bluuebunny/crossref_metadata_2025 huggingface dataset:
PDP1 Promotes Cell Malignant Behavior and Is Associated with Worse Clinical Features in Ovarian Cancer Patients: Evidence from Bioinformatics and In Vitro Level
Authors: Song Yan , Zhang Juan , Zhang Lei , Zhang Suxia , Shen Chengcheng
Published: October 2022

PDP1 has been reported in multiple diseases. However, it has not been fully explored in ovarian cancer (OC). The public data was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differentially expressed gene analysis was conducted out using the limma package. Prognosis analysis was performed using the survival package. Gene Set Enrichment Analysis (GSEA) was performed using the fgsea package. Immune infiltration analysis was performed based on the CIBERSORT algorithm. CCK8 assay was used to evaluate the cell proliferation ability of cancer cells. Transwell assay was used for the invasion and migration ability. Our result showed that PDP1 was overexpressed in OC tissue in RNA and protein level based on multiple databases (TCGA, GSE18520, GSE27651, and GSE54388). At the same time, we found PDP1 was correlated with poor prognosis and worse clinical parameters. In vitro experiment showed that PDP1 could significantly promote proliferation, invasion, and migration ability of OC cells. GSEA analysis showed that in the OC patients with high PDP1 expression, the pathway of IL6/JAK/STAT3 signaling, interferon-alpha response, apoptosis, adipogenesis, KRAS signaling, and IL2/STAT5 signaling was activated, which might be responsible for its oncogenic effect in OC. Immune infiltration analysis indicated that PDP1 was positively correlated with activated myeloid dendritic cells, resting CD4 memory T cells, neutrophil, and M1 and M2 macrophages, yet negatively correlated with M0 macrophages, plasma B cells, γδT cells, and activated CD4 memory T cells. Drug sensitivity analysis showed a negative correlation between PDP1 expression and the IC50 of bleomycin and gemcitabine, yet a positive correlation of cisplatin, indicating that the OC patients with high PDP1 expression might be more sensitive to bleomycin and gemcitabine and more resistant to cisplatin. PDP1 could facilitate OC progression and is associated with patient prognosis and chemosensitivity, making it an underlying biomarker of OC.
CNN-LSTM Facial Expression Recognition Method Fused with Two-Layer Attention Mechanism
Authors: Ming Ye , Qian Hu , Guangyuan Liu
Published: October 2022

When exploring facial expression recognition methods, it is found that existing algorithms make insufficient use of information about the key parts that express emotion. For this problem, on the basis of a convolutional neural network and long short-term memory (CNN-LSTM), we propose a facial expression recognition method that incorporates an attention mechanism (CNN-ALSTM). Compared with the general CNN-LSTM algorithm, it can mine the information of important regions more effectively. Furthermore, a CNN-LSTM facial expression recognition method incorporating a two-layer attention mechanism (ACNN-ALSTM) is proposed. We conducted comparative experiments on Fer2013 and processed CK  + datasets with CNN-ALSTM, ACNN-ALSTM, patch based ACNN (pACNN), Facial expression recognition with attention net (FERAtt), and other networks. The results show that the proposed ACNN-ALSTM hybrid neural network model is superior to related work in expression recognition.
MSeg-Net: A Melanoma Mole Segmentation Network Using CornerNet and Fuzzy
K
-Means Clustering
Authors: Nawaz Marriam , Nazir Tahira , Khan Muhammad Attique , Alhaisoni Majed , Kim Jung-Yeon , Nam Yunyoung
Published: October 2022

Melanoma is a dangerous form of skin cancer that results in the demise of patients at the developed stage. Researchers have attempted to develop automated systems for the timely recognition of this deadly disease. However, reliable and precise identification of melanoma moles is a tedious and complex activity as there exist huge differences in the mass, structure, and color of the skin lesions. Additionally, the incidence of noise, blurring, and chrominance changes in the suspected images further enhance the complexity of the detection procedure. In the proposed work, we try to overcome the limitations of the existing work by presenting a deep learning (DL) model. Descriptively, after accomplishing the preprocessing task, we have utilized an object detection approach named CornerNet model to detect melanoma lesions. Then the localized moles are passed as input to the fuzzy

K

-means (FLM) clustering approach to perform the segmentation task. To assess the segmentation power of the proposed approach, two standard databases named ISIC-2017 and ISIC-2018 are employed. Extensive experimentation has been conducted to demonstrate the robustness of the proposed approach through both numeric and pictorial results. The proposed approach is capable of detecting and segmenting the moles of arbitrary shapes and orientations. Furthermore, the presented work can tackle the presence of noise, blurring, and brightness variations as well. We have attained the segmentation accuracy values of 99.32% and 99.63% over the ISIC-2017 and ISIC-2018 databases correspondingly which clearly depicts the effectiveness of our model for the melanoma mole segmentation.
Downregulation of Circ-PITHD1 Suppressed Colorectal Cancer via Glycolysis Inhibition through miR-590-5p/HK2 Axis
Authors: Yang Shiguang , Zhao Kui , Yang Xiaodong , Xing Chungen
Published: October 2022

