bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality Status Analysis and Intrinsic Connection Research of Growing place, Morphological Characteristics, and Quality of Chinese Medicine: Cyperi Rhizoma (Xiangfu) as a Case Study
Authors: Lu Junrong , Li Wenbing , Xu Na , Yao Peifen , Wang Shengpeng , Fu Chaomei , Pei Jin , Chen Hulan , Wang Shu
Published: March 2022

Aim of the Study. We set out to investigate the quality status of CR in China objectively according to the Chinese Pharmacopeia (ChP). We also explored the correlation between its growth area, morphological characteristics, and quality by analyzing physical and chemical indexes from 47 batches of CR collected from 12 provinces belonging to six geographic divisions. Materials and Methods. The macroscopic characteristics of CR as well as its moisture, ethanol extract, essential oil, total ash, and acid-insoluble ash contents were examined and calculated. In addition, qualitative identification and quantitative determination of α-cyperone, cyperotundone, and nootkatone were simultaneously performed, and a high-performance liquid chromatography (HPLC) fingerprint chromatogram was established. Inductively coupled plasma mass spectrometry and gas chromatography methods recorded in ChP were used to measure the contents of residues of heavy metal and deleterious elements as well as residues of organochlorine pesticide, respectively. Hierarchical cluster analysis and typical canonical correlation analysis were performed using Origin 9.1 and SPSS 23.0 to explore the correlation between CR’s growth area, morphological characteristics, and quality. Results. Of the 47 batches of CR analyzed, only 4 collected from the province of Shandong had a flat appearance, which did not accord with the macroscopic characteristics of CR. Overall, only 4 batches met ChP standards for CR. In addition, 30 and 38 batches did not meet the requirements for moisture content and essential oil content, respectively. The similarity values of HPLC fingerprints ranged from 0.568 to 0.986. Results of hierarchical cluster analysis for ethanol extracts, essential oil, α-cyperone, cyperotundone, and nootkatone and the HPLC fingerprints (total peak time and peak area) suggested that the samples could be classified into four clusters, with no significant difference in growth geographic areas among them. Results of canonical correlation analysis indicated that the first canonical pair could represent the correlation between macroscopic characteristics (vector 1) and chemical quality (vector 2), with shorter diameter and length denoting lower ethanol extract content and higher nootkatone content in a single grain of CR. Conclusions. Crude medicinal materials were collected and examined in this study to reflect the overall quality status of CR in China. The methods chosen to detect, calculate, and analyze the quality of CR were suitable to the investigation, and the results are crucial not only for estimating the current quality status of CR, but also for conducting further research into its cultivation, quality assurance, and commodity specification. Besides, this mode of investigation could be used to evaluate other medicines.
Chemotherapy of Capecitabine plus Temozolomide for Refractory Pituitary Adenoma after Tumor Resection and Its Impact on Serum Prolactin, IGF-1, and Growth Hormone
Authors: Wang Xirui , Hu Changwei , Li Yabin , Ren Baowen , Yin Gangfeng
Published: March 2022

Objective. To investigate the efficiency of capecitabine (CAP) plus temozolomide (TEM) in refractory pituitary adenoma after tumor resection and its impact on serum prolactin (PRL), insulin-like growth factor 1 (IGF-1), and growth hormone (GH) levels. Methods. From January 2017 to January 2020, 80 patients assessed for eligibility receiving transsphenoidal tumor resection for refractory pituitary adenoma in the Department of Neurosurgery of our hospital were recruited. They were randomly distributed at a ratio of 1 : 1 via the random number table method to receive either bromocriptine and TEM (control group) or bromocriptine plus combination chemotherapy of TEM and CAP (study group). The two groups were compared in terms of clinical efficacy and serum levels of PRL, IGF-1, and GH. Results. The objective response rate (ORR) was 87.50% and 67.50% in the study group and the control group, respectively

P
=
0.032

. Before treatment, two groups had similar levels of PRL, IGF-1, and GH. After treatment, PRL levels in the study group were lower than that in the control group (278.35 ± 39.25 versus 326.35 ± 42.45,

P
<
0.001

). Compared with the control group, IGF-1 levels in the study group were also lower (311.78 ± 28.82 versus 364.35 ± 31.35,

P
<
0.001

). The study group presented markedly lower levels of thyroid-stimulating hormone (TSH) and higher serum levels of free thyroxine-4 (FT-4) and adrenocorticotropic hormone (ACTH) versus the control group

P
<
0.05

. The incidence of adverse events was comparable between the study group (30.0%) and the control group (22.5%)

P
>
0.05

. All eligible patients had similar progression-free survival (PFS) after chemotherapy. Conclusion. For patients with refractory pituitary adenoma, the combination chemotherapy of CAP and TEM significantly improves clinical outcomes and corrects hormonal disturbances, with a good safety profile, but its long-term efficacy requires further investigation.
Bile Acids and the Microbiome: Making Sense of This Dynamic Relationship in Their Role and Management in Crohn’s Disease
Authors: Kumar Aditi , Al-Hassi Hafid O. , Steed Helen , Phipps Oliver , Brookes Matthew J.
Published: March 2022

