bluuebunny/crossref_metadata_2025 huggingface dataset:
Liquid droplet entrainment in an annular flow boiling regime—A Bayesian regularization algorithm based study
Authors: Vyas Jayesh , Kohli Rishika , Gupta Shaifu , Pothukuchi Harish
Published: April 2024

Accurate prediction of the entrained liquid droplet fraction in an annular two-phase flow regime plays a crucial role for estimating the dryout type critical heat flux to identify the optimized flow characteristics in the thermal systems across different industries. Existing studies have provided different correlations based on the limited experimental data. However, these correlations are applicable to certain operating conditions. Therefore, the present study aims at applying a deep learning method, specifically an artificial neural network (ANN), to enhance the prediction of the entrained liquid droplet fraction. Experimental data from various works on annular flow, covering a wide spectrum of pressure and flow conditions, are utilized for training the ANN model. Eight input variables, viz, superficial gas velocity (JSG), superficial liquid velocity (JSL), gas viscosity (μG), liquid viscosity (μL), gas density (ρG), liquid density (ρL), pipe diameter (d) and liquid surface tension (σLV) are considered as input features. The entrained liquid droplet fraction is the single output feature. The present model employs the Bayesian regularization backpropagation algorithm for training. The present ANN model is compared against the performance of linear regression, decision tree and support vector machine algorithms, and found that the performance of the present Bayesian regularization neural network (BRNN) model is superior within ∼7.5% deviation. Further, the BRNN model is coupled with the film mass flow rate model to obtain the axial variation of the liquid film mass flow rate and good agreement is noticed when compared against the experimental data.
Direct numerical simulations of supersonic flat-plate turbulent boundary layers with uniform blowing
Authors: Guo Tongbiao , Tong Fulin , Ji Xiangxin , Li Xinliang
Published: April 2024

The effect of uniform blowing on a spatially developing flat-plate turbulent boundary layer at Mach 2.25 is investigated using direct numerical simulations. Two values of the wall blowing ratio are considered, corresponding to low and high blowing rates. Uniform blowing is found to significantly reduce the near-wall turbulence anisotropy, although the turbulent kinetic energy still exhibits near-wall asymptotic behavior and the Reynolds analogy is relatively insensitive to changes in the blowing ratio. The pre-multiplied spectra of turbulent kinetic energy production demonstrate that increasing the blowing ratio significantly energizes the large-scale structures in the outer region, while suppressing the inner small-scale structures. An increase in the blowing ratio also has a strong influence on the behavior of the fluctuating wall pressure, amplifying the fluctuation intensity and reducing the dominant frequencies in the power spectrum. Two-point space–time correlations indicate that the characteristic length scale of the pressure fluctuations increases with increasing blowing ratio, whereas the convection velocity exhibits the opposite trend. Analysis of the reduced mean wall heat flux reveals that it is dominated by the relative balance between the work of the Reynolds stress and the turbulent transport of heat, but is insensitive to uniform blowing. Importantly, bidimensional empirical mode decomposition of the turbulent structures highlights the increasingly dominant contributions related to the significantly energized outer large-scale structures in the blowing region.
Dissection and integration of bursty transcriptional dynamics for complex systems
Authors: Gao Cheng Frank , Vaikuntanathan Suriyanarayanan , Riesenfeld Samantha J.
Published: April 2024

RNA velocity estimation is a potentially powerful tool to reveal the directionality of transcriptional changes in single-cell RNA-sequencing data, but it lacks accuracy, absent advanced metabolic labeling techniques. We developed an approach,
TopicVelo
, that disentangles simultaneous, yet distinct, dynamics by using a probabilistic topic model, a highly interpretable form of latent space factorization, to infer cells and genes associated with individual processes, thereby capturing cellular pluripotency or multifaceted functionality. Focusing on process-associated cells and genes enables accurate estimation of process-specific velocities via a master equation for a transcriptional burst model accounting for intrinsic stochasticity. The method obtains a global transition matrix by leveraging cell topic weights to integrate process-specific signals. In challenging systems, this method accurately recovers complex transitions and terminal states, while our use of first-passage time analysis provides insights into transient transitions. These results expand the limits of RNA velocity, empowering future studies of cell fate and functional responses.
Machine learning enables identification of an alternative yeast galactose utilization pathway
Authors: Harrison Marie-Claire , Ubbelohde Emily J. , LaBella Abigail L. , Opulente Dana A. , Wolters John F. , Zhou Xiaofan , Shen Xing-Xing , Groenewald Marizeth , Hittinger Chris Todd , Rokas Antonis
Published: April 2024

How genomic differences contribute to phenotypic differences is a major question in biology. The recently characterized genomes, isolation environments, and qualitative patterns of growth on 122 sources and conditions of 1,154 strains from 1,049 fungal species (nearly all known) in the yeast subphylum Saccharomycotina provide a powerful, yet complex, dataset for addressing this question. We used a random forest algorithm trained on these genomic, metabolic, and environmental data to predict growth on several carbon sources with high accuracy. Known structural genes involved in assimilation of these sources and presence/absence patterns of growth in other sources were important features contributing to prediction accuracy. By further examining growth on galactose, we found that it can be predicted with high accuracy from either genomic (92.2%) or growth data (82.6%) but not from isolation environment data (65.6%). Prediction accuracy was even higher (93.3%) when we combined genomic and growth data. After the
GAL
actose utilization genes, the most important feature for predicting growth on galactose was growth on galactitol, raising the hypothesis that several species in two orders, Serinales and Pichiales (containing the emerging pathogen
Candida auris
and the genus
Ogataea
, respectively), have an alternative galactose utilization pathway because they lack the
GAL
genes. Growth and biochemical assays confirmed that several of these species utilize galactose through an alternative oxidoreductive D-galactose pathway, rather than the canonical
GAL
pathway. Machine learning approaches are powerful for investigating the evolution of the yeast genotype–phenotype map, and their application will uncover novel biology, even in well-studied traits.
Negative correlation between soil salinity and soil organic carbon variability
Authors: Hassani Amirhossein , Smith Pete , Shokri Nima
Published: April 2024

