bluuebunny/crossref_metadata_2025 huggingface dataset:
Principles of mRNA control by human PUM proteins elucidated from multi-modal experiments and integrative data analysis
Authors: Wolfe Michael B. , Schagat Trista L. , Paulsen Michelle T. , Magnuson Brian , Ljungman Mats , Park Daeyoon , Zhang Chi , Campbell Zachary T. , Goldstrohm Aaron C. , Freddolino Peter L.
Published: April 2020

The human PUF-family proteins, PUM1 and PUM2, post-transcriptionally regulate gene expression by binding to a PUM recognition element (PRE) in the 3’ UTR of target mRNAs. Hundreds of PUM1/2 targets have been identified from changes in steady state RNA levels; however, prior studies could not differentiate between the contributions of changes in transcription and RNA decay rates. We applied metabolic labeling to measure changes in RNA turnover in response to depletion of PUM1/2, showing that human PUM proteins regulate expression almost exclusively by changing RNA stability. We also applied an in vitro selection workflow to precisely identify the binding preferences of PUM1 and PUM2. By integrating our results with prior knowledge, we developed a ‘rulebook’ of key contextual features that differentiate functional vs. non-functional PREs, allowing us to train machine learning models that accurately predict the functional regulation of RNA targets by the human PUM proteins.
Two-Step Bacterial Artificial Chromosome (BAC) Engineering: Electroporation of Competent BAC Host Cells with the Recombinant Shuttle Vector
Authors: Heintz Nathaniel , Gong Shiaoching
Published: April 2020

Bacterial artificial chromosome (BAC) clones are rendered electrocompetent and transformed with the recombinant shuttle vector, pLD53SCAB/AB-box. Cointegrates are selected by growth on chloramphenicol and ampicillin to ensure recombination of the shuttle vector into the BAC.
Two-Step Bacterial Artificial Chromosome (BAC) Engineering: Verification of Co-Integrates and Selection of Resolved BAC Clones
Authors: Heintz Nathaniel , Gong Shiaoching
Published: April 2020

Successful modification of the bacterial artificial chromosome (BAC) after two-step BAC engineering is confirmed in two separate polymerase chain reactions (PCRs). The first reaction (5′ co-integrate PCR) uses a forward 5′ co-integrate primer (a sequence located upstream of the 5′ end of the A-box) and a reverse 3′ primer on the vector (175PA+50AT) or within the reporter sequence or mutated region as appropriate. The second reaction (3′ co-integrate PCR) uses a forward 5′ primer on the recA gene (RecA1300S) and a reverse 3′ co-integrate primer (a sequence located downstream from the 3′ end of the B-box). Those colonies shown to be positive in PCR analysis are further tested for sensitivity to UV light. After the resolution, colonies that have lost the excised recombination vector including sacB and recA genes become UV light sensitive.
Labeling Antibodies Using Europium
Authors: Berg Eric A. , Fishman Jordan B.
Published: April 2020

There are many uses for antibodies labeled with metal ions. Most of these methods involve first attaching a metal chelator to the antibody molecule. This is achieved using standard cross-linking chemistry and then adding the desired metal at appropriate concentration and pH. The method described here outlines a basic procedure for creating a lanthanide conjugate. Lanthanide conjugates are used for proximity assays, as MRI contrast agents, or for mass cytometry experiments. Different metals and chelators can be substituted, but the basic procedures are similar.
Bradford Assay for Determining Protein Concentration
Authors: Kielkopf Clara L. , Bauer William , Urbatsch Ina L.
Published: April 2020

The Bradford assay is a quick and fairly sensitive method for measuring the concentrations of proteins. It is based on the shift in absorbance maximum of Coomassie Brilliant Blue G-250 dye from 465 to 595 nm following binding to denatured proteins in solution.
Crystal structure of monomeric Amuc_1100 from Akkermansia muciniphila
Authors: Mou Luqiu , Peng Xi , Chen Yan , Xiao Qingjie , Liao Huijuan , Liu Mingfeng , Guo Li , Liu Yang , Zhang Xiaohu , Deng Dong
Published: April 2020

Many human diseases, such as obesity and diabetes, show annual increases in prevalence and often involve intestinal microbes. One such probiotic bacterium, Akkermansia muciniphila, which was discovered a decade ago, has been reported to influence glucose homeostasis and to contribute to gut health. Amuc_1100, a functionally uncharacterized protein of A. muciniphila, was found to be a key active component in reducing the body weight of mice. Here, the crystal structure of Amuc_1100 (residues 31–317), referred to as Amuc_1100*, is reported at 2.1 Å resolution. Amuc_1100* has a similar fold to three proteins related to pilus formation, PilO, PilN and EpsL, indicating a similar function. Biochemical investigations further confirmed a monomeric state for the soluble region of Amuc_1100, which differs from the dimeric states of PilO, PilN and EpsL. This study provides a structural basis for the elucidation of the molecular mechanism of Amuc_1100.
The impact of the reform of PIS/COFINS on the Brazilian industry
Authors: Vasconcelos Pedro Gomes , Paes Nelson Leitão
Published: April 2020

Purpose

In an attempt to reduce tax distortions and increase economic efficiency, in 2002 and 2003 Brazil promoted changes in the PIS/COFINS tax, the main federal tax on consumption. Thus, in addition to the old cumulative regime calculated on company revenues, the noncumulative regime was created with higher rates and the added value as a tax basis.

