bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrapulmonary concentrations of meropenem administered by continuous infusion in critically ill patients with nosocomial pneumonia: a randomized pharmacokinetic trial
Authors: Benítez-Cano Adela , Luque Sonia , Sorlí Luisa , Carazo Jesús , Ramos Isabel , Campillo Nuria , Curull Víctor , Sánchez-Font Albert , Vilaplana Carles , Horcajada Juan P. , Adalia Ramón , Bermejo Silvia , Samsó Enric , Hope William , Grau Santiago 
Published: February 2020

AbstractBackgroundOptimal antimicrobial drug exposure in the lung is required for successful treatment outcomes for nosocomial pneumonia. Little is known about the intrapulmonary pharmacokinetics (PK) of meropenem when administered by continuous infusion (CI). The aim of this study was to evaluate the PK of two dosages of meropenem (3 g vs 6 g/day by CI) in the plasma and epithelial lining fluid (ELF) in critically ill patients with nosocomial pneumonia.MethodsThirty-one patients (81% male, median (IQR) age 72 (22) years) were enrolled in a prospective, randomized, clinical trial. Sixteen patients received 1 g/8 h and 15 2 g/8 h by CI (8 h infusion). Plasma and ELF meropenem concentrations were modeled using a population methodology, and Monte Carlo simulations were performed to estimate the probability of attaining (PTA) a free ELF concentration of 50% of time above MIC (50%fT>MIC), which results in logarithmic killing and the suppression of resistance in experimental models of pneumonia.ResultsThe median (IQR) of meropenem AUC0–24 hin the plasma and ELF was 287.6 (190.2) and 84.1 (78.8) mg h/L in the 1 g/8 h group vs 448.1 (231.8) and 163.0 (201.8) mg h/L in the 2 g/8 h group, respectively. The penetration ratio was approximately 30% and was comparable between the dosage groups. In the Monte Carlo simulations, only the highest approved dose of meropenem of 2 g/8 h by CI allowed to achieve an optimal PTA for all isolates with a MIC < 4 mg/L.ConclusionsAn increase in the dose of meropenem administered by CI achieved a higher exposure in the plasma and ELF. The use of the highest licensed dose of 6 g/day may be necessary to achieve an optimal coverage in ELF for all susceptible isolates (MIC ≤ 2 mg/L) in patients with conserved renal function. An alternative therapy should be considered when the presence of microorganisms with a MIC greater than 2 mg/L is suspected.Trial registrationThe trial was registered in the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT-no.2016-002796-10). Registered on 27 December 2016.
Controlling mosquitoes with semiochemicals: a review
Authors: Wooding Madelien , Naudé Yvette , Rohwer Egmont , Bouwer Marc 
Published: February 2020

AbstractThe use of semiochemicals in odour-based traps for surveillance and control of vector mosquitoes is deemed a new and viable component for integrated vector management programmes. Over 114 semiochemicals have been identified, yet implementation of these for management of infectious diseases such as malaria, dengue, chikungunya and Rift Valley fever is still a major challenge. The difficulties arise due to variation in how different mosquito species respond to not only single chemical compounds but also complex chemical blends. Additionally, mosquitoes respond to different volatile blends when they are looking for a mating partner, oviposition sites or a meal. Analytically the challenge lies not only in correctly identifying these semiochemical signals and cues but also in developing formulations that effectively mimic blend ratios that different mosquito species respond to. Only then can the formulations be used to enhance the selectivity and efficacy of odour-based traps. Understanding how mosquitoes use semiochemical cues and signals to survive may be key to unravelling these complex interactions. An overview of the current studies of these chemical messages and the chemical ecology involved in complex behavioural patterns is given. This includes an updated list of the semiochemicals which can be used for integrated vector control management programmes. A thorough understanding of these semiochemical cues is of importance for the development of new vector control methods that can be integrated into established control strategies.
Tenascin-C expression controls the maturation of articular cartilage in mice
Authors: Gruber Bastian L. , Mienaltowski Michael J. , MacLeod James N. , Schittny Johannes , Kasper Stephanie , Flück Martin 
Published: February 2020

