bluuebunny/crossref_metadata_2025 huggingface dataset:
Anthropogenic noise disrupts mate choice behaviors in femaleGryllus bimaculatus
Authors: Bent Adam M , Ings Thomas C , Mowles Sophie L
Published: November 2020

By assessing the sexual signals produced by conspecifics, individuals can make informed decisions on the best choice of mate, which can lead to reproductive fitness benefits. However, these communication systems are often vulnerable to disruption by conflicting with stimuli present in the environment. Anthropogenic noise may act as one such disruptive stimulus, leading to inefficient mate choice decisions and, thus, reductions to an animal’s fitness. In this study, the mate choice behaviors of female Gryllus bimaculatus were tested when presented with artificial male courtship songs of differing “quality” under different acoustic conditions. In ambient noise conditions, females significantly preferred mates paired with higher-quality songs, indicated by increased mating rates and reduced latency to mate. However, this mate selection pattern was disrupted in both traffic and white noise conditions. Additionally, “high-quality” courtship songs had an increased mounting latency in traffic and white noise conditions, when compared to ambient noise conditions. Making nonoptimal mating decisions, such as the ones seen here, can lead to deleterious fitness consequences, alter population dynamics, and weaken sexual selection, unless individuals adapt to cope with anthropogenic interference.
A comprehensive survey on computational methods of non-coding RNA and disease association prediction
Authors: Lei Xiujuan , Mudiyanselage Thosini Bamunu , Zhang Yuchen , Bian Chen , Lan Wei , Yu Ning , Pan Yi
Published: November 2020

The studies on relationships between non-coding RNAs and diseases are widely carried out in recent years. A large number of experimental methods and technologies of producing biological data have also been developed. However, due to their high labor cost and production time, nowadays, calculation-based methods, especially machine learning and deep learning methods, have received a lot of attention and been used commonly to solve these problems. From a computational point of view, this survey mainly introduces three common non-coding RNAs, i.e. miRNAs, lncRNAs and circRNAs, and the related computational methods for predicting their association with diseases. First, the mainstream databases of above three non-coding RNAs are introduced in detail. Then, we present several methods for RNA similarity and disease similarity calculations. Later, we investigate ncRNA-disease prediction methods in details and classify these methods into five types: network propagating, recommend system, matrix completion, machine learning and deep learning. Furthermore, we provide a summary of the applications of these five types of computational methods in predicting the associations between diseases and miRNAs, lncRNAs and circRNAs, respectively. Finally, the advantages and limitations of various methods are identified, and future researches and challenges are also discussed.
Evaluating single-cell cluster stability using the Jaccard similarity index
Authors: Tang Ming , Kaymaz Yasin , Logeman Brandon L , Eichhorn Stephen , Liang Zhengzheng S , Dulac Catherine , Sackton Timothy B
Published: November 2020

Motivation

One major goal of single-cell RNA sequencing (scRNAseq) experiments is to identify novel cell types. With increasingly large scRNAseq datasets, unsupervised clustering methods can now produce detailed catalogues of transcriptionally distinct groups of cells in a sample. However, the interpretation of these clusters is challenging for both technical and biological reasons. Popular clustering algorithms are sensitive to parameter choices, and can produce different clustering solutions with even small changes in the number of principal components used, the k nearest neighbor and the resolution parameters, among others.

Results

Here, we present a set of tools to evaluate cluster stability by subsampling, which can guide parameter choice and aid in biological interpretation. The R package scclusteval and the accompanying Snakemake workflow implement all steps of the pipeline: subsampling the cells, repeating the clustering with Seurat and estimation of cluster stability using the Jaccard similarity index and providing rich visualizations.

Availabilityand implementation

R package scclusteval: https://github.com/crazyhottommy/scclusteval Snakemake workflow: https://github.com/crazyhottommy/pyflow_seuratv3_parameter Tutorial: https://crazyhottommy.github.io/EvaluateSingleCellClustering/.
RP-HPLC Analysis of Phenolic Lignin Monomers with DAD and Coulometric Array Detection
Authors: Fischer Klaus , Höffler Susanne
Published: November 2020

An high performance liquid chromatography (HPLC) method, applying diode array (DAD) and coulometric array detection simultaneously, was developed to determine monomeric phenolic compounds in lignin hydrolysates. To allow for additional mass spectrometric detection, a formic acid gradient was designed as an alternative to the non-volatile phosphate buffer gradient. Within a total run time of 28 min, 10 out of 14 analytes were baseline separated by the formic acid gradient, and 8 compounds were completely resolved by the phosphate gradient. The dependence of the coulometric detection on cell potential, potential step width, eluent pH and eluent composition was comprehensively tested. Detection limits ≤20 μg/L were achieved by DAD detection for nine analytes and by coulometric array detection for all analytes, demonstrating the superior sensitivity of electrochemical detection. DAD offered better linearity and reproducibility. Inter-day precision of peak heights spanned from 0.26 to 2.00% (formic acid gradient) and from 0.75 to 2.85% (phosphate buffer gradient) operating the DAD detector, but it exceeded 10% for several compounds applying the coulometric array detector. The simultaneous operation of both detectors offered an enhanced certainty of substance identification. The appropriateness of the method was confirmed by the analysis of various hydrolysates of lignin-containing materials.
HPLC Detection and Antioxidant Capacity Determination of Brown, Red and Green Algal Pigments in Seaweed Extracts
Authors: Yalçın Sibel , Karakaş Özge , Okudan Emine Şükran , Başkan Kevser Sözgen , Çekiç Sema Demirci , Apak Reşat
Published: November 2020