Soil organic carbon (SOC) is vital for terrestrial ecosystems, affecting biogeochemical processes, and soil health. It is known that soil salinity impacts SOC content, yet the specific direction and magnitude of SOC variability in relation to soil salinity remain poorly understood. Analyzing 43,459 mineral soil samples (SOC < 150 g kg−1) collected across different land covers since 1992, we approximate a soil salinity increase from 1 to 5 dS m−1in croplands would be associated with a decline in mineral soils SOC from 0.14 g kg−1above the mean predicted SOC (SOC¯c= 18.47 g kg−1) to 0.46 g kg−1belowSOC¯c(~−430%), while for noncroplands, such decline is sharper, from 0.96 aboveSOC¯nc= 35.96 g kg−1to 4.99 belowSOC¯nc(~−620%). Although salinity’s significance in explaining SOC variability is minor (<6%), we estimate a one SD increase in salinity of topsoil samples (0 to 7 cm) correlates with respectiveSOC¯declines of ~4.4% and ~9.26%, relative toSOC¯candSOC¯nc. TheSOC¯decline in croplands is greatest in vegetation/cropland mosaics while lands covered with evergreen needle-leaved trees are estimated with the highestSOC¯decline in noncroplands. We identify soil nitrogen, land cover, and precipitation Seasonality Index as the most significant parameters in explaining the SOC’s variability. The findings provide insights into SOC dynamics under increased soil salinity, improving understanding of SOC stock responses to land degradation and climate warming.
Cryo-EM reveals a nearly complete PCNA loading process and unique features of the human alternative clamp loader CTF18-RFC
Authors: He Qing , Wang Feng , O’Donnell Michael E. , Li Huilin
Published: April 2024

The DNA sliding clamp PCNA is a multipurpose platform for DNA polymerases and many other proteins involved in DNA metabolism. The topologically closed PCNA ring needs to be cracked open and loaded onto DNA by a clamp loader, e.g., the well-studied pentameric ATPase complex RFC (RFC1-5). The CTF18-RFC complex is an alternative clamp loader found recently to bind the leading strand DNA polymerase ε and load PCNA onto leading strand DNA, but its structure and the loading mechanism have been unknown. By cryo-EM analysis of in vitro assembled human CTF18-RFC–DNA–PCNA complex, we have captured seven loading intermediates, revealing a detailed PCNA loading mechanism onto a 3′-ss/dsDNA junction by CTF18-RFC. Interestingly, the alternative loader has evolved a highly mobile CTF18 AAA+ module likely to lower the loading activity, perhaps to avoid competition with the RFC and to limit its role to leading strand clamp loading. To compensate for the lost stability due to the mobile AAA+ module, CTF18 has evolved a unique β-hairpin motif that reaches across RFC2 to interact with RFC5, thereby stabilizing the pentameric complex. Further, we found that CTF18 also contains a separation pin to locally melt DNA from the 3′-end of the primer; this ensures its ability to load PCNA to any 3′-ss/dsDNA junction, facilitated by the binding energy of the E-plug to the major groove. Our study reveals unique structural features of the human CTF18-RFC and contributes to a broader understanding of PCNA loading by the alternative clamp loaders.
Acoustic manipulation of multi-body structures and dynamics
Authors: Lim Melody X , VanSaders Bryan , Jaeger Heinrich M
Published: April 2024

Sound can exert forces on objects of any material and shape. This has made the contactless manipulation of objects by intense ultrasound a fascinating area of research with wide-ranging applications. While much is understood for acoustic forcing of individual objects, sound-mediated interactions among multiple objects at close range gives rise to a rich set of structures and dynamics that are less explored and have been emerging as a frontier for research. We introduce the basic mechanisms giving rise to sound-mediated interactions among rigid as well as deformable particles, focusing on the regime where the particles’ size and spacing are much smaller than the sound wavelength. The interplay of secondary acoustic scattering, Bjerknes forces, and micro-streaming is discussed and the role of particle shape is highlighted. Furthermore, we present recent advances in characterizing non-conservative and non-pairwise additive contributions to the particle interactions, along with instabilities and active fluctuations. These excitations emerge at sufficiently strong sound energy density and can act as an effective temperature in otherwise athermal systems.
Further adoption of conservation tillage can increase maize yields in the western US Corn Belt
Authors: Cambron Trevor W , Deines Jillian M , Lopez Bruno , Patel Rinkal , Liang Sang-Zi , Lobell David B
Published: April 2024

