bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternative Splicing of the SLCO1B1 Gene: An Exploratory Analysis of Isoform Diversity in Pediatric Liver
Authors: van Groen Bianca D. , Bi Chengpeng , Gaedigk Roger , Staggs Vincent S. , Tibboel Dick , de Wildt Saskia N. , Leeder J. Steven
Published: January 2020

The hepatic influx transporter OATP1B1 (SLCO1B1) plays an important role in the disposition of endogenous substrates and drugs prescribed to children. Alternative splicing increases the diversity of protein products from > 90% of human genes and may be triggered by developmental signals. As concentrations of several endogenous OATP1B1 substrates change during growth and development, with this exploratory study we investigated age‐dependent alternative splicing of SLCO1B1 mRNA in 97 postmortem livers (fetus‐adolescents). Twenty‐seven splice variants were detected; 10 were confirmed by additional bioinformatic analyses and verified by quantitative polymerase chain reaction, and selected for detailed analysis based on relative abundance, association with age, and overlap with an adjacent gene. Two splice variants code for reference OATP1B1 protein, and eight code for truncated proteins. The expression of eight isoforms was associated with age. We conclude that alternative splicing of SLCO1B1 occurs frequently in children; although the functional consequences remain unknown, the data raise the possibility of a regulatory role for alternative splicing in mediating developmental changes in drug disposition.
Endoscopic full‐thickness resection for esophageal submucosal tumor
Authors: Muramoto Takashi , Sakai Eiji , Ohata Ken
Published: January 2020

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Involvement of Rev1 in alkylating agent‐induced loss of heterozygosity in Oryzias latipes
Authors: Fujikawa Yoshihiro , Ishikawa‐Fujiwara Tomoko , Kuo Tony , Shinkai Norio , Shoji Tatsuma , Kawasaki Takashi , Kamei Yasuhiro , Sakuraba Yoshiyuki , Sato Ayuko , Kinoshita Masato , Gondo Yoichi , Yuba Shunsuke , Tsujimura Tohru , Sese Jun , Todo Takeshi
Published: January 2020

Translesion synthesis (TLS) polymerases mediate DNA damage bypass during replication. The TLS polymerase Rev1 has two important functions in the TLS pathway, including dCMP transferase activity and acting as a scaffolding protein for other TLS polymerases at the C‐terminus. Because of the former activity, Rev1 bypasses apurinic/apyrimidinic sites by incorporating dCMP, whereas the latter activity mediates assembly of multipolymerase complexes at the DNA lesions. We generated rev1 mutants lacking each of these two activities in Oryzias latipes (medaka) fish and analyzed cytotoxicity and mutagenicity in response to the alkylating agent diethylnitrosamine (DENA). Mutant lacking the C‐terminus was highly sensitive to DENA cytotoxicity, whereas mutant with reduced dCMP transferase activity was slightly sensitive to DENA cytotoxicity, but exhibited a higher tumorigenic rate than wild‐type fish. There was no significant difference in the frequency of DENA‐induced mutations between mutant with reduced dCMP transferase activity and wild‐type cultured cell. However, loss of heterozygosity (LOH) occurred frequently in cells with reduced dCMP transferase activity. LOH is a common genetic event in many cancer types and plays an important role on carcinogenesis. To our knowledge, this is the first report to identify the involvement of the catalytic activity of Rev1 in suppression of LOH.
Engaging young African American women breast cancer survivors: A novel storytelling approach to identify patient‐centred research priorities
Authors: Yan Alice , Millon-Underwood Sandra , Walker Alonzo , Patten Caitlin , Nevels Debra , Dookeran Keith , Hennessy Rose , Knobloch Mary Jo , Egede Leonard , Stolley Melinda
Published: January 2020

Background

Patient‐centredness is considered an essential aspiration of a high‐quality health‐care system, and patient engagement is a critical precursor to patient‐centred care.

Objectives

To engage patients, health‐care providers and stakeholders in identifying recommendations to address research and practice gaps that impact young African American breast cancer survivors.

Methods

This paper reported an approach for research priority setting. This approach applies an engagement process (January‐September 2018) of using patient and stakeholder groups, patient storytelling workshops and a culminating storytelling conference in Wisconsin to generate relevant research topics and recommendations. Topics were prioritized using an iterative engagement process. Research priorities and recommendation were ranked over the conference by counting participants’ anonymous votes.

Results

One hundred attendees (43 patients/family members, 20 providers/researchers and 37 community members) participated in the conference. Five topics were identified as priorities. The results showed that three priority areas received the most votes, specifically community outreach and education, providing affordable health care and engaging in complementary care practice. Stakeholders also agreed it is critical to ‘include youth in the conversation’ when planning for cancer support and educational programmes for caregivers, friends and family members.

Conclusion

Storytelling as a patient engagement approach can build trust in the patient‐research partnership, ensure that patients are meaningfully engaged throughout the process and capture the diversity of patient experiences and perspectives.
Prediction models for the viability of pulmonary metastatic lesions after chemotherapy in nonseminomatous germ cell tumors
Authors: Tsunezuka Hiroaki , Nakamura Terukazu , Fujikawa Kei , Shimomura Masanori , Okada Satoru , Shimada Junichi , Teramukai Satoshi , Ukimura Osamu , Inoue Masayoshi
Published: January 2020

Objectives

To analyze predictors associated with viable cells in pulmonary residual lesions after chemotherapy for metastatic testicular nonseminomatous germ cell tumors and to develop models to prioritize pulmonary resection.

