bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine Learning Reinforced Genetic Algorithm for Massive Targeted Discovery of Selectively Cytotoxic Inorganic Nanoparticles
Authors: Jyakhwo Susan , Serov Nikita , Dmitrenko Andrei , Vinogradov Vladimir V.
Published: September 2023

Nanoparticles (NPs) have been employed as drug delivery systems (DDSs) for several decades, primarily as passive carriers, with limited selectivity. However, recent publications have shed light on the emerging phenomenon of NPs exhibiting selective cytotoxicity against cancer cell lines, attributable to distinct metabolic disparities between healthy and pathological cells. This study revisits the concept of NPs selective cytotoxicity, and for the first time proposes a high‐throughput in silico screening approach to massive targeted discovery of selectively cytotoxic inorganic NPs. In the first step, this work trains a gradient boosting regression model to predict viability of NP‐treated cell lines. The model achieves mean cross‐validation (CV) Q2 = 0.80 and root mean square error (RMSE) of 13.6. In the second step, this work develops a machine learning (ML) reinforced genetic algorithm (GA), capable of screening >14 900 candidates/min, to identify the best‐performing selectively cytotoxic NPs. As proof‐of‐concept, DDS candidates for the treatment of liver cancer are screened on HepG2 and hepatocytes cell lines resulting in Ag NPs with selective toxicity score of 42%. This approach opens the door for clinical translation of NPs, expanding their therapeutic application to a wider range of chemical space of NPs and living organisms such as bacteria and fungi.
Anisotropic Amorphization and Phase Transition in Na2Ti3O7 Anode Caused by Electron Beam Irradiation
Authors: Cheng Lixun , Shen Yaoling , Nan Pengfei , Wu Chuanqiang , Tai Yilin , Luo Xiaonan , Zhang YongSheng , Ge Binghui
Published: September 2023

Na2Ti3O7 is considered one of the most promising anode materials for sodium ion batteries due to its superior safety, environmental friendliness, and low manufacturing cost. However, its structural stability and reaction mechanism still have not been fully explored. As the electron beam irradiation introduces a similar impact on the Na2Ti3O7 anode as the extraction of Na+ ions during the battery discharge process, the microstructure evolution of the materials is investigated by advanced electron microscopy techniques at the atomic scale. Anisotropic amorphization is successfully observed. Through the integrated differential phase contrast‐scanning transmission electron microscopy technique and density functional theory calculation, a phase transition pathway involving a new phase, Na2Ti24O49, is proposed with the reduction of Na atoms. Additionally, it is found that the amorphization is dominated by the surface energy and electron dose rate. These findings will deepen the understanding of structural stability and deintercalation mechanism of the Na2Ti3O7 anode, providing new insight into exploring the failure mechanism of electrode materials.
Engineering the Physical Microenvironment into Neural Organoids for Neurogenesis and Neurodevelopment
Authors: Li Minghui , Sun Heng , Hou Zongkun , Hao Shilei , Jin Liang , Wang Bochu
Published: September 2023

Understanding the signals from the physical microenvironment is critical for deciphering the processes of neurogenesis and neurodevelopment. The discovery of how surrounding physical signals shape human developing neurons is hindered by the bottleneck of conventional cell culture and animal models. Notwithstanding neural organoids provide a promising platform for recapitulating human neurogenesis and neurodevelopment, building neuronal physical microenvironment that accurately mimics the native neurophysical features is largely ignored in current organoid technologies. Here, it is discussed how the physical microenvironment modulates critical events during the periods of neurogenesis and neurodevelopment, such as neural stem cell fates, neural tube closure, neuronal migration, axonal guidance, optic cup formation, and cortical folding. Although animal models are widely used to investigate the impacts of physical factors on neurodevelopment and neuropathy, the important roles of human stem cell‐derived neural organoids in this field are particularly highlighted. Considering the great promise of human organoids, building neural organoid microenvironments with mechanical forces, electrophysiological microsystems, and light manipulation will help to fully understand the physical cues in neurodevelopmental processes. Neural organoids combined with cutting‐edge techniques, such as advanced atomic force microscopes, microrobots, and structural color biomaterials might promote the development of neural organoid‐based research and neuroscience.
The Importance of Dean Flow in Microfluidic Nanoparticle Synthesis: A ZIF‐8 Case Study
Authors: Yu Xiangjiang , Andreo Jacopo , Walden Madeline , del Campo Javier F. , Basabe‐Desmonts Lourdes , Benito‐Lopez Fernando , Burg Thomas P. , Wuttke Stefan
Published: September 2023

The Dean Flow, a physics phenomenon that accounts for the impact of channel curvature on fluid dynamics, has great potential to be used in microfluidic synthesis of nanoparticles. This study explores the impact of the Dean Flow on the synthesis of ZIF‐8 particles. Several variables that influence the Dean Equation (the mathematical expression of Dean Flow) are tested to validate the applicability of this expression in microfluidic synthesis, including the flow rate, radius of curvature, channel cross sectional area, and reagent concentration. It is demonstrated that the current standard of reporting, providing only the flow rate and crucially not the radius of curvature, is an incomplete description that will invariably lead to irreproducible syntheses across different laboratories. An alternative standard of reporting is presented and it is demonstrated how the sleek and simple math of the Dean Equation can be used to precisely tune the final dimensions of high quality, monodisperse ZIF‐8 nanoparticles between 40 and 700 nm.
IMDAC: A robust intelligent software defect prediction model via multi‐objective optimization and end‐to‐end hybrid deep learning networks
Authors: Zhu Kun , Zhang Nana , Jiang Changjun , Zhu Dandan
Published: September 2023

