bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current practices and challenges of outpatient parenteral antimicrobial therapy: a narrative review
Authors: Wolie Zenaw T , Roberts Jason A , Gilchrist Mark , McCarthy Kate , Sime Fekade B 
Published: June 2024

Abstract
Extended hospitalization for infection management increases inpatient care costs and the risk of healthcare-associated adverse events, including infections. The growing global demand for healthcare, the diminishing availability of hospital beds and an increasing patient preference for care within their own home have been the primary drivers of the expansion of hospital-in-the-home programmes. Such programmes include the use of IV antimicrobials in outpatient settings, known as outpatient parenteral antimicrobial therapy (OPAT). However, OPAT practices vary globally. This review article aims to describe the current OPAT practices and challenges worldwide. OPAT practice begins with patient evaluation and selection using eligibility criteria, which requires collaboration between the interdisciplinary OPAT team, patients and caregivers. Depending on care requirements, eligible patients may be enrolled to various models of care, receiving medication by healthcare professionals at outpatient infusion centres, hospital clinics, home visits or through self-administration. OPAT can be used for the management of many infections where an effective oral treatment option is lacking. Various classes of parenteral antimicrobials, including β-lactams, aminoglycosides, glycopeptides, fluoroquinolones and antifungals such as echinocandins, are used globally in OPAT practice. Despite its benefits, OPAT has numerous challenges, including complications from medication administration devices, antimicrobial side effects, monitoring requirements, antimicrobial instability, patient non-adherence, patient OPAT rejection, and challenges related to OPAT team structure and administration, all of which impact its outcome. A negative outcome could include unplanned hospital readmission. Future research should focus on mitigating these challenges to enable optimization of the OPAT service and thereby maximize the documented benefits for the healthcare system, patients and healthcare providers.
Temperature dependence of the mutation rate towards antibiotic resistance
Authors: Van Eldijk Timo J B , Sheridan Eleanor A , Martin Guillaume , Weissing Franz J , Kuipers Oscar P , Van Doorn G Sander 
Published: June 2024

Abstract

Objectives
Environmental conditions can influence mutation rates in bacteria. Fever is a common response to infection that alters the growth conditions of infecting bacteria. Here we examine how a temperature change, such as is associated with fever, affects the mutation rate towards antibiotic resistance.

Methods
We used a fluctuation test to assess the mutation rate towards antibiotic resistance in Escherichia coli at two different temperatures: 37°C (normal temperature) and 40°C (fever temperature). We performed this measurement for three different antibiotics with different modes of action: ciprofloxacin, rifampicin and ampicillin.

Results
In all cases, the mutation rate towards antibiotic resistance turned out to be temperature dependent, but in different ways. Fever temperatures led to a reduced mutation rate towards ampicillin resistance and an elevated mutation rate towards ciprofloxacin and rifampicin resistance.

Conclusions
This study shows that the mutation rate towards antibiotic resistance is impacted by a small change in temperature, such as associated with fever. This opens a new avenue to mitigate the emergence of antibiotic resistance by coordinating the choice of an antibiotic with the decision of whether or not to suppress fever when treating a patient. Hence, optimized combinations of antibiotics and fever suppression strategies may be a new weapon in the battle against antibiotic resistance.
Activity of cefepime, carbapenems and new β-lactam/β-lactamase inhibitor combinations on Enterobacter cloacae complex and Klebsiella aerogenes in Spain (SMART 2016–2022)
Authors: Rodríguez-Villodres Ángel , Lepe-Balsalobre Esperanza , Ortiz De La Rosa José Manuel , Giner Almaraz Salvador , González De Herrero Elisa , Cercenado Emilia , García-Fernández Sergio , Benito Rafael , Ponz Mir Ricardo , Cantón Rafael , Lepe José Antonio 
Published: June 2024

Abstract

Objectives
To analyse the susceptibility profile to cefepime, carbapenems and new β-lactam/β-lactamase inhibitor combinations in Enterobacter cloacae complex and Klebsiella aerogenes isolated from intra-abdominal, urinary, respiratory and bloodstream infections in the SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance study in Spain.

Methods
The susceptibilities of 759 isolates (473 E. cloacae complex and 286 K. aerogenes) collected in 11 Spanish hospitals from 2016 to 2022 were analysed following the EUCAST 2023 criteria. Molecular characterization looking for β-lactamase genes was performed through PCR and DNA sequencing analysis.