Conservation tillage can reduce soil erosion, increase soil health, and decrease labor and fuel input costs. Despite these benefits, potential yield impacts remain an important concern for farmers considering adoption. Previous research suggests that conservation tillage is likely to have the largest yield benefits in more arid conditions, but a lack of field-level analyses across climatic, management and soil conditions limits confidence in such predictions. Satellite imagery provides the opportunity to monitor agricultural lands at sub-field resolution across large spatial scales and wide environmental gradients. Here we investigate the maize yield impacts of conservation tillage in the semi-arid western US Corn Belt, using sub-field resolution datasets on tillage practices and crop yields derived from satellite data spanning four states (Nebraska, Kansas, South Dakota, and North Dakota) between 2008 and 2020. On these datasets, we estimate heterogenous yield outcomes for several thousand maize fields across gradients in climate, soil quality and irrigation status by using a causal forests analysis, an adaptation of the random forests machine-learning algorithm for causal inference on observational data. We find that long-term adoption of conservation tillage increased rainfed maize yields by an average of 9.9% in the region. Impacts on irrigated yields were small and not statistically significant. These results, along with an analysis of variables related to greater than average yield benefits, indicate that improved water infiltration and retention are the primary reasons for conservation tillage benefits. Despite yield benefits, many fields estimated to see increased yields under long term low till have not adopted the practice. Therefore, we identify specific counties likely to benefit most from increased levels of adoption. Our results strengthen the understanding of the impacts of conservation agriculture on crop yields and help define environments and counties most likely to benefit from conservation tillage.
Investigation of an electrode-driven hydrogen plasma method for in situ cleaning of tin-based contamination
Authors: PENG 彭 Yichao 怡超 , YE 叶 Zongbiao 宗标 , WANG 王 Sishu 思蜀 , PU 蒲 Guo 国 , LIU 刘 Xianyang 显洋 , YUAN 苑 Congcong 聪聪 , LIAO 廖 Jiashu 加术 , WEI 韦 Jianjun 建军 , YU 余 Xingang 新刚 , GOU 芶 Fujun 富均
Published: April 2024

To prolong the service life of optics, the feasibility of in situ cleaning of the multilayer mirror (MLM) of tin and its oxidized contamination was investigated using hydrogen plasma at different power levels. Granular tin-based contamination consisting of micro- and macroparticles was deposited on silicon via physical vapor deposition (PVD). The electrode-driven hydrogen plasma at different power levels was systematically diagnosed using a Langmuir probe and a retarding field ion energy analyzer (RFEA). Moreover, the magnitude of the self-biasing voltage was measured at different power levels, and the peak ion energy was corrected for the difference between the RFEA measurements and the self-biasing voltage (

). XPS analysis of O 1s and Sn 3d peaks demonstrated the chemical reduction process after 1 W cleaning. Analysis of surface and cross-section morphology revealed that holes emerged on the upper part of the macroparticles while its bottom remained smooth. Hills and folds appeared on the upper part of the microparticles, confirming the top-down cleaning mode with hydrogen plasma. This study provides an in situ electrode-driven hydrogen plasma etching process for tin-based contamination and will provide meaningful guidance for understanding the chemical mechanism of reduction and etching.
Design of an enhanced spatial resolution indoor plantar strain and gait analysis setup for biomedical applications
Authors: Mishra Manish , Sahu Prasant Kumar , Datta Mrinal
Published: April 2024

In the recent years, measurement of plantar strain and gait analysis has gained huge attention and plays a pivotal role in monitoring posture related ailments or Diabetic Foot Ulcer (DFU). Fibre Bragg Grating Arrays (closely spaced FBGs), another category of optical sensors, are employed in this study to understand the strain and gait of human foot. These arrays offer critical advantages such as enhanced sensitivity, data acquisition, multiplexing abilities, and sensor location effect compensation. For experimentation, five arrays were distributed among different regions (Upper, Medial, and Heel) of foot and their strain patterns for six volunteers (three male and three female) were recorded for eighty seconds. The data was analysed in two ways, Combined (data of array sensors were averaged to target the whole area) and Individual (for independent analysis of each sensor in array). Incoherent transitions and strain patterns of FBGs within the same arrays observed in individual analysis, explains enhanced resolution capabilities of the arrays. Strain mapping of sensor behaviour also confirmed the identification of various forms of gait i.e., Heel Strike, Flat Foot, Heel Off, and Zero Contact. The average standard deviation values for the arrays was reported below 0.16.
Cohomology operations for moment-angle complexes and resolutions of Stanley–Reisner rings
Authors: Amelotte Steven , Briggs Benjamin
Published: April 2024

A fundamental result in toric topology identifies the cohomology ring of the moment-angle complex

Z

K

\mathcal {Z}_K

associated to a simplicial complex

K
K

with the Koszul homology of the Stanley–Reisner ring of

K
K

. By studying cohomology operations induced by the standard torus action on the moment-angle complex, we extend this to a topological interpretation of the minimal free resolution of the Stanley–Reisner ring. The exterior algebra module structure in cohomology induced by the torus action recovers the linear part of the minimal free resolution, and we show that higher cohomology operations induced by the action (in the sense of Goresky–Kottwitz–MacPherson [Invent. Math. 131 (1998), pp. 25–83]) can be assembled into an explicit differential on the resolution. Describing these operations in terms of Hochster’s formula, we recover and extend a result due to Katthän [Mathematics 7 (2019), no. 7, p. 605]. We then apply all of this to study the equivariant formality of torus actions on moment-angle complexes. For these spaces, we obtain complete algebraic and combinatorial characterisations of which subtori of the naturally acting torus act equivariantly formally.
Extensions of vector bundles on the Fargues–Fontaine curve II
Authors: Hong Serin
Published: April 2024

