bluuebunny/crossref_metadata_2025 huggingface dataset:
Declining ecological resilience and invasion resistance under climate change in the sagebrush region, United States
Authors: Schlaepfer Daniel R. , Chambers Jeanne C. , Urza Alexandra K. , Hanberry Brice B. , Brown Jessi L. , Board David I. , Campbell Steven B. , Clause Karen J. , Crist Michele R. , Bradford John B.
Published: November 2024

In water‐limited dryland ecosystems of the Western United States, climate change is intensifying the impacts of heat, drought, and wildfire. Disturbances often lead to increased abundance of invasive species, in part, because dryland restoration and rehabilitation are inhibited by limited moisture and infrequent plant recruitment events. Information on ecological resilience to disturbance (recovery potential) and resistance to invasive species can aid in addressing these challenges by informing long‐term restoration and conservation planning. Here, we quantified the impacts of projected future climate on ecological resilience and invasion resistance (R&R) in the sagebrush region using novel algorithms based on ecologically relevant and climate‐sensitive predictors of climate and ecological drought. We used a process‐based ecohydrological model to project these predictor variables and resulting R&R indicators for two future climate scenarios and 20 climate models. Results suggested widespread future R&R decreases (24%–34% of the 1.16 million km2 study area) that are generally consistent among climate models. Variables related to rising temperatures were most strongly linked to decreases in R&R indicators. New continuous R&R indices quantified responses to climate change; particularly useful for areas without projected change in the R&R category but where R&R still may decrease, for example, some of the areas with a historically low R&R category. Additionally, we found that areas currently characterized as having high sagebrush ecological integrity had the largest areal percentage with expected declines in R&R in the future, suggesting continuing declines in sagebrush ecosystems. One limitation of these R&R projections was relatively novel future climatic conditions in particularly hot and dry areas that were underrepresented in the training data. Including more data from these areas in future updates could further improve the reliability of the projections. Overall, these projected future declines in R&R highlight a growing challenge for natural resource managers in the region, and the resulting spatially explicit datasets provide information that can improve long‐term risk assessments, prioritizations, and climate adaptation efforts.
Evaluating multiplicity reporting in analgesic clinical trials: An analytical review
Authors: Khan Maaz S. , Zarmer Lori F. , Liang Jie , Saroukhani Sepideh , Lucas Anthony R. , McCartney Colin J. L. , Chaudhry Rabail
Published: November 2024

Background and Objectives

Analgesia trials often demands multiple comparisons to assess various treatment arms, outcomes, or repeated assessments. These multiple comparisons risk inflating the false positive rate. Multiplicity correction in recent analgesic randomized controlled trials (RCTs) remains unclear despite statistical method advancements and regulatory guidelines. Our study aimed to identify reporting inadequacies in multiple analysis adjustments and explanations to understand these deficiencies.

Databases and Data Treatment

This review analysed RCTs from the European Journal of Pain, the Journal of Pain, and PAIN, published between January 2018 and December 2022. We included randomized, double‐blind trials focusing on pain outcomes. Data extraction, managed by three researchers using predefined criteria, included trial characteristics, multiplicity presence, and correction methods. Descriptive statistical analyses included Fisher's exact, and Holm method for multiple comparisons.

Results

Out of 112 articles, 48 pre‐specified a primary analysis plan. Multiple analyses were observed in 65 articles, with 60% adjusting for all comparisons, primarily using the Bonferroni method. Compared with previous studies, no significant changes in multiplicity correction practices were noted when stratified by trial type, size, and sponsor.

Conclusions

The study reveals a persistent reliance on multiple comparisons in analgesic clinical trials without a corresponding increase in multiplicity corrections emphasizing a need for enhanced reporting and implementation of statistical adjustments. We acknowledge limitations in categorizing studies, the use of a surrogate for the trial stage, and sourcing data from journal webpages rather than a database.

Significance Statement

This study flags inadequate reporting on multiplicity correction in analgesic trials, stressing the risk of false positives and the urgent need for enhanced reporting to boost reproducibility.
Aberrant Energy Metabolism in Tumors and Potential Therapeutic Targets
Authors: Fan Shuhao , Guo Jianhua , Nie Hui , Xiong Huabao , Xia Yong
Published: November 2024

Energy metabolic reprogramming is frequently observed during tumor progression as tumor cells necessitate adequate energy production for rapid proliferation. Although current medical research shows promising prospects in studying the characteristics of tumor energy metabolism and developing anti‐tumor drugs targeting energy metabolism, there is a lack of systematic compendiums and comprehensive reviews in this field. The objective of this study is to conduct a systematic review on the characteristics of tumor cells' energy metabolism, with a specific focus on comparing abnormalities between tumor and normal cells, as well as summarizing potential targets for tumor therapy. Additionally, this review also elucidates the aberrant mechanisms underlying four major energy metabolic pathways (glucose, lipid, glutamine, and mitochondria‐dependent) during carcinogenesis and tumor progression. Through the utilization of graphical representations, we have identified anomalies in crucial energy metabolism pathways, encompassing transporter proteins (glucose transporter, CD36, and ASCT2), signaling molecules (Ras, AMPK, and PTEN), as well as transcription factors (Myc, HIF‐1α, CREB‐1, and p53). The key molecules responsible for aberrant energy metabolism in tumors may serve as potential targets for cancer therapy. Therefore, this review provides an overview of the distinct energy‐generating pathways within tumor cells, laying the groundwork for developing innovative strategies for precise cancer treatment.
Harnessing Cattail Biomass for Sustainable Fibers and Engineered Bioproducts: A Review
Authors: Parvin Mahmuda , Shadhin Md , Dulal Marzia , Rahman Mashiur
Published: November 2024

