bluuebunny/crossref_metadata_2025 huggingface dataset:
Helical close-packing of anisotropic tubes
Authors: Greenvall Benjamin R , Grason Gregory M
Published: July 2024

Helically close-packed states of filaments are common in natural and engineered material systems, ranging from nanoscopic biomolecules to macroscopic structural components. While the simplest models of helical close-packing, described by the ideal rope model, neglect anisotropy perpendicular to the backbone, physical filaments are often quite far from circular in their cross-section. Here, we consider an anisotropic generalization of the ideal rope model and show that cross-section anisotropy has a strongly non-linear impact on the helical close-packing configurations of helical filaments. We show that the topology and composition of the close-packing landscape depends on the cross-sectional aspect ratio and is characterized by several distinct states of self-contact. We characterize the local density of these distinct states based on the notion of confinement within a ‘virtual’ cylindrical capillary, and show that states of optimal density vary strongly with the degree of anisotropy. While isotropic filaments are densest in a straight configuration, any measure of anisotropy leads to helicity of the maximal density state. We show the maximally dense states exhibit a sequence of transitions in helical geometry and cross-sectional tilt with increasing anisotropy, from spiral tape to spiral screw packings. Furthermore, we show that maximal capillary density saturates in a lower bound for volume fraction of

π

/

4

in the large-anisotropy, spiral-screw limit. While cross-sectional anisotropy is well-known to impact the mechanical properties of filaments, our study shows its strong effects to shape the configuration space and packing efficiency of this elementary material motif.
Photometric and Spectroscopic Study of Ten Low Mass Ratio Contact Binary Systems: Orbital Stability, O’Connell Effect and Infrared Calcium Line Filling
Authors: Wadhwa Surjit S. , Popowicz Adam , Michel Raúl , Kostić Petar , Vince Oliver , Tothill Nick F. H. , De Horta Ain Y. , Filipović Miroslav D.
Published: July 2024

Low mass ratio contact binary systems are more likely to have unstable orbits and potentially merge. In addition, such systems exhibit characteristics such as starspots and high energy emissions (UV) suggestive of chromospheric and magnetic activity. Light curve modeling of ten contact binary systems is reported. All were found to be of extreme low mass ratio ranging from 0.122 to 0.24 and three were found to be potentially unstable and possible merger candidates. Filling of the infrared calcium absorption lines is a marker of increased chromospheric activity. We use the available Large Sky Area Multi-Object Fiber Spectroscopic Telescope spectra along with matched standard spectra (broadened for rotation) to measure the excess filling of the central core depression flux of the two main infrared calcium absorption lines λ8542 and λ8662. We find that all reported contact binaries have excess filling of the core flux in the infrared calcium lines. Three of the systems reported were also observed by the Galaxy Evolution Explorer mission and we find that all three have features of excess ultraviolet emissions further adding evidence for increased chromospheric activity in low mass ratio contact binaries. Analysis of both orbital stability and absorption line filling is dependent on the determination of geometric and absolute parameters from light curve modeling. Not an insignificant number of contact binary light curves exhibit the O’Connell effect, usually attributed to starspots. We discuss the inclusion of starspots in light curve solutions and how they influence the geometric and absolute parameters.
How general is the Jensen–Varadhan large deviation functional for 1D conservation laws?
Authors: Barré Julien , Feliachi Ouassim
Published: July 2024

Starting from a microscopic particle model whose hydrodynamic limit under hyperbolic space-time scaling is a 1D conservation law, we derive the large deviation rate function encoding the probability to observe a density profile which is a non entropic shock, and compare this large deviation rate function with the classical Jensen-Varadhan functional, valid for the totally asymmetric exclusion process and the weakly asymmetric exclusion process in the strong asymmetry limit. We find that these two functionals have no reason to coincide, and in this sense Jensen-Varadhan functional is not universal. However, they do coincide in a small Mach number limit, suggesting that universality is restored in this regime. We then compute the leading order correction to the Jensen-Varadhan functional.
Extraction and characterization of exosomes from the exhaled breath condensate and sputum of lung cancer patients and vulnerable tobacco consumers—potential noninvasive diagnostic biomarker source
Authors: Bano Afsareen , Yadav Pooja , Sharma Megha , Verma Deepika , Vats Ravina , Chaudhry Dhruva , Kumar Pawan , Bhardwaj Rashmi
Published: July 2024

Noninvasive sample sources of exosomes, such as exhaled breath and sputum, which are in close proximity to the tumor microenvironment and may contain biomarkers indicative of lung cancer, are far more permissive than invasive sample sources for biomarker screening. Standardized exosome extraction and characterization approaches for low-volume noninvasive samples are critically needed. We isolated and characterized exhaled breath condensate (EBC) and sputum exosomes from healthy nonsmokers (n = 30), tobacco smokers (n = 30), and lung cancer patients (n = 40) and correlated the findings with invasive sample sources. EBC samples were collected by using commercially available R-Tubes. To collect sputum samples the participants were directed to take deep breaths, hold their breath, and cough in a collection container. Dynamic light scattering, nanoparticle tracking analysis, and transmission electron microscopy were used to evaluate the exosome morphology. Protein isolation, western blotting, exosome quantification via EXOCET, and Fourier transform infrared spectroscopy were performed for molecular characterization. Exosomes were successfully isolated from EBC and sputum samples, and their yields were adequate and sufficiently pure for subsequent downstream processing and characterization. The exosomes were confirmed based on their size, shape, and surface marker expression. Remarkably, cancer exosomes were the largest in size not only in the plasma subgroups, but also in the EBC (p < 0.05) and sputum (p = 0.0036) subgroups, according to our findings. A significant difference in exosome concentrations were observed between the control sub-groups (p < 0.05). Our research confirmed that exosomes can be extracted from noninvasive sources, such as EBC and sputum, to investigate lung cancer diagnostic biomarkers for research, clinical, and early detection in smokers.
The adsorption capacity of robusta coffee peel-activated charcoal on the aqueous of lead and cadmium ions
Authors: Ratman  , Perodo C A K , Poba D , Napitupulu M , Walanda D K
Published: July 2024