Given two arbitrary vector bundles on the Fargues–Fontaine curve, we completely classify all vector bundles which arise as their extensions.
Global Fintech Revolution
Authors: Lu Lerong
Published: April 2024

This book is a timely work examining the ongoing Fintech revolution across the world. Fintech denotes the close interaction between the financial services industry and latest information technologies like big data, cloud computing, blockchain, and artificial intelligence. Fintech has produced novel financial services, products, institutions, and business models. The Fintech revolution has brought enormous benefits for financial institutions and their consumers, such as cutting service costs, improving business efficiency, and enabling high-quality product options. Nonetheless, Fintech has posed multiple legal, ethical, and regulatory challenges for policy-makers and financial authorities regarding data security, consumer protection, and financial stability. This book attempts to accomplish three tasks. First, it provides readers with a better understanding of Fintech by examining its conceptual meanings, main forms, special features, and social values. Second, it investigates the complex, dynamic, and multidimensional Fintech ecosystem. It assesses global Fintech hubs in six continents, while discussing the ecosystem’s key players like Fintech regulators (e.g., regulatory strategy, regulatory sandbox, and RegTech) and Fintech corporations (e.g., incumbent banks, financial holding companies, Fintech unicorns, BigTech firms, and Metaverse platforms). Third, this book conducts detailed Fintech case studies in three areas, including app-based banking, online P2P lending, and digital money and payment. It argues that Fintech contributes to a more equal, democratic, inclusive, and sustainable financial system. This book should appeal to a diverse readership across law, business, finance, computer science, and sociology disciplines, providing useful information for academics, university students, practitioners, policy-makers, and think tanks researching the global Fintech revolution.
Understanding Fintech
Authors: Lu Lerong
Published: April 2024

This chapter conducts an inquiry into Fintech’s conceptual meaning, business models, special characteristics, and social values. It clarifies what types of financial institutions, activities, products, and services will be covered by this novel concept. It would be necessary for readers to have a deep understanding of Fintech before studying relevant application scenarios, commercial implications, and regulatory challenges. The ‘fin’ (finance) part of Fintech represents the unchanged nature of finance that finds the best way to match money supply and demand in our economy. The ‘tech’ (technology) part of Fintech stands for cutting-edge technological innovations, including artificial intelligence, blockchain, cloud computing, data (big data), and e-commerce. The chapter summarises common features of Fintech businesses, such as disintermediation, automation, innovation, virtualisation, customer centricity, scalability, and accessibility. It recognises the economic and social values of Fintech that make the financial industry more efficient, equal, democratic, inclusive, and sustainable.
Fintech Ecosystem—Part One
Authors: Lu Lerong
Published: April 2024

This chapter investigates the so-called Fintech ecosystem. Fintech has evolved from technology-driven financial products and services to more complex and multidimensional ecosystems, with various players interacting with each other to shape the industry development. The key players include Fintech corporations, consumers, regulators, governments, and investors. This chapter studies two elements of the Fintech ecosystem: the venues (global Fintech hubs) and financial regulators. It assesses the competitive advantages, local features, and regulatory environments of Fintech centres in six continents, including San Francisco, New York, Sydney, Beijing, Shanghai, Shenzhen, Mumbai, Singapore, Paris, Frankfurt, London, Dubai, and Nairobi. It then investigates Fintech regulators’ strategies and toolkits, such as the regulatory sandbox and RegTech, and considers how financial authorities balance multiple policy objectives (e.g., promote financial innovation, ensure an adequate degree of consumer protection, and maintain financial stability) when supervising Fintech.
The Shackles of History
Authors: Oweidat Nadia
Published: April 2024

This chapter discusses Abu Zayd’s approach to history and its significance, showing why it is controversial and yet foundational to the Islamic modernist movement. Abu Zayd wrote, because “the two issues of history and religion are in fact tied to one another at the conceptual level as well as the methodological level. Settling one would inevitably and logically lead to settling the other.” If history were to be subjected to academic scrutiny, then the actions and judgments of those who speak in Islam’s name would inevitably be examined as well, causing a shift in their public perception. In this atmosphere, in which questioning history can quickly lead to questioning one’s faith, Abu Zayd asked, “How is it that we are supposed to study and learn from history?”
Conclusion
Authors: Oweidat Nadia
Published: April 2024

The conclusion discusses Abu Zayd’s enduring legacy, measuring its strengths and limitations, particularly his spearheading a historic process that would shake the foundations of traditional Islamic thought and open a new door for radical reform. This chapter explores the modernist attempt to find a connection between Islamic tradition and such modern values as equality between Muslims and non-Muslims or between men and women. Resolving, or at least clarifying, this issue remains a project of profound implications beyond abstract academic debate, as it has wide-ranging repercussions in the everyday life of Muslim communities across the globe.
Recent history and future trends in the study of insect behavior in North America
Authors: Evenden Maya L , Konopka Joanna K
Published: April 2024

