bluuebunny/crossref_metadata_2025 huggingface dataset:
Partial compliance with long-acting paliperidone palmitate and impact on hospitalization: a 6-year mirror-image study
Authors: Pappa Sofia , Mason Katy
Published: May 2020

Background:

Previous studies showed a linear correlation between partial compliance with an oral antipsychotic medication and hospitalisation risk among patients with schizophrenia. Long-acting injections (LAIs) may significantly improve adherence and reduce relapse in patients with psychosis. The aim of this study was to evaluate the relationship between the level of compliance with 1-monthly paliperidone palmitate (PP1M) and hospitalisation rates.

Methods:

This was a naturalistic, mirror-image study examining retention, compliance and hospitalisation rates 3 years pre- and 3 years post-PP1M initiation. Compliance was divided in three groups: full (no missed dose/year), good (6–11injections/year), poor (<6 injections/year).

Results:

A total of 173 patients suffering from a severe mental illness (70% with a diagnosis of schizophrenia and 30% with other diagnoses) were included; 77% of patients continued PP1M for 1 year, 66% for 2 years and 55% for 3 years. Of the 95 patients who remained on PP1 throughout the 3 years of follow up, 81% showed full, 13% good, and only 6% poor compliance. In the patients who were fully compliant, the mean number of hospital admissions decreased from 1.34 to 0.43, and the mean number of bed days from 82 to 19 days per patient 3 years before and 3 years after PP1M initiation ( p < 0.001). It is noteworthy that the reductions in hospital stay were statistically significant for the group of patients with full compliance but not for the other two groups. In fact, patients with poor compliance demonstrated higher hospitalisation rates both before and after PPM1 initiation. These findings were similar in the subgroup of patients with schizophrenia who continued treatment for 3 years ( n = 68).

Conclusion:

There was a direct association between partial compliance and re-hospitalisation; fully compliant patients maintained the best outcomes in terms of reduced bed use following PPM1 initiation.
Gender, Democracy, and National Development in Nigeria
Authors: Idike Adeline Nnenna , Okeke Remi Chukwudi , Okorie Cornelius O. , Ogba Francisca N. , Ugodulunwa Christiana A.
Published: May 2020

This study examines the relationship among gender, democracy, and national development in Nigeria. This translates to a discussion of the possible linkages among gender identity, gendered representation, and national development in the country. Beyond the typical gender theorization, this article squarely focuses on women’s political representation within the Nigerian state and the power implications of the inherent challenges. The work reechoes the issue of underdevelopment as a societal phenomenon. The methodology of the contribution is normative argumentation. The theoretical framework is the power theory. The study concludes that the disarticulations between gendered representation and democracy have invariably led to contentious national development in Nigeria.
The Development of a Critical–Creative Reading Assessment Based on Problem Solving
Authors: Priyatni Endah Tri , Martutik
Published: May 2020

The ability to think critically and creatively is essential for students to help them thrive in the 21st century. Creative and critical thinking can be measured through problem solving because the assessment contains tasks that require students to find problems, analyze and evaluate problems, and work out the solutions. Therefore, this study was designed to develop a critical and creative reading assessment model based on problem solving and test the validity and reliability of the assessment. The assessment contained problem-solving essay tests that were presented in the form of stories. The material stimulus was news item texts that focused on social problems. The data collected were in the form of mean scores of expert validity testing and practitioner inter-rater reliability testing. The assessment was tried out to 36 students. The validity of the instrument was analyzed descriptively, while the reliability of the instrument was analyzed using analysis of variance (ANOVA) and intraclass correlation coefficients (ICCs) with SPSS 26. The results of the study indicated that the mean score of the expert validity test was categorized high (3.74), and the result of the reliability test showed that there was no difference in the inter-rater assessment because p > .05 and the ICC obtained was excellent ( rxx = .716). It can be concluded that the assessment developed in this study was valid and reliable, and thus can be used as an assessment to improve the critical–creative reading skills which are the essential skills needed to survive and thrive in the 21st century.
Newspaper Coverage of Renewable Energy in Nigeria: Frames, Themes, and Actors
Authors: Mbamalu Marcel
Published: May 2020

Renewable energy in Nigeria suffers decades of negative public perception and poor understanding. However, current literature shows that technology developers and investors have made far-reaching steps toward improving renewable energy efficiency, giving newspapers strong basis to change the narrative. This study examines the themes, frames, and actors in renewable energy stories to ascertain whether newspapers are changing the narrative. The study adopts Framing Theory to explain the underlying importance of newspapers in shaping public perceptions. Using simple random sampling technique, the study selects four of Nigeria’s 24 national newspapers, with 364 editions as sample size. Findings indicate that newspapers cover a wide range of themes, which researchers see as areas of need. However, framing of themes and actors reflect more of pessimism than progress. Type of actors in stories significantly predicts type of frames used. Government is the most dominant actor, and newspapers frame it as an influencer and policy driver in renewable energy. Newspapers frame investors as technology-driven players, whereas consumers, apart from receiving low attention, are passive actors. The study concludes that too much use of news as content sacrifices the interpretive frames needed to contextualize renewable energy events and actors to influence public perception. The newspapers do not therefore address formerly held negative perceptions of renewable energy in Nigeria.
Promoting Middle School Students’ Engagement Through Incorporating iPad Apps in EFL/ESL Classes
Authors: Al-Bogami Basmah , Elyas Tariq
Published: May 2020