AbstractObjectiveExpression of the de-adhesive extracellular matrix protein tenascin-C (TNC) is associated with the early postnatal development of articular cartilage which is both load-dependent and associated with chondrocyte differentiation. We assessed morphological changes in the articular cartilage of TNC deficient mice at postnatal ages of 1, 4 and 8 weeks compared to age-matched wildtype mice.ResultsCartilage integrity was assessed based on hematoxylin and eosin stained-sections from the tibial bone using a modified Mankin score. Chondrocyte density and cartilage thickness were assessed morphometrically. TNC expression was localized based on immunostaining. At 8 weeks of age, the formed tangential/transitional zone of the articular cartilage was 27% thicker and the density of chondrocytes in the articular cartilage was 55% lower in wildtype than the TNC-deficient mice. TNC protein expression was associated with chondrocytes. No relevant changes were found in mice at 1 and 4 weeks of age. The findings indicate a role of tenascin-C in the post-natal maturation of the extracellular matrix in articular cartilage. This might be a compensatory mechanism to strengthen resilience against mechanical stress.
Synchronisation of two different uncertain fractional-order chaotic systems with unknown parameters using a modified adaptive sliding-mode controller
Authors: Almatroud A. Othman 
Published: February 2020

AbstractThis article investigates a modified adaptive sliding-mode controller to achieve synchronisation between two different fractional-order chaotic systems with fully unknown parameters. A suitable parameter updating law is designed to tackle the unknown parameters. For constructing the modified adaptive sliding-mode control, a simple sliding surface is designed and the stability of the suggested method is proved using Lyapunov stability theory. Finally, the proposed method is applied to gain chaos synchronisation between two different pairs of fractional-order chaotic systems with uncertain parameters. Numerical simulations are performed to demonstrate the robustness and efficiency of the proposed method.
Adolescents’ engagement in multiple risk behaviours is associated with concussion
Authors: Shore Joshua , Janssen Ian 
Published: February 2020

Abstract
Background
The objective of this study was to investigate the relationship between engagement in multiple risk behaviours (MRB) and concussion amongst youth.

Methods
This was a cross-sectional study that used survey data collected from 3059 students in grades 6–10 (approximate ages 11–15 years) from Ontario, Canada. Students reported whether or not they had a medically diagnosed concussion within the previous 12 months and the frequency that they participated in several risky behaviours including fighting, bullying, smoking, drinking alcohol, using illicit drugs, drinking caffeinated beverages, not using protective equipment, and having unsafe sex. Responses to the risky behavior items were used to create a MRB score. The association between MRB and concussion was explored using logistic regression that controlled for several confounding variables.

Results
Approximately 10.7% of students reported that they had a medically diagnosed concussion within the past year. A dose-response relationship was found between MRB and concussion among students in grades 9–10, while in grades 6–8 students only those in the highest MRB quartile had an increased likelihood of concussion. The relative odds for concussion in the highest versus the lowest MRB quartile were 4.67 (95% confidence interval: 2.33, 9.35) in grades 9–10 students and 2.94 (95% confidence interval, 1.90, 4.56) in grades 6–8 students.

Conclusions
Engagement in MRB may be an important etiologic component of adolescent concussion. Future studies should address whether behavioural interventions designed to decrease engagement in MRB reduce the risk of concussion and other injuries.
Biomanufacturing process for the production of bacteriocins from Bacillaceae family
Authors: Lajis Ahmad Firdaus B. 
Published: February 2020

AbstractMembers of Bacillaceae family are of major interest in medical industry due to vast antimicrobial peptides they produce as therapeutic agents. For decades, synthetic and natural occurring antibiotics have been used to treat infectious diseases, but heavy dependence on these drugs has led to significant drawbacks which propel continuous development of new antibiotics generation. Recent findings have shown several bacteriocins of Bacillaceae as promising alternatives to the conventional drugs to combat the emergence of new drug-resistant pathogens. In this present review, Bacillaceae bacteriocins’ classification such as lantibiotics and thiazole/oxazole-modified microcins as well as their biochemical characterization such as sensitivity to enzymes, temperature, pH and chemicals are described. This article enlightens on the medical application of several Bacillaceae bacteriocins emphasizing those that underwent and on-going preclinical trials. This review also discusses the development of Bacillaceae bacteriocins production, focusing strains selection and fermentation factors such as inocula size, medium (carbon, nitrogen, minerals sources), temperature, pH, agitation and aeration rate, dissolved oxygen tension (DOT), fermentation time, inducers and mode of operation via various statistical methods for their optimization. It also highlights recent advance in the production of bioengineered and recombinant bacteriocins in bioreactors system which are rarely disclosed in literature.
Unilateral antibiotic-induced acute eosinophilic pneumonia on the operative side after surgery for primary lung cancer: a case report
Authors: Goda Yasufumi , Shoji Tsuyoshi , Katakura Hiromichi 
Published: February 2020

