bluuebunny/crossref_metadata_2025 huggingface dataset:
Objectification of intracochlear electrocochleography using machine learning
Authors: Schuerch Klaus , Wimmer Wilhelm , Dalbert Adrian , Rummel Christian , Caversaccio Marco , Mantokoudis Georgios , Weder Stefan
Published: August 2022

Introduction

Electrocochleography (ECochG) measures inner ear potentials in response to acoustic stimulation. In patients with cochlear implant (CI), the technique is increasingly used to monitor residual inner ear function. So far, when analyzing ECochG potentials, the visual assessment has been the gold standard. However, visual assessment requires a high level of experience to interpret the signals. Furthermore, expert-dependent assessment leads to inconsistency and a lack of reproducibility. The aim of this study was to automate and objectify the analysis of cochlear microphonic (CM) signals in ECochG recordings.

Methods

Prospective cohort study including 41 implanted ears with residual hearing. We measured ECochG potentials at four different electrodes and only at stable electrode positions (after full insertion or postoperatively). When stimulating acoustically, depending on the individual residual hearing, we used three different intensity levels of pure tones (i.e., supra-, near-, and sub-threshold stimulation; 250–2,000 Hz). Our aim was to obtain ECochG potentials with differing SNRs. To objectify the detection of CM signals, we compared three different methods: correlation analysis, Hotelling's T2 test, and deep learning. We benchmarked these methods against the visual analysis of three ECochG experts.

Results

For the visual analysis of ECochG recordings, the Fleiss' kappa value demonstrated a substantial to almost perfect agreement among the three examiners. We used the labels as ground truth to train our objectification methods. Thereby, the deep learning algorithm performed best (area under curve = 0.97, accuracy = 0.92), closely followed by Hotelling's T2 test. The correlation method slightly underperformed due to its susceptibility to noise interference.

Conclusions

Objectification of ECochG signals is possible with the presented methods. Deep learning and Hotelling's T2 methods achieved excellent discrimination performance. Objective automatic analysis of CM signals enables standardized, fast, accurate, and examiner-independent evaluation of ECochG measurements.
Energy supply per neuron is constrained by capillary density in the mouse brain
Authors: Ventura-Antunes aLissa , Herculano-Houzel Suzana
Published: August 2022

Neuronal densities vary enormously across sites within a brain. Does the density of the capillary bed vary accompanying the presumably larger energy requirement of sites with more neurons, or with larger neurons, or is energy supply constrained by a mostly homogeneous capillary bed? Here we find evidence for the latter, with a capillary bed that represents typically between 0.7 and 1.5% of the volume of the parenchyma across various sites in the mouse brain, whereas neuronal densities vary by at least 100-fold. As a result, the ratio of capillary cells per neuron decreases uniformly with increasing neuronal density and therefore with smaller average neuronal size across sites. Thus, given the relatively constant capillary density compared to neuronal density in the brain, blood and energy availability per neuron is presumably dependent on how many neurons compete for the limited supply provided by a mostly homogeneous capillary bed. Additionally, we find that local capillary density is not correlated with local synapse densities, although there is a small but significant correlation between lower neuronal density (and therefore larger neuronal size) and more synapses per neuron within the restricted range of 6,500–9,500 across cortical sites. Further, local variations in the glial/neuron ratio are not correlated with local variations in the number of synapses per neuron or local synaptic densities. These findings suggest that it is not that larger neurons, neurons with more synapses, or even sites with more synapses demand more energy, but simply that larger neurons (in low density sites) have more energy available per cell and for the totality of its synapses than smaller neurons (in high density sites) due to competition for limited resources supplied by a capillary bed of fairly homogeneous density throughout the brain.
Exercise modulates central and peripheral inflammatory responses and ameliorates methamphetamine-induced anxiety-like symptoms in mice
Authors: Re Guo-Fen , Li Hong , Yang Ji-Qun , Li Yue , Zhang Zunyue , Wu Xiaocong , Zhou Ruiyi , Kong Deshenyue , Luo Huayou , Kuang Yi-Qun , Wang Kun-Hua
Published: August 2022

Anxiety-like symptoms are common symptoms of methamphetamine (METH) users, especially in the acute withdrawal period, which is an important factor for the high relapse rate during METH acute withdrawal. Exercise has been demonstrated to relieve anxiety-like symptoms during METH withdrawal, but the underlying mechanisms of this anti-anxiety effect are still unclear. Activated microglia and abnormal neuroinflammation play an important role in the pathogenesis of anxiety-like symptoms after METH withdrawal. Moreover, peripheral immune factors were also significantly associated with anxiety symptoms. However, the effects of treadmill exercise on microglial function and neuroinflammation in the striatum and hippocampus during acute METH withdrawal have not been reported. In the current study, we found severe peripheral immune dysfunction in METH users during acute withdrawal, which may in part contribute to anxiety symptoms during METH acute withdrawal. We also showed that 2 weeks of METH exposure induced anxiety-like symptoms in the acute withdrawal period. Additionally, METH exposure resulted in increased microglial activation and proinflammatory cytokines released in the mouse striatum and hippocampus during acute withdrawal. We next evaluated the effects of treadmill exercise in countering anxiety-like symptoms induced by METH acute withdrawal. The results showed that anxiety-like symptoms induced by acute METH withdrawal were attenuated by coadministration of treadmill exercise. In addition, treadmill exercise counteracted METH-induced microglial activation in the mouse striatum and various subregions of the hippocampus. Furthermore, treadmill exercise also reversed the increase in proinflammatory cytokines induced by acute METH withdrawal in the mouse striatum, hippocampus and serum. Our findings suggest that the anti-anxiety effect of treadmill exercise may be mediated by reducing microglial activation and regulating central and peripheral inflammatory responses.
Targeting prefrontal cortex GABAergic microcircuits for the treatment of alcohol use disorder
Authors: Fish Kenneth N. , Joffe Max E.
Published: August 2022

