bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical outcomes and prognostic factors of patients with sepsis caused by intra-abdominal infection in the intensive care unit: A post-hoc analysis of a prospective cohort study in Korea
Authors: Park Chan Hee , Lee Jeong Woo , Lee Hak Jae , Oh Dong Kyu , Park Mi Hyeon , Lim Chae-Man , Hong Suk Kyung
Published: August 2022

Background: Sepsis is the most common cause of death in hospitals, and intra-abdominal infection (IAI) accounts for a large portion of the causes of sepsis. We investigated the clinical outcomes and factors influencing mortality of patients with sepsis due to IAI.Methods: This post-hoc analysis of a prospective cohort study included 2,126 patients with sepsis who visited 16 tertiary care hospitals in Korea (September 2019–February 2020). The analysis included 219 patients aged > 19 years who were admitted to intensive care units owing to sepsis caused by IAI.Results: The incidence of septic shock was 47% and was significantly higher in the non-survivor group (58.7% vs 42.3%, p=0.028). The overall 28-day mortality was 28.8%. In multivariate logistic regression, after adjusting for age, sex, Charlson comorbidity index, and lactic acid, only coagulatory dysfunction (p=0.001, odds ratio: 2.78 [1.47­–5.23]) was independently associated, and after adjusting for each risk factor, only simplified acute physiology score III (p=0.014) and continuous renal replacement therapy (p<0.001) were independently associated with higher 28-day mortality.Conclusions: Considering the independent risk factors influencing 28-day mortality, more intensive care may be needed for patients with coagulopathy than for patients with other organ dysfunctions caused by IAI.
A novel prognostic model for cervical cancer patients with lymph node metastases: based on SEER database and an independent cohort
Authors: Liu Xueting , Wang Le , Song Jiayu , Liu Sijia , Yan Jiazhuo , Yang Shanshan , Zhang Yunyan
Published: August 2022

Introduction:
Cervical cancer with lymph node metastasis (LNM) has a poor prognosis, but the prognosis of patients varies among individuals to a great extent and depends on diverse factors. This study attempted to develop and externally validate a prognostic model based on risk factors to predict the probability of survival of patients with cervical cancer with LNM.
Methods
A population-based cohort with 4238 participants diagnosed with cervical cancer with LNM between 2000 and 2016 from the Surveillance, Epidemiology, and End Results database was used to select prognostic variables for inclusion in our model. Model performance was validated internally and externally using the concordance index (C-index), areas under the curve (AUC) of receiver operating characteristic (ROC) curves, calibration curves, and decision curve analyses (DCA). Kaplan–Meier survival curve was used to validate the risk stratification capability of the established model.
Results
Prognostic factors included marital status, age, pathological subtype, clinical stage, tumor size, surgical treatment, radiotherapy, and chemotherapy (all P < .05). The C-index (0.736, 0.727, and 0.701 for the training, internal validation, and external validation cohorts) and AUC values of the 3- and 5-year ROC curves (0.781 and 0.777 for the training cohort, 0.78 and 0.759 for the internal validation cohort, and 0.728 and 0.74 for the external validation cohort) demonstrated the satisfactory discrimination and excellent accuracy of the nomogram. Calibration plots showed the favorable agreement between the predicted and observed probabilities, and DCA indicated good clinical benefits. The nomogram-based risk stratification successfully discriminated patients into low-, intermediate-, and high-risk populations.
Conclusion
An easy-to-use online website of the dynamic nomogram was provided which could help predict overall survival of cervical cancer with LNM.
Preparation of Simulated Naturally-Derived Nanoplastics from Polypropylene-Food Packaging Material as Standard Substance
Authors: Wang Zhongtang , Gao Xianlei , Lu Xin , Zhang Hongyan , Jia Zhenzhen
Published: August 2022

Currently, numerous researchers use commercialized nanoplastic particles (NPs) to establish detection method or carry out toxicological researches. However, the significant differences between commercialized NPs and those formed under natural conditions certainly will affect the accuracy of the research on NPs to some extent. In the field of analytical chemistry, the selection criterion of a standard substance is that its physical and chemical properties should be as similar as possible to the target. Therefore, the NPs that are more similar to the naturally-derived NPs were preliminarily prepared under simulated natural conditions in the laboratory, which are more suitable for being used as standard substance. In this study, three kinds of NPs with the particle size range of 50 ~ 100/100 ~ 200/200 ~ 400 nm were prepared by simulating natural conditions and fractional filtration with nanofiltration membrane. The self-made NPs were more similar to the naturally-derived NPs than the commercialized ones. Besides, a method that simulates natural conditions for the preparation of NPs was also developed. The standard substance of NPs and its preparation method are expected to be widely applied to the establishment of detection methods or the toxicological studies of NPs to improve the study accuracy.
Mathematical modeling of apparent specific heat capacity of Channel catfish with different microwave heating time
Authors: Li Xuhai , Huang Han , Shi Liu , Xiong Guangquan , Wu Wenjing , Wang Lan
Published: August 2022

