bluuebunny/crossref_metadata_2025 huggingface dataset:
Learning From the Study Fleet: Maintenance of a Large-Scale Reference Fleet for Northeast U.S. Fisheries
Authors: Jones Andrew W. , Burchard Katie A. , Mercer Anna M. , Hoey John J. , Morin Michael D. , Gianesin Giovanni L. , Wilson Jacob A. , Alexander Calvin R. , Lowman Brooke A. , Duarte Debra G. , Goethel David , Ford James , Ruhle James , Sykes Rodman , Sawyer Troy
Published: May 2022

Logbook data from commercial fisheries are a vital component in the machinery of management, including tracking the volume of catches and allocating catch spatially. At the same time, logbooks can provide a unique window into the ecological and sociological conditions in marine fisheries, where fishermen interact with marine species and environments frequently and broadly. Traditional logbooks, however, often are not sufficiently standardized (when personal logs), or lack the detail (when regulatory documents) required to adequately understand fisheries ecosystems. The Study Fleet program, operated by the Northeast Fisheries Science Center’s Cooperative Research Branch, was developed to address these shortfalls by engaging members of the fishing industry in collecting high-resolution catch, effort, and environmental data using electronic logbooks. Since its inception, the Study Fleet has expanded from a small project focused on collecting detailed catch information from the New England multispecies groundfish fishery to a program with a wider scope encompassing a variety of fisheries, gears, and environmental parameters from North Carolina to Maine U.S. Over the years, a number of lessons have been learned about recruiting and supporting industry partners, managing the data, evolving technical specifications, and the challenges associated with analyzing and applying self-reported fisheries data. Here we describe the current state of the program and provide summaries of the Study Fleet program operations and outcomes from 2007-2020, with an eye towards successes, challenges, and applicability of the approach in other regions. We suggest other reference fleet programs, as well as other developing fishery dependent data collections (e.g., electronic monitoring programs), develop detailed roadmaps for each data collection to keep participants engaged as collaborators, target specific fisheries to keep resources from being stretched too thin, and partner with data users early. Additionally, we suggest programs invest in the long-term participation of individual fishermen, carefully weigh the pros and cons of involvement in regulatory reporting, and plan data products and applications well in advance to ensure that the sampling scheme and granularity of the data meet the needs of stock assessment, ecosystem, and oceanographic scientists.
Efficacy and Safety of Direct-Acting Antivirals in Kidney Transplantation From HCV-Viremic Donors to Negative Recipients: A Meta-Analysis
Authors: Feng Zepei , Zhang Jinwei , Tan Weilong , Wang Chunhui , Chen Qiong , Shen Chao , Fan Haozhi , Zhang Yun , Huang Peng , Yue Ming
Published: May 2022

Background:

With the development of direct-acting antiviral agents (DAAs), the research on kidney transplantation from Hepatitis C virus (HCV)-viremic donors to HCV-negative recipients has grown. The objective of this comprehensive analysis was to evaluate the efficacy and safety of DAAs in kidney transplantation from HCV-viremic donors to negative recipients.

Methods

Multiple databases were searched for a systematic and comprehensive up to March 2022. The primary outcomes included the percentage of sustained virological response at week 12 after the end of treatment (SVR12), adverse events (AEs; any grade), and severe adverse events (SAEs) as the endpoints. Publication bias was examined by using the funnel plots and Egger's test.

Results

In total, 16 studies with 454 subjects were included in the study and the pooled estimate of SVR12, AEs, and SAEs rates were 100.0% (95% CI: 99.2-100.0), 1.9%(95%CI: 0.0-4.9), and 0.0% (95%CI: 0.0-1.5). Subgroup analysis showed that pooled SVR12 rates were 100.0% (95%CI: 99.6-100.0) for genotype (GT)1a and 96.3% (95%CI: 83.3-100.0) for GT2; 100.0% (95%CI: 98.9-100.0) for DAAs treatments; and 100.0% (95%CI: 98.2-100.0) for prophylaxis subgroup. Egger's tests showed that no publication bias was found in this study.

Conclusion

This comprehensive analysis showed the high efficacy and safety of DAAs in kidney transplantation from HCV-viremic donors to HCV-negative recipients.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=246541.
COVID-19 and Intestinal Ischemia: A Multicenter Case Series
Authors: Sarkardeh Maryam , Meftah Elahe , Mohammadzadeh Narjes , Koushki Javad , Sadrzadeh Zahra
Published: May 2022

Introduction

Gastrointestinal symptoms are common among COVID-19 patients. Although gastrointestinal involvements are mostly benign, they rarely indicate a severe pathology like intestinal ischemia. The present case series describes 21 patients with bowel ischemia, necrosis, or perforation.

Methods

The present case series was conducted from April 2020 to February 2022 in the surgical wards of two Iranian hospitals. We retrospectively included adult patients with concomitant COVID-19 and intestinal ischemia. Primary outcomes were defined as the length of stay and survival.

Results

Twenty-four patients with a median age of 61.5 years were included in the study. Sixteen (67%) patients were male, and 13 (54%) were without any comorbidities. Macrovascular mesenteric ischemia was not identified in 21 patients (87.5%). Gastrointestinal manifestations appeared on the median of seven days (range 2–21) after the diagnosis of COVID-19, with the most common symptom being abdominal pain. All the patients had a significantly elevated C-Reactive Protein prior to surgery, ranging from 68 to 362. D-dimer was measured in eight patients and was significantly elevated, ranging from 1,878 to over 5,000 ng/mL. One patient was managed conservatively due to a good clinical condition. Except for one patient with angioinvasive mucormycosis and one other with leukocytoclastic vasculitis, pathologic evaluation revealed general features of intestinal necrosis, including ulcer, hemorrhage, necrosis, neutrophilic infiltration (in seven patients), neutrophilic abscess (in four patients), and edema. Bowel necrosis accompanied mortality of 15 (62.5%) patients and a median of 6.5 days of hospital stay.

