bluuebunny/crossref_metadata_2025 huggingface dataset:
Case report: The promising application of dynamic functional connectivity analysis on an individual with failed back surgery syndrome
Authors: Miao Jingya , Ailes Isaiah , Krisa Laura , Fleming Kristen , Middleton Devon , Talekar Kiran , Natale Peter , Mohamed Feroze B. , Hines Kevin , Matias Caio M. , Alizadeh Mahdi
Published: September 2022

Failed back surgery syndrome (FBSS), a chronic neuropathic pain condition, is a common indication for spinal cord stimulation (SCS). However, the mechanisms of SCS, especially its effects on supraspinal/brain functional connectivity, are still not fully understood. Resting state functional magnetic resonance imaging (rsfMRI) studies have shown characteristics in patients with chronic low back pain (cLBP). In this case study, we performed rsfMRI scanning (3.0 T) on an FBSS patient, who presented with chronic low back and leg pain following her previous lumbar microdiscectomy and had undergone permanent SCS. Appropriate MRI safety measures were undertaken to scan this subject. Seed-based functional connectivity (FC) was performed on the rsfMRI data acquired from the FBSS subject, and then compared to a group of 17 healthy controls. Seeds were identified by an atlas of resting state networks (RSNs), which is composed of 32 regions grouped into 8 networks. Sliding-window method and k-means clustering were used in dynamic FC analysis, which resulted in 4 brain states for each group. Our results demonstrated the safety and feasibility of 3T MRI scanning in a patient with implanted SCS system. Compared to the brain states of healthy controls, the FBSS subject presented very different FC patterns in less frequent brain states. The mean dwell time of brain states showed distinct distributions: the FBSS subject seemed to prefer a single state over the others. Although future studies with large sample sizes are needed to make statistical conclusions, our findings demonstrated the promising application of dynamic FC to provide more granularity with FC changes associated with different brain states in chronic pain.
Fluorescent transgenic mouse models for whole-brain imaging in health and disease
Authors: Arias Adrian , Manubens-Gil Linus , Dierssen Mara
Published: September 2022

A paradigm shift is occurring in neuroscience and in general in life sciences converting biomedical research from a descriptive discipline into a quantitative, predictive, actionable science. Living systems are becoming amenable to quantitative description, with profound consequences for our ability to predict biological phenomena. New experimental tools such as tissue clearing, whole-brain imaging, and genetic engineering technologies have opened the opportunity to embrace this new paradigm, allowing to extract anatomical features such as cell number, their full morphology, and even their structural connectivity. These tools will also allow the exploration of new features such as their geometrical arrangement, within and across brain regions. This would be especially important to better characterize brain function and pathological alterations in neurological, neurodevelopmental, and neurodegenerative disorders. New animal models for mapping fluorescent protein-expressing neurons and axon pathways in adult mice are key to this aim. As a result of both developments, relevant cell populations with endogenous fluorescence signals can be comprehensively and quantitatively mapped to whole-brain images acquired at submicron resolution. However, they present intrinsic limitations: weak fluorescent signals, unequal signal strength across the same cell type, lack of specificity of fluorescent labels, overlapping signals in cell types with dense labeling, or undetectable signal at distal parts of the neurons, among others. In this review, we discuss the recent advances in the development of fluorescent transgenic mouse models that overcome to some extent the technical and conceptual limitations and tradeoffs between different strategies. We also discuss the potential use of these strains for understanding disease.
The microbiota composition drives personalized nutrition: Gut microbes as predictive biomarkers for the success of weight loss diets
Authors: Hernández-Calderón Paula , Wiedemann Lara , Benítez-Páez Alfonso
Published: September 2022

The investigation of the human gut microbiome during recent years has permitted us to understand its relevance for human health at a systemic level, making it possible to establish different functional axes (e.g., the gut-brain, gut-liver, and gut-lung axes), which support the organ-like status conferred to this microecological component of our body. The human gut microbiota is extremely variable but modifiable via diet, a fact that allows targeting of microbes through defined dietary strategies to uncover cost-effective therapies to minimize the burden of non-communicable diseases such as pandemic obesity and overweight and its metabolic comorbidities. Nevertheless, randomly controlled dietary interventions regularly exhibit low to moderate degrees of success in weight control, making their implementation difficult in clinical practice. Here, we review the predictive value of the baseline gut microbiota configurations to anticipate the success of dietary interventions aimed at weight loss, mostly based on caloric restriction regimes and oral fiber supplementation. This emergent research concept fits into precision medicine by considering different diet patterns and adopting the best one, based on the individual microbiota composition, to reach significant adiposity reduction and improve metabolic status. We review the results from this fresh perspective of investigation, taking into account studies released very recently. We also discuss some future outlooks in the field and potential pitfalls to overcome with the aim of gaining knowledge in the field and achieving breakthroughs in personalized nutrition.
Dietary berberine alleviates high carbohydrate diet-induced intestinal damages and improves lipid metabolism in largemouth bass (Micropterus salmoides)
Authors: Gong Yulong , Lu Qisheng , Liu Yulong , Xi Longwei , Zhang Zhimin , Liu Haokun , Jin Junyan , Yang Yunxia , Zhu Xiaoming , Xie Shouqi , Han Dong
Published: September 2022

