bluuebunny/crossref_metadata_2025 huggingface dataset:
A Nutritional Metabolism Related Prognostic Scoring System for Patients With Newly Diagnosed Osteosarcoma
Authors: Li Longqing , Li Zhuangzhuang , He Xuanhong , Wang Yang , Lu Minxun , Gong Taojun , Chang Qing , Lin Jingqi , Luo Yi , Min Li , Zhou Yong , Tu Chongqi
Published: April 2022

Osteosarcoma is a primary malignant bone tumor with high metastatic potential. To date, achieving long-term survival of osteosarcoma patients remains a difficult task. Metabolic reprogramming has emerged as a new hallmark of cancer. However, studies on the prognostic value of hematological markers related to nutritional and metabolism in cancer patients are limited and contradictory. In this retrospective study, we extensively collected 16 hematological markers related to nutritional and metabolism in 223 osteosarcoma patients. A nutritional metabolism related prognostic scoring system (NMRS) in patients with osteosarcoma was constructed by least absolute contraction and selection operator (LASSO) cox regression analysis. Compared with individual hematological indicators, NMRS has stronger predictive power (training set: 0.811 vs. 0.362–2.638; validation set: 0.767 vs. 0.333–0.595). It is an independent prognostic factor for the survival of patients with osteosarcoma [HR: 1.957 (1.375–2.786) training set; HR: 3.146 (1.574–6.266) validation set]. NMRS-based nomograms have good and stable predictive power. NMRS facilitates further risk stratification of patients with the same clinical characteristics.
From Fitting the Average to Fitting the Individual: A Cautionary Tale for Mathematical Modelers
Authors: Luo Michael C. , Nikolopoulou Elpiniki , Gevertz Jana L.
Published: April 2022

An outstanding challenge in the clinical care of cancer is moving from a one-size-fits-all approach that relies on population-level statistics towards personalized therapeutic design. Mathematical modeling is a powerful tool in treatment personalization, as it allows for the incorporation of patient-specific data so that treatment can be tailor-designed to the individual. Herein, we work with a mathematical model of murine cancer immunotherapy that has been previously-validated against the average of an experimental dataset. We ask the question: what happens if we try to use this same model to perform personalized fits, and therefore make individualized treatment recommendations? Typically, this would be done by choosing a single fitting methodology, and a single cost function, identifying the individualized best-fit parameters, and extrapolating from there to make personalized treatment recommendations. Our analyses show the potentially problematic nature of this approach, as predicted personalized treatment response proved to be sensitive to the fitting methodology utilized. We also demonstrate how a small amount of the right additional experimental measurements could go a long way to improve consistency in personalized fits. Finally, we show how quantifying the robustness of the average response could also help improve confidence in personalized treatment recommendations.
Trabectedin and Radiation Therapy for Cardiac Metastasis From Leiomyosarcoma: A Case Report and Review of the Literature
Authors: Tortorelli Ilaria , Navarria Federico , Maggio Antonio Di , Banzato Alberto , Lestuzzi Chiara , Nicosia Luca , Chiusole Benedetta , Galiano Antonella , Sbaraglia Marta , Zagonel Vittorina , Brunello Antonella
Published: April 2022

Leiomyosarcoma (LMS) is one of the most frequent subtypes of soft-tissue sarcomas (STSs). Metastatic spread to the heart in cancer patients carries a poor prognosis and there is no known effective treatment. Cardiac metastases of STSs are very rare. Here we present the case of a 55-year-old patient who underwent surgical resection of a retroperitoneal leiomyosarcoma and then developed widespread metastatic disease, treated with a combination of local treatment and systemic therapy. Three years after surgical resection she presented with a cardiac intraventricular mass, which was treated with radiation therapy, while receiving systemic therapy with trabectedin. Such combination therapy was well-tolerated and effective, allowing a substantial dimensional reduction which is perduring to date, 18 months after diagnosis of cardiac metastasis. Available literature and data point to the feasibility and good tolerability of radiation therapy and trabectedin in metastatic sarcoma, yet this is the first report on the effectiveness of the combination for the treatment of cardiac disease. The extended survival since a metastatic relapse (more than 3 years) is likely the result of integrated systemic and loco-regional treatment, which should be always discussed within the framework of a multiprofessional and multidisciplinary setting.
Development of a Novel Reference Material for Tumor Mutational Burden Measurement Based on CRISPR/Cas9 Technology
Authors: Peng Rongxue , Lin Guigao , Li Lin , Li Jinming
Published: April 2022

As a biomarker that affects treatment decisions of immune checkpoint inhibitors, the accuracy, reliability, and comparability of tumor mutational burden (TMB) estimation is of paramount importance. To improve the consistency and reliability of these tests, qualified reference materials providing ground-truth data are crucial. In this study, we developed a set of formalin-fixed and paraffin-embedded (FFPE) samples with different TMB values as the novel reference materials for TMB estimation. By introducing several clinically relevant variants in MutS Homolog 2 (MSH2) gene and DNA polymerase epsilon (POLE) gene into human cell lines using CRISPR/Cas9 technology, we first constructed four typical cell lines which verified with hypermutator or ultramutator phenotype. Followed by cell mixing and paraffin embedding, the novel FFPE samples were prepared. It was confirmed that our novel FFPE samples have sufficient quantity of cells, high reproducibility, and they can provide matched wild type sample as the genetic background. The double-platform whole exome sequencing validation showed that our FFPE samples were also highly flexible as they containing different TMB values spanning a clinically relevant range (2.0–106.1 mut/Mb). Without limitations on production and TMB values, our novel FFPE samples based on CRISPR/Cas9 editing are suitable as candidate reference materials. From a practical point of view, these samples can be used for the validation, verification, internal quality control, and proficiency testing of TMB assessment.
Differentiation of Human GBM From Non-GBM Brain Tissue With Polarization Imaging Technique
Authors: Liu Yi-Rong , He Hong-Hui , Wu Jian
Published: April 2022

