bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum Tumor Markers Combined With Clinicopathological Characteristics for Predicting MMR and KRAS Status in 2279 Chinese Colorectal Cancer Patients: A Retrospective Analysis
Authors: Zhao Ning , Cao Yinghao , Yang Jia , Li Hang , Wu Ke , Wang Jiliang , Peng Tao , Cai Kailin
Published: June 2021

Although serum tumor markers (STMs), clinicopathological characteristics and the status of KRAS and MMR play an important role in optimizing the treatment and prognosis of colorectal cancer, their interrelationships remain largely unknown. A retrospective analysis of 2279 patients who tested for KRAS and MMR status, and STM measurements prior to treatment over the past four years was conducted. Of the 784 patients tested for KRAS and 2279 patients tested for MMR status, KRAS mutations and dMMR were identified in 276 patients (35.20%) and 177 patients (7.77%), respectively. Logistic regression analysis demonstrated that right colon, well and moderate differentiation and negative CA19-9 were independent predictors for KRAS mutations. The ROC curve yielded an AUC of 0.609 through the combination of these three factors. Age < 65 was an independent predictive factor for dMMR, along with tumor size > 4.6 cm, right colon, poor differentiation, harvested lymph nodes ≥ 22, no lymph node metastasis, no perineural invasion, negative CEA and positive CA72-4. When the nine criteria were used together, the AUC was 0.849. In summary, both STMs and clinicopathological characteristics were found to be significantly associated with the status of KRAS and MMR. The combination of these two factors possessed a strong predictive power for KRAS mutations and dMMR among CRC patients.
Does kV Image Guidance for Bone Metastases Improve Pain Control?
Authors: Tunceroglu Ahmet S. , Gui Bin , Lu Shou-En , Sison Julian , Parikh Rahul , Goyal Sharad , Haffty Bruce G. , Kim Sung , Jabbour Salma K.
Published: June 2021

Purpose/Objectives

Despite its widespread availability, the use of kilovoltage (kV) image guidance is often related to factors such as perceived adequacy of clinical patient setup and individual practice patterns. We sought to determine whether kV image guidance in the treatment of painful bone metastases would improve therapeutic efficacy.

Materials/Methods

Under an Institutional Review Board approved protocol, hospital records of 164 patients having received radiation therapy to 257 individual painful osseous metastases were retrospectively reviewed. Marginal logistic regression analyses using the generalized estimating equation (GEE) approach were used to investigate potential associations between pain reduction and several patient, disease, and treatment related variables. Correlation of kV image guidance with pain reduction was analyzed by univariate and multivariate GEE logistic regression analysis.

Results

Median time to pain reduction was 3 days (range 0~109 days) from the start of radiation therapy. Pain reduction ≥ 50% was noted in 196 (77%) metastatic lesions with 136 (53%) demonstrating complete pain relief. Patients with metastatic lesions from non-small cell lung cancer experienced less pain relief (p = 0.007). Disease extension outside of bone was a negative predictor for pain reduction (p = 0.02). On univariate and multivariate logistic regression, kV image guidance demonstrated a statistically significant correlation with improved pain control in cases involving treatment of the lower extremities (p = 0.03) and those with fewer treatment fractions (p = 0.01), particularly in the setting of extra-osseous disease extension (p = 0.003).

Conclusions

Kilovoltage image guidance in the treatment of painful bone metastases may offer greater pain control through improved patient setup, particularly for patients with tumors of the lower extremities, extraosseous disease extension, and fewer treatment fractions.
PD-1 Inhibitors Could Improve the Efficacy of Chemotherapy as First-Line Treatment in Biliary Tract Cancers: A Propensity Score Matching Based Analysis
Authors: Gou Miaomiao , Zhang Yong , Liu Tiee , Si Haiyan , Wang Zhikuan , Yan Huan , Qian Niansong , Dai Guanghai
Published: June 2021

Background

There are limited treatment options for advanced biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma, extrahepatic bile duct cancer, gallbladder cancer. We compared the efficacy and safety of PD-1 inhibitors plus chemotherapy and chemotherapy alone as first-line treatment in patients with advanced BTC.