This study was carried out to determine the main pigments in some different selected seaweeds and to reveal their antioxidant potential regarding the ever-increasing demand for utilization of marine pigments in human health and nutrition. The individual amounts of algal pigments were found by reverse phase high-performance liquid chromatography (HPLC) and their total antioxidant capacities (TAC) by two spectrophotometric TAC assays, namely: CUPRAC (CUPric ion Reducing Antioxidant Capacity) and ABTS/TEAC (2,2′-azinobis [3-ethyl benzo thiazoline-6-sulfonate])/(trolox equivalent antioxidant capacity). These two tests gave the same rank order for TAC. The TAC of HPLC-quantified compounds accounted for a relatively much lower percentage of the observed CUPRAC capacities of seaweed extracts, namely ranging from 11 to 68% for brown, from 4 to 41% for red and from 3 to 100% for green species, i.e., some TAC originated from chromatographically unidentified compounds. Fucoxanthin, chlorophyll a, and pheophytin a compounds were major pigments in brown algae. The relative carotenoid contents in red marine algae were generally lower than those of chlorophylls. Overall total quantities were quite low compared with those of brown species. In general, chlorophyll a and chlorophyll b were chiefly present in green algae, but β-carotene, violaxanthin and siphonaxanthin were also detected substantially higher in some species of green algae such as Caulerpa racemosa var. cylindracea and Codium fragile.
Very Low-Density Lipoprotein Cholesterol May Mediate a Substantial Component of the Effect of Obesity on Myocardial Infarction Risk: The Copenhagen General Population Study
Authors: Johansen Mia Ø , Nielsen Sune F , Afzal Shoaib , Vedel-Krogh Signe , Davey Smith George , Nordestgaard Børge G
Published: November 2020

Background

Individuals with obesity have higher concentrations of very low-density lipoprotein (VLDL) cholesterol and increased risk of myocardial infarction. We hypothesized that VLDL cholesterol explains a fraction of the excess myocardial infarction risk in individuals with obesity.

Methods

We included 29 010 individuals free of myocardial infarction at baseline, nested within 109 751 individuals from the Copenhagen General Population Study. During 10 years of follow-up, 2306 individuals developed myocardial infarction. Cholesterol content in large and small VLDLs, in intermediate-density lipoprotein (IDL), and in LDL was measured directly with nuclear magnetic resonance spectroscopy.

Results

Median concentrations of cholesterol in large and small VLDLs were 0.12 mmol/L (interquartile range [IQR], 0.07–0.20 mmol/L; 4.5 mg/dL [IQR, 2.6–6.9 mg/dL]) and 0.6 mmol/L (IQR, 0.5–0.8 mmol/L; 25 mg/dL [IQR, 20–30 mg/dL]) in individuals with obesity vs 0.06 mmol/L (IQR, 0.03–0.1 mmol/L; 2.2 mg/dL [IQR, 1.1–3.8 mg/dL]), and 0.5 mmol/L (IQR, 0.4–0.6 mmol/L; 20 mg/dL (IQR, 16–25 mg/dL]) in individuals with normal weight; in contrast, concentrations of IDL and LDL cholesterol were similar across body mass index (BMI) categories. Cholesterol in large and small VLDLs combined explained 40% (95% CI, 27%–53%) of the excess risk of myocardial infarction associated with higher BMI. In contrast, IDL and LDL cholesterol did not explain excess risk of myocardial infarction, whereas systolic blood pressure explained 17% (11%–23%) and diabetes mellitus explained 8.6% (3.2%–14%).

Conclusions

VLDL cholesterol explains a large fraction of excess myocardial infarction risk in individuals with obesity. These novel findings support a focus on cholesterol in VLDL for prevention of myocardial infarction and atherosclerotic cardiovascular disease in individuals with obesity.
MetaTropismDB: a database of organ-specific metastasis induced by human cancer cell lines in mouse models
Authors: Giulietti Matteo , Bastianoni Marco , Cecati Monia , Ruzzo Annamaria , Bracci Massimo , Malavolta Marco , Piacenza Francesco , Giacconi Robertina , Piva Francesco
Published: November 2020

The organotropism is the propensity of metastatic cancer cells to colonize preferably certain distant organs, resulting in a non-random distribution of metastases. In order to shed light on this behaviour, several studies were performed by the injection of human cancer cell lines into immunocompromised mouse models. However, the information about these experiments is spread in the literature. For each xenograft experiment reported in the literature, we annotated both the experimental conditions and outcomes, including details on inoculated human cell lines, mouse models, injection methods, sites of metastasis, organs not colonized, rate of metastasis, latency time, overall survival and the involved genes. We created MetaTropismDB, a freely available database collecting hand-curated data useful to highlight the mechanisms of organ-specific metastasis. Currently, it stores the results of 513 experiments in which injections of 219 human cell lines have been carried out in mouse models. Notably, 296 genes involved in organotropic metastases have been collected. This specialized database allows the researchers to compare the current results about organotropism and plan future experiments in order to identify which tumour molecular signatures establish if and where the metastasis will develop.

