bluuebunny/crossref_metadata_2025_split huggingface dataset:
Positive epistasis drives clavulanic acid resistance in double mutant libraries of BlaC β-lactamase
Authors: Radojković Marko , Ubbink Marcellus 
Published: February 2024

AbstractPhenotypic effects of mutations are highly dependent on the genetic backgrounds in which they occur, due to epistatic effects. To test how easily the loss of enzyme activity can be compensated for, we screen mutant libraries of BlaC, a β-lactamase from Mycobacterium tuberculosis, for fitness in the presence of carbenicillin and the inhibitor clavulanic acid. Using a semi-rational approach and deep sequencing, we prepare four double-site saturation libraries and determine the relative fitness effect for 1534/1540 (99.6%) of the unique library members at two temperatures. Each library comprises variants of a residue known to be relevant for clavulanic acid resistance as well as residue 105, which regulates access to the active site. Variants with greatly improved fitness were identified within each library, demonstrating that compensatory mutations for loss of activity can be readily found. In most cases, the fittest variants are a result of positive epistasis, indicating strong synergistic effects between the chosen residue pairs. Our study sheds light on a role of epistasis in the evolution of functional residues and underlines the highly adaptive potential of BlaC.
Predatory synapsid ecomorphology signals growing dynamism of late Palaeozoic terrestrial ecosystems
Authors: Singh Suresh A. , Elsler Armin , Stubbs Thomas L. , Rayfield Emily J. , Benton Michael J. 
Published: February 2024

AbstractTerrestrial ecosystems evolved substantially through the Palaeozoic, especially the Permian, gaining much new complexity, especially among predators. Key among these predators were non-mammalian synapsids. Predator ecomorphology reflect interactions with prey and competitors, which are key controls on carnivore diversity and ecology. Therefore, carnivorous synapsids may offer insight on wider ecological evolution as the first complex, tetrapod-dominated, terrestrial ecosystems formed through the late Palaeozoic. Using morphometric and phylogenetic comparative methods, we chart carnivorous synapsid trophic morphology from the latest Carboniferous to the earliest Triassic (307-251.2 Ma). We find a major morphofunctional shift in synapsid carnivory between the early and middle Permian, via the addition of new feeding modes increasingly specialised for greater biting power or speed that captures the growing antagonism and dynamism of terrestrial tetrapod predator-prey interactions. The further evolution of new hypo- and hypercarnivorous synapsids highlight the nascent intrinsic pressures and complexification of terrestrial ecosystems across the mid-late Permian.
Phenolic compounds induce ferroptosis-like death by promoting hydroxyl radical generation in the Fenton reaction
Authors: Sui Xinyue , Wang Jichao , Zhao Zhiqiang , Liu Bin , Liu Miaomiao , Liu Min , Shi Cong , Feng Xinjun , Fu Yingxin , Shi Dayong , Li Shengying , Qi Qingsheng , Xian Mo , Zhao Guang 
Published: February 2024

AbstractPhenolic compounds are industrially versatile chemicals, also the most ubiquitous pollutants. Recently, biosynthesis and biodegradation of phenols has attracted increasing attention, while phenols’ toxicity is a major issue. Here, we evolved phloroglucinol-tolerant Escherichia coli strains via adaptive evolution, and three mutations (ΔsodB, ΔclpX and fetAB overexpression) prove of great assistance in the tolerance improvement. We discover that phloroglucinol complexes with iron and promotes the generation of hydroxyl radicals in Fenton reaction, which leads to reducing power depletion, lipid peroxidation, and ferroptosis-like cell death of E. coli. Besides phloroglucinol, various phenols can trigger ferroptosis-like death in diverse organisms, from bacteria to mammalian cells. Furthermore, repressing this ferroptosis-like death improves phloroglucinol production and phenol degradation by corresponding strains respectively, showing great application potential in microbial degradation or production of desired phenolic compounds, and phloroglucinol-induced ferroptosis suppresses tumor growth in mice, indicating phloroglucinol as a promising drug for cancer treatment.
Smart polarization and spectroscopic holography for real-time microplastics identification
Authors: Zhu Yanmin , Li Yuxing , Huang Jianqing , Lam Edmund Y. 
Published: February 2024