Design/methodology/approach

This paper analyzes the effects of the PIS/COFINS reform in a context of deindustrialization in the Brazilian economy, using a neoclassical model with two sectors.

Findings

The results suggest that after a small improvement in the aggregate economy in the short term, in the long term there was a worsening of the macroeconomic indicators. From the sector perspective, the PIS/COFINS reform may have contributed to the loss of industry participation in the Brazilian economy.

Originality/value

The study of the impact of the PIS/COFINS reform on industry through a neoclassical model is unprecedented in the national literature and contributes to the investigation of changes in the tax regime that occurred in the country.
Status, stress and fit: comparing the faculty stress impact of university consolidations
Authors: Ribando Saundra J. , Slade Catherine P. , Fortner C. Kevin
Published: April 2020

Purpose

Institutions of higher education face challenges of fiscal responsibility and their value proposition for students and other stakeholders they serve. Strategies used in business sectors, such as merger and acquisition, are being increasingly adopted by higher education governing boards, especially for public institutions and systems. The purpose of this paper is to guide policy decisions related to university mergers.

Design/methodology/approach

This paper focuses on the interplay between the pre-merger status of the institution, the individual faculty member's sense of belonging, and their commitment to the organization on levels of job-related stress, which has well-established negative impacts on individual and organizational performance. Using survey data collected at the same time post-merger from two different universities within the same state system, we explore regression models to identify similarities and differences between the faculty responses in terms of the impact of the merger on faculty stress.

Findings

Differences are found between the two universities in terms of faculty stress with faculty of one low status institution pre-merger having significantly higher stress post-merger. A case is presented for differences in stress based on a part on differences in how the mergers were managed at the system and university levels.

Practical implications

This research is instructive for higher education policy makers and university administrators as the institution of higher education continues this type of transformation.

Originality/value

This paper examines the impact of mergers on a university's single-most important asset, faculty. Comparative and timely faculty survey results from two related universities early post-merger provide valuable insights for leaders in higher education.
If you build it, will they log on? Wi–Fi usage and behavior while attending National Basketball Association games
Authors: Naraine Michael L. , O'Reilly Norm , Levallet Nadège , Wanless Liz
Published: April 2020

Purpose

Although sports fans have increased their use of digital media to consume sport, especially at professional sport venues, it is unknown the extent to which patrons of said venues are utilizing venue services for these activities. As such, this study asks: (1) How much data do patrons at a sports venue consume via the provided Wi–Fi? and (2) What types of online activity behaviors do Wi–Fi users at sports venues exhibit?

Design/methodology/approach

This empirical study reports stadia Wi–Fi data usage and consumer behavior from three National Basketball Association venues in the United States: Amway Center in Orlando, FL, Barclays Center in Brooklyn, NY and Target Center in Minneapolis, MN, over a course of 7 games per venue.

Findings

The findings suggest that Wi–Fi usage is more limited than anticipated. Users who do utilize the venue Wi–Fi do so for very short periods, with the vast majority of user duration lasting between 1 and 10 min. Additionally, the halftime period of games experiences the peak of Wi–Fi usage.

Originality/value

By increasing our understanding of Wi–Fi usage in venues, this study informs relationship marketing theory research and contributes to the sport management literature. Practically, a better knowledge of Wi–Fi usage is critical, as it constitutes a critical antecedent to develop online marketing strategies.
Exception to the exception rule: synthetic and naturally occurring single chromosome Vibrio cholerae
Authors: Sozhamannan Shanmuga , Waldminghaus Torsten
Published: April 2020

The genome of Vibrio cholerae, the etiological agent of cholera, is an exception to the single chromosome rule found in the vast majority of bacteria and has its genome partitioned between two unequally sized chromosomes. This unusual two‐chromosome arrangement in V. cholerae has sparked considerable research interest since its discovery. It was demonstrated that the two chromosomes could be fused by deliberate genome engineering or forced to fuse spontaneously by blocking the replication of Chr2, the secondary chromosome. Recently, natural isolates of V. cholerae with chromosomal fusion have been found. Here, we summarize the pertinent findings on this exception to the exception rule and discuss the potential utility of single‐chromosome V. cholerae to address fundamental questions on chromosome biology in general and DNA replication in particular.
Painting/Politics/Photography: Marlene Dumas, Mme Lumumba and the Image of the African Woman
Authors: Garb Tamar
Published: April 2020

This essay looks at the politics of portrayal, photography and figuration in relation to the colonial/apartheid archive. It focuses on the Dutch/South African artist Marlene Dumas's reworking of a selection images – both personal and public – in order to question contemporary painting's capacity to deal with history, and in particular its spectacular or photogenic trace. By using the painted reworking of both her old school photograph as well as an iconic depiction of Mme Pauline Lumumba, it asks what painting can do when it takes on the photographic past. At the same time, it explores the interpretive filters that have coalesced around the figure of the ‘bare‐breasted African widow’.
Properties of novel chitosan incorporated with hexahydro‐β‐acids edible films and its effect on shelf life of pork
Authors: Chen Fengxia , Li Shuai , Zhong Genghui , Liu Yumei
Published: April 2020

