bluuebunny/crossref_metadata_2025 huggingface dataset:
A simple analytical model for a fast 3D assessment of peripheral photon dose during coplanar isocentric photon radiotherapy
Authors: Sánchez-Nieto Beatriz , López-Martínez Ignacio N. , Rodríguez-Mongua José Luis , Espinoza Ignacio
Published: October 2022

Considering that cancer survival rates have been growing and that nearly two-thirds of those survivors were exposed to clinical radiation during its treatment, the study of long-term radiation effects, especially secondary cancer induction, has become increasingly important. To correctly assess this risk, knowing the dose to out-of-field organs is essential. As it has been reported, commercial treatment planning systems do not accurately calculate the dose far away from the border of the field; analytical dose estimation models may help this purpose. In this work, the development and validation of a new three-dimensional (3D) analytical model to assess the photon peripheral dose during radiotherapy is presented. It needs only two treatment-specific input parameter values, plus information about the linac-specific leakage, when available. It is easy to use and generates 3D whole-body dose distributions and, particularly, the dose to out-of-field organs (as dose–volume histograms) outside the 5% isodose for any isocentric treatment using coplanar beams [including intensity modulated radiotherapy and volumetric modulated arc therapy (VMAT)]. The model was configured with the corresponding Monte Carlo simulation of the peripheral absorbed dose for a 6 MV abdomen treatment on the International Comission on Radiological Protection (ICRP) 110 computational phantom. It was then validated with experimental measurements using thermoluminescent dosimeters in the male ATOM anthropomorphic phantom irradiated with a VMAT treatment for prostate cancer. Additionally, its performance was challenged by applying it to a lung radiotherapy treatment very different from the one used for training. The model agreed well with measurements and simulated dose values. A graphical user interface was developed as a first step to making this work more approachable to a daily clinical application.
Enhanced lipid metabolism confers the immunosuppressive tumor microenvironment in CD5-positive non-MYC/BCL2 double expressor lymphoma
Authors: Liu Meng-Ke , Cheng Li-Li , Yi Hong-Mei , He Yang , Li Xiao , Fu Di , Dai Yu-Ting , Fang Hai , Cheng Shu , Xu Peng-Peng , Qian Ying , Feng Yan , Liu Qian , Wang Li , Zhao Wei-Li
Published: October 2022

Lymphoma cells expressing CD5 (CD5+) confer inferior outcome of diffuse large B-cell lymphoma (DLBCL), especially in non–MYC/BCL2 double expressor (non-DE) patients. In tumor microenvironment, CD5+ non-DE tumor revealed increased proportion of immunosuppressive M2 macrophages and enhanced pathways related to macrophage activation and migration. In accordance to M2 activation, lipid metabolism was upregulated, including fatty acid uptake and fatty acid oxidation, which supplied energy for M2 macrophage polarization and activation. Meanwhile, CD36 expression was upregulated and strongly correlated to the proportion of M2 macrophages in CD5+ non-DE DLBCL. In vitro, a DLBCL cell line (LY10) overexpressing CD5 significantly increased M2 proportion in comparison with control when cocultured with peripheral blood mononuclear cells (PBMCs). The addition of metformin significantly decreased the M2 proportion and the CD36 expression level in the coculture systems, indicating that metformin could target altered lipid metabolism and decrease M2 macrophages in DLBCL, especially in CD5+ non-DE lymphoma. In conclusion, enhanced lipid metabolism and M2 macrophage activation contributed to the immunosuppressive tumor microenvironment and could be potential therapeutic targets in CD5+ non-DE DLBCL.
Postoperative radiotherapy might be a risk factor for second primary lung cancer: A population-based study
Authors: Mo You , Chen Minxin , Wu Meng , Chen Dawei , Yu Jinming
Published: October 2022

Background

Surgery is the main curative therapeutic strategy for patients with initial primary lung cancer (IPLC). Most international guidelines recommend regular follow-ups after discharge to monitor patients for tumor recurrence and metastasis. As the overall survival (OS) in patients with lung cancer improves, their risk of secondary primary lung cancer (SPLC) increases. Previous studies on such patients lack separate assessment of different survival outcomes and evaluation of high-risk factors for SPLC. Therefore, we aimed to determine the correlation between high-risk factors and causes of death in patients with SPLC, based on the Surveillance, Epidemiology, and End Results (SEER) database.

Methods

We screened the SEER database for patients with IPLC and SPLC from 2004 to 2015 and included only patients who underwent surgery since the IPLC and in whom the cancer was pathologically verified of an International Classification of Diseases grade of 0-3 and to be non-small-cell lung cancer. The standardized incidence ratio (SIR) was calculated between variables and SPLC. Multivariable Cox proportional-hazards regression analyses were conducted to calculate the correlation of different variables with overall survival (OS) and cancer-specific survival (CSS). A competing-risk model was conducted for SPLC. The effect of baseline bias on survival outcomes by performing propensity score matching analysis in a 1: 6 ratio (SPLC: IPLC).

Results

For patients aged 0-49 years, the overall SIR was higher in older patients, reaching a maximum of 27.74 in those aged 40-49 years, and at 11.63 in patients aged 50-59 years. The overall SIR was higher for patients who were more recently diagnosed with IPLC and increased with time after diagnosis. Male sex, SPLC (hazard ratio, 1.6173; 95% confidence interval, 1.5505-1.6869; P < 0.001), cancer grade III or IV, lower lobe of the lung, advanced stage and postoperative radiotherapy (PORT) were independently detrimental to OS. In terms of CSS, PORT was a high-risk factor.

