bluuebunny/crossref_metadata_2025 huggingface dataset:
Ferroptosis: Opportunities and Challenges in Treating Endometrial Cancer
Authors: Wu Jianfa , Zhang Li , Wu Suqin , Liu Zhou
Published: July 2022

Ferroptosis, a new way of cell death, is involved in many cancers. A growing number of studies have focused on the unique role of ferroptosis on endometrial cancer. In this study, we made a comprehensive review of the relevant articles published to get deep insights in the association of ferroptosis with endometrial cancer and to present a summary of the roles of different ferroptosis-associated genes. Accordingly, we made an evaluation of the relationships between the ferroptosis-associated genes and TNM stage, tumor grade, histological type, primary therapy outcome, invasion and recurrence of tumor, and accessing the different prognosis molecular typing based on ferroptosis-associated genes. In addition, we presented an introduction of the common drugs, which targeted ferroptosis in endometrial cancer. In so doing, we clarified the opportunities and challenges of ferroptosis activator application in treating endometrial cancer, with a view to provide a novel approach to the disease.
Effects of the CarFreeMe Traumatic Injuries, a Community Mobility Group Intervention, to Increase Community Participation for People With Traumatic Injuries: A Randomized Controlled Trial With Crossover
Authors: George Stacey , Barr Christopher , Berndt Angela , Milte Rachel , Nussio Amy , Adey-Wakeling Zoe , Liddle Jacki
Published: July 2022

Introduction

After traumatic injuries community participation is a common goal, promoting wellbeing and independence. Community mobility and transportation influence an individual's independence in community participation. With the ability to drive safely often compromised after traumatic injuries, the adverse consequences of driving cessation include a loss of identity and reduced participation in chosen activities. In rehabilitation, individualized community mobility intervention is not routinely provided. The primary aim of this trial was to evaluate whether a group-based intervention, the CarFreeMe TI program was more effective than standard intervention, an information sheet of alternative transport, in improving community mobility for people following traumatic injuries. The secondary aim of this study was to evaluate the effect: types of transport used, transport satisfaction, community mobility self-efficacy, quality of life, goal satisfaction and performance, for people following traumatic injuries; and to undertake a preliminary assessment of the potential resource use associated with the intervention, and lessons for implementation.

Design

Prospective, pilot, randomized, blind observer, controlled trial with crossover.

Participants

Twenty individuals with traumatic injuries.

Intervention

Six-week group-based support and education program, the CarFreeMe TI delivered in community settings (intervention) and standard information related to transport options available (control).

Primary Outcome Measures

Community participation using a Global Positioning System device to record the location and number of outings from home.

Secondary Outcome Measures

CarFreeMe TI Transport Questionnaire, Community Mobility Self-efficacy Scale, quality of life measures, Modified Canadian Occupational Performance Measure for goals (importance and satisfaction), participant satisfaction survey results and researcher logs.

Results

Those who received the intervention were more likely to use public transport and transport services and had an improved quality of life, when compared to the control group. The intervention group also reported high levels of improvement in goal performance and satisfaction. Global Positioning System data collection was incomplete, with geolocation data unusable. There was no significant change in number/type of visits away from home.

Conclusions

A group-based community mobility education program promoted modes of active independent transport but did not impact on outings from home. Future research could include passive collection methods using a smartphone to record community participation.

Clinical Trial Registration

https://www.anzctr.org.au/, identifier: ACTRN12616001254482.
Human vs. Machine Learning Based Detection of Facial Weakness Using Video Analysis
Authors: Aldridge Chad M. , McDonald Mark M. , Wruble Mattia , Zhuang Yan , Uribe Omar , McMurry Timothy L. , Lin Iris , Pitchford Haydon , Schneider Brett J. , Dalrymple William A. , Carrera Joseph F. , Chapman Sherita , Worrall Bradford B. , Rohde Gustavo K. , Southerland Andrew M.
Published: July 2022

Background

Current EMS stroke screening tools facilitate early detection and triage, but the tools' accuracy and reliability are limited and highly variable. An automated stroke screening tool could improve stroke outcomes by facilitating more accurate prehospital diagnosis and delivery. We hypothesize that a machine learning algorithm using video analysis can detect common signs of stroke. As a proof-of-concept study, we trained a computer algorithm to detect presence and laterality of facial weakness in publically available videos with comparable accuracy, sensitivity, and specificity to paramedics.

Methods and Results

We curated videos of people with unilateral facial weakness (n = 93) and with a normal smile (n = 96) from publicly available web-based sources. Three board certified vascular neurologists categorized the videos according to the presence or absence of weakness and laterality. Three paramedics independently analyzed each video with a mean accuracy, sensitivity and specificity of 92.6% [95% CI 90.1–94.7%], 87.8% [95% CI 83.9–91.7%] and 99.3% [95% CI 98.2–100%]. Using a 5-fold cross validation scheme, we trained a computer vision algorithm to analyze the same videos producing an accuracy, sensitivity and specificity of 88.9% [95% CI 83.5–93%], 90.3% [95% CI 82.4–95.5%] and 87.5 [95% CI 79.2–93.4%].

