bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of protein concentration in downstream biomanufacturing processes by in‐line index of refraction
Authors: Harris Steven A. , Patel Bhumit A. , Gospodarek Adrian , Desai Jayesh , de Janon Gutiérrez Alejandro , Botonjic‐Sehic Edita , Brower Mark , Pinto Nuno D. S.
Published: June 2021

Protein concentration determination is a necessary in‐process control for the downstream operations within biomanufacturing. As production transitions from batch mode to an integrated continuous bioprocess paradigm, there is a growing need to move protein concentration quantitation from off‐line to in‐line analysis. One solution to fulfill this process analytical technology need is an in‐line index of refraction (IoR) sensor to measure protein concentration in real time. Here the performance of an IoR sensor is evaluated through a series of experiments to assess linear response, buffer matrix effects, dynamic range, sensor‐to‐sensor variability, and the limits of detection and quantitation. The performance of the sensor was also tested in two bioprocessing scenarios, ultrafiltration and capture chromatography. The implementation of this in‐line IoR sensor for real‐time protein concentration analysis and monitoring has the potential to improve continuous bioprocess manufacturing.
The promising role of antibody drug conjugate in cancer therapy: Combining targeting ability with cytotoxicity effectively
Authors: Li Wen‐Qian , Guo Han‐Fei , Li Ling‐Yu , Zhang Yong‐Fei , Cui Jiu‐Wei
Published: June 2021

Introduction

Traditional cancer therapy has many disadvantages such as low selectivity and high toxicity of chemotherapy, as well as insufficient efficacy of targeted therapy. To enhance the cytotoxic effect and targeting ability, while reducing the toxicity of antitumor drugs, an antibody drug conjugate (ADC) was developed to deliver small molecular cytotoxic payloads directly to tumor cells by binding to specific antibodies via linkers.

Method

By reviewing published literature and the current progress of ADCs, we aimed to summarize the basic characteristics, clinical progress, and challenges of ADCs to provide a reference for clinical practice and further research.

Results

ADC is a conjugate composed of three fundamental components, including monoclonal antibodies, cytotoxic payloads, and stable linkers. The mechanisms of ADC including the classical internalization pathway, antitumor activity of antibodies, bystander effect, and non‐internalizing mechanism. With the development of new drugs and advances in technology, various ADCs have achieved clinical efficacy. To date, nine ADCs have received US Food and Drug Administration (FDA) approval in the field of hematologic tumors and solid tumors, which have become routine clinical treatments.

Conclusion

ADC has changed traditional treatment patterns for cancer patients, which enable the same treatment for pancreatic cancer patients and promote individualized precision treatment. Further exploration of indications could focus on early‐stage cancer patients and combined therapy settings. Besides, the mechanisms of drug resistance, manufacturing techniques, optimized treatment regimens, and appropriate patient selection remain the major topics.
Integrative analysis of immune molecular subtypes and microenvironment characteristics of bladder cancer
Authors: Cao Jinlong , Li Jianpeng , Yang Xin , Li Pan , Yao Zhiqiang , Han Dali , Ying Lijun , Wang Lijie , Tian Junqiang
Published: June 2021

The emergence of immunotherapy has provided an option of treatment methods for bladder cancer (BC). However, the beneficiaries of immunotherapy are still limited to small‐scale patients, and immunotherapy‐related adverse events often occur. It is a major challenge for clinical work to study the immune subtypes of BC and the molecular mechanism of immune escape, and identify the immune responders accurately. Here, we explore the immune molecular subtypes of bladder cancer and potential escape mechanisms. First, we screened the expression profiles of 303 differentially expressed immune‐related genes in BC patients from the Cancer Genome Atlas (TCGA) database, and successfully identified 4 molecular subtypes of BC. By comparing the clinical characteristics, immune cells infiltration, the expression of checkpoint genes, human leukocyte antigen (HLA) genes, and gene mutation status of different subtypes, we identified different clinical and immunological characteristics of 4 subtypes. Among 4 subtypes, Cluster 2 met the general characteristics of immunotherapy responders and responded well to immunotherapy, while Cluster 4 had the highest expression of immune characteristics, and is similar to the immune environment of normal bladder tissue. Then, the weighted gene co‐expression network analysis (WGCNA) of immune‐related genes revealed that brown module was positively correlated with subtypes. Pathway enrichment analysis explored the major pathways associated with subtypes, which are also associated with immune escape mechanisms. Moreover, the decision tree model, which was constructed by the principle of random forest screening factors, was also validated in internal validation set and external validation set from the Gene Expression Omnibus (GEO) cohort (GSE133624), and could achieve accurate subtypes prediction for BC patients with high‐throughput sequencing. Taken together, we explored the immune molecular subtypes and their mechanisms of BC, and these results may provide guidance for the development of new BC immunotherapy strategies.
Detection of HPV infection in urothelial carcinoma using RNAscope: Clinicopathological characterization
Authors: Musangile Fidele Y. , Matsuzaki Ibu , Okodo Mitsuaki , Shirasaki Ayaka , Mikasa Yurina , Iwamoto Ryuta , Takahashi Yuichi , Kojima Fumiyoshi , Murata Shin‐ichi
Published: June 2021

Background

Human papillomavirus (HPV) is a well‐established mucosotropic carcinogen, but its impact on urothelial neoplasm is unclear. We aimed to clarify the clinical and pathological features of HPV‐related urothelial carcinoma (UC).

