bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacodynamic Interactions Between Ketamine and Psychiatric Medications Used in the Treatment of Depression: A Systematic Review
Authors: Veraart Jolien K E , Smith-Apeldoorn Sanne Y , Bakker Iris M , Visser Berber A E , Kamphuis Jeanine , Schoevers Robert A , Touw Daan J 
Published: June 2021

AbstractBackgroundThe use of ketamine for depression has increased rapidly in the past decades. Ketamine is often prescribed as an add-on to other drugs used in psychiatric patients, but clear information on drug-drug interactions is lacking. With this review, we aim to provide an overview of the pharmacodynamic interactions between ketamine and mood stabilizers, benzodiazepines, monoamine oxidase-inhibitors, antipsychotics, and psychostimulants.MethodsMEDLINE and Web of Science were searched.ResultsTwenty-four studies were included. For lithium, no significant interactions with ketamine were reported. Two out of 5 studies on lamotrigine indicated that the effects of ketamine were attenuated. Benzodiazepines were repeatedly shown to reduce the duration of ketamine’s antidepressant effect. For the monoamine oxidase-inhibitor tranylcypromine, case reports showed no relevant changes in vital signs during concurrent S-ketamine use. One paper indicated an interaction between ketamine and haloperidol, 2 other studies did not. Four papers investigated risperidone, including 3 neuroimaging studies showing an attenuating effect of risperidone on ketamine-induced brain perfusion changes. Clozapine significantly blunted ketamine-induced positive symptoms in patients with schizophrenia but not in healthy participants. One paper reported no effect of olanzapine on ketamine’s acute psychotomimetic effects.ConclusionCurrent literature shows that benzodiazepines and probably lamotrigine reduce ketamine’s treatment outcome, which should be taken into account when considering ketamine treatment. There is evidence for an interaction between ketamine and clozapine, haloperidol, and risperidone. Due to small sample sizes, different subject groups and various outcome parameters, the evidence is of low quality. More studies are needed to provide insight into pharmacodynamic interactions with ketamine.
Understanding complaints made about surgical departments in a UK district general hospital
Authors: CLAYDON Oliver , KEELER Barrie , KHANNA Achal 
Published: June 2021

Abstract

Background
Patient complaints are increasingly recognized to provide a valuable insight into patients’ experience of healthcare. Being local and subjective, they can bring to light previously under-appreciated causes of patient dissatisfaction. The focus of surgical care is usually an intervention, and the nature of complaints made about surgical care may vary substantially from that in non-surgical specialties. This may have specific implications for quality improvement in surgical departments.

Objective
To investigate the causes of patient dissatisfaction in surgical care.

Methods
We retrospectively examined the content and frequency of patient complaints received by surgical departments at a UK district general hospital in the calendar year 2017. Second-hand reports of complaints, documented by the members of the hospital’s complaints department, were collated from a prospectively maintained database and categorized by content.

Results
Three hundred and ninety-nine complaints were received over the study period. These related to the care of 327 different patients. One complaint was generated for every 111 patient encounters. Ninety-one per cent of the complaints were made by the patient, and 8.8% were made by a family member. Complaints cited communication with hospital staff in 25% of cases, out-of-hospital delays in 24%, clinical issues in 22%, hospital administration in 16% and in-hospital delays in 10%. Post-operative symptoms and complications accounted for only 2% of the complaints. Twenty-six per cent of the complaints resulted in the rescheduling of an operation or a clinic appointment. Seventeen per cent of the complaints prompted internal actions within the surgical department to investigate and learn from the incident.

Conclusion
The profile of complaints made about surgical departments is similar to that of non-surgical departments in other studies. Clinical issues represented only the third largest cause of complaints. More complaints implicated patient–staff communication, and around half implicated management-related issues. Improving staff communication training, clinical standards and hospital administration continues to represent opportunities to enhance the patients’ overall experience of surgical care.
Effect of multiple, compatible plasmids on the fitness of the bacterial host by inducing transcriptional changes
Authors: Lee Haejeong , Ko Kwan Soo 
Published: June 2021

Abstract

Objectives
Bacteria that acquire plasmids incur a biological cost. Despite this fact, clinical Enterobacteriaceae isolates commonly contain multiple co-existing plasmids harbouring carbapenemase genes.