Methods

Between 2008 and 2017, 40 patients underwent pulmonary metastasectomy after chemotherapy for nonseminomatous germ cell tumors. We evaluated these patients, and 326 pulmonary residual lesions were confirmed using computed tomography and pathological evaluations. Relationships with outcomes were analyzed using logistic regression analyses. Risk prediction models were developed, and predictive probabilities for the risk of viable cells were estimated.

Results

Histological examinations showed that 73 (22%) pulmonary residual lesions contained viable cells: teratomas, 46 (14%); and cancer cells, 37 (11%). Multivariate analyses showed that the predictors associated with cancer cells in the residual lesions were elevated tumor marker levels, multiregimen chemotherapy, increased tumor size 6 months before surgery and the histological composition of the primary lesion, including yolk sac tumors. Additional predictors associated with teratomas were aspect ratio and histological composition of the primary lesion, including teratomas.

Conclusions

Intratumoral heterogeneity contributes to nonseminomatous germ cell tumor chemoresistance, and primary lesion site yolk sac tumors and teratomas are associated with greater risks of viable cells. Increased residual lesion size during chemotherapy could also be a predictor. Our simple model can predict the presence of viable cells in residual lesions after chemotherapy, and it might assist in decision‐making and prioritizing pulmonary residual lesion resection.
The emerging role of cellular senescence in renal diseases
Authors: Zhou Bingru , Wan Ying , Chen Rong , Zhang Chunmei , Li Xuesen , Meng Fanyin , Glaser Shannon , Wu Nan , Zhou Tianhao , Li Siwen , Francis Heather , Alpini Gianfranco , Zou Ping
Published: January 2020

Cellular senescence represents the state of irreversible cell cycle arrest during cell division. Cellular senescence not only plays a role in diverse biological events such as embryogenesis, tissue regeneration and repair, ageing and tumour occurrence prevention, but it is also involved in many cardiovascular, renal and liver diseases through the senescence‐associated secretory phenotype (SASP). This review summarizes the molecular mechanisms underlying cellular senescence and its possible effects on a variety of renal diseases. We will also discuss the therapeutic approaches based on the regulation of senescent and SASP blockade, which is considered as a promising strategy for the management of renal diseases.
The role of maternal anxiety disorder subtype, parenting and infant stable temperamental inhibition in child anxiety: a prospective longitudinal study
Authors: Lawrence Peter J. , Creswell Cathy , Cooper Peter J. , Murray Lynne
Published: January 2020

Background

Social anxiety disorder (SAD) aggregates in families. To elucidate intergenerational transmission of risk, we examined whether childhood SAD and symptoms of anxiety were prospectively predicted by stable infant temperamental inhibition, maternal SAD, maternal generalized anxiety disorder (GAD) and maternal parenting behaviours.

Methods

We conducted a longitudinal study beginning prenatally with follow‐up at 4, 10, 14 and 58 months postnatally. Mothers were assessed for anxiety disorders prenatally and assigned to one of three groups: SAD (n = 67), GAD (n = 56) and nonanxious controls (n = 94). We assessed infant temperamental inhibition at 4 and 14 months, maternal parenting behaviours at 10 and 58 months, and child anxiety disorders and symptoms at 58 months.

Results

Child SAD at 58 months was predicted by prenatal maternal SAD (OR = 23.76, 95% CI = 1.15–60.37), but not by prenatal maternal GAD (OR = 7.44, 95% CI = 0.32–124.49), stable temperamental inhibition or maternal behaviours. Child anxiety symptoms at 58 months were predicted specifically by maternal SAD (but not GAD), and also by concurrent maternal intrusiveness. Stable temperamental inhibition moderated the association between 10‐month maternal encouragement and 58‐month child anxiety symptoms.

Conclusions

We found evidence for specificity of risk for child SAD and anxiety symptoms from maternal SAD compared to maternal GAD. Childhood anxiety symptoms were also predicted by an interaction between a lack of maternal encouragement in infancy and stable temperamental inhibition, as well as concurrent maternal intrusiveness. The findings have clinical implications for targeted prevention of child anxiety.
Augmented decision‐making for acral lentiginous melanoma detection using deep convolutional neural networks
Authors: Lee S. , Chu Y.S. , Yoo S.K. , Choi S. , Choe S.J. , Koh S.B. , Chung K.Y. , Xing L. , Oh B. , Yang S.
Published: January 2020

Background

Several studies have achieved high‐level performance of melanoma detection using convolutional neural networks (CNNs). However, few have described the extent to which the implementation ofCNNs improves the diagnostic performance of the physicians.

Objective

This study is aimed at developing aCNNfor detecting acral lentiginous melanoma (ALM) and investigating whether its implementation can improve the initial decision forALMdetection made by the physicians.

Methods

ACNNwas trained using 1072 dermoscopic images of acral benign nevi,ALMand intermediate tumours. To investigate whether the implementation ofCNNcan improve the initial decision forALMdetection, 60 physicians completed a three‐stage survey. In Stage I, they were asked for their decisions solely on the basis of dermoscopic images provided to them. In StageII, they were also provided with clinical information. In StageIII, they were provided with the additional diagnosis and probability predicted by theCNN.

