bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

BackgroundThe 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.MethodsPatients 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.ResultsOf 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.ConclusionAutotitration 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundBiohydrogen 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.ResultsIn 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.ConclusionsThe 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

Abstract
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

Abstract
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

AbstractThis 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

AbstractWe 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.