Channel catfish fillets with different microwave heating time were evaluated by differential scanning calorimetry (DSC) and low field nuclear magnetic resonance (LF-NMR) to build suitable modelling of apparent specific heat capacity (Cp) ranging from − 60 ℃ ~ 90 ℃ (except the obvious phase change region from − 20 to 20 ℃). The content of bound water (Wb), immobilized water (Wi) and free water (Wf) were weighted calculated. Non-linear fitting of experimental data, the obtained empirical equation of Cp, temperature (T), Wb, Wi and Wf of samples was: Cp = (a + bwb + cwi + dwf + eT)/(1 +fwb +gwi +hwf). The equation was in good correlation (R2 >0.95) with the experiment data and could provide a basis for improvement of processing paraments.Practical Application: It could provide a theoretical basis for processed parameters selection of prefabricated fish and predict thermal properties of fish.
Improvement on BAF53B mutation caused developmental and epileptic encephalopathy with a ketogenic diet
Authors: Wang Danli , Liu Yang , Fan Linlin , Yang Haoying , Pan Mingming , Shi Junping , Li Ang , Wang Nini , Xia Xue
Published: August 2022

Genetic mutation is the leading cause of Developmental and Epileptic Encephalopathy (DEE, OMIM 308350), a spectrum of disorders characterized by severe epilepsy and usually begins in infancy, accompanied with psychomotor development arrest and hypsarrhythmia on electroencephalogram (EEG). Up till now, mutations of 101 genes were confirmed as the cause of DEE, and were categorized accordingly into 101 different sub-types (DEE1-101). These genes encode membrane receptors, ion channels, ATP transports and involved in neurotransmitter synthesis etc. Here we report a DEE76 case caused by biallelic BAF53B mutation inherited in an autosomal recessive manner. Seizures commenced on day five and rapidly deteriorated. Patient’s brain magnetic resonance imaging (MRI) revealed rare structural abnormalities, and the EEG confirmed severe epileptiform abnormalities. After a series of therapeutic exploration, the patient has currently followed a ketogenic diet combined treatment, and the DEE associated symptom is now under control. By far most types of DEE still lack of sufficient investigation of their underlying mechanisms and treatment approaches are urgently to be explored. Gene therapy could shed light on rare diseases, yet incompetent to those remain unknown. Here we report a case of DEE76 induced by BAF53B mutations and highlighted the therapeutic potential of ketogenic diet, hoping to enlighten more interest in this field in the future.
Caliber of the deep veins of the arm in infants and neonates: the VEEIN study (Vascular Echography Evaluation in Infants and Neonates)
Authors: ZANABONI Clelia , BEVILACQUA Michela , BERNASCONI Filippo , APPIERTO Linda , ANNETTA Maria Giuseppina , PITTIRUTI Mauro
Published: August 2022

Purpose: Ultrasound-guided peripherally inserted central catheters (PICCs) are increasingly used in children, though their insertion may be limited by the small caliber of the deep veins of the arm. Previous studies have suggested to use age or weight as a guide to the feasibility of PICC insertion. We have planned an observational study with the purpose of identifying the actual feasibility of PICC insertion based on the ultrasound evaluation of the deep veins of the arm in groups of children of different weight range.Methods: We have studied 252 children weighing between 2.5 and 20 kg, divided in five different groups (group 1: 2.5-4 kg; group 2: 4.1-7 Kg; group 3: 7.1-10 Kg; group 4: 10.1-15 Kg; group 5: 15.1-20 Kg): the caliber of brachial vein, basilic vein and cephalic vein at mid-upper arm + the caliber of the axillary vein at the axilla were measured by ultrasound scan.Results: Veins of caliber > 3 mm (appropriate for insertion of a 3Fr non-tunneled PICC) were found at mid-upper arm in no child of group 1 or 2, in 13% of group 3, in 28% of group 4, and in 54% of group 5. An axillary vein > 3 mm (appropriate for insertion of a 3Fr tunneled PICC) were found in 5.8% of group 1, 30.6% of group 2, 67% of group 3, 82% of group 4, and 94% of group 5. Conclusions: The age and the weight of the child have a small role in predicting the caliber of the veins of the arm. Veins should be measured case by case through a proper and systematic ultrasound evaluation; however, the clinician can expect that PICC insertion may be feasible in one third of children weighing between 4 and 7 Kg, and in most children weighing more than 7 Kg, especially if adopting the tunneling technique.
Clear Cell Carcinoma of Uterine Cervix: A Clinicopathologic Review and Molecular Characterization
Authors: Pakbaz Sara , Esfahanian Nikki , Sanii Sanaz , Clarke Blaise , Bernardini Marcus , Han Kathy , Lheureux Stephanie , Park Nicole , Stockley Tracy , Rouzbahman Marjan
Published: August 2022