Cattail (Typha), a wetland plant, is emerging as a sustainable materials resource. While most of the Typha species are proven to be a fiber‐yielding crop, Typha latifolia exhibits the broadest leaf size (5–30 mm), yields highest amount of fiber (≈190.9 g), and captures maximum CO2 (≈1270 g). Alkaline retting is the most efficient degumming process for cattail fibers to achieve maximum fiber yield (30%–46%). Cattail leaves exhibit a distinctive bionic structural model consisting of epidermis and leaf blade at macro level and non‐diaphragm aerenchyma, fiber cables, partitions, and diaphragms at micro level. Cattail fibers hold promise to be utilized as a high‐performance composite part and as efficient energy storage devices in clean energy vehicles. The former is attributed to their lower density (≈1.26–1.39 gm/cm3) and higher tensile modulus (≈66.1 GPa after treatment), while the latter is attributed to their porous structure and chemical stability. Therefore, integrating the knowledge of plant biology and materials chemistry is crucial for enhancing fiber characteristics and producing engineered bioproducts. The environmental benefits of cattails, degumming methods, leaf and fiber structures, their properties and applications is reviewed. Finally, it discussed future research directions aimed at developing bioengineered, biodegradable products from it with minimal environmental impact.
Structural Disconnections Caused by White Matter Hyperintensities in Post‐Stroke Spatial Neglect
Authors: Röhrig Lisa , Karnath Hans‐Otto
Published: November 2024

White matter hyperintensities (WMH), a common feature of cerebral small vessel disease, affect a wide range of cognitive dysfunctions, including spatial neglect. The latter is a disorder of spatial attention and exploration typically after right hemisphere brain damage. To explore the impact of WMH on neglect‐related structural disconnections, the present study investigated the indirectly quantified structural disconnectome induced by either stroke lesion alone, WMH alone, or their combination. Furthermore, we compared different measures of structural disconnection—voxel‐wise, pairwise, tract‐wise, and parcel‐wise—to identify neural correlates and predict acute neglect severity. We observed that WMH‐derived disconnections alone were not associated with neglect behavior. However, when combined with disconnections derived from individual stroke lesions, pre‐stroke WMH contributed to post‐stroke neglect severity by affecting right frontal and subcortical substrates, like the middle frontal gyrus, basal ganglia, thalamus, and the fronto‐pontine tract. Predictive modeling demonstrated that voxel‐wise disconnection data outperformed other measures of structural disconnection, explaining 42% of the total variance; interestingly, the best model used predictors of stroke‐based disconnections only. We conclude that prestroke alterations in the white matter microstructure due to WMH contribute to poststroke deficits in spatial attention, likely by impairing the integrity of human attention networks.
The Blockchain for Healthcare 4.0 Apply in Standard Secure Medical Data Processing Architecture
Authors: Ozturk Bilal A. , Tayyeh Huda Kadhim , Namiq Heba Emad , Mahajan Hemant B. , Junnarkar Aparna A. , Uke Nilesh , Shamaileh Anas Atef , Deshpande Sarita D. , Futane Pravin R. , Rane Milind
Published: November 2024

Cloud‐based Electronic Health Records (EHRs) have seen a substantial increase in usage in recent years, especially for remote patient monitoring. Researchers are interested in investigating the use of Healthcare 4.0 in smart cities. This involves using Internet of Things (IoT) devices and cloud computing to remotely access medical processes. Healthcare 4.0 focuses on the systematic gathering, merging, transmission, sharing, and retention of medical information at regular intervals. Protecting the confidential and private information of patients presents several challenges in terms of thwarting illegal intrusion by hackers. Therefore, it is essential to prioritize the protection of patient medical data that is stored, accessed, and shared on the cloud to avoid unauthorized access or compromise by the authorized components of E‐healthcare systems. A multitude of cryptographic methodologies have been devised to offer safe storage, exchange, and access to medical data in cloud service provider (CSP) environments. Traditional methods have not been effective in providing a harmonious integration of the essential components for EHR security solutions, such as efficient computing, verification on the service side, verification on the user side, independence from a trusted third party, and strong security. Recently, there has been a lot of interest in security solutions that are based on blockchain technology. These solutions are highly effective in safeguarding data storage and exchange while using little computational resources. The researchers focused their efforts exclusively on blockchain technology, namely on Bitcoin. The present emphasis has been on the secure management of healthcare records through the utilization of blockchain technology. This study offers a thorough examination of modern blockchain‐based methods for protecting medical data, regardless of whether cloud computing is utilized or not. This study utilizes and evaluates several strategies that make use of blockchain. The study presents a comprehensive analysis of research gaps, issues, and a future roadmap that contributes to the progress of new Healthcare 4.0 technologies, as demonstrated by research investigations.
Unpacking the gender wage gap in the U.S.: The impact of rural employment, age, and occupation
Authors: Kim Ayoung , Waldorf Brigitte S.
Published: November 2024

