bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interpretable generalized neural additive models for mortality prediction of COVID-19 hospitalized patients in Hamadan, Iran
Authors: Moslehi Samad , Mahjub Hossein , Farhadian Maryam , Soltanian Ali Reza , Mamani Mojgan 
Published: December 2022

Abstract
Background
The high number of COVID-19 deaths is a serious threat to the world. Demographic and clinical biomarkers are significantly associated with the mortality risk of this disease. This study aimed to implement Generalized Neural Additive Model (GNAM) as an interpretable machine learning method to predict the COVID-19 mortality of patients.

Methods
This cohort study included 2181 COVID-19 patients admitted from February 2020 to July 2021 in Sina and Besat hospitals in Hamadan, west of Iran. A total of 22 baseline features including patients' demographic information and clinical biomarkers were collected. Four strategies including removing missing values, mean, K-Nearest Neighbor (KNN), and Multivariate Imputation by Chained Equations (MICE) imputation methods were used to deal with missing data. Firstly, the important features for predicting binary outcome (1: death, 0: recovery) were selected using the Random Forest (RF) method. Also, synthetic minority over-sampling technique (SMOTE) method was used for handling imbalanced data. Next, considering the selected features, the predictive performance of GNAM for predicting mortality outcome was compared with logistic regression, RF, generalized additive model (GAMs), gradient boosting decision tree (GBDT), and deep neural networks (DNNs) classification models. Each model trained on fifty different subsets of a train-test dataset to ensure a model performance. The average accuracy, F1-score and area under the curve (AUC) evaluation indices were used for comparison of the predictive performance of the models.

Results
Out of the 2181 COVID-19 patients, 624 died during hospitalization and 1557 recovered. The missing rate was 3 percent for each patient. The mean age of dead patients (71.17 ± 14.44 years) was statistically significant higher than recovered patients (58.25 ± 16.52 years). Based on RF, 10 features with the highest relative importance were selected as the best influential features; including blood urea nitrogen (BUN), lymphocytes (Lym), age, blood sugar (BS), serum glutamic-oxaloacetic transaminase (SGOT), monocytes (Mono), blood creatinine (CR), neutrophils (NUT), alkaline phosphatase (ALP) and hematocrit (HCT). The results of predictive performance comparisons showed GNAM with the mean accuracy, F1-score, and mean AUC in the test dataset of 0.847, 0.691, and 0.774, respectively, had the best performance. The smooth function graphs learned from the GNAM were descending for the Lym and ascending for the other important features.

Conclusions
Interpretable GNAM can perform well in predicting the mortality of COVID-19 patients. Therefore, the use of such a reliable model can help physicians to prioritize some important demographic and clinical biomarkers by identifying the effective features and the type of predictive trend in disease progression.
Risk factors for failed back surgery syndrome following open posterior lumbar surgery for degenerative lumbar disease
Authors: Xu Wenbo , Ran Bingbing , Zhao Jianhui , Luo Wenqi , Gu Rui 
Published: December 2022

Abstract
Background
With the growing number of traditional posterior open surgery, the incidence of failed back surgery syndrome (FBSS) increases gradually. We aimed to investigate the incidence and risk factors for FBSS following open posterior lumbar surgery for degenerative lumbar disease (DLD).

Method
A multivariable regression analysis was performed for 333 consecutive patients to identify potential risk factors for FBSS. Clinical outcomes were evaluated by the validated North American Spine Society (NASS) Questionnaire and numerical rating scale (NRS) for pain. Demographics, diagnostic characteristics, surgical data, radiographic parameters for each patient were analyzed.

Result
16.8% of the included patients were classified as FBSS. Univariate analysis showed that age, hypertension, symptom location, intermittent claudication, preoperative pain NRS-leg, HIZ, Modic changes (MCs), surgical strategy and postoperative rehabilitation were related to FBSS. Multivariable logistic regression analysis demonstrated that preoperative NRS-leg (OR:0.80, 95%CI:0.71–0.91, P = 0.001), hypertension (OR: 2.22, 95%CI: 1.10–4.51, P = 0.027), intermittent claudication with waking distance > 100 m (OR: 4.07, 95%CI: 1.75–9.47, P = 0.001) and waking distance ≤ 100 m (OR: 12.43, 95%CI: 5.54–27.92, P < 0.001), HIZ (OR: 8.26, 95%CI: 4.00–17.04, P < 0.001), MCs (OR: 3.41, 95%CI: 1.73–6.71, P < 0.001), postoperative rehabilitation (OR: 2.63, 95%CI: 1.13–6.12, P = 0.024) were risk factors for FBSS.