Conclusions

Postoperative radiotherapy is a risk factor for second primary lung cancer and detrimental to overall and cancer-specific survival in patients who had initial primary lung cancer. These data support the need for life-long follow-up of patients who undergo treatment for IPLC to screen for SPLC.
Application of systemic treatment in conversion therapy options for liver cancer
Authors: Bei Haoyang , Mai Weiheng , Chen Weifeng , Li Mingyi , Yang Yongguang
Published: October 2022

Radical hepatectomy is the main treatment method to improve the prognosis of patients with intermediate and early-stage liver cancer. Most liver cancer patients in China are in the advanced stage at the initial diagnosis, losing the opportunity for surgical treatment. Therefore, it is essential to down-stage unresectable liver cancer to resectable liver cancer clinically, which is an important way to improve patients’ survival and a hotspot of current clinical research. In recent years, with the increase in effective treatment methods for liver cancer, the resection rate of conversion surgery for unresectable advanced liver cancer has been significantly improved, and a growing number of patients benefit from conversion therapy. This article mainly reviews the connotation of conversion therapy for liver cancer, the patient selection, the selection of conversion strategy, the timing of sequential operations, the scheme and safety, etc.
Blockade of growth hormone receptor signaling by using pegvisomant: A functional therapeutic strategy in hepatocellular carcinoma
Authors: Kaseb Ahmed O. , Haque Abedul , Vishwamitra Deeksha , Hassan Manal M. , Xiao Lianchun , George Bhawana , Sahu Vishal , Mohamed Yehia I. , Carmagnani Pestana Roberto , Lombardo Jamie Lynne , Avritscher Rony , Yao James C. , Wolff Robert A. , Rashid Asif , Morris Jeffrey S. , Amin Hesham M.
Published: October 2022

Hepatocellular carcinoma (HCC) is an aggressive neoplasm with poor clinical outcome because most patients present at an advanced stage, at which point curative surgical options, such as tumor excision or liver transplantation, are not feasible. Therefore, the majority of HCC patients require systemic therapy. Nonetheless, the currently approved systemic therapies have limited effects, particularly in patients with advanced and resistant disease. Hence, there is a critical need to identify new molecular targets and effective systemic therapies to improve HCC outcome. The liver is a major target of the growth hormone receptor (GHR) signaling, and accumulating evidence suggests that GHR signaling plays an important role in HCC pathogenesis. We tested the hypothesis that GHR could represent a potential therapeutic target in this aggressive neoplasm. We measured GH levels in 767 HCC patients and 200 healthy controls, and then carried out clinicopathological correlation analyses. Moreover, specific inhibition of GHR was performed in vitro using siRNA and pegvisomant (a small peptide that blocks GHR signaling and is currently approved by the FDA to treat acromegaly) and in vivo, also using pegvisomant. GH was significantly elevated in 49.5% of HCC patients, and these patients had a more aggressive disease and poorer clinical outcome (P<0.0001). Blockade of GHR signaling with siRNA or pegvisomant induced substantial inhibitory cellular effects in vitro. In addition, pegvisomant potentiated the effects of sorafenib (P<0.01) and overcame sorafenib resistance (P<0.0001) in vivo. Mechanistically, pegvisomant decreased the phosphorylation of GHR downstream survival proteins including JAK2, STAT3, STAT5, IRS-1, AKT, ERK, and IGF-IR. In two patients with advanced-stage HCC and high GH who developed sorafenib resistance, pegvisomant caused tumor stability. Our data show that GHR signaling represents a novel “druggable” target, and pegvisomant may function as an effective systemic therapy in HCC. Our findings could also lead to testing GHR inhibition in other aggressive cancers.
Causes, consequences and clinical significance of aneuploidy across melanoma subtypes
Authors: Shteinman Eva R. , Wilmott James S. , da Silva Ines Pires , Long Georgina V. , Scolyer Richard A. , Vergara Ismael A.
Published: October 2022

Aneuploidy, the state of the cell in which the number of whole chromosomes or chromosome arms becomes imbalanced, has been recognized as playing a pivotal role in tumor evolution for over 100 years. In melanoma, the extent of aneuploidy, as well as the chromosomal regions that are affected differ across subtypes, indicative of distinct drivers of disease. Multiple studies have suggested a role for aneuploidy in diagnosis and prognosis of melanomas, as well as in the context of immunotherapy response. A number of key constituents of the cell cycle have been implicated in aneuploidy acquisition in melanoma, including several driver mutations. Here, we review the state of the art on aneuploidy in different melanoma subtypes, discuss the potential drivers, mechanisms underlying aneuploidy acquisition as well as its value in patient diagnosis, prognosis and response to immunotherapy treatment.
Infiltration of the spinal cord and peripheral nerves in multiple myeloma
Authors: Su Xiaoyun , Kong Xiangquan , Kong Xiangchuang , Lu Zuneng , Zheng Chuansheng
Published: October 2022

Background

Multiple myeloma (MM) is a hematological malignancy, and intramedullary spinal cord metastasis is extremely rare.

Methods

Clinical and radiological data were collected from electronic medical records as well as a literature review of reported cases.