The metal ion adsorption process is strongly influenced by the pH conditions and the amount of adsorbent used. The purpose of this study was to determine the optimum pH and weight of coffee peel-activated charcoal in the adsorption of lead (Pb) and cadmium (Cd) ions. Determination of the optimum pH for adsorption of activated charcoal on coffee peels was carried out by varying the pH of 4, 5, 6, 7, and 8. In contrast, the weight of the activated charcoal was 50, 75, 100, 125, and 150 mg, respectively. The study results showed that the optimum pH for adsorption of activated charcoal on lead (Pb) and cadmium (Cd) ions was pH 4 and 8, namely 99.80% and 96.95%. Meanwhile, the optimum adsorption weight of activated charcoal for Lead (Pb) and Cadmium (Cd) ions is 75 mg and 150 mg, namely 99.95% and 99.45%.
Ecocide as the serious crime: A discourse on global environmental protection
Authors: Arifin R , Masyhar A , Wulandari C , Kusuma B H , Wijayanto I , Rasdi  , Fikri S
Published: July 2024

This paper explores the concept of ecocide as a grave crime within the framework of global environmental preservation. Amid escalating environmental concerns, the discourse on establishing ecocide as an international criminal offense gains momentum. The abstract examines the implications, challenges, and potential advantages of adopting this transformative perspective. Ecocide refers to extensive, irreversible ecological damage caused primarily by human activities. This paper delves into the rationale behind designating ecocide as a serious crime, emphasizing the need to hold individuals, corporations, and even nations responsible for actions leading to widespread environmental destruction. By legally categorizing ecocide as a crime, the international community could establish a more compelling deterrent against actions that undermine global ecological equilibrium. Nonetheless, the global implementation of ecocide as a crime presents considerable hurdles. This paper addresses challenges related to defining the scope of ecocide, differentiating it from existing environmental offenses, and establishing universally applicable prosecution criteria. Furthermore, it explores enforcement complexities given the diversity of geopolitical contexts and the varying degrees of environmental impact worldwide. The potential benefits of acknowledging ecocide as a crime are profound. It could trigger a paradigm shift in public and corporate consciousness, fostering a sense of accountability and encouraging sustainable practices. The prospect of legal consequences might incentivize innovative approaches to prevent environmental harm and facilitate restoration efforts. Additionally, it could bolster the global commitment to environmental safeguarding by placing it on par with other serious international crimes.
The design strategy for the development of the west coast of Sumbawa Regency tourism area to support an increase in sustainable tourist visits
Authors: Tajidan T , Sukardi L , Padusung  , Fahrudin
Published: July 2024

The West Coast of Sumbawa Regency are new tourist areas that the Sumbawa Regency Government wants to develop as a tourist destination with the aim of designing appropriate development strategies so that they grow and develop as sustainable tourist destinations and have a positive impact on regional economic growth. The study method was carried out by combining descriptive and exploratory methods, as well as a combination of quantitative and qualitative research. The analysis used is SWOT with a weight value using an analytical hierarchy process, and a rating from 1 (one) to 4 (four). The strategic plan is to expand the tourist area from Meno Beach to Rhee Loka Beach and integrate natural beach tourism with cultural tourism of traditional houses and locus of sales of processed corn in order to increase sustainable tourist visits by completing main and supporting tourist facilities, developing scheduled tourist attractions every year. weekends, and tourism events for boat/canoe racing competitions.
Characterization of active carbon from cassava plant residuals for decolorization of batik bomba dye waste
Authors: Napitupulu M , Malik A , Anshary A , Suleman M
Published: July 2024

The purpose of this study was to make activated carbon from cassava rods, characterize its physical and chemical properties, and investigate its adsorption capacity to reduce Indigisol Blue 04-B in the bomba batik factory wastewater. The preparation is through a pyrolysis process, at 400 °C without oxygen. The carbon activation process by ZnCl2 aims to enlarge the pore diameter of the carbon, expand the volume in the pores, and open new pores so that the performance of the activated carbon is more optimal. Physical analysis of activated carbon is carried out by calculating the yield, moisture content, and ash content and the results are; that water content was 28%, 3.07%, and 7.7% respectively. Moisture content and ash content all comply with SNI 06-6989-3-2004 standards. The pore morphology of activated carbon was analyzed using a Scanning Electron Microscope (SEM), while the percentage of carbon and other elements in the sample was analyzed using Energy Dispersive X-Ray Spectroscopy (EDS).
The distribution of domestic wastewater effect on the Palu river
Authors: Nasir Al R , Zeffitni  , Kadir A I N K , Marjan M , Paembonan A A A
Published: July 2024