Abstract
Background
Acute eosinophilic pneumonia (AEP) is a rare idiopathic lung disease characterized by pulmonary eosinophilia. The epidemiology of AEP remains understudied; however, past reports have reported that AEP can be caused by an allergic reaction to medications, such as antibiotics or inhaled antigens, such as tobacco smoke. AEP usually occurs bilaterally. However, we encountered an unusual case of antibiotic-induced eosinophilic pneumonia showing unilateral consolidation just on the operative side, which was initially diagnosed as postoperative bacterial pneumonia and treated with antibiotic therapy. The prescribed antibiotics paradoxically provoked AEP and worsened the patient’s condition. Here, we report this antibiotic-induced AEP case showing unilateral consolidation only on the operative side which could be triggered by surgery for primary lung cancer.

Case presentation
A 74-year-old man underwent right upper lobectomy for lung adenocarcinoma. On postoperative day (POD) 9, an interstitial shadow appeared in the right lower lung field of the chest radiographs, along with a fever of 38.5 °C, dyspnea needing oxygen supplementation, and increased purulent sputum production, suggesting postoperative bacterial pneumonia. Despite administration of the broad-spectrum antibiotic, meropenem, the fever did not improve, and pulmonary opacity gradually worsened. Blood analysis showed increased peripheral eosinophils at 1182/mm3. The meropenem treatment was discontinued and bronchoscopy was performed for further evaluation, and the bronchoalveolar lavage fluid assessment showed a remarkable increase in the eosinophil population (51%). The drug lymphocyte stimulation test (DLST) for meropenem was positive. We diagnosed the patient with antibiotic-induced unilateral AEP, after which corticosteroid treatment was initiated. The patient subsequently improved and the infiltration in the right lower lung field completely disappeared. The patient was discharged on POD 43 without oxygen supplementation and is doing well without tumor recurrence 16 months after the surgery.

Conclusions
Unilateral drug-induced AEP is rare. Nonetheless, it should be recognized as a differential diagnosis of postoperative pneumonia even in cases of a unilateral radiographic infiltration, because the lung operation itself could trigger this type of AEP.
Can flipped classroom enhance class engagement and academic performance among undergraduate pediatric nursing students? A mixed-methods study
Authors: Busebaia Toqa Jameel Abbas , John Bindu 
Published: February 2020

AbstractThe study aimed to assess the nursing students’ class engagement and academic performance using flipped class using a mixed-methods research and explored their feedback and perceptions about the flipped classroom (FCR) in comparison to the current teaching methodology. Participants were 22 females and 4 males, selected through convenience sampling method, and were evaluated at pre-cycle with case-based learning, post-cycle I with FCR, and post-cycle II, using FCR with an extra class time, in a cyclical nature of inquiry. Data collection involved a triangulation technique using checklists to observe and assess students’ class engagement, quizzes for measuring class performance, and focus group interviews. The focus group interview reflections and feedback were used to refine and plan the next cycle.The quiz and the class engagement scores were highly significant at post-cycle II where the FCR was used with extra class time compared to post-cycle I and pre-cycle. The participants stated that they gained a deeper understanding of concepts, were motivated and more confident in learning the course material. The study findings support the use of FCR in learning pediatric course content. Further empirical evidence is required for adapting FCR to other courses in the curricula to determine its suitability to a particular teaching content.
Neurological soft signs for discrimination between euthymic patients with bipolar I disorder and healthy controls
Authors: El Safy Eman Roshdy , El Masry Nagda Mohamed , El Shabrawy Amany , Ellatif Ahmed Rafik Reda Abd 
Published: February 2020

Abstract
Background
Neurological soft signs in remitted state of bipolar disorder may represent trait deficits and the aim of this study was to examine the extent of neurological soft signs in euthymic patients with bipolar I disorder as compared to healthy controls. We conducted this study in Zagazig University Hospital upon 60 subjects divided into two groups: euthymic patients with bipolar I disorder group (30 patients) and control group (30 healthy individuals). Assessment of neurological soft signs was performed through Neurological Evaluation Scale and the euthymic state was determined by Young Mania Rating Scale and Hamilton Depression Rating Scale.

