bluuebunny/crossref_metadata_2025 huggingface dataset:
Fear of graft rejection after heart transplantation – a nationwide cross-sectional cohort study
Authors: Forsberg Anna , Kisch Annika M , Paulsson Annika , Ragntoft Cecilia , Dalvindt Marita , Lennerling Annette
Published: July 2020

Background

Cellular rejection is most common 3–6 months after heart transplantation while chronic rejection, that is, cardiac allograft vasculopathy and malignancy are the most common causes of death in heart-transplant recipients beyond the third year after transplantation. However, the heart transplantation recipient’s perceived threat of graft rejection has never been explored.

Aim

The aim was to explore perceived threat of the risk of graft rejection and its relationship to psychological wellbeing, fatigue, health literacy, adherence and self-efficacy 1–5 years after heart transplantation.

Methods

In a nationwide, cross-sectional study that constituted part of the Self-management after thoracic transplantation project, 79 heart recipients (68% men and 32% women with a mean age of 52.6 years) were investigated after one year (n=28), two years (n=17), three years (n=11), four years (n=17) and five years (n=6). The instruments used were: the Perceived Threat of the Risk of Graft Rejection, the Psychological General Well-being, Self-efficacy for Managing Chronic Disease, the Multidimensional Fatigue Inventory, the Newest Vital Sign and the Basel Assessment of Adherence to Immunosuppressive Medication Scale.

Results

Twenty-eight per cent of the heart transplantation recipients perceived graft rejection as a serious threat. Intrusive anxiety was low and 37% perceived the threat of the risk of graft rejection as being beyond their control. Heart transplant recipients with high level of fatigue and low psychological well-being reported stronger intrusive anxiety and less control.

Conclusion

A perceived threat of the risk of graft rejection is present in the everyday lives of heart transplantation recipients and is strongly related to overall psychological well-being.
PolyTile 2.0: Programmable microtextured ceramic architectural tiles embedded with environmentally responsive biofunctionality
Authors: Zhang Viola , Rosenwasser David , Sabin Jenny E
Published: July 2020

PolyTile 2.0 interrogates the potential of programmable biofunctionalities in our constructed architectural environments through the development of advanced ceramic bio-tiles. These tiles utilize novel patterning techniques and hydrogel biomaterials to tune surface conditions at the micro- and macroscale. This trans-disciplinary work builds upon recent advancements in the fields of three-dimensional printing, digital ceramics, materials science, bioengineering, chemical biology, and architecture. PolyTile 2.0 enables designers and architects to implement biofunctionality and microscale patterning fittingly and with the ability to continuously adjust design iterations across scales. The refinement utilizes glazing strategies as a directable fluidic device and biocompatible hydrogels as a sensing platform to further developments in responsive built environments. This article outlines methods for the production of bulk-scale hydrogel materials, stereolithography-based three-dimensional printed ceramic tiles, and scalable glazing techniques, which bring building-scale application of this technology to the foreground.
Evolving Trends in the Post-Arab Spring Era: Implications for Peace and Stability in the MENA Region
Authors: Fraihat Ibrahim , Yaseen Taha
Published: July 2020

The uprisings connected to the Arab Spring have thus far failed to produce social change. The dynamics of these uprisings instead generated a number of trends that are likely to continue to destabilise the Arab world and prevent peace and development. Prevailing trends in the post-Arab Spring era include the prevalence of counter revolutions, widespread violence and armed conflicts, new patterns of alliances, external interventions and thriving proxies, raising sectarian politics, ineffective governance, terrorism, and migration. While these trends have a negative impact on people’s basic demands for socio-economic and political stability and development, they will provide and shape the foundations for other revolutions in the future. To avoid future revolutions and civil wars and stimulate peace and development in the MENA region, those driving patterns of instability will need to be altered.
Observing Gender and Race Discourses in Probation Review Hearings
Authors: Romain Dagenhardt Danielle M.
Published: July 2020

Much of the prior court literature has demonstrated gender and racial disparity exist across various decision-points. Less understood are the processes that produce this disparity, particularly in problem-solving courts. This article utilizes 100 observations of probation review hearings in three domestic violence courts to examine how judges, probation agents, attorneys, and probationers construct a probationer’s non-compliance. Using a critical discourse analysis approach, the author examined how probationers and their actions are constructed based upon gender and racial discourses. Gender differences in parenting responsibilities, mental health, and domestic violence discourses emerged, with racial differences in responsibility and mental health discourses.
De novo intracranial arteriovenous malformation development after endovascular treatment for a pial arteriovenous fistula in capillary malformation-arteriovenous malformation syndrome
Authors: Ryu Bikei , Sato Shinsuke , Mochizuki Tatsuki , Inoue Tatsuya , Okada Yoshikazu , Niimi Yasunari
Published: July 2020

Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is a newly described entity characterized by autosomal dominantly inherited multifocal capillary malformations caused by RASA1 mutations (CM-AVM1) or EPHB4 mutations (CM-AVM2). Concurrent high-flow vascular anomalies in the brain are often present in the form of intracranial AVM or arteriovenous fistula (AVF). These high-flow lesions are often identified at or soon after birth because of the characteristic unique capillary malformations or a systemic disorder due to a high-flow shunt, such as respiratory distress or heart failure. However, de novo intracranial AVMs have not been reported in patients with CM-AVM syndrome. Herein, we report the case of a six-year-old boy with CM-AVM1 who had been treated for an intracranial pial arteriovenous fistula approximately five years previously, in whom a de novo intracranial AVM was identified on a follow-up angiographic study. To the best of our knowledge, this report is the first to document a de novo intracranial AVM in a patient with CM-AVM. We recommend careful neuroimaging follow-up even if initial neuroimaging screening is negative because of the risk of de novo AVM development.
Fault diagnosis of head sheaves based on vibration measurement and data mining method
Authors: Ma Chi , Yao Jiannan , Xiao Xinming , Zhang Xiaohan , Jiang Yuqiang
Published: July 2020

Head sheaves are critical components in a mine hoisting system. It is inconvenient for workers to climb up to the high platform for overhaul and maintenance, and there is an urgent need for condition monitoring and fault diagnosis of head sheaves. In this article, Fault Tree Analysis is employed to investigate the faults of head sheaves, and headframe inclination, bearing faults, and head sheave swing are the three focal faults discussed. A test rig is built to simulate these three faults and collect vibration signals at bearing blocks. Based on vibration signals, some characteristic parameters are calculated, and together with the fault labels, a sample set is established. Before the selection of an excellent data mining method, these features are screened according to their significance, and then, gain–percentile chart, response–percentile chart, and prediction accuracy are used as the criteria to make a comparison between data mining algorithms. The result shows the boosted tree algorithm outperforms others and presents excellent performance on the evaluation of head sheave faults. Finally, this method is verified on a data set of 20 samples, and each case is identified correctly, which illustrates its high applicability.
Worse prognosis in women, compared with men, after thrombolysis: An individual patient data pooling study of Asian acute stroke registries
Authors: Wang Xia , Carcel Cheryl , Wang Ruigang , Li Jingwei , Bae Hee-Joon , Wang Yilong , Wang Anxin , Wang Yongjun , Toyoda Kazunori , Sui Yi , Lee Tsong-Hai , Navarro Jose C , Sun Mu-Chien , Anderson Craig S , Sharma Vijay , Sandset Else C , Woodward Mark
Published: July 2020

Background and purpose

To examine sex differences in disease profiles and short-term outcomes after acute ischemic stroke treated with recombinant tissue plasminogen activator.

Methods

Eight national and regional stroke registries contributed individual participant data from mainland China, Japan, Philippines, Singapore, South Korea and Taiwan in 2005–2018. The primary outcome was ordinal-modified Rankin scale at 90 days. Key safety outcome was symptomatic intracerebral hemorrhage (sICH).

Results

Of 4453 patients included in the analyses, 1692 (36.3%) were women who were older, more likely to have a more severe neurological deficit, history of hypertension and atrial fibrillation, and a cardioembolic stroke compared to men. Women were more likely than men to have unfavorable shift of modified Rankin scale (fully adjusted odds ratio) (women vs. men) 1.14, 95% confidence interval 1.02–1.28). There was no significant sex difference for death 1.05 (0.84–1.31) or sICH (1.17, 0.89–1.54). Women were more likely to have unfavorable functional outcome with increasing age (P = 0.022 for interaction). In the age groups 70–80 and ≥80 years, women had a worse functional outcome compared to men (1.22, 1.02–1.47 and 1.43, and 1.06–1.92, respectively).

Conclusion

In this pooled data from Asian acute stroke registries, women had poorer prognosis than men after receiving recombinant tissue plasminogen activator for acute ischemic stroke, which worsened with age. Women older than 70 appear to have a worse outcome than men which could be explained by greater stroke severity, more AF, and cardioembolic stroke.
Synthesis and characterization of a triphenylamine-dibenzosuberenone-based conjugated organic material and an investigation of its photovoltaic properties
Authors: Erdoğan Musa , Horoz Sabit
Published: July 2020

3,7-Bis[4-(diphenylamino)phenyl]-5 H-dibenzo[ a,d][7]annulen-5-one, containing triphenylamine- and dibenzosuberenone-based donor-acceptor-donor (D-A-D) conjugated moieties, is synthesized in high yield by Suzuki coupling of 5 H-dibenzo[ a,d][7]annulen-5-one with [4-(diphenylamino)phenyl]boronic acid. The most important part of the present study is the creation of a dye-sensitized solar cell structure using the synthesized organic molecule for the first time and the power conversion efficiency of this structure. Three solar cell devices are prepared and are named as first device, second device, and third device. The power conversion efficiency (%) value for first device, second device, and third device is calculated as 2.54, 2.38, and 2.54, respectively. Moreover, the chemical structure of the synthesized compound is determined by nuclear magnetic resonance, infrared, ultraviolet visible, fluorescence spectroscopy, and high-resolution mass spectrometry.
Iron deficiency anaemia in pregnancy: A contemporary review
Authors: Benson Charlotte S , Shah Akshay , Frise Matthew C , Frise Charlotte J
Published: July 2020