Methods

Tissue samples of 228 cases of UC were obtained from the bladder, upper and lower urinary tract, and metastatic sites to construct a tissue microarray. The samples were analyzed for the presence of HPV by a highly sensitive and specific mRNA in situ hybridization (RISH) technique (RNAscope) with a probe that can detect 18 varieties of high‐risk HPV. We also conducted immunohistochemistry (IHC) for a major HPV capsid antibody and DNA‐PCR.

Results

The HPV detection rates varied among the methods; probably due to low HPV copy numbers in UC tissues and the insufficient specificity and sensitivity of the IHC and PCR assays. The RISH method had the highest accuracy and identified HPV infection in 12 (5.2%) of the cases. The histopathological analysis of the HPV‐positive UC showed six cases of usual type UC, five cases of UC with squamous differentiation (UC_SqD), and one case of micropapillary UC. The HPV detection rate was six‐fold higher in the cases of UC_SqD than in the other variants of UC (odds ratio [OR] =8.9, p = 0.002). In addition, HPV infection showed a significant association with tumor grade (OR =9.8, p = 0.03) and stage (OR =4.7, p = 0.03) of UC. Moreover, the metastatic rate was higher in HPV‐positive than in negative UC (OR =3.4).

Conclusion

These data indicate that although the incidence of HPV infection in UC is low, it is significantly associated with squamous differentiation and poor prognosis. Furthermore, our observations show that RNAscope is an ideal method for HPV detection in UC compared with the other standard approaches such as IHC and PCR assays.
Laparoscopy‐assisted immediate vaginal reconstruction with a vertical pedicled deep inferior epigastric perforator flap for primary melanoma of the vagina
Authors: Dupré Pierre‐François , Legoupil Delphine , Vigouroux Camille , Conan‐Charlet Virginie , Kergastel Isabelle , Merviel Philippe , Kerfant Nathalie
Published: June 2021

The vagina is a rare site for primary melanoma. Here, we report on a case of laparoscopy‐assisted immediate vaginal reconstruction with vertical pedicled deep inferior epigastric perforator flap.
Transseptal mitral valve‐in‐valve implantation in a degenerated mitral bioprosthesis: A case report and literature review
Authors: Perrin Nils , Müller Hajo , Noble Stephane
Published: June 2021

Transseptal TMViV should be considered for mitral bioprosthesis failure especially when large THV can be implanted. Elevated residual mean gradient and its effect on valve durability and potential valve thrombosis remains an unanswered question.
Spontaneous descending colon hematoma due to a rare complication of warfarin therapy: A case report
Authors: Yavari Negin , Majdi Nassab Farzaneh , Tajvidi Mohammad Amin , Shirani Shapour , Shirani Shahram , Ahmadi Tafti Seyed Hossein
Published: June 2021

Intramural hematoma of the colon should be considered as a diagnosis in anticoagulated patients who present with prolonged INR and GI symptoms. In stable cases, conservative medical treatment can be sufficient to avoid unnecessary procedures.
Wegener's granulomatosis and differential diagnosis of mucosal leishmaniasis
Authors: Rojas‐Jaimes Jesús , Hugo Rojas Figueroa Víctor , Corcuera‐Ciudad Rodrigo , Arenas José , García‐Reynoso Julio
Published: June 2021

Granulomatosis with polyangiitis with nasal septal perforation can be confused with infectious diseases such as mucosal leishmaniasis, so these cases warrant an in‐depth study in order to provide the correct treatment. Among the main characteristics to consider to define a Wegener's granulomatosis as opposed to an infectious disease are vasculitis, lymphadenopathy, and sinusopathy.
Doege‐Potter syndrome in a facial solitary fibrous tumor: Diagnose and clinical management discussion
Authors: Fort‐Culillas Roser , Barahona San Millán Rebeca , Garcia‐Fructuoso Isabel , Quera González Angels , Grau Martín Armand , Puigdemont Guinart Montserrat , Rubió‐Casadevall Jordi , Recasens Sala Mònica , Porta Balanyà Rut
Published: June 2021

Doege‐Potter syndrome is a rare hypoglycemic paraneoplastic disorder. This case describes that severe and symptomatic hypoglycemia can occasionally be due to a rare malignant neoplasm, and the differential diagnosis of malignancy should not be overlooked in this setting.
Xanthogranulomatous endometritis: A case report and literature review
Authors: Merviel Philippe , James Pandora , Carlier Marianne , Thomas‐Kergastel Isabelle , Guilloique Marine , Conan‐Charlet Virginie , Bastard Clara , Marcorelles Pascale , Jobic Yannick , Dupré Pierre‐François
Published: June 2021

Xanthogranulomatous endometritis is a rare benign pathology mimicking endometrial carcinoma.
A case of percutaneous tricuspid valve infective endocarditis vegetation debulking using the AngioJet rheolytic catheter system—A novel therapeutic use
Authors: Back Liam Marsden , Hurley Siobhan , Beardsley Justin , Kushwaha Virag
Published: June 2021

In patients with fulminant tricuspid valve infective endocarditis precluded from cardiothoracic intervention based on comorbidities or clinical status, percutaneous vegetation debulking utilizing the AngioJet rheolytic catheter system appears a viable rescue option to achieve source control.
Rare occurrence of lepra type 1 reaction in pure neuritic leprosy: A case report
Authors: Pathak Raksha , Agrawal Sudha , Paudyal Punam
Published: June 2021

