bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary Lasia spinosa Thw. improves reproductive performance of aged roosters
Authors: Hong Yongxing , Zhang Lang , Liu Xingting , Wu Sile , Wen Jian , Sun Haodong , Tian Kui , Jia Xiaoxuan , Liao Yuying , Suthikrai Wanwipa , Tharasanit Theerawat , Lu Yangqing
Published: August 2022

The application of artificial insemination is particularly, owing to which breeder animals are considered an important resource in breeding farms. However, the reproductive performance of roosters typically declines with age, and the economic loss experienced by breeders is attributable to this shortened reproductive lifespan.Lasia spinosaThw. (LST) reportedly improved reproductive capacity in male rodents. The objective of this study was to investigate the effects of LST on the reproductive performance of aged roosters. Male Guangxi Partridge chicken (mean weight, 3032.41 ± 34.48 g; age, 500 days;n= 72) randomly received the following three dietary treatments: LST0 group (a basal diet), LST2 group (a basal diet with 2% LST powder), and LST4 group (a basal diet with 4% LST powder). Computer-aided sperm analysis revealed that dietary LST supplementation significantly improved semen volume, sperm motility, and concentration. Furthermore, the most potent effects were observed in the treatment group with the administration of 2% LST, which significantly improved the weight of the testes. Hematoxylin-eosin staining revealed the increase in diameter of the seminiferous tubule and height of the seminiferous tubule epithelium possibly caused as a result of LST treatment. A significant increase in fructose and glucose concentrations were observed in the testis and seminal plasma; in addition, a significant increase was observed in the α-glycosidase levels in the testis and spermatozoa. However, the monoaldehyde levels in the spermatozoa appeared to decline significantly. Additionally, the fertility rate increased significantly following 2% LST supplementation. RNA-seq analysis revealed that 34 and 16 unigenes were upregulated and downregulated, respectively, in testicular tissues from roosters that received dietary supplementation of 2% LST. The assigned functions of the unigenes revealed that LST primarily influenced the mechanisms underlying catalytic activity and cellular processes. Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggested that spermatogenesis-related pathways were significantly enriched, including ABC transporters, ribosome biogenesis in eukaryotes, and VEGF, cAMP, and ErbB signaling pathways.
Scalable radiotherapy data curation infrastructure for deep-learning based autosegmentation of organs-at-risk: A case study in head and neck cancer
Authors: Tryggestad E. , Anand A. , Beltran C. , Brooks J. , Cimmiyotti J. , Grimaldi N. , Hodge T. , Hunzeker A. , Lucido J. J. , Laack N. N. , Momoh R. , Moseley D. J. , Patel S. H. , Ridgway A. , Seetamsetty S. , Shiraishi S. , Undahl L. , Foote R. L.
Published: August 2022

In this era of patient-centered, outcomes-driven and adaptive radiotherapy, deep learning is now being successfully applied to tackle imaging-related workflow bottlenecks such as autosegmentation and dose planning. These applications typically require supervised learning approaches enabled by relatively large, curated radiotherapy datasets which are highly reflective of the contemporary standard of care. However, little has been previously published describing technical infrastructure, recommendations, methods or standards for radiotherapy dataset curation in a holistic fashion. Our radiation oncology department has recently embarked on a large-scale project in partnership with an external partner to develop deep-learning-based tools to assist with our radiotherapy workflow, beginning with autosegmentation of organs-at-risk. This project will require thousands of carefully curated radiotherapy datasets comprising all body sites we routinely treat with radiotherapy. Given such a large project scope, we have approached the need for dataset curation rigorously, with an aim towards building infrastructure that is compatible with efficiency, automation and scalability. Focusing on our first use-case pertaining to head and neck cancer, we describe our developed infrastructure and novel methods applied to radiotherapy dataset curation, inclusive of personnel and workflow organization, dataset selection, expert organ-at-risk segmentation, quality assurance, patient de-identification, data archival and transfer. Over the course of approximately 13 months, our expert multidisciplinary team generated 490 curated head and neck radiotherapy datasets. This task required approximately 6000 human-expert hours in total (not including planning and infrastructure development time). This infrastructure continues to evolve and will support ongoing and future project efforts.
Atypical presentation of patients with chronic myeloid leukemia in chronic phase—Case report
Authors: Ramdohr Florian , Fabarius Alice , Maier Bettina , Bretschneider Daniela , Jauch Anna , Monecke Astrid , Metzeler Klaus H. , Janssen Johannes W. G. , Schlenk Richard F. , Kayser Sabine
Published: August 2022

The presence of the translocation t(9;22)(q34;q11), leading to the BCR::ABL1 fusion transcript, is the hallmark of chronic myeloid leukemia (CML). Nevertheless, atypical presentation at diagnosis can be challenging. However, although most patients with CML are diagnosed with the e13a2 or e14a2 BCR::ABL1 fusion transcripts, about 5% of them carry rare BCR::ABL1 fusion transcripts, such as e19a2, e8a2, e13a3, e14a3, e1a3, and e6a2. In particular, the e6a2 fusion transcript has been associated with clinically aggressive disease frequently presenting in accelerated or blast crisis phases. To date, there is limited evidence on the efficacy of front-line second-generation tyrosine kinase inhibitors for this genotype. Here, we report two patients, in whom the diagnosis of CML was challenging. The use of primers recognizing more distant exons from the common BCR::ABL1 breakpoint region correctly identified the atypical BCR::ABL1 e6a2 fusion transcript. Treatment with the second-generation tyrosine kinase inhibitor nilotinib was effective in our patient expressing the atypical e6a2 BCR::ABL1 fusion transcript.
Enhancing anti-tumour innate immunity by targeting the DNA damage response and pattern recognition receptors in combination with radiotherapy
Authors: Chan Wah Hak Charleen M. L. , Rullan Antonio , Patin Emmanuel C. , Pedersen Malin , Melcher Alan A. , Harrington Kevin J.
Published: August 2022

