bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of SolidWorks software in preoperative planning of high tibial osteotomy
Authors: Lu Yufeng , Wang Xue , Yang Bo , Xu Zhaochen , Zhang Baogang , Jia Bin , He Jinlong , Qi Liang , Wang Min , Qiao Feng
Published: January 2023

Purpose

Open-wedge high tibial osteotomy (HTO) is a common surgical treatment for medial osteoarthritis in young and active patients. The accuracy of osteotomy is closely associated with postoperative efficacy. The accuracy of digital preoperative planning is higher than that of the preoperative manual measurement and several computer software with varying accuracy and convenience are used for digital preoperative planning. This study aimed to use the SolidWorks software for HTO preoperative planning and to determine its accuracy and reliability in HTO preoperative planning.

Methods

We reviewed the data of 28 patients with 54 with medial compartment knee arthritis who underwent open-wedge HTO preoperative planning using SolidWorks between June 2019 and March 2021. The standard anteroposterior standing whole-leg radiographs were assessed before and 6 weeks after the surgery. The correction angle, weight-bearing line (WBL) ratio, mechanical femorotibial angle (mFTA), and medial proximal tibial angle (MPTA) before and after the surgery were compared. The clinical results were evaluated using the Knee Society score.

Results

At 6 weeks after the surgery, the WBL ratio was corrected from 16.8% to 50.5%, mFTA was corrected from 6.4° varus to 1.2° valgus, and MPTA was corrected from 83.4° to 89.3°. No significant difference was observed between the predicted correction angle before the surgery and the correction angle measured 6 weeks after the surgery (t = −1.745, p = 0.087). The knee score and function score of Knee Society increased from 76.4 and 80.7 before surgery to 95.0 and 95.7, respectively.

Conclusions

The SolidWorks software showed high accuracy and reliability in preoperative planning of open-wedge HTO in patients with medial compartment knee arthritis.
Case report: An intrauterine device hugging the musculus rectus abdominis through the center of a cesarean scar
Authors: Jing Jigang
Published: January 2023

A 34-year-old woman presented with an abscess of the abdominal wall, with a 10-day history of rupture and discharge. She had a history of cesarean section 17 years ago, intrauterine device (IUD) insertion 5 years ago, and intermittent lumbago and abdominal pain for the past 4 years. A V-shaped IUD was observed via ultrasound between the bladder and abdominal wall, clinging to the musculus rectus abdominis through the center of the cesarean scar. Pelvic computed tomography (CT) revealed a V-shaped metal density at the anterior upper edge of the bladder, one end of which seemed to penetrate the abdominal wall. IUD migration was confirmed by surgery 2 days later. The patient recovered after IUD removal. This case affirms that a migrated IUD can lead to serious complications, even if there are no obvious symptoms for many years. Apart from the fact that the IUD has fallen out of place, a migrated IUD should be removed promptly, regardless of obvious complications. Furthermore, regular ultrasound examination is important for early diagnosis of IUD displacement. Based on the relevant literature, we also hypothesize the possible mechanism of IUD migration between the anterior bladder wall and the abdominal wall.

Core tip

Uterine perforation and IUD migration to the organs in the abdominopelvic cavity are serious complications of IUD insertion. We present a case of uterine perforation complicated by IUD migration with the application of intraoperative ultrasound localization. This case highlights that ultrasound, especially intraoperative ultrasound, can provide objective information for the diagnosis and localization of IUD migration, with the advantages of point of care, real-time imaging, convenience, low cost, and lack of radiation. Based on this case and on the relevant literature, we hypothesized the possible mechanism of IUD migration between the anterior bladder wall and the abdominal wall. To the best of our knowledge, no previous research has discussed the process of IUD migration beyond the anterior wall of the bladder.
Construction of a nomogram for preoperative prediction of the risk of lymph node metastasis in early gastric cancer
Authors: Liu Zitao , Tian Huakai , Huang Yongshan , Liu Yu , Zou Feilong , Huang Chao
Published: January 2023

Background

The status of lymph node metastasis (LNM) in patients with early gastric cancer (EGC) is particularly important for the formulation of clinical treatment. The purpose of this study was to construct a nomogram to predict the risk of LNM in EGC before operation.

Methods

Univariate analysis and logistic regression analysis were used to determine the independent risk factors for LNM. The independent risk factors were included in the nomogram, and the prediction accuracy, discriminant ability and clinical practicability of the nomogram were evaluated by the receiver operating characteristic curve (ROC), calibration curve and clinical decision curve (DCA), and 100 times ten-fold cross-validation was used for internal validation.

Results

33 (11.3%) cases of AGC were pathologically confirmed as LNM. In multivariate analysis, T stage, presence of enlarged lymph nodes on CT examination, carbohydrate antigen 199 (CA199), undifferentiated histological type and systemic inflammatory response index (SIRI) were risk factors for LNM. The area under the ROC curve of the nomogram was 0.86, the average area under the ROC curve of the 100-fold ten-fold cross-validation was 0.85, and the P value of the Hosmer-Lemeshow test was 0.60. In addition, the clinical decision curve, net reclassification index (NRI) and Integrated Discriminant Improvement Index (IDI) showed that the nomogram had good clinical utility.

