bluuebunny/crossref_metadata_2025 huggingface dataset:
ALK-TPM3 rearrangement in adult renal cell carcinoma: a case report and literature review
Authors: Yang Jing , Dong Lei , Du Hong , Li Xiu-bo , Liang Yan-xiao , Liu Guo-rong
Published: October 2019

Background

Translocation-associated renal cell carcinoma involving ALK (ALK-tRCC) is a rare subtype of adult renal cell carcinoma (RCC) reported in recent years. It was recognized as a group of emerging /provisional RCC in the latest World Health Organization’s classification (2016).

Case presentation

A new Chinese case of ALK-tRCC was reported. The patient was a 58-year-old man with a tumor in kidney. The tumor was composed of sheets of large cells with abundant eosinophilic cytoplasm and indistinct cell borders but conspicuous intracytoplasmic vacuoles. The nuclei were enlarged with a nucleolar of grade 4. Immunohistochemically, tumor cells were diffusely positive for PAX8, keratin (AE1/AE3), epithelial membrane antigen (EMA) and CK7. Fluorescent in situ hybridization (FISH) showed a rearrangement of ALK in tumor cells.

Conclusion

ALK-tRCC is a rare subtype of adult RCC. Its diagnosis is very difficult because the histological spectrum is very wide. We suggested that RCCs should be screened for ALK expression by immunohistochemistry (IHC) for the patient might benefit from ALK inhibitors therapy.
Cognitive functioning in patients with classical galactosemia: a systematic review
Authors: Hermans Merel E. , Welsink-Karssies Mendy M. , Bosch Annet M. , Oostrom Kim J. , Geurtsen Gert J.
Published: October 2019

Background

Patients with the metabolic disorder classical galactosemia suffer from long-term complications despite a galactose-restricted diet, including a below average intelligence level. The aim of the current review was to investigate the incidence and profile of cognitive impairments in patients with classical galactosemia.

Method

MEDLINE, EMBASE and PsychINFO were searched up to 23 October 2018 for studies examining information processing speed, attention, memory, language, visuospatial functioning, executive functioning and social cognition in patients with confirmed classical galactosemia utilizing standardized neuropsychological tests. Data synthesis followed a narrative approach, since the planned meta-analysis was not possible due to large variability between the neuropsychological assessments.

Results

Eleven studies were included, including case-studies. The quality of most studies was moderate to low. As a group, patients with classical galactosemia exhibit below average to low scores on all cognitive domains. A large proportion of the patients perform on an impaired level on attention, memory and vocabulary. Evidence for impairments in information processing speed, language, visuospatial functioning and aspects of executive functioning was limited due to the small number of studies investigating these cognitive functions. Social cognition was not examined at all.

Conclusions

Given the moderate to low quality of the included studies and the limited evidence in many cognitive domains, the incidence of cognitive impairment in patients with classical galactosemia is not yet clear. Both clinicians and researchers encountering patients with classical galactosemia need to be aware of possible cognitive impairments. Future well-designed studies are needed to determine the cognitive profile of classical galactosemia. This can be the basis for the development of intervention strategies.
Hemolysis and its outcome following percutaneous closure of cardiac defects among children and adolescents: a prospective study
Authors: Amoozgar Hamid , Soltani Romeileh , Edraki Mohammadreza , Mehdizadegan Nima , Mohammadi Hamid , Ajami Gholamhossein , Borzouee Mohammad , Naghshzan Amir , Keshavarz Kambiz
Published: October 2019

Background

Transcatheter closure of intracardiac defects might be complicated by intravascular hemolysis. We evaluated hemolysis and its outcome after transcatheter closure of these defects.

Methods and patients

All patients who underwent transcatheter closure of patent ductus arteriosus, ventricular septal defect and atrial septal defect were included in this prospective study. Clinical data were obtained before and after the catheterization.

Results

One hundred and thirty-eight patients were enrolled; and four (3%) patients developed intravascular hemolysis; while two cases had residual shunt and two other cases had not residual flow.

Although residual shunt occurred in ten patients, only 2 of these cases developed hemolysis. Patent ductus arteriosus closure was done for one of these cases and the other one, underwent perimembranous ventricular septal defect closure.

Moreover, hemolysis occurred after device closure of patent ductus arteriosus in 2 of the other patients with no residual shunt.

In this study the hemolysis was eliminated by conservative management within 2 weeks although residual shunt continued in this time.

We observed a decline in lactate dehydrogenase value after catheterization in comparison with precatheterization, which was mainly among ventricular septal defect patients that might be due to mild chronic hemolysis in these patients.

