperm DNA fragmentation (SDF), like the sperm chromatin dispersion (SCD) test, determine the “global” SDF without discriminating between spermatozoa with single‐strand DNA breaks only (SDF‐SSBs) and those containing double‐strand DNA breaks (SDF‐DSBs).

Objectives

(a) To validate a test to distinguish human spermatozoa with massive DSBs (DSB‐SCD assay), (b) to study the baseline SDF‐SSBs and SDF‐DSBs, and (c) to assess their dynamics in vitro.

Materials and methods

(a) SDF‐DSBs were determined by visualization of diffused DNA fragments from spermatozoa lysed under non‐denaturing conditions. This was validated by in vitro incubation with DNase I and the comet assay. (b) Baseline SDF‐DSBs and SDF‐SSBs were determined in ejaculates from 95 males. (c) Their dynamic appearance was studied in samples untreated or exposed to hyperthermia, acidic pH, nitric oxide released by sodium nitroprusside (SNP), and the metabolic energy inhibitors 2‐deoxy‐D‐glucose and antimycin A.

Results

(a) DNase I and comet assay experiments confirmed that the assay successfully determined SDF‐DSBs. (b) The higher the SDF of the semen sample, the higher the frequency of SSBs, whereas DSBs behaved independently. Abnormal samples showed higher SDF than normozoospermic, the difference being only significant for SDF‐SSBs. (c) During the first hours of incubation, the linear rate of increase in SDF‐SSBs was 3.7 X higher than that of SDF‐DSBs. All hazardous agents accelerated the SDF rate when compared to untreated spermatozoa, primarily being associated with SDF‐SSBs. SNP treatment was the most damaging, rapidly inducing spermatozoa with SSBs which progressively evolved to DSBs. Remarkably, this phenomenon was also evidenced after acute SNP exposure, revealing cryptic sperm damage.

Conclusion

The DSBs‐SCD is an easy complement for SDF assessment. The dynamic study of SSBs and DSBs may improve the evaluation of sperm quality in clinical settings, particularly “unmasking” the presence of non‐specific cryptic sperm damage that might otherwise go undetected.
Risk factors of unsuccessful vaginal twin delivery
Authors: Ylilehto Elina , Palomäki Outi , Huhtala Heini , Uotila Jukka
Published: May 2020

Introduction

Twin trial of labor presents a challenge to obstetricians, as it is associated with a greater number of adverse birth outcomes compared with singleton deliveries. The risk of poor outcome has shown to be highest with unsuccessful vaginal twin delivery. The purpose of this study was to identify the clinical risk factors associated with intrapartum cesarean section in late preterm and term twin births.

Material and methods

All live diamniotic twin deliveries of at least 35+0 weeks of gestation with planned vaginal delivery were included in this retrospective single‐center cohort study. Maternal and newborn characteristics were compared between a vaginal delivery group and an intrapartum cesarean section group. Logistic regression analysis was carried out to determine independent risk factors of intrapartum cesarean section. Further, maternal and neonatal outcomes were compared between groups of vaginal delivery and cesarean section for both twins and also between groups of vaginal delivery and cesarean section for the second twin only (combined delivery). The impact of presentation of the second twin on the mode of twin delivery and on neonatal outcome was also examined.

Results

Among 821 twin pregnancies, 581 mothers (70.8%) attempted trial of labor and were eligible for the study. With a cephalic‐presenting first twin, the trial of labor rate was 89.3% and vaginal delivery was successful in 82.8%. Nulliparity (odds ratio [OR] 3.2, 95% confidence interval [CI] 2.0‐5.1) and non‐cephalic presentation of the second twin (OR 3.0, 95% CI 1.9‐4.8) were found to be independent risk factors of cesarean section. However, 76.1% of mothers with non‐cephalic second twins achieved vaginal delivery and perinatal outcomes were comparable with cases of cephalic‐presenting second twins. When comparing delivery modes, maternal outcomes were more favorable with vaginal delivery, whereas combined delivery increased the second twin’s risk of adverse neonatal outcome.