Conclusions

We found that SIRI is a novel biomarker for preoperative prediction of LNM in EGC, and constructed a nomogram for preoperative prediction of the risk of LNM in EGC, which is helpful for the formulation of the clinical treatment strategies.
Prognostic impact of tumor size on isolated hepatocellular carcinoma without vascular invasion may have age variance
Authors: Zhang Yi , Zhang Jun-Gang , Yu Wei , Liang Lei , Wu Chun , Zhang Cheng-Wu , Xie Ya-Ming , Huang Dong-Sheng , Shi Ying
Published: January 2023

Background

Previous studies suggested that tumor size was an independent risk factor of prognosis for hepatocellular carcinoma (HCC). However, the general prognostic analysis did not consider the interaction between variables. The purpose of this study was to investigate whether the effect of tumor size on the prognosis of isolated HCC without vascular invasion varies according to covariates.

Methods

Patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database to investigate whether there was an interaction between age and tumor size on the prognosis. Then the trend test and the value of per 1 SD of tumor size were calculated. In addition, the data of Zhejiang Provincial People's Hospital meeting the requirements were selected to verify the obtained conclusions.

Results

Multivariable Cox regression analysis of the database cohort showed that age, gender, tumor size, pathological grade and marital status were independent risk factors for prognosis. Interaction test showed that there was an interaction between age and tumor size (P for interaction < 0.05). Stratified analysis by age showed that tumor size was an independent risk factor for prognosis when age ≤65 years old (HR:1.010,95%CI1.007–1.013 P < 0.001), while tumor size was not an independent risk factor for prognosis when age >65 years old. This result was confirmed by trend analysis (P for trend < 0.001), and the prognostic risk increased by 42.1% for each standard deviation increase of tumor size among patients age ≤65 years. Consistent conclusion was obtained by multivariable cox regression analysis and interaction test on the verification cohort. In the validation cohort, for each standard deviation increase of tumor size in patients ≤65 years old, the risk of prognosis increased by 52.4%.

Conclusion

Tumor size is not an independent risk factor for the prognosis of isolated HCC without vascular invasion when patient's age >65 years. Therefore, when analyzing the relationship between tumor size and prognosis, stratified analysis should be performed according to age.
Analysis of the effect of phloroglucinol on pregnancy outcomes involving frozen embryo transfers in patients with endometriosis: A retrospective case-control study
Authors: Pang Wen-Juan , Feng Xu , Wang Xiang , Wang Liang , Sun Ning-Xia
Published: January 2023

Objective

Abnormal contraction of uterus and vascular smooth muscle lead to the formation of hypoxia environment in uterus. Abnormal contraction may be the basis of dysmenorrhea, endometriosis, infertility and other diseases. Phloroglucinol is a non-atropine and non-papaverine smooth muscle spasmolytic agent, which can reduce the abnormal contraction of uterine smooth muscle. This study investigated the effect of phloroglucinol on frozen embryo transfer in patients with endometriosis.

Methods

The data of patients with endometriosis who underwent a frozen embryo transfer in Shanghai Changzheng Hospital from August 2018 to August 2021, comprising a total of 453 cycles, were retrospectively analyzed. The patients for whom phloroglucinol was included over 217 cycles were administered intramuscully 40 mg phloroglucinol starting on the day of progesterone administration, then once daily up to day 7 after the embryo transfer. Those for whom phloroglucinol was not administered over 236 cycles were used as the control group. The age of 35 years was used as a boundary in this study to observe the pregnancy outcomes of patients in the two different age groups.

Results

The biochemical pregnancy rate (63.13% vs. 51.27%), embryo implantation rate (44.64% vs. 33.60%), clinical pregnancy rate (59.64% vs. 48.30%), and live birth rate (52.99% vs. 36.86%) after the administration of phloroglucinol were higher than for patients in the control group, and the early abortion rate (7.75% vs. 20.18%) was also lower. The differences were statistically significant (P < 0.05). In particular, in the age group <35 years old, the embryo implantation rate (51.81% vs. 39.38%), clinical pregnancy rate (69.34% vs. 57.55%), and the live birth rate (63.50% vs. 44.60%) after phloroglucinol intervention rose significantly, and the abortion rate dropped (6.32% vs. 17.5%), indicating a statistically significant difference (P < 0.05). However, pregnancy outcomes showed no difference in the age group ≥35 years old (P > 0.05).

Conclusion

Continuous low-dose phloroglucinol pretreatment before and after frozen embryo transfer can improve both the clinical pregnancy and live birth rates and reduce the risk of abortion in younger infertile patients with endometriosis.
Yeast derivatives as a source of bioactive components in animal nutrition: A brief review
Authors: Patterson Rob , Rogiewicz Anna , Kiarie Elijah G. , Slominski Bogdan A.
Published: January 2023

With a long history of inclusion within livestock feeding programs, yeast and their respective derivatives are well-understood from a nutritional perspective. Originally used as sources of highly digestible protein in young animal rations in order to offset the use of conventional protein sources such as soybean and fish meal, application strategies have expanded in recent years into non-nutritional uses for all animal categories. For the case of yeast derivatives, product streams coming from the downstream processing of nutritional yeast, the expansion in use cases across species groups has been driven by a greater understanding of the composition of each derivative along with deeper knowledge of mechanistic action of key functional components. From improving feed efficiency, to serving as alternatives to antibiotic growth promoters and supporting intestinal health and immunity while mitigating pathogen shedding, new use cases are driven by a recognition that yeast derivatives contain specific bioactive compounds that possess functional properties. This review will attempt to highlight key bioactive categories within industrially applicable yeast derivatives and provide context regarding identification and characterization and mechanisms of action related to efficacy within a range of experimental models.
Surveillance in a Neonatal Intensive Care Unit Allowed the Isolation of a Strain of VIM-Producing Pantoea brenneri
Authors: Merla Cristina , Mileto Irene , Gaiarsa Stefano , Achille Cristian , Ghirardello Stefano , Corbella Marta , Baldanti Fausto , Cambieri Patrizia
Published: January 2023