Results

The accuracy ofALMdetection in the participants was 74.7% (95% confidence interval [CI], 72.6–76.8%) in Stage I and 79.0% (95%CI, 76.7–81.2%) in StageII. In StageIII, it was 86.9% (95%CI, 85.3–88.4%), which exceeds the accuracy delivered in Stage I by 12.2%p (95%CI, 10.1–14.3%p) and StageIIby 7.9%p (95%CI, 6.0–9.9%p). Moreover, the concordance between the participants considerably increased (Fleiss‐κ of 0.436 [95%CI, 0.437–0.573] in Stage I, 0.506 [95%CI, 0.621–0.749] in StageIIand 0.684 [95%CI, 0.621–0.749] in StageIII).

Conclusions

Augmented decision‐making improved the performance of and concordance between the clinical decisions of a diverse group of experts. This study demonstrates the potential use ofCNNs as an adjoining, decision‐supporting system for physicians’ decisions.
Ophthalmic findings in neonates receiving sildenafil
Authors: Dunn Hamish P , Kim Leah N , Popat Himanshu , Walker Karen , Lock Jane , Smith James
Published: January 2020

Aim

To determine the risk of ocular complications of sildenafil therapy in neonates.

Methods

Retrospective case review of neonates with persistent pulmonary hypertension of the newborn who received sildenafil therapy between 2010 and 2015 in a single, tertiary surgical neonatal intensive care unit in Australia. Ophthalmic examination findings in the neonatal intensive care unit and follow‐up were examined.

Results

Twenty‐seven neonates with persistent pulmonary hypertension of the newborn received sildenafil. The median gestational age (GA) was 38 weeks (range 24–41 weeks), and median birthweight was 2690 g (range 454–4270 g). Ophthalmic review was undertaken in 23 neonates, and 16 neonates were term or near‐term infants (GA 31–40 weeks). All of them had a normal initial ophthalmic examination; one child was later diagnosed with hypermetropia and another with infantile esotropia. Amongst the seven premature infants (GA 24–30 weeks), three had retinopathy of prematurity (ROP) diagnosed at the first ophthalmic review and the other four had normal initial examinations. Two patients later developed ROP, one of whom was also diagnosed with congenital motor nystagmus. All five patients diagnosed with ROP were extremely preterm (<28 weeks) with low birthweight (454–635 g).

Conclusions

There were no short‐term complications attributable to sildenafil therapy identified in term or near‐term neonates (GA ≥31 weeks). This cohort of neonates does not typically undergo ophthalmic review as part of the ROP screening protocol in our institution. Routine ophthalmic review of neonates on sildenafil therapy, who are not at risk of ROP, is therefore unlikely to be warranted. Further research is required to clarify the relationship between sildenafil and ROP.
Human uniqueness explored from the uniquely human perspective: Epistemological and methodological challenges
Authors: Uher Jana
Published: January 2020

Exploring human uniqueness encounters fundamental challenges because we can approach this endeavour only from within our uniquely human perspective. The intrinsic presumptions that this involves may entail two types of anthropocentric, ethnocentric, and egocentric biases, which can influence research on both epistemological and methodological levels. Their impact may be particularly pronounced if quests for the origins of human sociality are based only on our knowledge about humans. Tomasello's (2019) research demonstrates that the comparative study of humans and nonhuman species offers unique opportunities to explore forms of social cooperation, underlying cognitive and meta‐cognitive abilities as well as pathways in their ontological and (possible) phylogenetic development. It also shows that comparative approaches are essential to unravel the ways in which humans are indeed unique. But species comparisons are challenged by the need to consider inherent trade‐offs between achieving operational comparability in empirical studies and establishing ecological validity for the species compared—challenges, which analogously occur in comparisons across human cultures as well. This shows that comparative research can also contribute meaningfully to methodology development in psychology.
Baveno VI and Expanded Baveno VI criteria successfully predicts the absence of high‐risk gastro‐oesophageal varices in a Chilean cohort
Authors: Gaete María I. , Díaz Luis A. , Arenas Alex , González Katherine , Cattaneo Máximo , Fuster Francisco , Henríquez Romina , Soza Alejandro , Arrese Marco , Barrera Francisco , Arab Juan P. , Benítez Carlos
Published: January 2020

Background

Baveno VI and expanded Baveno VI criteria have been recommended to circumvent the need for endoscopy screening in patients with a very low probability of varices needing treatment (VNT).

Aim

To validate these criteria in a Latin American population.

Methods

The ability of Baveno VI criteria (liver stiffness measurement (LSM) <20 kPa and platelet count >150 × 103/μL) and expanded Baveno VI criteria (LSM < 25kPa and platelet count >110 × 103/μL) to exclude the presence of VNT was tested in a prospectively recruited cohort of patients with Child‐Pugh A liver cirrhosis and with no previous variceal haemorrhage who attended the liver clinics of three major hospitals in Chile.

Results

Three hundred patients were included. The median (IQR) age was 61 [18‐86] years, median MELD was 8.0 (6‐17), median LSM was 17.2 (10.2‐77) kPa and median platelet count was 137 (23‐464) × 103/μL. The main aetiology was non‐alcoholic fatty liver disease (67.3%). VNT were present in 18% of patients. The Baveno VI criteria had a sensitivity of 98.1% and a specificity of 38.2%, potentially sparing 31.3% of upper endoscopies with a very low risk of missing VNT (1.1%). The expanded Baveno VI criteria had a sensitivity of 90.7% and a specificity of 61%, potentially sparing 51.3% of upper endoscopies with a risk of missing VNT of 3.6%. Both criteria were independently associated with the absence of VNT.