Conclusion

Intestinal ischemia in COVID-19 patients is associated with a high mortality rate. Further research is needed to elucidate the dynamics of intestinal ischemia in the setting of COVID-19.
Modeling Calcium Signaling in S. cerevisiae Highlights the Role and Regulation of the Calmodulin-Calcineurin Pathway in Response to Hypotonic Shock
Authors: Spolaor Simone , Rovetta Mattia , Nobile Marco S. , Cazzaniga Paolo , Tisi Renata , Besozzi Daniela
Published: May 2022

Calcium homeostasis and signaling processes in Saccharomyces cerevisiae, as well as in any eukaryotic organism, depend on various transporters and channels located on both the plasma and intracellular membranes. The activity of these proteins is regulated by a number of feedback mechanisms that act through the calmodulin-calcineurin pathway. When exposed to hypotonic shock (HTS), yeast cells respond with an increased cytosolic calcium transient, which seems to be conditioned by the opening of stretch-activated channels. To better understand the role of each channel and transporter involved in the generation and recovery of the calcium transient—and of their feedback regulations—we defined and analyzed a mathematical model of the calcium signaling response to HTS in yeast cells. The model was validated by comparing the simulation outcomes with calcium concentration variations before and during the HTS response, which were observed experimentally in both wild-type and mutant strains. Our results show that calcium normally enters the cell through the High Affinity Calcium influx System and mechanosensitive channels. The increase of the plasma membrane tension, caused by HTS, boosts the opening probability of mechanosensitive channels. This event causes a sudden calcium pulse that is rapidly dissipated by the activity of the vacuolar transporter Pmc1. According to model simulations, the role of another vacuolar transporter, Vcx1, is instead marginal, unless calcineurin is inhibited or removed. Our results also suggest that the mechanosensitive channels are subject to a calcium-dependent feedback inhibition, possibly involving calmodulin. Noteworthy, the model predictions are in accordance with literature results concerning some aspects of calcium homeostasis and signaling that were not specifically addressed within the model itself, suggesting that it actually depicts all the main cellular components and interactions that constitute the HTS calcium pathway, and thus can correctly reproduce the shaping of the calcium signature by calmodulin- and calcineurin-dependent complex regulations. The model predictions also allowed to provide an interpretation of different regulatory schemes involved in calcium handling in both wild-type and mutants yeast strains. The model could be easily extended to represent different calcium signals in other eukaryotic cells.
Neuropsychological Performance Is Correlated With Tau Protein Deposition and Glucose Metabolism in Patients With Alzheimer’s Disease
Authors: Qiao Zhen , Wang Guihong , Zhao Xiaobin , Wang Kai , Fan Di , Chen Qian , Ai Lin
Published: May 2022

Objective

This study characterizes glucose metabolism and tau protein deposition distribution in patients with Alzheimer’s disease (AD) and to evaluate the relationships between neuropsychological performance and tau protein deposition or glucose metabolism using 18F-FDG and 18F-AV1451 positron emission tomography/computed tomography (PET/CT).

Methods

Sixty-four patients with β-amyloid-positive (Aβ+) AD and twenty-five healthy participants were enrolled in this study. All participants underwent 18F-FDG and 18F-AV1451 PET/CT. Clinical data and neuropsychological scores were collected. Patients with AD were divided into mild, moderate, and severe groups according to mini-mental state examination (MMSE) scores. The standardized uptake value ratios (SUVRs) for both FDG and AV1451 PET images were calculated using the cerebellar vermis as reference. The SUVRs of the whole cerebral cortex and each brain region were calculated. The volume of interest (VOI) was obtained using automated anatomical atlas (AAL) and Brodmann regions. Student’s t-test was used to perform intergroup comparisons of SUVR. The partial correlation coefficient between SUVR and neuropsychological scores was computed in an inter-subject manner using age and education as covariates.

Results

The mild subgroup showed a reduction in glucose metabolism and aggregation of tau protein in the temporoparietal cortex. With a decline in neuropsychiatric performance, the SUVR on FDG PET decreased and SUVR on tau PET increased gradually. The areas of glucose metabolism reduction and tau protein deposition appeared first in the parietal cortex, followed by the temporal and frontal cortex, successively. Both FDG and tau SUVRs significantly correlated with MMSE, Montreal cognitive assessment (MOCA), auditory verbal learning test (AVLT), Boston naming test (BNT), clock drawing task (CDT), and verbal fluency test (VFT) (p < 0.05). The SUVR on FDG PET significantly correlated with activities of daily living (ADL) and the Hamilton depression scale (HAMD). There was no significant correlation between the tau SUVRs and ADL or HAMD.