The use of iPad and other handheld devices in classrooms is spreading. Their use can empower learners and expose them to a plethora of resources. Yet, when it comes to learning a foreign language, reasonably little has been done to empirically ascertain the influence of iPad apps on facilitating language learning as well as engaging language learners. Thus, this study endeavored to illumine the extent to which a selection of iPad applications, used as a pedagogical tool, augment young learners’ engagement and learning in English as a foreign language (EFL) environments. The participants were a group of 20 middle school girls in Saudi Arabia. The study adopted a mixed-methods approach by utilizing a self-reported Likert-type scale questionnaire divided into three constructs, namely, helpfulness, ease of use, and engagement to measure learners’ perception after the intervention of the iPad apps. In addition, observational data were gathered to record students’ primary actions toward the apps. Ultimately, based on the statistical evidence, learners exhibited highly positive attitudes toward the use of the apps in their EFL classes (reading and vocabulary) as they found the apps bolstering their level of engagement and learning compared to traditional teaching paradigms. It was also found that the apps helped foster more active learning in the classroom. This investigation hopes to assist EFL/English as a second language (ESL) practitioners, particularly in the growing domain of iPads in education.
Update on morbidity and mortality in systemic sclerosis–related interstitial lung disease
Authors: Volkmann Elizabeth R , Fischer Aryeh
Published: May 2020

Contemporary studies of systemic sclerosis consistently demonstrate that interstitial lung disease is a leading cause of disease-related death. This review summarizes morbidity and mortality outcomes in systemic sclerosis-related interstitial lung disease patients from high-quality observational and interventional studies over the last 50 years. The data presented suggest a trend for improved morbidity and mortality outcomes among present day systemic sclerosis–associated interstitial lung disease patients. Specifically, systemic sclerosis–associated interstitial lung disease patients appear to be living longer from the time of the initial diagnosis. Despite improved survival, the number one cause of death for most systemic sclerosis–associated interstitial lung disease patients remains respiratory failure from interstitial lung disease. This review describes the most important demographic, clinical, and biological factors, which affect mortality in systemic sclerosis–associated interstitial lung disease, and could be used to help stratify patients for closer monitoring and more aggressive initial treatment. The review concludes with an overview of future research needed to (1) understand how to personalize the care of systemic sclerosis–associated interstitial lung disease patients to improve morbidity and mortality outcomes; and (2) investigate whether novel therapeutic interventions (e.g. anti-fibrotics, hematopoietic stem cell transplantation) offer any meaningful long-term survival advantage over the current standard of care.
Monetary Policy Shocks and Macroeconomic Fundamentals in South Africa
Authors: Adelakun Ojo Johnson , Yousfi Karima
Published: May 2020

This South African case study controls for the fiscal side of the economy using government borrowing as a potential accelerator of asymmetry in a monetary function that follows Taylor’s rule. Through the linear and non-linear ARDL framework, we find significant asymmetry effects of monetary policy on output and inflation, respectively. We also find government borrowing as an important underlying source of asymmetries in the response of macroeconomic fundamentals to monetary policy shocks in South Africa. Thus, we recommend that monetary authorities consider not only the effectiveness or otherwise of monetary policy instruments to affect the target policy goals, but also the fact that not all the target variables react in a similar way to expansionary and contractionary monetary policy shocks.
Students and Perceived Screen Time: How Often Are Students in a Rural School District Looking at Screened Devices?
Authors: DiMartino Nicholas A. , Schultz Susan M.
Published: May 2020

As technology advances across the United States, schools should consider not only the benefits of using screened devices but also the short- and long-term effects on student health. Both the positive and negative effects of using devices are often intensified for students in rural schools, as online learning and the use of e-therapy becomes more prevalent. The purpose of this study was to investigate stakeholders’ perceptions of device use in one eighth-grade cohort in a rural school, differences between device use by students with and without disabilities, and to provide an awareness of student screen time exposure and its potential consequences. Basic qualitative methods were used to assess student, teacher, and parent perceptions of screen time use and perceptions of the recommended daily allowance of screen time in an eighth-grade cohort in a rural western New York school. Findings suggest that students, parents, and teachers perceive screen time as “excessive.” Implications for practice and future inquiry are reported.
Dose-adjusted enoxaparin thromboprophylaxis in hospitalized cancer patients: a randomized, double-blinded multicenter phase 2 trial
Authors: Zwicker Jeffrey I. , Roopkumar Joanna , Puligandla Maneka , Schlechter Benjamin L. , Sharda Anish V. , Peereboom David , Joyce Robin , Bockorny Bruno , Neuberg Donna , Bauer Kenneth A. , Khorana Alok A.
Published: May 2020

