bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Immune Cells and Immune Related Genes in the Tumor Microenvironment of Thyroid Cancer Implications for Immunotherapy
Authors: Li Xumei , Jian Jie , Zhang Anzhi , Xiang Jiang ming , Huang Jingjing , Chen Yanlin
Published: March 2024

In recent years, immunotherapy has developed rapidly and gradually become one of the important methods for treating THCA. The study of immune cells and immune related genes in the tumor microenvironment greatly promotes the development of immunotherapy. Use the CIBERSORT algorithm to analyze the gene expression profile obtained from TCGA, estimate the infiltration ratio of 22 immune cells in tumor and adjacent tissues, and then analyze the differential expression of immune related genes, and identify immune cells and immune related genes related to clinical progress and prognosis. We observed that a variety of immune cells were enriched in the microenvironment of THCA: 12 kinds of immune cells were closely related to TNM stage and found that two kinds of immune cells were closely related to the prognosis of patients with THCA. Analysis of immune related genes found that they are mainly enriched in immune related pathways. Through PPI network screening that one main module and 10 key genes were identified. Nine key genes were found to be closely related to TNM staging, with CD40LG being closely associated with the prognosis of THCA patients. The type and quantity of infiltrating immune cells in the microenvironment of THCA, as well as immune related genes, are closely related to tumor progression and can be used as important indicators for patient prognosis evaluation. This study is to explore the relationship between immune cells and immune related genes in the tumor microenvironment and the progression and prognosis of THCA.
Development of a magnesium/amorphous nano-SiO2 composite using accumulative extrusion method
Authors: Moradi Mohammad , Ghaei Abbas , Maleki Ali , Taherizadeh Aboozar , Issa Hasan Kaser
Published: March 2024

In this study, a Mg-X%SiO2 (X = 1, 2) nanocomposite was developed using amorphous silica nanoparticles via the accumulative extrusion method. The reinforcement phase was added to the matrix between extrusion passes. The study evaluated the mechanical properties of the composite samples via compression and hardness tests, while the microstructure and texture were analyzed using an optical microscope and X-ray diffraction analysis. To remove the deformation history and examine the effect of the reinforcement phase on mechanical properties, the samples were annealed in an argon atmosphere. In addition, monolithic magnesium samples were fabricated through the same process to serve as a basis for comparison. This study revealed that adding 1 wt.% amorphous silica nanoparticles to the magnesium matrix improved the overall mechanical properties. However, the nanocomposites displayed varying properties in different directions. Along the extrusion direction, the yield strength and ductility increased up to 57% and 5%, respectively, while the ultimate compressive strength decreased by about 8%. Along the normal direction, the yield strength and ductility increased up to 37% and 45%, respectively, while the ultimate compressive strength decreased by about 9%. The Mg/2%SiO2 nanocomposite sample showed superior Brinell hardness. The number of extrusion passes had a significant impact on the distribution of nanoparticles within the matrix. The optical microscope micrographs revealed that the reinforcement phase was uniformly distributed throughout the matrix, and no agglomeration of nanoparticles was observed. The X-ray diffraction results demonstrated that the texture of nanocomposite samples weakened after adding nanoparticles, resulting in improved ductility.
Evolution of new genes under intermittent selection
Authors: Näsvall Joakim , Abdalaal Hind
Published: March 2024

New genes can evolve by mutations that generate a new function in an existing gene1. However, these mutations often have a negative impact on the original function, leading to trade-offs that constrain their further evolution2. Genes that exhibit a strong trade-off between the original and the new function are expected to evolve through gene duplication, which can increase the expression of a weak new activity, buffer against negative effects on the original function, and provide more targets for beneficial mutations to arise3. The expected outcome of evolution in conditions where both functions are beneficial is a new pair of paralogs, each specialized for one function. Despite this, there are examples in nature where bi-functional generalist enzymes have evolved from a presumed specialist ancestor4. This study tests the hypothesis that generalist enzymes can evolve from specialist ancestral enzymes if selection for the new function is repeatedly interrupted by periods without selection (i.e. selection for the new function is intermittent). In evolution experiments using bacteria lacking an enzyme in the tryptophan synthesis pathway, with intermittent selection for restoring tryptophan synthesis, multiple examples were found where initially specialized enzymes in two different pathways evolved towards becoming bi-functional generalist enzymes supporting both their new and original functions. Our results highlight the importance of considering selection in nature not as a constant, but as a force that may fluctuate, and that fluctuating selection can drastically change the outcome by forcing evolution along paths that are highly constrained by conflicting selection pressures. Especially for duplications, which are mechanistically unstable and often costly, intermittent selection is expected to have a huge impact: If selection for a beneficial limiting function fluctuates, duplications may be counter selected and lost at regular intervals, forcing alternative paths of evolution that do not require duplications.
“One pastor advised him to stop taking HIV medication”: Promoters and barriers to HIV care among gay, bisexual, and men who have sex with men living with HIV in Ghana
Authors: Abu-Ba'are Gamji Rabiu , Aidoo-Frimpong Gloria , Amu-Adu Prince , Zigah Edem Yaw , Stockton Melissa , Amuah Samuel , Amoh-Otoo Richard Panix , Nyblade Laura , Torpey Kwasi , Nelson LaRon E.
Published: March 2024

