bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between acquired antimicrobial resistance genes in the upper respiratory tract and livestock farm exposures: a case–control study in COPD and non-COPD individuals
Authors: Cornu Hewitt Beatrice , Bossers Alex , van Kersen Warner , de Rooij Myrna M T , Smit Lidwien A M
Published: September 2024

Background

Livestock-related emissions have been associated with aggravations of respiratory symptoms in patients with chronic obstructive pulmonary disease (COPD), potentially by altering the respiratory resistome.

Objectives

This study investigates the structure of the acquired oropharyngeal (OP) resistome of patients with COPD and controls, its interplay with the respiratory microbiome and associations with residential livestock exposure.

Methods

In a matched case–control study in the rural Netherlands, we analysed OP swabs from 35 patients with COPD and 34 controls, none of whom had used antibiotics in the preceding 4 weeks. Resistome profiling was performed using ResCap, complemented by prior characterization of the microbiome via 16S rRNA-based sequencing. Residential livestock farm exposure was defined using distance-based variables alongside modelled concentrations of livestock-emitted microbial pollutants. We compared resistome profiles between patients with COPD and controls, examining alpha and beta diversity as well as differential abundance. Additionally, we assessed the interplay between the resistome and microbiome using co-occurrence networks and Procrustes analysis. Variations in resistome profiles were also analysed based on residential livestock exposures.

Results

Patients with COPD exhibited higher resistome diversity than controls (Shannon diversity, P = 0.047), though resistome composition remained similar between groups (PERMANOVA, P = 0.19). Significant correlations were observed between the OP resistome and microbiome compositions, with distinct patterns in co-occurrence networks. Residential exposure to livestock farms was not associated with resistome alterations.

Conclusions

Our findings reveal the COPD airway as a hospitable environment for antimicrobial resistance genes, irrespective of recent antimicrobial usage. Demonstrating the interplay between the resistome and microbiome, our study underscores the importance of a deeper understanding of the resistome in respiratory health.
Integration of multi-omics reveals the important role of the BBS10 gene in reproduction
Authors: Zhang Guoqing , Chu Mingxing , Wang Shoufeng , Feng Pingjie , Shi Jianxin , Li Hao , Li Xinyue , Pan Zhangyuan
Published: September 2024

Blood samples are easily obtained from sheep. Therefore, blood analysis can be a convenient method for evaluating reproductive traits in sheep by detecting genetic and metabolic changes in the ovary. By combining 167 RNA sequencing data and 60 untargeted metabolomics data, this study analyzed the relationship between genes and metabolites in the ovary and blood. The conjoint KEGG enrichment analysis enriched glutathione (GSH) metabolic pathways both in the ovary and blood. This finding provides an explanation for possible GSH metabolic processes in the ovary with metabolite exchange in the blood. The metabolite–gene–disease interaction network revealed a correlation between the expression of certain Bardet–Biedl syndrome (BBS) family genes in the ovary and blood. This indicates that BBS family genes, such as BBS10 in sheep blood, could be a potential biomarker for BBS. We investigated the relationship between BBS10 gene expression in the ovary and lambing numbers using whole-genome sequencing data from 450 ewes. Our findings suggest that g.112314188C>G may lead to decreased litter size in ewes carrying the FecB gene. These single nucleotide polymorphisms could be potential molecular markers for breeding sheep.
Short-term temperature changes affected the predation ability of Orius similis on Bemisia tabaci nymphs
Authors: Zhang Bo , Yang Dan , Zhang Jinlong , Yang Nian , Kong Jiao , Hu Ying , Liu Jihuan , Liu Qing , Chen Guohua , Zhang Xiaoming
Published: September 2024

Bemisia tabaci (Gennadius), a major pest that can adversely affect economies and agriculture globally, is particularly sensitive to climate change-induced temperature fluctuations, which can intensify its outbreaks. Orius similis Zheng, a primary natural predator of B. tabaci, also experiences temperature-related effects that influence its biocontrol efficacy. Thus, understanding the response of O. similis to temperature changes is pivotal for optimizing its biocontrol potential. Herein, our investigations showed that the functional response of O. similis to both high- and low-instar nymphs of B. tabaci adheres to the type II model at temperatures of 19, 22, 25, 28, and 31 °C. At 28 °C, O. similis exhibits the highest instantaneous attack rate (high-instar: 1.1580, low-instar: 1.2112), and the shortest handling time per prey (high-instar: 0.0218, low-instar: 0.0191). The efficacy of O. similis in controlling B. tabaci nymphs follows the sequence: 28 °C > 25 °C > 31 °C > 22 °C > 19 °C. Additionally, search efficiency inversely correlates with prey density. Simulations using the Hessell–Varley interference model indicate that increased density of O. similis under any temperature condition leads to reduced predation rates. Moreover, O. similis shows a predation preference for low-instar nymphs of B. tabaci, with higher predation level observed at the same temperature. In conclusion, for effective control of B. tabaci in field releases, O. similis should be optimally released at temperatures between 25 and 28 °C to preferably target the egg or early nymph stages of B. tabaci and determining the appropriate number of O. similis is important to minimize interference among individuals and enhance biocontrol efficacy.
Hierarchical three-body problem at high eccentricities = simple pendulum I: octupole
Authors: Klein Ygal Y , Katz Boaz
Published: September 2024