Radiotherapy is one of the most effective and frequently used treatments for a wide range of cancers. In addition to its direct anti-cancer cytotoxic effects, ionising radiation can augment the anti-tumour immune response by triggering pro-inflammatory signals, DNA damage-induced immunogenic cell death and innate immune activation. Anti-tumour innate immunity can result from recruitment and stimulation of dendritic cells (DCs) which leads to tumour-specific adaptive T-cell priming and immunostimulatory cell infiltration. Conversely, radiotherapy can also induce immunosuppressive and anti-inflammatory mediators that can confer radioresistance. Targeting the DNA damage response (DDR) concomitantly with radiotherapy is an attractive strategy for overcoming radioresistance, both by enhancing the radiosensitivity of tumour relative to normal tissues, and tipping the scales in favour of an immunostimulatory tumour microenvironment. This two-pronged approach exploits genomic instability to circumvent immune evasion, targeting both hallmarks of cancer. In this review, we describe targetable DDR proteins (PARP (poly[ADP-ribose] polymerase); ATM/ATR (ataxia–telangiectasia mutated and Rad3-related), DNA-PKcs (DNA-dependent protein kinase, catalytic subunit) and Wee1 (Wee1-like protein kinase) and their potential intersections with druggable immunomodulatory signalling pathways, including nucleic acid-sensing mechanisms (Toll-like receptors (TLR); cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) and retinoic acid-inducible gene-I (RIG-I)-like receptors), and how these might be exploited to enhance radiation therapy. We summarise current preclinical advances, recent and ongoing clinical trials and the challenges of therapeutic combinations with existing treatments such as immune checkpoint inhibitors.
Robust treatment planning in scanned carbon-ion radiotherapy for pancreatic cancer: Clinical verification using in-room computed tomography images
Authors: Kusano Yohsuke , Katoh Hiroyuki , Minohara Shinichi , Fujii Hajime , Miyasaka Yuya , Takayama Yoshiki , Imura Koh , Kusunoki Terufumi , Miyakawa Shin , Kamada Tadashi , Serizawa Itsuko , Takakusagi Yosuke , Mizoguchi Nobutaka , Tsuchida Keisuke , Yoshida Daisaku
Published: August 2022

Purpose

Carbon-ion beam (C-beam) has a sharp dose distribution called the Bragg peak. Carbon-ion radiation therapy, such as stereotactic body radiotherapy in photon radiotherapy, can be completed in a short period by concentrating the radiation dose on the tumor while minimizing the dose to organs at-risk. However, the stopping position of C-beam is sensitive to density variations along the beam path and such variations can lower the tumor dose as well as cause the delivery of an unexpectedly high dose to the organs at risk. We evaluated the clinical efficacy of a robust planning technique considering gastrointestinal gas (G-gas) to deliver accurate radiation doses in carbon-ion radiotherapy for pancreatic cancer.

Materials and methods

We focused on the computed tomography (CT) value replacement method. Replacement signifies the overwriting of CT values in the CT images. The most effective replacement method for robust treatment planning was determined by verifying the effects of the three replacement patterns. We selected 10 consecutive patients. Pattern 1 replaces the CT value of the G-gas contours with the value of the region without G-gas (P1). This condition indicates a no-gas state. Pattern 2 replaces each gastrointestinal contour using the mean CT value of each contour (P2). The effect of G-gas was included in the replacement value. Pattern 3 indicates no replacement (P3). We analyzed variations in the target coverage (TC) and homogeneity index (HI) from the initial plan using in-room CT images. We then performed correlation analysis on the variations in G-gas, TC, and HI to evaluate the robustness against G-gas.

Results

Analysis of variations in TC and HI revealed a significant difference between P1 and P3 and between P2 and P3. Although no statistically significant difference was observed between P1 and P2, variations, including the median, tended to be fewer in P2. The correlation analyses for G-gas, TC, and HI showed that P2 was less likely to be affected by G-gas.

Conclusion

For a treatment plan that is robust to G-gas, P2 mean replacement method should be used. This method does not necessitate any particular software or equipment, and is convenient to implement in clinical practice.
Olbert’s Balloon Dilatation as a Minimally Invasive Possibility of Treating Ureteral Stricture After Complicated URS-L in Children
Authors: Halinski Adam , Halinski Andrzej , Halinski Paweł
Published: August 2022