Hospitalized patients with cancer are at an increased risk of developing venous thromboembolism (VTE). The recommendation for routine pharmacologic thromboprophylaxis in hospitalized patients with cancer to prevent VTE is based on extrapolation of results from noncancer cohorts. There are limited data to support the efficacy and safety of fixed-dose low-molecular-weight heparin (LMWH) regimens in high-risk hospitalized patients with cancer. We conducted a randomized, double-blinded, phase 2 trial in hospitalized patients with active cancer at high risk of developing VTE based on Padua risk score. Patients were randomly assigned to fixed-dose enoxaparin (40 mg daily) vs weight-adjusted enoxaparin (1 mg/kg daily) during hospitalization. The primary objectives were to evaluate the safety of dose-adjusted enoxaparin and evaluate the incidence of VTE with fixed-dose enoxaparin. Blinded clinical assessments were performed at day 14, and patients randomly assigned to fixed-dose enoxaparin subsequently underwent a bilateral lower extremity ultrasound. A total of 50 patients were enrolled and randomized. The median weight of patients enrolled in weight-adjusted enoxaparin arm was 76 kg (range, 60.9-124.5 kg). There were no major hemorrhages or symptomatic VTE in either arm. At time of completion of the blinded clinical assessment, there was only 1 incidentally identified pulmonary embolus that occurred in the weight-adjusted arm. In the group randomly assigned to fixed-dose enoxaparin who subsequently underwent surveillance ultrasound, the cumulative incidence of DVT was 22% (90% binomial confidence interval, 0%-51.3%). This phase 2 trial confirms a high incidence of asymptomatic VTE among high-risk hospitalized patients with cancer and that weight-adjusted LMWH thromboprophylaxis is feasible and well-tolerated. This trial was registered at www.clinicaltrials.gov as #NCT02706249.
Autotitrating external positive end-expiratory airway pressure to abolish expiratory flow limitation during tidal breathing in patients with severe COPD: a physiological study
Authors: Suh Eui-Sik , Pompilio Pasquale , Mandal Swapna , Hill Peter , Kaltsakas Georgios , Murphy Patrick B. , Romano Robert , Moxham John , Dellaca Raffaele , Hart Nicholas
Published: May 2020

Background

The optimal noninvasive application of external positive end-expiratory pressure (EPAP) to abolish tidal-breathing expiratory flow limitation (EFLT) and minimise intrinsic positive end-expiratory pressure (PEEPi) is challenging in COPD patients. We investigated whether auto-titrating EPAP, using the forced oscillation technique (FOT) to detect and abolish EFLT, would minimise PEEPi, work of breathing and neural respiratory drive (NRD) in patients with severe COPD.

Methods

Patients with COPD with chronic respiratory failure underwent auto-titration of EPAP using a FOT-based algorithm that detected EFLT. Once optimal EPAP was identified, manual titration was performed to assess NRD (using diaphragm and parasternal intercostal muscle electromyography, EMGdiand EMGpara, respectively), transdiaphragmatic inspiratory pressure swings (ΔPdi), transdiaphragmatic pressure–time product (PTPdi) and PEEPi, between EPAP levels 2 cmH2O below to 3 cmH2O above optimal EPAP.

Results

Of 10 patients enrolled (age 65±6 years; male 60%; body mass index 27.6±7.2 kg.m−2; forced expiratory volume in 1 s 28.4±8.3% predicted), eight had EFLT, and optimal EPAP was 9 (range 4–13) cmH2O. NRD was reduced from baseline EPAP at 1 cmH2O below optimal EPAP on EMGdiand at optimal EPAP on EMGpara. In addition, at optimal EPAP, PEEPi(0.80±1.27 cmH2Oversus1.95± 1.70 cmH2O; p<0.05) was reduced compared with baseline. PTPdi(10.3±7.8 cmH2O·s−1versus16.8±8.8 cmH2O·s−1; p<0.05) and ΔPdi(12.4±7.8 cmH2Oversus18.2±5.1 cmH2O; p<0.05) were reduced at optimal EPAP+1 cmH2O compared with baseline.

Conclusion

Autotitration of EPAP, using a FOT-based algorithm to abolish EFLT, minimises transdiaphragmatic pressure swings and NRD in patients with COPD and chronic respiratory failure.
Circulating mRNAs are differentially expressed in pregnancies with severe placental insufficiency and at high risk of stillbirth
Authors: Hannan Natalie J. , Stock Owen , Spencer Rebecca , Whitehead Clare , David Anna L. , Groom Katie , Petersen Scott , Henry Amanda , Said Joanne M. , Seeho Sean , Kane Stefan C. , Gordon Lavinia , Beard Sally , Chindera Kantaraja , Karegodar Smita , Hiscock Richard , Pritchard Natasha , Kaitu’u-Lino Tu’uhevaha J. , Walker Susan P. , Tong Stephen
Published: May 2020

Background

Fetuses affected by placental insufficiency do not receive adequate nutrients and oxygenation, become growth restricted and acidemic, and can demise. Preterm fetal growth restriction is a severe form of placental insufficiency with a high risk of stillbirth. We set out to identify maternal circulating mRNA transcripts that are differentially expressed in preterm pregnancies complicated by very severe placental insufficiency, in utero fetal acidemia, and are at very high risk of stillbirth.

Methods

We performed a cohort study across six hospitals in Australia and New Zealand, prospectively collecting blood from 128 pregnancies complicated by preterm fetal growth restriction (delivery < 34 weeks’ gestation) and 42 controls. RNA-sequencing was done on all samples to discover circulating mRNAs associated with preterm fetal growth restriction and fetal acidemia in utero. We used RT-PCR to validate the associations between five lead candidate biomarkers of placental insufficiency in an independent cohort from Europe (46 with preterm fetal growth restriction) and in a third cohort of pregnancies ending in stillbirth.

