bluuebunny/crossref_metadata_2025 huggingface dataset:
Explicit criteria as clinical tools to minimize inappropriate medication use and its consequences
Authors: Curtin Denis , Gallagher Paul F. , O’Mahony Denis
Published: February 2019

Polypharmacy and prescribing of potentially inappropriate medications (PIMs) are the key elements of inappropriate medication use (IMU) in older multimorbid people. IMU is associated with a range of negative healthcare consequences including adverse drug events and unplanned hospitalizations. Furthermore, prescribing guidelines are commonly derived from randomized controlled clinical trials which have specifically excluded older adults with multimorbidity. Consequently, indiscriminate application of single disease pharmacotherapy guidelines to older multimorbid patients can lead to increased risk of drug–drug interactions, drug–disease interactions and poor drug adherence. Both polypharmacy and PIMs are highly prevalent in older people and strategies to improve the quality and safety of prescribing, largely through avoidance of IMU, are needed. In the last 30 years, numerous explicit PIM criteria-based tools have been developed to assist physicians with medication management in clinically complex multimorbid older people. Very few of these PIM criteria sets have been tested as an intervention compared with standard pharmaceutical care in well-designed clinical trials. In this review, we describe the most widely used sets of explicit PIM criteria to address inappropriate polypharmacy with particular focus on STOPP/START criteria and FORTA criteria which have been associated with positive patient-related outcomes when used as interventions in recent randomized controlled trials.
Trends in the scientific literature on atypical antipsychotic drugs in the United Kingdom: a bibliometric study
Authors: López-Muñoz Francisco , Tracy Derek K. , Povedano-Montero F. Javier , Breedvelt Josefien , García-Pacios Javier , Fernández-Martín Mª Poveda , Rubio Gabriel , Álamo Cecilio
Published: February 2019

Objective:

A bibliometric study was undertaken of peer-reviewed publications on atypical antipsychotic drugs (AADs) from the United Kingdom and the findings are presented herein.

Methods:

We selected the documents from the Scopus database. We applied several production and dispersion bibliometric indicators, including Price’s law on the growth of the scientific literature, and Bradford’s law. We also calculated a so-called ‘participation index’ across different countries. The bibliometric data were thereafter correlated with social and health data from the UK, including total per capita expenditure on health and gross domestic expenditure.

Results:

A total of 4156 original manuscripts were published within the timeframe 1967–2015. Our results are in accord with Price’s law, with scientific output demonstrating exponential growth ( r = 0.9227, as against an r = 0.8766 after adjustment). The drugs most widely evaluated were clozapine (465 documents), olanzapine (263) and risperidone (248). Stratification into Bradford zones produced a nucleus represented by the Journal of Psychopharmacology (168 articles) and British Journal of Psychiatry (159 articles). A total of 1250 different journals were evaluated.

Conclusions:

Publications on AADs in the UK have shown exponential growth across the studied period, which is in line with the progressively burgeoning novel AAD releases. No evidence of a saturation point was observed.
Arthroscopic bullet removal from the hip joint and concurrent treatment of associated full-thickness chondral defects: A case report
Authors: Ferro Fernando P , Bessa Felipe S , Ejnisman Leandro , Gurgel Henrique MC , Croci Alberto T , Vicente José RN
Published: February 2019

The diagnosis of a bullet inside the hip joint is a rare finding. The usual method to treat this condition has been open surgery, with its associated complications and morbidity. The arthroscopic approach has been increasingly utilized for the diagnosis and treatment of several hip conditions, and the number of indications for this technique has been steadily rising. We report the case of a 35-year-old man who suffered a gunshot wound and was operated on for abdominal perforation. He later presented with groin pain that worsened with weight-bearing on his right leg and then underwent arthroscopic removal of a bullet located inside his right hip joint. After a 2-year follow-up, the patient had an excellent clinical outcome, with no radiologic signs of arthritis. The removal of an intra-articular projectile is necessary to avoid complications such as synovitis, osteoarthritis, septic arthritis, and saturnism. The best access to the hip joint remains a topic of debate. Arthroscopy has the advantage of less soft-tissue damage and quicker recovery. The treatment of associated chondral lesions can be done with several techniques, including microfracture, autologous chondrocyte implantation, mosaicplasty, and fresh osteochondral allograft transplantation. There is no consensus as to the best course of treatment for associated chondral lesions in such cases. Hip arthroscopy can be a safe and effective technique for the removal of intra-articular bullets in the hip.
A case of Mayer-Rokitansky-Küster-Hauser syndrome in a low-resource tertiary hospital in Douala, Cameroon
Authors: Egbe Thomas Obinchemti , Kobenge Fidelia Mbi , Junette Arlette Metogo Mbengono , Nyemb Jacque-Ernest , Mbu Robinson Enow
Published: February 2019