Software defect prediction (SDP) aims to build an effective prediction model for historical defect data from software repositories by some specialized techniques or algorithms, and predict the defect proneness of new software modules. Nevertheless, the complex internal intrinsic structure hidden behind the defect data makes it challenging for the built prediction model to capture the most expressive defect feature representations, and largely limits the SDP performance. Fortunately, artificial intelligence is interacting closely with humans and provides powerful intelligent technical support for addressing these SDP issues. In this article, we propose a robust intelligent SDP model called IMDAC based on deep learning and soft computing techniques. This model has three main advantages: (1) an effective deep generative network—InfoGAN (information maximizing GANs) is employed to conduct data augmentation, namely generating sufficient defect instances and achieving defect class balance simultaneously. (2) Select the fewest representative feature subset for the minimum error via an advanced multi‐objective optimization approach—MSEA (multi‐stage evolutionary algorithm). (3) Build a powerful end‐to‐end deep defect predictor by hybrid deep learning techniques—DAE (Denoising AutoEncoder) and CNN (convolutional neural network), which can not only reconstruct a clean “repaired” input with strong robustness and generalization capabilities via DAE, but also learn the abstract deep semantic features with strong discriminating capability via CNN. Experimental results verify the superiority and robustness of the IMDAC model across 15 software projects.
Appreciating systems changes via multiparadigm inquiry: Architectural design, ecological anthropology, Classical Chinese Medicine and systems rhythms
Authors: Ing David
Published: September 2023

In which ways is the subject of systems change(s), as a first‐class concept, distinct from a reduction into (i) systems and (ii) changes? For practice, theory and methods to be authentically rigourous, the philosophy underlying an approach to systems changes can be explicated. Through an appreciative systems framework, presumptions are surfaced as to (i) what are and are not systems changes; (ii) when, where and for whom, systems changes are prioritized for attention; and (iii) how systems changes should be addressed. Philosophies of (i) architectural design, (ii) ecological anthropology, (iii) Classical Chinese Medicine and (iv) rhythms are explored through multiparadigm inquiry and open theorizing. The resulting influence of these four philosophies is considered, leading to a philosophy of systems rhythms more explicitly proposed as a foundation on which to approach systems changes.
Ecological characterization of 175 low‐pathogenicity avian influenza viruses isolated from wild birds in Mongolia, 2009–2013 and 2016–2018
Authors: Barkhasbaatar Ariunbaatar , Gilbert Martin , Fine Amanda E. , Shiilegdamba Enkhtuvshin , Damdinjav Batchuluun , Buuveibaatar Bayarbaatar , Khishgee Bodisaikhan , Johnson Christine K. , Leung Connie Y. H. , Ankhanbaatar Ulaankhuu , Purevtseren Dulam , Tuttle James M. , Mazet Jonna A. K. , Peiris Joseph S. Malik , Jambal Losolmaa , Shatar Munkhduuren , Sukhbaatar Tuvshintugs , Olson Sarah H.
Published: September 2023

Background

Since 2005, highly pathogenic avian influenza A H5N1 viruses have spread from Asia worldwide, infecting poultry, humans and wild birds. Subsequently, global interest in avian influenza (AI) surveillance increased.

Objectives

Mongolia presents an opportunity to study viruses in wild birds because the country has very low densities of domestic poultry and supports large concentrations of migratory water birds.

Methods

We conducted AI surveillance in Mongolia over two time periods, 2009–2013 and 2016–2018, utilizing environmental fecal sampling. Fresh fecal samples were collected from water bird congregation sites. Hemagglutinin (HA) and neuraminidase (NA) subtypes of positive samples were identified through viral isolation or molecular assays, with pathogenicity determined by HA subtype or sequencing the HA cleavage site.

Results

A total of 10,222 samples were collected. Of these, 7,025 fecal samples were collected from 2009 to 2013, and 3,197 fecal samples were collected from 2016 to 2018. Testing revealed 175 (1.7%) positive samples for low‐pathogenicity influenza A, including 118 samples from 2009 to 2013 (1.7%) and 57 samples from 2016 to 2018 (1.8%). HA and NA subtyping of all positives identified 11 subtypes of HA and nine subtypes of NA in 29 different combinations. Within periods, viruses were detected more frequently during the fall season than in the early summer.

