bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring Differences in Fertility Based on Experience of Intimate Partner Violence in Afghanistan
Authors: Ghahfarokhi Mehri Shams
Published: August 2023

Background
Intimate Partner Violence (IPV) is a primary manifestation of gender inequality in society and poses a significant obstacle to achieving global reproductive health goals due to its direct impact on women's access to healthcare and health outcomes. Despite the concerted efforts of global organizations, Afghanistan still experiences high levels of fertility. This paper aims to investigate differences in fertility based on the experience of violence and to answer the question of whether violence is a problem for fertility.
Methods
The data employed in this investigation were acquired from the 2015 Afghanistan Population and Health Survey. A discrete-time survival analysis model was employed to estimate the impact of violence on both probability and fertility patterns.
Results
The study findings indicate that women who have undergone IPV may have different reproductive outcomes compared to those who have not. Specifically, women with IPV experience may have slightly higher fertility rates and shorter birth intervals for certain birth orders. However, the differences between the two groups are generally small.
Conclusions
The study findings underscore the importance of policies and programs that tackle both intimate partner violence and reproductive health simultaneously. Addressing gender inequality and violence against women is crucial for improving reproductive health outcomes in Afghanistan. The outcomes of this study emphasize the necessity of integrating comprehensive and holistic approaches to reproductive health that recognize the complex interplay between violence and reproductive outcomes.
Strong-field photoelectron holography in the subcycle limit
Authors: Tsendsuren Khurelbaatar , Heo Jaewuk , Kim Dong Eon , Lai XuanYang , Yu ShaoGang , Liu Xiaojun
Published: August 2023

Strong-field photoelectron holography (SFPH) is promising for the study of electron dynamics and structure in atoms and molecules, with superior spatiotemporal resolution compared to conventional electron and X-ray diffractometry. However, the application of SFPH has been hindered by intercycle interference from multicycle fields. Here, we address this challenge by employing a near-single-cycle field to suppress the intercycle interference. We observed and separated two distinct holographic patterns for the first time. Our measurements allow us not only to identify the Gouy phase effect on electron wavepackets and holographic patterns but also to correctly extract the internuclear separation of the target molecule from the holographic pattern. Our work leads to a leap jump from theory to application in the field of SFPH-based ultrafast imaging of molecular structure.
Successful implantation of a leadless pacemaker in a patient after tricuspid valve replacement following cardiac tumor removal: a case report and literature review
Authors: Zou Qi , Chang Peng , Jiang Cheng , Lin Pengyang , Sun Shougang
Published: August 2023

Introduction
Intravenous-cardiac leiomyomatosis (ICL) is a rare condition characterized by the presence of leiomyomatous tumors within the cardiac venous system. Tricuspid valve replacement (TVR) is often required when the tricuspid valve (TV) is difficult to repair. However, complications such as atrioventricular block (AVB) can arise from damage to the cardiac conduction system during TVR surgery. This case highlights the successful implantation of a leadless pacemaker (LP) in a patient with advanced AVB following cardiac tumor removal combined with bioprosthetic TVR.
Case Presentation
Our patient, a 49-year-old female with a history of hysteromyoma and myomectomy, presented with sudden syncope and was diagnosed with ICL. Cardiac tumor removal was performed, and due to the inability to repair the TV, TVR with a bioprosthesis was undertaken. Postoperative assessments, including Electrocardiogram (ECG) and transthoracic echocardiography (TTE), revealed no significant abnormalities in electrocardiographic activity or structural changes in the heart. The patient was readmitted in November after surgery with syncope and was diagnosed with third-degree AVB, likely attributed to the TVR surgery. Considering the patient's age, medical history, and quality of life needs, the decision was made to proceed with implantation of a leadless pacemaker (LP), Micra, 11 months after cardiac tumor removal combined with bioprosthetic TVR.
Conclusion
This case represents the first reported instance of LP implantation in a patient following cardiac tumor removal combined with bioprosthetic TVR. The procedure was successful, and short-term follow-up indicated the safety and effectiveness of LP in treating advanced AVB after bioprosthetic TVR. These findings highlight the potential of LP as a treatment option for similar cases in the future.
Developing wideband antenna based on the metamaterial and dielectric silicon load for THz spectrum
Authors: Sharma Sachin , Ebrahimi Sepideh , Zarrabi Ferdows B.
Published: August 2023

THz antenna with wide bandwidth and high Q-factor is interesting for various application including 6G application and THz sensing and controlling the surface current of the antenna is known as a technique for bandwidth enhancement. The slot antenna with metasurface is a good candidate for this aim. In this research, we have suggested a multilayer slot antenna with metamaterial load to provide wide bandwidth which covers the 0.38 to 0.57 THz with bandwidth of 40%. The metamaterial loads make various paths for the current on the surface of the antenna that makes possible achieving the wider bandwidth. The proposed antenna has gain of 4 dBi. To achieve higher bandwidth the dielectric silicon (Si) load is placed over the metasurface. The result shows that the height and form of the Si element can impact the bandwidth of the antenna. To modify the results of the antenna, the shape, height and width of the dielectric load over the antenna is examined. The antenna bandwidth is enhanced more than 100% and it covers 0.371 to 0.616 THz with 49% bandwidth. The proposed antenna is simulated with full wave time domain technique of FIT (finite integrated technique).
Comparison of two advanced bipolar tissue sealer/dividers for laparoscopic ovariectomy in dogs: Articulating Enseal G2 versus Ligasure Maryland device
Authors: Driessen Floor , Marrero Javier Deniz , Grinwis Guy Cornelis Maria , Nimwegen Sebastiaan Alexander van
Published: August 2023