Conclusion

We validated the Baveno VI and expanded Baveno VI criteria in Chilean population, potentially sparing 31.3% and 51.3% of endoscopies, respectively, with a very low risk of missing VNT. Fondecyt 1191183.
Pyloric distensibility measurement after gastric surgery: Which surgeries are associated with pylorospasm?
Authors: Desprez Charlotte , Melchior Chloé , Wuestenberghs Fabien , Huet Emmanuel , Zalar Alberto , Jacques Jérémie , Leroi Anne-Marie , Gourcerol Guillaume
Published: January 2020

Background and study aims

History of gastric surgery is found in 10% of patients with gastroparesis, and vagal lesion is often suspected to be the cause of pylorospasm. Recently, pyloric distensibility measurement using the EndoFLIP® system showed that pylorospasm was present in 30%‐50% of gastroparetic patients. Our objective was to assess whether pylorospasm, diagnosed using EndoFLIP® system was observed in three different types of gastric surgeries: antireflux surgery, sleeve gastrectomy, and esophagectomy.

Patients and Methods

Pyloric distensibility and pressure were measured using the EndoFLIP® system in 43 patients from two centers (18 antireflux surgery, 16 sleeve gastrectomy, and nine esophagectomy) with dyspeptic symptoms after gastric surgery, and in 21 healthy volunteers. Altered pyloric distensibility was defined as distensibility below 10 mm2/mm Hg as previously reported.

Results

Compared to healthy volunteers (distensibility: 25.2 ± 2.4 mm2/mm Hg; pressure: 9.7 ± 4.4 mm Hg), pyloric distensibility was decreased in 61.1% of patients in the antireflux surgery group (14.5 ± 3.4 mm2/mm Hg; P < .01) and 75.0% of patients in the esophagectomy group (10.8 ± 2.1 mm2/mm Hg; P < .05), while pyloric pressure was only increased in the antireflux surgery group (18.9 ± 2.2 mm Hg; P < .01). Pyloric distensibility and pressure were similar in healthy volunteers and in sleeve gastrectomy (distensibility: 20.3 ± 3.8 mm2/mm Hg; pressure: 15.8 ± 1.6 mm Hg) groups, with decreased pyloric distensibility affecting 18.7% of sleeve gastrectomy patients.

Conclusion

Antireflux surgery and esophagectomy were associated with pylorospasm although pylorospasm was not found in all patients. Sleeve gastrectomy was not associated with altered pyloric distensibility nor altered pyloric pressure.
Related plants tend to share pollinators and herbivores, but strength of phylogenetic signal varies among plant families
Authors: Cirtwill Alyssa R. , Dalla Riva Giulio V. , Baker Nick J. , Ohlsson Mikael , Norström Isabelle , Wohlfarth Inger‐Marie , Thia Joshua A. , Stouffer Daniel B.
Published: January 2020

Related plants are often hypothesized to interact with similar sets of pollinators and herbivores, but this idea has only mixed empirical support. This may be because plant families vary in their tendency to share interaction partners.

We quantify overlap of interaction partners for all pairs of plants in 59 pollination and 11 herbivory networks based on the numbers of shared and unshared interaction partners (thereby capturing both proportional and absolute overlap). We test for relationships between phylogenetic distance and partner overlap within each network; whether these relationships varied with the composition of the plant community; and whether well‐represented plant families showed different relationships.

Across all networks, more closely related plants tended to have greater overlap. The strength of this relationship within a network was unrelated to the composition of the network's plant component, but, when considered separately, different plant families showed different relationships between phylogenetic distance and overlap of interaction partners.

The variety of relationships between phylogenetic distance and partner overlap in different plant families probably reflects a comparable variety of ecological and evolutionary processes. Considering factors affecting particular species‐rich groups within a community could be the key to understanding the distribution of interactions at the network level.
Observational Study of Total Knee Arthroplasty in Aseptic Revision Surgery: Clinical Results
Authors: Oliver Gabriel , Jaldin Luis , Camprubí Eric , Cortés Guillermo
Published: January 2020

Objective

To review the long‐term clinical results after revision surgery and the relationship between the different clinical variables involved with a failed total knee arthroplasty (TKA) and its evolution to provide a better understanding of the current treatment methods.

Methods

The present study involved 89 subjects with a failed knee arthroplasty that ended up requiring revision surgery and component replacement between 2011 and 2015. The study included patients with pain remaining after TKA and indication from the knee unit surgeon to review the implant, without presenting with thromboembolic or neurological changes that could bias the results. The demographic data, surgical information, type of implant, and causes of failure were analyzed. The patients subjected to replacement surgery were specifically asked to fill out clinical and satisfaction questionnaires (Lysholm and KOOS). The mean follow‐up was 5.6 years (range, 3–11 years) and the analysis was divided into early revision (<5 years) and late revision (>5 years). The R statistical package version 3.2.5 for Windows was used, with significance less than 0.05 Cohort observational study.