Background. Bile acids help maintain the physiological balance of the gut microbiome and the integrity of the intestinal epithelial barrier. Similarly, intestinal bacteria play a major role in bile acid metabolism as they are involved in crucial biotransformation steps in the enterohepatic circulation pathway. Understanding the relationship between bile acid signalling and the gut microbiome in Crohn’s disease can help target new and innovative treatment strategies. Aims. This review summarises the relationship between bile acids and the microbiome in Crohn’s disease and discusses potential novel therapeutic options. Methods. We performed a literature review on bile acid signalling, its effect on the gut microbiome, and therapeutic applications in Crohn’s disease. Results. Current research suggests that there is a strong interplay between the dysregulated microbiota, bile acid metabolism, and the mucosal immune system that can result in a changed immunological function, triggering the inflammatory response in Crohn’s disease. Recent studies have demonstrated an association with altering the enterohepatic circulation and activating the farnesoid X receptor signalling pathway with the use of probiotics and faecal microbial transplantation, respectively. Bile acid sequestrants have been shown to have anti-inflammatory, cytoprotective, and anti-apoptotic properties with the potential to alter the intestinal microbial composition, suggesting a possible role in inducing and maintaining Crohn’s disease. Conclusions. Active Crohn’s disease has been correlated with changes in bacterial concentrations, which may be associated with changes in bile acid modification. Further research should focus on targeting these areas for future therapeutic options.
[Retracted] The Exponentiated Exponential‐Inverse Weibull Model: Theory and Application to COVID‐19 Data in Saudi Arabia
Authors: Badr Majdah Mohammed , Sobahi Ghaida
Published: March 2022

The purpose of this study is to introduce a new T‐X family lifetime distribution known as exponentiated exponential‐inverse Weibull, and we refer to this distribution as EE‐IW. The new model’s basic mathematical characteristics are studied. The maximum likelihood (ML) estimator (MLE) approach is used to estimate the parameters. A Monte Carlo simulation is done to examine the behavior of the estimators. Finally, a real‐world dataset is utilized to show the utility of the proposed model in many industries and to compare it to well‐known distributions.
Data-Driven Optimal Scheduling Algorithm of Human Resources in Colleges and Universities
Authors: Liu Cong
Published: March 2022

At present, the development process of human resource management in Colleges and universities in China has gone through a period of time. In the whole process, the mode of human resource management in colleges and universities is gradually maturing, but there are also some problems. In this paper, data-driven stochastic optimal scheduling algorithm and robust optimal scheduling algorithm are used to model and analyze the human resources. Then, the two models are applied to the human resource management of Nanjing University and Southeast University. The data optimization results show that the robust optimal scheduling algorithm is helpful to the management of new teachers, while the random optimal scheduling algorithm can improve the management of teachers who have been in service for a long time, but there are still some disadvantages. If the combination of two data-driven scheduling algorithms is adopted, it can manage the human resources of colleges and universities well. In short, this paper provides some theoretical and experimental support for the specific application of data-driven human resources optimal scheduling algorithm in colleges and universities.
Genome Assembly and Genome Annotation of Leishmania martiniquensis Isolated from a Leishmaniasis Patient in Thailand
Authors: Anuntakarun Songtham , Phumee Atchara , Sawaswong Vorthon , Praianantathavorn Kesmanee , Poomipak Witthaya , Jitvaropas Rungrat , Siriyasatien Padet , Payungporn Sunchai
Published: March 2022

Leishmaniasis is a parasitic disease caused by Leishmania spp. with worldwide distribution. Autochthonous leishmaniasis has been reported to result from the infection by Leishmania martiniquensis in Thailand. This species was isolated in culture and subjected to high-throughput whole-genome sequencing. A total of 30.8 Mb in 36 chromosomes of the whole genome was assembled, annotated, and characterized. The L. martiniquensis under study was shown to segregate into the same clade and thus closely related to the previously identified L. martiniquensis (LU_Lmar_1.0), as determined by phylogenetic analysis of their genomic sequences along with those of representative kinetoplastid species. The total number of open reading frames genomewide predicts 8,209 protein-coding genes, of which 359 are putative virulence factors, including two previously known, e.g., cysteine proteinase C and superoxide dismutase B1. The results obtained from this study will be useful for further annotation and comparison with other Leishmania martiniquensis in the future.
A Nonlinear Prediction Model of Antislide Pile Top Displacement Based on MIC‐SVR for Jurassic Landslides
Authors: Huang Zhiping , Dong Manman , Du Xi , Guan Yongping
Published: March 2022

In this study, a nonlinear prediction model of antislide pile top displacement is proposed. Based on the quantitative analysis of the rock mass structure characteristics of the soft and hard interbedded sliding bed in the Jurassic strata, the post‐thrust force and geometric characteristics of the top of antislide pile displacement, and bending moment, the main controlling factors affecting the displacement of the top of antislide pile were determined by maximal information coefficient (MIC). Through orthogonal experiment design and 3DEC numerical experiment, a database of main controlling factors (sliding bedrock inclination, thrust size, embedded depth, and pile section size) of pile top displacement was established and a nonlinear prediction model of the displacement of the top of antislide pile based on the main controlling factors was proposed. Finally, two engineering examples were used to validate the performance of this model, with the comparisons of four prediction methods (SVR, MIC‐SVR, LSTM, and ELMAN). The results show that the MIC‐SVR model has a practical reference value for the prediction of the displacement of the top of an antislide pile in the Jurassic landslide in the Three Gorges Reservoir Area.
Association of Insulin Resistance and Elevated Androgen Levels with Polycystic Ovarian Syndrome (PCOS): A Review of Literature
Authors: Xu Yalan , Qiao Jie
Published: March 2022