Results
E. cloacae complex showed resistance to third-generation cephalosporins in 25% of the cases, whereas K. aerogenes was resistant in 35%. Regarding cefepime, resistance in E. cloacae was higher (10%) than in K. aerogenes (2%). Carbapenems showed &gt;85% activity in both microorganisms. Ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam had good activity against these microorganisms (&gt;95%). In contrast, the activity of ceftolozane/tazobactam was lower (80%). A high proportion of the isolates resistant to new β-lactam/β-lactamase inhibitor combinations carried a carbapenemase, mainly OXA-48-like and VIM-1.

Conclusions
Ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam show high activity against both E. cloacae complex and K. aerogenes isolates recovered in the SMART-Spain study. In contrast, differences have been found in the case of cefepime, showing more activity against K. aerogenes than E. cloacae complex. These results are useful for antimicrobial stewardship programmes and for the implementation of local and national guidelines.
Levels of Analysis and Variation in Civil War Violence and Restraint: Ideology and Contestation in Nicaragua
Authors: Thaler Kai M 
Published: June 2024

Abstract
How can we analyze violence against civilians in civil wars over time and with attention both to local context and international comparability? I argue that we should integrate theories across levels of analysis, applying this to testing existing theories of civil war violence and state repression in the case of the Frente Sandinista de Liberación Nacional (FSLN) in Nicaragua. Using interviews, archival evidence, and human rights reports, I argue that compared to domestic rivals and from an international perspective, the FSLN generally exhibited restraint, limiting violence against civilians due to an ideological commitment to discipline and civilian protection. Disaggregating the geographic and temporal contexts of violations at the subnational level reveals, however, that significant violence occurred where the FSLN had less territorial control, fewer civilian ties, and looser discipline, supporting contestation and command and control theories. Theories of violence may therefore explain variation at one level of analysis and not others within a given case, emphasizing the need for within-case disaggregation in explaining and comparing patterns of violence and state repression in civil wars, and the importance of unpacking violence committed by more restrained actors.
Chondroblastic osteosarcoma of the nasal cavity: an exceptional and misdiagnosed presentation
Authors: Aaboudech Taha Yassine , EL Ouazzani Hafsa , Kadiri Habiba , Benabdenbi Hanae , Rguieg Naji , EL Ouali Ibtissam , EL Kettani N Ech-cherif , Zouaidia Fouad , Cherradi Nadia 
Published: June 2024

Abstract
Chondroblastic osteosarcoma of the nasal cavity is a rare and aggressive tumor that presents diagnostic challenges due to its variable clinical and radiological features. Histological analysis is crucial for an accurate diagnosis, despite morphological similarities with chondrosarcoma. We present a case of primary craniofacial chondroblastic osteosarcoma originating from the nasal cavity in a 17-year-old adolescent. The tumor was characterized by cartilaginous lobules and spindle cell proliferation with osteoid matrix deposition. Immunohistochemical analysis supported the diagnosis. This case highlights the rarity of this particular presentation and emphasizes the significance of accurate diagnosis through histopathological evaluation to achieve optimal management.
WISDOM Project – XXI. Giant molecular clouds in the central region of the barred spiral galaxy NGC 613: a steep size–linewidth relation
Authors: Choi Woorak , Bureau Martin , Liu Lijie , Cappellari Michele , Davis Timothy A , Gensior Jindra , Liang Fu-Heng , Lu Anan , Moon Sanghyuk , Ruffa Ilaria , Williams Thomas G , Chung Aeree 
Published: June 2024