Summary

Iron deficiency anaemia is a global health problem, which particularly affects pregnant women. Iron deficiency anaemia during pregnancy is associated with increased maternal and perinatal morbidity and mortality. Maternal iron deficiency may also be associated with neurocognitive deficits in infants. Iron requirements increase during pregnancy and are influenced by hepcidin, the master regulator of iron homeostasis. The enduring global burden of maternal anaemia suggests that currently employed iron supplementation strategies are suboptimal. Recent developments in our understanding of systemic and placental iron homeostasis may improve therapeutic effectiveness by altering the dose and frequency of oral iron. Intravenous iron appears to be a safe treatment to correct maternal anaemia rapidly but research on patient-centred outcomes and cost-effectiveness is needed. Future trials should be adequately powered to assess outcomes relevant to pregnant women.
Friedrich Engels and his Contribution to Marxism
Authors: Mavroudeas Stavros
Published: July 2020

The 200th anniversary of the birth of F. Engels comes at a time when his contribution to Marxism is being disputed by Neue Lekture and Sraffian authors, based on the alleged discovery of him having distorted Capital. The evidence presented by the new anti-Engelsionists is flimsy and essentially philological hair-splitting arguments. The common ground uniting them is their abhorrence for the existence of Marxism as a coherent theoretical tradition and as a weapon for the revolutionary struggle of the working class for the emancipation of human society.
Feasibility of single and combined with other treatments using transcranial direct current stimulation for chronic stroke: A pilot study
Authors: Hyakutake Koichi , Morishita Takashi , Saita Kazuya , Ogata Toshiyasu , Uehara Yoshinari , Shiota Etsuji , Inoue Tooru
Published: July 2020

Objectives:

This pilot study aimed to investigate the safety and efficacy of transcranial direct current stimulation (tDCS) for chronic stroke in adult and pediatric patients. We also aimed to verify the efficacy of botulinum toxin A and peripheral neuromuscular electrical stimulation combined therapy involving bilateral tDCS in adult patients with chronic stroke.

Methods:

We conducted a pilot study applying an unblinded, non-randomized design. Eleven patients were recruited, and classified into three groups. Group I-a involved bilateral transcranial direct current stimulation and intensive occupational therapy for chronic stroke in adult patients. Group I-b involved bilateral tDCS and intensive occupational therapy for chronic stroke in pediatric patients. Group II involved bilateral tDCS, peripheral neuromuscular electrical stimulation, and intensive occupational therapy after botulinum toxin A injection for chronic stroke in adult patients. Clinical evaluations to assess motor function and spasticity were performed at baseline as well as in 2-week and 4-month follow-up visits. The questionnaire included questions regarding the presence of tDCS side effects, such as headache, redness, pain, itching, and fever.

Results:

There were clinically meaningful changes in total Fugl–Meyer Assessment Upper Extremity (FMA-UE) scores at the 2-week follow-up and in the Action Research Arm Test (ARAT) scores at 4-month follow-up in Group I-b. In addition, Group II showed significant improvement in total FMA-UE scores in the 2-week follow-up (p < 0.05) but not on the ARAT scores (p > 0.05). However, Group II showed improvements in total Motor Activity Log scores at both follow-up visits (p < 0.05). No serious adverse events were reported.

Conclusion:

The results of this study indicate that tDCS therapy is a potential treatment in pediatric patients with chronic stroke. Furthermore, our data indicate that botulinum toxin A and peripheral neuromuscular electrical stimulation combined therapy may enhance the efficacy of tDCS on motor function.
A Survey of Iranian Primiparous Women’s Perceptions of Vaginal Examination During Labor
Authors: Dabagh-Fekri Samaneh , Amiri-Farahani Leila , Amini Leila , Pezaro Sally
Published: July 2020

Objective: To assess perceptions about vaginal examinations (VEs) during labor among women referred to the Akbarabadi Hospital in Tehran, Iran. Methods: This was a cross-sectional study conducted from December 2015 to May 2016. It included 200 primiparous women. Convenience sampling was used to select participants. The data collection tool was a questionnaire that collected both demographic and obstetric data from participants, as well as data in relation to women’s experiences according to a designated and validated scale, 24 hours after childbirth. Higher scores were indicative of a more positive perception in relation to a participant’s experience of VE. Results: The mean ± SD score for the perception of the VE and number of examinations in the active phase of labor was 62.9 ± 26.2 and 7.4 ± 2.44, respectively. Multiple linear regression analysis showed a significant relationship between perceived duration of examination (short, average [B = −1.03], long [B = 3.84]), feeling of comfort with the examiner (B = 2.73), and number of examiners (B = −0.81) with the mean scores of their perceptions ( P < .05). These 3 variables accounted for 8% of the changes in the women’s perceptions score of VE. Conclusion: The majority of participants in this study underwent excessive VEs during labor. If obstetrically safe, a reduction in the number of examinations during labor along with decreased duration based on women’s perceptions could improve women’s perceptions of VE overall. Additionally, should each VE be performed by the same clinician, women’s perceptions in relation to VEs may also improve.
Cultural Entrepreneurship: Between-Organization Cultural Isomorphism and Within-Organization Culture Shaping
Authors: Lee Seungdoe , Chung Goo Hyeok
Published: July 2020