AbstractOptical microscopy technologies as prominent imaging methods can offer rapid, non-destructive, non-invasive detection, quantification, and characterization of tiny particles. However, optical systems generally incorporate spectroscopy and chromatography for precise material determination, which are usually time-consuming and labor-intensive. Here, we design a polarization and spectroscopic holography to automatically analyze the molecular structure and composition, namely smart polarization and spectroscopic holography (SPLASH). This smart approach improves the evaluation performance by integrating multi-dimensional features, thereby enabling highly accurate and efficient identification. It simultaneously captures the polarization states-related, holographic, and texture features as spectroscopy, without the physical implementation of a spectroscopic system. By leveraging a Stokes polarization mask (SPM), SPLASH achieves simultaneous imaging of four polarization states. Its effectiveness has been demonstrated in the application of microplastics (MP) identification. With machine learning methods, such as ensemble subspace discriminant classifier, k-nearest neighbors classifier, and support vector machine, SPLASH depicts MPs with anisotropy, interference fringes, refractive index, and morphological characteristics and performs explicit discrimination with over 0.8 in value of area under the curve and less than 0.05 variance. This technique is a promising tool for addressing the increasing public concerning issues in MP pollution assessment, MP source identification, and long-term water pollution monitoring.
Leveraging graph clustering techniques for cyber‐physical system analysis to enhance disturbance characterisation
Authors: Jacobs Nicholas , Hossain‐McKenzie Shamina , Sun Shining , Payne Emily , Summers Adam , Al‐Homoud Leen , Layton Astrid , Davis Kate , Goes Chris 
Published: February 2024

AbstractCyber‐physical systems have behaviour that crosses domain boundaries during events such as planned operational changes and malicious disturbances. Traditionally, the cyber and physical systems are monitored separately and use very different toolsets and analysis paradigms. The security and privacy of these cyber‐physical systems requires improved understanding of the combined cyber‐physical system behaviour and methods for holistic analysis. Therefore, the authors propose leveraging clustering techniques on cyber‐physical data from smart grid systems to analyse differences and similarities in behaviour during cyber‐, physical‐, and cyber‐physical disturbances. Since clustering methods are commonly used in data science to examine statistical similarities in order to sort large datasets, these algorithms can assist in identifying useful relationships in cyber‐physical systems. Through this analysis, deeper insights can be shared with decision‐makers on what cyber and physical components are strongly or weakly linked, what cyber‐physical pathways are most traversed, and the criticality of certain cyber‐physical nodes or edges. This paper presents several types of clustering methods for cyber‐physical graphs of smart grid systems and their application in assessing different types of disturbances for informing cyber‐physical situational awareness. The collection of these clustering techniques provide a foundational basis for cyber‐physical graph interdependency analysis.
A new transformerless buck‐boost converter with improved voltage gain and continuous input current
Authors: Hosseinpour Majid , Ahmadi Mahsa , Seifi Ali , Hosseini Seyed Hossein 
Published: February 2024

AbstractThis paper proposes a new transformerless buck‐boost converter with an extended voltage conversion ratio. This converter has semi‐quadratic voltage gain, which provides more gain with lower duty cycles. This converter has a simple structure and easy implementation, which reduces the cost and increases efficiency. The proposed converter operates in continuous conduction mode and provides two operation modes by turning on and off the switches. The suggested converter has continuous input current and low input current ripple, which is important when utilizing renewable energy sources. The calculation of the proposed converter includes ideal and practical voltage gain, current calculations, voltage stresses of the switches and diodes, current stress of the switches, parameter design, efficiency, and a brief analysis of discontinuous conduction mode and boundary conditions. The proposed converter provides efficiency of about 93.1% in boost mode and 92.14% in buck mode at 50 W output power. The suggested converter varies the input voltage from 20 to 48 V in boost mode and changes the input voltage from 20 to 10.4 V in buck mode. Finally, a laboratory prototype has been built to prove and evaluate the simulation results and theoretical analysis of the proposed converter.
New multilevel inverter based on reduced switch basic cell for high voltage levels
Authors: Seifi Ali , Hosseini Seyed Hossein , Hagh Mehrdad Tarafdar , Hosseinpour Majid 
Published: February 2024

