bluuebunny/crossref_metadata_2025_split huggingface dataset:
Limited Evolutionary Conservation of the Phenotypic Effects of Antibiotic Resistance Mutations
Authors: Apjok Gábor , Boross Gábor , Nyerges Ákos , Fekete Gergely , Lázár Viktória , Papp Balázs , Pál Csaba , Csörgő Bálint 
Published: April 2019

AbstractMultidrug-resistant clinical isolates are common in certain pathogens, but rare in others. This pattern may be due to the fact that mutations shaping resistance have species-specific effects. To investigate this issue, we transferred a range of resistance-conferring mutations and a full resistance gene into Escherichia coli and closely related bacteria. We found that resistance mutations in one bacterial species frequently provide no resistance, in fact even yielding drug hypersensitivity in close relatives. In depth analysis of a key gene involved in aminoglycoside resistance (trkH) indicated that preexisting mutations in other genes—intergenic epistasis—underlie such extreme differences in mutational effects between species. Finally, reconstruction of adaptive landscapes under multiple antibiotic stresses revealed that mutations frequently provide multidrug resistance or elevated drug susceptibility (i.e., collateral sensitivity) only with certain combinations of other resistance mutations. We conclude that resistance and collateral sensitivity are contingent upon the genetic makeup of the bacterial population, and such contingency could shape the long-term fate of resistant bacteria. These results underlie the importance of species-specific treatment strategies.
Comparative efficacy and acceptability of treatments for restless legs syndrome in end-stage renal disease: a systematic review and network meta-analysis
Authors: Huang Chien-Wei , Lee Min-Jing , Wang Liang-Jen , Lee Po-Tsang , Tu Yu-Kang , Hsu Chih-Wei , Lin Pao-Yen 
Published: April 2019

Abstract

Background
Restless legs syndrome (RLS) is common in end-stage renal disease (ESRD) patients and impairs health and quality of life significantly. However, the optimal treatment of RLS in ESRD patients is uncertain and less studied compared with idiopathic RLS patients.

Methods
We conducted a systematic review and network meta-analysis to compare the efficacy and acceptability of treatments for RLS in ESRD patients. Randomized controlled trials (RCTs) by February 2019 in the PubMed, Cochrane Library, Embase and ClinicalTrials.gov were reviewed. RLS severity reduction was treated as treatment efficacy, and adverse events were treated as acceptable. Both outcomes were appraised using a random effects model expressed as standardized mean differences and odds ratios with 95% confidence intervals (CIs), respectively, and were ranked using surface under the cumulative ranking curve (SUCRA) probabilities to obtain a hierarchy of interventions.

Results
A total of 12 RCTs were included, comprising 9 interventions and 498 participants. All the interventions significantly improved RLS severity without critical side effects compared with placebo. Gabapentin achieved the greatest decrease of RLS severity [standardized mean difference (SMD) = 1.95, 95% CI 0.81–3.09 (SUCRA: 79.3%)], despite its frequent adverse events [SMD = 0.18, 95% CI 0.02–1.50 (19.9%)]. The combination therapy of exercise plus dopamine agonist had better efficacy [SMD = 1.60, 95% CI 0.08–3.12 (59.8%)] and acceptability [SMD = 1.41, 95% CI 0.01–142.53 (63.9%)] compared with that of vitamin C plus vitamin E [SMD = 1.50, 95% CI 0.47–2.54 (56.6%); SMD = 0.32, 95% CI 0.04–2.86 (32.5%)].

Conclusions
This network meta-analysis supports that gabapentin is the most effective treatment for RLS in ESRD patients. Exercise plus dopamine agonist is a favorable combination therapy concerning side effects. Future large RCTs with long-term treatment outcomes are necessary.
Lyα view around a z = 2.84 hyperluminous QSO at a node of the cosmic web
Authors: Kikuta Satoshi , Matsuda Yuichi , Cen Renyue , Steidel Charles C , Yagi Masafumi , Hayashino Tomoki , Imanishi Masatoshi , Komiyama Yutaka , Momose Rieko , Saito Tomoki 
Published: April 2019