Conclusion

The extension of tau protein deposition was similar but not exactly consistent with the area of glucose metabolism reduction. Both tau and FDG SUVRs correlated with cognitive function in domain-specific patterns, and the results of FDG PET more closely correlated with neuropsychological function than tau PET results did.
A Longitudinal Magnetoencephalographic Study of the Effects of Deep Brain Stimulation on Neuronal Dynamics in Severe Anorexia Nervosa
Authors: Braeutigam Sven , Scaife Jessica Clare , Aziz Tipu , Park Rebecca J.
Published: May 2022

Anorexia Nervosa (AN) is a debilitating psychiatric disorder characterized by the relentless pursuit of thinness, leading to severe emaciation. Magnetoencephalography (MEG)was used to record the neuronal response in seven patients with treatment-resistant AN while completing a disorder-relevant food wanting task. The patients underwent a 15-month protocol, where MEG scans were conducted pre-operatively, post-operatively prior to deep brain stimulation (DBS) switch on, twice during a blind on/off month and at protocol end. Electrodes were implanted bilaterally into the nucleus accumbens with stimulation at the anterior limb of the internal capsule using rechargeable implantable pulse generators. Three patients met criteria as responders at 12 months of stimulation, showing reductions of eating disorder psychopathology of over 35%. An increase in alpha power, as well as evoked power at latencies typically associated with visual processing, working memory, and contextual integration was observed in ON compared to OFF sessions across all seven patients. Moreover, an increase in evoked power at P600-like latencies as well as an increase in γ-band phase-locking over anterior-to-posterior regions were observed for high- compared to low-calorie food image only in ON sessions. These findings indicate that DBS modulates neuronal process in regions far outside the stimulation target site and at latencies possibly reflecting task specific processing, thereby providing further evidence that deep brain stimulation can play a role in the treatment of otherwise intractable psychiatric disorders.
Microglia as a Hub for Suicide Neuropathology: Future Investigation and Prevention Targets
Authors: Gonçalves de Andrade Elisa , González Ibáñez Fernando , Tremblay Marie-Ève
Published: May 2022

Suicide is a complex public health challenge associated worldwide with one death every 40 s. Research advances in the neuropathology of suicidal behaviors (SB) have defined discrete brain changes which may hold the key to suicide prevention. Physiological differences in microglia, the resident immune cells of the brain, are present in post-mortem tissue samples of individuals who died by suicide. Furthermore, microglia are mechanistically implicated in the outcomes of important risk factors for SB, including early-life adversity, stressful life events, and psychiatric disorders. SB risk factors result in inflammatory and oxidative stress activities which could converge to microglial synaptic remodeling affecting susceptibility or resistance to SB. To push further this perspective, in this Review we summarize current areas of opportunity that could untangle the functional participation of microglia in the context of suicide. Our discussion centers around microglial state diversity in respect to morphology, gene and protein expression, as well as function, depending on various factors, namely brain region, age, and sex.
Does Virtual Reality Feedback at Infra-Low Frequency Improve Centralized Pain With Comorbid Insomnia While Mitigating Risks for Sedative Use Disorder?: A Case Report
Authors: Orakpo Nnamdi , Yuan Chujun , Olukitibi Olanrewaju , Burdette Jeff , Arrington Kim
Published: May 2022

This case report concerns a patient with clinically diagnosed moderate-severe insomnia secondary to chronic lower back pain and sciatica, previously treated with hydrocodone, naproxen, cyclobenzaprine and nightly diazepam. He underwent a trial of 20 sessions of virtual reality neurofeedback therapy (VR-NFB) at infra-low frequency, and by the end of 20 sessions achieved sustained analgesia and consequently, a complete resolution of his pain-related insomnia. Follow-up at 1 year confirmed his improvements were sustained, and he maintained his abstinence from sedatives, as observed on the Prescription Monitoring Program for controlled substances. This case highlights the importance of understanding chronic pain and its connection with restorative sleep: incorporating endogenous neuromodulation in behavioral sleep medicine helped to diminish the risk of benzodiazepine use disorder. This may be the first case of complete resolution of chronic pain with comorbid insomnia after treatment with VR-NFB at the infra-low frequency.
Visualizing Presynaptic Active Zones and Synaptic Vesicles
Authors: Heckmann Manfred , Pauli Martin
Published: May 2022

The presynaptic active zone (AZ) of chemical synapses is a highly dynamic compartment where synaptic vesicle fusion and neurotransmitter release take place. During evolution the AZ was optimized for speed, accuracy, and reliability of chemical synaptic transmission in combination with miniaturization and plasticity. Single-molecule localization microscopy (SMLM) offers nanometer spatial resolution as well as information about copy number, localization, and orientation of proteins of interest in AZs. This type of imaging allows quantifications of activity dependent AZ reorganizations, e.g., in the context of presynaptic homeostatic potentiation. In combination with high-pressure freezing and optogenetic or electrical stimulation AZs can be imaged with millisecond temporal resolution during synaptic activity. Therefore SMLM allows the determination of key parameters in the complex spatial environment of AZs, necessary for next generation simulations of chemical synapses with realistic protein arrangements.
Curcumin - The Nutraceutical With Pleiotropic Effects? Which Cardiometabolic Subjects Might Benefit the Most?
Authors: Surma Stanisław , Sahebkar Amirhossein , Urbański Jakub , Penson Peter E. , Banach Maciej
Published: May 2022

Despite continuous advances in pharmacotherapy, atherosclerotic cardiovascular disease remains the world's leading killer. Atherosclerosis relates not only to an increased level of cholesterol, but involves the development of atherosclerotic plaques, which are formed as a result of processes including inflammation and oxidative stress. Therefore, in addition to the classical risk factors for ASCVD (such as type 2 diabetes, overweight, obesity, hypertension and metabolic syndrome), residual risk factors such as inflammation and oxidative stress should also be reduced. The most important intervention in ASCVD is prevention, which includes promoting a healthy diet based on products of natural origin. Curcumin, which is often present in the diet, has been demonstrate to confer several benefits to health. It has been shown in numerous clinical trials that curcumin exhibited anti-diabetic, lipid-lowering, antihypertensive, antioxidant and anti-inflammatory effects, as well as promoting weight loss. All this means that curcumin has a comprehensive impact on the most important risk factors of ASCVD and may be a beneficial support in the treatment of these diseases. Recently, it has also been shown that curcumin may have a beneficial effect on the course of SARS-CoV-2 infection and might be helpful in the prevention of long-COVID complications. The aim of this review is to summarize the current knowledge regarding the safety and efficacy of curcumin in the prevention and treatment of cardiometabolic diseases.
Exploring Infant Caregivers' Provision of Modified Formulas: Potential Demographic Differences and Reasons for Provisions
Authors: Gershman Haley , Romo-Palafox Maria J. , Rajeh Tassneem , Fleming-Milici Frances , Harris Jennifer L.
Published: May 2022