Colorectal cancer (CRC) is a frequent malignancy around the globe. Circular RNAs (circRNAs) are implicated in CRC development. Nevertheless, the regulatory mechanisms and biological functions regarding circRNAs in CRC progression are largely unclear. The present investigation employed next-generation sequencing (NGS) to study the abnormal circRNA expression in CRC tissues. The regulatory mechanism and targets were then analyzed by bioinformatics, luciferase reporter analysis, CCK8, colony formation, and Transwell migration. In vivo metastasis and tumorigenesis assays were conducted to elucidate circ-PITHD1 roles regarding CRC. The data showed that circ-PITHD1 expression increased in a CRC cell line and tissues, which indicated that circ-PITHD1 functioned in CRC progression. circ-PITHD1 downregulation inhibited CRC invasion and proliferation in the experiments. Luciferase reporter results confirmed that both miR-590-5p and hexokinase 2 (HK2) were circ-PITHD1 downstream targets. HK2 overexpression or miR-590-5p suppression reversed CRC cell proliferation and invasion after silencing of circ-PITHD1 by regulation of glycolysis. Taken together, this investigation discovered that circ-PITHD1 downregulation suppressed CRC progression by inhibiting glycolysis via the miR-590-5p/HK2 axis.
Boosting Slime Mould Algorithm for High-Dimensional Gene Data Mining: Diversity Analysis and Feature Selection
Authors: Qiu Feng , Guo Ran , Chen Huiling , Liang Guoxi
Published: October 2022

Slime mould algorithm (SMA) is a new metaheuristic algorithm, which simulates the behavior and morphology changes of slime mould during foraging. The slime mould algorithm has good performance; however, the basic version of SMA still has some problems. When faced with some complex problems, it may fall into local optimum and cannot find the optimal solution. Aiming at this problem, an improved SMA is proposed to alleviate the disadvantages of SMA. Based on the original SMA, Gaussian mutation and Levy flight are introduced to improve the global search performance of the SMA. Adding Gaussian mutation to SMA can improve the diversity of the population, and Levy flight can alleviate the local optimum of SMA, so that the algorithm can find the optimal solution as soon as possible. In order to verify the effectiveness of the proposed algorithm, a continuous version of the proposed algorithm, GLSMA, is tested on 33 classical continuous optimization problems. Then, on 14 high-dimensional gene datasets, the effectiveness of the proposed discrete version, namely, BGLSMA, is verified by comparing with other feature selection algorithm. Experimental results reveal that the performance of the continuous version of the algorithm is better than the original algorithm, and the defects of the original algorithm are alleviated. Besides, the discrete version of the algorithm has a higher classification accuracy when fewer features are selected. This proves that the improved algorithm has practical value in high-dimensional gene feature selection.
Effect of Nursing Intervention on Promoting Healing of RW in Patients with Diabetic Foot: A Systematic Review and Meta-Analysis
Authors: Chen Huan , Lv Xiaoxia , Zhang Yingying
Published: October 2022

Objective. To systematically assess the effect of nursing intervention on promoting the healing of refractory wounds (RW) in patients with diabetic foot (DF). Methods. A computer search of PubMed, EMBASE, ScienceDirect, CochraneLibrary, China knowledge Network Database (CNKI), China VIP Database, Wanfang Database, and China Biomedical Literature Database (CBM) online database was conducted in a randomized controlled trial (RCT) of traditional Chinese and western medicine nursing intervention on patients with RW of DF. Retrieval time was limited to the period from the date the database was established to present. Separately, two researchers gathered the data. RevMan5.3 statistical software was used to analyze the collected data by meta-analysis according to Cochrane Handbook 5.3. Results. Finally, 8 articles were included with a total sample size of 772 cases. The meta-analysis of the wound healing time after intervention indicated that the wound healing time of the study group was notably shorter, and the difference was statistically significant (

P
<
0.05

). Qualitative, fixed-effect model analysis indicated that the nursing effective rate after treatment in the study group was notably higher, and the difference was statistically significant (

P
<
0.05

). Fasting blood glucose level in the study group after treatment was notably lower, and the difference was statistically significant (

P
<
0.05

). The life quality in the study group was notably higher, and the difference was statistically significant (

P
<
0.05

). Further subgroup analysis indicated that the score of physical function (PF), emotional function (RE), social function (SF), physical pain (BP), general health (GH), vitality (VT), and mental health (MH) in the study group were higher, and the difference was statistically significant (

P
<
0.05

). A publication bias analysis was conducted using the inverted funnel chart as the outcome indicator for this study. The results indicated that most of the funnel maps were symmetrical and a few were asymmetrical, suggesting that there exhibited a certain publication bias in the included literature. Conclusion. The application of traditional Chinese and western medicine nursing intervention when treating DF patients clinically can effectively promote the healing of foot ulcer wounds. Traditional Chinese and western medicine nursing can help patients heal wounds faster and enhance their life quality compared to simplistic western medicine nursing. According to the original literature, the conclusion deserves to be popularized in clinic.
Analytical Soliton Solutions of the Coupled Radhakrishnan‐Kundu‐Lakshmanan Equation via Three Techniques
Authors: Ali Khalid K. , Mehanna M. S. , Akbar M. Ali , Chakrabarti Prasun
Published: October 2022

The analytical soliton solutions to the coupled Radhakrishnan‐Kundu‐Lakshmanan (RKL) model are greatly important for birefringent fibers without the effect of four‐wave mixing (4WM). A significant number of general and standard analytical soliton solutions to this model have been extracted using three powerful techniques, namely the generalized Kudryashov’s method, the extended tanh method, and the (G′/G)‐expansion method in this article. The schematic profiles of the solitons are sketched using the symbolic mathematical program Mathematica and are presented in two and three dimensions. The reported solutions might be helpful in explaining the RKL equation’s physical significance as well as some other related nonlinear phenomena that appear in engineering and nonlinear sciences.
Linking Prioritized Occupational Performance in Patients Undergoing Spasticity-Correcting Upper Limb Surgery to the International Classification of Functioning, Disability, and Health
Authors: Ramström Therese , Wangdell Johanna , Reinholdt Carina , Bunketorp-Käll Lina
Published: October 2022