The Mayer-Rokitansky-Küster-Hauser syndrome is the congenital absence or underdevelopment of the uterus and vagina even though the external genitalia, ovaries and ovarian function are normal. This condition is uncommon in Cameroon. A 23-year-old woman of the Fulbé tribe, a predominantly Islamic tribe of the northern part of Cameroon, complained of the absence of menstruation after age of puberty and lower abdominal pain occurring almost at the same period every month. She has been married polygamously for 10 years and has been having normal, satisfactory sexual intercourse. The sonographic and laparoscopic findings of this patient were consistent with Mayer-Rokitansky-Küster-Hauser syndrome. The patient was counseled for in vitro fertilization and surrogacy. Patients with Mayer-Rokitansky-Küster-Hauser syndrome typically present with primary amenorrhea during adolescence. With the existing medical technology in Cameroon, this condition is easily accessible in tertiary healthcare facilities. Patients with Mayer-Rokitansky-Küster-Hauser syndrome could become mothers through in vitro fertilization and surrogacy, but the cost is prohibitive in Cameroon.
The market between symbolic violence and emancipation: The case of female hardcore gamers
Authors: Tiercelin Alexandre , Remy Eric
Published: February 2019

This article seeks to understand the process of market-based identity-building by looking at the life stories of female hardcore gamers. A dual theoretical framework is used: identity-building through consumption and gender via symbolic violence. Analysis of the meaning attributed to the underlying consumption practices and identity mindsets in the face of a masculine market norm reveals the following: (1) the relationship between female hardcore gamers and the gendered norm of the gaming market for hyper-players; (2) the ways in which this norm is appropriated and (3) the typical path of the female gamers concerned. The findings enable a discussion about the notion of symbolic violence driven by the market, where gender becomes an identity resource that can be manipulated through consumption practices that can lead to a certain emancipation, primarily linked to the possession of capital.
Subjective cognitive concern in multiple sclerosis is associated with reduced thalamic and cortical gray matter volumes
Authors: Kletenik Isaiah , Alvarez Enrique , Honce Justin M , Valdez Brooke , Vollmer Timothy L , Medina Luis D
Published: February 2019

Objective

Brain atrophy has been correlated with objective cognitive dysfunction in multiple sclerosis but few studies have explored self-reported subjective cognitive concerns and their relationship to brain volume changes. This study explores the relationship between subjective cognitive concerns in multiple sclerosis and reduced brain volume in regions of interest implicated in cognitive dysfunction.

Methods

A total of 158 patients with multiple sclerosis completed the Quality of Life in Neurologic Disorders Measures (Neuro-QoL) short forms to assess subjective cognitive concerns and underwent brain magnetic resonance imaging. Regional brain volumes from regions of interest implicated in cognitive dysfunction were measured using NeuroQuant automated volumetric quantitation. Linear regression was used to analyze the relationship between subjective cognitive concerns and brain volume.

Results

Controlling for age, disease duration, gender, depression and fatigue, increased subjective cognitive concerns were associated with reduced thalamic volume (standardized β = 0.223, t150 =2.406, P = 0.017) and reduced cortical gray matter volume (standardized β = 0.240, t150 = 2.777, P = 0.006). Increased subjective cognitive concerns were not associated with any other regions of interest that were analyzed.

Conclusions

Subjective cognitive concern in MS is associated with reduced thalamic and cortical gray matter volumes, areas of the brain that have been implicated in objective cognitive impairment. These findings may lend neuroanatomical significance to subjective cognitive concerns and patient-reported outcomes as measured by Neuro-QoL.
Explanatory Factors of the Environmental Disclosure of Potentially Polluting Companies: Evidence From Brazil
Authors: Santos Lívia Maria da Silva , Lucena Wenner Glaucio Lopes , da Silva Wesley Vieira , Bach Tatiana Marceda , da Veiga Claudimar Pereira
Published: February 2019

This research aims at identifying explanatory factors of the environmental disclosure of potentially polluting Brazilian companies listed on the São Paulo Security, Commodities, and Futures Exchange (BM&FBOVESPA), from 2005 to 2015. Financial and environmental disclosure information of 182 Brazilian companies of the high-, medium-, and low-polluting potential sectors were collected. Data were analyzed through content analysis of documents and Regression with Panel Data. Results indicate that the company’s size, profitability, internationalization, and sustainability report are explanatory factors of the disclosure of environmental information, while indebtedness presents an inverse relationship. This study concludes that the explanatory factors of environmental disclosure of potentially polluting Brazilian companies are, with a higher weight, the publication of the sustainability report and stock market internationalization and, with lower weight, size, indebtedness, and profitability. This study discusses the relevance of environmental disclosure to companies that perform potentially polluting activities to provide support for different agents linked to these companies they may have access. It presents as theoretical contribution the explanatory variables for environmental disclosure of potentially polluting companies, an analysis not yet carried out in the literature. The practical contribution is to present information to interested users that potentially polluting companies, larger in size, internationalized, and with more profitability, disclose their environmental information.
Measuring Municipal Capacity to Respond to Mobility
Authors: Blaser Mapitsa Caitlin , Landau Loren
Published: February 2019

Mobility and urbanization are shaping cities in Southern Africa. Peri-urban areas in particular are transforming at such a pace that municipalities are struggling to keep up with the changes. Local government is trying to build appropriate capacity to respond to a mobile population, but it is not always clear where to focus capacity development efforts. Applying a diagnostic tool on local government capacity to respond to mobility, researchers both tested the tool and drew conclusions about the capacity of local government. This provides lessons for both how we measure the readiness of municipalities to respond to a mobile population and how we may focus capacity-building efforts.
Abdominal Aortic Calcification Is a Significant Poor Prognostic Factor for Clinical Outcomes After Decompressive Laminotomy for Lumbar Spinal Canal Stenosis
Authors: Sakaura Hironobu , Ikegami Daisuke , Fujimori Takahito , Sugiura Tsuyoshi , Owaki Hajime , Fuji Takeshi
Published: February 2019

Study Design:

Retrospective study.