Clear cell carcinoma of uterine cervix (CCCUC) is an uncommon variant of cervical adenocarcinoma unrelated to Human Papilloma Virus (HPV). With widespread Pap test screening and HPV vaccination resulting decline in incidence of cervical HPV-related cancers, it is important to develop better understanding of the less common HPV-independent variants of cervical adenocarcinoma, including CCCUC. In this study, 10 cases of CCCUCs diagnosed over a 15 year period were retrospectively reviewed for clinicopathological and immunohistochemistry characteristics and HPV DNA PCR; and next generation sequencing (NGS) was performed in cases with available pathology material. Mean age of patients was 39.6 (range of 18–82) and all presented with vaginal bleeding. Most cases (6/10) were diagnosed at FIGO stage IIB. Eight patients had surgery, with lymph nodes dissection in 7. Adjuvant therapy followed in 5 cases. Median follow up period was 38 months. HPV DNA PCR proved negative HPV status in all cases. For immunohistochemistry, all cases showed wild-type p53 expression, positive PAX8 and HNF1β, and negative ER and PR. MMR protein expression was intact in 4 cases. Two cases had lost/equivocal MSH2/MSH6 expression, one of which proved negative for microsatellite instability in NGS. Based on combined positive score (CPS), more than half of cases with available PD-L1 (4/7) were positive. 70 genetic variants were identified in testing of tumor tissue DNA from 6 cases with an NGS panel assessing 562 cancer-associated genes for single-nucleotide and copy-number variations for selected genes, and insertions/deletions. Variants occurred most frequently in genes ATM, CDH23, CSMD3, KDM5C, LRP1B, NIN, PKHD1, and RNF213. Pathways that were enriched for genes in this data set include apoptosis regulation, cell cycle and DNA repair, PI3K-AKT signaling, and NGF signaling. Multiple genes were associated with receptor tyrosine kinase activity, chromatin remodeling, and transcriptional regulation. This is the first study to explore the genomic landscape of CCCUC using Next Generation Sequencing. Some potentially actionable molecular alterations are present in these tumors. However, genetic findings are heterogeneous and further studies with larger sample size is required to better characterize this rare malignancy and to allow development of novel diagnostic and therapeutic techniques.
Bias against parents in science hits women harder
Authors: Staniscuaski Fernanda , Machado Arthur , Soletti Rossana , Reichert Fernanda , Zandonà Eugenia , Mello-Carpes Pâmela , Almeida Camila Infanger , Ludwig Zelia , Oliveira Leticia
Published: August 2022

Worldwide, parenthood remains a major driver for the reduced participation of women in the job market, where discrimination stems from people's biases against mothers, based on stereotypes and misconceptions surrounding the vision of motherhood in our society. In academia, parenthood may be equally perceived as negatively affecting scientists' commitment and dedication, especially for women. Our survey conducted amongst Brazilian scientists found that mothers self-reported a higher prevalence of negative bias in their workplace when compared to fathers. The perception of a negative bias was influenced by gender and career status, but not by race, scientific field or number of children. Regarding intersections, mothers with less than 15 years of hiring reported having suffered a higher rate of negative bias against them. We discuss implications of these results and suggest how this negative bias should be addressed in order to promote an equitable environment that does not harm women in science.
Effective CO2 Capture and Selective Photocatalytic Conversion into CH3OH by Hierarchical Nanostructured Photocatalysts GO-TiO2-Ag2O and GO-TiO2-Ag2O-Arg
Authors: Nosrati Aliakbar , Javanshir Shahrzad , Feyzi Farzaneh
Published: August 2022

The attenuation of greenhouse gases especially CO2 as one of the main causes of global warming and its conversion into valuable materials are among the challenges that must be met in the 21st century. For this purpose, hierarchical ternary and quaternary hybrid photocatalysts based on graphene oxide, TiO2, Ag2O, and Arginine have been developed for combined CO2 capture and photocatalytic reductive conversion to methanol under visible and UV light irradiation. The material’s bandgap energy was estimated from diffuse reflectance spectra (DRS) Tauc analysis algorithm. Structural and morphological properties of the synthesized photocatalysts were studied using various analytical techniques such as Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscope (SEM), and transmission electron microscopy (TEM). The calculated band for GO-TiO2-Ag2O and GO-TiO2-Ag2O-Arg were 3.18 eV and 2.62 eV respectively. This reduction in the bandgap showed that GO-TiO2-Ag2O-Arg has a significant visible light photocatalytic ability. The investigation of CO2 capture for the designed catalyst shown that GO-TiO2-Ag2O-Arg and GO-TiO2-Ag2O have high CO2 absorption capacity (1250 and 1185 mmol g-1 respectively at 10 bar and 273 K under visible light). The amount of methanol produced by GO-TiO2-Ag2O and GO-TiO2-Ag2O-Arg was 8.154 µmol. gcat-1.h-1 and 5.1 µmol. gcat-1.h-1 respectively. The main advantages of this study are the high efficiencies and selectivity of catalysts toward methanol formation. The reaction mechanism to understand the role of hybrid photocatalysts for CO2 conversion is deliberated. In addition, these catalysts remain stable during the photocatalytic process and can be used repeatedly, and enlightening for environmental researches.
Correlation study between multiplanar reconstruction trigeminal nerve angulation and trigeminal neuralgia
Authors: Sun Tao , Huang Qinghao , Li Chuangfeng , Yang Wensheng , Wang Wentao , He Longshuang , Liu Jinlong , Yang Chao
Published: August 2022

Objectives
Despite neurovascular compression (NVC) is now widely accepted mechanism of trigeminal neuralgia (TN), there were some patients found no NVC, and also NVC was found in asymptomatic individuals. Here, we aimed to explore the correlation between multiplanar reconstruction (MPR) trigeminal nerve angulation (TNA) and TN.
Methods
From May 2020 to November 2021, 50 healthy controls were enrolled as control group (CG), 95 patients with primary TN were enrolled as observation group (OG), which was further subtyped into young patients (YP), middle-aged patients (MP) and old patients (OP) according to onset age of TN symptoms. Patients was also divided into patients with or without evoked actions according to the presence of evoked actions or not. Bilateral TNA measurements were carried out in OG and CG, image parameters were compared between different groups or subgroups. All images were interpreted by two radiologists who were blinded to the study.
Result
No statistical difference of bilateral TNA of CG was found, TNA of OG was significantly smaller than CG. In OG, TNA on the affected side was significantly smaller than the unaffected side. TNA showed a positive correlation with age, as TNA on the affected side of YP was significantly smaller than MP and OP. Patients with evoked actions showed smaller TNA than patients without evoked actions.
Conclusions
This study suggested that TNA might play a role in TN, small TNA could be a risk factor of TN. Furthermore, patients with small TNA are more likely to combine with evoked actions., but more studies are needed to explore the exact role of TNA in TN.
Employment risks of all employed working-age cancer survivors after cancer diagnosis: a retrospective cohort analysis of population-based administrative data
Authors: Choi Yoon-Joo , Lee Weon-Young
Published: August 2022

