bluuebunny/crossref_metadata_2025 huggingface dataset:
From cell lines to cancer patients: personalized drug synergy prediction
Authors: Kuru Halil Ibrahim , Cicek A Ercument , Tastan Oznur
Published: May 2024

Motivation

Combination drug therapies are effective treatments for cancer. However, the genetic heterogeneity of the patients and exponentially large space of drug pairings pose significant challenges for finding the right combination for a specific patient. Current in silico prediction methods can be instrumental in reducing the vast number of candidate drug combinations. However, existing powerful methods are trained with cancer cell line gene expression data, which limits their applicability in clinical settings. While synergy measurements on cell line models are available at large scale, patient-derived samples are too few to train a complex model. On the other hand, patient-specific single-drug response data are relatively more available.

Results

In this work, we propose a deep learning framework, Personalized Deep Synergy Predictor (PDSP), that enables us to use the patient-specific single drug response data for customizing patient drug synergy predictions. PDSP is first trained to learn synergy scores of drug pairs and their single drug responses for a given cell line using drug structures and large scale cell line gene expression data. Then, the model is fine-tuned for patients with their patient gene expression data and associated single drug response measured on the patient ex vivo samples. In this study, we evaluate PDSP on data from three leukemia patients and observe that it improves the prediction accuracy by 27% compared to models trained on cancer cell line data.

Availability and implementation

PDSP is available at https://github.com/hikuru/PDSP.
DeepPPAPredMut: deep ensemble method for predicting the binding affinity change in protein–protein complexes upon mutation
Authors: Nikam Rahul , Jemimah Sherlyn , Gromiha M Michael
Published: May 2024

Motivation

Protein–protein interactions underpin many cellular processes and their disruption due to mutations can lead to diseases. With the evolution of protein structure prediction methods like AlphaFold2 and the availability of extensive experimental affinity data, there is a pressing need for updated computational tools that can efficiently predict changes in binding affinity caused by mutations in protein–protein complexes.

Results

We developed a deep ensemble model that leverages protein sequences, predicted structure-based features, and protein functional classes to accurately predict the change in binding affinity due to mutations. The model achieved a correlation of 0.97 and a mean absolute error (MAE) of 0.35 kcal/mol on the training dataset, and maintained robust performance on the test set with a correlation of 0.72 and a MAE of 0.83 kcal/mol. Further validation using Leave-One-Out Complex (LOOC) cross-validation exhibited a correlation of 0.83 and a MAE of 0.51 kcal/mol, indicating consistent performance.

Availability and implementation

https://web.iitm.ac.in/bioinfo2/DeepPPAPredMut/index.html.
Mobilizing Metaphors in Criminological Analysis: A Case Study of Emotions in the Penal Voluntary Sector
Authors: Quinn Kaitlyn , Buck Gillian , Tomczak Philippa
Published: May 2024

Metaphors pervade media and political constructions of crime and justice, provoking responses and shaping actions. Scholarship in adjacent disciplines illustrates that emotion-metaphors offer unique insight into emotional and interpretive processes, valuably illuminating sense-making, problem solving and action. Yet, metaphors are rarely analysed within criminology, leaving an important opportunity for theorizing emotions and their implications largely unrealized. We explore the analytical and theoretical potential of emotion-metaphors for criminology, using empirical research conducted in the penal voluntary sectors of England and Scotland. Drawing on focus groups with volunteers and paid staff, we analyse the metaphors that non-profit practitioners mobilized to convey how their work felt: (1) absurd and unstable, (2) vulnerable and constrained, (3) devalued and discarded and (4) risky and all-consuming.
Painful papulonodules and plaques on the buttocks and limbs
Authors: Wang Xiaopo
Published: May 2024

An 8-year-old girl presented with a 6-month history of painful skin lesions on her buttocks and extremities.
LC and LC–MS/MS Studies for the Separation and Identification of Impurities and Degradation Products of Betaxolol
Authors: Chmangui Anis , Safta Mehdi , Driss Mohamed Ridha , Touil Soufiane , Bouabdallah Sondes
Published: May 2024

Betaxolol (Bx) is a selective β1 receptor blocker used in the treatment of hypertension and glaucoma. The aim of the present work was to demonstrate an approach involving use of liquid chromatography (LC) and liquid chromatography-electrospray ionization mass spectrometry (LC-ESI/MS) for the simultaneous separation, identification and characterization of impurities and of degradation products of betaxolol without their isolation from the reaction mixtures. At optimum condition, and according to ICH guidelines, the limit of detection (LOD) and limit of quantification (LOQ) for Bx are found to be 5.46 and 16.54 μg mL−1, respectively. However, the LOD and LOQ for the major degradation product P6 were 2.15 and 6.53 μg mL−1. Betaxolol was subjected to hydrolytic (acidic and basic) and oxidative, stress conditions according to International Conference on Harmonization (ICH) guideline Q1A (R2), and as results, the drug was found to be labile in acidic, basic and oxidative stress conditions. Based on LC-ESI/MS analysis, the found results revealed that Bx decomposes in acidic, basic and oxidizing environments. All degradation products were identified with the help of their fragmentation pattern and the masses obtained upon the MS analysis.
Enhancing Legal Convergence in the GBA through Harmonization of the Digital Dispute Resolution Legal Framework
Authors: Chen Hui , Zhao Yun
Published: May 2024