Objective:

To examine whether the presence of chronic kidney disease (CKD) or advanced abdominal aortic calcification (AAC) negatively affects clinical outcomes after decompression surgery for lumbar spinal canal stenosis (LSCS).

Methods:

The subjects comprised 143 patients who underwent decompressive laminotomy for LSCS and were followed for ≥2 years. Fifty-five patients had CKD (Stage 3-4). Clinical outcome was assessed using the Japanese Orthopaedic Association (JOA) score before surgery and at 2-year postoperatively. According to the scoring system by Kauppila et al, the AAC score (a surrogate marker of systemic atherosclerosis) was assessed using preoperative lateral radiographs of the lumbar spine.

Results:

Patient age had weak but significantly negative correlations with both the preoperative JOA score and the JOA score at 2 years after surgery, but did not have a significant correlation with the recovery rate of the JOA score at 2 years postoperatively. The JOA score before surgery, the JOA score at 2-year follow-up, and the recovery rate of the JOA score were slightly lower in the CKD patients than in those without CKD, although there were no significant differences between the 2 groups. On the contrary, the AAC score had a weak but significantly negative correlation with the preoperative JOA score, and had relatively strong and significantly negative correlations with both the JOA score at 2 years after surgery and the recovery rate of the JOA score.

Conclusions:

At 2 years after surgery, advanced AAC was a significant poor prognostic factor for clinical outcomes of decompression surgery for LSCS.
The Quantitative Implications of Definitions of Giftedness
Authors: McBee Matthew T. , Makel Matthew C.
Published: February 2019

Educational psychology is replete with verbal or qualitative definitions through which students can be considered members of categories, such as learning disabled, autistic, or gifted. These conceptions carry quantitative implications regarding the incidence rates of the phenomena they describe. To be scientifically useful, such definitions should have sufficient specificity and internal consistency. We analyzed four influential definitions of giftedness and assessed their internal consistency by computing the giftedness rate implied by each. Results reveal that the proportion of individuals who meet the standard of giftedness under some definitions is unrealistically high (e.g., >75% in some conditions). The implication of this work is that the rigor and internal self-consistency of educational concepts requires improvement. The field must carefully consider the quantitative implications of its concepts, statements, and definitions. An Open Science Framework project page containing R code, a technical appendix, and all figures and tables from this paper is available at https://osf.io/6e7g9/ .
Faculty Benefits From Medical Student Learning Communities: A Junior and Senior Faculty Members’ Perspectives
Authors: Ngo Thuy L , Whipple Mark
Published: February 2019

Medical school learning communities have many benefits for students. In this perspective, the authors briefly describe how learning communities have benefited them as faculty. These include finding other like-minded faculty, improving communication and clinical skills, career advancement through scholarly work associated with the learning community, and above all, developing mutually beneficial relationships with students. Here, they offer viewpoints from junior and senior faculty members on how the learning community has positively affected them.
Online Medical Education for Doctors: Identifying Potential Gaps to the Traditional, Face-to-Face Modality
Authors: Ifediora Chris O
Published: February 2019

Background:

Online education options increasingly complement traditional face-to-face (F2F) approaches. Few studies have compared both formats on doctors, and little evidence exists to prove that the online approach is universally effective. This gap needs to be addressed to ensure that the quality of education and health care delivery is not compromised.

Methods:

A quantitative survey targeting 881 doctors that required online and F2F teaching sessions offers identical contents over a 12-month period. The surveyed doctors work in the Australian after-hours house-call (AHHC) industry, and the teachings were parts of their continuing professional development activities.

Results:

In all, 89 responses were received; 10 (11.2%) participated exclusively online, while 23 (25.8%) did so by F2F; 52 (58.4%) engaged through both modalities. No statistical differences existed based on sex, specialty, and post-graduate fellowship status, as well as on the perceptions with teaching structure, contents, and duration of the education programmes. However, F2F-only doctors were likely to be junior and younger than 40 years (odds ratio [OR]: 3.85; P = .01). They also admit easy access to effective teaching environment (OR: 4.07; P = .01) and receive better feedbacks (OR: 3.75; P = .01). Conversely, online-only participants were more likely to combine AHHC duties with regular-hours general practice (OR: 0.15; P = .02) and are generally more satisfied with the programme frequency (OR: 6.90; P = .01).

Conclusions:

On multiple areas, no differences exist in the medical education delivered by online and the F2F methods to doctors and both should be encouraged. However, younger and junior practitioners, who tend to need feedbacks on their jobs, should participate more in the F2F sessions.
Genetic deletion of genes in the cerebellar rhombic lip lineage can stimulate compensation through adaptive reprogramming of ventricular zone-derived progenitors
Authors: Wojcinski Alexandre , Morabito Morgane , Lawton Andrew K. , Stephen Daniel N. , Joyner Alexandra L.
Published: February 2019

Background

The cerebellum is a foliated posterior brain structure involved in coordination of motor movements and cognition. The cerebellum undergoes rapid growth postnataly due to Sonic Hedgehog (SHH) signaling-dependent proliferation of ATOH1+ granule cell precursors (GCPs) in the external granule cell layer (EGL), a key step for generating cerebellar foliation and the correct number of granule cells. Due to its late development, the cerebellum is particularly vulnerable to injury from preterm birth and stress around birth. We recently uncovered an intrinsic capacity of the developing cerebellum to replenish ablated GCPs via adaptive reprogramming of Nestin-expressing progenitors (NEPs). However, whether this compensation mechanism occurs in mouse mutants affecting the developing cerebellum and could lead to mis-interpretation of phenotypes was not known.

