bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the effects of importin a1 on the nuclear translocation of IL-1a in HeLa cells
Authors: Yamada Akiko , Wake Kiyotaka , Imaoka Saya , Motoyoshi Mitsuru , Yamamoto Takenori , Asano Masatake
Published: March 2023

Interleukin-1α (IL-1α), a cytokine released by necrotic cells, causes sterile inflammation. On the other hand, IL-1α is present in the nucleus and also regulates the expression of many proteins. A protein substrate containing a nuclear localization signal (NLS) typically forms a substrate/importin α/β complex, which is subsequently transported to the nucleus. To the best of our knowledge, no study has directly investigated whether IL-1α—which includes NLS—is imported into the nucleus in an importin-dependent manner. In this study, we noted that all detected importin subtypes interacted with IL-1α. In HeLa cells, importin α1-mediated nuclear translocation of IL-1α occurred at steady state and was independent of importin β1. Importin α1 not only was engaged in IL-1α nuclear transport but also concurrently functioned as a molecule that regulated IL-1α protein level in the cell. Furthermore, we discussed the underlying mechanism of IL-1α nuclear translocation by importin α1 based on our findings.
Expert level of detection of interictal discharges with a deep neural network
Authors: Lourenço Catarina da Silva , Tjepkema-Cloostermans Marleen , Putten Michel van
Published: March 2023

Deep learning methods have shown potential in automating interictal epileptiform discharge (IED) detection in electroencephalograms (EEGs). To implement this in a clinical setting, it needs to have similar performance to visual assessment. We aim to compare a neural network trained for IED detection with a group of experts for validation and assessment of its potential applicability in a clinical setting. We processed EEGs from 20 patients with focal and generalized epilepsy and 30 controls with a neural network. Seven experts labeled the IEDs in the dataset. Kappa scores, sensitivity and specificity were calculated. Network performance was compared to the experts at EEG and at IED level, as well as with an industry standard, Persyst. For EEG level classification, the neural network showed a similar trend to the experts. For individual IED detection, sensitivities between experts ranged from 20.7–86.4%. The sensitivity of our network was 82.5% at 99.0% specificity, and it outperformed Persyst. The network can detect IEDs in agreement with the experts with a high sensitivity and specificity. This indicates that the algorithm can potentially be used in the clinic to support visual EEG analysis or provide access to diagnostics if human resources are limited.
CircHIPK3 negatively regulates autophagy by blocking VCP binding to the Beclin 1 complex in bladder cancer
Authors: wang chong , Liu Tiantian , Wang Jiawei , Cheng Chao , Zhang Ze , Zhang Jingwei , Huang Houbao , Li Yawei
Published: March 2023

Circular RNA HIPK3 (circHIPK3) mediates the progression of multiple cancers, including bladder cancer, by regulating cell migration, autophagy and epithelial mesenchymal transition. However, the mechanism by which circHIPK3 regulates autophagy in bladder cancer cells remains unclear. Autophagy is a common self-protection mechanism in eukaryotic cells and is essential for cell survival and death regulation. However, it is unclear whether circHIPK3 affects the level of autophagy in bladder cancer through binding proteins, and the potential regulatory mechanism is unknown. Here, we found that circHIPK3 levels were significantly lower and autophagy-related proteins were significantly upregulated in bladder cancer cells and tissues compared to normal controls. CircHIPK3 downregulation promoted bladder cancer cell proliferation, while circHIPK3 overexpression inhibited proliferation. CircHIPK3 overexpression significantly suppressed autophagy in bladder cancer cells. Overexpression of circHIPK3 did not affect VCP protein expression but inhibited the VCP/Beclin 1 interaction. VCP also stabilized Beclin 1 and promoted autophagy in bladder cancer cells by downregulating ataxin-3. Thus, circHIPK3 may play an important role in bladder cancer by inhibiting VCP-mediated autophagy.
Are we there yet? A Mapping review to identify and organize bias research in medical education curriculum
Authors: Lewis Brianne E , Naik Akshata R.
Published: March 2023

BACKGROUND
Medical schools and residency programs often incorporate training to reduce physician biases towards patients and their conditions. In order to organize available literature, a mapping review was conducted to identify the categories of bias studied within medical student (MS), resident (Res) and mixed populations. Studies were further characterized based on their research goal as either documenting evidence of bias or bias intervention or both.
METHODS
Online databases (PubMed, PsycINFO, WebofScience) between 1980 and 2021 were searched for articles. All references were imported into Covidence for independent screening of studies. Conflicts were resolved by reviewers and the same protocol was followed for full text reviews. Studies were sorted by goal: ‘evidence of bias’ (EOB) and/or ‘bias intervention’ (BI), and by population (MS or Res or mixed). Further, biases were mapped into descriptive categories.
RESULTS
A total of 139 articles fit the inclusion criteria for data extraction. The mapping analysis generated 11 categories of bias and showed that bias against race/ethnicity, specific diseases/conditions, and weight were the most researched topics. Of the studies included, there was a higher ratio of EOB:BI studies at the MS level. While at the Res level, a lower ratio of EOB:BI was found.
CONCLUSIONS
This study should be of interest to institutions, program directors and medical educators who wish to specifically address a category of bias and identify where there is a dearth of research. This study also underscores the need to introduce bias interventions at the MS level.
Effects of the porous structure of cement sheaths on the deformation failure mechanism of wellbore cement sheaths
Authors: Yang Yongming , Li Xiwen , Sun Mengke
Published: March 2023