Conclusion

Mongolia's critical wild bird habitat is positioned as a crossroad of multiple migratory flyways. Our work demonstrates the feasibility of using an affordable environmental fecal sampling approach for AI surveillance and contributes to understanding the prevalence and ecology of low‐pathogenicity avian influenza viruses in this important location, where birds from multiple flyways mix.
Cross‐cultural adaptation and validation of the KOOS, JR questionnaire for assessing knee osteoarthritis in Spanish‐speaking patients
Authors: Guiloff Rodrigo , Iñiguez Magaly , Prado Tomás , Figueroa Francisco , Olavarría Nicolás , Carrasco Eduardo , Ergas Enrique , Salgado Martín , Lyman Stephen
Published: September 2023

Purpose

The present study aims to translate, adapt and validate a Spanish version of the Knee Injury and Osteoarthritis Outcome Score, Joint Replacement (KOOS, JR), including a reliability and validity analysis in patients with knee osteoarthritis (OA).

Methods

This study conducted a prospective validation study following the six stages of the “Guidelines for the Process of Cross‐Cultural Adaptation of Self‐Report Measures”. Psychometric testing was conducted in patients with knee osteoarthritis. Subjects answered the Spanish KOOS, JR (S‐KOOS, JR) and a validated Spanish Oxford Knee Score (S‐OKS). Retest was conducted at 10 days. Acceptability, floor and ceiling effect, internal consistency (Cronbach’s α), reproducibility (mixed‐effect model coefficient [MEMC]) and construct validity (Spearman’s correlation; p = 0.05) were assessed.

Results

Forty‐one patients (mean age: 65.6 ± 5.39; 48.8% female) participated in the study. All patients (100%) answered both scores during the first assessment and 38 (92.7%) during the second assessment. All patient‐reported outcomes measures were answered completely (100%). The S‐KOOS, JR resulted in 100% acceptability when answered. There were no ceiling or floor effects detected. The Cronbach’s α for the S‐KOOS, JR was 0.927 and its MEMC was 0.852 (CI 95% 0.636–1.078). The Spearman’s correlation between the S‐KOOS, JR and the S‐OKS was 0.711 (CI 0.345–0.608; p < 0.001) and 0.870 (CI 0.444–0.651; p < 0.001) for the first and second assessments, respectively.

Conclusion

The S‐KOOS, JR has very high internal consistency and reproducibility, with a high correlation with the S‐OKS; it is a reliable and valid instrument for characterising Spanish‐speaking patients suffering from knee OA.

Level of evidence

IV.
Flavobacterium okayamense sp. nov. isolated from surface seawater
Authors: Kitahara Kei , Muzembo Basilua Andre , Morohoshi Sho , Kunihiro Tadao , Tazato Nozomi , Ohno Ayumu , Uesaka Kazuma , Taniguchi Makoto , Miyoshi Shin-ichi
Published: September 2023

Strain KK2020170T, a Gram-stain negative, yellow colony-forming bacterium, was isolated from surface seawater sampled in Kojima Bay, Okayama, Japan. Phylogenetic analysis based on the 16S rRNA gene revealed that strain KK2020170T belongs to the genus Flavobacterium, with Flavobacterium haoranii LQY-7T (98.1% similarity) being its closest relative, followed by Flavobacterium sediminis MEBiC07310T (96.9%) and Flavobacterium urocaniciphilum YIT 12746T (96.0%). Whole-genome shotgun sequencing showed that strain KK2020170T, when paralleled with F. haoranii LQY-7 T, had 81.3% average nucleotide identity, and 24.6% in silico DNA–DNA hybridization values, respectively. The DNA G + C content of strain KK2020170T was 31.1 mol%. The most abundant fatty acids (> 10%) of strain KK2020170T were iso-C15: 0, iso-C17: 0 3-OH and iso-C15: 1 G. The dominant respiratory quinone of the strain was menaquinone MK-6. Based on the phylogenetic and phenotypic analysis results, we propose that strain KK2020170T represents a novel species, for which the name Flavobacterium okayamense sp. nov. has been proposed. The type strain is KK2020170T (= ATCC TSD-280 T = NBRC 115344 T).
Disparities in paediatric radiology research publications from low- and lower middle-income countries: a time for change
Authors: Offiah Amaka C. , Atalabi Omolola M. , Epelman Monica , Khanna Geetika
Published: September 2023

The positive impact of diversity on health research and outcomes is well-recognised and widely published. Despite this, published evidence shows that at every step of the research pathway, issues of equity, diversity and inclusion (EDI) arise. There is evidence of a lack of diversity within research teams, in the research questions asked/research participants recruited, on grant review/funding panels, amongst funded researchers and on the editorial boards and reviewer pools of the journals to which results are submitted for peer-reviewed publication. Considering the journal PediatricRadiology, while its editorial board of 92 members has at least one member affiliated to a country in every region of the world, the majority are in North America (n=52, 57%) and Europe (n=30, 33%) and only two (2%) are affiliated to institutions in a lower middle-income country (LMIC) (India, Nigeria), with one (1%) affiliated to an institution in an upper middle-income country (UMIC) (Peru) and none in a low-income country (LIC). Pediatric Radiology is “…the official journal of the European Society of Paediatric Radiology, the Society for Pediatric Radiology, the Asian and Oceanic Society for Pediatric Radiology and the Latin American Society of Pediatric Radiology”. However, of the total number of manuscripts submitted for potential publication in the four years 2019 through 2022, only 0.03% were from a LIC and only 7.9% were from a LMIC. Further, the frequency of acceptance of manuscripts from UMIC was seven times higher than that from LMIC (no manuscripts were published from LIC). Increased collaboration is required between researchers across the globe to better understand the barriers to equity in the funding, conduct and publication of research from LIC and LMIC and to identify ways in which we can overcome them together.