Olbert’s balloon dilatation is a surgical technique used for the treatment of ureteral stricture. Although it is more frequently used in adults, due to the advancing miniaturization of the equipment, this technique has become possible in children. We would like to present five cases of Olbert’s balloon dilatation carried out in children with ureteral stricture, aged 12–17 years. All of these children were diagnosed for at least 6 months. Ureteral stricture has been noticed in those patients with a time of a stone residence in the ureter longer than 6 months. The duration of the stone in the ureter varied from 6 to 18 months. The symptoms were abdominal pain, renal colic pain, UTI, fever, vomiting, and nausea. Ultrasound (US) revealed hydronephrosis and ureter dilatation above the stone. All of these children had grade-3 hydronephrosis based on the Onen grading system during admission to the hospital. The lack of renal function on the DMSA scan was observed with an average of 22%. JJ-stent was inserted as a first-line treatment. A retrograde pyelogram revealed ureteral stricture at a length from 1 to 1.7 cm in the place where the stone was ingrown. Olbert’s balloon dilatation under fluoroscopy was performed successfully in all children. We achieved an efficacy of 60% in our series. Renal function increased to an average of 36% on DMSA 3 months after surgery. The level of creatinine is shaped at an average of 0.6. On US, two children had no hydronephrosis while one child had grade-1 hydronephrosis. The longest follow-up is now 4 years, with the same good results. In conclusion, Olbert’s balloon dilatation is an effective, safe, and minimally invasive tool for ureteral stricture in the hands of the endourological experienced pediatric urologist. But more prospective, randomized trials are still needed.
Time to death and its predictors among neonates who were admitted to the neonatal intensive care unit at tertiary hospital, Addis Ababa, Ethiopia: Retrospective follow up study
Authors: Menalu Mulat Mossie , Gebremichael Bereket , Desta Kalkidan Wondwossen , Kebede Worku Misganaw , Tarekegn Fetene Nigussie , Mulu Getaneh Baye , Atinafu Bantalem Tilaye
Published: August 2022

Backgrounds

Neonatal death is the major problem in developing world. Burden and predictors of neonatal mortality vary across countries and even among regions of a country, so understanding the problem concerning these factors is essential to overcome the problem. Therefore, this study aimed to determine time to death and its predictors of neonatal mortality among neonates who were admitted to the neonatal intensive care unit of Tertiary Hospital, Addis Ababa, Ethiopia.

Methods

A hospital-based retrospective cohort study was employed among 434 neonates admitted in Tertiary hospital, Addis Ababa, Ethiopia. A Kaplan Meier curve and a log-rank test were used to estimate the survival time and compare survival curves between variables. The cox proportional hazard model was also fitted to identify predictors.

Results

A total of 434 neonates included in the study, 11.1% of which were died, and the incidence rate was 19.2 per 1000 live births. The time to death of neonates was 17 days. Independent predictors of neonatal mortality were incomplete maternal antenatal follow up[AHR: 3.7 (95% CI:1.86,7.60)], low(Appearance, Pulse, Grimily, Activity, and Respiration(APGAR)score[AHR:5.0 (95%CI:1.51–15.04)], perinatal asphyxia [AHR:5.2 (95%CI:1.92–14.30)], preterm 4.2 (95%CI: 1.32–8.83)]. Moreover, small for gestational age [AHR:4.8 (95%CI:2.33–9.72)], respiratory distress[AHR: 2.5 (95%CI: 1.24–5.09)], sepsis [AHR: 3.4 (95%CI: 1.71–4.01)], low birth weight[AHR: 7.3 (95%CI:2.69,1.91)], and tracheoesophageal fistula [AHR: 2.2 (95%CI: 1.13–4.32)].

Conclusion

The overall incidence rate was 19.2 deaths per 1,000 live births. Emphasis should be given to incomplete Antenatal care follow up, small for gestation, preterm, low birth weight, low 5th min APGAR score, neonatal sepsis, respiratory distress, perinatal asphyxia, and tracheoesophageal fistula.
The effects of fresh Gastrodia elata Blume on the cognitive deficits induced by chronic restraint stress
Authors: Huang Hong , Zhang Yiwen , Yao Caihong , He Qinghu , Chen Fang , Yu Han , Lu Guanghua , Jiang Ning , Liu Xinmin
Published: August 2022

Chronic restraint stress (CRS) is a classic animal model of stress that can lead to various physiological and psychological dysfunctions, including systemic neuroinflammation and memory deficits. Fresh Gastrodia elata Blume (FG), the unprocessed raw tuber of Gastrodia elata Blume, has been reported to alleviate the symptoms of headache, convulsions, and neurodegenerative diseases, while the protective effects of FG on CRS-induced cognitive deficits remain unclear. This work aimed to evaluate the effects of FG on CRS-induced cognitive deficits through multiplex animal behavior tests and to further explore the related mechanism by observing the expression of mitochondrial apoptosis-related proteins in the mouse hippocampus. In in vivo experiments, mice were subjected to the object location recognition test (OLRT), new object recognition test (NORT), Morris water maze test (MWMT), and passive avoidance test (PAT) to evaluate the learning and memory ability. In in vitro experiments, the expression of the AKT/CREB pathway, the fission- and apoptosis-related proteins (Drp1, Cyt C, and BAX), and the proinflammatory cytokines’ (TNF‐α and IL‐1β) level in the hippocampus was examined. Our results demonstrated that in spontaneous behavior experiments, FG significantly improved the cognitive performance of CRS model mice in OLRT (p < 0.05) and NORT (p < 0.05). In punitive behavior experiments, FG shortened the escape latency in long-term spatial memory test (MWMT, p < 0.01) and prolonged the latency into the dark chamber in non-spatial memory test (PAT, p < 0.01). Biochemical analysis showed that FG treatment significantly suppressed CRS‐induced Cyt C, Drp1, and BAX activation (p < 0.001, p < 0.01 and p < 0.05), promoted the CREB, p-CREB, AKT, and p-AKT level (p < 0.05, p < 0.01 and p < 0.001), and inhibited the CRS‐induced proinflammatory cytokines (TNF‐α and IL‐1β, p < 0.05 and p < 0.001) level in the hippocampus. Taken together, these results suggested that FG could attenuate cognitive deficits induced by CRS on multiple learning and memory behavioral tests.
Efficacy and safety of curcumin in psoriasis: preclinical and clinical evidence and possible mechanisms
Authors: Zhang Shuo , Wang Jiao , Liu Liu , Sun Xiaoying , Zhou Yaqiong , Chen Siting , Lu Yi , Cai Xiaoce , Hu Manqi , Yan Ge , Miao Xiao , Li Xin
Published: August 2022

Background: Psoriasis is a chronic and immune-mediated inflammatory skin disease. Many studies have shown that curcumin (CUR) has strong anti-inflammatory effects and can improve psoriasis; however, its efficacy and safety have not been confirmed, and the specific mechanism remains to be elucidated.