This article examines theories of legal convergence and the practice of rule harmonization for online dispute resolution (ODR) in the Greater Bay Area (GBA). The ODR platforms in the GBA employ collaborative mechanisms, institutional alliances, international standards, and multi-jurisdiction remote hearings to promote the convergence of ODR rules. However, to date, the efforts made to promote ODR rule harmonization have not resolved the fundamental issue of a lack of uniform ODR legislation within the GBA. It is posited here that an independent model of legal convergence would be more applicable in the GBA context. The article calls for the GBA Legal Department Joint Conferences to provide general ODR standards and principles, with specific laws and regulations then formulated in the respective jurisdictions. Public and private ODR providers are found to play distinct roles in legal convergence, and specialized procedural rules should be formulated to ensure due process and cybersecurity in remote hearings.
Urbanization does not affect red foxes’ interest in anthropogenic food, but increases their initial cautiousness
Authors: Lazzaroni Martina , Brogi Rudy , Napolitano Valentina , Apollonio Marco , Range Friederike , Marshall-Pescini Sarah
Published: May 2024

Human presence and activities have profoundly altered animals’ habitats, exposing them to greater risks but also providing new opportunities and resources. The animals’ capacity to effectively navigate and strike a balance between risks and benefits is crucial for their survival in the Anthropocene era. Red foxes (Vulpes vulpes), adept urban dwellers, exhibit behavioral plasticity in human-altered environments. We investigated variations in detection frequency on trail cameras and the behavioral responses (explorative, bold, and fearful) of wild red foxes living along an urbanization gradient when exposed to a metal bin initially presented clean and then filled with anthropogenic food. All fox populations displayed an increased interest and similar explorative behavioral responses toward the anthropogenic food source, irrespective of the urbanization gradient. Despite no impact on explorative behaviors, foxes in more urbanized areas initially showed heightened fear toward the empty bin, indicating increased apprehension toward novel objects. However, this fear diminished over time, and in the presence of food, urban foxes displayed slightly reduced fear compared with their less urban counterparts. Our results highlight foxes’ potential for adaptability to human landscapes, additionally underscoring the nuanced interplay of fear and explorative behavioral response of populations living along the urbanization gradient.
Colorectal Cancer in Inflammatory Bowel Disease: A Review of the Role of Gut Microbiota and Bacterial Biofilms in Disease Pathogenesis
Authors: Muñiz Pedrogo David A , Sears Cynthia L , Melia Joanna M P
Published: May 2024

The risk of colorectal cancer [CRC] is increased in patients with inflammatory bowel disease [IBD], particularly in extensive ulcerative colitis [UC] and Crohn’s colitis. Gut microbiota have been implicated in the pathogenesis of CRC via multiple mechanisms, including the release of reactive oxygen species and genotoxins, and induction of inflammation, as well as activation of the immune response. Gut microbiota can enhance their carcinogenic and proinflammatory properties by organising into biofilms, potentially making them more resistant to the host’s immune system and to antibiotics. Colonic biofilms have the capacity to invade colonic tissue and accelerate tumorigenesis in tumour-prone models of mice. In the context of IBD, the prevalence of biofilms has been estimated to be up to 95%. Although the relationship between chronic inflammation and molecular mediators that contribute to IBD-associated CRC is well established, the role of gut microbiota and biofilms in this sequence is not fully understood. Because CRC can still arise in the absence of histological inflammation, there is a growing interest in identifying chemopreventive agents against IBD-associated CRC. Commonly used in the treatment of UC, 5-aminosalicylates have antimicrobial and anticarcinogenic properties that might have a role in the chemoprevention of CRC via the inhibition or modulation of carcinogenic gut microbiota and potentially of biofilm formation. Whether biologics and other IBD-targeted therapies can decrease the progression towards dysplasia and CRC, via mechanisms independent of inflammation, is still unknown. Further research is warranted to identify potential new microbial targets in therapy for chemoprevention of dysplasia and CRC in IBD.
What factors influence the uptake of bowel, breast and cervical cancer screening? An overview of international research
Authors: Prowse Sarah R , Brazzelli Miriam , Treweek Shaun
Published: May 2024

Background

For cancer screening programmes to be effective in early detection it is important that those invited can access screening services and understand the benefits of participation. A better understanding of the factors that matter to potential participants of cancer screening programmes can assist in developing strategies to increase current uptake.

Methods

We conducted an overview of systematic reviews to answer the question: What factors influence the uptake of cancer screening services (breast, bowel and cervical) in high-income countries? A thematic approach supported by tabular summaries and qualitative heat maps was used to categorize factors, described as ‘barriers’ or ‘facilitators’.

Results

A total of 41 systematic reviews met the criteria for inclusion. The barrier with the greatest number of ‘hot spots’ across all three screening programmes was a fear of the unknown regarding a possible diagnosis of cancer or abnormal screening results, followed closely by a general lack of knowledge surrounding cancer screening programmes. The greatest collective facilitator to uptake was recommendation by a healthcare provider to attend screening.