Background

Formula brands have modified the ingredients in standard infant formulas and extensively market modified formulas, claiming benefits for infants that are not supported by scientific evidence. This exploratory study examined the proportion of infant caregivers who reported serving modified formula, demographic differences, and reasons for providing them.

Methods

This is a cross-sectional online survey of US caregivers of infants (6–11 months) who provided formula in the past month (N = 436). Participants reported the type of formula served most often and agreement with potential reasons for provision. Logistic regression assessed the odds of serving modified formula by demographic characteristics. MANOVA examined differences in agreement with purchase reasons between caregivers by the type of formula provided.

Results

Approximately one-half (47%) of participants reported serving modified formula most often; sensitive and organic/non-GMO were the most common types provided. Caregivers in the middle-income group were most likely to serve modified formulas, but the provision did not differ by other demographic characteristics. Agreement with reasons for providing was highest for “pediatricians recommend” and “benefits my child” (M = 4.2 out of 5). Agreement with “my pediatrician prescribed” and “natural ingredients” was significantly higher for modified vs. standard formula providers.

Conclusion

Widespread provision of modified formula by infant caregivers raises concerns due to its higher cost and the lack of scientific evidence supporting benefits for babies. These findings suggest that regulations limiting unsubstantiated formula claims and restrictions on misleading marketing to consumers are necessary. Additional research is needed to understand pediatricians' perceptions of modified formulas and reasons for recommending them to patients.
Application of Green Technologies in Design-Based Extraction of Celastrus paniculatus (Jyotishmati) Seeds, SEM, GC-MS Analysis, and Evaluation for Memory Enhancing Potential
Authors: Arya Ashwani , Kaushik Deepak , Almeer Rafa , Bungau Simona G. , Sayed Amany A. , Abdel-Daim Mohamed M. , Bhatia Saurabh , Mittal Vineet
Published: May 2022

Background

The Celastrus paniculatus (CP), commonly known as Jyotishmati, is considered as “elixir of life” by Indian people for the prevention or management of many ailments. The seed powder and its extract have widely used commercially for the preparation of various Ayurvedic formulations for the improvement of memory. CP seeds were generally extracted by conventional extraction methods (CEMs) which are assumed to impact environment burden and also produce low extract yield. Green extraction with possible improvement in extract yield has always been the need of hour for selected medicinal plant.

Objective

In the present research, we aimed to optimize the different extraction factors in microwave and ultrasound-based extraction. The various extracts obtained in conventional and green methods are also evaluated for the possible improvement in memory enhancing potential.

Materials and Methods

The selected medicinal herb was extracted by CEM (maceration and percolation). In green methods such microwave-assisted extraction (MAE) and ultrasound assisted-extraction (UAE), various parameters were optimized using Box-Behnken design coupled with response surface methodology. The scanning electron microscopy (SEM) and gas chromatography–mass spectroscopy (GC-MS) analyses were also done to confirm the possible improvement in concentration of plant actives. The Swiss albino mice were used to evaluate memory enhancing potential of different extracts.

Results

At the optimized conditions MAE and UAE the extraction yield, total phenolic content (TPC) and Total flavonoid content (TFC) are significantly improved. The GC-MS analysis further confirms the improvement in concentration of certain fatty acid esters, pilocarpine, and steroidal compounds in optimized extracts. The optimized extracts also exhibited the significant improvement in behavioral parameters, oxidative stress-induced parameters, and acetylcholinesterase inhibitory potential.

Discussion and Conclusion

From the results, we can say that the application of green technologies in design-based extraction of selected herb not only significantly reduces the extraction time but also improves the extract yield and concentration of plant actives. In nutshell, it can be concluded that the green approaches for extraction of seeds of Celastrus paniculatus could be scale up at a commercial level to meet the rising demand for herbal extract.
The Progress of the Prevention and Treatment of Vitamin D to Tuberculosis
Authors: Cai Li , Wang Gaoming , Zhang Peijun , Hu Xinyi , Zhang Hao , Wang Fan , Tong Yeqing
Published: May 2022

The progressions of a number of lung diseases, including acute lung injury, cystic fibrosis, asthma, chronic obstructive pulmonary disease, pneumonia and tuberculosis (TB) are found to be highly associated with inflammatory responses. As a signaling nutrient, Vitamin D modulates the activities of dendritic cells, monocytes/macrophages, T and B cells, and tissue epithelial cells in the body to induce inflammatory responses and boost immune functions. Given the high prevalence of vitamin D deficiency among pulmonary insufficiency and inflammation-related cases, researchers indicated vitamin D supplementation could have a potential role in the prevention and treatment of lung disease, especially tuberculosis. In this paper, we reviewed published studies on the role of vitamin D in the prevention and treatment of tuberculosis. The paper identified vitamin D’s potential as an adjunctive therapy and demonstrated its safety so as to provide an impetus for further studies and clinical applications.
Butyric Acid Ameliorates Myocardial Fibrosis by Regulating M1/M2 Polarization of Macrophages and Promoting Recovery of Mitochondrial Function
Authors: Li Xiaogang , Li Ruixuan , You Nana , Zhao Xiexiong , Li Jiaying , Jiang Weihong
Published: May 2022

Background

We aimed to investigate the effect and mechanism of butyric acid on rat myocardial fibrosis (MF).