AbstractIn this study, to solve total harmonic distortion (THD) and voltage stress on switches, challenges have been made by presenting a new multi‐level inverter (MLI). The proposed topology can operate with both symmetric and asymmetric sources. The proposed topology in symmetric and asymmetric mode with 18 switches can produce 17 and 49 voltage levels, respectively, with THD values of 4.14% and 1.45%, which passes the IEEE harmonic standard. The main advantage of the proposed topology is reducing the number of circuit devices, which reduces the price, volume, and complexity of the circuit by reducing the number of circuit devices. The proposed topology reduces the THD, the number of power electronics components, and voltage stress by increasing the output levels. The proposed topology is compared with other topologies and the advantage of the proposed topology is shown in terms of the number of switches and drivers. In addition, the proposed topology is compared in terms of the cost function. The power losses based on the thermal model of the proposed topology have been analysed and simulated. Simulation and experimental results are presented for different scenarios such as load type, load changes, and modulation index changes to validate the proposed topology.
Gelenkerhaltende Eingriffe bei rheumatischen Erkrankungen –
Aktueller Stand
Authors: Carl Hans-Dieter 
Published: February 2024

ZusammenfassungMit dem Wandel der medikamentösen Therapie
entzündlich-rheumatischer Erkrankungen seit Beginn dieses Jahrtausends
hat sich auch das Spektrum der operativen Rheumatologie deutlich
geändert. Neben den klassischen gelenkserhaltenden rheumachirurgischen
Eingriffen wie der Synovektomie werden etablierte Verfahren aus der
orthopädischen Chirurgie, wie gelenknahe Umstellungsoperation oder
gelenkerhaltende Vorfuß-Korrekturen, bei entzündlichen
Erkrankungen durchgeführt. Der folgende Artikel soll die aktuellen
Möglichkeiten und Grenzen gelenkerhaltender Eingriffe bei rheumatischen
Erkrankungen darstellen.
Pharmakologisches Neuroenhancement unter jungen Erwachsenen:
Ergebnisse einer Längsschnittstudie zur Verbreitung und zu Risiko- und
Schutzfaktoren
Authors: Schulz Wolfgang , Wolter Emilie , Job Ann-Katrin 
Published: February 2024

Zusammenfassung
Ziel Pharmakologisches Neuroenhancement (PNE) bezeichnet die Einnahme
verschreibungspflichtiger Medikamente ohne medizinische Notwendigkeit, um eine
kognitive Leistungssteigerung oder eine Verbesserung des psychischen
Wohnbefindens hervorzurufen. In der vorliegenden Studie wird PNE im jungen
Erwachsenenalter untersucht.
Materialien und Methodik Die betrachtete Stichprobe umfasst junge
Erwachsene (N=279) mit einem überwiegend mittleren und hohen
sozioökonomischen Status aus Deutschland. Untersucht werden neben der
Lebenszeit- und 12-Monatsprävalenz querschnittliche
Zusammenhänge zu soziodemographischen und psychischen Merkmalen
(psychische Belastung, Resilienz, Alkohol-, Zigaretten- und Cannabiskonsum)
sowie in einem 8-Jahres-Längsschnitt, ob sich der PNE-Konsum im jungen
Erwachsenenalter aufgrund von Merkmalen während der Adoleszenz
vorhersagen lässt. Betrachtet werden weiterhin im Quer- und im
Längsschnitt Zusammenhänge zu Elternmerkmalen.
Ergebnisse Die Lebenszeitprävalenz für PNE beträgt
9,3%, die 12-Monats-Prävalenz 6,5%. Das Geschlecht
erwies sich durchgängig als wichtigster Prädiktor: Junge
Männer nutzen PNE sowohl häufiger zur Steigerung ihrer
kognitiven Leistungsfähigkeit als auch zur Verbesserung ihres
psychischen Wohnbefindens als junge Frauen. PNE-Nutzende geben häufiger
depressive Symptome an und bei ihnen besteht häufiger der Verdacht auf
einen Missbrauch/eine Abhängigkeit von Alkohol oder Cannabis.
Der PNE-Konsum im jungen Erwachsenenalter lässt sich signifikant durch
externale Verhaltensauffälligkeiten und Drogenkonsum im Jugendalter
vorhersagen, im multivariaten Modell werden diese Effekte unter Kontrolle des
Geschlechts allerdings nicht mehr signifikant. Zusammenhänge zu
Elternmerkmalen ließen sich weder im Quer- noch im Längsschnitt
ermitteln.
Schlussfolgerung Angesichts der zunehmenden Prävalenzen sollten
verstärkt präventive Maßnahmen angeboten und
über Alternativen zu PNE nachgedacht werden.
Exercise-induced Hypertension and Carotid Intima-media Thickness in
Male Marathon Runners
Authors: Yoon Eun Sun , Kim Young-Joo 
Published: February 2024