Methods
Six different plasmids carrying blaNDM-1, blaNDM-5, blaCTX-M-15, blaKPC-2, blaOXA-181 and blaOXA-232 genes were obtained from Klebsiella pneumoniae and Escherichia coli clinical isolates. Using the E. coli DH5α strain as recipient, 14 transconjugants with diverse plasmid combinations (single or double plasmids) were generated. For each of these, the effects of plasmid carriage on the bacterial host were investigated using in vitro and in vivo competition assays; additionally, the effects were investigated in the context of biofilm formation, serum resistance and survival inside macrophages. Transcriptomic changes in single- and double-plasmid recipients were also investigated.

Results
Increased in vitro and in vivo competitiveness was observed when two plasmids carrying blaNDM-1 and blaOXA-232 were co-introduced into the host bacteria. However, DH5α::pNDM5 + pOXA232 and other double-plasmid recipients did not show such competitiveness. DH5α::pNDM5 + pOXA181 did not show any fitness cost compared with a plasmid-free host and single-plasmid transconjugants, while both the double-plasmid recipients with pCTXM15 or pKPC2 exhibited a fitness burden. The double-plasmid recipient DH5α::pNDM1 + pOXA232 also exhibited increased biofilm formation, serum resistance and survival inside macrophages. Transcriptomic analysis revealed that the genes of DH5α::pNDM1 + pOXA232 involved in metabolic pathways, transport and stress response were up-regulated, while those involved in translation were down-regulated.

Conclusions
Our study suggests that bacterial strains can gain fitness through the acquisition of multiple plasmids harbouring antibiotic resistance genes, which may be mediated by transcriptomic changes in the chromosomal genes of the bacterial host.
The relationship between cybersecurity ratings and the risk of hospital data breaches
Authors: Choi Sung J , Johnson M Eric 
Published: June 2021

AbstractObjectiveWe investigated the progression of healthcare cybersecurity over 2014–2019 as measured by external risk ratings. We further examined the relationship between hospital data breaches and cybersecurity ratings.Materials and MethodsUsing Fortune 1000 firms as a benchmark, time trends in hospital cybersecurity ratings were compared using linear regression. Further, the relationship between hospital data breaches and cybersecurity ratings was modeled using logistic regression. Hospital breach data were collected from US HHS, and cybersecurity ratings were provided by BitSight. The resulting study sample yielded 3528 hospital-year observations.ResultsIn aggregate, we found that hospitals had significantly lower cybersecurity ratings than Fortune 1000 firms, however, hospitals have closed the gap in recent years. We also found that hospitals with the low security ratings were associated with significant risk of a data breach, with the probability of a breach in a given year ranging from 14% to 33%.DiscussionRecent cyber-attacks in healthcare continue to illustrate the need to better secure information systems. While hospitals have reduced cyber risk over the past decade, they remain statistically more vulnerable than the Fortune 1000 firms against botnets, spam, and malware.ConclusionPolicy makers should continue encouraging acute-care hospitals to proactively invest in security controls that reduce cyber risk. Best practices from other sectors like the financial services sector could provide useful guides and benchmarks for improvement.
A Note on the Cardinalities of Sets of Scalar Alternatives
Authors: Mascarenhas Salvador 
Published: June 2021

AbstractFormal theories of scalar implicature appeal crucially to a set of alternatives. These are the alternative statements that a speaker could have made but chose not to in pragmatic accounts, and the alternative statements that figure in the computation of exhaustivity operators in grammatical approaches. I show that the three sufficiently explicit theories of alternatives in the literature generate sets of alternatives that grow at least exponentially as a function of the input, and that these theories generate very large sets even for relatively small inputs. For pragmatic accounts of scalar implicature, I argue these results are hard or impossible to square with what we know independently about manipulating alternatives from the psychology of human reasoning. I propose that they pose a weaker but more general challenge for grammatical approaches, since alternatives as required by exhaustivity operators occur elsewhere in grammar, for example as part of the semantics of operators like “only” and “even.”
Decomposing the iron cross-correlation signal of the ultra-hot Jupiter WASP-76b in transmission using 3D Monte Carlo radiative transfer
Authors: Wardenier Joost P , Parmentier Vivien , Lee Elspeth K H , Line Michael R , Gharib-Nezhad Ehsan 
Published: June 2021