Database URL:  http://www.introni.it/Metastasis/metastasis.html
Exploring consensus for the optimal sealant use to prevent air leak following lung surgery: a modified Delphi survey from The European Society of Thoracic Surgeons
Authors: Brunelli Alessandro , Bölükbas Servet , Falcoz Pierre Emmanuel , Hansen Henrik , Jimenez Marcelo F. , Lardinois Didier , Scarci Marco , Viti Andrea , Walker Ian , Warren Tim
Published: November 2020

OBJECTIVES

The use of sealants is one of the methods available to reduce the occurrence of intraoperative air leaks. The objective of this modified Delphi survey among ESTS members is to understand the attitudes of clinicians to the optimal use of sealants in air leak management.

METHODS

To understand the attitudes of a wider sample of clinicians, a questionnaire was developed highlighting key issues through 37 statements. Respondents were invited to score their level of agreement with each. A modified Delphi methodology was used to review responses with a threshold of agreement for consensus of 75%.

RESULTS

A total of 258 responses were received (response rate 17%). Respondents agreed that prolonged air leaks are a common complication in thoracic surgery presenting a burden to the patient and increasing the costs of care. There is clear support for the use of sealants to reduce costs and improve the efficiency of healthcare provision and duration of chest tube use in selected high-risk patients with intraoperative air leak at the end of the lung surgery. Respondents also agreed that, due to often complex nature of thoracic surgery, sealants should be developed specifically for this application.

CONCLUSION

There is a clear role for sealants in the management of air leaks and certain surgical procedures demand their use (i.e. lung volume reduction surgery, decortication). This opinion-based consensus review helps to raise the debate about the burden of air leaks in thoracic surgery in order that this issue is recognized in practice and informs the optimal use of sealants in lung surgery.
Selective Sweeps in a Nutshell: The Genomic Footprint of Rapid Insecticide Resistance Evolution in the Almond Agroecosystem
Authors: Calla Bernarda , Demkovich Mark , Siegel Joel P , Viana João Paulo Gomes , Walden Kim K O , Robertson Hugh M , Berenbaum May R
Published: November 2020

Among the most familiar forms of human-driven evolution on ecological time scales is the rapid acquisition of resistance to pesticides by insects. Since the widespread adoption of synthetic organic insecticides in the mid-twentieth century, over 500 arthropod species have evolved resistance to at least one insecticide. Efforts to determine the genetic bases of insecticide resistance have historically focused on individual loci, but the availability of genomic tools has facilitated the screening of genome-wide characteristics. We resequenced three contemporary populations of the navel orangeworm (Amyelois transitella), the principal pest of almond orchards in California, differing in bifenthrin resistance status to examine insecticide-induced changes in the population genomic landscape of this species. We detected an exceptionally large region with virtually no polymorphisms, extending to up to 1.3 Mb in the resistant population. This selective sweep includes genes associated with pyrethroid and DDT resistance, including a cytochrome P450 gene cluster and the gene encoding the voltage-gated sodium channel para. Moreover, the sequence along the sweep is nearly identical in the genome assembled from a population founded in 1966, suggesting that the foundation for insecticide resistance may date back a half-century, when California’s Central Valley experienced massive area-wide applications of DDT for pest control.
Spousal Support, Spousal Strain, and Loneliness in Older Mexican Couples
Authors: Saenz Joseph L
Published: November 2020

Objectives

A growing body of research has identified factors related to loneliness among older adults. Fewer have investigated predictors of loneliness within married couples. This analysis investigates how spousal support and strain relate with loneliness within older couples (age 50+), and whether these associations are modified by functional limitation. The study focuses on Mexico, a country experiencing rapid aging occurring alongside historically limited institutional support for older adults, and where traditional gender roles extend to marriage.

Methods

The analytic sample consisted of 3,584 husband–wife dyads from the 2012 and 2015 Mexican Health and Aging Study. Loneliness was measured using the Three-Item Loneliness Scale. Associations between spousal support, strain, and loneliness were estimated within husband–wife dyads using the Actor–Partner Interdependence Model.

Results

Experiencing more spousal support was associated with less loneliness, whereas experiencing spousal strain was associated with more loneliness 3 years later among married adults. The associations between spousal support/strain and loneliness were stronger among husbands with limitations in activities of daily living (ADL) when compared to their counterparts without ADL limitations.

Discussion

Among married adults, spousal support and strain may be important factors to understand loneliness within marriage. Effects should be interpreted within the context of functional limitation.
Therapeutic effects of hysterosalpingography contrast media in infertile women: what do we know about the H2O in the H2Oil trial and why does it matter?
Authors: Peart Jane M , Sim Robert G , Hofman Paul L
Published: November 2020

