bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating benefits and costs: a case of fish passages in Lao PDR and the development of the Lower Mekong Fishway Support Tool
Authors: Cooper Bethany , Crase Lin , Baumgartner Lee J.
Published: July 2019

Fishways are often presented as a parsimonious way of assisting water infrastructure development in developing countries while preserving some ecosystem values. More specifically, fishways help preserve migratory freshwater fish species, which are often a main source of protein and other nutrients for many rural communities. To date, much of the literature regarding fishway development focuses on increasing understanding of the interaction between the fish populations and engineering interventions. Accordingly, there is limited analysis that considers fishway construction relative to the specific benefits and costs that subsequently accrue to humans. In this study we outline the development of a decision support tool designed to assist officials in the Lower Mekong evaluate the merits of constructing fishways to address barriers to fish passage. Arguably, the tool can also be modified to assess the avoided cost of building additional barriers that constrain fish migration. The Lower Mekong Fishway Support Tool (LMFST) is underpinned by economic notions and populated with input from experts involved in fishway construction. The LMFST is intended to provide indicative monetary estimates and does not replace comprehensive engineering and social analysis; rather, it guides users in assessing those locations and structures that are more likely to deliver a positive outcome for local communities. The LMFST is buttressed in benefit–cost analysis and encourages decision making to be more transparent and this is one of the major contributions of this work.
Three-dimensional structure of the basketweave Z-band in midshipman fish sonic muscle
Authors: Burgoyne Thomas , Heumann John M. , Morris Edward P. , Knupp Carlo , Liu Jun , Reedy Michael K. , Taylor Kenneth A. , Wang Kuan , Luther Pradeep K.
Published: July 2019

Striated muscle enables movement in all animals by the contraction of myriads of sarcomeres joined end to end by the Z-bands. The contraction is due to tension generated in each sarcomere between overlapping arrays of actin and myosin filaments. At the Z-band, actin filaments from adjoining sarcomeres overlap and are cross-linked in a regular pattern mainly by the protein α-actinin. The Z-band is dynamic, reflected by the 2 regular patterns seen in transverse section electron micrographs; the so-called small-square and basketweave forms. Although these forms are attributed, respectively, to relaxed and actively contracting muscles, the basketweave form occurs in certain relaxed muscles as in the muscle studied here. We used electron tomography and subtomogram averaging to derive the 3D structure of the Z-band in the swimbladder sonic muscle of type I male plainfin midshipman fish (
Porichthys notatus)
, into which we docked the crystallographic structures of actin and α-actinin. The α-actinin links run diagonally between connected pairs of antiparallel actin filaments and are oriented at an angle of about 25° away from the actin filament axes. The slightly curved and flattened structure of the α-actinin rod has a distinct fit into the map. The Z-band model provides a detailed understanding of the role of α-actinin in transmitting tension between actin filaments in adjoining sarcomeres.
A four-electrode method to study dynamics of ion activity and transport in skeletal muscle fibers
Authors: Heiny Judith A. , Cannon Stephen C. , DiFranco Marino
Published: July 2019

Ion movements across biological membranes, driven by electrochemical gradients or active transport mechanisms, control essential cell functions. Membrane ion movements can manifest as electrogenic currents or electroneutral fluxes, and either process can alter the extracellular and/or intracellular concentration of the transported ions. Classic electrophysiological methods allow accurate measurement of membrane ion movements when the transport mechanism produces a net ionic current; however, they cannot directly measure electroneutral fluxes and do not detect any accompanying change in intracellular ion concentrations. Here, we developed a method for simultaneously measuring ion movements and the accompanying dynamic changes in intracellular ion concentrations in intact skeletal muscle fibers under voltage or current clamp in real time. The method combines a two-microelectrode voltage clamp with ion-selective and reference microelectrodes (four-electrode system). We validate the electrical stability of the system and the viability of the preparation for periods of ∼1 h. We demonstrate the power of this method with measurements of intracellular Cl−, H+, and Na+ to show (a) voltage-dependent redistribution of Cl− ions; (b) intracellular pH changes induced by changes in extracellular pCO2; and (c) electroneutral and electrogenic Na+ movements controlled by the Na,K-ATPase. The method is useful for studying a range of transport mechanisms in many cell types, particularly when the transmembrane ion movements are electrically silent and/or when the transport activity measurably changes the intracellular activity of a transported ion.
Universal fault-tolerant quantum computation using fault-tolerant conversion schemes
Authors: Luo Lan , Ma Zhi
Published: July 2019

In this paper, we present the fault-tolerant conversion between quantum Reed–Muller (QRM)(2, 5) and QRM(2, 7), and also the conversion between QBCH(15, 7) and QRM(2, 7). Either of the two schemes provides a method to realize universal fault-tolerant quantum computation. In particular, the gate overhead and logical error rate of a logical T gate are provided, as well as the comparison with magic state distillation scheme. In addition, we propose two other fault-tolerant conversion schemes based on

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constructions.
Future of nuclear medicine- an overview
Authors: Othman Siti Amira , Abu Bakar Nurul Fathihah , Amirah Nor Azman Nor Farah , Jasrin Nurin Saqinah
Published: July 2019