The gradual evolution of the restricted hierarchical three body problem is analysed analytically, focusing on conditions of Kozai–Lidov cycles that may lead to orbital flips from prograde to retrograde motion due to the octupole (third order) term which are associated with extremely high eccentricities. We revisit the approach described by Katz, Dong and Malhotra (2011) and show that for most initial conditions, to an excellent approximation, the analytical derivation can be greatly simplified and reduces to a simple pendulum model allowing an explicit flip criterion. The resulting flip criterion is much simpler than the previous one but the latter is still needed in a small fraction of phase space. We identify a logical error in the earlier derivation but clarify why it does not affect the final results.
Urbanization and Urban Development in Zambia
Authors: Hampwaye Godfrey , Siame Gilbert , Muchindu Mazuba , Nchito Wilma S.
Published: September 2024

This chapter provides a comprehensive overview of the urbanization process and urban development trajectory in Zambia. The chapter takes a historical approach by examining drivers, processes, and impacts of Zambia’s urbanization and urban development in the pre-colonial, colonial, and post-colonial periods. The chapter mainly draws upon data from documentary analysis. The chapter demonstrates the intentions and the role played by early missionaries and colonialists in the establishment of urban centres. The chapter further demonstrates the transformational imprints of the rural–urban migration during early post-political independence years on the country’s urbanization trajectory. The chapter shows that after the early 1970s, urbanization trends and urban development processes become very closely linked to economic performance of the country, especially performance of the mining sector. To further demonstrate the impact of the economy on urbanization trends and prospects, this chapter uses Solwezi town as a case study. Solwezi town recorded exponential growth following the opening of three mines in the region.
International Economic Relations
Authors: Muyeba Singumbe
Published: September 2024

This chapter describes Zambia’s international economic relations. The chapter employs the International Futures (IFs) model and World Development Indicators for its analysis. It argues that the deep roots of Zambia’s present and future performances stem in part from a paradigm of international relations by state actors that is informed by liberalism, and in part from unequal foreign trade. Zambia initially occupied a strong position in the world economy that eventually weakened, occupies a lower-middle income position in the present, and is currently on a path towards its goals that will keep it as a weak economic power for the long-term future. To achieve higher income from its interaction with the world economy, state actors need to incorporate world systems and grand strategic thought and develop a grand development strategy that is less dependent on unequal foreign trade.
Agriculture in Zambia
Authors: Mataa Mebelo , Chikopela Louis
Published: September 2024

This chapter is a synopsis of the agricultural sector in Zambia, outlining the general performance—potentials and limitations. The first section is a historical perspective outlining the evolution of agriculture in Zambia—starting with the colonial era, where the sector developed to meet food demands of the emerging mining industry. The second section describes the range and variety of key commodities produced, included are cereals, root, tubers, oil crops, and grain legumes. Also included are crops of industrial importance such as cotton, sugarcane, and tobacco. The last group includes beverages such as tea and coffee. Production statistics for the past ten years where possible are shown. The sections that follow are on agricultural programmes and policies and on support systems, such as research and development, extension and technology transfer, agricultural supply chains and marketing. Postharvest losses have a major impact on the supply and availability of produce, especially perishable products. Generally postharvest losses and food waste are high due to a rudimentary processing industry, challenges with cold chain, and poor storage facilities. The last part of the review is devoted to emerging issues such as climate change, food systems (local regional and global) and food safety, quality, and standards, with a short conclusion.
External Financing and Economic Growth in Malawi
Authors: Gondwe Grace
Published: September 2024

This chapter applies the VAR framework to assess the performance of external financing on growth in Malawi. Despite it being a dominant source of foreign capital, the results show a weaker impact of aid on growth relative to FDI and savings, mainly due to weak institutions and the resultant fungibility of grants, and poor alignment of aid to Malawi’s development priorities within and across sectors. Accordingly, gradual reduction of grants while rationalizing concessional loans remains the best policy option for eliminating fungible resources, particularly if accompanied by the strengthening of domestic institutions to enhance accountability of loans. A thorough understanding of the respective roles of the sectors in the country’s growth process will be key in realigning future aid to the country’s growth and development priorities. These should be complemented by policies that enhance FDI inflows and domestic resource mobilization with a broader focus on reducing its dependency on foreign aid.
The Congress Party in Decline
Authors: Hasan Zoya
Published: September 2024

Political scientists tend to explain the decline and fall of parties in terms of institutional factors that are internally specific to the party concerned. The interface between parties and the role of internal and external factors is frequently ignored. This chapter seeks to understand the decline of the Congress party by emphasising internal factors, specifically organization and ideology, and also, external factors, especially the growth of majoritarianism in the decline of the Congress, and while doing so, estimating its impact on Indian politics and on the once dominant party. The crisis in the Congress may owe more to the party’s inability to effectively counter Hindu nationalism which hastened its decline in the midst of the ideological consolidation of the Right in India.
Oral toxicity evaluation of Bacillus clausii M31 isolated from the children’s feces in the northern province of Vietnam
Authors: Ngo Nguyen Quynh Anh , Nguyen Huong Thi , Dam Xuan Thanh , Bui Dinh Nhi , Minh Thi Thao
Published: September 2024