Recent interest in the use of oil-soluble contrast media (OSCM) for hysterosalpingography (HSG) and other tubal flushing procedures is largely the result of publication of the large, multicentre, randomized controlled H2Oil trial in the New England Journal of Medicine in 2017, addressing the long-held suspicion that pregnancy rates following HSG with OSCM are higher than if a water-soluble contrast media (WSCM) is used. However, the findings of this trial have been compromised by the WSCM selected for comparison with OSCM. The chosen WSCM belongs to a superceded class of ionic media, with an iodine concentration, osmolality and viscosity all lying at the extreme end of the range for water-soluble radiographic contrast. The requirement for safe, cheap, versatile WSCM for intravascular use during computerized tomography, angiography and interventional procedures has resulted in considerable refinement of WSCM, with current widespread use of non-ionic, low osmolality or iso-osmolar WSCM in radiology, including for HSG. However, the use of the earlier ionic, high osmolality agents such as that selected for the H2Oil trial persists for HSG in some centres, despite potential adverse effects on the endometrium and fallopian tubal epithelium compared with more modern, less toxic WSCM. Knowledge of the variety of physical and chemical characteristics of the available WSCM is essential for interpretation of the current literature and establishing the most effective and safe water-soluble agent to use for HSG. Design of future clinical trials to establish the potential superiority of OSCM over WSCM for fertility enhancement must include the use of the readily available, inexpensive modern WSCM. While the fertility rates following OSCM HSG have been shown to be high in women with idiopathic infertility, more robust trials are required before the widespread use of OSCM for HSG or other modalities such as ultrasound and laparoscopy should be adopted.
A three-dimensional printing navigational template combined with mixed reality technique for localizing pulmonary nodules
Authors: Fu Rui , Zhang Chao , Zhang Tao , Chu Xiang-Peng , Tang Wen-Fang , Yang Xue-Ning , Huang Mei-Ping , Zhuang Jian , Wu Yi-Long , Zhong Wen-Zhao
Published: November 2020

OBJECTIVES

Localizing non-palpable pulmonary nodules is challenging for thoracic surgeons. Here, we investigated the accuracy of three-dimensional (3D) printing technology combined with mixed reality (MR) for localizing ground glass opacity-dominant pulmonary nodules.

METHODS

In this single-arm study, we prospectively enrolled patients with small pulmonary nodules (<2 cm) that required accurate localization. A 3D-printing physical navigational template was designed based on the reconstruction of computed tomography images, and a 3D model was generated through the MR glasses. We set the deviation distance as the primary end point for efficacy evaluation. Clinicopathological and surgical data were obtained for further analysis.

RESULTS

Sixteen patients with 17 non-palpable pulmonary nodules were enrolled in this study. Sixteen nodules were localized successfully (16/17; 94.1%) using this novel approach with a median deviation of 9 mm. The mean time required for localization was 25 ± 5.2 min. For the nodules in the upper/middle and lower lobes, the median deviation was 6 mm (range, 0–12.0) and 16 mm (range, 15.0–20.0), respectively. The deviation difference between the groups was significant (Z = −2.957, P = 0.003). The pathological evaluation of resection margins was negative.

CONCLUSIONS

The 3D printing navigational template combined with MR can be a feasible approach for localizing pulmonary nodules.
Lamin B receptor-mediated chromatin tethering to the nuclear envelope is detrimental to theXenopusblastula
Authors: Oda Haruka , Kato Satsuki , Ohsumi Keita , Iwabuchi Mari
Published: November 2020

In the nucleus of eukaryotic cells, chromatin is tethered to the nuclear envelope (NE), wherein inner nuclear membrane proteins (INMPs) play major roles. However, in Xenopus blastula, chromatin tethering to the NE depends on nuclear filamentous actin that develops in a blastula-specific manner. To investigate whether chromatin tethering operates in the blastula through INMPs, we experimentally introduced INMPs into Xenopus egg extracts that recapitulate nuclear formation in fertilized eggs. When expressed in extracts in which polymerization of actin is inhibited, only lamin B receptor (LBR), among the five INMPs tested, tethered chromatin to the NE, depending on its N2 and N3 domains responsible for chromatin-protein binding. N2–3-deleted LBR did not tether chromatin, although it was localized in the nuclei. We subsequently found that the LBR level was very low in the Xenopus blastula but was elevated after the blastula stage. When the LBR level was precociously elevated in the blastula by injecting LBR mRNA, it induced alterations in nuclear lamina architecture and nuclear morphology and caused DNA damage and abnormal mitotic spindles, depending on the N2–3 domains. These results suggest that LBR-mediated chromatin tethering is circumvented in the Xenopus blastula, as it is detrimental to embryonic development.
Efficacy of Cultured Allogenic Keratinocytes in Treatment of Deep Second-Degree Burn
Authors: Kim Eung Hyun , Lee Soo Hyang
Published: November 2020

Cultured allogenic keratinocytes, produced as Kaloderm® (Tego Science, Seoul, Korea), are an effective dressing material for burn wounds. Generally, deep second-degree contact, steam, and flame burns tend to progress to third-degree burns. This study reviews the efficacy of cultured allogenic keratinocytes in deep second-degree burn patients. This is a retrospective study of 64 patients treated between November 2013 and April 2019. A half of deep second-degree contact, steam, and flame burn patients were treated with cultured allogenic keratinocytes. The other half were treated with chlorhexidine gauze and antibiotic ointment. The primary outcome was time to wound closure. A secondary outcome was the number of Kaloderm sheets used. Groups were compared based on the type of burn and treatment. In the experimental group, the median times to reepithelization were 10.0 days for the contact burn group, 13.5 days for the flame burn group, and 11.0 days for the steam burn group. Progression to a third-degree burn occurred in only one patient in the experimental group and four patients in the control group. Patients treated with cultured allogenic keratinocytes required a mean time of 11.7 ± 2.4 days for complete closure, whereas the mean time to complete closure in the control group was 16.4 ± 5.3 days. Patients with deep second-degree burns from flame, steam, and contact treated with cultured allogenic keratinocytes reepithelialized faster than those treated with chlorhexidine dressings.
Risk Factors for Mortality and Prolonged Hospitalization in Electric Burn Injuries
Authors: Schweizer Riccardo , Pedrazzi Nadine , Klein Holger J , Gentzsch Tony , Kim Bong-Sung , Giovanoli Pietro , Plock Jan A
Published: November 2020