The development of nuclear medicine has led to an entire subset of extremely effective strategies in diagnosis and disease therapy. The emerging advancements in nuclear medicine are vast and diverse. Nuclear medicine tests and treatments involve the use of small amounts of radioactive material in order to diagnose and determine the severity of a variety of conditions and diseases. Basically, nuclear medicine involves the use of the latest imaging facilities such as magnetic resonance imaging, computed tomography scans and positron emission tomography which will find in many modern medical institutions today. One significant advantage of using nuclear medicine is the ability to make complex medical procedures simpler and safer for patients. With this technology, physicians and medical professionals are able to examine in great detail the most sensitive areas. All examinations can happen without subjecting patients to possibly dangerous and invasive procedures and surgeries. This medical technology has enabled the development of treatment options for patients suffering from serious illnesses, such as cancer either through radiation or chemotherapy. Health care professionals now face many challenges in their profession such as new rules and the latest practices that enable them to learn new skills and new ways of practicing their daily tasks in nuclear medicine areas. As a result, they are confronted with new skills and new ways of practicing in nuclear medicine area every day.
Activation of the Ca2+sensing receptor and the PKC/WNK4 downstream signaling cascade induces incorporation of ZO-2 to tight junctions and its separation from 14-3-3
Authors: Amaya Elida , Alarcón Lourdes , Martín-Tapia Dolores , Cuellar-Pérez Francisco , Cano-Cortina Misael , Ortega-Olvera Jose Mario , Cisneros Bulmaro , Rodriguez Alexis J. , Gamba Gerardo , González-Mariscal Lorenza
Published: July 2019

Zonula occludens-2 (ZO-2) is a tight junction (TJ) cytoplasmic protein, whose localization varies according to cell density and Ca2+in the media. In cells cultured in low calcium (LC), ZO-2 displays a diffuse cytoplasmic distribution, but activation of the Ca2+sensing receptor (CaSR) with Gd3+triggers the appearance of ZO-2 at the cell borders. CaSR downstream signaling involves activation of protein kinase C, which phosphorylates and activates with no lysine kinase-4 that phosphorylates ZO-2 inducing its concentration at TJs. In LC, ZO-2 is protected from degradation by association to 14-3-3 proteins. When monolayers are transferred to normal calcium, the complexes ZO-2/14-3-3ζ and ZO-2/14-3-3σ move to the cell borders and dissociate. The 14-3-3 proteins are then degraded in proteosomes, whereas ZO-2 integrates to TJs. From the plasma membrane residual ZO-2 is endocyted and degradaded in lysosomes. The unique region 2 of ZO-2, and S261 located within a nuclear localization signal, are critical for the interaction with 14-3-3 ζ and σ and for the efficient nuclear importation of ZO-2. These results explain the molecular mechanism through which extracellular Ca2+triggers the appearance of ZO-2 at TJs in epithelial cells and reveal the novel interaction between ZO-2 and 14-3-3 proteins, which is critical for ZO-2 protection and intracellular traffic.
Reticulon 4a promotes exocytosis in mammalian cells
Authors: Mukherjee Richik Nilay , Levy Daniel L.
Published: July 2019

Endoplasmic reticulum (ER) tubules and sheets conventionally correspond to smooth and rough ER, respectively. The ratio of ER tubules-to-sheets varies in different cell types and changes in response to cellular conditions, potentially impacting the functional output of the ER. To directly test whether ER morphology impacts vesicular trafficking, we increased the tubule-to-sheet ratio in three different ways, by overexpressing Rtn4a, Rtn4b, or REEP5. Only Rtn4a overexpression increased exocytosis, but not overall levels, of several cell surface and secreted proteins. Furthermore, Rtn4a depletion reduced cell surface trafficking without affecting ER morphology. Similar results were observed in three different mammalian cell lines, suggesting that Rtn4a generally enhances exocytosis independently of changes in ER morphology. Finally, we show that Rtn4a levels modulate cell adhesion, possibly by regulating trafficking of integrins to the cell surface. Taking the results together, we find that altering ER morphology does not necessarily affect protein trafficking, but that Rtn4a specifically enhances exocytosis.
PI3Kβ links integrin activation and PI(3,4)P2 production during invadopodial maturation
Authors: Erami Zahra , Heitz Samantha , Bresnick Anne R. , Backer Jonathan M.
Published: July 2019

The invasion of tumor cells from the primary tumor is mediated by invadopodia, actin-rich protrusive organelles that secrete matrix metalloproteases and degrade the extracellular matrix. This coupling between protrusive activity and matrix degradation facilitates tumor invasion. We previously reported that the PI3Kβ isoform of PI 3-kinase, which is regulated by both receptor tyrosine kinases and G protein–coupled receptors, is required for invasion and gelatin degradation in breast cancer cells. We have now defined the mechanism by which PI3Kβ regulates invadopodia. We find that PI3Kβ is specifically activated downstream from integrins, and is required for integrin-stimulated spreading and haptotaxis as well as integrin-stimulated invadopodia formation. Surprisingly, these integrin-stimulated and PI3Kβ-dependent responses require the production of PI(3,4)P2 by the phosphoinositide 5′-phosphatase SHIP2. Thus, integrin activation of PI3Kβ is coupled to the SHIP2-dependent production of PI(3,4)P2, which regulates the recruitment of PH domain-containing scaffolds such as lamellipodin to invadopodia. These findings provide novel mechanistic insight into the role of PI3Kβ in the regulation of invadopodia in breast cancer cells.
The Crk adapter protein is essential forDrosophilaembryogenesis, where it regulates multiple actin-dependent morphogenic events
Authors: Spracklen Andrew J. , Thornton-Kolbe Emma M. , Bonner Alison N. , Florea Alexandru , Compton Peter J. , Fernandez-Gonzalez Rodrigo , Peifer Mark
Published: July 2019