Background. Spasticity is generally caused by damage to the spinal cord or the areas of the brain that controls movements, which poses significant limitations in occupational tasks. Objectives. The aims of the study were to (I) describe prioritized occupational performance problems (POPP) among patients who underwent upper limb spasticity-correcting surgery and map them to the International Classification of Function, Disability, and Health (ICF); (II) assess outcomes postsurgery; (III) assess whether the results are influenced by the diagnosis, gender, and residual muscle function; and (IV) assess correlation between changes in COPM and gains in grasp ability and grip strength. Methods. In this retrospective study, assessments occurred pre- and postsurgery, including the Canadian Occupational Performance Measure (COPM), grip strength, and grasp ability. POPP were transformed to prioritized occupational performance goals (POPG) during subsequent rehabilitation. Results. 60 patients with a history of spinal cord injury (SCI) (

n
=
42

; 59%), stroke (

n
=
25

; 34%), traumatic brain injury (TBI) (

n
=
4

; 6%), and reason unknown (

n
=
1

; 1%) were included, with a mean age of 57 (±13) years. Of those, 11 had bilateral surgery, generating 71 COPM forms and 320 POPG. The POPG were mapped to the ICF activity and participation chapter, most often to self-care (

n
=
131

; 41%), domestic life (

n
=
68

; 21%), and mobility (

n
=
58

; 18%). COPM scores were significantly increased postsurgery, irrespective of diagnosis, gender, and muscle function. No clear correlation between COPM improvement and hand function gains was shown. Conclusion. Patients who underwent spasticity-correcting upper limb surgery identified difficulties with a wide range of occupational tasks that they considered as important to regain. Treatment-induced gains in occupational performance were significant but had no clear correlation with gains in grasp ability and hand strength. Independent of diagnosis, gender, and residual muscle function, it seems important to address the activity- and participation-specific aspects in the assessment and rehabilitation of patients.
Investigation of the Composition, Antimicrobial, Antioxidant, and Cytotoxicity Properties of Salvia abrotanoides Essential Oil
Authors: Jaderi Zeinab , Tabatabaei Yazdi Farideh , Mortazavi Seyed Ali , Koocheki Arash
Published: October 2022

Medicinal plants present promising attributes in traditional medicine based on earlier published documents. Most of the essential oils derived from vascular plants display a significant role in dealing with microbial and inflammation infections. This research aimed to provide informative knowledge about the composition, antimicrobial, and anticytotoxicity of Salvia abrotanoides essential oil. In this study, the chemical composition of S. abrotanoides was determined using FTIR and GC-MS analysis which demonstrated the significant number of monoterpenes in the constitutes. The antimicrobial activity of EO demonstrated a dose-related effect on several pathogenic bacteria and fungi; among bacteria, Gram-positive bacteria exhibited more sensitivity to the essential oil antimicrobial compounds. On the other hand, S. abrotanoides essential oil did not present antifungal activity as high as Fluconazole on Aspergillus niger and Candida albicans. The total phenolic and flavonoid content of essential oil were determined as 14.70 ± 1.4 mg·GA/g essential oil and 2.93 ± 0.41 mg Q/g essential oil, respectively. The antioxidant activity of essential oils was investigated, and it was not as high as positive controls. Moreover, the microscopic changes of S. aureus and E. coli were investigated using SEM images. The cytotoxicity potential of essential oil was evaluated on L929 and A459 cell lines and also it was estimated to be stronger on A459 cell line than that of L929.
Initiation of Liver Transplant in Nepal: A Milestone
Authors: Shrestha Pukar Chandra , Joshi Neeraj , Gurubacharya Dipesh Lal , Devbhandari Mohan , Rai Aarati , Bhandari Tika Ram , Shrestha Prakriti , Paneru Pragya , Gupta Subhash , Kwon Choon Hyuck David
Published: October 2022

Background. The incidence of chronic liver disease is increasing in the Nepalese population. Liver transplantation (LT) is the best option for patients with end-stage liver disease (ESLD). Nepal’s first liver transplant was performed in 2016 in an international collaborative effort at Shahid Dharmabhakta National Transplant Centre (SDNTC), Bhaktapur, Nepal. We aim to report details of the first five patients who had undergone liver transplantation in SDNTC before the beginning of the COVID-19 outbreak in the history of transplantation in Nepal. Method. A descriptive analysis of the clinical data of five adult recipients of liver transplantation at SDNTC was done. We described the patient’s demographics, length of stay, and survival of all the first five patients who had undergone four living donor liver transplantations and one brain-dead donor liver transplantation in SDNTC before the beginning of the COVID-19 outbreak. Results. Recipients were between 36 and 63 years old. The recipients of the four live donor liver transplants (LDLT) and one brain-dead donor liver transplant (DDLT) had alcoholic liver disease and cryptogenic liver disease, leading to end-stage liver disease. The model for end-stage liver disease (MELD) scores ranged from 23 to 34. Out of five, four recipients and four donors are doing well and relishing the prospect of a normal life, while the recipient of a brain-dead donor liver transplant passed away due to postoperative primary graft failure. Conclusion. Despite the small number of liver transplants that have been done, the success of these has created confidence in a sustainable liver transplantation program in Nepal.
Feasibility Study on the Initial Kartini Reactor Core Using Plate Type Fuel Elements
Authors: Wicaksono Argo Satrio , Takeda Satoshi , Kitada Takanori
Published: October 2022