Conclusion

Incidence of hemolysis after device closure was low, and occurred with and without residual flow and was eliminated by conservative management in 2 weeks, without the need for surgery, although the residual shunt was continued.
DeepImpute: an accurate, fast, and scalable deep neural network method to impute single-cell RNA-seq data
Authors: Arisdakessian Cédric , Poirion Olivier , Yunits Breck , Zhu Xun , Garmire Lana X.
Published: October 2019

Single-cell RNA sequencing (scRNA-seq) offers new opportunities to study gene expression of tens of thousands of single cells simultaneously. We present DeepImpute, a deep neural network-based imputation algorithm that uses dropout layers and loss functions to learn patterns in the data, allowing for accurate imputation. Overall, DeepImpute yields better accuracy than other six publicly available scRNA-seq imputation methods on experimental data, as measured by the mean squared error or Pearson’s correlation coefficient. DeepImpute is an accurate, fast, and scalable imputation tool that is suited to handle the ever-increasing volume of scRNA-seq data, and is freely available athttps://github.com/lanagarmire/DeepImpute.
Giardia duodenalis infection in the context of a community-based deworming and water, sanitation and hygiene trial in Timor-Leste
Authors: Aw Jessica Y. H. , Clarke Naomi E. , McCarthy James S. , Traub Rebecca J. , Amaral Salvador , Huque Md Hamidul , Andrews Ross M. , Gray Darren J. , Clements Archie C. A. , Vaz Nery Susana
Published: October 2019

Background

Giardiasis is a common diarrhoeal disease caused by the protozoan Giardia duodenalis. It is prevalent in low-income countries in the context of inadequate access to water, sanitation and hygiene (WASH), and is frequently co-endemic with neglected tropical diseases such as soil-transmitted helminth (STH) infections. Large-scale periodic deworming programmes are often implemented in these settings; however, there is limited evidence for the impact of regular anthelminthic treatment on G. duodenalis infection. Additionally, few studies have examined the impact of WASH interventions on G. duodenalis.

Methods

The WASH for WORMS cluster randomised controlled trial was conducted in remote communities in Manufahi municipality, Timor-Leste, between 2012 and 2016. All study communities received four rounds of deworming with albendazole at six-monthly intervals. Half were randomised to additionally receive a community-level WASH intervention following study baseline. We measured G. duodenalis infection in study participants every six months for two years, immediately prior to deworming, as a pre-specified secondary outcome of the trial. WASH access and behaviours were measured using questionnaires.

Results

There was no significant change in G. duodenalis prevalence in either study arm between baseline and the final study follow-up. We found no additional benefit of the community-level WASH intervention on G. duodenalis infection (relative risk: 1.05, 95% CI: 0.72–1.54). Risk factors for G. duodenalis infection included living in a household with a child under five years of age (adjusted odds ratio, aOR: 1.35, 95% CI: 1.04–1.75), living in a household with more than six people (aOR: 1.32, 95% CI: 1.02–1.72), and sampling during the rainy season (aOR: 1.23, 95% CI: 1.04–1.45). Individuals infected with the hookworm Necator americanus were less likely to have G. duodenalis infection (aOR: 0.71, 95% CI: 0.57–0.88).

Conclusions

Prevalence of G. duodenalis was not affected by a community WASH intervention or by two years of regular deworming with albendazole. Direct household contacts appear to play a dominant role in driving transmission. We found evidence of antagonistic effects between G. duodenalis and hookworm infection, which warrants further investigation in the context of global deworming efforts.

Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12614000680662. Registered 27 June 2014, retrospectively registered. https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366540.
Evaluation of the Vibrant DNA microarray for the high-throughput multiplex detection of enteric pathogens in clinical samples
Authors: Yang Yuanyuan , Rajendran Vinod , Jayaraman Vasanth , Wang Tianhao , Bei Kang , Krishna Karthik , Rajasekaran Karenah , Rajasekaran John J. , Krishnamurthy Hari
Published: October 2019

Background

Rapid detection of a wide range of etiologic agents is essential for appropriate treatment and control of gastrointestinal (GI) infections. A variety of microbial species including bacteria, viruses, parasites, and fungi have been recognized as diarrheagenic enteric pathogens. However, multiplex testing of various targets in a single reaction needs further improvement because of its limitation in species and throughput.

Results

This study aims at developing and evaluating a DNA microarray-based qualitative multiplexed polymerase chain reaction (PCR) assay, Vibrant GI pathogen panel (GPP), for simultaneous detection of 27 enteric GI pathogenic targets (16 bacteria, 5 viruses, 4 parasites, and 2 fungi) directly from stool specimens. Limits of detection ranged from 102 to 104 cells/mL for bacteria, 102 to 103 cells/mL for parasites, 102 to 103 RNA copies/mL for viruses, and 102 to 103 cells/mL for fungi. Performance characteristics were determined using 27 Quantitative Genomic DNAs, 212 spiked stool specimens, 1067 clinical and archived stool specimens. Overall sensitivity was 95.9% (95% CI 92.4–98.1) and specificity was 100% (95% CI 99.9–100). Polymicrobial detections contained either two or three organisms was 20.2% (35/173) of positive clinical specimens and 3.3% (35/1055) of all clinical specimens.

Conclusion

The Vibrant GPP is a comprehensive, high-throughput, and rapid DNA microarray to provide etiologic diagnosis of GI infections in the laboratory setting.
Investigating the association between anxiety symptoms and mood disorder in high-risk offspring of bipolar parents: a comparison of Joint and Cox models
Authors: Dong Ruoxi , Stefan George , Horrocks Julie , Goodday Sarah M. , Duffy Anne
Published: October 2019

Background

Anxiety is associated with mood disorders including bipolar disorder. Two statistical modelling frameworks were compared to investigate the longitudinal relationship between repeatedly measured anxiety symptoms and the onset of depression and bipolar disorder in youth at confirmed familial risk.