High carbohydrate diet (HCD) causes metabolism disorder and intestinal damages in aquaculture fish. Berberine has been applied to improve obesity, diabetes and NAFLD. However, whether berberine contributes to the alleviation of HCD-induced intestinal damages in aquaculture fish is still unclear. Here we investigated the effects and mechanism of berberine on HCD-induced intestinal damages in largemouth bass (Micropterus salmoides). We found dietary berberine (50 mg/kg) improved the physical indexes (VSI and HSI) without affecting the growth performance and survival rate of largemouth bass. Importantly, the results showed that dietary berberine reduced the HCD-induced tissue damages and repaired the barrier in the intestine of largemouth bass. We observed dietary berberine significantly suppressed HCD-induced intestinal apoptosis rate (from 31.21 to 8.35%) and the activity level of Caspase3/9 (P < 0.05) by alleviating the inflammation (il1β, il8, tgfβ, and IL-6, P < 0.05) and ER stress (atf6, xbp1, perk, eif2α, chopa, chopb, and BIP, P < 0.05) in largemouth bass. Further results showed that dietary berberine declined the HCD-induced excessive lipogenesis (oil red O area, TG content, acaca, fasn, scd, pparγ, and srebp1, P < 0.05) and promoted the lipolysis (hsl, lpl, cpt1a, and cpt2, P < 0.05) via activating adenosine monophosphate-activated protein kinase (AMPK, P < 0.05) and inhibiting sterol regulatory element-binding protein 1 (SREBP1, P < 0.05) in the intestine of largemouth bass. Besides, we also found that dietary berberine significantly promoted the hepatic lipid catabolism (hsl, lpl, cpt1a, and cpt2, P < 0.05) and glycolysis (pk and ira, P < 0.05) to reduce the systematic lipid deposition in largemouth bass fed with HCD. Therefore, we elucidated that 50 mg/kg dietary berberine alleviated HCD-induced intestinal damages and improved AMPK/SREBP1-mediated lipid metabolism in largemouth bass, and evaluated the feasibility for berberine as an aquafeed additive to enhance the intestinal function of aquaculture species.
Association between red blood cell distribution width to albumin ratio and prognosis of patients with sepsis: A retrospective cohort study
Authors: Xu Weigan , Huo Jianyang , Chen Guojun , Yang Kangyi , Huang Zuhua , Peng Lina , Xu Jingtao , Jiang Jun
Published: September 2022

Background

Red blood cell distribution width (RDW) to albumin ratio (RAR) is associated with poor prognosis in diabetic comorbidities and cancer. However, the association between RAR and prognosis in patients with sepsis remains unclear, which was investigated in this study.

Methods

We conducted a retrospective cohort study based on the Medical Information Mart for Intensive Care (MIMIC) IV version 2.0 database. The primary outcome of this study was 28-day mortality. Secondary outcomes included 90-day mortality, in-hospital mortality, length of hospital stay, and length of intensive care unit (ICU) stay. Multivariate regression analysis and subgroup analysis were performed to investigate the association between RAR and prognosis in patients with sepsis.

Results

A total of 14,639 participants were included in this study. The mean age of the participants was 65.2 ± 16.3 years and the mean RAR was 5.5 ± 1.9 % /g/dl. For 28-day mortality, after adjusting for covariates, HRs [95% confidence intervals (CIs)] for tertiles 2 (4.4–5.8) and 3 (RAR > 5.8) were 1.33 (1.20, 1.46) and 1.98 (1.79, 2.19), respectively. Similar results were observed for 90-day mortality and in-hospital mortality. According to Kaplan-Meier curve analysis, the higher RAR group had higher 28-day mortality and 90-day mortality.

Conclusion

Our study shows that RAR is significantly associated with poor clinical prognosis in sepsis. The higher the RAR, the higher the 28-day, 90-day, and in-hospital mortality.
Vegetarian Diet Was Associated With a Lower Risk of Chronic Kidney Disease in Diabetic Patients
Authors: Hou Yi-Chou , Huang Hui-Fen , Tsai Wen-Hsin , Huang Sin-Yi , Liu Hao-Wen , Liu Jia-Sin , Kuo Ko-Lin
Published: September 2022

Introduction

Diabetes mellitus (DM) is a pathological hyperglycemic state related to the dysregulation of insulin. Chronic kidney disease (CKD) is a common chronic complication in diabetic patients. A vegetarian diet could be one of the preventive strategies for the occurrence of CKD in patients with diabetes mellitus. However, it is still unknown whether a vegetarian diet lowers the occurrence of CKD in DM patients.

Research Design and Methods

This retrospective study was conducted at Taipei Tzu Chi Hospital from 5 September 2005 to 31 December 2016. Subjects with an HbA1c level > 6.5% or previous history of diabetes mellitus elder than 40 years were grouped based on self-reported dietary habits (vegetarians, lacto-ovo vegetarians and omnivores) in the structured questionnaire. Structural equation modeling (SEM) was applied to estimate the direct and indirect effects of variables on the occurrence of chronic kidney disease.

Results

Among these 2,797 subjects, the participants were grouped into dietary habits as vegans (n = 207), lacto-ovo vegetarians (n = 941) and omnivores (n = 1,649). The incidence of overall CKD was higher in the omnivore group [36.6% vs 30.4% (vegans) and 28.5% (lacto-ovo vegetarian), p < 0.001]. In the SEM model, after adjusting for age and sex, the lacto-ovo vegetarian [OR: 0.68, 95% confidence interval (CI): 0.57–0.82] and vegan groups (OR 0.68, 95% CI: 0.49–0.94) were both associated with a lower risk of CKD occurrence than the omnivore group. The vegan diet and lacto-ovo diet lowered the risk related to a high BMI (OR: 0.45, p < 0.001, OR: 0.58, p < 0.001) and hyperuricemia (OR: 0.53, p < 0.001; OR: 0.55, p < 0.001) for the occurrence of CKD.

