bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and optimization of orthotopic liver metastasis xenograft mouse models in uveal melanoma
Authors: Sugase Takahito , Lam Bao Q. , Danielson Meggie , Terai Mizue , Aplin Andrew E. , Gutkind J. Silvio , Sato Takami
Published: May 2020

Background

Patients with metastatic uveal melanoma (MUM) in the liver usually die within 1 year. The development of new treatments for MUM has been limited by the lack of diverse MUM cell lines and appropriate animal models. We previously reported that orthotopic xenograft mouse models established by direct injection of MUM cells into the liver were useful for the analysis associated with tumor microenvironment in the liver. However, considering that patients with UM metastasize to the liver hematogenously, direct liver injection model might not be suitable for investigation on various mechanisms of liver metastasis. Here, we aim to establish new orthotopic xenograft models via hematogenous dissemination of tumor cells to the liver, and to compare their characteristics with the hepatic injection model. We also determine if hepatic tumors could be effectively monitored with non-invasive live imaging.

Methods

tdtTomate-labeled, patient-derived MUM cells were injected into the liver, spleen or tail vein of immunodeficient NSG mice. Tumor growth was serially assessed with In Vivo Imaging System (IVIS) images once every week. Established hepatic tumors were evaluated with CT scan and then analyzed histologically.

Results

We found that splenic injection could consistently establish hepatic tumors. Non-invasive imaging showed that the splenic injection model had more consistent and stronger fluorescent intensity compared to the hepatic injection model. There were no significant differences in tumor growth between splenic injection with splenectomy and without splenectomy. The splenic injection established hepatic tumors diffusely throughout the liver, while the hepatic injection of tumor cells established a single localized tumor. Long-term monitoring of tumor development showed that tumor growth, tumor distribution in the liver, and overall survival depended on the number of tumor cells injected to the spleen.

Conclusion

We established a new orthotopic hepatic metastatic xenograft mouse model by splenic injection of MUM cells. The growth of orthotopic hepatic tumors could be monitored with non-invasive IVIS imaging. Moreover, we evaluated the therapeutic effect of a MEK inhibitor by using this model. Our findings suggest that our new orthotopic liver metastatic mouse model may be useful for preclinical drug screening experiments and for the analysis of liver metastasis mechanisms.
Modern contraceptive use among female refugee adolescents in northern Uganda: prevalence and associated factors
Authors: Bakesiima Ritah , Cleeve Amanda , Larsson Elin , Tumwine James K. , Ndeezi Grace , Danielsson Kristina Gemzell , Nabirye Rose Chalo , Kashesya Jolly Beyeza
Published: May 2020

Background

Adolescent pregnancies are persistently high among refugees. The pregnancies have been attributed to low contraceptive use in this population. The aim of this study was to determine the prevalence and factors associated with modern contraceptive use among female refugee adolescents in northern Uganda.

Methods

This was a cross sectional study using both descriptive and analytical techniques. The study was carried out in Palabek refugee settlement in Northern Uganda from May to July 2019. A total of 839 refugee adolescents who were sexually active or in-union were consecutively enrolled. Interviewer administered questionnaires were used for data collection.

Results

Modern contraceptive prevalence was 8.7% (95% CI: 7.0 to 10.8). The injectable was the most commonly used modern contraceptive method [42.5% (95% CI: 31.5 to 54.3)], and most of the participants had used the contraceptives for 6 months or less (59.7%). Reasons for not using modern contraceptives included fear of side effects (39.3%), partner prohibition (16.4%), and the desire to become pregnant (7.0%). Participants who were married (OR = 0.11, 95% CI: 0.04 to 0.35, p < 0.001), cohabiting (OR = 0.43, 95% CI: 0.20 to 0.93, p = 0.032) or having an older partner (OR = 0.93, 95% CI: 0.86 to 0.99, p = 0.046) were less likely to use modern contraceptives.

Conclusion

Modern contraceptive use among female refugee adolescents was very low, and few reported a desire to become pregnant, leaving them vulnerable to unplanned pregnancies. Least likely to use modern contraceptives were participants who were married/cohabiting and those having older partners implying a gender power imbalance in fertility decision making. There is an urgent need for innovations to address the gender and power imbalances within relationships, which could shape fertility decision-making and increase modern contraceptive use among refugee adolescents.
Binge-drinking and household role’s associations with prevalence of domestic violence: findings from the Thailand smoking and drinking behaviour survey 2017
Authors: Wichaidit Wit , Assanangkornchai Sawitri
Published: May 2020

Introduction

Alcohol consumption is associated with domestic violence, but the extent that binge-drinking and the household role of drinkers strengthens this association is unknown. We assessed the extent that binge-drinking behavior and the household role of the drinker were associated with alcohol-related domestic violence.

Methods

We analyzed data from a nationally-representative census survey of 36,364 households in Thailand, of whom 17,759 households had one or more drinkers (n = 17,759 households). We aggregated the interview data of individuals living in the same households to create household-level attributes. We used multivariate log-binomial regression analyses to calculate prevalence ratios (PR) and measure the association between drinking behavior of household members and reported domestic violence during the previous 12 months.