Methods

Prospectively collected data on 156 offspring of a parent with confirmed bipolar disorder participating in the Canadian Flourish high-risk offspring longitudinal cohort study were used for this analysis. As part of the research protocol at approximately yearly visits, a research psychiatrist completed the HAM-A and a semi-structured diagnostic research interview following KSADS-PL format. Diagnoses using DSM-IV criteria were made on blind consensus review of all available clinical information. We investigated two statistical approaches, Cox model and Joint model, to evaluate the relationship between repeated HAM-A scores and the onset of major depressive or bipolar disorder. The Joint model estimates the trajectory of the longitudinal variable using a longitudinal sub-model and incorporates this estimated trajectory into a Cox sub-model.

Results

There was evidence of an increased hazard of major mood disorder for high-risk individuals with higher HAM-A scores under both modelling frameworks. After adjusting for other covariates, a one-unit increase in log-transformed HAM-A score was associated with a hazard ratio of 1.74 (95% CI (1.12, 2.72)) in the Cox model compared to 2.91(95% CI (1.29, 6.52)) in the Joint model. In an exploratory analysis there was no evidence that family clustering substantially affected the conclusions.

Conclusions

Estimated effects from the conventional Cox model, which is often the model of choice, were dramatically lower in this dataset, compared to the Joint model. While the Cox model is often considered the approach of choice for analysis, research has shown that the Joint model may be more efficient and less biased. Our analysis based on a Joint model suggests that the magnitude of association between anxiety and mood disorder in individuals at familial risk of developing bipolar disorder may be stronger than previously reported.
Progression of intervention-focused research for Gulf War illness
Authors: Chester Jeremy E. , Rowneki Mazhgan , Van Doren William , Helmer Drew A.
Published: October 2019

The Persian Gulf War of 1990 to 1991 involved the deployment of nearly 700,000 American troops to the Middle East. Deployment-related exposures to toxic substances such as pesticides, nerve agents, pyridostigmine bromide (PB), smoke from burning oil wells, and petrochemicals may have contributed to medical illness in as many as 250,000 of those American troops. The cluster of chronic symptoms, now referred to as Gulf War Illness (GWI), has been studied by many researchers over the past two decades. Although over $500 million has been spent on GWI research, to date, no cures or condition-specific treatments have been discovered, and the exact pathophysiology remains elusive.

Using the 2007 National Institute of Health (NIH) Roadmap for Medical Research model as a reference framework, we reviewed studies of interventions involving GWI patients to assess the progress of treatment-related GWI research. All GWI clinical trial studies reviewed involved investigations of existing interventions that have shown efficacy in other diseases with analogous symptoms. After reviewing the published and ongoing registered clinical trials for cognitive-behavioral therapy, exercise therapy, acupuncture, coenzyme Q10, mifepristone, and carnosine in GWI patients, we identified only four treatments (cognitive-behavioral therapy, exercise therapy, CoQ10, and mifepristone) that have progressed beyond a phase II trial.

We conclude that progress in the scientific study of therapies for GWI has not followed the NIH Roadmap for Medical Research model. Establishment of a standard case definition, prioritized GWI research funding for the characterization of the pathophysiology of the condition, and rapid replication and adaptation of early phase, single site clinical trials could substantially advance research progress and treatment discovery for this condition.
An introduction to the civil registration and vital statistics systems with applications in low- and middle-income countries
Authors: Mills Samuel , Lee Jane Kim , Rassekh Bahie Mary
Published: October 2019

In collaboration with development partners, the World Bank Group (WBG) has been working to strengthen civil registration and vital statistics (CRVS) systems in low- and middle-income countries through lending operations, technical assistance projects, advisory services and analytics, and knowledge sharing at various international, regional, and national conferences and fora and through publications. In 2017, it launched a comprehensive CRVS eLearning course, which provides practical tools and approaches to achieving twenty-first-century state-of-the-art CRVS systems that are linked to identity management systems and are tailored to local contexts. Some of the key lessons learned from the various initiatives and projects are presented in the eight peer-reviewed manuscripts included in this issue.
Seroprevalence of an antibody against diphtheria, tetanus, and pertussis among the elderly in Khon Kaen, Thailand
Authors: Chinchai Teeraporn , Posuwan Nawarat , Vuthitanachot Viboonsak , Wanlapakorn Nasamon , Poovorawan Yong
Published: October 2019

Background

Owing to a declining birth rate and longer lifespan, the number of elderly people (≥ 60 years) in Thailand has grown rapidly. However, the elderly are at significant risk of infectious diseases because they have never been immunized, because they have not been completely immunized, or because their immunity has waned. Immunity against infectious diseases in the elderly is an important means of controlling diseases in the community. Our objective was to evaluate the seroprotective rate against diphtheria, tetanus, and pertussis in the elderly Thai population.