Type 1 reaction in pure neuritic leprosy usually occurs in the form of neuritis. The development of new skin lesion during reaction is rare. Clinicians should be aware about occurrence of type 1 reaction in pure neuritic leprosy.
Process modelling and simulation of bitumen partial upgrading: Analysis of solvent deasphalting‐thermal cracking configuration
Authors: Gholami Rahman , Alvarez‐Majmutov Anton , Chen Jinwen
Published: June 2021

In this study, we investigate a process for partial upgrading of Canadian oil sands bitumen by means of modelling and simulation. In continuation of our previous study focused on a different process configuration for partial upgrading, the process scheme analyzed in this work consists of a solvent deasphalting step to reject asphaltenes from bitumen, a thermal cracking of the deasphalted product step, and a hydrotreating step to saturate the olefins generated by thermal cracking. The model was built using commercial simulation software, incorporating customized models for the solvent deasphalting and thermal cracking units. Trends in partial upgrader product yields and quality are examined under two operating scenarios: one where the thermal cracker operates in once‐through mode and the other where the heavy portion of the thermal cracker product is recycled. Both scenarios were observed to have difficulties in achieving the product quality targets set for partial upgrading (density <0.9400 g/cm3 at 15.6°C and viscosity <350 cSt at 7°C) without any diluent addition. A key factor that significantly impacts final product yield and quality in this partial upgrading process is the formation of new asphaltenes during thermal cracking.
The Deflagrating Davy Lamp – Renaissance of an chemical masterstroke to substitute hazardous substances in modern experimental courses
Authors: Reinmold Marco , Lühken Arnim
Published: June 2021

Im Experimentalunterricht wird die heterogene Katalyse oft am Experiment der oszillierenden Verpuffung eines Methanol‐Luftgemisches an einem Kupfer‐ oder Platindraht vorgestellt. Dieses Experiment wird seit etwa 30 Jahren von verschiedenen Autor:innen weiterentwickelt. Jedoch birgt die Verwendung von Methanol in diesem Experiment einige Gefahren, da unabhängig von dessen toxischer Wirkung bei der Reaktion Methanal entsteht. Aufgrund der Gefahreneinstufungen von Methanol und Methanal ist die Durchführung dieses Experimentes im Chemieunterricht als kritisch zu bewerten. In diesem Beitrag wird nun durch Rückgriff auf einen historischen Erkenntnisstand zur heterogen‐katalytischen Wirkung des Platins ein neuartiger Schulversuch zur oszillierenden Reaktion von Alkanen mit Luftsauerstoff vorgestellt. Die Verwendung von haushaltsüblichem Waschbenzin ermöglicht die Durchführung als Schülerexperiment ab der 4. Klasse und vereinfacht die Handhabung des Versuchs.
Development of LM98, a Small‐Molecule TEAD Inhibitor Derived from Flufenamic Acid
Authors: Mélin Léa , Abdullayev Shuay , Fnaiche Ahmed , Vu Victoria , González Suárez Narjara , Zeng Hong , Szewczyk Magdalena M. , Li Fengling , Senisterra Guillermo , Allali‐Hassani Abdellah , Chau Irene , Dong Aiping , Woo Simon , Annabi Borhane , Halabelian Levon , LaPlante Steven R. , Vedadi Masoud , Barsyte‐Lovejoy Dalia , Santhakumar Vijayaratnam , Gagnon Alexandre
Published: June 2021

The YAP‐TEAD transcriptional complex is responsible for the expression of genes that regulate cancer cell growth and proliferation. Dysregulation of the Hippo pathway due to overexpression of TEAD has been reported in a wide range of cancers. Inhibition of TEAD represses the expression of associated genes, demonstrating the value of this transcription factor for the development of novel anti‐cancer therapies. We report herein the design, synthesis and biological evaluation of LM98, a flufenamic acid analogue. LM98 shows strong affinity to TEAD, inhibits its autopalmitoylation and reduces the YAP‐TEAD transcriptional activity. Binding of LM98 to TEAD was supported by 19F‐NMR studies while co‐crystallization experiments confirmed that LM98 is anchored within the palmitic acid pocket of TEAD. LM98 reduces the expression of CTGF and Cyr61, inhibits MDA‐MB‐231 breast cancer cell migration and arrests cell cycling in the S phase during cell division.
Photooxygenation of Naphthalene
Authors: Fudickar Werner , Linker Torsten
Published: June 2021

The photooxygenation of naphthalene to the corresponding endoperoxide (EPO) under various conditions is described. Substantial conversion is only observed at −10 °C and after more than two days, indicating that the [4+2] cycloaddition of singlet oxygen to this acene proceeds much more slowly than corresponding reactions of substituted naphthalenes, a rate constant of k=5.4±0.3 M−1s−1 was determined by competition kinetics. Another problem is the thermal lability and photochemical cleavage of the naphthalene EPO. We investigated the mechanism of this radical process depending on the light source and sensitizer in comparison to known cyclohexadiene EPO. Thus, bisepoxides and keto epoxides are formed after homolysis of the O−O bond by irradiation with sodium lamps or blue LEDs and subsequent cyclization. This process is accelerated by the sensitizers methylene blue and 9,10‐dicyanoanthracene, indicating an electron transfer mechanism. Finally, the cleavage of the peroxidic bond is inhibited with red LEDs, and photooxygenation under such conditions affords 20 % EPO. Thus, we could demonstrate that contrary to literature statements singlet oxygen does indeed react with naphthalene.
Mapping the vulnerability of giant sequoias after extreme drought in California using remote sensing
Authors: Baeza Andres , Martin Roberta E. , Stephenson Nathan L. , Das Adrian J. , Hardwick Paul , Nydick Koren , Mallory Jeff , Slaton Michèle , Evans Kirk , Asner Gregory P.
Published: June 2021