Results

Among households with one current drinker, households with a binge-drinker had higher prevalence of reported domestic violence than households where the drinker did not binge (Adjusted PR = 7.13; 95% CI = 4.79, 10.61), and households where the female head drank had significantly lower domestic violence compared to households where the male head drank (Adjusted PR = 0.12; 95% CI = 0.04, 0.33). Among households with two or more drinkers, households with one and two or more binge-drinkers had significantly higher prevalence of domestic violence compared to households with no binge-drinker (Adjusted PR = 2.86; 95% CI = 1.68, 4.86; and Adjusted PR = 4.62; 95% CI = 2.78, 7.67, respectively).

Conclusions

Binge-drinking and household role of the drinker were associated with domestic violence at the household level. However, the study methods did not allow for disentangling of the stated associations, which limited the contribution of the study beyond its reported findings.
Normalization of the right heart and the preoperative factors that influence the emergence PAH after surgical closure of atrial septal defect
Authors: Supomo Supomo , Widhinugroho Agung , Nugraha Aditya Agam
Published: May 2020

Background

Surgical closure of atrial septal defect (ASD) is contraindicated in the condition with severe pulmonary arterial hypertension (PAH), whereas ASD closure in an effective intervention to normalize the structure and function of the right heart after previously experiencing volume overload due to shunting from the defect. This study aimed to evaluate normalization of the right heart and emergence of PAH after surgical closure of ASD.

Methods

This retrospective study was carried out in 45 patients over 18 years who had undergone surgical closure of ASD. The study has the aim to evaluate the morphological and functional parameters before and after the surgical approach and the preoperative factors that influenced the development of pulmonary arterial hypertension (PAP) after the ASD closure.

Results

The majority of subjects were female (73.3%) although there were no significant differences between males and females from the various parameters. The average of mPAP in the group that experienced PAH was higher than non-PAH group after ASD closure (p = 0.019, 31.23 ± 12.70 mmHg vs 24.07 ± 13.08 mmHg). Significant differences were found in the Right Atrium (RA) dimension, Right Ventricle (RV) dimension, Tricuspid Regurgitation Velocity (TRV) and Tricuspid Annular Plane Systolic Excursion (TAPSE) between before and at 6 months after ASD closure (p = 0.000, p = 0.000, p = 0.000, p = 000, respectively). The sensitivity of the predictive model to estimate PAH at 6 months after surgical closure of ASD was 58%, with a specificity of 62.5%.

Conclusion

Structural and functional normalization of the right heart occurs at 6 months after surgical closure of ASD with the decrease of RA and RV dimensions and improvement from tricuspid regurgitation. Emergence of PAH after ASD closure was influenced by higher mPAP before surgical approach.
Short-term outcomes of modified Y-graft technique in acute type a aortic dissection using the femoral artery bypass and one minute systemic circulatory arrest technique
Authors: Sun Xiangfei , Zhao Qi , Huo Yufeng , Zhou Jinfeng , Zhao Fen , Liu Yimin , Du Yonghai , He Songxiong , Liu Chao , Jiang Detian , Sun Wenyu
Published: May 2020

Objective

Aortic arch replacement in acute type A aortic dissection patients remains the most challenging cardiovascular operation. Herein, we described our modified Y-graft technique using the Femoral Artery Bypass (FAB) and the One Minute Systemic Circulatory Arrest (OSCA) technique, and assessed the short-term outcomes of the patients.

Methods

Between February 2015 and November 2017, 51 patients with acute type A aortic dissection underwent aortic arch replacement. Among them, 23 patients underwent FAB while 28 patients underwent both FAB and OSCA. The intraoperative data and postoperative follow-up data were recorded. The follow-up data of patients with traditional Y-graft technique were collected from previously reported studies.

Results

In the FAB group, two patients died due to pulmonary infection (30-day survival rate, 91.3%), and two patients were paralyzed from the waist down. Hemodialysis was performed for five patients (21.7%) before hospital discharge. Fifteen patients (65.2%) received respiratory support for more than 2-days and eight patients (34.8%) for more than 5-days. These follow-up results were comparable or better than the patients with traditional Y-graft technique. Furthermore, compared to the FAB group, the morbidity due to neurological dysfunction and acute renal failure was significantly reduced in the FAB+OSCA group. Moreover, the respiratory support, length of postoperative stay and ICU stay were shortened.

Conclusions

This study clarified the feasibility of FAB and OSCA technique in modifying Y-graft technique. The acute type A aortic dissection patients showed less surgical complications and favorable short-term outcomes after this surgery.
Metabolic active peritoneal sites affect tumor debulking in ovarian and peritoneal cancers
Authors: Tsoi Tung Tung , Chiu Keith W. H. , Chu M. Y. , Ngan Hextan Y. S. , Lee Elaine Y. P.
Published: May 2020

Rationale and objectives

To evaluate the impact of metabolic parameters in the peritoneal cavity on the likelihood of achieving complete tumor debulking in patients with ovarian and peritoneal cancers.

Materials and methods

Forty-nine patients with ovarian and peritoneal cancers were included, who underwent pre-operative 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT). The immediate surgical outcome was dichotomized into complete and incomplete tumor debulking. 18F-FDG PET/CT was qualitatively and quantitatively assessed by scrutinizing 15 anatomical sites for the presence of peritoneal carcinomatosis (PC). Patient-based and site-based diagnostic characteristics were described. Metabolic parameters (SUVmax, metabolic tumor volume and total lesion glycolysis) and the number of 18F-FDG avid peritoneal sites were evaluated between the two groups. Receiver operating curve (ROC) analysis was performed to determine the optimal cut-off value in predicting incomplete tumor debulking.