Small Src homology domain 2 (SH2) and 3 (SH3) adapter proteins regulate cell fate and behavior by mediating interactions between cell surface receptors and downstream signaling effectors in many signal transduction pathways. The CT10 regulator of kinase (Crk) family has tissue-specific roles in phagocytosis, cell migration, and neuronal development and mediates oncogenic signaling in pathways like that of Abelson kinase. However, redundancy among the two mammalian family members and the position of the Drosophila gene on the fourth chromosome precluded assessment of Crk’s full role in embryogenesis. We circumvented these limitations with short hairpin RNA and CRISPR technology to assess Crk’s function in Drosophila morphogenesis. We found that Crk is essential beginning in the first few hours of development, where it ensures accurate mitosis by regulating orchestrated dynamics of the actin cytoskeleton to keep mitotic spindles in syncytial embryos from colliding. In this role, it positively regulates cortical localization of the actin-related protein 2/3 complex (Arp2/3), its regulator suppressor of cAMP receptor (SCAR), and filamentous actin to actin caps and pseudocleavage furrows. Crk loss leads to the loss of nuclei and formation of multinucleate cells. We also found roles for Crk in embryonic wound healing and in axon patterning in the nervous system, where it localizes to the axons and midline glia. Thus, Crk regulates diverse events in embryogenesis that require orchestrated cytoskeletal dynamics.
Investigating the Feasibility of Child Mortality Surveillance With Postmortem Tissue Sampling: Generating Constructs and Variables to Strengthen Validity and Reliability in Qualitative Research
Authors: O’Mara Sage Elizabeth , Munguambe Khátia R , Blevins John , Guilaze Rui , Kosia Baindu , Maixenchs Maria , Bassat Quique , Mandomando Inácio , Kaiser Reinhard , Kone Ahoua , Jambai Amara , Myburgh Nellie D , Ngwenya Noni , Madhi Shabir A , Degefa Ketema , Ackley Caroline , Breiman Robert F , Raghunathan Pratima L
Published: July 2019

Background

The Child Health and Mortality Prevention Surveillance (CHAMPS) network aims to generate reliable data on the causes of death among children aged <5 years using all available information, including minimally invasive tissue sampling (MITS). The sensitive nature of MITS inevitably evokes religious, cultural, and ethical questions influencing the feasibility and sustainability of CHAMPS.

Methods

Due to limited behavioral studies related to child MITS, we developed an innovative qualitative methodology to determine the barriers, facilitators, and other factors that affect the implementation and sustainability of CHAMPS surveillance across 7 diverse locations in sub-Saharan Africa and South Asia. We employed a multimethod grounded theory approach and analytical structure based on culturally specific conceptual frameworks. The methodology guided data interpretation and collective analyses confirming how to define dimensions of CHAMPS feasibility within the cultural context of each site while reducing subjectivity and bias in the process of interpretation and reporting.

Results

Findings showed that the approach to gain consent to conduct the MITS procedure involves religious factors associated with timing of burial, use of certain terminology, and methods of transporting the body. Community misperceptions and uncertainties resulted in rumor surveillance and consistency in information sharing. Religious pronouncements, recognition of health priorities, attention to pregnancy, and advancement of child health facilitated community acceptability.

Conclusions

These findings helped formulate program priorities, guided site-specific adaptations in surveillance procedures, and verified inferences drawn from CHAMPS epidemiological and formative research data. Results informed appropriate community sensitization and engagement activities for introducing and sustaining mortality surveillance, including MITS.
DOZ047.11: Survival rates of infants with esophageal atresia: data of Turkish Esophageal Atresia Registry
Authors: Öztan M O , Soyer T , Öztorun C I , Fırıncı B , Durakbaşa Ç U , Dökümcü Z , Bahadır G G , Akkoyun I , Demirel B D , Karaman A , Çiftçi I , Ilhan H , Parlak A , Özden Ö , Yalçın S , Oral A , Tekant G T , Kıyan G , Erginel B , Güvenç Ü , Erdem A O , Ertürk N , Yıldız A
Published: July 2019

Aim

The data of the Turkish Esophageal Atresia Registry (TEAR) was evaluated to define the survival rate and risk factors of mortality in infants with esophageal atresia (EA).

Methods

The data of 389 cases registered by 23 centers between 2014 and 2018 were evaluated for demographic features, associated anomalies, surgical treatment and mortality-related outcome. Each parameter was evaluated for cases with mortality (CM) and compared with the results of survivors. Also, prognostic factors were investigated in CM.

Results

The overall survival rate was 81.09% and the mortality was 19.02% (n = 74). The male/female ratio was 1:1 in CM and 1.2:1 in survivors. The mean weight and height measurements in CM were lower than in survivors (1956 ± 658 g- 43.2 ± 5.7 cm vs 2534 ± 609 g-46.4 ± 4.3 cm) (P < 0.05). The incidence of associated anomalies was 90.6% in CM and significantly higher than survivors (59.6%) (P < 0.05). Neurological, cardiovascular, vertebral, and extremity anomalies were significantly higher in CM (P < 0.001). The most common type of anomaly was EA with distal fistula 89.2% in CM and 74.6% in survivors. The rate of primary anastomosis was also significantly lower in CM (67.6% vs 84.3%, P < 0.05). The gap length did not show statistical difference between CM and survivors (P > 0.05). Tube feeding was more common in CM and the incidence of full oral feedings was significantly higher in survivors (P < 0.01). According to the Spitz classification, the survival rate was 87.1% in Class I, 55.3% in Class II, and 16.7% in Class III. The most common causes of mortality were associated with cardiovascular disease, pneumonia, and sepsis.