Developing novel treatments for alcohol use disorders (AUDs) is of paramount importance for improving patient outcomes and alleviating the suffering related to the disease. A better understanding of the molecular and neurocircuit mechanisms through which alcohol alters brain function will be instrumental in the rational development of new efficacious treatments. Clinical studies have consistently associated the prefrontal cortex (PFC) function with symptoms of AUDs. Population-level analyses have linked the PFC structure and function with heavy drinking and/or AUD diagnosis. Thus, targeting specific PFC cell types and neural circuits holds promise for the development of new treatments. Here, we overview the tremendous diversity in the form and function of inhibitory neuron subtypes within PFC and describe their therapeutic potential. We then summarize AUD population genetics studies, clinical neurophysiology findings, and translational neuroscience discoveries. This study collectively suggests that changes in fast transmission through PFC inhibitory microcircuits are a central component of the neurobiological effects of ethanol and the core symptoms of AUDs. Finally, we submit that there is a significant and timely need to examine sex as a biological variable and human postmortem brain tissue to maximize the efforts in translating findings to new clinical treatments.
DCE-MRI radiomics models predicting the expression of radioresistant-related factors of LRP-1 and survivin in locally advanced rectal cancer
Authors: Li Zhiheng , Huang Huizhen , Wang Chuchu , Zhao Zhenhua , Ma Weili , Wang Dandan , Mao Haijia , Liu Fang , Yang Ye , Pan Weihuo , Lu Zengxin
Published: August 2022

Objective

Low-density lipoprotein receptor-related protein-1 (LRP-1) and survivin are associated with radiotherapy resistance in patients with locally advanced rectal cancer (LARC). This study aimed to evaluate the value of a radiomics model based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the preoperative assessment of LRP-1 and survivin expressions in these patients.

Methods

One hundred patients with pathologically confirmed LARC who underwent DCE-MRI before surgery between February 2017 and September 2021 were included in this retrospective study. DCE-MRI perfusion histogram parameters were calculated for the entire lesion using post-processing software (Omni Kinetics, G.E. Healthcare, China), with three quantitative parameter maps. LRP-1 and survivin expressions were assessed by immunohistochemical methods and patients were classified into low- and high-expression groups.

Results

Four radiomics features were selected to construct the LRP-1 discrimination model. The LRP-1 predictive model achieved excellent diagnostic performance, with areas under the receiver operating curve (AUCs) of 0.853 and 0.747 in the training and validation cohorts, respectively. The other four radiomics characteristics were screened to construct the survivin predictive model, with AUCs of 0.780 and 0.800 in the training and validation cohorts, respectively. Decision curve analysis confirmed the clinical usefulness of the radiomics models.

Conclusion

DCE-MRI radiomics models are particularly useful for evaluating LRP-1 and survivin expressions in patients with LARC. Our model has significant potential for the preoperative identification of patients with radiotherapy resistance and can serve as an essential reference for treatment planning.
Influence of the external breast prosthesis on the postural control of women who underwent mastectomy: Cross-sectional study
Authors: Koralewska Anna , Domagalska-Szopa Małgorzata , Łukowski Robert , Szopa Andrzej
Published: August 2022

Background:

Women after mastectomy may decide to either have a breast reconstruction or use an external breast prosthesis. Aim: The aim of the presented research was to evaluate the influence of external breast prosthesis on postural stability in women after mastectomy. Methods and Procedures: In the study 52 women after unilateral mastectomy took part. The study consisted of 4 parts: 1) anthropometric measurements; 2) measurements of upper limb circumference; 3) assessment of weight-bearing (WB); and 4) posturographic tests (PT). Outcomes and Results: Differences in the arm circumferences on the amputated (A) and non-amputated (NA) sides did not confirm the occurrence of lymphedema in limb on amputated side. The results of the WB between the A and NA body sides in both tested conditions, i.e., with open and closed eyes, showed no significant differences between the test with and without an external prosthesis. No statistically differences have been observed between posturometric parameters with and without breast prosthesis during both PT. In comparing the posturometric parameters between the PT with open and closed eyes, the sway path of the center of pressure was statistically significantly longer when eyes were closed in both conditions, i.e., with and without breast prosthesis. Conclusion and Implications: The finding show that 1) external breast prosthesis does not have a significant influence on the symmetry of loading on the A and NA body sides and on the postural stability of women after unilateral mastectomy and 2) exclusion visual control during PT increases postural instability in women after unilateral mastectomy.
Improving the clinical workflow of a MR-Linac by dosimetric evaluation of synthetic CT
Authors: Tang Bin , Liu Min , Wang Bingjie , Diao Peng , Li Jie , Feng Xi , Wu Fan , Yao Xinghong , Liao Xiongfei , Hou Qing , Orlandini Lucia Clara
Published: August 2022