Graphical abstract
Prediction of high Ki-67 proliferation index of gastrointestinal stromal tumors based on CT at non-contrast-enhanced and different contrast-enhanced phases
Authors: Xie Zhenhui , Suo Shiteng , Zhang Wang , Zhang Qingwei , Dai Yongming , Song Yang , Li Xiaobo , Zhou Yan
Published: September 2023

Objectives

To evaluate and analyze radiomics models based on non-contrast-enhanced computed tomography (CT) and different phases of contrast-enhanced CT in predicting Ki-67 proliferation index (PI) among patients with pathologically confirmed gastrointestinal stromal tumors (GISTs).

Methods

A total of 383 patients with pathologically proven GIST were divided into a training set (n = 218, vendor 1) and 2 validation sets (n = 96, vendor 2; n = 69, vendors 3–5). Radiomics features extracted from the most recent non-contrast-enhanced and three contrast-enhanced CT scan prior to pathological examination. Random forest models were trained for each phase to predict tumors with high Ki-67 proliferation index (Ki-67>10%) and were evaluated using the area under the receiver operating characteristic curve (AUC) and other metrics on the validation sets.

Results

Out of 107 radiomics features extracted from each phase of CT images, four were selected for analysis. The model trained using the non-contrast-enhanced phase achieved an AUC of 0.792 in the training set and 0.822 and 0.711 in the two validation sets, similar to models trained on different contrast-enhanced phases (p > 0.05). Several relevant features, including NGTDM Busyness and tumor size, remained predictive in non-contrast-enhanced and different contrast-enhanced images.

Conclusion

The results of this study indicate that a radiomics model based on non-contrast-enhanced CT matches that of models based on different phases of contrast-enhanced CT in predicting the Ki-67 PI of GIST. GIST may exhibit similar radiological patterns irrespective of the use of contrast agent, and such radiomics features may help quantify these patterns to predict Ki-67 PI of GISTs.

Clinical relevance statement

GIST may exhibit similar radiomics patterns irrespective of contrast agent; thus, radiomics models based on non-contrast-enhanced CT could be an alternative for risk stratification in GIST patients with contraindication to contrast agent.

Key Points

• Performance of radiomics models in predicting Ki-67 proliferation based on different CT phases is evaluated.

• Non-contrast-enhanced CT–based radiomics models performed similarly to contrast-enhanced CT in risk stratification in GIST patients.

• NGTDM Busyness remains stable to contrast agents in GISTs in radiomics models.
Evaluating skill in predicting the Interdecadal Pacific Oscillation in initialized decadal climate prediction hindcasts in E3SMv1 and CESM1 using two different initialization methods and a small set of start years
Authors: Meehl Gerald A. , Kirtman Ben , Glanville Anne A. , Richter Jadwiga , Rosenbloom Nan , Yeager Stephen
Published: September 2023

It is a daunting challenge to conduct initialized hindcasts with enough ensemble members and associated start years to form a drifted climatology from which to compute the anomalies necessary to quantify the skill of the hindcasts when compared to observations. This limits the ability to experiment with case studies and other applications where only a few initial years are needed. Here we run a set of hindcasts with CESM1 and E3SMv1 using two different initialization methods for a limited set of start years and use the respective uninitialized free-running historical simulations to form the model climatologies. Since the drifts from the observed initial states in the hindcasts toward the uninitialized model state are large and rapid, after a few years the drifted initialized models approach the uninitialized model climatological errors. Therefore, hindcasts from the limited start years can use the uninitialized climatology to represent the drifted model states after about lead year 3, providing a means to compute forecast anomalies in the absence of a large hindcast sample. There is comparable skill for predicting spatial patterns of multi-year Pacific sea surface temperature anomalies in the domain of the Interdecadal Pacific Oscillation using this method compared to the conventional methodology with a large hindcast data set, though there is a model dependence to the drifts in the two initialization methods.
Assessing the morphology and bone mineral density of the immature pars lateralis as an indicator of age
Authors: Thornton Roxanne , Mendelow Mira G. , Hutchinson Erin F.
Published: September 2023