Between 2012 and 2016, California suffered one of the most severe droughts on record. During this periodSequoiadendron giganteum(giant sequoias) in the Sequoia and Kings Canyon National Parks (SEKI), California, USA experienced canopy water content (CWC) loss, unprecedented foliage senescence, and, in a few cases, death. We present an assessment of the vulnerability of giant sequoia populations to droughts that is currently lacking and needed for management. We used a temporal trend of remotely sensed CWC obtained between 2015 and 2017, and recently georeferenced giant sequoia crowns to quantify the vulnerability of 7,408 individuals in 10 groves in the northern portion of SEKI. CWC is sensitive to changes in liquid water in tree canopies; therefore, it is a useful metric for quantifying the response of sequoia trees to drought. Temporal trends indicated that 9% of giant sequoias had a significant decline or consistently low CWC, suggesting these trees were likely operating at low photosynthetic capacity and potentially at high risk to drought stress. We also found that 20% of the giant sequoias had an increase or consistently high level of CWC, indicating these trees were at low risk to drought stress. These vulnerability categories were used in a random forest model with a combination of topographic, fire‐related, and climate variables to generate high‐resolution vulnerability risk maps. These maps show that higher risk is associated with lower elevation and higher climate water deficit. We also found that sequoias at higher elevations but located near meadows had higher vulnerability risk. These results and the vulnerability maps can identify vulnerable sequoias that may be difficult to save or locations of refugia to be protected, and thus may aid forest managers in preparation for future droughts.
Performance of Danaini larvae is affected by both exotic host plants and abiotic conditions
Authors: Ferreira Pedro Paulo da Silva , Rodrigues Daniela
Published: June 2021

The consequences of the introduction of invasive plants for the diet of herbivorous insects have been little explored in nature where, potentially, abiotic and biotic factors operate. In this study, we examined the larval performance of two Neotropical Danaini butterflies when using either a native or an exotic Apocynaceae species as host plant in both field and laboratory experiments. Hosts greatly differ in their amount of latex exudation and other physicochemical traits, as well as in the amount of evolutionary time they have interacted with herbivores. First, herbivore performance on the hosts was investigated under laboratory conditions. Larvae of both Danaini species took more time to develop on the exotic host; larval survivorship did not vary between hosts. Second, first instar survivorship on both hosts was evaluated in two field sites, one site per host. To do so, in both sites half of the larvae were bagged (protected against both abiotic and biotic factors) while the remainder were nonbagged (exposed). The interaction between larval exposure with the use of the exotic host reduced larval survival. We concluded that the combined effects of host plant traits and abiotic factors reduced survival of herbivores in field conditions. Therefore, the performance of herbivores when using hosts of different origins should be considered together with the multiple ecological factors found in natural environments, as these factors can modify the result of plant–herbivore interactions.
Differential impacts of alternate primary producers on carbon cycling
Authors: Miranda Khashiff K. , Weigel Brooke L. , McCoy Sophie J. , Pfister Catherine A.
Published: June 2021

Disturbance impacts the spatial distribution of primary producers, which can have cascading effects on ecosystem function. The lower‐intertidal zone on the rocky shores of the Pacific Northwest is one such place where wave energy creates a mosaic‐like distribution between two assemblages: surfgrass (Phyllospadix scouleri) meadows and macroalgal forests dominated by kelp. We simulated wave disturbance by experimentally removing patches of surfgrass monocultures, resulting in a macroalgal assemblage with increased diversity, biomass, and net primary productivity in the following year. Although surfgrass had a higher C:N compared to macroalgal assemblages, macroalgal assemblages achieved a higher biomass, fixed carbon at a faster rate, and released more dissolved organic carbon (DOC) during photosynthesis. Thus, despite similar standing amounts of carbon, macroalgal assemblages have increased carbon turnover—from fixation to DOC release. Comparative photophysiology indicated that surfgrasses have a competitive advantage over other macrophytes at low light levels, allowing them to persist when disturbance is reduced. Unexpectedly, disturbance in this system increased the potential for carbon sequestration when surfgrass monocultures were replaced by diverse macroalgae.
Breeding responses to environmental variation are age‐ and trait‐dependent in female Nazca boobies
Authors: Tompkins Emily M. , Anderson David J.
Published: June 2021