Conclusion

The majority of national TEAR data comes from tertiary healthcare centers in Turkey. Therefore, the slightly increased mortality rates could be related to the inclusion of more complex and complicated cases. Birth weight–height, associated anomalies, and Spitz classification are significant risk factors of mortality in cases with EA.
Evaluating Vacancy Referrals and the Roles of Sanctions and Sickness Absence*
Authors: van den Berg Gerard J , Hofmann Barbara , Uhlendorff Arne
Published: July 2019

Job vacancy referrals are a common active labor market policy measure. Unemployment insurance agencies may combat moral hazard by punishing refusals to apply to assigned vacancies. During sickness spells, minimum requirements on search behaviour do not apply. This may reduce the threat effect of sanctions. We study effects of vacancy referrals and sanctions on unemployment durations and job match quality. We find that a vacancy referral increases the transition rate into work. We also find a positive effect of a vacancy referral on the probability of reporting sick.
CWL-Airflow: a lightweight pipeline manager supporting Common Workflow Language
Authors: Kotliar Michael , Kartashov Andrey V , Barski Artem
Published: July 2019

Background

Massive growth in the amount of research data and computational analysis has led to increased use of pipeline managers in biomedical computational research. However, each of the >100 such managers uses its own way to describe pipelines, leading to difficulty porting workflows to different environments and therefore poor reproducibility of computational studies. For this reason, the Common Workflow Language (CWL) was recently introduced as a specification for platform-independent workflow description, and work began to transition existing pipelines and workflow managers to CWL.

Findings

Herein, we present CWL-Airflow, a package that adds support for CWL to the Apache Airflow pipeline manager. CWL-Airflow uses CWL version 1.0 specification and can run workflows on stand-alone MacOS/Linux servers, on clusters, or on a variety of cloud platforms. A sample CWL pipeline for processing of chromatin immunoprecipitation sequencing data is provided.

Conclusions

CWL-Airflow will provide users with the features of a fully fledged pipeline manager and the ability to execute CWL workflows anywhere Airflow can run—from a laptop to a cluster or cloud environment. CWL-Airflow is available under Apache License, version 2.0 (Apache-2.0), and can be downloaded from https://barski-lab.github.io/cwl-airflow, https://scicrunch.org/resolver/RRID:SCR_017196.
A Contact Camel Theorem
Authors: Allais Simon
Published: July 2019

We provide a contact analogue of the symplectic camel theorem that holds in $\mathbb {R}^{2n}\times S^1$ and generalizes the symplectic camel. Our proof is based on the generating function techniques introduced by Viterbo, extended to the contact case by Bhupal and Sandon, and builds on Viterbo’s proof of the symplectic camel.
Using Social Media to Build Patient Engagement in Breast Radiology
Authors: Kuhl Elsa , Rapelyea Jocelyn
Published: July 2019

Breast radiologists can use social media to promote their brand and further connections with their patients, other physicians, and the greater community as a whole. This article offers a discussion and a guide by which breast radiologists can successfully navigate in the era of social media. The discussion is guided by three principles that, when used in collaboration with one another, will increase overall engagement between breast radiologists and the communities they serve. Ultimately, social media can be used by breast radiologists as an effective tool to facilitate engagement and advocate for and educate patients beyond the walls of the clinic.
Ureteric reimplantation via vaginal route: a new surgical technique
Authors: Toia Bogdan , Ockrim Jeremy J , Greenwell Tamsin J
Published: July 2019

Vesicovaginal fistulae (VVF) and ureteric reimplantation are two rare complications of obstetric surgery. VVF can be repaired via a vaginal approach utilizing Martius fat pad interposition to minimize urethral complications and improve surgical outcomes, while ureteric reimplantation into the bladder classically necessitates an abdominal or laparoscopic approach. We present a new technique of ureteric reimplantation via vaginal approach with concomitant repair of a 5-cm VVF in a 25-year-old woman after an emergency caesarean section with bladder injury and ureteric transection. Good drainage was confirmed on MAG3 and successful vaginal birth (albeit preterm) was subsequently achieved.
Paget Disease of Bone: Current Concepts
Authors: Skaggs John W. , Lather Jason D. , Yu Joseph S.
Published: July 2019

The first description of Paget disease of bone was reported by Sir James Paget, an English surgeon, in 1887.1 He described a progressive osseous disorder that caused increased bone turnover; produced architectural changes that enlarged and deformed bones; and increased fragility, making involved bones susceptible to fractures, thus coining the term “osteitis deformans.”
Improving Immunotherapy Against B-Cell Malignancies Using γδ T-Cell–specific Stimulation and Therapeutic Monoclonal Antibodies
Authors: Hoeres Timm , Pretscher Dominik , Holzmann Elisabeth , Smetak Manfred , Birkmann Josef , Triebel Jakob , Bertsch Thomas , Wilhelm Martin
Published: July 2019