The Palu River is one of the largest rivers in Central Sulawesi and acts as a tourist attraction and a mode of commercial economy for local communities. These activities contribute to the production of domestic wastewater that can be a pollutant for rivers and affect the survival of aquatic organisms. This research aims to determine the distribution of domestic wastewater on the Palu River by identifying the physical and chemical quality of the water. This research is quantitative by direct measurements in the field and by testing river water quality in the laboratory. Sampling used the grab sampling method at three location points, they are at the outlet, before the outlet (point I), and after the outlet (point II), carried out at two different times, in the morning and afternoon. The tested parameters consist of TSS, turbidity, temperature, pH, COD, BOD, DO, and oil and fat. Modeling the distribution of river water quality after being contaminated by domestic waste used by surfers 13. The results showed that at point I and point II, the overall parameters did not exceed the river water quality standards for class III, but at the outlet, oil, and fat failed (1.275 mg/L). Based on the sampling time, in the morning TSS and BOD were the only parameters that approached the limit for both point I (99 mg/L and 5.80 ppm) and point II (97 mg/L and 5.47 ppm). In the afternoon, the COD value was so close to the standard of 40 ppm (35.64 ppm), and TSS at the point I (247 mg/L) and point II (297 mg/L) excelled the safe limit but did not make it at the outlet (15 mg/L). The rest parameters remained at safe limits. Overall, the physical and chemical quality of the river at all sampling points for BOD, oil and fat, turbidity, and temperature parameters tended to be higher in the morning than in the afternoon, while COD, DO, TSS, and pH did reversely.
Analysis of community preferences for industrial forest plantation development in Sumbawa district
Authors: Ichsan A C
Published: July 2024

This study aims to explore information and provide input related to developing industrial timber plantations in 21 villages in the KPH Batulanteh and KPH Ropang areas of Sumbawa Regency, using a combination of qualitative and quantitative methods. Analysis was conducted on aspects related to the HTI development program. Based on the results of this study, three crucial components are used as the basis for developing strategies to encourage HTI development in the study area. These components include the situation, structure, and role of the parties, with three technical approaches in optimizing HTI development activities from the socio-economic perspective of the local community, such Social and Economic Approach, Institutional Approach, and Technological Approach in the form of technical procedures that can be used to carry out environmental management.
Development of green infrastructure to optimize landscape ecosystem services in flood control efforts in the coastal area of Palu city
Authors: Achsan A C , Rizkhi  , Mulyati S
Published: July 2024

Urban development is characterized by increasing population implications of changes in the structure of the city landscape. Various problems are found in the course of urban development. One of the problems caused by increased urban activity and also experienced by the city of Palu is flooding. The role of landscapes through the development of green infrastructure is expected to provide ecosystem services in particular in its function for flood control. The aim of this research is to formulate the development of green infrastructure to optimize the services of landscape ecosystems in flood control efforts in the coastal area of Kota Palu. The method used is to use the method of determining the spread of flood stagnation using cloud computing-based image processing techniques to further formulate the development of green infrastructure on the coastal landscape of Kota Palu spatially using geographic information systems. Observations of estimated flood shelter spread show that flood scales are present almost throughout the research area. According to the results of the spatial analysis of the determination of the area of development of green infrastructure obtained five classes of development area i.e. the area is very suitable for an area of 8233.63 ha, respectively of 5030.24 ha, quite suited for 3157.93 ha. less suitable of 2847.36 ha and not suited of 171.01 ha. Green infrastructure development in the coastal area of the City of Palu is focused on the zone according to very high and available location refers to the highest accumulation score of each criterion scores which has an area of 626.74 ha spread over several areas of sub district namely Pantoloan, Baiya, Lambara, Panau, Mamboro, Layana Indah, Tondo, Talise, Mid, Besusu West, Tanodamare Balaroa, Lodi, Donggala, Kabon, Sila, Tipo, Buluri. The development of green infrastructure as an effort to control flooding in the coastal area of Palu City can be pursued through the provision of green open space and retention ponds allocated in a predetermined space.
Anomaly-based fault detection in wind turbines using unsupervised learning: a comparative study.
Authors: Vásquez-Rodríguez Génesis , Maldonado-Correa Jorge
Published: July 2024

Wind energy has experienced significant growth in recent years thanks to the technological development of wind turbines (WTs). However, one of the main challenges for the wind industry remains the early detection of WT failures. An effective strategy to address this challenge is implementing condition monitoring (CM) to detect changes in WT operation that could indicate the onset of a potential failure. This paper uses data from the SCADA (Supervisory Control and Data Acquisition) system of a wind farm located in Ecuador to test three unsupervised machine learning (ML) methods to detect anomalies in the data, allowing for predicting potential WT failures. Evaluation metrics showed that the Mahalanobis Distance (MD) algorithm performed better in anomaly detection over Isolation Forest (IF) and Density-Based Spatial Clustering of Applications with Noise (DBSCAN), achieving an accuracy of 0.94, 0.90 and 0.74 respectively; however, IF more effectively detected the points determined as anomalies.
Design and sensitivity analysis of a vertical TFET with dielectric pocket for its use as label free biosensor
Authors: Das Debika , Chakraborty Ujjal , Borah Pranjal
Published: July 2024