Methods

In total, 430 healthy individuals from the northeastern region of Thailand were enrolled in this study and stratified into five age groups: 60–65, 66–70, 71–75, 76–80, and > 80 years. Serum samples were collected and quantitatively analyzed for diphtheria, tetanus, and pertussis IgG antibody by using commercial ELISA kits. For anti-diphtheria toxoid and anti-tetanus toxoid ELISA, values < 0.01 IU/ml were interpreted as seronegative, and for anti-Bordetella pertussistoxin ELISA, values < 5 IU/ml were interpreted as seronegative; these definitions were in accord with previous studies.

Results

For diphtheria toxoid Ab, the majority of the population had antibody levels > 0.01 IU/ml. For tetanus anti-toxoid Ab, the majority of the population had antibody levels of > 0.01 IU/ml, of which approximately 34% had durable antibody protection levels (DAPL) of ≥ 1 IU/ml. Meanwhile, nearly 45% of the population had an Ab level against pertussis lower than the protectivity level.

Conclusions

In total, 97.2%, 83.5%, and 55.8% of the population had a higher antibody level than the minimal protective level for diphtheria, tetanus, and pertussis, respectively. In order to prevent an outbreak of these diseases in the future, the elderly should be administered with Tdap revaccination to provide diphtheria herd immunity in the population; this will increase cocoon phenomenon for pertussis and protect the population from tetanus-prone injury.
Individual and combined impact of nuclear polyhedrosis virus and spinosad to control the tropical armyworm, Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae), in cotton in Pakistan
Authors: Ayyub Muhammad Bilal , Nawaz Ahmad , Arif Muhammad Jalal , Amrao Luqman
Published: October 2019

The tropical armyworm, Spodoptera litura Fabricius (Noctuidae; Lepidoptera), is among the most harmful pests causing economic loss in the quality and production of a variety of crops, particularly cotton. Entomopathogens play an important role in insect pest management. The nuclear polyhedrosis virus (NPV) isolate of S. litura (V-SpltNPV) was isolated from infected larvae in a cotton crop, and viral occlusion bodies were confirmed, using an inverted microscope. The pathogenicity of V-SpltNPV against 2nd, 3rd, and 4th larval instars of S. litura was evaluated at various concentrations (1 × 104 to 1 × 108 OBs/ml). Mortality rate was high (37.65–96.82%) in early instar larvae against tested concentrations. LC50 and LT50 values increased with increasing larval age. There was 689,865 times increase in LC50 value (1.35 × 102 OBs/ml) for 2nd instar larvae to LC50 value (6.90 × 105 OBs/ml) for 4th instar larvae. LT50 values enhanced from 4.99 days for 2nd instar larvae to 7.49 days for 4th instar larvae, due to a decrease in efficacy of NPVs with the increasing age of larvae. In a greenhouse experiment, a combined application of spinosad with V-SpltNPV (1 × 108 OBs/ml) caused (100%) mortality of 2nd instar larvae. A single application of V-SpltNPV (1 × 108 OBs/ml) resulted to mean mortality (52.63%) of tested larvae. The native isolate V-SpltNPV seems to have a potential to be used in integrated manner with other IPM tactics to significantly reduce the use of toxic chemical pesticides.
Genomic analysis on broiler-associated Clostridium perfringens strains and exploratory caecal microbiome investigation reveals key factors linked to poultry necrotic enteritis
Authors: Kiu Raymond , Brown Joseph , Bedwell Harley , Leclaire Charlotte , Caim Shabhonam , Pickard Derek , Dougan Gordon , Dixon Ronald A. , Hall Lindsay J.
Published: October 2019

Background

Clostridium perfringens is a key pathogen in poultry-associated necrotic enteritis (NE). To date there are limited Whole Genome Sequencing based studies describing broiler-associated C. perfringens in healthy and diseased birds. Moreover, changes in the caecal microbiome during NE is currently not well characterised. Thus, the aim of this present study was to investigate C. perfringens virulence factors linked to health and diseased chickens, including identifying putative caecal microbiota signatures associated with NE.

Results

We analysed 88 broiler chicken C. perfringens genomes (representing 66 publicly available genomes and 22 newly sequenced genomes) using different phylogenomics approaches and identified a potential hypervirulent and globally-distributed clone spanning 20-year time-frame (1993–2013). These isolates harbored a greater number of virulence genes (including toxin and collagen adhesin genes) when compared to other isolates. Further genomic analysis indicated exclusive and overabundant presence of important NE-linked toxin genes including netB and tpeL in NE-associated broiler isolates. Secondary virulence genes including pfoA, cpb2, and collagen adhesin genes cna, cnaA and cnaD were also enriched in the NE-linked C. perfringens genomes. Moreover, an environmental isolate obtained from farm animal feeds was found to encode netB, suggesting potential reservoirs of NetB-positive C. perfringens strains (toxinotype G). We also analysed caecal samples from a small sub-set of 11 diseased and healthy broilers for exploratory microbiome investigation using 16S rRNA amplicon sequencing, which indicated a significant and positive correlation in genus Clostridium within the wider microbiota of those broilers diagnosed with NE, alongside reductions in beneficial microbiota members.