Two types of cement sheaths with different porosities were prepared by using cement materials and liquid silicon suspension. The distribution characteristics of the pore radius and space location of two types of cement sheaths were analyzed using CT scanning experiments and statistical principles to obtain their probability density distribution functions. Based on the distribution functions, the “single-layer” and “double-layer” porous models of two types of cement sheaths were constructed using a self-developed program incorporated with the FLAC 3D program. A series of numerical simulations were conducted to study the deformation and failure laws of wellbore cement sheaths under in situ stress and hydraulic pressure. The effects of the porosity and double-layer structure on the breakdown pressure, plastic failure zone, radial deformation, and stress distribution of the cement sheaths were analyzed. As a result, the effect mechanisms of the porosity and double-layer structure on the failure mode, failure path, and interaction between the cement sheath and metal casing were revealed. The failure modes and paths of single- and double-layer cement sheaths were obtained. This research provides a basis for understanding the characteristics of stress distribution, deformation, and failure mode of porous cement sheaths under hydraulic pressure.
Central circuit controlling thermoregulatory inversion and torpor-like state
Authors: Tupone Domenico , Hernan Shelby , Chiavetta Pierfrancesco , Morrison Shaun , Cano Georgina
Published: March 2023

To maintain core body temperature in mammals, the CNS thermoregulatory networks respond to cold exposure by increasing brown adipose tissue and shivering thermogenesis. However, in hibernation or torpor, this normal thermoregulatory response is supplanted by “thermoregulatory inversion”, an altered homeostatic state in which cold exposure causes inhibition of thermogenesis and warm exposure stimulates thermogenesis. Here we demonstrate the existence of a novel, dynorphinergic thermoregulatory reflex pathway between the dorsolateral parabrachial nucleus and the dorsomedial hypothalamus that bypasses the normal thermoregulatory integrator in the hypothalamic preoptic area to play a critical role in mediating the inhibition of thermogenesis during thermoregulatory inversion. Our results indicate the existence of a neural circuit mechanism for thermoregulatory inversion within the CNS thermoregulatory pathways and support the potential for inducing a homeostatically-regulated, therapeutic hypothermia in non-hibernating species, including humans.
Bearing damage characteristics of countersunk thin-ply/thick-ply laminated joints using an interference fit bolt
Authors: Wang Anyang , Wang Zhongqi , Zhao Menglin , Zhao Yang , Men Xingchen , Chang Zhengping , Kang Yonggang
Published: March 2023

In this study, experimental investigations were carried out on thin-ply and thick-ply countersunk interference fit joints. A comparative study of the mechanical behaviour and hole wall damage during static installation of thin-ply and thick-ply specimens with varied interference sizes were carried out. The effect of interference fit on the strength of countersunk composite bolted joints with different thicknesses of prepreg was investigated in detail under quasi-static tensile loading. The internal damage and failure mechanisms of thin-ply and thick-ply interference joints were investigated by SEM micrographs. The thin-ply specimens had lower installation forces and the initial damage of the thin-ply interference interface was less than that of the thick-ply for the same interference size. The thin-ply can still suppress the generation and propagation of the damage in the load-bearing of the interference connection. More importantly, thin-ply laminates can accommodate more substantial interference sizes than thick-ply laminates and have higher load-bearing strengths of approximately 10–20% more for the same interference size. Thin prepregs can be used to facilitate the design process and improve the structural properties of composites, providing new perspectives for improvements and innovative applications of interference joining technology.
Protective Effects of Thymoquinone on Doxorubicin-induced Anti/oxidant Levels in Rat Peripheral Tissues
Authors: AKPINAR Deniz , MERCAN Tanju , DEMIR Halit , OZDEMIR Semir , DEMIR Canan , KAVAK Servet
Published: March 2023

We aimed to investigate the effects of thymoquinone (TQ) against Doxorubicin (DOX)-induced toxicity in liver, lung, kidney, testis, diaphragm and stomach tissues of rats. Healthy twenty-eight male Wistar albino rats aged three months, were divided into four groups, each contained seven animals: Group 1: Control (C), Group 2: Rats treated with thymoquinone (T) (10 mg/kg given by gavage), Group 3: Rats treated with doxorubicin (D) were injected intraperitoneally (3 mg/kg) and Group 4: Rats treated with doxorubicin (injected intraperitoneally with 3 mg/kg DOX) and thymoquinone (10 mg/kg given by gavage) (DT). At the end of the experiment, the animals were euthanized with sodium pentobarbital (50 mg/kg) and their lung, liver, stomach, kidney, diaphragm and testicular tissues were dissected for the measurement of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) levels. It was observed that DOX administration (in group D) increased lipid peroxidation and decreased antioxidant enzyme levels in peripheral tissues of rats. It was determined that TQ treatment (in the DT group) given with DOX decreased lipid peroxidation and increased antioxidant enzyme levels. In our study, it was determined that TQ treatment eliminated the toxic effects of DOX and the protective effects of TQ were revealed.
Clinical Significance of Urinary Exosomal microRNAs in patients with IgA nephropathy
Authors: Yoon Soo-Young , Kim Jin Sug , Jung Su-Woong , Kim Yang Gyun , Hwang Hyeon Seok , Moon Ju Young , Lee Sang-Ho , Seo Jung-Woo , Seok Junhee , Tae Donghyun , Jeong Kyunghwan
Published: March 2023