Results

Twenty-seven out of the 49 patients had PC and 11 had incomplete debulking. Patient-based and site-based accuracies for detection of PC were 87.8 and 97.6%, respectively. The number of 18F-FDG avid peritoneal sites was significantly different between complete and incomplete debulking groups (0.6 ± 0.8 versus 2.3 ± 1.7 sites respectively, p = 0.001), and the only independent significant risk factor among other metabolic parameters tested (odd ratio = 2.983, 95% CI 1.104–8.062) for incomplete tumor debulking with an optimal cut-off value of ≥4 (AUC = 0.816).

Conclusion

The number of 18F-FDG avid peritoneal sites increased the risk of incomplete tumor debulking after surgery and potentially useful in assisting treatment stratification in patients with ovarian and peritoneal cancers.
The tree that hides the forest: cryptic diversity and phylogenetic relationships in the Palaearctic vector Obsoletus/Scoticus Complex (Diptera: Ceratopogonidae) at the European level
Authors: Mignotte Antoine , Garros Claire , Gardès Laetitia , Balenghien Thomas , Duhayon Maxime , Rakotoarivony Ignace , Tabourin Laura , Poujol Léa , Mathieu Bruno , Ibañez-Justicia Adolfo , Deniz Ahmet , Cvetkovikj Aleksandar , Purse Bethan V. , Ramilo David W. , Stougiou Despoina , Werner Doreen , Pudar Dubravka , Petrić Dušan , Veronesi Eva , Jacobs Frans , Kampen Helge , Pereira da Fonseca Isabel , Lucientes Javier , Navarro Javier , de la Puente Josue Martinez , Stefanovska Jovana , Searle Kate R. , Khallaayoune Khalid , Culverwell C. Lorna , Larska Magdalena , Bourquia Maria , Goffredo Maria , Bisia Marina , England Marion , Robin Matthew , Quaglia Michela , Miranda-Chueca Miguel Ángel , Bødker René , Estrada-Peña Rosa , Carpenter Simon , Tchakarova Simona , Boutsini Sofia , Sviland Ståle , Schäfer Stefanie M. , Ozoliņa Zanda , Segliņa Zanda , Vatansever Zati , Huber Karine
Published: May 2020

Background

Culicoides obsoletus is an abundant and widely distributed Holarctic biting midge species, involved in the transmission of bluetongue virus (BTV) and Schmallenberg virus (SBV) to wild and domestic ruminants. Females of this vector species are often reported jointly with two morphologically very close species, C. scoticus and C. montanus, forming the Obsoletus/Scoticus Complex. Recently, cryptic diversity within C. obsoletus was reported in geographically distant sites. Clear delineation of species and characterization of genetic variability is mandatory to revise their taxonomic status and assess the vector role of each taxonomic entity. Our objectives were to characterize and map the cryptic diversity within the Obsoletus/Scoticus Complex.

Methods

Portion of the cox1 mitochondrial gene of 3763 individuals belonging to the Obsoletus/Scoticus Complex was sequenced. Populations from 20 countries along a Palaearctic Mediterranean transect covering Scandinavia to Canary islands (North to South) and Canary islands to Turkey (West to East) were included. Genetic diversity based on cox1 barcoding was supported by 16S rDNA mitochondrial gene sequences and a gene coding for ribosomal 28S rDNA. Species delimitation using a multi-marker methodology was used to revise the current taxonomic scheme of the Obsoletus/Scoticus Complex.

Results

Our analysis showed the existence of three phylogenetic clades (C. obsoletus clade O2, C. obsoletus clade dark and one not yet named and identified) within C. obsoletus. These analyses also revealed two intra-specific clades within C. scoticus and raised questions about the taxonomic status of C. montanus.

Conclusions

To our knowledge, our study provides the first genetic characterization of the Obsoletus/Scoticus Complex on a large geographical scale and allows a revision of the current taxonomic classification for an important group of vector species of livestock viruses in the Palaearctic region.
Correction to: Protocol for a double-blind, randomized controlled trial on the dose-related efficacy of omalizumab in multi-food oral immunotherapy
Authors: Langlois Alexandra , Lavergne Marie-Hélène , Leroux Hélène , Killer Kerstin , Azzano Pauline , Paradis Louis , Samaan Kathryn , Lacombe-Barrios Jonathan , Eiwegger Thomas , Upton Julia , Sussman Gordon , Poder Thomas , Mâsse Benoît , Roches Anne Des , Bégin Philippe
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
Correction to: miR-205-5p inhibits human endometriosis progression by targeting ANGPT2 in endometrial stromal cells
Authors: Zhou Chen-Fei , Liu Min-Juan , Wang Wei , Wu Sha , Huang Yu-Xin , Chen Guo-Bin , Liu Li-Min , Peng Dong-Xian , Wang Xue-Feng , Cai Xu-Zi , Li Xiao-Xuan , Feng Wan-Qin , Ma Ying
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
Funerary colors in Pre-classical Maya culture: the red pigment in the 19th tomb of Rio Azul (Peten, Guatemala)
Authors: Doménech-Carbó María Teresa , Vázquez de Agredos-Pascual María Luisa , Osete-Cortina Laura , Doménech-Carbó Antonio , Guasch-Ferré Nuria , Vidal-Lorenzo Cristina
Published: May 2020