ABSTRACT
Ultra-hot Jupiters are tidally locked gas giants with dayside temperatures high enough to dissociate hydrogen and other molecules. Their atmospheres are vastly non-uniform in terms of chemistry, temperature, and dynamics, and this makes their high-resolution transmission spectra and cross-correlation signal difficult to interpret. In this work, we use the SPARC/MITgcm global circulation model to simulate the atmosphere of the ultra-hot Jupiter WASP-76b under different conditions, such as atmospheric drag and the absence of TiO and VO. We then employ a 3D Monte Carlo radiative transfer code, hires-mcrt, to self-consistently model high-resolution transmission spectra with iron (Fe i) lines at different phases during the transit. To untangle the structure of the resulting cross-correlation map, we decompose the limb of the planet into four sectors, and we analyse each of their contributions separately. Our experiments demonstrate that the cross-correlation signal of an ultra-hot Jupiter is primarily driven by its temperature structure, rotation, and dynamics, while being less sensitive to the precise distribution of iron across the atmosphere. We also show that the previously published iron signal of WASP-76b can be reproduced by a model featuring iron condensation on the leading limb. Alternatively, the signal may be explained by a substantial temperature asymmetry between the trailing and leading limb, where iron condensation is not strictly required to match the data. Finally, we compute the Kp–Vsys maps of the simulated WASP-76b atmospheres, and we show that rotation and dynamics can lead to multiple peaks that are displaced from zero in the planetary rest frame.
Plastic Rewiring of Sef1 Transcriptional Networks and the Potential of Nonfunctional Transcription Factor Binding in Facilitating Adaptive Evolution
Authors: Hsu Po-Chen , Lu Tzu-Chiao , Hung Po-Hsiang , Jhou Yu-Ting , Amine Ahmed A A , Liao Chia-Wei , Leu Jun-Yi 
Published: June 2021

Abstract
Prior and extensive plastic rewiring of a transcriptional network, followed by a functional switch of the conserved transcriptional regulator, can shape the evolution of a new network with diverged functions. The presence of three distinct iron regulatory systems in fungi that use orthologous transcriptional regulators suggests that these systems evolved in that manner. Orthologs of the transcriptional activator Sef1 are believed to be central to how iron regulatory systems developed in fungi, involving gene gain, plastic network rewiring, and switches in regulatory function. We show that, in the protoploid yeast Lachancea kluyveri, plastic rewiring of the L. kluyveri Sef1 (Lk-Sef1) network, together with a functional switch, enabled Lk-Sef1 to regulate TCA cycle genes, unlike Candida albicans Sef1 that mainly regulates iron-uptake genes. Moreover, we observed pervasive nonfunctional binding of Sef1 to its target genes. Enhancing Lk-Sef1 activity resuscitated the corresponding transcriptional network, providing immediate adaptive benefits in changing environments. Our study not only sheds light on the evolution of Sef1-centered transcriptional networks but also shows the adaptive potential of nonfunctional transcription factor binding for evolving phenotypic novelty and diversity.
Adaptive Resistance Mutations at Suprainhibitory Concentrations Independent of SOS Mutagenesis
Authors: Gutiérrez Ricardo , Ram Yoav , Berman Judith , de Sousa Keyla Carstens Marques , Nachum-Biala Yaarit , Britzi Malka , Elad Daniel , Glaser Gad , Covo Shay , Harrus Shimon 
Published: June 2021