Conclusion

Across all factors ‘trust’ and ‘building trusted relationships’ can be seen as integral to the success of cancer screening programmes and must be reflective of collaborative efforts to mitigate barriers and enhance facilitators to uptake. There is future scope to consider interventions that (i) increase demand for screening services, (ii) reduce barriers to uptake of services and/or (iii) are relevant to the healthcare system and those providing services.
High-latitude ocean habitats are a crucible of fish body shape diversification
Authors: Burns Michael D , Friedman Sarah T , Corn Katherine A , Larouche Olivier , Price Samantha A , Wainwright Peter C , Burress Edward D
Published: May 2024

A decline in diversity from the equator to the poles is a common feature of Earth’s biodiversity. Here, we examine body shape diversity in marine fishes across latitudes and explore the role of time and evolutionary rate in explaining the diversity gradient. Marine fishes’ occupation of upper latitude environments has increased substantially over the last 80 million years. Fishes in the highest latitudes exhibit twice the rate of body shape evolution and one and a third times the disparity compared to equatorial latitudes. The faster evolution of body shape may be a response to increased ecological opportunity in polar and subpolar oceans due to (1) the evolution of antifreeze proteins allowing certain lineages to invade regions of cold water, (2) environmental disturbances driven by cyclical warming and cooling in high latitudes, and (3) rapid transitions across depth gradients. Our results add to growing evidence that evolutionary rates are often faster at temperate, not tropical, latitudes.
Acidic Apple Snails: Effects of Climate Change on the Mechanical Properties of an Invasive Gastropod
Authors: Cretini Cody P , Galloway Katherine A
Published: May 2024

Synopsis

Climate change can directly and indirectly affect species distribution. Warming may allow for invasive species, such as apple snails, to migrate to higher latitudes where temperatures are more conducive to their survival and invasion success. Higher temperatures and lower pH ranges have been previously documented to affect the form and function of calcium carbonate shells, which serve many functions, including protection from predators and thermoregulation. This study aimed to quantify differences in the morphology and mechanical properties of invasive apple snail, Pomacea maculata, shells after altering temperature and pH. We mechanically tested shells among three five-week treatments: control, higher temperature, and lower pH. Ultimate Strength increased in shells that were exposed to higher temperatures, but Young’s Modulus and Peak Load did not differ among control, temperature, and pH treatments. Apple snails in higher temperature tanks increased their shell length over the five-week trials. Although snail morphometrics did not differ between sexes, male shells exhibited a higher Peak Load, Young’s Modulus, and Ultimate Strength compared to female shells. Our findings are consistent with previous gastropod studies, in that a lower pH is associated with a decrease in shell size, and higher temperatures yield larger snail shells with a higher ultimate strength. Peak Load did not significantly differ among treatments, which suggests that the cross-sectional area is relatively important when considering this species mechanical performance today and in future climates. Due to the intense nutritional and calcium demands of egg production, female snails may be more susceptible to weakened shells due to low pH environments caused by climate change.
Comparison of Hydric and Thermal Physiology in an Environmentally Diverse Clade of Caribbean Anoles
Authors: Alomar Nathalie , Bodensteiner Brooke L , Hernández-Rodríguez Isabela , Landestoy Miguel A , Domínguez-Guerrero Saúl F , Muñoz Martha M
Published: May 2024

Synopsis

As the world becomes warmer and precipitation patterns less predictable, organisms will experience greater heat and water stress. It is crucial to understand the factors that predict variation in thermal and hydric physiology among species. This study focuses on investigating the relationships between thermal and hydric diversity and their environmental predictors in a clade of Hispaniolan anole lizards, which are part of a broader Caribbean adaptive radiation. This clade, the “cybotoid” anoles, occupies a wide range of thermal habitats (from sea level to several kilometers above it) and hydric habitats (such as xeric scrub, broadleaf forest, and pine forest), setting up the possibility for ecophysiological specialization among species. Among the thermal traits, only cold tolerance is correlated with environmental temperature, and none of our climate variables are correlated with hydric physiology. Nevertheless, we found a negative relationship between heat tolerance (critical thermal maximum) and evaporative water loss at higher temperatures, such that more heat-tolerant lizards are also more desiccation-tolerant at higher temperatures. This finding hints at shared thermal and hydric specialization at higher temperatures, underscoring the importance of considering the interactive effects of temperature and water balance in ecophysiological studies. While ecophysiological differentiation is a core feature of the anole adaptive radiation, our results suggest that close relatives in this lineage do not diverge in hydric physiology and only diverge partially in thermal physiology.
In-hospital thromboprophylaxis variation and the risk of venous thromboembolism after lung cancer surgery: a nationwide cohort study
Authors: Christensen Thomas Decker , Ording Anne Gulbech , Skjøth Flemming , Mørkved Amalie Lambert , Jakobsen Erik , Meldgaard Peter , Petersen Rene Horsleben , Søgaard Mette
Published: May 2024

OBJECTIVES

Venous thromboembolic event (VTE) is a severe complication in patients with lung cancer undergoing thoracic surgery. Nevertheless, because of insufficient evidence, there are no clear guidelines, and VTE prophylaxis practices vary widely. This nationwide cohort study was a comparative study investigating VTE risk in surgical departments that routinely administered in-hospital thromboprophylaxis with low-molecular-weight heparin compared to those that did not.