Results

We report a rare case of IgA-LAM stage IIB MM with involvement of the spinal cord and peripheral nervous system. Laboratory studies showed elevated levels of serum β2-macroglobulin and cerebrospinal fluid protein. Electromyography revealed a demyelinating process with motor conduction blocks. On MRI, the lesions of MM bone marrow are characterized as a type of diffuse infiltration. MR neurography demonstrated an enhanced nodule in the thoracic segment with swelling of the cervicothoracic segments of the spinal cord. Moreover, swelling and hypertrophy of the entire nerve branchial, lumbosacral plexus, and cauda equina were detected, accompanied by myofascitis and denervated muscles. Ultimately, the condition of the patient deteriorated quickly and she died with a diagnosis of refractory MM.

Conclusion

MRI not only has the advantage of displaying the primary involved site of the bone marrow but also facilitates detecting extramedullary hematopoietic MM, such as infiltrating sites of the central and/or peripheral nervous system.
The risk and prognostic factors for G1 pancreatic neuroendocrine tumors: A retrospective analysis of the SEER database
Authors: Wu Zhengqi , Qiu Xiaotong , Zhi Yao , Shi Xiaoju , Lv Guoyue
Published: October 2022

Background

Pancreatic neuroendocrine tumors (pNETs) are rare neuroendocrine neoplasms (NENs) for which little is known about their clinical features, treatment options, and survival prognosis. The purpose of this study is to evaluate the risk factors affecting the overall survival (OS) and cancer-specific survival (CSS) in patients with grade 1 pNETs (G1 pNETs) and to provide a new theoretical basis for clinical diagnosis and treatment.

Methods

A retrospective analysis of individuals with G1 pNETs registered in the Surveillance, Epidemiology, End Results (SEER) database was performed. Risk factors affecting OS and CSS were analyzed using Kaplan-Meier analysis, Cox proportional hazards model, and Fine-Gray competing-risk model.

Results

A total of 751 patients were included, most of whom were white (77.2%) women (53.9%) under the age of 60 years (54.9%), of whom 66 died of pNETs (8.78%) and 34 died of other causes (4.52%). Patients who were older than 60 years at diagnosis (hazard ratio [HR] = 1.866, 95% confidence interval [CI]: 1.242-2.805) had worse OS. And stage in the regional extent (HR = 1.777, 95% CI: 1.006-3.137) or distance extent (HR = 4.540, 95% CI: 2.439-8.453) had worse OS. Patients who delayed treatment after diagnosis had shorter CSS (delayed treatment < 1 month: HR = 1.933, 95% CI: 0.863-4.333; delayed treatment ≥ 1 month: HR = 2.208; 95% CI:1.047-4.654). Patients with lymph node metastasis (HR = 1.989, 95% CI: 1.137-3.479) or distant metastasis (HR = 5.625, 95% CI: 1.892-16.726) had worse CSS. Acceptance of surgery can significantly improve the patient’s OS and CSS. OS (partial pancreatectomy [PP]: HR = 0.350, 95% CI: 0.182-0.672; pancreatectomy and duodenectomy [PD]: HR = 0.426, 95% CI: 0.222-0.815; total pancreatectomy [TP]: HR = 0.495, 95% CI: 0.193-1.267). CSS(PP: HR = 0.148, 95% CI: 0.0054-0.401; PD: HR = 0.332, 95% CI: 0.150-0.730; TP: HR = 0.69, 95% CI: 0.254-1.872).

Conclusion

Age and stage were identified as independent risk factors for OS. Delayed treatment, N stage and M stage were independent risk factors for CSS. Only surgery was identified as independent protective factors for OS and CSS.
Obesity may not be related to pathologic response in locally advanced rectal cancer following neoadjuvant chemoradiotherapy
Authors: Bao Quoc Riccardo , Crimì Filippo , Valotto Giovanni , Chiminazzo Valentina , Bergamo Francesca , Prete Alessandra Anna , Galuppo Sara , El Khouzai Badr , Quaia Emilio , Pucciarelli Salvatore , Urso Emanuele Damiano Luca
Published: October 2022

Background

The aim of this study is to evaluate the correlation between body mass index (BMI) and body fat composition (measured with radiological fat parameters (RFP)) and pathological response after neoadjuvant chemoradiotherapy for locally advanced rectal cancer patients. The secondary aim of the study was to assess the role of BMI and RFP on major surgical complications, overall survival (OS), and disease-free survival (DFS).

Methods

All patients who underwent surgical resection following nCRT between 2005 and 2017 for mid-low rectal cancer were retrospectively collected. Visceral fat area (VFA), superficial fat area (SFA), visceral/superficial fat area ratio (V/S), perinephric fat thickness (PNF), and waist circumference (WC) were estimated by baseline CT scan. Predictors of pathologic response and postoperative complications were investigated using logistic regression analysis. The correlations between BMI and radiologic fat parameters and survival were investigated using the Kaplan–Meier method and log-rank test.

Results

Out of 144 patients included, a complete (TRG1) and major (TRG1+2) pathologic response was reported in 32 (22%) and 60 (45.5%) cases, respectively. A statistically significant correlation between BMI and all the RFP was found. At a median follow-up of 60 (35–103) months, no differences in terms of OS and DFS were found considering BMI and radiologic fat parameters. At univariable analysis, neither BMI nor radiologic fat parameters were predictors of complete or major pathologic response; nevertheless, VFA, V/S>1, and BMI were predictors of postoperative major complications.