Here, we describe the isolation of a strain of the genus Pantoea encoding a VIM carbapenemase, the first to our knowledge. The strain, isolated from a rectal swab of a 10-day-old newborn admitted to a neonatal intensive care unit (NICU), was identified through whole-genome sequencing analyses as Pantoea brenneri. The strain harbored the carbapenemases gene blaVIM-1. The prompt application of contact measures and the isolation of the newborn prevented the dissemination of VIM-producing P. brenneri and of the plasmid carrying the VIM-1 gene to other newborns.
Extreme Heights of 15 January 2022 Tonga Volcanic Plume and Its Initial Evolution Inferred from COSMIC-2 RO Measurements
Authors: Ravindra Babu Saginela , Lin Neng-Huei
Published: January 2023

The Hunga Tonga–Hunga Ha’apai underwater volcano (20.57° S, 175.38° W) violently erupted on 15 January 2022. The volcanic cloud’s top height and initial evolution are delineated by using the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC)-2 radio occultation (RO) measurements. The bending angle (BA) anomaly over the Tonga volcanic plume (within 200 km of the eruption center) at 5:17 UTC on 15 January showed a prominent peak at higher stratospheric heights. The top of the BA anomaly revealed that negative to positive change occurred at ~38 km, indicating the first height where the RO line-of-sight encountered the volcanic plume. The BA anomaly further revealed an increase of ~50% at ~36.1 km, and confirmed that the volcanic plume reached above ~36 km. Furthermore, the evolution of BA perturbations within 24 h after the initial explosion is also discussed herein. From collocated RO profiles with the volcanic plume, we can find a clear descent of the peak altitude of the BA perturbation from ~36.1 km to ~29 km within 24 h after the initial eruption. The results from this study will provide some insights into advancing our understanding of volcanic cloud dynamics and their implementation in volcanic plume modeling.
Assessment of Bacterial Aerosols in a Herbal Processing Plant
Authors: Bulski Karol , Frączek Krzysztof
Published: January 2023

The aim of this study was to assess bacterial aerosols in a herbal processing plant in Poland. Bioaerosol measurements of indoor and outdoor air of the herbal processing plant were performed in four measurement rounds, in a seasonal cycle—in spring, summer, autumn, and winter—using a six-stage Andersen’s cascade air sampler. At each measuring point, during the bioaerosol sampling, the values of relative humidity and air temperature were simultaneously measured using the Kestrel 4000 device, and the concentration of particulate matter (fractions 1.0 μm, 2.5 μm, 4.0 µm, and 10.0 µm) using a DustTrak II dust analyzer. The results showed that the production process affects the bacterial aerosol concentrations in the tested plant. There were statistically significant differences in the concentrations of bacterial aerosol between indoor and outdoor air, and between production rooms, taking into account the seasons of the year. The concentrations of bacterial aerosol in the production rooms did not exceed 7.6 ×·103 cfu·m−3 and were lower than the permissible concentration values proposed for production rooms contaminated with organic dust. The calculations showed a significant correlation between the concentration of bacterial aerosol and air temperature. Qualitative analysis of microorganisms isolated from the air of production rooms showed the dominance of Gram-positive cocci of the genus Micrococcus and spore-forming rods of the Bacillus genus. The study confirmed that herbal processing plants may be related to exposure to microbiological agents.
Intravascular Large B-Cell Lymphoma: Two Cases Observed at a Single Institution
Authors: Miccolis Rosanna Maria , De Santis Gaetano , Buquicchio Caterina , Santeramo Teresa Maria , Leo Mariangela , Germano Candida Rosaria , Lerario Giovanna , Carluccio Vera , Mallano Sonia , Cardisciani Lina , Di Sciascio Luisa , Tarantini Giuseppe
Published: January 2023

Intravascular large B-cell Lymphoma (IVLBCL) is a rare subtype of extranodal non-Hodgkin’s lymphoma that is challenging to diagnose and has a poor prognosis. Here, we describe two patients newly diagnosed with IVLBCL at our institution: an African man with hemophagocytic-syndrome-associated IVLBCL and an Italian woman with a cutaneous variant of IVLBCL. They presented with very different clinical manifestations. Both cases were diagnosed in a timely manner, successfully treated, and achieved long-lasting remissions.
Neuronal Cytoglobin in the Auditory Brainstem of Rat and Mouse: Distribution, Cochlear Projection, and Nitric Oxide Production
Authors: Reuss Stefan , Balmaceda Daniel , Elgurt Mirra , Riemann Randolf
Published: January 2023