Methods

We used two different approaches to remove the main SHH signaling activator GLI2 in GCPs: 1) Our mosaic mutant analysis with spatial and temporal control of recombination (MASTR) technique to delete Gli2 in a small subset of GCPs; 2) An Atoh1-Cre transgene to delete Gli2 in most of the EGL. Genetic Inducible Fate Mapping (GIFM) and live imaging were used to analyze the behavior of NEPs after Gli2 deletion.

Results

Mosaic analysis demonstrated that SHH-GLI2 signaling is critical for generating the correct pool of granule cells by maintaining GCPs in an undifferentiated proliferative state and promoting their survival. Despite this, inactivation of GLI2 in a large proportion of GCPs in the embryo did not lead to the expected dramatic reduction in the size of the adult cerebellum. GIFM uncovered that NEPs do indeed replenish GCPs in Gli2 conditional mutants, and then expand and partially restore the production of granule cells. Furthermore, the SHH signaling-dependent NEP compensation requires Gli2, demonstrating that the activator side of the pathway is involved.

Conclusion

We demonstrate that a mouse conditional mutation that results in loss of SHH signaling in GCPs is not sufficient to induce long term severe cerebellum hypoplasia. The ability of the neonatal cerebellum to regenerate after loss of cells via a response by NEPs must therefore be considered when interpreting the phenotypes of Atoh1-Cre conditional mutants affecting GCPs.
Efficacy of Internet-Based Cognitive Behavioral Therapy for Treatment-Induced Menopausal Symptoms in Breast Cancer Survivors: Results of a Randomized Controlled Trial
Authors: Atema Vera , van Leeuwen Marieke , Kieffer Jacobien M. , Oldenburg Hester S.A. , van Beurden Marc , Gerritsma Miranda A. , Kuenen Marianne A. , Plaisier Peter W. , Lopes Cardozo Alexander M.F. , van Riet Yvonne E.A. , Heuff Gijsbert , Rijna Herman , van der Meij Suzan , Noorda Eva M. , Timmers Gert-Jan , Vrouenraets Bart C. , Bollen Matthé , van der Veen Henk , Bijker Nina , Hunter Myra S. , Aaronson Neil K.
Published: February 2019

PURPOSE

We evaluated the effect of Internet-based cognitive behavioral therapy (iCBT), with or without therapist support, on the perceived impact of hot flushes and night sweats (HF/NS) and overall levels of menopausal symptoms (primary outcomes), sleep quality, HF/NS frequency, sexual functioning, psychological distress, and health-related quality of life in breast cancer survivors with treatment-induced menopausal symptoms.

PATIENTS AND METHODS

We randomly assigned 254 breast cancer survivors to a therapist-guided or a self-managed iCBT group or to a waiting list control group. The 6-week iCBT program included psycho-education, behavior monitoring, and cognitive restructuring. Questionnaires were administered at baseline and at 10 weeks and 24 weeks postrandomization. We used mixed-effects models to compare the intervention groups with the control group over time. Significance was set at P < .01. An effect size (ES) of .20 was considered small, .50 moderate and clinically significant, and .80 large.

RESULTS

Compared with the control group, the guided and self-managed iCBT groups reported a significant decrease in the perceived impact of HF/NS (ES, .63 and .56, respectively; both P < .001) and improvement in sleep quality (ES, .57 and .41; both P < .001). The guided group also reported significant improvement in overall levels of menopausal symptoms (ES, .33; P = .003), and NS frequency (ES, .64; P < .001). At longer-term follow-up (24 weeks), the effects remained significant, with a smaller ES for the guided group on perceived impact of HF/NS and sleep quality and for the self-managed group on overall levels of menopausal symptoms. Additional longer-term effects for both intervention groups were found for hot flush frequency.

CONCLUSION

iCBT, with or without therapist support, has clinically significant, salutary effects on the perceived impact and frequency of HF/NS, overall levels of menopausal symptoms, and sleep quality.
Oral Anticancer Therapy: Management of Drug Interactions
Authors: Rogala Britny G. , Charpentier Margaret M. , Nguyen Michelle K. , Landolf Kaitlin M. , Hamad Lamya , Gaertner Kelly M.
Published: February 2019

Oral anticancer therapy is increasingly integrated into the care of patients with cancer. Recognition and management of drug-drug interactions (DDIs) is critical to providing efficacious and safe anticancer treatment. DDIs with QTc-prolonging agents, anticoagulants, enzyme inducers and inhibitors, antidepressants, and acid suppressants are commonly encountered with anticancer therapies. Here, we review frequently observed DDIs and outline literature-supported suggestions for their management.
In Vivo Ablation of the Conserved GATA-Binding Motif in the Amh Promoter Impairs Amh Expression in the Male Mouse
Authors: Bouchard Marie France , Bergeron Francis , Grenier Delaney Jasmine , Harvey Louis-Mathieu , Viger Robert S
Published: February 2019