PURPOSE : Discussions on the employment status of cancer survivors should be actively examined worldwide as the cancer survival rate increases. This study attempted to examine the status of working status changes after cancer diagnosis to improve the quality of life of cancer survivors.METHODS: We established a nationwide cohort to determine long-term changes of work after cancer diagnosis. All patients aged 19 to 50 years who were newly diagnosed with cancer while working for the previous 3 years were considered as the case group in 2010. Using propensity score matching (PSM), the cases were matched by sex and age at a ratio 1:3 with the control group. The Kaplan-Meier curve and Cox hazard model analyses were performed to determine the occurrence of unemployment and return to work in the case and control groups on a yearly basis.RESULTS: According to the 6-year follow-up after cancer diagnosis, 26.5% of cancer patients and 23.2% of controls had lost their jobs by the end of the follow-up (P<.0001). Meanwhile, 50.5% of cancer patients and 57.4% of control patients returned to work after unemployment (P<.0001). Subsequently, based on the Cox hazard model, the unemployment risk of cancer patients was 1.42 times higher while the proportion of return to work was 1.15 times lower than those of the general population.CONCLUSIONS: Employment is very closely related to the quality of life of cancer survivors. These results highlight that there is a need for a system that can support cancer survivors' work maintenance and return to work after unemployment during the treatment period, and that awareness of this needs to be improved.
Autoimmune Gene Expression Profiling of Fingerstick Whole Blood in Chronic Fatigue Syndrome
Authors: Wang Zheng , Waldman Michelle F. , Basavanhally Tara J. , Jacobs Aviva R. , Lopez Gonzalo , Perichon Regis Y. , Ma Johnny J. , Mackenzie Elyse M. , Healy James , Wang Yixin , Hersey Sarah A.
Published: August 2022

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition that can lead to severe impairment of physical, psychological, cognitive, social, and occupational functions. The cause of ME/CFS remains incompletely understood. There is no clinical diagnostic test for ME/CFS. Although many therapies have been used off-label to manage symptoms of ME/CFS, there are limited, if any, specific therapies or cure for ME/CFS. In this study, we investigated the expression of genes specific to key immune functions, and viral infection status in ME/CFS patients with an aim of identifying biomarkers for characterization and/or treatment of the disease. Methods In 2021, one-hundred and sixty-six (166) patients diagnosed with ME/CFS and 83 healthy controls in the US participated in this study via a social media-based application (app). The patients and heathy volunteers consented to the study and provided self-collected finger-stick blood and first morning void urine samples from home. RNA from the fingerstick blood was tested using DxTerity’s 51-gene autoimmune RNA expression panel (AIP). In addition, DNA from the same fingerstick blood sample was extracted to detect viral load of 4 known ME/CFS associated viruses (HHV6, HHV7, CMV and EBV) using a real-time PCR method. Results Among the 166 ME/CFS participants in the study, approximately half (49%) of the ME/CFS patients reported being house-bound or bedridden due to severe symptoms of the disease. From the AIP testing, ME/CFS patients with severe, bedridden conditions displayed significant increases in gene expression of IKZF2, IKZF3, HSPA8, BACH2, ABCE1 and CD3D, as compared to patients with mild to moderate disease conditions. These six aforementioned genes were further upregulated in the 22 bedridden participants who suffer not only from ME/CFS but also from other autoimmune diseases. These genes are involved in T cell, B cell and autoimmunity functions. Furthermore, IKZF3 (Aiolos) and IKZF2 (Helios), and BACH2 have been implicated in other autoimmune diseases such as systemic lupus erythematosus (SLE) and Rheumatoid Arthritis (RA). Among the 240 participants tested with the viral assays, 9 samples showed positive results (including 1 EBV positive and 8 HHV6 positives). Conclusions Our study indicates that gene expression biomarkers may be used in identifying or differentiating subsets of ME/CFS patients having different levels of disease severity. These gene targets may also represent opportunities for new therapeutic modalities for the treatment of ME/CFS. The use of social media engaged patient recruitment and at-home sample collection represents a novel approach for conducting clinical research which saves cost, time and eliminates travel for office visits.
Correlation between intracerebral pH and expression of Hv1 proton channel and myelin-related proteins after hypoxic-ischemic brain injury in newborn pigs
Authors: Zheng Yang , Wang Xiaoming
Published: August 2022