Conclusions

This study, with high rates of trial of labor and successful vaginal twin delivery, found nulliparity and non‐cephalic presentation of the second twin to be risk factors of intrapartum cesarean section in twin pregnancies.
Management of pregnancy after fertility‐sparing surgery for cervical cancer
Authors: Šimják Patrik , Cibula David , Pařízek Antonín , Sláma Jiří
Published: May 2020

Cervical cancer is increasingly diagnosed in women who have not yet completed their reproductive plans. For women with early‐stage disease (FIGO stage IA1‐IB1), fertility‐sparing procedures, such as conization, trachelectomy or radical trachelectomy, represent the treatments of choice. However, women who undergo repeated conization or trachelectomy represent a challenge for obstetricians because they are at increased risk of infertility, mid‐trimester miscarriage, preterm premature rupture of membranes and preterm delivery. So far, the evidence‐based guidance on the management of these pregnancies is limited. This article reviews the literature discussing pregnancy management in women after fertility‐sparing surgery for early cervical cancer. Although the evidence is limited, certain measures are desirable, including screening and treatment of asymptomatic bacteriuria, screening for cervical incompetence and progressive cervical shortening by transvaginal ultrasonography, and fetal fibronectin testing. Vaginal progesterone supplementation should be primary prevention for all women after trachelectomy. Women with a history of preterm delivery or late miscarriage may benefit from cervical cerclage. Elective delivery by cesarean section in the early‐term period is desirable.
Characteristics and outcomes of gastrointestinal bleeding in patients with continuous‐flow left ventricular assist devices: A systematic review
Authors: Carlson Laura A. , Maynes Elizabeth J. , Choi Jae Hwan , Hallett Andrew M. , Horan Dylan P. , Weber Matthew P. , Deb Avijit K. , Patel Sinal , Samuels Louis E. , Morris Rohinton J. , Entwistle John W. , Todd Massey H. , Tchantchaleishvili Vakhtang
Published: May 2020

Gastrointestinal bleeding (GIB) is a common adverse event after continuous‐flow left ventricular assist device (CF‐LVAD) implantation. We sought to evaluate patterns of GIB development and related outcomes in CF‐LVAD recipients. An electronic search was performed to identify all articles related to GIB in the setting of CF‐LVAD implantation. A total of 34 studies involving 1087 patients were pooled for analysis. Mean patient age was 60 years (95% CI 57‐64) and 24% (95% CI 21‐28%) were female. The mean time from CF‐LVAD implantation to the first GIB was 54 days (95% CI 24‐84) with 40% (95% CI 34‐45%) of patients having multiple episodes of GIB. Anemia was present in 75% (95% CI 41‐93%) and the most common etiology of bleeding was arteriovenous malformations (36% [95% CI 24‐50%]). The mean duration of follow‐up was 14.6 months (95% CI 6.9‐22.3) during which the all‐cause mortality rate was 21% (95% CI 12‐36%) and the mortality rate from GIB was 4% (95% CI 2‐9%). Thromboembolic events occurred in 32% (95% CI 22‐44%) of patients with an ischemic stroke rate of 16% (95% CI 3‐51%) and a pump thrombosis rate of 8% (95%CI 3‐22%). Heart transplantation was performed in 31% (95% CI 18‐47%) of patients, after which 0% (95% CI 0‐10%) experienced recurrent GIB. GIB is a major source of morbidity among CF‐LVAD recipients. While death due to GIB is rare, cessation of anticoagulation during treatment increases the risk of subsequent thrombotic events. Heart transplant in these patients appears to reliably resolve the risk of future GIB.
The Mitigating Role of Trait Core Confidence on Psychological Distress in Entrepreneurship
Authors: Sergent Kayla , Lee Dongseop , Stajkovic Alexander D. , Greenwald Jessica M. , Younger Shannon , Raffiee Joe
Published: May 2020