Conclusions

These preliminary results suggest that a machine learning algorithm using computer vision analysis can detect unilateral facial weakness in pre-recorded videos with an accuracy and sensitivity comparable to trained paramedics. Further research is warranted to pursue the concept of augmented facial weakness detection and external validation of this algorithm in independent data sets and prospective patient encounters.
Enlarged Perivascular Spaces Are Negatively Associated With Montreal Cognitive Assessment Scores in Older Adults
Authors: Libecap Timothy J. , Zachariou Valentinos , Bauer Christopher E. , Wilcock Donna M. , Jicha Gregory A. , Raslau Flavius D. , Gold Brian T.
Published: July 2022

Emerging evidence suggests that enlarged perivascular spaces (ePVS) may be a clinically significant neuroimaging marker of global cognitive function related to cerebral small vessel disease (cSVD). We tested this possibility by assessing the relationship between ePVS and both a standardized measure of global cognitive function, the Montreal Cognitive Assessment (MoCA), and an established marker of cSVD, white matter hyperintensity volume (WMH) volume. One hundred and eleven community-dwelling older adults (56–86) underwent neuroimaging and MoCA testing. Quantification of region-specific ePVS burden was performed using a previously validated visual rating method and WMH volumes were computed using the standard ADNI pipeline. Separate linear regression models were run with ePVS as a predictor of MoCA scores and whole brain WMH volume. Results indicated a negative association between MoCA scores and both total ePVS counts (P ≤ 0.001) and centrum semiovale ePVS counts (P ≤ 0.001), after controlling for other relevant cSVD variables. Further, WMH volumes were positively associated with total ePVS (P = 0.010), basal ganglia ePVS (P ≤ 0.001), and centrum semiovale ePVS (P = 0.027). Our results suggest that ePVS burden, particularly in the centrum semiovale, may be a clinically significant neuroimaging marker of global cognitive dysfunction related to cSVD.
Alterations in White Matter Fiber Tracts Characterized by Automated Fiber-Tract Quantification and Their Correlations With Cognitive Impairment in Neuromyelitis Optica Spectrum Disorder Patients
Authors: Yan Zichun , Wang Xiaohua , Zhu Qiyuan , Shi Zhuowei , Chen Xiaoya , Han Yongliang , Zheng Qiao , Wei Yiqiu , Wang Jingjie , Li Yongmei
Published: July 2022

Objectives

To investigate whether patients with neuromyelitis optica spectrum disorder (NMOSD) have tract-specific alterations in the white matter (WM) and the correlations between the alterations and cognitive impairment.

Materials and Methods

In total, 40 patients with NMOSD and 20 healthy controls (HCs) who underwent diffusion tensor imaging (DTI) scan and neuropsychological scale assessments were enrolled. Automated fiber-tract quantification (AFQ) was applied to identify and quantify 100 equally spaced nodes of 18 specific WM fiber tracts for each participant. Then the group comparisons in DTI metrics and correlations between different DTI metrics and neuropsychological scales were performed.

Results

Regardless of the entire or pointwise level in WM fiber tracts, patients with NMOSD exhibited a decreased fractional anisotropy (FA) in the left inferior fronto-occipital fasciculus (L_IFOF) and widespread increased mean diffusion (MD), axial diffusivity (AD), and radial diffusivity (RD), especially for the thalamic radiation (TR), corticospinal tract (CST), IFOF, inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF) [p < 0.05, false discovery rate (FDR) correction], and the pointwise analyses performed more sensitive. Furthermore, the negative correlations among MD, AD, RD, and symbol digit modalities test (SDMT) scores in the left TR (L_TR) were found in NMOSD.

Conclusion

Patients with NMOSD exhibited the specific nodes of WM fiber tract damage, which can enhance our understanding of WM microstructural abnormalities in NMOSD. In addition, the altered DTI metrics were correlated with cognitive impairment, which can be used as imaging markers for the early identification of NMOSD cognitive impairment.
Schizophrenia Hypothesis: Autonomic Nervous System Dysregulation of Fetal and Adult Immune Tolerance
Authors: Carnac Tamara
Published: July 2022

The autonomic nervous system can control immune cell activation via both sympathetic adrenergic and parasympathetic cholinergic nerve release of norepinephrine and acetylcholine. The hypothesis put forward in this paper suggests that autonomic nervous system dysfunction leads to dysregulation of immune tolerance mechanisms in brain-resident and peripheral immune cells leading to excessive production of pro-inflammatory cytokines such as Tumor Necrosis Factor alpha (TNF-α). Inactivation of Glycogen Synthase Kinase-3β (GSK3β) is a process that takes place in macrophages and microglia when a toll-like receptor 4 (TLR4) ligand binds to the TLR4 receptor. When Damage-Associated Molecular Patterns (DAMPS) and Pathogen-Associated Molecular Patterns (PAMPS) bind to TLR4s, the phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) pathway should be activated, leading to inactivation of GSK3β. This switches the macrophage from producing pro-inflammatory cytokines to anti-inflammatory cytokines. Acetylcholine activation of the α7 subunit of the nicotinic acetylcholine receptor (α7 nAChR) on the cell surface of immune cells leads to PI3K/Akt pathway activation and can control immune cell polarization. Dysregulation of this pathway due to dysfunction of the prenatal autonomic nervous system could lead to impaired fetal immune tolerance mechanisms and a greater vulnerability to Maternal Immune Activation (MIA) resulting in neurodevelopmental abnormalities. It could also lead to the adult schizophrenia patient’s immune system being more vulnerable to chronic stress-induced DAMP release. If a schizophrenia patient experiences chronic stress, an increased production of pro-inflammatory cytokines such as TNF-α could cause significant damage. TNF-α could increase the permeability of the intestinal and blood brain barrier, resulting in lipopolysaccharide (LPS) and TNF-α translocation to the brain and consequent increases in glutamate release. MIA has been found to reduce Glutamic Acid Decarboxylase mRNA expression, resulting in reduced Gamma-aminobutyric acid (GABA) synthesis, which combined with an increase of glutamate release could result in an imbalance of glutamate and GABA neurotransmitters. Schizophrenia could be a “two-hit” illness comprised of a genetic “hit” of autonomic nervous system dysfunction and an environmental hit of MIA. This combination of factors could lead to neurotransmitter imbalance and the development of psychotic symptoms.
Gaz Alafi: A Traditional Dessert in the Middle East With Anticancer, Immunomodulatory, and Antimicrobial Activities
Authors: Al Safi Meena A. , Rashid Hasan M. , Afifi Fatma U. , Talib Wamidh H.
Published: July 2022