The plate type fuel element conversion is proposed to solve a supply problem of TRIGA standard rod type fresh fuel in the long term and to extend the lifetime by reducing the dependence of buying imported elements. The plate type fuel is an alternative since the Indonesian industry has been able to produce such fuel elements. The change of core configuration is expected to improve the reactor performance for irradiation facilities and fuel element lifetime. The SRAC2006 is used to perform neutronic calculations while the nuclear fuel lifetime is calculated by SWAT. This study begins with performing a core properties comparison of UZrH1.6 as the current fuel material and U3Si2-Al as the fuel material candidate. The results show that the Kartini reactor core is possible to load U3Si2-Al as the fuel material and makes higher excess reactivity compared to the current fuel material. Furthermore, U3Si2-Al in the plate type element geometry is variedly arranged in the new reactor core configuration to optimize the neutronic core parameters. The new core configuration is composed of 10 standard fuel elements, 4 fuel control elements, and the graphite material baffle that is located between the active core and annular reflector for serves as an additional reflector. The configuration produced sufficient core excess reactivity and adequate shutdown margin. It also produced negative temperature feedback reactivity and power peaking factor that fulfilled the safety requirements. Improvement of new reactor core performance was obtained by more irradiation facilities, higher thermal neutron flux, and longer maximum estimated burn up compared to the current core configuration.
Lisaftoclax in Combination with Alrizomadlin Overcomes Venetoclax Resistance in Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia: Preclinical Studies
Authors: Zhai Yifan , Tang Qiuqiong , Fang Douglas D. , Deng Jing , Zhang Kaixiang , Wang Qixin , Yin Yan , Fu Chengcheng , Xue Sheng-Li , Li Na , Zhou Feng , Yang Dajun
Published: October 2022

Purpose:

Despite approval of B-cell lymphoma (BCL)-2 inhibitor venetoclax for certain hematologic malignancies, its broader clinical benefit is curtailed by resistance. Our study aimed to determine if treatment with novel anticancer agents targeting BCL-2 and mouse double minute 2 (MDM2) could overcome venetoclax resistance in preclinical models.

Experimental Design:

Venetoclax-sensitive and venetoclax-resistant acute myeloid leukemia (AML) and acute lymphoblastic leukemia cells and xenograft models were used to evaluate antitumor effects and underlying mechanisms associated with combined BCL-2 inhibitor lisaftoclax (APG-2575) and MDM2 inhibitor alrizomadlin (APG-115).

Results:

The combination exhibited synergistic antiproliferative and apoptogenic activities in TP53 wild-type AML cell lines in vitro. This synergy was further exemplified by deep antitumor responses and prolonged survival in AML cell line–derived and patient-derived xenograft models. Interestingly, the combination treatment resensitized (to apoptosis) venetoclax-resistant cellular and mouse models established via chronic drug exposure or genetically engineered with clinically relevant BCL-2 gene mutations. Synergistic effects in reducing cellular viability and proliferation were also demonstrated in primary samples of patients with venetoclax-resistant AML treated with lisaftoclax and alrizomadlin ex vivo. Mechanistically, alrizomadlin likely primes cancer cells to BCL-2 inhibition-induced cellular apoptosis by downregulating expression of antiapoptotic proteins myeloid cell leukemia-1 and BCL–extra-large and upregulating pro-death BCL-2–associated X protein.

Conclusions:

Lisaftoclax in combination with alrizomadlin overcomes venetoclax resistance mediated by various mechanisms, including BCL-2 mutations. In addition, we posit further, putative molecular mechanisms. Our data rationalize clinical development of this treatment combination in patients with diseases that are insensitive or resistant to venetoclax.
Pegylated Liposomal Doxorubicin Combined with Ifosfamide for Treating Advanced or Metastatic Soft-tissue Sarcoma: A Prospective, Single-arm Phase II Study
Authors: Liu Xin , Jiang Shiyu , Wang Huijie , Wu Xianghua , Yan Wangjun , Chen Yong , Xu Yu , Wang Chunmeng , Yao Weiqiang , Wang Jian , Yu Lin , Miao Jiashun , Chen Hao , Xia Jing , Huang Mengli , Zhang Xiaowei , Luo Zhiguo
Published: October 2022

Purpose:

This prospective single-arm phase II clinical trial aimed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) combined with ifosfamide (IFO) as the first-line treatment for patients with advanced or metastatic soft-tissue sarcoma (STS).

Patients and Methods:

Patients received PLD (30 mg/m2; day 1) in combination with IFO (1.8 g/m2; days 1–5) every 21 days until disease progression, unacceptable toxicities, patient death, or for up to six cycles. The primary endpoint was progression-free survival (PFS; NCT03268772).

Results:

Overall, 69 patients with chemotherapy-naïve advanced or metastatic STS were enrolled between May 2015 and November 2019. At a median follow-up of 47.2 months, the median PFS and overall survival (OS) were found to be 7.3 [95% confidence interval (CI): 5.7–8.9] and 20.6 (95% CI: 16.3–25.0) months, respectively. The response and disease control rates were 26.1% and 81.2%, respectively. Adverse events were manageable, and no grade 3–4 cardiotoxicities were observed. There was no significant change in left ventricular ejection fraction values between baseline and after treatment (P = 0.669). Exploratory biomarker analysis suggested NF1 single-nucleotide variant was associated with poor OS (P < 0.0001) and PFS (P = 0.044). In addition, 2 patients with BRCA2 loss progressed in the initial 2 months and died within 10 months. Improved OS was observed in homologous recombination deficiency (HRD)-negative patients compared with their HRD-positive counterparts (P = 0.0056).