ABSTRACT
NGC 613 is a nearby barred spiral galaxy with a nuclear ring. Exploiting high spatial resolution (≈20 pc) Atacama Large Millimetre/submillimetre Array 12CO(1–0) observations, we study the giant molecular clouds (GMCs) in the nuclear ring and its vicinity, identifying 158 spatially and spectrally resolved GMCs. The GMC sizes (Rc) are comparable to those of the clouds in the Milky Way (MW) disc, but their gas masses, observed linewidths (σobs,los), and gas mass surface densities are larger. The GMC size–linewidth relation ($\sigma _{\mathrm{obs,los}}\propto R_{\mathrm{c}}^{0.77}$) is steeper than that of the clouds of the MW disc and centre, and the GMCs are on average only marginally gravitationally bound (with a mean virial parameter 〈αobs,vir〉 ≈ 1.7). We discuss the possible origins of the steep size–linewidth relation and enhanced observed linewidths of the clouds and suggest that a combination of mechanisms such as stellar feedback, gas accretion, and cloud–cloud collisions, as well as the gas inflows driven by the large-scale bar, may play a role.
A Bayesian approach to the cosmic dipole in radio galaxy surveys: joint analysis of NVSS & RACS
Authors: Oayda Oliver T , Mittal Vasudev , Lewis Geraint F , Murphy Tara 
Published: June 2024

ABSTRACT
We examine the sky distribution of radio galaxies in the NRAO VLA Sky Survey (NVSS) and the Rapid ASKAP Continuum Survey (RACS). Analyses of these samples have reported tension between their inferred dipoles and the kinematic dipole of the cosmic microwave background (CMB). This represents a challenge to the traditional assumption that the Universe is homogeneous and isotropic on large scales: the cosmological principle. We find that NVSS and RACS contain local radio sources that give a non-negligible contribution to the overall dipole signal. These need to be adequately accounted for since the aim is to probe the composition of the Universe at large scales. By appropriately considering these sources, the inferred dipole amplitude in either sample is reduced. None the less, we find support for a dipole aligning with that of the CMB but larger in amplitude, especially in the joint analysis. However, the ‘clustering dipole’ – the contribution of local sources to the net inferred dipole – appears to align with the direction of the CMB dipole, and its magnitude increases as deeper nearby sources are considered up to a comoving distance of ≈130 Mpc (h = 0.7). The significance of this observation in the context of the cosmological principle is unclear and prompts further inquiry.
Local versus global environment: the suppression of star formation in the vicinity of galaxy clusters
Authors: de Vos K , Merrifield M R , Hatch N A 
Published: June 2024

ABSTRACT
In order to examine where, how and why the quenching of star formation begins in the outskirts of galaxy clusters, we investigate the de-projected radial distribution of a large sample of quenched and star-forming galaxies (SFGs) out to 30R500 around clusters. We identify the SFG sample using radio continuum emission from the Low-Frequency Array Two-metre Sky Survey. We find that the SFG fraction starts to decrease from the field fraction as far out as 10R500, well outside the virial radius of the clusters. We investigate how the SFG fraction depends on both large-scale and local environments, using radial distance from a cluster to characterise the former, and distance from fifth nearest neighbour for the latter. The fraction of SFGs in high-density local environments is consistently lower than that found in low-density local environments, indicating that galaxies’ immediate surroundings have a significant impact on star formation. However, for high-mass galaxies – and low mass galaxies to a lesser extent – high-density local environments appear to act as a protective barrier for those SFGs that survived this pre-processing, shielding them from the external quenching mechanisms of the cluster outskirts. For those galaxies that are not in a dense local environment, the global environment causes the fraction of SFGs to decrease toward the cluster centre in a manner that is independent of galaxy mass. Thus, the fraction of SFGs depends on quite a complex interplay between the galaxies’ mass, their local environment, and their more global cluster-centric distance.
Adaptation of a eukaryote-like ProRS to a prokaryote-like tRNAPro
Authors: Ivanesthi Indira Rizqita , Latifah Emi , Amrullah Luqman Fikri , Tseng Yi-Kuan , Chuang Tsung-Hsien , Pan Hung-Chuan , Yang Chih-Shiang , Liu Shih-Yang , Wang Chien-Chia 
Published: June 2024