Conclusions

We found no associations between BMI and body fat composition and pathological response to nCRT, although VFA, V/S, and BMI were predictors of major complications. BMI and RFP are not related to worse long-term OS and DFS.
Exposure to heavy metals and red blood cell parameters in children: A systematic review of observational studies
Authors: Capitão Carolina , Martins Raquel , Santos Osvaldo , Bicho Manuel , Szigeti Tamás , Katsonouri Andromachi , Bocca Beatrice , Ruggieri Flavia , Wasowicz Wojciech , Tolonen Hanna , Virgolino Ana
Published: October 2022

Background

Mechanistic studies show that heavy metals interfere with the hematopoietic system by inhibiting key enzymes, which could lead to anemia. However, the link between children's exposure and red blood cell (RBC) parameters has been inconsistent. We aimed to summarize evidence on human studies exploring the association between exposure to lead, mercury, cadmium, arsenic, and chromium VI and RBC parameters in children.

Methods

Following the PRISMA guidelines, we searched PubMed, Scopus, and Web of Science databases for studies published between January 2010 and April 2022. Eligible papers included human observational studies that directly assessed exposure (internal dose) to the heavy metals under study and RBC parameters in participants aged ≤ 18 years. We excluded studies using hospital-based samples. Study quality was assessed using the National Institutes of Health's Quality Assessment Tools for Cohort and Cross-Sectional Studies. We synthesized the evidence using vote counting based on the direction of the relationship.

Results

Out of 6,652 retrieved papers, we included a total of 38 (33 assessing lead, four mercury, two cadmium, and two arsenic; chromium VI was not assessed in any included paper). More than half of the studies were conducted in Asia. We found evidence of a positive relationship between lead concentration and hemoglobin (proportion of studies reporting negative relationships = 0.750; 95% Confidence Interval (CI) 0.583, 0.874) and mean corpuscular hemoglobin (0.875; 95% CI 0.546, 0.986), and a positive relationship with red cell distribution width (0.000; 95%CI 0.000, 0.379). When considering only good-quality studies (24% of the Pb studies), only the relationship with hemoglobin levels remained (0.875; 95% CI: 0.546, 0.986).

Conclusion

We found evidence of a negative relationship between lead concentration and hemoglobin and mean corpuscular hemoglobin and of a positive relationship with red cell distribution width in children. We also identified a need to conduct more studies in European countries. Future studies should use standardized practices and make efforts to increase study quality, namely by conducting comprehensive longitudinal studies. Our findings support the need to take further actions to limit heavy metal exposure during childhood.
Case report: Robust response of metastatic clear cell sarcoma treated with cabozantinib and immunotherapy
Authors: Sidlik Muskatel Rakefet , Pillar Nir , Godefroy Jeremy , Lotem Michal , Goldstein Gal
Published: October 2022

Clear Cell Sarcoma (CCS), also referred to as malignant melanoma of soft parts, is a rare and aggressive malignant tumor. It comprises 1% of all soft tissue sarcomas and is known to be radio- and chemotherapy resistant. CCS shares morphological and immunohistochemical features with malignant melanoma, including melanin biosynthesis and melanocytic markers. However, it is distinct for the presence of EWSR1-ATF1 translocation which activates MITF transcription factor. We report here of an aggressive case of CCS in a 9-year-old patient, which demonstrates the critical role of molecular analysis in the diagnosis and treatment of uncommon cancer variants in the era of personalized medicine. The EWSR1-ATF1 translocation induces pathological c-Met activation, and so, following unsuccessful CTLA4 and PD-1 blockade immunotherapy, the child received cabozantinib, a small molecule tyrosine kinase inhibitor, with the intent to block c-Met oncogenic effect. In parallel, active immunization, using hapten di-nitrophenyl modified autologous tumor cells was administered with monotherapy PD-1 inhibitor nivolumab. Under this “triplet” therapy, the patient attained an initial partial response and was progression-free for 2 years, in good performance status and resumed schooling. Based on our observation, cabozantinib can be used as an effective and potentially life-prolonging treatment in CCS. We suggest that priming the child’s immune system using her autologous tumor and combating T cell exhaustion with PD-1 blockade may have synergized with the targeted therapy. Combining targeted and immunotherapy is a rapidly growing practice in solid tumors and provides a glimpse of hope in situations that previously lacked any treatment option.
Safety and effectiveness of ferric carboxymaltose intravenous therapy in pediatric patients with chronic kidney disease
Authors: Garcia-Ortega Patricia , Jimenez-Lozano Ines , Cruz Álejandro , Polo Aurora Fernandez , Lopez Mercedes , Ariceta Gema
Published: October 2022

Iron-deficiency anemia is the most common reason for worsening of the anemia characteristically seen in chronic kidney disease (CKD). Ferric carboxymaltose (FCM) is a macromolecular hydroxide ferric carbohydrate complex that allows high-dose iron to be administered parenterally for gradual, controlled release. The aim of this study was to retrospectively evaluate the safety and effectiveness of FCM treatment in pediatric patients with CKD non-dependent of hemodialysis, seen at a tertiary hospital. Data were collected on demographics, dosage, infusion time, laboratory results, and tolerability of the medicinal product. A total of 79 patients (40.5% girls) were included; the median age [25th percentile (P25) to 75th percentile (P75)] was 9 years (5–13). Laboratory results at 15–45 days post-infusion revealed a median increase of 1.4 g/dL (0.9–1.9) in hemoglobin, 224 μg/L (136–378.5) in ferritin, 37 μg/dL (17.5–71) in serum iron, and 18% (9.3–27.8) in transferrin saturation. All patients tolerated FCM infusions well, and no serious hypersensitivity reactions or anaphylactic reactions were observed. Only one adverse event was identified: drug extravasation at the end of the infusion in a 16-year-old patient. These data provide further evidence for the use of FCM as a safe and effective therapeutic option in pediatric patients with CKD, based on the low incidence of adverse effects, minor intervention required, and anemia improvement based on laboratory results.
Function and therapeutic potential of transient receptor potential ankyrin 1 in fibrosis
Authors: Wei Yicheng , Cai Jialuo , Zhu Ruiqiu , Xu Ke , Li Hongchang , Li Jianxin
Published: October 2022