Introduction: Few studies examine Ghanaian gay, bisexual, and other men who have sex with men (GBMSM) experience with HIV diagnoses and linkage to care. This article provides qualitative accounts of promoters and barriers to care among GBMSM living with HIV in Ghana.
Methods: We recruited and interviewed 10 GBMSM living with HIV in two Ghanaian cities. We transcribed the interviews, coded the data, and used thematic content analysis.
Results: We found that community and healthcare facility (HCF) level HIV and sexual stigma, confidentiality issues, alternative medicine, and substance use remain the key barriers to care. Other barriers include healthcare system issues such as long wait times and economic problems (e.g., health insurance and financial difficulties). Nonetheless, HCF-level factors such as positive experiences with providers, HIV counseling, and detailed medication information facilitate adherence to care among GBMSM.
Conclusion: This study highlights the need for interventions that address linkage to care issues, especially substance use, disinformation, and misinformation among GBMSM and other Ghanaian communities.
USP1 activates the Wnt/β-catenin pathway by deubiquitinating KRT17, thereby facilitating thyroid cancer proliferation
Authors: Zeng Hong , Zhou Xuanrui , Geng Xitong , Wan Hao , Ding Yongqi , Zhou Minqin , Pan Jingying , Yu Zichuan , Huang Da
Published: March 2024

Post-translational modification through ubiquitination is widely acknowledged for its pivotal regulatory role in tumor onset and progression. Ubiquitin ligases and deubiquitinases can modulate tumor advancement by impacting the expression of key proteins. Nonetheless, the precise contribution of ubiquitination and deubiquitinases in the onset of thyroid cancer (TC) remains to be comprehensively understood. Initially, Weighted Gene Co-expression Network Analysis (WGCNA) revealed the deubiquitinase USP1 as closely associated with TC and protein ubiquitination. Subsequently, our findings demonstrated the aberrant upregulation of USP1 expression in clinical TC samples. Moreover, interference with USP1 expression inhibited the proliferative ability of TC cells in vitro by colony formation and CCK8 assays. Notably, our findings have revealed that USP1 facilitates the proliferation of TC by modulating the Wnt/β-catenin pathway. Further, we identified KRT17 as a critical factor in the USP1-mediated Wnt/β-catenin pathway. Next, we validated that USP1 directly interacted with KRT17 and deubiquitinated it. Ultimately, we discovered that parthenolide exerted inhibitory effects on TC proliferation both in vivo and in vitro by modulating the USP1-KRT17-Wnt/β-catenin axis. To sum up, Our findings offer compelling evidence that underscores the pivotal role of USP1 in promoting TC proliferation. This is accomplished by stabilizing KRT17 expression through deubiquitination, which in turn activates the Wnt/β-catenin pathway. These results provide novel insights into potential therapeutic targets for TC treatment.
Competing effects of wind and buoyancy forcing on recent ocean oxygen trends
Authors: Hollitzer Helene , Patara Lavinia , Terhaar Jens , Oschlies Andreas
Published: March 2024

Ocean deoxygenation is becoming a major stressor for marine ecosystems. Climate change affects ocean oxygen by altering wind fields and air-sea heat and freshwater fluxes. However, the quantitative contribution of these drivers to ocean deoxygenation remains uncertain. Here, we use a global ocean biogeochemistry model run under historical atmospheric forcing to show that deoxygenation since the late 1960s has been driven mainly by changing air-sea heat and freshwater fluxes and associated changes in solubility and ocean circulation. However, ~60% of this deoxygenation was offset by a wind-driven increase in ventilation and interior oxygen supply, mainly in the Southern Ocean. In the coming decades, the projected slowdown in wind stress intensification, combined with continued ocean warming, could greatly accelerate ocean deoxygenation. While ocean biogeochemistry models under historical atmospheric forcing struggle to reproduce the observed deoxygenation after 2000, fully coupled Earth system models capture the trend, indicating systematic problems in hindcast simulations.
The impact of a Virtual Antimicrobial stewardship Team (VAT) on antibiotic prescriptions in Dutch nursing homes: a protocol for a randomised controlled trial
Authors: Paap Kelly C. , Kolodziej Lisa M. , Buul Laura W. , Jong Menno D. , Loeff Maarten F. Schim , Kuil Sacha D.
Published: March 2024