Conclusion

Vegetarian dietary habits were associated with a lower occurrence of CKD in DM patients.
Innovations in Immunosuppression for Intestinal Transplantation
Authors: Dogra Harween , Hind Jonathan
Published: September 2022

It has been 57 years since the first intestinal transplant. An increased incidence of graft rejection has been described compared to other solid organ transplants due to high immunogenicity of the bowel, which in health allows the balance between of dietary antigen with defense against pathogens. Expanding clinical experience, knowledge of gastrointestinal physiology and immunology have progress post-transplant immunosuppressive drug regimens. Current regimes aim to find the window between prevention of rejection and the risk of infection (the leading cause of death) and malignancy. The ultimate aim is to achieve graft tolerance. In this review we discuss advances in mucosal immunology and technologies informing the development of new anti-rejection strategies with the hope of improved survival in the next generation of transplant recipients.
The Environmental Footprint Associated With the Mediterranean Diet, EAT-Lancet Diet, and the Sustainable Healthy Diet Index: A Population-Based Study
Authors: Tepper Sigal , Kissinger Meidad , Avital Kerem , Shahar Danit Rivkah
Published: September 2022

Providing a growing global population with healthy and sustainable diets is an immediate challenge. In the current study, estimates were obtained for the environmental footprints (land, water, and greenhouse gas (GHG) emissions) in association with the Mediterranean diet (MED) and the EAT-Lancet reference diet, which represents a healthy diet derived from sustainable food systems. We used a newly developed Sustainable Healthy Diet (SHED) index that was validated for the Israeli population by Tepper et al. in 2020.

Methods

A group of 525 participants were recruited via social media, email, and phone. Demographic characteristics, quality of life, and answers to the SHED-index questionnaire were obtained. Dietary assessment was performed using the 116-item Food Frequency Questionnaire (FFQ), which was developed for the Israeli population. Adherence to the MED was calculated using a 9-point score. Adherence to the EAT-Lancet reference diet was assessed through the consumption of 14 food components. The environmental pressure of these dietary patterns was determined based on the “footprint family indicators,” which include land, water, and carbon footprints per unit of agricultural and food products. We assigned values for each food comprising the FFQ and calculated the environmental load for each dietary pattern. Statistical analyses were performed using the R package version 4.1.1 to compare environmental footprint values according to tertiles of the MED score, EAT-Lancet score, and SHED score.

Results

The participants (n = 525) were 49% women, educated (82% had academic education), and physically active, and only 13% were smokers. The highest tertiles of adherence to the MED, adherence to the EAT-Lancet reference diet, and the SHED index were associated with the lowest GHG emissions and land use, as well as higher water use. Meat consumption contributed the most to land use, while dairy contributed the most to GHG emissions, and fruits contributed the most to water use.

Conclusions

Our analysis reveals that animal protein is the highest contributor to GHG emissions and land use, while fruits and vegetables contribute the most to water consumption. Nevertheless, most of the fruits and vegetables are grown using treated wastewater, which reduces environmental pressure. Given these findings, we suggest that MED and EAT-Lancet dietary patterns should be included in national dietary guidelines.
Validation of the food frequency questionnaire for the assessment of dietary vitamin D intake
Authors: Hribar Maša , Žlavs Katarina , Pravst Igor , Žmitek Katja
Published: September 2022

Vitamin D and its adequate status are related to many aspects of human health; therefore, an appropriate tool is needed for the valid assessment of vitamin D status. The main contributor to vitamin D status is endogenous synthesis after cutaneous exposure to ultraviolet B light (UVB), but in the absence of UVB radiation, vitamin D intake becomes an important source of vitamin D. Various tools are available for vitamin D intake assessments, with the Food Frequency Questionnaire (FFQ) being among the fastest, cheapest, and most convenient; however, until now, these tools have not been adapted for the Slovenia (SI). To enable valid vitamin D intake estimation, we developed a simple one-page semi-quantitative FFQ (sqFFQ/SI) and tested its validity using a 5-day dietary record (DR) as a reference method. The reproducibility was tested with the second sqFFQ/SI (sqFFQ/SI2) 6 weeks after the first (sqFFQ/SI1). The validity and reproducibility of this method were tested on 54 participants using Bland–Altman plots, Spearman’s correlation, and Kappa analyses of tertiles. The mean daily vitamin D intake was 3.50 ± 1.91 μg according to the 5-day DR, and 2.99 ± 1.35 and 3.31 ± 1.67 μg according to the sqFFQ/SI1 and repeated sqFFQ/SI (sqFFQ/SI2), respectively. When analyzing for validity, the sqFFQ/SI1 was found to be significantly correlated (p < 0.05) with the 5-day DR, with an acceptable correlation coefficient of 0.268 and a Bland–Altman index of 3.7%. For reproducibility, the correlation between the sqFFQ/SI1 and sqFFQ/SI2 was highly significant (p < 0.001), with a good correlation coefficient of 0.689 and a Bland–Altman index of 3.7%. Kappa analyses of tertiles showed a poor validity and acceptable reproducibility. Overall, we observed a higher reproducibility than validity. Validation and reproducibility analyses demonstrated that the proposed sqFFQ/SI is acceptable and is, therefore, an appropriate tool for the effective assessment of habitual vitamin D intake on an individual level. With this consideration, this tool will be used in further population studies to assess vitamin D intake and for the development of a screening tool for the assessment of the risk for vitamin D deficiency, which will be used as a foundation for evidence-based policy-making decisions.
Breaking new frontiers: Assessment and re-evaluation of clinical trial design for nutraceuticals
Authors: Evans Malkanthi , Lewis Erin D. , Antony Joseph M. , Crowley David C. , Guthrie Najla , Blumberg Jeffrey B.
Published: September 2022