The pigments were important in the funerary customs of the ancient Maya. They could be introduced as an offering inside the tombs or burials, and were also used to wrap the dead bodies, as if it were a funeral shroud. In the tombs and burials of royalty and high social classes the use of pigments for this purpose is well documented, and physicochemical studies are focused on their identification. This scientific contribution shows the results obtained when analyzing two reddish pigmenting materials from the grave goods of the tomb 19 of the archaeological site of Rio Azul, (Guatemalan Department of Petén), using a multi-technique approach including microscopy, diffraction, spectroscopic, electrochemical and chromatographic techniques. The results have enabled the identification of the inorganic and organic materials composing these pigmenting materials found in a ceramic posthumous offering dish and further discussion mainly has been focused on the geological source of the inorganic materials and the possible origin of the organic matter accompanying these two pigmenting materials.
Using a zero-inflated model to assess gene flow risk and coexistence of Brassica napus L. and Brassica rapa L. on a field scale in Taiwan
Authors: Su Yuan-Chih , Wang Po-Shung , Yang Jhih-Ling , Hong Hong , Lin Tzu-Kai , Tu Yuan-Kai , Kuo Bo-Jein
Published: May 2020

Background

The cropping area of genetically modified (GM) crops has constantly increased since 1996. However, currently, cultivating GM crops is associated with many concerns. Transgenes are transferred to non-GM crops through pollen-mediated gene flow, which causes environmental problems such as superweeds and introgressive hybridization. Rapeseed (Brassica napus L.), which has many GM varieties, is one of the most crucial oil crops in the world. Hybridization between Brassica species occurs spontaneously. B. rapa grows in fields as a weed and is cultivated as a crop for various purposes. Both B. rapa weeds and crops participate in gene flow among rapeseed. Therefore, gene flow risk and the coexistence of these two species should be studied.

Results

In this study, field experiments were conducted at two sites for 4 years to evaluate gene flow risk. In addition, zero-inflated models were used to address the problem of excess zero values and data overdispersion. The difference in the number of cross-pollination (CP) events was nonsignificant between upwind and downwind plots. The CP rate decreased as the distance increased. The average CP rates at distances of 0.35 and 12.95 m were 2.78% and 0.028%, respectively. In our results, zero-inflated negative binomial models were comprehensively superior to zero-inflated Poisson models. The models predicted isolation distances of approximately 1.36 and 0.43 m for the 0.9% and 3% threshold labeling levels, respectively.

Conclusions

Cultivating GM crops is prohibited in Taiwan; however, the study results can provide a reference for the assessment of gene flow risk and the coexistence of these two species in Asian countries establishing policies for GM crops.
Sewing transnational textures of labour regulation: towards an integrative perspective
Authors: Pries Ludger
Published: May 2020

Labour regulation is often approached either by methodological nationalism or methodological globalism. Main arguments are that labour and its regulation are increasingly dis-embedded and commodified. As an alternative framing we propose a (neo-)institutionalist multi-level and multi-actors approach. Based on literature review and own studies we argue that there is empirical evidence of transnational labour regulation combining different logics of action and institutional contexts. Taking the example of the Bangladesh Accord on Fire and Building Safety, we demonstrate the multi-level, multi-dimensional institutional settings and sketch out basic elements of an integrative perspective on sewing transnational textures of labour regulation.

Key terms

Labour regulation, globalization, transnationalization, Bangladesh Accord, neo-institutionalism, multi-level multi-actor approach.
A non-flagellated biocontrol bacterium employs a PilZ-PilB complex to provoke twitching motility associated with its predation behavior
Authors: Lin Long , Zhou Mimi , Shen Danyu , Han Sen , Fulano Alex M. , Chou Shan-Ho , Qian Guoliang
Published: May 2020

Lysobacter enzymogenesOH11 is a non-flagellated, ubiquitous soil bacterium with broad-spectrum antifungal activities. Although lacking flagella, it employs another type of motile behavior, known as twitching motility that is powered by type IV pilus (T4P) to move towards neighboring crop fungal pathogens to kill them as food. At present, little is known about how this non-flagellated bacterium controls twitching motility that is crucial for its predatory lifestyle. Herein, we present a report on how a non-canonical PilZ domain, PilZLe3639, controls such motility in the non-flagellatedL. enzymogenes; it failed to bind with c-di-GMP but seemed to be required for twitching motility. Using bacterial two-hybrid and pull-down approaches, we identified PilBLe0708, one of the PilZLe3639-binding proteins that are essential for the bacterial twitching motility, could serve as an ATPase to supply energy for T4P extension. Through site-mutagenesis approaches, we identified one essential residue of PilZLe3639that is required for its binding affinity with PilBLe0708and its regulatory function. Besides, two critical residues within the ATPase catalytic domains of PilBLe0708were detected to be essential for regulating twitching behavior but not involved in binding with PilZLe3639. Overall, we illustrated that the PilZ-PilB complex formation is indispensable for twitching motility in a non-flagellated bacterium.
A prospective comparative study of local infiltration versus adductor block versus combined use of the two techniques following knee arthroplasty
Authors: Marya S. K. S. , Arora Deep , Singh Chandeep , Kacker Shitij , Desai Rahul , Lodha Vikas
Published: May 2020

Background

Pain management after total knee arthroplasty (TKA) is important as acute postoperative pain can affect patient’s ability to walk and participate in rehabilitation required for good functional outcome. This is achieved by effective intra-operative and post-operative analgesia to facilitate early recovery. Adductor canal block (ACB) and local infiltration analgesia (LIA) are analgesic regimens and commonly used for effective post-operative analgesia after TKA. Our aim was to compare the efficacy and outcomes of these two methods, combined and independently.