This paper examines three dimensions influencing the gender wage gap: rural employment, type of occupation, and workers' career stage. The findings suggest that (1) rural workplaces are associated with lower wages; (2) women face a higher wage penalty than men in rural, low‐paying jobs; (3) wage determinants differ between low‐ and high‐paying jobs, leading to variable impacts on the gender wage gap; (4) gender wage gaps are significantly narrower for early‐career workers than for older workers; and (5) even minor annual wage disparities contribute to significant wealth gaps by the end of the working life.
A novel approach for quantitative determination of lignin content in tobacco via multiCP/MAS NMR spectroscopy
Authors: Wang Ying , Huang Lan , Tian Zhenfeng , Ge Shaolin , Zhang Bing , Zhang Zhao , Chen Mingxi , Xu Bingxia , Hao Jinghang , Yang Jun
Published: November 2024

As the main structural component of tobacco cell wall, lignin content is an important factor affecting the safety of tobacco smoking. However, it is time‐consuming to quantify lignin by conventional wet chemical analysis methods. In this work, a 13C multiCP/MAS NMR spectral analysis method for tobacco lignin was established. The multiCP/MAS NMR sequence was optimized for tobacco lignin. The optimized nuclear magnetic sequence parameters were 9 CP cycles of 1.5 ms, repolarization time of 0.7 s, and a total acquisition time of 130 min. Subsequently, TMSP was used as the internal standard substance to establish the working curve, and the correlation coefficient was 0.9946. The relative standard deviation (RSD, n = 5) was 3.26%. This method was applied to the determination of lignin content in different types of tobacco samples. The relative error in the determination of lignin content by this method did not exceed 4.46% compared to the results of the chemical method. The results showed that the 13C multiCP/MAS NMR spectral analysis method had the advantages of accuracy and rapidity, which provided a new technical means for the quantitative study of tobacco cell wall substances.
I Don't Deserve Anything Good: Perfectionistic Self‐Recrimination in a Case of Comorbid Personality and Eating Disorder
Authors: Cheli Simone , Cavalletti Veronica , Gazzillo Francesco , Brüne Martin , Hewitt Paul L.
Published: November 2024

In this case study we present the course of the psychotherapy of Myriam, a 19‐year old female with a severe personality disorder and comorbid eating disorder. During the initial assessment she reported high levels of neuroticism that parallel the diagnosis of obsessive‐compulsive personality disorder, borderline personality disorder, and anorexia nervosa. Myriam showed a severely impaired personality functioning defined by perfectionism, self‐criticism, interpersonal guilt and overcontrol. Her daily experience was shaped by a self‐recriminative inner dialogue associated with maladaptive patterns in the form of food, water and sleep restrictions, self‐harm behaviors, and suicidal ideation. She accessed an integrative treatment based on individual (Evolutionary Systems Therapy) and group psychotherapy (Mindful Compassion for Perfectionism). At the end of 14‐month intervention she remitted from all the categorical diagnoses and showed reliable changes in several measures. These outcomes were maintained at 3‐month follow‐up. We describe the integrative conceptualization based on Myriam's perfectionistic self‐recrimination patterns, and the consequent treatment that targeted these patterns rather than focusing on symptom reduction exclusively.
Dihydroxyacetone phosphate is a novel predictor of hepatic fibrosis in Latino adolescents with obesity
Authors: Schenker Rachel B. , Ramirez Cuauhtemoc B. , Jang Cholsoon , Allayee Hooman , Zhao Xueheng , Setchell Kenneth D. R. , Kohli Rohit , Goran Michael I.
Published: November 2024

Objectives

Metabolic dysfunction‐associated steatotic liver disease (MASLD) is the most common pediatric liver disease and can progress to liver fibrosis. Latino adolescents have increased MASLD and fibrosis risk. While fibrosis is diagnosed by biopsy or imaging, more accessible, noninvasive, and economical screening methods are needed. We aimed to use plasma metabolomics/lipidomics to identify potential fibrosis biomarkers in Latino adolescents with obesity.

Methods

Liver stiffness (LS) was measured in 93 Latino adolescents with obesity using magnetic resonance elastography. Metabolites and lipids were extracted from plasma and identified on Compound Discoverer. Associations between metabolites/lipids and fibrosis (LS > 2.73 kPa) were determined using linear regression models after covariate adjustment. False discovery rate (FDR) adjusted Pearson's correlations were performed. Analytes yielding significant FDR‐adjusted correlations were examined further by receiver operator curve analysis.

Results

Mean (±standard deviation) alanine transaminase (ALT) was 45.7(±65.2) IU/L, hepatic fat fraction was 12.7(±9.1)%, and LS was 2.4(±0.3) kPa. We identified 795 metabolites and 413 lipids in plasma, but only one single metabolite, dihydroxyacetone phosphate (DHAP), a marker of triglyceride synthesis, was significantly associated with fibrosis after FDR adjustment (p < 0.05). In terms of predicting fibrosis, ALT had an area under the curve (AUC) of 0.79, and DHAP had an AUC of 0.79. When combined, ALT + DHAP had an AUC of 0.89.