Cytoglobin (Cygb), a hemoprotein of the globin family, is expressed in the supportive tissue cells of the fibroblast lineage and in distinct neuronal cell populations. The expression pattern and regulatory parameters of fibroblasts and related cells were studied in organs such as the kidney and liver in a variety of animal models. In contrast, knowledge about cytoglobin-expressing neurons is sparse. Only a few papers described the distribution in the brain as ubiquitous with a restricted number of neurons in focal regions. Although there is evidence for cytoglobin involvement in neuronal hypoxia tolerance, its presence in the auditory system was not studied despite high metabolism rates and oxygen demands of the cochlea and related brainstem centers. In a continuation of a previous study demonstrating Cygb-neurons in, inter alia, auditory regions of the mouse brain, we concentrated on the superior olivary complex (SOC) in the present study. We sought to investigate the distribution, projection pattern and neurochemistry of Cygb-neurons in the SOC. We conducted immunohistochemistry using a Cygb antibody and found that this brainstem region, functionally competent for bilateral hearing and providing cochlear hair cell innervation, contains a considerable number of Cygb-expressing neurons (averaging 2067 ± 211 making up 10 ±1% percent of total neuron number) in rats, and 514 ± 138 (6 ± 1%) in mice. They were observed in all regions of the SOC. Retrograde neuronal tract tracing with Fluorogold injected into the cochlea demonstrated that 1243 ± 100 (6 ± 1% of total neuron number in rat SOC)) were olivocochlear neurons. Approximately 56% of total Cygb neurons were retrogradely labelled, while the majority of olivocochlear neurons of both lateral and medial systems were Cygb-immunoreactive. We also conducted double immunofluorescence staining for Cygb and neuronal nitric oxide synthase (nNOS), the enzyme responsible for nitric oxide production, and observed that cytoglobin in the SOC frequently co-localized with nNOS. Our findings suggest that cytoglobin plays an important physiologic role in the oxygen homeostasis of the peripheral and central auditory nervous system. Further studies, also including transgenic animal models, are required to shed more light on the function(s) of Cygb in neurons, in particular of the auditory system.
Bladder Wall Stiffness after Cystectomy in Bladder Cancer Patients: A Preliminary Study
Authors: Monteiro-Reis Sara , Ferreira João P. S. , Pires Ricardo A. , Lobo João , Carvalho João A. , Reis Rui L. , Jorge Renato Natal , Jerónimo Carmen
Published: January 2023

Bladder cancer (BlCa), specifically urothelial carcinomas, is a heterogeneous disease that derives from the urothelial lining. Two main classes of BlCa are acknowledged: the non-muscle invasive BlCa and the muscle-invasive BlCa; the latter constituting an aggressive disease which invades locally and metastasizes systemically. Distinguishing the specific microenvironment that cancer cells experience between mucosa and muscularis propria layers can help elucidate how these cells acquire invasive capacities. In this work, we propose to measure the micromechanical properties of both mucosa and muscularis propria layers of the bladder wall of BlCa patients, using atomic force microscopy (AFM). To do that, two cross-sections of both the macroscopically normal urinary bladder wall and the bladder wall adjacent to the tumor were collected and immediately frozen, prior to AFM samples analysis. The respective “twin” formalin-fixed paraffin-embedded tissue fragments were processed and later evaluated for histopathological examination. H&E staining suggested that tumors promoted the development of muscle-like structures in the mucosa surrounding the neoplastic region. The average Young’s modulus (cell stiffness) in tumor-adjacent specimens was significantly higher in the muscularis propria than in the mucosa. Similarly, the tumor-free specimens had significantly higher Young’s moduli in the muscularis propria than in the urothelium. Young’s moduli were higher in all layers of tumor-adjacent tissues when compared with tumor-free samples. Here we provide insights into the stiffness of the bladder wall layers, and we show that the presence of tumor in the surrounding mucosa leads to an alteration of its smooth muscle content. The quantitative assessment of stiffness range here presented provides essential data for future research on BlCa and for understanding how the biomechanical stimuli can modulate cancer cells’ capacity to invade through the different bladder layers.
Epigenetics of Thymic Epithelial Tumors
Authors: Nicolì Vanessa , Coppedè Fabio
Published: January 2023

Thymic epithelial tumors (TETs) arise from the epithelial cells of the thymus and consist in the 1% of all adult malignancies, despite the fact that they are the most common lesions of the anterior mediastinum. TETs can be divided mainly into thymomas, thymic carcinomas, and the rarest ad aggressive neuroendocrine forms. Despite the surgical resection is quite resolving, the diagnosis of TETs is complicated by the absence of symptoms and the clinical presentation aggravated by several paraneoplastic disorders, including myasthenia gravis. Thus, the heterogeneity of TETs prompts the search for molecular biomarkers that could be helpful for tumor characterization and clinical outcomes prediction. With these aims, several researchers investigated the epigenetic profiles of TETs. In this manuscript, we narratively review the works investigating the deregulation of epigenetic mechanisms in TETs, highlighting the need for further studies combining genetic, epigenetic, and expression data to better characterize the different molecular subtypes and identify, for each of them, the most relevant epigenetic biomarkers of clinical utility.
Prognostic Value of CD8+ Lymphocytes in Hepatocellular Carcinoma and Perineoplastic Parenchyma Assessed by Interface Density Profiles in Liver Resection Samples
Authors: Stulpinas Rokas , Zilenaite-Petrulaitiene Dovile , Rasmusson Allan , Gulla Aiste , Grigonyte Agne , Strupas Kestutis , Laurinavicius Arvydas
Published: January 2023