Methods

Our study included 120 patients undergoing unilateral TKA, who were randomized into three groups: LIA (Group I), ACB (Group II) and combined LIA + ACB (Group III). Patients were operated by a single surgeon. The outcome was defined by post-operative analgesia achieved by the three techniques (measured by the NPRS) and amount of fentanyl consumed postoperatively. Secondary outcome was evaluated based on postoperative functional outcomes in terms of ability to stand, distance covered, range of motion of knee on the 1st post-operative day, complications and WOMAC (Western Ontario & McMaster Universities Osteoarthritis Index) scores.

Results

All patients were available for analysis. Numerical Pain Rating Scale for pain showed significant differences at 24 h between Group I and Group II, with a p value of 0.018 (GroupI was better), significant differences were found at 24 h between Group III and Group II, with p values being 0.023 and 0.004 (GroupIII was better). No significant differences were found between Group I and Group III at 24 h. Total fentanyl consumption was significantly less in Group III than in Group I and Group II, with p value being 0.042 and 0.005, respectively (Group III was better and consumed less fentanyl). No significant differences were found in WOMAC scores between the three groups at baseline, 2 and 6 weeks after operation.

Conclusion

In patients undergoing TKA, analgesic effect of combined ACB and LIA was superior, as indicated by reduced opioid consumption and no differences in functional outcomes and complications were observed as compared to separate use of the two techniques.
Competition dynamics in Nigerian aviation industry: a game theoretic approach
Authors: Shobande Olatunji Abdul , Akinbomi Mobolaji Daniel
Published: May 2020

Background

This paper develops a game theoretic model that analyses the dynamics of competition among the leading domestic aviation firms in the Nigerian aviation industry. It probes the abilities of the prisoner dilemma to describe the subjective behaviour of the firms, which provide a yardstick for assessing the optimal competitive strategies available to the firm to survive the business environment.

Results

The solution of the game provides different optimal competitive strategies for the firms. While findings show that Aero Contractors placed more weight on flight pricing to survive in the industry, Arik Air needed to retain non-pricing competitive strategy to remain the leading domestic aviation firm in Nigeria.

Conclusion

Based on our findings, we conclude that if both firms stick to the optimal strategy, they would both share the market.
A Design of Experiment (DoE) based approach for development and optimization of nanosuspensions of telmisartan, a BCS class II antihypertensive drug
Authors: Bhargav E. , Chaithanya Barghav G. , Padmanabha Reddy Y. , Pavan kumar Chintamaneni , Ramalingam P. , Haranath C.
Published: May 2020

Background

The present study was aimed to enhance the solubility and dissolution of BCS class II drug, telmisartan (TEM), by nanoformulation approach. Several attempts were made to develop a nanosuspension by bottom-up and top-down techniques. In our study, we found in situ nanoamorphization technique to be incompatible and hence was not selected for further development of nanoformulation. Bottom-up techniques such as anti-solvent precipitation and emulsification solvent evaporation methods failed to reduce the size of the drug to nanoform by HPMC E15 and PVP K-25 at 1500–2000 rpm but resulted in micron-sized particles.

Results

However, the acid-base neutralization method has produced nanosuspension with a particle size of 243.9 nm and 0.119 PDI. Formulation and analytical development were carried out by statistical factorial design using the Design-Expert software (version 11.0). The nanosuspensions remained stable even after 90 days without any aggregations with particle size 338.1 nm and PDI 0.146. Zeta potential of optimized formulation was found to be − 16.2 mV. Drug content and its release were estimated by the developed and validated in-house HPLC method. In vitro drug diffusion studies on the optimized formulation have shown a drug release of 82.6% by the end of 3 h, whereas plain drug suspension has shown only 42.8% release, indicating a 2-fold increase of drug diffusion with nanosuspension. Ex vivo drug permeation studies performed using excised goat gastric mucosa revealed much faster permeation of TEM from nanosuspension than the plain drug suspension.

Conclusions

Hence, from the results, it can be concluded that TEM, when formulated by acid-base neutralization method as a nanosuspension, leads to enhanced solubility, dissolution, and stability.
Integrated Computational Pipeline for Single-Cell Genomic Profiling
Authors: Chorbadjiev Lubomir , Kendall Jude , Alexander Joan , Zhygulin Viacheslav , Song Junyan , Wigler Michael , Krasnitz Alexander
Published: May 2020

PURPOSE

Copy-number profiling of multiple individual cells from sparse sequencing may be used to reveal a detailed picture of genomic heterogeneity and clonal organization in a tissue biopsy specimen. We sought to provide a comprehensive computational pipeline for single-cell genomics, to facilitate adoption of this molecular technology for basic and translational research.

MATERIALS AND METHODS

The pipeline comprises software tools programmed in Python and in R and depends on Bowtie, HISAT2, Matplotlib, and Qt. It is installed and used with Anaconda.