The polycystic ovary syndrome (PCOS) is the disease featured by elevated levels of androgens, ovulatory dysfunction, and morphological abnormalities. At reproductive stage of women, the rate of PCOS occurrence is measured as 6–10% and the prevalence rate may be double. There are different pathophysiological factors involved in PCOS, and they play a major role in various abnormalities in individual patient. It is clear that there is noteworthy elevation of androgen in PCOS, causing substantial misery and infertility problems. The overexposure of androgen is directly linked with insulin resistance and hyperinsulinaemia. It has been reported previously that PCOS is related to cardiac metabolic miseries and potently increases the risk of heart diseases. Endometrial cancer is also a serious concern which is reported with exceedingly high incidence in women with PCOS. However, the overexposure of androgen has direct and specific influence on the development of insulin resistance. Although many factors are involved, resistance to the insulin and enhanced level of androgen are considered the major causes of PCOS. In the present review, we have focused on the pathophysiology and major revolutions of insulin resistance and excessive levels of androgen in females with PCOS.
Natural Adrenocorticotropic Hormone (ACTH) Relieves Acute Inflammation in Gout Patients by Changing the Function of Macrophages
Authors: Xu Rui , Zhao Li , Liu Jiyu , Cao Lin , Zhao Tianyi , Yu Yiyun , Xuan Dandan , Wan Weiguo , Xue Yu , Zou Hejian
Published: March 2022

Gout is a common arthritis caused by deposition of monosodium urate crystals. Macrophage is crucial in the process of monosodium urate (MSU)-induced inflammation. Although it has been reported that adrenocorticotropic hormone (ACTH) in nature can be used to cure urarthritis, the mechanism concerning macrophage is still not clear. However, gout patients manifest other complications, such as hypertension, diabetes, chronic kidney disease, and hormone intolerance, which limit efficacy of some of these first-line drugs. Therefore, this study aims to explore how natural ACTH can alleviate urarthritis through functional changes in macrophage. We analyzed the variations in VAS pain scores of five patients, knowing the time of action and detecting the level of cortisol and ACTH in patients 24 hours after the application of ACTH. The effect of natural ACTH on joint inflammation and the level of cortisol in blood in the mouse model was evaluated by studies in vivo. In vitro studies, we evaluated the effect of natural ACTH on macrophages and revealed different functions of ACTH and dexamethasone on macrophages in the transcriptional level. In patients with acute gout, natural ACTH can quickly alleviate pain and does not affect the level of cortisol and ACTH. Natural ACTH is able to ease the swelling and inflammatory cell infiltration caused by arthritis, without changing the level of cortisol. Besides, natural ACTH in vitro can alleviate acute gouty inflammation by regulating phagocytosis and polarization of macrophage, which also exerts different effects on the transcription of some related genes. Natural ACTH is able to alleviate acute gouty inflammation by regulating macrophage, and this effect differs from that of dexamethasone at the transcriptional level.
Mass Spectrometric Behavior and Molecular Mechanisms of Fermented Deoxyanthocyanidins to Alleviate Ulcerative Colitis Based on Network Pharmacology
Authors: Bai Yunpeng , Wang Guangwen , Lan Jinhua , Wu Ping , Liang Guowu , Huang Jinhui , Wu Zheng , Wang Yirong , Chen Chunbo
Published: March 2022

Aims. Ulcerative colitis (UC) is a type of chronic idiopathic inflammatory bowel disease with a multifactorial pathogenesis and limited treatment options. The aim of the present study is to investigate the hydrogen deuterium exchange mass spectrometry (HDX-MS) behaviors of fermented deoxyanthocyanidins and their molecular mechanisms to alleviate UC by using quantum chemistry and network pharmacology. Methods. Tandem MS indicated at least two fragmentation pathways through which deuterated vinylphenol-deoxyanthocyanidins could generate different product ions. Quantum calculations were conducted to determine the transition states of the relevant molecules and analyze their optimized configuration, vibrational characteristics, intrinsic reaction coordinates, and corresponding energies. The potential targets of deoxyanthocyanidins in UC were screened from a public database. The R package was used for Gene Ontology (GO) and KEGG pathway analyses, and the protein–protein interactions (PPIs) of the targets were assessed using Search Tool for the Retrieval of Interacting Genes (STRING). Finally, molecular docking was implemented to analyze the binding energies and action modes of the target compounds through the online tool CB-Dock. Results. Quantum calculations indicated two potential fragmentation pathways involving the six-membered ring and dihydrogen cooperative transfer reactions of the vinylphenol-deoxyanthocyanidins. A total of 146 and 57 intersecting targets of natural and fermented deoxyanthocyanidins were separately screened out from the UC database and significant overlaps in GO terms and KEGG pathways were noted. Three shared hub targets (i.e., PTGS2, ESR1, and EGFR) were selected from the two PPI networks by STRING. Molecular docking results showed that all deoxyanthocyanidins have a good binding potential with the hub target proteins and that fermented deoxyanthocyanidins have lower binding energies and more stable conformations compared with natural ones. Conclusions. Deoxyanthocyanidins may provide anti-inflammatory, antioxidative, and immune system regulatory effects to suppress UC progression. It is proposed for the first time that fermentation of deoxyanthocyanidins can help adjust the structure of the intestinal microbiota and increase the biological activity of the natural compounds against UC. Furthermore, HDX-MS is a helpful strategy to analyze deoxyanthocyanidin metabolites with unknown structures.
Craniofacial Morphology of Orthodontic Patients with and without Temporomandibular Disorders: A Cross-Sectional Study
Authors: Yan Zhe-Bin , Wan Yi-Dan , Xiao Chu-Qiao , Li Ya-Qi , Zhang Yu-Yao , An Yang , Xiong Xin
Published: March 2022