Background: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. The clinical relevance of 11 urinary exosomal microRNAs (miRNAs) was evaluated in patients with IgAN.
Methods: From January 2009 to November 2018, IgAN (n = 93), disease control (n = 11), and normal control (n = 19) groups were enrolled. We evaluated the expression levels of urinary exosomal miRNAs at the baseline and their relationship with clinical and pathological features. The primary endpoint of this study was to discriminate statistically powerful urinary exosomal miRNAs for the prognosis of IgAN.
Results: IgAN group showed dysregulated urinary exosomal miRNA levels compared with the normal and disease control groups. Urinary exosomal miRNA levels of miR-16-5p, miR-29a-3p, miR-124-3p, miR-126-3p, miR-199a-3p, miR-199b-5p, and miR-335-3p showed significant correlation with both estimated glomerular ﬁltration rate (eGFR) and urine protein-to-creatinine ratio (uPCR). In univariate analysis, age, body mass index, hypertension, eGFR, uPCR, and five miRNAs (miR-16-5p, miR-29a-3p, miR-124-3p, miR-199a-3p, and miR-335-3p) were signiﬁcantly associated with disease progression in patients with IgAN. MiR-199a-3p with the lowest p-value in disease progression analysis, showed an area under the curve (AUC) of 0.727, while the AUC of miR-124-3p, with the second lowest p-value, was 0.718. When these two miRNAs were combined, the AUC was high enough (0.786), considering that the AUC of the International IgAN Risk Prediction Tool was 0.890.
Conclusion: Urinary exosomal miRNAs may serve as alternative prognostic biomarkers of IgAN. Further studies are needed to elucidate the physiological mechanisms and clarify the results of this study.
1D photonic crystal biosensor for detection of SARS-CoV-2
Authors: Bilgili Nurettin , Çetin Ali
Published: March 2023

In this study, we theoretically investigate one-dimensional photonic crystal (1D PC) with a defect layer as a biosensor for the detection of COVID-19 (SARS-CoV-2) through human blood. Finite-difference time-domain method (FDTD) is used to calculate the transmission spectrum of the biosensor by using OptiFDTD software. The photonic crystal biosensor performance is measured by the transmission peak shift in resonant wavelength. The effect of the defect layer thicknesses over sensor performance is studied and optimum sensitivity of the 107,0085 nm/RIU, quality factor of 0.3702x103 and detection limit of 3.37086x10-6 RIU is achieved for designed biosensor. The simple structure, easy analysis, and available fabrication techniques make the proposed design a suitable candidate for biosensing applications.
Serum phosphorylated α-synuclein: A potential biomarker of poststroke cognitive impairment
Authors: Wang Yi , Li Yuning , Gu Yakun , Ma Wei , Guan Yuying , Guo Mengyuan , Shao Qianqian , Ji Xunming , Liu Jia
Published: March 2023

Background
Ischemic stroke (IS) is characterized by cerebral infarction caused by acute cerebral vascular occlusion, with high rates of morbidity, mortality, and disability. Poststroke cognitive impairment, one of the major secondary impairments, is associated with greatly reduced quality of life in many patients with IS. Because poststroke cognitive impairment has insidious onset and progressive progression, the development of early warning biomarkers is essential for this disease.
Methods
In this study, we detected phosphorylated α-synuclein (p-α-syn) pathology in the brain of distal middle cerebral artery occlusion (dMCAO) mice and hypoxia mice. We collected blood samples and routine biochemistry data of patients with IS and those who underwent physical examination in Beijing Boai Hospital from July to December 2021. We examined the serum level of p-α-syn in those people by ELISA.
Results
The level of p-α-syn was significantly increased and showed pathological aggregation around the cerebral infarct in dMCAO mice. And the similar aggregation in neurons were also observed in the brain of chronic hypoxia mice, thus suggesting that hypoxia is the internal cause of α-syn pathology. The serum level of p-α-syn in patients with IS was significantly lower than that of control group, and this lower serum level was positively correlated with the cognitive level of these patients. Further association analysis revealed that the decrease in the serum high-density lipoprotein level of patients with stroke was significantly correlated with their decreased p-α-syn level.
Conclusions
Serum p-α-syn has the potential to serve as a biomarker for poststroke cognitive impairment.
Recombinant Erythropoietin Treatment Improves Serum Podocyte Marker Levels in Diabetic Kidney Disease
Authors: ZENG Lingfeng , NG Jack Kit-Chung , FUNG Winston Wing-Shing , CHAN Gordon Chun-Kau , CHOW Kai-Ming , SZETO Cheuk-Chun
Published: March 2023