We examine the recent history and future trends in the field of insect behavior in North America. This project stemmed from participation in a section symposium at a Joint Meeting of the Entomological Societies of America (ESA), Canada (ESC), and British Columbia (ESBC) in Vancouver, British Columbia, Canada, in 2022. Each participating team in the symposium was asked to address 3 questions about their subdiscipline: (i) How has your subdiscipline changed in the last 15 yr? (ii) How will your subdiscipline change as a discipline over the next 15 yr? (iii) What can ESA and the Plant-Insect Ecosystem section (P-IE) do to help members who study your subdiscipline and improve the understanding of the subdiscipline? To address the first question, we used data from 2008 to 2022 on presentations given at ESA meetings, literature searches, and funding databases. To predict changes in the discipline of insect behavior in the future, we examined data pertaining to student participation in the field and educational opportunities in insect behavior. Our main findings are that insect behavior is an integral part of entomological research with an important future role to play in understanding insect biology under climate change. We provide multiple lines of evidence illustrating the importance of insect behavior in multidisciplinary research across a variety of scientific fields. We conclude by answering the third question with suggestions for the promotion of insect behavior research at annual ESA meetings and for gathering more information to further understand the importance of the subdiscipline of insect behavior.
Feminizing Gender Affirming Breast Surgery: Procedural Outcomes at a Single Academic Institution
Authors: Sanchez Figueroa Nicole , Kuruoglu Doga , Fahradyan Vahe , Tran Nho , Sharaf Basel , Martínez-Jorge Jorys
Published: April 2024

Background

Implant-based breast augmentation is a gold standard procedure for transfeminine patients to create a more feminine-appearing chest. In many cases, ancillary procedures are performed simultaneously to achieve an optimal aesthetic result.

Objectives

To determine the clinical outcomes of patients undergoing feminizing gender-affirming breast surgery in a single academic institution.

Methods

A retrospective electronic chart review of feminizing gender-affirming breast surgery patients at Mayo Clinic, Rochester from 2017 to 2022 was conducted. Patients demographics and surgical outcomes were gathered. A survival analysis was performed to obtain the time-to-event complication rate.

Results

Over 5 years, 46 patients (92 breasts) were included. The mean age was 39 years (SD ±15), and most had an above-normal Body Mass Index (58.7%). Thirty (65%) had previous gender-affirming surgeries. The mean implant volume was 289 ml (SD ±95; 140 - 520). Most implants were placed in a subglandular plane (81%) with an inframammary fold incision (91.3%). All implants used were smooth round cohesive silicone gel implants. Ancillary procedures were performed in thirty-two patients (69.57%). Eight patients presented complications (4 major vs 4 minor) in a median postoperative follow-up of 372 vs 392 days; at 1-month follow-up, the probability of a complication to have occurred is 2.17% (95% CI: 0–6.3%) vs 5% (95% CI: 0–11.5%) and at 1 year is 10.21% (95% CI: 0–20.9%) vs 12.5% (95% CI: 0–23.4%) ​which remain the same up to 4 years.

Conclusions

Breast augmentation with implants is a safe procedure to achieve feminization of the breast with a low rate of complications.
Re-discovery of MS-347a as a fungicide candidate through a new drug discovery platform with a multidrug-sensitive Saccharomyces cerevisiae screening system and the introduction of a global secondary metabolism regulator, laeA gene
Authors: Honma Sota , Kimishima Aoi , Kimishima Atsushi , Honsho Masako , Kojima Hiroki , Tokiwa Toshiyuki , Nishitomi Atsuka , Kato Satoshi , Kondo Naozumi , Araki Yasuko , Takahashi Tadashi , Chinen Takumi , Usui Takeo , Fuji Shin-ichi , Ito Kotaro , Asami Yukihiro
Published: April 2024

We found that the culture broth of fungi showed anti-fungal activity against multidrug-sensitive budding yeast. However, we could not identify the anti-fungal compound due to the small quantity. Therefore, we attempted to increase the productivity of the target compound by the introduction of a global secondary metabolism regulator, laeA to the strain, which led to the successful isolation of 10-folds greater amount of MS-347a (1) than Aspergillus sp. FKI-5362. Compound 1 was not effective against Candida albicans and the detailed anti-fungal activity of 1 remains unverified. After our anti-fungal activity screening, 1 was found to inhibit the growth of broad plant pathogenic fungal species belonging to the Ascomycota. It is noteworthy that 1 showed little insecticidal activity against silkworms, suggesting its selective biological activity against plant pathogenic fungi. Our study implies that the combination strategy of multidrug-sensitive yeast and the introduction of laeA is useful for new anti-fungal drug discovery.
Macro-based collagen quantification and segmentation in picrosirius red-stained heart sections using light microscopy
Authors: Kammerer Julian , Cirnu Alexandra , Williams Tatjana , Hasselmeier Melanie , Nörpel Mike , Chen Ruping , Gerull Brenda
Published: April 2024

Picrosirius red staining constitutes an important and broadly used tool to visualize collagen and fibrosis in various tissues. Although multiple qualitative and quantitative analysis methods to evaluate fibrosis are available, many require specialized devices and software or lack objectivity and scalability. Here, we aimed to develop a versatile and powerful “QuantSeg” macro in the FIJI image processing software capable of automated, robust, and quick collagen quantification in cardiac tissue from light micrographs. To examine different patterns of fibrosis, an optional segmentation algorithm was implemented. To ensure the method’s validity, we quantified the collagen content in a set of wild-type versus plakoglobin-knockout murine hearts exhibiting extensive fibrosis using both the macro and an established, fluorescence microscopy-based method, and compared results. To demonstrate the capabilities of the segmentation feature, rat hearts were examined post-myocardial infarction. We found the QuantSeg macro to robustly detect the differences in fibrosis between knockout and control hearts. In sections with low collagen content, the macro yielded more consistent results than using the fluorescence microscopy-based technique. With its wide range of output parameters, ease of use, cost effectiveness, and objectivity, the QuantSeg macro has the potential to become an established method for analysis of PSR-stained tissue. The novel segmentation feature allows for automated evaluation of different patterns of cardiac fibrosis for the first time.
Expanding global health dermatology leadership: launching the GLODERM international mentorship programme
Authors: Strahan Alexis G , Davies Olivia M  T , Fernández Lucía T , Gaylord Inena Wa Inena , Mekonnen Yared Getachew , Grijsen Marlous L , Ollague Jose E , Sabushimike Doriane , Polo Silveira Luisa , Maurer Toby , Dodiuk-Gad Roni P , Singal Archana , Lim Henry W , Bhose Arpita , Lubov Janet E , Jain Shivani , Zehtab Morvarid , Allison Tom , Guerin Maud , Enbiale Wendemagegn , Rehmus Wingfield , Wanat Karolyn A , Fuller L Claire , Bailey Elizabeth , Freeman Esther E
Published: April 2024