Purpose. We aimed to explore the relationship between temporomandibular disorders (TMDs) and craniofacial morphology in orthodontic patients. Methods. Altogether, 262 orthodontic patients were included and divided into two groups according to their Fonseca Anamnestic Index (FAI) scores: a no-TMD group (control group, FAI < 20) and a TMD group (FAI ≥ 20). Cephalometric parameters including cranial, maxillary, mandibular, and dental parameters were traced on cephalograms. Craniofacial morphology was compared between TMD and control groups, followed by subgroup analyses based on TMD severity, gender, age, and temporomandibular joint (TMJ) symptoms. Results. The prevalence of TMDs was 52.7% among included patients (138/262). The mean age of TMD patients was higher than that of the control group. No significant difference in gender distribution between the groups was observed. The most commonly reported FAI items were misaligned teeth, neck pain, and emotional tension. The Frankfort-mandibular plane angle (FMA) was larger in the TMD patients than in the control group, whereas no significant differences in other parameters were observed. Subgroup analysis based on TMD severity revealed that FMA and anterior facial height of moderate/severe TMD patients were significantly larger than those of mild or no-TMD patients. Among male patients, the anterior cranial base length was smaller, and the anterior facial height was larger in the TMD group. Among female patients, no significant differences in craniofacial morphology between the groups were observed. In juvenile patients, overjet and overbite were smaller in the TMD group. In adult patients, SNA, ANB, FMA, and gonial angle were larger in the TMD group. Within the TMD group, patients with TMJ pain or noises exhibited characteristic craniofacial features compared to patients without these symptoms. Conclusions. Orthodontic patients with TMDs have specific craniofacial morphology, suggesting a relationship between TMDs and particular craniofacial features in orthodontic patients.
Nitric Oxide Inhalation Therapy Attenuates Postoperative Hypoxemia in Obese Patients with Acute Type A Aortic Dissection
Authors: Zheng Ping , Jiang Dingsheng , Liu Chun , Wei Xiang , Li Shiliang
Published: March 2022

Objective. To investigate the differences between inhaled nitric oxide (iNO) treatment and conventional therapy in the treatment of postoperative hypoxemia in obese patients with acute type A aortic dissection (ATAAD). Methods. ATAAD patients diagnosed and treated with emergency surgery in our hospital from June 2017 to December 2019 were retrospectively analyzed. Patients with postoperative hypoxemia were divided into the iNO group and control group. Propensity score matching was used to analyze clinical characteristics and results of the two groups. Results. A total of 218 ATAAD patients with

BMI
≥
25

were treated with surgery. Among them, 115 patients developed refractory hypoxemia (64 in the control group and 51 in the iNO group). Patients in the iNO group had significantly shorter invasive mechanical ventilation time, intensive care unit (ICU) stay, and hospital stay. After 6 h of iNO treatment, the PaO2/FiO2 ratio in the iNO group increased significantly, and this ratio was higher than that in the control group at 6, 12, 24, 48, and 72 h after treatment. Conclusion. Low-dose iNO could improve oxygenation and shorten mechanical ventilation and ICU stay in patients with hypoxemia after ATAAD surgery, but without significant side effects or increase in postoperative mortality or morbidity. These findings provide a basis for a randomized multicenter controlled trial to assess the efficacy of iNO in the treatment of hypoxemia after ATAAD surgery.
Prevalence and Associated Factors of Poststroke Depression among Outpatient Stroke Patients Who Have a Follow-Up at the Outpatient Neurology Clinic of Zewditu Memorial Hospital in Addis Ababa, Ethiopia
Authors: Wubshet Tsion Yehualashet , Geberemichael Sisay Gizaw , Adilo Takle Menna , Arusi Temesgen Tantu , Gutulo Muluken Gunta , Assefa Dereje Zewdu , Asfaw Mekete Wondesen
Published: March 2022

Background. Poststroke depression is the most common and burdensome poststroke psychiatric complication. Studies showed discrepancies in reporting frequencies and risk factors for poststroke depression. Updated local data are relevant for efficient strategies of poststroke depression screening and prevention. Objectives. To determine the prevalence and associated factors of poststroke depression among outpatient stroke patients from the outpatient neurology clinic of Zewditu Memorial Hospital in Addis Ababa, Ethiopia. Methods. An institution-based cross-sectional study was conducted on 249 stroke patients. Data was collected through structured questionnaire using interviews and a review of medical charts. PHQ-9 depression questionnaire was used to diagnose poststroke depression. Descriptive analysis was used to see the nature of the characteristics of interests. Bivariate analysis was used to sort out variables at

p

values less than 0.05 for multivariate logistic regression. Significance level was obtained using an odds ratio with 95% CI and

p

value < 0.05. Results. Point prevalence for poststroke depression was 27.5 percent. Female gender, unemployment, low social support level, diabetes mellitus, and poststroke period under 2 years were statistically significant and independent predictors for poststroke depression. Conclusions. The point prevalence estimate of poststroke depression was comparable with other studies. Low social support levels increased the odds for poststroke depression by more than eight folds. It appeared that external factors are more important in the pathogenesis of poststroke depression in the African population. Detection and prevention programs should consider disparities of poststroke depression incidence and risk factors.
Modeling and Analysis of the Relationship between Aerobic Exercise and Obesity Reduction in Adolescents
Authors: Fu Nan , Li Kesen
Published: March 2022