Conclusions

These data indicate a positive association of virulence genes including netB, pfoA, cpb2, tpeL and cna variants linked to NE-linked isolates. Potential global dissemination of specific hypervirulent lineage, coupled with distinctive microbiome profiles, highlights the need for further investigations, which will require a large worldwide sample collection from healthy and NE-associated birds.
The association between health conditions and cannabis use in patients with opioid use disorder receiving methadone maintenance treatment
Authors: Shams Ieta , Sanger Nitika , Bhatt Meha , Rosic Tea , Luo Candice , Shahid Hamnah , Mouravska Natalia , Tam Sabrina Lue , Hillmer Alannah , Chawar Caroul , D'Elia Alessia , Hudson Jacqueline , Marsh David , Thabane Lehana , Samaan Zainab
Published: October 2019

Background

Cannabis is the most commonly used substance among patients in methadone maintenance treatment (MMT) for opioid use disorder. Current treatment programmes neither screen nor manage cannabis use. The recent legalisation of cannabis in Canada incites consideration into how this may affect the current opioid crisis.

Aims

Investigate the health status of cannabis users in MMT.

Method

Patients were recruited from addiction clinics in Ontario, Canada. Regression analyses were used to assess the association between adverse health conditions and cannabis use. Further analyses were used to assess sex differences and heaviness of cannabis use.

Results

We included 672 patients (49.9% cannabis users). Cannabis users were more likely to consume alcohol (odds ratio 1.46, 95% CI 1.04–2.06, P = 0.029) and have anxiety disorders (odds ratio 1.75, 95% CI 1.02–3.02, P = 0.043), but were less likely to use heroin (odds ratio 0.45, 95% CI 0.24–0.86, P = 0.016). There was no association between cannabis use and pain (odds ratio 0.98, 95% CI 0.94–1.03, P = 0.463). A significant association was seen between alcohol and cannabis use in women (odds ratio 1.79, 95% CI 1.06–3.02, P = 0.028), and anxiety disorders and cannabis use in men (odds ratio 2.59, 95% CI 1.21–5.53, P = 0.014). Heaviness of cannabis use was not associated with health outcomes.

Conclusions

Our results suggest that cannabis use is common and associated with psychiatric comorbidities and substance use among patients in MMT, advocating for screening of cannabis use in this population.

Declaration of interest

None.
Subsequent Cancer Prevention and Control Activities Among Low- and Middle-Income Country Participants in the US National Cancer Institute’s Summer Curriculum in Cancer Prevention
Authors: Vogel Amanda L. , Morgan Camille , Duncan Kalina , Williams Makeda J.
Published: October 2019

PURPOSE

A dramatic shift in the burden of cancer from high-income countries to low- and middle-income countries (LMICs) is predicted to occur over the next few decades. An effective response requires a range of approaches to capacity building in cancer prevention and control in LMICs, including training of cancer prevention and control professionals. Toward this end, the US National Cancer Institute includes LMIC-based participants in its Summer Curriculum in Cancer Prevention, which is an annual, short-term in-person training program.

METHODS

In 2015 and 2016, the US National Cancer Institute fielded a survey to all Summer Curriculum alumni who were based in LMICs when they participated in the program, between 1998 and 2015. Its aims were to learn about subsequent engagement in cancer prevention and control in LMICs and attribution of activities/accomplishments to participation in the Summer Curriculum in Cancer Prevention.

RESULTS

Respondents (N = 138) worked in academia/research (n = 61), health care (n = 41), and health policy/Ministries of Health (n = 36) in all six world regions. Most respondents (90.6%) worked in the same LMIC as when they participated in the Summer Curriculum in Cancer Prevention. When asked about activities/accomplishments completed as a result of participation, 92.8% reported at least one cancer prevention and control practice activity/accomplishment, 81.2% reported at least one cancer research activity/accomplishment, and 44.2% reported authoring one or more peer-reviewed publications. Reported ways that the Summer Curriculum in Cancer Prevention contributed to these activities/accomplishments were emphasizing a public health approach; focusing on research priorities, methods, and scientific writing; and highlighting the importance of research and publications. Finally, 79.7% of respondents reported using Summer Curriculum in Cancer Prevention materials to train others.

CONCLUSION

These findings have implications for the design of future training initiatives for LMIC-based cancer prevention and control professionals.
Archival Practice in Premodern Korea: Record-Keeping as Archive and Historiography
Authors: Vermeersch Sem
Published: October 2019

Historians of premodern Korea struggle with the apparent absence of any genuine archives. Although documents that are traditionally seen to belong in an archive have been transmitted, they are nearly all unique samples. In other words, they do not form part of an organic collection; they are random examples that somehow have been preserved. The term archive has become the staple of European history writing since the nineteenth century, when Leopold von Ranke turned to archives as the prime hunting ground for historical research. Yet he only discovered and used systematically what was there—vast collections of documents hoarded by institutions. By contrast, in Korea, history writing had always been monopolized by the state, and while a vast amount of written documents must have been produced to keep the bureaucracy running, barely any of them have survived. Rather than being kept, they were simply reflected in the vast collections of what I call “processed” records or “meta-archives,” of which the most well-known is the sillok (veritable records). Thus we are dealing with a different “recording culture,” one that obviated the need for “archives” in the sense of (more or less) organized collections of primary documents.
Compiling Diplomacy: Record-Keeping and Archival Practices in Chosŏn Korea
Authors: Wang Sixiang
Published: October 2019