A comprehensive analysis of a dielectrically modulated vertical tunnel field effect transistor (VTFET) as a label free biosensor is presented in this article. The proposed structure considers an n+ pocket at the source /channel interface and a dielectric pocket at channel/drain interface. The sensitivity of the VTFET biosensor has been investigated, introducing neutral and charged biomolecules of different dielectric constants at the nanogap cavity. The n+ doped pocket introduced at the source/channel junction improves the output characteristics of the proposed VTFET due to its conduction mechanism in both lateral and vertical directions, thereby improving the sensitivity of VTFET biosensor as well. The proposed VTFET biosensor gains the sensitivity in the order of 105 for a fully filled cavity. Moreover, the HfO2 dielectric pocket at the channel/drain interface suppresses the deteriorating ambipolar behaviour and also enhances the ambipolar current sensitivity compared to a VTFET biosensor without dielectric pocket. Thus, it is perceived that the main drawback of TFET, ambipolar nature, has evolved as an advantage for sensing applications. The VTFET biosensor has been analyzed with regards to variations in dielectric constant of cavity, density of charge, length and height of cavity, mole fraction and also operating temperature at a particular bias condition to judge its sensing capability. A status map has been presented where the proposed VTFET biosensor has been compared with some of the significant works reported in literature in terms of sensitivity and selectivity.
Intimate relationships regulate female brain activity in a competitive context: evidence from EEG and functional connectivity analysis
Authors: Liu Yingjie , Jia Shuyu , Meng Yujia , Xing Miao , Guan Jiaqi , Jiang Jinru , Wang He
Published: July 2024

Competition is common in life, and intimate relationships are essential. Understanding how intimate relationships impact an individual’s competitive process is crucial. This study explored the impact of competitor gender on female competition using electroencephalography analysis. The results revealed that females exhibited a smaller median of the absolute value of reaction time difference (DRT) between their partners and their competitors when their partners were absent compared to when their partners were present. Additionally, females showed greater average amplitudes of N2 posterior contralateral component (N2pc) and Late Positive Potential (LPP), increased activation of the alpha frequency band, and enhanced theta frequency band functional connectivity between the central parietal lobe and occipital lobe. Furthermore, when competing with individuals of the same gender as opposed to individuals of the opposite gender, females exhibited greater average amplitudes of percentage of wins and N2pc. A significant negative correlation was noted between the DRT and the average wave amplitudes of N2pc and LPP. These findings suggest that females are more engaged in competitive tasks when partners are not present and have improved decision-making when competing with same-gender individuals. This study provides evidence for the influence of lovers on female competition, helping females adapt to social competition and promoting healthy relationships.
X marks the spot: catheter aspiration using the Inari FlowTriever device to debulk defibrillator lead vegetations prior to transvenous lead extraction—a case report
Authors: Clark James , Zaidi Abbas , O’Callaghan Peter , von Oppell Ulrich , Sharp Andrew S P
Published: July 2024

Background

When cardiac implantable electronic device infection occurs, standard therapy is usually total system extraction. Transvenous lead extraction is preferable to open heart surgical extraction, unless contraindicated because of the presence of very large vegetations on the intravenous leads according to the European Society of Cardiology guidelines. Extraction of transvenous leads with vegetations risks distal embolism resulting in obstruction and/or infection in the pulmonary arteries. Catheter aspiration of vegetations or thrombi has been performed prior to transvenous lead extraction using a partial veno-venous extracorporeal bypass circuit. We report the use of a single-access aspiration system using the Inari FlowTriever 24 French system to debulk a defibrillator lead before percutaneous extraction.

Case summary

A 79-year-old male presented with fever 18 years after his first implantable cardioverter defibrillator implant and 9 years after his most recent pulse generator change. Two large vegetations were identified on his transvenous defibrillator lead on the atrial aspect, near the tricuspid annulus, which were aspirated using the Inari Medical 24Fr FlowTriever aspiration catheter. We describe anatomical considerations during the approach and a technique to localize the vegetations based on a combination of fluoroscopy and transoesophageal echocardiogram guidance.

Discussion

This case demonstrates the safe and effective use of the Inari Medical 24Fr FlowTriever aspiration catheter in debulking a defibrillator lead before transvenous lead extraction. This method uses a single venous puncture and is not dependent on extracorporeal bypass. Apart from reducing complexity, this technique may be advantageous in patients where anticoagulation needs to be minimised.
Pushing the hybrid approach to the edges, three stories in one: a case report
Authors: Dardas Sotirios , Dardas Petros , Mezilis Nikolaos , Tsikaderis Dimitrios , Kofidis Theodoros
Published: July 2024

Background

Mitral annular calcification (MAC) is common in the elderly. Extensive calcification has been historically challenging for the cardiac surgeons, with traditional surgical approaches carrying significant risks. Less invasive approaches have recently been explored in an attempt to reduce this risk.