Results

The results indicated that implant revisions accounted for 5.57% of total primary implants, with a mean survival of 6 years for primary prosthesis failure. The mean revision surgery result on the Lysholm knee scoring scale was 68.73 out of 100 points. A better score was obtained for revisions undertaken on TKA with over 5 years' survival and there were no significant differences in terms of the type of implant used. The causes of TKA failure were aseptic loosening (77.38%), instability (9.52%), and painful prosthesis (13.10%). The results were statistically significant when isolated revisions were performed on one component. Rating worse on most of the questionnaire subscales.

Conclusion

The clinical results were better in primary implant replacements with at least 5 years' survival. The replacement of only one of the components (tibial or femoral) provided worse clinical results than total replacement.
HvAKT2 and HvHAK1 confer drought tolerance in barley through enhanced leaf mesophyll H+ homoeostasis
Authors: Feng Xue , Liu Wenxing , Qiu Cheng‐Wei , Zeng Fanrong , Wang Yizhou , Zhang Guoping , Chen Zhong‐Hua , Wu Feibo
Published: January 2020

Plant K+ uptake typically consists low—affinity mechanisms mediated by Shaker K+ channels (AKT/KAT/KC) and high‐affinity mechanisms regulated by HAK/KUP/KT transporters, which are extensively studied. However, the evolutionary and genetic roles of both K+ uptake mechanisms for drought tolerance are not fully explored in crops adapted to dryland agriculture. Here, we employed evolutionary bioinformatics, biotechnological and electrophysiological approaches to determine the role of two important K+ transporters HvAKT2 and HvHAK1 in drought tolerance in barley. HvAKT2 and HvHAK1 were cloned and functionally characterized using barley stripe mosaic virus‐induced gene silencing (BSMV‐VIGS) in drought‐tolerant wild barley XZ5 and agrobacterium‐mediated gene transfer in the barley cultivar Golden Promise. The hallmarks of the K+ selective filters of AKT2 and HAK1 are both found in homologues from strepotophyte algae, and they are evolutionarily conserved in strepotophyte algae and land plants. HvAKT2 and HvHAK1 are both localized to the plasma membrane and have high selectivity to K+ and Rb+ over other tested cations. Overexpression of HvAKT2 and HvHAK1 enhanced K+ uptake and H+ homoeostasis leading to drought tolerance in these transgenic lines. Moreover, HvAKT2‐ and HvHAK1‐overexpressing lines showed distinct response of K+, H+ and Ca2+ fluxes across plasma membrane and production of nitric oxide and hydrogen peroxide in leaves as compared to the wild type and silenced lines. High‐ and low‐affinity K+ uptake mechanisms and their coordination with H+ homoeostasis play essential roles in drought adaptation of wild barley. These findings can potentially facilitate future breeding programs for resilient cereal crops in a changing global climate.
Understanding the Choice of Online Resale Channel for Used Electronics
Authors: Esenduran Gökçe , Hill James A. , Noh In Joon
Published: January 2020

Each year, global consumers dispose of 20 million–50 million tons of electronic products, including laptops, tablets, and, most commonly, cell phones. Realizing the residual value in used electronics, consumers frequently look for ways to sell their devices, whereas independent parties (IPs) such as Gazelle and NextWorth and original equipment manufacturers (OEMs) such as Apple compete in acquiring them. These firms also compete with online marketplaces such as eBay, which offer a channel for individuals to sell used devices to others. To succeed in this highly competitive market, buying firms (i.e., OEMs andIPs) must understand factors that influence sellers’ estimated utility and their decisions in a resale process. We conduct laboratory experiments with a two‐stage resale process, where subjects in the first stage choose a resale channel to sell their used cell phone. In the second stage, subjects evaluate a potential counteroffer decision, that is, post‐choice decision. Our results from the resale‐channel choice stage show that individuals have a higher sensitivity to price, time until payment, and online ratings when selling to an IP than when selling to an OEM or through an OM. No significant difference exists, however, in their sensitivity to IP or OEM data security policies. Our results from the post‐choice decision stage show that a seller's share in the counteroffer increases the likelihood of acceptance in all resale channels, whereas higher online ratings might increase or decrease the likelihood of accepting a counteroffer depending on the resale channel. Our laboratory experiment results generally are consistent, with some differences, when replicated on Amazon's Mechanical Turk (MTurk).
The Roadside Healthcare Facility Location Problem A Managerial Network Design Challenge
Authors: de Vries Harwin , van de Klundert Joris , Wagelmans Albert P.M.
Published: January 2020

The population of truck drivers plays a key role in the spread of HIV and other infectious diseases in sub‐Saharan Africa. Truck drivers thereby affect the health and lives of many, but also suffer from poor health and significantly reduced life expectancy themselves. Due to professional circumstances, their health service needs are generally not well addressed. Therefore, the non‐governmental organization North Star Alliance builds a network of healthcare facilities along the largest trucking routes in sub‐Saharan Africa. This paper studies the problem where to place additional facilities, and which health service packages to offer at each facility. The objective combines the maximization of the patient volume at these facilities and the maximization of the effectiveness of the health service delivery to the population served. The latter criterion is modeled through three novel access measures which capture the needs for effective service provisioning. The resulting optimization problem is essentially different from previously studied healthcare facility location problems because of the specific mobile nature of health service demand of truck drivers. Applying our model to the network of major transport corridors in South‐East Africa, we investigate several prominent questions managers and decision‐makers face. We show that the present network expansion strategy, which primarily focuses on patient volumes, may need to be reconsidered: substantial gains in effectiveness can be made when allowing a small reduction in patient volumes. We furthermore show that solutions are rather robust to data impreciseness and that long‐term network planning can bring substantial benefits, particularly in greenfield situations.
Competitive Revenue Management with Sequential Bargaining
Authors: Feng Qi , Li Yuanchen , Shanthikumar J. George
Published: January 2020