Despite sophisticated study designs and measurement tools, we have yet to create an innovative space for diet and dietary supplements in the health care system. The path is challenging due to current hierarchies of scientific evidence and regulatory affairs. The role of the randomized, double-blind, placebo-controlled clinical trial (RCT) as a research approach functions well to characterize the benefits and risks of drugs but lacks the sensitivity to capture the efficacy and safety of nutraceuticals. While some facets of RCTs can be relevant and useful when applied to nutraceuticals, other aspects are limiting and potentially misleading when taken in their entirety. A differentiation between guidelines for evidence-based medicine and the evidence required for nutrition spotlight the need to reconceptualize constituents of the RCT and their applicability with relevance to health promotion. This perspective identifies the limitations of the traditional RCT to capture the complexities of nutraceuticals and proposes the N-of-1 as Level 1 evidence better suited for the proof of efficacy of nutraceuticals.
Effects of addition of 2-fucosyllactose to infant formula on growth and specific pathways of utilization by Bifidobacterium in healthy term infants
Authors: Wallingford John C. , Neve Myers Pernille , Barber Cynthia M.
Published: September 2022

Oligosaccharides in human milk support healthviaintestinal microbiome. We studied effects of addition of 2-fucosyllactose (2′FL) to the infant formula on infant growth, occurrence of adverse events (AE), and infant microbiome, including expression of microbial genes that metabolize 2′FL. Our hypothesis was that while 2′FL would not affect growth, it would cause changes in microbiome metabolism. In a double-blinded randomized controlled study fashion, the infant formula ± 2′FL or human milk was fed to healthy term infants for 16 weeks. Fecal samples obtained at baseline and week 16 were analyzed for microbial populations, metagenomic species concept (MGS), and genetics of gut metabolic modules (GMMs). There were no effects of addition of 2′FL on growth or AEs. There were no significant differences by feeding group in MGS richness or Shannon diversity at baseline, but formula groups each had significantly greater richness (p< 0.05) and diversity (p< 0.05) after 16 weeks of feeding than the breastfed group. While two glycosyl hydrolase (GH) families (GH42 and GH112) were significantly increased, two other GH families (GH20 and GH2) were significantly decreased in the test formula group compared to the control formula group; although modest, addition of 2′FL resulted in changes in microbiome in the direction of breastfed infants, consistent with internal metabolism of HMOs byBifidobacterium.
Prognostic nutritional index before surgical treatment may serve as a prognostic biomarker for patients with upper tract urothelial carcinoma: A systematic review and meta-analysis
Authors: Meng Chunyang , Gan Lijian , Li Kangsen , Yi Fulin , Peng Lei , Li Jinze , Li Yunxiang
Published: September 2022

Objective

This meta-analysis aims to assess whether the prognostic nutritional index (PNI) score before treatment can be an independent biomarker of the prognosis of patients with upper tract urothelial carcinoma (UTUC).

Materials and methods

We systematically search PubMed, Embase, Scopus database, and Cochrane Library, and the search time is up to April 2021. Use STATA 16.0 software for data processing and statistical analysis.

Results

Six studies, including seven cohorts, were eventually included in our meta-analysis. The meta-analysis results showed that low PNI scores are associated with worse OS (HR: 1.92; 95% CI 1.60 to 2.30; P < 0.01), DFS/RFS/PFS (HR: 1.57; 95% CI 1.33 to 1.85; P < 0.01), and CSS/DSS (HR: 1.79; 95% CI 1.49 to 2.16; P < 0.01), which supported the PNI score as an independent prognostic biomarker for survival outcomes. The subgroup analysis and Begg’s test showed that the results were stable.

Conclusion

Based on current evidence, this meta-analysis proves that the PNI score of UTUC patients before treatment is an independent prognostic biomarker. It performs well on OS, DFS/RFS/PFS, and CSS/DSS. This conclusion needs to be verified by a prospective cohort study with larger sample size and a more rigorous design.

Systematic review registration

[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022338503], identifier [CRD42022338503].
Comprehensive analysis of the prognostic signature and tumor microenvironment infiltration characteristics of cuproptosis-related lncRNAs for patients with colon adenocarcinoma
Authors: Cui Guoliang , Liu Jinhui , Wang Can , Gu Renjun , Wang Manli , Sun Zhiguang , Wei Fei
Published: September 2022

Background

Cuproptosis, a newly described method of regulatory cell death (RCD), may be a viable new therapy option for cancers. Long noncoding RNAs (lncRNAs) have been confirmed to be correlated with epigenetic controllers and regulate histone protein modification or DNA methylation during gene transcription. The roles of cuproptosis-related lncRNAs (CRLs) in Colon adenocarcinoma (COAD), however, remain unknown.

Methods

COAD transcriptome data was obtained from the TCGA database. Thirteen genes associated to cuproptosis were identified in published papers. Following that, correlation analysis was used to identify CRLs. The cuproptosis associated prognostic signature was built and evaluated using Lasso regression and COX regression analysis. A prognostic signature comprising six CRLs was established and the expression patterns of these CRLs were analyzed by qRT-PCR. To assess the clinical utility of prognostic signature, we performed tumor microenvironment (TME) analysis, mutation analysis, nomogram generation, and medication sensitivity analysis.

Results

We identified 49 prognosis-related CRLs in COAD and constructed a prognostic signature consisting of six CRLs. Each patient can be calculated for a risk score and the calculation formula is: Risk score =TNFRSF10A-AS1 * (-0.2449) + AC006449.3 * 1.407 + AC093382.1 *1.812 + AC099850.3 * (-0.0899) + ZEB1-AS1 * 0.4332 + NIFK-AS1 * 0.3956. Six CRLs expressions were investigated by qRT-PCR in three colorectal cancer cell lines. In three cohorts, COAD patients were identified with different risk groups, with the high-risk group having a worse prognosis than the low-risk group. Furthermore, there were differences in immune cell infiltration and tumor mutation burden (TMB) between the two risk groups. We also identified certain drugs that were more sensitive to the high-risk group: Paclitaxel, Vinblastine, Sunitinib and Elescloml.