Case summary

We report the case of a 75-year-old woman who presented with recurrent pulmonary oedema, due to severe MAC and mitral regurgitation. Her past medical history included bioprosthetic aortic valve replacement 5 years ago. Given the extensive MAC and the patient’s frailty, a minimally invasive hybrid approach with direct implantation of a transcatheter balloon expandable Sapien 3 valve was selected to manage her. Although the post-surgical result was initially excellent with elimination of the mitral regurgitation, the patient’s post-operative course was marked by two serious complications, namely, acute severe aortic regurgitation, due to rupture of the bioprosthetic valve’s right cusp, and severe paravalvular leak of the Sapien valve, due to posterior migration towards the left atrium. These were managed successfully with emergency valve-in-valve implantation using the ‘double chimney’ technique for the bioprosthetic aortic valve, as well as transeptal valve-in-valve implantation of a 2nd Sapien valve in the mitral valve, which sealed the gap between the 1st Sapien and the calcified mitral annulus.

Discussion

This case illustrates a less invasive approach for the management of severe MAC. Complications can still occur in this high-risk group of patients, and therefore, such cases should be managed with close collaboration between cardiac surgeons and cardiologists, in centres with high expertise.
The tomato WRKY-B transcription factor modulates lateral branching by targeting BLIND, PIN4, and IAA15
Authors: Yang Huanhuan , Zhou Ke , Wu Qingfei , Jia Xinyi , Wang Hexuan , Yang Wenhui , Lin Lihao , Hu Xiaomeng , Pan Bingqing , Li Ping , Huang Tingting , Xu Xiangyang , Li Jingfu , Jiang Jingbin , Du Minmin
Published: July 2024

Lateral branching is a crucial agronomic trait that impacts crop yield. In tomato (Solanum lycopersicum), excessive lateral branching is unfavorable and results in substantial labor and management costs. Therefore, optimizing lateral branching is a primary objective in tomato breeding. Although many genes related to lateral branching have been reported in tomato, the molecular mechanism underlying their network remains elusive. In this study, we found that the expression profile of a WRKY gene, WRKY-B (for WRKY-BRANCING), was associated with the auxin-dependent axillary bud development process. Wrky-b mutants generated by the CRISPR/Cas9 editing system presented fewer lateral branches, while WRKY-B overexpression lines presented more lateral branches than did wild-type plants. Furthermore, WRKY-B can directly target the well-known branching gene BLIND (BL) and the auxin efflux carrier gene PIN4 to activate their expression. Both the bl and pin4 mutants exhibited reduced lateral branching, similar to the wrky-b mutant. The IAA contents in the axillary buds of the wrky-b, bl, and pin4 mutant plants were significantly higher than those in the wild-type plants. In addition, WRKY-B can also directly target the AUX/IAA gene IAA15 and repress its expression. In summary, WRKY-B works upstream of BL, PIN4, and IAA15 to regulate the development of lateral branches in tomato.
Estimating lead-attributable mortality burden by socioeconomic status in the USA
Authors: Tao Chengzhe , Li Zhi , Fan Yun , Huang Yuna , Wan Tingya , Shu Mingxue , Han Shuwen , Qian Hong , Yan Wenkai , Xu Qiaoqiao , Xia Yankai , Lu Chuncheng , Li You
Published: July 2024

Background

This study aimed to estimate population-level and state-level lead-attributable mortality burdens stratified by socioeconomic status (SES) class in the USA.

Methods

Based on the National Health and Nutrition Examination Survey (NHANES), we constructed individual-level SES scores from income, employment, education and insurance data. We assessed the association between the blood lead levels (BLL) and all-cause mortality by Cox regression in the NHANES cohort (n = 31 311, 4467 deaths). With estimated hazard ratios (HR) and prevalences of medium (2–5 μg/dL) and high (≥ 5 μg/dL) BLL, we computed SES-stratified population-attributable fractions (PAFs) of all-cause mortality from lead exposure across 1999–2019. We additionally conducted a systematic review to estimate the lead-attributable mortality burden at state-level.

Results

The HR for every 2-fold increase in the BLL decreased from 1.23 (1.10–1.38) for the lowest SES class to 1.05 (0.90–1.23) for the highest SES class. Across all SES quintiles, medium BLL exhibited a greater mortality burden. Individuals with lower SES had higher lead-attributable burdens, and such disparities haver persisted over the past two decades. In 2017–19, annually 67 000 (32 000–112 000) deaths in the USA were attributable to lead exposure, with 18 000 (2000–41 000) of these deaths occurring in the lowest SES class. Substantial disparities in the state-level mortality burden attributable to lead exposure were also highlighted.

Conclusions

These findings suggested that disparities in lead-attributable mortality burden persisted within US adults, due to heterogeneities in the effect sizes of lead exposure as well as in the BLL among different SES classes.
Mapping complex public health problems with causal loop diagrams
Authors: Uleman Jeroen F , Stronks Karien , Rutter Harry , Arah Onyebuchi A , Rod Naja Hulvej
Published: July 2024