Cultural entrepreneurship is a process that focuses on entrepreneurial resources, identifies and legitimates new startups, and improves organizational performance. Although scholars of this subject have viewed entrepreneurs as cultural agents, for example, who either strike a balance between cultural resources and constraints or decouple their ventures from cultural constraints while coupling them with cultural resources, they have overlooked another possible behavior that cultural agents might display. In the present study, the authors attempt to uncover another facet of cultural entrepreneurship and conduct a case study focusing on a new entrepreneurial organization (subcontractor) that became a parts supplier for an automaker (user company). Our findings show that the subcontractor’s entrepreneurs shaped its culture by drawing on the external cultural constraints coded by the user company’s culture ( between-organization cultural isomorphism), and they also used internal cultural resources to foster an entrepreneurial culture and to stimulate exploratory innovations ( within-organization culture shaping).
Surgeon and Patient Upper Extremity Dominance Does Not Influence Clinical Outcomes After Total Shoulder Arthroplasty
Authors: Berthold Daniel P. , Muench Lukas N. , Kia Cameron , Ziegler Connor G. , Laurencin Samuel J. , Witmer Daniel , Reed Dale N. , Cote Mark P. , Arciero Robert A. , Mazzocca Augustus D.
Published: July 2020

Background:

Surgeon- and patient-specific characteristics as they pertain to total shoulder arthroplasty (TSA) are limited in the literature. The influence of surgeon upper extremity dominance in TSA and whether outcomes vary among patients undergoing right or left TSA with respect to surgeon handedness have yet to be investigated.

Purpose:

To determine whether surgeon or patient upper extremity dominance has an effect on clinical outcomes after primary TSA at short-term follow-up.

Study Design:

Case series; Level of evidence, 4.

Methods:

A retrospective chart review was performed on prospectively collected data from an institutional shoulder registry. Patients who underwent primary TSA for glenohumeral osteoarthritis from June 2008 to August 2012 were included in the study. Preoperative and postoperative American Shoulder and Elbow Surgeons (ASES), Simple Shoulder Test (SST), and visual analog scale (VAS) pain scores were evaluated. To determine the clinical relevance of ASES scores, the minimal clinically important difference (MCID), the substantial clinical benefit (SCB), and the patient acceptable symptom state (PASS) were used. Active forward elevation, abduction, and external rotation were recorded for each patient. Glenoid version was also evaluated preoperatively on standard radiographs.

Results:

Included in this study were 40 patients (n = 44 shoulders; mean age, 69.0 ± 7.3 years) with a mean follow-up of 36.5 ± 16.2 months. Final active range of motion between patients who underwent dominant versus nondominant and left versus right TSA by a right-handed surgeon was not significantly different. Clinical outcomes including the ASES, SST, and VAS pain scores were compared, and no statistical significance was identified between groups. With regard to the ASES score, 89% of patients achieved the MCID, 64% achieved the SCB, and 60% reached or exceeded the PASS. No significant difference in preoperative glenoid version between groups could be found.

Conclusion:

With the numbers available, neither patient nor surgeon upper extremity dominance had a significant influence on clinical outcomes after primary TSA at short-term follow-up.

Clinical Relevance:

The influence of surgeon and patient upper extremity dominance on TSA outcomes is an important consideration, given the preferential use of the dominant extremity exhibited by most patients during activities of daily living. To this, operating on a right shoulder might be technically more demanding for a right-handed surgeon and vice versa, as it is considered in other subspecialties.
Expanded Phenotypic Definition Identifies Hundreds of Potential Causative Genes for Leukodystrophies and Leukoencephalopathies
Authors: Urbik Veronica M. , Schmiedel Marilyn , Soderholm Haille , Bonkowsky Joshua L.
Published: July 2020

Background:

The genes responsible for genetic white matter disorders (GWMD; leukodystrophies and leukoencephalopathies) are incompletely known. Our goal was to revise the list of genes considered to cause GWMD. We considered a GWMD to consist of any genetic disease causing T2 signal white matter changes in magnetic resonance images.

Methods and Results:

Using a systematic review of PubMed, Google, published literature reviews, and commercial gene panels, we identified 399 unique genes meeting the GWMD definition. Of this, 87 (22%) genes were hypomyelinating. Only 3 genes had contrast enhancement on magnetic resonance imaging (MRI): ABCD1, GFAP, and UNC13D.

Conclusions:

A significantly greater number of genes than previously recognized, 399, are associated with white matter signal changes on T2 MRI. This expansion of GWMD genes can be useful in analysis and interpretation of next-generation sequencing results for GWMD diagnosis, and for understanding shared pathophysiological mechanisms of GWMDs.
Comparison of the Conceptual Map and Traditional Lecture Methods on Students’ Learning Based on the VARK Learning Style Model: A Randomized Controlled Trial
Authors: Amaniyan Sara , Pouyesh Vahideh , Bashiri Yousef , Snelgrove Sherrill , Vaismoradi Mojtaba
Published: July 2020