Age and environment are important determinants of reproductive parameters in long‐lived organisms. These factors may interact to determine breeding responses to environmental change, yet few studies have examined the environmental dependence of aging patterns across the entire life span. We do so, using a 20‐yr longitudinal data set of reproductive phenotypes in long‐lived female Nazca boobies (Sula granti), a monogamous seabird breeding in the eastern tropical Pacific. Young and old females may suffer from inexperience and senescence, respectively, and/or practice reproductive restraint. Breeding performance (for breeding participation, breeding date, clutch size, egg volume, and offspring production) was expected to be lower in these age classes, particularly under environmental challenge, in comparison with middle‐aged breeders. Sea surface temperature anomalies (SSTA) represented interannual variation in the El Niño–Southern Oscillation (ENSO) and were one proxy for environmental quality (a population count of clutch initiations was a second). Although only females lay eggs, both sexes care for eggs and nestlings, and the male partner’s age, alone or in interaction with female age, was evaluated as a predictor of breeding performance. Middle‐aged females performed better than young and old birds for all reproductive traits. Pairing with a young male delayed breeding (particularly for old females) and reduced clutch size, and pairing with an old male reduced offspring production. Challenging environments increased age effects on breeding probability and breeding date across young to middle ages and for offspring production across middle to old ages. However, important exceptions to the predicted patterns for clutch size and fledging success across young to middle ages suggested that trade‐offs between fitness components may complicate patterns of trait expression across the life span. Relationships between breeding participation, environment, and individual quality and/or experience in young females may also contribute to unexpected patterns for clutch size and fledging success, traits expressed only in breeders. Finally, independent of age, breeding responses of female Nazca boobies to the ENSO did not follow expectations derived from oceanic forcing of primary productivity. During El Niño‐like conditions, egg‐laying traits (clutch size, breeding date) improved, but offspring production declined, whereas La Niña‐like conditions were “poor” environments throughout the breeding cycle.
Impact of mitral regurgitation in patients with worsening heart failure: insights from BIOSTAT‐CHF
Authors: Pagnesi Matteo , Adamo Marianna , Sama Iziah E. , Anker Stefan D. , Cleland John G. , Dickstein Kenneth , Filippatos Gerasimos S. , Lang Chim C. , Ng Leong L. , Ponikowski Piotr , Ravera Alice , Samani Nilesh J. , Zannad Faiez , van Veldhuisen Dirk J. , Voors Adriaan A. , Metra Marco
Published: June 2021

Aims

Few data regarding the prevalence and prognostic impact of mitral regurgitation (MR) in patients with worsening chronic or new‐onset acute heart failure (HF) are available. We investigated the role of MR in the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT‐CHF).

Methods and results

We performed a retrospective post‐hoc analysis including patients from both the index and validation BIOSTAT‐CHF cohorts with data regarding MR status. The primary endpoint was a composite of all‐cause death or HF hospitalization. Among 4023 patients included, 1653 patients (41.1%) had moderate–severe MR. Compared to others, patients with moderate–severe MR were more likely to have atrial fibrillation and chronic kidney disease and had larger left ventricular (LV) dimensions, lower LV ejection fraction (LVEF), worse quality of life, and higher plasma concentrations of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP). A primary outcome event occurred in 697 patients with, compared to 836 patients without, moderate–severe MR [Kaplan–Meier 2‐year estimate: 42.2% vs. 35.3%; hazard ratio (HR) 1.28; 95% confidence interval (CI) 1.16–1.41; log‐rank P < 0.0001]. The association between MR and the primary endpoint remained significant after adjusting for baseline variables and the previously validated BIOSTAT‐CHF risk score (adjusted HR 1.11; 95% CI 1.00–1.23; P = 0.041). Subgroup analyses showed a numerically larger impact of MR on the primary endpoint in patients with lower LVEF, larger LV end‐diastolic diameter, and higher plasma NT‐proBNP.

Conclusions

Moderate–severe MR is common in patients with worsening chronic or new‐onset acute HF and is strongly associated with outcome, independently of other features related to HF severity.
The consequences ofshort‐terminstitutional change in the rule of law for entrepreneurship
Authors: Mickiewicz Tomasz , Stephan Ute , Shami Muntasir
Published: June 2021

Research Summary

Past research views institutions as stable and slow to change and uses institutional differences to explain cross‐national variation in entrepreneurship. This article introduces a new perspective to institutional theory, that of short‐term institutional change. Integrating insights from cognitive science allows us to theorize not just about the significance of short‐term institutional change but also about why and how deterioration versus improvements in institutions have distinct effects. We test how short‐term institutional change impacts entrepreneurship in a cross‐country multilevel study. We find that short‐term change in the rule of law affects entrepreneurial entry and that institutional deterioration weighs heavier than institutional improvement. We argue and find that changes in the rule of law are more consequential for entrepreneurship compared to changes in business regulations.

Managerial Summary

It is known that the quality of institutions affects individuals' decisions to pursue entrepreneurship. Yet, we newly investigate effects of year‐to‐yearchangesin national institutions. Not only changes in business regulations matter, but also changes in more fundamental institutional aspects, especially in the rule of law. We find that institutional change has an impact because, on its basis, potential entrepreneurs form expectations about the future and therefore about the riskiness of their investment. Deteriorations compared to improvements in the rule of law are more consequential for entrepreneurship, consistent with the fact that losses loom larger than gains in human decisions.
Graph theoretical analysis of evoked potentials shows network influence of epileptogenic mesial temporal region
Authors: Hays Mark A. , Coogan Christopher , Crone Nathan E. , Kang Joon Y.
Published: June 2021

It is now widely accepted that seizures arise from the coordinated activity of epileptic networks, and as a result, traditional methods of analyzing seizures have been augmented by techniques like single‐pulse electrical stimulation (SPES) that estimate effective connectivity in brain networks. We used SPES and graph analytics in 18 patients undergoing intracranial EEG monitoring to investigate effective connectivity between recording sites within and outside mesial temporal structures. We compared evoked potential amplitude, network density, and centrality measures inside and outside the mesial temporal region (MTR) across three patient groups: focal epileptogenic MTR, multifocal epileptogenic MTR, and non‐epileptogenic MTR. Effective connectivity within the MTR had significantly greater magnitude (evoked potential amplitude) and network density, regardless of epileptogenicity. However, effective connectivity between MTR and surrounding non‐epileptogenic regions was of greater magnitude and density in patients with focal epileptogenic MTR compared to patients with multifocal epileptogenic MTR and those with non‐epileptogenic MTR. Moreover, electrodes within focal epileptogenic MTR had significantly greater outward network centrality compared to electrodes outside non‐epileptogenic regions and to multifocal and non‐epileptogenic MTR. Our results indicate that the MTR is a robustly connected subnetwork that can exert an overall elevated propagative influence over other brain regions when it is epileptogenic. Understanding the underlying effective connectivity and roles of epileptogenic regions within the larger network may provide insights that eventually lead to improved surgical outcomes.
Modelling the impact of prevention strategies on cervical cancer incidence in South Africa
Authors: van Schalkwyk Cari , Moodley Jennifer , Welte Alex , Johnson Leigh F.
Published: June 2021