In order to solve the relationship between youth aerobic exercise and obesity reduction, an improved ant colony algorithm-oriented aerobic exercise method was proposed. Firstly, the changes in body shape, weight, BMI, body fat, body circumference, and other indicators of obese adolescents before and after aerobic exercise were used as the initial pheromone distribution matrix, and the random evolution factor and evolutionary drift threshold were introduced to establish the target function of reducing obesity caused by aerobic exercise in adolescents. The constraint conditions of the relationship between aerobic exercise and adolescent obesity reduction were explained, and the particle algorithm was introduced to establish the optimal model of aerobic exercise for adolescent obesity reduction. The experimental results show that with the increasing number of experiments, the advantages of this method are more obvious. From the overall level, the average modeling error of this method is about 0.053%, while the average error of the traditional method is about 0.186%, which shows that this method can control the error within a reasonable range, and it is proved that the improved ant colony algorithm can have a good correlation with the method of aerobic exercise.
The Dual Role of USP11 in Cancer
Authors: Guo Tuanjie , Tang Heting , Yuan Zhihao , Zhang Encheng , Wang Xiang
Published: March 2022

Ubiquitination is one of the most crucial ways of protein degradation and plays an indispensable role in various living activities of cells. The deubiquitinating enzyme (DUB) is the main practitioner of the reversal of ubiquitination. Up till the present moment, nearly 100 DUBs from six families have been confirmed. USP11 is a member of the largest subfamily of cysteine protease DUBs, involving in the regulation of cell cycle, DNA repair, regulating signaling pathways, tumor development, and other important biological behaviors. This review briefly describes the structure and function of USP11 and comprehensively describes its dual role in tumorigenesis and development, as well as its targeted therapy.
Loss of H3K27 Trimethylation Promotes Radiotherapy Resistance in Medulloblastoma and Induces an Actionable Vulnerability to BET Inhibition
Authors: Gabriel Nishanth , Balaji Kumaresh , Jayachandran Kay , Inkman Matthew , Zhang Jin , Dahiya Sonika , Goldstein Michael
Published: March 2022

Medulloblastoma has been categorized into four subgroups based on genetic, epigenetic, and transcriptional profiling. Radiation is used for treating medulloblastoma regardless of the subgroup. A better understanding of the molecular pathways determining radiotherapy response could help improve medulloblastoma treatment. Here, we investigated the role of the EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit)-dependent histone H3K27 trimethylation in radiotherapy response in medulloblastoma. The tumors in 47.2% of patients with group 3 and 4 medulloblastoma displayed H3K27me3 deficiency. Loss of H3K27me3 was associated with a radioresistant phenotype, high relapse rates, and poor overall survival. In H3K27me3-deficient medulloblastoma cells, an epigenetic switch from H3K27me3 to H3K27ac occurred at specific genomic loci, altering the transcriptional profile. The resulting upregulation of EPHA2 stimulated excessive activation of the prosurvival AKT signaling pathway, leading to radiotherapy resistance. Bromodomain and extraterminal motif (BET) inhibition overcame radiation resistance in H3K27me3-deficient medulloblastoma cells by suppressing H3K27ac levels, blunting EPHA2 overexpression, and mitigating excessive AKT signaling. In addition, BET inhibition sensitized medulloblastoma cells to radiation by enhancing the apoptotic response through suppression of Bcl-xL and upregulation of Bim. This work demonstrates a novel mechanism of radiation resistance in medulloblastoma and identifies an epigenetic marker predictive of radiotherapy response. On the basis of these findings, we propose an epigenetically guided treatment approach targeting radiotherapy resistance in patients with medulloblastoma.

Significance:

This study demonstrates a novel epigenetic mechanism of radiation resistance in medulloblastoma and identifies a therapeutic approach to improve outcomes in these patients.
Establishing 24-Hour Urinary Sucrose Plus Fructose as a Predictive Biomarker for Total Sugars Intake
Authors: Freedman Laurence S. , Kipnis Victor , Midthune Douglas , Commins John , Barrett Brian , Sagi-Kiss Virag , Palma-Duran Susana A. , Johnston Carol S. , O’Brien Diane M. , Tasevska Natasha
Published: March 2022

Background:

Twenty-four–hour urinary sucrose and fructose (24uSF) has been studied as a biomarker of total sugars intake in two feeding studies conducted in the United Kingdom (UK) and Arizona (AZ). We compare the biomarker performance in these populations, testing whether it meets the criteria for a predictive biomarker.

Methods:

The UK and AZ feeding studies included 13 and 98 participants, respectively, aged 18 to 70 years, consuming their usual diet under controlled conditions. Linear mixed models relating 24uSF to total sugars and personal characteristics were developed in each study and compared. The AZ calibrated biomarker equation was applied to generate biomarker-estimated total sugars intake in UK participants. Stability of the model across AZ study subpopulations was also examined.