Background

From the earliest times, manna has been widely used as a tasty local sweet or folk medicine. The type of manna being investigated in the present study is called Gaz-alafi, a mixture of insect and Quercus brantii leaves secretions from oak forests in the north of Iraq and west of Iran.

Methods

Aqueous and ethanol extracts were prepared as decoction. Various phytochemical tests were conducted to analyze manna composition, including total phenolic contents using the Folin-Ciocalteu method and LC-MS. Gallic acid and catechin were detected in both extracts, in addition to tiliroside presence in ethanol extract, which added more value to the phenolic content of ethanol extract. Cytotoxic activities of Gaz alafi were evaluated against breast cancer cell lines and compared to normal cell lines and doxorubicin using the MTT assay. Antimicrobial properties were assessed against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, and Candida albicans using the dilution method of the micro-titer plate. Serum levels of IFN-γ, interleukin-2 (IL-2), interleukin-4 (IL-4), and interleukin-10 (IL-10) were measured using ELISA. The effect of extracts on splenocyte proliferation was evaluated using the lymphocytes proliferation assay. Macrophage function was evaluated using the nitro blue tetrazolium assay, whereas pinocytosis was evaluated using the neutral red uptake assay. Ten days after tumor inoculation, changes in tumor size, survival rates, levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine were measured.

Results

The growth of cancer cells was inhibited by Gaz alafi ethanol extract. An alteration in IFN- γ, IL-2, and IL-4 levels toward antiproliferation immune response were reported for both extracts. The aqueous extract efficiently stimulated lymphocyte proliferation, phagocytosis, and pinocytosis, followed by the ethanol extracts with moderate activity. After treating the mice with ethanol extracts, a significant reduction in tumor size and several undetected tumors were recorded.

Conclusions

Gaz alafi extracts (aqueous and ethanol) are promising sources for anticancer and immunostimulatory agents. Further studies are needed to fully identify the chemical composition of Gaz alafi extracts.
Case Report: A Case of Locally Advanced Pancreatic Cancer Which Achieved Progression Free for Over 12 Months by Subsequent Therapy with Anlotinib Hydrochloride Plus Tegafur-Gimeracil-Oteracil Potassium (TS-1)
Authors: Luo Dongcheng , Liao Sina , Li Qian , Lin Youzhi , Wei Junbao , Li Yongqiang , Liao Xiaoli
Published: July 2022

Titled the “most destructive of all cancers”, pancreatic cancer is a malignant tumor with a very poor prognosis and has a poor response to systemic therapy. At present, several studies have shown that tegafur-gimeracil-oteracil potassium (hereinafter referred to as TS-1) is no less superior to gemcitabine in the treatment of advanced pancreatic cancer. In addition, a number of current clinical studies have shown that targeted therapy combined with chemotherapy reflects therapeutic advantages in pancreatic cancer. Moreover, in vitro and in vivo experiments have also demonstrated that anlotinib can curb the proliferation of pancreatic cancer cells and induce their apoptosis. Here, we report for the first time that a patient with locally advanced pancreatic cancer achieved good efficacy after switching to TS-1 chemotherapy combined with anlotinib targeted therapy. Previously, the disease of the patient still rapidly progressed without control following the first switch to abraxane combined with gemcitabine chemotherapy (AG regimen) due to the progression after chemo-radiotherapy. In this case, the patient achieved progression-free survival (PFS) of over 14 months via the treatment with anlotinib targeted therapy combined with TS-1 chemotherapy and secondary radiotherapy (prior to secondary radiotherapy, the patient achieved a PFS of nearly 12 months via the treatment with oral anlotinib combined with TS-1). Up to now, the progress of the disease is ceased. The oral administration of targeted therapy and chemotherapy are still in progress and the general condition of the patient is good. This suggests that patients with advanced pancreatic cancer may benefit from treatment with the anlotinib targeted therapy combined with TS-1 chemotherapy.
IDO Inhibitor and Gallic Acid Cross-Linked Small Molecule Drug Synergistic Treatment of Melanoma
Authors: Liu Hongmei , Gao Huan , Chen Cheng , Jia Wenyu , Xu Delong , Jiang Guan
Published: July 2022