Conclusions:

Combination therapy comprising PLD and IFO is an effective and well-tolerated first-line treatment for patients with advanced or metastatic STS.
Diminution of STING Expression in the Blood of Patients with Severe or Critical COVID-19 Pneumonia
Authors: Rezaei Mitra , Marjani Majid , Mirahmadi Alireza , Bineshfar Niloufar , Mohammadpour Hadiseh , Pourabdollah Toutkaboni Mihan , Nasr Azadani Farinaz , Amanzade Zahra , Tabarsi Payam , Ziai Seyed Ali , Casanova Jean Laurent , Mansouri Davood
Published: October 2022

Introduction: Cytokine storm and critical COVID-19 pneumonia are caused in at least 10% of patients by inborn errors of or auto-Abs to type I IFNs. The pathogenesis of life-threatening COVID-19 pneumonia in other patients remains unknown. Methods: This study was conducted at Masih Daneshvari Hospital, Tehran, Iran. In the period of study, 75 confirmed cases of COVID-19 with presentations ranging from mild upper respiratory tract infection to lower respiratory tract infection, including moderate, severe, and critical disease, were recruited. Expression of STING mRNA was measured in peripheral blood mononuclear cells (PBMCs) and compared between patients with different severity and outcome. Results: There was a significant negative correlation between age and STING expression level (p value = 0.010). Patients with “severe to critical” illness had a 20-fold lower STING expression level compared to the “mild to moderate” group (p value = 0.001). Also, the results showed lower expressions of STING in the patients admitted to the ICU (p value = 0.015). Patients who finally died had lower expression of STING at the time of sampling (p value = 0.041). Conclusion: STING mRNA expression in PBMCs was significantly lower in older COVID-19 cases, the patients with more severe illness, who needed intensive care, and who eventually died.
Prospective Evaluation of Health-Related Quality of Life in Patients with Metastatic Urothelial Carcinoma Undergoing Immunotherapy with Pembrolizumab: Symptom Burden Can Predict Survival
Authors: Schneidewind Laila , Dräger Desirée Louise , Roßberg Vanessa , Nolting Julia , Hakenberg Oliver W.
Published: October 2022

Introduction: Despite the fact that guidelines recommend monitoring of quality of life during all phases of treatment in urothelial carcinoma, prospective data about health-related quality of life (HRQoL) in metastatic urothelial carcinoma undergoing immunotherapy are sparse. Consequently, we performed a prospective clinical pilot study about HRQoL using the Functional Assessment of Cancer Therapy – Immune Checkpoint Modulator (FACT-ICM) questionnaire. Materials and Methods: Formally, this study is a prospective uni-centric noninterventional observation from January 2021 to December 2021. Results: Fourteen patients with a mean age of 73.9 years (SD 8.8) participated in the study. The physical well-being subscale of FACT-G is most impaired during therapy with mean scores of 7.5, 6.2, and 4.0 followed by the emotional well-being. The FACT-G total score is stable during therapy with mean scores of 51.1, 50.4, and 48.0 and it is not significantly decreasing during therapy (p = 0.317). Furthermore, the symptom burden of these patients is low and not significantly changing over time (p = 0.500), but survival decreases significantly if symptom burden is high (FACT-ICM score over 40; p < 0.001). Conclusion: Physical and emotional needs have a strong impact on HRQoL and should be dealt with during treatment. If symptom burden is high, survival decreases. This needs further evaluation.
Affordability of Alcoholic Beverages in the European Union
Authors: Kilian Carolin , Manthey Jakob , Neufeld Maria , Rehm Jürgen
Published: October 2022

Background: From a public health perspective, alcohol taxation should be designed to reduce alcohol affordability and thus alcohol consumption and related harms. Objectives: In this brief report, we estimate alcohol affordability in European Union Member States and associated countries and investigate whether affordability is related to national alcohol excise duties. Method: Beverage-specific affordability for beer, wine, and spirits were estimated based on the number of standard drinks a household could purchase based on their median monthly disposable household income in 2020. To determine the pooled affordability of alcohol, the beverage-specific estimates were weighted by the share of the beverage-specific per capita consumption in total recorded consumption. Pearson and Spearman rank correlations were calculated to establish the association between alcohol affordability and alcohol excise duty rates. All data were retrieved from official sources. Results: On average, a European household can purchase 1,628 standard drinks of alcohol with its monthly income, with affordability being highest in Germany, Austria, France, and Luxembourg. The affordability of spirits, but not that of beer or wine, was inversely correlated with the beverage-specific excise duty rates. Conclusions: Alcohol is affordable in the Member States of the European Union and associated countries, and low levels of excise duties on beer and wine appear to be unrelated to their affordability. Alcohol taxes should be increased to effectively reduce the affordability of alcoholic beverages in order to lower the alcohol-related health burden in Europe.
Genomically Stable Gastric Cancer Characterized by Hypomethylation in Wnt Signal Cascade
Authors: Toshima Toshiaki , Tanioka Hiroaki , Mori Yoshiko , Tanaka Takehiro , Yasui Kazuya , Kimura Keisuke , Umeda Yuzo , Fujiwara Toshiyoshi , Nyuya Akihiro , Yano Shuya , Nagasaka Takeshi
Published: October 2022