Edible packaging films have been widely studied because of its safety, green, and effective characteristics. In this paper, chitosan (CH) edible films containing hexahydro‐β‐acids (HBA) were prepared, and its physical and mechanical properties, bioactivity, and their impact on the shelf life of pork were investigated. The infrared spectra indicated that the molecular interaction between CH and HBA was observed. Scanning electron microscopy was used to analyze the surface morphology of the film, and light transmittance analysis displayed that the addition of HBA enhanced the film's UV blocking performance. Compared to the CH film, the tensile strength of CH–HBA film increased to 29.19 ± 0.45 MPa, and the scavenging activity of 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) reached 1.40 ± 0.01 mg rutin/cm2 of the film. The antibacterial activity of the CH–HBA film on Escherichia coli (44825) and Staphylococcus aureus (26001) showed that the CH–HBA film is a feasible antibacterial package. Furthermore, compared to pork packaged in CH and polyethylene films, fresh pork packaged with CH–HBA films displayed prolongation of shelf life due to reduction in microbial proliferation, thiobarbituric values, pH, and total volatile base nitrogen contents during storage at 4 °C for 16 days. The freshness of pork was prolonged by 7−8 days when the dosage of HBA was increased to 0.3% from 0.1% (w/v). These results revealed that the CH–HBA film can effectively extend the shelf life of pork.

Practical Application

This study effectively prolonged the shelf life of pork. A chitosan‐edible film combined with hexahydro‐β‐acids has a potential application value in replacing traditional packaged fresh meat.
Evaluation of the introduction of a ‘traffic light protocol’ for dose‐volume histogram constraints of organs at risk in definitive radiotherapy at Liverpool and Macarthur Cancer Therapy Centres
Authors: Kasraei Farshad , Ochoa Cesar , Vial Phillip , Lee Mark T
Published: April 2020

Introduction

Protocols have been developed in our department with recommended dose constraints for organs at risk (OAR) for each tumour site receiving definitive radiotherapy. We have developed a colour coding system to indicate when constraints are meeting objectives (green), have minor variation from planning objectives (yellow) and have major variation from planning objectives (red). We performed a quality audit to assess adherence to the protocol and to determine the rate of acute and subacute toxicities.

Methods

All definitive radiotherapy dose‐volume histogram (DVH) reports generated in the first 6 months of 2017 at Liverpool and Macarthur cancer therapy centres were collected. For each radiotherapy group, the overridden dose constraints were evaluated and categorized to red and yellow. For all patients in our data set, follow‐up documents/assessments were searched for grade 3 or higher acute or subacute radiotherapy toxicity and compared with those who had overridden dose constraints.

Results

There were 210 (34%) plans accepted with at least one major variation and 161 (26%) plans with minor variation. Head and neck group had the most rate of major variations (77%). The best groups in adherence to protocol were lymphoma and breast groups. In general, grade 3 toxicity was observed in 1%, 4% and 9% of patients who were in green, yellow and red categories. Overall, we noted a correlation with grade 3 toxicities between acceptable plans (green) and ones with a minor or major variation (yellow or red) (1% vs. 7% P = 0.0001).

Conclusion

In conclusion this study showed an increased risk of higher grade toxicities when DVHs were beyond our departmental constraints using a ‘Traffic Light System’. With this new colour coding system, we can facilitate auditing of the dose constraints in order to improve the quality of radiotherapy plans and potentially provide benchmarking for reducing toxicities in radiotherapy treatments.
Effects of simulated sample sizes on the mortality effect estimates in three randomized intensive care unit trials
Authors: Kofoed Andreas , Perner Anders , Marker Søren , Haase Nicolai , Holst Lars B. , Møller Morten Hylander
Published: April 2020

Background

Randomized clinical trials (RCTs) are occasionally stopped prematurely before reaching their planned sample sizes. It has been suggested that early stopped RCTs are associated with under‐ and overestimation of the effect estimates. We simulated the effect of hypothetical premature stopping of three large RCTs done in the intensive care unit (ICU) setting.

Methods

In this post hoc study, we simulated the impact of stopping trials early by calculating mortality effect estimates continuously after the inclusion of each individual patient in three large RCTs, that is the 6S trial on hydroxyethyl starch vs Ringer's acetate in sepsis in ICU, the TRISS trial on lower vs higher haemoglobin threshold for transfusion in septic shock in ICU and the SUP‐ICU trial on pantoprazole in patients at risk for gastrointestinal bleeding in the ICU.

Results

The three trials included a total of 5087 patients; 798 from the 6S trial, 998 from the TRISS trial and 3291 patients from the SUP‐ICU trial. The premature mortality effect estimates showed considerable fluctuations until at least 20%‐30% of the sample size was included. The premature estimates became stable after inclusion of 205 patients (26% of the final sample size) in the 6S trial, 133 patients(13%) in the TRISS trial and 1926 patients(59%) in the SUP‐ICU trial.