Electrical injuries are rare, but very destructive with high morbidity and mortality, prolonged hospital length of stay and need for repeated procedures. The aim of study was to investigate characteristics and management of electrical injuries and predisposing factors for mortality and prolonged length of stay. Patient charts were reviewed retrospectively to identify patients admitted with electrical injuries at the Zurich Burns Center (2005–2019). Patient characteristics, management, and outcome were analyzed and risk factors for mortality and prolonged hospitalization were assessed. Eighty-nine patients were included, mostly males (86.5%), between 21 and 40 years (50.6%), with high-voltage (74.2%) occupational injuries (66.3%). Median intensive care unit and hospital stays were 6 (first and third IQR: 2.0; 30.0) and 18 (9.0; 48.0) days. Low-voltage patients had a median of 2 (1.5; 3.0) procedures, compared to 4 (2.0; 10.8) in high-voltage. The amputation rate was 13.5%, and a total of 46 flaps were required. Fifty-four patients had at least one serious complication. Mortality was 18% in high-voltage patients, mostly after multiple organ failure (35%). High total body surface area (TBSA), renal failure and cardiovascular complications were risk factors for mortality (P < .001) in multivariate regression models. Determinants for prolonged hospital stay were TBSA and sepsis (P < .01), and additionally abdominal complications and limb loss for intensive care unit stay (P < .05). Electrical injuries are still cause of significant morbidity and mortality, mostly involve young men in their earning period. Several risk factors for in-hospital mortality and prolonged stay were identified and can support physicians in the management and decision making in these patients.
Knockdown-Mortality Responses of Six Stored-Product Beetle Species on Different Surfaces Treated With Thiamethoxam, Using a Standardized Lethality Index
Authors: Tsaganou Fotoula K , Vassilakos Thomas N , Athanassiou Christos G
Published: November 2020

Bioassays were conducted to evaluate the effectiveness of thiamethoxam in different surfaces, against six stored-grain insects, Sitophilus granarius (L.) (Coleoptera: Curculionidae), Sitophilus oryzae (L.) (Coleoptera: Curculionidae), Tribolium confusum Jacquelin du Val (Coleoptera: Tenebrionidae), Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae), Cryptolestes ferrugineus (Stephens) (Coleoptera: Laemophloeidae), and Oryzaephilus surinamensis (L.) (Coleoptera: Silvanidae). Six different surfaces (concrete, plywood, galvanized steel, linen, plastic, and ceramic tile) treated with thiamethoxam at 0.05 and 0.1 mg/cm2 were used as substrate for adult exposure. Knockdown was recorded after 1, 3, and 7 d of exposure to the treated surface, in order to calculate a Standardized Lethality Index (SLI). Knockdown counts were ranked from ‘0’ to ‘4’, with ‘0’ representing adult insects ‘moved generally’ and ‘4’ representing dead insects. Based on the results, insect knockdown seems leading to mortality than to recovery and the SLI ranking of the target species according to their susceptibility to thiamethoxam showed that S. granarius being more susceptible and decreasing susceptibility in an order of S. oryzae > T. castaneum ≥ O. surinamenis ≥ C. ferrugineus ≥ T. confusum. In general, among the surfaces, thiamethoxam efficacy was lower on linen, wooden, and concrete surfaces, as compared to metallic and plastic surfaces. Nevertheless, at the end of 7-d exposure, all surfaces equally affected thiamethoxam toxicity.
Modest efficacy of nivolumab plus ipilimumab in patients with papillary renal cell carcinoma
Authors: Tachibana Hidekazu , Kondo Tsunenori , Ishihara Hiroki , Fukuda Hironori , Yoshida Kazuhiko , Takagi Toshio , Izuka Junpei , Kobayashi Hirohito , Tanabe Kazunari
Published: November 2020

Purpose

Combined immunotherapy of nivolumab plus ipilimumab for intermediate- and poor-risk metastatic clear cell renal cell carcinoma showed prolonged progression-free survival and high objective response rate in a randomized phase III clinical trial. However, the efficacy of this treatment for papillary renal cell carcinoma remains unclear. In the present study, we analysed the efficacy of nivolumab plus ipilimumab therapy for papillary renal cell carcinoma compared with that for clear cell renal cell carcinoma.

Materials and Methods

This is a retrospective study of 30 patients with metastatic renal cell carcinoma who received nivolumab and ipilimumab as first-line therapy between December 2015 and May 2020. The objective response rate, progression-free survival and toxicity were compared between the two groups (clear cell renal cell carcinoma and papillary renal cell carcinoma).