Background
Advanced bipolar tissue sealer/dividers provide the most reliable and efficient means of tissue dissection and blood vessel ligation in laparoscopic surgery and techniques are continuously improved. In veterinary practice cost-effectiveness is of major impact, leading to re-use of instruments designed and sold for single use. Two high-end devices were evaluated and compared in a highly standardized laparoscopic ovariectomy procedure in dogs in the present study: The new generation Ligasure Maryland Sealer/Divider (LMSD) with improved atraumatic curved jaw shape for delicate tissue handling and dissection and non-stick nanocoating, and the new-generation Articulating Enseal G2 (AENG2) with several proclaimed features improving surgical performance, including articulation of the forceps tip; improved tissue compression during sealing; unique offset electrode configuration; and specific nanoparticle coating minimizing thermal spread and tissue sticking. Twenty-one client-owned dogs admitted for elective laparoscopic ovariectomy were randomly assigned to one of two groups: ovariectomy using AENG2 on the left ovary and LMSD in the right ovary or vice-versa. Procedural video recordings were used to assess ovarian ligament fat score, smoke formation, occurrence of bleeding, and excision duration. Excised tissues were examined histopathologically and collateral thermal damage was scored in three anatomic zones: suspensory ligament, vascular pedicle, and uterine junction. Tissue sealers were used repeatedly following standardized cleaning protocol with instrument washing machine and Ethylene Oxide gas sterilization and the number of uses until device failure was recorded.
Results
Excision times were significantly increased for AENG2 (median 01:35 min) compared to LMSD (median 01:00 min). Minor hemorrhage from incomplete sealing occurred in 3 sites in 2 patients (2x AENG2, 1x LMSD) and was not significantly different between groups. Smoke production as scored on videos and thermal tissue damage scores on histopathology also did not differ between AENG2 and LMSD. Both vessel sealers could be re-used repeatedly.
Conclusion
AENG2 provides a good alternative to LMSD in laparoscopic ovariectomy, with only minor differences in measured variables. Subjectively, the articulating feature of AENG2 did not improve surgical performance in laparoscopic ovariectomy and the use of LMSD appeared more straight-forward. However, differences in operating these devices may be subject to personal preference.
Juvenile Dermatomyositis: Association between Nail Fold Capillary End Row Loops Area Under the Curve and Disease Damage Indicators
Authors: Khojah Amer , Morgan Gabrielle , Klein-Gitelman Marisa S. , Pachman Lauren M.
Published: August 2023

Background

Juvenile Dermatomyositis (JDM) is a rare autoimmune disease characterized by skin and muscle inflammation. The loss of nail fold capillary end row loops (ERL) is evidence of small vessel involvement in JDM. This study aimed to examine the association of ERL over the disease course and evidence of disease damage.

Methods

We analyzed data from 68 initially treatment-naïve JDM children who had been observed for at least five years with multiple ERL density assessments. The JDM disease courses were categorized into monocyclic short, monocyclic long, polycyclic, and chronic. The ERL capillary count was cumulatively evaluated using the area under the curve (AUC) method.

Results

The mean ERL density for the treatment-naive JDM was significantly lower than that of their healthy controls (4.8±1.6 /mm vs. 7.9±0.9 /mm; p <0.0001). The ERL AUC was significantly lower in children with chronic disease course compared to those with monocyclic short (p =0.001) or monocyclic long disease course (p =0.013). JDM patients with lipodystrophy had lower ERL AUC than those without lipodystrophy (p =0.04). There was no association between ERL AUC and calcifications or fractures.

Conclusion

Persistently decreased ERL capillary density, evident by low ERL AUC, is associated with chronic disease course and lipodystrophy in JDM. Despite medical therapy, the mean ERL count remained below normal even after five years, particularly in polycyclic and chronic cases. Therefore, the goal of restoring normal capillary density in children with JDM might be challenging and require novel therapeutic strategies targeting their underlying endothelial dysfunction.
Changes and driving forces of reservoir landscape pattern vulnerability: A case study of Qianping Reservoir, Luoyang City, Henan Province, China
Authors: Xu Enkai , Li Ying , Lei Yakai , Tian Guohang , Hu Yongge , Li Congshi , Wei Dianwei
Published: August 2023

Based on the land use data of Qianping Reservoir from 2000 to 2020 before and after the construction of Qianping Reservoir, this paper studies the spatial and temporal distribution and change characteristics of landscape pattern and ecological fragility of Qianping Reservoir, and analyzes the driving forces. The results showed (a) the dominant types of landscape were mainly cultivated land and forest land, and the area of construction land and water area increased steadily, while cultivated land showed a decreasing trend. (b) The vulnerability of the study area was mainly in the high vulnerability area and the medium vulnerability area, mainly distributed in the forest land and construction land area, but the overall pattern vulnerability showed a downward trend. Vulnerability is closely related to human activities, has a certain correlation with topography, and is not significantly affected by climate change, but it still reflects some problems. The research results provide a scientific basis for the landscape planning and construction of Qianping Reservoir to promote the sustainable development of the environment, and also provide a reference for the analysis of landscape vulnerability in similar areas.
Integrating CAx with the Chemical Synthesis for Chemical Printer Architecting in Additive Manufacturing with Logic in Materials
Authors: de Lima Edilson Gomes
Published: August 2023