Background
Inappropriate prescribing of antibiotics for suspected urinary tract infections (UTI), respiratory tract infections (RTI) and skin and soft tissue infections (SSTI) in nursing homes (NHs) is common. Antimicrobial stewardship (AMS) has proven effectiveness in reducing inappropriate antibiotic prescriptions in hospitals. As the effectiveness of AMS has not yet been demonstrated in NHs, AMS has not yet been widely adopted in NHs. Therefore, the aim of this study is to evaluate the effect of a virtual antimicrobial stewardship team (VAT) on inappropriate antibiotic prescribing in NHs. An additional aim is to determine internal and external validity and identify barriers and facilitators of implementing VAT.
Methods
This study is a multicentre, two-arm, randomised, controlled, non-blinded trial to evaluate a VAT intervention in Dutch NHs. Four Medical Microbiology Laboratories (MMLs) and seven NHs will collaborate in this study, with in total 54 clinicians (27 per arm). Clinicians will be randomly assigned to either VAT (intervention) or usual care (control) in a 1:1 ratio. The clinicians in the intervention group will participate in a weekly VAT meeting for 36 weeks. The primary outcome is the incidence rate of inappropriate antibiotic prescriptions per clinician per week. The sample size is sufficient to demonstrate a reduction of 35% in the incidence rate of inappropriate prescriptions, with a power of 90% at alpha of 0.05. Secondary outcomes are the incidence rate (IR) of total antibiotic prescriptions, and the internal and external validity, and facilitators and barriers to VAT implementation through process evaluation.
Discussion
This protocol describes an RCT to evaluate whether an AMS intervention in Dutch NHs results in a reduction in the incidence rate of inappropriate antibiotic prescriptions for UTI, RTI and SSTI. A potential limitation is that researchers and clinicians cannot be blinded due to the nature of the intervention and there is risk of contamination between the intervention and control arm, as clinicians working in the same NH may be randomised to different arms; this may dilute the observed effect of the intervention.
Trial registration
ClinicalTrials.gov Identifier: NCT05998226
Feasibility of enzalutamide on patients with recurrent non-muscle-invasive bladder cancer with marker tumors: Phase I study
Authors: Kawahara Takashi , Kandori Shuya , Kojima Takahiro , Mathis Bryan J. , Shiga Masanobu , Kawai Koji , Nishiyama Hiroyuki
Published: March 2024

Objective: Recent preclinical and retrospective clinical evidence shows that androgen receptor (AR)-mediated signals have significant roles in development of non-muscle invasive bladder cancer (NMIBC). Here, we conducted a single-center, phase I study to assess the feasibility and efficacy of enzalutamide in patients having recurrent NMIBC with marker tumors. Patients with NMIBC who cannot achieve complete transurethral resection (TUR) or with recurrence within a year after the TUR, were enrolled. The patients were administered oral enzalutamide at 160 mg dose, once daily for four weeks. Clinical response at the end of the treatment was evaluated using cystoscopy.
Results: Of the six patients enrolled, two experienced multiple recurrences. All the patients received the planned administration of enzalutamide. Enzalutamide was tolerable and all patients were able to complete the planed treatment, although four patients experienced mild treatment-related adverse events (AEs), but AEs with grade 2 or more were not observed. As for efficacy, three patients showed no change while the remaining three showed disease progression. Immunohistochemical analysis did not showed the strong staining of AR in the latest tumors. This is the first clinical study on enzalutamide treatment for NMIBC patients. In this study, four weeks of enzalutamide administration was well tolerated, however showed no clinical response for non-strong staining of AR.
Calotropis induced Ocular toxicity Insilco Strategy.
Authors: Harke Shivali S , Bagchi Preenon , Shinde Ashok A.
Published: March 2024

The Calotropis Procera plant is a soft-wooded evergreen, perennial shrub, and its medicinal value has been described in older pharmacopeias. Accidental contact with Calotropis latex can lead to violent kerato-conjunctivitis, which is associated with corneal edema and significant vision impairment without causing pain. The ocular toxicity is primarily attributed to the alkaloids present in the latex. Our objective is to identify the specific alkaloid responsible for causing ocular toxicity and to investigate the corneal proteins involved in the cause of Ocular toxicity. To achieve this, we conducted Receptor-Ligand molecular docking using Maestro software. In this analysis, the alkaloids Calotoxin, Gigantin, Calotropin, and Calcin were considered as ligands, while different layers of the cornea's proteins serve as receptors. The docking scores were carefully analyzed, and we were able to conclude that Calotoxin exhibited the highest docking score and appeared to bind to numerous corneal proteins.
Effects of Tai Chi on lower limb motor function in patients with Parkinson's disease: A systematic review and meta-analysis
Authors: Lou Lijie , Yang Jiapeng , Hu Yingliang , Xiang Chunyu
Published: March 2024

This study aimed to systematically evaluate the effect of Tai Chi on the balance function, mobility function, and gait function (including gait endurance, gait amplitude, and gait speed) of the lower limbs in patients with Parkinson's disease. The “PICOS” principle was used to search seven English and six Chinese databases. Search for relevant studies published up to September 11, 2023, from the date of database creation. Two authors independently screened all eligible studies. The included studies were assessed for risk of bias based on the criteria outlined in Cochrane Handbook 5.1.0. Quantitative statistics and meta-analyses were conducted using Review Manager 5.4 software. The 18 studies that met the inclusion criteria, 16 of which were included in the meta-analysis, included a sample of 963 cases from four countries. The meta-analysis revealed that Tai Chi was effective compared with conventional medication in improving balance function (MD = 2.06, 95% CI [1.35, 2.78], P < 0.00001, I2 = 0%), mobility function (MD = -1.59, 95% CI [-2.28, -0.91], P < 0.00001, I2 = 14%), and gait speed (SMD = 0.59, 95% CI [0.28, 0.91], P = 0.0002, I2 = 29%). However, there was no significant improvement in gait endurance (SMD = 0.14, 95% CI [-0.41, 0.68], P = 0.62, I2 = 0%) or gait amplitude (SMD = 0.30, 95% CI [-0.00, 0.61], P = 0.05, I2 = 0%). Compared with other exercise therapies, Tai Chi was significantly superior in improving balance function (MD = 3.05, 95% CI [1.94, 4.16], P < 0.00001, I2 = 38%), mobility function (MD = -0.70, 95% CI [-1.23, -0.17], P = 0.01, I2 = 0%), and gait range (SMD = 0.36, 95% CI [0.14, 0.58], P = 0.002, I2 = 45%). However, the advantage of improving gait speed (SMD = 0.00, 95% CI [-0.28, 0.29], P = 0.98, I2 = 0%) was uncertain. Tai chi is a safe and effective rehabilitation intervention that can enhance the balance and mobility functions of the lower limbs in patients with Parkinson's disease.
Post-transcriptional RNA stabilization of telomere-proximal RNAs FRG2, DBET, D4Z4 at human 4q35 in response to genotoxic stress and D4Z4 macrosatellite repeat length
Authors: Salsi Valentina , Losi Francesca , Salani Monica , Kaufman Paul , Tupler Rossella
Published: March 2024