Background
Recombinant human erythropoietins (rHuEPO) is an effective treatment for renal anemia. Recently, there is evidence to suggest that rHuEPO may reduce podocyte injury in diabetic kidney disease (DKD). However, there is no published study on the change in podocyte injury marker levels before and after rHuEPO treatment in DKD.
Methods
We measured serum nephrin and podocalyxin level, and their corresponding plasma mRNA levels, in 49 DKD patients before rHuEPO treatment, and then 12 and 36 weeks afterward.
Results
There were reductions in serum nephrin (p = 0.002) and podocalyxin levels (p = 0.09), as well as their corresponding plasma mRNA levels (p < 0.0001 for both) after rHuEPO treatment. The change in serum nephrin and podocin level had significant inverse correlation with the concomitant change in hemoglobin level (r = -0.670 and − 0.739 respectively, p < 0.0001 for both), but not with the change in kidney function or proteinuria.
Conclusion
Serum nephrin and podocalyxin levels and their corresponding plasma mRNA levels were significant reduced after rHuEPO treatment in DKD patients, and the change in serum nephrin and podocalyxin levels correlated with the change in hemoglobin level. The effect of rHuEPO on podocyte injury deserves further study.
Molecular dynamics investigation on micro-friction behavior of cylinder liner-piston ring assembly
Authors: Li Tongyang , Wu Jing , Ge Chang , Wang Lujie , Yu Yuan , Ma Xuan , Qiao Zhuhui , Tang Huaguo
Published: March 2023

The prediction of tribological characteristics of the piston ring-cylinder liner friction (PRCL) assembly near the top dead center has been a difficult area of research. This study explores the micro-friction behavior of PRCL assemblies near the top dead center in engines using the molecular dynamics approach. The tribological characteristics of the PRCL were analyzed under various operating conditions such as ring sliding speed, ring back load, operating temperature, and lubricant supply amount. The liner surface morphology, liner wear, and lubricant film distribution were used to evaluate the tribological characteristics. It was determined that the lubricant supply amount has the most significant impact on the micro-friction behavior of the PRCL assembly.
Exploring and targeting potential druggable antimicrobial resistance targets ArgS, SecY and MurA in Staphylococcus sciuri with TCM inhibitors through subtractive genomics strategy
Authors: Aafareen Aafareen Khan , Saman Saman Sohail , Zarrin Zarrin Basharat , Irfan Muhammad Irfan , Kashif Syed Kashif Raza , Carlos Carlos M. Morel , Hassan Syed Shah Hassan
Published: March 2023

Staphylococcus sciuri (also currently Mammaliicoccus sciuri) are anaerobic facultative and non-motile bacteria that causes significant human pathogenesis such as endocarditis, wound infections, peritonitis, UTI and septic shock. Some methicillin-resistant S. sciuri (MRSS) also infects animals that include healthy broilers, cattle, dogs and pigs. The emergence of MRSS strains thereby poses a serious health threat and thrives the scientific community towards novel treatment options. Herein, we investigated the druggable genome of S. sciuri by employing subtractive genomics that resulted in 7 genes/proteins where only 3 of them were predicted as final targets. Further mining the literature showed that the ArgS (WP_058610923), SecY (WP_058611897) and MurA (WP_058612677) are involved in multi-drug resistance phenomenon. The 3D protein homology models were built and validated, followed by screening against a Traditional Chinese Medicine library (n = 36,043 compounds). The molecular docking and simulation studies revealed the physicochemical stability parameters of the docked TCM inhibitors in the druggable cavities of each protein targets by identifying their druggability potential and maximum Hydrogen bonding interactions. The RMSD graph showed fluctuations due to structural changes in the helix-coil-helix and beta-turn-beta changes at specific points. Additionally, the transitional changes in protein targets due to “relational dynamics” significantly impact the receptor-ligand binding mechanism. It is assumed that such findings might facilitate researchers to robustly discover and develop effective therapeutics against S. sciuri alongside other enteric infections.
Results from TB screening using ultraportable x-ray and artificial intelligence in remote populations in northeast Nigeria
Authors: John Stephen , Abdulkarim Suraj , Usman Salisu , Rahman Md. Toufiq , Creswell Jacob
Published: March 2023

Background:
Ultraportable X-ray devices coupled with artificial intelligence (AI) are beginning to be used widely to screen for TB in remote settings. Few studies have documented their performance.
Methods:
We organized screening camps in Gombe and Adamawa states of Northeast Nigeria using a team of a registration officer, data entry staff, a radiographer, and a coordination officer. All consenting individuals ≥ 15 years were screened for TB symptoms (cough, fever, night sweats, and weight loss) and received a CXR. We used a MinXray Impact system interpreted by AI (qXR V3), which is a fully integrated wireless setup, can be run without electricity, and weighs approximately 30kg. We collected sputum samples from individuals with an abnormality score of .30 or higher or if they reported any TB symptoms. Samples were transported for testing with Xpert MTB/RIF. We documented the TB screening cascade and evaluated the performance of screening with different combinations of CXR read by AI and symptoms.
Results:
We screened 5,298 individuals during 66 camps; 2,685 (51%) were females, and 2,613 (49%) were males. Using ≥ 2 weeks of cough to define presumptive TB, 1,056 people (20%) would be identified. If a cough of any duration was used, the number with presumptive TB increased to 1,889 (36%) and to 3,084 (58%) if any of the four symptoms were used. Overall, 770 (14.5%) had abnormality scores of 0.3 or higher, and 447 (8.4%) had a score of 0.5 or higher. We collected 1,022 samples for Xpert testing and detected 85 (8%) individuals with TB. Traditional symptom screening of prolonged cough only identified 40% of people with TB, while using any symptom detected 90.6% of people with TB, but specificity was 11.4%. Using an AI abnormality score of .50, only used 424 tests to identify 89.4% of people with TB with a specificity of 62.8%.
Conclusion:
Ultra-portable CXR can be used to provide better TB screening in hard-to-reach areas. Symptom screening may miss large proportions of people with bacteriologically confirmed TB. Employing AI to read CXR can improve triaging when human readers are unavailable and can save expensive diagnostic testing costs.
Melatonin Alleviates Chronic Intermittent Hypoxia-induced Microbiota Dysbiosis and Attenuates Intestinal Barrier Dysfunction via STAT3/Th17 signalling pathway
Authors: Xu Huajun , Wang Fan , Gao Zhenfei , Huang Weijun , Zhang Xiaoman , Liu Feng , Yi Hongliang , Guan Jian , Li Xinyi , Wu Xiaolin , Yin Shankai
Published: March 2023