In this study, we synthesized a molecule GA-1MT (GM) composed of indoleamine 2,3-dioxygenase (IDO) inhibitor (1-methyl-d-tryptophan, 1MT) called NLG8189 and gallic acid (GA) and verified its therapeutic effect on B16F10 melanoma cells and an orthotopic tumor-bearing mouse model. The synthesized molecule GM was analyzed by 1H NMR and mass spectrometry (MS). In addition, we confirmed that GM could mediate the immune response in the B16F10 cell tumor model by flow cytometry and immunofluorescence. The synthesized GM molecule could increase the solubility of 1MT to enhance the drug efficacy and lower costs. Moreover, GM could inhibit melanoma growth by combining 1MT and GA. In vivo experiments showed that GM could effectively inhibit the expression of tyrosinase, regulate the proportion of CD4+ T cells, CD8+ T cells, and regulatory T cells (Treg cells) in tumors, and significantly suppress melanoma growth. The newly synthesized drug GM could more effectively inhibit melanoma than GA and 1MT alone or in combination.
A Systematic Review and Meta-Analysis of Prognostic Nomograms After UTUC Surgery
Authors: Pallauf Maximilian , König Frederik , D’Andrea David , Laukhtina Ekaterina , Mostafaei Hadi , Motlagh Reza Sari , Quhal Fahad , Aydh Abdulmajeed , Yanagisawa Takafumi , Kawada Tatsushi , Rajwa Pawel , Lusuardi Lukas , Soria Francesco , Karakiewicz Pierre I. , Rouprêt Morgan , Rink Michael , Lotan Yair , Margulis Vitaly , Singla Nirmish , Xylinas Evanguelos , Shariat Shahrokh F. , Pradere Benjamin
Published: July 2022

Background

Current guidelines recommend assessing the prognosis in high-risk upper tract urothelial carcinoma patients (UTUC) after surgery. However, no specific method is endorsed. Among the various prognostic models, nomograms represent an easy and accurate tool to predict the individual probability for a specific event. Therefore, identifying the best-suited nomogram for each setting seems of great interest to the patient and provider.

Objectives

To identify, summarize and compare postoperative UTUC nomograms predicting oncologic outcomes. To estimate the overall performance of the nomograms and identify the most reliable predictors. To create a reference tool for postoperative UTUC nomograms, physicians can use in clinical practice.

Design

A systematic review was conducted following the recommendations of Cochrane’s Prognosis Methods Group. Medline and EMBASE databases were searched for studies published before December 2021. Nomograms were grouped according to outcome measurements, the purpose of use, and inclusion and exclusion criteria. Random-effects meta-analyses were performed to estimate nomogram group performance and predictor reliability. Reference tables summarizing the nomograms’ important characteristics were created.

Results

The systematic review identified 26 nomograms. Only four were externally validated. Study heterogeneity was significant, and the overall Risk of Bias (RoB) was high. Nomogram groups predicting overall survival (OS), recurrence-free survival (RFS), and intravesical recurrence (IVR) had moderate discrimination accuracy (c-Index summary estimate with 95% confidence interval [95% CI] and prediction interval [PI] > 0.6). Nomogram groups predicting cancer-specific survival (CSS) had good discrimination accuracy (c-Index summary estimate with 95% CI and PI > 0.7). Advanced pathological tumor stage (≥ pT3) was the most reliable predictor of OS. Pathological tumor stage (≥ pT2), age, and lymphovascular invasion (LVI) were the most reliable predictors of CSS. LVI was the most reliable predictor of RFS.

Conclusions

Despite a moderate to good discrimination accuracy, severe heterogeneity discourages the uninformed use of postoperative prognostic UTUC nomograms. For nomograms to become of value in a generalizable population, future research must invest in external validation and assessment of clinical utility. Meanwhile, this systematic review serves as a reference tool for physicians choosing nomograms based on individual needs.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=282596, identifier PROSPERO [CRD42021282596].
Comprehensive Analysis of Regulatory Networks of m6A Regulators and Reveals Prognosis Biomarkers in Sarcoma
Authors: Pang Boran , Luo Dinghao , Cao Bojun , Wu Wen , Wang Lei , Hao Yongqiang
Published: July 2022

Sarcomas are rare malignant tumors that may arise from anywhere of the body, such as bone, adipose, muscle and vascular. However, the conventional pathogenesis of sarcomas has not been found. Therefore, there is an urgent need to identify novel therapeutic strategies and improve prognosis effects for sarcomas. Methylation of N6 adenosine (m6A) regulation is a novel proposed regulatory pattern that works in post-transcription level, which was also the most widely distributed methylation modification in eukaryotic mRNA. Growing evidences have demonstrated that m6A modification played an indispensable role in tumorigenesis. Here, we integrated multi-omics data including genetic alterations, gene expression and epigenomics regulation to systematically analysis the regulatory atlas of 21 m6A regulators in sarcoma. Firstly, we investigated the genetic alterations of m6A regulators and found that ~44% TCGA sarcoma patients have genetic mutations. We also investigated the basic annotation of 21 regulators, such as expression correlation and PPI interactions. Then we identified the upstream and downstream regulatory networks of between transcription factors (TFs)/non-coding RNAs and m6A regulators in sarcoma based on motif analysis and gene expression. These results implied that m6A regulator mediated regulatory axes could be used as prognostic biomarkers in sarcoma. Knockdown experiment results revealed that m6A regulators, YTHDF2 and HNRNPA2B1 participated in the cancer cell invasion and metastasis. Moreover, we also found that the expression levels of m6A regulators were related to immune cell infiltration of sarcoma patients.
Three-Dimensional Arterial Spin Labeling-Guided Sub-Volume Segmentation of Radiotherapy in Adult Non-Enhancing Low-Grade Gliomas
Authors: Zhu Zihong , Gong Guanzhong , Wang Lizhen , Su Ya , Lu Jie , Yin Yong
Published: July 2022

Objective

The present study aimed to evaluate the feasibility of sub-volume segmentation for radiotherapy planning of adult non-enhancing low-grade gliomas (NE-LGGs) guided by three-dimensional arterial spin labeling (3D-ASL). The differences in high- and low-perfusion areas of NE-LGGs were analyzed using multi-sequence magnetic resonance imaging (MRI) radiomics.