This study proposal presents a hybrid and gradual method for biologic artificialization, engineering its fundamental structure with 3D printing, conferring incremental intelligence on its superficial and deep areas for its control to classify and mimic genetic events over organic or hybrid materials. Thus, functionalized computational blocks to be used as a mechanical computer, driving materials through its most fundamental state material as computing. The route for this research is the mechanical synthesis of material computation architecture drives through quantum control in their fundamental structure using particle computational logic integration to drive molecular structures. This research aims to include the precision techniques of mechanical engineering in the biosciences, i.e., metrology and anthropometry through biometrology, to measure genetic particle components to obtain patterns, through quantum digitization to generate complex mechanical, chemical, and hybrid syntheses in the state-of-the-art for biological circuit process control. It was concluded that cutting-edge CAx intelligence for material sciences can use chemical synthesis artificially for computerizing materials for additive manufacturing.
Targeting HER2/VEGFR2 dual tyrosine kinases with novel Lapatinib and Neratinib hybrid analogues lead to potential apoptotic induction in HER2 positive breast cancers: Design, synthesis, in-vitro, in-vivo and molecular docking studies.
Authors: Varikalla Rajashakar , gangarapu kiran
Published: August 2023

A high percentage of women worldwide will develop breast cancer during their lifetime, and there will always be a need to look for novel breast cancer treatment possibilities. The co-expression of HER2 and VEGFR2 in some breast cancers has been associated with a more aggressive tumour phenotype and poorer prognosis. As part of continuing research focusing on the possibility of simultaneously targeting HER2 and VEGFR2, we describe the design and synthesis of new lapatinib and neratinib hybrid analogues and their in vitro and in vivo evaluation for anti-cancer activity. We used the drug extension strategy to tailor the designed compounds to fit the RTKs, such as EGFR VEGFR2 and HER2 hydrophobic subpocket and cleft regions. The designed lapatinib and neratinib derivatives were successfully synthesized using established synthetic procedures and characterized using 1H, 13C-NMR, HRMS, and elemental analysis. The synthesized compounds were initially tested for their RTK inhibition capabilities, and compounds 15i and 15g were found to possess potential HER2 and VEGFR2 kinase inhibition abilities in-vitro with an IC50 less than the standards lapatinib and sorafenib used. The anti-proliferative capability of all derivatives demonstrated that compounds 15i and 15g potentially suppressed the growth of HER2 positive T-47D and BT-474 cells having a differential expression of HER2 and VEGFR2 with superior activity than lapatinib and sorafenib. SAR revealed that the trifluoromethyl group on the pyridinyl moiety of the side chain at the fourth position of the scaffold made compound 15i the most promising candidate among the other candidates. Flowcytometric apoptotic evaluation of compound 15i demonstrated potential induction of apoptosis at its IC50 in both T-47D and BT-474 cells, which was proved by examining the caspases (Caspase-3, 8, and 9) and Cytochrome-c release. Western blot analysis further determined HER2, VEGFR2, and their downstream signalling partner’s inhibition by the treatment of 15i. Further in-vivo tumour growth reduction by 15i was assessed in the T-47D xenograft mice model stating its potential anti-tumour capability. Based on docking studies, compound 15i was confirmed as a new lead candidate for the dual inhibition of HER2 and VEGFR2.
Pre-existing autoimmune disease as a risk factor for immune-related adverse events in cancer patients receiving immune checkpoint inhibitors
Authors: Sumimoto Hidetoshi , Noda Satoshi , Koide Hiroyoshi , Douke Yutaro , Sakai Kosuke , Nishikawa Akihito , Tomioka Azumi , Hori Maki , Nakato Hiromi , Kimura Yuri , Tokuda Aya , Takano Atsushi , Teramoto Koji , Murata Satoshi , Daigo Yataro
Published: August 2023

Immune checkpoint inhibitors (ICIs) are widely used for cancer treatment, but approximately 30% of cases experience immune-related adverse events (irAEs). Patients with pre-existing autoimmune diseases (AIs) are often advised against ICIs due to the higher risk of irAEs. However, there hasn't been sufficient risk assessment for AIs. We analyzed 478 cases receiving anti-PD-(L)1 Ab and/or anti-CTLA4 Ab at our hospital between April 2017 and May 2022, of which 28 (5.9%) had pre-existing AI. We analyzed the odds ratio (OR) of gender, age, performance status, cancer type, ICI type, combined agents, best overall response, and pre-existing AI using logistic regression. The results showed that pre-existing AI increased the risk of irAE occurrence (OR: 2.52, p = 0.033) and ICI discontinuation due to irAE (OR: 3.32, p = 0.006). Patients with AI had shorter irAE-free survival (median: 5.7 months) compared to those without AI (10.4 months) (p = 0.035). Frequent irAEs; dermatitis, pneumonitis, hepatitis, and hypothyroidism, were often associated with pre-existing AI. AI flared up in 6 cases (37.5%). AI activity didn't affect irAE occurrence. Grade 3 or higher irAEs were seen in 6 out of 21 (28.6%) AI cases with irAEs. Although complicated AI increases the risk of irAEs, closely monitoring patients may allow ICI treatment.
Optimizing Traffic Signal Control: A Scalable Approach with Federated Reinforcement Learning
Authors: Bao Jingjing , Wu Celimuge , Lin Yangfei , Zhong Lei , Chen Xianfu , Yin Rui
Published: August 2023