Conclusions

Our findings may be used to further investigate RCD, comprehension of the prognosis and tumor microenvironment infiltration characteristics in COAD.
Inoperable or incompletely resected craniofacial osteosarcoma treated by particle radiotherapy
Authors: Seidensaal Katharina , Dostal Matthias , Liermann Jakob , Adeberg Sebastian , Weykamp Fabian , Schmid Maximillian P. , Freudlsperger Christian , Hoffmann Jürgen , Hompland Ivar , Herfarth Klaus , Debus Jürgen , Harrabi Semi B.
Published: September 2022

Background

To report survival of craniofacial osteosarcoma patients treated by particle radiotherapy.

Methods

Between January 2010 and December 2021, 51 patients with primary (N = 35) or recurrent (N = 16) inoperable or incompletely resected craniofacial osteosarcoma were treated. In most cases, intracranial infiltration (59%) and macroscopic tumor on MRI/CT (75%) were present. Thirteen had a secondary osteosarcoma (25%). Treatment concepts included combined ion beam radiotherapy (CIBRT, N = 18), protons only (N = 3), carbon ions only (N = 12), IMRT with a carbon ion boost (N = 5), and carbon ion re-irradiation (N = 13). Eighty percent (N = 41) received additionally chemotherapy, most frequently EURAMOS-1 (47%) or EURO-B.O.S.S. (18%).

Results

The median age was 38, and all patients finished treatment predominantly as outpatients (N = 44). Information on overall survival was available for N = 49 patients. The median follow-up of the survivors was 55 months. For the whole cohort 1-, 2-, 3-, and 5-year overall survival (OS) was 82.8%, 60.4%, 55.2%, and 51.7%, respectively. Those treated by CIBRT (N = 17) demonstrated a superior OS with 92.9% after 1 and 2 years and 83.6% after 3 and 5 years. The median clinical target volume (CTV) was 192.7 and 95.2 cc for the primary and boost plan, respectively. CIBRT, primary diagnosis, age ≤40a, and no macroscopic residual tumor were associated with improved survival in univariate analysis (p = 0.006, p = 0.004, p = 0.002, p = 0.026, respectively), while any foregoing resection compared to biopsy was not identified as a prognostic factor. CIBRT and no macroscopic residual tumor were confirmed as independent predictors of OS on multivariate analysis (HR = 0.107, 95% CI = [0.014, 0.797], p = 0.029 and HR = 0.130, 95% CI = [0.023, 0.724], p = 0.020, respectively). No acute toxicity > grade III was observed.

Conclusion

CIBRT shows promising results for patients with inoperable or incompletely resected craniofacial osteosarcoma.
Outcomes of “sandwich” chemoradiotherapy compared with chemotherapy alone for the adjuvant treatment of FIGO stage III endometrial cancer
Authors: Wang Shao-Jing , Wang Lily , Sun Lou , Shih Yu-Hsiang , Hsu Shih-Tien , Liu Chin-Ku , Hwang Sheau-Feng , Lu Chien-Hsing
Published: September 2022

Objective

To analyze and compare outcomes of adjuvant chemoradiotherapy in patients with International Federation of Gynecology and Obstetrics (FIGO) stage III endometrial cancer (EC) patients using the “Sandwich” sequence and chemotherapy (CT) alone.

Methods

From, 2005 to, 2019, we retrospectively reviewed 80 patients with FIGO stage III EC who received treatment at our institute. We analyzed 66 patients who had undergone complete surgical staging followed by adjuvant treatment with sandwich chemoradiotherapy (39 patients) and CT alone (27 patients). The 5-year overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS) were calculated using the Kaplan–Meier method. Additional prognostic factors were analyzed using Cox proportional hazards regression.

Results

Herein, the analysis was conducted using 66 patients with a median follow-up period of 50 and 85 months in the sandwich and CT-alone arms. Comparing the sandwich sequence and CT-alone groups, the 5-year OS and PFS were 87% vs. 70% (p = 0.097) and 77% vs. 65% (p = 0.209), respectively. The sandwich therapy conferred an improved 5-year DSS (92% vs. 70%, p = 0.041) and a lower local recurrence rate (0% vs. 11%, p = 0.031). In multivariable analyses, grade 3 histology and deep myometrial invasion were independent risk factors for 5-year OS and DSS. The sandwich sequence was a positive predictor for 5-year DSS (hazard ratio [HR] = 0.23, p = 0.029). The sandwich arm demonstrated higher acute hematologic toxicity than the CT-alone arm. CT dose delay/reduction and treatment completion rates were similar in both groups.