Conclusion
Open posterior lumbar surgery is an effective treatment for DLD which provides pain reduction and lumbar curve improvement with a considerable satisfaction rate. Lower preoperative NRS-leg, hypertension, intermittent claudication, HIZ, MCs and postoperative rehabilitation are risk factors for FBSS, which can serve as a tool for clinicians to identify at-risk population and provide more effective management to mitigate the doctor-patient contradictions and further occupation of medical resources.
Genetic profiling of different phenotypic subsets of breast cancer stem cells (BCSCs) in breast cancer patients
Authors: Zekri Abdel-Rahman N. , Bahnassy Abeer , Mourad Magda , Malash Ibrahim , Ahmed Ola , Abdellateif Mona S. 
Published: December 2022

Abstract
Background
Breast cancer stem cells (BCSCs) have a crucial role in breast carcinogenesis, development, and progression. The aim of the current study is to characterize the BCSCs through the genetic profiling of different BCSCs phenotypic subsets to determine their related genetic pathways.

Methods
Fresh tumor tissue samples were obtained from 31 breast cancer (BC) patients for (1) Mammosphere culture. (2) Magnetic separation of the BCSCs subsets using CD24, CD44, and CD326 Microbeads. (3) Flow cytometry (FCM) assay using CD44, CD24, and EpCAM. (4) RT-PCR profiler Arrays using stem cell (SC) panel of 84 genes for four group of cells (1) CD44+/CD24−/EpCAM− BCSCs, (2) CD44+/CD24− /EpCAM+ BCSCs, (3) mammospheres, and (4) normal breast tissues.

Results
The BCSCs (CD44+/CD24−/EpCAM−) showed significant downregulation in 13 genes and upregulation in 15, where the CD44, GJB1 and GDF3 showed the maximal expression (P = 0.001, P = 0.003 and P = 0.007); respectively).
The CD44+/CD24−/EpCAM+ BCSCs showed significant upregulation in 28 genes, where the CD44, GDF3, and GJB1 showed maximal expression (P < 0.001, P = 0.001 and P = 0.003; respectively). The mammospheres showed significant downregulation in 9 genes and a significant upregulation in 35 genes. The maximal overexpression was observed in GJB1 and FGF2 (P = 0.001, P = 0.001; respectively).
The genes which achieved significant overexpression in all SC subsets were CD44, COL9A1, FGF1, FGF2, GDF3, GJA1, GJB1, GJB2, HSPA9, and KRT15. While significant downregulation in BMP2, BMP3, EP300, and KAT8.
The genes which were differentially expressed by the mammospheres compared to the other BCSC subsets were CCND2, FGF3, CD4, WNT1, KAT2A, NUMB, ACAN, COL2A1, TUBB3, ASCL2, FOXA2, ISL1, DTX1, and DVL1.

Conclusion
BCSCs have specific molecular profiles that differ according to their phenotypes which could affect patients’ prognosis and outcome.
Expansion of regulatory T cells by CD28 superagonistic antibodies attenuates neurodegeneration in A53T-α-synuclein Parkinson’s disease mice
Authors: Badr Mohammad , McFleder Rhonda L. , Wu Jingjing , Knorr Susanne , Koprich James B. , Hünig Thomas , Brotchie Jonathan M. , Volkmann Jens , Lutz Manfred B. , Ip Chi Wang 
Published: December 2022

AbstractBackgroundRegulatory CD4+CD25+FoxP3+T cells (Treg) are a subgroup of T lymphocytes involved in maintaining immune balance. Disturbance of Treg number and impaired suppressive function of Treg correlate with Parkinson’s disease severity. Superagonistic anti-CD28 monoclonal antibodies (CD28SA) activate Treg and cause their expansion to create an anti-inflammatory environment.MethodsUsing the AAV1/2-A53T-α-synuclein Parkinson’s disease mouse model that overexpresses the pathogenic human A53T-α-synuclein (hαSyn) variant in dopaminergic neurons of the substantia nigra, we assessed the neuroprotective and disease-modifying efficacy of a single intraperitoneal dose of CD28SA given at an early disease stage.ResultsCD28SA led to Treg expansion 3 days after delivery in hαSyn Parkinson’s disease mice. At this timepoint, an early pro-inflammation was observed in vehicle-treated hαSyn Parkinson’s disease mice with elevated percentages of CD8+CD69+T cells in brain and increased levels of interleukin-2 (IL-2) in the cervical lymph nodes and spleen. These immune responses were suppressed in CD28SA-treated hαSyn Parkinson’s disease mice. Early treatment with CD28SA attenuated dopaminergic neurodegeneration in the SN of hαSyn Parkinson’s disease mice accompanied with reduced brain numbers of activated CD4+, CD8+T cells and CD11b+microglia observed at the late disease-stage 10 weeks after AAV injection. In contrast, a later treatment 4 weeks after AAV delivery failed to reduce dopaminergic neurodegeneration.ConclusionsOur data indicate that immune modulation by Treg expansion at a timepoint of overt inflammation is effective for treatment of hαSyn Parkinson’s disease mice and suggest that the concept of early immune therapy could pose a disease-modifying option for Parkinson’s disease patients.
Effects of syphilis infection among HIV-1-positive individuals on suppressive antiretroviral therapy
Authors: Chan Phillip , Tang Tommy H. C. , Kwong Ruby T. S. , Chan Lawrence , Chan Helen S. Y. , Lam K. W. , Ting W. M. , Yung S. K. , Lam Emily C. T. , Chu M. Y. , Lam Wilson , Wu T. C. , Li Patrick , Lee M. P. 
Published: December 2022