Intelligent Transportation has seen significant advancements with Deep Learning (DL) and Internet of Things, making Traffic Signal Control (TSC) research crucial for reducing congestion, travel time, emissions, and energy consumption. Reinforcement Learning (RL) has emerged as the primary method for TSC, but centralized learning poses communication and computing challenges, while distributed learning struggles to adapt across intersections. This paper presents a novel approach using Federated Learning (FL)-based RL for TSC. FL integrates knowledge from local agents into a global model, overcoming intersection variations with a unified agent state structure. Additionally, the output layer's parameters are not aggregated to handle different intersection settings; instead, fine-tuning is performed after model training for deployment. Extensive experiments demonstrate reduced queuing and waiting times globally, and successful scalability of the proposed model is validated on a real-world traffic network in Monaco, showing its potential for new intersections.
Concomitant training in robotic and laparoscopic liver resections of low-to-intermediate difficulty score: a retrospective analysis of the learning curve
Authors: Bernardi Lorenzo , Balzano Emanuele , Roesel Raffaello , Ghinolfi Davide , Vagelli Filippo , Menconi Giacomo , Petrusic Antonietta , Mongelli Francesco , Majno-Hurst Pietro , De Simone Paolo , Cristaudi Alessandra
Published: August 2023

In the setting of minimally invasive liver surgery (MILS), training in robotic liver resections (RLR) usually follows previous experience in laparoscopic liver resections (LLR). The aim of our study was to assess the learning curve (LC) of RLR in case of concomitant training with LLR. We analyzed consecutive RLRs and LLRs by a surgeon trained simultaneously in both techniques (Surg1); while a second surgeon trained only in LLRs was used as control (Surg2). A regression model was used to adjust for confounders and a Cumulative Sum (CUSUM) analysis was carried out to assess the learning phases according to operative time and difficulty of the procedures (IWATE score). Two-hundred-forty-five procedures were identified (RobSurg1, n = 75, LapSurg1, n = 102, LapSurg2, n = 68). Mean IWATE was 4.0, 4.3 and 5.8 (p < 0.001) in each group. The CUSUM analysis of the adjusted operative times estimated the learning phase in 40 cases (RobSurg1), 40 cases (LapSurg1), 48 cases (LapSurg2); for IWATE score it was 38 cases (RobSurg1), 33 cases (LapSurg1), 38 cases (LapSurg2) respectively. Our preliminary experience showed a similar LC of 40 cases for low and intermediate difficulty RLR and LLR. Concomitant training in both techniques was safe and may be a practical option for starting a MILS program.
PyPI: an internet-enabled learning tool to boost learner motivation for pest science
Authors: Takefuji Yoshiyasu
Published: August 2023

Instructors are always interested in methods to activate learner incentives and motivation to increase learning effectiveness. This paper introduces the Python Package Index (PyPI) as a powerful tool to maximize learner incentives on software and presents an example of its application in pest science. The more useful the PyPI application is, the more it will be downloaded worldwide, providing an external review for the learner and strengthening their incentive. However, many existing tutorials on PyPI, including the official site, are not updated on the twine library for uploading files to the PyPI site. This paper presents an updated tutorial on using PyPI for counting disaggregated objects such as bugs and pests, and for software reproducibility validation via Code Ocean. Additionally, generative AI is introduced as an indispensable assistant for tasks such as understanding technical terms and providing solutions for encountered problems.
Urban community engagement through “student-led science” for dengue prevention during the COVID-19 pandemic in Córdoba, Argentina
Authors: Estallo Elizabet , Madelon Magali , Benitez Elisabet , Martín Mía Elisa , Stewart Anna , Ludueña Francisco
Published: August 2023

Traditional mosquito vector control methods, such as insecticide applications, have proved ineffective in controlling the spread of dengue fever. The study aimed to assess the effectiveness of community engagement through student-led science assignments in promoting dengue fever prevention and socio-ecological factors in the temperate urban city of Córdoba, Argentina. This study assesses community perceptions, knowledge, attitudes, and preventive practices regarding dengue fever and its vector. It was cross-sectional, conducted during the COVID-19 quarantine, when schools switched to online education, serving as a basis for further research. The results showed a significant increase in knowledge about the vector and disease and the adoption of good preventive practices by the respondents. The findings underscore the importance of community engagement as a means of modifying the behavior of individuals and the community. Student-led science was identified as a useful tool in reaching households and leading to a change in attitudes in the home. Furthermore, the results highlighted the need for school programs with curricula that address vector biology and the prevention of vector-borne diseases throughout the year. The study provides valuable insights into the effectiveness of community engagement through student-led science assignments in promoting dengue fever prevention and socio-ecological factors. The findings suggest that this approach could be used as a strategy to control the spread of dengue fever in other regions affected by the disease. Additionally, the study emphasizes the importance of developing sustainable and effective methods of vector control that take into account the local ecological-community context.
YKL-40 serum levels are predicted by inflammatory state, age and diagnosis of idiopathic inflammatory myopathies
Authors: Mercado Mónica Vázquez-Del , Perez-Vazquez Felipe , Marquez-Aguirre Ana L , Martínez-García Erika-Aurora , Chavarria-Avila Efrain , Ramos-Becerra Carlos , Aguilar-Vazquez Andrea , Godínez-Rubí Marisol , Martín-Márquez Beatriz-Teresita , Gómez-Limón Livier , Márquez-De-La-Paz Jesús-Guillermo , Rubio-Arellano Edy-David , Pizano-Martínez Oscar
Published: August 2023