The transient receptor potential (TRP) protein superfamily is a special group of cation channels expressed in different cell types and signaling pathways. In this review, we focus on TRPA1 (transient receptor potential ankyrin 1), an ion channel in this family that exists in the cell membrane and shows a different function from other TRP channels. TRPA1 usually has a special activation effect that can induce cation ions, especially calcium ions, to flow into activated cells. In this paper, we review the role of TRPA1 in fibroblasts. To clarify the relationship between fibroblasts and TRPA1, we have also paid special attention to the interactions between TRPA1 and inflammatory factors leading to fibroblast activation. TRPA1 has different functions in the fibrosis process in different organs, and there have also been interesting discussions of the mechanism of TRPA1 in fibroblasts. Therefore, this review aims to describe the function of TRP channels in controlling fibrosis through fibroblasts in different organ inflammatory and immune-mediated diseases. We attempt to prove that TRPA1 is a target for fibrosis. In fact, some clinical trials have already proven that TRPA1 is a potential adjuvant therapy for treating fibrosis.
Early ascorbic acid administration prevents vascular endothelial cell damage in septic mice
Authors: Madokoro Yutaro , Kamikokuryo Chinatsu , Niiyama Shuhei , Ito Takashi , Hara Satoshi , Ichinose Hiroshi , Kakihana Yasuyuki
Published: October 2022

Oxidation of BH4, a cofactor of nitric oxide synthase (NOS), produces reactive oxygen species (ROS) through uncoupling of NOS and affects vascular endothelial dysfunction. Ascorbic acid (AsA) inhibits the oxidation of BH4 and reduces ROS. However, the kinetic changes of BH4 in sepsis and its effect on the kinetic changes in AsA administration therapy, as well as the appropriate timing of AsA administration for AsA therapy to be effective, are unclear. Mice with sepsis, induced by cecal ligation and puncture (CLP), were examined for the effect of AsA administration (200 mg/kg) on vascular endothelial cell dysfunction at two administration timings: early group (AsA administered immediately after CLP) and late group (AsA administered 12 h after CLP). Survival rates were compared between the early and late administration groups, and vascular endothelial cell damage, indicated by the dihydrobiopterin/tetrahydrobiopterin ratio, serum syndecan-1, and endothelial nitric oxide synthase, as well as liver damage, were examined. The early group showed significantly improved survival compared to the non-treatment group (p < 0.05), while the late group showed no improved survival compared to the non-treatment group. Compared to the non-treated group, the early AsA group showed less oxidation of BH4 in sepsis. Syndecan1, a marker of vascular endothelial cell damage, was less elevated and organ damage was reduced in the early AsA-treated group. In septic mice, early AsA administration immediately after CLP may protect vascular endothelial cells by inhibiting BH4 oxidation, thereby reducing organ dysfunction and improving survival.
The regulatory role of PDE4B in the progression of inflammatory function study
Authors: Su Yue , Ding Jiaxiang , Yang Fan , He Cuixia , Xu Yuanyuan , Zhu Xingyu , Zhou Huan , Li Hongtao
Published: October 2022

Inflammation is a response of the body to external stimuli (eg. chemical irritants, bacteria, viruses, etc.), and when the stimuli are persistent, they tend to trigger chronic inflammation. The presence of chronic inflammation is an important component of the tumor microenvironment produced by a variety of inflammatory cells (eg. macrophages, neutrophils, leukocytes, etc.). The relationship between chronic inflammation and cancer development has been widely accepted, and chronic inflammation has been associated with the development of many cancers, including chronic bronchitis and lung cancer, cystitis inducing bladder cancer. Moreover, chronic colorectitis is more likely to develop into colorectal cancer. Therefore, the specific relationship and cellular mechanisms between inflammation and cancer are a hot topic of research. Recent studies have identified phosphodiesterase 4B (PDE4B), a member of the phosphodiesterase (PDEs) protein family, as a major cyclic AMP (cAMP) metabolizing enzyme in inflammatory cells, and the therapeutic role of PDE4B as chronic inflammation, cancer. In this review, we will present the tumors associated with chronic inflammation, and PDE4B potential clinical application.
Antioxidant-based neuroprotective effect of dimethylsulfoxide against induced traumatic brain injury in a rats model
Authors: Bulama Ibrahim , Nasiru Suleiman , Bello Abubakar , Abbas Abdullahi Yahaya , Nasiru Jinjiri Ismail , Saidu Yusuf , Chiroma Musa Samaila , Mohd Moklas Mohamad Aris , Mat Taib Che Norma , Waziri Ali , Suleman Bilbis Lawal
Published: October 2022