Methods

16S rRNA sequencing was used to analyze the gut microbiota characteristics of the Sham group and MF group. HPLC was applied to measure butyric acid in the feces and serum. In vitro, rat macrophages RMa-bm were stimulated with LPS and IL-4, respectively, and then butyrate was added to study the influences of butyrate on M1/M2 polarization and mitochondrial function of rat macrophages. The rat macrophages and rat myocardial fibroblasts were co-cultured to explore the effect of butyrate on rat myocardial fibroblasts. In addition, MF rats were fed with butyric acid diet.

Results

Compared with the Sham group, collagen deposition in the MF group was increased, and fibrosis was serious. The abundance of Desulfovibrionaceae and Helicobacteraceae in the MF group was increased compared with the Sham group. Gut epithelial cells were destroyed in the MF group compared with the Sham group. Compared with the Sham group, LPS content in the MF group was increased and butyric acid was decreased. Butyrate inhibited M1 and promoted M2. Furthermore, butyrate may promote mitochondrial function recovery by regulating M1/M2 polarization of macrophages. After adding butyrate, cell proliferation ability was decreased, and aging and apoptosis were increased, which indicated that butyrate inhibited rat myocardial fibroblasts activity. Moreover, butyric acid could protect mitochondria and improve the symptoms of rats with MF.

Conclusions

Butyric acid ameliorated MF by regulating M1/M2 polarization of macrophages and promoting recovery of mitochondrial function.
Ultrasonic-Assisted Dual-Alkali Pretreatment and Enzymatic Hydrolysis of Sugarcane Bagasse Followed by Candida tropicalis Fermentation to Produce Xylitol
Authors: Gai Lili , Ren Er-Fang , Tian Wen , Niu Debao , Sun Weidong , Hang Fangxue , Li Kai
Published: May 2022

In this work, the investigation mainly focused on ultrasonic-assisted dual-alkali pretreatment and enzymatic hydrolysis of sugarcane bagasse followed by Candida tropicalis fermentation to produce xylitol. The results showed that the combination of NaOH and ammonia water had the best effect by comparing the effects of the four single-alkali (NaOH, KOH, ammonia water, Ca(OH)2) and their mixed double-alkali pretreatments on xylose content. Then, the optimal conditions for ultrasonic-assisted pretreatment and enzymatic hydrolysis of sugarcane bagasse were obtained by response surface methodology. When the ratio of NaOH and ammonia water was 2:1, the mixed alkali concentration (v/v) was 17%, the ultrasonic temperature was 45°C, the ultrasonic power was 300 W, and the ultrasonic time was 40 min, the content of xylose reached a maximum of 2.431 g/L. Scanning electron microscopy showed that sugarcane bagasse by ultrasonic-assisted alkali pretreatment aggravated with more folds and furrows. Moreover, the fermentation results showed that the concentration ratio of enzymatic hydrolysate of sugarcane bagasse affected the xylitol yield, and when concentrated three times, the highest yield of xylitol (54.42%) was obtained.
The Application and Value of 3T Magnetic Resonance Imaging in the Display of Pulmonary Nodules
Authors: Feng Hui , Shi Gaofeng , Liu Hui , Xu Qian , Wang Lijia , Zhang Ning
Published: May 2022

Objective

The aim of this study was to evaluate the sensitivity and accuracy of multi-sequence 3T magnetic resonance imaging (MRI) in the detection of different types of pulmonary nodules.

Methods

A total of 68 patients with pulmonary nodules identified using computed tomography (CT) subsequently underwent MRI. Using CT images with a slice thickness of 1 mm as the gold standard, the sensitivity of three MRI sequences in detecting different types of pulmonary nodules was calculated, and the image quality was also evaluated. Nodule types included solid nodules, ground glass nodules (GGN), and part-solid nodules (PSN). Statistical analyses of data were conducted using the software SPSS 21.0. The intra-class correlation coefficient was calculated in order to compare the consistency of nodule size in both MRI and CT.

Results

CT detected 188 pulmonary nodules in 68 patients, including 87 solid nodules and 101 sub-solid nodules, the latter comprising 46 PSNs and 55 GGNs. The average nodule diameter was approximately 7.7 mm. The sensitivity of MRI in detecting nodules ≥ 6 mm in diameter and those of > 8 mm in diameter was 92% and 100%, respectively, and the sequence with the highest detection rate was T2-BLADE. In relation to solid nodules, the sequence with the highest detection rate was T1 Star-VIBE, while the T2-BLADE sequence demonstrated the highest detection rate of sub-solid nodules. The image quality of the T1 Star-VIBE sequence was better than that of both the T2-HASTE and the T2-BLADE sequences. The consistency of CT and MRI sequences for nodule size was high with a consistency coefficient of 0.94–0.98.

Conclusion

The detection rate of MRI for nodules with a diameter of > 8 mm was 100%. The T2-BLADE sequence had the highest detection sensitivity. The sequence with the best image quality was the T1 Star-VIBE.
Molecular Landscape and Prognostic Biomarker Analysis of Advanced Pancreatic Cancer and Predictors of Treatment Efficacy of AG Chemotherapy
Authors: Du Juan , Qiu Xin , Lu Changchang , Zhu Yahui , Kong Weiwei , Xu Mian , Zhang Xin , Tang Min , Chen Jun , Li Qi , Li Aimei , He Jian , Gu Qing , Wang Lei , Qiu Yudong , Liu Baorui
Published: May 2022

Purpose

Although mutational analysis of pancreatic cancer has provided valuable clinical information, it has not significantly changed treatment prospects. The purpose of this study is to further investigate molecular alterations in locally advanced pancreatic cancer and identify predictors of the efficacy of nab-paclitaxel plus gemcitabine (AG) chemotherapy.