Methods

Fifteen adult patients with NE-LGGs were included in the study. MR images, including T1-weighted imaging (T1WI), T2 Propeller, T2 fluid-attenuated inversion recovery (T2 Flair), 3D-ASL, and contrast-enhanced T1WI (CE-T1WI), were obtained. The gross tumor volume (GTV) was delineated according to the hyperintensity on T2 Flair. The GTV was divided into high- and low-perfusion areas, namely GTV-ASL and GTV-SUB, respectively, based on the differences in cerebral blood flow (CBF) value. The volumes and CBF values of high- and low-perfusion areas were measured and compared. The least absolute shrinkage and selection operator (LASSO) regression was used to select the optimal features of all MR maps. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic accuracy of the absolute CBFmean (aCBFmean), relative CBFmean (rCBFmean, normalized by the CBF value of the normal gray matter), and screened features in differentiating high- and low-perfusion areas.

Results

Among the enrolled patients, three (20%) patients with NE-LGGs showed focal intra- and post-radiotherapy contrast enhancement within a prior high-perfusion area of 3D-ASL. The volume ratio of the GTV-ASL to the GTV was (37.08% ± 17.88)% (46.26 ± 44.51 vs. 167.46 ± 209.64 cm3, P = 0.000). The CBFmean in the high-perfusion area was approximately two times of that in the edema area or normal gray matter (66.98 ± 18.03 vs. 35.19 ± 7.75 or 33.92 ± 8.48 ml/100g/min, P = 0.000). Thirteen features were screened, seven of which were extracted from 3D-ASL. The area undercurve (AUC) values of aCBFmean, rCBFmean, and firstorder_10Percentile from 3D-ASL were more than 0.9, of which firstorder_10Percentile was the highest. Their cut-off values were 44.16 ml/100 g/min, 1.49 and 31, respectively.

Conclusion

The difference in blood perfusion in the GTV can be quantified and analyzed based on 3D-ASL images for NE-LGGs, which could guide the sub-volume segmentation of the GTV. 3D-ASL should become a routine method for NE-LGGs during simulation and radiotherapy.
Acute Pancreatitis in Jordanian Children: A Single Center Experience
Authors: Al Droubi Belal , Altamimi Eyad
Published: July 2022

Background

There is still much to understand and discover regarding pediatric pancreatitis. The etiology, clinical presentation, and prognosis of pancreatitis differs considerably between young children and adults. The incidence of pancreatitis has been increasing; it is no longer as rare in children as previously thought and could cause significant morbidity and mortality when severe.

Methods

In this retrospective study conducted at a tertiary care hospital in Jordan, we present a cohort of children with 64 episodes of acute pancreatitis.

Results

While abdominal pain was the most common presenting complaint in our cohort (97%), the classical features of radiation to the back and relief by the forward-lean position were observed in only one-third of our patients. Compared to serum amylase, serum lipase had a higher sensitivity for detecting pancreatitis (98 vs. 67%). Abdominal ultrasound is a non-invasive, widely available imaging modality; when performed, it revealed an enlarged pancreas in almost 60% of the patients. However, abdominal ultrasonography is often limited by the presence of excessive bowel gas. Anatomical abnormalities were the most common etiologies of pancreatitis (29%), followed by idiopathic pancreatitis (21%), and biliary causes (21%).

Conclusion

In our cohort, serum lipase was a better diagnostic tool compared to serum amylase. Congenital biliary-pancreatic abnormalities were the most common causes of acute pancreatitis in our cohort. Almost half of these patients developed recurrent acute pancreatitis. The prevalence of pancreatic pseudocysts was 16.7%, and nearly half of them required an intervention.
Risk of Fracture With Dipeptidyl Peptidase-4 Inhibitors, Glucagon-like Peptide-1 Receptor Agonists, or Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Network Meta-analysis Combining 177 Randomized Controlled Trials With a Median Follow-Up of 26 weeks
Authors: Chai Sanbao , Liu Fengqi , Yang Zhirong , Yu Shuqing , Liu Zuoxiang , Yang Qingqing , Sun Feng
Published: July 2022

Aim: This study aims to investigate the association between the use of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), or sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and the risk of fracture among patients with type 2 diabetes mellitus.

Methods: Medline, Embase, Cochrane Library, and Clinical-Trials.gov databases were searched for randomized controlled trials (RCTs). Network meta-analysis was performed for total fracture and a series of secondary outcomes.