Background:Chronic intermittent hypoxia (CIH) triggers subclinical intestinal barrier disruption prior to systemic low-grade inflammation. Increasing evidence suggests therapeutic effects of melatonin on systemic inflammation and gut microbiota remodelling. However, whether and how melatonin alleviates CIH-induced intestinal barrier dysfunction remains unclear.Methods:C57BL/6J mice and Caco-2 cell line were treated. We evaluated gut barrier function spectrophotometrically using fluorescein isothiocyanate (FITC)-labelled dextran. Immunohistochemical and immunofluorescent staining were used to detect morphological changes in the mechanical barrier. Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) revealed the expression of tight junctions, signal transducer and activator of transcription 3 (STAT3) levels. 16S rRNA analysis of the colonic contents microflora. Flow cytometry was used to detect cytokines and Th17 cells with and without melatonin supplementation.Results: We found that CIH could induce colonic mucosal injury, including reduction in the number of goblet cells and over expression of intestinal tight junction proteins CIH could decrease the abundance of the beneficial generaClostridium,Akkermansia,andBacteroides, while increasing the abundance of the pathogenic generaDesulfovibrioandBifidobacterium. Finally, CIH facilitated Th17 differentiation via the phosphorylation of signal transducer and activator of transcription 3 (STAT3)in vitroand elevated the circulating pro-inflammatory cytokine including interleukin (IL)-1β, IL-6, tumor necrosis factor-α, tumor growth factor-β, IL-17A, IL-17F, IL-21, IL-22, IL-23, and C-C motif chemokine ligand 20 in vivo. Melatonin supplementation ameliorated CIH-induced intestinal mucosal injury, gut microbiota dysbiosis, enteric Th17 polarization, and systemic low-grade inflammation reactions mentioned-above.Conclusions:Melatonin attenuated CIH-induced intestinal barrier dysfunction by regulating gut flora dysbiosis, mucosal epithelium integrity, and Th17 polarization via STAT3 signalling.
Data-driven Digital Twin for Board-Level Packaging Interconnects under Multi-physics Loading
Authors: Luo Jing , Liu Yang , Li Ke , Pan Zhen , Ma Chiyuan , Lu Jicun
Published: March 2023

Solder joints of electronic packaging devices are used as mechanical fixation and electrical interconnection between chips and circuit boards, which provides protection for the normal operation of electronic equipment. Therefore, real-time monitoring of the status of solder joints is essential for predictive maintenance of equipment. In this paper, we propose a digital twin based on semi-supervised learning for diagnosing faults in chip interconnection solder joints. In order to achieve maximum generalization of limited label information, the interdependence between sample labels with similar feature distributions is fully exploited by semi-supervised learning. Additionally, we use real-time monitoring data to update the learning model, and reveal the evolution of solder joint failure under different loads through diagnostic results of model. A dynamic model is formed by stimulated fault evolution characteristics into a solder joint failure model to form a diagnose fault dynamic model in a virtual space. Finally, we designed a thermal-vibration coupling experiment to verify the effectiveness of the digital twin-based solder joint failure diagnosis model. The results show that the digital twin maintains good consistency with the performance degradation process of the solder joint throughout its life cycle. Moreover, the diagnostic accuracy of the digital twin model can reach 85%, which proves that our method can monitor the service status of physical entities online, and intelligently predict the failure mode and life cycles under load conditions.
Risk factors for postoperative recurrence of ulcerative colitis-associated colorectal cancer
Authors: Horio Yuki , Uchino Motoi , Igeta Masataka , Nagano Kentaro , Kusunoki Kurando , Kuwahara Ryuichi , Kimura Kei , Kataoka Kozo , Beppu Naohito , Ikeda Masataka , Ikeuchi Hiroki
Published: March 2023