Introduction: Gastric cancer is divided into four subtypes by their molecular features linked with genetic alterations, e.g., Epstein-Barr virus (EBV), microsatellite instability-high (MSI-high), chromosomal instability (CIN), and genomically stable (GS), called as TCGA classification. In this study, we tried to clarify the epigenetic features of the four GC subtypes according to aberrant methylation status in 23 loci. Methods: A total of 98 gastric cancers and their normal gastric mucosa samples were included in this study. We divided gastric cancers into TCGA subtypes which were determined in line with MSI-high, EBV, CIN, to GS by their molecular features. The 13 loci of polymorphic microsatellite sequences were used to determine loss of heterogeneity for the detection of CIN. The MSI status was determined by three mononucleotide repeat markers. Infection of EBV was determined by recovering EBV BNRF1 sequence from genomic DNA collected from gastric cancers. Methylation status of 23 loci was investigated by the combined bisulfite restriction analysis. Status of other findings, e.g., KRAS mutations, HER2 expression status, and infection of helicobacter pylori were confirmed. Results: Gastric cancers were divided into MSI (13%), EBV (7%), CIN (53%), and GS (27%). By histological classification, poorly differentiated adenocarcinoma was more in tumors categorized in MSI-high, and GS and signet-ring cell carcinoma (sig) were more in GS. Among the 23 loci investigated their methylation status, 18 loci were significantly hypermethylated in caner tissues. An unsupervised clustering divided gastric cancers into two clusters and revealed that most GS tumors clustered together in a cluster that exhibited lower methylation levels, distinct from the other subtypes. The inter-variable clustering revealed that a cluster contained the three loci (SFRP2-region 1/2 and APC) belonging to the Wnt signal cascade (Wnt-associated loci). The mean methylation score of Wnt-associated loci was the lowest in GS tumors (MSI-high: 2.7 [95% confidence interval, 2.3–2.9]; EBV: 2.1 [1.2–3.1]; CIN: 2.4 [2.2–2.7]; GS: 1.3 [0.8–0.7]). In contrast, the mean methylation score of the other 15 loci was significantly higher in MSI-high, while that in GS was as same as that in EBV or CIN (MSI-high: 10.4 [8.3–12.4]; EBV: 5.7 [1.7–9.7]; CIN: 4.4 [3.6–5.1]; GS: 3.4 [2.2–4.6]). Additionally, the lower methylation score of Wnt-associated loci was observed only in sig tumors. Conclusions: GS subtype tumors have the potential to possess distinct signatures in DNA hypomethylation profiles in Wnt signaling pathway, especially in sig.
CA19-9 in Combination with Methylated HOXA1 and SST Is Useful to Diagnose Stage I Pancreatic Cancer
Authors: Suehiro Yutaka , Suenaga Shigeyuki , Kunimune Yuki , Yada Shoko , Hamamoto Kaori , Tsuyama Takanori , Amano Shogo , Matsui Hiroto , Higaki Shingo , Fujii Ikuei , Suzuki Chieko , Hoshida Tomomi , Matsumoto Toshihiko , Fujimoto Yuko , Kaino Seiji , Shinjo Keiko , Kondo Yutaka , Sakaida Isao , Takami Taro , Nagano Hiroaki , Yamasaki Takahiro
Published: October 2022

Introduction: We previously developed a novel methylation assay, the combined restriction digital PCR (CORD) assay, consisting of treatment of DNA with methylation-sensitive restriction enzymes and droplet digital PCR. Methods: In this study, we assessed the diagnostic performance of serum methylated Homeobox A1 (mHOXA1) and methylated somatostatin (mSST) using the CORD assay in combination with CA19-9 for pancreatic cancer using serum samples from 82 healthy individuals, 13 patients with benign pancreatic disease, 3 patients with branched-duct intraductal papillary mucinous neoplasm, and 91 patients with pancreatic cancer. Results: For the single marker tests, sensitivity for all stages of pancreatic cancer, stage I cancer, and specificity were, respectively, 71.4%, 50.0%, and 94.9% for CA19-9; 51.6%, 68.8%, and 90.8% for mHOXA1; and 50.1%, 68.8%, and 94.9% for mSST. Those for the combined marker tests were, respectively, 86.8%, 81.3%, and 85.7% for combined mHOXA1 and CA19-9; 86.8%, 87.5%, and 89.8% for combined mSST and CA19-9; and 89.0%, 87.5%, and 85.7% for all three markers combined. Conclusion: The combination of mHOXA1 and mSST with CA19-9 appears to be useful to detect pancreatic cancer even at an early stage.
Reconstructing Phylogenies of Alocasia spp. (Araceae) Distributed in Indonesia for Conservation Prioritization
Authors:   Bali Botanic Garden, Tabanan, Indonesia National Research and Innovation Agency (BRIN), Jakarta, Indonesia, Asih Ni , Erlinawati Ina ,   Herbarium Bogoriense, Botany Division, Research Center for Biology, Cibinong, Indonesia National Research and Innovation Agency (BRIN), Jakarta, Indonesia, Priyadi Arief ,   National Research and Innovation Agency (BRIN), Jakarta, Indonesia
Published: October 2022

Phylogenetic analysis is beneficial to plant conservation prioritization. Conservation does not only deal with species but also their evolutionary potential. A phylogenetic tree is usually reconstructed by using the alignment of DNA sequences. However, with the availability of megatrees, subsetting with a list of species of concern is possible. Here we reconstructed a list of 53 Alocasia spp. (Araceae) from Indonesia and adjacent regions using available megatrees and publicly available DNA sequences in the GenBank. The result showed placed and unplaced Alocasia spp. on the terminal nodes of reconstructed phylogenetic trees. The unplaced species show that publicly available DNA sequences are not yet available, therefore should be prioritized for sequencing. The placed species in the phylogeny could be used for conservation prioritization of these Alocasia spp. Keywords: Alocasia, Indonesia, Megatree, Phylogeny, Plant conservation
MED1 Regulates BMP/TGF-β in Endothelium: Implication for Pulmonary Hypertension
Authors: Wang Chen , Xing Yuanming , Zhang Jiao , He Ming , Dong Jianjie , Chen Shanshan , Wu Haoyu , Huang Hsi-Yuan , Chou Chih-Hung , Bai Liang , He Fangzhou , She Jianqing , Su Ailing , Wang Youhua , Thistlethwaite Patricia A. , Huang Hsien-Da , Yuan Jason X.-J. , Yuan Zu-Yi , Shyy John Y-J.
Published: October 2022

Background:

Dysregulated BMP (bone morphogenetic protein) or TGF-β (transforming growth factor beta) signaling pathways are imperative in idiopathic and familial pulmonary arterial hypertension (PAH) as well as experimental pulmonary hypertension (PH) in rodent models. MED1 (mediator complex subunit 1) is a key transcriptional co-activator and KLF4 (Krüppel-like factor 4) is a master transcription factor in endothelium. However, MED1 and KLF4 epigenetic and transcriptional regulations of the BMP/TGF-β axes in pulmonary endothelium and their dysregulations leading to PAH remain elusive. We investigate the MED1/KLF4 co-regulation of the BMP/TGF-β axes in endothelium by studying the epigenetic regulation of BMPR2 (BMP receptor type II), ETS-related gene (
ERG
), and TGFBR2 (TGF-β receptor 2) and their involvement in the PH.