We conceptualize the mitigating role of trait core confidence on psychological distress in entrepreneurship manifested by occupational stress, anxiety, and depression. To facilitate field research, we first developed a short trait core confidence scale and validated it in six independent samples (N = 2,434). To test our hypothesis that trait core confidence negatively relates to base‐line levels of psychological distress as well as reduces fluctuations of distress in entrepreneurship, we collected data from a 3‐day entrepreneurial event called Startup Weekend across seven occasions in the United States. High trait core confidence was related to lower psychological distress both at the start of the event on Friday and at the end of it on Sunday. Core confidence remained stable from Friday to Sunday, as well as 1 month following the event, affirming its trait properties. Additionally, we measured team confidence during the event and found that high team confidence reduced psychological distress of team members. This research contributes to the research on the role of dispositions in occupational health psychology and to a better understanding of how distress of aspiring entrepreneurs is mitigated by trait core confidence.
Effectiveness of ustekinumab dose escalation in Crohn’s disease patients with insufficient response to standard‐dose subcutaneous maintenance therapy
Authors: Kopylov Uri , Hanzel Jurij , Liefferinckx Claire , De Marco Davide , Imperatore Nicola , Plevris Nikolas , Baston‐Rey Iria , Harris Richard J. , Truyens Marie , Domislovic Viktor , Vavricka Stephan , Biemans Vince , Myers Sally , Sebastian Shaji , Ben‐Horin Shomron , González Lama Yago , Gilletta Cyrielle , Ariella Bar‐Gil Shitrit , Zelinkova Zuzana , Weisshof Roni , Storan Darragh , Zittan Eran , Farkas Klaudia , Molnar Tamas , Franchimont Denis , Cremer Anneline , Afif Waqqas , Castiglione Fabiana , Lees Charles , Barreiro‐de Acosta Manuel , Lobaton Triana , Doherty Glen , Krznaric Zeljko , Pierik Marieke , Hoentjen Frank , Drobne David
Published: May 2020

Background

Ustekinumab is effective in Crohn's disease. However, a substantial proportion of patients will not respond or lose response to ustekinumab. The current evidence to support the effectiveness of dose‐optimisation for ustekinumab nonresponse is limited.

Aim

To assess the effectiveness of dose escalation of ustekinumab.

Methods

This was a multicentre retrospective cohort study. We included active Crohn's disease patients who received a standard‐dose intravenous induction and at least one subcutaneous ustekinumab 90 mg dose. All enrolled patients received dose escalation by either shortening the interval between the doses to every 4 or 6 weeks, intravenous reinduction or a combination of strategies. The primary outcome of the study was clinical response at week 16 after dose escalation.

Results

A total of 142 patients (22 centres/14 countries) were included. The patients were dose‐escalated after a median treatment duration of 30 weeks. At week 16 from escalation, 73/142 (51.4%) responded to treatment, including 55/142 (38.7%) in clinical remission. Corticosteroid‐free remission was achieved in 6/34 (17.6%) patients on corticosteroids at the time of escalation; 118/142 (83%) continued treatment beyond week 16. Follow‐up data beyond week 16 were available for 74/118 (62.7%) patients. On the last follow‐up, 51/98 (52%) patients with available data responded to treatment, including 41/98 (42%) in clinical remission.

Conclusions

Intensification of ustekinumab maintenance dosage was effective in over 50% of the patients. This strategy should be considered in patients who are nonresponsive to every 8 weeks ustekinumab maintenance dosing.
Mass balance, pharmacokinetics and pharmacodynamics of intravenous HSK3486, a novel anaesthetic, administered to healthy subjects
Authors: Bian Yicong , Zhang Hua , Ma Sheng , Jiao Yongyi , Yan Pangke , Liu Xiao , Ma Shiping , Xiong Yating , Gu Zheming , Yu Zhenwen , Huang Chenrong , Miao Liyan
Published: May 2020

Aims

This trial (NCT03751956) investigated the mass balance, pharmacokinetics and pharmacodynamics of HSK3486, a novel anaesthetic, in healthy subjects.

Methods

A single dose of 0.4 mg/kg [14C]HSK3486 was administered to six healthy subjects. Blood, urine and faecal samples were collected, analysed for radioactivity, unchanged HSK3486 and profiled for metabolites. The Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale and vital signs were closely monitored during the study.