GATA4 is an essential transcriptional regulator required for gonadal development, differentiation, and function. In the developing testis, proposed GATA4-regulated genes include steroidogenic factor 1 (Nr5a1), SRY-related HMG box 9 (Sox9), and anti-Müllerian hormone (Amh). Although some of these genes have been validated as genuine GATA4 targets, it remains unclear whether GATA4 is a direct regulator of endogenous Amh transcription. We used a CRISPR/Cas9-based approach to specifically inactivate or delete the sole GATA-binding motif of the proximal mouse Amh promoter. AMH mRNA and protein levels were assessed at developmental time points corresponding to elevated AMH levels: fetal and neonate testes in males and adult ovaries in females. In males, loss of GATA binding to the Amh promoter significantly reduced Amh expression. Although the loss of GATA binding did not block the initiation of Amh transcription, AMH mRNA and protein levels failed to upregulate in the developing fetal and neonate testis. Interestingly, adult male mice presented no anatomical anomalies and had no evidence of retained Müllerian duct structures, suggesting that AMH levels, although markedly reduced, were sufficient to masculinize the male embryo. In contrast to males, GATA binding to the Amh promoter was dispensable for Amh expression in the adult ovary. These results provide conclusive evidence that in males, GATA4 is a positive modulator of Amh expression that works in concert with other key transcription factors to ensure that the Amh gene is sufficiently expressed in a correct spatiotemporal manner during fetal and prepubertal testis development.
Reverse genetic screen reveals that Il34 facilitates yolk sac macrophage distribution and seeding of the brain
Authors: Kuil Laura E. , Oosterhof Nynke , Geurts Samuël N. , van der Linde Herma C. , Meijering Erik , van Ham Tjakko J.
Published: February 2019

Microglia are brain resident macrophages, which have specialized functions important in brain development and in disease. They colonize the brain in early embryonic stages, but few factors that drive the migration of yolk sac macrophages (YSMs) into the embryonic brain , or regulate their acquisition of specialized properties are currently known.

Here, we present a CRISPR/Cas9-based in vivo reverse genetic screening pipeline to identify new microglia regulators using zebrafish. Zebrafish larvae are particularly suitable due to their external development, transparency and conserved microglia features. We targeted putative microglia regulators, by Cas9/gRNA-complex injections, followed by neutral red-based visualization of microglia. Microglia were quantified automatically in 3-day-old larvae using a software tool we called SpotNGlia. We identified that loss of the zebrafish colony stimulating factor 1 receptor (CSF1R) ligand IL34, caused reduced microglia numbers. Previous studies on the role of the IL34 on microglia development in vivo were ambiguous. Our data, and a concurrent paper, show that in zebrafish, il34 is required during the earliest seeding of the brain by microglia. Our data also indicate that Il34 is required for YSM distribution to other organs. Disruption of the other CSF1R ligand, Csf1, did not reduce microglia numbers in mutants, whereas overexpression increased the number of microglia. This shows Csf1 can influence microglia numbers, but might not be essential for the early seeding of the brain. In all, we identified il34 as a modifier of microglia colonization, by affecting distribution of YSMs to target organs, validating our reverse genetic screening pipeline in zebrafish.
Cancer cells in the tumor core exhibit spatially coordinated migration patterns
Authors: Staneva Ralitza , El Marjou Fatima , Barbazan Jorge , Krndija Denis , Richon Sophie , Clark Andrew G. , Vignjevic Danijela Matic
Published: February 2019

In the early stages of metastasis, cancer cells exit the primary tumor and enter the vasculature. Although most studies have focused on the tumor invasive front, cancer cells from the tumor core can also potentially metastasize. To address cell motility in the tumor core, we imaged tumor explants from spontaneously forming tumors in mice in real time using long-term two-photon microscopy. Cancer cells in the tumor core are remarkably dynamic and exhibit correlated migration patterns, giving rise to local ‘currents’ and large-scale tissue dynamics. Although cells exhibit stop-and-start migration with intermittent pauses, pausing does not appear to be required during division. Use of pharmacological inhibitors indicates that migration patterns in tumors are actively driven by the actin cytoskeleton. Under these conditions, we also observed a relationship between migration speed and correlation length, suggesting that cells in tumors are near a jamming transition. Our study provides new insight into the dynamics of cancer cells in the tumor core, opening new avenues of research in understanding the migratory properties of cancer cells and later metastasis.

This article has an associated First Person interview with the first author of the paper.
Polyubiquitylation of α-tubulin at K304 is required for flagellar disassembly in Chlamydomonas
Authors: Wang Qiyu , Peng Zhao , Long Huan , Deng Xuan , Huang Kaiyao
Published: February 2019

Cilia/flagella are structurally conserved and dynamic organelles; their assembly and disassembly are coordinated with the cell cycle and cell differentiation. Several post-translational modifications, including acetylation, methylation, phosphorylation and ubiquitylation, participate in ciliary disassembly. However, the detailed mechanism and the role of ubiquitylation in ciliary disassembly are unclear. This study identified 20 proteins that were ubiquitylated in shortening flagella of Chlamydomonas. α-Tubulin was the most abundant ubiquitylated protein and it was labeled with K63 polyubiquitin chains primarily at K304. Expression of an α-tubulin mutant (K304R), which could not be ubiquitylated, decreased the rate of flagellar disassembly and resulted in an enrichment of the mutant form in the axoneme, suggesting that ubiquitylation of α-tubulin is required for the normal kinetics of axonemal disassembly. Immunoprecipitation and glutathione-S-transferase pulldown assays demonstrated that the retrograde intraflagellar transport (IFT) protein, IFT139, interacted with a variety of ubiquitylated proteins, including α-tubulin, suggesting that IFT-A was responsible for transporting ubiquitylated proteins out of the flagella. Our data suggest an important role for ubiquitylation and retrograde IFT in ciliary disassembly.