RESULTS

Here we describe a complete pipeline for sparse single-cell genomic data, encompassing all steps of single-nucleus DNA copy-number profiling, from raw sequence processing to clonal structure analysis and visualization. For the latter, a specialized graphical user interface termed the single-cell genome viewer (SCGV) is provided. With applications to cancer diagnostics in mind, the SCGV allows for zooming and linkage to the University of California at Santa Cruz Genome Browser from each of the multiple integrated views of single-cell copy-number profiles. The latter can be organized by clonal substructure or by any of the associated metadata such as anatomic location and histologic characterization.

CONCLUSION

The pipeline is available as open-source software for Linux and OS X. Its modular structure, extensive documentation, and ease of deployment using Anaconda facilitate its adoption by researchers and practitioners of single-cell genomics. With open-source availability and Massachusetts Institute of Technology licensing, it provides a basis for additional development by the cancer bioinformatics community.
Remission of Pituitary Autoimmunity Induced by Gluten-Free Diet in Patients With Celiac Disease
Authors: Bellastella Giuseppe , Maiorino Maria Ida , Cirillo Paolo , Longo Miriam , Pernice Vlenia , Costantino Angela , Annunziata Carmen , Bellastella Antonio , Esposito Katherine , De Bellis Annamaria
Published: May 2020

Context

An improvement of some autoimmune diseases associated with celiac disease (CD) has been observed after a gluten-free diet (GFD).

Objective

The aim of this longitudinal study was to evaluate the effect of a GFD on autoimmune pituitary impairment in patients with CD and potential/subclinical lymphocytic hypophysitis (LYH).

Design

Five-year longitudinal observational study.

Setting

Tertiary referral center for immunoendocrinology at the University of Campania “Luigi Vanvitelli”.

Patients

Ninety-three newly diagnosed LYH patients (high titer of antipituitary antibodies [APA] and normal or subclinically impaired pituitary function) were enrolled from 2000 to 2013 and grouped as follows: group 1, consisting of 43 patients with LYH + CD, and group 2, consisting of 50 patients with isolated LYH only.

Intervention

A GFD was started in patients in group 1 after the diagnosis of CD.

Main outcome measures

APA titers and pituitary function were evaluated at the beginning of the study and then yearly for 5 years in both groups. Patients progressing to a clinically overt LYH were excluded from the follow-up.

Results

Complete remission of LYH (disappearance of APA and recovery of pituitary function in patients with previous subclinical hypopituitarism) occurred in 15 patients in group 1 after a GFD (34%) and spontaneously in only 1 patient in group 2 (2%) (P < .001). Two patients in group 1 and 25 in group 2 progressed to a clinically overt hypopituitarism and dropped out from the study to receive an appropriate replacement therapy. The presence of CD was the only independent predictor of pituitary function recovery (hazard ratio [HR] 0.059, 95% confidence interval [CI] 0.01–0.54, P = .012).

Conclusion

In patients with LYH and CD, a GFD may be able to induce remission of subclinical LYH, or prevent the progression to clinical stage of this disease.
Neural dysfunction correlates with heat coma and CTmax in Drosophila but does not set the boundaries for heat stress survival
Authors: Jørgensen Lisa B. , Robertson R. Meldrum , Overgaard Johannes
Published: May 2020

When heated, insects lose coordinated movement followed by the onset of heat coma (CTmax). These traits are popular measures to quantify inter- and intraspecific differences in insect heat tolerance, and CTmax correlate well with current species distributions of insects, including Drosophila. Here we examined the function of the central nervous system (CNS) in five species of Drosophila with different heat tolerances, while they were exposed to either constant high temperature or a gradual increasing temperature (ramp). Tolerant species were able to preserve CNS function at higher temperatures and for longer durations than sensitive species and similar differences were found for the behavioural indices (loss of coordination and onset of heat coma). Furthermore, the timing and temperature (constant and ramp exposure, respectively) for loss of coordination or complete coma coincided with the occurrence of spreading depolarisation (SD) events in the CNS. These SD events disrupt neurological function and silence the CNS suggesting that CNS failure is the primary cause of impaired coordination and heat coma. Heat mortality occurs soon after heat coma in insects and to examine if CNS failure could also be the proximal cause of heat death, we used selective heating of the head (CNS) and abdomen (visceral tissues). When comparing the temperature causing 50% mortality (LT50) of each body part to that of the whole animal, we found that the head was not particularly heat sensitive compared to the abdomen. Accordingly, it is unlikely that nervous failure is the principal/proximate cause of heat mortality in Drosophila.
Recent advances in managing Peyronie’s disease
Authors: Babu Asrit , Kayes Oliver
Published: May 2020

Treating men with Peyronie’s disease remains a challenging problem facing clinicians working across urology and sexual medicine fields. Patients can often be left disappointed by current treatment paradigms, and an overall lack of suitable molecular targets has limited the options for novel, effective medical therapy. Managing men with Peyronie’s disease often involves careful counselling alongside multifaceted and possible combination treatments to help improve symptoms whilst ameliorating potential side effects of therapy. We review the latest medical literature and evidence in the contemporary management of Peyronie’s disease.
Mortalidad por accidentes de tránsito: su determinación social. Distrito Metropolitano de Quito, 2013
Authors: Montero Gonzalo
Published: May 2020