Purpose: Although ulcerative colitis-associated carcinoma (UC-CRC) has been described, there are few reports regarding recurrent cases of UC-CRC. In this study, we investigated the risk factors for recurrence of UC-CRC.
Methods: Recurrence-free survival (RFS) was determined for 144 stage 1-3 patients among 210 UC-CRC cases from August 2002 to August 2019. The Kaplan‒Meier method was used to obtain cumulative RFS, and the Cox proportional hazard model was used to extract recurrence risk factors. The interaction term between cancer stage and prognostic factors specific to UC-CRC was evaluated using the Cox model. The Kaplan‒Meier method was applied by cancer stage to the UC-CRC-specific prognostic factors for which interaction effects were indicated.
Results: There were 18 recurrence cases involving stages 1 to 3, and the recurrence rate was 12.5%. The cumulative 5-year RFS rate was 87.5%. Multivariable analysis showed that age at surgery (hazard ratio [HR]: 0.95, 95% CI: 0.91-0.99, p=0.02), undifferentiated carcinoma (HR: 4.42, 95% CI: 1.13-17.24, p=0.03), lymph node metastasis (HR: 4.11, 95% CI: 1.08-15.69, p=0.03), and vascular invasion (HR: 8.01, 95% CI: 1.54-41.65, p=0.01) were significant risk factors for recurrence. Patients with stage 3 CRC in the young adult (age <50 years) group had a significantly worse prognosis than those in the adult (age ≥50 years) group (p<0.01).
Conclusion: Age at surgery was identified as a risk factor for recurrence of UC-CRC. Young adult patients have a poor prognosis and may require preoperative surveillance endoscopy as well as aggressive postoperative adjuvant chemotherapy in stage 3.
Prognostic nomogram for resectable gastric cancer after preoperative chemotherapy to assist in decision-making for adjuvant chemotherapy: a retrospective study combined with external validation
Authors: Zhou Shengzhu , Lu Chang
Published: March 2023

Background
Neoadjuvant chemotherapy combined with radical gastrectomy is the standard treatment for resectable gastric cancer, but whether these patients can benefit from adjuvant chemotherapy remains unclear.
Methods
A total of 732 patients with initially diagnosed non-metastatic resectable gastric cancer between 2004 and 2016 were screened using the Surveillance, Epidemiology, and Results database of the National Cancer Institute of the United States and retrospectively analyzed. Among them, 366 patients received postoperative chemotherapy and 506 patients did not. The propensity score matching was used to balance the two groups of confounding factors, the Kaplan–Meier method was used for survival analysis, and the logrank test was used to compare the differences between the survival curves. The Cox proportional hazards regression model was used to screen independent prognostic factors and establish a nomogram survival prediction model. The patients were divided into high-, moderate-, and low-risk groups according to the overall survival prediction score generated by X-tile software based on the nomogram.
Results
Multivariate analysis showed that the independent prognostic factors of gastric cancer in the group not receiving chemotherapy were history, ypT stage, ypN stage, and examined lymph node count, which were included in the nomogram prediction model. The C-index for the model was 0.727 (95% confidence interval, 0.65056–0.80344). The patients were divided into three different risk level groups based on the nomogram prediction score. Low- and moderate-risk patients did not benefit from adjuvant chemotherapy, while high-risk patients did.
Conclusion
The nomogram model in the present study can effectively evaluate the prognosis of patients with resectable gastric cancer. In addition, postoperative chemotherapy can be recommended for high-risk patients, but not for low-risk patients.
Dual discriminator conditional sheep flock generative adversarial network-based intrusion detection system in MAC-based SDN framework
Authors: Nanavath Kiran Singh Nayak , Bhattacharyya Budhaditya
Published: March 2023

The authors have requested that this preprint be removed from Research Square.
CATANIC: Automatic generation model of image captions based on multiple attention mechanism
Authors: Zhang Tingting , Zhang Tao , Zhuo Yanhong , Ma Feng
Published: March 2023

As a cross-field of computer vision and natural language processing, image caption generation has been a widely concerned researched topic. However, it is challenging because the automatically generated captioning needs to conform to the image content and language logic. In this paper, we propose a novel image caption generation model based on the DenseNet169 pre-training network and the modified Transformer model, which follows an encoding-decoding architecture. First, we use the DenseNet169 network as the encoder to extract the initial features of the image, and then introduce the “Attention on Attention” module between the encoder and the decoder to correct the initial features of the picture and filter out the attention results that do not match the picture content. At the same time, we introduce the “Attention on Attention” module into the internal decoder of the Transformer model, which strengthens the correlation between the image feature and textual descriptions, and applies the modified Transformer model as a decoder to transform the modified image feature vectors into textual descriptions. Experimental results show that our model is not only able to generate captions that match the content of the pictures as well as the linguistic logic, but also has fewer training parameters and requires less training time cost than a number of different image captioning models with pre-trained convolutional networks as encoders.
Relationship between cancer stem cell-related SNPs and survival outcomes in patients with primary lung cancer
Authors: Xu Xinying , Liu Yuhang , Hu Huiyi , Wang Jinshen , Cai Yuxin , Xie Jun , Kang Mingqiang , He Fei
Published: March 2023