Abstract
Introduction
Incident syphilis leads to changes in plasma HIV-1 RNA and CD4 + T-cell level in people with HIV (PWH) with viraemia. Its effect in PWH on suppressive antiretroviral therapy (ART) is less clear.

Methods
PWH on suppressive ART (plasma HIV-1 RNA < 50copies/mL) followed at the Queen Elizabeth Hospital, Hong Kong, China were regularly screened for syphilis. Their plasma HIV-1 RNA, CD4 + and CD8 + T-cell, and total lymphocyte levels before syphilis, during syphilis, and after successful treatment were compared.

Results
Between 2005 and 2020, 288 syphilis episodes from 180 individuals were
identified; 287 episodes were related to male, with a median age of 41 at
diagnosis; 221 (77%) were syphilis re-infection. The rates of plasma HIV-1
suppression were statistically unchanged across the time-points (97% pre-syphilis,
98% during syphilis, and 99% post-treatment).
Total lymphocyte, CD4+ and CD8+ T-cell levels decreased during
incident syphilis (p<0.01), and rebounded post-treatment (p<0.01). VDRL
titre was associated with declines in CD4+ T-cell (p=0.045), CD8+ T-cell
(p=0.004), and total lymphocyte levels (p=0.021). Pre-syphilis CD4/CD8 ratio
was associated with increases in CD8+ T-cell (p=0.001) and total lymphocyte
levels (p=0.046) during syphilis. Syphilis re-infection was associated with an
increase in total lymphocyte level (p=0.037). In the multivariable analysis,
only pre-syphilis CD4/CD8 ratio was independently associated with increases in CD8+
T-cell (p=0.014) and total lymphocyte levels (p=0.039) during syphilis.

Conclusions
Among virally-suppressed PWH, total lymphocyte, CD4+, and CD8+ T-cell
levels declined during
incident syphilis but rebounded post-treatment. The status of plasma HIV suppression
was unaffected
by syphilis.
Mechanism of autophagy induced by activation of the AMPK/ERK/mTOR signaling pathway after TRIM22-mediated DENV-2 infection of HUVECs
Authors: Wu Ning , Gou Xiaoqin , Hu Pan , Chen Yao , Ji Jinzhong , Wang Yuanying , Zuo Li 
Published: December 2022

Abstract
Background
Dengue virus type 2 (DENV-2) was used to infect primary human umbilical vein endothelial cells (HUVECs) to examine autophagy induced by activation of the adenosine monophosphate-activated protein kinase (AMPK)/extracellular signal-regulated kinase (ERK)/mammalian target of rapamycin (mTOR) signaling pathway following tripartite motif-containing 22 (TRIM22)-mediated DENV-2 infection to further reveal the underlying pathogenic mechanism of DENV-2 infection.

Methods
Quantitative real-time polymerase chain reaction (qRT-PCR) was used to screen putative interference targets of TRIM22 and determine the knockdown efficiency. The effect of TRIM22 knockdown on HUVEC proliferation was determined using the CCK8 assay. Following TRIM22 knockdown, transmission electron microscopy (TEM) was used to determine the ultrastructure of HUVEC autophagosomes and expression of HUVEC autophagy and AMPK pathway-related genes were measured by qRT-PCR. Moreover, HUVEC autophagy and AMPK pathway-related protein expression levels were determined by western blot analysis. Cell cycle and apoptosis were assessed by flow cytometry (FCM) and the autophagosome structure of the HUVECs was observed by TEM.