This study investigated the acute and repeated 28-day dose toxicity profiles of Bacillus clausii M31, isolated from children’s feces, in Swiss rats and New Zealand rabbits. To investigate acute toxicity, rats were given varied doses of B. clausii M31 (1 × 1011 CFU/mL, 3 × 1011 CFU/mL, and 5 × 1011 CFU/mL) orally once daily for 14 days, in accordance with OECD recommendations No. 423. To evaluate toxicity, rabbits were given either a low dosage (1 × 1011 CFU/mL) or a high dose (5 × 1011 CFU/mL) during a 28-day period using the OECD Test Guideline 407 protocol. Neither death nor significant abnormalities were observed in the rats during the experiment. The microscopic examination of key organs revealed no substantial changes in organ morphology. Furthermore, analyses of serum biochemistry and hematological parameters did not reveal any treatment-associated variations. In sum, these findings suggest that the oral intake of B. clausii M31 at concentrations up to 5 × 1011 CFU/mL for 28 days poses no discernible risks.
Identification of Cercospora spp. on Corn in North America and Baseline Flutriafol Fungicide Sensitivity
Authors: Nikzainalalam Nik N. , Copeland Drake J. , Wiggins Matthew S. , Telenko Darcy E. P. , Wise Kiersten A. , Kleczewski Nathan M. , Jackson-Ziems Tamra A. , Robertson Alison E. , Bergstrom Gary C. , Tenuta Albert U. , McCoy Austin G. , Jacobs Janette L. , Chilvers Martin I.
Published: September 2024

Gray leaf spot (GLS) is an important corn disease reportedly caused by Cercospora zeae-maydis and C. zeina. Recently, flutriafol, a demethylation inhibitor (azole) fungicide, received Environmental Protection Agency registration as Xyway LFR, a product that is applied at planting for management of fungal diseases in corn, including suppression of GLS. In this study, 448 Cercospora spp. isolates were collected in 2020 and 2021 from symptomatic corn leaf samples submitted from the United States and Ontario, Canada. The Cercospora spp. were identified using multilocus genotyping of the internal transcribed spacer, elongation factor 1-α, calmodulin, histone H3, and actin genes. Based on the multilocus phylogenetic analyses, six species were identified; C. cf. flagellaris (n = 77), C. kikuchii (n = 4), C. zeae-maydis (n = 361), Cercospora sp. M (n = 2), Cercospora sp. Q (n = 1), and Cercospora sp. T (n = 3). In subsequent pathogenicity tests using selected isolates from each of these species, only C. zeae-maydis resulted in symptoms on corn, with no disease symptoms observed after inoculation with C. cf. flagellaris, C. kikuchii, Cercospora sp. M, Cercospora sp. Q, and Cercospora sp. T. Disease symptoms were observed on soybean following inoculation with C. cf. flagellaris, C. kikuchii, and Cercospora sp. Q, but not the other three species. Fungicide sensitivity of Cercospora spp. to flutriafol was assessed using a subset of 340 isolates. The minimum inhibitory concentration (MIC) to inhibit the growth of Cercospora spp. completely was determined based on growth of each species on flutriafol-amended clarified V8 agar at nine concentrations. The effective concentration of fungicide required for 50% growth inhibition (EC50) was also calculated from the same trial by measuring relative growth as compared with the nonamended control. Cercospora zeae-maydis was sensitive to flutriafol, with mean MIC values of 2.5 μg/ml and EC50 values ranging from 0.016 to 1.020 μg/ml with a mean of 0.346 μg/ml. Cercospora cf. flagellaris, C. kikuchii, Cercospora sp. M, Cercospora sp. Q, and Cercospora sp. T had mean EC50 values of 1.25, 7.14, 2.48, 1.81, and 2.24 μg/ml, respectively. These findings will assist in monitoring the sensitivity to the flutriafol fungicide in Cercospora spp. populations.
Development of a Recombinase Polymerase Amplification Method Combined with a Lateral Flow Dipstick Assay for Rapid Detection of the Larch Pathogen Neofusicoccum laricinum
Authors: Ju Fangyi , Qi Zhongqiang , Tan Jiajin , Liu Tingli , Dai Tingting
Published: September 2024

Neofusicoccum laricinum, an important pathogenic species, causes shoot blight of larch. In China, large areas of Larix principis-rupprechtii forests are threatened by this pathogen. Currently, this pathogen is on the list of quarantine pests in China. Because of the widespread and severe damage caused by N. laricinum, a reliable and accurate diagnostic tool is urgently needed. In this study, we first identified Nlar12009 as a N. laricinum-specific gene through genomic sequence data and bioinformatic analysis. Specific primer pairs and DNA probes were designed to detect the target pathogen using a novel recombinase polymerase amplification assay with a lateral flow dipstick (RPA-LFD) method. We optimized the RPA-LFD assay to ensure high specificity to N. laricinum. Our results showed that the assay exclusively detected N. laricinum isolates with no cross-reaction with other isolates of fungal and oomycete species and nematodes. Furthermore, our detection technique exhibited a 10-fold higher sensitivity (10 fg/ml) than conventional polymerase chain reaction for N. laricinum detection. Our developed RPA-LFD assay is proved to be a highly specific, sensitive, time-saving, and convenient method for the diagnosis of N. laricinum and shows great potential in field application.
International medical graduates and PAs
Authors: Cawley James F.
Published: September 2024