Results

The mean recovery of total radioactivity in excreta was 87.3% in 240 h, including 84.6% in urine and 2.65% in faeces. The exposure (AUC0‐t) of total radioactivity was much higher than that of unchanged HSK3486 in plasma, indicating there were circulating metabolites in plasma. The glucuronide conjugate of HSK3486 (M4) was found as the only major circulating metabolite in plasma (79.3%), while unchanged HSK3486 accounted for only 3.97% of the total radiation exposure. M4 also resulted in a longer estimated elimination half‐life (t1/2) of total radioactivity than that of unchanged HSK3486 in plasma. Fortunately, the metabolite was detected to be not specific to red blood cells and was suggested to be nonhypnotic and nontoxic. All the subjects were quickly anaesthetized (2 min) after drug administration and woke up smoothly after a short time (5.5–14.1 min) with few residual effects. The only adverse event in the study was mild (grade 1) and consisted of hypotension.

Conclusion

HSK3486 is a promising anaesthetic candidate with rapid onset of action and clear absorption, distribution, metabolism, excretion (ADME) processes. HSK3486 showed favourable pharmacokinetic characteristics, pharmacodynamic responses and safety at the study dose.
Evaluation of pharmacokinetic‐pharmacodynamic relationships and selection of drug combinations for tuberculosis
Authors: Muliaditan Morris , Della Pasqua Oscar
Published: May 2020

Aims

Despite evidence of the efficacy of anti‐tubercular drug regimens in clinical practice, the rationale underpinning the selection of doses and companion drugs for combination therapy remains empirical. Novel methods are needed to optimise the antibacterial activity in combination therapies. A drug–disease modelling framework for rational selection of dose and drug combinations in tuberculosis is presented here.

Methods

A model‐based meta‐analysis was performed to assess the antibacterial activity of different combinations in infected mice. Data retrieved from the published literature were analysed using a two‐state bacterial growth dynamics model, including fast‐ and slow‐growing bacterial populations. The contribution of each drug to the overall antibacterial activity of the combination was parameterised as relative change to the potency of the backbone drug (EC50‐F and/or EC50‐S). Rifampicin and bedaquiline were selected as paradigm drugs to evaluate the predictive performance of the modelling approach.

Results

Pyrazinamide increased the potency (EC50‐F and EC50‐S) of rifampicin (RZ) and bedaquiline (BZ) by almost two‐fold. By contrast, pretomanid and isoniazid were found to worsen the antibacterial activity of BZ and RZ, respectively. Following extrapolation of in vivo pharmacokinetic‐pharmacodynamic relationships, the dose of rifampicin showing maximum bactericidal effect in tuberculosis patients was predicted to be 70 mg·kg−1 when given in combination with pyrazinamide.

Conclusions

The use of a drug–disease modelling framework may provide a more robust rationale for extrapolation and selection of dose and companion drugs in humans. Our analysis demonstrates that RZ and BZ should be considered as a backbone therapy in prospective novel combination regimens against tuberculosis.
Robust and efficient semi‐supervised estimation of average treatment effects with application to electronic health records data
Authors: Cheng David , Ananthakrishnan Ashwin N. , Cai Tianxi
Published: May 2020

We consider the problem of estimating the average treatment effect (ATE) in a semi‐supervised learning setting, where a very small proportion of the entire set of observations are labeled with the true outcome but features predictive of the outcome are available among all observations. This problem arises, for example, when estimating treatment effects in electronic health records (EHR) data because gold‐standard outcomes are often not directly observable from the records but are observed for a limited number of patients through small‐scale manual chart review. We develop an imputation‐based approach for estimating the ATE that is robust to misspecification of the imputation model. This effectively allows information from the predictive features to be safely leveraged to improve efficiency in estimating the ATE. The estimator is additionally doubly‐robust in that it is consistent under correct specification of either an initial propensity score model or a baseline outcome model. It is also locally semiparametric efficient under an ideal semi‐supervised model where the distribution of the unlabeled data is known. Simulations exhibit the efficiency and robustness of the proposed method compared to existing approaches in finite samples. We illustrate the method by comparing rates of treatment response to two biologic agents for treatment inflammatory bowel disease using EHR data from Partners' Healthcare.
The Motivational Thought Frequency Scales for increased physical activity and reduced high‐energy snacking
Authors: Kavanagh David J. , Teixeira Hugo , Connolly Jennifer , Andrade Jackie , May Jon , Godfrey Shaneen , Carroll Amanda , Taylor Kimberly , Connor Jason P.
Published: May 2020