Abstract
Emergence of resistant bacteria during antimicrobial treatment is one of the most critical and universal health threats. It is known that several stress-induced mutagenesis and heteroresistance mechanisms can enhance microbial adaptation to antibiotics. Here, we demonstrate that the pathogen Bartonella can undergo stress-induced mutagenesis despite the fact it lacks error-prone polymerases, the rpoS gene and functional UV-induced mutagenesis. We demonstrate that Bartonella acquire de novo single mutations during rifampicin exposure at suprainhibitory concentrations at a much higher rate than expected from spontaneous fluctuations. This is while exhibiting a minimal heteroresistance capacity. The emerged resistant mutants acquired a single rpoB mutation, whereas no other mutations were found in their whole genome. Interestingly, the emergence of resistance in Bartonella occurred only during gradual exposure to the antibiotic, indicating that Bartonella sense and react to the changing environment. Using a mathematical model, we demonstrated that, to reproduce the experimental results, mutation rates should be transiently increased over 1,000-folds, and a larger population size or greater heteroresistance capacity is required. RNA expression analysis suggests that the increased mutation rate is due to downregulation of key DNA repair genes (mutS, mutY, and recA), associated with DNA breaks caused by massive prophage inductions. These results provide new evidence of the hazard of antibiotic overuse in medicine and agriculture.
RqcH and RqcP catalyze processive poly-alanine synthesis in a reconstituted ribosome-associated quality control system
Authors: Takada Hiraku , Crowe-McAuliffe Caillan , Polte Christine , Sidorova Zhanna Yu , Murina Victoriia , Atkinson Gemma C , Konevega Andrey L , Ignatova Zoya , Wilson Daniel N , Hauryliuk Vasili 
Published: June 2021

AbstractIn the cell, stalled ribosomes are rescued through ribosome-associated protein quality-control (RQC) pathways. After splitting of the stalled ribosome, a C-terminal polyalanine ‘tail’ is added to the unfinished polypeptide attached to the tRNA on the 50S ribosomal subunit. In Bacillus subtilis, polyalanine tailing is catalyzed by the NEMF family protein RqcH, in cooperation with RqcP. However, the mechanistic details of this process remain unclear. Here we demonstrate that RqcH is responsible for tRNAAla selection during RQC elongation, whereas RqcP lacks any tRNA specificity. The ribosomal protein uL11 is crucial for RqcH, but not RqcP, recruitment to the 50S subunit, and B. subtilis lacking uL11 are RQC-deficient. Through mutational mapping, we identify critical residues within RqcH and RqcP that are important for interaction with the P-site tRNA and/or the 50S subunit. Additionally, we have reconstituted polyalanine-tailing in vitro and can demonstrate that RqcH and RqcP are necessary and sufficient for processivity in a minimal system. Moreover, the in vitro reconstituted system recapitulates our in vivo findings by reproducing the importance of conserved residues of RqcH and RqcP for functionality. Collectively, our findings provide mechanistic insight into the role of RqcH and RqcP in the bacterial RQC pathway.
Single molecule analysis indicates stimulation of MUTYH by UV-DDB through enzyme turnover
Authors: Jang Sunbok , Schaich Matthew A , Khuu Cindy , Schnable Brittani L , Majumdar Chandrima , Watkins Simon C , David Sheila S , Van Houten Bennett 
Published: June 2021

Abstract
The oxidative base damage, 8-oxo-7,8-dihydroguanine (8-oxoG) is a highly mutagenic lesion because replicative DNA polymerases insert adenine (A) opposite 8-oxoG. In mammalian cells, the removal of A incorporated across from 8-oxoG is mediated by the glycosylase MUTYH during base excision repair (BER). After A excision, MUTYH binds avidly to the abasic site and is thus product inhibited. We have previously reported that UV-DDB plays a non-canonical role in BER during the removal of 8-oxoG by 8-oxoG glycosylase, OGG1 and presented preliminary data that UV-DDB can also increase MUTYH activity. In this present study we examine the mechanism of how UV-DDB stimulates MUTYH. Bulk kinetic assays show that UV-DDB can stimulate the turnover rate of MUTYH excision of A across from 8-oxoG by 4–5-fold. Electrophoretic mobility shift assays and atomic force microscopy suggest transient complex formation between MUTYH and UV-DDB, which displaces MUTYH from abasic sites. Using single molecule fluorescence analysis of MUTYH bound to abasic sites, we show that UV-DDB interacts directly with MUTYH and increases the mobility and dissociation rate of MUTYH. UV-DDB decreases MUTYH half-life on abasic sites in DNA from 8800 to 590 seconds. Together these data suggest that UV-DDB facilitates productive turnover of MUTYH at abasic sites during 8-oxoG:A repair.
SNO and EANO practice guideline update: Anticonvulsant prophylaxis in patients with newly diagnosed brain tumors
Authors: Walbert Tobias , Harrison Rebecca A , Schiff David , Avila Edward K , Chen Merry , Kandula Padmaja , Lee Jong Woo , Le Rhun Emilie , Stevens Glen H J , Vogelbaum Michael A , Wick Wolfgang , Weller Michael , Wen Patrick Y , Gerstner Elizabeth R 
Published: June 2021

Abstract

Objective
To update the 2000 American Academy of Neurology (AAN) practice parameter on anticonvulsant prophylaxis in patients with newly diagnosed brain tumors.