Introducción: los accidentes de tránsito (AT) constituyen una importante causa de mortalidad en el mundo, y en los últimos años han ocupado los primeros lugares en el Distrito Metropolitano de Quito (DMQ). Los marcos conceptuales clásicos para el abordaje de la mortalidad por AT han sido: el enfoque de salud pública, el modelo sistémico y la matriz de Haddon. Desarrollo: se describen las características de los modelos clásicos y, desde la mirada de la Epidemiología Crítica (EC) y de la teoría crítica del espacio, se analizan cuatro formas de reducción de la realidad: primero, la reducción de su explicación a la acción de una causa externa (fuerza cinética) ejercida sobre el cuerpo humano que supera la resistencia del mismo. Segundo, la mirada del espacio como mero continente físico o unidad administrativa. Tercero, la consideración del carácter social de los eventos de tránsito como sumatoria de los hechos individuales. Cuarto, la organización de los grupos sociales con criterios de estratificación y no con base en la clase social. Además, se describe cómo, mediante un estudio exploratorio de varias fases, que comprendió revisión documental, enlace de archivos, encuesta a un familiar de la persona fallecida y georreferenciación de la residencia de la persona fallecida, se analizó la mortalidad por AT en el DMQ, con base en las categorías de la Epidemiología Crítica: segregación social del espacio, clase social y perfil epidemiológico, en el contexto de la mortalidad por AT en el DMQ. Conclusión: el abordaje desde la EC permite una comprensión más integral de la mortalidad de los AT, como resultado de determinaciones socioeconómicas, de procesos de orden etnocultural y de construcción social del género, propios de los modos de vida de las diferentes clases sociales.
A Conditional Gradient Approach for Nonparametric Estimation of Mixing Distributions
Authors: Jagabathula Srikanth , Subramanian Lakshminarayanan , Venkataraman Ashwin
Published: May 2020

Mixture models are versatile tools that are used extensively in many fields, including operations, marketing, and econometrics. The main challenge in estimating mixture models is that the mixing distribution is often unknown, and imposing a priori parametric assumptions can lead to model misspecification issues. In this paper, we propose a new methodology for nonparametric estimation of the mixing distribution of a mixture of logit models. We formulate the likelihood-based estimation problem as a constrained convex program and apply the conditional gradient (also known as Frank–Wolfe) algorithm to solve this convex program. We show that our method iteratively generates the support of the mixing distribution and the mixing proportions. Theoretically, we establish the sublinear convergence rate of our estimator and characterize the structure of the recovered mixing distribution. Empirically, we test our approach on real-world datasets. We show that it outperforms the standard expectation-maximization (EM) benchmark on speed (16 times faster), in-sample fit (up to 24% reduction in the log-likelihood loss), and predictive (average 28% reduction in standard error metrics) and decision accuracies (extracts around 23% more revenue). On synthetic data, we show that our estimator is robust to different ground-truth mixing distributions and can also account for endogeneity.

This paper was accepted by Serguei Netessine, operations management.
Task Selection and Workload: A Focus on Completing Easy Tasks Hurts Performance
Authors: KC Diwas S. , Staats Bradley R. , Kouchaki Maryam , Gino Francesca
Published: May 2020

How individuals manage, organize, and complete their tasks is central to operations management. Recent research in operations focuses on how under conditions of increasing workload individuals can decrease their service time, up to a point, to complete work more quickly. As the number of tasks increases, however, workers may also manage their workload by a different process—task selection. Drawing on research on workload, individual discretion, and behavioral decision making, we theorize and then test that under conditions of increased workload, individuals may choose to complete easier tasks to manage their load. We label this behavior task completion preference (TCP). Using six years of data from a hospital emergency department, we find that physicians engage in TCP, with implications for their performance. Specifically, TCP helps physicians manage variance in service times; however, although it initially appears to improve shift-level throughput volume, after adjusting for the complexity of the work completed, TCP is related to worse throughput. Moreover, we find that engaging in easier tasks compared with hard ones is related to lower learning in service times. We then turn to the laboratory to replicate conceptually the short-term task selection effect under increased workload and show that it occurs because of both fatigue and the sense of progress individuals get from task completion. These findings provide another mechanism for the workload-speedup effect from the literature. We also discuss implications for both the research and the practice of operations in building systems to help people succeed.

This paper was accepted by Serguei Netessine, operations management.
Comment on “Newsvendor Demand Chasing Revisited”
Authors: Kirshner Samuel N. , Moritz Brent B.
Published: May 2020

Based on a simulation, the authors of “Newsvendor Demand Chasing Revisited” recommended using correlation of orders with lagged demand to measure chasing behavior. They concluded that measuring chasing with regression based on partial adjustment is prone to false positives. We show the purported false positives are due to autocorrelation and recommend using partial adjustment regression-based approaches to evaluate chasing.

This paper was accepted by Jayashankar Swaminathan, operations management.
Incremental vs. Breakthrough Innovation: The Role of Technology Spillovers
Authors: Byun Seong K. , Oh Jong-Min , Xia Han
Published: May 2020

We show that technology spillovers shift the composition of corporate research and development by promoting innovation based on the exploitation of existing knowledge while disincentivizing innovation that explores new areas and breaks new ground. Accordingly, firms facing large technology spillovers attain fewer superstar inventors among their human capital, who are important drivers of breakthrough technology advancement. These findings complement the existing studies documenting the positive effect of technology spillovers in increasing firms’ overall innovation outputs; they highlight potential downsides of technology spillovers in reducing firm investment in technology breakthrough and valuable human capital.