Background
Reduced copy number of the D4Z4 macrosatellite at human chromosome 4q35 is associated with facioscapulohumeral muscular dystrophy (FSHD). A pervasive idea is that chromatin alterations at the 4q35 locus following D4Z4 repeat unit deletion lead to disease via inappropriate expression of nearby genes. Here, we sought to analyze transcription and chromatin characteristics across 4q35 and how these are affected by D4Z4 deletions and exogenous stresses.
Results
We found that the 4q subtelomere is subdivided into discrete domains, each with characteristic chromatin features associated with distinct gene expression profiles. Centromere-proximal genes within 4q35 (ANT1, FAT1 and FRG1) display active histone marks at their promoters. In contrast, poised or repressed markings are present at telomere-proximal loci including FRG2, DBE-T and D4Z4. We discovered that these discrete domains undergo region-specific chromatin changes upon treatment with chromatin enzyme inhibitors or genotoxic drugs. We demonstrated that the 4q35 telomere-proximal FRG2, DBE-T and D4Z4-derived transcripts are induced upon DNA damage to levels inversely correlated with the D4Z4 repeat number, are stabilized through post-transcriptional mechanisms upon DNA damage, and are bound to chromatin.
Conclusion
Our study reveals unforeseen biochemical features of RNAs from clustered transcription units within the 4q35 subtelomere. Specifically, the FRG2, DBE-T and D4Z4-derived transcripts are chromatin-associated and are stabilized post-transcriptionally after induction by genotoxic stress. Remarkably, the extent of this response is modulated by the copy number of the D4Z4 repeats, raising new hypotheses about their regulation and function in human biology and disease.
ANN Based Clusterhead Selection Process in WSN
Authors: GANGAL Volkan , SESLI Erhan , HACIOGLU Gokce
Published: March 2024

Wireless sensor networks often face a significant challenge due to their limited energy capacity. To address this challenge, numerous studies are currently underway to explore innovative ways to optimize energy usage. This study proposes an energy-efficient cluster head selection method that is supported by artificial neural networks for cluster-based sensor networks, thereby enhancing their energy efficiency. The neural network is placed in each sensor node. The nodes decide to be the cluster head according to the threshold they set using the ANN, without the need for centralized control. According to the simulation studies conducted, the ANN trained with 5-5-5 neurons survived for 3497 rounds and successfully transmitted 96757 packets to the sink. In contrast, the LEACH algorithm could only survive for 1773 rounds and transmitted 61766 packets to the sink under the same conditions. The study confidently concluded that there was a significant and noteworthy improvement in both the network lifetime and the number of packets sent to the base station. On the other hand, it was also observed that the proposed method showed a notable improvement when compared with similar recent studies conducted with the same parameters by a factor ranging from 3.63 to 6.26.
Prediction of Meteorological Drought in Xinjiang at Multiple Temporal Scales Based on GWO-SA-ConvBiLSTM
Authors: Gu Lei , Ma Wen Yu , Yu MeiShuang , Chen PengYu , Hou Shuo
Published: March 2024

Drought is one of the most serious climatic disasters affecting human society. Effective drought prediction can provide a reliable basis for the formulation of anti-drought measures. According to drought characteristics, we construct a multi-time scale GWO-SA-ConvBiLSTM network. In this model, we combine Bidirectional Long Short-Term Memory (BiLSTM) and Convolutional Neural Networks (CNN), and add the self-attention mechanism (SA). On this basis, the grey Wolf optimizer(GWO) is added to make the model choose the optimal hyperparameter faster. We selected Atel region of Xinjiang as the research object, sorted out the meteorological data of 5 meteorological stations in the study area from 1960 to 2018, and imported their SPEI values of 1, 3, 6, 12 and 24 months into the model for training. Compared with other models, our model has better performance in the scenario of drought prediction.
Catharanthine, an anticancer vinca alkaloid: an in silico and in vitro analysis of the autophagic system as the major mechanism of cell death in liver HepG2 cells
Authors: Gholami Farnoosh , Seyedalipour Bagher , Heidari-Kalvani Nafiseh , Nabi-Afjadi Mohsen , Yaghoubzad-Maleki Mohammad , Fathi Zeinab , Alipourfard Iraj , Barjesteh Fereshte , Bahreini Elham
Published: March 2024