Results

Out of 30 patients, 7 and 23 were diagnosed with papillary renal cell carcinoma and clear cell renal cell carcinoma, respectively. With a median follow-up of 7.2 months, the median progression-free survival was significantly shorter in papillary renal cell carcinoma than in clear cell renal cell carcinoma (2.4 vs. 28.1 months, P = 0.014). Of the seven patients with papillary renal cell carcinoma, one had partial response, one had stable disease and five had progressive disease, resulting in an objective response rate of 14.2%, which was lower compared to that of clear cell renal cell carcinoma (14.2 vs. 52.1%, P = 0.06). Discontinuation due to toxicity was not observed with papillary renal cell carcinoma, meanwhile 60.8% of patient with clear cell renal cell carcinoma discontinued treatment due to toxicity.

Conclusion

Nivolumab plus ipilimumab had modest efficacy for papillary renal cell carcinoma compared with that for clear cell renal cell carcinoma. Nivolumab plus ipilimumab remains an option for a limited number of patients with intermediate- or poor-risk papillary renal cell carcinoma.
Gut Microbiota-targeted Interventions for Reducing the Incidence, Duration, and Severity of Respiratory Tract Infections in Healthy Non-elderly Adults
Authors: Karl J Philip
Published: November 2020

Introduction

Respiratory tract infections (RTI), such as those caused by influenza viruses and, more recently, the severe acute respiratory syndrome coronavirus-2, pose a significant burden to military health care systems and force readiness. The gut microbiota influences immune function, is malleable, and may provide a target for interventions aiming to reduce RTI burden. This narrative review summarizes existing evidence regarding the effectiveness of probiotics, prebiotics, and synbiotics, all of which are gut microbiota-targeted interventions, for reducing the burden of RTI in military-relevant populations (i.e., healthy non-elderly adults).

Materials and Methods

A systematic search strategy was used to identify recent meta-analyses and systematic reviews of randomized controlled trials conducted in healthy non-elderly adults which examined effects of probiotics, prebiotics, or synbiotics on the incidence, duration, and/or severity of RTI, or on immune responses to vaccinations against viruses that cause RTI. Relevant randomized controlled clinical trials not included in those reports were also identified.

Results

Meta-analyses and multiple randomized controlled trials have demonstrated that certain probiotic strains may reduce the incidence, duration, and/or severity of RTI and improve immune responses to vaccination against RTI-causing pathogens in various populations including healthy non-elderly adults. Fewer randomized controlled trials have examined the effects of prebiotics or synbiotics on RTI-related outcomes in healthy non-elderly adults. Nevertheless, some studies conducted within that population and other populations have observed that certain prebiotics and synbiotics reduce the incidence, duration, and/or severity of RTI or improve immune responses to vaccinations against RTI-causing viruses. However, across all product classes, not all product formulations have shown benefit, and most have not been tested in multiple randomized controlled trials in military-relevant populations.

Conclusion

Dietary supplementation with certain gut microbiota-targeted interventions, and certain probiotics in particular, may provide viable strategies for reducing RTI-related illness in military personnel. Research in military populations is warranted to fully understand the magnitude of any military health and cost benefits, and to establish definitive recommendations for use.
Effects of Reduced-Nicotine Cigarettes Across Regulatory Environments in the Experimental Tobacco Marketplace: A Randomized Trial
Authors: Kaplan Brent A , Koffarnus Mikhail N , Franck Christopher T , Bickel Warren K
Published: November 2020

Introduction

Cigarette smoking remains the leading preventable cause of death in the United States. Recent efforts have explored the potential health and policy benefits of reducing nicotine, an addictive component, in combustible cigarettes. To date, an experimental, prospective analysis directly comparing the effects of varying regulatory environments on purchases of multiple products has yet to be conducted. The present study compared real purchasing of conventional cigarettes, reduced-nicotine cigarettes, and a variety of other nicotine and tobacco products across a range of regulatory environments.

Methods

Participants were assigned to one of five groups, each associated with a different nicotine level (mg of nicotine to g of tobacco) in SPECTRUM investigational cigarettes (15.8, 5.2, 2.4, 1.3, and 0.4 mg/g). Across sessions, participants made real purchases for nicotine/tobacco products in an Experimental Tobacco Marketplace. Each session corresponded with a distinct regulatory environment wherein different nicotine/tobacco products were available for purchase.

Results

Our results suggest that the primary drivers of cigarette and nicotine purchasing are regulatory environment and the presence/absence of alternative nicotine and tobacco products. Perhaps surprisingly, nicotine level does not appear to be such a driver of purchasing behavior under these experimental conditions. Investigational cigarette purchasing is lowest when other preferred combustible products are available and highest when investigational cigarettes are the only combustible product available for purchase.

Conclusions

If a reduced-nicotine policy is implemented, great care should be taken in determining and making available less-harmful nicotine/tobacco products as the availability of preferred combustible products may result in undesirable levels of purchasing.