Methods:

High-throughput screening involving data from RNA-seq, MED1 ChIP-seq, H3K27ac ChIP-seq, ATAC-seq, and high-throughput chromosome conformation capture together with in silico computations were used to explore the epigenetic and transcriptional regulation of BMPR2, ERG, and TGFBR2 by MED1 and KLF4. In vitro experiments with cultured pulmonary arterial endothelial cells (ECs) and bulk assays were used to validate results from these in silico analyses. Lung tissue from patients with idiopathic PAH, animals with experimental PH, and mice with endothelial ablation of MED1 (EC-
MED1
−/−
) were used to study the PH-protective effect of MED1.

Results:

Levels of MED1 were decreased in lung tissue or pulmonary arterial endothelial cells from idiopathic PAH patients and rodent PH models. Mechanistically, MED1 acted synergistically with KLF4 to transactivate BMPR2, ERG, and TGFBR2 via chromatin remodeling and enhancer-promoter interactions. EC-
MED1
−/−
mice showed PH susceptibility. In contrast, MED1 overexpression mitigated the PH phenotype in rodents.

Conclusions:

A homeostatic regulation of BMPR2, ERG, and TGFBR2 in ECs by MED1 synergistic with KLF4 is essential for the normal function of the pulmonary endothelium. Dysregulation of MED1 and the resulting impairment of the BMP/TGF-β signaling is implicated in the disease progression of PAH in humans and PH in rodent models.
Intravenous Thrombolysis in Patients With Ischemic Stroke Aged ≥90 Years: A Cohort Study From the TRISP Collaboration
Authors: Altersberger Valerian L. , Rusche Norman , Martinez-Majander Nicolas , Hametner Christian , Scheitz Jan F. , Henon Hilde , Dell’Acqua Maria Luisa , Strambo Davide , Stolp Jeffrey , Heldner Mirjam R. , Grisendi Ilaria , Jovanovic Dejana R. , Bejot Yannick , Pezzini Alessandro , Leker Ronen R. , Kägi Georg , Wegener Susanne , Cereda Carlo W. , Lindgren Erik , Ntaios George , Piot Ines , Polymeris Alexandros A. , Lyrer Philippe A. , Räty Silja , Sibolt Gerli , Tiainen Marjaana , Heyse Miriam , Erdur Hebun , Kaaouana Olfa , Padjen Visnja , Zedde Marialuisa , Arnold Marcel , Nederkoorn Paul J. , Michel Patrik , Bigliardi Guido , Zini Andrea , Cordonnier Charlotte , Nolte Christian H. , Ringleb Peter A. , Curtze Sami , Engelter Stefan T. , Gensicke Henrik ,   for the Thrombolysis in Stroke Patients (TRISP) Collaborators
Published: October 2022

Background:

The probability to receive intravenous thrombolysis (IVT) for treatment of acute ischemic stroke declines with increasing age and is consequently the lowest in very elderly patients. Safety concerns likely influence individual IVT treatment decisions. Using data from a large IVT registry, we aimed to provide more evidence on safety of IVT in the very elderly.

Methods:

In this prospective multicenter study from the TRISP (Thrombolysis in Ischemic Stroke Patients) registry, we compared patients ≥90 years with those <90 years using symptomatic intracranial hemorrhage (ECASS [European Cooperative Acute Stroke Study]-II criteria), death, and poor functional outcome in survivors (modified Rankin Scale score 3–5 for patients with prestroke modified Rankin Scale score ≤2 and modified Rankin Scale score 4–5 for patients prestroke modified Rankin Scale ≥3) at 3 months as outcomes. We calculated adjusted odds ratio with 95% CI using logistic regression models.

Results:

Of 16 974 eligible patients, 976 (5.7%) were ≥90 years. Patients ≥90 years had higher median National Institutes of Health Stroke Scale on admission (12 versus 8) and were more often dependent prior to the index stroke (prestroke modified Rankin Scale score of ≥3; 45.2% versus 7.4%). Occurrence of symptomatic intracranial hemorrhage (5.7% versus 4.4%, odds ratio
adjusted
1.14 [0.83–1.57]) did not differ significantly between both groups. However, the probability of death (odds ratio
adjusted
3.77 [3.14–4.53]) and poor functional outcome (odds ratio
adjusted
2.63 [2.13–3.25]) was higher in patients aged ≥90 years. Results for the sample of centenarians (n=21) were similar.

Conclusions:

The probability of symptomatic intracranial hemorrhage after IVT in very elderly patients with stroke did not exceed that of their younger counterparts. The higher probability of death and poor functional outcome during follow-up in the very elderly seems not to be related to IVT treatment. Very high age itself should not be a reason to withhold IVT.
Network Meta-Analysis of Non-Conventional Therapies for Improving Upper Limb Motor Impairment Poststroke
Authors: Saikaley Marcus , Pauli Griffin , Sun Hao , Serra Julisa Rodriguez , Iruthayarajah Jerome , Teasell Robert
Published: October 2022

Background:

Network meta-analysis is a method that can estimate relative efficacy between treatments that may not have been compared directly within the literature. The purpose of this study is to present a network meta-analysis of non-conventional interventions to improve upper extremity motor impairment after stroke.