Tumor antigen–targeting monoclonal antibodies (mAbs) are an important element of current cancer therapies. Some of these therapeutic mAbs enable antibody-dependent cell mediated cytotoxicity (ADCC) against tumor cells. However, cancer-related functional impairment of immune effector cells may limit the clinical efficacy of antibody treatments. We reckoned that combining mAbs with cell-based immunotherapies would provide a clinically relevant synergism and benefit for cancer patients. Here, we focus on γδ T cells, as earlier studies demonstrated that γδ T-cell–based therapies are safe and promising for several types of malignancies. Similar to natural killer cells, their antitumor effects can be enhanced using antibodies, and they could, therefore, become a versatile effector cell platform for use with a variety of licensed therapeutic mAbs against cancer. In this study, we explore the potential of a combination therapy of activated γδ T cells with rituximab and the more recently developed mAbs (obinutuzumab and daratumumab) in different B-cell malignancies in vitro. Obinutuzumab outperformed the other mAbs with regard to direct target cell lysis and ADCC by γδ T cells in several CD20+ cell lines and primary lymphoma specimens. We demonstrate that comparatively few CD16low γδ T cells are sufficient to mediate a strong ADCC. Using Fc-receptor-positive B-cell lymphomas as target cells, ADCC cannot be blocked by high concentrations of immunoglobulins or anti-CD16 antibodies, but both substances can promote cell mediated target cell lysis. This study expands on earlier reports on the therapeutic potential of distinctive tumor antigen–targeting mAbs and facilitates the understanding of the mechanism and potential of ADCC by γδ T-cell subsets.
Case Study
Authors: Reynolds Emily , Noska Kelly
Published: July 2019

Cutaneous renal cell carcinoma is a rare finding in the outpatient dermatology clinic. This case portrays an uncommon presentation of cutaneous metastases and provides an overview of the epidemiology and clinical presentation of cutaneous renal cell carcinoma. It also highlights the need to consider cutaneous metastases as a diagnosis in patients, especially those with known underlying malignancies.
Upper and Lower Extremity Ulcerating Lesions
Authors: Grossman Julie , Guccione Jack
Published: July 2019

Teledermatology is a term to describe the provision of dermatologic medical services through telecommunication technology. This is a teledermatology case of seven nonhealing lesions located on the right arm and left leg.
Hearing Preservation With the Use of Flex20 and Flex24 Electrodes in Patients With Partial Deafness
Authors: Skarzynski Piotr H. , Skarzynski Henryk , Dziendziel Beata , Rajchel Joanna J. , Gos Elzbieta , Lorens Artur
Published: July 2019

Objective:

To evaluate the impact of electrode length on hearing preservation (HP) in Partial Deafness Treatment–Electrical Complement (PDT-EC) subjects.

Study Design:

Retrospective case review.

Setting:

Tertiary referral center.

Patients:

Twenty-three PDT-EC patients (with preoperative air-conduction thresholds ≤30 dB up to 500 Hz) were divided into two groups: Flex20 electrode (Med-EL GmbH, Innsbruck, Austria) (12 patients) and Flex24 electrode (Med-EL GmbH, Innsbruck, Austria) (11 patients).

Interventions:

All participants were subjected to minimally invasive cochlear implantation using the round window approach.

Main Outcome Measure(s):

Pure tone audiometry (125–8000 Hz) was performed preoperatively and at 1, 6, 12, and 24 months postoperatively. HP was established using the HEARRING group formula. Speech understanding was assessed preoperatively and at 12 and 24 months postoperatively.

Results:

Analysis of HP for every individual indicates that more than half the patients with Flex20 and Flex24 had complete HP at 6 months follow-up. None of the patients from either group had complete loss of hearing. At activation, average air-conduction thresholds for low frequencies (125–500 Hz) were slightly better for the short electrode (M = 29.03) than for the long (M = 39.10) but the difference was not statistically significant (p = 0.067). The effect of electrode (Flex20 versus Flex24) was not significant in terms of pure tone audiometry and speech recognition at long-term follow-up.

Conclusions:

In the early postoperative period, complete HP was possible in a majority of patients from both groups, but slightly better HP outcomes were achieved by Flex20. In the long term, the length of the electrodes does not affect the degree of HP or speech understanding.
Anatomical Correlates and Surgical Considerations for Localized Therapeutic Hypothermia Application in Cochlear Implantation Surgery
Authors: Perez Enrique , Viziano Andrea , Al-Zaghal Zaid , Telischi Fred F. , Sangaletti Rachele , Jiang Weitao , Dietrich William Dalton , King Curtis , Hoffer Michael E. , Rajguru Suhrud M.
Published: July 2019

Hypothesis:

Application of localized, mild therapeutic hypothermia during cochlear implantation (CI) surgery is feasible for residual hearing preservation.

Background:

CI surgery often results in a loss of residual hearing. In preclinical studies, local application of controlled, mild therapeutic hypothermia has shown promising results as a hearing preservation strategy. This study investigated a suitable surgical approach to deliver local hypothermia in patients utilizing anatomical and radiologic measurements and experimental measurements from cadaveric human temporal bones.

Methods:

Ten human cadaveric temporal bones were scanned with micro-computed tomography and anatomical features and measurements predicting round window (RW) visibility were characterized. For each bone, the standard facial recess and myringotomy approaches for delivery of hypothermia were developed. The St. Thomas Hospital (STH) classification was used to record degree of RW visibility with and without placement of custom hypothermia probe. Therapeutic hypothermia was delivered through both approaches and temperatures recorded at the RW, RW niche, over the lateral semicircular canal and the supero-lateral mastoid edge.

Results:

The average facial recess area was 13.87 ± 5.52 mm2. The introduction of the cooling probe through either approach did not impede visualization of the RW or cochleostomy as determined by STH grading. The average temperatures at RW using the FR approach reduced by 4.57 ± 1.68 °C for RW, while using the myringotomy approach reduced by 4.11 ± 0.98 °C for RW.