The lack of access to dermatological care is a global health crisis. Providing intentional mentorship to emerging leaders in low- and middle-income countries is foundational to increasing access to care. The GLODERM Mentorship Programme is a first-of-its-kind programme created to support changemakers in global health dermatology in enhancement of leadership skills.
A Validated Chiral Chromatography Method for Enantiomeric Separation of Pomalidomide in Human Plasma
Authors: Vardhan Gyan , Kumar Vikas , Sahu Puran Lal , Prakash Anuj , Prasad Ramasare , Handu Shailendra , Nath Uttam Kumar , Dhamija Puneet
Published: April 2024

In the present work, new chiral stationary phase high-performance liquid chromatography (CSP-HPLC) method was established and validated for the quantification of pomalidomide (PMD) enantiomers in human plasma. The chromatographic enantiomeric separation was achieved on a Daicel-CSP, Chiralpack IA 4.6 × 250 mm, 5 μm; because of its advantages of high degree of retention, high resolution capacity, better reproducibility, ability to produce lower back pressure and low degree of tailing. The mobile phase was maintained as methanol: glacial acetic acid (499.50 ml:50 μL). Ultraviolet wavelength for detection was 220 nm. PMD enantiomer-I and enantiomer-II were separated at 8.83 and 15.34 min, respectively. Limit of detection and limit of quantification for each enantiomer and the calibration curve of standard PMD was linear in range between 10–5,000 ng mL−1. The method was validated according to The International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use (ICH(Q2R1)) specific guidelines. We found no interference peak with PMD chromatogram obtained. This is a simple, reliable and specific method for detection and quantification of enantiomer of PMD in human plasma sample.
The association between hydrochlorothiazide use and non-melanoma skin cancer in kidney transplant recipients
Authors: Rahamimov Ruth , Telem Shay , Davidovichi Batia , Bielopolski Dana , Steinmetz Tali , Nesher Eviatar , Lichtenberg Shelly , Rozen-Zvi Benaya
Published: April 2024

Background

hydrochlorothiazide (HCTZ) diuretics were correlated with an increased risk of non-melanoma skin cancer (NMSC) and melanoma in the general population. Information is a scarce regarding this effect in kidney transplant recipients who are at increased risk of skin malignancies under immunosuppression.

Methods

Single-center retrospective analysis of adult kidney transplant recipients between 1 January 2010 and 31 December 2015. The primary outcome of the study was the first diagnosis of skin cancer that was removed and pathologically analyzed. Exposure to thiazides was defined as HCTZ use daily for at least one year at a dose of 12.5 mg.

Results

Among 520 kidney transplant recipients, 50 (9.4%) were treated with HCTZ. During a median follow-up of 9.8 years, 67 patients underwent surgical removal and pathological analysis of at least one skin cancer. Exposure to HCTZ during the 3 years following transplantation was associated with an increased risk of skin cancer (P = 0.004). In a multivariate model, there was a significant association between HCTZ exposure and NMSC (HR 2.54, 95%CI 1.26–5.15, P = 0.007). There was a higher rate of basal cell carcinoma with HCTZ exposure, according to both univariate and multivariate analyses (HR 2.61, 95%CI 1.06–6.43, P = 0.037) and (HR 3.03, 95%CI 1.22–7.55, P = 0.017, respectively). However, no significant association was observed between HCTZ exposure and squamous cell carcinoma.

Conclusions

These findings suggest a benefit of increased frequency of dermatologist inspection in kidney transplant recipients receiving HCTZ especially in increased ultraviolet exposure area.
Differential sex-dependent susceptibility to diastolic dysfunction and arrhythmia in cardiomyocytes from obese diabetic heart failure with preserved ejection fraction model
Authors: Mira Hernandez Juliana , Shen Erin Y , Ko Christopher Y , Hourani Zaynab , Spencer Emily R , Smoliarchuk Daria , Bossuyt Julie , Granzier Henk , Bers Donald M , Hegyi Bence
Published: April 2024

Aims

Sex differences in heart failure with preserved ejection fraction (HFpEF) are important, but key mechanisms involved are incompletely understood. While animal models can inform about sex-dependent cellular and molecular changes, many previous pre-clinical HFpEF models have failed to recapitulate sex-dependent characteristics of human HFpEF. We tested for sex differences in HFpEF using a two-hit mouse model (leptin receptor–deficient db/db mice plus aldosterone infusion for 4 weeks; db/db + Aldo).