Conclusion

For patients with stage III EC, postoperative sandwich chemoradiotherapy appears to offer a superior 5-year DSS and local control with tolerable toxicity when compared with CT alone.
Thyroid and renal cancers: A bidirectional association
Authors: Bellini Maria Irene , Lori Eleonora , Forte Flavio , Lauro Augusto , Tripodi Domenico , Amabile Maria Ida , Cantisani Vito , Varanese Marzia , Ferent Iulia Catalina , Baldini Enke , Ulisse Salvatore , D’Andrea Vito , Pironi Daniele , Sorrenti Salvatore
Published: September 2022

There is a deep interrelation between the thyroid gland and the kidney parenchyma, with dysfunction of the first leading to significant changes in renal metabolism and vice versa. Given the recognition of cancer as a systemic disease, the raise of thyroid tumors and the common association of several malignancies, such as breast cancer, prostate cancer, colorectal cancer, and other, with an increased risk of kidney disease, public health alert for these conditions is warranted. A systematic review of the current evidence on the bidirectional relationship between thyroid and renal cancers was conducted including 18 studies, highlighting patient’s characteristics, histology, time for secondary malignancy to develop from the first diagnosis, treatment, and follow-up. A total of 776 patients were identified; median age was 64 years (range: 7–76 years). Obesity and family history were identified as the most common risk factors, and genetic susceptibility was suggested with a potential strong association with Cowden syndrome. Controversy on chemo and radiotherapy effects was found, as not all patients were previously exposed to these treatments. Men were more likely to develop kidney cancer after a primary thyroid malignancy, with 423/776 (54%) experiencing renal disease secondarily. Median time after the first malignancy was 5.2 years (range: 0–20 years). With the advancement of current oncological therapy, the prognosis for thyroid cancer patients has improved, although there has been a corresponding rise in the incidence of multiple secondary malignancy within the same population, particularly concerning the kidney. Surgery can achieve disease-free survival, if surveillance follow-up allows for an early localized form, where radical treatment is recommended.
Molecular testing for adolescent and young adult central nervous system tumors: A Canadian guideline
Authors: Lim-Fat Mary Jane , Macdonald Maria , Lapointe Sarah , Climans Seth Andrew , Cacciotti Chantel , Chahal Manik , Perreault Sebastien , Tsang Derek S. , Gao Andrew , Yip Stephen , Keith Julia , Bennett Julie , Ramaswamy Vijay , Detsky Jay , Tabori Uri , Das Sunit , Hawkins Cynthia
Published: September 2022

The 2021 World Health Organization (WHO) classification of CNS tumors incorporates molecular signatures with histology and has highlighted differences across pediatric vs adult-type CNS tumors. However, adolescent and young adults (AYA; aged 15–39), can suffer from tumors across this spectrum and is a recognized orphan population that requires multidisciplinary, specialized care, and often through a transition phase. To advocate for a uniform testing strategy in AYAs, pediatric and adult specialists from neuro-oncology, radiation oncology, neuropathology, and neurosurgery helped develop this review and testing framework through the Canadian AYA Neuro-Oncology Consortium. We propose a comprehensive approach to molecular testing in this unique population, based on the recent tumor classification and within the clinical framework of the provincial health care systems in Canada.

Contributions to the field

While there are guidelines for testing in adult and pediatric CNS tumor populations, there is no consensus testing for AYA patients whose care occur in both pediatric and adult hospitals. Our review of the literature and guideline adopts a resource-effective and clinically-oriented approach to improve diagnosis and prognostication of brain tumors in the AYA population, as part of a nation-wide initiative to improve care for AYA patients.
Effects of the COVID-19 pandemic on elderly patients with head and neck squamous cell carcinoma
Authors: Ye Pei-Jing , Xi Yan , Sun Chuan-Zheng , Lei Qian , Li Lei
Published: September 2022

Background

The 2019 novel coronavirus disease (COVID-19) strongly affects health care activities in countries around the world. The diagnosis and treatment of cancer have also been involved, and elderly head and neck squamous carcinoma is one of them. This study aimed to assess the impact of COVID-19 on elderly patients with head and neck squamous cell carcinoma (HNSCC) in our center.

Methods

This retrospective study analyzed the clinical characteristics of 400 HNSCC patients over 65 years of age, calculated their treatment interruption rates, and compared the time of delayed diagnosis.

Results

The rate of elderly patients with HNSCC with a delayed diagnosis was higher in the “during COVID-19 pandemic” group (DCOV19 group) than in the “during COVID-19 pandemic” group (BCOV19 group), and the difference was statistically significant (p=0.0017). There was a substantial difference in the rate of treatment interruption between the two groups (p=0.002).

Conclusions

This is the first study to explore the effect of the COVID-19 pandemic on visits and treatment interruptions in elderly patients with HNSCC. The current impact of the COVID-19 pandemic on HNSCC treatment has resulted in reductions and delays in diagnosing cancer and providing treatment.
Inspiration to mRNA-based COVID-19 vaccination: Serious adverse case reports with hepatitis B vaccine in real-world
Authors: Lu Jinmiao , Zhang Xunjie , Xu Hong , Li Zhiping
Published: September 2022

Objectives

The hepatitis B vaccine comprises hepatitis B surface antigen (HBsAg) produced by transgenic yeast cells. There are few serious adverse events (SAE) reports after Hepatitis B vaccination.

Methods

The authors searched the Chinese legal documents database for all SAE with Hepatitis B vaccination from January 2010 to January 2022.

Results

All seven patients received yeast-derived recombinant hepatitis B vaccine. Three cases of myocarditis (death), 2 cases of interstitial pneumonia (death), and 2 cases of encephalitis. The mean time of onset of SAE was 8.3 ± 4.3 h after vaccination.

Conclusion

The mechanism of vaccine-induced myocarditis may come from immune protein reactions. Based on the experience of Hepatitis B vaccine adverse events, we present new insights into the mechanism of myocarditis caused by the COVID-19 vaccine.
Low gamma-glutamyl transpeptidase levels at presentation are associated with severity of liver illness and poor outcome in biliary atresia
Authors: Sun Song , Zheng Shan , Shen Chun , Dong Rui , Dong Kuiran , Jiang Jingying , Yang Yifan , Chen Gong
Published: September 2022

Objective

To investigate the clinical features and prognosis of biliary atresia (BA) with normal or minimally elevated gamma-glutamyl transpeptidase (GGT).