Background
Catharanthine, a component of the anticancer drug vinblastine along with vindoline, disrupts the cell cycle by interfering with mitotic spindle formation. Apart from their antioxidant properties, vinca alkaloids like catharanthine inhibit phosphodiesterase activity and elevate intracellular cAMP levels.
Methods
This study conducted experiments on HepG2 liver carcinoma cells with varying doses of catharanthine to evaluate cell death rates, viability, and determine the IC50 concentration via MTT assays. The apoptotic and autophagic effects of catharanthine were assessed using flow cytometry with annexin V and PI staining, while the expression of autophagy-related genes was analyzed through quantitative PCR. Additionally, molecular docking and molecular dynamics simulations were employed to further investigate catharanthine's impact on autophagy mechanisms.
Results
The study showed that catharanthine reduced oxidative stress and triggered apoptosis in HepG2 cells in a dose-dependent manner. Catharanthine also upregulated the expression of autophagy-related genes like LC3, Beclin1, and ULK1. Notably, catharanthine increased sirtuin-1 levels, a known autophagy inducer, while decreasing Akt expression compared to untreated cells. Molecular docking results indicated rapamycin had a stronger binding affinity with FRB (-10.7 KJ/mol⁻¹) than catharanthine (-7.3 KJ/mol⁻¹). Additionally, molecular dynamics simulations revealed that catharanthine interacted effectively with the FRB domain of mTOR, displaying stability and a strong binding affinity, although not as potent as rapamycin.
Conclusions
In summary, besides its cytotoxic and pro-apoptotic effects, catharanthine activates autophagy signaling pathways and induces autophagic necrosis by inhibiting mTOR.
Socio-demographic and clinical determinants of self-care in Chinese adults with type 2 diabetes: a multicenter cross-sectional study
Authors: LAN XUEFEN , Ji Xiaozhen , Zheng Xiaojia , Ding Xiaoyu , Mou Hongyi , Lu Shunfei , Ye Bin
Published: March 2024

Background
Self-care is essential for the management of type 2 diabetes. This study aims to explore self-care level as a dynamic process and investigate its socio-demographic and clinical determinants among Chinese adults with type 2 diabetes.
Methods
In this multicenter cross-sectional study, we enrolled 495 Chinese adults with type 2 diabetes from outpatient settings of three tertiary hospitals in Zhejiang province, China. The Self-Care of Diabetes Inventory (SCODI) was used to measure self-care maintenance, self-care monitoring, self-care management, and self-care confidence as four critical components of the dynamic self-care process. Multiple quantile regression models were used to identify the determinants of each self-care dimension.
Results
The median scores for self-care maintenance, self-care monitoring, and self-care management were 66.67, 47.06, and 53.13, respectively. Over half of the participants exhibited inadequate self-care maintenance, self-care monitoring, and self-care management (score less than 70), whereas their self-care confidence was adequate (median = 70.45). Lower level of self-care maintenance was associated with being male (p = 0.002), younger (p = 0.006), having at least one complication (p = 0.014), not living in city A (p < 0.001), and lower self-care confidence (p < 0.001). Lower level of self-care monitoring was associated with being female (p = 0.035), belonging to ethnic minorities (p = 0.002), not attending diabetes self-management education in the last year (p = 0.003), not living in city B (p < 0.001), and having lower self-care confidence (p < 0.001). Lower level of self-care management was associated with not having any complications (p = 0.003), not living in city B (p < 0.001), and having lower self-care confidence (p < 0.001). Lower level of self-care confidence was associated with not having any complications (p = 0.009), not attending diabetes self-management education (p = 0.004), and not living in city B (p < 0.001) or C (p = 0.001).
Conclusions/interpretation:
Among Chinese adults with type 2 diabetes, the degree of self-care maintenance, self-care monitoring, and self-care management was poor, whereas self-care confidence was relatively sufficient. More attention should be paid to the self-care of younger male patients belonging to ethnic minorities who live in less-developed cities. Modifiable determinants, such as self-care confidence and participation in diabetes self-management education, can be targeted to develop tailored self-care interventions.
Effect of methylparaben on the expression of genes involved in the in vitro maturation of porcine oocytes
Authors: Barajas-Salinas Adyeni , Bahena Iván , Rodríguez-Mercado Juan José , Juárez-Rojas Lizbeth , Betancourt Miguel , López Alma , Casas Eduardo , Bonilla Edmundo , Salazar Zayil , Casillas Fahiel
Published: March 2024

Background
Parabens (PBs) are widely used due to their antimicrobial properties in drugs, cosmetics, and food; however, previous studies have reported that methylparaben (MePB) may adversely interfere with female reproduction. MePB decreases oocyte in vitro maturation (IVM) at a maturation inhibition concentration 50 (MIC50) of 780.31 µM but also their viability at a lethal concentration 50 (LC50) of 2028.38 µM. It was reported that PBs are endocrine disruptors (EDs), affecting steroidogenesis as well as the cumulus cells (CC) expansion. Therefore, the aim of this study was to elucidate some of the mechanisms by which MePB alters CC expansion and decreases oocyte maturation through the evaluation of gene expression, Has2 for CC expansion, and Stard1, Cyp11a1, Hsd3b1, and Pr, for progesterone (P4) synthesis. Also, CC expansion and P4 concentrations in culture media were evaluated.
Methods
Oocytes were exposed to different MePB concentrations of 0 (control), 650, 780 and 1000 µM during 20 and 44 h of IVM. After 44 h of IVM, CC expansion, and IVM rates were evaluated. Gene expression of Has2, Stard1, Cyp11a1, Hsd3b1, and Pr were evaluated by qPCR at 20 and 44 h. P4 concentrations in culture media were evaluated at 20 and 44 h of IVM.
Results
MePB decreased CC expansion and the IVM of porcine oocytes. The expression of genes involved in steroidogenesis and CC expansion were also altered by MePB, as well as P4 concentrations in culture media, suggesting its potential role as ED.
Conclusions
This study provides insights into the mechanisms underlying MePB influence on IVM of porcine oocytes. Maturation is an important event that provides the oocyte the capacity to be fertilized, so any alteration produced during this period can impair fertility. Porcine oocytes are P4-dependent and require the CC expansion to reach the metaphase II (MII) stage. At sublethal concentrations of MePB, subexpression of Has2 resulted in decreased CC expansion and IVM. Also, MePB altered the expression of the genes involved in the first step of steroidogenesis from cholesterol to P4, suggesting its role as ED. These findings could partially explain some of the mechanisms by which MePB alters female fertility.
Precise Fiducial Marker Placement for CyberKnife Stereotactic Radiosurgery of Superficial Tumor
Authors: Huang Jing , Wang Ruijie , Chen Cheng , Jiang Wen , Dai ZhiTao
Published: March 2024