Adaptive radiotherapy performed on the daily magnetic resonance imaging (MRI) is an option to improve the treatment quality. In the adapt-to-shape workflow of 1.5-T MR-Linac, the contours of structures are adjusted on the basis of patient daily MRI, and the adapted plan is recalculated on the MRI-based synthetic computed tomography (syCT) generated by bulk density assignment. Because dosimetric accuracy of this strategy is a priority and requires evaluation, this study aims to explore the usefulness of adding an assessment of dosimetric errors associated with recalculation on syCT to the clinical workflow. Sixty-one patients, with various tumor sites, treated using a 1.5-T MR-Linac were included in this study. In Monaco V5.4, the target and organs at risk (OARs) were contoured, and a reference CT plan that contains information about the outlined contours, their average electron density (ED), and the priority of ED assignment was generated. To evaluate the dosimetric error of syCT caused by the inherent approximation within bulk density assignment, the reference CT plan was recalculated on the syCT obtained from the reference CT by forcing all contoured structures to their mean ED defined on the reference plan. The dose–volume histogram (DVH) and dose distribution of the CT and syCT plan were compared. The causes of dosimetric discrepancies were investigated, and the reference plan was reworked to minimize errors if needed. For 54 patients, gamma analysis of the dose distribution on syCT and CT show a median pass rate of 99.7% and 98.5% with the criteria of 3%/3 mm and 2%/2 mm, respectively. DVH difference of targets and OARs remained less than 1.5% or 1 Gy. For the remaining patients, factors (i.e., inappropriate ED assignments) influenced the dosimetric agreement of the syCT vs. CT reference DVH by up to 21%. The causes of the errors were promptly identified, and the DVH dosimetry was realigned except for two lung treatments for which a significant discrepancy remained. The recalculation on the syCT obtained from the planning CT is a powerful tool to assess and decrease the minimal error committed during the adaptive plan on the MRI-based syCT.
In-vivo thermodynamic exploration of gas-based intraperitoneal hyperthermia
Authors: Diakun Agata , Khosrawipour Tanja , Mikolajczyk-Martinez Agata , Kuropka Piotr , Nicpoń Jakub , Kiełbowicz Zdzisław , Prządka Przemysław , Liszka Bartłomiej , Li Shiri , Lau Hien , Kielan Wojciech , Khosrawipour Veria
Published: August 2022

Background

While hyperthermic intraperitoneal (i.p) applications are highly efficient in treating peritoneal metastases (PM), they are currently limited to temperatures of 41 – 43° Celsius (C). First data on gas-based i.p. hyperthermia is promising, as this novel method allows a significant temperature rise in superficial peritoneal layers without increasing core temperatures. Until now, key mechanisms of this novel tool, e.g. thermodynamic energy transfer, have not been investigated. This study aims to explore the volume of thermodynamic energy transfer during gas-based i.p. hyperthermia at 48-50°C and its peritoneal effects.

Methods

For this study, three swine were subjected to gas-based i.p. hyperthermia at varying temperatures (48°, 49° and 50°C) in a diagnostic laparoscopy setting with a high-flow air stream. Temperatures of the i.p. cavity, in- and outflow airstream at the trocar were measured and the thermodynamic energy transfer was calculated. Tissue samples were collected on postoperative day 7 for histopathologic analyses.

Results

According to our data, temperatures within the intraabdominal cavity and at the outflow site remain relatively stable at < 40°C. An increase in thermodynamic energy transfer is observed with increasing applied temperatures. Gas-based i.p. hyperthermia induced capillary coagulation and white blood cell infiltration within peritoneal layers.

Conclusions

Gas-based i.p. hyperthermia is an innovative approach which enables the i.p. delivery of specific amounts of thermodynamic energy. Following this procedure, our data indicate remarkable histologic changes on the superficial peritoneal layer most likely attributable to the applied thermodynamic energy. Further studies are required to investigate how these findings can be applied in PM management.
Role of echogenic foci in ultrasonographic risk stratification of thyroid nodules: Echogenic focus scoring in the American College of Radiology Thyroid Imaging Reporting and Data System
Authors: Li Renxu , Liang Zhenwei , Wang Xiangyu , Chen Luzeng
Published: August 2022

Background

Although echogenic foci may raise malignancy rates in thyroid nodules, the association between peripheral calcification or macrocalcification and thyroid carcinoma is controversial. We evaluated the malignancy probability of various echogenic foci and explored whether the method of determining a thyroid nodule’s point score in the echogenic focus category of the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) is reasonable.

Methods

We retrospectively evaluated 819 patients with 852 nodules. The patterns of echogenic foci on ultrasonography were classified into the following four categories: punctate echogenic foci, macrocalcification, peripheral calcification, and multiple different types of echogenic foci. The core needle biopsy results were divided into two groups: benign and malignant or suspicious for malignancy.

Results

Among the 852 nodules, 471 (55.3%) had echogenic foci on ultrasonography. Of these nodules, there was no significant statistical difference in the malignant or suspicious for malignancy rate between nodules with peripheral calcification and those with macrocalcification [40.0% (8/20) vs. 30.6% (11/36), respectively; p = 0.474]. The incidence of malignancy or suspicious for malignancy for nodules with peripheral calcification, macrocalcification, or multiple different types of echogenic foci was significantly lower than the incidence for punctate echogenic foci alone, with odds ratios of 0.265 [95% confidence interval (CI): 0.105–0.667; p = 0.005], 0.175 (95% CI: 0.083–0.368; p = 0.000), and 0.256 (95% CI: 0.136–0.482; p = 0.000), respectively.