Age estimation is crucial when the state of personhood is a mitigating factor in the identification of immature human remains. The maturation sequence of immature bones is a valuable alternative to dental development and eruption standards. Bordering the foramen magnum and pars basilaris, the pars lateralis is somewhat understudied. The aim of this study was to comprehensively describe the morphology of the immature human pars lateralis bone. Human pars laterali were sourced from the crania of 103 immature individuals of unknown provenance from the Johannesburg Forensic Paediatric Collection (JFPC), University of the Witwatersrand (HREC-Medical: M210855). The study sample was subdivided into early prenatal (younger than 30 gestational weeks; n = 32), prenatal (30–40 gestational weeks, n = 41) and postnatal (birth to 7.5 months, n = 30) age groups. The morphology of the pars laterali was studied using a combination of bone mineral density pattern assessments, geometric morphometrics and stereomicroscopy. Bone mineral density in postnatal individuals was lower when compared with the prenatal individuals. No statistically significant differences between density points were noted. The overall shape of the pars lateralis changed from a triangular shape in the early prenatal individuals to a fan-like quadrilateral bone in postnatal individuals. The angulation of the medial border for the foramen magnum highlighted a change in shape between straight in the early prenatal cohort to V-shaped in the postnatal individuals. The various technical approaches used in the current study provided detailed descriptions of the pars lateralis which establishes a valuable foundation for diagnostic criteria employing morphological predictors for biological profiling.
Dirofilaria immitis conquering the regions in Slovakia previously endemic for D. repens
Authors: Miterpáková Martina , Valentová Daniela , Hurníková Zuzana
Published: September 2023

The present study was focused on the current state of Dirofilaria species distribution in the territory of the Slovak Danubian Lowland, a region previously identified endemic for Dirofilaria repens. For the research, blood samples of 330 dogs tested positive for dirofilariosis using concentration tests or “rapid heartworm tests” were sent by private veterinary practitioners for further DNA analyses and species determination. The results revealed an unquestionable change in the pattern of Dirofilaria species distribution with Dirofilaria immitis, diagnosed as the agent of mono- and co-infections with D. repens, responsible for 60.00% of all cases. The results showed that in the course of the last 5 years, D. immitis has spread significantly in Slovakia and has become the dominant causal agent of dirofilariosis in the former endemic areas of D. repens distribution, which increases infection risk for both dogs and humans.
MAES: a ROS 2-compatible simulation tool for exploration and coverage algorithms
Authors: Andreasen Malte Z. , Holler Philip I. , Jensen Magnus K. , Albano Michele
Published: September 2023

With the aim of allowing the efficient and realistic simulation of swarm algorithms for exploration and coverage, we present the tool Multi-Agent Exploration Simulator (MAES), which is an open-source physics-based discrete step multi-robot simulator. MAES features movement in a continuous 2D space, realistic physics based on the Unity framework, advanced visualization techniques such as heatmaps, custom wireless signal degradation, both randomly generated and custom user-provided maps, and a ROS (Robot Operating System) interface. This latter characteristic could allow to port the simulated algorithms to real-world robots. We present performance tests, conducted with rather modest hardware, showing that MAES is able to simulate up to 5 robots in ROSMode (using the ROS integration) and up to 120 robots in UnityMode (development performed directly into the C# Unity Editor). A usability test was conducted which hinted that the target audience of robotics researchers and developers is able to quickly install, setup, and use MAES for implementing simple robot logic.
Beyond the Implicit/Explicit Dichotomy: The Pragmatics of Plausible Deniability
Authors: Bonalumi Francesca , Mahr Johannes B. , Marie Pauline , Pouscoulous Nausicaa
Published: September 2023

In everyday conversation, messages are often communicated indirectly, implicitly. Why do we seem to communicate so inefficiently? How speakers choose to express a message (modulating confidence, using less explicit formulations) has been proposed to impact how committed they will appear to be to its content. This commitment can be assessed in terms of accountability – is the speaker held accountable for what they communicated? – and deniability – can the speaker plausibly deny they intended to communicate it? We investigated two factors that may influence commitment to implicitly conveyed messages. In a preregistered online study, we tested the hypothesis that the degree of meaning strength (strongly or weakly communicated) and the level of meaning used by the speaker (an enrichment or a conversational implicature) modulate accountability and plausible deniability. Our results show that both meaning strength and level of meaning influence speaker accountability and plausible deniability. Participants perceived enrichments to be harder to deny than conversational implicatures, and strongly implied content as more difficult to deny than weakly implied content. Furthermore, participants held the speaker more accountable to content conveyed via an enrichment than to content conveyed via an implicature. These results corroborate previously found differences between levels of meaning (enrichment vs. implicature). They also highlight the largely understudied role of meaning strength as a cue to speaker commitment in communication.
Production of phenolic compounds from argan shell waste by reductive catalytic fractionation
Authors: Afailal Zainab , Gil-Lalaguna Noemí , Høj Martin , Cornejo Alfonso , Sánchez José Luis , Jensen Anker Degn
Published: September 2023

For efficient utilization of lignocellulosic biomass components, reductive catalytic fractionation appears as a promising biorefinery strategy. In this work, this concept of biomass valorization was used to study the potential of an unexplored feedstock, argan shells. This material was processed in a non-catalytic route and over a Pd/C catalyst in two different reaction media. The effects of the treatment temperature (250, 275, and 300 °C), as well as the catalyst loading (catalyst/argan shells mass ratio of 0.05 and 0.1 g/g), were also studied. The main product (lignin-derived oil) was thoroughly characterized using GC/MS/FID, SEC, and NMR. The highest monomer yields of 48–49 wt% based on the lignin content were obtained for n-butanol/water reaction medium at 300 °C using a Pd/C catalyst load of 0.1 g/g and for methanol reaction medium at 275 °C and 0.05 g/g. Significantly lower monomeric phenol yields were obtained in the non-catalytic route (4–19 wt% for n-butanol/water and 9–16 wt% for methanol). The main phenolic monomers in the catalytic pathway were 4-n-propanolguaiacol, 4-n-propanolsyringol, and 4-alkyl guaiacols and syringols, with some differences in the selectivities from one solvent to another.