Methods

We retrospectively reviewed patients with BTC treated at the oncology department of the Chinese PLA general hospital receiving PD-1 inhibitor with chemotherapy (anti-PD-1+C group) or chemotherapy alone (C group). Propensity Score Matching (PSM) (1:1) was performed to balance potential baseline confounding factors. Progression-free survival (PFS) was analyzed using Kaplan–Meier survival curves with log-rank tests. Objective response rate (ORR), disease control rate (DCR), and safety were also analyzed.

Results

This study included 75 patients who received PD-1 inhibitors (including Pembrolizumab, Nivolumab, Sintilimab, Toripalimab) plus chemotherapy and 59 patients who received chemotherapy alone. After matching, there were no significant differences between the two groups for baseline characteristics. Within the matched cohort, the median PFS was 5.8m in the anti-PD-1+C group, which was significantly longer than the C group, at 3.2m (HR: 0.47, 95% CI 0.29 to 0.76, P = 0.004). The ORR was 21.7% and DCR was 80.4% in the anti-PD-1+C group, while the ORR was 15.2% and DCR was 69.6% in the C group. No significant differences were found in the ORR and DCR between the two groups (P=0.423, P=0.231). Grade 3 or 4 treatment was related to adverse events (AEs) that occurred in the anti-PD-1+C group, namely hypothyroidism (n=3, 6.5%), rash (n=2, 4.2%), and hepatitis (n=1, 2.2%). There was no AE-related death. The grade 3-4 leukopenia rate was similar in the two groups (4.3% vs. 6.5%).

Conclusions

Anti-PD-1 therapy plus chemotherapy prolonged the PFS compared with chemotherapy alone in advanced BTC with controllable AEs. Further clinical trials are needed to confirm this result.
De Novo Mutation in Non-Tyrosine Kinase Domain of ROS1 as a Potential Predictor of Immune Checkpoint Inhibitors in Melanoma
Authors: Ma Si-Cong , Zhu Hong-Bo , Wang Jian , Zhang Yan-Pei , Guo Xue-Jun , Long Li-Li , Guo Ze-Qin , Wu De-Hua , Dong Zhong-Yi , Bai Xue
Published: June 2021

Purpose

Despite the success of targeted therapy in c-ros oncogene 1 (ROS1)-rearranged cancers, especially non-small cell lung cancer (NSCLC), the clinical significance of ROS1 de novo mutation has not yet been understood. We sought to elucidate the predictive effect of ROS1 mutation for immune checkpoint inhibitor (ICI) therapy in melanoma.

Methods

The Cancer Genome Atlas [TCGA (n = 10967)] and Memorial Sloan Kettering Cancer Center [MSK (n = 10,945)] datasets, as well as two clinical cohorts of melanoma received ICI [CA209-038 (n = 73) and MEL-IPI (n = 110)], were included to explore the prevalence, prognostic effect, and immunotherapeutic predictive effect of ROS1 mutation in melanoma. Overall survival (OS) was defined as the primary outcome.

Results

Overall, melanoma accounted for the highest proportion of ROS1 mutation (~20%) which made up the majority (~95%) of the ROS1-alterated cases. Remarkably, ROS1 mutation yielded longer OS from ICI than the wild-type counterpart in the MSK melanoma population [hazard ratio (HR) 0.47, 95% confidence interval (CI) 0.30–0.74], and two external melanoma cohorts (CA209-038: HR 0.42, 95% CI 0.20–0.89; MEL-IPI: HR 0.55, 95% CI 0.34–0.91), without affecting the prognosis of patients. Elevated tumor mutational burden and enrichment of DNA damage repair was observed in ROS1 mutated patients, providing an explanation for the favorable responses to ICI therapy. Precisely, ROS1 mutation in non-protein tyrosine kinase (PTK) domain but not PTK mutation was responsible for the immunotherapy-specific responses of the ROS1 mutated patients in melanoma.

Conclusions

Collectively, ROS1 mutation, specifically the non-PTK mutation, is a potential predictor of ICI therapy in melanoma, which is distinct from the well-established role of ROS1 rearrangement for targeted therapy in NSCLC.
Development and Validation of a Nomogram for the Prediction of Inguinal Lymph Node Metastasis Extranodal Extension in Penile Cancer
Authors: Wu Chong , Li Zaishang , Guo Shengjie , Zhou Fangjian , Han Hui
Published: June 2021

Purpose

To determine whether a clinicopathologic and laboratory-based nomogram is capable of predicting the risk of lymph node extranodal extension (ENE) in patients with penile cancer.