As for optical techniques, it is difficult for the 5-aminolevulinic (5-ALA) fluorescence guidance technique to completely detect glioma due to residual cells in the blind area and the dead angle of vision under microscopy. The purpose of this research is to characterize different microstructural information and optical properties of formalin-soaked unstained glioblastoma (GBM) and non-GBM tissue with the polarization imaging technique (PIT), and provide a novel method to detect GBM during surgery. In this paper, a 3×3 Mueller matrix polarization experimental system in backscattering mode was built to detect the GBM and non-GBM tissue bulk. The Mueller matrix decomposition and transformation parameters of GBM and non-GBM tissue were calculated and analyzed, and showed that parameters (1−Δ) and t are good indicators for distinguishing GBM from non-GBM tissues. Furthermore, the central moment coefficients (CMCs) of the frequency distribution histogram (FDH) were also calculated and used to distinguish the cancerous tissues. The results of the experiments confirmed the feasibility of PIT applied in the clinic to detect glioma, laying the foundation for the subsequent non-invasive, non-staining glioma detection.
Prognostic Relevance of Estrogen Receptor Status in Circulating Tumor Cells in Breast Cancer Patients Treated With Endocrine Therapy
Authors: Zhou Ying , Zhou Jinmei , Xiao Jinyi , Wang Yuehua , Wang Hao , Shi Haoyuan , Yue Chunyan , Jia Fei , Li Ping , Hu Zhiyuan , Yang Yanlian , Jiang Zefei , Wang Tao
Published: April 2022

Recently, female breast cancer (BC) has surpassed lung cancer to occupy the first place of the most commonly diagnosed cancer. The unsatisfactory prognosis of endocrine therapy for breast cancer might be attributed to the discordance in estrogen receptor (ER) status between primary tumors and corresponding metastases, as well as temporal and spatial receptor status heterogeneity at point-in-time between biopsy and treatment. The purpose of this study was to evaluate the prognostic and predictive value of ER status in circulating tumor cells (CTCs) in BC patients. We analyzed ER expression on CTCs isolated using the Pep@MNPs method in 2.0 ml of blood samples from 70 patients with BC and 67 female controls. The predictive and prognostic value of ER expression in CTCs and immunohistochemistry results of biopsies for progression-free survival (PFS) and overall survival (OS) of patients in response to therapies were assessed. The detection rate for CTCs was 95.71% (67/70 patients), with a median of 8 CTCs within 2 ml of peripheral venous blood (PVB). A concordance of 76.56% in ER status between CTCs and corresponding primary tumor and 69.23% between CTCs and corresponding metastases was observed. We also found that patients with ER-positive CTCs (CTC ER+) had longer PFS and OS than those without ER-positive CTCs (CTC ER-). Our findings suggested that ER status in CTCs of BC patients may provide valuable predictive and prognostic insights into endocrine therapies, although further evaluation in larger prospective trials is required.
The Role of RNA Methyltransferase METTL3 in Normal and Malignant Hematopoiesis
Authors: Wu Xia , Ye Wu , Gong Yuping
Published: April 2022

m6A modification is the most common modification in eukaryotes. METTL3, as a core methyltransferase of m6A modification, plays a vital role in normal and malignant hematopoiesis. Recent studies have shown that METTL3 is required for normal and symmetric differentiation of hematopoietic stem/progenitor cells (HSPCs). Moreover, METTL3 strongly impacts the process and development of hematological neoplasms, including the differentiation, apoptosis, proliferation, chemoresistance, and risk of tumors. Novel inhibitors of METTL3 have been identified and studied in acute myeloid leukemia (AML) cells. STM2457, a selective inhibitor of METTL3, has been identified to block proliferation and promote differentiation and apoptosis of AML cells without impacting normal hematopoiesis. Therefore, in our present review, we focus on the structure of METTL3, the role of METTL3 in both normal and malignant hematopoiesis, and the potential of METTL3 for treating hematological neoplasms.
Case Report: Retroperitoneal Sarcoma in Six Operations: Our Experience in Operative Management of Blood Vessels
Authors: Guo Jinhui , Qiu Fabo , Zhao Jie , Lu Qiliang , Fu Wen , Xu Qiuran , Huang Dongsheng
Published: April 2022

Here we introduce a case of retroperitoneal liposarcoma, which is characterized by repeated recurrences after surgery, and has undergone a total of 6 operations. The diameter of the tumor was about 26 cm at the time of the patient's diagnosis. The imaging examination revealed that the surrounding organs and blood vessels were invaded, which brought great challenges to radical resection. The postoperative pathology of the patient’s first operation was dedifferentiated liposarcoma, and some areas showed myxofibrosarcoma differentiation. With the recurrence of sarcoma, myxofibrosarcoma dedifferentiated into rhabdomyosarcoma, and malignant fibrous histiocytoma appeared in some areas. How to treat this type of patient after recurrence? How to deal with blood vessels wrapped by sarcoma during surgery? The medical community has not yet reached the same conclusion. We describe the process of treating the patient and the experience of dealing with blood vessels during surgery.
Pseudomonas aeruginosa in Cancer Therapy: Current Knowledge, Challenges and Future Perspectives
Authors: Pang Zheng , Gu Meng-Di , Tang Tong
Published: April 2022