Conclusions

In this post hoc study of three international RCTs within intensive care, we found that the simulated interim mortality effect estimates showed considerable fluctuations until at least 20%‐30% of the sample size was included, but remained instable until the final sample sizes had been included. Thus, this study illustrates the necessity for cautious interpretations of prematurely stopped trials.
Sociomaterial movements of students' engagement in a school's makerspace
Authors: Kumpulainen Kristiina , Kajamaa Anu
Published: April 2020

This study investigates the sociomaterial movements of student engagement in a school's makerspace. Here, we understand sociomaterial movements as emergent and relational, comprising complex dynamics of agency across students, teachers and materials in situated, culturally framed activities. Our study draws on data comprising 85 hours of video recordings of 9–12‐year‐old students' (N = 94) engagement in a technology‐rich makerspace in a Finnish elementary school. The video data were transcribed and analyzed qualitatively using a multimodal interaction analysis. The sociomaterial movements were found to be displayed across a tension‐laden continuum between (1) procedural activity—analysis and reflection; (2) individual activity—collaboration; (3) “doing school”—empowerment; and d) alienation—identification. Together, the study offers a potential approach for investigating and understanding the often overlooked workings of sociomateriality that constitutes students' emergent engagement and learning opportunities in science, technology, engineering and mathematics (STEAM) learning contexts.
A five‐year follow‐up of untreated patients with chronic lymphocytic leukaemia treated with ofatumumab and chlorambucil: final analysis of the Complement 1 phase 3 trial
Authors: Offner Fritz , Robak Tadeusz , Janssens Ann , Govind Babu K. , Kloczko Janusz , Grosicki Sebastian , Mayer Jiri , Panagiotidis Panagiotis , Schuh Anna , Pettitt Andrew , Montillo Marco , Werner Olena , Vincent Ghislaine , Khanna Sadhvi , Hillmen Peter
Published: April 2020

The Complement 1 trial investigated the efficacy and safety of ofatumumab + chlorambucil with chlorambucil monotherapy in patients with previously untreated chronic lymphocytic leukaemia (CLL). On long‐term follow‐up in the chemoimmunotherapy arm vs. the chemotherapy arm there was an estimated 12% (not significant) and 39% risk reduction in overall survival and progression‐free survival, respectively. A high rate (61%) of treatment with next‐line therapies in both the treatment arms may dilute any potential OS difference and confound the interpretation of the OS results. Addition of ofatumumab to chlorambucil demonstrated clinical benefit and tolerability as a frontline treatment option in patients unfit for fludarabine‐containing therapy, with no new safety concerns.
Making sense of complexity: A qualitative investigation into forensic learning disability nurses’ interpretation of the contribution of personal history to offending behaviour
Authors: Lovell Andrew , Skellern Joanne
Published: April 2020

Accessible Summary

The role of an individual's personal history is important in influencing their development, especially whether they are likely to offend or engage in violent behaviour

Learning disability nurses relationships with those with a history of violence or offending will improve with a more informed knowledge of how someone's offending behaviour is related to their background

People with a learning disability can be supported best when the complexity of their lives is fully understood and properly informs the therapeutic relationship.

Background

There is growing recognition that an individual's personal history can be extremely influential in shaping their future experience, though there has been a limited exploration in the context of learning disability and offending behaviour.

Method

Research questions related to participant interpretation of offending behaviour and individual and service responses. A series of focus groups comprising learning disability forensic nurses were conducted across all secure settings, high, medium and low.

Results

Three themes were produced: interpreting offending behaviour; the impact of personal history; responding therapeutically. The difficulties relating to understanding the relationship between offending behaviour and personal history significantly informed the construction of the most effective therapeutic relationships.

Conclusions

An increased focus on the impact of someone's background might inform nursing as it seeks to deliver care to individuals with increasingly complex needs in a time of service transition.
Symbiotic prodrugs (SymProDs) dual targeting of NFkappaB and CDK
Authors: Rana Sandeep , Kour Smit , Sonawane Yogesh A. , Robb Caroline M. , Contreras Jacob I. , Kizhake Smitha , Zahid Muhammad , Karpf Adam R. , Natarajan Amarnath
Published: April 2020

The release of an active drug from the prodrug generates a pro‐fragment that typically has no biological activity and could result in adverse effects. By combining two drugs, wherein each drug acts as a pro‐fragment of the other drug will eliminate the pro‐fragment in the prodrug. As they are prodrugs of each other and are symbiotic, we termed these as symbiotic prodrugs (SymProDs). To test this idea, we generated SymProDs using NFκB inhibitors that contain the reactive α‐methylene‐γ‐butyrolactone moiety and CDK inhibitors with solvent exposed secondary nitrogen atoms. We show that secondary amine prodrugs of α‐methylene‐γ‐butyrolactone containing NFκB inhibitors undergo slow release over a 72 hr period. Using an alkyne‐tagged secondary amine prodrug of α‐methylene‐γ‐butyrolactone containing NFκB inhibitor, we demonstrate target engagement. The NFκB‐CDK SymProDs were ~20‐ to 200‐fold less active against the corresponding CDK inhibitors in in vitro CDK kinase assays. Growth inhibition studies in a panel of ovarian cancer cell lines revealed potency trends of the SymProDs mirrored those of the single treatments suggesting their dissociation in cells. In conclusion, our results suggest that SymProDs offer a productive path forward for advancing compounds with reactive functionality and can be used as dual targeting agents.
Long‐term prognosis of Japanese Lambert–Eaton myasthenic syndrome patients with or without small‐cell lung carcinoma
Authors: Kojima Yuta , Uzawa Akiyuki , Shibuya Kazumoto , Yasuda Manato , Ozawa Yukiko , Oda Fumiko , Shiraishi Hirokazu , Motomura Masakatsu , Kuwabara Satoshi
Published: April 2020

Objective

Lambert–Eaton myasthenic syndrome (LEMS) is a paraneoplastic neurological syndrome, most frequently associated with small‐cell lung carcinoma (SCLC). The survival of LEMS patients depends on the presence of SCLC, whereas the functional outcome in patients without SCLC has not been fully clarified. The aim of this study was to elucidate the long‐term prognosis of LEMS patients with or without SCLC.