Materials and Methods

From June 2006 to January 2021, 234 patients who underwent bilateral inguinal lymph node dissection (ILND) surgery were included in the analysis. A Lasso regression model was utilized to select the most useful predictive features from among 46 laboratory variables. Then, a logistic regression analysis was used to develop the prediction model. Calibration curves, concordance index (C-index) and Areas under the receiver-operating characteristic curves (AUCs) were performed to evaluate the performance of the nomogram. We also investigated model fit using changes in Akaike Information Criteria (AICs). Decision curve analyses (DCAs) were applied to assess the clinical usefulness of this nomograms. Its internal validation was confirmed.

Results

Among the 234 patients, 53 were confirmed to have ENE. The platelet-lymphocyte ratio (PLR) and Squamous cell carcinoma antigen (SCC-Ag) were significantly associated with ENE (P<0.05). The individualized prediction nomogram, including the PLR, SCC-Ag, lymphovascular invasion (LVI), and pathologic tumor stage(pT-stage), showed good discrimination, with a C-index of 0.817 (95% CI, 0.745 to 0.890) and good calibration. Clinical-laboratory nomogram (AIC, 180.034) become the best-fitting model. DCA findings revealed that the clinical-laboratory nomogram was more clinically useful than the pT-stage or tumor grade.

Conclusions

This study presents a clinicopathologic and laboratory-based nomogram that incorporates PLR, SCC-Ag, lymphovascular invasion (LVI), and pT-stage, which can be conveniently utilized to facilitate the individualized prediction of lymph node metastasis ENE in patients with penile cancer.
Hypoxia-Related Gene FUT11 Promotes Pancreatic Cancer Progression by Maintaining the Stability of PDK1
Authors: Cao Wenpeng , Zeng Zhirui , Pan Runsang , Wu Hao , Zhang Xiangyan , Chen Hui , Nie Yingjie , Yu Zijiang , Lei Shan
Published: June 2021

Background

Hypoxia is associated with the development of pancreatic cancer (PC). However, genes associated with hypoxia response and their regulatory mechanism in PC cells were unclear. The current study aims to investigate the role of the hypoxia associated gene fucosyltransferase 11 (FUT11) in the progression of PC.

Methods

In the preliminary study, bioinformatics analysis predicted FUT11 as a key hypoxia associated gene in PC. The expression of FUT11 in PC was evaluated using quantitative real-time PCR (qRT-PCR), Western blot and immunohistochemistry. The effects of FUT11 on PC cells proliferation and migration under normoxia and hypoxia were evaluated using Cell Counting Kit 8, 5-ethynyl-2’-deoxyuridine (EDU) assay, colony formation assay and transwell assay. The effects of FUT11 in vivo was examined in mouse tumor models of liver metastasis and subcutaneous xenograft. Furthermore, Western blot, luciferase assay and immunoprecipitation were performed to explore the regulatory relationship among FUT11, hypoxia-inducible factor 1α (HIF1α) and pyruvate dehydrogenase kinase 1 (PDK1) in PC.

Results

FUT11 was markedly increased of PC cells with hypoxia, upregulated in the PC clinical tissues, and predicted a poor outcome of PC patients. Inhibition of FUT11 reduced PC cell growth and migratory ability of PC cells under normoxia and hypoxia conditions in vitro, and growth and tumor cell metastasis in vivo. FUT11 bound to PDK1 and regulated the expression PDK1 under normoxia and hypoxia. FUT11 interacted with PDK1 and decreased the ubiquitination of PDK1, lead to the activation of AKT/mTOR signaling pathway. FUT11 knockdown significantly increased the degradation of PDK1 under hypoxia, while treatment with MG132 can relieve the degradation of PDK1 induced by FUT11 knockdown. Overexpression of PDK1 in PC cells under hypoxia conditions reversed the suppressive impacts of FUT11 knockdown on PC cell growth and migration. In addition, HIF1α bound to the promoter of FUT11 and increased its expression, as well as co-expressed with FUT11 in PC tissues. Furthermore, overexpression of FUT11 partially rescued the suppressive effects of HIF1α knockdown on PC cell growth and migration in hypoxia condition.