In 2020, the World Health Organisation (WHO) published a strategy to eliminate cervical cancer as a public health concern. In South Africa, despite having a national screening policy in place since 2000, diagnosed cervical cancer incidence has shown no signs of decline. We extend a previously developed individual‐based model for human immunodeficiency virus (HIV) and human papillomavirus (HPV) infection to include progression to cervical cancer. The model accounts for future reductions in HIV incidence and prevalence and includes a detailed cervical cancer screening algorithm, based on individual‐level data from the public health sector. We estimate the impact of the current prevention programme and alternative screening scenarios on cervical cancer incidence. The South African screening programme prevented 8600 (95%CI 4700‐12 300) cervical cancer cases between 2000 and 2019. At current levels of prevention (status quo vaccination, screening, and treatment), age‐standardised cervical cancer incidence will reduce from 49.4 per 100 000 women (95%CI 36.6‐67.2) in 2020, to 12.0 per 100 000 women (95%CI 8.0‐17.2) in 2120. Reaching WHO's prevention targets by 2030 could help South Africa reach elimination (at the 10/100 000 threshold) by 2077 (94% probability of elimination by 2120). Using new screening technologies could reduce incidence to 4.7 per 100 000 women (95%CI 2.8‐6.7) in 2120 (44% probability of elimination at the 4/100 000 threshold). HPV vaccination and decreasing HIV prevalence will substantially reduce cervical cancer incidence in the long term, but improvements to South Africa's current screening strategy will be required to prevent cases in the short term. Switching to new screening technologies will have the greatest impact.
Intrapartum cesarean delivery and the risk of perinatal complications in women with and without a single prior cesarean delivery
Authors: Ashwal Eran , Lavie Anat , Blecher Yair , Attali Emmanuel , Aviram Amir , Hadar Eran , Lasry Ariel , Yogev Yariv , Hiersch Liran
Published: June 2021

Objective

To determine maternal and neonatal complications associated with an intrapartum cesarean delivery (CD) with and without a history of a previous CD.

Methods

A retrospective cohort study of all women who underwent an unplanned intrapartum CD following a trial of labor in a university‐affiliated tertiary hospital, between 2009 and 2016. Perinatal outcomes of women with and without a history of a previous CD were compared. Composite adverse maternal outcome included one or more of the following: postpartum hemorrhage, need for blood transfusion, or cesarean hysterectomy. Composite adverse neonatal outcome included one or more of the following: 5‐min Apgar score <7, neonatal seizure, need for intubation, meconium‐aspiration‐syndrome, or hypoxic‐ischemic encephalopathy.

Results

During the study period, 42 275 women attempted vaginal delivery. Of them, 2229 (5.3%) women underwent an unplanned intrapartum CD and met inclusion criteria: 337 (15.1%) with (study group) and 1892 (84.9%) without (control group) a previous CD. Women without a previous CD were younger and were characterized by higher rates of nulliparity and induction of labor compared with women with a previous CD. Other demographic and obstetrical characteristics did not differ between the groups. Indications for CD were also comparable between the groups. Uterine rupture complicated 2.3% of trials of labor among women with a previous CD. Adverse maternal (2.7% vs 2.9%, P = 1.0) and neonatal (3.9% vs 4.3%, P = 0.88) outcomes were comparable between the groups. After adjusting for potential confounders, a previous CD was not associated independently with adverse maternal outcomes (adjusted odds ratio [aOR] 0.86, 95% confidence interval [CI] 0.31–2.38; P = 0.78) or neonatal outcomes (aOR 0.79, 95% CI 0.36–1.75; P = 0.56).

Conclusion

Our study provides evidence that perinatal outcomes of intrapartum CD delivery among women with a previous CD do not differ from those in women without a previous CD. These findings might improve the consultation and informed decision‐making process for couples considering a trial of labor after CD.
Transient association between semen exposure and biomarkers of genital inflammation in South African women at risk of HIV infection
Authors: Jewanraj Janine , Ngcapu Sinaye , Osman Farzana , Ramsuran Veron , Fish Maryam , Mtshali Andile , Singh Ravesh , Mansoor Leila E , Abdool Karim Salim S , Abdool Karim Quarraisha , Passmore Jo‐Ann S , Liebenberg Lenine J P
Published: June 2021

Introduction

Semen induces mucosal changes in the female reproductive tract to improve pregnancy outcomes. Since semen‐induced alterations are likely short‐lived and genital inflammation is linked to HIV acquisition in women, we investigated the contribution of recent semen exposure on biomarkers of genital inflammation in women at high HIV risk and the persistence of these associations.