When firms post prices to sell their products in a competitive market, buyers often seek to bargain down the prices. The existing studies on dynamic competition, however, focus on firms’ dynamic pricing strategies without considering the possibility of bargaining. We model a random stream of buyers with heterogeneous valuations who may choose to negotiate for a discount from a posted price. When bargaining is allowed, a seller firm's competing strategy depends not only on her reservation value (i.e., her gain from an unsold item when losing the current buyer to the opponent) but also on her disagreement point (i.e., the value of an unsold item when the negotiation with an arriving buyer breaks down). We show that the reservation values and the disagreement points can play opposite roles in competition—the seller firms’ posted prices are increasing in their reservation values but are decreasing in their disagreement points. In general, a seller becomes more aggressive in price competition when her reservation value becomes lower. However, it is not always the case that a seller with a lower reservation value can successfully win the deal from an arriving buyer, as it is in pure price competition. Because of the possibility of bargaining, the buyer may end up purchasing from a seller who has a higher inventory level and a higher reservation value when the seller's disagreement point is lower than that of her opponent. Interestingly, such an equilibrium outcome can only arise when the selling season is sufficiently long. Our analysis highlights the intriguing role played by negotiation in dynamic competition for sequential selling.
Acetaminophen use during pregnancy and the risk of attention deficit hyperactivity disorder: A causal association or bias?
Authors: Masarwa Reem , Platt Robert W. , Filion Kristian B.
Published: January 2020

Background

The association between acetaminophen use during pregnancy and the development of attention deficit hyperactivity disorder (ADHD) in the offspring may be due to bias.

Objectives

The primary objective was to assess the role of potential unmeasured confounding in the estimation of the association between acetaminophen use during pregnancy and the risk of ADHD, through bias analysis. The secondary objective was to assess the roles of selection bias and exposure misclassification.

Data sources

We searched MEDLINE, Embase, Scopus, and the Cochrane Library up to December 2018.

Study selection and data extraction

We included observational studies examining the association between acetaminophen use during pregnancy and the risk of ADHD.

Synthesis

We meta‐analysed data across studies, using random‐effects model. We conducted a bias analysis to studies that did not adjust for important confounders, to explore systematic errors related to unmeasured confounding, selection bias, and exposure misclassification.

Results

The search resulted in seven studies included in our meta‐analysis. When adjusted estimates were pooled across all studies, the risk ratio (RR) for ADHD was 1.35 (95% confidence interval [CI] 1.25, 1.46; I2 = 48%). Sensitivity analysis for unmeasured confounding in this meta‐analysis showed that a confounder of 1.69 on the RR scale would reduce to 10% the proportion of studies with a true effect size of RR >1.10. Unmeasured confounding bias analysis decreased the point estimate in five of the seven studies and increased in two studies, suggesting that the observed association could be confounded by parental ADHD. Unadjusted and bias‐corrected risk ratios (bcRRs) were: RR = 1.34, bcRR = 1.13; RR = 1.51, bcRR = 1.17; RR = 1.63, bcRR = 1.38; RR = 1.44, bcRR = 1.17; RR = 1.16, bcRR = 1.18; RR = 1.25, bcRR = 1.05; and RR = 0.99, bcRR = 1.18.

Conclusions

Bias analysis suggests that the previously reported association between acetaminophen use during pregnancy and an increased risk of ADHD in the offspring may be due to unmeasured confounding. Our ability to conclude a causal association is limited.
Silicon and nitric oxide‐mediated mechanisms of cadmium toxicity alleviation in wheat seedlings
Authors: Singh Swati , Prasad Sheo Mohan , Sharma Shivesh , Dubey Nawal Kishore , Ramawat Naleeni , Prasad Rajendra , Singh Vijay Pratap , Tripathi Durgesh Kumar , Chauhan Devendra Kumar
Published: January 2020

The individual impact of silicon (Si) and nitric oxide (NO, as sodium nitroprusside) on metal toxicity in various plant species has been well documented; however, their combined action in the regulation of metal stress has never been tested yet. Therefore, this study investigates the effects of the combined application of Si and NO in the mitigation of Cd toxicity in wheat seedlings. Seedlings grown on Cd has a significantly declined growth due to an increased accumulation of Cd and oxidative stress markers (due to downregulation of antioxidant defense system particularly ascorbate‐glutathione cycle) and a decreased accumulation of NO and Si. Additionally, the altered leaf and root structures resulted into a declined photosynthetic efficiency. However, the addition of Si and NO alone as well as combined significantly alleviated Cd toxicity in wheat seedlings by lowering the accumulation of Cd and oxidative stress markers and improving leaf and root structures, which are collectively responsible for a better photosynthetic rate under Cd toxicity, and hence an improved growth was noticed. Particularly, the application of Si and NO in combination lowered the oxidative stress markers via upregulating the antioxidant defense system (particularly AsA‐GSH cycle) suggesting the increased efficacy of Si + NO against the Cd toxicity in wheat seedlings as compared to their alone treatments.
Pregnancy loss due to amnionitis in anglo‐arabian mare—Case report
Authors: Campos Isabela , Batista Barbara , Matos Ana Carina , Dutra Fernanda , Gomes Gustavo , Pinna Aline , Leite Juliana , Ferreira Ana
Published: January 2020