Objective: To evaluate the efficacy, safety, and possible mechanisms of CUR in the treatment of psoriasis.

Methods: The Cochrane Library, Embase, PubMed, Web of Science, China National Knowledge Infrastructure, Wanfang, and VIP (China Science and Technology Journal Database) were systematically searched for clinical trials and preclinical studies on the use of CUR in psoriasis treatment. All databases were searched from inception to January 2022. The meta-analysis was performed using RevMan 5.3 software.

Results: Our meta-analysis included 26 studies, comprising seven clinical randomized controlled trials and 19 preclinical studies. A meta-analysis of clinical trials showed that both CUR monotherapy and combination therapy improved Psoriasis Area and Severity Index (PASI) scores in patients compared to controls (standard mean difference [std.MD]: −0.83%; 95% confidence interval [CI]: −1.53 to 0.14; p = 0.02). In preclinical studies, CUR showed better performance in improving the phenotype of psoriatic dermatitis mice compared to controls, including total PASI score (std.MD: 6.50%; 95% CI: 10.10 to −2.90; p = 0.0004); ear thickness (p = 0.01); and the expression of inflammatory cytokines such as interleukin (IL)-17, tumor necrosis factor (TNF)-α, IL-17F, and IL-22 (p < 0.05). In cell studies, CUR inhibited cell proliferation (p = 0.04) and the cell cycle (p = 0.03) and downregulated the inflammatory cytokines IL-6 and IL-8 (p < 0.05).

Conclusions: CUR has excellent efficacy and broad potential to treat psoriasis in multiple ways. Its use also plays a crucial role in improving the psoriasis phenotype and reducing the inflammatory microenvironment. In conclusion, our findings suggest that CUR alone or in combination with other conventional treatments can effectively treat psoriasis.
The progress and prospect of natural components in rhubarb (Rheum ribes L.) in the treatment of renal fibrosis
Authors: Wang Yangyang , Yu Fangwei , Li Ao , He Zijia , Qu Caiyan , He Caiying , Ma Xiao , Zhan Huakui
Published: August 2022

Background: Renal fibrosis is a key pathological change that occurs in the progression of almost all chronic kidney diseases . CKD has the characteristics of high morbidity and mortality. Its prevalence is increasing each year on a global scale, which seriously affects people’s health and quality of life. Natural products have been used for new drug development and disease treatment for many years. The abundant natural products in R. ribes L. can intervene in the process of renal fibrosis in different ways and have considerable therapeutic prospects.

Purpose: The etiology and pathology of renal fibrosis were analyzed, and the different ways in which the natural components of R. ribes L. can intervene and provide curative effects on the process of renal fibrosis were summarized. Methods: Electronic databases, such as PubMed, Life Science, MEDLINE, and Web of Science, were searched using the keywords ‘R. ribes L.’, ‘kidney fibrosis’, ‘emodin’ and ‘rhein’, and the various ways in which the natural ingredients protect against renal fibrosis were collected and sorted out.

Results: We analyzed several factors that play a leading role in the pathogenesis of renal fibrosis, such as the mechanism of the TGF-β/Smad and Wnt/β-catenin signaling pathways. Additionally, we reviewed the progress of the treatment of renal fibrosis with natural components in R. ribes L. and the intervention mechanism of the crucial therapeutic targets.

Conclusion: The natural components of R. ribes L. have a wide range of intervention effects on renal fibrosis targets, which provides new ideas for the development of new anti-kidney fibrosis drugs.
Tripterygium wilfordii glycosides ameliorates collagen-induced arthritis and aberrant lipid metabolism in rats
Authors: Zhu Yitian , Zhang Luyun , Zhang Xiafeng , Wu Dehong , Chen Leiming , Hu Changfeng , Wen Chengping , Zhou Jia
Published: August 2022

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and the dysregulation of lipid metabolism has been found to play an important role in the pathogenesis of RA and is related to the severity and prognosis of patients. Tripterygium wilfordii glycosides (TWG) is extracted from the roots of Tripterygium wilfordii Hook F. with anti-inflammatory and immunosuppressive effects, and numerous clinical trials have supported its efficacy in the treatment of RA. Some evidence suggested that TWG can modulate the formation of lipid mediators in various innate immune cells; however whether it can improve RA-related lipid disorders has not been systematically studied. In the study, type Ⅱ collagen-induced arthritis (CIA) model was used to investigate the efficacy of TWG in the treatment of RA and its effect on lipid metabolism. Paw volume, arthritis score, pathological changes of ankle joint, serum autoantibodies and inflammatory cytokines were detected to assess the therapeutic effect on arthritis in CIA rats. Then, shotgun lipidomics based on multi-dimensional mass spectrometry platform was performed to explore the alterations in serum lipidome caused by TWG. The study showed that TWG could effectively ameliorate arthritis in CIA rats, such as reducing paw volume and arthritis score, alleviating the pathological damages of joint, and preventing the production of anti-CII autoantibodies and IL-1β cytokine. Significant increase in ceramide and decrease in lysophosphatidylcholine were observed in CIA rats, and were highly correlated with arthritis score and IL-1β level. After TWG treatment, these lipid abnormalities can be corrected to a great extent. These data demonstrate that TWG exerts a beneficial therapeutic effect on aberrant lipid metabolism which may provide new insights for further exploring the role and mechanism of TWG in the treatment of RA.
Discovering monoacylglycerol lipase inhibitors by a combination of fluorogenic substrate assay and activity-based protein profiling
Authors: Deng Hui , Zhang Qianwen , Lei Qian , Yang Na , Yang Kai , Jiang Jianbing , Yu Zhiyi
Published: August 2022