METHODS

We identified all patients with non-small-cell lung cancer (NSCLC) who underwent surgery in Denmark during 2010–2021. Thoracic surgery was exclusively performed in the 4 university hospitals. Three hospitals implemented in-hospital thromboprophylaxis as standard care since 2000, while the fourth adopted this practice in September 2016. VTE events were assessed at 6-month follow-up according to hospital and study period, using an inverse probability of treatment weighting approach.

RESULTS

We identified 9615 patients. During 6-month follow-up, a total of 190 VTE events were observed, resulting in a weighted rate of 4.5 events per 100 person-years and an absolute risk of 2.2%. There was no clear trend according to hospital site or use of in-hospital thromboprophylaxis with a 2.2% risk in the hospital not using thromboprophylaxis compared to 1.7–3.1% in those that did.

CONCLUSIONS

Use of in-hospital thromboprophylaxis did not affect the risk of VTE after surgery for NSCLC, suggesting that relying solely on in-hospital thromboprophylaxis may be insufficient to mitigate VTE risk in these patients. Further research is warranted to investigate the potential benefits of extended thromboprophylaxis in reducing VTE risk in selected NSCLC surgical patients.
Effect of sex and milk replacer with or without supplemental carnitine and arginine on growth characteristics, carcass, and meat quality of artificially reared low-birth weight pigs
Authors: Madsen Johannes G , Kreuzer Michael , Silacci Paolo , Bee Giuseppe
Published: May 2024

This study compared milk replacer either remaining unsupplemented (CON) or supplemented with 0.5 g L-carnitine plus 16.7 g L-arginine/kg (CarArg) and fed to 48 low-birth weight (L-BtW) artificially reared piglets (24 per group) from days 7 to 28 of age. Eight farrowing series were needed to complete the study. On day 28, the lightest piglets were slaughtered, and the heaviest pigs were weaned. The heaviest pigs were weaned on day 28 and offered free access to a starter (weaning to 25 kg body weight [BW]), grower (25 to 60 kg BW), and finisher diet (60 to 96 kg BW on day 170 of age). After euthanization on days 28 and 170, blood was sampled for assessment of serum metabolite and hormone concentrations, and the semitendinosus muscle (STM) was weighed, and later subjected to enzyme activity analysis and assessment of myofiber characteristics. In the 170-d-old pigs carcass and meat quality traits were assessed. Growth data were analyzed accordingtoatwo-way analysis of variance (ANOVA), with dietary treatment and farrowing series as fixed effects, while remaining data were analyzed with dietary treatment, sex, their interaction, and farrowing series as main factors. Dietary treatments affected (P ≤ 0.049) muscle enzyme activity at both day 28, with greater citrate synthase (CS) and LDH activities and lower HAD:CS ratio in STM light portion, and lower LDH:CS ratio in STM dark portion, and 170 of age with lower HAD:CS ratio. In the starter period, CarArg pigs had greater average daily gain (P = 0.021) and average daily feed intake (P = 0.010). At slaughter, these pigs had lower (P = 0.013) glucose and greater (P = 0.022) urea serum concentrations. However, supplementing the milk replacer with carnitine and arginine had no long-term effects on growth performance, carcass composition, and meat quality of L-BtW pigs. In addition, muscle morphology and myofiber-related properties remained unaffected by the supplementation.
Factors Related to Electrical Burn Injuries in Occupational and Nonoccupational Settings From 2010 to 2021 in Colombia: Cross-Sectional Design
Authors: Ayala Karen P , Pombo Luis M , Camero-Ramos Gabriel , Teherán Aníbal A , Ávila Albert A , Tocanchón Ginna P , Zuluaga-Ortíz Carol A
Published: May 2024

Burns affect 11 million people worldwide annually. Electrical burns (EBs) are renowned for inflicting extensive harm and long-term consequences that can lead to severe illnesses and fatalities. People in both occupational and nonoccupational settings may be exposed to EBs, leading to functional or anatomical consequences. We identified sociodemographic features related to EBs in both settings. A cross-sectional design, using an open dataset of electrical shock injuries that occurred in Colombia during the 2010-2021 period, was carried out. Sociodemographic features of people injured in occupational and nonoccupational settings were described in counts (%), incidence per 100 000 people (I0; 95% CI). To identify related factors (age-sex adjusted) with injuries in occupational and nonoccupational settings, we applied a binary logistic regression. Over the 12-year period, there were 1.274 EBs (I0: 2.47; 2.34-2.61), 287 in the occupational setting (I0: 1.35; 1.20-1.51), and 987 in the nonoccupational setting (I0: 3.25; 3.05-3.46). Age median was 31 years, and most cases were distributed in middle adulthood (52.8%), males (88.1%), high school/technician (42.8%), urban location (73.7%), weekdays (95.3%), and daytime hours (85.5%). Factors related to EBs in the occupational setting were males, middle adulthood, high school/technician, Thursday, and daytime hours. Other factors related to EBs in the nonoccupational setting were early childhood, primary school, urban location, and weekends. Both settings pose a risk of injuries to individuals. We have identified sociodemographic factors related to these injuries in both occupational and nonoccupational settings, which could aid in preventing damages and long-term complications, especially among vulnerable subgroups such as those determined above.
Reworking uneven geographical development: the spatial logic of China’s rural banking reforms
Authors: Yu Leqian , Yin Jie
Published: May 2024