YKL-40 increase according to the aging process, and its functions have been associated with tissue remodeling and systemic inflammation. In Rheumatoid Arthritis (RA) it has been proposed as a possible biomarker of activity and severity, however; in the field of idiopathic inflammatory myopathies (IIM) the role of YKL-40 in IIM is not clear. Thus, we aimed to evaluate if there is an association between the serum levels and muscle tissue expression of YKL-40 with age, IIM phenotype, muscle strength and myositis disease activity. The main finding was that age is the most important variable that affects the YKL-40 serum levels. In muscle biopsy, we observed that YKL-40 is mainly expressed in infiltrating lymphoid cells than in muscle tissue. Using ANCOVA according to the b-coefficients, YKL-40 serum levels are predicted by inflammatory state, age, and IIM diagnosis.
Spectra of Multiply Charged Hydrogen and Nitrogen Ions in the Composition of Two and Multi-element Laser Plasma
Authors: Japakov A. I. , Bedilov R. M. , Azamatov Z. T. , Kamalova J. O. , Davletov I. Y.
Published: August 2023

The charge, energy, and spatial characteristics of multiply charged ions (hydrogen and nitrogen) of a two and multi-element laser plasma were studied using the laser ionization mass spectrometry method. The targets were made of pure C (i.e. graphite), Cu, polyethylene (CH2)n (consisting of hydrogen atoms (H) in a bound state), Cu[H] (with embedded H atoms) and Ti[H,N], Zr[H,N] (consisting of hydrogen atoms (H) and (N)) in the form of a thick cylinder with a thickness of l = 2 mm and a radius of R = 0.5 cm. It has been experimentally shown that the properties of both light and heavy ions in plasma depend both on the conditions for the entry of gas atoms into the target and on secondary processes occurring after the formation of a dense plasma on the surface of the sample. It has been found that the presence of light gas atoms significantly affects the parameters (for example, intensity and charge multiplicity) of heavier ions.
Gafchromic EBT3 film provides equivalent dosimetric performance to EBT-XD film for stereotactic radiosurgery dosimetry
Authors: Smyth Lloyd , Alves Andrew , Collins Katherine , Beveridge Sabeena
Published: August 2023

The accurate assessment of film results is highly dependent on the methodology and techniques used to process film. This study aims to compare the performance of EBT3 and EBT-XD film for SRS dosimetry using two different film processing methods. Experiments were performed in a solid water slab and an anthropomorphic head phantom. For each experiment, the net optical density of the film was calculated using two different methods; taking the background (initial) optical density from 1) unirradiated film from the same film lot as the irradiated film (stock to stock (S-S) method), and 2) a scan of the same piece of film taken prior to irradiation (film to film (F-F) method). EBT3 and EBT-XD performed similarly across the suite of experiments when using the green channel only or with triple channel RGB dosimetry. The dosimetric performance of EBT-XD was improved across all colour channels by using an F-F method, particularly for the blue channel. In contrast, EBT3 performed similarly well regardless of the net optical density method used. Across 21 SRS treatment plans, the average per-pixel agreement between EBT3 and EBT-XD films, normalised to the 20 Gy prescription dose, was within 2% and 4% for the non-target (2 - 10 Gy) and target (>10 Gy) regions, respectively, when using the F-F method. At doses relevant to SRS, EBT3 provides comparable dosimetric performance to EBT-XD. In addition, an S-S dosimetry method is suitable for EBT3 while an F-F method should be adopted if using EBT-XD.
Development of a neutralization monoclonal antibody with a broad neutralizing effect against SARS-CoV-2 variants
Authors: Ko Hae Li , Lee Deuk-ki , Kim Younghyeon , Jang Hui Jeong , Lee Youn Woo , Lee Ho-Young , Seok Sang-Hyuk , Park Jun Won , Limb Jin-Kyung , On Da In , Yun Jun-Won , Lyoo Kwang-Soo , Song Daesub , Yeom Minjoo , Lee Hanbyeul , Seong Je Kyung , Lee Sungjin
Published: August 2023

Background
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has challenged the effectiveness of current therapeutic regimens. Here, we aimed to develop a potent and broad SARS-CoV-2 antibody therapeutic by screening a scFv library with the spike protein receptor-binding domain (RBD) via phage display.
Methods
SKAI-DS84 was identified through phage display, and it underwent pseudovirus neutralization assays, authentic virus neutralization assays, and in vivo neutralization efficacy evaluations. Furthermore, surface plasmon resonance (SPR) analysis was conducted to assess the antibody's physical characteristics and measure its affinity.
Results
The selected clones were converted to human IgG, their binding affinities with the variant RBDs were confirmed, and SKAI-DS84 was selected. Using pseudoviruses, we confirmed its high neutralizing effects against SARS-CoV-2 wild-type, B.1.617.2, B.1.1.52, and subvariants. SKAI-DS84 showed potent neutralizing activity against various SARS-CoV-2 variants. We also tested the neutralizing effect of SKAI-DS84 on authentic viruses in vivo and observed a reduction in viral replication and improved lung pathology. We performed binding and epitope mapping experiments to understand the mechanism underlying neutralization and identified quaternary epitopes formed by the interaction between the RBDs as the target for SKAI-DS84.
Conclusions
Overall, this study highlights the potential of SKAI-DS84 as a neutralizing antibody against broadly SARS-CoV-2 and its variants.
Complexes of Cationic Monoheteryl-Substituted Porphyrin with Synthetic and Natural Nucleic Acids
Authors: Lebedeva Natalia , Yurina Elena , Guseinov Sabir S.
Published: August 2023