Abstract
We report on the results of deep and wide-field (1.1 deg2) narrow-band observations with Subaru/Hyper Suprime-Cam (HSC) of a field around a hyperluminous QSO (HLQSO), HS$\, 1549+$1919, residing in a protocluster at z = 2.84, to map the large-scale structure of Lyα emitters (LAEs). One HSC pointing enables us to detect 3490 LAEs and 76 extended Lyα blobs (LABs), probing diverse environments from voids to protoclusters. The HLQSO is found to be near the center of the protocluster, which corresponds to the intersection of $\sim \,$100 comoving Mpc-scale structures of LAEs. LABs are basically distributed along the large-scale structure, with larger ones particularly clustering around the HLQSO, confirming a previously noted tendency of LABs to prefer denser environments. Moreover, the shapes of LABs near the HLQSO appear to be aligned with the large-scale structure. Finally, a deep Lyα image reveals a diffuse Lyα nebula along a filamentary structure with no luminous UV/sub-mm counterpart. We suggest that the diffuse nebula is due to a cold filament with high clumping factor illuminated by the QSO, with the required high clumpiness provided by unresolved residing halos of mass $\le 10^{9-10}\, M_\odot$.
Prevalence and Risk Factors of Exposure Keratopathy Across Different Intensive Care Units
Authors: Hartford Juliet Beth , Bian Yandong , Mathews Priya Mary , De Rojas Joaquin , Garg Aakriti , Rasool Nailyn , Schroder Sara Kjerstin , Trief Danielle 
Published: April 2019

Purpose:
To determine the prevalence and risk factors of exposure keratopathy (EK) across different intensive care units (ICU) at Columbia University Medical Center, including the Pediatric ICU (PICU), Medical ICU (MICU), and Neurologic ICU (NICU).

Methods:
In this prospective cohort study, 65 patients were examined daily during their admission in the PICU (27 patients), MICU (15 patients), and NICU (23 patients). Data on eyelid position, conjunctival and corneal changes, Bell's and blink reflexes, medications, Glasgow Coma Scale rating, and ventilation type were collected.

Results:
Overall EK percentages were as follows: PICU 19%, MICU 60%, and NICU 48%. The prevalence of EK was lowest in the PICU (P = 0.013). Factors associated with EK were lagophthalmos (P < 0.001), an absent Bell's reflex (P = 0.003), an absent blink reflex (P < 0.001), conjunctival injection (P < 0.001), a low Glasgow Coma Scale score (P < 0.001), intubation (P < 0.001), surgery before examination (P < 0.001), dialysis (P = 0.002), and administration of opioid (P < 0.001), sedative (P < 0.001), and neuromuscular blocking medications (P = 0.006).

Conclusions:
This is the first study to examine the rates and risk factors of EK across different ICU settings. The prevalence of EK was lowest in the PICU, which may partly be explained by the increased number of PICU patients receiving noninvasive ventilation and the absence of conjunctival chemosis.
Investigating the Impact of Intensive Care Unit Interruptions on Patient Safety Events and Electronic Health Records Use: An Observational Study
Authors: Khairat Saif , Whitt Stevan , Craven Catherine K. , Pak Youngju , Shyu Chi-Ren , Gong Yang 
Published: April 2019

Background
Constant interruptions and continual data flow result in information overload for clinicians and become barriers to identification and extraction of relevant patient data and its correct interpretation. The aim of the study was to describe the types, frequencies, and impact of intensive care unit (ICU) interruptions on patient safety event occurrences and electronic health records (EHR) use.

Methods
We conducted a live observational study for 6 weeks, observing critical care physicians’ and other providers’ communication while recording interruptions, patient safety events, and EHR use.

Results
Across 55 hours, the researchers observed 7515 ICU tasks, 15.7% of which were interrupted. We found that technological interruptions directly influences the occurrence of patient safety events: an increase in technological interruptions directly contributes to patient safety event occurrence (P = 0.004). Technological interruptions had a direct effect on human interruptions, as the frequency of technological interruptions increase, human interruptions also increase (P = 0.02).