Implications

This is the first experimental study investigating different potential regulatory effects related to a reduced-nicotine policy by examining purchasing across a range of nicotine/tobacco products. Our results suggest the presence of affordable, highly preferred combustible products is likely to maintain tobacco purchasing at undesirable levels. To promote switching to less-harmful products, affordable alternate nicotine and tobacco products should be readily available. Finally, our results suggest that the availability of noncigarette products, not cigarette nicotine level, will most likely affect purchasing of reduced-nicotine cigarettes.
The Opaqueness of Rules†
Authors: Hass Binesh
Published: November 2020

This article takes up the question of whether legal rules are reasons for action. They are commonly regarded in this way, yet are legal rules reasons for action themselves (the reflexivity thesis) or are they instead merely statements of other reasons that we may already have (the paraphrastic thesis)? I argue for a version of the paraphrastic thesis. In doing so, considerable attention is given to the neglected but important puzzle of the opaqueness of rules, which arises out of what some regard as the gap between the evaluative grounds of legal rules and what makes them into reasons for action. After examining an important articulation of the puzzle in the work of Joseph Raz, I argue that the reflexivity thesis is (i) undermined by certain features of rule making and (ii) defeated by the principle of presumptive sufficiency. The result is that it is possible for legal rules to be paraphrastic statements of reasons but, conversely, impossible for them to be reasons in themselves.
Is Majority Rule Justified in Constitutional Adjudication?
Authors: Caviedes Cristóbal
Published: November 2020

In this article, I challenge the use of a majority voting rule (majority rule) to declare statutes unconstitutional in many constitutional courts. To do this, I briefly present four main features of majority rule and assess whether these features (separately and jointly considered) provide definitive reasons for using this voting rule over others in constitutional adjudication. I conclude that these features do not provide such reasons either individually or taken together. This conclusion enables one to analyse whether constitutional courts should use other voting rules in constitutional adjudication, such as supermajority rules.
Learning to Apply Mindfulness to Pain (LAMP): Design for a Pragmatic Clinical Trial of Two Mindfulness-Based Interventions for Chronic Pain
Authors: Burgess Diana J , Evans Roni , Allen Kelli D , Bangerter, Ann , Bronfort Gert , Cross Lee J , Ferguson John E , Haley Alex , Hagel Campbell Emily M , Mahaffey Mallory R , Matthias Marianne S , Meis Laura A , Polusny Melissa A , Serpa J Greg , Taylor Stephanie L , Taylor Brent C
Published: November 2020

Background

Mindfulness-based interventions (MBIs) are evidence-based nonpharmacological treatments for treating chronic pain. However, the predominant MBI, mindfulness-based stress reduction, has features that pose significant implementation barriers.

Objectives

This study will test two approaches to delivering MBIs for improving Veterans’ chronic pain and mental health comorbidities. These two approaches address key implementation barriers.

Methods

We will conduct a four-site, three-arm pragmatic randomized controlled trial, Learning to Apply Mindfulness to Pain (LAMP), to test the effectiveness of two MBIs at improving pain and mental health comorbidities. Mobile+Group LAMP consists of prerecorded modules presented by a mindfulness instructor that are viewed in an online group setting and interspersed with discussions led by a facilitator. Mobile LAMP consists of the same prerecorded modules but does not include a group component. We will test whether either of these MBIs will be more effective than usual care at improving chronic pain and whether the Mobile+Group LAMP will be more effective than Mobile LAMP at improving chronic pain. Comparisons for the primary hypotheses will be conducted with continuous outcomes (Brief Pain Inventory interference score) repeated at 10 weeks, 6 months, and 12 months. The secondary hypotheses are that Mobile+Group LAMP and Mobile LAMP will be more effective than usual care at improving secondary outcomes (e.g., post-traumatic stress disorder, depression). We will also confirm the comparisons for the primary and secondary hypotheses in gender-specific strata.

Implications

This trial is expected to result in two approaches for delivering MBIs that will optimize engagement, adherence, and sustainability and be able to reach large numbers of Veterans.
Browsing versus Studying: A Pro-market Case for Regulation
Authors: Heidhues Paul , Johnen Johannes , Kőszegi Botond
Published: November 2020

We identify a competition-policy-based argument for regulating the secondary features of complex or complexly priced products when consumers have limited attention. Limited attention implies that consumers can only “study” a small number of complex products in full, while—by failing to check secondary features—they can superficially “browse” more. Interventions limiting ex post consumer harm through safety regulations, caps on certain fees, or other methods induce consumers to do more or more meaningful browsing, enhancing competition. We show that for a pro-competitive effect to obtain, the regulation must apply to the secondary features, and not to the total price or value of the product. As an auxiliary positive prediction, we establish that because low-value consumers are often more likely to study—and therefore less likely to browse—than high-value consumers, the average price consumers pay can be increasing in the share of low-value consumers. We discuss applications of our insights to health-insurance choice, the European Union’s principle on unfair contract terms, food safety in developing countries, and the shopping behaviour of (and prices paid by) low-income and high-income consumers.
The Aggregate Implications of Mergers and Acquisitions
Authors: David Joel M
Published: November 2020

This article develops a search and matching model of mergers and acquisitions (M&A) and uses it to evaluate the implications of merger activity for aggregate economic outcomes. The theory is consistent with a rich set of facts on U.S. M&A, including sorting among merging firms, a substantial merger premium and serial acquisition. It provides a sharp link between these facts and the nature of merger gains. At the micro-level, both complementarities between merging firms and productivity improvements of target firms are important in generating gains. At the macro-level, the model suggests a significant beneficial impact of M&A on aggregate outcomes—the contribution to steady state output is 14$\%$ and 4$\%$ for consumption—which occurs through the reallocation of resources across firms and equilibrium effects on firm selection and new entrepreneurship. Nevertheless, the economy is not efficient, suggesting a scope for policy improvements—a simple flat tax on M&A can raise steady state consumption as much as 2$\%$ relative to the laissez-faire equilibrium. In short, the boundaries of the firm can matter for macroeconomic outcomes.
A SURVEY STUDY OF RADIATION PROTECTION AWARENESS AMONG RADIOLOGY TECHNICIANS IN MOGADISHU, SOMALIA
Authors: Aras Serhat , Tanzer Ihsan Oguz , Ikizceli Turkan
Published: November 2020