This paper was accepted by Gustavo Manso, finance.
Industrial Need Analysis in Bakery to Develop Bakepreneurship Learning Model
Authors: Syarbini Muhammad Husin , Santosa Budi , Sayuti Muhammad
Published: May 2020

Vocational education has an important role in preparing students to have the skills needed by the industry. This study aims to analyze the needs of the bakery industry to develop a learning model of Bakepreneurship. This study using descriptive qualitative approach by analyzing the needs in the aspect of 1) student, 2) teacher, 3) curriculum, and 4) industry. Based on the analysis results of the stakeholders, we found an idea to develop a Bakepreneurship learning model that can be used as a reference in pastry and bakery learning in the vocational school. Bakepreneurship learning model is a learning model that combines comprehensively aspects of soft skills, hard skills, and entrepreneurship that aim to equip students with the competencies needed by the bakery industry.
Heroes and others: tensions and challenges in implementing Mentors in Violence Prevention in Swedish schools
Authors: Bruno Linnéa , Joelsson Tanja , Franzén Anna G. , Gottzén Lucas
Published: May 2020

This article explores the challenges that were detected in the first evaluation of the violence prevention programme Mentors in Violence Prevention at senior levels of compulsory schools and upper-secondary schools in Sweden. In particular, we analyse how the gender-transformative dimension and the bystander perspective aspect of the programme played out in the classroom. What are the implications of implementing a gender-transformative violence prevention programme such as Mentors in Violence Prevention when it is carried out by teachers in the school setting? The empirical basis for this study includes classroom observations during all seven Mentors in Violence Prevention sessions in two schools, and group interviews with a total of 14 teachers and 26 pupils (aged 13–19) from five schools. Our findings suggest that most teachers did not appear to be comfortable with either the Mentors in Violence Prevention programme’s pedagogical model or its theoretical approach. Consequently, they occasionally worked in manners contrary to the programme’s intentions. However, observations and interviews demonstrated that a learning process about gender-based violence had been initiated. It may be necessary to make further adjustments if Mentors in Violence Prevention is to be used in schools in Sweden, particularly if teachers are to be the programme leaders.
Designing miniature x-ray optics for the SmallSat lunar science mission concept CubeX
Authors: Kashyap Vinay L. , Hong Jaesub , Romaine Suzanne , Sethares Leandra , Cotroneo Vincenzo , Spiga Daniele , Nittler Larry
Published: May 2020

Planetary remote-sensing instruments are often required to cover a relatively large field of view, ideally with a uniform angular resolution over the field, due to relatively large apparent sizes of planetary targets at close proximities. They also have to comply with relatively tight mass and volume constraints. For these reasons, planetary x-ray telescopes in the past were mainly collimation-based x-ray spectrometers without focusing optics. Recent advances in x-ray optics technology now enable compact focusing x-ray telescopes suitable for planetary science (e.g., BepiColombo). We present two design options for compact Wolter-I x-ray optics for a SmallSat lunar mission concept—the CubeSat X-ray telescope (CubeX). The primary objectives of CubeX are to map surface elemental abundances of selected lunar impact craters and to assess the feasibility of millisecond x-ray pulsar timing navigation in realistic deep space navigation environments. The Miniature X-ray Optics (MiXO) in CubeX utilizes electroformed NiCo alloy replication (ENR) technology, which provides many advantages over micro-pore optics (MPO) employed in BepiColombo. We carry out extensive ray traces over a grid of mirror parameters and explore a novel tapered shaped design of tightly nested shells, where both shell length and focal-plane offsets vary with shell diameter. One of the two configurations is optimized for large effective areas at low energies, while the other for lower mass and high-energy response. We compare their performances with those of conventional designs through the spatial resolution and effective area estimated by ray traces.
EIA metamaterials based on hybrid metal/dielectric structures with dark-mode-enhanced absorption
Authors: Zhang Fuli , Huang Xinchao , Cai Weiqi , Yang Ruisheng , Fu Quanhong , Fan Yuancheng , Hu Yujin , Qiu Kepeng , Zhang Weihong , Li Chang , Li Qiang
Published: May 2020

Metamaterial analogue of electromagnetically induced absorption (EIA) has promising applications in spectroscopy and sensing. Here we propose an EIA metamaterial based on hybrid metal/dielectric structures, which are composed of a metallic wire and a dielectric block, and investigate the EIA-like effect by simulations, experiments, and the two-oscillator model. An EIA-like effect emerges in virtue of the near-field coupling between metallic wire and dielectric block, and the dielectric block exhibiting magnetic dipolar resonance makes a major contribution to the resonance absorption. The magnetic flux through the dielectric block engendered by the near filed of the metallic wire determines the coupling between dielectric block and metallic wire. With the variation of the separation between dielectric block and metallic wire, the EIA-like effect is preserved and does not convert into the EIT-like effect although the coupling and consequently the absorbance are altered. Based on the two-oscillator model, the absorption spectrum of the EIA metamaterial is quantitatively analyzed and the parameters of the oscillator system are retrieved.