Drug resistance, undesirable toxicity and lack of selectivity are the major challenges of conventional cancer therapies, which cause poor clinical outcomes and high mortality in many cancer patients. Development of alternative cancer therapeutics are highly required for the patients who are resistant to the conventional cancer therapies, including radiotherapy and chemotherapy. The success of a new cancer therapy depends on its high specificity to cancer cells and low toxicity to normal cells. Utilization of bacteria has emerged as a promising strategy for cancer treatment. Attenuated or genetically modified bacteria were used to inhibit tumor growth, modulate host immunity, or deliver anti-tumor agents. The bacteria-derived immunotoxins were capable of destructing tumors with high specificity. These bacteria-based strategies for cancer treatment have shown potent anti-tumor effects both in vivo and in vitro, and some of them have proceeded to clinical trials. Pseudomonas aeruginosa, a Gram-negative bacterial pathogen, is one of the common bacteria used in development of bacteria-based cancer therapy, particularly known for the Pseudomonas exotoxin A-based immunotoxins, which have shown remarkable anti-tumor efficacy and specificity. This review concisely summarizes the current knowledge regarding the utilization of P. aeruginosa in cancer treatment, and discusses the challenges and future perspectives of the P. aeruginosa-based therapeutic strategies.
Exosome-Based Nanoplatforms: The Emerging Tools for Breast Cancer Therapy
Authors: Liu Quan , Zhang Xian , Zhang Jun
Published: April 2022

Breast cancer (BC) remains the leading malignant tumor type among females worldwide. The patients with BC are still faced with undesirable metastasis, relapse rate, and drug resistance. Exosomes are defined as naturally occurring extracellular vesicles (EVs) with typical biomarkers that reflect the characteristics of the parent cells. Exosomes are crucial mediators involved in intercellular communication. By transferring multiple cargoes, represented by proteins, nucleic acids, lipids, metabolites, exosomes contribute to reshaping the recipient cell function and fate. Growing evidence has documented that exosomes originating from BC cells are important participants involved in BC progression and treatments. Nanoparticle-based technology is the cutting-edge field for renewing pharmaceuticals and has endowed deep improvements in precise BC treatment. Additionally, due to their perfect features of the low immune prototype, limited adverse effects, prolongated circulation, and easy modification, exosomes have received much attention as candidates in nano-medicine of BC. The nanoplatforms constructed by exosomes have safety, intelligence, biomimetic, and controlled released advantages for combating BC. Here, we emphasize the multiple exosomes from a variety of cell sources in constructing nanoplatforms for BC therapy, mainly including exosomes and their cargoes, genetically engineered exosomes, and exosome-based carriers. This field would shed light on the promising exosome-based delivery system in BC therapy.
Neurogenesis Is Reduced at 48 h in the Subventricular Zone Independent of Cell Death in a Piglet Model of Perinatal Hypoxia-Ischemia
Authors: Alonso-Alconada Daniel , Gressens Pierre , Golay Xavier , Robertson Nicola J.
Published: April 2022

Cellular and tissue damage triggered after hypoxia-ischemia (HI) can be generalized and affect the neurogenic niches present in the central nervous system. As neuroregeneration may be critical for optimizing functional recovery in neonatal encephalopathy, the goal of the present work was to investigate the neurogenic response to HI in the neurogenic niche of the subventricular zone (SVZ) in the neonatal piglet. A total of 13 large white male piglets aged <24 h were randomized into two groups: i) HI group (n = 7), animals submitted to transient cerebral HI and resuscitation; and ii) Control group (n = 6), non-HI animals. At 48 h, piglets were euthanized, and the SVZ and its surrounding regions, such as caudate and periventricular white matter, were analyzed for histology using hematoxylin-eosin staining and immunohistochemistry by evaluating the presence of cleaved caspase 3 and TUNEL positive cells, together with the cell proliferation/neurogenesis markers Ki67 (cell proliferation), GFAP (neural stem cells processes), Sox2 (neural stem/progenitor cells), and doublecortin (DCX, a marker of immature migrating neuroblasts). Hypoxic-ischemic piglets showed a decrease in cellularity in the SVZ independent of cell death, together with decreased length of neural stem cells processes, neuroblast chains area, DCX immunoreactivity, and lower number of Ki67 + and Ki67 + Sox2 + cells. These data suggest a reduction in both cell proliferation and neurogenesis in the SVZ of the neonatal piglet, which could in turn compromise the replacement of the lost neurons and the achievement of global repair.
Periconceptional Folic Acid Supplementation and Newborn Birth Weights
Authors: Lin Jing , Wang Cheng , Li Sisi , Zhang Jie , Jin Lei , Tong Mingkun , Meng Wenying , Ren Aiguo , Chen Lei , Jin Lei
Published: April 2022

Background

The relationship between maternal folic acid supplementation and the birth weights of offspring remains inconclusive.

Aim

To examine the associations between maternal supplementation with folic acid only (FAO) or multiple micronutrients containing folic acid (MMFA) and newborn birth weights, as well as the risk of small for gestational week age (SGA) and large for gestational week age (LGA) newborns.

Methods

Data on 31,107 births from 2015 to 2018 were extracted from the population-based prenatal health care system in a district of Beijing. Generalized linear and logistic regression models were used to evaluate the association between maternal periconceptional folic acid supplementation and birth weights or with risk of small for gestational week age (SGA) and large for gestational week age (LGA).