Developing skills and knowledge in nursing education remains a considerable challenge. Nurse instructors need to be aware of students’ learning styles so as to meet students’ individual learning preferences and optimize knowledge and understanding. The aim of this study was to compare the effects of the conceptual map and the traditional lecture methods on students’ learning based on the VARK learning styles model. In this randomized controlled trial, 160 students from nursing, nurse anesthetics, and midwifery disciplines with four different learning styles of visual, auditory, reading/writing, and kinesthetic were selected using the convenience sampling method. Participants were randomly assigned to the intervention (conceptual map method) or control (traditional lecture method) groups. A medical-surgical nursing course was taught to the students in both groups over 6 weeks. Data collection tools consisted of the VARK questionnaire and pre- and postassessments. Data were analyzed using descriptive and inferential statistics via the SPSS software. Teaching using the conceptual map method had different effects on the students’ learning outcomes based on their learning styles. The conceptual map method had a statistically significant impact on the students’ learning in the intervention group compared with the control group in the students with a visual learning style ( p = .036). No statistically significant differences were reported between the groups in other three learning styles. Nurse instructors should assess students’ learning styles based on the VARK model before the application of a particular teaching method to improve the quality of nursing education and facilitate deeper learning.
Medical Students’ Participation in Longitudinal Community Service During Preclerkship Years: A Qualitative Study on Experiences and Perceived Outcomes
Authors: Haidar Amier , Erickson Samuel G , Champagne-Langabeer Tiffany
Published: July 2020

The aim of this study was to qualitatively evaluate medical students perspectives of the benefits of a longitudinal volunteering experience compared with a 1-day community service experience. Fifteen medical students participated in 2 types of community service: (1) longitudinal, weekly volunteering from February to April of 2019 and (2) a single day of community service in March of 2019. Semistructured interviews were conducted to identify medical students perspectives of the impact of volunteering. Interview data was analyzed thematically based on the common ideas expressed by the participants. Four themes emerged: development of communication and interpersonal skills; understanding how to teach; ability to understand community issues in a low socioeconomic status (SES) neighborhood and the improvement of overall well-being. Medical students’ participation in a longitudinal nutrition education volunteer program was perceived as being an effective way to develop communication, interpersonal, and teaching skills. Medical students were able to interact with a diverse and vulnerable community located in a low SES neighborhood, to help them understand current community issues and risk factors.
Route planning for blind pedestrians using OpenStreetMap
Authors: Cohen Achituv , Dalyot Sagi
Published: July 2020

While most of us take wayfinding and orientation for granted, instinctively utilizing our visual channels to do so, millions of blind people around the world face challenges and obstacles when attempting to perform the most basic tasks, such as walking to the corner store or using public transportation. As blind pedestrians lack critical information about the space they traverse outside the familiarity of their home, they are restricted, dependent on others, and have decreased quality of life. While assistive technologies for providing specific navigation solutions do exist, research is still limited regarding customized wayfinding solutions for blind pedestrians. This research aims at developing a wayfinding algorithm that relies on the OpenStreetMap mapping catalogue for planning accessible and safe routes specifically suited to blind pedestrians. In-depth investigations, observations, and interviews were conducted with blind people and with orientation and mobility instructors, in order to define and categorize spatial criteria relating to mobility, accessibility, and safety. Using controlled iterative experiments, weighted network graph criteria were defined, leading to the development of a route planning software that generates optimized routes for blind pedestrians. The developed software was then tested on a variety of routes, with the help of blind volunteers and orientation and mobility instructors. The results show that the optimal routes generated by the software were identical or very similar to those suggested by the experienced orientation and mobility instructors. Moreover, the blind volunteers also stated that the software planned routes were indeed more accessible and safer for them to walk along compared to routes suggested by existing commercial software developed for seeing pedestrians. The findings of this research indicate that our solution, based on OpenStreetMap and developed for the benefit of blind pedestrians, is effective and practical, and could improve the mobility, independence, and quality of life of this population, as well as increasing their integration into society.
Single-cell genomics reveals the genetic and molecular bases for escape from mutational epistasis in myeloid neoplasms
Authors: Taylor Justin , Mi Xiaoli , North Khrystyna , Binder Moritz , Penson Alexander , Lasho Terra , Knorr Katherine , Haddadin Michael , Liu Bo , Pangallo Joseph , Benbarche Salima , Wiseman Daniel , Tefferi Ayalew , Halene Stephanie , Liang Yang , Patnaik Mrinal M. , Bradley Robert K. , Abdel-Wahab Omar
Published: July 2020

Large-scale sequencing studies of hematologic malignancies have revealed notable epistasis among high-frequency mutations. One of the most striking examples of epistasis occurs for mutations in RNA splicing factors. These lesions are among the most common alterations in myeloid neoplasms and generally occur in a mutually exclusive manner, a finding attributed to their synthetic lethal interactions and/or convergent effects. Curiously, however, patients with multiple-concomitant splicing factor mutations have been observed, challenging our understanding of one of the most common examples of epistasis in hematologic malignancies. In this study, we performed bulk and single-cell analyses of patients with myeloid malignancy who were harboring ≥2 splicing factor mutations, to understand the frequency and basis for the coexistence of these mutations. Although mutations in splicing factors were strongly mutually exclusive across 4231 patients (q < .001), 0.85% harbored 2 concomitant bona fide splicing factor mutations, ∼50% of which were present in the same individual cells. However, the distribution of mutations in patients with double mutations deviated from that in those with single mutations, with selection against the most common alleles, SF3B1K700E and SRSF2P95H/L/R, and selection for less common alleles, such as SF3B1 non-K700E mutations, rare amino acid substitutions at SRSF2P95, and combined U2AF1S34/Q157 mutations. SF3B1 and SRSF2 alleles enriched in those with double-mutations had reduced effects on RNA splicing and/or binding compared with the most common alleles. Moreover, dual U2AF1 mutations occurred in cis with preservation of the wild-type allele. These data highlight allele-specific differences as critical in regulating the molecular effects of splicing factor mutations as well as their cooccurrences/exclusivities with one another.
Expression of Nras
Q61R and MYC transgene in germinal center B cells induces a highly malignant multiple myeloma in mice
Authors: Wen Zhi , Rajagopalan Adhithi , Flietner Evan D. , Yun Grant , Chesi Marta , Furumo Quinlan , Burns Robert T. , Papadas Athanasios , Ranheim Erik A. , Pagenkopf Adam C. , Morrow Zachary T. , Finn Remington , Zhou Yun , Li Shuyi , You Xiaona , Jensen Jeffrey , Yu Mei , Cicala Alexander , Menting James , Mitsiades Constantine S. , Callander Natalie S. , Bergsagel P. Leif , Wang Demin , Asimakopoulos Fotis , Zhang Jing
Published: July 2020