Conclusion

Our data implicate that hypoxia-induced FUT11 contributes to proliferation and metastasis of PC by maintaining the stability of PDK1, thus mediating activation of AKT/mTOR signaling pathway, and suggest that FUT11 could be a novel and effective target for the treatment of pancreatic cancer.
Development and Longitudinal Analysis of Plan-Based Streamlined Quality Assurance on Multiple Positioning Guidance Systems With Single Phantom Setup
Authors: Zhou Shun , Li Junyu , Du Yi , Yu Songmao , Wang Meijiao , Wu Hao , Yue Haizhen
Published: June 2021

Purpose

This study was to propose and validate an efficient and streamlined quality assurance (QA) method with a single phantom setup to check performances of patient positioning guidance systems including six-degree-of-freedom (6DoF) couch, X-ray modalities (kV–kV, MV–MV and CBCT), optical surface imaging system (AlignRT), lasers and optical distance indicator (ODI).

Methods and Materials

The QA method was based on a pseudo-patient treatment plan using the AlignRT cube phantom. The cube was first randomly set up on the couch, and the initial position offsets were acquired by AlignRT and CBCT. The cube was restored to its reference position by 6DoF couch shift, during which the couch motion accuracy and tracking performances of AlignRT and CBCT were derived. After that, the residual offsets were acquired by kV–kV, MV–MV and AlignRT to derive the isocenter discrepancies. Finally, the laser alignment and ODI values were visually inspected. The QA procedure had been internally approved as a standard weekly QA test, and the results over 50 weeks were longitudinally analyzed for clinical validation.

Results

The 6DoF couch motion errors as well as the tracking errors of AlignRT were sub-millimeter and sub-degree, and no deviation over 1 mm or 1 deg was identified. The ROI mode of isocenter (ISO) in AlignRT exhibited more consistent results than the centroid (CEN). While the isocenter discrepancy between CBCT and kV–kV was negligible, the maximal discrepancies between CBCT and MV–MV were 0.4 mm in LNG and 0.3 deg in PITCH. The isocenter discrepancies between CBCT and AlignRT were <0.5 mm in translation and <0.3 deg in rotation. For AlignRT, the isocenter discrepancies between the DICOM and SGRT references were about 0.6 mm in VRT, 0.5 mm in LNG and 0.2 deg in PITCH. As the therapists became familiar with the workflow, the average time to complete the whole procedure was around 23 min.

Conclusions

The streamlined QA exhibits desirable practicality as an efficient multipurpose performance check on positioning guidance systems. The stability, tracking performance and isocenter congruence of the positioning guidance systems have been fully validated for all clinical image guidance RT application, even SRS/SBRT, which requires the strictest tolerance.
An Investigation of Descending Pain Modulation in Women With Provoked Vestibulodynia: Alterations of Brain Connectivity
Authors: Yessick Lindsey R. , Pukall Caroline F. , Ioachim Gabriela , Chamberlain Susan M. , Stroman Patrick W.
Published: June 2021

Provoked Vestibulodynia (PVD) is the most common vulvodynia subtype (idiopathic chronic vulvar pain). Functional magnetic resonance imaging (fMRI) studies indicate that women with PVD exhibit altered function in a number of pain modulatory regions in response to noxious stimulation, such as in the secondary somatosensory cortex, insula, dorsal midcingulate, posterior cingulate, and thalamus. However, previous neuroimaging studies of PVD have not examined periods of time before and after noxious stimulation or investigated functional connectivity among pain modulatory regions. Fourteen women with PVD and 14 matched Control participants underwent five fMRI runs with no painful stimuli interleaved randomly with five runs with calibrated, moderately painful heat stimuli applied to the thenar eminence. As recent findings indicate that pain processing begins before and continues after painful stimulation, 2-min periods were included in each run before and after the stimulus. Functional brain connectivity was assessed during both trials of Pain and No Pain stimulation for each group using structural equation modeling (SEM). Analyses of variance (ANOVAs) on connectivity values demonstrated significant main effects of study condition, and group, for connectivity among pain modulatory regions. Most of the differences between the Pain and No Pain conditions found only in the PVD group take place before (i.e., thalamus to INS, ACC to S1, thalamus to S1, and thalamus to S2) and after pain stimulation (i.e., INS to amygdala, PPC to S1, and thalamus to S2). Such differences were not observed in the Control group. These findings further support previous results indicating that women with PVD have altered pain processing compared to pain-free women.
Clinical Study of Paliperidone Palmitate Long-Acting Injection Combined With Electroacupuncture in the Treatment of Methamphetamine Addicts
Authors: Chen Yu , Li Mingchao , Ji Qiuming , Su Zou , Yang Ziyu , Xu Yin , Chen Qian , Liao Dan , Zeng Jihua , Yang Yuhong
Published: June 2021