Results:

Model coefficients were similar between the two studies [e.g., log(total sugars): UK 0.99, AZ 1.03, P = 0.67], as was the ratio of calibrated biomarker person-specific bias to between-person variance (UK 0.32, AZ 0.25, P = 0.68). The AZ equation estimated UK log(total sugar intakes) with mean squared prediction error of 0.27, similar to the AZ study estimate (0.28). Within the AZ study, the regression coefficients of log(total sugars) were similar across age, gender, and body mass index subpopulations.

Conclusions:

Similar model coefficients in the two studies and good prediction of UK sugar intakes by the AZ equation suggest that 24uSF meets the criteria for a predictive biomarker. Testing the biomarker performance in other populations is advisable.

Impact:

Applications of the 24uSF biomarker will enable improved assessment of the role of sugars intake in risk of chronic disease, including cancer.

See related commentary by Prentice, p. 1151
A Contemporary Analysis of Racial and Ethnic Disparities in Diagnosis of Early-Stage Breast Cancer and Stage-Specific Survival by Molecular Subtype
Authors: Primm Kristin M. , Zhao Hui , Hernandez Daphne C. , Chang Shine
Published: March 2022

Background:

Prior studies of breast cancer disparities have focused primarily on differences between Black and White women, yet contemporary patterns of disparity for other groups are not well understood. We examine breast cancer disparities by stage at diagnosis across nine racial and ethnic groups.

Methods:

The SEER 18 registries identified 841,975 women diagnosed with breast cancer from 2000 to 2017. Joinpoint models assessed trends in diagnosis stage and survival. Multivariable logistic regression evaluated associations between race/ethnicity and diagnosis stage. Multivariable Cox models compared survival of groups by stage and molecular subtype.

Results:

Black, American Indian, Southeast Asian, South Asian, Pacific Islander, and Hispanic women were less likely than white women to be diagnosed with early stage breast cancer. Among those diagnosed at early stage, Hispanic, American Indian, Pacific Islander and Black women were 9%, 14%, 22%, and 39% (respectively) more likely than White women to die from breast cancer, whereas Asian subgroups had lower risk of death. Among those diagnosed at late stage, Black women were 18% more likely than White counterparts to die from breast cancer, and survival disparities for Black women persisted across all subtypes and stages, (except late stage HR−/HER2−). East Asian women with early stage HR+/HER2− tumors had better survival than White women.

Conclusions:

Persistent disparities in early detection and survival of breast cancer demand further work to address and reduce disparities across the cancer continuum.

Impact:

Results have implications for efforts to reduce entrenched racial and ethnic disparities in breast cancer early detection and survival.
A Digital Storytelling Intervention for Vietnamese American Mothers to Promote Their Children's HPV Vaccination
Authors: Chen Angela Chia-Chen , Kim Wonsun Sunny , Todd Michael , Larkey Linda
Published: March 2022

Despite higher rates of human papillomavirus (HPV)-associated cancer in Vietnamese Americans (VA), their vaccination rate remains low. Culturally grounded narratives incorporating culture-specific beliefs and practices may be a promising approach to promote HPV vaccination and potentially mitigate HPV-associated cancer disparities experienced by VAs. We codeveloped personal, audiovisual digital stories about HPV vaccination with VA mothers of vaccinated children, and examined the effects of the digital storytelling (DST) intervention on vaccination intention among VA mothers of unvaccinated children ages 11–14. The stories (3 minutes each) were produced in both English and Vietnamese through a 2-day workshop in collaboration with two VA first-generation immigrant mothers. A community sample of 114 VA mothers of unvaccinated children viewed the stories and filled out an anonymous survey before and after the intervention. Of these mothers (mean age = 41.5 years; SD = 5.4), 35.2% were immigrants, and about half (51%) reported having a child who received free or reduced-price lunch at school. After the intervention, changes in two items indicating mothers’ positive attitudes toward HPV vaccination were significant. Mothers’ intention to vaccinate their children increased from 53% to 74%; the difference was large (OR = 9.12; Cohen g = 0.40) and statistically significant, χ2(1, N = 114) = 17.63, P < 0.001. Mothers’ scores on the narrative quality assessment scale were high, suggesting high levels of identification and engagement with the stories. This brief intervention using digital stories was feasible and showed preliminary effects on promoting VA mothers’ intention to vaccinate their children against HPV.

Prevention Relevance:

HPV vaccination has effectively prevented its related cancers. A culturally and linguistically congruent DST intervention targeting HPV vaccination can increase mothers’ intention to vaccinate their children.