Methods

We assessed stored genital specimens from 152 HIV‐negative KwaZulu‐Natal women who participated in the CAPRISA 008 trial between November 2012 and October 2014. During the two‐year study period, 651 vaginal specimens were collected biannually (mean five samples per woman). Cervicovaginal lavage (CVL) was screened for prostate‐specific antigen (PSA) by ELISA, whereas Y‐chromosome DNA (YcDNA) detection and quantification were conducted by RT‐PCR, representing semen exposure within 48 hours (PSA+YcDNA+) and semen exposure within three to fifteen days (PSA−YcDNA+). Soluble protein concentrations were measured in CVLs by multiplexed ELISA. T‐cell frequencies were assessed in cytobrushes by flow‐cytometry, and vulvovaginal swabs were used to detect common vaginal microbes by PCR. Linear mixed models adjusting for factors associated with genital inflammation and HIV risk were used to assess the impact of semen exposure on biomarkers of inflammation over multiple visits.

Results

Here, 19% (125/651) of CVLs were PSA+YcDNA+, 14% (93/651) were PSA−YcDNA+ and 67% (433/651) were PSA−YcDNA−. Semen exposure was associated with how often women saw their partners, the frequency of vaginal sex in the past month, HSV‐2 antibody detection, current gonorrhoea infection and Nugent Score. Both PSA detection (PSA+YcDNA+) and higher cervicovaginal YcDNA concentrations predicted increases in several cytokines, barrier‐related proteins (MMP‐2, TIMP‐1 and TIMP‐4) and activated CD4+CCR5+HLA‐DR+ T cells (β = 0.050; CI 0.001 to 0.098; p = 0.046) and CD4+HLA‐DR+ T cells (β = 0.177; CI 0.016 to 0.339; p = 0.032) respectively. PSA detection was specifically associated with raised pro‐inflammatory cytokines (including IL‐6, TNF‐α, IP‐10 and RANTES), and with the detection of BVAB2 (OR = 1.755; CI 1.116 to 2.760; p = 0.015), P. bivia (OR = 1.886; CI 1.102 to 3.228; p = 0.021) and Gardnerella vaginalis (OR = 1.815; CI 1.093 to 3.015; p = 0.021).

Conclusions

More recent semen exposure was associated with raised levels of inflammatory biomarkers and the detection of BV‐associated microbes, which declined by three to fifteen days of post‐exposure. Although transient, semen‐induced alterations may have implications for HIV susceptibility in women.
Large lamellar bodies and their role in the growing oocytes of the armadillo Chaetophractus villosus
Authors: Rossi Luis F. , Solari Alberto J.
Published: June 2021

Oogenesis in the armadillo Chaetophractus villosus, a representative species of a mammalian basal clade, was investigated by light microscopy, transmission electron microscopy, and immunohistochemical localization of keratin. At the beginning of the growth phase, oocyte follicles showed one, and sometimes several, large bodies composed of lamellae (multilamellar bodies [MLBs]), which entrap other cytoplasmic organelles at more advanced stages. Lamellae diameter is described in cross‐section (37 nm) and tangential sections (50 nm). The MLB of early oocytes is most frequently located close to the nucleus. In large oocytes, both, this body and the free organelles are relocated at the oocyte periphery. The MLB grows from the primary follicle up to its full development at the follicular phase characterized by tall granulosa cells. Mitochondria, smooth small vesicles, and lipofuscin granules are trapped between lamellae. MLBs engage in the formation of different sets of organelles, both trapped and free ones. When oocytes are well developed and the zona pellucida is formed, the MLB is reduced to small remnants detected only by transmission electron microscopy. The MLB disintegrates when an antrum develops. Immunohistochemical localization techniques showed the presence of cytokeratin in the MLBs. This cytokeratin pool may be involved in the filament and desmosome formation found in the periphery of late oocytes.
The survey of electrophysiology lab activity during the COVID‐19 pandemic
Authors: Shahabi Javad , Askari Mozhde , Azhari Amirhossein , Kermani‐Alghoraishi Mohammad
Published: June 2021

Background

With the onset and spread of the COVID‐19 pandemic, the hospitalization and treatment of noncovid patients were dramatically affected. The aim of this study is to evaluate the electrophysiology (EP) lab activity in a referral center in Iran during the COVID‐19 era.

Methods

A cross‐sectional descriptive survey was conducted on EP lab activity in Shahid Chamran Heart Center, Isfahan, Iran. Two periods of COVID‐19 occurrence peaks in Iran were compared with same date in 2019. Information was collected on number of diagnostic and therapeutic electrophysiology studies (EPSs) and implantation of intracardiac devices such as permanent pacemaker (PPM), implantable cardioverter defibrillator (ICD), and cardiac resynchronization therapy (CRT).

Results

In the first peak of COVID‐19 pandemic, both of EPSs and intracardiac device implantations decreased by 80% compared to the same period in 2019. The most common type of device implanted during this period was PPM (70%); however, at the time of control, the ICD (73%) was the most common. Paroxysmal supraventricular tachyarrhythmia (PSVT) was the best indication for diagnostic and therapeutic EPSs in covid and control periods. In the second peak of prevalence of COVID‐19 virus infection in Iran, 6% and 36% decreases in device implantations and EPSs were seen, respectively. During this period, the number of procedures increased, although it was still lower than in 2019.

Conclusion

A significant reduction in the EP lab activity has been observed during both the COVID‐19 pandemic peaks.
Can functional electrical stimulation–assisted cycle ergometry replace insulin infusion in patients? A nested substudy in a randomized controlled trial with 6 months’ follow‐up
Authors: Waldauf Petr , Urban Tomáš , Krajčová Adéla , Jiroutková Kateřina , Blahutová Barbora , Bakalář Bob , Řasová Kamila , Grünerová‐Lippertová Marcela , Gojda Jan , Duška František
Published: June 2021

Background

Functional electrical stimulation–assisted cycle ergometry (FESCE) can deliver active exercise to critically ill patients, including those who are sedated. Aerobic exercise is known to stimulate skeletal muscle glucose uptake. We asked whether FESCE can reduce intravenous insulin requirements and improve insulin sensitivity in intensive care unit (ICU) patients.