The CyberKnife, a renowned non-invasive stereotactic radiotherapy technique, has gained widespread adoption for its effective treatment of various cancers. The success of CyberKnife treatment relies significantly on the accurate placement of fiducial markers. This study introduces a Fiducial marker placement planning algorithm, specifically for superficial tumors that are located 20-50 mm beneath the epidermis. Three patients with treatment sites of thymus, breast, and submandibular gland were retrospectively selected for this study. The algorithm proposes numerous potential implantation sites by constructing and optimizing a B-spline surface. The site selection is predominantly based on the distance between markers, the angles among them, and the necessity for all fiducial markers to be visible in 45° oblique views without overlap. By leveraging the kd-tree, we enhanced spatial querying and addressed the challenge using graph theory, specifically through the Bron-Kerbosch algorithm. The time complexity of the algorithm proposed in this study is \(O(m\log m + m^2 + 3^{\frac{n}{3}})\), significantly faster than the brute-force \(O(n^3)\) approach. Experimental outcomes show that our algorithm can efficiently plan Fiducial marker placements, simplifying the planning process and providing valuable technical support for CyberKnife treatments.
Proposed intelligent learning algorithm to improve the diagnosis and classification of breast cancer masses
Authors: Eftekharian Mohsen
Published: March 2024

In today's world, intelligent medical diagnostic systems, with their remarkable advances, have greatly contributed to the medical world and have accelerated and increased the accuracy of many diagnoses, including the system for diagnosing and classifying breast cancer masses. Unfortunately, breast cancer is one of the most dangerous diseases and has led to many deaths among women. Early detection can, firstly, increase treatment options and, secondly, increase life expectancy in women with earlier treatment. Early detection methods include mammography, MRI and ultrasound. Early detection methods for breast cancer, include mammography, MRI, and ultrasound. In all diagnostic methods, image processing and artificial intelligence methods can be significantly effective in the process of noise detection and reduction, tumor area detection and classification. In this paper, first we reduce the noise in mammographic images using Directional filters, then extract the tumor area by combining the support vector machine and the Evolutionary Algorithms, and finally, using deep learning, To classify the type of mass. The proposed method has better performance compared to previous methods and offers 99.1% accuracy, 98.4% sensitivity and specificity with 100%. in diagnosis and classification.
Cyclin E and p53: The Dynamic Duo in Ovarian Tumor Pathogenesis
Authors: Zahran Amal , Abu-Salih Abdel Qader , Al-Bdour Mohammad , Abu-Salih Leen , Bani-Hani Kamal E.
Published: March 2024

Objectives: The aim of this study is to report on the expression of p53 and cyclin E in ovarian tumors and to analyze their correlations with the clinicopathological parameters. Another aim is to examine if aberrant expression of both cyclin E and p53 might increase the malignant potential of ovarian tumors.
Methods: Seventy-two paraffin-embedded ovarian tumor tissues were immuno-histochemically investigated for expression of p53, and cyclin E. The tumor tissues were benign (15), borderline (12), and malignant ovarian tumors (45). The expression of these two markers was analyzed with the correlations with the clinicopathological parameters in a subgroup of 34 epithelial ovarian cancers.
Results: p53 and cyclin E expression was markedly increased in malignant ovarian tumors as compared to benign tumors p-value= (0.002, 0.014) respectively. Expression of p53 in epithelial ovarian cancer tissues was significantly correlated with the stage of the tumor (p=0.015), whereas cyclin E expression was significantly associated with the histomorphologic tumor type (p= 0.001). There was significant correlation between p53 and cyclin E expression in the 72 ovarian tumor tissues p= 0.019.
Conclusions: There was a positive association between the expression of p53 and cyclin E and malignant progression of ovarian tumors. In epithelial ovarian cancers, p53 and cyclin E expressions were significantly correlated with the stage and histomorphologic tumor type, respectively.
Primary cutaneous nocardiosis of the ankle caused by N. brasiliensis: a case report
Authors: Şahin Suzan , Fidan Ebru , Tekol Serap Demir , Kaya Bülent
Published: March 2024