AbstractThis study aimed to identify the relationship between exercise-induced
hypertension and carotid artery intima-media thickness in long-distance runners.
Sixty healthy male runners aged 40 to 60 years were assigned to the following
three groups based on resting blood pressure and maximal systolic blood pressure
during a maximal exercise test: normal blood pressure response, exercise-induced
hypertension, and complex hypertension. An exaggerated systolic blood pressure
response was defined as a maximal systolic blood pressure+≥+210 mmHg during the
maximal exercise test, while carotid intima-media thickness was measured using
B-mode ultrasonography. The carotid intima-media thickness mean values were the
highest in the complex hypertension group (0.72±0.11 mm), followed by
exercise-induced hypertension (0.62±0.12 mm) and normal blood pressure groups
(0.55±0.13 mm), with a significant difference between the groups (p+<+0.002).
In linear regression analysis, the mean intima-media thickness was independently
associated with age (p=0.015) and maximal systolic blood pressure (p=0.046) but
not with resting systolic blood pressure. These results suggest that
exercise-induced hypertension is associated with carotid intima-media thickness,
a surrogate marker of cardiovascular disease, in long-distance runners.
Therefore, evaluating the blood pressure response during exercise is important
for the early detection of potential cardiovascular disease risks in
long-distance runners.
Impaired Whole-Blood Fibrinolysis is a Predictor of Mortality in Intensive Care Patients
Authors: Brewer Julie S. , Hvas Christine L. , Hvas Anne-Mette , Larsen Julie B. 
Published: February 2024

Abstract
Background Altered fibrinolysis is considered to play a crucial role in the development of coagulopathy in sepsis. However, routine laboratory tests for fibrinolysis are currently very limited, and the impact of fibrinolytic capacity on clinical outcome is poorly investigated.
Objectives To assess whole-blood fibrinolysis in patients admitted to the intensive care unit (ICU) and compare fibrinolysis in sepsis patients with nonsepsis patients. Further, to investigate associations between fibrinolytic capacity and 30-day mortality and venous thromboembolism (VTE).
Methods This study was designed as a prospective cohort study. Adult ICU patients were included at the Aarhus University Hospital, Denmark. All patients had a blood sample obtained the morning after admission. A modified thromboelastometry (ROTEM®) analysis with tissue plasminogen activator (ROTEM®-tPA) was used to assess fibrinolysis. The primary endpoint was difference in ROTEM®-tPA lysis time between sepsis patients and nonsepsis patients.
Results ROTEM®-tPA revealed fibrinolytic impairment in sepsis patients (n = 30) compared with nonsepsis ICU controls (n = 129), with longer lysis time (median [interquartile range] 3,600 [3,352–3,600] vs. 3,374 seconds [2,175–3,600], p < 0.01), lower maximum lysis (23 [8–90] vs. 94% [14–100], p = 0.02), and lower fibrinolysis speed (0.41 [0.0–1.4] vs. 1.6 mm/min [0.1–2.7], p = 0.01). In the composite ICU population, 61% (97/159) demonstrated prolonged lysis time indicating impaired fibrinolytic capacity. These patients had higher 30-day mortality (adjusted odds ratio [OR]: 2.26 [0.83–6.69]) and VTE risk (OR: 3.84 [0.87–17.8]) than patients with normal lysis time.
Conclusion Sepsis patients showed impaired fibrinolysis measured with ROTEM®-tPA compared with nonsepsis patients and ROTEM®-tPA lysis time was associated with 30-day mortality and VTE in the entire ICU cohort.
Olfaction and Quality of Life in Patients with Eosinophilic CRS Undergoing Endoscopic Sinus Surgery
Authors: Tepedino Miguel Soares , Voegels Richard Louis , Pezato Rogério , Thamboo Andrew , Kosug Eduardo Macoto , Ferrão Ana Clara Miotello , Neves Raíssa de Figueiredo , Castilla Valéria Maria Barcia , Gregório Luis Carlos 
Published: February 2024