Graphical Abstract
Implications of Climate Change and Anopheles stephensi Liston in Africa: Knowledge Gaps and Lessons from History
Authors: Pecor David B. , Potter Alexander M. , Linton Yvonne-Marie
Published: September 2023

Purpose of Review

The invasive Asian mosquito vector—Anopheles stephensi Liston, 1901—is poised to greatly complicate malaria eradication efforts across Africa. This species has been reported in an increasing number of African nations and has the potential to introduce malaria into most of Africa’s largest cities. Climate change is a dominant force changing population dynamics across the continent and driving human populations to migrate to urban centers.

Recent Findings

This work presents all high-quality surveillance data documenting An. stephensi to date, including an overlooked report of the species collected in Egypt in 1966. Finally, we provide detailed images of adult and larval morphology and bionomics descriptions.

Based on our current knowledge of Anopheles stephensi, we explore how climate change may impact its distribution and malaria rates in the coming decades. We also identify key knowledge gaps related to this species invasion including the most up-to-date information on the taxonomy, morphological characters, and bionomics of An. stephensi. Tools that are publicly available via VectorMap are also presented along with guidance on strengthening surveillance programs targeting An. stephensi using these tools.
Effectiveness of a Staphylococcus aureus mupirocin decolonization protocol in a neonatal intensive care unit
Authors: Ankrum Andrea , Huang Felicia Scaggs , Schaffzin Joshua
Published: September 2023

Background:Staphylococcus aureus infections are a significant cause of morbidity in neonatal intensive care units (NICUs), and they are typically preceded by nasal colonization. Mupirocin decolonization protocols as an infection prevention tool can halt S. aureus outbreaks and prevent infections. We examined the effect of a mupirocin treatment protocol on S. aureus incidence, prevalence, decolonization, and infections in a level IV NICU. Methods: We conducted a retrospective before-and-after observational study from June 1, 2018, to May 31, 2020. Beginning June 1, 2019, patients identified with either methicillin-sensitive or -resistant S. aureus (MSSA or MRSA) received mupirocin ointment to bilateral nares 3 times daily for 5 days. Patients with central lines or surgical incisions were treated every 30 days. All NICU patients were screened weekly unless positive for MRSA. We defined MSSA decolonization as 3 consecutive negative screens following mupirocin treatment. We calculated monthly S. aureus incidence as any new positive per 1,000 patient days and monthly prevalence as a percentage of the average daily number of patients with S. aureus per the average monthly census. Total number of infections were compared. Statistical significance was determined using a 2 sample proportions test and P < .05. Decolonization was calculated as percentage of occurrences among treated patients. Results: Overall, 190 patients received mupirocin; 142 patients received 1 course and 48 received 2 or more courses. There was no difference in incidence of MSSA (P = .09), but prevalence decreased from 18.8% to 14.4% (P < .05) (Fig. 1). Of 66 patients with MSSA, 35% were decolonized. An additional mupirocin treatment for 16 of these patients had a 50% decolonization rate. For MRSA, incidence decreased from 0.24 to 0.20 (P = .36) and prevalence decreased from 21.9% to 18.6% (P < .05) (Fig. 1). There was no statistical difference in the number of total S. aureus infections (P = .91) or when stratified by MSSA (P = .72) or MRSA (P = .82). In the postmupirocin population, there were 5 MRSA and 7 MSSA infections. Of the MSSA-infected patients, 6 remained colonized at the time of infection. Conclusions: Implementing a single mupirocin treatment course for S. aureus decolonization in NICU was only effective in one-third of patients and had no effect on infection occurrence. Changes in incidence and prevalence could be confounded by other infection prevention practices. Further study is needed to determine whether continued screening and additional mupirocin treatment could improve effectiveness of S. aureus decolonization programs.

Disclosure: None
Approach for sustainable district-led production and distribution of alcohol-based hand rub in Uganda
Authors: Kesande Maureen
Published: September 2023

Background: A sustainable, continuous supply of alcohol-based hand rub (ABHR) is essential for healthcare workers in health facilities. The WHO provides guidance for production in individual health facilities. In Uganda, using this guidance, an innovative approach was implemented at the district local government level to produce and subsequently distribute ABHR to primary-care health facilities that have limited capacity for local facility-level production. This project was supported by the CDC in collaboration with the Infectious Diseases Institute (IDI) and targeted governmental or district engagement with local partners to ensure sustainability. Methods: District stakeholders were engaged to obtain buy-in and define roles and responsibilities. Overall, 4 staff members in each of 6 supported districts were nominated by District Health Officers for training: 2 staff members were trained to produce ABHR and conduct internal quality control and 2 were trained on external quality control. Districts provided ABHR production-unit facilities and facilitated integration within the government essential supplies delivery system, National Medical Stores in Uganda, which supports last-mile delivery to facilities. An implementing partner purchased initial raw materials necessary for production. The cost of materials for local production was compared to the price of commercial ABHR available in Uganda. Results: Between January and August 2021, 23 staff members were trained, and 380 batches of quality-assured ABHR (17,820 L) were produced and distributed to 278 health facilities. Consumption of ABHR in the first distribution was used to benchmark predicted ABHR consumption per targeted facility in subsequent months. Increased demand for ABHR due to the COVID-19 pandemic and the Ebola virus disease outbreak in central Uganda (September 2022) was addressed through emergency requests on a case-by-case basis. ABHR local production costs $3 per liter for materials, less than half of commercial ABHR ($8 per liter). Conclusions: Early results suggest that this approach is potentially sustainable but requires national advocacy as well. Leveraging existing distribution systems while building local capacity for ABHR production and distribution may improve longevity of such innovations in similar resource-limited settings.