Objective: To explore the clinical efficacy of paliperidone palmitate long-acting injection combined with electroacupuncture in the treatment of methamphetamine addicts.

Methods: This study focused on methamphetamine addicts who were admitted to our hospital from January 2020 to December 2020 as the main research object, with a total of 89 cases. The patients were divided into a control group of 45 cases and a study group of 44 cases according to the treatment method. The control group was treated with electroacupuncture, and the study group was treated with paliperidone palmitate long-acting injection on the basis of electroacupuncture in the control group. After 6 months of continuous treatment, the treatment effect of methamphetamine withdrawal symptom score before and after treatment was used; Hamilton Anxiety Scale score and Hamilton Depression Scale were used to compare the anxiety and depression situation of the two groups; the brain wave α and θ wave situation of the two groups were compared.

Result: The results showed that there was no significant difference in the scores of Ma withdrawal symptoms, Hamilton Anxiety and Hamilton Depression between the two groups before treatment (p < 0.05); after 3 and 6 months of treatment, the scores of Ma withdrawal symptoms, Hamilton Anxiety and Hamilton Depression in the study group were significantly lower than those in the control group and the difference was statistically significant (p < 0.05); 6 months after the completion of the treatment, the α wave amplitude and Fourier transformed α brain wave (FFTα) in the study group were significantly higher than those in the control group, and the difference was statistically significant (p < 0.05).

Conclusion: Paliperidone palmitate long-acting injection combined with electroacupuncture is better than electroacupuncture alone in the treatment of methamphetamine addicts, and can significantly improve anxiety, depression and brain waves, thereby preventing addicts from relapse.
Effects of Glucose Oxidase Supplementation on the Growth Performance, Antioxidative and Inflammatory Status, Gut Function, and Microbiota Composition of Broilers Fed Moldy Corn
Authors: Qu Wenhui , Liu Jiaguo
Published: June 2021

Background

Glucose oxidase is widely used as a livestock feed additive owing to its beneficial effects on growth performance and antioxidant activity. However, little is known about the effects of the enzyme on intestinal health.

Methods

To investigate the effects of glucose oxidase supplementation on the growth performance, intestinal function, and microbiota composition of broilers fed moldy corn, newly hatched Arbor Acres broilers were each randomly assigned to one of four groups, which were fed a basal diet (CON), a contaminated diet (10% moldy corn) (MC), a basal diet supplemented with 0.01% glucose oxidase (GOD), or a contaminated diet supplemented with 0.01% glucose oxidase (MCG).

Results

We found that the average weight gain (ADG) of the MC group was significantly lower than those of the CON and GOD groups, and there were no significant differences in ADG between the MCG group and the CON and GOD groups. Intestinal morphology results revealed irregularly arranged villi and microvilli in the ilea from the MC group, whereas those from the other three groups were aligned regularly. Tight-junction protein analysis showed that both ZO-1 expression and claudin-4 expression in the MC group were significantly lower than those in the other groups. Inflammation cytokines analysis showed lower serum concentration of interleukin-10, as well as its mRNA expression in the ileum of the MC group, when compared with those of the other groups. Additionally, we observed lower glutathione peroxidase and total superoxide dismutase activity and higher malonaldehyde concentration in the MC group than those in the MCG group. The α and β diversity of microbiota profiling indicated that the cecal microbiota in the MC group differed from those in the other three groups.