Abstract
Introduction Chronic rhinosinusitis (CRS) is a common inflammatory disease. This high prevalence leads to high direct and indirect public health costs, which include medical visits, laboratory tests and imaging, pharmacotherapy, hospitalizations, and surgical treatment. Furthermore, CRS has a substantial impact on patient quality of life, affecting productivity and being a common cause of absence from work CRS-associated olfactory dysfunction is highly prevalent, the actual effectiveness of surgical intervention remains inconsistent. Although there are studies evaluating the postoperative course of patients with eosinophilic Chronic rhinosinusitis (eCRS) treated with high-volume budesonide irrigation, there is little objective information regarding the impact of this intervention on olfactory status and quality of life.
Objective To conduct a pre- and postoperative analysis of olfaction and quality of life in patients with eCRS treated with surgical intervention followed by high-volume budesonide nasal irrigation.
Methods Prospective, descriptive, uncontrolled study of patients with eCRS. All patients underwent pre- and postoperative nasal endoscopy, SNOT-22 questionnaire, and the University of Pennsylvania Smell Identification Text (UPSIT), always by the same previously trained examiner. The SNOT-22 questionnaire and the UPSIT were readministered to all patients at 3 months, 6 months, and 1 year postoperatively, and scores compared with those obtained preoperatively.
Results Twenty patients were included in the study, 13 males and 7 females, between the ages of 23 and 65; 8 patients had comorbid asthma. Quantitative evaluation using the UPSIT test showed a significant improvement in olfaction 3 months after surgery, which remained 6 months and 1 year after surgery (p = 0.0063).There was no significant association between eosinophil concentrations in polypoid tissue and postoperative SNOT-22 and UPSIT results. Patients with tissue eosinophils >50 had a lower preoperative UPSIT score. As early as 3 months postoperatively, a significant improvement in quality of life was already noticeable, as represented by a decrease in SNOT-22 values, which persisted through the 1-year postoperative follow-up evaluation (p = 0.0005). Quantitative evaluation using the UPSIT test showed a significant improvement in olfaction 3 months after surgery, which remained 6 months and 1 year after surgery (p = 0.0063).
Conclusion Surgery effectively controlled eCRS in patients who adhered to high-volume budesonide nasal irrigation postoperatively. There were significant improvements in quality of life and olfaction, which persisted at least up to one year postoperatively.
Phenobarbital as a Sedation Strategy to Reduce Opioid and Benzodiazepine Burden in Neonatal Extracorporeal Membrane Oxygenation
Authors: Cardona Vilmaris Quinones , Byrne Emma , Mejia Michelle , Joshi Swosti , Menkiti Ogechukwu 
Published: February 2024

Objective The study aims to describe our experience with the implementation of phenobarbital as a primary sedation strategy during neonatal extracorporeal membrane oxygenation (ECMO).
Study Design Retrospective chart review in a level IV neonatal intensive care unit between 2011 and 2021 comparing neonatal ECMO patients before and after the implementation of a sedation-analgesia (SA) protocol using scheduled phenobarbital as the primary sedative. Groups were compared for neonatal and ECMO characteristics, cumulative SA doses, and in-hospital outcomes. Comparison between groups was performed using Mann–Whitney test on continuous variables and chi-square on nominal variables.
Results Forty-two patients were included, 23 preprotocol and 19 postprotocol. Birth, pre-ECMO, and ECMO clinical characteristics were similar between groups except for a lower birth weight in the postprotocol group (p = 0.024). After standardization of phenobarbital SA protocol, there was a statistically significant reduction in median total morphine dose (31.38–17.65 mg/kg, p = 0.006) and median total midazolam dose (36.21–6.36 mg/kg, p < 0.001). There was also a reduction in median total days on morphine by 7.5 days (p = 0.026) and midazolam by 6.6 days (p = 0.003). There were no differences in ECMO duration or in-hospital outcomes between groups.
Conclusion In this cohort, short-term use of phenobarbital as primary sedation strategy during neonatal ECMO was associated with reduced opioid and midazolam burden. Such reduction, however, did not affect in-hospital outcomes.
Key Points
Atypical May-Thurner Syndrome Caused by Large Lumbar Osteophyte
Authors: Schaper Nicholas , Pereira Keith 
Published: February 2024

AbstractAn 82-year-old man presented to the emergency department with intermittent left lower extremity swelling for the last 4 to 5 months that limited his daily activities. The patient had a negative lower extremity venous duplex 3 months prior and had been treating symptoms with compression stockings but experienced no improvement. Venography showed venous outflow obstruction in his left common iliac vein and the etiology was confirmed to be a lumbar vertebral osteophyte compressing the vein. The patient underwent endovascular treatment with balloon venoplasty and stent placement over the lesion with return of adequate outflow. This report describes treatment of symptomatic left common iliac venous compression with endovascular therapy alone.