The endocannabinoid 2-arachidonoylglycerol (2-AG) is predominantly metabolized by monoacylglycerol lipase (MAGL) in the brain. Selective inhibitors of MAGL provide valuable insights into the role of 2-AG in a variety of (patho)physiological processes and are potential therapeutics for the treatment of diseases such as neurodegenerative disease and inflammation, pain, as well as cancer. Despite a number of MAGL inhibitors been reported, inhibitors with new chemotypes are still required. Here, we developed a substrate-based fluorescence assay by using a new fluorogenic probe AA-HNA and successfully screened a focused library containing 320 natural organic compounds. Furthermore, we applied activity-based protein profiling (ABPP) as an orthogonal method to confirm the inhibitory activity against MAGL in the primary substrate-based screening. Our investigations culminated in the identification of two major compound classes, including quinoid diterpene (23, cryptotanshinone) and β-carbolines (82 and 93, cis- and trans-isomers), with significant potency towards MAGL and good selectivity over other 2-AG hydrolases (ABHD6 and ABHD12). Moreover, these compounds also showed antiproliferative activities against multiple cancer cells, including A431, H1975, B16-F10, OVCAR-3, and A549. Remarkably, 23 achieved complete inhibition towards endogenous MAGL in most cancer cells determined by ABPP. Our results demonstrate the potential utility of the substrate-based fluorescence assay in combination with ABPP for rapidly discovering MAGL inhibitors, as well as providing an effective approach to identify potential targets for compounds with significant biological activities.
Investigating brain uptake of a non-targeting monoclonal antibody after intravenous and intracerebroventricular administration
Authors: Van De Vyver Arthur J. , Walz Antje-Christine , Heins Mariette S. , Abdolzade-Bavil Afsaneh , Kraft Thomas E. , Waldhauer Inja , Otteneder Michael B.
Published: August 2022

Monoclonal antibodies play an important role in the treatment of various diseases. However, the development of these drugs against neurological disorders where the drug target is located in the brain is challenging and requires a good understanding of the local drug concentration in the brain. In this original research, we investigated the systemic and local pharmacokinetics in the brain of healthy rats after either intravenous (IV) or intracerebroventricular (ICV) administration of EGFRvIII-T-Cell bispecific (TCB), a bispecific monoclonal antibody. We established an experimental protocol that allows serial sampling in serum, cerebrospinal fluid (CSF) and interstitial fluid (ISF) of the prefrontal cortex in freely moving rats. For detection of drug concentration in ISF, a push-pull microdialysis technique with large pore membranes was applied. Brain uptake into CSF and ISF was characterized and quantified with a reduced brain physiologically-based pharmacokinetic model. The model allowed us to interpret the pharmacokinetic processes of brain uptake after different routes of administration. The proposed model capturing the pharmacokinetics in serum, CSF and ISF of the prefrontal cortex suggests a barrier function between the CSF and ISF that impedes free antibody transfer. This finding suggests that ICV administration may not be better suited to reach higher local drug exposure as compared to IV administration. The model enabled us to quantify the relative contribution of the blood-brain barrier (BBB) and Blood-CSF-Barrier to the uptake into the interstitial fluid of the brain. In addition, we compared the brain uptake of three monoclonal antibodies after IV dosing. In summary, the presented approach can be applied to profile compounds based on their relative uptake in the brain and provides quantitative insights into which pathways are contributing to the net exposure in the brain.
Case Report: Respiratory paralysis associated with polymyxin B therapy
Authors: Ning Yachan , Chu Yanqi , Wu You , Huang Ying , Wang Chunmei , Jiang Li
Published: August 2022

Polymyxin B (PMB) and colistin are bactericidal polypeptide antibiotics discovered in 1947 and 1949 for the treatment of gram-negative bacterial infections. Polymyxin was used clinically in the 1950s, but it was gradually replaced by other antibiotics in the 1980s because of its high nephrotoxicity and neurotoxicity. In recent years, the increase of multidrug-resistant negative bacteria has led to the resurgence of polymyxin use. However, its side effects are not clear. Respiratory paralysis caused by PMB-related neuromuscular blockade is a rare but potentially fatal effect. We report a case of respiratory paralysis probably caused by polymyxin B infusion.
Roxadustat: Not just for anemia
Authors: Zhu Xiaoyu , Jiang Lili , Wei Xuejiao , Long Mengtuan , Du Yujun
Published: August 2022

Roxadustat is a recently approved hypoxia-inducible factor prolyl hydroxylase inhibitor that has demonstrated favorable safety and efficacy in the treatment of renal anemia. Recent studies found it also has potential for the treatment of other hypoxia-related diseases. Although clinical studies have not yet found significant adverse or off-target effects of roxadustat, clinicians must be vigilant about these possible effects. Hypoxia-inducible factor regulates the expression of many genes and physiological processes in response to a decreased level of oxygen, but its role in the pathogenesis of different diseases is complex and controversial. In addition to increasing the expression of hypoxia-inducible factor, roxadustat also has some effects that may be HIF-independent, indicating some potential off-target effects. This article reviews the pharmacological characteristics of roxadustat, its current status in the treatment of renal anemia, and its possible effects on other pathological mechanisms.
Drug repurposing in cancer neuroscience: From the viewpoint of the autophagy-mediated innervated niche
Authors: Shi Jiayan , Xu Jia , Li Yang , Li Bowen , Ming Hui , Nice Edouard C. , Huang Canhua , Li Qifu , Wang Chuang
Published: August 2022