Conclusions

The combination of ALT + DHAP may have the potential as an accurate, noninvasive test for liver fibrosis. Our data are limited to Latino children with obesity, and a larger cohort should be examined to further validate this novel biomarker.
Serum adropin is unaltered in adolescents with histology‐confirmed steatotic liver disease
Authors: Bays Jordan A. , Bartlett Alyssa M. , Boone Alison M. , Kim Youngsil , Yu Zhongxin , Palle Sirish K. , Short Kevin R.
Published: November 2024

Objectives

Metabolic dysfunction‐associated steatotic liver disease (MASLD) in adolescents is increasing. Adropin is a liver‐derived peptide involved in glucose and lipid homeostasis that was shown to be reduced in adults with metabolic disorders and cardiovascular disease (CVD). Serum adropin may also be higher in young men than women. A prior study reported that serum adropin was reduced in adolescents with MASLD, but the relationship between liver histology and CVD risk factors was not reported. We tested the hypotheses that adropin is (1) reduced in adolescents with MASLD compared to adolescents with obesity (Ob) or normal weight (NW) without MASLD, (2) correlated with blood pressure (BP), arterial stiffness, and liver histopathology, and (3) higher in boys than girls.

Methods

Serum adropin was measured in 47 patients with MASLD, and 27 and 29 control participants with Ob or NW, respectively.

Results

Adropin was not reduced but was instead 5% and 20% higher (p > 0.42) in the MASLD compared to the Ob and NW groups, respectively. Adropin concentration was not correlated with arterial stiffness or BP. Adropin was 20% higher in boys than girls in the entire study cohort (p = 0.034). This difference was evident in the Ob group (p = 0.018), but not in the NW (p = 0.537) or the MASLD (p = 0.893) groups. Adropin was positively correlated with age within the MASLD group only (r = 0.46, p < 0.001).

Conclusion

Serum adropin was not reduced in adolescents with Ob or MASLD as reported previously. The positive relationship between age and adropin in adolescents with MASLD requires further examination.
The first radiocarbon and stable isotope data for megafauna remains in Kaliningrad Province, Russia
Authors: Kuzmin Yaroslav V. , Martynovich Nikolai V. , van der Plicht Johannes
Published: November 2024

The first 14C dates for representatives of the Late Pleistocene – Early Holocene megafauna are reported from sites in Kaliningrad Province, Russia. The dates for woolly mammoth and cave lion are older than ca. 45 000 
bp, and could have corresponded to the Middle Weichselian interglacial (Marine Isotope Stage 3). The age of reindeer is ca. 10 000 
bp, and of aurochs ca. 7000 
bp. This shows that megafauna existed in this part of the Eastern Baltic region prior to the Last Glacial Maximum (LGM). After the LGM, Kaliningrad Province was recolonized by reindeer.
AI powered detection and assessment of onychomycosis: A spotlight on yellow and deep learning
Authors: Agostini C. , Ranjan R. , Molnarova M. , Hadzic A. , Kubesch O. , Schnidar V. , Schnidar H.
Published: November 2024

Background

Despite significant advances in computer‐aided diagnostics, onychomycosis, a widespread fungal nail infection, lacks an automated approach for objective analysis and classification.

Objectives

Our study aimed to develop and validate automated machine learning models to accurately detect and classify onychomycosis‐affected areas in toenails.

Methods

The images in this study were captured using the Scarletred® Vision mobile App and SkinPatch, a CE certified medical device system working seamlessly together to deliver auto‐color calibrated, high‐resolution clinical images. Considering a total of 1687 images from 440 subjects, the research explores various degrees of onychomycosis and evaluates the infection extent in the toenails detected. We developed an advanced machine learning algorithm for precise segmentation and classification of onychomycosis‐affected toenails, utilizing expert annotations and advanced post‐processing techniques. Additionally, an analysis of nail growth was performed, and a comparison graph with the percentage of infection was estimated.

Results

Using advanced machine learning algorithms, we successfully detected toenails, enabling detailed analysis of intricate structures within the images. We achieved a final validation loss of 0.0236 and an F1 score of 0.8566 for accurate toenail detection, while the Random Forest algorithm demonstrated 81% accuracy in classifying and distinguishing between infected and healthy toenail areas. Our applied superpixel method furthermore improved the algorithm's precision in identifying the infected regions.

Conclusions

Our AI‐powered image analysis method, initially focused on the big toe's toenail, shows great promise for broader validation on comprehensive datasets, enabling more detailed assessments of onychomycosis severity and disease dynamics. The potential impact of limited patient diversity, particularly with darker skin tones, needs further assessment. Proven to measure nail growth and assess treatment effectiveness over time, our developed AI is the first of its kind to demonstrate this capability, representing a significant advancement as a novel decision support tool for clinical research and routine medical practice.
Influence of gut and lung dysbiosis on lung cancer progression and their modulation as promising therapeutic targets: a comprehensive review
Authors: Thapa Rajan , Magar Anjana Thapa , Shrestha Jesus , Panth Nisha , Idrees Sobia , Sadaf Tayyaba , Bashyal Saroj , Elwakil Bassma H. , Sugandhi Vrashabh V. , Rojekar Satish , Nikhate Ram , Gupta Gaurav , Singh Sachin Kumar , Dua Kamal , Hansbro Philip M , Paudel Keshav Raj
Published: November 2024