Porphyrins, owing to their unique physicochemical properties, hold great potential as candidates for the synthesis of new materials and active pharmaceutical drugs. The introduction of functional groups into porphyrin structures enables the creation of novel compounds with finely tuned structural and optical properties, as well as complex-forming abilities. In this study, spectral and thermochemical investigations were conducted to explore the complex formation of a cationic porphyrin containing benzimidazole residues with synthetic (poly[d(GC)2], poly[d(AT)2]) and natural (ssDNA, ctDNA) nucleic acids. It was observed that the porphyrin forms complexes with poly[d(AT)2] and ssDNA, localized within the major groove of the biopolymer. Additionally, the porphyrin forms multiple intercalation complexes with varying geometries when interacting with poly[d(GC)2] and ctDNA. These findings demonstrate a new potential for enhancing the selective binding of ligands with nucleic acids (NA). Moreover, the study highlights the methodological aspect that establishing the type of formed complexes based on ligands' electronic absorption spectra, known as "fingerprints," may lead to incorrect conclusions.
Population-based assessment of hypogonadism and testosterone replacement therapy in hypogonadal men: is there a potential prostate cancer risk?
Authors: Asanad Kian , Horns Joshua , Driggs Nathan , Samplaski Mary , Hotaling James
Published: August 2023

We sought to understand the relationship between hypogonadism and testosterone replacement therapy (TRT) in hypogonadal men on the risk of developing localized and metastatic prostate cancer. We used the Merative MarketScan database of commercial claims encounters to identify men diagnosed with hypogonadism. These men were matched to eugonadal men who served as controls. Multivariate negative binomial regression analysis of prostate cancer diagnoses, hypogonadism, and TRT in hypogonadal men adjusting for various known confounding factors was used understand the impact of hypogonadism and TRT on prostate cancer risk. We identified 3,222,904 men who met inclusion criteria, of which 50% were diagnosed with hypogonadism (1,611,452) and each were matched to a control (1,611,452). The incidence of prostate cancer was 2.16%, 1.55%, and 1.99% in controls, hypogonadal men on TRT, and hypogonadal men without TRT, respectively (p < 0.001). Untreated hypogonadism was independently associated with a decreased the risk of localized prostate cancer (IRR 0.46, 95% CI 0.43–0.50, p < 0.001) compared to eugonadal controls. Hypogonadal men on TRT also had a significantly decreased risk of localized prostate cancer (IRR 0.49, 95% CI 0.45–0.53, p < 0.001). Furthermore, hypogonadal men on TRT (IRR 0.21, 95% CI 0.19–0.24, p < 0.001) or without TRT (IRR 0.20, 95% CI 0.18–0.22, p < 0.001) both had significantly decreased risk of metastatic prostate cancer, respectively. Our population-based assessment suggests that untreated hypogonadism in men is associated with a 50% decreased incidence of localized prostate cancer and an 80% decreased incidence of metastatic prostate cancer. TRT in hypogonadal men was also associated with a decreased risk of subsequent prostate cancer. Further research is needed to better understand the relationship between testosterone deficiency and TRT in hypogonadal men on the of risk prostate cancer.
The investigation of circRNA profiling reveals the regulatory role of the has_circ_0000375/miR-7706 pathway in breast cancer
Authors: Wang Haoqi , Liu Fei , Xue Jing , Liu Yaping , Gao Wei , Yang Shan , Mi Yunzhe , Zhang Xi , Gao Shan , Geng Cuizhi
Published: August 2023

Circular RNAs (circRNAs) take an effect on tumorigenesis and progression. However, circRNAs have not been systematically identified in breast cancer (BC) as crucial regulators in multitudinous biological processes. This study is conducted to explore novel circRNAs in BC and the corresponding mechanisms of their action. The circRNA expression profile and RNA-sequencing data about BC were respectively downloaded from public database. Differentially expressed circRNAs, miRNA, and mRNA were identified by fold change filtering. The competing endogenous RNAs (ceRNAs) network was established based on the relationship between circular RNAs, miRNAs and mRNAs. GO and KEGG enrichment analysis of the overlapped genes were carried out to predict the potential functions and mechanisms of circRNAs in BC. The CytoHubba plugin in Cytoscape was applied to identify the hub genes from the PPI regulatory network. Kaplan–Meier plotter was used to perform survival analysis of these hub genes further. Real-time PCR was performed to test the expression of circRNA in breast cancer tissues. Cell function studies including transwell analysis and CCK-8 analysis were used to investigate circRNAs’ biological functions. We identified a total of 7 differentially expressed circRNAs. After the intersection between the predicted target miRNA and the down-regulated differential miRNAs (DEmiRNAs), circRNA-miRNA interactions involving 3 circRNAs (hsa_circ_0028899, hsa_circ_0000375, hsa_circ_0000376) and 4 miRNAs (hsa-miR-934, hsa-miR-7706, hsa-miR-4443, hsa-miR-4784) were identified. Venn diagram was utilized to intersect the predicted target genes of the 4 miRNAs and the down-regulated differential genes in BC, and 149 overlapped genes were screened out ulteriorly. Additionally, we built a protein-protein interaction (PPI) network and selected six hub genes. Moreover, the survival data of BC patients suggested that low expression of ADIPOQ, LPL and LEP were significantly correlated with poor prognosis. Results from real-time PCR indicated that has_circ_0000375 was significantly down-regulated in breast cancer tissues. Functional in vitro experiments showed that over-expression of hsa_circ_0000375 can restrain proliferation, migration and invasion abilities of breast cancer cells. Further verification indicated that hsa_circ_0000375 exerted its anti-oncogene effect via sponge of miR-7706. This study constructed and analyzed a circRNA-associated ceRNA regulatory network and uncovered that hsa_circ_0000375 exerted its anti-oncogene effect via sponge of miR-7706.
Evaluation of topical adjuvant treatment of psoriasis with recombinant epidermal growth factor to control the e-regulation of EGFR: a clinical study
Authors: Sisakht Mahsa Mollapour , Rezaeinejad Aida , Didehvar Kimia , Doust-Vaghe Yasaman Kiani , Behrangi Elham , Goodarzi Azadeh , Nilforoushzadeh Mohammad Ali , Siahpoosh Zahra , Amirkhani Mohammad Amir
Published: August 2023