The amnion is a layer of the foetal membrane that has mechanical protection function and allows expansion and growth. The diseases that affect amnion have rarely been reported in horses. Amnionitis and funiculitis have been implicated as components of abortions as observed in abortions caused by the mare reproductive loss syndrome. Here, we report an abortion at 240‐day gestation of a 7‐year‐old Anglo‐Arabian mare with a history of previous stillbirth. Blood samples from both mare and foetus were collected for serological testing. Fragments from the placenta were taken for macroscopic and histopathological examinations. The results of these tests ruled out leptospirosis and concluded that the cause of the abortion was non‐infectious chronic amnionitis. Moreover, the decreased vascularization in the placenta was consistent with placental insufficiency. This case highlights the importance of monthly ultrasound monitoring in equine pregnancy in order to diagnose placental insufficiency. The study also confirmed the efficiency of the histopathological examination for the definitive diagnosis of placental inflammation and for the study of foetal vascularization to rule out placental insufficiency in equine reproduction.
Bayesian Protein Sequence and Structure Alignment
Authors: Fallaize Christopher J. , Green Peter J. , Mardia Kanti V. , Barber Stuart
Published: January 2020

The structure of a protein is crucial in determining its functionality and is much more conserved than sequence during evolution. A key task in structural biology is to compare protein structures to determine evolutionary relationships, to estimate the function of newly discovered structures and to predict unknown structures. We propose a Bayesian method for protein structure alignment, with the prior on alignments based on functions which penalize ‘gaps’ in the aligned sequences. We show how a broad class of penalty functions fits into this framework, and how the resulting posterior distribution can be efficiently sampled. A commonly used gap penalty function is shown to be a special case, and we propose a new penalty function which alleviates an undesirable feature of the commonly used penalty. We illustrate our method on benchmark data sets and find that it competes well with popular tools from computational biology. Our method has the benefit of being able potentially to explore multiple competing alignments and to quantify their merits probabilistically. The framework naturally enables further information such as amino acid sequence to be included and could be adapted to other situations such as flexible proteins or domain swaps.
Peter and the Walrus, or Petersburg at the Limits of Intertextuality
Authors: LIVAK LEONID
Published: January 2020

Intertextual analysis is a stock‐in‐trade of Russian modernist studies, especially when it comes to high modernism, bent as it was on countering the vague suggestiveness of the early modernist discourse with another kind of allusiveness that similarly relied on active readership but demoted metaphysical speculation in favor of cultural erudition manifest in the reader's ability to position a literary text within a network of verbal, visual, or musical artifacts. Andrei Bely's Petersburg (1913) exemplifies this practice. Yet there comes a time when newly identified subtexts fail to enrich our understanding of the novel, thereby testing the limits of intertextual interpretation as an analytical method deaf to cultural knowledge that is not formally codified and, by this token, is less accessible to latter‐day readers than to modernist artists and their interpretive communities. This essay explores obscene humor as one such presently invisible aspect of Petersburg. The identification and interpretation of the bawdy in the novel are predicated on the reader's familiarity with the lowest discursive register of Bely's day, a register whose taboo nature hinders cultural codification, defying the tried‐and‐true tools of intertextual analysis. Pushing the limits of intertextuality, Petersburg's bawdiness reflects the epistemological crisis of Russian modernism transitioning between its historical iterations. A veteran of the post‐1905 polemics in the modernist cultural community, Bely ridicules in Petersburg the values and ideals he still holds dear, better to safeguard them from the neophytes of “new art,” who mock the metaphysical bent of early modernism, and from its epigones, who devalue these metaphysics by inflationary overuse. Reviving the practice of romantic irony, Bely at once codifies and ridicules his innermost aspirations, following Vladimir Solovyov's example.
Coefficients of Wronskian Hermite polynomials
Authors: Bonneux Niels , Dunning Clare , Stevens Marco
Published: January 2020

We study Wronskians of Hermite polynomials labeled by partitions and use the combinatorial concepts of cores and quotients to derive explicit expressions for their coefficients. These coefficients can be expressed in terms of the characters of irreducible representations of the symmetric group, and also in terms of hook lengths. Further, we derive the asymptotic behavior of the Wronskian Hermite polynomials when the length of the core tends to infinity, while fixing the quotient. Via this combinatorial setting, we obtain in a natural way the generalization of the correspondence between Hermite and Laguerre polynomials to Wronskian Hermite polynomials and Wronskians involving Laguerre polynomials. Lastly, we generalize most of our results to polynomials that have zeros on thep‐star.
Classification and characteristics of periorbital hyperpigmentation
Authors: Fatin Amira M. , Mathana Sundram Thavin K. , Tan Sin Sing E. , Seghayat Marjan Sadat , Lee Chew Kek , Rehman Navedur , Tan Chung Keat
Published: January 2020

Introduction

Periorbital hyperpigmentation (POH) is among the commonest esthetic and dermatological complaints. Despite its frequency, there are inadequate information detailing its incidence and prevalence. This subsequently leads to lack of comprehensive POH classification and stratification of impact on an individual's general well'being. Malaysia, a multiracial country with an expansive expatriate population, provides a unique opportunity to identify demographics of POH and subsequently attempts to group this esthetic and dermatological entity.