Objectives

The Motivational Thought Frequency (MTF) Scale has previously demonstrated a coherent four‐factor internal structure (Intensity, Incentives Imagery, Self‐Efficacy Imagery, Availability) in control of alcohol and effective self‐management of diabetes. The current research tested the factorial structure and concurrent associations of versions of the MTF for increasing physical activity (MTF‐PA) and reducing high‐energy snacks (MTF‐S).

Design

Study 1 examined the internal structure of the MTF‐PA and its concurrent relationship with retrospective reports of vigorous physical activity. Study 2 attempted to replicate these results, also testing the internal structure of the MTF‐S and examining whether higher MTF‐S scores were found in participants scoring more highly on a screening test for eating disorder.

Methods

In Study 1, 626 participants completed the MTF‐PA online and reported minutes of activity in the previous week. In Study 2, 313 participants undertook an online survey that also included the MTF‐S and the Eating Attitudes Test (EAT‐26).

Results

The studies replicated acceptable fit for the four‐factor structure on the MTF‐PA and MTF‐S. Significant associations of the MTF‐PA with recent vigorous activity and of the MTF‐S with EAT‐26 scores were seen, although associations were stronger in Study 1.

Conclusions

Strong preliminary support for both the MTF‐PA and MTF‐S was obtained, although more data on their predictive validity are needed. Associations of the MTF‐S with potential eating disorder illustrate that high scores may not always be beneficial to health maintenance.
COVID‐19: Concerns and behaviours in Croatia
Authors: Lauri Korajlija Anita , Jokic‐Begic Natasa
Published: May 2020

Objectives

The COVID‐19 pandemic has created uncertainty that has heightened fear and worry worldwide, thus elevating the potential for a growth in anxiety. This study aims to examine changes in levels of COVID‐19 concern and safety behaviours among persons living in Croatia during the period in which the first COVID‐19 case was identified and when the country recorded its first fatality. These changes were examined with respect to gender and family circumstances.

Design

The repeated cross‐sectional data were conducted over two time points over the 3 weeks (N1 = 888; N2 = 966).

Methods

Participants completed online questionnaire regarding various COVID‐19 concerns and safety behaviours aimed at disease prevention.

Results

Findings demonstrate dramatic increase in concern and safety behaviours among participants during the 3 weeks between the first identified case and the first fatality. The results suggest that parents, and mothers especially, represent the most concerned group, regardless of age. People with chronic health conditions also expressed greater concern and safety behaviour than healthy participants, but with small effect size.

Conclusion

These findings highlight the importance of developing clear guidelines for alleviating the negative effects on mental health through effective communication strategies that minimize fear and emphasize positive behavioural change.

Statement of contribution

What is already known on this subject?

In times of pandemic, people react with elevated levels of anxiety and some will adjust their behaviours in order to protect themselves as well as their family and friends.

Some of the measures introduced to protect the spread of the COVID‐19 disease have induced an atmosphere of fear, which in turn can lead to an increase in maladaptive anxiety and a greater burden on mental health.

What does this study add?

By conducting the research in two waves representing two critical time points in the developing COVID‐19 situation in Croatia, we were able to trace a large increase in anxiety levels and safety behaviours among the general population.

There is a discordance between those who are at most risk from serious consequences of the disease and those who are at greatest risk for maladaptive anxiety. Parents, and mothers in particular, represent the most concerned group, regardless of age.

Lockdown measures have allowed us to ensure the safety of those vulnerable for serious COVID‐19 illness. Now, we must focus on preserving the mental health of our whole community.