Deregulation of the epidermal growth factor receptor, which belongs to the ErbB family of receptor tyrosine kinases, is detectable in psoriasis lesions and leads to uncontrolled cell growth, proliferation and differentiation of skin cells. To investigate the effect of epidermal growth factor receptor saturation with a high concentration of epidermal growth factor in a topical cream in the clinical setting in patients with mild to moderate psoriasis, we applied the cream with 5% growth factor in 11 patients and a cream with clobetasol, urea, salicylic acid and Eucerin without growth factor as control on 11 patients in parallel. The therapeutic effect was assessed by blinded clinicians using the Psoriasis Area and Severity Index (PASI) based on severity, erythema, induration and scaling. The result of the clinical trial showed that the PASI index for the standard treatment group was 3.76±1.93 before treatment and 2.9±1.83 after treatment, and for the group receiving EGF was 3.23±2.2 before intervention and 2.52±2.05 after intervention. Although the decrease in PASI was highly significant (p <.001) in both the standard and intervention groups before and after the study, individual comparison of each patient before and after treatment showed a significant (p <.001) decrease for the intervention group compared with the control group. We conclude that EGF as an adjuvant therapy can effectively control mild to moderate psoriatic lesions without causing side effects. Future clinical trials should be conducted to explore the therapeutic effects.
Design, synthesis, and molecular dynamics simulation studies of some novel kojic acid fused 2-amino-3-cyano-4H-pyran derivatives as tyrosinase inhibitors
Authors: Najafi Zahra , Haramabadi Maryam Zandi , Chehardoli Gholamabbas , Ebadi Ahmad , Iraji Aida
Published: August 2023

A new series of novel kojic acid fused 2-amino-3-cyano-4H-pyran derivatives as tyrosinase inhibitors were designed, synthesized, and assessed against tyrosinase enzyme. The designed compounds can be categorized into three series: 1) 4-benzyloxy-phenyl kojopyran 6a-e, 2) 3-benzyloxy- phenyl kojopyran derivatives 6f-j, and 3) 4-benzyloxy-3-methoxy-phenyl kojopyran derivative 6k-o. Among them, 2-amino-4-(4-((4-fluorobenzyl)oxy)phenyl)-6-(hydroxymethyl)-8-oxo-4,8-dihydropyrano[3,2-b]pyran-3-carbonitrile (6b) was detected as the most potent antityrosinase compound with an IC50 value of 7.69 ± 1.99 µM with a competitive mode of kinetic inhibition as compared to kojic acid as control agent 23.64 ± 2.56 µM. Because compound 6b was produced as a racemic mixture, in silico studies were performed for both R and S enantiomers. The R- enantiomer showed critical interactions compared with the S-enantiomer. The R- enantiomer was found to establish hydrogen bonds and hydrophobic interactions with critical and highly conserved amino acids in the target protein within the enzyme's binding site. Moreover, the molecular dynamics simulations revealed that compound 6b demonstrated significant interactions with essential residues of the binding site, resulting in a stable complex throughout the entire simulation run. The drug-like and ADMET properties predictions showed an acceptable profile for these agents. Accoring to our results, it was proposed that compound 6b can serve as a drug candidate to develop more potent antityrosinase agents.
Controllability in Multiplex Biological Networks withInsights into Virus-Related Diseases
Authors: Behrouzinia Soudeh , Khanteymoori Alireza , Dehghanian Fariba
Published: August 2023

Complex networks, inspired by biological systems and grounded in mathematical and computational models, have beenextensively employed to represent diverse biological phenomena. The significance of network controllability in comprehendingintricate biological systems is universally acknowledged, leading to the development of several algorithms aimed at analyzingnetwork controllability. These algorithms serve the purpose of manipulating input signals to guide biological system dynamicstowards desired states. New studies have shown that there are complicated connections between things that are hard to showin simple networks, and this makes us question the idea that things are isolated. In response to these complexities, multiplexnetworks have emerged as robust constructs capable of accommodating and capturing multiple relationships simultaneouslywithin high-dimensional spaces. This research introduces a novel framework designed to regulate the behavior of biologicalmultiplex networks through the identification of pivotal driver nodes. This challenge is formulated as the identification ofminimum driver nodes, with the framework’s efficacy evaluated through its application to authentic biological multiplexes.Applied to three virus multiplexes, the framework underscores the potential for specific nodes to serve as targets for drugenrichment or as subjects for the investigation of intricate diseases. The implications of this research extend to the identificationof potential driver genes for a variety of virus-related diseases within the landscape of biological multiplex networks.
Prolonged Administration of the Granisetron Transdermal Delivery System Reduces Capecitabine plus Oxaliplatin Regimen–Induced Nausea and Vomiting
Authors: Wang Cong , Jiang Zhansheng , Zhang Jie , Zhuang Yan , Sun Lining , Zhang Jing , Quan Manman , Lan Lan , Li Yanwei , Wang Bin , Pan Zhanyu , Yan Zhuchen
Published: August 2023