Lung cancer (LC) continues to pose the highest mortality and exhibits a common prevalence among all types of cancer. The genetic interaction between human eukaryotes and microbial cells plays a vital role in orchestrating every physiological activity of the host. The dynamic crosstalk between gut and lung microbiomes and the gut–lung axis communication network has been widely accepted as promising factors influencing LC progression. The advent of the 16s rDNA sequencing technique has opened new horizons for elucidating the lung microbiome and its potential pathophysiological role in LC and other infectious lung diseases using a molecular approach. Numerous studies have reported the direct involvement of the host microbiome in lung tumorigenesis processes and their impact on current treatment strategies such as radiotherapy, chemotherapy, or immunotherapy. The genetic and metabolomic cross‐interaction, microbiome‐dependent host immune modulation, and the close association between microbiota composition and treatment outcomes strongly suggest that designing microbiome‐based treatment strategies and investigating new molecules targeting the common holobiome could offer potential alternatives to develop effective therapeutic principles for LC treatment. This review aims to highlight the interaction between the host and microbiome in LC progression and the possibility of manipulating altered microbiome ecology as therapeutic targets.
“You sure she's not making this up?”: A qualitative investigation of stigma toward adults with borderline personality disorder in physical healthcare settings
Authors: Navarre Kellyann M.
Published: November 2024

Borderline personality disorder (BPD) is associated with pervasive stigma that contributes to several consequences, such as inaccessible and inadequate healthcare. Existing literature concerning the experiences of BPD stigma within healthcare settings predominantly centers on mental healthcare contexts. However, individuals with BPD also present with elevated physical disabilities and health concerns, demonstrating a need for regular contact with medical professionals to manage and coordinate physical healthcare. The current qualitative study analyzes the dynamics of stigma and consequences in medical settings for physical healthcare among individuals diagnosed with BPD. Community adults (N = 16, Mage = 29.50, 44% cisgender women) provided qualitative responses describing their experiences with stigma in medical settings other than for mental health purposes. The inductive thematic analysis generated six key themes: (1) Dismissal and Misattribution of Physical Symptoms, (2) Delayed or Inappropriate Medical Diagnosis and Intervention, (3) Communication and Advocacy Challenges, (4) Invalidation of Emotional Well‐Being and Distress, (5) Self‐Harm Stigma, and (6) Presumed Drug‐Seeking Behavior. This article demonstrates the persistent and complex role of stigma across physical healthcare settings for individuals with BPD, affecting their physical and mental healthcare outcomes. It also identifies areas for future research and improvement and offers insights to ameliorate these issues.
Dawn of an era of effective treatments for MAFLD
Authors: Gofton Cameron , George Jacob
Published: November 2024

Fatty liver disease is a commonly occurring disease resulting in hepatic and extrahepatic complications. To date, there have been few available treatments beyond conventional lifestyle modification. While lifestyle modifications resulting in weight loss >10% have shown to be beneficial for metabolic dysfunction‐associated steatohepatitis (MASH), for the majority of patients, this is difficult to achieve. The recent approval of resmetirom (a thyroid hormone receptor beta agonist) by the Food and Drug Administration following positive results for histological outcomes in a phase 3 trial has opened the door for new treatments for metabolic (dysfunction)‐associated fatty liver disease (MAFLD) and MASH. There are currently a number of phase 3 trials targeting a variety of signaling pathways involved in the pathogenesis of metabolic steatohepatitis that are also promising. This review focuses on the currently available treatments for MAFLD and MASH, ongoing phase 3 clinical trials, and unresolved controversies in clinical trials in this area.
Comparative studies of seafood and reptile α‐ and β‐parvalbumins
Authors: O'Malley Andrea , Ray Joshua M. , Kitlas Patrycja , Ruethers Thimo , Kapingidza A. Brenda , Cierpicki Tomasz , Lopata Andreas , Kowal Krzysztof , Chruszcz Maksymilian
Published: November 2024

Small calcium‐binding proteins such as parvalbumins (PVs) are major seafood and fish allergens. However, the impact of structural changes on their capacity to bind IgE has not been studied in detail. Therefore, fish and reptilian PVs, as well as human α‐PV, were selected for biochemical, structural, and IgE binding studies. Likely due to their high solubility, crystallization proved difficult, so additional techniques were used to promote crystallization of the proteins. Novel crystal structures were determined for human PV, cod allergen Gad m 1.0201, saltwater crocodile allergen Cro p 1.0101, and the α‐PV from thornback ray. β‐PVs are considered the major fish allergens, while α‐PVs are rarely categorized as allergens. To explain these differences, the results of structural and IgE binding studies were combined. This approach allowed us to provide new insight into IgE binding epitopes present on PVs, focusing on cross‐reactivity among the selected α‐ and β‐PVs. In addition, we have shown that these proteins display remarkable thermal stability across a range of pH conditions, which is relevant in the case of food allergens and food processing. Moreover, it is shown that the presence of calcium cations is critical for stability of the studied PVs via their protein folding, which has an impact on the formation of IgE binding epitopes. These studies shows the stability of fish and reptile PV allergens, and it allows for further evaluation of their IgE cross‐reactivity.
Unraveling GPCRs Allosteric Modulation. Cannabinoid 1 Receptor as a Case Study
Authors: Cruz Alejandro , Warshel Arieh
Published: November 2024