Results: A total of 177 RCTs (n = 165,081) involving the risk of fracture were identified (a median follow-up of 26 weeks). DPP-4i, GLP-1 RAs, and SGLT-2i did not increase total fracture risk compared with insulin (odds ratio: 0.86, 95% confidence interval: 0.39–1.90; 1.05, 0.54–2.04; 0.88, and 0.39–1.97, respectively), metformin (1.41, 0.48–4.19; 1.72, 0.55–5.38; 1.44, 0.48–4.30), sulfonylureas (0.77, 0.50–1.20; 0.94, 0.55–1.62; 0.79, 0.48–1.31), thiazolidinediones (0.82, 0.27–2.44; 1.00, 0.32–3.10; 0.83, 0.27–2.57), α-glucosidase inhibitor (4.92, 0.23–103.83; 5.99, 0.28–130.37; 5.01, 0.23–107.48), and placebo (1.04, 0.84–1.29; 1.27, 0.88–1.83; 1.06, 0.81–1.39).

Conclusions: The use of DPP-4i, GLP-1 RAs, or SGLT-2i is unlikely to increase the risk of fracture among type 2 diabetes mellitus patients.
Identification of Selective CYP3A7 and CYP3A4 Substrates and Inhibitors Using a High-Throughput Screening Platform
Authors: Kabir Md , Padilha Elias C. , Shah Pranav , Huang Ruili , Sakamuru Srilatha , Gonzalez Eric , Ye Lin , Hu Xin , Henderson Mark J. , Xia Menghang , Xu Xin
Published: July 2022

Cytochrome P450 (CYP) 3A7 is one of the major xenobiotic metabolizing enzymes in human embryonic, fetal, and newborn liver. CYP3A7 expression has also been observed in a subset of the adult population, including pregnant women, as well as in various cancer patients. The characterization of CYP3A7 is not as extensive as other CYPs, and health authorities have yet to provide guidance towards DDI assessment. To identify potential CYP3A7-specific molecules, we used a P450-Glo CYP3A7 enzyme assay to screen a library of ∼5,000 compounds, including FDA-approved drugs and drug-like molecules, and compared these screening data with that from a P450-Glo CYP3A4 assay. Additionally, a subset of 1,000 randomly selected compounds were tested in a metabolic stability assay. By combining the data from the qHTS P450-Glo and metabolic stability assays, we identified several chemical features important for CYP3A7 selectivity. Halometasone was chosen for further evaluation as a potential CYP3A7-selective inhibitor using molecular docking. From the metabolic stability assay, we identified twenty-two CYP3A7-selective substrates over CYP3A4 in supersome setting. Our data shows that CYP3A7 has ligand promiscuity, much like CYP3A4. Furthermore, we have established a large, high-quality dataset that can be used in predictive modeling for future drug metabolism and interaction studies.
Application Perspectives of Nanomedicine in Cancer Treatment
Authors: Hou Shanshan , Hasnat Muhammad , Chen Ziwei , Liu Yinong , Faran Ashraf Baig Mirza Muhammad , Liu Fuhe , Chen Zelong
Published: July 2022

Cancer is a disease that seriously threatens human health. Based on the improvement of traditional treatment methods and the development of new treatment modes, the pattern of cancer treatment is constantly being optimized. Nanomedicine plays an important role in these evolving tumor treatment modalities. In this article, we outline the applications of nanomedicine in three important tumor-related fields: chemotherapy, gene therapy, and immunotherapy. According to the current common problems, such as poor targeting of first-line chemotherapy drugs, easy destruction of nucleic acid drugs, and common immune-related adverse events in immunotherapy, we discuss how nanomedicine can be combined with these treatment modalities, provide typical examples, and summarize the advantages brought by the application of nanomedicine.
Structural Modification in Anesthetic Drug Development for Prodrugs and Soft Drugs
Authors: Deng Chaoyi , Liu Jin , Zhang Wensheng
Published: July 2022

Among the advancements in drug structural modifications, the increased focus on drug metabolic and pharmacokinetic properties in the anesthetic drug design process has led to significant developments. Drug metabolism also plays a key role in optimizing the pharmacokinetics, pharmacodynamics, and safety of drug molecules. Thus, in the field of anesthesiology, the applications of pharmacokinetic strategies are discussed in the context of sedatives, analgesics, and muscle relaxants. In this review, we summarize two approaches for structural optimization to develop anesthetic drugs, by designing prodrugs and soft drugs. Drugs that both failed and succeeded during the developmental stage are highlighted to illustrate how drug metabolism and pharmacokinetic optimization strategies may help improve their physical and chemical properties.
Light and Scanning Electron Microscopy of Red Blood Cells From Humans and Animal Species Providing Insights into Molecular Cell Biology
Authors: Benga Gheorghe , Cox Guy
Published: July 2022

We reviewed the many discoveries in cell biology, made since the 17th century, which have been based on red blood cells (RBCs). The advances in molecular and structural biology in the past 40 years have enabled the discovery with these cells, most notably, of the first water channel protein (WCP) called today aquaporin1 (AQP1). The main aim of our work reviewed was to examine by light and electron microscopy a very wide range of RBCs from reptiles, birds, monotremes, marsupials and placentals, in order to estimate from these images the RBC cell volume and surface area. The diffusional water permeability of the RBC membrane from these species has further been measured with a nuclear magnetic resonance (NMR) spectroscopy technique. The significance of the observed permeability of RBCs to water and possible influences on the whole body are discussed.
Estimating Nitrogen Use Efficiency, Profitability, and Greenhouse Gas Emission Using Different Methods of Fertilization
Authors: Nasrullah Muhammad , Liang Lizhi , Rizwanullah Muhammad , Yu Xiuyuan , Majrashi Ali , Alharby Hesham F. , Alharbi Basmah M. , Fahad Shah
Published: July 2022