Results

In the Australia and New Zealand cohort, we identified five mRNAs that were highly differentially expressed among pregnancies with preterm fetal growth restriction: NR4A2, EMP1, PGM5, SKIL, and UGT2B1. Combining three yielded an area under the receiver operative curve (AUC) of 0.95. Circulating NR4A2 and RCBTB2 in the maternal blood were dysregulated in the presence of fetal acidemia in utero. We validated the association between preterm fetal growth restriction and circulating EMP1, NR4A2, and PGM5 mRNA in a cohort from Europe. Combining EMP1 and PGM5 identified fetal growth restriction with an AUC of 0.92. Several of these genes were differentially expressed in the presence of ultrasound parameters that reflect placental insufficiency. Circulating NR4A2, EMP1, and RCBTB2 mRNA were differentially regulated in another cohort destined for stillbirth, compared to ongoing pregnancies. EMP1 mRNA appeared to have the most consistent association with placental insufficiency in all cohorts.

Conclusions

Measuring circulating mRNA offers potential as a test to identify pregnancies with severe placental insufficiency and at very high risk of stillbirth. Circulating mRNA EMP1 may be promising as a biomarker of severe placental insufficiency.
Factors affecting outcome in frameless non-isocentric stereotactic radiosurgery for trigeminal neuralgia: a multicentric cohort study
Authors: Conti Alfredo , Acker Gueliz , Pontoriero Antonio , Hardt Juliane , Kluge Anne , Cacciola Alberto , Iatì Giuseppe , Kufeld Markus , Budach Volker , Vajkoczy Peter , Beltramo Giancarlo , Pergolizzi Stefano , Bergantin Achille , Loebel Franziska , Parisi Silvana , Senger Carolin , Romanelli Pantaleo
Published: May 2020

Background

Stereotactic radiosurgery (SRS) is an effective treatment for trigeminal neuralgia (TN). Nevertheless, a proportion of patients will experience recurrence and treatment-related sensory disturbances. In order to evaluate the predictors of efficacy and safety of image-guided non-isocentric radiosurgery, we analyzed the impact of trigeminal nerve volume and the nerve dose/volume relationship, together with relevant clinical characteristics.

Methods

Two-hundred and ninety-six procedures were performed on 262 patients at three centers. In 17 patients the TN was secondary to multiple sclerosis (MS). Trigeminal pain and sensory disturbances were classified according to the Barrow Neurological Institute (BNI) scale. Pain-free-intervals were investigated using Kaplan Meier analyses. Univariate and multivariate Cox regression analyses were performed to identify predictors.

Results

The median follow-up period was 38 months, median maximal dose 72.4 Gy, median target nerve volume 25 mm3, and median prescription dose 60 Gy. Pain control rate (BNI I-III) at 6, 12, 24, 36, 48, and 60 months were 96.8, 90.9, 84.2, 81.4, 74.2, and 71.2%, respectively. Overall, 18% of patients developed sensory disturbances. Patients with volume ≥ 30 mm3 were more likely to maintain pain relief (p = 0.031), and low integral dose (< 1.4 mJ) tended to be associated with more pain recurrence than intermediate (1.4–2.7 mJ) or high integral dose (> 2.7 mJ; low vs. intermediate: log-rank test, χ2 = 5.02, p = 0.019; low vs. high: log-rank test, χ2 = 6.026, p = 0.014). MS, integral dose, and mean dose were the factors associated with pain recurrence, while re-irradiation and MS were predictors for sensory disturbance in the multivariate analysis.

Conclusions

The dose to nerve volume ratio is predictive of pain recurrence in TN, and re-irradiation has a major impact on the development of sensory disturbances after non-isocentric SRS. Interestingly, the integral dose may differ significantly in treatments using apparently similar dose and volume constraints.
Acceptability of genetically engineered algae biofuels in Europe: opinions of experts and stakeholders
Authors: Varela Villarreal Jessica , Burgués Cecilia , Rösch Christine
Published: May 2020

Background

The development of alternative pathways for sustainable fuel production is a crucial task for politics, industry and research, since the current use of fossil fuels contributes to resource depletion and climate change. Microalgae are a promising option, but the technology readiness level (TRL) is low and cannot compete economically with fossil fuels. Novel genetic engineering technologies are being investigated to improve productivity and reduce the cost of harvesting products extracted from or excreted by microalgae for fuel production. However, high resource efficiency and low costs alone are no guarantee that algae fuels will find their way into the market. Technologies must be accepted by the public to become valuable for society. Despite strong efforts in algae research and development, as well as political commitments at different scales to promote algae biofuels for transport sectors, little is known about public acceptance of this alternative transport fuel. Despite the advantages of algae technology, genetically engineered (GE) microalgae can be controversial in Europe due to risk perception. Therefore, the aim of this study was to investigate, for the first time, the knowledge and views of European experts and stakeholders on the conditions and requirements for acceptability of GE microalgae for next generation biofuel production.

Results

The results of the survey-based study indicate that the majority of the respondents believe that GE algae biofuels could provide strong benefits compared to other fuels. The majority would choose to be final consumers of engineered algae biofuels, if there is clear evidence of their benefits and open communication of potential risks. They believe that closed production systems with high security standards and rigorous risk assessment should be applied to avoid unintended impacts on humans and nature. Some respondents, however, are not convinced about the need to alter natural occurring algae strains to increase productivity, arguing that there is a huge unexplored variety, and that the consequences of using genome editing are still unknown.