Abstract
Prolyl-tRNA synthetases (ProRSs) are unique among aminoacyl-tRNA synthetases (aaRSs) in having two distinct structural architectures across different organisms: prokaryote-like (P-type) and eukaryote/archaeon-like (E-type). Interestingly, Bacillus thuringiensis harbors both types, with P-type (BtProRS1) and E-type ProRS (BtProRS2) coexisting. Despite their differences, both enzymes are constitutively expressed and functional in vivo. Similar to BtProRS1, BtProRS2 selectively charges the P-type tRNAPro and displays higher halofuginone tolerance than canonical E-type ProRS. However, these two isozymes recognize the primary identity elements of the P-type tRNAPro―G72 and A73 in the acceptor stem―through distinct mechanisms. Moreover, BtProRS2 exhibits significantly higher tolerance to stresses (such as heat, hydrogen peroxide, and dithiothreitol) than BtProRS1 does. This study underscores how an E-type ProRS adapts to a P-type tRNAPro and how it may contribute to the bacterium's survival under stress conditions.
In vivo modeling recapitulates radiotherapy delivery and late-effect profile for childhood medulloblastoma
Authors: Castle Jemma , Shaw Gary , Weller Dominic , Fielder Edward , Egnuni Teklu , Singh Mankaran , Skinner Roderick , von Zglinicki Thomas , Clifford Steven C , Short Susan C , Miwa Satomi , Hicks Debbie 
Published: June 2024

Abstract

Background
Medulloblastoma (MB) is the most common malignant pediatric brain tumor, with 5-year survival rates &gt; 70%. Cranial radiotherapy (CRT) to the whole brain, with posterior fossa boost (PFB), underpins treatment for non-infants; however, radiotherapeutic insult to the normal brain has deleterious consequences to neurocognitive and physical functioning, and causes accelerated aging/frailty. Approaches to ameliorate radiotherapy-induced late-effects are lacking and a paucity of appropriate model systems hinders their development.

Methods
We have developed a clinically relevant in vivo model system that recapitulates the radiotherapy dose, targeting, and developmental stage of childhood medulloblastoma. Consistent with human regimens, age-equivalent (postnatal days 35–37) male C57Bl/6J mice received computerized tomography image-guided CRT (human-equivalent 37.5 Gy EQD2, n = 12) ± PFB (human-equivalent 48.7 Gy EQD2, n = 12), via the small animal radiation research platform and were longitudinally assessed for &gt; 12 months.

Results
CRT was well tolerated, independent of PFB receipt. Compared to a sham-irradiated group (n = 12), irradiated mice were significantly frailer following irradiation (frailty index; P = .0002) and had reduced physical functioning; time to fall from a rotating rod (rotarod; P = .026) and grip strength (P = .006) were significantly lower. Neurocognitive deficits were consistent with childhood MB survivors; irradiated mice displayed significantly worse working memory (Y-maze; P = .009) and exhibited spatial memory deficits (Barnes maze; P = .029). Receipt of PFB did not induce a more severe late-effect profile.

Conclusions
Our in vivo model mirrored childhood MB radiotherapy and recapitulated features observed in the late-effect profile of MB survivors. Our clinically relevant model will facilitate both the elucidation of novel/target mechanisms underpinning MB late effects and the development of novel interventions for their amelioration.
Optimizing paediatric specialist referrals for short stature in an era of multiple growth hormone indications
Authors: Krishnamoorthy Preetha , Gagné Nancy , Girgis Rose , Marks Seth , Saoudi Zoraida , Zenlea Ian , Kirsch Susan 
Published: June 2024

Abstract
The assessment of growth during infancy and childhood is an essential component of paediatric medicine, as atypical growth may point to the existence of an underlying health condition. To reduce morbidity, it is vital that treatment for growth disorders is provided in a timely fashion. However, although there are guidelines regarding referral criteria for short stature in Europe and the USA, there are no such guidelines in Canada. To address this, a series of consultations and workshops with paediatricians, paediatric endocrinologists, family physicians and nurses were held, with the aim of developing a consensus-based set of recommendations for children in Canada showing atypical growth and to identify red flags for children who might benefit from early referral. To achieve this, a referral algorithm and referral form for primary care providers were developed to ensure timely and appropriate referrals, and transmission of the most relevant details to the secondary care consultant.
Pattern of CYP3A5 and MDR-1 single-nucleotide polymorphism and its impact on Tacrolimus levels and clinical outcomes in living renal allograft recipient
Authors: Sangha Sukhwinder Singh , Yadav Sushma , Yadav Raj Kanwar , Kumar Asheesh , Seenu Vuthaluru , Agarwal Sanjay Kumar , Kabra Madhulika , Chowdhury Madhumita Roy , Vishwakarma Vishal Kumar , Bhowmik Dipankar 
Published: June 2024

Abstract

Introduction
Renal transplant is the best form of renal replacement therapy. The most favored immunosuppression includes Tacrolimus, mycophenolate mofetil, and steroids. Tacrolimus has a narrow therapeutic index and requires therapeutic drug monitoring (TDM). However, there is wide variation in tacrolimus level with weight-based fixed dosage regimens. This variability is due to polymorphism of major pathways of metabolism ie CYP3A5 and MDR1 genes. Fast metabolizers require higher dosage and slow metabolizers require lower dosage. Genotype-based dosing strategy may be useful to achieve early therapeutic level and reduce infections and rejections.