This article has an associated First Person interview with the first author of the paper.
Zonation of Ca2+ transport and enzyme activity in the caeca of rainbow trout – a simple structure with complex functions
Authors: Williams Melanie , Barranca Domenico , Bucking Carol
Published: February 2019

Trout caeca are vermiform structures projecting from the anterior intestine of the gastrointestinal tract. Despite their simple gross morphology, these appendages are physically distinct along the anterior-posterior axis and ultrastructural evidence suggests zonation of function within the structures. Individual caeca from three sections (anterior, middle, posterior) were removed from the intestine of freshwater rainbow trout and investigated for ion transport and enzyme activity. Ca2+ absorption appeared as a combination of active and passive movement, with Michaelis-Menten kinetics observable under symmetrical conditions, and was inhibited by several pharmacological agents (ouabain, La3+, and a calmodulin antagonist). There was a decrease in ion transport function from adjacent to the intestine (proximal) to the distal tip of each caeca, along with decreasing transport from anterior to posterior for the proximal portion alone. Feeding increased the JMax and KM for Ca2+ absorption within all sections, while Ion-Poor Water (IPW) exposure further increased the JMax and KM for Ca2+ transport in the anterior and middle sections alone. Increased Na+-K+-ATPase (NKA) and Citrate Synthase (CS) activity rates paralleled trends seen in Ca2+ transport. Feeding in freshwater and IPW exposure increased the glycolytic capacity of the caeca via increased Pyruvate Kinase (PK) and decreased Lactate Dehydrogenase (LDH) activity, while amino acid metabolism increased with IPW exposure through increased Glutamate Dehydrogenase (GDH) activity. Overall, feeding and IPW exposure each altered ionoregulation within the caeca of freshwater rainbow trout in a zone-specific pattern, with the anterior and proximal portions of the caeca being most affected. Increased carbohydrate and protein metabolism fueled the increased ATP demand of NKA through CS.
Quantitative diagnosis of osteoporosis using lumbar spine signal intensity in magnetic resonance imaging
Authors: Shayganfar Azin , Khodayi Maede , Ebrahimian Shadi , Tabrizi Zhale
Published: February 2019

Objective:

Osteoporosis is the most common metabolic bone disease that is not recognized in many elderly people. To determine the cause of low back pain, lumbosacral MRI is done for a large population who may not have gone under dual energy X-ray absorptiometry (DXA). The aim of this study was to predict bone density using lumbar spine signals in lumbosacral MRI in high risk patients for osteoporosis including post-menopausal females and calculate a threshold for a new quantitative MRI-based score to be used in estimation of lumbar spine bone mass density.

Methods:

82 menopaused females, who had undergone DXA before, were selected and MRI was done within 6 months after DXA. 69 healthy females aged 20–29 years who had undergone lumbar MRI were selected as reference group. Results were analyzed and threshold and diagnostic performance of MRI-based score (M-score) on the method of T-score was calculated.

Results:

Negative correlation between M-score and T-score was detected. Cut off point of 2.05 was found for M-score with near sensitivity of 90% and specificity of 87% for detecting osteoporotic patients from non-osteoporotic individuals.

Conclusion:

M-score is a MRI-based method which can identify patients at risk of osteoporosis. Early diagnosis of osteoporosis can reduce morbidity and mortality caused by it.

Advances in knowledge:

The research introduced cut of points for M-score as a new MRI quantitative method to be used as an opportunistic technique for detecting osteoporotic patients.
Massive open online courses on biomedical informatics
Authors: Quispe-Juli Cender Udai , Moquillaza-Alcántara Victor Hugo , Arapa-Apaza Katherine
Published: February 2019

This study aimed to identify the characteristics of massive open online courses (MOOCs) related to biomedical informatics offered in several plataforms. We conducted an observational study on specialized MOOCs platforms to find courses related to biomedical informatics, in 2018. Our search identified 67 MOOCs on biomedical informatics. The majority of MOOCs were offered by Coursera (71.6%, 48/67), English was the most common language (95.5%, 64/67). The United States developed the majority of courses (73.1%, 49/67), with the vast majority of MOOCs being offered by universities (94%, 63/67). The majority of MOOCs were in bioinformatics (56.7%, 38/67) and data science (47.7%, 32/67). In conclusion, the MOOCs on biomedical informatics were focused in bioinformatics and data science, and were offered in English by institutions in the developing world.
How ‘smart’ is smart dentistry?
Authors: Kokol Peter , Blažun Vošner Helena , Završnik Jernej , Turčin Marko
Published: February 2019

Background:Latest advances in information and health technologies enabled dentistry to follow the paradigm shift occurring in medicine – the transition to so called smart medicine. Consequently, the aim of this paper is to assess how ‘smart’ is smart dentistry as of the end of 2018.