Fertilization is a way to better use nitrogen fertilizers and increase productivity, but in another way, fertilization is also a source of anthropogenic greenhouse gas emissions. The study was carried out to measure the profitability ratio, technical efficiency, and CO2 from the top dressing (TD) and deep placement (DP) fertilization. The study was based on primary data, which were collected from different respondents and areas through a well-designed questionnaire. The study finds that DP fertilization is more profitable, least costly, and more efficient than TD fertilization. The finding observed that the yield of the TD growers is 727.82 kg/ha more than that of TD respondents. The efficiency score shows that to reach the 90% efficiency level, the farmers of TD need to use DP fertilization. The farmers of TD and DP can still increase their efficiency up to 12% and 9% by using the same inputs. The findings also clarify that manufacturing of synthetic nitrogen (N), direct use of N, Yield, and Area-Scaled greenhouse gas (GHG) emissions from the use of synthetic N through TD fertilization are greater than that of the DP group. The farming community needs to be aware of greenhouse gas emissions and how they can be reduced. It is also suggested that farmers need to shift toward DP fertilization to increase yield, profit, efficiency, food security, and reduce GHG emissions.
Transcription Factor DOF4.1 Regulates Seed Longevity in Arabidopsis via Seed Permeability and Modulation of Seed Storage Protein Accumulation
Authors: Niñoles Regina , Ruiz-Pastor Carmen Maria , Arjona-Mudarra Paloma , Casañ Jose , Renard Joan , Bueso Eduardo , Mateos Ruben , Serrano Ramón , Gadea Jose
Published: July 2022

Seed longevity is modulated by multiple genetic factors in Arabidopsis thaliana. A previous genome-wide association study using the Elevated Partial Pressure of Oxygen (EPPO) aging assay pinpointed a genetic locus associated with this trait. Reverse genetics identified the transcription factor DOF4.1 as a novel seed longevity factor. dof4.1 loss-of-function plants generate seeds exhibiting higher germination after accelerated aging assays. DOF4.1 is expressed during seed development and RNAseq data show several putative factors that could contribute to the dof4.1 seed longevity phenotype. dof4.1 has reduced seed permeability and a higher levels of seed storage proteins mRNAs (cruciferins and napins) in developing seeds, as compared to wild-type seeds. It has been reported that mutant lines defective in cruciferins or napins present reduced seed longevity. The improved longevity of dof4.1 is totally lost in the quadruple mutant dof4.1 cra crb crc, but not in a dof4.1 line depleted of napins, suggesting a prominent role for cruciferins in this process. Moreover, a negative regulation of DOF4.1 expression by the transcription factor DOF1.8 is suggested by co-inoculation assays in Nicotiana benthamiana. Indeed, DOF1.8 expression anticorrelates with that of DOF4.1 during seed development. In summary, modulation of DOF4.1 levels during seed development contributes to regulate seed longevity.
Surprisingness and Occupational Engagement Influence Affective Forecasting in Career-Relevant Contexts
Authors: Lu Di , Jiao Runkai , Li Feifei , Lin Xiaoqing , Yin Hang
Published: July 2022

People tend to misestimate their future emotions. This phenomenon is thought to be associated with information accessibility. However, few studies have demonstrated the impact of context-specific information accessibility on affective forecasting. This research investigated the effects of information accessibility on affective forecasting in career context (i.e., occupational engagement was seen as information accessibility), during which surprise or not surprise context was played simultaneously. We found that affective forecasting appeared stably across emotional response types. Specifically, there was an underestimation in interest appraisals and an overestimation in satisfaction. These biases were influenced by occupational engagement, which only worked in career interest appraisals. High occupational engagement made people estimate their future emotions more accurately and overcome their forecasting bias. Surprisingness was then manipulated further to explain whether it could impact the effect of occupational engagement on affective forecasting. The emotional responses in both prediction and experience were affected by surprisingness, thus causing no affective forecasting biases. These results suggest the role of occupational engagement in affective forecasting and provide evidence supporting the information accessibility model about the mechanism in affective forecasting.
Feeling Ostracized by Others’ Smartphone Use: The Effect of Phubbing on Fundamental Needs, Mood, and Trust
Authors: Knausenberger Judith , Giesen-Leuchter Anna , Echterhoff Gerald
Published: July 2022

With phubbing (i.e., “The act of snubbing someone… by looking at your phone instead of paying attention”) being a widespread phenomenon, a sound understanding of its emotional reverberations and consequences for interpersonal relationships is required. To the extent that phubbing is perceived as a momentary act of ostracism, it should influence both emotional and behavioral reactions. To address this issue empirically, we investigated effects of phubbing on variables previously shown to be affected by ostracism. Specifically, we examined in two studies how being phubbed affects participants’ mood, satisfaction of fundamental needs, feelings of being ostracized (Study 1 and 2) and trust (Study 2). In Study 1, participants remembered a situation in which they were either phubbed, phubbed someone else or experienced an attentive conversation. In Study 2 different phubbing behaviors were manipulated during an ongoing conversation. Results from both studies suggest that phubbing triggers negative mood and feelings of ostracism, and threatens fundamental needs. Study 2 revealed that these effects were stronger when phubbing occurred three times (vs. once). Study 2 further demonstrated behavioral consequences of phubbing, namely that trust in a trust game was reduced when participants were phubbed three times (vs. once). We discuss conceptual and practical implications of smartphone use for emotion regulation and interpersonal relations.
Authentic Leadership and Employee Resilience: A Moderated Mediation Analysis
Authors: Mao Yanhui , Lai Yao , Zhai Yuxi , Xie Mei , Yu Junkai , Wang Qiutong , Lu Shaokai , Ma Jianhong , Bonaiuto Marino
Published: July 2022