Methods

We collected data from seven consecutive Japanese patients with LEMS without SCLC (n = 4) or LEMS with SCLC (n = 3) consulting Chiba university hospital, Chiba, Japan from 2003 to 2019. The functional disability was assessed with the modified Rankin Scale.

Results

The median observation period was 52 months (range 18–168 months); one LEMS with SCLC patient died as a result of SCLC 18 months after diagnosis, whereas the remaining two LEMS with SCLC patients with complete remission of their tumor still showed improvement in neurological symptoms 52 and 168 months after treatment, respectively. All LEMS patients without SCLC showed a favorable response to treatment and good functional prognosis (modified Rankin Scale 1 or 2) during the follow‐up period (48–120 months).

Conclusions

In Japanese LEMS patients, the long‐term neurological outcome is generally favorable. Our results also suggest that even in LEMS with SCLC patients, successful treatment for their cancer could result in sustained improvement in neurological symptoms.
Monocenter study on epidemiology, outcomes, and risk factors of infections in recipients of 166 allogeneic stem cell transplantations during 1 year
Authors: Samek Markus , Iversen Katharina , Belmar Campos Cristina , Berneking Laura , Langebrake Claudia , Wolschke Christine , Ayuk Francis , Kröger Nicolaus , Christopeit Maximilian
Published: April 2020

Objectives

During allogeneic hematopoietic stem cell transplantation (allo‐SCT), infections significantly contribute to morbidity and mortality. A monocentric prospective analysis was performed to assess epidemiology, risk factors, and outcomes of infections during the peri‐transplant period.

Methods

Data were recorded prospectively using a predefined questionnaire.

Results

In 2015, 163 consecutive patients, 37.4% female, median age 59 (range 18‐79) years received 166 allo‐SCT. Median duration of leukopenia <109/L was 14.5 days (range 4‐43 days). Fever of unknown origin (FUO) occurred in 118/166 patients (71.1%). Severe sepsis developed in 95, and septic shock developed in 26 patients. Intensive diagnostic workup helped to identify causative microorganisms only in a small number of infectious courses. All but 13 patients needed antibiotic therapy, each according to the standard operating procedures of the department. Cumulative incidence of death by infection after 1 year was 16.6% (95% CI: 11.3‐22.7). The only risk factor for FUO in neutropenia was duration of neutropenia </≥14 days (55.4% vs 85.5%, P < .001).

Conclusion

Results of an elaborate diagnostic workup of infections in the peri‐transplant period are scarce. Attention to risk factors might help to identify patients at risk for severe infections.
An adaptive stacked hourglass network with Kalman filter for estimating 2D human pose in video
Authors: Hu Tao , Xiao Chunxia , Min Geyong , Najjari Noushin
Published: April 2020

One of the main challenges in computer science and image processing is 2D human pose estimation. Specifically, occlusion and in particular occlusion of human joints caused by camera angle are of paramount importance. In this paper, a new highly accurate network was proposed that can estimate 2D human poses in video images using deep learning. We employ the Single Shot MultiBox Detector network to detect the centre position of each human within a video frame and then use the stacked hourglass network to estimate the 2D human pose. We approximate the human motion as a linear motion between different frames in a certain period; and optimize the human centres based on the local outlier factor and Kalman filters. The same method is applied to optimize the human pose estimations in video, which can address the inaccurate prediction caused by human joints occlusion. The proposed adaptive network is tested using the two well‐known benchmarks for human pose estimation (MPII and Joint‐annotated Human Motion Data Base datasets), and we also generate some 2D human pose estimating qualitative results of single and multiple people in Internet videos. The experimental results show that the proposed network has strong practicability and can achieve high accuracy on adaptive estimating the 2D human pose in video.
Accreditation in the American Association of Family and Consumer Sciences
Authors: Anderson Carol L.
Published: April 2020

The purpose of accreditation is to recognize that an undergraduate program in home economics/family and consumer science in the United States provides a high standard of academic quality, demonstrates accountability, and encourages improvement as needed. The process for accreditation includes several steps that usually occur over an 18‐ to 24‐month period of time. The process includes a Self‐Study Report, a prereview, a site visit and report, and a decision for one of three actions: accreditation, provisional accreditation, or denial.
The practical and symbolic regulation of multi‐parenthood
Authors: Bureau Marie‐Christine , Rist Barbara
Published: April 2020