Results
The euthymic patient group exhibited a significantly worse performance in the total Neurological Evaluation Scale and the whole four subtest scores than healthy control subjects. There was a statistically significant association between total neurological soft sign score and mood stabilizer therapy in the studied patients. The age of onset of the disorder was correlated to the total score of Neurological Evaluation Scale which is statistically significant. The best cutoff points of the total neurological soft signs score in the discrimination between the euthymic patient group and control group was 3.5 according to the receiver operating characteristic curve.

Conclusion
This study may emphasize the role of neurological soft signs as a sign of organic brain disorder; however, further studies may be able to extend our findings to explore the etiology and pathogenesis of bipolar I disorder.
KEYNOTE-365 cohort A updated results: Pembrolizumab (pembro) plus olaparib in docetaxel-pretreated patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Yu Evan Y. , Piulats Josep M. , Gravis Gwenaelle , Laguerre Brigitte , Arranz Arija Jose Angel , Oudard Stephane , Fong Peter C.C. , Kolinsky Michael Paul , Augustin Marinela , Feyerabend Susan , Kam Audrey E. , Gurney Howard , Tafreshi Ali , Retz Margitta , Berry William R. , Mar Nataliya , Wu Helen , Schloss Charles , Poehlein Christian Heinrich , De Bono Johann S. 
Published: February 2020

100 Background: KEYNOTE-365 (NCT02861573) is a phase 1b/2 study evaluating pembro + other agents in mCRPC. Updated results from cohort A (pembro + olaparib) are reported. Methods: Docetaxel-pretreated, molecularly unselected pts with mCRPC with progression within 6 mo of screening per PSA or radiologic bone/soft tissue progression enrolled. Pts may have received 1 other chemotherapy and ≤2 2nd-generation hormone therapy (HT). Pts received pembro 200 mg IV Q3W + olaparib 400 mg PO BID. Primary end points: safety, PSA response rate (confirmed PSA decline ≥50%), and ORR per blinded independent central review. Results: Of 84 treated pts, 42 discontinued, primarily due to progression (n=29). Median age was 71 y (range, 47-83); 26% were PD-L1+, 26% had visceral disease, and 57% had RECIST-measurable disease. Median follow-up was 3 mo for all pts (n=81) and 14 mo for pts with ≥27 wks’ follow-up (n=41). See Table for efficacy outcomes. Treatment-related AEs occurred in 70 (83%) pts. Most frequent (≥30%) were nausea (33%) and anemia (31%). Grade 3-5 treatment-related AEs occurred in 29 (35%) pts. Three pts died of AEs (2 treatment related [l myocardial infarction, 1 unknown cause]). Conclusions: With additional follow-up, pembro + olaparib continued to show activity in docetaxel-pretreated, molecularly unselected pts who previously received HT for mCRPC. Safety of the combination was consistent with individual profiles of each agent. Clinical trial information: NCT02861573. [Table: see text]
Randomized phase II study of sipuleucel-T (SipT) with or without radium-223 (Ra223) in men with asymptomatic bone-metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Marshall Catherine Handy , Park Jong Chul , DeWeese Theodore L. , King Serina , Afful Michaella , Hurrelbrink Julia , Manogue Charlotte , Cotogno Patrick , Moldawer Nancy P. , Barata Pedro C. , Drake Charles G. , Posadas Edwin M. , Armstrong Andrew J. , Sartor A. Oliver , Antonarakis Emmanuel S. 
Published: February 2020