The Chosŏn court kept meticulous records of its interactions with their Ming, and later, their Qing neighbors. These materials, especially those that predate the nineteenth century, survive not in the form of original materials but rather as entries in court-sponsored compilations. For instance, the monumental Tongmun hwigo, published in 1788, categorizes diplomatic activity according to areas of policy concern. Its organizational scheme, handy for a Chosŏn official searching for relevant precedents, has also provided ready material for historical case studies. What has been less appreciated, however, are how such records came into being in the first place. By interrogating the status of these compilations as “archives,” this article follows how diplomatic documents were produced, used, and compiled as both products and instruments of diplomatic practice. In reading these materials as instruments of knowledge, rather than mere sources of historical documentation, this essay also makes the case for going beyond diplomatic history as interstate relations and towards a cultural and epistemic history of Korean diplomatic practice.
Heparan sulfate negatively regulates intestinal stem cell proliferation in Drosophila adult midgut
Authors: Ma Hubing , Zhao Huiqing , Liu Fuli , Zhao Hang , Kong Ruiyan , Shi Lin , Wei Min , Li Zhouhua
Published: October 2019

Tissue homeostasis is maintained by differentiated progeny of residential stem cells. Both extrinsic signals and intrinsic factors play critical roles in the proliferation and differentiation of adult intestinal stem cells (ISCs). However, how extrinsic signals are transduced into ISCs still remains unclear. Here, we find that heparan sulfate (HS), a class of glycosaminoglycan (GAG) chains, negatively regulates progenitor proliferation and differentiation to maintain midgut homeostasis under physiological conditions. Interestingly, HS depletion in progenitors results in inactivation of Decapentaplegic (Dpp) signaling. Dpp signal inactivation in progenitors resembles HS-deficient intestines. Ectopic Dpp signaling completely rescued the defects caused by HS depletion. Taken together, these data demonstrate that HS is required for Dpp signaling to maintain midgut homeostasis. Our results provide insight into the regulatory mechanisms of how extrinsic signals are transduced into stem cells to regulate their proliferation and differentiation.
Cell signaling stabilizes morphogenesis against noise
Authors: Hagolani Pascal F. , Zimm Roland , Marin-Riera Miquel , Salazar-Ciudad Isaac
Published: October 2019

Embryonic development involves gene networks, extracellular signaling, cell behaviors (cell division, adhesion, etc.) and mechanical interactions. How should these be coordinated to lead to complex and robust morphologies? To explore this question, we randomly wired genes and cell behaviors into a huge number of networks in EmbryoMaker. EmbryoMaker is a computational model of animal development that simulates how the 3D positions of cells, i.e. morphology, change over time due to such networks. We found that any gene network can lead to complex morphologies if this activates cell behaviors over large regions of the embryo. Importantly, however, for such complex morphologies to be robust to noise, gene networks should include cell signaling that compartmentalizes the embryo into small regions where cell behaviors are regulated differently. If, instead, cell behaviors are equally regulated over large regions, complex but non-robust morphologies arise. We explain how compartmentalization enhances robustness and why it is a general feature of animal development. Our results are consistent with theories proposing that robustness evolved by the co-option of gene networks and extracellular cell signaling in early animal evolution.
Scribble and discs-large direct initial assembly and positioning of adherens junctions during establishment of apical-basal polarity
Authors: Bonello Teresa T. , Choi Wangsun , Peifer Mark
Published: October 2019

Apical-basal polarity is a fundamental property of animal tissues. Drosophila embryos provide an outstanding model for defining mechanisms initiating and maintaining polarity. Polarity is initiated during cellularization, when cell-cell adherens junctions are positioned at the future boundary of apical and basolateral domains. Polarity maintenance then involves complementary and antagonistic interplay between apical and basal polarity complexes. The Scribble/Dlg module is well-known for promoting basolateral identity during polarity maintenance. Here we report a surprising role for Scribble/Dlg in polarity initiation, placing it near the top of the network positioning adherens junctions. Scribble and Dlg are enriched in nascent adherens junctions, are essential for adherens junction positioning and supermolecular assembly, and also play a role in basal junction assembly. We test hypotheses for the underlying mechanisms, exploring potential effects on protein trafficking, cytoskeletal polarity, or Par-1 localization/function. Our data suggest that the Scribble/Dlg module plays multiple roles in polarity initiation. Different domains of Scribble contribute to these distinct roles. Together these data reveal novel roles for Scribble/Dlg as master scaffolds regulating assembly of distinct junctional complexes at different times and places.
Novel mouse model of encephalocele: post-neurulation origin and relationship to open neural tube defects
Authors: Rolo Ana , Galea Gabriel L. , Savery Dawn , Greene Nicholas D. E. , Copp Andrew J.
Published: October 2019