G‐protein‐coupled receptors (GPCRs) constitute one of the most prominent families of integral membrane receptor proteins that mediate most transmembrane signaling processes. Malfunction of these signal transduction processes is one of the underlying causes of many human pathologies (Parkinson's, Huntington's, heart diseases, etc), provoking that GPCRs are the largest family of druggable proteins. However, these receptors have been targeted traditionally by orthosteric ligands, which usually causes side effects due to the simultaneous targeting of homologous receptor subtypes. Allosteric modulation offers a promising alternative approach to circumvent this problematic and, thus, comprehending its details is a most important task. Here we use the Cannabinoid type‐1 receptor (CB1R) in trying to shed light on this issue, focusing on positive allosteric modulation. This is done by using the protein‐dipole Langevin‐dipole (PDLD) within the linear response approximation (LRA) framework (PDLD/S‐2000) along with our coarse‐grained (CG) model of membrane proteins to evaluate the dissociation constants (KBs) and cooperativity factors (αs) for a diverse series of CB1R positive allosteric modulators belonging to the 2‐phenylindole structural class, considering CP55940 as an agonist. The agreement with the experimental data evinces that significantly populated allosteric modulator:CB1R and allosteric modulator:CP55940:CB1R complexes have been identified and characterized successfully. Analyzing them, it has been determined that CB1R positive allosteric modulation lies in an outwards displacement of transmembrane α helix (TM) 4 extracellular end and in the regulation of the range of motion of a compound TM7 movement for binary and ternary complexes, respectively. In this respect, we achieved a better comprehension of the molecular architecture of CB1R positive allosteric site, identifying Lys1923.28 and Gly1943.30 as key residues regarding electrostatic interactions inside this cavity, and to rationalize (at both structural and molecular level) the exhibited stereoselectivity in relation to positive allosteric modulation activity by considered CB1R allosteric modulators. Additionally, putative/postulated allosteric binding sites have been screened successfully, identifying the real CB1R positive allosteric site, and most structure–activity relationship (SAR) studies of CB1R 2‐phenylindole allosteric modulators have been rationalized. All these findings point out towards the predictive value of the methodology used in the current work, which can be applied to other biophysical systems of interest. The results presented in this study contribute significantly to understand GPCRs allosteric modulation and, hopefully, will encourage a more thorough exploration of the topic.
Semantic segmentation for weed detection in corn
Authors: Liu Teng , Jin Xiaojun , Han Kang , He Feiyu , Wang Jinxu , Chen Xin , Kong Xiaotong , Yu Jialin
Published: November 2024

BACKGROUND

Reliable, fast, and accurate weed detection in farmland is crucial for precision weed management but remains challenging due to the diverse weed species present across different fields. While deep learning models for direct weed detection have been developed in previous studies, creating a training dataset that encompasses all possible weed species, ecotypes, and growth stages is practically unfeasible. This study proposes a novel approach to detect weeds by integrating semantic segmentation with image processing. The primary aim is to simplify the weed detection process by segmenting crop pixels and identifying all vegetation outside the crop mask as weeds.

RESULTS

The proposed method employs a semantic segmentation model to generate a mask of corn (Zea mays L.) crops, identifying all green plant pixels outside the mask as weeds. This indirect segmentation approach reduces model complexity by avoiding the need for direct detection of diverse weed species. To enhance real‐time performance, the semantic segmentation model was optimized through knowledge distillation, resulting in a faster, lighter‐weight inference. Experimental results demonstrated that the DeepLabV3+ model, after applying knowledge distillation, achieved an average accuracy (aAcc) exceeding 99.5% and a mean intersection over union (mIoU) across all categories above 95.5%. Furthermore, the model's operating speed surpassed 34 frames per second (FPS).

CONCLUSION

This study introduces a novel method that accurately segments crop pixels to form a mask, identifying vegetation outside this mask as weeds. By focusing on crop segmentation, the method avoids the complexity associated with diverse weed species, varying densities, and different growth stages. This approach offers a practical and efficient solution to facilitate the training of effective computer vision models for precision weed detection and control. © 2024 Society of Chemical Industry.
Testing low‐risk bioactive compounds on Halyomorpha halys: an improved pipeline of analyses to investigate their effects on the bacterial endosymbiont Candidatus Pantoea carbekii
Authors: Checchia Ilaria , Andreolli Marco , Lanza Francesco , Santoiemma Giacomo , Mori Nicola , Pasini Massimiliano , Lampis Silvia , Felis Giovanna E
Published: November 2024

BACKGROUND

The brown marmorated stink bug Halyomorpha halys has become an invasive insect pest of many crops. A promising control strategy to manage the proliferation of H. halys is based on the suppression of its obligate and vertically transmitted uncultivated symbiotic bacterium Candidatus Pantoea carbekii through surface‐sterilization of H. halys eggs. Indeed, the application of antimicrobial formulations on the eggs of H. halys could cause mortality of endosymbiont and consequently of newly emerged nymphs.