Conclusion

The results indicated that glucose oxidase supplementation was able to prevent the adverse effects from mycotoxin exposure on growth performance, antioxidant activity, inflammatory response, intestinal function, and microbiota composition in broilers. We suggested that glucose oxidase supplementation can be used in broilers to mitigate the adverse effects of moldy feed, and its benefits are due to its effect on intestinal microbiota composition.
Seed Shattering: A Trait of Evolutionary Importance in Plants
Authors: Maity Aniruddha , Lamichaney Amrit , Joshi Dinesh Chandra , Bajwa Ali , Subramanian Nithya , Walsh Michael , Bagavathiannan Muthukumar
Published: June 2021

Seed shattering refers to the natural shedding of seeds when they ripe, a phenomenon typically observed in wild and weedy plant species. The timing and extent of this phenomenon varies considerably among plant species. Seed shattering is primarily a genetically controlled trait; however, it is significantly influenced by environmental conditions, management practices and their interactions, especially in agro-ecosystems. This trait is undesirable in domesticated crops where consistent efforts have been made to minimize it through conventional and molecular breeding approaches. However, this evolutionary trait serves as an important fitness and survival mechanism for most weeds that utilize it to ensure efficient dispersal of their seeds, paving the way for persistent soil seedbank development and sustained future populations. Weeds have continuously evolved variations in seed shattering as an adaptation under changing management regimes. High seed retention is common in many cropping weeds where weed maturity coincides with crop harvest, facilitating seed dispersal through harvesting operations, though some weeds have notoriously high seed shattering before crop harvest. However, high seed retention in some of the most problematic agricultural weed species such as annual ryegrass (Lolium rigidum), wild radish (Raphanus raphanistrum), and weedy amaranths (Amaranthus spp.) provides an opportunity to implement innovative weed management approaches such as harvest weed seed control, which aims at capturing and destroying weed seeds retained at crop harvest. The integration of such management options with other practices is important to avoid the rapid evolution of high seed shattering in target weed species. Advances in genetics and molecular biology have shown promise for reducing seed shattering in important crops, which could be exploited for manipulating seed shattering in weed species. Future research should focus on developing a better understanding of various seed shattering mechanisms in plants in relation to changing climatic and management regimes.
Effect of LED Spectrum on the Quality and Nitrogen Metabolism of Lettuce Under Recycled Hydroponics
Authors: Li Jie , Wu Tao , Huang Ke , Liu Yubing , Liu Mingyue , Wang Junwei
Published: June 2021

Light quality optimization is an efficient method for improving the growth and quality of lettuce in plant factories. In this study, lettuce seedlings were illuminated under different light-emitting diode (LED) lights, namely, red-blue (RB), red-blue-green (RBG), red-blue-purple (RBP), and red-blue-far-red (RBF) LED lights, to investigate the effect of light quality on growth, quality, and nitrogen metabolism. The combination of 75% red and 25% blue light was set as the basic light source, and 20% of green, purple and far-red light were added to basic light source, respectively. All the treatments were set to 200 μmol m–2 s–1. Results showed that the fresh weight and dry weight of aboveground lettuce under RBG, RBP, and RBF treatments were significantly lower than those under the RB treatment because of the decrease in the effective photon flux density for chlorophyll absorption. The vitamin C content of the lettuce leaves was increased by about 23% with the addition of purple light. For nitrate reduction, the addition of green light significantly increased the nitrite content of the lettuce leaves. It also promoted the reduction from nitrite to ammonium through the activation of the nitrite reductase (NiR) expression and enzyme activity. The nitrate and ammonium content decreased with the addition of purple light because of the inhibited NR and NiR expression and enzyme activity. For nitrogen assimilation, individual (e.g., Asp, Glu, and Leu) and total amino acids were induced to increase by adding green, purple, and far-red light. The addition of light was hypothesized to have inhibited protein biosynthesis, thereby causing the accumulation of amino acids. Correlation analysis showed that the relative expression levels between HY5 and NR/NiR presented a significantly negative correlation. Transcription factor HY5 might mediate the regulation of light quality on nitrogen metabolism by inhibiting NR and NiR expressions. It might also exert a negative effect on nitrate reduction. Further studies via genome editing techniques on the identification of HY5 functions for nitrate assimilation will be valuable. Nevertheless, the results of this work enrich the understanding of the effect of light quality on nitrate metabolism at the level of gene expression and enzyme activity.
Minor Physical Anomalies in Bipolar Disorder—A Meta-Analysis
Authors: Varga Eszter , Hajnal András , Soós Alexandra , Hegyi Péter , Kovács Dóra , Farkas Nelli , Szebényi Júlia , Mikó Alexandra , Tényi Tamás , Herold Róbert
Published: June 2021