During the 1980s and 1990s, international medical graduates (IMGs) sought legal and educational measures aimed at obtaining licensure as physician associates/assistants (PAs). Proponents of IMGs asserted that their ethnic backgrounds and identification with their respective communities could increase access to care for some segments of the population and therefore should be permitted pathways to qualify as PAs. A variety of legal measures were introduced into state legislatures in at least five states and were firmly opposed and defeated by the PA profession. Recent attempts by IMGs to obtain licensure as PAs have occurred in Puerto Rico and Arizona. In their haste to address healthcare access and satisfy various constituencies, state legislators and regulatory boards fail to recognize established professional norms. This is occurring as medical organizations are examining alternative pathways for state licensure of physicians who have completed training and/or practiced outside of the United States. PA organizations, particularly state chapters, must be vigilant in upholding qualifications for practice and licensure standards, and state PA organizations must work to convince legislators to avoid using PA professional regulations to solve a workforce issue that is essentially an issue of physician medical education remediation.
Hangman’s Fractures: A Review of Current Concepts in Evaluation and Management
Authors: Mizels Joshua , Connelly James W. , Spina Nicholas , Lawrence Brandon , Karamian Brian A.
Published: September 2024

Study design:

Review article.

Objective:

To provide a comprehensive review and update on the evaluation and management of Hangman’s fractures.

Summary of background data:

Hangman’s fractures are the second most common fracture of the C2 vertebrae, and the prevalence is increasing with our aging population. Although these injuries are associated with good clinical outcomes and low rates of neurologic injury, they must be promptly recognized and treated according to patient and fracture factors.

Methods:

A review of the literature.

Results:

Neurologic injuries are uncommon in typical Hangman’s fractures but are more of a concern in atypical Hangman’s fractures due to lack of dissociation of the posterior ring of C2. The nonoperative treatment of stable type I, II, and atypical fractures with external immobilization leads to excellent long-term outcomes as does the operative treatment of unstable type IIa, III, and atypical fractures.

Conclusions:

Stable injury patterns can be treated with immobilization alone, whereas unstable injury patterns necessitate surgical treatment. Prompt diagnosis and treatment Hangman’s fractures is paramount, and when managed properly, patients can have excellent clinical and neurologic outcomes.
Coronary Artery Anomalies: Diagnosis & Management
Authors: Chandrasekhar Sanjay , Woods Edward , Bennett Josiah , Newman Noah , McLean Patrick , Alam Mahboob , Jneid Hani , Sharma Samin , Khawaja Muzamil , Krittanawong Chayakrit
Published: September 2024

Coronary artery anomalies encompass a spectrum of congenital abnormalities affecting the origin, course, or termination of the major epicardial coronary arteries. Despite their rarity, coronary artery anomalies represent a significant burden on cardiovascular health due to their potential to disrupt myocardial blood flow and precipitate adverse cardiac events. While historically diagnosed postmortem, the widespread availability of imaging modalities has led to an increased recognition of coronary artery anomalies, particularly in adults. This review synthesizes current knowledge on the classification, mechanisms, and clinical implications of coronary anomalies, focusing on prevalent variants with significant clinical impact. We discuss strategies for medical and surgical management, as well as contemporary screening recommendations, acknowledging the evolving understanding of these anomalies. Given the breadth of possible variants and the limited data on some presentations, this review provides a framework to aid clinicians in the recognition and management of coronary anomalies, with a particular emphasis on their stratification by anatomical location. By consolidating existing knowledge and highlighting areas of uncertainty, this review aims to enhance clinical decision-making and improve outcomes for individuals with coronary anomalies.
Interactive Effects of Long-term Exposure to Air Pollutants on SARS-CoV-2 Infection and Severity: A Northern Italian Population-based Cohort Study
Authors: Veronesi Giovanni , De Matteis Sara , Silibello Camillo , Giusti Emanuele M. , Ageno Walter , Ferrario Marco M.
Published: September 2024

Background:

We examined interactions, to our knowledge not yet explored, between long-term exposures to particulate matter (PM10) with nitrogen dioxide (NO2) and ozone (O3) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity and severity.

Methods:

We followed 709,864 adult residents of Varese Province from 1 February 2020 until the first positive test, COVID-19 hospitalization, or death, up to 31 December 2020. We estimated residential annual means of PM10, NO2, and O3 in 2019 from chemical transport and random-forest models. We estimated the interactive effects of pollutants with urbanicity on SARS-CoV-2 infectivity, hospitalization, and mortality endpoints using Cox regression models adjusted for socio-demographic factors and comorbidities, and additional cases due to interactions using Poisson models.

Results:

In total 41,065 individuals were infected, 5203 were hospitalized and 1543 died from COVID-19 during follow-up. Mean PM10 was 1.6 times higher and NO2 2.6 times higher than WHO limits, with wide gradients between urban and nonurban areas. PM10 and NO2 were positively associated with SARS-CoV-2 infectivity and mortality, and PM10 with hospitalizations in urban areas. Interaction analyses estimated that the effect of PM10 (per 3.5 µg/m3) on infectivity was strongest in urban areas [hazard ratio (HR) = 1.12; 95% CI =1.09, 1.16], corresponding to 854 additional cases per 100,000 person-years, and in areas at high NO2 co-exposure (HR = 1.15; 1.08, 1.22). At higher levels of PM10 co-exposure, the protective association of O3 reversed (HR =1.32, 1.17, 1.49), yielding 278 additional cases per µg/m3 increase in O3. We estimated similar interactive effects for severity endpoints.