Conclusions
A prospective, observational study was conducted to understand the relationship between interruptions and patient safety events and EHR use, in a time-sensitive, activity-based study in a large academic medical center with a certified EHR system. We found that technological interruptions were statistically correlated to the occurrence of patient safety events, and human interruptions significantly affected the level of EHR use. This study recommends that ICUs adopt a safety culture that promotes minimizing unnecessary interruptions, such as side conversations during rounds, for improved quality of care.
Breast Reduction Following Hormonal Therapy in a Transgender Female Patient
Authors: Margulies Ilana G. , Xu Hope , Kozato Aki , Facque Alexander , Taub Peter J. 
Published: April 2019

Abstract
In male-to-female gender transition, individuals request a number of interventions, including hormonal therapy, to promote feminizing characteristics. Estrogen-based medication is prescribed to increase breast development, decrease facial hair, promote feminine adipose tissue deposition, and soften skin. Surgical breast augmentation to supplement unsatisfying breast growth after hormonal therapy is a common and well-studied course of management for such transgender patients. In a departure from convention, the authors present a case of symptomatic macromastia requiring surgical breast reduction in a transgender woman following 24 years of hormonal therapy and illicit silicone injections in multiple areas of her body, including the breasts.
Concentration of Chondrogenic Soluble Factors in Freshly Harvested Lipoaspirate
Authors: Ruhl Tim , Stromps Jan-Philipp , Depenau Lisa-Marie Maxi , Kim Bong-Sung , Pallua Norbert 
Published: April 2019

BackgroundCartilage tissue has a limited capacity for healing with the consequence that patients are often treated symptomatically until they become candidates for osteotomy or total joint replacement. Alternative biological therapies, for example, application of platelet-rich plasma and implantation of chondrocytes and mesenchymal stem cells, have emerged as a new treatment modality to repair articular cartilage. In addition, autologous fat transfer is performed for treatment of cartilage defects, example given, in osteoarthrosis, but several questions regarding basic biochemical properties of the transplant remain unanswered. Bone morphogenetic protein 4 (BMP4), matrix metalloproteinase (MMP)-8, cartilage oligomeric matrix protein (COMP), and chitinase-3-like protein 1 (CHI3L1) have been shown to be involved in chondrogenic regeneration and represent potential therapeutic agents for cartilage repair. However, no study regarding naturally occurring levels of these soluble factors in transplanted adipose tissue has yet been performed.MethodsTo investigate the influence of age, body mass index, donor site, and sex on the concentration of BMP4, MMP-8, COMP, and CHI3L1 in freshly aspirated adipose tissue, their content was measured by means of enzyme-linked immunosorbent assay readings.ResultsThere were significant quantities of BMP4, MMP-8, COMP, and CHI3L1 (23.6, 249.9, 298.0, and 540.6 pg/mg, respectively) in the lipoaspirate harvested for transplantation. There was no correlation between the content of soluble factors and the patients' age or body mass index. Furthermore, the sex did not affect the amount of the investigated factors. However, there were significantly lower contents of BMP4, COMP, and CHI3L1 found in lipoaspirates harvested from the abdomen compared with nonabdominal donor sites.ConclusionsNaturally occurring differences in the concentrations of the investigated soluble factors will favor certain donor sites for autologous fat transfer in the field of cartilage repair. Thus, increasing knowledge will enable researchers and clinicians to make autologous fat transfer procedures more reliable and efficient for treatment of articular cartilage defects.
Buprenorphine Markedly Elevates a Panel of Surrogate Markers in a Murine Model of Sepsis
Authors: Chen Weiqiang , Brenner Max , Aziz Monowar , Chavan Sangeeta S. , Deutschman Clifford S. , Diamond Betty , Pavlov Valentin A. , Sherry Barbara , Wang Ping , Tracey Kevin J. , Wang Haichao 
Published: April 2019

ABSTRACT
Sepsis can be simulated in animals by perforating the cecum via a surgical procedure termed “cecal ligation and puncture” (CLP), which induces similar inflammatory responses as observed during the clinical course of human sepsis. In addition to anesthetic agents, many Institutional Animal Care and Use Committees often recommend the use of additional analgesic agents (such as opioid) to further augment the initial anesthetic effects. However, emerging evidence suggest that a commonly recommended opioid, buprenorphine, dramatically elevated circulating interleukin (IL)-6 levels, and reduced animal survival in male C57BL/6 mice, but not in female mice possibly due to the complex interference of estrous cycles, fueling an ongoing debate regarding the possible impact of analgesic administration on the sepsis-induced systemic inflammation. As per the recommendation of a local government agency, we performed a pilot study and confirmed that repetitive administration of buprenorphine indeed markedly elevated circulating levels of four sepsis surrogate markers (e.g., IL-6, KC, monocyte chemoattractant protein-1, and granulocyte-colony stimulating factor) in 20% to 60% of septic animals. This complication may adversely jeopardize our ability to use the CLP model to reliably simulate human sepsis, and to understand the complex mechanism underlying the pathogenesis of lethal sepsis. Thus, for experimental sepsis studies set to survey systemic inflammation and animal lethality at relatively later stages (e.g., at 24 h post CLP and beyond), we strongly recommend not to repetitively administer buprenorphine to eliminate its potential complication to animal sepsis models.
Remote Ischemic Conditioning in Emergency Medicine—Clinical Frontiers and Research Opportunities
Authors: Ho Andrew Fu Wah , Chong Jun , Ong Marcus Eng Hock , Hausenloy Derek J. 
Published: April 2019