Methods and results

We performed echocardiography, electrophysiology, intracellular Ca2+ imaging, and protein analysis. Female HFpEF mice exhibited more severe diastolic dysfunction in line with increased titin N2B isoform expression and PEVK element phosphorylation and reduced troponin-I phosphorylation. Female HFpEF mice had lower BNP levels than males despite similar comorbidity burden (obesity, diabetes) and cardiac hypertrophy in both sexes. Male HFpEF mice were more susceptible to cardiac alternans. Male HFpEF cardiomyocytes (vs. female) exhibited higher diastolic [Ca2+], slower Ca2+ transient decay, reduced L-type Ca2+ current, more pronounced enhancement of the late Na+ current, and increased short-term variability of action potential duration (APD). However, male and female HFpEF myocytes showed similar downregulation of inward rectifier and transient outward K+ currents, APD prolongation, and frequency of delayed afterdepolarizations. Inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII) reversed all pathological APD changes in HFpEF in both sexes, and empagliflozin pre-treatment mimicked these effects of CaMKII inhibition. Vericiguat had only slight benefits, and these effects were larger in HFpEF females.

Conclusion

We conclude that the db/db + Aldo pre-clinical HFpEF murine model recapitulates key sex-specific mechanisms in HFpEF and provides mechanistic insights into impaired excitation–contraction coupling and sex-dependent differential arrhythmia susceptibility in HFpEF with potential therapeutic implications. In male HFpEF myocytes, altered Ca2+ handling and electrophysiology aligned with diastolic dysfunction and arrhythmias, while worse diastolic dysfunction in females may depend more on altered myofilament properties.
The influence of the post-autotomy regeneration of a sexual trait and mating tactics in a fiddler crab
Authors: Ribeiro Pablo D , Farías Nahuel E , Ocampo Emiliano H , Nuñez Jesús D , Luppi Tomás A
Published: April 2024

Male fiddler crabs own an enlarged claw which is a weapon and an ornament. The enlargement of this claw begins from the juvenile stage and continues throughout life. Males may voluntarily lose (i.e., autotomize) this claw. After several molts males may regenerate a new claw, called leptochelous, which acquires a similar length but a lower muscle mass area than the original one, called brachychelous. In some species, regenerated claws develop permanently as leptochelous, the population having 2 discrete claw morphologies. Other species present morphological variations with leptochelous and brachychelous being 2 ends of a continuum. In the species Leptuca uruguayensis, we studied the morphological variation of this enlarged claw, whether it may be caused by its regeneration at different male sizes, and its consequences on mating success. We found that claws could not be discriminated as discrete morphs, suggesting a morphological continuum from brachychelous to leptochelous. Regenerated claws in the laboratory were initially small and proportional to body size, although a field experiment confirmed that claw size is recovered after several molts. Morphological variation may be caused by energetic limitations where males of different sizes must differently trade-off between restitution of claw length (ornament function) or claw muscle area (weapon function). Fiddler crabs use 2 mating tactics with different levels of female choice. However, regardless of the mating tactic, leptochelous males were at a disadvantage at high densities, although not at low densities, suggesting that the consequences of autotomy and regeneration on mating success may depend on the social context.
Association between lipoprotein(a) and premature atherosclerotic cardiovascular disease: a systematic review and meta-analysis
Authors: Tian Xu , Zhang Nan , Tse Gary , Li Guangping , Sun Yihong , Liu Tong
Published: April 2024

Aims

High lipoprotein(a) [Lp(a)] level has been demonstrated as an important risk factor for atherosclerotic cardiovascular diseases (ASCVD) amongst the older populations, whereas its effects in the younger population remain unclear. This study evaluated the associations between Lp(a) and the risk of premature ASCVD.

Method and results

PubMed and Embase were searched for related studies until 12 November 2023. Fifty-one studies including 100 540 participants were included. Mean age of patients ranged from 35.3 to 62.3 years. The proportion of male participants ranged from 0% to 100%. The mean follow-up was provided in five studies ranging from 1 year to 40 years. The definition of elevated Lp(a) varied among studies, such as >30 mg/dL, >50 mg/dL, the top tertiles, the top quartiles, the top quintiles, and so on. Higher Lp(a) was significantly associated with the composite ASCVD [odds ratio (OR): 2.15, 95% confidence interval (95% CI): 1.53–3.02, P < 0.001], especially for coronary artery disease (OR: 2.44, 95% CI: 2.06–2.90, P < 0.001) and peripheral arterial disease (OR: 2.56, 95% CI: 1.56–4.21, P < 0.001). This association remained significant in familial hypercholesterolaemia (FH) (OR: 3.11, 95% CI: 1.63–5.96, P < 0.001) and type 2 diabetes mellitus (T2DM) patients (OR: 2.23; 95% CI: 1.54–3.23, P < 0.001).Significant results were observed in South Asians (OR: 3.71, 95% CI: 2.31–5.96, P < 0.001), Caucasians (OR: 3.17, 95% CI: 2.22–4.52, P < 0.001), and patients with baseline low-density lipoprotein cholesterol (LDL-c) level ≥ 2.6 mmol/L.

Conclusion

Elevated Lp(a) predicts the risk of the composite or individual ASCVD in young, regardless of study design, gender, population characteristics (community or hospitalized), different premature definitions, and various Lp(a) measurement approaches. This association was important in South Asians, Caucasians, FH patients, T2DM patients, and patients with baseline LDL-c level ≥ 2.6 mmol/L.
Frequency of misdiagnosis in hypertrophic cardiomyopathy
Authors: Nielsen Søren K , Rasmussen Torsten B , Hey Thomas M , Zaremba Tomas , Lassen Jens F , Mogensen Jens
Published: April 2024

Background and aims

Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy (LVH) ≥15 mm. The condition is often hereditary, and family screening is recommended to reduce the risk of adverse disease complications and premature death among relatives. Correct diagnosis of index patients is important to ensure that only relatives at risk of disease development are invited for family screening. To investigate whether patients with International Classification of Disease, Tenth Revision (ICD-10) codes for HCM (DI421) or hypertrophic obstructive cardiomyopathy (HOCM) (DI422) fulfilled recognized diagnostic criteria.