Conclusions:

We estimate that interactive effects between pollutants exacerbated the burden of the SARS-CoV-2 pandemic in urban areas.
Temperature-mortality associations by age and cause: a multi-country multi-city study
Authors: Scovronick Noah , Sera Francesco , Vu Bryan , Vicedo-Cabrera Ana M. , Roye Dominic , Tobias Aurelio , Seposo Xerxes , Forsberg Bertil , Guo Yuming , Li Shanshan , Honda Yasushi , Abrutzky Rosana , de Sousa Zanotti Stagliorio Coelho Micheline , Nascimento Saldiva Paulo H. , Lavigne Eric , Kan Haidong , Osorio Samuel , Kyselý Jan , Urban Aleš , Orru Hans , Indermitte Ene , Jaakkola Jouni J. , Ryti Niilo , Pascal Mathilde , Katsouyanni Klea , Mayvaneh Fatemeh , Entezari Alireza , Goodman Patrick , Zeka Ariana , Michelozzi Paola , de’Donato Francesca , Hashizume Masahiro , Alahmad Barak , Zanobetti Antonella , Schwartz Joel , Hurtado Diaz Miguel , De La Cruz Valencia C. , Rao Shilpa , Madureira Joana , Acquaotta Fiorella , Kim Ho , Lee Whanhee , Iniguez Carmen , Ragettli Martina S. , Guo Yue L. , Dang Tran Ngoc , Dung Do V. , Armstrong Benedict , Gasparrini Antonio
Published: September 2024

Background:

Heterogeneity in temperature-mortality relationships across locations may partly result from differences in the demographic structure of populations and their cause-specific vulnerabilities. Here we conduct the largest epidemiological study to date on the association between ambient temperature and mortality by age and cause using data from 532 cities in 33 countries.

Methods:

We collected daily temperature and mortality data from each country. Mortality data was provided as daily death counts within age groups from all, cardiovascular, respiratory, or noncardiorespiratory causes. We first fit quasi-Poisson regression models to estimate location-specific associations for each age-by-cause group. For each cause, we then pooled location-specific results in a dose-response multivariate meta-regression model that enabled us to estimate overall temperature-mortality curves at any age. The age analysis was limited to adults.

Results:

We observed high temperature effects on mortality from both cardiovascular and respiratory causes compared to noncardiorespiratory causes, with the highest cold-related risks from cardiovascular causes and the highest heat-related risks from respiratory causes. Risks generally increased with age, a pattern most consistent for cold and for nonrespiratory causes. For every cause group, risks at both temperature extremes were strongest at the oldest age (age 85 years). Excess mortality fractions were highest for cold at the oldest ages.

Conclusions:

There is a differential pattern of risk associated with heat and cold by cause and age; cardiorespiratory causes show stronger effects than noncardiorespiratory causes, and older adults have higher risks than younger adults.
Plate osteosynthesis of phalanx fractures using wide-awake local anesthesia no tourniquet technique is cost-effective and associated with less postoperative pain
Authors: Chen Wei-Chieh , Chen Chun-Yu , Lin Yen-Chang
Published: September 2024

Background:

The wide-awake local anesthesia no tourniquet (WALANT) technique, which is based on the local infiltration of lidocaine and epinephrine, is widely used in hand and wrist surgery. However, few studies have been conducted on the cost–benefit analysis of phalanx fracture surgery using the WALANT technique. This study aimed to investigate the clinical condition, as well as the time spent for anesthesia and operation. We also performed an economic analysis to compare general anesthesia, local anesthesia with a tourniquet, and the WALANT technique for plate fixation of phalanx fractures.

Methods:

This retrospective study included all patients with single phalanx fractures who underwent open reduction internal fixation with plating between January 2015 and December 2019. Patients were divided into three groups according to the anesthesia method: general anesthesia with a tourniquet (GA group), local anesthesia with a tourniquet (LA group), and the WALANT technique (WALANT group). Data, including demographics, anesthesia and surgical time, postoperative pain score, and vomiting ratio, were collected and analyzed.

Results:

A total of 62 patients were included in this study. Of the 62 patients, 15 were included in the GA group, 32 in the LA group, and 15 in the WALANT group. No complications were reported during surgery or follow-up in any group. The GA group exhibited a significantly longer anesthesia time than the other two groups, with an average of 32.4 minutes. However, no significant difference in surgical time was observed among the three groups. The WALANT group exhibited a significantly lower postoperative day 1 pain score than the other two groups. The additional cost of general anesthesia was approximately 350 US dollars (USD), accounting for approximately one-third to one-fourth of the total expenses for phalanx surgery.

Conclusion:

Open reduction with plate fixation of phalanx fractures using the WALANT technique or local anesthesia was cost-effective compared with general anesthesia. Patients who underwent phalanx fracture surgery using the WALANT technique experienced less pain on the first postoperative day because of the adequate tumescent technique and not using a tourniquet during surgery.
Polarized light detection in bumblebees varies with light intensity and is mediated by both the ocelli and compound eyes
Authors: Araújo Priscila , Belušič Gregor , Ilić Marko , Foster James , Pfeiffer Keram , Baird Emily
Published: September 2024