ABSTRACT
Time-critical acute ischemic conditions such as ST-elevation myocardial infarction and acute ischemic stroke are staples in Emergency Medicine practice. While timely reperfusion therapy is a priority, the resultant acute ischemia/reperfusion injury contributes to significant mortality and morbidity. Among therapeutics targeting ischemia/reperfusion injury (IRI), remote ischemic conditioning (RIC) has emerged as the most promising.
RIC, which consists of repetitive inflation and deflation of a pneumatic cuff on a limb, was first demonstrated to have protective effect on IRI through various neural and humoral mechanisms. Its attractiveness stems from its simplicity, low-cost, safety, and efficacy, while at the same time it does not impede reperfusion treatment. There is now good evidence for RIC as an effective adjunct to reperfusion in ST-elevation myocardial infarction patients for improving clinical outcomes. For other applications such as acute ischemic stroke, subarachnoid hemorrhage, traumatic brain injury, cardiac arrest, and spinal injury, there is varying level of evidence.
This review aims to describe the RIC phenomenon, briefly recount its historical development, and appraise the experimental and clinical evidence for RIC in selected emergency conditions. Finally, it describes the practical issues with RIC clinical application and research in Emergency Medicine.
Examining the Increased Rates of Deceased Donor Kidney Nonutilization in Australia: What Has Changed?
Authors: Sypek Matthew P. , Ullah Shahid , Hughes Peter D. , Clayton Philip A. , McDonald Stephen P. 
Published: April 2019

Background.
From 2013, Australia has experienced a sustained increase in the proportion of deceased donor kidneys that are retrieved but not utilized for transplantation. We aimed to determine whether this could be explained by changes in donor characteristics over time.

Methods.
Registry data were used to examine predictors of kidney nonutilization over the period 2005–2017. Multilevel mixed effect logistic regression modeling and propensity score analysis were used to determine whether era of donation (2013–2017 versus 2005–2012) was an independent predictor of organ nonutilization after controlling for donor characteristics.

Results.
A total of 7810 kidneys were retrieved for the purpose of transplantation with 334 (4.3%) not utilized. The nonutilization rate was 5.8% in 2013–2017 compared to 2.7% in 2005–2012. Despite adjustment for donor characteristics, donation in the more recent era remained a significant predictor of kidney nonutilization (adjusted odds ratio, 1.98; 95% confidence interval, 1.54-2.54; P < 0.001). This finding was confirmed in the propensity score analysis.

Conclusions.
Kidneys retrieved in Australia since 2013 were more likely not to be utilized for transplantation even after adjusting for changes in donor characteristics. The abrupt increase may be explained by increased clinical risk aversion, changes in unmeasured donor factors or logistical issues. Although nonutilization rates in Australia remain low by international standards, further clinical auditing of the reasons for offer decline may help to optimize resource utilization and maximize transplant opportunities.
Sero-epidemiology of scrub typhus among suspected cases in selected areas of Nepal
Authors: Gautam Rajendra , Parajuli Keshab , Sherchand Jeevan Bahadur 
Published: April 2019

Introduction
Scrub typhus is an acute, febrile, infectious disease which is caused by Orientia tsutsugamushi. In the current days of Nepal huge burden of scrub typhus have been found, mainly Southern Nepal.

Methodology
Blood samples were collected from the suspected patients of scrub typhus who is having acute febrile illness. Detection of Immunoglobulin M (IgM) antibody to Orientia tsutsugamushi was performed by using Scrub Typhus Detect™ kit, In Bios International USA.