Methods:We analysed the state of the art in smart dentistry, performing bibliometric mapping on a corpus of smart dentistry papers found in the Scopus bibliographical database.

Results:The search resulted in a corpus of 3451 papers, revealing that smart dentistry research is following the progress in smart medicine; however, there are some gaps in some specific areas like gamification and use of holistic smart dentistry systems.

Conclusions:Smart dentistry is smart; however, it must become smarter.
Case Report: Rare comorbidity of celiac disease and Evans syndrome
Authors: Uddin Syed Mohammad Mazhar , Haq Aatera , Haq Zara , Yaqoob Uzair
Published: February 2019

Background: Celiac disease is an immune-mediated enteropathy due to permanent sensitivity to gluten in genetically predisposed individuals. Evans syndrome is an autoimmune disorder designated with simultaneous or successive development of autoimmune hemolytic anemia and immune thrombocytopenia and/or immune neutropenia in the absence of any cause.

Case Report: We report a rare case of Celiac disease and Evans syndrome in a 20-year-old female who presented to us with generalized weakness and shortness of breath. Her examination finding included anemia, jaundice, and raised jugular venous pulse. Her abdominal exam revealed hepatosplenomegaly. Her laboratory values showed microcytic anemia, leukocytosis and thrombocytopenia. To rule out secondary causes of idiopathic thrombocytopenia purpura, we tested viral markers for Human immunodeficiency virus, Epstein bar virus, Cytomegalovirus and performed a Helicobacter pylori test, all of which were negative. We also ruled out idiopathic thrombocytopenia purpura associated with any thyroid disorder.  For celiac disease, we took anti-tissue transgulataminase titers of IgA and IgG which confirmed the diagnosis of celiac disease. For the diagnosis of Evans syndrome, despite a negative serum coombs test initially, her bone marrow sample showed a positive Coombs test along with immune mediated hemolytic anemia and immune mediated thrombocytopenia. The patient was treated with prednisone which was tapered off and counseling was provided regarding a gluten free diet.

Conclusion: Although rare, tests for Evans syndrome (and other coexisting autoimmune problems) should be performed in patients with celiac disease.
Separate and Concentrate: Accounting for Patient Complexity in General Hospitals
Authors: Kuntz Ludwig , Scholtes Stefan , Sülz Sandra
Published: February 2019

Scholars have recently suggested the reorganization of general hospitals into organizationally separate divisions for routine and non-routine services to overcome operational misalignments between the two types of services. We provide empirical evidence for this proposal from a quality perspective, using over 250,000 patient discharge records from 60 German hospitals across 39 high-mortality disease segments, and focusing on in-hospital mortality as outcome. Disentangling the effects of high, absolute, and relative hospital volumes in a disease group, our analysis suggests that routine and complex patients would benefit from a hospital organization with a multi-specialty hub for emergency and non-routine elective services at its core, complemented by organizationally separate disease-focused hospitals-within-hospitals for routine services. We also provide evidence that the hub hospital can further improve service quality for complex patients by adopting a disease-based rather than medical specialty-based departmental routing strategy for newly arriving patients. A counterfactual analysis, based on a simultaneous equations probit model that simultaneously controls for endogeneity of volume, focus, and routing strategy, suggests that the proposed reorganization could have reduced mortality in the sample by 13.43% (95% CI [6.87%; 18.95%]) for routine patients and by 11.67% (95% CI [6.13%; 16.86%]) for the most complex patients.

The supplementary material is available at https://doi.org/10.1287/mnsc.2018.3064 .

This paper was accepted by Serguei Netessine, operations management.
Portfolio Manager Ownership and Mutual Fund Risk Taking
Authors: Ma Linlin , Tang Yuehua
Published: February 2019

This paper studies the effect of portfolio manager ownership (i.e., “skin in the game”) on mutual fund risk taking. Using holdings-based risk change measures that capture managers’ ex ante risk choices, we find that portfolio manager ownership reduces both intrayear and across-year risk-taking activities. The relationship between ownership and risk reduction is particularly strong among managers with high agency issue–induced risk-taking incentives—for example, managers who face a more convex flow-performance relationship, have poor past performance, or are not compensated based on long-term fund performance. Funds with greater managerial ownership are also associated with lower levels of total risk and downside risk. Overall, portfolio manager ownership serves as an incentive alignment mechanism and has important implications for mutual fund investors.

This paper was accepted by Amit Seru, finance.
Capacity Uncertainty in Airline Revenue Management: Models, Algorithms, and Computations
Authors: Büsing Christina , Kadatz Daniel , Cleophas Catherine
Published: February 2019

Most airline revenue optimization models assume capacity to be fixed by fleet assignment, and thus treat it as deterministic. However, empirical data show that on 40% of flights, capacity is updated at least once within the booking horizon. Capacity updates can be caused by fleet-assignment reoptimizations or by short-term operational problems. This paper proposes a first model to integrate the resulting capacity uncertainty in the leg-based airline revenue management process. While assuming deterministic demand, the proposed model includes stochastic scenarios to represent potential capacity updates. To derive optimal inventory controls, we provide both a mixed-integer program and a combinatorial solution approach, and discuss efficient ways of optimizing the special case of a single capacity update. We also explore effects of denied boarding cost and the model’s relationship to the static overbooking problem. We numerically evaluate the model on empirically calibrated demand instances and benchmark it on the established deterministic approach and an upper bound based on perfect hindsight. In addition, we show that the combinatorial solution approach reduces the computational effort. Finally, we compare the static overbooking approach derived from the capacity uncertainty model to existing approaches based on the expected marginal seat revenue (EMSR).
Double-Setting Seed-Metering Device for Precision Planting of Soybean at High Speeds
Authors: Xue Pan , Xia Xuyu , Gao Pengyang , Ren Di , Hao Yujun , Zheng Zhiqi , Zhang Junchang , Zhu Ruixiang , Hu Bin , Huang Yuxiang
Published: February 2019

Abstract.