In this study, a microbial live/dead assay was applied directly on H. halys eggs to evaluate Ca. P. carbekii loss of viability after treatments with seven commercial formulations including fungicides (copper hydroxide, sulphur, sweet orange essential oil) and plant biostimulants (flavonoids and chestnut tannin extract) compared with two disinfectants for civil and industrial use (sodium hypochlorite/hydrated sodium/tetraborate decahydrate and peracetic acid/hydrogen peroxide). Impact of mode of application was also evaluated, as surface treatment of egg masses was performed through spraying and dipping in laboratory conditions. Antimicrobial activity data were finally complemented with observations of egg hatching and vitality of the nymphs.

RESULTS

The optimization of live/dead staining is useful for evaluating Ca. P. carbekii mortality directly on eggs, providing a rapid and reliable culture‐independent approach. Sodium hypochlorite, copper, sulphur, tannins and sweet orange essential oil showed an antimicrobial effect against Ca. P. carbekii and a H. halys egg hatching reduction and nymph's vitality.

CONCLUSIONS

The antimicrobial and insecticidal effects of these commercial products should be further studied to assess their in‐field efficiency as well as the impact of these substances on non‐target organisms. The approach followed in this study could be considered a robust pipeline of analyses to evaluate the effectiveness of antimicrobial eco‐friendly compounds in symbiotic control of H. halys. © 2024 Society of Chemical Industry.
Effect of Fe Doping on the Crystal Structure and Dielectric Properties of LiGaCr4O8 Breathing Pyrochlore
Authors: Wang Xiaotian , Liu Hui , Tao Rongrong , Bian Jian , Zu Hao , Gao Xianhe
Published: November 2024

In this study, LiGaCr4−xFexO8 (x = 0, 0.2, 0.4, 0.6) ceramics are synthesized using the solid‐phase reaction method. The effects of Fe doping on the lattice structure and dielectric properties are systematically examined using X‐ray diffraction (XRD), scanning electron microscopy (SEM), Raman spectroscopy, and dielectric measurements. It is found from XRD analysis that the evolution of lattice constant decreases from 8.2552 Å at x = 0 to 8.2449 Å at x = 0.6, demonstrating a lattice contraction with doping. SEM shows a grain size reduction and irregular structures with higher Fe doping levels developed. The grain size decreases from 1.716 μm at x = 0 to 1.155 μm at x = 0.6. Due to Fe doping, the Raman spectroscopy obviously changes in high‐frequency phonon modes. The F2g1 and A1g modes shift to higher frequencies due to the reduction in lattice constant, while the F2g2, F2g3, and Eg modes shift to lower frequencies due to the increased ionic mass caused by the heavier Fe ions. Notably, Fe doping increases the dielectric constant and reduces the dielectric loss, especially at higher doping level. In these results, it is suggested that moderate Fe doping improves dielectric properties, offering potential applications in microwave and high‐frequency devices.
Case report: A finding of PVOD and PAH in first degree relatives suggests shared heritable risk and overlapping features of both pulmonary vascular diseases
Authors: Winters Roger , Forbes Lindsay M. , Ivy Dunbar , Cool Carlyne , Park Bryan D. , Hountras Peter , Badesch David , Gu Sue , Spiekerkoetter Edda , Zamanian Roham , LeierGluck Stacey , Bull Todd M.
Published: November 2024

Pulmonary veno‐occlusive disease (PVOD) is a rare form of pulmonary vascular disease that is difficult to distinguish clinically from pulmonary arterial hypertension (PAH). Multiple genes have been implicated in disease pathogenesis in PAH and PVOD and the diseases are thought to be genetically distinct. In this report we present a case of first‐degree relatives with pathological evidence of PVOD and PAH. The index patient was diagnosed with PAH at age 42, was treated with escalating pulmonary vasodilator therapy, but eventually succumbed to her disease. On autopsy, her pathology was consistent with PAH. Her son was diagnosed with PAH at age 16, did well on pulmonary vasodilator therapy for over 10 years, but ultimately developed refractory right ventricular failure and received a heart and lung transplantation. Pathology of his explanted lung was consistent with PVOD, and genetic testing was negative for recognized variants that cause PAH or PVOD.
Unveiling a rare haemorrhagic malignant pleural effusion: The role of medical thoracoscopy in diagnosing primary pleural angiosarcoma
Authors: Chong Ad Rian , Ng Khai Lip , Huan Nai‐Chien , Mohd Aminudin Nur Husna , Ahmad Sharifuddin Maryam , Raja Rahaizat Raja Nor Adilla , Mohamed Nordin Kasuma
Published: November 2024

Primary pleural angiosarcoma (PPA) is a rare and challenging tumour to diagnose, often mistaken for other malignancies such as mesothelioma and lung cancer due to overlapping clinical and imaging features. We report a 52‐year‐old woman who presented with progressive shortness of breath and pleuritic chest pain. Imaging studies and thoracentesis revealed a large haemorrhagic left pleural effusion. Medical thoracoscopy (MT) showed a thickened and lobulated parietal pleura with multiple nodular lesions. Histopathological examination confirmed a diagnosis of angiosarcoma, characterized by pleomorphic tumour cells, a high Ki67 proliferation index and positive immunohistochemical markers, including CD31, D2‐40, Vimentin, and Factor VIII. Tragically, the patient developed a hospital‐acquired infection and passed away before any definitive treatment for the angiosarcoma could be initiated. This case underscores the diagnostic complexities of PPA and highlights the utility of MT in identifying this rare malignancy.
Binary Observation‐Based FIR System Identification Against Replay Attacks
Authors: Zhang Qingxiang , Guo Jin
Published: November 2024