Drawing on financial geography literature and the concept of state rescaling, this article investigates the state–finance nexus with an emphasis on state spatial reconfiguration. Through a historically and geographically informed political economic analysis, it argues that China’s state-led, market-oriented rural banking reforms are not merely the outcome of a deepening market logic within the financial administration of the rural sector. They are also crucial for state spatial reconfiguration to address uneven rural and urban development. The article calls for greater sensitivity towards relational spatiotemporality and uneven development to comprehend fully the spatiality of the state–finance nexus.
Hibernacula of bats in Mexico, the southernmost records of hibernation in North America
Authors: Ramos-H. Daniel , Marín Ganesh , Cafaggi Daniela , Sierra-Durán Cárol , Romero-Ruíz Aarón , Medellín Rodrigo A
Published: May 2024

Although Mexico holds the southernmost hibernating bats in North America, information on winter behavior and hibernacula microclimate use of temperate Mexican bats is limited. We studied hibernating bats at high altitudes (>1,000 m a.s.l.) in northern and central Mexico during 5 consecutive winters. Our aims were to document and describe the hibernacula, winter behavior (such as abundance and roost pattern), and microclimates (estimated as adjacent substrate temperature) of cave-hibernating bats in Mexico. We found 78 hibernacula and 6,089 torpid bats of 10 vespertilionid species, increasing by over 50% the number of cave-hibernating bat species and quadrupling the number of hibernacula for Mexico. Hibernacula were at altitudes between 1,049 and 3,633 m a.s.l., located in 3 mountain ranges, mainly in oak and conifer forests. Myotis velifer was the most common species, followed by Corynorhinus townsendii and C. mexicanus. We recorded the adjacent substrate temperatures from 9 species totaling 1,106 torpid bats and found differences in microclimate use among the 3 most common species. In general, abundance of torpid bats in our region of study was similar to those in the western United States, with aggregations of tens to a few hundred individuals per cave, and was lower than in the eastern United States where a cave may hold thousands of individuals. Knowledge of bat hibernation is crucial for developing conservation and management strategies on current conditions while accommodating environmental changes and other threats such as emerging diseases.
Structure-specific nucleases in genome dynamics and strategies for targeting cancers
Authors: Sun Haitao , Luo Megan , Zhou Mian , Zheng Li , Li Hongzhi , Esworthy R Steven , Shen Binghui
Published: May 2024

Nucleases are a super family of enzymes that hydrolyze phosphodiester bonds present in genomes. They widely vary in substrates, causing differentiation in cleavage patterns and having a diversified role in maintaining genetic material. Through cellular evolution of prokaryotic to eukaryotic, nucleases become structure-specific in recognizing its own or foreign genomic DNA/RNA configurations as its substrates, including flaps, bubbles, and Holliday junctions. These special structural configurations are commonly found as intermediates in processes like DNA replication, repair, and recombination. The structure-specific nature and diversified functions make them essential to maintaining genome integrity and evolution in normal and cancer cells. In this article, we review their roles in various pathways, including Okazaki fragment maturation during DNA replication, end resection in homology-directed recombination repair of DNA double-strand breaks, DNA excision repair and apoptosis DNA fragmentation in response to exogenous DNA damage, and HIV life cycle. As the nucleases serve as key points for the DNA dynamics, cellular apoptosis, and cancer cell survival pathways, we discuss the efforts in the field in developing the therapeutic regimens, taking advantage of recently available knowledge of their diversified structures and functions.
Momentum-resolved EELS and CL study on 1D-plasmonic crystal prepared by FIB method
Authors: Yasuhara Akira , Shibata Masateru , Yamamoto Wakaba , Machfuudzoh Izzah , Yanagimoto Sotatsu , Sannomiya Takumi
Published: May 2024

We investigate a one-dimensional plasmonic crystal using momentum-resolved electron energy-loss spectroscopy (EELS) and cathodoluminescence (CL) techniques, which are complementary in terms of available optical information. The plasmonic crystal sample is fabricated from large aluminum grains through the focused ion beam method. This approach allows curving nanostructures with high crystallinity, providing platforms for detailed analysis of plasmonic nanostructures using both EELS and CL. The momentum-resolved EELS visualizes dispersion curves outside the light cone, confirming the existence of the surface plasmon polaritons and local modes, while the momentum-resolved CL mapping analysis identified these surface plasmon polaritons and local modes. Such synergetic approach of two electron-beam techniques offers full insights into both radiative and non-radiative optical properties in plasmonic or photonic structures.
Enteric Fever in Children: An Epidemiological and Clinical Review of Cases in Southeast Texas
Authors: Foughty Zachary C , Niles Denver T , Cruz Andrea T
Published: May 2024