Conclusion

We found no significant statistical difference in the risk of malignancy or suspicious for malignancy rate between peripheral calcification and macrocalcification in thyroid nodules. We observed that nodules with multiple different types of echogenic foci were not associated with higher malignant or suspicious for malignancy rates compared with nodules with punctate echogenic foci alone.
Adjuvant crizotinib in high-risk uveal melanoma following definitive therapy
Authors: Khan Shaheer , Lutzky Jose , Shoushtari Alexander N. , Jeter Joanne , Marr Brian , Olencki Thomas E. , Cebulla Colleen M. , Abdel-Rahman Mohamed , Harbour J. William , Sender Naomi , Nesson Alexandra , Singh-Kandah Shahnaz , Hernandez Susana , King Jeanelle , Katari Manpreet S. , Dimapanat Lyssa , Izard Stephanie , Ambrosini Grazia , Surriga Oliver , Rai Alex J. , Chiuzan Codruta , Schwartz Gary K. , Carvajal Richard D.
Published: August 2022

Introduction

Approximately 40% of patients with uveal melanoma (UM) will develop metastatic disease. Tumors measuring at least 12mm in basal diameter with a class 2 signature, as defined by a widely used gene expression-profiling test, are associated with significantly higher risk of metastasis, with a median time to recurrence of 32 months. No therapy has been shown to reduce this risk.

Materials and Methods

This was a single-arm, multicenter study in patients with high-risk UM who received definitive treatment of primary disease and had no evidence of metastasis. Patients were consecutively enrolled to receive 12 four-week cycles of adjuvant crizotinib at a starting dose of 250mg twice daily and were subsequently monitored for 36 months. The primary outcome of this study was to assess recurrence-free survival (RFS) of patients with high-risk UM who received adjuvant crizotinib.

Results

34 patients enrolled and received at least one dose of crizotinib. Two patients were unevaluable due to early withdrawal and loss to follow-up, leaving 32 patients evaluable for efficacy. Eight patients (25%) did not complete the planned 48-week course of treatment due to disease recurrence (n=5) or toxicity (n=3). All patients experienced at least one adverse event (AE), with 11/34 (32%) experiencing a Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or 4 AE. After a median duration of follow up of 47.1 months, 21 patients developed distant recurrent disease. The median RFS was 34.9 months (95% CI (Confidence Interval), 23-55 months), with a 32-month recurrence rate of 50% (95% CI, 33-67%). Analysis of protein contents from peripheral blood extracellular vesicles in a subset of patient samples from baseline, on-treatment, and off-treatment, revealed a change in protein content associated with crizotinib exposure, however without a clear association with disease outcome.

Conclusions

The use of adjuvant crizotinib in patients with high-risk UM did not result in improved RFS when compared to historical controls. Analysis of blood extracellular vesicles revealed changes in protein content associated with treatment, raising the possibility of future use as a biomarker. Further investigation of adjuvant treatment options are necessary for this challenging disease.
Leveraging teachable moments in cancer prevention by improving HPV vaccination in health professional students (HPS): A systematic review
Authors: Levy Morgan S. , Finch Lindsey , Lindsay Kara A. , Jeudin Patricia , Huang Marilyn
Published: August 2022

Introduction

Vaccination against HPV is safe and effective in cancer prevention, yet vaccination uptake remains low. Strong recommendation of HPV vaccination by healthcare providers increases immunization rates, but gaps in knowledge persist surrounding HPV and HPV vaccination amongst health professional students (HPS). It is critical to educate HPS in all professions to maximize vaccination opportunities and increase vaccine uptake. The objective of this study is to evaluate evidence on HPV knowledge, vaccine uptake, and educational interventions in HPS to identify specific deficits to improve education.

Methods

A systematic literature search for articles on HPV vaccine uptake, knowledge, and educational interventions in HPS was performed in PubMed, Embase, Web of Science, CINAHL, and Scopus from January 1, 2006 – July 21, 2021. Included studies assessed HPS for HPV vaccine uptake, knowledge, counseling comfort, or educational interventions to increase HPV vaccine knowledge. Studies were screened for inclusion by 2 independent reviewers and evaluated for risk of bias. PRISMA guidelines for reporting were followed.

Results

Twenty-one unique articles met inclusion criteria and were included in the analysis. Of the studies included, 20 included knowledge, 11 included vaccine uptake, 8 included interventions, and 12 included counseling comfort. The students in the studies included medical (n=14), dental (n=7), dental hygiene (n=6), nursing (n=3), physician assistant (n=2), public health (n=1), and pharmacy (n=1). Across studies, HPV vaccine series initiation ranged from 34.6-70.3%, with 28.3-58.3% up to date on vaccination. Most students knew that HPV causes cervical cancer (99%), but fewer knew that HPV causes head and neck cancer (40-47%) and oropharyngeal cancer (45%). Educational interventions included team-based approaches and lectures, and improved outcomes including vaccine knowledge, vaccination schedule, and cancer knowledge. Medical students with lower knowledge of HPV were more hesitant to recommend vaccination at baseline but were more likely to recommend vaccination after an education session.