Conclusion:

Local application of therapeutic hypothermia is clinically feasible both through the facial recess and myringotomy approaches without limiting optimal surgical visualization.
Game On
Authors: Woolwine Sarah , Romp Celeste R. , Jackson Barbara
Published: July 2019

The purpose of this descriptive correlational study was to determine if implementing gamification teaching methodologies in nondigital format into nursing orientation has a positive effect on orientees’ motivation and knowledge retention. The study included a convenience sample of 152 registered nurses who attended the nursing orientation class at a Midwestern acute care facility. This study found that gamification had a positive effect on the orientees’ motivation and knowledge retention.
Prognostic Value of Poorly Differentiated Clusters in Liver Metastatic Lesions of Colorectal Carcinoma
Authors: Yonemura Keisuke , Kajiwara Yoshiki , Ao Tadakazu , Mochizuki Satsuki , Shinto Eiji , Okamoto Koichi , Hase Kazuo , Ueno Hideki
Published: July 2019

Colorectal liver metastasis (CRLM) is the most common pattern of metastases or recurrence in colorectal carcinoma; however, no robust pathologic prognostic factors have been identified. This study aimed to verify the prognostic value of poorly differentiated clusters (PDC) in liver metastatic lesions and to clarify the correlation between PDC in liver metastatic lesions (PDCliver) and the primary tumor histology. Consecutive patients who underwent resection for CRLM were pathologically reviewed. PDC was defined as cancer clusters comprising ≥5 cancer cells and lacking glandular formation and was quantifiably graded as G1 (<5 clusters), G2 (5 to 9 clusters), and G3 (≥10 clusters) based on the highest number of clusters observed under ×20 magnification. The cohort comprised 204 patients. PDCliver was classified as G1, G2, and G3 for 68, 69, and 67 patients, respectively, and it was significantly associated with PDC grade in the primary tumor (P<0.001). Among the potential prognostic factors, tumor budding in the primary tumor, PDC in the primary tumor, the number of liver metastases, extrahepatic metastasis, and PDCliver significantly influenced overall survival (OS) after CRLM resection. According to the PDCliver grade, the 5-year OS rates were 68.9%, 48.3%, and 39.5% for G1, G2, and G3 (P<0.001), respectively. Multivariate analysis for OS showed that PDCliver grade, tumor budding in the primary tumor, the number of liver metastasis and extrahepatic metastasis were independent prognostic factors. In conclusion, there is a correlation in the PDC grade between the primary tumor and liver metastatic lesion, and PDCliver grade could be a promising new prognostic factor after CRLM resection.
The Significance of Visceral Protection in Preventing Enteroatmospheric Fistulae During Open Abdomen Treatment in Patients With Secondary Peritonitis
Authors: Willms Arnulf G. , Schaaf Sebastian , Zimmermann Nicolay , Schwab Robert , Güsgen Christoph , Vilz Tim O. , Kalff Jörg C. , von Websky Martin W.
Published: July 2019

Objective:

To evaluate the influence of a visceral protective layer (VPL) on the formation of enteroatmospheric fistulae (EAF) in open abdomen treatment (OAT) for peritonitis.

Background:

EAF formation is a severe complication of OAT. Despite the widespread use of OAT, there are no robust evidence-based recommendations for preventing EAF.

Methods:

A total of 120 peritonitis patients with secondary peritonitis as a result of a perforation of a hollow viscus or anastomotic insufficiency who had undergone OAT were included, and 14 clinical parameters were recorded in prospective OAT databases at 2 tertiary referral centers. For this analysis, patients with a VPL were assigned to the treatment group and those without a VPL to the control group. Propensity Score (PS) matching was performed. Known risk factors in OAT such as malignant disease, mortality, emergency operation, OAT duration, and fascial closure were matching variables. The influence of VPL on EAF formation was statistically evaluated using logistic regression analysis.

Results:

With 34 patients in each group, no notable differences were identified with regard to age, sex, underlying disease, mortality, emergency operation, fascial closure, and OAT duration. Overall, a mortality rate of 22.1% for OAT due to peritonitis was observed. Mean OAT duration was approximately 9 days, and secondary fascial closure was achieved in more than two-thirds of all patients. Fascial traction was used in more than 75% of cases. EAF formation was significantly more frequent in the control group (EAF formation: VPL group 2.9% vs control 26.5%; P = 0.00). In the final regression analysis, the use of VPL resulted in a significant reduction in the risk of EAF formation (odds ratio 0.08; 95% confidence interval 0.01–0.71, P = 0.02), which translates to a relative risk reduction of 89.1%.

Conclusion:

VPL effectively prevents EAF formation during OAT in patients with peritonitis. We recommend the consistent use of VPL as part of a standardized OAT treatment algorithm.
Risk of Contamination of Voided Urine Specimen in Women With Pelvic Organ Prolapse
Authors: Soriano Alex , Sansone Stephanie , Arora Ena , Arya Lily , Andy Uduak
Published: July 2019

Objectives

The primary aim of this study was to determine if urine cultures are more likely to be contaminated in women with pelvic organ prolapse (POP). The secondary aim was to evaluate the test characteristics of a urine dipstick in women with POP.

Methods

A retrospective cohort study was conducted of women who presented to the urogynecology clinic between September 1, 2017, and August 31, 2018. Associations between the presence of POP and contaminated urine culture results were estimated using univariable and multivariable analyses. The sensitivity and specificity of a urine dipstick in women with POP were calculated.