It is assumed that multi‐parenthood continues to be a very minor form of family organisation, even among same‐sex couples. Nevertheless there is a great variety of situations within these minority configurations, which can be characterised by various linkages between couple relationships and parenthood relationships. Moreover, the families in question invent tools and rituals which allow daily situations to be regulated and new family narratives to be constructed. It must be stressed that these inventions require significant material and cultural resources. While practical regulation is fairly similar in the case of all blended families, symbolic regulation is both simpler and more difficult, according to the family configurations involved. Indeed, co‐parenthood avoids the consequences of couples breaking up, which often alters the life of blended families. In contrast, symbolisation requires much imagination. Above all, the absence of any legal recognition of “additional” parents remains a permanent source of insecurity and tension.
Ivermectin suppresses tumour growth and metastasis through degradation of PAK1 in oesophageal squamous cell carcinoma
Authors: Chen Liang , Bi Shuning , Wei Qiuren , Zhao Zhijun , Wang Chaojie , Xie Songqiang
Published: April 2020

Oesophageal squamous cell carcinoma (ESCC), the most common form of oesophageal malignancies in the Asia‐Pacific region, remains a major clinical challenge. In this study, we found that ivermectin, an effective antiparasitic drug that has been approved for patients to orally treat onchocerciasis for over 30 years, displayed potent antitumour activity against ESCC cells in vitro and in nude mice. We demonstrated that ivermectin significantly inhibited cell viability and colony formation, and induced apoptosis through a mitochondrial‐dependent manner in ESCC cells. Ivermectin also abrogated ESCC cell migration, invasion, as well as the protein levels of MMP‐2 and MMP‐9. Mechanistically, ivermectin strongly inhibited the expression of PAK1; by further gain‐ and loss‐of‐function experiments, we confirmed that PAK1 played a crucial role in ivermectin‐mediated inhibitory effects on ESCC cells. In addition, the data indicated that ivermectin promoted PAK1 degradation through the proteasome‐dependent pathway. Additionally, ivermectin synergized with chemotherapeutic drugs including cisplatin and 5‐fluorouracil to induce apoptosis of ESCC cells. Interestingly, the in vivo experiments also confirmed that ivermectin effectively suppressed tumour growth and lung metastasis of ESCC. Collectively, these results indicate that ivermectin exerts a potent antitumour activity against ESCC and is a promising therapeutic candidate drug for ESCC patients, even those carrying metastasis.
Machine‐Learning prediction of comorbid substance use disorders in ADHD youth using Swedish registry data
Authors: Zhang‐James Yanli , Chen Qi , Kuja‐Halkola Ralf , Lichtenstein Paul , Larsson Henrik , Faraone Stephen V.
Published: April 2020

Background

Children with attention‐deficit/hyperactivity disorder (ADHD) have a high risk for substance use disorders (SUDs). Early identification of at‐risk youth would help allocate scarce resources for prevention programs.

Methods

Psychiatric and somatic diagnoses, family history of these disorders, measures of socioeconomic distress, and information about birth complications were obtained from the national registers in Sweden for 19,787 children with ADHD born between 1989 and 1993. We trained (a) a cross‐sectional random forest (RF) model using data available by age 17 to predict SUD diagnosis between ages 18 and 19; and (b) a longitudinal recurrent neural network (RNN) model with the Long Short‐Term Memory (LSTM) architecture to predict new diagnoses at each age.

Results

The area under the receiver operating characteristic curve (AUC) was 0.73(95%CI 0.70–0.76) for the random forest model (RF). Removing prior diagnosis from the predictors, the RF model was still able to achieve significant AUCs when predicting all SUD diagnoses (0.69, 95%CI 0.66–0.72) or new diagnoses (0.67, 95%CI: 0.64, 0.71) during age 18–19. For the model predicting new diagnoses, model calibration was good with a low Brier score of 0.086. Longitudinal LSTM model was able to predict later SUD risks at as early as 2 years age, 10 years before the earliest diagnosis. The average AUC from longitudinal models predicting new diagnoses 1, 2, 5 and 10 years in the future was 0.63.

Conclusions

Population registry data can be used to predict at‐risk comorbid SUDs in individuals with ADHD. Such predictions can be made many years prior to age of the onset, and their SUD risks can be monitored using longitudinal models over years during child development. Nevertheless, more work is needed to create prediction models based on electronic health records or linked population registers that are sufficiently accurate for use in the clinic.
Floodplain losses and increasing flood risk in the context of recent historic land use changes and settlement developments: Austrian case studies
Authors: Schober Bernhard , Hauer Christoph , Habersack Helmut
Published: April 2020

Floodplains play a central role in flood risk management since they function as retention areas which attenuate and decelerate flood waves. However, during the last decades land use has changed distinctly on floodplains which has led to a change in topography due to the construction of levees and dykes. Using geographic information system analysis we assessed floodplain developments over 60 years for five Austrian rivers. We used these findings as input for hydrodynamic‐numerical modelling. A comparison of computations of current and historic floodplain topographies demonstrated the complex impacts that changes on floodplains have on catchment level flood risk. Results showed that the losses of floodplains were in general linked to a deterioration in hydrological (flood peaks and travel times) and hydraulic (water level) parameters. In rare cases the unintentional overtopping of dykes resulted in an improved reduction of the peak of the flood wave, but included a worsening of local hydraulic conditions. Hence, this study demonstrates that general conclusions about an alteration of flood risk cannot be easily reached, with a demand for further site‐specific assessment. This novel way of investigating the trends of flooding characteristics by including the historic development within a catchment offers valuable information to planners for a future flood risk management.
Light signaling and UV‐B‐mediated plant growth regulation
Authors: Yadav Arpita , Singh Deeksha , Lingwan Maneesh , Yadukrishnan Premachandran , Masakapalli Shyam Kumar , Datta Sourav
Published: April 2020