Methodology
One hundred and sixty transplant patients at tertiary care hospitals in India were included in this study from 2016 to 2018. Genetic polymorphism analysis in CYP3A5 and MDR1 genes was carried out at the time of transplant. All patients were given a fixed weight-based dosage of Tacrolimus. Data were analyzed in relation to genotype polymorphism.

Results and discussion
69.2% of wild variants of CYP 3A5 (Fast metabolizers) have low initial tacrolimus levels. 51.5% of Homo variants (Slow metabolizers) have high initial tac levels. However, all variants achieve optimum tacrolimus levels at the same time (mean 12.4 days). There were higher number of infections among slow metabolizers.

Conclusion
A fixed dosing regimen with TDM results in high and low initial tacrolimus levels in slow and fast metabolizers respectively and more infections in slow metabolizers. However, graft rejections being fewer in number, were not different. A larger sample with genotype-based dosing is required to test such a strategy.
In flagranti—functional morphology of copulatory organs of odontopygid millipedes (Diplopoda: Juliformia: Spirostreptida)
Authors: Brandt Justus , Reip Hans S , Naumann Benjamin 
Published: June 2024

Abstract
The copulatory organs of many animal groups exhibit a high degree of morphological complexity and diversity that is thought to have evolved on the basis of different selective mechanisms, including lock-and-key mechanism, pleiotropy, sperm competition, internal courtship, and female choice. Identifying the effects of these different selective mechanisms on the copulatory organs is one of the central topics of the study of sexual selection. To tackle this challenge, knowledge of the functions of all parts of the copulatory organs is indispensable. Here we study the functional morphology of the gonopods (male copulatory organs) and vulvae (female copulatory organs) in the odontopygid millipede Spinotarsus sp. (Diplopoda: Spirostreptida: Odontopygidae). While the vulvae of female odontopygids are rather simple, male gonopods are complex, walking leg-derived copulatory organs that exhibit many movable sub-parts. Using X-ray microscopy-based 3D reconstruction, confocal laser scanning microscopy, and mating observations, we revise the functional morphology of odontopygid gonopods, propose biological roles, and evaluate the possible involvement of different selective mechanisms underlying their evolution.
Remimazolam: its clinical pharmacology and evolving role in anesthesia and sedation practice
Authors: Masui Kenichi 
Published: June 2024

Purpose of review
Remimazolam is a novel benzodiazepine anesthetic/sedative, designed as a rapidly metabolized carboxylic acid. Since its recent launch, the role of remimazolam in modern anesthesia and sedation practice is still evolving. This review aims to outline the clinical pharmacology and clinical utility of remimazolam to elucidate its potential advantages and limitations.

Recent findings
Remimazolam is “short-acting” but not ultra-short-acting compared with propofol based on context-sensitive decrement times. But compared to propofol, the availability of the benzodiazepine antagonist, flumazenil, is considered an advantage, particularly in certain emergency situations such as in patients with difficult airways. However, because flumazenil is shorter acting than remimazolam when remimazolam accumulates or is present in a high concentration, the reappearance of remimazolam sedation may occur after the initial reversal of anesthesia/sedation from flumazenil administration. Although it is beneficial that remimazolam causes less respiratory depression and hypotension than propofol, serious respiratory depression and hypotension can still occur. Remimazolam administration causes minimal or no pain on injection. Remimazolam is associated with less postoperative nausea and vomiting than inhaled anesthetics, but propofol is clearly superior in this regard. The anesthetic/sedative effects may be prolonged by severe hepatic impairment; remimazolam tolerance can occur in long-term benzodiazepine users.

Summary
Remimazolam may be beneficial to use in procedural sedation and general anesthesia for patients with difficult airways or hemodynamic instability. Further clinical studies with remimazolam are warranted to identify the potential benefits in other settings and patient populations.