Background Myelin sheath injury after cerebral hypoxia-ischemia is well known and is associated with multiple factors. In this study, changes in pH and expression of voltage-gated proton channel (Hv1) as well as myelin-related proteins in the brain, after hypoxic-ischemic brain injury (HIBI) in neonatal pigs were analyzed. Methods A total of 53 healthy male neonatal pigs were used to establish an HIBI model. The control group was without HI process. The model group underwent hypoxic-ischemic process for 40 min. The pH and expression of Hv1, myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), and myelin-associated glycoprotein (MAG) in the brain tissue of neonatal pigs were then analyzed at different time points after HI. Results After HIBI, the expression of Hv1 expression reached a peak at 2–6 h. The pH in this brain region reached a minimum at 0–2 h after HI, and was then gradually restored. Regarding the expression of myelin-related proteins, we observed an initial decrease in their levels, followed by an increase. MAG and MBP expression reached a minimum at 6–12 h, while MOG expression reached a minimum at 2–6 h. Furthermore, a correlation was found between pH and Hv1, MBP, and MOG expression, but not with MAG expression. Conclusions Our findings indicate that brain pH is correlated with Hv1, MBP, and MOG expression after HIBI, suggesting that changes in the brain environment impact myelin damage and repair to some extent.
Development of a Mobile-accessible Web Application in Wound Management: A Pilot Study
Authors: Yılmaz Ayşe Çelik , Bayraktar Abdullah Salih , Özbek Uğur , Çeken Celal , Açıl Hande Cengiz , Erkin Alper , Aygin Dilek
Published: August 2022

Introduction and purpose: With the development of technology, new applications have started to deliver health services. These applications, which are described as mobile health applications, provide a systematic approach to managing chronic wounds and increase patients' quality of life and their compliance with treatment. In this direction, the study was carried out to develop an application that can be used by patients and healthcare professionals in chronic wound management.Material and Method: To develop the application, first of all, the user panels and their contents were drafted, and the servers and infrastructure works were started. Interfaces were developed based on the page designs created, and separate pages were designed for patients and healthcare personnel. After the development of the main operation and management platform, the definition of services, the editing of image processing features, and the security tests, the mobile application was made ready for use. In the pilot study, eight patients with diabetic foot wounds were followed up with the application used on Android systems via web browsers, both tablets, and smartphones, via mobile application.Results: In the study, it was determined that both the patients followed by the wound tracking system and the health personnel using the system were satisfied with the application.Conclusion: Using mobile applications in the long-term treatment process of chronic wounds increases the patients' follow-up outside the hospital, their compliance with the treatment, and their comfort. In terms of health personnel, it also reduces the intensity and workload in the hospital and ensures that patient records are kept regularly. Patients with chronic wounds with no indication for hospitalization can be followed up with the mobile application.
Regulation of pseurotin A biosynthesis by GliZ and the synergetic effects of gliotoxin and pseurotin A biosynthesis on virulence of Aspergillus fumigatus
Authors: Seo Hyewon , Kang Suzie , Lee Dongho , Yun Cheol-Won
Published: August 2022

Recently, we reported that zinc regulates gliotoxin biosynthesis via ZafA, which is a zinc-responsive transcriptional activator. From an HPLC analysis of culture media of Aspergillus fumigatus, we found a trend of decreasing gliotoxin production but increasing pseurotin A and fumagillin production in proportion to the zinc concentration. The expression of the genes involved in pseurotin A biosynthesis was upregulated under high zinc concentrations. Furthermore, upregulated expression of pseurotin A biosynthetic genes and higher production of pseurotin A were observed in the ZafA deletion strain. Interestingly, the deletion of GliZ, a transcriptional activator of gliotoxin biosynthesis genes, resulted in upregulated expression of pseurotin A biosynthetic genes and increased production of pseurotin A. We detected upregulation of FumR expression in the GliZ and ZafA deletion mutants. The overexpression of GliZ observed in the ZafA deletion mutant resulted in the failure of the mutant to increase pseurotin A production, which is a phenotype of the ZafA deletion mutant. These results suggest that ZafA sequentially regulates pseurotin A biosynthesis through GliZ. Finally, we found through a murine virulence test that the GliZ and FumR double-deletion mutants showed a delayed death rate compared with the single-deletion mutants of either GliZ or FumR. Taken together, these results suggested that the biosyntheses of gliotoxin and pseurotin A are regulated in opposite ways by zinc utilization and that each secondary metabolite is synthesized when the synthesis of another secondary metabolite fails to protect it against the defense system of the host.
Cabozantinib-induced serum creatine kinase elevation and rhabdomyolysis: a retrospective study
Authors: Yamanaka Taro , Takemura Kohji , Hayashida Michikata , Suyama Koichi , Urakami Shinji , Miura Yuji
Published: August 2022

BackgroundRhabdomyolysis is a potentially fatal disease, and elevated serum creatine kinase (CK) is one of the key laboratory findings suggestive of this disease. It is important to distinguish rhabdomyolysis from other diseases because CK elevation can occur in a variety of etiologies. Cabozantinib is one of the standard treatments for patients with renal cell carcinoma, but the frequency of CK elevation with this drug is still unknown.MethodsTo investigate the frequency of serum CK elevation induced by cabozantinib, we retrospectively reviewed the electronic medical records of patients with advanced renal cell carcinoma who received cabozantinib at our institution from April 2020 to March 2021.ResultsSeven patients were included in the study; six experienced serum CK elevation, four were classified as grade 1, and the remaining two as grade 3 according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. In five patients, the time from cabozantinib administration to CK elevation was 14 days. Hypothyroidism can be one of the causes of CK elevation; however, two patients who had hypothyroidism caused by previous treatment were in the euthyroid condition due to hormone replacement. One patient with grade 1 CK elevation developed late-onset immune-related adverse event (irAE) myositis comorbid with suspected myasthenia gravis. One patient with grade 3 CK elevation developed muscle weakness and rhabdomyolysis.ConclusionsCK elevation is a common adverse event induced by cabozantinib. Most patients are asymptomatic and may not be clinically ill. However, physicians should be careful with the rare occurrence of symptomatic serum CK elevation, indicating rhabdomyolysis and neuromuscular irAEs, especially in patients who receive immune checkpoint inhibitors (ICIs).
Current knowledge and attitudes of students towards biotechnology: A long way to go
Authors: Alberro Ainhoa , Ortega-Lasuen Unai , Diez José Ramón
Published: August 2022