Extensively drug-resistant (XDR) strains of Salmonella enterica serotype Typhi have emerged in Pakistan and Iraq. We report 13 children with enteric fever in Southeast Texas seen over 3.5 years, of whom 23.1% had XDR isolates.
Direct Observation of Trace Elements in Barium Titanate of Multilayer Ceramic Capacitors Using Atom Probe Tomography
Authors: Jang Kyuseon , Kim Mi-Yang , Jung Chanwon , Kim Se-Ho , Choi Daechul , Park Seong-Chan , Scheu Christina , Choi Pyuck-Pa
Published: May 2024

Accurately controlling trace additives in dielectric barium titanate (BaTiO3) layers is important for optimizing the performance of multilayer ceramic capacitors (MLCCs). However, characterizing the spatial distribution and local concentration of the additives, which strongly influence the MLCC performance, poses a significant challenge. Atom probe tomography (APT) is an ideal technique for obtaining this information, but the extremely low electrical conductivity and piezoelectricity of BaTiO3 render its analysis with existing sample preparation approaches difficult. In this study, we developed a new APT sample preparation method involving W coating and heat treatment to investigate the trace additives in the BaTiO3 layer of MLCCs. This method enables determination of the local concentration and distribution of all trace elements in the BaTiO3 layer, including additives and undesired impurities. The developed method is expected to pave the way for the further optimization and advancement of MLCC technology.
Integrated enhancer regulatory network by enhancer–promoter looping in gastric cancer
Authors: Zhu Tianhui , Okabe Atsushi , Usui Genki , Fujiki Ryoji , Komiyama Daichi , Huang Kie Kyon , Seki Motoaki , Fukuyo Masaki , Abe Hiroyuki , Ning Meng , Okada Tomoka , Minami Mizuki , Matsumoto Makoto , Fan Qin , Rahmutulla Bahityar , Hoshii Takayuki , Tan Patrick , Morikawa Teppei , Ushiku Tetsuo , Kaneda Atsushi
Published: May 2024

Enhancer cis-regulatory elements play critical roles in gene regulation at many stages of cell growth. Enhancers in cancer cells also regulate the transcription of oncogenes. In this study, we performed a comprehensive analysis of long-range chromatin interactions, histone modifications, chromatin accessibility and expression in two gastric cancer (GC) cell lines compared to normal gastric epithelial cells. We found that GC-specific enhancers marked by histone modifications can activate a population of genes, including some oncogenes, by interacting with their proximal promoters. In addition, motif analysis of enhancer–promoter interacting enhancers showed that GC-specific transcription factors are enriched. Among them, we found that MYB is crucial for GC cell growth and activated by the enhancer with an enhancer–promoter loop and TCF7 upregulation. Clinical GC samples showed epigenetic activation of enhancers at the MYB locus and significant upregulation of TCF7 and MYB, regardless of molecular GC subtype and clinicopathological factors. Single-cell RNA sequencing of gastric mucosa with intestinal metaplasia showed high expression of TCF7 and MYB in intestinal stem cells. When we inactivated the loop-forming enhancer at the MYB locus using CRISPR interference (dCas9-KRAB), GC cell growth was significantly inhibited. In conclusion, we identified MYB as an oncogene activated by a loop-forming enhancer and contributing to GC cell growth.
Outcomes and Predictors of Mortality in Patients With KPC-Kp Infections Treated With Meropenem Vaborbactam: An Observational Multicenter Study
Authors: Tumbarello Mario , Raffaelli Francesca , Giannella Maddalena , De Pascale Gennaro , Cascio Antonio , De Rosa Francesco Giuseppe , Cattelan Anna Maria , Oliva Alessandra , Saracino Annalisa , Bassetti Matteo , Mussini Cristina , Luzzati Roberto , Capone Alessandro , Signorini Liana , Bartoletti Michele , Sambo Margherita , Sarmati Loredana , Antinori Spinello , Mularoni Alessandra , Tascini Carlo , Corona Alberto , Pascale Renato , Rubino Raffaella , Corcione Silvia , Mazzitelli Maria , Giuliano Gabriele , Lovecchio Antonio , Bavaro Davide Fiore , Meschiari Marianna , Montagnani Francesca , Fabbiani Massimiliano , De Benedetto Ilaria , Antonelli Massimo , Venditti Mario , Viale Pierluigi
Published: May 2024

Background

Meropenem-vaborbactam is a recent and promising option for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp) infections, including those resistant to ceftazidime-avibactam.

Methods

We conducted a retrospective analysis of observational data from 19 Italian hospitals on use and outcomes of patients treated with meropenem-vaborbactam for at least ≥24 hours for KPC-Kp infections. Crude and propensity-weighted multiple Cox regression models were performed to ascertain risk factors independently associated with 30-day mortality.