Authentic leadership is essential for predicting employee resilience. However, despite fruitful findings, more adapted models of authentic leadership – employee resilience based on empirical findings can serve as a guide to understand the complex mediators and moderators in different industries such as in construction engineering project organizations during the turbulent pandemic. This study, therefore, based on the organizational identification theory and flow theory through the lens of positive organizational psychology, aims to disentangle the authentic leadership—employee resilience association by investigating their underlying mechanism and their boundary condition. To test our hypothetical model, we applied a cross-sectional design with data collected from a large sample of 884 employees from a big enterprise in China. Findings from confirmatory factor analysis, structural equation modeling analysis, and Hayes’s conditional process model indicated that: authentic leadership positively predicted employee resilience through the partial mediation effect of organizational identification, and such a mediation model was moderated by the experience of flow. In other words, flow moderated the relationships between authentic leadership, organizational identification, and employee resilience. Findings provide evidence for cultivating leaders’ authenticity in promoting their subordinates’ resilience; findings also highlight the significance of organizational identification in bridging authentic leadership and employee resilience and the essential role of flow experience in supporting the relationships mentioned above.
Role of Resistance to Innovation, Lack of Intercultural Communication, and Student Interest on the Student Demotivation Results Towards the English Education System
Authors: Wang Jin , Pan Lei
Published: July 2022

Recently, second-language learning success depends upon the students' interest and motivation by adopting innovations that require regulators' and new researchers' emphasis. Hence, this article explores the role of resistance to innovation, lack of intercultural communication, and students' interest on the students' demotivation. The article also examines the mediating role of students' demotivation among resistance to innovation, lack of intercultural communication, lack of students' interest, and failure of the English education system in China. This study has gathered the data using survey questionnaires and analyzed the collected data using smart-PLS. The results exposed that the resistance to innovation, lack of intercultural communication, and students' interest have a significant and positive linkage with students' demotivation. The findings also indicated that students' demotivation significantly mediates among resistance to innovation, lack of intercultural communication, lack of students' interest, and failure of the English education system in China. This study guides the policymakers to develop the policies related to improving the English education system in China using innovation that enhances students' interest and motivation.

JEL Classifications

O31, O32, H75.
Effect of Peer Attachment on Legal Emotion Among Junior Middle School Students: The Mediation Role of Self-Esteem
Authors: Xu Shuhui , Fan Lu , Su Chunjing
Published: July 2022

Legal consciousness is the individual consciousness which reflects legal phenomena. Well-developed legal consciousness plays a crucial role in informing citizens of his legal right and ability to exercise these rights, therefore forms certain connections of individuals and society, and its development is a key part of individual’s socialization process. Here, we investigated the emotion aspect of legal consciousness (henceforth legal emotion) and tried to identify several factors affecting the development of legal emotion and several factors affected by legal emotion. A large sample of Chinese junior middle school students (N = 967) completed a battery of self-reported questionnaires regarding legal emotion, peer attachment, self-esteem, prosocial tendencies, and interpersonal trust. The results indicated that for early adolescents, peer attachment predicts both positive and negative legal emotion. Importantly, peer attachment affects legal emotion partially through self-esteem. We also showed that negative legal emotion acted as a mediator on the relationship between interpersonal trust and prosocial tendencies. The results provided important insights into the role of legal emotion, the emotion aspect of legal consciousness, in the social interactions and its potential psychological mechanism.
Effects of Teacher Engagement on Students’ Achievement in an Online English as a Foreign Language Classroom: The Mediating Role of Autonomous Motivation and Positive Emotions
Authors: Wang Jianhua , Zhang Xi , Zhang Lawrence Jun
Published: July 2022

As an important factor promoting students’ learning behavior and achievement, teacher engagement has been largely neglected in the research literature on English as a foreign language (EFL) and applied linguistics. Moreover, the few studies have focused more on conventional classrooms rather than online learning contexts and failed to reveal how teacher engagement in the online foreign language classroom affected students’ achievement. The present study assessed 546 university students in China using self-report questionnaires to examine the relationship between teacher engagement and students’ achievement in an online EFL course over an 18-week semester, taking into account the possible mediating effects of autonomous motivation and positive academic emotions. The results showed that teacher engagement exerted a direct and positive impact on students’ English achievement. Students’ autonomous motivation and enjoyment mediated the association between teacher engagement and English achievement, but the mediating effects of relief were not significant. Additionally, teacher engagement affected students’ English achievement through the chain mediation of autonomous motivation and positive academic emotions (enjoyment and relief). Relief displayed a smaller effect on students’ English achievement than enjoyment did. These findings elucidate the impact of teacher engagement on students’ English achievement in the online environment and support the utility of self-determination theory and control-value theory in explaining foreign language learning. Directions for future research and implications for education are also presented.