Methods
Following the 2017 AAN methodologies, a systematic literature review utilizing PubMed, EMBASE Library, Cochrane, and Web of Science databases was performed. The studies were rated based on the AAN therapeutic or causation classification of evidence (class I-IV).

Results
Thirty-seven articles were selected for final analysis. There were limited high-level, class I studies and mostly class II and III studies. The AAN affirmed the value of these guidelines.

Recommendations
In patients with newly diagnosed brain tumors who have not had a seizure, clinicians should not prescribe antiepileptic drugs (AEDs) to reduce the risk of seizures (level A). In brain tumor patients undergoing surgery, there is insufficient evidence to recommend prescribing AEDs to reduce the risk of seizures in the peri- or postoperative period (level C). There is insufficient evidence to support prescribing valproic acid or levetiracetam with the intent to prolong progression-free or overall survival (level C). Physicians may consider the use of levetiracetam over older AEDs to reduce side effects (level C). There is insufficient evidence to support using tumor location, histology, grade, molecular/imaging features when deciding whether or not to prescribe prophylactic AEDs (level U).
Description of the ‘pronation manoeuvre’ for the diagnosis of developmental hip dysplasia
Authors: de-la-Garza-Salazar José Fernando , Rodríguez-de-Ita Julieta , Garza-Ornelas Bárbara M , Martínez-Cardona Jorge A 
Published: June 2021

Abstract

Introduction
Without a prompt diagnosis, developmental dysplasia of the hip (DDH) in infants can lead to severe sequelae. Current screening strategies emphasize the use of Ortolani and Barlow physical examination manoeuvres, yet they exhibit low sensitivity. The purpose of this study is to evaluate the performance of a new physical examination tool (the pronation manoeuvre) as a screening tool for DDH.

Methods
To evaluate the new manoeuvre, a cross-sectional and analytic study was performed with a nonprobabilistic sampling method. Patients with either a positive Ortolani or Barlow manoeuver were evaluated with the new manoeuvre and hip ultrasound. Controls were infants with negative Ortolani, Barlow and pronation manoeuvres and also had ultrasound performed.

Results
DDH was confirmed in 83 of 130 cases (64%) and 2 of 130 controls (2%). The new pronation manoeuvre had a sensitivity of 76% and a specificity of 94% as compared to the Ortolani and Barlow manoeuvres (sensitivity 31 to 32%, specificity 93 to 100%) (P&lt;0.05).

Conclusion
This new physical examination manoeuvre could serve as another clinical tool for the initial screening of DDH in newborns. Its promising results against traditional screening procedures might potentially impact diagnosis and prognosis for patients with DDH.
Resources for image-based high-throughput phenotyping in crops and data sharing challenges
Authors: Danilevicz Monica F. , Bayer Philipp E. , Nestor Benjamin J. , Bennamoun Mohammed , Edwards David 
Published: June 2021

Abstract
High-throughput phenotyping (HTP) platforms are capable of monitoring the phenotypic variation of plants through multiple types of sensors, such as red green and blue (RGB) cameras, hyperspectral sensors, and computed tomography, which can be associated with environmental and genotypic data. Because of the wide range of information provided, HTP datasets represent a valuable asset to characterize crop phenotypes. As HTP becomes widely employed with more tools and data being released, it is important that researchers are aware of these resources and how they can be applied to accelerate crop improvement. Researchers may exploit these datasets either for phenotype comparison or employ them as a benchmark to assess tool performance and to support the development of tools that are better at generalizing between different crops and environments. In this review, we describe the use of image-based HTP for yield prediction, root phenotyping, development of climate-resilient crops, detecting pathogen and pest infestation, and quantitative trait measurement. We emphasize the need for researchers to share phenotypic data, and offer a comprehensive list of available datasets to assist crop breeders and tool developers to leverage these resources in order to accelerate crop breeding.