Like many insects, bumblebees use polarized light (PL) to orient and navigate. The celestial PL pattern is strongest when the sun is close to the horizon, during the dim light of dawn and dusk. In the dim light, the sensitivity of the compound eyes may not be sufficient for detecting PL or landmarks, and it has previously been hypothesized that bumblebees rely on PL from their more sensitive ocelli to navigate at dawn and dusk. Here, we tested this hypothesis using a combination of electrophysiological and behavioural tests. Specifically, we investigate whether bumblebee ocelli can detect PL and explore how the PL contribution from the ocelli and compound eyes is affected by light intensity. We find that bumblebee ocelli do indeed have PL sensitivity and that PL information can be used to guide behaviour in dim light. In bright light, however, both the compound eyes and ocelli are important for the detection of PL. Our results support the hypothesis that bumblebees use PL information from the ocelli at the low light levels that occur around dawn and dusk, and this may support their ability to forage during these periods.
William Joseph Whelan. 14 November 1924—5 June 2021
Authors: Azzi Angelo
Published: September 2024

William Whelan was an exceptionally celebrated scientist recognized equally for his work in research, education, publishing and international scientific organizations. He studied organic chemistry at the University of Birmingham. He taught at the University College of North Wales and the University of London and became head of the Department of Biochemistry of the Royal Free Hospital School of Medicine, University of London, in 1964. In 1967 he moved to the United States and served as professor and chairman of the Department of Biochemistry and Molecular Biology of the University of Miami Medical School for the rest of his career. Bill is known for his pioneering research on the structure of starch and glycogen. He discovered that glycogen contained the protein glycogenin, an enzyme with primer function in the synthesis of glycogen. This discovery filled a crucial gap in understanding the biosynthetic process that transforms glucose into glycogen. Bill's contributions, including his innovative methods for isolating and characterizing molecular structures like glycogen, have since become established scientific practices, and he established some of the fundamental concepts and nomenclature used in the carbohydrate field today.
pH-Responsive supramolecular vesicles for imaging-guided drug delivery: Harnessing aggregation-induced emission
Authors: Wang Xin-Rui , Lin Wei-Xiu , Lu Yi-Long , Kuck Dietmar , Xu Wen-Rong
Published: September 2024

The water-soluble tribenzotriquinacene-based hexacarboxylic acid ammonium salt,
TBTQ-C

6

, acts as the host component (
H
) forming host–guest complexes with tetraphenylethylene (TPE)-functionalized monotopic and tetratopic quaternary ammonium derivatives,
G1
and
G2
, to yield supra-amphiphiles. These supra-amphiphiles self-assemble to form pH-responsive fluorescent vesicles, which have allowed us to capitalize on the aggregation-induced emission (AIE) effect for imaging-guided drug delivery systems. These systems exhibit efficient drug loading and pH-responsive delivery capabilities. Upon encapsulation of the anticancer drug doxorubicin (DOX), both the TPE and DOX chromophores undergo dual-fluorescence deactivation due to the energy transfer relay (ETR) effect. Under acidic conditions, the release of DOX interrupts the ETR effect, resulting in the fluorescence recovery of TPE fluorogens and DOX, allowing for real-time visual monitoring of the drug release process. Cytotoxicity experiments confirmed the low toxicity of the unloaded vectors to normal cells, while the DOX-loaded vectors were found to significantly enhance the anticancer activity of DOX against cancer cells
in vitro
. The AIE-featured supramolecular vesicles presented in this research hold great potential for imaging-guided drug delivery systems.
The catabolic nature of fermentative substrates influence proteomic rewiring inEscherichia coliunder anoxic growth
Authors: Momin Huda , Appukuttan Deepti , Venkatesh K.V
Published: September 2024

During anaerobic batch fermentation byEscherichia coli, there is a decline in cell proliferation rates and a huge demand is placed on cellular proteome to cater its catabolic and anabolic needs under anoxic growth. Previous studies have established a direct relationship betweenE. coligrowth rate and cellular ribosomal content for fast proliferating cells. In this study, we integrated experimental findings with a systemic coarse-grained model of proteome allocation, to characterize the physiological outcomes at slow growth rate during anaerobic fermentative catabolism of different glycolytic and non-glycolytic substrates. The anaerobic catabolism of substrates favored high ribosomal abundances at lower growth rates. Interestingly, a modification of previously discussed “growth law”, the ratio of active to inactive ribosomal proteome was found to be linearly related to growth rate for cells proliferating in slow to moderate regime (growth rate < 0.8 h-1). Also, under nutrient- and oxygen-limited growth conditions, the proteome proportion allocated for ribosomal activity was reduced, and resources were channelized towards catabolic and metabolic activities to overcome the limitations imposed while uptake and metabolizing substrate. The energy intensive uptake mechanism or lower substrate affinity, expended more catabolic proteome, which reduced its availability to other cellular functions. Conclusively, the nature of catabolic substrates imposed either uptake limitation or metabolic limitation coupled with ribosomal limitation (arising due to anoxic and nutritional stress), which resulted in higher proteome expenditure leading to sub-optimal phenotype.
Insights into the triggering factors and determination mechanisms of host alternation in aphids
Authors: Etier Aurelie , Ghosh Rituparna , Vericel Théo , Cloteau Romuald , Denis Gaëtan , Le Floch Maïwenn , Outreman Yannick , Le Trionnaire Gaël , Simon Jean-Christophe
Published: September 2024