Hepatocellular carcinoma (HCC) often emerges in the setting of long-standing inflammatory liver disease. CD8 lymphocytes are involved in both the antitumoral response and hepatocyte damage in the remaining parenchyma. We investigated the dual role of CD8 lymphocytes by assessing density profiles at the interfaces of both HCC and perineoplastic liver parenchyma with surrounding stroma in whole-slide immunohistochemistry images of surgical resection samples. We applied a hexagonal grid-based digital image analysis method to sample the interface zones and compute the CD8 density profiles within them. The prognostic value of the indicators was explored in the context of clinicopathological, peripheral blood testing, and surgery data. Independent predictors of worse OS were a low standard deviation of CD8+ density along the tumor edge, high mean CD8+ density within the epithelial aspect of the perineoplastic liver-stroma interface, longer duration of surgery, a higher level of aspartate transaminase (AST), and a higher basophil count in the peripheral blood. A combined score, derived from these five independent predictors, enabled risk stratification of the patients into three prognostic categories with a 5-year OS probability of 76%, 40%, and 8%. Independent predictors of longer RFS were stage pT1, shorter duration of surgery, larger tumor size, wider tumor-free margin, and higher mean CD8+ density in the epithelial aspect of the tumor-stroma interface. We conclude that (1) our computational models reveal independent and opposite prognostic impacts of CD8+ cell densities at the interfaces of the malignant and non-malignant epithelium interfaces with the surrounding stroma; and (2) together with pathology, surgery, and laboratory data, comprehensive prognostic models can be constructed to predict patient outcomes after liver resection due to HCC.
Continuous Relationship of Operative Duration with Risk of Adverse Perioperative Outcomes and Early Discharge Undergoing Thoracoscopic Lung Cancer Surgery
Authors: Tong Chaoyang , Shen Yaofeng , Zhu Hongwei , Zheng Jijian , Xu Yuanyuan , Wu Jingxiang
Published: January 2023

Background: For thoracoscopic lung cancer surgery, the continuous relationship and the trigger point of operative duration with a risk of adverse perioperative outcomes (APOs) and early discharge remain unknown. Methods: This study enrolled 12,392 patients who underwent this surgical treatment. Five groups were stratified by operative duration: <60 min, 60–120 min, 120–180 min, 180–240 min, and ≥240 min. APOs included intraoperative hypoxemia, delayed extubation, postoperative pulmonary complications (PPCs), prolonged air leakage (PAL), postoperative atrial fibrillation (POAF), and transfusion. A restricted cubic spline (RCS) plot was used to characterize the continuous relationship of operative duration with the risk of APOs and early discharge. Results: The risks of the aforementioned APOs increased with each additional hour after the first hour. A J-shaped association with APOs was observed, with a higher risk in those with prolonged operative duration compared with those with shorter values. However, the probability of early discharge decreased from 0.465 to 0.350, 0.217, and 0.227 for each additional hour of operative duration compared with counterparts (<60 min), showing an inverse J-shaped association. The 90 min procedure appears to be a tipping point for a sharp increase in APOs and a significant reduction in early discharge. Conclusions: Our findings have important and meaningful implications for risk predictions and clinical interventions, and early rehabilitation, for APOs.
BCL2L11 Induction Mediates Sensitivity to Src and MEK1/2 Inhibition in Thyroid Cancer
Authors: Rose Madison M. , Espinoza Veronica L. , Hoff Katelyn J. , Pike Laura A. , Sharma Vibha , Hofmann Marie-Claude , Tan Aik Choon , Pozdeyev Nikita , Schweppe Rebecca E.
Published: January 2023

Patients with advanced thyroid cancer, including advanced papillary thyroid cancer and anaplastic thyroid cancer (ATC), have low survival rates because of the lack of efficient therapies available that can combat their aggressiveness. A total of 90% of thyroid cancers have identifiable driver mutations, which often are components of the MAPK pathway, including BRAF, RAS, and RET-fusions. In addition, Src is a non-receptor tyrosine kinase that is overexpressed and activated in thyroid cancer, which we and others have shown is a clinically relevant target. We have previously demonstrated that combined inhibition of Src with dasatinib and the MAPK pathway with trametinib synergistically inhibits growth and induces apoptosis in BRAF- and RAS-mutant thyroid cancer cells. Herein, we identified the pro-apoptotic protein BCL2L11 (BIM) as being a key mediator of sensitivity in response to combined dasatinib and trametinib treatment. Specifically, cells that are sensitive to combined dasatinib and trametinib treatment have inhibition of FAK/Src, MEK/ERK, and AKT, resulting in the dramatic upregulation of BIM, while cells that are resistant lack inhibition of AKT and have a dampened induction of BIM. Inhibition of AKT directly sensitizes resistant cells to combined dasatinib and trametinib but will not be clinically feasible. Importantly, targeting BCL-XL with the BH3-mimeitc ABT-263 is sufficient to overcome lack of BIM induction and sensitize resistant cells to combined dasatinib and trametinib treatment. This study provides evidence that combined Src and MEK1/2 inhibition is a promising therapeutic option for patients with advanced thyroid cancer and identifies BIM induction as a potential biomarker of response.
Gene Screening for Prognosis of Non-Muscle-Invasive Bladder Carcinoma under Competing Risks Endpoints
Authors: Ke Chenlu , Bandyopadhyay Dipankar , Sarkar Devanand
Published: January 2023