Light plays an important role in plants’ growth and development throughout their life cycle. Plants alter their morphological features in response to light cues of varying intensity and quality. Dedicated photoreceptors help plants to perceive light signals of different wavelengths. Activated photoreceptors stimulate the downstream signaling cascades that lead to extensive gene expression changes responsible for physiological and developmental responses. Proteins such as ELONGATED HYPOCOTYL5 (HY5) and CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) act as important factors which modulate light‐regulated gene expression, especially during seedling development. These factors function as central regulatory intermediates not only in red, far‐red, and blue light pathways but also in the UV‐B signaling pathway. UV‐B radiation makes up only a minor fraction of sunlight, yet it imparts many positive and negative effects on plant growth. Studies on UV‐B perception, signaling, and response in plants has considerably surged in recent times. Plants have developed different strategies to use UV‐B as a developmental cue as well as to withstand high doses of UV‐B radiation. Plants’ responses to UV‐B are an integration of its cross‐talks with both environmental factors and phytohormones. This review outlines the current developments in light signaling with a major focus on UV‐B‐mediated plant growth regulation.
Flowering phenology as a core domestication trait in soybean
Authors: Gong Zhizhong
Published: April 2020

Flowering time variation in soybean is well characterized within domesticated germplasms and is critical for modern production, but its importance during domestication is unclear. Recently, Lu et al. (Nature Genetics, 2020) reported that two homeologous pseudo‐response‐regulator genes, Tof12 and Tof11, were sequentially selected in early soybean evolution for ancient flowering time adaptation and intensification of crop cultivation.
Effects of postoperative active warming and early exercise on postoperative body temperature distribution: Non‐blinded and randomized controlled trial
Authors: Kameda Norihiro , Isono Shiroh , Okada Shinobu
Published: April 2020

Aim

We tested a hypothesis that postoperative active warming and/or arm leg stretches reduce the difference between core and skin temperatures (primary variable) improving the peripheral circulation immediately after major abdominal surgery.

Methods

Fifty‐one patients undergoing major abdominal surgeries were randomly assigned to receive one of three interventions immediately after surgery; routine care (control group), mild intermittent exercise on the bed (exercise group), and forced‐air warming (warming group). Core and skin temperatures and perfusion index were continuously measured from anesthesia induction to 12 h after arrival at the ward.

Results

Core body temperature was maintained over 37°C with a relatively greater gap between core and skin temperatures over 1°C and reduced perfusion index in the early postoperative period in the control group. In the warming group, the reduced skin temperature at arrival at the ward approximated to the core temperature leading to significant reduction of the temperature gap and increasing the perfusion index to the preoperative level. Although less evident, both the temperature gap and peripheral perfusion significantly improved in the exercise group after 6 and 8 h after arrival at the ward, respectively.

Conclusions

Vasoconstriction in response to cessation after anesthesia and surgery serves to maintain core temperature, but impairs peripheral circulation. Active warming and intermittent mild exercise immediately after arrival at the ward reduces the temperature gap and improves peripheral circulation during the early postoperative period. While cost‐effectiveness needs to be considered before clinical application of the intervention, the cost‐free mild exercise may be a feasible option for improving postoperative patient care.
Hemangiopericytomas: Spatial Intracranial Location in a Voxel‐Based Mapping Study
Authors: Li Lianwang , Song Ming , Zhang Chuanbao , Qian Zenghui , Li Yiming , Li Runting , Li Chao , Yang Zhengyi , Zhou Dabiao
Published: April 2020

BACKGROUND AND PURPOSE

To investigate the preferred location of intracranial hemangiopericytomas (IHPCs) with voxel‐based mapping and 3‐dimensional reconstruction from MRI data.

METHODS

Gadolinium‐enhanced tumors of 258 primary and single IHPCs were segmented semi‐automatically, followed by manual checking and editing of boundaries. The lesions were registered to Montreal Neurological Institute standard anatomical space, and heat‐map and 3‐dimensional rendered frequency images were generated. All tumors were then superimposed on the Anatomical Automatic Labeling (AAL) template to further investigate the difference in the tumor location based on the voxel‐wise frequency of occurrence with respect to laterality, sex, age, and pathologic grade.

RESULTS

The 3‐dimensional rendered images show that the tumors commonly located in the posterior cranial cavity, surrounding the tentorium. The posterior third of the superior sagittal sinus and the confluence of sinuses were commonly affected. According to the analysis of tumor occurrence frequency in the AAL template, IHPCs were mainly observed in the limbic lobe, occipital lobe, and cerebellum. Tumors in younger patients preferentially located in the right occipital region (P = .027), whereas those with higher pathological grade more often located in the left parietal lobe (P = .034).