Conclusions

This evaluation of the opinions held by European experts and stakeholders regarding GE algae biofuels provides valuable and differentiated insights, both for future research and for the development of feasible socio-technical algae systems for next generation biofuel production. The identified conditions and requirements for achieving public acceptability can support the (re-)design of this innovative technology and adaptation of the framework conditions towards the implementation of algae biofuels in Europe.
Rational engineering of the Trichoderma reesei RUT-C30 strain into an industrially relevant platform for cellulase production
Authors: Fonseca Lucas Miranda , Parreiras Lucas Salera , Murakami Mario Tyago
Published: May 2020

Background

The path for the development of hypersecreting strains of Trichoderma reesei capable of producing industrially relevant enzyme titers remains elusive despite over 70 years of research and industrial utilization. Herein, we describe the rational engineering of the publicly available T. reesei RUT-C30 strain and a customized process for cellulase production based on agroindustrial by-products.

Results

A CRISPR/Cas9 system was used to introduce six genetic modifications in RUT-C30. Implemented changes included the constitutive expression of a mutated allele of the cellulase master regulator XYR1, the expression of two heterologous enzymes, the β-glucosidase CEL3A from Talaromyces emersonii and the invertase SUC1 from Aspergillus niger, and the deletion of genes encoding the cellulase repressor ACE1 and the extracellular proteases SLP1 and PEP1. These alterations resulted in a remarkable increase of protein secretion rates by RUT-C30 and amended its well described β-glucosidase deficiency while enabling the utilization of sucrose and eliminating the requirement of inducing sugars for enzyme production. With a developed sugarcane molasses-based bioprocess, the engineered strain reached an extracellular protein titer of 80.6 g L−1 (0.24 g L−1 h−1), which is the highest experimentally supported titer so far reported for T. reesei. The produced enzyme cocktail displayed increased levels of cellulase and hemicellulase activities, with particularly large increments being observed for the specific activities of β-glucosidase (72-fold) and xylanase (42-fold). Notably, it also exhibited a saccharification efficiency similar to that of a commercially available cellulase preparation in the deconstruction of industrially pretreated sugarcane straw.

Conclusion

This work demonstrates the rational steps for the development of a cellulase hyperproducing strain from a well-characterized genetic background available in the public domain, the RUT-C30, associated with an industrially relevant bioprocess, paving new perspectives for Trichoderma research on cellulase production.
Enhanced biohydrogen production from cotton stalk hydrolysate of Enterobacter cloacae WL1318 by overexpression of the formate hydrogen lyase activator gene
Authors: Zhang Qin , You Shaolin , Li Yanbin , Qu Xiaowei , Jiang Hui
Published: May 2020

Background

Biohydrogen production from lignocellulose has become an important hydrogen production method due to its diversity, renewability, and cheapness. Overexpression of the formate hydrogen lyase activator (fhlA) gene is a promising tactic for enhancement of hydrogen production in facultative anaerobicEnterobacter. As a species ofEnterobacter,Enterobacter cloacaewas reported as a highly efficient hydrogen-producing bacterium. However, little work has been reported in terms of cloning and expressing thefhlAgene inE. cloacaefor lignocellulose-based hydrogen production.

Results

In this study, the formate hydrogen lyase activator (fhlA) gene was cloned and overexpressed inEnterobacter cloacaeWL1318. We found that the recombinant strain significantly enhanced cumulative hydrogen production by 188% following fermentation of cotton stalk hydrolysate for 24 h, and maintained improved production above 30% throughout the fermentation process compared to the wild strain. Accordingly, overexpression of thefhlAgene resulted in an enhanced hydrogen production potential (P) and maximum hydrogen production rate (Rm), as well as a shortened lag phase time (λ) for the recombinant strain. Additionally, the recombinant strain also displayed improved glucose (12%) and xylose (3.4%) consumption and hydrogen yield Y(H2/S) (37.0%) compared to the wild strain. Moreover, the metabolites and specific enzyme profiles demonstrated that reduced flux in the competitive branch, including succinic, acetic, and lactic acids, and ethanol generation, coupled with increased flux in the pyruvate node and formate splitting branch, benefited hydrogen synthesis.

Conclusions

The results conclusively prove that overexpression offhlAgene inE. cloacaeWL1318 can effectively enhance the hydrogen production from cotton stalk hydrolysate, and reduce the metabolic flux in the competitive branch. It is the first attempt to engineer thefhlAgene in the hydrogen-producing bacteriumE. cloacae. This work provides a highly efficient engineered bacterium for biohydrogen production from fermentation of lignocellulosic hydrolysate in the future.
Clostridioides difficile ribotype distribution in a large teaching hospital in Serbia
Authors: Korać Miloš , Rupnik Maja , Nikolić Nataša , Jovanović Milica , Tošić Tanja , Malinić Jovan , Mitrović Nikola , Marković Marko , Vujović Ankica , Peruničić Sanja , Bojović Ksenija , Djordjević Vladimir , Barać Aleksandra , Milošević Ivana
Published: May 2020

Background

The global epidemic of nosocomial diarrhea caused by Clostridioides (Clostridium) difficile started in 2000, with high mortality rates and emergence of a new hypervirulent strain NAP1/BI/027. The aim of this study was to assess the presence of ribotype 027 and other C. difficile ribotypes in a Serbian University Hospital, compare the temporal variability of ribotypes 3 years apart, as well as to compare clinical, demographic and laboratory characteristics and disease outcome among patients infected with 027 and non-027 ribotype. This was a prospective observational cohort study addressing 4-month intervals during 2014/2015 and 2017/2018.