Results

Compared with newborns whose mothers did not use any folic acid supplements, the newborns with maternal periconceptional folic acid supplementation had similar median birth weight but had a lower risk of SGA [adjusted odds ratio (aOR) = 0.81 (95% CI: 0.68–0.97)], however newborns born to mothers who took multiple micronutrients with folic acid (MMFA) with high compliance had a 25.59 g (95% CI: 6.49–44.69) higher median birth weight. Periconceptional women took folic acid only (FAO) (aOR = 0.83; 95%CI: 0.67–1.01) or MMFA (aOR = 0.74; 95%CI: 0.60–0.91) with high compliance decreased the risk of SGA, but has no impact on the risk of LGA.

Conclusion

Periconceptional FAO supplementation has no impact on the median birth weight of offspring and the risk of LGA. Compared with FAO, MMFA supplementation may increase the average birth weight, and a high compliance of supplementation with FAO or MMFA may reduce the risk of SGA, with MMFA having ad stronger effect than FAO.
Hereditary Systemic Autoinflammatory Diseases: Therapeutic Stratification
Authors: Kul Cinar Ovgu , Putland Amber , Wynne Karen , Eleftheriou Despina , Brogan Paul A.
Published: April 2022

Hereditary systemic autoinflammatory diseases (SAIDs) are rare, often severe conditions characterised by mutations in the key regulators of innate immune responses. Dramatic advances in the molecular genetics and next-generation sequencing in the past decade enabled identification of novel mutations that play a pivotal role in the mechanistic pathways of inflammation. Although genetic testing may not always provide straightforward guidance in diagnosis and clinical decision making, through translational research, it sheds light into molecular immunopathogenesis, particularly in IL-1 inflammasome and cytokine signalling pathways. These remarkable insights provided a better understanding of autoinflammatory conditions and their association with the innate and adaptive immune systems, as well as leading to development of cytokine-targetted biologic treatments. Use of targetted therapeutics not only helps control disease flares, reduce acute-phase responses and prevent devastating complications such as amyloidosis, but also improves health-related quality of lives and support patients to pursue almost a normal life. Herein, we discuss the commonest monogenic SAIDs, describe their immunopathology, and summarise the approaches in the management and targetted treatment of these conditions, including presentation of novel data based on a cohort of children with these rare diseases from a single quaternary referral centre in London.
Compensatory Upregulation of Anti-Beta-Adrenergic Receptor Antibody Levels Might Prevent Heart Failure Presentation in Pediatric Myocarditis
Authors: Seidel Franziska , Scheibenbogen Carmen , Heidecke Harald , Opgen-Rhein Bernd , Pickardt Thomas , Klingel Karin , Berger Felix , Messroghli Daniel , Schubert Stephan
Published: April 2022

Background

Myocarditis can be associated with severe heart failure and is caused by different inflammatory and autoimmune responses. The aim of this study was to describe the immunological response in children with myocarditis by analyzing anti-beta-adrenergic receptor antibodies (anti-β-AR Abs).

Methods

Sera of children who were hospitalized with biopsy-proven myocarditis were prospectively collected between April 2017 and March 2019. Anti-β1-AR Ab, anti-β2-AR Ab, and anti-β3-AR Ab were quantified by a CE-certified ELISA kit. According to normal values for immunoglobulin G (IgG), three age groups, <1, 1–5, and >5–17 years, were defined. Children without inflammatory cardiac pathology and no heart failure signs were served as a control group.

Results

We compared 22 patients with biopsy-proven myocarditis and 28 controls. The median age (interquartile range) of the myocarditis group (MYC) was 12.1 (2.7–16.4) years, 13 men, left ventricular ejection fraction (LVEF) 51% and for control group, the median age was 5.0 (3.0–6.8) years, nine men, LVEF 64%. Myocarditis patients in the age group >5–17 years showed significantly higher anti-β3-AR Ab levels as compared to controls (p = 0.014). Lower anti-β2-AR Ab and anti-β3-AR Ab levels were significantly correlated with higher left ventricular diameters in myocarditis patients. The event-free survival using a combined endpoint (mechanical circulatory support [MCS], transplantation, and/or death) was significantly lower in myocarditis patients with antibody levels below the median as compared to myocarditis patients with antibody levels ≥ the median.

Conclusion

Anti-β-AR Ab levels are increased in children with myocarditis and >5 years of age. These antibodies might be upregulated compensatory to prevent further cardiac deterioration. A worse event-free survival in patients with lower anti-β-AR Ab levels might be a therapeutic target for immunoglobulin substitution.
Venous Thromboembolic Complications in Pediatric Gastrointestinal Diseases: Inflammatory Bowel Disease and Intestinal Failure
Authors: Klomberg Renz C. W. , Vlug Lotte E. , de Koning Barbara A. E. , de Ridder Lissy
Published: April 2022