Based on the bidirectional interactions between neurology and cancer science, the burgeoning field “cancer neuroscience” has been proposed. An important node in the communications between nerves and cancer is the innervated niche, which has physical contact with the cancer parenchyma or nerve located in the proximity of the tumor. In the innervated niche, autophagy has recently been reported to be a double-edged sword that plays a significant role in maintaining homeostasis. Therefore, regulating the innervated niche by targeting the autophagy pathway may represent a novel therapeutic strategy for cancer treatment. Drug repurposing has received considerable attention for its advantages in cost-effectiveness and safety. The utilization of existing drugs that potentially regulate the innervated niche via the autophagy pathway is therefore a promising pharmacological approach for clinical practice and treatment selection in cancer neuroscience. Herein, we present the cancer neuroscience landscape with an emphasis on the crosstalk between the innervated niche and autophagy, while also summarizing the underlying mechanisms of candidate drugs in modulating the autophagy pathway. This review provides a strong rationale for drug repurposing in cancer treatment from the viewpoint of the autophagy-mediated innervated niche.
On-line adaptive and real-time intrafraction motion management of spine-SBRT on an MR-linac
Authors: Cunningham Justine M. , Chin Snyder Karen , Kim Joshua P. , Siddiqui Salim M. , Parikh Parag , Chetty Indrin J. , Dolan Jennifer L.
Published: August 2022

Purpose: The superior soft-tissue contrast of MRI-guided radiotherapy offers enhanced localization accuracy of the spinal cord in spine Stereotactic Body Radiotherapy (SBRT). This work includes a planning study for spine-SBRT on an MR-Linac. Additionally, a patient with spine metastasis was treated using an adaptive radiation therapy workflow. We report our initial experience of targeting accuracy, image-guided localization, on-line adaptive planning, and treatment with real-time intrafraction imaging with automatic beam gating.

Methods: Six spine-SBRT patients were retrospectively re-planned to 18 Gy in 1-fraction on a commercial, Monte Carlo-based MR-Linac treatment planning system. Plans were generated using 9–13 step-and-shoot intensity-modulated radiation therapy 6 MV-flattening filter free beams and optimized to achieve plan quality criteria recommended by RTOG-0631. One thoracic vertebral body clinical case was treated to 27 Gy in 3-fractions utilizing ART, where daily anatomical changes were accounted for via re-planning and treatment in an on-line manner to account for limited ability to correct rotational setup uncertainties.

Results: Plans met all critical-tissue constraints outlined in RTOG-0631 and AAPM Task Group-101, while covering 90% of the target with the prescription dose. Clinically, visibility of the spinal cord allowed for patient setup focusing on spinal cord-alignment. Utilization of the online ART workflow, while re-contouring the target and spinal cord, enabled an increase in prescription dose coverage from 89 to 95% in two of three fractions while maintaining acceptable doses to organs-at-risk. Real-time MR-cine imaging demonstrated sufficient quality for the automatic beam gating algorithm to provide intrafraction motion management of the spinal canal utilizing a 3.0 mm gating boundary and 1–2% region of excursion allowance, in the sagittal plane. A decrease in coverage, below the 95% threshold was noted in post-treatment volumetric imaging due to lateral movement not observed during real-time gating.

Conclusion: Achieved plan quality and deliverability was within accepted standards. MR-guidance with an on-line ART workflow offered increased accuracy in the localization of the spinal cord at the time of treatment to enhance both tissue sparing and target volume coverage. Increased spatial resolution of cine-images, and tracking in three-dimensions would be beneficial for future spine-SBRT treatments on the MR-Linac.
On the role of chirality flips for the muon magnetic moment and its relation to the muon mass
Authors: Stöckinger Dominik , Stöckinger-Kim Hyejung
Published: August 2022

The muon mass and the anomalous magnetic moment aμ are quantities which require chirality flips, i.e., transitions between left- and right-handed muons. Muon chirality flips are connected to electroweak symmetry breaking and Yukawa couplings. Scenarios for physics beyond the Standard Model motivated by the quest to understand electroweak symmetry breaking and/or the origin of flavour often introduce new sources of chirality flips; they hence provide potentially large contributions to aμ, and the current aμ measurement provides relevant constraints on such scenarios. This connection between aμ, chirality flips, and the muon mass generation mechanism is important and underlies much of the current research on aμ. The present article provides a brief pedagogical introduction to this role of chirality flips and an overview of general relationships. The general statements are illustrated with several concrete models involving e.g., leptoquarks and supersymmetry.
High-sensitivity multi-channel DPSK system with real-time phase lock controller for free-space optical communication
Authors: Gao Duorui , Li Tianlun , Xie Zhuang , Meng Jiacheng , Jia Shuaiwei , Bai Zhaofeng , Wang Wei , Xie Xiaoping
Published: August 2022