We investigate the ionizing radiation exposure awareness and subject matter knowledge among clinical radiology technicians working in state and private hospitals in Mogadishu, Somalia. Research data are collected via face to face interviews with a prepared questionnaire performed between April and May 2018 in Mogadishu, Somalia. A total of 61 clinical radiology technicians working in 10 state and private hospitals in Mogadishu volunteered to be part of this study.

Among the participants, awareness of the harmful effects of ionizing radiation and sufficient subject matter knowledge were lacking. In addition, radiation protection equipment during radiological examinations were not adequately used by clinical radiology technicians. Our results indicate a necessity to retrain and improve the technician education curriculum before and after graduation to create a safer environment both for hospital staff and patients during radiological examinations.
The Resting Brain Sets Support-Giving in Motion: Dorsomedial Prefrontal Cortex Activity During Momentary Rest Primes Supportive Responding
Authors: Inagaki Tristen K , Brietzke Sasha , Meyer Meghan L
Published: November 2020

Humans give support, care, and assistance to others on a daily basis. However, the brain mechanisms that set such supportive behavior in motion are unknown. Based on previous findings demonstrating that activity in a portion of the brain’s default network—the dorsomedial prefrontal cortex (DMPFC)—during brief rest primes social thinking and behavior, momentary fluctuations in this brain region at rest may prime supportive responding. To test this hypothesis, 26 participants underwent functional magnetic resonance imaging (fMRI) while they alternated between deciding whether to give support to a close other in financial need, receive support for themselves, and make arbitrary decisions unrelated to support. Decisions were interleaved with brief periods of rest. Results showed that, within participants, spontaneous activity in the DMPFC during momentary periods of rest primed supportive-responding: greater activity in this region at the onset of a brief period of rest predicted, on a trial-by-trial basis, faster decisions to give support to the close other. Thus, activating the DMPFC as soon as our minds are free from external demands to attention may help individuals “default” to support-giving. Implications for understanding the prosocial functions of the resting brain are discussed.
Diagnostic point-of-care ultrasound in medical inpatients at Queen Elizabeth Central Hospital, Malawi: an observational study of practice and evaluation of implementation
Authors: Limani Fumbani , Dula Dingase , Keeley Alexander J , Joekes Elizabeth , Phiri Tamara , Tembo Ephraim , Gadama Luis , Nnensa Victoria , Jordan Sabine , Mallewa Jane , Kreuels Benno
Published: November 2020

Background

In less well-resourced settings, where access to radiology services is limited, point-of-care ultrasound (POCUS) can be used to assess patients and guide clinical management. The aim of this study was to describe ultrasound practice in the assessment of medical inpatients at Queen Elizabeth Central Hospital, Blantyre, Malawi, and evaluate uptake and impact of POCUS following the introduction of a training programme at the college of Medicine, Blantyre, Malawi.

Methods

: A weekly prospective record review of sequential adult medical inpatients who had received an ultrasound examination was conducted.

Results

Of 835 patients screened, 250 patients were included; 267 ultrasound examinations were performed, of which 133 (50%) were POCUS (defined as performed by a clinician at the bedside). The time from request to performance of examination was shorter for POCUS examinations than radiology department ultrasound (RDUS) (median 0 [IQR 0–2, range 0–11] vs 2 [IQR 1–4, range 0–15] d, p=0.002); 104/133 (78.2%) POCUS and 90/133 (67.7%) RDUS examinations were deemed to have an impact on management.

Conclusion

Following the introduction of a training programme in POCUS, half of all ultrasound examinations were delivered as POCUS. POCUS was performed rapidly and impacted on patient management. POCUS may relieve the burden on radiology services in less well-resourced settings.
Molecular analysis reveals a cryptic species ofChthamalus(Crustacea: Cirripedia) in the Cape Verde Islands
Authors: Tikochinski Yaron , Motro Uzi , Simon-Blecher Noa , Achituv Yair
Published: November 2020

The intertidal barnacle Chthamalus stellatus has a broad distribution, occurring in the Mediterranean, the east Atlantic shores and east Atlantic Macaronesian Islands (Madeira, the Canaries and the Azores). Traditionally, based on morphological characters, Chthamalus of the Cape Verde Islands were also regarded as C. stellatus. However, using a mitochondrial gene and two nuclear genes, we found that although Chthamalus from Cape Verde is morphologically similar to C. stellatus, there are genetic differences between the two that are larger than those found between different species of Chthamalus. We thus claim that these genetic differences justify the assignment of the Cape Verde populations as an evolutionarily significant unit and a sister clade to C. stellatus. We also show that the connection between taxonomic units that are close to each other lies not only in the resemblance between DNA sequences. We have found that numerous point mutations characterizing the Cape Verde Chthamalus are present as infrequent alleles in C. stellatus, indicating that two close taxonomic units can also share polymorphisms present in their common ancestor.