This paper presents causal loop diagrams (CLDs) as tools for studying complex public health problems like health inequality. These problems often involve feedback loops—a characteristic of complex systems not fully integrated into mainstream epidemiology. CLDs are conceptual models that visualize connections between system variables. They are commonly developed through literature reviews or participatory methods with stakeholder groups. These diagrams often uncover feedback loops among variables across scales (e.g. biological, psychological and social), facilitating cross-disciplinary insights. We illustrate their use through a case example involving the feedback loop between sleep problems and depressive symptoms. We outline a typical step-by-step process for developing CLDs in epidemiology. These steps are defining a specific problem, identifying the key system variables involved, mapping these variables and analysing the CLD to find new insights and possible intervention targets. Throughout this process, we suggest triangulating between diverse sources of evidence, including domain knowledge, scientific literature and empirical data. CLDs can also be evaluated to guide policy changes and future research by revealing knowledge gaps. Finally, CLDs may be iteratively refined as new evidence emerges. We advocate for more widespread use of complex systems tools, like CLDs, in epidemiology to better understand and address complex public health problems.
Specific Depletion of Myeloid-Derived Suppressor Cells by the Chemotherapy Agent 5-Fluorouracil Enhances Protective Immune Response in Paracoccidioidomycosis
Authors: Preite Nycolas Willian , Kaminski Valéria de Lima , Borges Bruno Montanari , dos Santos Bianca Vieira , Calich Vera Lúcia Garcia , Loures Flávio Vieira
Published: July 2024

Background

Paracoccidioidomycosis (PCM) is regulated by suppressive mechanisms mediated by plasmacytoid-dendritic cells, regulatory T cells and myeloid-derived suppressor cells (MDSCs). MDSC suppressive activity on Th1/Th17 immunity was shown to be mediated by inhibitory effect of IL-10, IDO-1, and PD-L1. Studies revealed the 5-fluorouracil (5-FU) as a selective MDSC apoptosis-inducing agent, but its in vivo effect on infectious processes remains poorly investigated.

Methods

MDSCs and other leukocytes were evaluated in the lungs of 5-FU–treated mice after 4, 6, and 8 weeks of Paracoccidioides brasiliensis infection. Disease severity and immunological response were evaluated in MDSCs-depleted mice.

Results

5-FU treatment caused a reduction of pulmonary MDSCs and fungal loads. The specific depletion of MDSCs reduced all pulmonary CD4+ T-cell populations resulting in improved tissue pathology and increased survival. This reduction was concomitant with increased frequencies of Th1/Th17 cells and the increased levels of Th1/Th2/Th17 cytokines in the lungs and liver of treated mice, suggesting an early and efficient protective effect of these cells. Furthermore, the immune protection conferred by the 5-FU treatment could be reversed by the MDSC-adoptive transfer.

Conclusions

5-FU depletes MDSCs of P. brasiliensis-infected mice, resulting in enhanced immunity. This protective effect can be viewed as a potential immunotherapeutic tool for PCM.
Nasal commensals reduce Staphylococcus aureus proliferation by restricting siderophore availability
Authors: Zhao Yanfeng , Bitzer Alina , Power Jeffrey John , Belikova Darya , Torres Salazar Benjamin Orlando , Adolf Lea Antje , Gerlach David , Krismer Bernhard , Heilbronner Simon
Published: July 2024

The human microbiome is critically associated with human health and disease. One aspect of this is that antibiotic-resistant opportunistic bacterial pathogens, such as methicillin-resistant Staphylococcus aureus, can reside within the nasal microbiota, which increases the risk of infection. Epidemiological studies of the nasal microbiome have revealed positive and negative correlations between non-pathogenic species and S. aureus, but the underlying molecular mechanisms remain poorly understood. The nasal cavity is iron-limited, and bacteria are known to produce iron-scavenging siderophores to proliferate in such environments. Siderophores are public goods that can be consumed by all members of a bacterial community. Accordingly, siderophores are known to mediate bacterial competition and collaboration, but their role in the nasal microbiome is unknown. Here, we show that siderophore acquisition is crucial for S. aureus nasal colonization in vivo. We screened 94 nasal bacterial strains from seven genera for their capacity to produce siderophores as well as to consume the siderophores produced by S. aureus. We found that 80% of the strains engaged in siderophore-mediated interactions with S. aureus. Non-pathogenic corynebacterial species were found to be prominent consumers of S. aureus siderophores. In co-culture experiments, consumption of siderophores by competitors reduced S. aureus growth in an iron-dependent fashion. Our data show a wide network of siderophore-mediated interactions between the species of the human nasal microbiome and provide mechanistic evidence for inter-species competition and collaboration impacting pathogen proliferation. This opens avenues for designing nasal probiotics to displace S. aureus from the nasal cavity of humans.
Network Context and the Effectiveness of International Agreements
Authors: Kinne Brandon J
Published: July 2024

Why do some international agreements yield more cooperation than others? I argue that the network context of agreements conditions their effectiveness. I focus on bilateral defense cooperation agreements (DCAs), which promote defense activities like joint military exercises, peacekeeping, arms trade, and the sharing of classified information. Because DCAs emphasize ongoing cooperative actions, they offer an ideal setting to assess treaty effectiveness. The analysis shows that when agreements are embedded in transitive “friend of friend” relations, characterized by extensive ties to common third parties, they generate higher levels of cooperation. I argue that this network effect is the result of policy convergence. When states share ties with common third parties, their own policies become more closely aligned, and this alignment in turn reduces the costs and increases the benefits of cooperative actions. The theory and findings developed here apply to a wide array of cooperative interactions across multiple issue areas. The effectiveness of international agreements depends on network context.
Identification of antimicrobial-susceptible Pseudomonas aeruginosa RpoA variant strains through positional conservation pattern
Authors: Chen Huali , Zhou Xiaoqing , Dai Weijun
Published: July 2024

Background

Bacterial RNA polymerase (RNAP) is a promising target for antimicrobial chemotherapy due to its indispensable role in bacterial growth and survival. Among its components, only the rpoB gene encoding the β-subunit is known for its association with rifampicin resistance. We recently identified a variant of the RNAP α-subunit (RpoA) in Pseudomonas aeruginosa, conferring heightened bacterial susceptibility to antimicrobials. This susceptibility was attributed to the specific down-regulation of the MexEF-OprN efflux pump.