In children with gastrointestinal disorders such as inflammatory bowel disease (IBD) and intestinal failure (IF), the risk of venous thromboembolism (VTE) is increased. VTE may lead to pulmonary embolism, sepsis and central line infection, stroke and post-thrombotic syndrome. The purpose of this review is to summarize current knowledge and recent advances around VTE management in pediatric gastroenterology with a focus on IBD and IF. The VTE incidence in children with IBD is reported to be around 4–30 per 10,000 patient-years, with higher incidences for hospitalized children. While in general, IF is less common than IBD, the VTE incidence in children with IF is around 750 per 10,000 patient-years. The most common risk factors for development of VTE involve deviations leading to Virchow's triad (endothelial damage, stasis, and hypercoagulability) and include active inflammation, particularly with colonic involvement, presence of a central venous catheter, underlying thrombophilia, reduced mobility, surgery, and hospitalization. Classes of anticoagulants used for treatment of VTE are low molecular weight heparins and vitamin K antagonists. However, the use of direct oral anticoagulants for treatment or prevention of VTE has not been studied in this pediatric population yet. Pediatric gastroenterologists apply different VTE prevention and treatment strategies due to lack of literature and lack of consensus. We discuss the role of primary and secondary prophylactic use of anticoagulants, and provide tools and recommendations for screening, prevention and management for the specific pediatric populations.
Polymyxin B-Associated Nephrotoxicity and Its Predictors: A Retrospective Study in Carbapenem-Resistant Gram-Negative Bacterial Infections
Authors: Wu Xiao-Li , Long Wen-Ming , Lu Qiong , Teng Xin-Qi , Qi Ting-Ting , Qu Qiang , He Ge-Fei , Qu Jian
Published: April 2022

Polymyxin B (PMB), a kind of polymyxin, was widely used in carbapenem-resistant Gram-negative bacterial (CR-GNB) infections. However, adverse reactions such as nephrotoxicity and neurotoxicity limit its use in clinical practice. The aim of this study was to explore PMB associated with nephrotoxicity and its predictors. Patients who received PMB intravenous drip for more than 72 h were eligible for the study. Characteristics of patients, concomitant nephrotoxic agents, underlying disease, and antimicrobial susceptibility were submitted for descriptive analysis. Univariate analysis and binary logistic regression were used to assess the factors leading to acute kidney injury (AKI). AKI was assessed with serum creatinine variations according to the classification of risk (stage R), injury (stage I), failure (stage F), loss, and end-stage of kidney disease. Among 234 patients with CR-GNB infections who used PMB in our study, 67 (28.63%) patients developed AKI, including 31 (14.25%) patients in stage R, 15 (6.41%) patients in stage I, and 21 (8.97%) patients in stage F. The incident rate of PMB-related nephrotoxicity in patients with normal renal function was 32.82% (43/131). The higher risk factors of AKI include males [odds ratio (OR) = 3.237; 95% confidence interval (95%CI) = 1.426–7.350], digestive system diseases [OR = 2.481 (1.127–5.463)], using furosemide (>20 mg/day) [OR = 2.473 (1.102–5.551)], and baseline serum creatinine [OR = 0.994 (0.990–0.999)]. Nonparametric tests of K-independent samples showed that baseline serum creatinine and the PMB maintenance dose were associated with the severity of nephrotoxicity (both p < 0.05). Male, digestive system diseases, using furosemide (>20 mg/day), and high baseline serum creatinine were the independent risk factors of PMB-associated AKI development. The maintenance dose of PMB may be related to the severity of AKI. These risk factors should be taken into consideration when initiating PMB-based therapy. The serum creatinine value should be closely monitored when using PMB.
Use of Herbal Medicines Among Breastfeeding Mothers in Tanzania: A Cross-Sectional Study
Authors: Millinga Valeria Phelician , Im Hyea Bin , Hwang Jung Hye , Choi Soo Jeung , Han Dongwoon
Published: April 2022

Background: There are limited data on the use of herbal medicines (HM) among breastfeeding mothers, despite the fact that knowledge of the possible benefits or harms of HM use has a direct relationship with the health of infants, especially in resource-limited countries. The study aims to determine the prevalence and factors associated with HM use among breastfeeding mothers in Tanzania.

Methods: The study followed a cross-sectional design using a structured survey questionnaire. Survey participants were recruited from the reproductive and child health clinic at Uhuru health center in Morogoro, Tanzania. The survey instrument comprised of 34 questions, including demographic information, the pattern of HM use during breastfeeding, and women’s perceptions of HM. Chi-square test and logistic regression were used for data analysis using SPSS ver. 24.0.

Results: The majority of the respondents (53.8%) used HM during breastfeeding. The most commonly used HM was black pepper (Piper nigrum L.; 80.0%), followed by pumpkin seeds (Cucurbita pepo L.; 18.0%). About one-third (27.5%) of HM users discussed their use with their healthcare providers. In addition, higher education levels and low breastmilk supply were identified as potential predictors of HM use.

Conclusion: The practice of HM use among breastfeeding mothers in Tanzania is popular to ease breastfeeding difficulties. However, the issue of the safety or effectiveness of HM is still an unknown agenda. This awakens the need to evaluate HM’s safety, efficacy, and quality through pharmacological studies for scientific evidence. Lastly, a clinical guideline should be developed in healthcare settings to promote open dialogues between the healthcare providers and mothers to ensure the safe use of HM.
Inflammation-Independent Antinociceptive Effects of DF2755A, a CXCR1/2 Selective Inhibitor: A New Potential Therapeutic Treatment for Peripheral Neuropathy Associated to Non-Ulcerative Interstitial Cystitis/Bladder Pain Syndrome
Authors: Brandolini Laura , Aramini Andrea , Bianchini Gianluca , Ruocco Anna , Bertini Riccardo , Novelli Rubina , Angelico Patrizia , Valsecchi Anna Elisa , Russo Roberto , Castelli Vanessa , Cimini Annamaria , Allegretti Marcello
Published: April 2022

Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a chronic bladder disease of unknown etiology characterized by urinary frequency and episodic and chronic pain. Analgesic treatments for IC/BPS are limited, especially for patients with non-Hunner (non-ulcerative) type IC who usually have poor overall outcomes. Here, we demonstrate that oral treatment with DF2755A, a potent and selective inhibitor of chemokine receptors CXCR1/2, can prevent and reverse peripheral neuropathy associated to non-Hunner IC/BPS by directly inhibiting chemokine-induced excitation of sensory neurons. We tested DF2755A antinociceptive effects in a cyclophosphamide (CYP)-induced non-ulcerative IC rat model characterized by severe peripheral neuropathy in the absence of bladder inflammatory infiltrate, urothelial hyperplasia, and hemorrhage. Treatment with DF2755A prevented the onset of peripheral neuropathy and reversed its development in CYP-induced IC rats, showing a strong and long-lasting anti-hyperalgesic effect. Ex vivo and in vitro studies showed that DF2755A treatment strongly inhibited the expression of CXCR2 agonists, CXCL1/KC, and CXCL5 and of transient receptor potential vanilloid 1 (TRPV1) compared to vehicle, suggesting that its effects can be due to the inhibition of the nociceptive signaling passing through the CXCL1/CXCR1-2 axis and TRPV1. In conclusion, our results highlight the key pathophysiological role played by the CXCL1/CXCR1-2 axis and TRPV1 in the onset and development of peripheral neuropathy in non-Hunner IC and propose DF2755A as a potential therapeutic approach for the treatment of not only inflammatory painful conditions but also neuropathic ones and in particular non-Hunner IC/BPS.
Protective Effects of 6-Gingerol on Cardiotoxicity Induced by Arsenic Trioxide Through AMPK/SIRT1/PGC-1α Signaling Pathway
Authors: Han Xue , Yang Yakun , Zhang Muqing , Chu Xi , Zheng Bin , Liu Chenxu , Xue Yucong , Guan Shengjiang , Sun Shijiang , Jia Qingzhong
Published: April 2022

Background and Objective: Arsenic trioxide (As2O3) induced cardiotoxicity to limit the clinical applications of the effective anticancer agent. 6-Gingerol (6G) is the main active ingredient of ginger, a food with many health benefits. The present study aims to investigate the potential pharmacological mechanisms of 6G on As2O3-induced myocardial injury.

Methods and Results: Fifty KunMing mice were divided into five groups (n = 10) receiving: 1) physiological saline; 2) 6G (20 mg/kg) alone; 3) As2O3 (5 mg/kg); 4) 6G (10 mg/kg) and As2O3 (5 mg/kg); 5) 6G (20 mg/kg) and As2O3 (5 mg/kg). 6G was given orally and As2O3 was given intraperitoneally once per day for seven consecutive days. Biochemical, histopathological, transmission electron microscopy, ELISA, and western blotting analyses were then performed. Based on the resultant data, As2O3 was found to induce cardiotoxicity in mice. 6G significantly ameliorated As2O3-induced heart injury, histopathological changes, oxidative stress, myocardial mitochondrial damage, inflammation, and cardiomyocyte apoptosis, while reversed As2O3-induced inhibition of the AMPK/SIRT1/PGC-1α pathway.

Conclusion: Our experimental results reveal that 6G effectively counteracts As2O3-induced cardiotoxicity including oxidative stress, inflammation and apoptosis, which might be attributed to its activation action on AMPK/SIRT1/PGC-1α signaling pathway.
Quantum Cooperative Multicast in a Quantum Hybrid Topology Network
Authors: Chen Si-Yi , Xu Gang , Chen Xiu-Bo , Shang Tao , Yang Yi-Xian
Published: April 2022

Quantum multicast is a significant transmission mode in a multiparty communication scenario. Multisource collaboration can further enhance the efficient multicast. However, it remains a challenge to realize quantum multicast with a cooperative way in a complex topology network. In this article, we propose a scheme of quantum cooperative multicast in a hybrid topology network. It provides information aggregation and simultaneous multipoint transmission services. First, collaborative information aggregation allows central network data to be integrated into the aggregation node. By exploiting the quantum multicast mode, the aggregation node can simultaneously deliver integrated quantum states to multiple targets. Second, our scheme is feasible for dynamic network expansion. It is capable of extending the network architecture iteratively, while the peer network requests can be handled in parallel. Finally, the new scheme shows great application potential in the distributed quantum network. It is a promising candidate for the implementation of quantum data disaster backup in future.
The Accuracy of Cerenkov Photons Simulation in Geant4/Gate Depends on the Parameterization of Primary Electron Propagation
Authors: Trigila Carlotta , Ariño‐Estrada Gerard , Kwon Sun Il , Roncali Emilie
Published: April 2022

Energetic electrons traveling in a dispersive medium can produce Cerenkov radiation. Cerenkov photons’ prompt emission, combined with their predominantly forward emission direction with respect to the parent electron, makes them extremely promising to improve radiation detector timing resolution. Triggering gamma detections based on Cerenkov photons to achieve superior timing resolution is challenging due to the low number of photons produced per interaction. Monte Carlo simulations are fundamental to understanding their behavior and optimizing their pathway to detection. Therefore, accurately modeling the electron propagation and Cerenkov photons emission is crucial for reliable simulation results. In this work, we investigated the physics characteristics of the primary electrons (velocity, energy) and those of all emitted Cerenkov photons (spatial and timing distributions) generated by 511 keV photoelectric interactions in a bismuth germanate crystal using simulations with Geant4/GATE. Geant4 uses a stepwise particle tracking approach, and users can limit the electron velocity change per step. Without limiting it (default Geant4 settings), an electron mean step length of ∼250 μm was obtained, providing only macroscopic modeling of electron transport, with all Cerenkov photons emitted in the forward direction with respect to the incident gamma direction. Limiting the electron velocity change per step reduced the electron mean step length (∼0.200 μm), leading to a microscopic approach to its transport which more accurately modeled the electron physical properties in BGO at 511 keV. The electron and Cerenkov photons rapidly lost directionality, affecting Cerenkov photons’ transport and, ultimately, their detection.