Results

We included 351 women (143 with and 208 without POP). Women with POP were older (65.4 ± 15.8 vs 60.7 ± 11.0 years, P < 0.01), had a lower body mass index (26.6 ± 4.8 vs 29.2 ± 7.7 kg/m2, P < 0.01), and were less likely to have recurrent urinary tract infections (3.5% vs 9.6%, P=0.03). Women with POP were more likely to have a contaminated urine culture than women without POP (55.9% vs 40.9%, P < 0.01). Rates of contaminated urine culture were higher in women with stage 3 and 4 prolapse than in women with stage 2 prolapse (59.6% vs 41.0%, P < 0.01). On multivariate analysis, the odds of contaminated urine culture remained higher in women with POP (odds ratio, 1.89; 95% confidence interval, 1.20–2.99). In women with POP, the sensitivity (23.5%) and positive predictive value (66.7%) of a urine dipstick were poor.

Conclusions

Women with POP are more likely to provide a contaminated urine culture when collecting a midstream urine specimen.
Helmet use is associated with higher Injury Severity Scores in alpine skiers and snowboarders evaluated at a Level I trauma center
Authors: Porter Eleah D. , Trooboff Spencer W. , Haff Madeleine G. , Cooros James C. , Wolffing Andrea B. , Briggs Alexandra , Rhynhart Kurt K. , Crockett Andrew O.
Published: July 2019

BACKGROUND

There is uncertainty regarding the efficacy of ski helmets in preventing traumatic injury. We investigated the relationship between helmet use, injury types, and injury severity among skiers and snowboarders.

METHODS

The trauma registry at a Northeast American College of Surgeons Level I trauma center was queried by International Classification of Diseases Codes—9th or 10th Revision for skiing and snowboarding injury between 2010 and 2018. The primary exposure was helmet use and primary outcome was severe injury (Injury Severity Score >15). We performed univariate and multivariable logistic regression to assess for injury types and severity associated with helmet use.

RESULTS

Seven hundred twenty-one patients (65% helmeted, 35% unhelmeted) met inclusion criteria. Helmet use doubled during the study period (43% to 81%, p < 0.001), but the rate of any head injury did not significantly change (49% to 43%, p = 0.499). On multivariable regression, helmeted patients were significantly more likely to suffer severe injury (odds ratio [OR], 2.01; 95% confidence interval [CI], 1.30–3.11), intracranial hemorrhage (OR, 1.81; 95% CI, 1.10–2.96), chest injury (OR, 1.66; 95% CI, 1.05–2.61), and/or lumbosacral spine injury (OR, 1.84; 95% CI, 1.04–3.25) than unhelmeted patients. Helmeted patients were half as likely to suffer cervical spine injury (OR, 0.51; 95% CI, 0.30–0.89) and a third as likely to sustain skull fracture and/or scalp laceration (OR, 0.30; 95% CI, 0.14–0.64). More patients who hit a stationary object were helmeted compared with those who fell from standing height onto snow (70% vs. 56% respectively, p < 0.001). After adjustment, hitting a stationary object was the injury mechanism most significantly associated with severe injury (OR, 2.80; 95% CI, 1.79–4.38).

CONCLUSION

Helmeted skiers and snowboarders evaluated at a Level I trauma center were more likely to suffer severe injury, including intracranial hemorrhage, as compared with unhelmeted participants. However, they were less likely to sustain skull fractures or cervical spine injuries. Helmeted patients were also more likely to hit a stationary object. Our findings reinforce the importance of safe skiing practices and trauma evaluation after high-impact injury, regardless of helmet use.

LEVEL OF EVIDENCE

Prognostic and epidemiological, level IV.
Emergence of artemisinin-resistantPlasmodium falciparumwithkelch13C580Y mutations on the island of New Guinea
Authors: Miotto Olivo , Sekihara Makoto , Tachibana Shin-Ichiro , Yamauchi Masato , Pearson Richard D , Amato Roberto , Gonçalves Sonia , Mehra Somya , Noviyanti Rintis , Marfurt Jutta , Auburn Sarah , Price Ric N , Mueller Ivo , Ikeda Mie , Mori Toshiyuki , Hirai Makoto , Tavul Livingstone , Hetzel Manuel , Laman Moses , Barry Alyssa , Ringwald Pascal , Ohashi Jun , Hombhanje Francis , Kwiatkowski Dominic P , Mita Toshihiro
Published: July 2019

The rapid and aggressive spread of artemisinin-resistant Plasmodium falciparum carrying the kelch13 C580Y mutation is a growing threat to malaria elimination in Southeast Asia, but there is no evidence of their spread to other regions. We conducted cross-sectional surveys in 2016 and 2017 at two clinics in Wewak, Papua New Guinea (PNG) where we identified three infections caused by C580Y mutants among 239 genotyped clinical samples. One of these mutants exhibited the highest survival rate (6.8%) among all parasites surveyed in ring-stage survival assays (RSA) for artemisinin. Analyses of kelch13 flanking regions, and comparisons of deep sequencing data from 389 clinical samples from PNG, Indonesian Papua and Western Cambodia, suggested an independent origin of the Wewak C580Y mutation, showing that the mutants possess several distinctive genetic features. Identity by descent (IBD) showed that multiple portions of the mutants’ genomes share a common origin with parasites found in Indonesian Papua, comprising several mutations within genes previously associated with drug resistance, such as mdr1, ferredoxin, atg18 and pnp. These findings suggest that a P. falciparum lineage circulating on the island of New Guinea has gradually acquired a complex ensemble of variants, including kelch13 C580Y, which have affected the parasites’ drug sensitivity. This worrying development reinforces the need for increased surveillance of the evolving parasite populations on the island, to contain the spread of resistance.
Response to “Expression reduction of biallelically transcribed X-linked genes during the female human preimplantation development”
Authors: Moreira de Mello JC , Vibranovski MD , Pereira LV
Published: July 2019