Results

The cohort included 342 adults with bloodstream infections (n = 172) and nonbacteremic infections (n = 170), of which 107 were lower respiratory tract infections, 30 were complicated urinary tract infections, and 33 were infections involving other sites. Most infections (62.3%) were managed with meropenem-vaborbactam monotherapy, or in combination with at least 1 other active drug (usually fosfomycin, tigecycline, or gentamicin) (37.7%). The 30-day mortality rate was 31.6% (108/342). In multiple Cox regression model, 30-day mortality was independently associated with septic shock at infection onset, Charlson comorbidity index ≥ 3, dialysis, concomitant COVID-19, and INCREMENT score ≥ 8. Administration of meropenem-vaborbactam within 48 hours from infection onset was a negative predictor of mortality. All predictors, except administration of meropenem-vaborbactam within 48 hours, remained significant when the multiple Cox regression model was repeated after adjustment for the propensity score for receipt of combination therapy.

Conclusions

Despite the limits of a retrospective study, the data derived from this multicenter cohort provide additional evidence on the efficacy of meropenem-vaborbactam in treating severe KPC-Kp infections, even when used as monotherapy.
Reference optical turbulence characteristics at the Large Solar Vacuum Telescope site
Authors: Shikhovtsev Artem Yu
Published: May 2024

Large ground-based solar telescopes are equipped with adaptive optics systems to correct wavefront distortions induced in the turbulent atmosphere. The design of the adaptive optics system strongly depends on the vertical profiles of the optical turbulence. In particular, the characteristics of the optical turbulence determine the design of tomographic adaptive optics systems, which provide image correction within a wide field of view. In the article, a new method to estimate reference optical turbulence characteristics from Era-5 reanalysis assimilated data is presented. This method is based on the dependence of the air refractive index structure constant $C_n^2$ on the vertical shears of wind speed as well as the outer scale of turbulence L0. The L0 parameter is estimated by minimization of the dispersion between the modeled and measured values of the refractive index structure constant $C_n^2$ within the surface layer. For the first time, parametrization coefficients and reference profiles of optical turbulence averaged for the period 1940–2022 are calculated for the Large Solar Vacuum Telescope (LSVT) site. The calculated optical turbulence profiles are representative; these profiles correspond to typical changes of the measured values of the Fried parameter, the isoplanatic angle, and the outer scale of turbulence at the LSVT site. The model turbulence profiles are verified taking into account the Shack–Hartmann wavefront sensor measurements at the LSVT. The higher accuracy of estimation of the optical turbulence characteristics makes it possible to refine parameters relevant to the LSVT adaptive optics system. The obtained results can be used in order to develop high-resolution solar adaptive optics technologies as applied to ground-based telescopes including those using the principles of atmospheric tomography.
Seasonal abundance, lipid storage, and energy density ofCalanus finmarchicusand other copepod preyfields along the Northwest Atlantic continental shelf
Authors: Carlowicz Lee Rachel M , Keiling Toniann D , Warren Joseph D
Published: May 2024

Calanus finmarchicus is an abundant calanoid copepod in the New York Bight (NYB) that has energy-dense lipid stores. This study measured C. finmarchicus abundance, lipid storage and energy density and compared it to two other abundant calanoid species in the region. We compared the NYB C. finmarchicus preyfield characteristics with data from two other NW Atlantic coastal ecosystems, the Gulf of Maine (GoM) and Cape Cod Bay (CCB). Copepods from net tows were identified, enumerated, photographed and measured. These data were used to calculate animal biovolume and lipid content as well as the volumetric energy density of the copepod preyfield. C. finmarchicus were most abundant in spring and summer and the mean lipid storage of C. finmarchicus remained largely constant regardless of season and location within the NYB. Centropages typicus were abundant enough in the winter to be more energy-rich than C. finmarchicus. Temora longicornis, while also abundant, never surpassed the energy density of C. finmarchicus. C. finmarchicus in the NYB were comparably lipid-rich to those from the GoM and CCB. C. finmarchicus in the NYB can be a reliable energy source for local predators due to their high spring and summer abundances and year-round storage of high-energy wax esters.
Use of UK faith Centre as a COVID-19 community vaccination clinic: exploring a potential model for community-based health care delivery
Authors: Wehling Helena , Weston Dale , Hall Charlotte , Mills Freya , Amlôt Richard , Dennis Amelia , Forbes Lindsay , Armes Jo , Mohamed Munira , Buckley Seema , Dar Osman A , Mohamed Amran , Wurie Fatima , Shafi Shuja , Zumla Sir Alimuddin , Ala Aftab
Published: May 2024

Introduction

Effective and safe vaccines against COVID-19 are essential to achieve global control of the coronavirus (SARS-CoV-2). Using faith centres may offer a promising route for promoting higher vaccine uptake from certain minority ethnic groups known to be more likely to be vaccine hesitant.

Methods

This cross-sectional study explored attendees’ perceptions, experiences of being offered, and receiving COVID-19 vaccination in a local mosque in Woking, Surrey, UK. About 199 attendees completed a brief questionnaire on experiences, views, motivations about attending the mosque and vaccination on site.