Disclosure: None
The effectiveness of the appropriate prophylactic antibiotic use program for surgery
Authors: Lee Eunjung , Kim Tae Hyong , Park Se Yoon , Jung Jongtak , Baek Yae Jee
Published: September 2023

Background: Evaluation of the adequacy of prophylactic antibiotics in surgery has been implemented as a national policy in Korea since August 2007, and the appropriate use of prophylactic antibiotics has improved. However, antibiotic prescriptions that are not recommended or discontinuation of prophylactic antibiotic administration within 24 hours after surgery are still not well done. This study introduced a program to improve the adequacy of prophylactic antibiotics for surgery and analyzed its effects. Methods: We retrospectively analyzed the effectiveness of the appropriate prophylactic antibiotic use program for surgery conducted at a university hospital in Seoul. The participants were patients aged ≥18 years who underwent any of 18 types of surgery. The program started was implemented in June 2020. First, a computer system was used to confirm the antibiotic prescription recommended for each surgery. It also assessed whether the number of days of administration was exceeded, whether antibiotics were prescribed in combination, and whether antibiotics prescribed for discharge medicine were checked in 4 steps. A pop-up window appeared in each patient record to enter the reason for the prescription. If the reason was appropriate, the prescription was allowed, but if not, the prescription was restricted. In addition, infectious diseases physicians and an insurance review team visited each department to conduct an education session. To analyze the effect 3 months before activity (January–March 2020) and 3 months after activity (October–December 2020), we compared the first antibiotic administration rate within 1 hour prior to skin incision, the recommended prophylactic antibiotic administration rate, and surgery type. The rate of discontinuation of prophylactic antibiotics within 24 hours after administration and the rate of prescription of prophylactic antibiotics at discharge were compared. Results: In total, 1,339 surgeries during the study period were included in the analysis. There were 695 cases before the introduction of the program and 644 cases after the introduction. The rate of first antibiotic use within 1 hour prior to skin incision was 93.1%–99.5% (P < .001), the rate of recommended prophylactic antibiotic administration was 85.0%–99.2% (P < .001), and the rate of discontinuation of antibiotic administration within 24 hours after surgery improved from 51.8% to 98.3% (P < .001), respectively. The prescription rate of antibiotics at discharge improved from 20.7% to 0.8% (P <.001) (Table 1). Conclusions: A computerized program to improve the adequacy of prophylactic antibiotic use in surgery combined with education of medical staff was very effective.

Disclosure: None
High prevalence of antibiotic use in a tertiary-care hospital in Sierra Leone: We need to handle antibiotics with care
Authors: Kamara Ibrahim Franklyn , Fofanah Bobson , Sheriff Bockarie Pharaj , Katawera Victoria , Musoke Robert , Lakoh Sulaiman , Kamara Kadijatu Nabie , Kanu Joseph Sam
Published: September 2023

Background: Antimicrobial resistance (AMR) is a global public health concern that has the potential to reverse decades of progress aimed at decreasing morbidity and mortality attributed to infectious diseases. In 2019, ~5 million deaths were associated with AMR, of which 1.2 million were attributed to antibacterial-resistant infections. Healthcare facilities where antimicrobials are frequently used are high-risk settings for the selection and spread of resistant bacteria, and they further contribute to the increase in the burden of AMR. We have documented the prevalence and indication of antibiotic use in a tertiary-care referral hospital in Freetown, Sierra Leone. Methods: This point-prevalence survey was conducted at Connaught hospital, a tertiary-care hospital in Sierra Leone, in November 2021. The hospital offers a range of medical and surgical services through 25 units and has 16 wards with >300 beds. Data on patient-level antibiotic use, including indications for use, were extracted from medical records using WHO point-prevalence survey (PPS) forms that had been pretested and validated. Data collection was conducted in all the wards over a 10-day period by trained healthcare personnel. On the day of the survey, only the medical records of patients on admission before 8:00 a.m. on that day were included in the study. Data entry, cleaning, and analysis were conducted using the WHO PPS platform. Ethical approval was obtained. Results: In total, 87 patient records were included in the survey. Most (71%) were women, and the average age was 30.6 years. The prevalence of antibiotic use was 66%, and the average number of antibiotics prescribed to patients since admission was 2. The 5 most prescribed antibiotics were metronidazole, ceftriaxone, amoxicillin and clavulanic acid, ampicillin and cloxacillin, and azithromycin. The parenteral route of drug administration was the mainstay. The most frequent indications for antibiotic prescription were community-acquired infection and surgical prophylaxis. Blood-culture requests were not ordered before the initiation of antibiotic treatment. Conclusions: This study was the first study to be conducted in Connaught hospital using the WHO PPS methodology. The survey reports a high prevalence (60%) of antibiotic use, and most treatment was done empirically. This finding is contrary to the WHO recommendation of <30% antibiotic use. This high prevalence of antibiotic use has the potential to increase the burden of AMR in the country. Therefore, there is an urgent need to strengthen Connaught hospital’s antibiotic stewardship program.