Background: Discovering clinically useful molecular markers for predicting the survival of patients diagnosed with non–muscle-invasive bladder cancer can provide insights into cancer dynamics and improve treatment outcomes. However, the presence of competing risks (CR) endpoints complicates the estimation and inferential framework. There is also a lack of statistical analysis tools and software for coping with the high-throughput nature of these data, in terms of marker screening and selection. Aims: To propose a gene screening procedure for proportional subdistribution hazards regression under a CR framework, and illustrate its application in using molecular profiling to predict survival for non-muscle invasive bladder carcinoma. Methods: Tumors from 300 patients diagnosed with bladder cancer were analyzed for genomic abnormalities while controlling for clinically important covariates. Genes with expression patterns that were associated with survival were identified through a screening procedure based on proportional subdistribution hazards regression. A molecular predictor of risk was constructed and examined for prediction accuracy. Results: A six-gene signature was found to be a significant predictor associated with survival of non–muscle-invasive bladder cancer, subject to competing risks after adjusting for age, gender, reevaluated WHO grade, stage and BCG/MMC treatment (p-value < 0.001). Conclusion: The proposed gene screening procedure can be used to discover molecular determinants of survival for non–muscle-invasive bladder cancer and in general facilitate high-throughput competing risks data analysis with easy implementation.
Multiple Copies of microRNA Binding Sites in Long 3′UTR Variants Regulate Axonal Translation
Authors: Farberov Luba , Ionescu Ariel , Zoabi Yazeed , Shapira Guy , Ibraheem Amjd , Azan Yosi , Perlson Eran , Shomron Noam
Published: January 2023

Rapid responses to changes within subcellular compartments of highly polarized cells, such as neuron axons, depend on local translation and post-transcriptional regulation. The mechanism by which microRNAs (miRNAs) regulate this process is not fully understood. Here, using live cell imaging and RNA sequencing analysis, we demonstrated how miRNAs can differentially control hundreds of transcripts at the subcellular level. We demonstrated that the seed match length of the miRNA target-sequence regulates both mRNA stability and protein translation rates. While longer seed matches have an increased inhibitory effect, transcriptome analysis did not reveal differences in seed match length between axonal and somata mRNAs of motor neurons. However, mRNA variants with longer 3′UTR are enriched in axons and contain multiple repeats of specific miRNA target sequences. Finally, we demonstrated that the long 3′UTR mRNA variant of the motor protein Kif5b is enriched explicitly in motor neuron axons and contains multiple sequence repeats for binding miR-129-5p. This subsequently results in the differential post-transcriptional regulation of kif5b and its synthesis in axons. Thus, we suggest that the number of miRNA binding sites at the 3′UTR of the mRNA, rather than the miRNA seed match length, regulates the axonal transcriptome.
Effects of Dupilumab on Itch-Related Events in Atopic Dermatitis: Implications for Assessing Treatment Efficacy in Clinical Practice
Authors: Kishi Ryoma , Toyama Sumika , Tominaga Mitsutoshi , Kamata Yayoi , Komiya Eriko , Kaneko Takahide , Suga Yasushi , Takamori Kenji
Published: January 2023

Dupilumab attenuates itch and skin inflammation in patients with atopic dermatitis (AD). However, itch-related events that are improved by dupilumab remain unclear. Therefore, the present study investigated changes in clinical scores, serum biomarkers, and the number of intraepidermal nerve fibers (IENFs) using skin biopsies and blood samples from 12 patients with moderate to severe AD before and after treatment with dupilumab. Clinical manifestations were assessed using eczema area and severity index (EASI) and visual analogue scale (VAS) scores at baseline and after 8 and 16 weeks of treatment. Serum levels of total immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), interleukin (IL)-4, IL-13, IL-22, and IL-31 were examined by electrochemiluminescence, chemiluminescent enzyme immunoassays, ProQuantum immunoassays, and enzyme-linked immunosorbent assays (ELISA) at baseline and after 8 and 16 weeks of treatment. In skin biopsies from AD patients at baseline and after 16 weeks of treatment, IENFs were examined immunohistochemically with the anti-protein gene product (PGP) 9.5 antibody. The dupilumab treatment significantly improved EASI and VAS scores and decreased serum levels of TARC, IgE, and IL-22, whereas those of IL-13 and IL-31, and the number of IENFs remained unchanged and those of IL-4 increased. VAS scores were positively correlated with serum TARC, IL-22, and IgE levels and the degree of epidermal thickening. Serum IL-31 levels were positively correlated with the number of IENFs. These results suggest that serum TARC, IL-22, and IgE levels and epidermal thickness are itch-related events associated with dupilumab treatment and that serum IL-31 levels may reflect the degree of IENF density in AD patients. Therefore, dynamic changes may be used to assess the efficacy of dupilumab treatment to treat itching and inflammation in patients with AD.
Influence of Seawater Erosion on The Strength and Pore Structure of Cement Soil with Ferronickel Slag Powder
Authors: Chen Feng , Tong Shenghao , Wang Hao , Chen Weizhen
Published: January 2023

To promote the recycling of industrial waste residues in the reinforcement of foundation soil, the anti−seawater erosion of cement soil with ferronickel slag powder in the marine environment was studied. Specifically, this paper employed ferronickel slag powder to partially replace the cement. Then, the apparent morphology, unconfined compressive strength, and nuclear magnetic resonance (NMR) tests were performed on specimens of cement soil with ferronickel slag powder soaked in purified water and seawater. The research results reveal that with the rise in the content of ferronickel slag powder, the erosive effect of seawater on cement soil weakens, while the compressive strength of cement soil increases first and then decreases. With an excessive amount of ferronickel slag powder added to the cement soil, its chemically active effect decreases, leading to a decrease in the strength of the cement soil. When the admixture of ferronickel slag powder in cement soil is 45%, it achieves good performance. The addition of ferronickel slag powder improves the plasticity of cement soil. The higher the content of ferronickel slag powder, the greater the failure strain and residual strength of the cement soil. Microscopic studies indicate that with the increase in the content of ferronickel slag powder, the pores in the cement soil become smaller and smaller, the total pore volume decreases, the continuity of the pore size distribution improves, and the structure becomes more compact, thus enhancing the erosion resistance of cement soil.
Investigation into Corrosive Wear of the CoCrFeNiTax Laser-Clad Coatings on TC4 in the Neutral and Alkaline Circumstance
Authors: Yan Yanan , Li Jun , Li Ruoliu , Shao Meng , Li Jing
Published: January 2023