To overcome the power jitters in satellite-to-ground communications caused by atmospheric turbulence, a type of DPSK free-space communication system, assisted by a self-designed real-time phase lock controller, has been established. The system can effectively compensate for power swings in communication links and hence achieve high sensitivity. The wavelength division multiplexing technique is applied to a four-channel DPSK system to provide greater link capacity. With the data rate of a single channel as 2.5 Gbps and unencoded BER as 1 × 10–3, reception sensitivity has been obtained at −53.58 dBm (13.69 photons/bit), −53.59 dBm (13.66 photons/bit), −53.61 dBm (13.59 photons/bit), and −53.63 dBm (13.53 photons/bit) for each independent channel, respectively. The gap between our sensitivity result and the theoretical limit has narrowed to about −3.5 dB. Simultaneously, the DPSK receiver, with our self-designed phase lock controller, has stabilized reception of optical power fluctuations that range from 0 to 40 dB. Additionally, the impact of a four-wave mixing effect on multi-channel system performance has been investigated in detail. Our experimental results present a novel solution for the superior performance of free-space communication links.
Computer-aided diagnosis of prostate cancer based on deep neural networks from multi-parametric magnetic resonance imaging
Authors: Yi Zhenglin , Ou Zhenyu , Hu Jiao , Qiu Dongxu , Quan Chao , Othmane Belaydi , Wang Yongjie , Wu Longxiang
Published: August 2022

Objectives: To evaluate a new deep neural network (DNN)–based computer-aided diagnosis (CAD) method, namely, a prostate cancer localization network and an integrated multi-modal classification network, to automatically localize prostate cancer on multi-parametric magnetic resonance imaging (mp-MRI) and classify prostate cancer and non-cancerous tissues.

Materials and methods: The PROSTAREx database consists of a “training set” (330 suspected lesions from 204 cases) and a “test set” (208 suspected lesions from 104 cases). Sequences include T2-weighted, diffusion-weighted, Ktrans, and apparent diffusion coefficient (ADC) images. For the task of abnormal localization, inspired by V-net, we designed a prostate cancer localization network with mp-MRI data as input to achieve automatic localization of prostate cancer. Combining the concepts of multi-modal learning and ensemble learning, the integrated multi-modal classification network is based on the combination of mp-MRI data as input to distinguish prostate cancer from non-cancerous tissues through a series of operations such as convolution and pooling. The performance of each network in predicting prostate cancer was examined using the receiver operating curve (ROC), and the area under the ROC curve (AUC), sensitivity (TPR), specificity (TNR), accuracy, and Dice similarity coefficient (DSC) were calculated.

Results: The prostate cancer localization network exhibited excellent performance in localizing prostate cancer, with an average error of only 1.64 mm compared to the labeled results, an error of about 6%. On the test dataset, the network had a sensitivity of 0.92, specificity of 0.90, PPV of 0.91, NPV of 0.93, and DSC of 0.84. Compared with multi-modal classification networks, the performance of single-modal classification networks is slightly inadequate. The integrated multi-modal classification network performed best in classifying prostate cancer and non-cancerous tissues with a TPR of 0.95, TNR of 0.82, F1-Score of 0.8920, AUC of 0.912, and accuracy of 0.885, which fully confirmed the feasibility of the ensemble learning approach.

Conclusion: The proposed DNN-based prostate cancer localization network and integrated multi-modal classification network yielded high performance in experiments, demonstrating that the prostate cancer localization network and integrated multi-modal classification network can be used for computer-aided diagnosis (CAD) of prostate cancer localization and classification.
Adaptations of postural sway dynamics and cortical response to unstable stance with stroboscopic vision in older adults
Authors: Tsai Yi-Ying , Chen Yi-Ching , Zhao Chen-Guang , Hwang Ing-Shiou
Published: August 2022

Background: Stroboscopic vision (SV), intermittent visual blocking, has recently been incorporated into postural training in rehabilitation. This study investigated interactions of postural fluctuation dynamics and cortical processing for the elderly during stabilometer stance with SV.

Methods: Thirty-five healthy elderly maintained an upright stance on a stabilometer. Along with postural fluctuation dynamics, EEG relative power and EEG-EEG connectivity were used to contrast neuromechanical controls of stabilometer stance with SV and full-vision.

Results: Compared with the full-vision, SV led to greater postural fluctuations with lower sample entropy and mean frequency (MF). SV also reduced regional power in the mid-frontal theta cluster, which was correlated to SV-dependent changes in the size of postural fluctuations. SV also enhanced the alpha band supra-threshold connectivity in the visual dorsal and frontal–occipital loops of the right hemisphere, and the supra-threshold connectivity from Fp2 positively related to variations in the MF of postural fluctuations.

Conclusion: SV adds challenge to postural regulation on the stabilometer, with the increasing regularity of postural movements and fewer corrective attempts to achieve the postural goal. The elderly shift over-reliance on visual inputs for posture control with more non-visual awareness, considering deactivation of the dorsal visual stream and visual error processing.
The role of tumor-associated macrophages in oral squamous cell carcinoma
Authors: Xue Yiwen , Song Xiao , Fan Siyu , Deng Runzhi
Published: August 2022

Oral squamous cell carcinoma (OSCC) is a common head and neck cancer with a high recurrence rate and a low 5-year survival rate. Tumor-associated macrophages (TAMs) are important immune cells in the tumor microenvironment, which play an important role in the progression of many tumors. This article reviews the origin, and the role of TAMs in the invasion, metastasis, angiogenesis and immunosuppression of OSCC. Therapeutic strategies targeting TAMs are also discussed in hopes of providing new ideas for the treatment of OSCC.
Exposure to dim light at night alters daily rhythms of glucose and lipid metabolism in rats
Authors: Rumanova Valentina Sophia , Okuliarova Monika , Foppen Ewout , Kalsbeek Andries , Zeman Michal
Published: August 2022