Discussion

Across HPS, inadequacies persist in HPV vaccine uptake, knowledge, and counseling comfort. It is critical to target vaccine uptake in this population and improve existing educational efforts to reduce preventable cancers. Institutions must prioritize HPV vaccine education to impact HPV related death.
Reprogramming lipid metabolism as potential strategy for hematological malignancy therapy
Authors: Zhang Leqiang , Chang Ning , Liu Jia , Liu Zhuojun , Wu Yajin , Sui Linlin , Chen Wei
Published: August 2022

Hematological malignancies are one of the most lethal illnesses that seriously threaten human life and health. Lipids are important constituents of various biological membranes and substances for energy storage and cell signaling. Furthermore, lipids are critical in the normal physiological activities of cells. In the process of the lethal transformation of hematological malignancies, lipid metabolism reprogramming meets the material and energy requirements of rapidly proliferating and dividing tumor cells. A large number of studies have shown that dysregulated lipid metabolism, commonly occurs in hematological malignancies, mediating the proliferation, growth, migration, invasion, apoptosis, drug resistance and immune escape of tumor cells. Targeting the lipid metabolism pathway of hematological malignancies has become an effective therapeutic approach. This article reviews the oncogenic mechanisms of lipid metabolism reprogramming in hematological malignancies, including fatty acid, cholesterol and phospholipid metabolism, thereby offering an insight into targeting lipid metabolism in the treatment of hematological malignancies.
#childhoodobesity – A brief literature review of the role of social media in body image shaping and eating patterns among children and adolescents
Authors: Modrzejewska Adriana , Czepczor-Bernat Kamila , Modrzejewska Justyna , Roszkowska Agnieszka , Zembura Marcela , Matusik Paweł
Published: August 2022

Children’s food preferences are closely related to their parents’ food preferences and knowledge of food is linked to what their parents share with them. Parents, however, are not the only people who model such behavior. Paradoxically, the ubiquitous technological development can also pose a huge threat. In developed countries, 94% of teenagers use social media platforms such as: Instagram, Snapchat, Facebook, or TikTok, and this also applies to children. It can therefore be argued that parents’ nutritional preferences and behavior are related to the same behaviors of children and there is an extensive literature on this subject. It is therefore important to check how other factors – new technology (and social media in particular) – can influence changes in this area. A literature search was conducted in the following databases: Google Scholar, PubMed, EBSCO in December 2021. After applying all the filters and verification of relevance in terms of the research on the topic of interest to us, 4 articles related to research on body image and social media and 4 articles related to research on food choices and social media among children and adolescents were obtained. The conducted analysis showed that various studies so far indicate that social media can have a very strong influence on the development of eating patterns and body image in children and adolescents, which in turn may be one of the risk factors for developing obesity when promoted behaviors are not associated with a healthy lifestyle. It is also worth pointing out that social media can be used as a resource in the prevention and treatment of obesity. A closer look at this topic seems to be particularly important due to the fact that, among adults, social media is not only a very important source of information about lifestyle, but also a source of social support when people attempting to lose weight. Therefore, by increasing preventive activity in social media and using modern solutions related to social media (including the use of hashtag signs), we can have a greater impact on the health awareness of children and adolescents around the world.
Quantitative comparison of the efficacies and safety profiles of three first-line non-platinum chemotherapy regimens for advanced non-small cell lung cancer
Authors: Yang Qian-Yu , Zhu Lin , Liu Hong-Xia , Zheng Qing-Shan , Li Lu-Jin
Published: August 2022

Objectives:The purpose of this study was to quantify the efficacies and safety profiles of the three first-line non-platinum chemotherapy regimens recommended in the National Comprehensive Cancer Network guidelines.

Materials and Methods:The PubMed and Cochrane Library databases were searched comprehensively, and clinical trials involving patients with advanced non-small cell lung cancer treated with one of three first-line non-platinum regimens (gemcitabine combined with vinorelbine, gemcitabine combined with docetaxel, or gemcitabine alone) were included in the analysis. A parametric proportional hazard survival model was established to analyze the time course of overall survival (OS). The objective response rate (ORR) and incidence rates of grade 3–4 adverse events (AEs) were summarized using a single-arm meta-analysis with a random-effects model.

Results:Seventeen studies met the inclusion criteria. Age and performance status (PS) scores were significant predictors of OS. For each 10-years increase in age, mortality risk increased by 18.5%, and the mortality risk increased by 4% for every 10% increase in the proportion of patients with a PS score of 2. After correcting for the above factors, we found that the three first-line non-platinum chemotherapy regimens did not differ based on OS or toxicity.

Conclusion:There was no significant difference in OS or toxicity among the three first-line non-platinum chemotherapy regimens. Age and PS scores were significant predictors of OS, and their heterogeneity across different studies should be considered in cross-study comparisons and sample size estimations when designing clinical trials.
Study on plasma metabolomics for HIV/AIDS patients treated by HAART based on LC/MS-MS
Authors: Lao Donghui , Liu Rong , Liang Jianying
Published: August 2022

Background: Metabolomics can be applied to the clinical diagnosis and treatment evaluation of acquired immune deficiency syndrome (AIDS). AIDS biomarkers have become a new direction of AIDS research providing clinical guidance for diagnosis.

Objective: We sought to apply both untargeted and targeted metabolomic profiling to identify potential biomarkers for AIDS patients.

Methods: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) based untargeted metabolomic profiling was performed on plasma samples of patients before and after highly active antiretroviral therapy (HAART) treatment as well as healthy volunteers to identify potential AIDS biomarkers. Targeted quantitative analysis was performed on the potential biomarkers screened from untargeted metabolic profiling for verification.

Results: Using the Mass Profiler Professional and the MassHunter, several potential biomarkers have been found by LC-MS/MS in the untargeted metabolomic study. High-resolution MS and MS/MS were used to analyze fragmentation rules of the metabolites, with comparisons of related standards. Several potential biomarkers have been identified, including PS(O-18:0/0:0), sphingosine, PE (21:0/0:0), and 1-Linoleoyl Glycerol. Targeted quantitative analysis showed that sphingosine and 1-Linoleoyl Glycerol might be closely related to HIV/AIDS, which may be the potential biomarkers to the diagnosis.