Results suggested that a deep understanding of low energy physics is crucial to perform accurate optical Monte Carlo simulations and ultimately use them in TOF PET detectors.
Terahertz Non-Destructive Testing and Imaging of High-Voltage Cables
Authors: Zhenwei Zhang , Jing Xu , Rui Jia , Yinghong Wu , Hao Guan , Siyi Han , Cunlin Zhang , Yuejin Zhao
Published: April 2022

The evaluation of the internal defects in high-voltage cross-linked polyethylene cables is highly crucial for the security and reliability of power transmission. Here, a terahertz (THz) frequency-modulated-continuous-wave non-destructive testing (NDT) imaging system is used to demonstrate the non-contact detection of a high-voltage cable (35 KV). Combined with linear scanning and axial rotation, the three-dimensional (3D) data of the columnar target is acquired, and a 3D perspective image is reconstructed. The correspondence between the target in the real space and image space is determined to accurately show the internal spiral structure and strand number of metal wires. The results indicate that prefabricated air and water holes in the polyethylene insulation layer can be displayed. Furthermore, feature defect signals are automatically classified and recognised by combining the principal component analysis dimension reduction method and the support vector machine classification method, which can predict abnormal defects more efficiently in mass data. These results provide technical guidance for the non-contact NDT and visual evaluation of the internal state of detected cable targets.
Protein Restriction in the Peri-Pubertal Period Induces Autonomic Dysfunction and Cardiac and Vascular Structural Changes in Adult Rats
Authors: Ferreira Anna Rebeka Oliveira , Ribeiro Maiara Vanusa Guedes , Peres Maria Natalia Chimirri , Piovan Silvano , Gonçalves Géssica Dutra , Saavedra Lucas Paulo Jacinto , Martins Juliana Nunes de Lima , Junior Marcos Divino Ferreira , Cavalcante Keilah Valeria Naves , Lopes Gabriel kian Guimarães , Carneiro Mariane , Almeida Douglas Lopes , Gomes Rodrigo Mello , Comar Jurandir Fernando , Armitage James Andrew , Mathias Paulo Cezar de Freitas , Palma-Rigo Kesia
Published: April 2022

Perturbations to nutrition during critical periods are associated with changes in embryonic, fetal or postnatal developmental patterns that may render the offspring more likely to develop cardiovascular disease in later life. The aim of this study was to evaluate whether autonomic nervous system imbalance underpins in the long-term hypertension induced by dietary protein restriction during peri-pubertal period. Male Wistar rats were assigned to groups fed with a low protein (4% protein, LP) or control diet (20.5% protein; NP) during peri-puberty, from post-natal day (PN) 30 until PN60, and then all were returned to a normal protein diet until evaluation of cardiovascular and autonomic function at PN120. LP rats showed long-term increased mean arterial pressure (p = 0.002) and sympathetic arousal; increased power of the low frequency (LF) band of the arterial pressure spectral (p = 0.080) compared with NP animals. The depressor response to the ganglion blocker hexamethonium was increased in LP compared with control animals (p = 0.006). Pulse interval variability showed an increase in the LF band and LF/HF ratio (p = 0.062 and p = 0.048) in LP animals. The cardiac response to atenolol and/or methylatropine and the baroreflex sensitivity were similar between groups. LP animals showed ventricular hypertrophy (p = 0.044) and increased interstitial fibrosis (p = 0.028) compared with controls. Reduced protein carbonyls (PC) (p = 0.030) and catalase activity (p = 0.001) were observed in hearts from LP animals compared with control. In the brainstem, the levels of PC (p = 0.002) and the activity of superoxide dismutase and catalase (p = 0.044 and p = 0.012) were reduced in LP animals, while the levels of GSH and total glutathione were higher (p = 0.039 and p = 0.038) compared with NP animals. Protein restriction during peri-pubertal period leads to hypertension later in life accompanied by sustained sympathetic arousal, which may be associated with a disorganization of brain and cardiac redox state and structural cardiac alteration.
Ptch2 is a Potential Regulator of Mesenchymal Stem Cells
Authors: Juuri Emma , Tikka Pauli , Domanskyi Andrii , Corfe Ian , Morita Wataru , Mckinnon Peter J. , Jandova Nela , Balic Anamaria
Published: April 2022

Ptch receptors 1 and 2 mediate Hedgehog signaling pivotal for organ development and homeostasis. In contrast to embryonic lethal Ptch1−/− phenotype, Ptch2−/− mice display no effect on gross phenotype. In this brief report, we provide evidence of changes in the putative incisor mesenchymal stem cell (MSC) niches that contribute to accelerated incisor growth, as well as intriguing changes in the bones and skin which suggest a role for Ptch2 in the regulation of MSCs and their regenerative potential. We employed histological, immunostaining, and computed tomography (µCT) analyses to analyze morphological differences between Ptch2−/− and wild-type incisors, long bones, and skins. In vitro CFU and differentiation assays were used to demonstrate the MSC content and differentiation potential of Ptch2−/− bone marrow stromal cells. Wound healing assay was performed in vivo and in vitro on 8-week-old mice to assess the effect of Ptch2 on the wound closure. Loss of Ptch2 causes increases in the number of putative MSCs in the continuously growing incisor, associated with increased vascularization observed in the tooth mesenchyme and the neurovascular bundle. Increased length and volume of Ptch2−/− bones is linked with the increased number and augmented in vitro differentiation potential of MSCs in the bone marrow. Dynamic changes in the Ptch2−/− skin thickness relate to changes in the mesenchymal compartment and impact the wound closure potential. The effects of Ptch2 abrogation on the postnatal MSCs suggest a crucial role for Ptch2 in Hedgehog signaling regulation of the organ regenerative potential.
GSK-3β Inhibition in Birds Affects Social Behavior and Increases Motor Activity
Authors: Moaraf Stan , Rippin Ido , Terkel Joseph , Eldar-Finkelman Hagit , Barnea Anat
Published: April 2022