Thanks to technological innovations, science is rapidly evolving, and therefore, development of effective and engaging learning strategies is needed to ensure knowledge transmission. But first, we need to know what the current situation is. In this work, we focused on biotechnology, a scientific branch that is present in many of aspects of our daily life, but also a source of controversy. We described the knowledge of Baccalaureate students about biotechnology and its uses, as well as their awareness about the transgenic food as a socioscientific issue, and their attitudes towards applications of transgenics. Most students cannot give an appropriate definition of biotechnology. Besides, students have misconceptions about transgenics, and easily change their attitudes. Thus, new strategies to get students interest and improve knowledge transfer should be implemented.
Influence of childhood maltreatment on major depressive disorder in adulthood: mediating role of social support
Authors: Zeng Zhi , Lv Xiaozhen , Zhou Shuzhe , Liu Qi , Si Tianmei , Zhu Gang , Chen Qiaoling , Tian Hongjun , Zhang Nan , Zhang Kerang , Wang Xueyi , Wei Jing , Wang Gang , Yu Xin
Published: August 2022

Background: Childhood maltreatment is strongly associated with major depressive disorder (MDD) in adulthood, social support can buffer the effect of childhood maltreatment on MDD, but there are few studies on the role of different types of social support and gender differences in mediating models.Methods: The study included 965 MDD patients and 443 healthy participants from nine centers. MDD patients are diagnosed using the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV). The Childhood Trauma Questionnaire-Short Form (CTQ-SF), 17-item Hamilton Depression Rating Scale and Social Support Rate Scale (SSRS) were used to assess the status of childhood maltreatment, MDD and social support. Multivariable mediation analyses were used to examine the mediating role of social support between childhood maltreatment and MDD.Results: After controlling for sex, age, ethnicity, educational level, family history, work status and marriage, childhood maltreatment increases the risk of MDD (OR=1.07, 95%CI: 1.05-1.09). Total social support (OR=0.88, 95%CI: 0.86-0.90) , subjective social support (OR=0.83, 95%CI：0.80-0.86), objective social support (OR=0.84, 95%CI: 0.80-0.89) and support utilization (OR=0.73, 95%CI: 0.68-0.78) all significantly reduced the risk of MDD. Total social support, subjective support and support utilization played a mediating role in childhood maltreatment and MDD, but not objective social support. For males, only subjective social support mediated the relationship between childhood maltreatment and MDD, while for females, both subjective social support and support utilization mediated the relationship.Conclusions: For those who experienced childhood maltreatment, suitable social support, especially subjective support and support utilization, may reduce the risk of MDD. Different social support seems necessary for male and female for alleviating the influence of childhood maltreatment on MDD.
Silencing of MEG3 gene promoted anti-cancer activity and drug sensitivity in glioma
Authors: Avsar Timucin , Degirmenci Zehra , Kilic Turker
Published: August 2022

Aberrant expression of MEG3 has been shown in various cancers. The purpose of this study is to evaluate the effect of MEG3 on glioma cells including U87MG and patient-derived primary tumors cells and compare with nonglial HUVEC cells. Cell viability, migration and chemo sensitivity was assayed. Apoptosis was evaluated in MEG3 overexpressing and MEG3 suppressed cells. MEG3 expression was compared in patient-derived tumor cells with respect to IDH1 mutation status and WHO-grades. Silencing of MEG3 inhibited cell proliferation and reduced cell migration while overexpression of MEG3 promoted cell proliferation in glioma cells. MEG3 inhibition improved chemo sensitivity of glioma cells to 5-fluorouracil(5FU) but not to navitoclax. Suppression of MEG3 gene in patient-derived oligodendroglioma cells also showed the same effect whereas glioblastoma cell proliferation and chemo sensitivity were not affected by MEG3 inhibition. Further, cell death mechanism of action was found as apoptosis. Although MEG3 is a widely known tumor suppressor gene and its loss is associated with several cancer types, here we reported that MEG3 inhibition can be used in drug sensitivity for improving efficiency of known chemotherapeutics. We propose that the level of MEG3 should be evaluated in treatment of different glioma subtypes that are resistant to effective drugs.
Development of Ultra High-Performance Liquid Chromatography-Tandem Mass Spectrometry Method for Enantiomer Resolution of Thyroxine on a Chiral Crown Ether Derived Chiral Stationary Phase
Authors: Lee Jisun , Adhikari Suraj , Lee Wonjae , Yoon Hye-Ran
Published: August 2022