Disclosures: None
Implementing a health-system–wide antibiotic stewardship program in ambulatory surgery centers
Authors: Hickman Kasey , Forcade Nicolas , Cooper Mandelin , Bhagwandeen Shivanne , Russell Brandy
Published: September 2023

Background: In 2016, the CDC released the Core Elements of Outpatient Antibiotic Stewardship, which extended the requirements previously released for hospital facilities and nursing homes to the outpatient setting. Several regulatory agencies focused on outpatient antimicrobial use. However, The Joint Commission and the Ambulatory Surgery Center (ASC) Leapfrog Group excluded ambulatory surgery centers from their medication management standards and questions. Due to the public health and patient safety benefits of implementing an antimicrobial stewardship program (ASP) and increasing regulatory interest in the matter, the Hospital Corporation of America (HCA) Ambulatory Surgery Division formally launched a nationwide ASP for its ambulatory surgery centers in March 2021. Methods: HCA is a large healthcare system with 146 ASCs in 16 states in 2021. The structure of the ASCs are local surgery centers with a medical director, a nurse responsible for infection prevention, and a pharmacist at a regional level. The types of surgeries vary based on location and ASC site. In 2019, a multidisciplinary team formed the corporate planning committee. The program was modeled after the CDC Core Elements and The Joint Commission’s requirements for an ASP. Each ASC was asked to build a local ASP team, led by a local physician and a regionally based pharmacist. In addition, a stewardship goal was established to update all preoperative antibiotic surgical-site infection prophylaxis order sets. The corporate committee provided educational resources, including evidence-based guidelines for appropriate antibiotic selection for surgical-site infections. They collected antibiotic cost per case as a baseline metric to track and analyze. Pediatric, ophthalmic, and gastrointestinal endoscopic procedures were excluded from the program. Results: From January 1, 2020, through December 31, 2021, including only centers that were operational during this period and excluding single specialty endoscopy centers, antibiotic cost per case decreased annually from $2.38 to $1.84 (t = 4.157; P < .005), and the postoperative infection rate also declined from 0.370 to 0.304 (t = 2.079; P = .040). Conclusions: Our findings suggest that implementing a health-system–wide outpatient antibiotic stewardship program in the ambulatory surgery center setting is feasible and may contribute to decreased antibiotic cost per case and improved postoperative surgical site infection rates.

Disclosures: None
Understanding clinician perspectives on antibiotic associated adverse events to inform feedback
Authors: Cherian Jerald , Jones George , Helsel Taylor , Virk Zunaira , Salinas Alejandra , Grieb Suzanne , Keller Sara , Tamma Pranita , Cosgrove Sara
Published: September 2023

Background: Feedback regarding antibiotic-associated adverse events (ABX-AEs) may assist clinicians with antibiotic decision making. We sought to understand how clinicians account for ABX-AEs when prescribing and their preferences for ABX-AE feedback. Methods: We conducted 1-hour virtual focus groups with 3–5 physicians or advance practice practitioners (APPs) per session at Johns Hopkins Hospital. Participants discussed the role of ABX-AEs in antibiotic decision making and feedback preferences. Participants evaluated prespecified categorization (mildly, moderately, or very concerning) of several ABX-AEs. Focus groups were recorded and transcribed. Transcripts were coded inductively by 2 independent reviewers; discrepancies were resolved by consensus. Codes were used to conduct thematic analysis. Results: Overall, 3 focus groups were conducted with 12 participants: 41.6% were house staff, 16.7% were attending physicians, and 41.6% were APPs. Most were female (91.6%) and were white (41.7%) or Asian (41.7%). Clinicians generally agreed with the prespecified categorizations of ABX-AEs based on degree of clinical concern (Table). We identified 5 themes: (1) The risk of ABX-AE is considered during initial prescribing but influences agent selection more than the decision to prescribe antibiotics. (2) The occurrence of an ABX-AE leads to assessment of need for continued antibiotic therapy. (3) The impact of an ABX-AE on other management decisions is as important as the direct harm of the ABX-AE when assessing severity. (4) Feedback must be curated to prevent clinicians from being overwhelmed with data. (5) Clinicians will be more receptive to feedback regarding ABX-AEs if feedback is contextualized (Fig.). Conclusions: The themes identified and assessment of ABX-AEs of greatest clinical concern may help inform the development of effective ABX-AE feedback methods to improve antibiotic safety.

Disclosures: None