Methods:

A literature search was conducted in 5 databases from their inception until April 1, 2021. Terms were used to narrow down articles related to stroke, the upper extremity, and interventional therapies. Randomized controlled trials written in English were eligible if; 50% poststroke patients; ≥18 years old; applied an intervention for the upper extremity, and/or used the Fugl-Meyer upper extremity scale as an outcome measure; the intervention had ≥3 randomized controlled trials with comparisons against a conventional care group; conventional care groups were dose matched for therapy time. A Bayesian network meta-analysis approach was taken to estimate mean difference (MD) and 95% CI.

Results:

One hundred seventy-six randomized controlled trials containing 6781 participants examining 20 non-conventional interventions were identified for inclusion within the final model. Eight of the identified interventions proved significantly better than conventional care, with modified constraint induced movement therapy (MD, 6.7 [95% CI, 4.3–8.9]), high frequency repetitive transcranial magnetic stimulation (MD, 5.4 [95% CI, 1.9–8.9]), mental imagery (MD, 5.4 [95% CI, 1.8–8.9]), bilateral arm training (MD, 5.2 [95% CI, 2.2–8.1]), and intermittent theta-burst stimulation (MD, 5.1 [95% CI, 0.62–9.5]) occupying the top 5 spots according to the surface under the cumulative ranking curve.

Conclusions:

Overall, it would seem that modified constraint induced movement therapy has the greatest probability of being the most effective intervention, with high-frequency repetitive transcranial magnetic stimulation, mental imagery, and bilateral arm training all having similar probabilities of occupying the next spot in the rankings. We think this analysis can provide a guide for where future resources and clinical trials should be directed, and where a clinician may begin when considering alternative therapeutic interventions.
Taking the Warp for the Weft: Gendered Anger in the Lienüzhuan
Authors: Curry Alba , Raphals Lisa
Published: October 2022

The emotion of anger has received overall negative treatment in recent moral philosophy. This article explores the gendered representations of anger in the Lienüzhuan 《列女傳》 of Liu Xiang 劉向 (77–6 BCE). It begins with a brief account of the semantic field of anger and its representation in the Lienüzhuan, focusing on three important patterns. Perhaps most important is the didactic role of anger; and how female teachers use it (or avoid it) in instructing male sons, husbands and rulers. Second is the treatment of women’s distinct strategies for addressing the effects of being the object of the anger of others. The third is the representation of female anger in accounts of female vice. The representations of anger in the LNZ provides an important alternative to views of anger as motivated by the desire for payback and status. The LNZ, like other pre-Qin texts, understands anger very differently, and focuses on other-regarding anger, based on perceptions of wrongdoing and injustice.
Recovering Ontology in Anglo-American Interpretations of Hermeneutics: Chung-ying Cheng and Hans-Georg Gadamer
Authors: Fuyarchuk Andrew
Published: October 2022

Whereas a selective yet representative sample of Anglo-American scholarship undermines its own intentions to explain Gadamer’s language-ontology and theory of time by confusing the ground of beings with beings, Cheng and Gadamer explain how a transformation in human existence allows for a temporalization of Being in time that incorporates the subjectivity of the human subject. This argument draws on the dual structure of their cosmogenic worldview in the source and origins of their traditions (Lao Zi/Heraclitus) and has implications for Cheng’s organistic model of causality: It depends on mechanical causation to understand things in themselves.
Service and Reciprocity: Confucian Political Authority
Authors: Hong Cheng
Published: October 2022

Confucian political authority is often assumed illegitimate and it is regarded as meritocratic rather than democratic. However, I disagree with such an assumption, because from my perspective, Confucian political authority actually has a potential legitimacy which may contribute to establishing a responsive and harmonious state. Doing so, I argue that, since Confucian political authority is derived from the idea of “service” and “reciprocity,” it therefore advocates non-coercive moral persuasion and reciprocal obligations. In the following discussion, I will point out that certain modern democratic theories on political authority, such as those concerning “general acceptability,” “consent,” “autonomy,” and “paternalism,” are inadequate to refute the legitimacy of Confucian political authority. Accordingly, I will propose that our contemplation over whether Confucian political authority is legitimate or not ought to be furthermore widened and deepened.
ʿAli al-Aʿlā and the Early History of Horufism
Authors: Arslan Hüseyin Ongan
Published: October 2022

This article examines the life and activities of ʿAli al-Aʿlā (d. 1419/822), the principal successor of the founder of Horufism, Fazlollāh Astarābādi (d. 1394/796), and early Horufi history. Widely known as “Khalifatollāh (Vice-gerent of God)” in Horufi literature, the prolific ʿAli al-Aʿlā compiled five Persian books in the first two decades of the fifteenth century, namely the Korsi-nāma, Towhid-nāma, Qeyāmat-nāma, Ferāq-nāma, and Mahshar-nāma. By principally working on ʿAli al-Aʿlā’s corpus, I construct his biography, as well as explore Fazlollāh’s life and his Horufi doctrine. By critically engaging with the modern scholarship on Horufism, I discuss the crisis among Horufis following the execution of Fazlollāh, their political positioning among different political entities in western Asia, e.g., the Timurids and Qara Qoyunlus, and Horufi missionary activities in Syria, Anatolia, and the Ottoman Balkans in the first decades of the fifteenth century. By doing so, I attempt to add another dimension to the existing Horufi literature.