Nocardia is a genus of aerobic, Gram-positive bacteria known for their filamentous and branching morphology. N. brasiliensis is the most common species causing cutaneous nocardiosis. We present a 67-year-old woman who developed abscess-like lesions on the back of her right ankle after walking barefoot on soil. Cultures from the cutaneous lesions grew N. brasiliensis. Antibiotic therapy with trimethoprim-sulfamethoxazole given for a month provided near-complete resolution of her lesions.
Tricuspid valve rupture after blunt thoracic trauma
Authors: Shah Savan , Khan Arsalan , Bishop Michael , Alex Gillian
Published: March 2024

Background
Tricuspid valvular injuries are rare and often go undiagnosed, which can lead to right ventricular failure and death.
Case Presentation:
A 35-year-old female who presented after motor vehicle collision with multiple injuries was discovered to have a tricuspid valve rupture requiring valve replacement. In the case presented, the diagnosis was made with transthoracic echocardiography (TTE), however a subtler finding of new onset right bundle branch block was present during initial evaluation. The tricuspid valve rupture was managed with early valve replacement.
Conclusions
Although rare, tricuspid valve injuries can occur after blunt chest trauma and can be difficult to diagnose. Early recognition and swift treatment can prevent deadly complications.
Fires in the Mediterranean Ecosystem (Turkey) in July 2021
Authors: YILMAZ Fatma KAFALI , BOZYURT Okan , AVCI İlyas
Published: March 2024

Turkey has an ecologically rich ecology, including three main climate zones and three transition zones. Main climate zones; Black Sea, Mediterranean and Continental climate zones, and transition zones are Marmara, Mediterranean and Southeastern Anatolia regions. Of these ecological regions, a large area was damaged by the fire that broke out in July 2021 in the Mediterranean region in the south of Turkey and the Aegean region in the west (Mediterranean climate zone). The fire first started in Manavgat and Gündoğmuş districts of Antalya, and then broke out in various parts of Adana, Osmaniye and Muğla provinces. The fires that occurred in Adana took place in a wide area in the north of Adana, within the borders of four districts. In Osmaniye, fires occurred in the central district and Kadirli. These fires, which occurred in Osmaniye and Adana, took place in the forest area at an altitude of 500–1000 m. Since the fires that occurred in Antalya and Mersin were effective in the altitude zone starting from the coast and up to 1500 m, the mountain belt forest as well as the climax vegetation of the Mediterranean were burned. The fires that occurred in Muğla reached up to 2000 m and damaged a wide forest ecosystem. Due to the fire being at different altitude levels, Pinus brutia within the orobiome, Pinus nigra, Cedrus libani and Cedrus cilicia, which are mountain forests, and the understory were damaged. The fire also destroyed underground and aboveground fauna within the forest ecosystem, which could not be recorded statistically.
Examining the Impact of a GI Hospitalist Model on the Outcomes of Double Balloon Enteroscopy: A Single Center Retrospective Study
Authors: Babbar Shaili , Latorre Melissa
Published: March 2024

Background
A GI hospitalist (GIH) is a physician who practices in the inpatient setting performing consultations and endoscopic procedures. Obscure small bowel bleeding is a common inpatient diagnosis that is difficult to manage and associated with longer hospitalizations. Having an onsite GIH physician with expertise in video capsule endoscopy (VCE) and double balloon enteroscopy (DBE) has the potential to improve patient outcomes.
Aims
This study will be the first to explore how implementing a GIH model and providing a GIH with training in DBE can affect the outcomes of patients with small bowel pathology.
Methods
We performed a retrospective study of patients who received an inpatient DBE at an academic medical center before and after initiation of a GIH model and credentialing of a GIH in DBE. We compared outcomes, including procedure volumes, diagnostic and therapeutic yields, procedure duration, time-to-procedure, and length of stay.
Results
There was a 46.5% increase in the number of DBEs performed by the GIH. The diagnostic yield increased from 56.3–74.0% (OR 2.2, 95% CI 1.2–4.2), and the proportion of DBEs with a therapeutic intervention increased from 38.0–65.4% (OR 3.1, 95% CI 1.4-7.0). The total procedure time increased from 77.8 minutes to 96.4 minutes (p < 0.05) with a GIH.
Conclusions
Having a GIH perform inpatient DBEs was associated with an increased number of procedures, duration of procedures, diagnostic yield, and therapeutic interventions. The onsite presence of a GIH with competency in DBE improves the care of hospitalized patients with small bowel pathology.
The protective effect of sildenafil on colon anastomosis in a rat model undergoing hypertermic intraperitoneal chemotherapy
Authors: Başak Ahmet , Aydın Mehmet Timuçin , Fersahoğlu Mehmet Mahir , Taşdelen İksan , Somay Adnan , Teke Emre , Durum Erdem , Memişoğlu Kemal
Published: March 2024

Aim: The aim of the study is to investigate the effects of sildenafil on colonic anastomosis healing in rats treated with hyperthermic intraperitoneal chemotherapy.
Method: In our study, 30 Wistar-albino rats were used. 10 rats were used in each 3 groups: sildenafil, control and sham group. Left colon anastomosis was performed on rats in all three groups. HIPEC procedure was applied to sildenafil group and control group. At postoperative process, sildenafil was given orally to the sildenafil group. On the 7th day, the anastomotic loop was excised, and bursting pressure, and adhesion were evaluated. Anastomotic loop was evaluated histopathologically. The results were compared statistically.
Results: When the results were evaluated, considering bursting pressure, and adhesion between the sildenafil group and control group, there was no difference. Considering adhesion, the sham group was superior to the other two groups. In the histopathological examination, it was observed tha the sham group was significantly superior to the other two groups in terms of anastomototic re-epitelization and muscle seperation. There was significant difference between the sildenafil group and the control group in terms of fibrosis and granulation.
Conclusion: On colon anastomosis performed together with HIPEC application, histopathologically positive effects of sildenafil were observed. There was no difference considering burst pressure of colon anastomosis.
Measuring the degree of congestion in two-stage DEA: A case of Chinese textile, wearing apparel, and accessories industry
Authors: Ren Xian-tong , Song Yao-yao , Yang Guoliang
Published: March 2024