Objective

This study aims to develop a new and clinically relevant POH classification system and to measure impact on quality of life of POH individuals.

Methods

One hundred patients with POH were enrolled, of which all underwent clinical assessment by a clinician. Objective assessment with mexameter and digital analysis were performed. All recruited patients also completed a questionnaire based on dermatology life quality index (DLQI).

Results

Assessments noted the commonest type of POH among the subjects was vascular (51%) with the least being pigmentary (6%). The location of POH majority involved both the upper and lower eyelids (65%). DLQI scoring shows that a majority (58%) did not disrupt their quality of life.

Conclusion

Vascular type POH was the frequent most form observed, and involvement tends to occur on both eyelids. A majority of noted that POH does not affect they QOL, but the due consideration must be given in those whom are moderately and minimally affected. A thorough and comprehensive holistic approach is required in managing POH despite its focal presentation as it does affect a patient's quality of life.
Chitosan‐based agent use for hemostasis after cryptorchidectomy in a horse
Authors: Tucker Michelle L. , Wilson David G. , Barber Spencer M.
Published: January 2020

Objective

To document marked hemorrhage as a complication of inguinal cryptorchidectomy and its successful treatment with a novel chitosan‐based hemostatic agent.

Study design

Case report.

Animals

One healthy 5‐year old quarter horse cryptorchid.

Methods

The horse was presented for routine unilateral cryptorchidectomy after prior hemicastration. An inguinal approach was made to the abdomen, and the right external pudendal artery was lacerated at the level of the internal inguinal ring, requiring multiple anesthetic events over a 2‐week period in attempts to control hemorrhage. A chitosan‐based hemostatic agent was packed into the wound to gain control.

Results

Chitosan granules placed in the wound successfully controlled the hemorrhage, whereas the use of gauze packing alone failed. There were no immediate or long‐term complications to the chitosan granules; the horse was doing well 18 months postoperatively, and the client was satisfied with the outcome.

Conclusion

Major hemorrhage was demonstrated from the external pudendal artery and caused difficulties because it occurred deep within the inguinal canal during an inguinal cryptorchidectomy. A chitosan‐based hemostatic agent was successfully used to achieve hemostasis.

Clinical significance

The external pudendal artery should be avoided in the medial commissure of the inguinal canal. The use of chitosan‐based hemostatic agents warrants further investigation in horses because these products may be useful for controlling major hemorrhage from various causes in equine practice.
The Association Between Time-Use Behaviors and Physical and Mental Well-Being in Adults: A Compositional Isotemporal Substitution Analysis
Authors: Curtis Rachel G. , Dumuid Dorothea , Olds Timothy , Plotnikoff Ronald , Vandelanotte Corneel , Ryan Jillian , Edney Sarah , Maher Carol
Published: January 2020

Background: Substantial evidence links activity domains with health and well-being; however, research has typically examined time-use behaviors independently, rather than considering daily activity as a 24-hour time-use composition. This study used compositional data analysis to estimate the difference in physical and mental well-being associated with reallocating time between behaviors. Methods: Participants (n = 430; 74% female; 41 [12] y) wore an accelerometer for 7 days and reported their body mass index; health-related quality of life (QoL); and symptoms of depression, anxiety, and stress. Regression models determined whether time-use composition, comprising sleep, sedentary behavior, light physical activity (LPA), and moderate to vigorous physical activity (MVPA), was associated with well-being. Compositional isotemporal substitution models estimated the difference in well-being associated with reallocating time between behaviors. Results: Time-use composition was associated with body mass index and physical health-related QoL. Reallocating time to MVPA from sleep, sedentary behavior, and LPA showed favorable associations with body mass index and physical health-related QoL, whereas reallocations from MVPA to other behaviors showed unfavorable associations. Reallocations from LPA to sedentary behavior were associated with better physical health–related QoL and vice versa. Conclusion: Results reinforce the importance of MVPA for physical health but do not suggest that replacing sedentary behavior with LPA is beneficial for health and well-being.
Eastward shift and extension of ENSO-induced tropical precipitation anomalies under global warming
Authors: Yan Zixiang , Wu Bo , Li Tim , Collins Mat , Clark Robin , Zhou Tianjun , Murphy James , Tan Guirong
Published: January 2020

Under global warming, ENSO-driven precipitation anomalies over central eastern Pacific shift eastward because of narrowing ENSO SSTA.
Epidermal autonomous VEGFA/Flt1/Nrp1 functions mediate psoriasis-like disease
Authors: Benhadou Farida , Glitzner Elisabeth , Brisebarre Audrey , Swedlund Benjamin , Song Yura , Dubois Christine , Rozzi Milena , Paulissen Catherine , del Marmol Veronique , Sibilia Maria , Blanpain Cédric
Published: January 2020

Vefga induces psoriasis by acting on keratinocytes through Flt1 and Nrp1 receptors.
Reduction of AMPA receptor activity on mature oligodendrocytes attenuates loss of myelinated axons in autoimmune neuroinflammation
Authors: Evonuk Kirsten S. , Doyle Ryan E. , Moseley Carson E. , Thornell Ian M. , Adler Keith , Bingaman Amanda M. , Bevensee Mark O. , Weaver Casey T. , Min Booki , DeSilva Tara M.
Published: January 2020

Decreased AMPA receptor signaling on myelin selectively reduces loss of myelinated axons in autoimmune neuroinflammation.