The bird cherry-oat aphidRhopalosiphum padi, is one of the ten percent of aphids that are host alternating. The annual life cycle ofR. padientails an obligatory migration between a primary woody host,Prunus padus(Rosaceae), where sexual reproduction occurs, and many secondary hosts of the Poaceae family, where successive generations reproduce parthenogenetically. Migration between the two types of host plants is achieved by specialized migrant morphs. Very little is known about the cues that trigger migrant development, host alternation establishment and the underlying mechanisms. In this study, we aimed to elucidate the key steps involved in migrant induction and determination of host alternation, and to shed light on these intricate processes. We showed that a specific stage of leaf maturity triggers the development into a migrant morph when presented toR. padiat the first or second larval instar stages. We also demonstrated the gradual establishment of acclimation to the secondary hosts that precedes the migration step. Finally, we showed that the switch to feeding on the alternative hosts is irreversible once emigrants have reached adulthood. These results not only allowed us to define the critical periods of the leaf stage associated with morph induction and determination, but also to pinpoint the emigrants’ developmental stages when acclimation to secondary hosts begins. These novel insights of these critical periods will facilitate the investigation of molecular changes associated with host alternation in aphids.
Dynamic responses of human lung innate and adaptive immune cells highlight the roles of genes at asthma risk loci
Authors: Tian Funing , Decker Donna C , Sperling Anne I , Schoettler Nathan
Published: September 2024

Rationale: The lung is a unique immunological niche with diverse immune cell types. The effects of stimulation through innate and adaptive immune receptors on human lung immune cells has largely been extrapolated from studies of blood immune cells. While multiple immune cell types and many genes have been implicated as contributing to asthma, the dynamics of these in human lung immune cells following activation will yield insights into asthma pathogenesis and lung immunity more broadly. Methods and Measurements: Human lung immune cells from 6 donors were isolated. Mixed leukocytes were treated separately with lipopolysaccharide (LPS), F(ab)2-anti-human-IgM/IgG + IL4 and anti-CD3/CD28 for 4 and 18 hours and underwent single cell RNA sequencing (scRNAseq). Lung immune cell types were annotated, and gene expression compared across conditions. Genes at prior asthma-associated genetic loci were characterized across cell types, treatments and timepoints. Expression of non-classical class II genes associated with asthma, HLA-DQA2 and HLA-DQB2, and their protein products was characterized with immunohistochemistry. Main Results: We characterized gene expression in 116,697 lung immune cells. Cell-, treatment-, and timepoint-specific effects on gene expression were detected in all lung immune cell populations. Correlation of gene expression between lung and blood lymphocyte populations decreased following stimulation. Among the genes that were differentially expressed, 97 receptor:ligand pairs had changes with treatments. 96.0% of genes at asthma risk loci demonstrated differential expression in at least one cell type and at least one treatment. B cells were the cell type with the highest expression of HLA-DQA2 and HLA-DQB2 which increased with anti-IgM/IgG treatment and the HLA-DQB2 protein was identified in lung B cells from a donor with asthma. Conclusions: Human lung immune activation elicits a broad range of cellular responses that deviate from those of blood immune cells and are relevant to asthma. Lung B cells expressing HLA-DQA2 and HLA-DQB2 appear to be involved in a novel antigen presentation pathway that contributes to asthma risk.
Evaluation of tick salivary and midgut extracellular vesicles as anti-tick vaccines in White-tailed deer (Odocoileus virginianus)
Authors: Gonzalez Julia , Harvey Cristina , de Souza Ribeiro-Silva Cárita , Leal-Galvan Brenda , Persinger Kelly A. , Olafson Pia U. , Johnson Tammi L. , Chavez Adela Oliva
Published: September 2024

Current tick control measures are focused on the use of synthetic acaricides and personal protective measures. However, the emergence of acaricide resistance and the maintenance of tick populations in wildlife has precluded the efficient management of ticks. Thus, host-targeted, non-chemical control measures are needed to reliably reduce ticks parasitizing sylvatic reservoirs. This project aimed to evaluate extracellular vesicles (EVs) fromAmblyomma americanumas vaccine candidates for white-tailed deer (Odocoileus virginianus; WTD). Salivary gland (SG) and midgut (MG) EVs were isolated by ultracentrifugation. Three deer were vaccinated with SG and MG EVs and received two boosters at days 28 and 50. Two control deer were injected with adjuvant and PBS only. On day 58, WTD were infested with 100A. americanumnymphs, 50 females, and 50 males that were allowed to feed to repletion. On-host and off-host mortality, tick engorgement weight, nymph molting, time to oviposition, and egg hatchability were evaluated. Serum samples were recovered every seven days until the last day of tick drop off, and then at one year (Y1) and 1-year and 1-month (Y1M1). Vaccination resulted in seroconversion and significant increases in total IgG levels that remained significantly higher than controls and pre-vaccination levels at Y1 and Y1M1. No negative effects were observed in nymphs, but on-host mortality of femaleA. americanumwas significantly higher in vaccinated animals. No effects were observed on reproductive parameters. These results indicate that proteins within female tick SG and MG vesicles are not good candidates for vaccine design against nymphs; however, the on-host adult mortality suggests that tick EVs harbor protective antigens againstA. americanumfemales.
Prodrug BMP-7 attenuates pulmonary fibrosis through downregulation of bone marrow derived ApoE+ alveolar macrophage
Authors: Kim Nam Eun , Cho Sue Bean , Shin Mi Hwa , Shim Hyo Sup , Suh Young Joo , Ha Eun Kim , Lee Jin Gu , Han Dawool , Choi Hyun Kyu , Jang Si Hwan , Hwang Sung-Joo , Kim Nam Hee , Yook Jong In , Kim Hyun Sil , Park Moo Suk
Published: September 2024

Background

Bone morphogenetic protein-7 (BMP-7) antagonises transforming growth factor-β (TGF-β). This study investigated the ability of a prodrug BMP-7, designed as micelle nanoparticles for nasal inhalation, to ameliorate pulmonary fibrosis in a bleomycin (BLM)-induced murine model.