Conclusion: We conducted untargeted metabolomic profiling, which indicates that several metabolites should be considered potential biomarkers for AIDS patients. Further targeted metabolomic research verified that d-Sphingosine and 1-Linoleoyl glycerol as the diagnostic biomarker of AIDS.
System Xc−/GSH/GPX4 axis: An important antioxidant system for the ferroptosis in drug-resistant solid tumor therapy
Authors: Li Feng-Jiao , Long Hui-Zhi , Zhou Zi-Wei , Luo Hong-Yu , Xu Shuo-Guo , Gao Li-Chen
Published: August 2022

The activation of ferroptosis is a new effective way to treat drug-resistant solid tumors. Ferroptosis is an iron-mediated form of cell death caused by the accumulation of lipid peroxides. The intracellular imbalance between oxidant and antioxidant due to the abnormal expression of multiple redox active enzymes will promote the produce of reactive oxygen species (ROS). So far, a few pathways and regulators have been discovered to regulate ferroptosis. In particular, the cystine/glutamate antiporter (System Xc−), glutathione peroxidase 4 (GPX4) and glutathione (GSH) (System Xc−/GSH/GPX4 axis) plays a key role in preventing lipid peroxidation-mediated ferroptosis, because of which could be inhibited by blocking System Xc−/GSH/GPX4 axis. This review aims to present the current understanding of the mechanism of ferroptosis based on the System Xc−/GSH/GPX4 axis in the treatment of drug-resistant solid tumors.
Arecae pericarpium water extract alleviates chronic pancreatitis by deactivating pancreatic stellate cells
Authors: Kweon Bitna , Kim Dong-Uk , Oh Jin-Young , Oh Hyuncheol , Kim Youn-Chul , Mun Yeun-Ja , Bae Gi-Sang , Park Sung-Joo
Published: August 2022

Chronic pancreatitis (CP) is a chronic inflammatory disease of the pancreas with irreversible morphological changes. Arecae pericarpium (ARP), known to improve gastrointestinal disorders, has not yet been reported to inhibit fibrosis in CP. Therefore, we investigated the beneficial effects of ARP on cerulein-induced CP. Cerulein (50 μg/kg) was administered intraperitoneally to mice every hour, six times a day, four times a week for a total of 3 weeks to induce CP. To ascertain the prophylactic effects of ARP, ARP water extract (50, 100, or 200 mg/kg) or saline was administered intraperitoneally 1 h before the onset of CP. To determine the therapeutic effects of ARP, ARP water extract (200 mg/kg) or saline was administered for a total of 1 week or 2 weeks, starting 2 weeks or 1 week after the onset of CP. The pancreas was collected immediately for histological analysis. Additionally, to determine the effectiveness and mechanism of ARP in alleviating pancreatic fibrosis, pancreatic stellate cells (PSCs) were isolated. ARP treatment considerably improved glandular atrophy and inflammation and repressed collagen deposition in the pancreas. Furthermore, ARP water extract inhibited extracellular matrix (ECM) constituents such as alpha-smooth muscle actin (α-SMA), collagen I, and fibronectin 1 (FN1) in pancreatic tissue and PSCs. ARP also suppressed transforming growth factor-β (TGF-β) signaling by inhibiting Smad2 phosphorylation. Our study suggests that ARP exhibits anti-fibrotic effects in cerulein-induced CP by inhibiting TGF-β/Smad signaling.
Treatment options of traditional Chinese patent medicines for dyslipidemia in patients with prediabetes: A systematic review and network meta-analysis
Authors: Jiang Li , Wang Shidong , Zhao Jinxi , Chien Chieh , Zhang Yaofu , Su Guanxun , Chen Xiaoyu , Song Dechao , Chen Yu , Huang Weijun , Xiao Yonghua , Cao Yandong , Hu Zixian
Published: August 2022

Objective: To compare the clinical efficacy and safety of SIX Traditional Chinese Patent Medicines (TCPM) recommended by guidelines in improving lipids for patients with prediabetes by network meta-analysis.

Methods: Randomized controlled trials of 6 TCPM in the treatment of prediabetes were searched systematically in various databases. After extracting effective data, the risk of bias was assessed using Review Manager 5.3 and Cochrane Collaboration Systems Evaluator’s Manual. Network meta-analysis was performed using STATA 15.0 based on the frequency statistical model. The effect size and credibility of the evidence for the intervention were summarized based on a minimal contextualized framework.

Results: A total of 27 studies involving 2,227 patients were included. Compared with lifestyle modification (LM), Shenqi + LM [SMD −0.49 (95% CI: −0.85, −0.12)] and Jinqi + LM [SMD −0.44 (95% CI: −0.81, −0.06)] showed statistically significant effect in lowering TG, Shenqi + LM [SMD −0.51 (95%CI: −0.86, −0.17)] and Jinqi + LM [SMD −0.44 (95%CI: −0.80, −0.08)] in lowering TC, Jinlida + LM [SMD −0.31 (95%CI: −0.59, −0.04)] in lowering LDL-C, Shenqi + LM [SMD 0.29 (95%CI: 0.06, 0.51)] and Jinqi + LM [SMD 0.16 (95%CI: 0.01, 0.31)] in increasing HDL-C.