Experimental design

Tumor samples from 118 pancreatic cancer patients who received AG chemotherapy as first-line treatment were sequenced and genomic profile was generated. Molecular alterations and the involved signaling pathways were analyzed. Genes with a significant difference in mutation frequency between primary and metastatic tumors were identified, and prognostic-related mutant genes were screened using SPSS version 22.0.

Results

The most common altered genes in the patients were KRAS (94.9%), TP53 (81.4%), CDKN2A (36.4%), and SMAD4 (22.9%). The mutational frequencies of CDKN2B (14.8% vs. 0%, p = 0.001), FAT3 (7.4% vs. 0%, p = 0.041), MTAP (13% vs. 1.6%, p = 0.023), and SMAD4 (31.4% vs. 15.6%, p = 0.049) in metastatic tumors were significantly higher than that in primary tumors. TP35 and KRAS mutations were significantly correlated with objective response rate, while EPHA7, RNF43, and HMGA2 mutations were significantly correlated with disease control rate. Additionally, patients with TGFR2B, FGF23, EPHA7, SMARCA4, CARD11, ADGRA2, CCNE1, and ACVR2A alterations had a worse overall survival. Further, EPHA7, CARD11, NOTCH1, GATA6, ACVR2A, and HMGA2 mutations indicated undesirable progression-free survival.

Conclusions

CDKN2B, FAT3, MTAP, and SMAD4 may be biomarkers that distinguish primary tumors from metastases. EPHA7 mutation may serve as a prognostic biomarker to predict the treatment efficacy of AG chemotherapy in locally advanced pancreatic cancer.
Assessment of Statistical Process Control Based DVH Action Levels for Systematic Multi-Leaf Collimator Errors in Cervical Cancer RapidArc Plans
Authors: Zhang Hanyin , Lu Wenli , Cui Haixia , Li Ying , Yi Xin
Published: May 2022

Background

In the patient-specific quality assurance (QA), DVH is a critical clinically relevant parameter that is finally used to determine the safety and effectiveness of radiotherapy. However, a consensus on DVH-based action levels has not been reached yet. The aim of this study is to explore reasonable DVH-based action levels and optimal DVH metrics in detecting systematic MLC errors for cervical cancer RapidArc plans.

Methods

In this study, a total of 148 cervical cancer RapidArc plans were selected and measured with COMPASS 3D dosimetry system. Firstly, the patient-specific QA results of 110 RapidArc plans were retrospectively reviewed. Then, DVH-based action limits (AL) and tolerance limits (TL) were obtained by statistical process control. Secondly, systematic MLC errors were introduced in 20 RapidArc plans, generating 380 modified plans. Then, the dose difference (%DE) in DVH metrics between modified plans and original plans was extracted from measurement results. After that, the linear regression model was used to investigate the detection limits of DVH-based action levels between %DE and systematic MLC errors. Finally, a total of 180 test plans (including 162 error-introduced plans and 18 original plans) were prepared for validation. The error detection rate of DVH-based action levels was compared in different DVH metrics of 180 test plans.

Results

A linear correlation was found between systematic MLC errors and %DE in all DVH metrics. Based on linear regression model, the systematic MLC errors between -0.94 mm and 0.88 mm could be caught by the TL of PTV95 ([-1.54%, 1.51%]), and the systematic MLC errors between -1.00 mm and 0.80 mm could also be caught by the TL of PTVmean ([-2.06%, 0.38%]). In the validation, for original plans, PTV95 showed the minimum error detection rate of 5.56%. For error-introduced plans with systematic MLC errors more than 1mm, PTVmean showed the maximum error detection rate of 88.89%, and then was followed by PTV95 (86.67%). All the TL of DVH metrics showed a poor error detection rate in identifying error-induced plans with systematic MLC errors less than 1mm.

Conclusion

In 3D quality assurance of cervical cancer RapidArc plans, process-based tolerance limits showed greater advantages in distinguishing plans introduced with systematic MLC errors more than 1mm, and reasonable DVH-based action levels can be acquired through statistical process control. During DVH-based verification, main focus should be on the DVH metrics of target volume. OARs in low-dose regions were found to have a relatively higher dose sensitivity to smaller systematic MLC errors, but may be accompanied with higher false error detection rate.
Role of GPER1 in the Mechanism of EGFR-TKIs Resistance in Lung Adenocarcinoma
Authors: Li Zhenhua , Pan Yaqiang , Liu Qinghua , Wang Jian , Liu Chang , Qu Laihao , Li Dingbiao
Published: May 2022