Encephalocele is a clinically important birth defect that can lead to severe disability in childhood and beyond. The embryonic and early fetal pathogenesis of encephalocele is poorly understood and, while usually classified as a ‘neural tube defect’, there is conflicting evidence on whether encephalocele results from defective neural tube closure, or is a post-neurulation defect. It is also unclear whether encephalocele can result from the same causative factors as anencephaly and open spina bifida, or whether it is aetiologically distinct. This lack of information results largely from the scarce availability of animal models of encephalocele, particularly ones that resemble the commonest, non-syndromic human defects. Here, we report a novel mouse model of occipito-parietal encephalocele, in which the small GTPase Rac1 is conditionally ablated in the (non-neural) surface ectoderm. Most mutant fetuses have open spina bifida, and some also exhibit exencephaly/anencephaly. However, a proportion of mutant fetuses exhibit brain herniation, affecting the occipito-parietal region and closely resembling encephalocele. The encephalocele phenotype does not result from defective neural tube closure, but rather from a later disruption of the surface ectoderm covering the already closed neural tube, allowing the brain to herniate. The neuroepithelium itself shows no down-regulation of Rac1 and appears morphologically normal until late gestation. A large skull defect overlies the region of brain herniation. Our work provides a new genetic model of occipito-parietal encephalocele, particularly resembling non-syndromic human cases. While encephalocele has a different, later-arising pathogenesis than open neural tube defects, both can share the same genetic causation.
SILAC-based quantitative mass spectrometry-based proteomics quantifies endoplasmic reticulum stress in whole HeLa cells
Authors: Itzhak Daniel N. , Sacco Francesca , Nagaraj Nagarjuna , Tyanova Stefka , Mann Matthias , Murgia Marta
Published: October 2019

The unfolded protein response (UPR) involves extensive proteome remodeling in many cellular compartments. So far, a comprehensive analysis has been missing due to technological limitations. Here we employ Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC)-based proteomics to quantify over 6200 proteins at increasing concentrations of tunicamycin in HeLa cells. We further compare the effects of tunicamycin (5 ug/ml) to those of thapsigargin (1 µM) and DTT (2mM), both activating the UPR through different mechanisms. The systematic quantification of the proteome-wide expression changes following proteostatic stress is a resource for the scientific community, which enables the discovery of novel players involved in the pathophysiology of the broad range of disorders linked to proteostasis. We identified 38 proteins not previously linked to the UPR, whose expression increases, of which 15 likely remediate ER stress, and the remainder may contribute to pathological outcomes. Unexpectedly, there are few strongly downregulated proteins, despite expression of the pro-apoptotic transcription factor CHOP, suggesting that IRE1-dependent mRNA decay (RIDD) has a limited contribution to ER-stress mediated cell death in our system.
NGOs’ experiences of navigating the open access landscape
Authors: McGrath Nilam
Published: October 2019

Grant-led consortia working in the global development sector rely on the input of local and national non-government organisations in low- and middle-income countries. However, the open access mandates and mechanisms embedded within grants and promoted by funders and publishers are designed almost exclusively with large universities and research institutions in mind. Experiences from the consortium of health research non-government organisations comprising the Communicable Diseases Health Service Delivery research programme show that implementing open access mandates is not as simple or frictionless as it initially appears.
Preliminary assessment of adaptive evolution of mitochondrial protein coding genes in darters (Percidae: Etheostomatinae)
Authors: Kral Leos G. , Watson Sara
Published: October 2019

Background:Mitochondrial DNA of vertebrates contains genes for 13 proteins involved in oxidative phosphorylation. Some of these genes have been shown to undergo adaptive evolution in a variety of species. This study examines all mitochondrial protein coding genes in 11 darter species to determine if any of these genes show evidence of positive selection.

Methods:The mitogenome from four darter was sequenced and annotated. Mitogenome sequences for another seven species were obtained from GenBank. Alignments of each of the protein coding genes were subject to codon-based identification of positive selection by Selecton, MEME and FEL.

Results:Evidence of positive selection was obtained for six of the genes by at least one of the methods.CYTBwas identified as having evolved under positive selection by all three methods at the same codon location.

Conclusions:Given the evidence for positive selection of mitochondrial protein coding genes in darters, a more extensive analysis of mitochondrial gene evolution in all the extant darter species is warranted.
How Do Accelerators Impact the Performance of High-Technology Ventures?
Authors: Yu Sandy
Published: October 2019

Accelerators aim to help nascent companies reach successful outcomes by providing capital, enabling industry connections, and increasing exposure to investors. Critically, however, accelerators also provide informative signals to founders about the probability of success. Founders use this information to decide whether to continue or shut down. To better understand these issues, I provide a model of accelerator participation and performance and then test empirical predictions from the model using a novel data set of approximately 900 accelerator companies across 13 accelerators and 900 matched nonaccelerator companies. I find that, through accelerator feedback effects, accelerator companies close down earlier and more often, raise less money conditional on closing, and appear to be more efficient investments compared with non-accelerator companies. Additional analysis using a separate sample of rejected accelerator applicants further supports these findings. These results suggest that accelerators help resolve uncertainty around company quality sooner, allowing founders to make funding and exit decisions accordingly.