Conclusion: For patients with prediabetes, Traditional Chinese patent medicine Jinqi and Shenqi combined with lifestyle modification were associated with a significant reduction in TG and TC, while Shenqi + LM was among the most effective. Jinlida + LM was among the least effective.

Systematic Review Registration:https://clinicaltrials.gov/, identifier PROSPERO(CRD42021279332).
Comparison of prognosis between neoadjuvant imatinib and upfront surgery for GIST: A systematic review and meta-analysis
Authors: Liu Zhen , Zhang Zimu , Sun Juan , Li Jie , Zeng Ziyang , Ma Mingwei , Ye Xin , Feng Fan , Kang Weiming
Published: August 2022

Background: Significant survival benefit of adjuvant imatinib therapy has been observed in gastrointestinal stromal tumor (GIST). However, the impact of neoadjuvant imatinib on prognosis of GIST remains unclear. This meta-analysis aimed to compare the prognostic impact between upfront surgery and neoadjuvant imatinib plus surgery on GIST.

Methods: A comprehensive literature search was performed to identify eligible studies up to 30 Sep 2021, through PubMed, Embase, Web of Science, and Cochrane Library. Studies compared the impact of upfront surgery and neoadjuvant imatinib plus surgery on disease-free (DFS) or overall survival (OS) in patients with GIST were selected.

Results: Seven eligible studies with 17,171 patients were included. The reduction rates of tumor size in rectal and mixed site GIST were 33% and 29.8%, respectively. Neoadjuvant imatinib was not significantly associated with DFS compared with no-neoadjuvant therapy in rectal GIST (HR: 0.71, 95% CI: 0.35–1.41). The OS of rectal GIST was significantly improved by neoadjuvant imatinib compared with no-neoadjuvant therapy (HR: 0.36, 95% CI: 0.17–0.75).

Conclusion: Neoadjuvant imatinib therapy contributed to tumor shrinkage and R0 resection of rectal GIST. Neoadjuvant imatinib plus surgery significantly improved overall survival of rectal GIST in comparison with upfront surgery.
Population pharmacokinetics of intravenous colistin sulfate and dosage optimization in critically ill patients
Authors: Xie Yue-liang , Jin Xin , Yan Shan-shan , Wu Cui-fang , Xiang Bi-xiao , Wang Hui , Liang Wu , Yang Bing-chang , Xiao Xue-fei , Li Zhi-ling , Pei Qi , Zuo Xiao-cong , Peng Yue
Published: August 2022

Aims: To explore the population pharmacokinetics of colistin sulfate and to optimize the dosing strategy for critically ill patients.

Methods: The study enrolled critically ill adult patients who received colistin sulfate intravenously for more than 72 h with at least one measurement of plasma concentration. Colistin concentrations in plasma or urine samples were measured by ultraperformance liquid chromatography tandem mass spectrometry (LC-MS/MS). The population pharmacokinetics (PPK) model for colistin sulfate was developed using the Phoenix NLME program. Monte Carlo simulation was conducted to evaluate the probability of target attainment (PTA) for optimizing dosing regimens.

Results: A total of 98 plasma concentrations from 20 patients were recorded for PPK modeling. The data were adequately described by a two-compartment model with linear elimination. During modeling, creatinine clearance (CrCL) and alanine aminotransferase (ALT) were identified as covariates of the clearance (CL) and volume of peripheral compartment distribution (V2), respectively. In addition, colistin sulfate was predominantly cleared by the nonrenal pathway with a median urinary recovery of 10.05% with large inter-individual variability. Monte Carlo simulations revealed a greater creatinine clearance associated with a higher risk of sub-therapeutic exposure to colistin sulfate. The target PTA (≥90%) of dosage regimens recommended by the label sheet was achievable only in patients infected by pathogens with MIC ≤0.5 mg/L or with renal impairments.

Conclusion: Our study showed that the dose of intravenous colistin sulfate was best adjusted by CrCL and ALT. Importantly, the recommended dosing regimen of 1.0–1.5 million units daily was insufficient for patients with normal renal functions (CrCL ≥80 ml/min) or those infected by pathogens with MIC ≥1.0 mg/L. The dosage of colistin sulfate should be adjusted according to renal function and drug exposure.
Identification of hepatoprotective traditional Chinese medicines based on the structure–activity relationship, molecular network, and machine learning techniques
Authors: He Shuaibing , Yi Yanfeng , Hou Diandong , Fu Xuyan , Zhang Juan , Ru Xiaochen , Xie Jinlu , Wang Juan
Published: August 2022

The efforts focused on discovering potential hepatoprotective drugs are critical for relieving the burdens caused by liver diseases. Traditional Chinese medicine (TCM) is an important resource for discovering hepatoprotective agents. Currently, there are hundreds of hepatoprotective products derived from TCM available in the literature, providing crucial clues to discover novel potential hepatoprotectants from TCMs based on predictive research. In the current study, a large-scale dataset focused on TCM-induced hepatoprotection was established, including 676 hepatoprotective ingredients and 205 hepatoprotective TCMs. Then, a comprehensive analysis based on the structure–activity relationship, molecular network, and machine learning techniques was performed at molecular and holistic TCM levels, respectively. As a result, we developed an in silico model for predicting the hepatoprotective activity of ingredients derived from TCMs, in which the accuracy exceeded 85%. In addition, we originally proposed a material basis and a drug property-based approach to identify potential hepatoprotective TCMs. Consequently, a total of 12 TCMs were predicted to hold potential hepatoprotective activity, nine of which have been proven to be beneficial to the liver in previous publications. The high rate of consistency between our predictive results and the literature reports demonstrated that our methods were technically sound and reliable. In summary, systematical predictive research focused on the hepatoprotection of TCM was conducted in this work, which would not only assist screening of potential hepatoprotectants from TCMs but also provide a novel research mode for discovering the potential activities of TCMs.
Efficacy of Ficus tikoua Bur. extract in ethylene glycol-induced urolithiasis model in SD rats
Authors: Bervinova Arina V. , Palikov Viktor A. , Mikhailov Evgeny S. , Palikova Yulia A. , Borozdina Natalya A. , Kazakov Vitaly A. , Rudenko Pavel A. , Tukhovskaya Elena A. , Dyachenko Igor A. , Slashcheva Gulsara A. , Goryacheva Natalya A. , Sadovnikova Elena S. , Kravchenko Irina N. , Kalabina Elena A. , Shinelev Maksim V. , Wu Peng , Murashev Arkady N.
Published: August 2022