NRAS Q61 mutations are prevalent in advanced/relapsed multiple myeloma (MM) and correlate with poor patient outcomes. Thus, we generated a novel MM model by conditionally activating expression of endogenous NrasQ61R and an MYC transgene in germinal center (GC) B cells (VQ mice). VQ mice developed a highly malignant MM characterized by a high proliferation index, hyperactivation of extracellular signal-regulated kinase and AKT signaling, impaired hematopoiesis, widespread extramedullary disease, bone lesions, kidney abnormalities, preserved programmed cell death protein 1 and T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain immune-checkpoint pathways, and expression of human high-risk MM gene signatures. VQ MM mice recapitulate most of the biological and clinical features of human advanced/high-risk MM. These MM phenotypes are serially transplantable in syngeneic recipients. Two MM cell lines were also derived to facilitate future genetic manipulations. Combination therapies based on MEK inhibition significantly prolonged the survival of VQ mice with advanced-stage MM. Our study provides a strong rationale to develop MEK inhibition–based therapies for treating advanced/relapsed MM.
Investigating the effects of rehabilitation and the use of curved-integrated members on the behavior of chairs
Authors: Hosseini-Tabatabaei Mahmoud-Reza , Bayatkashkoli Ali , Mollaeinia Mahmoud Reza , Kool Farhad , Rahmani Ardakani Mohsen , Madahi Narjes Khaton
Published: July 2020

Expanding the service life length of wooden made furniture, and consequently decreasing the demand for raw wood could help the economy of the world society and environmental safety. In this research, an experimental inquiry was conducted to determine the effects of curved members, the frame integrity, chair scheme, and rehabilitation of even the failed chairs on the behavior of chairs. The flexural properties of the curved specimens were firstly determined using the ASTM D143-94 test. Then, three layouts of chairs (A, B, and C) made from poplar wood were examined under the DIN EN-1729-1&2 standard. Finally, the failed chairs were rehabilitated using the sheets of glass fiber-reinforcing polymers (GFRP) and re-tested. The results showed that the rehabilitation of the curved samples causes rebounding of their mechanical properties. Besides, the rehabilitated samples are more flexible than primary ones. Furthermore, the results demonstrate that the capability of the proposed normalized modulus of rupture (NMOR) criterion, in contrast to the current modulus of rupture (MOR) one, for predicting the failure modes and regions of the wooden and composite structures. The experiments on the chairs showed that all rehabilitated patterns are more robust than primary schemes. That means, the discarded (or discarding) chairs (due to failure of joints, legs, or, in general, a part of the chairs) return to their service life, and massively reduce the demand for wood, which is strongly favored by environmental aspects. Moreover, rehabilitated layout B (RB), which has two continuous-main-curved members is at least 2.4 times stronger than other rehabilitated patterns, and rehabilitated layout C (RC) having three continuous-main-curved members is about 40% stronger than a rehabilitated custom chair (RA), that illustrates more integrity and strength. Besides that, the strength of RB is 2.22 and 2.04 times that of the corresponding primary chairs, depending on front-to-back and up-to-down loading, respectively. Finally, univariate analyses of variance and least significant difference (LSD) showed the high precision of the results. Consequently, the research provides a facility not only to save original material resources, but also to eliminate furniture waste going in the landfill.
Neuropeptide FF receptor 2 inhibits capsaicin-induced CGRP Upregulation in mouse trigeminal ganglion
Authors: Lin Ya-Tin , Yu Zachary , Tsai Sze-Chi , Hsu Po-Hung , Chen Jin-Chung
Published: July 2020

Background

Stimulation of trigeminovascular pathway is widely used to establish the headache animal model. Headache is a common neurological disorder, in which symptomatic attacks are mediated by calcitonin-gene-related peptide (CGRP). CGRP is synthesized and released from the trigeminal ganglion to transmit pain signals under stimulation. On the other hand, Neuropeptide FF (NPFF) is a candidate transmitter/modulator for migraine, and stimulation of its receptor, NPFFR2, increases the expression and release of CGRP in mice sensory neurons. Here, we investigate the impact of NPFFR2 on trigeminal CGRP level in a capsaicin-induced headache mouse model.