Results

Ribotyping was performed in 64 non-duplicate C. difficile strains. Ribotype 027 was the most prevalent, and was detected in 53 (82.8%) patients (43/45 and 10/19 patients in 2014–2015 and 2017/2018, respectively). Other detected ribotypes were 001/072 in 4 (6.3%), 002 in 4 (6.3%), 014/020 in 2 (3.1%) and 176 in 1 (1.5%) patient. The percentage of the patients infected with ribotype 027 significantly decreased during the 3-year period, from 95.6 to 52.6% (p < 0.001). Ribotype 027 infection was associated with fluoroquinolone treatment more frequently than infection with other ribotypes [33 (62.3%) vs. 2 (18.2%), p = 0.010)]. A severe C. difficile infection was diagnosed more often in patients with the detected ribotype 027 compared to those infected with non-027 ribotypes (p = 0.006). No significant difference in the mortality and recurrence rates was found between the patients infected with ribotype 027 and those infected with other ribotypes [10/53 (18.8%) vs. 2/11 (18.2%), p = 0.708, and 10/35 (28.6%) vs. 0/2 (0%), p = 1.000, respectively].

Conclusion

Clostridium difficile ribotype 027 was the most prevalent ribotype among patients in a large Serbian hospital, but there is a clear decreasing trend.
Emergency department visits at Rambam health care campus, Israel: non-trauma related dental conditions
Authors: Bilder Leon , Horwitz Jacob , Zigdon-Giladi Hadar , Gutmacher Zvi
Published: May 2020

Objectives

Studies of emergency department (ED) visits for non-traumatic dental conditions (NTDCs) have been carried out in the USA and Canada. In Israel, there is a shortage of such studies. In the current retrospective study, we report on the frequency and distribution of NTDCs ED visits at Rambam Health Care Campus (Rambam), in Haifa, which is an academic hospital serving more than 2.4 million residents of Northern Israel.

Materials and methods

The data concerning ED visits at Rambam between 2010 and 2017 were obtained retrospectively from Rambam’s computerized clinical and personal database of adult patients (≥18 years) visiting the ED for NTDCs.

Results

Overall, 1.8% of the patients who visited the Rambam ED, were identified as presenting with NTDCs. From 2010 until 2017, the number of NTDCs admissions increased by 45%, while the total ED admissions rose by 16%. The average waiting time for maxillofacial consultations for patients with NTDCs increased from 102 min in 2010 to 138 min in 2017. The busiest hours in the ED for NTDCs were during the morning shifts (47% of daily visits).

Conclusions

The results of the study show that systemic and conceptual changes are needed to reduce the number of non-trauma related applications to ED.These changes can be by increasing the number of personnel or by introducing recent advances such as tele-medicine for prescreening of patients. This change calls for a greater involvement of the health policy leaders to provide alternative solutions for emergency dental care.
Microencapsulation of microbial antioxidants from Mucor circinelloides, their physico-chemical characterization, in vitro digestion and releasing behaviors in food
Authors: Hameed Ahsan , Hussain Syed Ammar , Nosheen Shaista , Muhammad Zafarullah , Wu Yang , Ullah Samee , Suleria Hafiz Ansar Rasul , Song Yuanda
Published: May 2020

This study aimed at increasing the stability of heat-labile and pH-sensitive microbial antioxidants by the microencapsulation. Microbial antioxidants from Mucor circinelloides were microencapsulated. The physico-chemical and powder flowing properties of resulting microcapsules were evaluated. The initial safety studies were evaluated by in vivo acute oral toxicity tests. The bio-accessibility of powders vs. extracts was analyzed in in vitro digestion models with further application of microcapsules to model food system. Physico-chemical properties were significantly different (p < 0.0001) for all microcapsules regardless of their non-substantial variations (p > 0.05) in powder flowing properties. The microencapsulation of extract with 5% whey protein hydrogels (WPHG) + 5% pectin (TA) showed higher retain-ability of polyphenols accompanying low degradation in gastric and intestinal digestion and with no major toxicity signs. The addition of TA microcapsule did not produce any nutritional, physico-chemical, compositional, and nutritional distinctions in cheese. Microencapsulation proved to be appropriate approach for not only protecting the thermo-labile and pH-sensitive microbial antioxidants but also for enhanced bioavailability, and targeted release of bioactive extracts.
Monetary policy uncertainty spillovers in time and frequency domains
Authors: Gupta Rangan , Lau Chi Keung Marco , Nel Jacobus A. , Sheng Xin
Published: May 2020

We use the recently created monthly Interest Rate Uncertainty measure, to investigate monetary policy uncertainty across the US, Germany, France, Italy, Spain, UK, Japan, Canada, and Sweden in both the time and frequency domains. We find that the largest spillover indices are from innovations in the country itself; however, there are some instances where spillover indices between countries are large. These relationships change over time and we observe large variances in pairwise spillovers during the global financial crisis. We find that most of the volatility is confined to the crisis period. Policy makers should consider accounting for the spillovers from the US, Germany, France and Spain, as we found that they are the most consistent net transmitters of monetary policy uncertainty.
Frequent upregulation of G9a promotes RelB-dependent proliferation and survival in multiple myeloma
Authors: Zhang Xi Yun , Rajagopalan Deepa , Chung Tae-Hoon , Hooi Lissa , Toh Tan Boon , Tian Johann Shane , Rashid Masturah Bte Mohd Abdul , Sahib Noor Rashidha Bte Meera , Gu Mengjie , Lim Jhin Jieh , Wang Wilson , Chng Wee Joo , Jha Sudhakar , Chow Edward Kai-Hua
Published: May 2020

Background

Multiple myeloma is an incurable hematological malignancy characterized by a heterogeneous genetic and epigenetic landscape. Although a number of genetic aberrations associated with myeloma pathogenesis, progression and prognosis have been well characterized, the role of many epigenetic aberrations in multiple myeloma remain elusive. G9a, a histone methyltransferase, has been found to promote disease progression, proliferation and metastasis via diverse mechanisms in several cancers. A role for G9a in multiple myeloma, however, has not been previously explored.