Nocturnal light pollution has been rapidly increasing during the last decades and even though dim artificial light at night (ALAN) has been associated with metabolic diseases, its mechanism is still far from clear. Therefore, the aim of our study was to thoroughly analyze the effects of ALAN on energy metabolism, metabolites, metabolic hormones, and gene expression. Male Wistar rats were kept in either the standard light:dark (12:12) cycle or exposed to ALAN (∼2 lx) during the whole 12-h dark phase for 2 weeks. Energy metabolism was measured in metabolic cages. In addition, we measured plasma and hepatic metabolites, clock and metabolic gene expression in the liver and epididymal adipose tissue, and plasma hormone levels. In ALAN rats, we observed an unexpected transitory daytime peak of locomotor activity and a suppression of the peak in locomotor activity at the beginning of the dark period. These changes were mirrored in the respiratory exchange ratio. Plasma metabolites became arrhythmic, and plasma and hepatic cholesterol levels were increased. Lost rhythmicity of metabolites was associated with disrupted behavioral rhythms and expression of metabolic genes. In the liver, the rhythms of metabolic sensors were either phase-advanced (Ppara, Pgc1a, Nampt) or arrhythmic (Sirt1, Lxra) after ALAN. The rhythmic pattern of Ppara and Sirt1 was abolished in the adipose tissue. In the liver, the amplitude of the daily rhythm in glycogen content was attenuated, the Glut2 rhythm was phase-advanced and Foxo1 lost its daily rhythmicity. Moreover, hepatic Foxo1 and Gck were up-regulated after ALAN. Interestingly, several parameters of lipid metabolism gained rhythmicity (adiponectin, Hmgcs2, Lpl, Srebf1c) in the liver, whereas Noct became arrhythmic in the adipose tissue. Peripheral clock genes maintained their robust oscillations with small shifts in their acrophases. Our data show that even a low level of ALAN can induce changes in the daily pattern of behavior and energy metabolism, and disturb daily rhythms of genes encoding key metabolic sensors and components of metabolic pathways in the liver and adipose tissue. Disturbed metabolic rhythms by ALAN could represent a serious risk factor for the development and progression of metabolic diseases.
Increased extent of waterfowl grazing lengthens the recovery time of a colonizing seagrass (Halophila ovalis) with implications for seagrass resilience
Authors: O’Dea Caitlyn M. , Lavery Paul S. , Webster Chanelle L. , McMahon Kathryn M.
Published: August 2022

Herbivore distributions and abundance are shifting because of climate change, leading to intensified grazing pressure on foundation species such as seagrasses. This, combined with rapidly increasing magnitudes of change in estuarine ecosystems, may affect seagrass resilience. While the overall resilience of seagrasses is generally well-studied, the timeframes of recovery has received comparatively little attention, particularly in temperate estuaries. We investigated how the recovery time (RT) of seagrass is affected by simulated grazing in a southwestern Australian estuary. Whilst excluding swans, we simulated different grazing intensities (25, 50, 75, and 100% removal from 1 m2 plots) at four locations in the Swan-Canning Estuary, Western Australia during summer and tracked the recovery of seagrass over 3 months, using seagrass cover as the main measure of recovery. We found that seagrass recovered within 4–6 weeks from the lower grazing intensities (25 and 50%) and 7–19 weeks from the higher grazing intensities (75 and 100%) across the estuary. Increased grazing intensity led to not only longer recovery times (RTs), but also greater variability in the RT among experimental locations. The RT from the higher grazing intensities at one location in particular was more than double other locations. Seagrass recovery was through vegetative mechanisms and not through sexual reproduction. There was a significant grazing treatment effect on seagrass meadow characteristics, particularly belowground biomass which had not recovered 3 months following grazing. As the pressure of climate change on estuarine environments increases, these quantified RTs for seagrass provide a baseline for understanding grazing pressure as a singular disturbance. Future work can now examine how grazing and other potentially interacting pressures in our changing climate could impact seagrass recovery even further.
Comparative transcriptome analysis of compatible and incompatible Brassica napus—Xanthomonas campestris interactions
Authors: Yang Li , Zhao Chuanji , Bai Zetao , Yang Lingli , Schranz M. Eric , Liu Shengyi , Bouwmeester Klaas
Published: August 2022

Black rot caused by the vascular pathogenic bacterium Xanthomonas campestris pv. campestris (Xcc) is widespread in Brassicaceae plants and an infectious disease that causes large yield losses in oil seed rape (Brassica napus L.). Improvement of resistance through breeding is a crucial strategy to prevent black rot disease in B. napus, but presently hampered by insufficient understanding of Xcc-Brassica interactions. This study compares two EMS-mutagenized B. napus lines that show contrasting resistance levels to their susceptible progenitor. Patterns of differential gene expression between these B. napus lines were evaluated at three time points post inoculation by comparative RNA-seq analysis. In line with the observed disease phenotypes, the susceptible line ZS9mXccS-1 displayed a steady amount of differentially expressed genes (DEGs) at different time points of infection, whereas the resistant line ZS9mXccR-1 displayed a gradual increase in DEGs throughout the course of infection. Weighted gene co-expression network analysis (WGCNA) pinpointed multiple defense-related hub genes with potential central roles in immunity, including the cell surface receptor genes CRK11 and BIR1, and the associated downstream regulatory genes WRKY11 and PBL30. KEGG analysis of DEGs belonging to two distinct co-expression modules revealed enriched pathways associated with defense, including Ca2+-signaling, receptor-mediated immunity, and phytohormone balance. Taken together, our comparative transcriptome analysis provides new avenues to unravel the mechanisms underlying black rot resistance in B. napus.