Traumatic brain injury (TBI) has been the result of neurological deficit and oxidative stress. This study evaluated the antioxidative neuroprotective property and learning and memory-enhancing effects of dimethyl sulfoxide (DMSO) in a rat model after the induction of TBI. 21 albino rats with 7 rats per group were used in this study. Group I was induced with TBI and treated with DMSO at 67.5 mg/kg orally once daily which started 30 min after the induction of TBI and lasted 21 days. Group II was induced with TBI but not treated while Group III was neither induced with TBI nor treated. Assessment of behavioral function (Learning and memory, anxiety and motor function), the level of an antioxidant enzymes and their gene expression (superoxide dismutase, catalase, glutathione peroxidase), the biomarkers of oxidative stress (malondialdehyde) and S100B levels as well as brain tissues histological studies were conducted. Administration of DMSO to rats with induced TBI has improved learning and memory, locomotor function and decreased anxiety in Group I compared to Group II. Moreover, the level of S100B was significantly (p < 0.05) lower in Group I compared to Group II. Treatment with DMSO also decreased lipid peroxidation significantly (p < 0.05) compared to Group II. There exists a significant (p < 0.05) increase in CAT, SOD, and GPX activities in Group I compared to Group II. Therefore, DMSO has demonstrated a potential antioxidative neuroprotective effect through its ability to increase the level of antioxidant enzymes which they quench and inhibit the formation of ROS, thereby improving cognitive functions.
Recent progress in continuously tunable low-noise all-solid-state single-frequency continuous-wave laser based on intracavity locked etalon
Authors: Jin Pixian , Wei Jiao , Su Jing , Lu Huadong , Peng Kunchi
Published: October 2022

All-solid-state single-frequency continuous-wave (CW) lasers have been applied in many fields of scientific research owing to their intrinsic advantages of high beam quality, low noise, narrow linewidth, and high coherence. In atom-based applications, single-frequency lasers should also be continuously tuned to precisely match their wavelengths with the transition lines of the corresponding atoms. Continuous frequency tuning of the laser is mainly achieved by continuously scanning the laser cavity length after the intracavity tuning element etalon is locked to an oscillating laser mode. However, the modulation signals necessary in current etalon locking systems increase the noise of the continuously tunable lasers and in some respects limit their applications in Frontier scientific research. Moreover, the obtained continuous frequency tuning range with the etalon locking technique is restricted by the free spectrum range of the adopted etalon. In this paper, we systematically summarize recent progress of the continuously tunable single-frequency CW lasers based on intracavity locked etalon, including the advanced etalon locking techniques and the tuning range expansion approach. As a result, the low noise and high stable all-solid-state single-frequency CW tunable lasers are successfully developed.
Omani Frankincense nanoemulsion formulation efficacy and its latent effects on biological aspects of the spiny bollworm Earias insulana (Boisd.)
Authors: Metayi Mervat H. , Abd El-Naby Shimaa S. , El-Habal Noha A. , Fahmy Heba H. , Abdou Mona S. , Ali Baber , Abdel-Rheim Khaled H. , Abdel-Megeed Ahmed
Published: October 2022

Our research shed light on the perspective of formulation technology regarding its responsibility to provide phyto-insecticides that are worthy of research into potential novel applications. There has been an increase in interest in using nanoemulsion as a new formulation in a variety of sectors during the last several decades. Boswellia sacra essential oil (Fam: Burseraceae) from the resin of frankincense trees has been recently proposed as a promising ingredient in a new generation of botanical insecticides. Frankincense nanoemulsion was formulated in 5% ratios comprising frankincense oil, surfactants, and water. A frankincense nanoemulsion was prepared using a high-energy ultra-sonication process and characterized by dynamic light scattering transmission electron microscopy surface tension, viscosity, and zeta potential value. Gas chromatography/mass spectrometry (GC/MS) was used to identify the chemical profiles of frankincense essential oil. Furthermore, insecticidal effects against second instar larvae of the spiny bollworm, Earias insulana, as well as their latent effects on the larvae were studied. In the present study, the formulation was a good nanoemulsion. The surface tension was 53.69, the viscosity was 4.76 cPs, the zeta potential was-10 mV, and the size distribution was 41.30 nm. The polydispersity index (PDI) of the nanoemulsion was found to be 0.26, and the morphology of the frankincense nanoemulsion was visualized in a spherical shape. The main constituents identified in frankincense oil were α-pinene (15.52%); monolinolenin (12.92%); and geranylgeranyl acetate (9.99%). The results showed significant insecticidal activity against the larval stage and considerably decreased the pupation percentage with increasing the volume of the frankincense nanoemulsion. On the other hand, the latent effects of the frankincense nanoemulsion on E. insulana resulted in a higher prolongation of larval and pupal durations as well as a significant reduction in the weight of larvae and pupae of E. insulana. Additionally, frankincense nanoemulsion dramatically influenced the adult emergence percentage. It also caused a significantly lower hatchability percentage compared to the untreated control. The concentrations used and the types of mating combination have a significant effect on the fecundity of E. insulana. This novel frankincense nanoemulsion formulation could be used in strategies to control the spiny bollworm on cotton plants.
Acupuncture vs. antispasmodics in the treatment of irritable bowel syndrome: An adjusted indirect treatment comparison meta-analysis
Authors: Shi Yun-zhou , Tao Qing-feng , Qin Di , Chen Min , Yu Shu-guang , Zheng Hui
Published: October 2022

Background: Acupuncture has been extensively applied to manage irritable bowel syndrome (IBS) in clinical practice in China. Some randomized controlled trials (RCTs) have demonstrated their efficacy, but it has rarely been compared with first-line antispasmodics to verify their effectiveness. Therefore, we compare acupuncture with antispasmodics in the treatment of IBS by using an adjusted indirect treatment comparison meta-analysis.