Methods

The clinical data of patients with BA in our hospital between 2012 and 2017 were retrospectively studied. The patients were divided into a low-GGT group (GGT ≤ 300 IU/L) and a high-GGT group (GGT > 300 IU/L) according to the preoperative GGT level. The perioperative clinical parameters, the postoperative jaundice clearance within 6 months, and the 2-year native liver survival were compared among the groups.

Results

A total of 1,998 children were included in this study, namely, 496 in the low-GGT group and 1,502 in the high-GGT group. The ages and weights at the surgery in the low-GGT group were significantly lower than those in the high-GGT group (64.71 ± 21.35 vs. 68.64 ± 22.42 days, P = 0.001; 4.67 ± 1.03 vs. 4.89 ± 0.98 kg, P < 0.001). The levels of serum ALP, ALT, and AST in the low-GGT group were significantly higher than those in the high-GGT group before and 2 weeks after the surgery (ALP: 647.52 ± 244.10 vs. 594.14 ± 228.33 U/L, P < 0.001; ALT: 119.62 ± 97.14 vs. 96.01 ± 66.28 U/L, P < 0.001; AST: 218.00 ± 173.82 vs. 160.71 ± 96.32 U/L; P < 0.001). The INR of the low-GGT group was higher than that of the high-GGT group (1.05 ± 0.34 vs. 0.98 ± 0.20, P < 0.001), while FIB was lower than the high-GGT group (2.54 ± 0.67 vs. 2.73 ± 1.44 g/L; P = 0.006). The decreasing amplitude of TB and DB within 2 weeks after surgery in the low-GGT group was smaller than those in the high-GGT group (TB: 51.62 ± 71.22 vs. 61.67 ± 53.99 μmol/L, P = 0.003; DB: 33.22 ± 35.57 vs. 40.20 ± 35.93 μmol/L, P < 0.001). The jaundice clearance rate in the low-GGT group was significantly lower than that in the high-GGT group at 1, 3, and 6 months after surgery (17.70 vs. 26.05%; 35.17 vs. 48.58%; 38.62 vs. 54.64%, P < 0.001). In addition, the 2-year native liver survival rate in the low-GGT group was significantly lower than that of the high-GGT group (52.5 vs. 66.3%, P < 0.001 HR 1.80, 95% CI 1.38–2.33).

Conclusion

Compared to patients with high GGT, patients with normal or minimally elevated pre-operative GGT in BA were found to have poorer pre-operative liver function parameters, and post-operatively had lower jaundice clearance rates and worse 2-year native liver survival. This suggests a lower GGT at presentation in biliary atresia could be a sign of more severe liver injury.
Rutin bioconjugates as potential nutraceutical prodrugs: An in vitro and in ovo toxicological screening
Authors: Dehelean Cristina Adriana , Coricovac Dorina , Pinzaru Iulia , Marcovici Iasmina , Macasoi Ioana Gabriela , Semenescu Alexandra , Lazar Geza , Cinta Pinzaru Simona , Radulov Isidora , Alexa Ersilia , Cretu Octavian
Published: September 2022

Rutin (RUT) is considered one the most attractive flavonoids from a therapeutic perspective due to its multispectral pharmacological activities including antiradical, anti-inflammatory, antiproliferative, and antimetastatic among others. Still, this compound presents a low bioavailability what narrows its clinical applications. To overcome this inconvenience, the current paper was focused on the synthesis, characterization, and toxicological assessment of two RUT bioconjugates obtained by enzymatic esterification with oleic acid (OA) and linoleic acid (LA)—rutin oleate (RUT-O) and rutin linoleate (RUT-L), as flavonoid precursors with improved physicochemical and biological properties. Following the enzymatic synthesis in the presence of Novozyme® 435, the two bioconjugates were obtained, their formation being confirmed by RAMAN and FT-IR spectroscopy. The in vitro and in ovo toxicological assessment of RUT bioconjugates (1–100 µM) was performed using 2D consecrated cell lines (cardiomyoblasts - H9c2(2-1), hepatocytes—HepaRG, and keratinocytes—HaCaT), 3D reconstructed human epidermis tissue (EpiDerm™), and chick chorioallantoic membranes, respectively. The results obtained were test compound, concentration—and cell-type dependent, as follows: RUT-O reduced the viability of H9c2(2-1), HepaRG, and HaCaT cells at 100 µM (to 77.53%, 83.17%, and 78.32%, respectively), and induced cell rounding and floating, as well as apoptotic-like features in the nuclei of all cell lines, whereas RUT-L exerted no signs of cytotoxicity in all cell lines in terms of cell viability, morphology, and nuclear integrity. Both RUT esters impaired the migration of HepaRG cells (at 25 µM) and lack irritative potential (at 100 µM) in vitro (tissue viability >50%) and in ovo (irritation scores of 0.70 for RUT-O, and 0.49 for RUT-L, respectively). Computational predictions revealed an increased lipophilicity, and reduced solubility, drug-likeness and drug score of RUT-O and RUT-L compared to their parent compounds—RUT, OA, and LA. In conclusion, we report a favorable toxicological profile for RUT-L, while RUT-O is dosage-limited since at high concentrations were noticed cytotoxic effects.
DJ-1 administration exerts cardioprotection in a mouse model of acute myocardial infarction
Authors: Gallinat Alex , Mendieta Guiomar , Vilahur Gemma , Padró Teresa , Badimon Lina
Published: September 2022