Glycogen synthase kinase-3 (GSK-3) is a highly conserved serine/threonine protein kinase that plays a central role in a wide variety of cellular processes, cognition and behaviour. In a previous study we showed that its α and β isozymes are highly conserved in vertebrates, however the α gene is missing in birds. This selective loss offers a unique opportunity to study the role of GSK-3β independently. Accordingly, in the present study we aimed to investigate the role of GSK-3β in social behaviour, motivation, and motor activity in zebra finches (Taeniopygia guttata). We did that by selective inhibition of GSK-3β and by using tests that were specifically designed in our laboratory. Our results show that GSK-3β inhibition: 1) Affected social recognition, because the treated birds tended to move closer towards a stranger, unlike the control birds that stood closer to a familiar bird. 2) Caused the treated birds to spend more time in the more middle parts of the cage compared to controls, a behaviour that might indicate anxiety. 3) As the experiment progressed, the treated birds took less time to make a decision where to stand in the cage compared to controls, suggesting an effect on decision-making. 4) Increased in the motor activity of the treated birds compared to the controls, which can be regarded as hyperactivity. 5) Caused the treated birds to pass through a barrier in order to join their flock members faster compared to controls, and regardless of the increase in the level of difficulty, possibly suggesting increased motivation. Our study calls for further investigation, because GSK-3 is well acknowledged as a central player in regulating mood behaviour, cognitive functions, and neuronal viability. Therefore, studying its impact on normal behaviour as we did in the current study, unlike most studies that were done in diseases models, can advance our understanding regarding GSK-3 various roles and can contribute to the discovery and development of effective treatments to repair cognition and behaviour.
Sulfatases: Critical Enzymes for Algal Polysaccharide Processing
Authors: Hettle Andrew G. , Vickers Chelsea J. , Boraston Alisdair B.
Published: April 2022

Microbial sulfatases are important biocatalysts in the marine environment where they play a key role in the catabolic biotransformation of abundant sulphated algal polysaccharides. The sulphate esters decorating algal polysaccharides, such as carrageenan, fucoidan and ulvan, can constitute up to 40% of the biopolymer dry weight. The use of this plentiful carbon and energy source by heterotrophic microbes is enabled in part by the sulfatases encoded in their genomes. Sulfatase catalysed hydrolytic removal of sulphate esters is a key reaction at various stages of the enzymatic cascade that depolymerises sulphated polysaccharides into monosaccharides that can enter energy yielding metabolic pathways. As the critical roles of sulfatases in the metabolism of sulphated polysaccharides from marine algae is increasingly revealed, the structural and functional analysis of these enzymes becomes an important component of understanding these metabolic pathways. The S1 family of formylglycine-dependent sulfatases is the largest and most functionally diverse sulfatase family that is frequently active on polysaccharides. Here, we review this important sulfatase family with emphasis on recent developments in studying the structural and functional relationship between sulfatases and their sulphated algal polysaccharide substrates. This analysis utilises the recently proposed active site nomenclature for sulfatases. We will highlight the key role of sulfatases, not only in marine carbon cycling, but also as potential biocatalysts for the production of a variety of novel tailor made sulphated oligomers, which are useful products in, for example, pharmaceutical or cosmetic applications.
Influence of Pollen Dispersal and Mating Pattern in Domestication of Intermediate Wheatgrass, a Novel Perennial Food Crop
Authors: Bajgain Prabin , Brandvain Yaniv , Anderson James A.
Published: April 2022

Intermediate wheatgrass (IWG) is a perennial forage grass that is currently being domesticated as a grain crop. It is a primarily wind-pollinated outcrossing species and expresses severe inbreeding depression when self-pollinated. Characterization of pollen dispersal, mating parameters, and change in genetic diversity due to pollen movement is currently lacking in IWG. In this study, we examined pollen dispersal in an IWG selection nursery by evaluating 846 progeny from 15 mother plants and traced their parentage to 374 fathers. A set of 2,500 genomic loci was used to characterize the population. We assigned paternity to 769 (91%) progeny and the average number of fathers per mother plant was 37, from an average of 56 progeny examined per mother. An extensive number (80%) of pollination events occurred within 10 m of the mother plants. Pollination success was not correlated with trait attributes of the paternal genotypes. Mating system analysis confirmed that IWG is highly outcrossing and inbreeding was virtually absent. Neither genetic diversity nor the genome-estimated trait values of progeny were significantly affected by pollinator distance. The distance of pollinator in an IWG breeding nursery therefore was not found to be a major contributor in maintaining genetic diversity. These findings reveal the pollen dispersal model in IWG for the first time and its effect on genetic diversity, which will be valuable in designing future IWG breeding populations. Information generated and discussed in this study could be applied in understanding gene flow and genetic diversity of other open-pollinated species.