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have a good clinical efficacy in lung adenocarcinoma harboring activating-mutation EGFR. Such EGFR mutations are more frequently observed in women and non-smokers. EGFR mutations are frequently reported to correlate with estrogen receptor (ER) α and/or β-expressions in lung adenocarcinoma. However, the role of GPER1, a novel G-protein-coupled estrogen receptor, in the estrogen signaling pathway and the association between its expression and EGFR mutation in lung adenocarcinoma are less well understood. Here, we aimed to examine ERα, Erβ, and GPER1 expressions, and to analyze their roles in the mechanism of EGFR-TKIs resistance in lung adenocarcinoma. We report an enhanced cytoplasmic expression of GPER1 in tissue samples. The nuclear GPER1 positively correlated with ER expression while the nuclear and also cytoplasmic expressing GPER1 negatively correlated with ER expression. Further, TKI resistance results in higher cytoplasmic GPER1 expression and decreased ER and nuclear GPER1 expression with evidence for GPER1 translocation to cell surface during the resistance. GPER1 itself is capable of regulating ER expression with concomitant regulation of MAPK signaling, and co-inhibition of GPER1 and ERs attenuates ERK1/2 and Akt phosphorylation. The results were also verified in vivo in mice where GPER1 silencing slowed tumor progression which was further potentiated by gefitinib.
Anlotinib Downregulates RGC32 Which Provoked by Bevacizumab
Authors: Liu Zhujun , Qin Tingting , Yuan Xiaohan , Yang Jie , Shi Wei , Zhang Xiaoling , Jia Yanan , Liu Shaochuan , Wang Jing , Li Kai
Published: May 2022

Background

Bevacizumab is the representative drug in antiangiogenic therapy for lung cancer. However, it induced resistance in some neoplasm. Anlotinib, a novel multi-target tyrosine kinase inhibitor which has an inhibitory action on both angiogenesis and malignancy, is possible to reverse the resistance.

Methods

Transwell migration and invasion experiments of bevacizumab with or without anlotinib were conducted to verify the activated/inhibited ability of lung adenocarcinoma cells. We sequenced A549 cells with enhanced migration and invasion abilities after bevacizumab treatment, screened out the differentially expressed gene and further confirmed by western blot and q-PCR assays. We also investigated immunohistochemical staining of tumor tissue in mice and human lung adenocarcinoma.

Results

Bevacizumab facilitated migration and invasion of lung adenocarcinoma cells. Differentially expressed gene RGC32 was screened out. Bevacizumab upregulated the expression of RGC32, N-cadherin, and MMP2 through ERK-MAPK and PI3K-AKT pathways. Anlotinib downregulated their expression and reversed the effect of bevacizumab on A549 cells. In vivo experiments confirmed that higher-dose bevacizumab facilitated metastasis in tumor-bearing nude mice and upregulated the expression of RGC32, N-cadherin, and MMP2, whereas anlotinib abrogated its effect. Expression of both RGC32 and N-cadherin positively correlated with lymph node metastasis and stage in lung adenocarcinoma was found. Survival analysis revealed that higher expressions of RGC32 and N-cadherin were associated with poor progression-free survival and overall survival.

Conclusions

Bevacizumab may promote invasion and metastasis of lung adenocarcinoma cells by upregulating RGC32 through ERK-MAPK and PI3K-AKT pathways to promote epithelial–mesenchymal transition, whereas anlotinib reverses the effect. RGC32 and N-cadherin are independent prognostic factors in lung adenocarcinoma.
Long Noncoding RNA HAGLROS Promotes the Malignant Progression of Bladder Cancer by Regulating the miR-330-5p/SPRR1B Axis
Authors: Xiao Shiwei , Zuo Yigang , Li Yanan , Huang Yinglong , Fu Shi , Yuan Dongbo , Qiao Xuhua , Wang Haifeng , Wang Jiansong
Published: May 2022

Bladder cancer (BC) is the most common genitourinary malignancy worldwide, and its aetiology and pathogenesis remain unclear. Accumulating evidence has shown that HAGLROS is closely related to the occurrence and progression of various cancers. However, the biological functions and underlying mechanisms of HAGLROS in BC remain unknown. In the present study, the expression of HAGLROS in BC was determined by public dataset analysis, transcriptome sequencing analysis, qRT–PCR and ISH assays. Gain- or loss-of-function assays were performed to study the biological roles of HAGLROS in BC cells and nude mouse xenograft model. Bioinformatic analysis, qRT–PCR, western blot, immunohistochemistry, FISH assays, subcellular fractionation assays and luciferase reporter assays were performed to explore the underlying molecular mechanisms of HAGLROS in BC. Here, we found that HAGLROS expression is significantly upregulated in BC tissues and cells, and elevated HAGLROS expression was related to higher pathologic grade and advanced clinical stage, which is significant for BC diagnosis. HAGLROS can enhance the growth and metastasis of BC in vitro and in vivo. Furthermore, miR-330-5p downregulation reversed the BC cells proliferation, migration and invasion inhibited by silencing HAGLROS. SPRR1B silencing restored the malignant phenotypes of BC cells promoted by miR-330--5p inhibitor. Mechanistically, we found that HAGLROS functions as a microRNA sponge to positively regulate SPRR1B expression by sponging miR-330-5p. Together, these results demonstrate that HAGLROS plays an oncogenic role and may serve as a potential biomarker for the diagnosis and treatment of BC.
Evaluation of a CD13 and Integrin αvβ3 Dual-Receptor Targeted Tracer 68Ga-NGR-RGD for Ovarian Tumor Imaging: Comparison With 18F-FDG
Authors: Long Yu , Shao Fuqiang , Ji Hao , Song Xiangming , Lv Xiaoying , Xia Xiaotian , Liu Qingyao , Zhang Yongxue , Zeng Dexing , Lan Xiaoli , Gai Yongkang
Published: May 2022