Cardiovascular diseases, and particularly acute myocardial infarction (MI), are the most common causes of death worldwide. Infarct size is the major predictor of clinical outcomes in MI. The Parkinson’s disease associated protein, DJ-1 (also known as PARK7), is a multifunctional protein with chaperone, redox sensing and mitochondrial homeostasis activities. Previously, we provided the evidence for a central role of endogenous DJ-1 in the cardioprotection of post-conditioning. In the present study, we tested the hypothesis that systemic administration of recombinant DJ-1 exerts cardioprotective effects in a mouse model of MI and also explored the associated transcriptional response. We report a significant treatment-induced reduction in infarct size, leukocyte infiltration, apoptosis and oxidative stress. Effects potentially mediated by G-protein-coupled receptor signaling and modulation of the immune response. Collectively, our results indicate a protective role for the exogenously administrated DJ-1 upon MI, and provide the first line of evidence for an extracellular activity of DJ-1 regulating cardiac injury in vivo.
Topical Antibiofilm Agents With Potential Utility in the Treatment of Chronic Rhinosinusitis: A Narrative Review
Authors: Hale Samuel J. M. , Wagner Mackenzie Brett , Lux Christian A. , Biswas Kristi , Kim Raymond , Douglas Richard G.
Published: September 2022

The role of bacterial biofilms in chronic and recalcitrant diseases is widely appreciated, and the treatment of biofilm infection is an increasingly important area of research. Chronic rhinosinusitis (CRS) is a complex disease associated with sinonasal dysbiosis and the presence of bacterial biofilms. While most biofilm-related diseases are associated with highly persistent but relatively less severe inflammation, the presence of biofilms in CRS is associated with greater severity of inflammation and recalcitrance despite appropriate treatment. Oral antibiotics are commonly used to treat CRS but they are often ineffective, due to poor penetration of the sinonasal mucosa and the inherently antibiotic resistant nature of bacteria in biofilms. Topical non-antibiotic antibiofilm agents may prove more effective, but few such agents are available for sinonasal application. We review compounds with antibiofilm activity that may be useful for treating biofilm-associated CRS, including halogen-based compounds, quaternary ammonium compounds and derivatives, biguanides, antimicrobial peptides, chelating agents and natural products. These include preparations that are currently available and those still in development. For each compound, antibiofilm efficacy, mechanism of action, and toxicity as it relates to sinonasal application are summarised. We highlight the antibiofilm agents that we believe hold the greatest promise for the treatment of biofilm-associated CRS in order to inform future research on the management of this difficult condition.
Mangiferin Alleviates Postpartum Depression–Like Behaviors by Inhibiting MAPK Signaling in Microglia
Authors: Yan Meichen , Bo Xuena , Zhang Xinchao , Zhang Jingdan , Liao Yajin , Zhang Haiyan , Cheng Yong , Guo Junxia , Cheng Jinbo
Published: September 2022

Postpartum depression (PPD), a severe mental health disorder, is closely associated with decreased gonadal hormone levels during the postpartum period. Mangiferin (MGF) possesses a wide range of pharmacological activities, including anti-inflammation. Growing evidence has suggested that neuroinflammation is involved in the development of depression. However, the role of MGF in the development of PPD is largely unknown. In the present study, by establishing a hormone-simulated pregnancy PPD mouse model, we found that the administration of MGF significantly alleviated PPD-like behaviors. Mechanistically, MGF treatment inhibited microglial activation and neuroinflammation. Moreover, we found that MGF treatment inhibited mitogen-activated protein kinase (MAPK) signaling in vivo and in vitro. Together, these results highlight an important role of MGF in microglial activation and thus give insights into the potential therapeutic strategy for PPD treatment.
Using omics approaches to dissect the therapeutic effects of Chinese herbal medicines on gastrointestinal cancers
Authors: Li Si-Yi , Wang Wei-Jia , Li Qiu-Yue , Yang Peng-Hui , Li Xin-Long , Yan Yan , Yuan Yong , Feng Yi-Bin , Hong Ming
Published: September 2022

Chinese herbal medicines offer a rich source of anti-cancer drugs. Differences between the pharmacology of Chinese herbal medicines and modern synthetic chemicals hinder the development of drugs derived from herbal products. To address this challenge, novel omics approaches including transcriptomics, proteomics, genomics, metabolomics, and microbiomics have been applied to dissect the pharmacological benefits of Chinese herbal medicines in cancer treatments. Numerous Chinese herbal medicines have shown potential anti-tumor effects on different gastrointestinal (GI) cancers while eliminating the side effects associated with conventional cancer therapies. The present study aimed to provide an overview of recent research focusing on Chinese herbal medicines in GI cancer treatment, based on omics approaches. This review also illustrates the potential utility of omics approaches in herbal-derived drug discovery. Omics approaches can precisely and efficiently reveal the key molecular targets and intracellular interaction networks of Chinese herbal medicines in GI cancer treatment. This study summarizes the application of different omics-based approaches in investigating the effects and mechanisms of Chinese herbal medicines in GI cancers. Future research directions are also proposed for this area of study.
Traditional Chinese Medicine and Natural Products: Potential Approaches for Inflammatory Bowel Disease
Authors: Yuan Shuo , Li You , Li Jiao , Xue Jia-Chen , Wang Qi , Hou Xiao-Ting , Meng Huan , Nan Ji-Xing , Zhang Qing-Gao
Published: September 2022

Inflammatory bowel disease (IBD) is a rare, recurrent, and intractable inflammation obstruction of the stomach tract, usually accompanied by inflammation of cell proliferation and inflammation of the colon and carries a particular cause of inflammation. The clinical use of drugs in western countries affects IBD treatment, but various adverse effects and high prices limit their application. For these reasons, Traditional Chinese Medicine (TCM) is more advantageous in treating IBD. This paper reviews the mechanism and research status of TCM and natural products in IBD treatment by analyzing the relevant literature to provide a scientific and theoretical basis for IBD treatment.