Methods

Expression levels of G9a/EHMT2 of multiple myeloma cell lines and control cells Peripheral Blood Mononuclear Cells (PBMCs) were analyzed. Correlation of G9a expression and overall survival of multiple myeloma patients were analyzed using patient sample database. To further study the function of G9a in multiple myeloma, G9a depleted multiple myeloma cells were built by lentiviral transduction, of which proliferation, colony formation assays as well as tumorigenesis were measured. RNA-seq of G9a depleted multiple myeloma with controls were performed to explore the downstream mechanism of G9a regulation in multiple myeloma.

Results

G9a is upregulated in a range of multiple myeloma cell lines. G9a expression portends poorer survival outcomes in a cohort of multiple myeloma patients. Depletion of G9a inhibited proliferation and tumorigenesis in multiple myeloma. RelB was significantly downregulated by G9a depletion or small molecule inhibition of G9a/GLP inhibitor UNC0642, inducing transcription of proapoptotic genes Bim and BMF. Rescuing RelB eliminated the inhibition in proliferation and tumorigenesis by G9a depletion.

Conclusions

In this study, we demonstrated that G9a is upregulated in most multiple myeloma cell lines. Furthermore, G9a loss-of-function analysis provided evidence that G9a contributes to multiple myeloma cell survival and proliferation. This study found that G9a interacts with NF-κB pathway as a key regulator of RelB in multiple myeloma and regulates RelB-dependent multiple myeloma survival. G9a therefore is a promising therapeutic target for multiple myeloma.
No evidence for Wolbachia as a nutritional co-obligate endosymbiont in the aphid Pentalonia nigronervosa
Authors: Manzano-Marín Alejandro
Published: May 2020

Obligate symbiotic associations are present in a wide variety of animals with a nutrient-restricted diet. Aphids (hemiptera: Aphididae) almost-universally host Buchnera aphidicola bacteria in specialised organs (called bacteriomes). These bacteria supply the aphid with essential nutrients lacking from their diet (i.e. essential amino acids and some B vitamins). Some aphid lineages, such as species from the Lacninae subfamily, have evolved co-obligate associations with secondary endosymbionts, deriving from a loss of biotin- and riboflavin-biosynthetic genes. In this study, I re-analyse previously published sequencing data from the banana aphid Pentalonia nigronervosa. I show that the metabolic inference results from De Clerck et al. (Microbiome 3:63, 2015) are incorrect and possibly arise from the use of inadequate methods. Additionally, I discuss how the seemingly biased interpretation of their antibiotic treatment analyses together with an incorrect genome-based metabolic inference resulted in the erroneous suggestion “that a co-obligatory symbiosis between B. aphidicola and Wolbachia occurs in the banana aphid”.
Relationship between circulating miR-132 and non-alcoholic fatty liver disease in a Chinese population
Authors: Zong Yicen , Yan Jing , Jin Li , Xu Bo , He Zhen , Zhang Rong , Hu Cheng , Jia Weiping
Published: May 2020

Background

Non-invasive diagnostic markers are of great importance for early screening nonalcoholic fatty liver disease (NAFLD). MicroRNAs (miRNAs) play significant roles in many metabolic disease, including NAFLD. Therefore, this study focusd on a Chinese population to explore the possible correlation between circulating miR-132 and NAFLD.

Results

Serum miR-132 was positively associated with NAFLD in non-type 2 diabetes mellitus (T2DM) groups by logistic regression (OR = 3.082 [1.057, 8.988],P = 0.039) after adjusting age, sex, and body mass index (BMI). Additionally, in non-T2DM subgroup, after adjusting age, sex, bmi, serum miR-132 was significantly associated with ALT (β ± SE = 0.005 ± 0.002,P = 0.018), TG (β ± SE = 0.072 ± 0.029,P = 0.015), FPG (β ± SE = 0.123 ± 0.058,P = 0.036), γ-GT (β ± SE = 0.002 ± 0.001,P = 0.047), apoE (β ± SE = 0.038 ± 0.002,P = 0.017) .