See related Spotlight, p. 419
Valproic Acid Inhibits Glial Scar Formation after Ischemic Stroke
Authors: Gao Xue , Zeb Salman , He Yuan-Yuan , Guo Yi , Zhu Yong-Ming , Zhou Xian-Yong , Zhang Hui-Ling
Published: March 2022

Introduction: Cerebral ischemia induces reactive proliferation of astrocytes (astrogliosis) and glial scar formation. As a physical and biochemical barrier, the glial scar not only hinders spontaneous axonal regeneration and neuronal repair but also deteriorates the neuroinflammation in the recovery phase of ischemic stroke. Objectives: Previous studies have shown the neuroprotective effects of the valproic acid (2-n-propylpentanoic acid, VPA) against ischemic stroke, but its effects on the ischemia-induced formation of astrogliosis and glial scar are still unknown. As targeting astrogliosis has become a therapeutic strategy for ischemic stroke, this study was designed to determine whether VPA can inhibit the ischemic stroke-induced glial scar formation and to explore its molecular mechanisms. Methods: Glial scar formation was induced by an ischemia-reperfusion (I/R) model in vivo and an oxygen and glucose deprivation (OGD)-reoxygenation (OGD/Re) model in vitro. Animals were treated with an intraperitoneal injection of VPA (250 mg/kg/day) for 28 days, and the ischemic stroke-related behaviors were assessed. Results: Four weeks of VPA treatment could markedly reduce the brain atrophy volume and improve the behavioral deficits in rats’ I/R injury model. The results showed that VPA administrated upon reperfusion or 1 day post-reperfusion could also decrease the expression of the glial scar makers such as glial fibrillary acidic protein, neurocan, and phosphacan in the peri-infarct region after I/R. Consistent with the in vivo data, VPA treatment showed a protective effect against OGD/Re-induced astrocytic cell death in the in vitro model and also decreased the expression of GFAP, neurocan, and phosphacan. Further studies revealed that VPA significantly upregulated the expression of acetylated histone 3, acetylated histone 4, and heat-shock protein 70.1B in the OGD/Re-induced glial scar formation model. Conclusion: VPA produces neuroprotective effects and inhibits the glial scar formation during the recovery period of ischemic stroke via inhibition of histone deacetylase and induction of Hsp70.1B.
Implementing an Online Program to Change Benzodiazepine Prescription: Protocol of a Hybrid Type 1 Cluster-Randomised Trial
Authors: Reis Teresa , Serra Helena , Azeredo Sofia , Xavier Miguel
Published: March 2022

Introduction: Excessive benzodiazepine (BZD) prescription has long been considered a serious mental health concern in many countries. Many interventions using different methodologies have been implemented to change BZD prescription patterns in primary health care settings, with limited positive results. Objectives: The primary objective of our study was to analyse the effectiveness and implementation process of an intervention aimed at changing BZD prescription patterns in a primary health care setting in Portugal. Methodology: We chose as methodology an effectiveness-implementation hybrid type 1 intervention. Our intervention was based on the development of an online platform, named ePrimaPrescribe, which was delivered using a Digital Behaviour Change Intervention (DBCI), using a two-arm cluster-randomised clinical trial. Results: We primarily aimed to evaluate the effectiveness of our DBCI in changing BZD prescription patterns using the frequency of BZD prescriptions issued per month as an outcome measure. Secondarily, we aimed to analyse the effect of ePrimaPrescribe on antidepressant prescriptions, to study the effect of the platform on diagnosis registration associated with BZDs and antidepressant prescription, and to perform a cost analysis considering the monthly National Health Service spending on BZD co-payments. Finally, we aimed to analyse the implementation process using quantitative and qualitative methods. Conclusion: With this study, we expect to contribute with a cost-effective intervention to change the complex matter of excessive BZD prescriptions, and also to improve insight into the challenges to intervention implementation processes in primary health care settings. We believe that our findings are relevant not only to the specific setting where the study was implemented, but also to all countries where primary health care plays a central role in care provision.
Chronic Pain and the Endocannabinoid System: Smart Lipids – A Novel Therapeutic Option?
Authors: Zieglgänsberger Walter , Brenneisen Rudolf , Berthele Achim , Wotjak Carsten T. , Bandelow Borwin , Tölle Thomas R. , Lutz Beat
Published: March 2022

The development of a high-end cannabinoid-based therapy is the result of intense translational research, aiming to convert recent discoveries in the laboratory into better treatments for patients. Novel compounds and new regimes for drug treatment are emerging. Given that previously unreported signaling mechanisms for cannabinoids have been uncovered, clinical studies detailing their high therapeutic potential are mandatory. The advent of novel genomic, optogenetic, and viral tracing and imaging techniques will help to further detail therapeutically relevant functional and structural features. An evolutionarily highly conserved group of neuromodulatory lipids, their receptors, and anabolic and catabolic enzymes are involved in a remarkable variety of physiological and pathological processes and has been termed the endocannabinoid system (ECS). A large body of data has emerged in recent years, pointing to a crucial role of this system in the regulation of the behavioral domains of acquired fear, anxiety, and stress-coping. Besides neurons, also glia cells and components of the immune system can differentially fine-tune patterns of neuronal activity. Dysregulation of ECS signaling can lead to a lowering of stress resilience and increased incidence of psychiatric disorders. Chronic pain may be understood as a disease process evoked by fear-conditioned nociceptive input and appears as the dark side of neuronal plasticity. By taking a toll on every part of your life, this abnormal persistent memory of an aversive state can be more damaging than its initial experience. All strategies for the treatment of chronic pain conditions must consider stress-related comorbid conditions since cognitive factors such as beliefs, expectations, and prior experience (memory of pain) are key modulators of the perception of pain. The anxiolytic and anti-stress effects of medical cannabinoids can substantially modulate the efficacy and tolerability of therapeutic interventions and will help to pave the way to a successful multimodal therapy. Why some individuals are more susceptible to the effects of stress remains to be uncovered. The development of personalized prevention or treatment strategies for anxiety and depression related to chronic pain must also consider gender differences. An emotional basis of chronic pain opens a new horizon of opportunities for developing treatment strategies beyond the repeated sole use of acutely acting analgesics. A phase I trial to determine the pharmacokinetics, psychotropic effects, and safety profile of a novel nanoparticle-based cannabinoid spray for oromucosal delivery highlights a remarkable innovation in galenic technology and urges clinical studies further detailing the huge therapeutic potential of medical cannabis (Lorenzl et al.; this issue).
Microwave Ablation for Malignant Central Airway Obstruction: A Pilot Study
Authors: Senitko Michal , Oberg Catherine L. , Abraham George E. , Hillegass William B. , Akhtar Israh , Folch Erik
Published: March 2022