Precision planting has been proven to be an effective method for seeding row crops with uniform seed spacing, which favors crop yields. However, most precision planters were developed for low field operating speeds. In this study, a mechanical seed-metering device was developed with double-setting seed pickers, which allows high-quality planting at high field operating speeds. A discrete element model (DEM) was used to examine the effects of the design parameters on the metering performance, as indicated by the quality index (Iq), miss index (Imiss), and multiples index (Imult). Based on the model results, a seed-metering device was fabricated with the optimal design parameters and tested in laboratory conditions for model validation. Results showed that the critical parameters for the seed picker design were the lengths of the first and second setting plates (L1 and L2, respectively) and the seed cell and seed holder angles (a and ß, respectively). The Iq was generally high and the Imiss and Imult were generally low over the ranges of L1 from 15.5 to 17.5 mm, L2 from 4.6 to 5.5 mm, a from 57.5° to 65.0°, and ß from 50.0° to 70.0°. The most influential factors were ß and L2 and their interactions. The best performance, represented by the highest Iq, occurred at L2 = 5.18 mm and ß = 61.9°, where the Iq was 99.59%. The model results agreed well with the test results, as demonstrated by the low relative error (2.5%). Keywords: DEM, Modeling, Precision metering, Quality index, Seed, Travel speed.
Influencia de las migraciones protestantes estadounidenses en el partido político ARENA en El Salvador
Authors: Sánchez Gina Marcela Reyes , Sánchez María Camila Cárdenas
Published: February 2019

Este artículo analiza la incidencia de la segunda oleada migratoria de misiones protestantes estadounidenses hacia Centro y Sudamérica a finales de la década de 1980 y su influencia en la organización interna, las estrategias para acceder al poder y el desarrollo del proyecto político del partido Alianza Republicana Nacionalista (ARENA) de El Salvador. En la investigación se usó una metodología cualitativa. El impacto de las misiones protestantes en El Salvador implicó una aceptación de la occidentalización, contrastándola con los presupuestos comunistas apoyados por la teología latinoamericana de la liberación, especialmente en el catolicismo romano. Esa distinción evidenció que en ARENA confluían intereses religiosos, políticos y expansionistas.

Palabras clave: Misiones protestantes, protestantismo, fundamentalismo, partido político ARENA, El Salvador, teología latinoamericana de la liberación.
Rapid Calcification of Myocardium as Sequela from Severe Sepsis
Authors: Kunz Andreas S. , Beissert Matthias , Klink Thorsten
Published: February 2019

No Abstract
Sampling Defective Pathways in Parkinson Disease
Authors: Fernández-Martínez Juan Luis , deAndrés-Galiana Enrique J. , deAndrés-Galiana Enrique J. , Cernea Ana , Fernández-Ovies Francisco Javier , Menéndez Manuel
Published: February 2019

Discrimination of case-control status based on gene expression differences has potential to identify novel pathways relevant to neurodegenerative diseases including Parkinson’s disease (PD). In this paper we applied two different novel algorithms to predict dysregulated pathways of gene expression across several different regions of the brain in PD and controls. The Fisher’s ratio sampler uses the Fisher’s ratio of the most discriminatory genes as prior probability distribution to sample the genetic networks and their likelihood (accuracy) was established via Leave-One-Out-Cross Validation (LOOCV). The holdout sampler finds the minimum-scale signatures corresponding to different random holdouts, establishing their likelihood using the validation dataset in each holdout. Phenotype prediction problems have by genesis a very high underdetermined character. We used both approaches to sample different lists of genes that optimally discriminate PD from controls and subsequently used gene ontology to identify pathways affected by disease. Both algorithms identified common pathways of Insulin signaling, FOXA1 Transcription Factor Network, HIF-1 Signaling, p53 Signaling and Chromatin Regulation/Acetylation. This analysis provides new therapeutic targets to treat PD.
Endoscopic Ultrasound-Guided Coil Injection Therapy for Gastric Variceal Bleeding Not Amenable to Interventional Radiology-Guided Therapies
Authors: Bazarbashi Ahmad Najdat , Ryou Marvin
Published: February 2019

Gastric varices account for 10%–30% of all variceal bleeds and are associated with significant morbidity and mortality. Interventional radiology–guided therapies such as balloon-occluded retrograde transvenous obliteration and coil-assisted retrograde transvenous obliteration can provide hemostasis when traditional endoscopic treatments such as cyanoacrylate injection fail. However, their applicability in certain cases can be limited because of anatomical constraints. We describe the use of endoscopic ultrasound–guided coil and absorbable gelatin sponge injection for the treatment of bleeding gastric varices arising from pancreatitis-induced splenic vein thrombosis not amenable to interventional radiology–guided therapies.