Methods: Embase, OVID Medline, and the Cochrane Central Register of Controlled Trials databases were searched from inception to 14 March 2022, with no language restrictions. RCTs comparing antispasmodics or acupuncture with placebo or one of the antispasmodics were enrolled. The primary outcome of interest was the improvement of abdominal pain. And the secondary outcomes of interest were the relief of global IBS symptoms and adverse events. The random-effects model was utilized to pool data. The effect size was measured by standardized mean difference (SMD) or relative ratio, and the effectiveness of acupuncture and different antispasmodics were ranked by P-scores.

Results: Thirty-five RCTs (n = 5,190) were included. The analysis showed that cimetropium, drotaverine, acupuncture, and pinarverium were superior over placebo in relieving abdominal pain; cimetropium (SMD, −3.00 [95%CI, −4.47 to −1.53], P-score = 0.99) ranked the most effective. In pairwise comparisons, acupuncture had a greater improvement than most antispasmodics except cimetropium and drotaverine in relieving abdominal pain, although the between-group difference was statistically insignificant. In the analysis of continuous outcome in the relief of global IBS symptoms, the result showed that pinaverium was more effective (SMD, 1.72 [95%CI, 0.53 to 2.92], P-score = 0.90) than placebo. Trimebutine and acupuncture had greater improvements than placebo, but no significant difference was shown between groups. In pairwise comparisons, acupuncture was more effective than pinaverium (SMD, −1.11 [95%CI, −1.94 to −0.28]) in relieving global IBS symptoms. In the analysis of adverse events, acupuncture had a lower adverse event rate than most of the other antispasmodics.

Conclusion: Cimetropium, drotaverine, and acupuncture were all better than placebo in improving abdominal pain. Acupuncture was preferred over pinaverium in relieving global IBS symptoms, and acupuncture had lower adverse events than most antispasmodics.
Multi-scale mechanobiological model for skeletal muscle hypertrophy
Authors: Villota-Narvaez Yesid , Garzón-Alvarado Diego A. , Röhrle Oliver , Ramírez-Martínez Angelica M.
Published: October 2022

Skeletal muscle adaptation is correlated to training exercise by triggering different signaling pathways that target many functions; in particular, the IGF1-AKT pathway controls protein synthesis and degradation. These two functions regulate the adaptation in size and strength of muscles. Computational models for muscle adaptation have focused on: the biochemical description of signaling pathways or the mechanical description of muscle function at organ scale; however, an interrelation between these two models should be considered to understand how an adaptation in muscle size affects the protein synthesis rate. In this research, a dynamical model for the IGF1-AKT signaling pathway is linked to a continuum-mechanical model describing the active and passive mechanical response of a muscle; this model is used to study the impact of the adaptive muscle geometry on the protein synthesis at the fiber scale. This new computational model links the signaling pathway to the mechanical response by introducing a growth tensor, and links the mechanical response to the signaling pathway through the evolution of the protein synthesis rate. The predicted increase in cross sectional area (CSA) due to an 8 weeks training protocol excellently agreed with experimental data. Further, our results show that muscle growth rate decreases, if the correlation between protein synthesis and CSA is negative. The outcome of this study suggests that multi-scale models coupling continuum mechanical properties and molecular functions may improve muscular therapies and training protocols.
Suprachiasmatic to paraventricular nuclei interaction generates normal food searching rhythms in mice
Authors: Olejniczak Iwona , Campbell Benjamin , Tsai Yuan-Chen , Tyagarajan Shiva K. , Albrecht Urs , Ripperger Jürgen A.
Published: October 2022

Searching for food follows a well-organized decision process in mammals to take up food only if necessary. Moreover, scavenging is preferred during their activity phase. Various time-dependent regulatory processes have been identified originating from the suprachiasmatic nuclei (SCN), which convert external light information into synchronizing output signals. However, a direct impact of the SCN on the timing of normal food searching has not yet been found. Here, we revisited the function of the SCN to affect when mice look for food. We found that this process was independent of light but modified by the palatability of the food source. Surprisingly, reducing the output from the SCN, in particular from the vasopressin releasing neurons, reduced the amount of scavenging during the early activity phase. The SCN appeared to transmit a signal to the paraventricular nuclei (PVN) via GABA receptor A1. Finally, the interaction of SCN and PVN was verified by retrograde transport-mediated complementation. None of the genetic manipulations affected the uptake of more palatable food. The data indicate that the PVN are sufficient to produce blunted food searching rhythms and are responsive to hedonistic feeding. Nevertheless, the search for normal food during the early activity phase is significantly enhanced by the SCN.
Characterization of the chicken melanocortin 5 receptor and its potential role in regulating hepatic glucolipid metabolism
Authors: Zhang Xiao , Su Jiancheng , Huang Tianjiao , Wang Xinglong , Wu Chenlei , Li Jing , Li Juan , Zhang Jiannan , Wang Yajun
Published: October 2022