CoCrFeNiTax (x = 0, 1) coatings were prepared on the surface of TC4 by laser-cladding to improve the corrosive wear property of TC4 and extend its service life in corrosive media, ultimately aiming to improve its surface performance. The effects of Ta addition on the phase constituent and microstructure of the coatings were first investigated. Given the wide application of TC4 in corrosive media (even undergoing friction), the corrosive wear of TC4 covered with the coatings was especially focused in two media (neutral and alkaline). The results showed that the coatings were composed of primary α(Ti) and eutecticum (α(Ti) + Ti2Ni) as the matrix and TiC as the reinforcement. The introduction of Ta increased the volume fraction of eutecticum and TiC and made the microstructure more uniform. The coating with Ta performed more outstanding corrosive wear resistance than the other two samples in the two media. The wear rate of the coating with Ta was 4.7458 × 10−4 mm3·N−1·m−1 in the neutral environment and 6.6808 × 10−4 mm3·N−1·m−1 in the alkaline environment, 64.45% and 61.79% lower than those of TC4, respectively. The wear mechanism of the samples is a combination of serious micro-cutting, active dissolution, and oxidation, and the introduction of Ta effectively improved the resistance to micro-cutting.
Jedi Spinel from Man Sin, Myanmar: Color, Inclusion, and Chemical Features
Authors: Gao Yujie , He Mingyue , Sun Xueying , Zhen Cuiling , Li Huihuang , Wei Xiaotao , Zhao Yizhi
Published: January 2023

In the present study, we collected and investigated spinels from the Man Sin deposit in Myanmar using standard gemological testing, microscopic observation, EDXRF, and Raman spectrometry. The color observation was performed under various lighting conditions to show color differences. A very high Cr/Fe ratio is linked with exceptionally strong red fluorescence. Microscopic observation and Raman spectroscopy identified mineral inclusions of colorless phlogopite, molybdenite, hauerite, native sulfur, and calcite. Man Sin spinels are typical Fe– and Zn–poor spinels. Binary and ternary diagrams were used to discriminate each deposit (i.e., Man Sin, Mogok, and Namya in Myanmar) with high reliability. Jedi spinel fever in the Asian market, due to their unique neon color appearance and exceptionally strong fluorescence, is also discussed.
Temperature−Dependent Raman Scattering Investigation on vdW Epitaxial PbI2/CrOCl Heterostructure
Authors: You Siwen , Guo Xiao , Jiang Junjie , Yang Dingbang , Li Mingjun , Ouyang Fangping , Xie Haipeng , Huang Han , Gao Yongli
Published: January 2023

Van der Waals (vdW) epitaxial growth provides an efficient strategy to prepare heterostructures with atomically and electronically sharp interfaces. Herein, PbI2 was in situ thermally deposited onto exfoliated thin−layered CrOCl nanoflakes in high vacuum to fabricate vdW PbI2/CrOCl heterostructures. Optical microscopy, atomic force microscopy, X−ray diffraction, and temperature−dependent Raman spectroscopy were used to investigate the structural properties and phonon behaviors of the heterostructures. The morphology of PbI2 films on the CrOCl substrate obviously depended on the substrate temperature, changing from hemispherical granules to 2D nanoflakes with flat top surfaces. In addition, anomalous blueshift of the Ag1 and Au2 modes as the temperature increased in PbI2/CrOCl heterostructure was observed for the first time. Our results provide a novel material platform for the vdW heterostructure and a possible method for optimizing heterostructure growth behaviors.
Immune-Based Combinations versus Sorafenib as First-Line Treatment for Advanced Hepatocellular Carcinoma: A Meta-Analysis
Authors: Rizzo Alessandro , Ricci Angela Dalia , Fanizzi Annarita , Massafra Raffaella , De Luca Raffaele , Brandi Giovanni
Published: January 2023

Recent years have observed the emergence of novel therapeutic opportunities for advanced hepatocellular carcinoma (HCC), such as combination therapies including immune checkpoint inhibitors. We performed a meta-analysis with the aim to compare median overall survival (OS), median progression-free survival (PFS), complete response (CR) rate, and partial response (PR) rate in advanced HCC patients receiving immune-based combinations versus sorafenib. A total of 2176 HCC patients were available for the meta-analysis (immune-based combinations = 1334; sorafenib = 842) and four trials were included. Immune-based combinations decreased the risk of death by 27% (HR, 0.73; 95% CI, 0.65–0.83; p < 0.001); similarly, a PFS benefit was observed (HR, 0.64; 95% CI, 0.5–0.84; p < 0.001). In addition, immune-based combinations showed better CR rate and PR rate, with ORs of 12.4 (95% CI, 3.02–50.85; p < 0.001) and 3.48 (95% CI, 2.52–4.8; p < 0.03), respectively. The current study further confirms that first-line immune-based combinations have a place in the management of HCC. The CR rate observed in HCC patients receiving immune-based combinations appears more than twelve times higher compared with sorafenib monotherapy, supporting the long-term benefit of these combinatorial strategies, with even the possibility to cure advanced disease.
Analysis of Inbreeding Effects on Survival at Birth of Pannon White Rabbits Using the Inbreeding-Purging Model
Authors: Kövér György , Curik Ino , Vostry Lubos , Farkas János , Mezőszentgyörgyi Dávid , Nagy István
Published: January 2023