Results
A total 1585 cases, 358 (22.58 %) were positive for IgM Antibodies to Orientia tsutsugamushi. Multivariate analysis demonstrated that the following factors were significantly associated with the scrub typhus. 1. Females (odd ratio [OR]= 2.037, P=< 0.001, confidence interval [CI]= 1.465 – 2.831) 2. Rural residential location (odd ratio [OR]= 0.431, P=0.001, confidence interval [CI]= 0.261 – 0.714), 3. House near grassland (odd ratio [OR]= 3.279, P=<0.001, confidence interval [CI]= 1.932 – 5.563), 4. Presence of mouse inside the house (odd ratio [OR]= 5.462, P=<0.001, confidence interval [CI]= 4.048 – 7.371), 5. Working in the field (odd ratio [OR]= 9.845, P=0.004, confidence interval [CI]= 2.068 – 46.954).

Conclusion
The study indicated that Scub typhus is a big burden of Nepal, where we have identified the prevalence rate was 23  % . Use of IgM ELISA test will help for early diagnosis and it is urgent to investigate to save the life of people who lives endemic areas of Scrub typhus in Nepal.
Optimisation of an in vitro cell system using pseudoviruses to investigate HBV entry mechanisms
Authors: Goddard Chun , Irving William , Tarr Alexander 
Published: April 2019

Aim
To explore the roles of large (L), middle (M) and small (S) surface antigens in an in vitro model of hepatitis B virus (HBV) entry, and thereby to achieve an optimal in vitro cell system using pseudoviruses to investigate HBV entry mechanisms.

Methods
RNA encoding sodium taurocholate co-transporting polypeptide (NTCP) was extracted from human hepatocytes and cloned into the pHIV-EGFP expression vector. The resulting pHIV-NTCP-EGFP construct was delivered into Huh7 hepatoma cells with the aid of pCMVR87.4 (packaging vector) and pCMV.VSV.G (glycoprotein), subsequently, a cell line over-expressing NTCP was generated. Meanwhile, by silencing start codons at L, M or S, seven constructs were obtained, i.e. L + M -S-, L-M + S -, l -M-S+, L + M + S-, L-M + S +, L + M -S+, l -M-S-. A matrix with various amounts of the seven constructs was used to generate HBV pseudoparticles (HBVpp) using a Luciferase-based HIV (pNL4.3.luc.R-E-) pseudotype entry model system. The infectivity of the HBVpp was tested in NTCP naïve and NTCP over-expressing Huh7 hepatoma cells.

Results
The relative amounts of L, M and S were critical in determining the efficiency of entry of HBVpp into NTCP + ve Huh7 cells.

Conclusions
Creation of NTCP-over expressing cells together with optimisation of conditions to maximise HBVpp entry provides an important tool to investigate the entry step in the HBV life cycle, and may allow identification of non-NTCP-dependent viral entry pathways.
Comparison of MRSA skin infection models with HaCaT keratinocytes and a 3D-organotypic skin model
Authors: Barua Nilakshi 
Published: April 2019

Background and Aims
Skin is a major site for Staphylococcus aureus colonization and invasion. A 3D-organotypic skin model was generated by co-culturing keratinocytes with fibroblasts at air-liquid interface enabling the proliferation, migration and differentiation of the keratinocyte to mimic terminal differentiation of the epidermis.

Methods
The adherence and internalization of MRSA strain types ST8, ST30, ST59, ST22, ST45 and ST239 were evaluated in the HaCaT keratinocytes and a 3-D organotypic skin model. Acridine orange staining and/or anti-Staphylococcus aureus antibody were used for bacterial localization. TUNEL assay was used to evaluate cell death due to apoptosis.

Results
Maximum adherence to HaCaT cells were exhibited by both MRSA ST59 and ST8 strain types (P=0.129, Tukey post-hoc test). The maximum percentage of internalization was exhibited by both ST59 and ST30. With ST8, ST30, ST59 and ST239 types, bacteria were present within the cytoplasm whereas localization of ST22 and ST45in the phagosomes of HaCaT keratinocytes were observed. Study of cell death in HaCaT keratinocytes was limited to 24 h due to dislodgement of the keratinocytes with all six strains. The 3-D skin model proved to be better to study MRSA transmigration and cell death which could be monitored for longer time points. ST59 exhibited maximum adhesion and internalization.

Conclusion
The 3-D skin model proves to be a better model to study MRSA skin infections.