Method

We performed an a priori–planned secondary analysis of data from an outcome‐based randomized controlled trial (NCT 02864745) of FESCE‐based early‐mobility program vs standard of care in mechanically ventilated patients. We analyzed glucose profile, glucose intake, and insulin requirements during ICU stay in all enrolled patients. In a nested subgroup, we performed hyperinsulinemic (120 mIU/min/m2) euglycemic clamps at days 0, 7, and 180 (n = 30, 23, and 11, respectively).

Results

We randomized 150 patients 1:1 to receive intervention or standard of care. Seventeen (23%) patients in each study arm had a history of diabetes. During ICU stay, patients received 137 ± 65 and 137 ± 88 g/day carbohydrate (P = .97), and 31 vs 35 (P = .62) of them required insulin infusion to maintain blood glucose 8.61 ± 2.82 vs 8.73 ± 2.67 mM (P = .75, n = 11,254). In those treated with insulin, median daily dose was 53 IU (interquartile range [IQR], 25–95) vs 62 IU (IQR, 26–96) in the intervention and control arm, respectively (P = .44). In the subgroup of patients undergoing hyperglycemic clamps, insulin sensitivities improved similarly and significantly from acute and protracted critical illness to 6 months after discharge.

Conclusion

The FESCE‐based early‐mobility program does not significantly reduce insulin requirements in critically ill patients on mechanical ventilation.
The influence of selected indigenous yeasts on Pinot Noir wine colour properties
Authors: Topić Božič Jelena , Butinar Lorena , Antalick Guillaume , Sternad Lemut Melita , Martelanc Mitja , Albreht Alen , Korte Dorota , Mozetič Vodopivec Branka
Published: June 2021

BACKGROUND

The use of indigenous selected starters in winemaking is gaining interest due to certain advantages for the sensory quality of the wine. The present work shows the results of a laboratory experiment in which the influence of selected indigenous yeasts on the colour characteristics of Pinot Noir was studied with the use of high hydroxycinnamate decarboxylase activity yeasts. Pichia guilliermondii ZIM624 and Wickerhamomyces anomalus S138 yeasts were used in sequential fermentation with two strains of Saccharomyces cerevisiae, the native ZIM2180 strain and commercial Fermol Premier Cru (FPC).

RESULTS

In co‐inoculation fermentations, non‐Saccharomyces yeasts decreased colour intensity (on average by 25.5%). In wines fermented with ZIM624, the concentration of vinylphenolic pyranoanthocyanins increased (average concentration 1.5 mg L−1). However, vitisin concentration was significantly higher in S138 + FPC fermentation (1.3 mg L−1 and an average of 0.9 mg L−1, respectively). Pinot Noir wines fermented with only ZIM2180 and sequential inoculation of ZIM624 + ZIM2180 resulted in significantly higher colour intensity (6.1 ± 0.0 AU and 4.4 ± 0.0 AU, respectively) and lower wine hue parameters compared to other wines. Sensory evaluation also showed that both wines had the highest perceived colour intensity and purple colour suggesting improvement in wine quality parameters.

CONCLUSIONS

The results confirmed that selected indigenous starters made out of Saccharomyces and non‐Saccharomyces yeasts can alter Pinot Noir wine colour parameters and improve wine colour properties. Those yeasts properties should be investigated prior to the development of new commercial starters but also be considered in large scale spontaneous fermentations of low colour intensity red wines like Pinot Noir. © 2021 Society of Chemical Industry.
Predictive value of the Eustachian Tube Dysfunction Questionnaire‐7 for identifying obstructive Eustachian tube dysfunction: A systematic review
Authors: Andresen Nicholas S. , Sharon Jeffrey D. , Nieman Carrie L. , Seal Stella M. , Ward Bryan K.
Published: June 2021

Objective

To perform a systematic review to determine if a total score of ≥14.5 (mean score ≥ 2.1) on the ETDQ‐7 accurately identifies patients with obstructive Eustachian tube dysfunction (OETD) on impedance tympanometry (peak compliance <0.2 mL or middle ear pressure of −100 daPa) or other objective measures of OETD.

Methods

A systematic review without a meta‐analysis was performed of studies in four electronic databases (Pubmed, Embase, Web of Science, and Scopus) that used the ETDQ‐7 and at least one objective measure of OETD.

Results

Six‐hundred and fifty‐two studies were identified in the initial literature search. Abstracts from 337 studies were screened, followed by full‐text review of 61 studies, and qualitative synthesis of 12 studies. Tympanometry was used as an objective measure in ten studies. Eight of the 12 included studies had patient cohort selection bias. Eight studies administered the ETDQ‐7 in cohorts of patients with or without OETD, already confirmed on tympanometry, and found a sensitivity of 91%‐100% and specificity of 67%‐100%. Four studies administered the ETDQ‐7 to patients who had not previously undergone objective testing and found a sensitivity of 49%‐80% and specificity of 24%‐78%.

Conclusions

The ETDQ‐7 is an important patient‐reported outcome measure. However, based upon existing literature, the ETDQ‐7 appears limited as a diagnostic tool for OETD or as an objective measure of Eustachian tube function.