CONCLUSIONS

This is the first voxel‐based study to explore the predilection site of IHPCs. Our study suggests that these tumors commonly affect the posterior cranial cavity, adjoining the tentorium and venous sinus. Further research is needed to investigate the possible factors underlying these topographic preferences.
The Effects of Distribution of Image Matched Fiducial Markers on Accuracy of Computer‐Guided Implant Surgery
Authors: Choi Yong‐Do , Mai Hang‐Nga , Mai Hai Yen , Ha Jung‐Hong , Li Lin‐Jie , Lee Du‐Hyeong
Published: April 2020

Purpose

Image registration of the optical intraoral scan to computed tomography image is essential for computer‐guided implant surgery. The remaining teeth, which are considered to be congruent structures observed in the scan and radiographic images, are used to perform the image registration. The purpose of this study was to evaluate the effects of the distribution of matching fiducial points on the accuracy of the image registration.

Materials and Methods

A partially edentulous model with three anterior remaining teeth was prepared. Two mini dental implants were inserted in the posterior edentulous areas on both sides, and computed tomography and surface scan data were obtained. Three groups were set according to the distribution of the image matching points used: localized distribution, unilateral distribution, and bilateral distribution. Fifteen graduate students performed the registration process in each group using the same image matching method. The accuracy of image registration was evaluated by measuring the geometric discrepancies between the radiographic and registered scan images in the anterior, middle, and posterior regions. One‐way and two‐way analysis of variance with the Tukey HSD post hoc test were used for statistical analysis (α = 0.05)

Results

In general, the registration discrepancy was lowest in the bilateral distribution group, followed by the unilateral distribution and localized distribution groups (p< 0.001). In the regional analysis, the registration error tended to increase as the measurement region moved farther from the matching points. The distribution of the matching points and measurement regions had a statistical interaction in the accuracy of image registration.

Conclusion

The accuracy of image registration of the surface scan to the computed tomography is affected by the matching point distribution that can be improved by placing artificial markers in the edentulous areas.
Evidence to Support Universal Blood Pressure Screening in School‐Based Clinical Settings
Authors: Silberstein Juliet , Gwynn Lisa , Mathew M. Sunil , Arheart Kristopher L. , Messiah Sarah E.
Published: April 2020

BACKGROUND

Most pediatric elevated blood pressure (BP) remains undiagnosed. The American Academy of Pediatrics states “there is limited evidence to support school‐based measurement of children's BP.” We explored the utility school‐based BP screening.

METHODS

A cross‐sectional sample of 4096 students ages 6 to 17 from Title 1 Miami‐Dade Public Schools (50% female, 71% non‐Hispanic black, 26% Hispanic) had their systolic/diastolic BP (SBP/DBP) and body mass index (BMI) collected over the 2016 to 2017 or 2017 to 2018 school years. Relative risks (RRs) ratios were calculated to estimate normal/elevated SBP/DBP by BMI percentile, ethnicity, and
sex.

RESULTS

Overall, 26.4% had at least one elevated BP measurement, of which 59% were not obese. RR for obese status was significant for all categories of elevated BP (RRs > 1.88, p < .0001). Being either female (RR = 1.34, p = .009) or Hispanic (RR = 1.31, p = .014) was significantly associated with elevated DBP. BMI accounted for <10% of the variation in BP (SBP: F(1, 4095) = 367.6, adjusted R2 = .08, p < .0001; DBP: F(1, 4095) = 93.3, adjusted R2 = .02, p < .0001).

CONCLUSION

These findings support providing BP screenings in school settings. Low‐income and minority students often have limited access to health care, higher obesity rates, and unhealthy behaviors. Our findings support universal school‐based BP screening regardless of weight status, particularly among ethnically diverse populations.
Immunohistochemical and ultrastructural evidence for the pathogenesis of white matter degeneration in patients with panencephalopathic‐type Creutzfeldt–Jakob disease: Inducible nitric oxide synthase overexpression in bizarre astrocytes
Authors: Kohama Hiroshi , Kusunoki‐Ii Masahiro , Kato Kiyota , Kato Masako , Kato Shinsuke
Published: April 2020

Excessive production of nitric oxide (NO) due to the overinduction of inducible nitric oxide synthase (iNOS) has a severe cytotoxic effect, which may relate to the pathogenesis of neurodegenerative disorders. In this study, we report the novel finding that iNOS is overinduced in a large number of bizarre astrocytes in the white matter of patients with panencephalopathic (PE)‐type Creutzfeldt–Jakob disease (CJD). This study was carried out on brain tissue from seven patients with PE‐type CJD. As controls, 12 normal individuals and nine patients with cerebral infarction were examined. We identified a large number of bizarre astrocytes in the degenerative cerebral white matter in PE‐type CJD. Using immunohistochemistry, only bizarre astrocytes in PE‐type CJD showed strong immunoreactivity for both iNOS and superoxide dismutase 1 (SOD1). Ultrastructural examination demonstrated that these bizarre astrocytes contained many free polyribosome‐like granules. No significant iNOS immunoreactivity was observed in either the astrocytes of patients with cerebral infarcts or in the normal controls. This study suggests that the iNOS‐overexpressing astrocytes, especially iNOS‐overexpressing bizarre astrocytes, could play an important role in the development of white matter lesions in PE‐type CJD. Our data also suggest that the bizarre astrocytes could be protecting themselves from the cytotoxicity of NO by producing SOD1. These immunohistochemical findings are supported by the ultrastructural observation of numerous polyribosome granules restricted to the cytoplasm of these bizarre astrocytes.