This paper was accepted by Ashish Arora, entrepreneurship and innovation.
Improving Air Crew Rostering by Considering Crew Preferences in the Crew Pairing Problem
Authors: Quesnel Frédéric , Desaulniers Guy , Soumis François
Published: October 2019

A common strategy used by airlines to improve employee satisfaction is to create schedules that take into account crew preferences such as preferred legs or desired off-periods. Air crew scheduling usually involves two steps: the crew pairing problem (CPP) and the crew rostering problem (CRP). A pairing is a sequence of legs and deadheads separated by connections and rest periods that starts and ends at the same crew base and can legally be operated by a crew member. The CPP generates a set of pairings that covers every leg of a given schedule exactly once at a minimum cost. The CRP uses these pairings to create rosters composed of personalized schedules, with the goal of granting as many crew preferences as possible. A downside of this two-step approach is that the CPP does not take the crew preferences into account, resulting in CPP solutions that are often ill suited for the CRP. In this paper, we propose a new variant of the CPP, called the CPP with complex features (CPPCF), that considers the crew preferences in order to create pairings that are better suited for the CRP. Specifically, we identify six pairing features related to crew preferences that are beneficial for the CRP, and the objective function of the CPPCF rewards pairings that contain these features. We solve the CPPCF using a column generation algorithm in which new pairings are generated by solving subproblems consisting of constrained shortest path problems. For this purpose, we introduce a new type of path resources designed to handle complex features, and we adapt the dominance rules accordingly. We test the proposed CPPCF approach on seven real-world instances from a major North American airline and show that a combination of these features significantly improves the solutions of the CRP.
Webcare in healthcare: providers' responses to patients' online reviews
Authors: Zwier Sandra
Published: October 2019

Background/Aims

Providers face a paradox between professional conduct and reputation management when they respond to patients' online reviews. This article aims to establish when and how health professionals respond to patients' online reviews, and how these reviews differ compared to other, non-medical, industries, such as driving schools and jewellery stores.

Methods

Predictors of providers' responses to 180 patient reviews on NHS Choices were identified and compared against the predictors of responses to 180 customer reviews by non-medical providers.

Results

Responses to patients' online reviews could be significantly predicted by the number of patient reviews received on NHS Choices and the providers' response routines, but not by characteristics of the patients' reviews. The non-medical providers, on the other hand, were responsive to characteristics of the online reviews and particularly the rating stars allocated to the provider.

Conclusions

Responses to reviews seem to be a distinctive way of ‘responding without reacting’.
Development of an Automated Enzymatic Method to Quantify Pyruvate Kinase in Red Blood Cells
Authors: Lu Jun , Grenache David G
Published: October 2019

Background

Pyruvate kinase (PK) deficiency is the most common cause of nonspherocytic hemolytic anemia owing to defective glycolysis. This study developed and validated an automated method to measure PK activity in red blood cells (RBCs).

Methods

PK catalyzes the reaction of phosphoenolpyruvate with ADP to form pyruvate and ATP. The pyruvate is reduced in the presence of lactate dehydrogenase and NADH to produce lactate and NAD+. The rate of absorbance decrease at 340 nm is proportional to PK activity. PK and hemoglobin (Hb) measurements were performed on a Roche cobas c501 analyzer. After establishing a k-factor, accuracy, linearity, imprecision, sensitivity, and stability were validated and the reference interval was verified.

Results

The k-factor was −9477. Accuracy was evaluated by method comparison (n = 56). Linear regression yielded y = 1.0x − 0.57, and R2 of 0.93. Linearity was determined by combining a high sample with hemolyzing solution in 6 different ratios. Linear regression analysis yielded y = 1.02x − 2.68, and R2 of 1.0. The assay was linear to 87 U/dL. Precision was evaluated by testing hemolysates in 3 replicates/day for 10 days. Within-run imprecision was 1.9% and 2.5% and total imprecision was 4.0% and 5.6% at 14.0 and 8.1 U/g Hb, respectively. The limit of blank was 0.0, and the limit of detection was 1.0 U/dL. Stability was determined in 4 sample types at 3 different temperatures; the changes were all <10% when compared with t0. The current PK reference interval of 4.6 to 11.2 U/g Hb was verified.

Conclusions

This automated assay for quantifying PK in RBCs has acceptable performance characteristics and is fit for intended use.
Accessibility and participation in the use of an inclusive musical instrument: The case of MotionComposer
Authors: Peñalba Alicia , Valles María-José , Partesotti Elena , Sevillano María-Ángeles , Castañón Rosario
Published: October 2019

Digital musical instruments (DMI) can make musical practice accessible to non-trained persons or to persons with limitations related to their age, gender or musical experience. The present study explores accessibility and participation in a sample of 266 individuals using a device named MotionComposer, a digital instrument based on motion capture. By experimenting with this device during four minutes in two different environments (one causal, the other one more aprioristically determined), we study the kind of participant interaction that takes place. Results show that MotionComposer allows for a statistically significant similar interaction in people of different ages and genders and with different disabilities. However, there are two exceptions that can be accounted for in connection with the causality-randomness of the two environments where the experimentation takes place.