130 Background: SipT-induced antigen-specific immune responses in mCRPC patients correlate with survival. Due to the immunomodulatory effects of radiopharmaceutical agents (e.g. enhancing tumor-antigen display), we hypothesized that combined use of Ra223 and SipT would augment SipT-related immune response and improve outcomes compared to SipT alone. Methods: Patients with asymptomatic mCRPC and bone-predominant mets, without visceral mets >1.0 cm, were randomized (1:1) to standard SipT alone or combined with 6 doses of Ra223 (NCT02463799). Men in the SipT+Ra223 arm received SipT between the 2nd and 3rd dose of Ra223. Clinical endpoints were radiographic/clinical PFS, PSA response (≥50% decline), AlkPhos response (≥30% decline), and safety. Immunologic endpoints were PA2024-specific T-cell proliferation 6 wks after the first SipT infusion, PA2024-specific ELISPOT response, PAP-specific proliferation and ELISPOT, humoral responses against both antigens, and antigen spread. Results: 32 men were randomized, 16 per arm. Baseline characteristics in SipT and SipT+Ra223 arms were matched with respect to age (median 70 vs 71 yrs), Gleason (8-10: 69% vs 69%), PSA (median 82 vs 72 ng/mL), AlkPhos (median 125 vs 125 U/L) and ECOG scores (≥1: 19% vs 31%). After median follow up of 5.3 (range 2.8–26.6) mo, median PFS was longer in the SipT+Ra223 arm (10.7 vs 3.1 mo; HR 0.35, 95% CI 0.15–0.81; P=0.02). Outcomes were also better in the SipT+Ra223 arm with respect to PSA responses (5/15=33% vs 0/14=0%; P=0.04) and AlkPhos responses (9/15=60% vs 1/15=7%; P=0.01). No safety concerns were observed with the combination (grade 3 AEs shown in the Table). Conclusions: SipT combined with Ra223 was associated with improved clinical outcomes compared to SipT alone. Since neither agent reliably induces PSA responses alone, these data suggest a synergistic effect of the combination. Immunologic endpoints will be presented at the meeting. Larger randomized studies of this combination are warranted. Clinical trial information: NCT02463799. [Table: see text]
Nivolumab (NIVO) in combination with stereotactic body radiotherapy (SBRT) in pretreated patients (pts) with metastatic renal cell carcinoma (mRCC): First results of phase II NIVES study.
Authors: Masini Cristina , Iotti Cinzia , De Giorgi Ugo , Bellia Roberto Salvatore , Buti Sebastiano , Salaroli Francesco , Zampiva Ilaria , Mazzarotto Renzo , Mucciarini Claudia , Baldessari Cinzia , Bruni Alessio , Procopio Giuseppe , Kinspergher Stefania , Nole Franco , Morelli Franco , Baier Susanne , Buttigliero Consuelo , Berselli Annalisa , Pinto Carmine 
Published: February 2020

613 Background: NIVO showed an increased on OS in pre-treated mRCC. The introduction of metastasis SBRT could improve the clinical outcomes. NIVES Study evaluated the efficacy and safety of SBRT in combination with NIVO in II and III line of mRCC pts. Methods: This is a phase II, single arm, multicentre study in mRCC pts with PD after ≤2 prior anti-angiogenic therapies with measurable metastatic sites, and at least one suitable for SBRT. The pts received hypofractionated radiation in 1 lesion at dose of 10 Gy/3 fractions after 7 days from the first infusion of NIVO. NIVO is given as flat dose of 240 mg on day 1 every 14 days for 6 months, then 480 mg q4-weekly in responding pts until PD or unacceptable toxicity. The primary end point is ORR. Secondary endpoints are PFS, OS, ORR of irradiated and non-irradiated metastasis and safety profile. Results: 69 pts were enrolled from July 2017 to March 2019 in 12 Italian centers. Pt characteristics were: 79.7% clear cell histology, 82.6% males, 79.7%% IMDC intermediate/poor, median age 67 yrs (43-85), 18.8% third line, 21.7% non-nephrectomy. The most frequent sites of SBRT were lung (37.7%), lymphonodes (15.9%), bone (11.6%). At the time of this analysis, median number of NIVO doses received was 12 (1-32). The ORR was 19% (1 CR) and DCR 63.5% (no statistically difference between site of SBRT and ORR); the largest benefit in pts with clear cell histology (p=0.01). Median PFS was 4 months (95%CI, 2.8-7.1), median OS 22.1 months (95%CI, 18.1-NR). With a median follow-up of 15 months (0-25.6), 6-month and 9-month survival rates were 80.3% and 56.1% respectively. 7 pts (10.1%) discontinued treatment due to AEs; grade(G) 3-4 toxicities related to NIVO were experienced in 17 pts (24.6%). The most frequent G3-4 toxicities included diarrhea (5.8%), amylase/lipase increased (4.3%) and hypothyroidism (4.3%); no G3-4 toxicities related to SBRT. Conclusions: The NIVES Study represents the first prospective trial of NIVO and SBRT combination in pre-treated mRCC pts. At present the Study showed a high DCR and no-increase of toxicity. It is ongoing the analysis of correlation between efficacy and PD-L1 expression. Clinical trial information: NCT03469713.