Objectives

We asked how to distinguish antimicrobial-susceptible variant strains from clinical isolates.

Methods

In this study, we identified various P. aeruginosa RpoA variants from clinical sources. Using the sequence alignment of different bacterial RpoA species, we computed the positional conservation of substitutions in RpoA variants using Shannon Entropy.

Results

Our findings revealed that selective RpoA variant strains exhibited distinct profiles of antimicrobial susceptibility. Notably, RpoA variant strains, containing single-substitutions in the C-terminal domain (α-CTD) but not the N-terminal domain (α-NTD), showed attenuated MexEF-OprN expression and increased susceptibility to MexEF-OprN-specific antibiotics. Furthermore, we observed a close correlation between the susceptibility of these α-CTD RpoA variant strains to antibiotics and the conservation degrees of positional substitutions.

Conclusions

Our findings demonstrate the prevalence of antimicrobial-susceptible RpoA variant strains among P. aeruginosa clinical isolates. The identified positional conservation pattern in our study facilitates the rapid classification of RpoA variant strains with distinct drug resistances. Given the high conservation of RNAP across bacterial species, our findings open a new therapeutic perspective for precisely and efficiently combating pathogenic RpoA variant strains with specific antimicrobials.
Measuring the Scientific Impact of Growth Hormone Treatment in Burns: A Bibliometric Analysis Based on CiteSpace
Authors: Shao Yang , Han Mei , Song Guodong
Published: July 2024

This study utilized CiteSpace software to conduct a bibliometric analysis of the literature related to the use of growth hormones in treating burns. The results showed that the research on this topic has attracted increasing attention from scholars worldwide, with the number of publications increasing annually. The research teams and institutions involved in this field are mainly concentrated in China, followed by the United States, Russia, and other countries. The analysis also revealed the prominent co-cited literature and the most influential authors in the field, such as D. N. Herndon and Y. Li. The main research themes identified in the literature included the effects of growth hormones on wound healing, tissue repair and regeneration, inflammatory responses, and cell proliferation. In addition, the research on the clinical applications of growth hormone in burn treatment has been expanded to include areas such as metabolic regulation, immune function, and the prevention of infections. The findings of this study provide useful insights into the current status and future directions of research in the field of growth hormone treatment of burns.
Breeding phenology drives variation in reproductive output, reproductive costs, and offspring fitness in a viviparous ectotherm
Authors: Bodineau Théo , de Villemereuil Pierre , Agostini Simon , Decencière Beatriz , Le Galliard Jean-François , Meylan Sandrine
Published: July 2024

Phenological advances are a widespread response to global warming and can contribute to determine the climate vulnerability of organisms, particularly in ectothermic species, which are highly dependent on ambient temperatures to complete their life cycle. Yet, the relative contribution of breeding dates and temperature conditions during gestation on fitness of females and their offspring is poorly documented in reptiles. Here, we exposed females of the common lizard Zootoca vivipara to contrasting thermal scenarios (cold vs. hot treatment) during gestation and quantified effects of parturition dates and thermal treatment on life-history traits of females and their offspring for 1 year. Overall, our results suggest that parturition date has a greater impact than thermal conditions during gestation on life history strategies. In particular, we found positive effects of an earlier parturition date on juvenile survival, growth, and recruitment suggesting that environmental-dependent selection and/or differences in parental quality between early and late breeders underlie seasonal changes in offspring fitness. Yet, an earlier parturition date compromised the energetic condition of gravid females, which suggests the existence of a mother–offspring conflict regarding the optimization of parturition dates. While numerous studies focused on the direct effects of alterations in incubation temperatures on reptile life-history traits, our results highlight the importance of considering the role of breeding phenology in assessing the short- and long-term effects of thermal developmental plasticity.
Exploring the anxiolytic mechanism of Fructus gardeniae based on metabolomics, network pharmacology, and molecular docking
Authors: Tian Yue , Yuan Fuli , Kong Jiao , Yuan Zhenshuang , Jia Chunxue , Kui Hongqian , Yin Ziqiang , Liu Chuanxin , Huang Jianmei
Published: July 2024

Objective

To explore the effect and anxiolytic mechanism of a natural remedy called Fructus gardeniae (FG).

Methods

The elevated-plus maze (EPM) test was used to confirm the anxiolytic effect of FG. The potential and anxiolytic components, targets, and route processes of FG were investigated using the network pharmacology method in conjunction with metabolomics and molecular docking technologies.