Methods

All patients with ICD-10 codes for HCM or HOCM at a Department of Cardiology were identified and had their diagnosis validated by a cardiac investigation or a review of their medical records and previous investigations.

Results

A total of 240 patients had ICD-10 codes for HCM/HOCM, of whom 202 (84%, 202/240) underwent re-examination, while 38 (16%, 38/240) had their hospital notes reviewed. A total of 76 patients (32%, n = 76/240) did not fulfil diagnostic criteria, of whom 39 (51%, n = 39/76) had normal (10 mm) or modest LV wall thickness (11–14 mm). The remaining 37 patients (49%, n = 37/76) had LVH ≥15 mm, which was well explained by uncontrolled hypertension (32%, n = 24/76), aortic valve stenosis (19%, n = 7/76), or wild-type amyloidosis (16%, n = 6/76).

Conclusion

One-third of patients with ICD-10 codes for HCM or HOCM did not fulfil recognized diagnostic criteria. Incorrect diagnosis of HCM may cause unnecessary family investigations, which may be associated with anxiety, and a waste of healthcare resources. This highlights the need for specialized cardiomyopathy services to ensure correct diagnosis and management of HCM.
Celiac artery mesenteric fat measurement with endosonography (CAMEUS) reliably correlates with obesity and related comorbidities
Authors: Bazerbachi Fateh , Baroud Serge , Levy Michael J , Maselli Daniel B , Vargas Eric J , Bofill-Garcia Aliana , Law Ryan J , Chandrasekhara Vinay , Storm Andrew C , Gleeson Ferga C , Rajan Elizabeth , Iyer Prasad G , Watt Kymberly D , Abu Dayyeh Barham K
Published: April 2024

Background

Visceral fat represents a metabolically active entity linked to adverse metabolic sequelae of obesity. We aimed to determine if celiac artery mesenteric fat thickness can be reliably measured during endoscopic ultrasound (EUS), and if these measurements correlate with metabolic disease burden.

Methods

This was a retrospective analysis of patients who underwent celiac artery mesenteric fat measurement with endosonography (CAMEUS) measurement at a tertiary referral center, and a validation prospective trial of patients with obesity and nonalcoholic steatohepatitis who received paired EUS exams with CAMEUS measurement before and after six months of treatment with an intragastric balloon.

Results

CAMEUS was measured in 154 patients [56.5% females, mean age 56.5 ± 18.0 years, body mass index (BMI) 29.8 ± 8.0 kg/m2] and was estimated at 14.7 ± 6.5 mm. CAMEUS better correlated with the presence of non-alcoholic fatty liver disease (NAFLD) (R2 = 0.248, P < 0.001) than BMI (R2 = 0.153, P < 0.001), and significantly correlated with metabolic parameters and diseases. After six months of intragastric balloon placement, the prospective cohort experienced 11.7% total body weight loss, 1.3 points improvement in hemoglobin A1c (P = 0.001), and a 29.4% average decrease in CAMEUS (−6.4 ± 5.2 mm, P < 0.001). CAMEUS correlated with improvements in weight (R2 = 0.368), aspartate aminotransferase to platelet ratio index (R2 = 0.138), and NAFLD activity score (R2 = 0.156) (all P < 0.05).

Conclusions

CAMEUS is a novel measure that is significantly correlated with critical metabolic indices and can be easily captured during routine EUS to risk-stratify susceptible patients. This station could allow for EUS access to sampling and therapeutics of this metabolic region.
Females Present Reduced Minimum Toe Clearance During Walking As Compared to Males in Active Older Adults
Authors: Faria Aurélio , Sousa Tiago , Vaz João R , Gabriel Ronaldo , Gama Jorge , Stergiou Nikolaos
Published: April 2024

Background

Physical decline due to aging has been associated with the risk of falls. Minimum toe clearance (MTC) is a gait parameter that might play a role in the mechanism of tripping and falling. However, it is unclear if there are any sex-related effects regarding MTC as people age. The present study investigated if there are sex-related differences in MTC in older active adults.

Methods

Twenty-three females and 23 males (F: 65.5 ± 4.8 years; M: 61.9 ± 5.2 years) walked on a treadmill at a preferred walking speed, while kinematic data were obtained at a sampling frequency of 100 Hz and up-sampled to 120 and 240 Hz. MTC was calculated from the kinematics data and evaluated concerning its magnitude (ie, MTC and MTC/leg length), the time between left/right MTC (ie, T-MTC), amount of variability (ie, coefficient of variation [CV] and coefficient of variation modified [CVm]), and temporal structure of variability, that is, the complexity of the time series (ie, MTC α, T-MTC α).

Results

No sex effects were found for MTC/leg length, for the amount of variability (ie, CV and CVm), and for the complexity of the time series (MTC α, T-MTC α). However, females exhibited significantly lower MTC and T-MTC after adjusting for walking speed, mass, and age as covariates.

Conclusions

The reduced MTC in females suggests a potential sex-related disparity in the risk of tripping and falling among active older adults.