Background: Stem cells may be the source of cancer-causing mutant cells and are closely related to the prognosis of cancer. Our study aim to investigate the association between single nucleotide polymorphisms of cancer stem cell related genes and prognosis of lung cancer patients.
Methods: Matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) was used to genotype SNPs loci. Log-rank test was used to analyze and compare the difference of total survival time among different demographic data, clinical data and genotypes. Cox regression model was used to analyze the correlation between survival time and quality of life of lung cancer under codominant, dominant, recessive and additive genetic models. Test levelα=0.05.
Results: Stratified analysis showed that rs3740535 had recessive AA genotype and additive GG genotype. Rs3130932 Dominant GT+GG genotype, additive TT genotype; Rs13409 additive TT genotype; Rs6815391 recessive CC genotype and additional TT genotype were associated with increased risk of lung cancer death. Rs3130932 recessive GG genotype was associated with reduced risk of lung cancer death.
Conclusion: Rs3130932, rs13409 and rs6815391 are associated with the prognosis of lung cancer patients, and can affect the prognostic survival time of lung cancer patients.
Exploring the common pathogenesis of calcific aortic valve disease and atherosclerotic cardiovascular disease through bioinformatics analysis
Authors: Chen Wentao , Qiu Xiaohan , Wang Chunlin , Chen Wenqiang
Published: March 2023

Background
There are many similarities in the pathogenesis of calcified aortic valve disease (CAVD) and atherosclerotic cardiovascular disease (ASCVD). In this study, we aim to find potential key genes and pathways connected with both diseases, using bioinformatics approaches, we hope to search for some new targets to treat the two diseases.
Methods
We download gene expression profiles of CAVD (GSE12644, GSE51472) and ASCVD(GSE100927) from the Gene Expression Omnibus (GEO) database. After identifying the common differentially expressed genes (co-DEGs) for CAVD and ASCVD, we perform enrichment analysis of these co-DEGs and construct a PPI network. Subsequently, the hub genes were screened, and we validated the hub genes in other datasets. Finally, we validated the diagnostic value of these genes. Besides, we also performed an immune infiltration analysis.
Results
We eventually identified 55 co-DEGs from the two disease datasets which will be used for subsequent analysis. Enrichment analysis of these common genes showed that both chemokines and cytokines play an important role in CAVD and ASCVD. By using Cytohubba and MCODE plug-ins, we identified 14 hub genes, and after validation in other datasets, "CCR1", "TREM1", "MMP9", "CCL5", "TYROBP", "LY86", "LAPTM5" were selected as the final hub genes for this study. These 7 hub genes have high value in the diagnosis of CAVD and ASCVD. In addition, immune infiltration analysis also revealed dysregulation of immune cells in both CAVD and ASCVD.
Conclusions
Our study found common key genes of CAVD and ASCVD, which may be closely related to the pathogenesis of the two diseases. Our study identified key genes common to CAVD and ASCVD, which may be closely related to the occurrence and development of both diseases
Evaluating reduced bone bridge formation through a modified rat epiphyseal plate injury model
Authors: Mu Ying , Wang Wei , Wang Enbo , Yuan Xiangnan , Yao Peng , LI Jianjun
Published: March 2023

Approximately, one-third of all pediatric fractures involve the metaphyseal region, causing damage to the growth plate (also known as the epiphyseal plate), leading to unwanted bone repair tissue through the growth plate, known as a bone bridge (or bony bar). In some cases, the bony bar affects the longitudinal growth of long bones, resulting in limb shortening and angulation deformity and affecting children's physical and mental health. In clinical practice, the primary methods used to prevent the formation of bone bridges are fat interposition, anatomic reduction, and appropriate fixation. Once a bone bridge is formed, resection is the main treatment, but its formation usually takes one to two months, and limb shortening and angulation deformity usually take longer or even years. Therefore, prevention has become the focus of clinical and basic research. In this study, a modified rat central growth plate drilling injury model of the proximal tibia was established based on the original research using a silicone gel membrane to seal the holes. The modified model was provided for the study of reducing bone bridge formation. The hole's volume was evaluated using intraoperative and postoperative imaging examinations to determine the maximum volume of drug administration. Prevention of bone bridge formation was achieved using noninvasive medication; its effect was verified using various methods, providing a new in vivo animal experiment for the prevention and treatment of bone bridge formation after epiphyseal plate injury to guide clinical practice.
A note on the invariantsa of L-functions
Authors: Kaczorowski Jerzy , Perelli Alberto
Published: March 2023

We explain the exact meaning of a statement we made in a previous paper on invariants, namely that a complex-valued function of the data of the functional equation of an L-function is an invariant if and only if it is stable under the multiplication and factorial formulae. To this end, we show that every invariant has a so-called rational extension, having some desired invariance properties. The existence of such an extension, which enables to express formally the above heuristic concept, is not obvious and its construction is the main novelty of the paper.
Mathematics Subject Classification (2010): 11M41
The role of centralised project management approach on the implementation of large-scale Electronic Health Record systems: A Mixed-methods study
Authors: Alzghaibi Haitham , Hutchings Hayley A
Published: March 2023