Conclusions

Serum miR-132 was found to be associated with NAFLD risk in a Chinese cross-section study. This finding provides a prospective research direction for early screening and diagnosing NAFLD.
Genomic Profiling of Smoldering Multiple Myeloma Identifies Patients at a High Risk of Disease Progression
Authors: Bustoros Mark , Sklavenitis-Pistofidis Romanos , Park Jihye , Redd Robert , Zhitomirsky Benny , Dunford Andrew J. , Salem Karma , Tai Yu-Tzu , Anand Shankara , Mouhieddine Tarek H. , Chavda Selina J. , Boehner Cody , Elagina Liudmila , Neuse Carl Jannes , Cha Justin , Rahmat Mahshid , Taylor-Weiner Amaro , Van Allen Eliezer , Kumar Shaji , Kastritis Efstathis , Leshchiner Ignaty , Morgan Elizabeth A. , Laubach Jacob , Casneuf Tineke , Richardson Paul , Munshi Nikhil C. , Anderson Kenneth C. , Trippa Lorenzo , Aguet François , Stewart Chip , Dimopoulos Meletios-Athanasios , Yong Kwee , Bergsagel P. Leif , Manier Salomon , Getz Gad , Ghobrial Irene M.
Published: May 2020

PURPOSE

Smoldering multiple myeloma (SMM) is a precursor condition of multiple myeloma (MM) with a 10% annual risk of progression. Various prognostic models exist for risk stratification; however, those are based on solely clinical metrics. The discovery of genomic alterations that underlie disease progression to MM could improve current risk models.

METHODS

We used next-generation sequencing to study 214 patients with SMM. We performed whole-exome sequencing on 166 tumors, including 5 with serial samples, and deep targeted sequencing on 48 tumors.

RESULTS

We observed that most of the genetic alterations necessary for progression have already been acquired by the diagnosis of SMM. Particularly, we found that alterations of the mitogen-activated protein kinase pathway ( KRAS and NRAS single nucleotide variants [SNVs]), the DNA repair pathway (deletion 17p, TP53, and ATM SNVs), and MYC (translocations or copy number variations) were all independent risk factors of progression after accounting for clinical risk staging. We validated these findings in an external SMM cohort by showing that patients who have any of these three features have a higher risk of progressing to MM. Moreover, APOBEC associated mutations were enriched in patients who progressed and were associated with a shorter time to progression in our cohort.

CONCLUSION

SMM is a genetically mature entity whereby most driver genetic alterations have already occurred, which suggests the existence of a right-skewed model of genetic evolution from monoclonal gammopathy of undetermined significance to MM. We identified and externally validated genomic predictors of progression that could distinguish patients at high risk of progression to MM and, thus, improve on the precision of current clinical models.
R package “QRISK3”: an unofficial research purposed implementation of ClinRisk’s QRISK3 algorithm into R
Authors: Li Yan , Sperrin Matthew , van Staa Tjeerd
Published: May 2020

Cardiovascular disease has been the leading cause of death for decades. Risk prediction models are used to identify high risk patients; the most common model used in the UK is ClinRisk’s QRISK3. In this paper we describe the implementation of the QRISK3 algorithm into an R package. The package was successfully validated by the open sourced QRISK3 algorithm and QRISK3 SAS program. We provide detailed examples of the use of the package, including assigning QRISK3 scores for a large cohort of patients. This R package could help the research community to improve future risk prediction models based on a currently used risk prediction model. The package is available from CRAN: https://cran.r-project.org/web/packages/QRISK3/index.html.
Sequence variation at 8q24.21 and risk of back pain
Authors: Williams Frances M.K. , Tsepilov Yakov A. , Freidin Maxim B. , Shashkova Tatiana I. , Suri Pradeep , Aulchenko Yurii S.
Published: May 2020

Back pain (BP) is a common condition of major social importance and poorly understood pathogenesis. Intervertebral lumbar disc degeneration in all its guises is one of the major biological risk factors for BP. Previously, we identified the locus at 8q24.21 associated with chronic BP, which has been found elsewhere associated with sciatica after surgery for lumbar disc herniation. In the current study we used co-localisation methods to identify the gene most likely to harbor the causal variant. We show that the same functional variant at the 8q24.21 locus is responsible for both lumbar disc degeneration and BP, and we also studied the effects of this locus on related phenotypes. Our results link the locus to intervertebral disc and bone mineral density, but not to anthropometric measurements, thus corroborating the epidemiological evidence. Moreover, the same functional variant at the locus is more likely to affect the expression of the nearby FAM49B gene, rather than the GSDMC gene, which was previously proposed as a causative one for BP.
The effects of a temporal processing-based auditory training program on the auditory skills of elderly users of hearing aids: a study protocol for a randomized clinical trial
Authors: Rahbar Nariman , Sattari Karim , Ahadi Mohsen , Haghani Hamid
Published: May 2020

Background: One of the most important effects of age-related declines in neural processing speed is the impairment of temporal resolution, which leads to difficulty hearing in noisy environments. Since the central auditory system is highly plastic, by designing and implementing a temporal processing-based auditory training program, we can help the elderly improve their listening skills and speech understanding in noisy environments.

Methods:In the first phase of this research, based on the theoretical framework of temporal processing, an auditory training solution was developed as a software program. In the second phase, which will be described in the present study, the effects of the designed program on the listening skills of the elderly users of hearing aids (age: 60-75 years) will be studied in the control and intervention groups. In the intervention group, the auditory training program will be implemented for three months (36 sessions), and the results of central tests (GIN, DPT, QuickSIN) and the electrophysiological speech-ABR test will be compared in both groups before, immediately and one month after the intervention.

Discussion: Since temporal processing is not sufficient in auditory training programs for the elderly with hearing impairments, implementation of a temporal processing-based auditory training program can reduce hearing problems in noisy environments among elderly users of hearing aids.

Trial registration:This study was registered as a clinical trial in the Iranian Registry of Clinical Trials (IRCT20190921044838N1) on December 25, 2019.