Purpose
The completion rate and intensity of Capecitabine plus oxaliplatin (CapeOX) combination therapy are low in clinical practice because of chemotherapy-induced nausea and vomiting. This open-label, prospective, multi-center phase II trial was designed to initially assess the safety and efficacy of granisetron transdermal delivery system (GTDS) and Dexamethasone for patients who were scheduled to receive CapeOX chemotherapy.
Methods
Patients received the GTDS (3.1 mg attached to the upper arm 48 h before chemotherapy, replaced on day 5 and discarded on day 12), and Dexamethasone. The primary end point was complete control rate. Secondary efficacy endpoints included dates of delayed complete control during the overall phase, complete control rate in the acute phase, safety and quality of life.
Results
Among three institutions, 29 participants were enrolled in the study. The complete control rate in delayed nausea and vomiting for the whole periods (25–480 hours) was 70.4% (95% CI 0.50–0.86). The dates of delayed complete control were 17.1 ± 4.9 days. 59.3% of patients did not experience any grade of nausea during the delayed phase. The complete control rate in the acute phase was 85.2% (95% CI 0.65–0.95). In terms of safety, there were no serious adverse events attributed to the antiemetic regimen.
Conclusion
Prolonged administration of the GTDS is safe and effective for preventing chemotherapy-induced nausea and vomiting in patients with gastrointestinal malignancies treated with CapeOX. This study is registered at the ClinicalTrials.gov registry (NCT05325190). The date of registration was October 10, 2021.
Cellulose-based surface-modified heterogeneously feasible novel solid acid catalyst to access bioactive heterocycles
Authors: Karhale Shrikrishna , Kadam Ankush
Published: August 2023

Surface-modified cellulose-based heterogeneously active catalyst was prepared by covalent anchoring of chlorosulphonic acid on amino-functionalized cellulose (SA@Cell-AEPC). The structure of synthesized catalyst was confirmed by analytical methods such as FT-IR, FE-SEM, EDX, TGA and CP/MAS 13C-NMR spectroscopy. The catalytic effect was evaluated for the formation of oxygen and nitrogen heterocycles. Reusability, shorter reaction time, high conversion, wide substrate scope, easy work-up procedure are noteworthy measures of this synthetic route.
Pair barracuda swarm optimization algorithm a natural-inspired metaheuristic method for high dimensional optimization problems
Authors: Guo Jia , Zhou Guoyuan , Ke Yan , Sato Yuji , Di Yi
Published: August 2023

The high-dimensional optimization is a new research difficulty in the field of intelligent computing.Traditional evolutionary tools are prone to dimensional catastrophes and local optimal in high dimensional spaces, thus failing to provide highly accurate results. In this paper, to solve the high-dimensional optimization problem, a novel pair barracuda swarm optimization algorithm (PBSOA) is proposed. In PBSOA, a novel construction of barracuda pairs is proposed to reduce dimensional catastrophes.A support barracuda is also used to enhance the global search ability of the leader barracuda pair.To verify the performance of the barracuda algorithm, the CEC2017 standard function is used for experiments, and five excellent optimization algorithms are selected in control groups. Finally, in a total of 29 test functions, PBSOA gets 18 firsts, 4 seconds, 3 thirds, 3 fourths, and 1 sixth, and the average rank is 1.83.The experimental results demonstrate that PBSOA presents the best performance in all algorithms and is able to provide trustworthy results for high-dimensional optimization problems.
Identification and analysis of dysregulated genes in the pathogenesis of keloid
Authors: Tao Anqi , Tian Tian
Published: August 2023

Objective
Keloid is a fibroproliferative disorder that primarily arises from cutaneous traumas. However, the pathogenesis of keloid remains uncertain and is likely involved in multiple signaling pathways and is likely involved in multiple signaling pathways. This study aims to identify the key signaling pathways and explore the potential roles of immune cells in keloid development.
Methods
Two keloid datasets, GSE44270 and GSE145275 from, obtained from the Gene Expression Omnibus (GEO) database, were integrated with the elimination of batch effects. Differentially expressed genes (DEGs) were identified using the Linear Models for Microarray Data (LIMMA) package. The Weighted Gene Co-expression Network Analysis (WGCNA) was then applied to identify keloid-associated genes. The common genes (CGs) were subsequently obtained by overlapping the DEGs with genes in the most significant module. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using these CGs. Additionally, the CIBERSORT algorithm was used to calculate the relative proportions of 22 types of infiltrating immune cells.
Result
We identified 51 DEGs using the R package limma. 18 modules were constructed via WGCNA, with the pink module showing the highest correlation with keloid and was further intersected with the DEGs to obtain 28 CGs. Pathway enrichment analysis revealed that the CGs were primarily associated with the regulation of transcription and O-glycan biosynthesis. Furthermore, immune infiltration analysis demonstrated significant changes in the levels of macrophages, T cells gamma delta and NK cells compared to the control group.
Conclusion
This study revealed several novel keloid-associated genes that can induce inflammatory response immune cell infiltration and extracellular matrix deposition, ultimately resulting in the development of keloid disorder.