Results
Western blot results indicated that TRIM22 protein expression levels increased significantly 36 h after DENV-2 infection, which was consistent with the proteomics prediction. The CCK8 assay revealed that HUVEC proliferation was reduced following TRIM22 knockdown (P < 0.001). The TEM results indicated that HUVEC autolysosomes increased and autophagy was inhibited after TRIM22 knockdown. The qRT-PCR results revealed that after TRIM22 knockdown, the expression levels of antithymocyte globulin 7 (ATG7), antithymocyte globulin 5 (ATG5), Beclin1, ERK, and mTOR genes decreased (P < 0.01); however, the expression of AMPK genes (P < 0.05) and P62 genes (P < 0.001) increased. FCM revealed that following TRIM22 knockdown, the percentage of HUVECs in the G2 phase increased (P < 0.001) along with cell apoptosis. The effect of TRIM22 overexpression on HUVEC autophagy induced by DENV-2 infection and AMPK pathways decreased after adding an autophagy inhibitor.

Conclusions
In HUVECs, TRIM22 protein positively regulates autophagy and may affect autophagy through the AMPK/ERK/mTOR signaling pathway. Autophagy is induced by activation of the AMPK/ERK/mTOR signaling pathway following TRIM22-mediated DENV-2 infection of HUVECs.
Experiences of mothers of NICU preterm infants in milk management out of the hospital: a qualitative study
Authors: Yang Rui , Chen Danqi , Wang Hua , Xu Xinfen 
Published: December 2022

Abstract
Background
Human milk is important for the health and development of preterm infants. China’s neonatal intensive care units (NICUs) have adopted the management system of maternal–infant separation. Human milk received and used by NICUs is managed by the infants’ families in the out-of-hospital environment. There is scant publication on mothers’ opinions on out-of-hospital human milk management. This study aimed to explore the experiences of Chinese mothers providing their infants in the NICUs with human milk expressed outside of the hospital.

Methods
Semi-structured interviews were conducted with 23 participants recruited from June 2020 to November 2020, who transported their human milk to the human milk bank of Women’s Hospital School of Medicine Zhejiang University during the hospitalization of their preterm infants. This study adopted a qualitative research approach with thematic analysis.

Results
Three main themes were identified: 1) awareness of human milk management and a willingness to adopt it; 2) lack of standardization regarding expressing, storing, and transporting expressed human milk; and 3) the need for more external support. Theme 2 additionally has three sub-themes: I) differentiation of preparations before human milk expression; II) differentiation of devices for human milk expression; and III) insufficient knowledge and understanding.

Conclusions
In this study, all participants who received health education showed enthusiasm for participating in out-of-hospital human milk management. However, most participants had questions during the implementation process. Medical staff should provide professional and continuous external support to support mothers in implementing human milk management.
Ultrasound-guided modified pectoral plane (PECS II) block versus erector spinae plane (ESP) block for perioperative analgesia of surgical treatment of gynecomastia
Authors: Rashad Manal Mohamed , Abdelhay Anas Ahmed 
Published: December 2022

Abstract
Background
Nerve block reduces anesthetics requirement, allows faster recovery, and reduces postoperative pain. The modified pectoral plane block (PECS II) and the erector spinae plane block (ESP) have been proposed for nerve block in men undergoing breast surgery for gynecomastia.
This study aimed to compare the efficacy of PECS II and ESP for perioperative analgesia in men undergoing surgical treatment of gynecomastia.
We conducted a randomized clinical trial on 46 males (with ASA I and II, age range from 18 to 25 years) undergoing surgical gynecomastia treatment in a tertiary medical center. Patients were randomly allocated to receive nerve blocks with either PECS II or ESP in addition to the general anesthesia. The postoperative opioid requirement, analgesic doses, pain intensity on the VAS score, hemodynamic parameters throughout the operation, and complications were recorded and compared for both groups.

Results
PECS II group had more favorable outcomes compared to the ESP group, evident by the significantly less total morphine consumption in 24 h (6.09 vs. 14.26 mg, P ≤ 0.001) and the significantly higher effective analgesic time (6.57 vs. 4.91 h, P ≤ 0.001). In addition, there were no intraoperative or postoperative complications recorded in both groups.