This paper develops a method to identify congestion and measure the degree of congestion in two-stage data envelopment analysis (DEA). First, the congestion in the two-stage DEA is defined. Next, based on the definition, a slack-based method is proposed to identify congestion and measure the degree of congestion in the two-stage DEA. We compare our method with the congestion identification method in one-stage DEA and find that the two-stage DEA can provide more accurate congestion information than treating the production process as a black box. The method we propose is used to assess congestion in the Chinese textile, wearing apparel, and accessories industry. The empirical results show that the degree of congestion in the Chinese textile, wearing apparel, and accessories is getting worse, although it has been weakening from 2013–2014. The information can be used to support the corresponding policymaking for the managers of both government and enterprises.
MS275 induces tumor immunosuppression by up-regulating PD-L1 and enhances the efficacy of anti-PD-1 immunotherapy in colorectal cancer
Authors: Chen Sihan , Mao Zhigang , Tang Deng , Su Mi , lai Meng , Yan Xiya , Yan Ruiting , Lan Siqi , Zhang Ji , Wang Yufang
Published: March 2024

The histone deacetylase inhibitor MS275 (Entinostat) demonstrates anti-tumor effects against various types of solid tumors in vitro. But its effectiveness in clinical trials is limited. The underlying reasons remain to be determined. The purpose of this study was to explore how to enhance the anti-tumor effects of MS275 in colorectal cancer(CRC). Our data showed that MS275 inhibited CRC cell proliferation and induced apoptosis, irrespective of gene mutation status. However, MS275 did not effectively suppress tumor growth in the AOM-DSS CRC model as observed in vitro. MS275 decreased CD3 + T cell tumor infiltration and created an anti-tumor immunosuppressive microenvironment in the AOM-DSS CRC model. MS275 also decreased the percentage of CD8 + T cells while increasing the percentage of CD4 + T cells in tumor-lymphocyte mixed culture. Reshaping tumor immune response may contribute to the less pronounced anti-tumor effect of MS275 observed in vivo compared to in vitro. Further study show that the increased PD-L1 expression in CRC both in vivo and in vitro following MS275 treatment. Moreover, the anti-tumor effects of MS275 were enhanced by combining it with an anti-PD-1 antibody. This combination treatment also increased CD3 + T cell tumor infiltration and M1 macrophage polarization in the AOM-DSS CRC model, thereby leading to an anti-tumor immune response. Therefore, the combination of MS275 and anti-PD-1 immunotherapy represents a potential strategy for low PD-L1 expression tumors and should be considered a promising treatment approach for colon cancer.
A accessory renal artery arising from the lumbar artery
Authors: Li Jiawei , Shi Mengwei , Ji Qingyu
Published: March 2024

Background
The presence of accessory renal arteries is a common variation of the renal artery and is important for surgical planning. These arteries are typically reported to originate from the abdominal aorta, common iliac artery, or mesenteric arteries, but there have been no reports of accessory renal arteries originating from the lumbar artery.
Case presentation
A dynamic enhanced scan of the kidneys with virtual reality display showed two blood supply vessels to the left kidney. One vessel originated from the abdominal aorta and supplied the upper and middle portions of the kidney, while another vessel originated from the left lumbar artery and supplied the lower portion of the kidney.
Conclusion
This case highlights a rare variation of the renal artery, where an accessory renal artery originates from the lumbar artery. Understanding such variations is crucial in surgery to avoid complications.
Utilizing Phonetic Similarity for Cross-source and Cross-language Toponym Matching - a Benchmark and Prototype
Authors: Sagi Tomer , Zaga Moran , Rusinek Sinai , Fekete Marcell Richard , Bjerva Johannes , Hose Katja
Published: March 2024

The writings of one ancient civilization often overlap in time and space with others. Many of these sources comprise unstructured text in ancient languages, causing scholars studying these civilizations to be siloed, often relying on sources in a single language. Recent efforts to extract structured information from historical scripts into place (toponym) and people databases (prospographies) have followed this pattern, focusing on one civilization or even one scholar. The path to creating a common database runs through aligning names or toponyms between sources from disparate languages utilizing different scripts. Existing multi-lingual orthographic (string-based) comparison often relies on transliteration to a common script (Latin/English). Transliteration often creates multiple options and even more confusion. However, when integrating sources that overlap in space and time, the languages often share a common phonetic background. This commonality may prove beneficial. In this work, we present a benchmark for comparing toponyms from two linguistically and culturally related languages, namely Hebrew and Arabic. We provide a benchmark comprised of a set of dataset pairs created from both historical sources written in ancient variants of these languages as well as a modern dataset curated from Wikidata. We empirically evaluate several toponym comparison approaches over the benchmark: transliteration to a common script, direct transliteration, and phonetic comparison using a common phonetic representation. We discuss the results and the limitations of the various methods and outline future work.