Melanocortin receptors (MC1R-MC5R) and their accessory proteins (MRAPs) are involved in a variety of physiological processes, including pigmentation, lipolysis, adrenal steroidogenesis, and immunology. However, the physiological roles of MC5R are rarely characterized in vertebrates, particularly in birds. In this work, we cloned the full-length cDNA of chicken MC5R and identified its core promoter region. Functional studies revealed that cMC5R was more sensitive to ACTH/α-MSH than β-MSH/γ-MSH, and was coupled to the cAMP/PKA signaling pathway. We demonstrated that MRAP2 decreased MC5R sensitivity to α-MSH, whereas MRAP1 did not have a similar effect, and that both MRAPs significantly reduced MC5R expression on the cell membrane surface. Transcriptome and qPCR data showed that both MRAP1 and MC5R were highly expressed in chicken liver. Additionally, we observed that ACTH might increase hepatic glucose production and decrease lipogenesis in primary hepatocytes, and dose-dependently downregulated the expression levels of ELOVL6 and THRSPA genes. These findings indicated that ACTH may act directly on hepatocytes to regulate glucolipid metabolism, which will help to understand the function of MC5R in avian.
Hydroxytyrosol-rich extract from olive juice as an additive in gilthead sea bream juveniles fed a high-fat diet: Regulation of somatic growth
Authors: Balbuena-Pecino Sara , Montblanch Manel , García-Meilán Irene , Fontanillas Ramon , Gallardo Ángeles , Gutiérrez Joaquim , Navarro Isabel , Capilla Encarnación
Published: October 2022

The dietary inclusion of plant-based products in fish feeds formulation is required for the sustainable development of aquaculture. Moreover, considering functional diets, hydroxytyrosol, one of the major phenolic compounds found in olives (Olea europaea), has been identified as a potential candidate to be used in the aquafeeds industry due to its health promoting abilities. The aim of this study was to evaluate the effects of the inclusion of an olive juice extract rich in hydroxytyrosol as an additive (0.52 g HT/kg feed) in a high-fat (24% lipids) diet in gilthead sea bream (Sparus aurata) juveniles. Moreover, the experimental diets, with or without the extract, were administered daily at a standard (3% of total biomass in the tank) or restricted ration (40% reduction) for 8–9 weeks. Growth and biometric parameters, insulin-like growth factor 1 (IGF-1) plasma levels and growth hormone/IGF axis-, myogenic- and osteogenic-related genes expression in liver, white muscle and/or bone were analyzed. Moreover, in vitro cultures of vertebra bone-derived cells from fish fed the diets at a standard ration were performed at weeks 3 and 9 to explore the effects of hydroxytyrosol on osteoblasts development. Although neither body weight or any other biometric parameter were affected by diet composition after 4 or 8 weeks, the addition of the hydroxytyrosol-rich extract to the diet increased IGF-1 plasma levels, regardless of the ration regime, suggesting an anabolic condition. In muscle, the higher mRNA levels of the binding protein igfbp-5b and the myoblast fusion marker dock5 in fish fed with the hydroxytyrosol-rich diet suggested that this compound may have a role in muscle, inducing development and a better muscular condition. Furthermore in bone, increased osteogenic potential while delayed matrix mineralization after addition to the diet of the olive juice extract was supported by the upregulated expression of igf-1 and bmp4 and reduced transcript levels of osteopontin. Overall, this study provides new insights into the beneficial use of hydroxytyrosol as a dietary additive in gilthead sea bream functional diets to improve muscle-skeletal condition and, the aquaculture industry.
Characterization of chronic lung allograft dysfunction phenotypes using spectral and intrabreath oscillometry
Authors: Fu Anne , Vasileva Anastasiia , Hanafi Nour , Belousova Natalia , Wu Joyce , Rajyam Sarada Sriya , Ryan Clodagh M. , Hantos Zoltán , Chow Chung-Wai
Published: October 2022

Background: Chronic lung allograft dysfunction (CLAD) is the major cause of death beyond 2 years after lung transplantation and develops in 50% of all patients by 5 years post-transplant. CLAD is diagnosed on the basis of a sustained drop of 20% for at least 3 months in the forced expiratory volume (FEV1), compared to the best baseline value achieved post-transplant. CLAD presents as two main phenotypes: bronchiolitis obliterans syndrome (BOS) is more common and has better prognosis than restrictive allograft syndrome (RAS). Respiratory oscillometry is a different modality of lung function testing that is highly sensitive to lung mechanics. The current study investigated whether spectral and intrabreath oscillometry can differentiate between CLAD-free, BOS- and RAS-CLAD at CLAD onset, i.e., at the time of the initial 20% drop in the FEV1.

Methods: A retrospective, cross-sectional analysis of 263 double lung transplant recipients who underwent paired testing with oscillometry and spirometry at the Toronto General Pulmonary Function Laboratory from 2017 to 2022 was conducted. All pulmonary function testing and CLAD diagnostics were performed following international guidelines. Statistical analysis was conducted using multiple comparisons.

Findings: The RAS (n = 6) spectral oscillometry pattern differs from CLAD-free (n = 225) by right-ward shift of reactance curve similar to idiopathic pulmonary fibrosis whereas BOS (n = 32) has a pattern similar to obstructive lung disease. Significant differences were found in most spectral and intrabreath parameters between BOS, RAS, and time-matched CLAD-free patients. Post-hoc analysis revealed these differences were primarily driven by BOS instead of RAS. While no differences were found between CLAD-free and RAS patients with regards to spectral oscillometry, the intrabreath metric of reactance at end-inspiration (XeI) was significantly different (p < 0.05). BOS and RAS were differentiated by spectral oscillometry measure R5, and intrabreath resistance at end expiration, ReE (p < 0.05 for both).

Conclusion: Both spectral and intrabreath oscillometry can differentiate BOS-CLAD from CLAD-free states while intrabreath oscillometry, specifically XeI, can uniquely distinguish RAS-CLAD from CLAD-free. Spectral and intrabreath oscillometry offer complementary information regarding lung mechanics in CLAD patients to help distinguish the two phenotypes and could prove useful in prognostication.