Chiral discrimination of thyroxine (T4) enantiomers was performed using ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) on a chiral crown ether-derived ChiroSil SCA(-) column. The different composition of mobile phases and the effect of column oven temperatures were investigated and the optimum chromatographic separation with respect to resolution and analysis time was achieved using a mixture of 60% methanol/water (v/v) with 0.1% formic acid at 40°C having a flow rate of 1.4 mL min− 1. The thermodynamic data from van’t Hoff plots of temperature experiments revealed that the enantioseparation was enthalpically favored process. The method was validated in the concentration range of 0.5–100 µg mL− 1 for both enantiomers and proved to be rapid, precise, sensitive, and selective method for the enantiodiscrimination of T4 under the optimized conditions. The calibration curves of both D- and L-T4 showed an excellent linearity with coefficient of determination (R2) > 0.9997. The developed chiral method was successfully applied for a quantitative assay to check the enantiomeric purities of the six pharmaceutical formulations of levothyroxine sodium tablets and the enantiomeric impurities identified were in the range of 0.11–0.29%. This method could be applied for the determination of enantiomeric purity on pharmaceuticals and also for the monitoring of thyroid hormone levels.
Proton Beam Therapy with Pencil Beam Scanning is Safe and Effective for Advanced Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: A Single Center Experience
Authors: Yang Alexander H. , Urrunaga Nathalie H. , Siddiqui Osman , Wu Angela , Schliep Matthew , Molitoris Jason K. , Shetty Kirti , Lominadze Zurabi
Published: August 2022

Background Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) are the two most common primary liver tumors. Proton Beam Therapy (PBT) is a non-surgical treatment that spares adjacent tissues compared to photon radiation, limiting damage to nearby structures. We present a single center experience on liver toxicity, tumor response, and survival in patients with HCC and iCCA treated with PBT with Pencil Beam Scanning (PBS).MethodsConsecutive patients receiving PBT for HCC or iCCA were reviewed. PBT was delivered with hypofractionated or stereotactic body radiation therapy using PBS. Tumor size was approximated by clinical target volume (CTV). Liver toxicity was determined by changes in MELD-Na and albumin-bilirubin (ALBI) grade. Tumor response was determined by imaging at six to eight weeks post-therapy.Results44 consecutive patients were included, 22 patients in each group. 35% of patients had multifocal disease and median CTV was 232.5cc. Overall survival was 82%. For both cancer types, tumor size, laboratory values, and total radiation dose were not associated with liver toxicity. All iCCA patients had stable or improved ALBI grade following treatment, however there were 4 deaths. Among HCC patients, ALBI grade was stable in 83%, average MELD-Na score remained stable, and there was only one death.ConclusionsOur results indicate that PBT for unresectable HCC and iCCA is safe and effective, even for large and multifocal tumors. Liver function was preserved even in those with baseline cirrhosis who received biologically effective doses ≥80.5 Gy. Overall survival was 86.4%, similar between HCC and iCCA.
Investigation of cryoprotectants -treated protein deterioration during chilled and frozen storage: Electrophoretic pattern, functional properties and kinetic modeling
Authors: Maghsoudi Leila , Moosavi-Nasab Marzieh , Abedi Elahe , Maleki Shahrzad
Published: August 2022

The relative cryoprotective effects of flaxseed protein and pectin in comparison with conventional cryoprotectant on stability of Capoor (Cyprinus carpio) surimi proteins during storage at -20°C for 4 months and at 4°C for 10 days were investigated. The results show that the reaction rate constants of second order kinetic, k, in samples stored at -20°C were much smaller than similar samples stored at 4°C, indicating decreased the rate of protein denaturation in frozen samples. Although, pectin caused to improve water-holding capacity (27.8%; 4°C and 21.5%; -20°C) on account of the formation of a separate gel and represent highly more inhibitory impact on the ice crystals growth, during the overnight soaking, protein denaturation may have been occurred. The flaxseed protein -treated sample showed the lowest decrease of SH content and reaction rate constant at both − 20°C and 4°C than others. The results exhibited that salt extractable protein and sulfhydryl content changes were in good agreement with the second order kinetic model. Regarding to SDS- PAGE results, no major changes were observed in intensity of myosin heavy chain, actin and myosin light chain bands in flaxseed proteins treated surimi over chilled and frozen storage.
Surgical Intervention Provides Better Outcomes for Hip Fracture in Extremely Old Patients: A Retrospective Observational Study
Authors: Wang Suo-hsien , Chang Chia-Wei , Chai Shion Wei , Huang Ting-shuo , Soong Rueyshyang , Fu Tsai-sheng , Lau Ngi-Chiong , Chien Chih Ying
Published: August 2022

BACKGROUND: Hip fracture is a common disease in the elderly. Among these patients, surgical intervention for hip fracture should be carefully considered because of old age and multiple comorbidities. There are still insufficient comparisons between patients treated with surgery and those treated non-surgically.OBJECTIVES: We studied hip fracture patients >90 years of age to compare the different outcomes between surgical and non-surgical treatments.DESIGN: Retrospective observational study.METHODS: Patients aged > 90 years who visited the emergency department with hip fractures between March 2010 and October 2019 were identified. Overall survival was estimated using multivariate Cox proportional hazards models. We compared the mortality rates at 30 days, 1 year, and 2 years between surgical and non-surgical patients. We also recorded the length of hospital stay, intra-admission, and 30-day complication and readmission rates.RESULTS: A total of 152 patients who underwent surgery (OP group) and 32 who received conservative treatment (non-OP group) were included. The estimated median survival time was 58.47 months in the OP group, which was significantly higher than the 24.28 months in the non-OP group. After adjusting for covariates, including age, sex, Charlson Comorbidity Index (CCI), injury severity score, and fracture type, the risk of death was reduced by surgery (hazard ratio [HR]=0.427; 95% confidence interval [CI]: 0.207-0.882; p=0.021). CCI was also an independent risk factor for poor survival rate (HR=1.3; 95% CI: 1.115-1.515; p=0.001). After adjusting for several factors, surgery within 48 h improved overall survival (HR: 2.518; 95% CI: 1.299-4.879; p=0.006).CONCLUSION: Our study suggests that surgery is likely to provide better outcomes for extremely old patients with hip fractures. Operative management should be recommended because it decreases the short-term complication rate and provides better long-term survival than non-operative management. Operation performed within 48 h of admission has better overall survival than that performed after >48 hours.
GIS-Based Mapping of Geotechnical and Geophysical Properties of Lahore Soils
Authors: Daniyal Muhammad , Sohail Ghulam Mohyuddin , Rashid Hafiz Muhammad Awais
Published: August 2022