Results

FG could greatly enhance the proportion of time and times of opening arms, according to the EPM data. As to the metabolomics findings, a total of 61 distinct metabolites were found, mainly involved in glycine, serine, and threonine metabolism as well as alanine, aspartate, and glutamate metabolism. The primary active ingredients of FG, nicotiflorin, jasminodiol, and crocetin, demonstrated substantial binding affinities with monoamine oxidase A (MAOA), monoamine oxidase A (ACHE), malate dehydrogenase 2 (MDH2), glutamate decarboxylase 2 (GAD2), glutamate decarboxylase 1 (GAD1), and nitric oxide synthase (NOS1), according to the findings of network pharmacology and molecular docking.

Conclusion

FG exerts an anxiolytic action via targeting MAOA, ACHE, MDH2, GAD2, GAD1, and NOS1, and regulating the metabolism of glycine, serine, and threonine as well as alanine, aspartic acid, and glutamic acid.
Safety of topical sildenafil cream, 3.6% in a randomized, placebo-controlled trial for the treatment of female sexual arousal disorder
Authors: Thurman Andrea R , Johnson Isabella , Cornell Katherine A , Hatheway Jessica , Kim Noel N , Parish Sharon J , Dart Clint , Friend David R , Goldstein Andrew
Published: July 2024

Background

There are currently no Food and Drug Administration–approved treatments for female sexual arousal disorder (FSAD), which is physiologically analogous to male erectile dysfunction.

Aims

The study sought to test the systemic and local genital safety of topical sildenafil cream, 3.6% (sildenafil cream) among healthy premenopausal women with FSAD and their sexual partners over a 12-week treatment period.

Methods

This was a phase 2b, exploratory, randomized, placebo-controlled, double-blind study of sildenafil cream among healthy premenopausal women with FSAD. Safety was assessed by the frequency and incidence of treatment-emergent adverse events (TEAEs) among participants and their sexual partners. Participants recorded the incidence of TEAEs in a daily eDiary (electronic diary). Sexual partners were contacted within 72 hours of each sexual event in which investigational product was used. All participants used placebo cream for 1 month, during a single-blind run-in period, and then if eligible, were randomized 1:1 to sildenafil cream or placebo cream. Participants used their assigned investigational product over a 12-week double-blind dosing period. They attended monthly follow-up visits, in which their eDiary TEAE data were reviewed by the study staff and graded for severity and relationship to study product.

Outcomes

The frequency and incidence of TEAEs among participants and their sexual partners.

Results

During the 12-week double-blind dosing period, there were 78 TEAEs reported by 29 of 99 sildenafil-assigned participants and 65 TEAEs reported by 28 of 94 placebo-assigned participants (P = .76). All TEAEs were mild or moderate in severity. The most common treatment-related TEAE among active and placebo-assigned participants was application site discomfort. There were no differences in the number of treatment-related TEAEs among sildenafil cream vs placebo cream users (P > .99). Four sildenafil cream participants and 3 placebo cream participants discontinued the study due to TEAEs involving application site discomfort (P > .99). There were 9 TEAEs reported by 7 of 91 sexual partners exposed to sildenafil cream vs 4 TEAEs reported by 4 of 84 sexual partners exposed to placebo cream (P = .54).

Clinical Implications

These data support further clinical development of topical sildenafil cream for the treatment of FSAD.

Strengths and Limitations

Safety was assessed among participants and their sexual partners after 1357 and 1160 sexual experiences in which sildenafil cream or placebo cream were used, respectively. The phase 2b study was powered for the primary objectives of efficacy, rather than safety.

Conclusion

These data demonstrate that topically applied sildenafil cream was safe and well tolerated by exposed users and their sexual partners.
Partial wrapping of single-stranded DNA by replication protein A and modulation through phosphorylation
Authors: Chadda Rahul , Kaushik Vikas , Ahmad Iram Munir , Deveryshetty Jaigeeth , Holehouse Alex S , Sigurdsson Snorri Th , Biswas Gargi , Levy Yaakov , Bothner Brian , Cooley Richard B , Mehl Ryan A , Dastvan Reza , Origanti Sofia , Antony Edwin
Published: July 2024

Single-stranded DNA (ssDNA) intermediates which emerge during DNA metabolic processes are shielded by replication protein A (RPA). RPA binds to ssDNA and acts as a gatekeeper to direct the ssDNA towards downstream DNA metabolic pathways with exceptional specificity. Understanding the mechanistic basis for such RPA-dependent functional specificity requires knowledge of the structural conformation of ssDNA when RPA-bound. Previous studies suggested a stretching of ssDNA by RPA. However, structural investigations uncovered a partial wrapping of ssDNA around RPA. Therefore, to reconcile the models, in this study, we measured the end-to-end distances of free ssDNA and RPA–ssDNA complexes using single-molecule FRET and double electron–electron resonance (DEER) spectroscopy and found only a small systematic increase in the end-to-end distance of ssDNA upon RPA binding. This change does not align with a linear stretching model but rather supports partial wrapping of ssDNA around the contour of DNA binding domains of RPA. Furthermore, we reveal how phosphorylation at the key Ser-384 site in the RPA70 subunit provides access to the wrapped ssDNA by remodeling the DNA-binding domains. These findings establish a precise structural model for RPA-bound ssDNA, providing valuable insights into how RPA facilitates the remodeling of ssDNA for subsequent downstream processes.