Mating between related animals is an inevitable consequence of a closed population structure especially when it coincides with a small population size. As a result, inbreeding depression may be encountered especially when considering fitness traits. However, under certain circumstances, the joint effects of inbreeding and selection may at least partly purge the detrimental genes from the population. In the course of this study, our objective was to determine the status of purging and to quantify the magnitude of the eliminated genetic load for the survival at birth of Pannon White rabbit kits maintained in a closed nucleus population. The evolution of the survival at birth was evaluated by applying the PurgeR R package based on the inbreeding-purging model. In the period from 1992 to 2017, 22.718 kindling records were analyzed. According to the heuristic approach, the purging coefficient reached the maximum possible value of 0.5 when estimating between 1992 and 1997. Based on the expected fitness over generations and on the expressed opportunity of purging, the beneficial effects of purging could be expected after 10 generations. The proportion of the purged genetic load could be between 20% and 60%. While the results obtained are not entirely conclusive, they do raise the possibility that some of the inbreeding load was caused, at least in part, by genes that could be successfully removed from the population by purging.
Tree Species Classification over Cloudy Mountainous Regions by Spatiotemporal Fusion and Ensemble Classifier
Authors: Cui Liang , Chen Shengbo , Mu Yongling , Xu Xitong , Zhang Bin , Zhao Xiuying
Published: January 2023

Accurate mapping of tree species is critical for the sustainable development of the forestry industry. However, the lack of cloud-free optical images makes it challenging to map tree species accurately in cloudy mountainous regions. In order to improve tree species identification in this context, a classification method using spatiotemporal fusion and ensemble classifier is proposed. The applicability of three spatiotemporal fusion methods, i.e., the spatial and temporal adaptive reflectance fusion model (STARFM), the flexible spatiotemporal data fusion (FSDAF), and the spatial and temporal nonlocal filter-based fusion model (STNLFFM), in fusing MODIS and Landsat 8 images was investigated. The fusion results in Helong City show that the STNLFFM algorithm generated the best fused images. The correlation coefficients between the fusion images and actual Landsat images on May 28 and October 19 were 0.9746 and 0.9226, respectively, with an average of 0.9486. Dense Landsat-like time series at 8-day time intervals were generated using this method. This time series imagery and topography-derived features were used as predictor variables. Four machine learning methods, i.e., K-nearest neighbors (KNN), random forest (RF), artificial neural networks (ANNs), and light gradient boosting machine (LightGBM), were selected for tree species classification in Helong City, Jilin Province. An ensemble classifier combining these classifiers was constructed to further improve the accuracy. The ensemble classifier consistently achieved the highest accuracy in almost all classification scenarios, with a maximum overall accuracy improvement of approximately 3.4% compared to the best base classifier. Compared to only using a single temporal image, utilizing dense time series and the ensemble classifier can improve the classification accuracy by about 20%, and the overall accuracy reaches 84.32%. In conclusion, using spatiotemporal fusion and the ensemble classifier can significantly enhance tree species identification in cloudy mountainous areas with poor data availability.
Influence of Upcycled Post-Treatment Bark Biomass Addition to the Binder on Produced Plywood Properties
Authors: Jeżo Aleksandra , Wronka Anita , Dębiński Aleksander , Kristak Lubos , Reh Roman , Rizhikovs Janis , Kowaluk Grzegorz
Published: January 2023

The valorization of tree bark through chemical treatment into valuable products, such as bark acid, leads to the formation of process residues with a high solids content. Since they are of natural origin and are able to be suspended in water and acid, research was carried out on the recycling of suberic acid residues (SAR) as a bi-functional component of binder mixtures in the production of plywood. The 5%–20% (5%–30% for curing time) mass content of SAR has been investigated with urea-formaldehyde (UF) resin of about 66% of dry content. The results show that the curing time of the bonding mixture can be reduced to about 38% and 10%, respectively, for hot and cold curing, of the initial curing time for the lowest SAR content. The decreasing curing time of the tested binder mixtures with the increase in SAR content was caused by the increasing amount of acidic filler, since amine resins as UF require acidification hardening, and the curing dynamics are strongly dependent, among others, on the content of the acid medium (curing agent). In the case of hot curing, a SAR content of about 20% allowed us to achieve the curing time of bonding mass with an industrial hardener. Investigations into the mechanical properties of examined panels showed a significant modulus of elasticity (MOE) increase with filler content increase. Similar conclusions can be drawn when analyzing the results of the modulus of rupture (MOR) investigations; however, these were only significant regarding hot-pressed samples. The shear strength of the plywood samples increased with the SAR rise for both cold- and hot-pressed panels. The in-wood damage of samples with SAR filler, hot-pressed, rose up to about 30% for the highest SAR filler content. For cold-pressed samples, no in-wood damage was found. The positive effect of veneer impregnation limiter by resin was identified for SAR acting as a filler. Moreover, a higher density of SAR-containing bonding lines was reached for hot-pressed panels. Therefore, the results confirmed the ability to use the SAR as an upcycled component of the bonding mixture for plywood production.