Methods

Mice were intracisternally injected with capsaicin into the cisterna magna to activate the trigeminovascular pathway and induce headache symptoms. Mice pretreated with Npffr2-shRNA or NPFFR2 knockouts were adopted to test the impact of NPFFR2 on capsaicin-induced CGRP upregulation in trigeminal ganglion. The gene silencing effect of Npffr2-shRNA in trigeminal ganglion was confirmed by real-time PCR. Trigeminal CGRP level was determined by immunofluorescence staining, and the percentage of CGRP-positive cell was calculated after setting the signal intensity threshold by Image J software. Amount of trigeminal CGRP in NPFFR2 overexpressed mice was also measured by CGRP ELISA.

Findings

Infusion of capsaicin into the cisterna magna upregulated the CGRP in trigeminal ganglion and induced spontaneous pain behaviors including the reduction of locomotor activity and the increase of freezing behavior. Intracisternal injection of Npffr2-shRNA reduced the mRNA of Npffr2 in trigeminal ganglion. Mice pretreatment with Npffr2-shRNA prevented capsaicin-induced CGRP upregulation in trigeminal ganglion. Similarly, CGRP upregulation was also reduced in NPFFR2 knockout mice. On the contrary, trigeminal CGRP was increased in NPFFR2 overexpressed mice.

Conclusions

Reducing the level of NPFFR2 leads to the downregulation of capsaicin-induced CGRP in trigeminal ganglion, which would consequently attenuate the activation of trigeminovascular pathway. Thus, NPFFR2 could serve as a potential target for neuromodulation of cephalic pain.
Degradation of key photosynthetic genes in the critically endangered semi-aquatic flowering plant Saniculiphyllum guangxiense (Saxifragaceae)
Authors: Folk Ryan A. , Sewnath Neeka , Xiang Chun-Lei , Sinn Brandon T. , Guralnick Robert P.
Published: July 2020

Background

Plastid gene loss and pseudogenization has been widely documented in parasitic and mycoheterotrophic plants, which have relaxed selective constraints on photosynthetic function. More enigmatic are sporadic reports of pseudogenization and loss of important photosynthesis genes in lineages thought to be fully photosynthetic. Here we report the complete plastid genome of Saniculiphyllum guangxiense, a critically endangered and phylogenetically isolated plant lineage, along with genomic evidence of reduced chloroplast function. We also report 22 additional plastid genomes representing the diversity of its containing clade Saxifragales, characterizing gene content and placing variation in a broader phylogenetic context.

Results

We find that the plastid genome of Saniculiphyllum has experienced pseudogenization of five genes of the ndh complex (ndhA, ndhB, ndhD, ndhF, and ndhK), previously reported in flowering plants with an aquatic habit, as well as the surprising pseudogenization of two genes more central to photosynthesis (ccsA and cemA), contrasting with strong phylogenetic conservatism of plastid gene content in all other sampled Saxifragales. These genes participate in photooxidative protection, cytochrome synthesis, and carbon uptake. Nuclear paralogs exist for all seven plastid pseudogenes, yet these are also unlikely to be functional.

Conclusions

Saniculiphyllum appears to represent the greatest degree of plastid gene loss observed to date in any fully photosynthetic lineage, perhaps related to its extreme habitat specialization, yet plastid genome length, structure, and substitution rate are within the variation previously reported for photosynthetic plants. These results highlight the increasingly appreciated dynamism of plastid genomes, otherwise highly conserved across a billion years of green plant evolution, in plants with highly specialized life history traits.
Multivariate network meta-analysis incorporating class effects
Authors: Owen Rhiannon K. , Bujkiewicz Sylwia , Tincello Douglas G. , Abrams Keith R.
Published: July 2020

Background

Network meta-analysis synthesises data from a number of clinical trials in order to assess the comparative efficacy of multiple healthcare interventions in similar patient populations. In situations where clinical trial data are heterogeneously reported i.e. data are missing for one or more outcomes of interest, synthesising such data can lead to disconnected networks of evidence, increased uncertainty, and potentially biased estimates which can have severe implications for decision-making. To overcome this issue, strength can be borrowed between outcomes of interest in multivariate network meta-analyses. Furthermore, in situations where there are relatively few trials informing each treatment comparison, there is a potential issue with the sparsity of data in the treatment networks, which can lead to substantial parameter uncertainty. A multivariate network meta-analysis approach can be further extended to borrow strength between interventions of the same class using hierarchical models.

Methods

We extend the trivariate network meta-analysis model to incorporate the exchangeability between treatment effects belonging to the same class of intervention to increase precision in treatment effect estimates. We further incorporate a missing data framework to estimate uncertainty in trials that did not report measures of variability in order to maximise the use of all available information for healthcare decision-making. The methods are applied to a motivating dataset in overactive bladder syndrome. The outcomes of interest were mean change from baseline in incontinence, voiding and urgency episodes. All models were fitted using Bayesian Markov Chain Monte Carlo (MCMC) methods in WinBUGS.

Results

All models (univariate, multivariate, and multivariate models incorporating class effects) produced similar point estimates for all treatment effects. Incorporating class effects in multivariate models often increased precision in treatment effect estimates.

Conclusions

Multivariate network meta-analysis incorporating class effects allowed for the comparison of all interventions across all outcome measures to ameliorate the potential impact of outcome reporting bias, and further borrowed strength between interventions belonging to the same class of treatment to increase the precision in treatment effect estimates for healthcare policy and decision-making.
Multiple imputation with missing indicators as proxies for unmeasured variables: simulation study
Authors: Sperrin Matthew , Martin Glen P.
Published: July 2020

Background

Within routinely collected health data, missing data for an individual might provide useful information in itself. This occurs, for example, in the case of electronic health records, where the presence or absence of data is informative. While the naive use of missing indicators to try to exploit such information can introduce bias, its use in conjunction with multiple imputation may unlock the potential value of missingness to reduce bias in causal effect estimation, particularly in missing not at random scenarios and where missingness might be associated with unmeasured confounders.