The development of new herbal preparations for the treatment of urolithiasis is an urgent task of medical science. Ficus have attracted the attention of pharmacologists due to a wide range of biological properties, including antioxidant, anti-inflammatory, antibacterial and antifungal activity. We studied the effectiveness of Ficus tikoua Bur. in SD rats in which urolithiasis was induced by 6 weeks of oral administration of ethylene glycol 0.5% ad libitum instead of drinking water. Administration of the extract of Ficus tikoua Bur., as well as comparative drug Cystone® after modeling of urolithiasis lead to the restoration of diuresis and the concentration of inorganic phosphates starting from the 6th week of the experiment. The use of the Ficus tikoua Bur. extract for 6 weeks, both during the modeling of urolithiasis and during the recovery period, led to the restoration of the percentage of lymphocytes in the blood, content of sodium, chlorine and inorganic phosphates in the blood to the control level. Thus, the extract of Ficus tikoua Bur. seems to be a promising drug for effective treatment of the initial stages of the development of urolithiasis.
Medicine-related problems: A recurrent issue among residents living in nursing homes
Authors: Dorj Gereltuya , Lim Renly , Ellett Lisa Kalisch , Kelly Thu-Lan , Andrade Andre , Widagdo Imaina , Pratt Nicole , Bilton Rebecca , Roughead Elizabeth
Published: August 2022

Aim: To examine the incidence and nature of medicine-related problems over time experienced by nursing home residents.

Method: We analyzed records collected in the Reducing Medicine-Induced Deterioration and Adverse Events (ReMInDAR) trial. The trial pharmacists provided services to reduce medicine-induced deterioration and adverse reactions for residents every 8-weeks over a year. The problems identified by the pharmacists were documented in reports and subsequently classified independently by research pharmacists using the D.O.C.U.M.E.N.T system. The number and type of problems at each service and time to develop a new problem post first session were assessed. All analyses were performed using R software (Version 4.1.1).

Results: The cohort was 115 nursing home residents who received 575 services. In the 12-months, a total of 673 medicine-related problems or symptom reports were identified in 112 residents. Most residents (75%) experienced a new medicine-related problem by the fourth month post the first assessment. After the first session, the proportion of residents with a new medicine-related problem or symptom report declined at each repeated pharmacy session (59% at visit 2 vs. 28% at visit 6, p < 0.01).

Conclusion: Residents living in nursing homes frequently experience medicine-related problems. Our results suggest clinical pharmacist services performed every 4-months may have the potential to reduce the medicine-related problems in nursing homes.
Review of phytomedicine, phytochemistry, ethnopharmacology, toxicology, and pharmacological activities of Cymbopogon genus
Authors: Tibenda Jonnea Japhet , Yi Qiong , Wang Xiaobo , Zhao Qipeng
Published: August 2022

The Cymbopogon genus belongs to the Andropoganeae family of the family Poaceae, which is famous for its high essential oil concentration. Cymbopogon possesses a diverse set of characteristics that supports its applications in cosmetic, pharmaceuticals and phytotherapy. The purpose of this review is to summarize and connect the evidence supporting the use of phytotherapy, phytomedicine, phytochemistry, ethnopharmacology, toxicology, pharmacological activities, and quality control of the Cymbopogon species and their extracts. To ensure the successful completion of this review, data and studies relating to this review were strategically searched and obtained from scientific databases like PubMed, Google Scholar, ResearchGate, ScienceDirect, and Elsevier. Approximately 120 acceptable reviews, original research articles, and other observational studies were included and incorporated for further analysis. Studies showed that the genus Cymbopogon mainly contained flavonoids and phenolic compounds, which were the pivotal pharmacological active ingredients. When combined with the complex β-cyclodextrin, phytochemicals such as citronellal have been shown to have their own mechanism of action in inhibiting the descending pain pathway. Another mechanism of action described in this review is that of geraniol and citral phytochemicals, which have rose and lemon-like scents and can be exploited in soaps, detergents, mouthwash, cosmetics, and other products. Many other pharmacological effects, such as anti-protozoal, anti-bacterial, anti-inflammatory and anti-cancer have been discussed sequentially, along with how and which phytochemicals are responsible for the observed effect. Cymbopogon species have proven to be extremely valuable, with many applications. Its phytotherapy is proven to be due to its rich phytochemicals, obtained from different parts of the plant like leaves, roots, aerial parts, rhizomes, and even its essential oils. For herbs of Cymbopogon genus as a characteristic plant therapy, significant research is required to ensure their efficacy and safety for a variety of ailments.