Background: Malignant central airway obstruction (CAO) is a debilitating complication of primary lung cancer and pulmonary metastases. Therapeutic bronchoscopy is used to palliate symptoms and/or bridge to further therapy. Microwave ablation (MWA) heats tissue by creating an electromagnetic field around an ablation device. We present a pilot study utilizing endobronchial MWA via flexible bronchoscopy as a novel modality for the management of malignant CAO. Methods: Therapeutic bronchoscopy with a flexible MWA probe was performed in 8 cases. We reviewed tumor size, previous ablative techniques, number of applications, ablation time, amount of energy delivered, rate of successful recanalization, complications, and 30-day follow-up. Results: Successful airway recanalization was achieved in all cases. No complications were noted. In 1 case, tumor in-growth within a silicone stent was ablated with no damage to the stent. Discussion: Endobronchial MWA is a novel technique for tumor destruction while maintaining an airway axis. The oven effect and air gap around a tumor allow for safe and effective tissue devitalization and hemostasis without a thermal effect on structures surrounding the airway.
Peroneal Electrical Transcutaneous NeuroModulation as a New Treatment for Patients with Overactive Bladder: An Initial Clinical Experience
Authors: Krhut Jan , Rejchrt Michal , Skugarevska Barbora , Grepl Michal , Zvara Peter
Published: March 2022

Introduction: The aim of this study was to determine whether peroneal electrical Transcutaneous NeuroModulation (peroneal eTNM®) using the URIS® neuromodulation system can be used in individuals with refractory overactive bladder (OAB). Methods: Eighteen female patients with idiopathic OAB who failed previous behavioral and pharmacological therapy were enrolled. Patients were treated with the URIS® neuromodulation system using active electrodes placed on the popliteal fossa, targeting the peroneal nerve for 30 min once a week for 12 weeks. Changes in OAB symptoms and patient-reported outcomes from baseline to the end of the study were analyzed. A nonparametric Wilcoxon signed-rank test was used to assess changes in variables. Statistical significance was defined as p ≤ 0.05. Results: We observed a significant reduction in micturition frequency (p = 0.022), number of severe urgency episodes (p < 0.001), urgency incontinence episodes (p = 0.001), and nocturia episodes (p = 0.027). A decrease in Patient Perception of Bladder Condition score (p < 0.001) was also observed. Posttreatment, 15 patients (83.3%) reported a moderate or significant reduction in their bladder bother. Throughout the study, two adverse events were recorded with no causal relationship to the study treatment. Discussion/Conclusions: Our study documented a significant reduction in all OAB symptoms and an improvement in all patient-reported outcomes in patients treated with peroneal eTNM® using the URIS® neuromodulation system.
The DiaCoVAb Study in South Italy: Immune Response to SARS-CoV-2 Vaccination in Dialysis Patients
Authors: Fucci Alessandra , Giacobbe Simona , Guerriero Ilaria , Suzumoto Yoko , D’Andrea Egildo Luca , Scrima Marianna , Nolli Maria Luisa , Iervolino Anna , Chiuchiolo Luigi Amedeo , Salvatore Ermanno , Renzulli Roberta , La Peccerella Ludovico , Marra Giuseppe , Liuzzi Marco , Santoro Domenico , Zulli Enrico , Gentile Romolo , Clemente Gennaro , Capasso Giovambattista
Published: March 2022

Introduction: Since the pandemic of COVID-19 started from December 2019, remarkable numbers of infections and deaths associated with COVID-19 have been recorded worldwide. End-stage kidney disease patients on dialysis are particularly at high risk of infections due to impairments in the innate and adaptive immune systems. Vaccination on dialysis patients (DP) still remains challenging because of the variable response and a low seroconversion rate compared with healthy participants (HP). Therefore, it is urgently necessary to establish a different vaccination strategy for DP, in terms of the dose and administration time. Methods: Here, we report an observational prospective cohort study in which the immunogenic efficacies of SARS-CoV-2 vaccine BNT162b2 on DP and HP were evaluated by absolute quantification of IgG levels in the blood. Results: DP showed a delayed seroconversion after two vaccine doses, with a low absolute IgG levels compared to HP. While HP reached complete seroconversion within 10 days from the administration of a second dose, only 76% of DP were seropositive. After the booster dose, DP had a strongly improved seroconversion rate as well as antibody levels, reaching 97% seropositivity and 50 times enhancement on antibody levels. Discussion/Conclusion: These results prompt to suggest an additional vaccine dose in DP, reducing the interval of time from the second dose. Since limited data are available on immune response in DP overtime after three vaccine doses currently, our study is among the first reports demonstrating the improved seropositivity and IgG levels in DP after the booster vaccine dose.