Methods

We conducted a simulation study to determine when the use of a missing indicator, combined with multiple imputation, would reduce bias for causal effect estimation, under a range of scenarios including unmeasured variables, missing not at random, and missing at random mechanisms. We use directed acyclic graphs and structural models to elucidate a variety of causal structures of interest. We handled missing data using complete case analysis, and multiple imputation with and without missing indicator terms.

Results

We find that multiple imputation combined with a missing indicator gives minimal bias for causal effect estimation in most scenarios. In particular the approach: 1) does not introduce bias in missing (completely) at random scenarios; 2) reduces bias in missing not at random scenarios where the missing mechanism depends on the missing variable itself; and 3) may reduce or increase bias when unmeasured confounding is present.

Conclusion

In the presence of missing data, careful use of missing indicators, combined with multiple imputation, can improve causal effect estimation when missingness is informative, and is not detrimental when missingness is at random.
Optimisation of medications used in residential aged care facilities: a systematic review and meta-analysis of randomised controlled trials
Authors: Almutairi Hend , Stafford Andrew , Etherton-Beer Christopher , Flicker Leon
Published: July 2020

Background

Frail older adults living in residential aged care facilities (RACFs) usually experience comorbidities and are frequently prescribed multiple medications. This increases the potential risk of inappropriate prescribing and its negative consequences. Thus, optimising prescribed medications in RACFs is a challenge for healthcare providers.

Objective

Our aim was to systematically review interventions that increase the appropriateness of medications used in RACFs and the outcomes of these interventions.

Methods

Systematic review and meta-analysis of randomised control trials (RCTs) and cluster randomised control trials (cRCTs) were performed by searching specified databases (MEDLINE, PubMed, Google scholar, PsycINFO) for publications from inception to May 2019 based on defined inclusion criteria. Data were extracted, study quality was assessed and statistically analysed using RevMan v5.3. Medication appropriateness, hospital admissions, mortality, falls, quality of life (QoL), Behavioural and Psychological Symptoms of Dementia (BPSD), adverse drug events (ADEs) and cognitive function could be meta-analysed.

Results

A total of 25 RCTs and cRCTs comprising 19,576 participants met the inclusion criteria. The studies tested various interventions including medication review (n = 13), staff education (n = 9), multi-disciplinary case conferencing (n = 4) and computerised clinical decision support systems (n = 2). There was an effect of interventions on medication appropriateness (RR 0.71; 95% confidence interval (CI): 0.60,0.84) (10 studies), and on medication appropriateness scales (standardised mean difference = − 0.67; 95% CI: − 0.97, − 0.36) (2 studies). There were no apparent effects on hospital admission (RR 1.00; 95% CI: 0.93, 1.06), mortality (RR 0.98; 95% CI: 0.86, 1.11), falls (RR 1.06; 95% CI: 0.89,1.26), ADEs (RR 1.04; 95% CI: 0.96,1.13), QoL (standardised mean difference = 0.16; 95% CI:-0.13, 0.45), cognitive function (weighted mean difference = 0.69; 95% CI: − 1.25, 2.64) and BPSD (RR 0.68; 95% CI: 0.44,1.06) (2 studies).

Conclusion

Modest improvements in medication appropriateness were observed in the studies included in this systematic review. However, the effect on clinical measures was limited to drive strong conclusions.
Tolerability and safety of urotainer® polihexanide 0.02% in catheterized patients: a prospective cohort study
Authors: Pannek Jürgen , Everaert Karel , Möhr Sandra , Vance Will , Van der Aa Frank , Kesselring Jürg
Published: July 2020

Background

In patients with indwelling bladder catheters for > 2 weeks, bacterial colonization is inevitable, leading to urinary tract infections or encrustations with subsequent catheter blockage. Currently, bladder irrigations are the most frequently used prophylactic means, but the best solution remains yet to be determined. In vitro studies demonstrate that polihexanide is a promising option for catheter irrigation, but no data about safety and tolerability exist.

Methods

In a prospective observational study in patients with indwelling bladder catheter for > 2 weeks, a 0.02% polihexanide solution was used to rinse the catheter on five consecutive days. Adverse events, tolerability and vital signs were assessed before, during, after and at the end of the treatment period.

Results

There was no serious adverse event in the study. A total of 28 adverse events (AEs) in 15 (46.88%) participants were experienced. Absolute changes in pain scores were not clinically relevant. No incidences of either flushing or sweating were found during instillation. Bladder spasms during instillation were reported in two cases during a single instillation. Mean pulse rates did not change by more than 3 beats per minute. Mean changes in body temperature did not exceed 0.12 °C. Clinically relevant changes in blood pressure were recorded for 3 patients.

Conclusions

This is the first study to demonstrate that a 0.02% polihexanide solution can safely be used for catheter irrigation.

Trial registration

ClinicalTrials.gov (NCT02157415), June 6th, 2014.