Results

The most common ethnic groups reported were White British (39.2%) and Pakistani (22.6%); 36.2% identified as Christian, 23.6% as Muslim, 5.5% as Hindu, and 17.1% had no religion. Genders was relatively equal with 90 men (45.2%) and 98 women (49.2%), and 35–44-year-olds represented the most common age group (28.1%). Views and experiences around receiving vaccinations at the mosque were predominantly positive. Primary reasons for getting vaccinated at the mosque included convenience, accessibility, positive aspects of the venue’s intercultural relations, and intentions to protect oneself against COVID-19, regardless of venue type. Negative views and experiences in regards to receiving the vaccination at the mosque were less common (7% expressed no intention of recommending the centre to others), and disliked aspects mostly referred to the travel distance and long waiting times.

Conclusions

Offering COVID-19 vaccination in faith centres appears acceptable for different faith groups, ensuring convenient access for communities from all religions and ethnic backgrounds.
The Health Costs of Cost Sharing
Authors: Chandra Amitabh , Flack Evan , Obermeyer Ziad
Published: May 2024

What happens when patients suddenly stop their medications? We study the health consequences of drug interruptions caused by large, abrupt, and arbitrary changes in price. Medicare’s prescription drug benefit as-if-randomly assigns 65-year-olds a drug budget as a function of their birth month, beyond which out-of-pocket costs suddenly increase. Those facing smaller budgets consume fewer drugs and die more: mortality increases 0.0164 percentage points per month (13.9%) for each $100 per month budget decrease (24.4%). This estimate is robust to a range of falsification checks and lies in the 97.8th percentile of 544 placebo estimates from similar populations that lack the same idiosyncratic budget policy. Several facts help make sense of this large effect. First, patients stop taking drugs that are both high value and suspected to cause life-threatening withdrawal syndromes when stopped. Second, using machine learning, we identify patients at the highest risk of drug-preventable adverse events. Contrary to the predictions of standard economic models, high-risk patients (e.g., those most likely to have a heart attack) cut back more than low-risk patients on exactly those drugs that would benefit them the most (e.g., statins). Finally, patients appear unaware of these risks. In a survey of 65-year-olds, only one-third believe that stopping their drugs for up to a month could have any serious consequences. We conclude that far from curbing waste, cost sharing is itself highly inefficient, resulting in missed opportunities to buy health at very low cost ($11,321 per life-year).
A review of primary freshwater crab mandible morphology: terminology and systematic importance (Crustacea: Decapoda: Brachyura)
Authors: Cumberlidge Neil , Krajenka Grace E , Clark Brett , Clark Paul F
Published: May 2024

The primary freshwater crab mandibular palp is described as possessing two or three divisions (joints) and its terminal article as being either unbranched (simple) or bilobed. Currently, this provides two important familial characters. Addressed here are the long-standing differences in the number of mandibular palp articles between some freshwater crabs and other brachyurans by adopting a standardized terminology based on a generalized brachyuran limb using homology-based terms that allow comparisons with all brachyurans. As a result, the freshwater crab mandible is redescribed as a four-part appendage comprising the coxa (biting jaw) and basis, from which originates a two-articled inner ramus (endopod). A detailed examination of the joint between the basis and the first endopod article of the palp indicates that its expression varies from distinct to obscure, but it is nevertheless present in all freshwater and marine crab families examined here, including those species currently described as possessing a two-articled palp. The coxa, basis, and first endopod articles of the mandibular palp are all uniform and generally not diagnostic within the Brachyura. The terminal endopod article of freshwater crabs, however, is morphologically diverse and provides a familial diagnostic character. The wider implications of these findings for the Brachyura are discussed.
Long noncoding RNA BMPR1B‐AS1 stability regulated by IGF2BP2 affects the decidualization in endometriosis patients through the SMAD1/5/9 pathway
Authors: Que Xiaohong , Ren Lulu , Yang Lin , Wang Lemeng , Li Junzui , Wu Rongfeng , Chen Qionghua
Published: May 2024

Endometriosis (EMs)‐related infertility commonly has decreased endometrial receptivity and normal decidualization is the basis for establishing and maintaining endometrial receptivity. However, the potential molecular regulatory mechanisms of impaired endometrial decidualization in patients with EMs have not been fully clarified. We confirmed the existence of reduced endometrial receptivity in patients with EMs by scanning electron microscopy and quantitative real‐time PCR. Here we identified an lncRNA, named BMPR1B‐AS1, which is significantly downregulated in eutopic endometrium in EMs patients and plays an essential role in decidual formation. Furthermore, RNA pull‐down, mass spectrometry, RNA immunoprecipitation, and rescue analyses revealed that BMPR1B‐AS1 positively regulates decidual formation through interaction with the RNA‐binding protein insulin‐like growth factor 2 mRNA‐binding protein 2 (IGF2BP2). Downregulation of IGF2BP2 led to a decreased stability of BMPR1B‐AS1 and inhibition of activation of the SMAD1/5/9 pathway, an inhibitory effect which diminished decidualization in human endometrial stromal cells (hESCs) decidualization. In conclusion, our identified a novel regulatory mechanism in which the IGF2BP2‐BMPR1B‐AS1‐SMAD1/5/9 axis plays a key role in the regulation of decidualization, providing insights into the potential link between abnormal decidualization and infertility in patients with EMs, which will be of clinical significance for the management and treatment of infertility in patients with EMs.