Conclusions
For men undergoing elective surgical treatment of gynecomastia, the ultrasound-guided modified PECS II is superior to the ESP in terms of opioid requirement, analgesic doses, and pain intensity.
Serum levels of kynurenine in pregnancies with fetal growth restriction and oligohydramnios
Authors: Yaman Selen , Ceyhan Meryem , Hancerliogullari Necati , Koc Esin Merve , Candar Tuba , Tokmak Aytekin 
Published: December 2022

Abstract

Objectives
Kynurinine (KYN) and its metabolites, which are released during the metabolism of tryptophan, an essential amino acid, have many important functions, such as cellular energy production, regulation of vascular tone, and regulation of the immune system. In this study, we aimed to detect serum KYN levels, which may be an indicator of KYN pathway activity, in idiopathic fetal growth restriction (FGR) and oligohydramnios cases whose pathophysiology is known to be affected by multiple factors, such as placental hypoperfusion, immune dysregulation, and maternal nutrition disorder, and to investigate their relationship with these common obstetric complications.

Methods
This cross-sectional case-control study was carried out in the antenatal outpatient clinics of Ankara City Hospital between July and December 2021. While the study group consisted of pregnant women with idiopathic isolated FGR and oligohydramnios, the control group consisted of low-risk patients who did not have any problems. The clinical features of the patients, such as age, body mass indexes, and gestational week, were recorded by measuring basic laboratory parameters and serum KYN levels.

Results
A total of 110 patients were included in this study. The patients were divided into three groups: FGR, oligohydramnios, and the control group. There was no significant difference between the patients’ ages, weeks of gestation, or body mass indexes. Serum KYN level was calculated as 57.8 ± 13.4 pg/mL in IUGR, 75.3 ± 10.8 pg/mL in oligohydramnios and 95.1 ± 13.3 pg/mL in the control group (p<0.001).

Conclusions
Serum KYN levels were lower in pregnant women complicated with FGR and oligohydramnios more prominently in pregnant women diagnosed with FGR than in normal pregnancies. The results suggest that KYN plays an important role in either the etiopathogenesis or the response to these two obstetric pathologies.
Biosynthesis and Cytotoxic Activity of In Vitro Expressed Scygonadin Protein
Authors: Rosli Nurfarhana , Zainathan Sandra Catherine , Addis Siti Nor Khadijah 
Published: December 2022

Antimicrobial peptides (AMP) are key components of an innate immune response which represent immediate action of the defence mechanism of an organism. It is considered a novel therapeutic agent due to its abundance in nature and a broad range of defence activity against microbial. Preceding research has shown that scygonadin AMPs isolated from seminal plasma of mud crab had the potential as a novel antimicrobial agent. However, its cytotoxicity properties on cultured cells have never been experimentally addressed. In this study, the scygonadin protein was expressed in vitro, followed by cytotoxicity assessment via MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. A full-length sequence of the scygonadin gene of 387 bp was cloned into pBAD/Myc-His A vector and expressed in TOP10 cells. The protein expression was induced, purified and quantified before being subjected to cytotoxicity analysis. Next, an African green monkey kidney (Vero) cell was chosen to evaluate the cytotoxicity level of scygonadin in vitro. A total of 1x104 cells/mL were seeded into a 96-well plate before being treated to various concentrations of scygonadin protein and hydrogen peroxide as a positive control for the toxicity test. The cells’ viability treated with scygonadin AMP and hydrogen peroxide was also verified with fluorescent analysis. The result demonstrated that the scygonadin did not cause any cytotoxicity effects while hydrogen peroxide showed an IC50 value at 0.003mM and this was further confirmed by fluorescent staining analysis. The absence of scygonadin toxicity in cells indicates its potential for biopharmaceutical use.
Improved Intrusion Detection System using Quantal Response Equilibrium-based Game Model and Rule-based Classification
Authors: Belavagi Manjula C , Muniyal Balachandra 
Published: December 2022

Wireless sensor network has large number of low-cost tiny nodes with sensing capability. These provide low cost solutions to many real world problems such as such as defence, Internet of things, healthcare, environment monitoring and so on. The sensor nodes of these networks are placed in vulnerable environment. Hence, the security of these networks is very important. Intrusion Detection System (IDS) plays an important role in providing a security to such type of networks. The sensor nodes of the network have limited power and, traditional security mechanisms such as key-management, encryption decryption and authentication techniques cannot be installed on the nodes. Hence, there is a need of special security mechanism to handle the intrusions. In this paper, intrusion detection system is designed and implemented using game theory and machine learning to identify multiple attacks. Game theory is designed and used to apply the IDS optimally in WSN. The game model is designed by defining the players and the corresponding strategies. Quantal Response Equilibrium (QRE) concept of game theory is used to select the strategies in optimal way for the intrusion’s detection. Further, these intrusions are classified as denial of service attack, rank attack or selective forwarding attacks using supervised machine learning technique based on different parameters and rules. Results show that all the attacks are detected with good detection rate and the proposed approach provides optimal usage of IDS.