In the context of the increasing security issues of cyber‐physical systems (CPSs), this paper addresses the parameter identification of binary observation‐based finite impulse response (FIR) systems under replay attacks, overcoming the problem of high nonlinearity of quantized systems and greater data sparsity caused by replay attacks. For the attacker, based on the energy‐constrained condition, an optimization attack model is established to maximize the absolute error of identification, giving the method of obtaining the optimal attack strategy. Following the defender, the identifiability of unknown parameters is discussed and a robust defense scheme is proposed. This scheme involves a joint identification strategy for both the attack strategy and unknown parameters. By enhancing the excitability of system inputs, consistent identification is ensured despite replay attacks. An algorithm for the accomplishment of the joint identification strategy is presented based on the grid search method. Rationality of the method is confirmed with performing numerical simulations.
Response‐Adaptive Randomization Procedure in Clinical Trials with Surrogate Endpoints
Authors: Gao Jingya , Hu Feifang , Ma Wei
Published: November 2024

In clinical trials, subjects are usually recruited sequentially. According to the outcomes amassed thus far in a trial, the response‐adaptive randomization (RAR) design has been shown to be an advantageous treatment assignment procedure that skews the treatment allocation proportion to pre‐specified objectives, such as sending more patients to a more promising treatment. Unfortunately, there are circumstances under which very few data of the primary endpoints are collected in the recruitment period, such as circumstances relating to public health emergencies and chronic diseases, and RAR is thus difficult to apply in allocating treatments using available outcomes. To overcome this problem, if an informative surrogate endpoint can be acquired much earlier than the primary endpoint, the surrogate endpoint can be used as a substitute for the primary endpoint in the RAR procedure. In this paper, we propose an RAR procedure that relies only on surrogate endpoints. The validity of the statistical inference on the primary endpoint and the patient benefit of this approach are justified by both theory and simulation. Furthermore, different types of surrogate endpoint and primary endpoint are considered. The results reassure that RAR with surrogate endpoints can be a viable option in some cases for clinical trials when primary endpoints are unavailable for adaptation.
Applications and Efficacy of Minoxidil in Dermatology
Authors: Hussein Ramadan S. , Dayel Salman Bin , Abahussein Othman , El-Sherbiny Abeer Ali
Published: November 2024

Minoxidil, originally developed as an antihypertensive medication, has evolved into a versatile therapeutic agent within dermatology, notably for its effectiveness in promoting hair growth. Despite its widespread use, understanding its precise mechanism of action remains a challenge. This paper addresses this gap by providing a comprehensive review of pharmacological properties, action mechanisms, clinical effectiveness and side effects associated with topical minoxidil. Furthermore, it highlights emerging trends and applications, including its role in treating androgenetic alopecia, its potential for alopecia areata management and its utilization in combination therapies. Additionally, this paper explores novel applications in scar treatment and wound healing. By synthesizing current knowledge and insights, this review adds clarity to the diverse applications of minoxidil, providing valuable guidance for clinicians and researchers aiming to optimize its therapeutic use in dermatology.
Microwave Assisted One‐Pot Synthesis of Fused[1,2,3]Triazolo[4′,5′:3,4]Pyrrolo[1,2‐c]Pyrimidines as Potent Anticancer Agents
Authors: Thatikonda Raveendar Reddy , Merugu Karuna Sree
Published: November 2024

Synthetic chemists have organized easy and effective ways to achieve perfect synthesis in response to the requirement for scaffolds that are crucial for medical applications. A general strategy was developed for the synthesis of fused [1,2,3]triazolo[4′,5′:3,4]pyrrolo[1,2‐c]pyrimidines using one‐pot CuI‐catalyzed cycloaddition followed by C─C bong coupling. The cancer activity of the synthesized compounds was then tested in vitro against two lung cancer cell lines and some compounds showed potent activity compared to the primary standard, 5‐FU. We also found EGFR properties in the potent compounds and the results showed that compounds 1‐(3,5‐difluorophenyl)‐7‐methyl‐1,4‐dihydro‐6H‐[1,2,3]triazolo[4′,5′:3,4]pyrrolo[1,2‐c]pyrimidine‐6,8(7H)‐dione, and 1‐(3,5‐dichlorophenyl)‐7‐methyl‐1,4‐dihydro‐6H‐[1,2,3]triazolo[4′,5′:3,4]pyrrolo[1,2‐c]pyrimidine‐6,8(7H)‐dione were strong EGFR inhibitors compared to remaining compounds. We also carried out in silico studies to assess the molecular interactions of more potent compounds with EGFR proteins (PDB: 4HJO). Our findings revealed that all potent compounds exhibited more binding interactions than standard erlotinib (‐7.69 K cal/mol) with binding energies from −8.22 to −9.45 K cal/mol.