Ovarian cancer has the highest mortality rate of gynecologic malignancy. 18F-FDG positron emission tomography (PET) adds an important superiority over traditional anatomic imaging modalities in oncological imaging but has drawbacks including false negative results at the early stage of ovarian cancer, and false positives when inflammatory comorbidities are present. Aminopeptidase N (APN, also known as CD13) and integrin αvβ3 are two important targets overexpressed on tumor neo-vessels and frequently on ovarian cancerous cells. In this study, we used subcutaneous and metastatic models of ovarian cancer and muscular inflammation models to identify 68Ga-NGR-RGD, a heterodimeric tracer consisting of NGR and RGD peptides targeting CD13 and integrin αvβ3, respectively, and compared it with 18F-FDG. We found that 68Ga-NGR-RGD showed greater contrast in SKOV3 and ES-2 tumors than 18F-FDG. Low accumulation of 68Ga-NGR-RGD but avid uptake of 18F-FDG were observed in inflammatory muscle. In abdominal metastasis models, PET imaging with 68Ga-NGR-RGD allowed for rapid and clear delineation of both peritoneal and liver metastases (3-6 mm), whereas, 18F-FDG could not distinguish the metastasis lesions due to the relatively low metabolic activity in tumors and the interference of intestinal physiological 18F-FDG uptake. Due to the high tumor-targeting efficacy, low inflammatory uptake, and higher tumor-to-background ratios compared to that of 18F-FDG, 68Ga-NGR-RGD presents a promising imaging agent for diagnosis, staging, and follow-up of ovarian tumors.
Identification of Novel Immune Ferropotosis-Related Genes Associated With Clinical and Prognostic Features in Gastric Cancer
Authors: Xiao Chen , Dong Tao , Yang Linhui , Jin Liangzi , Lin Weiguo , Zhang Faqin , Han Yuanyuan , Huang Zhijian
Published: May 2022

Background

Gastric cancer (GC) is the fifth commonest cancer and the third commonest reason of death causing by cancer worldwide. Currently, tumor immunology and ferropotosis develop rapidly that has made gastric cancer be treated in new directions. So, finding the potential targets and prognostic biomarkers for immunotherapy combined with ferropotosis is urgent.

Methods

By mining TCGA, immune-related genes, ferropotosis-related genes and immune-ferropotosis-related differentially expressed genes (IFR-DEGs) were identified. The independent prognostic value of IFR-DEGs was determined by differential expression analysis, prognostic analysis, and univariate and lasso regression analysis. Then, based on the prognostic risk model, the correlation between IFR-DEGs and immune scores, immune checkpoints were evaluated. Besides, we predicted the response of high and low risk groups to drugs.

Results

A 15-gene prognostic feature was constructed. The high-risk group had a poorer prognosis than the low-risk group. High-risk group had higher level of Treg immune cell infiltration compared with that in the low-risk group, and the tumor purity, immune checkpoint PD-1 and CTLA4, and immunity in the high-risk group were higher than those in the low-risk group. These results indicate that immune ferropotosis-related genes migh be potential predictors of STAD’s response to ICI immunotherapy biomarkers. In addition, the response of small molecule drugs such as Nilotini, Sunitinib, Imatinib, etc. for high and low risk groups was predicted.

Conclusion

IFRSig can be regarded as an independent prognostic feature and may estimate OS and clinical treatment response in patients with STAD. IFRSig also has important correlation with immune microenvironment. A new understanding of the immune-ferropotosis-related genes during the occurrence and development of STAD is provided in this study.
Effect of Training Healthcare Providers in Helping Babies Breathe Program on Neonatal Mortality Rates
Authors: Mayer Maria M. , Xhinti Nomvuyo , Mashao Lolly , Mlisana Zolile , Bobotyana Luzuko , Lowman Casey , Patterson Janna , Perlman Jeffrey M. , Velaphi Sithembiso
Published: May 2022

Background

Training in the Helping Babies Breathe (HBB) Program has been associated with a reduction in early neonatal mortality rate (ENMR), the neonatal mortality rate (NMR), and fresh stillbirth rate (FSBR) in low- and middle-income countries (LMICs). This program was implemented in five different healthcare facilities in the Oliver Reginald Tambo (ORT) District, South Africa from September 2015 to December 2020.

Objective

To determine and compare the FSBR, ENMR, and NMR between 2015 before initiation of the program (baseline) and subsequent years up to 2020 following the implementation of facility-based training of HBB in five hospitals in ORT District.

Methods

Records of perinatal statistics from January 2015 to December 2020 were reviewed to calculate FSBR, ENMR, and NMR. Data were collected from the five healthcare facilities which included two district hospitals (Hospital A&B), two regional hospitals (Hospital C&D), and one tertiary hospital (Hospital E). Comparisons were made between pre- (2015) and post- (2016–2020) HBB implementation periods. Differences in changes over time were also assessed using linear regression analysis.

Results

There were 19,275 births in 2015, increasing to 22,192 in 2020 with the majority (55.3%) of births occurring in regional hospitals. There were significant reductions in ENMR (OR−0.78, 95% CI 0.70–0.87) and NMR (OR−0.81, 95% CI 0.73–0.90), but not in FSBR, in the five hospitals combined when comparing the two time periods. Significant reduction was also noted in trends over time in ENMR (r2 = 0.45, p = 0.001) and NMR (r2 = 0.23, p = 0.026), but not in FSBR (r2 = 0.0, p = 0.984) with all hospitals combined. In looking at individual hospitals, Hospital A (r2 = 0.61, p < 0.001) and Hospital E (r2 = 0.19, p = 0.048) showed a significant reduction in ENMR over time, but there were no significant changes in all mortality rates for Hospitals B, C, and D, and for the district or regional hospitals combined.

Conclusion

There was an overall reduction of 22% and 19% in ENMR and NMR, respectively, from pre- to post-HBB implementation periods, although there were variations from year to year over the 5-year period and, across hospitals. These differences suggest that there were other factors that affected the perinatal/neonatal outcomes in the hospital sites in addition to the implementation of training in HBB.