Background: In the last three decades, the Electronic Health Records Systems (EHRS) become on the top priorities of policymakers globally. Nowadays, EHRS reform is fast becoming a priority in developed countries. The introduction of EHRS in Saudi healthcare organisations is considered one of the highest priorities of the policymakers. Saudi Arabian e-health strategy pays reasonable attention to the EHRS implementation project. According to the Saudi vision 2030 E-health transformation will be on top if IT projects in the country. However, an estimation of 50% of EHRS implementation have failed. Project leadership and type of project management have been found to be crucial components of effective EHRS implementation
Aim of the study: To evaluate the role of Centralised Project Management (CPM) on the implementation of large-scale EHRS in PHCs in SA.
Methods: A sequential explanatory mixed-methods approach involving a survey and semi-structured qualitative interview methods were utilised.
Results: Thirty-nine (75%) out of 53 policymakers at the Saudi Ministry of Health completed the survey while 14 policymakers were interviewed. Findings from both illustrated that adopting centralised project management approaches to implementation was beneficial in facilitating large-scale EHRs implementation and helped to overcome barriers that may have otherwise led to the failure of the project. Electronic Health Record System interoperability and software selection were the factors that centralised project management influenced most positively.
Impact of Right Ventricular Surface Area-to-Volume Ratio on Ventricular Remodeling after Pulmonary Valve Replacement
Authors: Thatte Nikhil , Sleeper Lynn , Lu Minmin , Tang Dalin , Geva Tal
Published: March 2023

Background
Optimal reverse remodeling of the right ventricle (RV), a sentinel goal of pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot, is not fully predicted by volume-based pre-PVR parameters. Our objectives were to characterize novel geometric RV parameters in patients receiving PVR and in controls, and to identify associations between these parameters and chamber remodeling post-PVR.
Methods
Secondary analysis was performed on cardiac magnetic resonance (CMR) data from 60 patients enrolled in a randomized trial of PVR with and without surgical RV remodeling. 20 healthy age-matched subjects served as controls. The primary outcome was optimal post-PVR RV remodeling (end-diastolic volume index (EDVi) ≤ 114 ml/m2 and ejection fraction (EF) ≥ 48%) vs. suboptimal remodeling (EDVi ≥ 120 ml/m2 and EF ≤ 45%).
Results
RV geometry was markedly different in PVR patients compared with controls, with lower systolic surface area-to-volume ratio (SAVR) (1.16 ± 0.26 vs.1.44 ± 0.21 cm2/mL, p < 0.001) and lower systolic circumferential curvature (0.87 ± 0.27 vs. 1.07 ± 0.30 cm− 1, p = 0.007) but similar longitudinal curvature. In the PVR cohort, higher systolic SAVR was associated with higher RVEF both pre- and post-PVR (p < 0.001). Among PVR patients, 15 had optimal and 19 had suboptimal remodeling post-PVR. Multivariable modeling showed that among the geometric parameters, higher systolic SAVR (OR 1.68 per 0.1 cm2/mL increase; p = 0.049) and shorter systolic RV long-axis length (OR 0.92 per 0.1 cm increase; p = 0.035) were independently associated with optimal remodeling.
Conclusions
Compared with controls, PVR patients have lower SAVR and lower circumferential but not longitudinal curvature. Higher pre-PVR systolic SAVR is associated with optimal remodeling post-PVR.
ISO/IEC 25010- based Quality evaluation of three mobile applications for reproductive health services in Morocco
Authors: Moumane Karima , Idri Ali , aouni fatiha el
Published: March 2023

Background and objective. Mobile apps for postnatal, contraception, and prenatal care are crucial for enhancing the health of mothers and babies. These apps provide daily monitoring and resources, including reliable infant care, feeding, and maternal recovery information. Contraception apps give individuals the means to make informed family planning decisions and access various contraception methods. Prenatal apps offer expectant mothers educational resources, tracking tools for pregnancy milestones, and a connection to healthcare providers for important check-ups and screenings, all while boosting doctor-patient communication. The apps also often include discussion forums where users can connect and share experiences. By providing access to care, information, and support, these mobile apps significantly ensure mothers and babies receive the necessary resources and care to thrive. This study assesses the software quality (SQ) of three reproductive health monitoring mobile apps using ISO/IEC 25010 and ISO/IEC 25023 standards. The aim of the study is to identify the strengths and weaknesses of each app in terms of SQ, with the goal of providing valuable information for users who are considering using one of these apps. By examining the positive aspects of each app, the study provides insights into what makes them a valuable choice. Similarly, by identifying negative points in terms of quality, the study provides an opportunity to identify areas for improvement, so that the apps can be evaluated and improved over time.
Methods. A three-step analysis process was implemented, of which the initial step involved examining the sub-features and features of the ISO/IEC 25010 standard for Software Product Quality (SPQ). The next step involved developing a checklist that summarizes the effect of the three mobile apps on SPQ. Finally, a calculation was performed to assess the impact of each requirement block on both the SPQ and the Quality in Use model.
Results. The findings indicate the Functional Suitability SPQ characteristic is greatly influenced by the predefined requirements, followed by the Operability, Performance Efficiency, Reliability, and Security SQ characteristics. Therefore, developers, designers, and testers must factor in these requirements throughout the development cycle of health mobile apps to produce a high-quality, patient-centered product with significant added value.
Conclusion. This study generated various requirements for pregnancy monitoring and childcare apps, providing a useful reference for developers in creating high-quality apps also assessing the quality of these kinds of apps. The software development process must consider SPQ characteristics to create a high-quality product with crucial KPIs, leading to better evaluations in app stores and increased user adoption and satisfaction.