Reinius and Sandberg (2019) have recently shown that X-linked balletic gene expression decreases during human preimplantation embryonic development, corroborating their previous hypothesis of X dampening as a mechanism of dosage compensation. Here we demonstrate that their analyses are based on biologically false premises, thus not demonstrating the phenomena of X dampening in humans.
Neurological disorder drug discovery from gene expression with tensor decomposition
Authors: Taguchi Y-h. , Turki Turki
Published: July 2019

Background

Identifying effective candidate drug compounds in patients with neurological disorders based on gene expression data is of great importance to the neurology field. By identifying effective candidate drugs to a given neurological disorder, neurologists would (1) reduce the time searching for effective treatments; and (2) gain additional useful information that leads to a better treatment outcome. Although there are many strategies to screen drug candidate in pre-clinical stage, it is not easy to check if candidate drug compounds can be also effective to human.

Objective

We tried to propose a strategy to screen genes whose expression is altered in model animal experiments to be compared with gene expressed differentically with drug treatment to human cell lines.

Methods

Recently proposed tensor decomposition (TD) based unsupervised feature extraction (FE) is applied to single cell (sc) RNA-seq experiments of Alzheimer’s disease model animal mouse brain.

Results

Four hundreds and one genes are screened as those differentially expressed during Aβaccumulation as age progresses. These genes are significantly overlapped with those expressed differentially with the known drug treatments for three independent data sets: LINCS, DrugMatrix and GEO.

Conclusion

Our strategy, application of TD based unsupervised FE, is useful one to screen drug candidate compounds using scRNA-seq data set.
A lab-on-a-chip model of glaucoma
Authors: Nafian Fatemeh , Azad Babak Kamali Doust , Yazdani Shahin , Rasaee Mohammad Javad , Daftarian Narsis
Published: July 2019

We developed a glaucoma-on-a-chip (GOC) model to evaluate the viability of retinal ganglion cells (RGCs) against high pressure and the potential effect of neuroprotection. A three-layered chip consisting of interconnecting microchannels and culture wells was designed based on simulation of physical parameters. The chip layers were fabricated from poly-methyl methacrylate sheets. Multiple inlet ports allow culture media and gas into the wells under elevated hydrostatic pressure (EHP). The bottom surface of the wells was modified by air plasma and coated with different membranes to model an extracellular microenvironment. The SH-SY5Y neuroblastoma cell line served as model cells to determine the best supporting membrane which was revealed to be PDL/laminin. Thereafter, the study experiments were performed using RGCs obtained from postnatal 5-7 Wistar rats purified by magnetic assisted cell sorting. Flow cytometry and immunocytochemistry assays demonstrated 70% purification for RGCs. The cultured RGCs were exposed to normal (15 mmHg) or elevated pressure (33 mmHg) for 6, 12, 24, 36 and 48 hours, with and without adding brain-derived neurotrophic factor (BDNF) or a novel BDNF mimetic (RNYK). RGC survival rates were 85, 78, 70, 67 and 61 percent under normal pressure versus 40, 22, 18, 12 and 10 percent under high pressure at 6, 12, 24, 36 and 48 hours, respectively (P <0.0001). BDNF and RNYK treatments induced separately an approximate two-fold decrease in the rate of RGC death under both normal and elevated pressures (p <0.01 to 0.0001). This GOC model recapitulated the effects of elevated pressure during relatively short time periods and demonstrated the neuroprotective effects of BDNF and RNYK.
A screen for gene paralogies delineating evolutionary branching order of early Metazoa
Authors: Erives Albert , Fritzsch Bernd
Published: July 2019

The evolutionary diversification of animals is one of Earth’s greatest triumphs, yet its origins are still shrouded in mystery. Animals, the monophyletic clade known as Metazoa, evolved wildly divergent multicellular life strategies featuring ciliated sensory epithelia. In many lineages epithelial sensoria became coupled to increasingly complex nervous systems. Currently, different phylogenetic analyses of single-copy genes support mutually-exclusive possibilities that either Porifera or Ctenophora is sister to all other animals. Resolving this dilemma would advance the ecological and evolutionary understanding of the first animals and the evolution of nervous systems. Here we describe a comparative phylogenetic approach based on gene duplications. We computationally identify and analyze gene families with early metazoan duplications using an approach that mitigates apparent gene loss resulting from the miscalling of paralogs. In the transmembrane channel-like (TMC) family of mechano-transducing channels, we find ancient duplications that define separate clades for Eumetazoa (Placozoa + Cnidaria + Bilateria) versus Ctenophora, and one duplication that is shared only by Eumetazoa and Porifera. In the MLX/MLXIP family of bHLH-ZIP regulators of metabolism, we find that all major lineages from Eumetazoa and Porifera (sponges) share a duplication, absent in Ctenophora. These results suggest a new avenue for deducing deep phylogeny by choosing rather than avoiding ancient gene paralogies.