Materials and Methods

Fluorescently labelled BMP-7 was delivered to murine lungs via nasal inhalation. Thirty-eight C57BL/6J mice were divided into three groups: control, BLM and BLM with prodrug BMP-7. We then administered the prodrug BMP-7 and vehicle nasally every 72 hours for 21 days. Single-cell RNA sequencing was performed on bronchoalveolar lavage fluid (BALF) from 18 mice, divided into four groups: control, prodrug BMP-7 alone, BLM and BLM with prodrug BMP-7, to assess effects on alveolar macrophages (AM). The expression of ApoE+ AM was compared between normal and idiopathic pulmonary fibrosis (IPF) patients.

Results

The prodrug BMP-7 group showed reduced BALF inflammatory cells and significant fibrosis reduction compared to the BLM group. Western blot showed decreased levels of collagen I, α-SMA and fibronectin in the prodrug BMP-7 group, along with downregulation of TGF-β/SMAD signalling. ELISA indicated decreased levels of chemokines CXCL10 and CXCL2 in tissue and BALF. Single-cell RNA sequencing revealed a significant increase in bone marrow-derived ApoE+ AM in the BLM group, which was reduced with prodrug BMP-7. Additionally, ApoE+ expression was higher in IPF patients compared to controls.

Conclusions

Prodrug BMP-7 shows potential as a therapeutic agent for pulmonary fibrosis by modulating ApoE+ AM.
Characterization and implication of the Orai3 channel and ABC type transporters in the phenomenon of chemoresistance to cisplatin and pemetrexed in lung cancer
Authors: Redoane Daoudi
Published: September 2024

Orai3 channels have been associated with cell proliferation, survival and metastasis in several cancers. Previous studies have shown that Orai3 seems to be involved in the development of acquired chemo-resistance of cisplatin in non-small cell lung cancer via ABC transporters that transport certain chemotherapeutic agents, such as cisplatin, out of the cells. Based on these studies, we hypothesize that Orai3 may be involved in the development of acquired chemo-resistance of pemetrexed. By using MTT assay, we show that pemetrexed is efficient (IC50 =0,4µM)and significantly decreases cell viability in a dose dependent manner. Furthermore, we demonstrate using siRNA-mediated Orai3 knockdown that Orai3 silencing has no effect on the chemoresistance against pemetrexed. Then, calcium imaging reveals that pemetrexed doesn’t affect the activity of calcium channels like Orai3. As transcription factors are central to the regulation of gene expression, we wonder if pemetrexed could impact on Orai3 expression. To address the issue,Mn2+-quench assays are performed in siOrai3 transfected A549 cells incubated with1µMpemetrexed for 72h. Finally, RT-PCR is used in order to determine the mRNA expression profile for Orai3 and ABC transporters in A549 cells. We demonstrate that pemetrexed increases Orai3 expression. Taken together, these results suggest that Orai3 is not involved in the development of acquired chemo-resistance of pemetrexed in non- small cell lung cancer. Pemetrexed upregulates Orai3 expression but doesn’t affect the activity of Orai3 channels. As Orai3 channels are known to be involved in the development of acquired chemo-resistance of cisplatin in non-small cell lung cancer, pemetrexed could reduce the therapeutic efficacy of cisplatin if Orai3 protein levels are linked to Orai3 mRNA levels. Moreover, cisplatin has been shown to both increase expression and function of Orai3, resulting in increased chemoresistance. Therefore, our results show that Orai3 could constitute a robust therapeutic target in non-small cells lung cancer.
Heterogeneous Kinetics of Nanobubble Ultrasound Contrast Agent and Angiogenic Signaling in Head and Neck Cancer
Authors: Van Court Benjamin , Ciccaglione Mark , Neupert Brooke , Knitz Michael W. , Maroney Sean P. , Nguyen Diemmy , Abdelazeem Khalid N.M. , Exner Agata A. , Saviola Anthony J. , Benninger Richard K.P. , Karam Sana D.
Published: September 2024

Recently developednanobubbleultrasound contrast agents are a promising tool for imaging and drug delivery in tumors. To better understand their unusual kinetics, we implemented a novel pixel clustering analysis, which provides unique information by accounting for spatial heterogeneity. By combining ultrasound results with proteomics of the imaged tumors, we show that this analysis is highly predictive of protein expression and that specific types of nanobubble time-intensity curve are associated with upregulation of different metabolic pathways. We applied this method to study the effects of two proteins, EphB4 and ephrinB2, which control tumor angiogenesis through bidirectional juxtacrine signaling, in mouse models of head and neck cancer. We show that ephrinB2 expression by endothelial cells and EphB4 expression by cancer cells have similar effects on tumor vasculature, despite sometimes opposite effects on tumor growth. This implicates a cancer-cell-intrinsic effect of EphB4 forward signaling and not angiogenesis in EphB4’s action as a tumor suppressor.