The spatial distribution of geotechnical and geophysical properties of soil delineates the subsurface soil type and condition necessary to ensure structural safety and serviceability, detailed investigations for engineering projects, and the foundation design under static and seismic loading conditions. This study presents the spatial distribution of soil type, standard penetration test (SPT) N values, bearing capacity, groundwater depth, and shear wave velocity using the database from sixty-five boreholes in GIS (geographical information system) software. The data were processed and interpreted through geostatistical contouring techniques (e.g., kriging and inverse distance weightage). The cross-plots were generated further to facilitate the interpretation of contour maps at unsampled locations. A correlation was established between measured and estimated shear wave velocity and standard penetration test N-values for the study area. It was then tested against the literature-based correlations to enhance the reliability of predicted geotechnical properties. A correlation coefficient of 0.77 between measured and predicted SPT N values improves the reliability of estimated properties (e.g., bearing capacity, shear wave velocity) at unsampled locations. The SPT N values, shear wave velocity, and allowable bearing capacity seem to be interdependent and varied with soil type and may be used for soil characterization and shallow foundation design at undrilled locations. The geotechnical maps generated in this study for Lahore city are novel and consistent with the soil types of the study area. Geotechnical engineers can use these maps for preparing geotechnical reports for the study area.
Evaluation of Visual and Patient-Reported Outcomes After Implantation of Extended Depth of Focus Intraocular Lenses in Patients Not Suitable for Multifocal Lenses
Authors: Álvarez-García María Teresa , Fuente-García Carlota , Muñoz-Puyol Cristina , Piñero David P
Published: August 2022

Purpose
To evaluate the visual and patient-reported outcomes of patients undergoing cataract surgery with implantation of an extended depth of focus (EDOF) intraocular lens (IOL) who were not good candidates for multifocal IOL implantation
Methods
Retrospective analysis of data from 30 eyes (23 patients) undergoing cataract surgery with implantation of one of two EDOF IOLs (follow-up: 37.9 ± 16.2 months), and prospective observational study including 106 eyes (78 patients) implanted with one of 6 different EDOF models (follow-up: 8.0 ± 7.7 months). Patients recruited had one of the following conditions: monofocal IOL implanted in the fellow eye, previous corneal refractive surgery, mild and non-progressive maculopathy or glaucoma, age > 75 years, amblyopia, or previous vitrectomy.
Results
In the retrospective phase, significant improvements were found in uncorrected distance (UDVA), corrected distance (CDVA) and corrected near visual acuity (CNVA) (p ≤ 0.013), with a non-significant trend to improvement in uncorrected near visual acuity (UNVA). A total of 90% of patients were completely to moderately satisfied with the outcome achieved. In the prospective phase, significant improvements were found in UDVA, CDVA, UNVA and CNVA (p ≤ 0.032), with a total of 85.5% of patients being completely to moderately satisfied (dissatisfaction 3.3%). In both phases, extreme difficulties were only reported by a limited percentage of patients for performing some near vision activities.
Conclusions
EDOF IOLs should be considered as a new therapeutic option in this type of patients, being a viable alternative to monofocal IOLs.
The association of serum immunoglobulins with risk of cardiovascular disease and mortality: the Rotterdam Study
Authors: Khan Samer R. , Dalm Virgil A.S.H. , Ikram M. Kamran , Peeters Robin P. , Hagen P. Martin van , Kavousi Maryam , Chaker Layal
Published: August 2022

Purpose: Inflammation is implicated in cardiovascular disease (CVD), but the association of total serum immunoglobulin (Ig) A, G, and M with CVD across the whole spectrum of atherosclerosis in community-dwelling elderly is unknown. Methods: This study was embedded in the Rotterdam Study, an ongoing population-based cohort study. We performed Cox regression for the associations of Igs with incident atherosclerotic CVD (ACVD; composite of myocardial infarction, revascularization, and stroke), cardiovascular mortality, and all-cause mortality, and multinomial logistic regression for the association between Igs and coronary artery calcification (CAC) scores. We adjusted for age, sex, lifestyle, and cardiovascular risk factors and presented results per standard deviation increase. Results: We included 8,767 participants (median age 62.2 years, 57% women). IgG was associated with an increased ACVD risk (hazard ratio [HR]: 1.08; 95% confidence interval [95% CI]: 1.01-1.15). IgA and IgG were associated with an increased cardiovascular mortality risk, mainly within Ig reference ranges, and with an increased all-cause mortality risk, although less marked. IgA was associated with severe atherosclerosis, i.e. CAC score >400 (odds ratio: 1.29; 95% CI: 1.03-1.62), while for IgG a trend was seen with severe atherosclerosis. Conclusion: In middle-aged and older individuals from the general population, serum IgA and IgG, but not IgM, are associated with CVD, cardiovascular mortality, and severe atherosclerosis, particularly within Ig reference ranges and independent of serum C-reactive protein. Future studies are needed to elucidate potential causality of the reported associations.