Introduction: Minor physical anomalies (MPAs) may reflect basic neurobiological features underlying bipolar disorders (BPD), as they are sensitive physical indicators of morphogenetic failure of the brain. Despite several researches about the presence of MPAs in BPD, the results are still controversial.

Objectives: The aim of the present meta-analysis was to assess the standardized weighted mean effect sizes of MPAs in BPD and to examine if MPAs may be found predominantly in the head and/or facial regions in BPD patients compared to controls (HC).

Methods: Four studies, involving 155 patients with BPD, and 187 HC, were involved in the analysis after searching the literature. For the investigation of MPAs in the peripheral (MPA-P) and in the head and facial regions (MPA-CF), two studies involving 121 BPD patients, and 133 HC passed the inclusion criteria.

Results: The number of the MPAs in the BPD group was significantly higher compared to HC. Another important finding of the present study is that BPD patients' MPA-P scores do not significantly differ from those of the HC. In contrast, BPD patients' MPA-CF scores were found to be significantly higher compared to HC subjects. It is important to note that there was a low number of eligible publications included, which caused higher heterogeneity.

Conclusions: Low quality of evidence suggests that MPAs are more common in patients with BPD than in HC and the higher rate of MPAs is found predominantly in the head and facial regions.
Social Injustice in the Neoliberal Pandemic Era for Homeless Persons With Mental Illness: A Qualitative Inquiry From India
Authors: Bhattacharya Prama , Khemka Gunjan Chandak , Roy Laboni , Roy Sarbani Das
Published: June 2021

The Corona Virus Disease 2019 (COVID-19) pandemic has presented an unprecedented challenge globally. It is much bigger than a bio-medical concern now with the multitudes of socio-economic, socio-political, socio-cultural, and psycho-social impact, which are likely to outlast the pandemic itself by far and long. The pandemic and the resulting challenges across societies highlighted the existing social injustices in a neoliberal world for historically marginalized populations like homeless persons with mental illness (HPMI). The nationwide lockdown in India to resist the spread of the virus posed a unique challenge to this vulnerable population. The present study thus attempts to understand the experience of HPMI during the COVID-19 induced lockdown through the theoretical framework of social justice vis-à-vis injustice. Semi-structured interviews have been conducted on seven HPMI rehabilitated in the community through an NGO situated in Kolkata, India. Seven stakeholders have also been interviewed to understand their experience in providing services to the HPMI during the COVID-19 induced lockdown. Analyses of the narratives have been done using initial coding, focused coding and axial coding through the process of constant comparison of constructivist grounded theory (CGT) methodology. Critical insights from the study bring out experiences of HPMI during COVID-19 as a victim of structural violence, highlighting their exclusion and victimization due to the existing marginalized status, living closer to the edge as a consequence of the lockdown, lack of awareness of the gravity of the pandemic situation. The experiences of the stakeholders, on the other hand, pointed out the role of community members and social workers in partially mitigating the challenges. This study indicates that to mitigate the aftermaths, stakeholders, including community members, need to work together for rebuilding and enhancing the strength and resilience of the marginalized populations like HPMI, who are historically victims of social injustice in the neoliberal pandemic era.
Staff SARS-CoV-2 Seroprevalence and Mental Health as Key Factors in University Response to COVID-19 Pandemic
Authors: Lopes David G. , Henriques Ana Rita , Santos-Dias Margarida , Nunes-da-Silva Catarina , Gonçalves Juliana , de Sousa Rute D. , Abdulghani Saba , Eletério Jair , Braga Sofia Jacinto , Soares Helena , Branco Jaime C. , Canhão Helena , Rodrigues Ana M.
Published: June 2021

Background: In response to rapid global spread of the newly emerged coronavirus disease 2019 (COVID-19), universities transitioned to online learning and telework to decrease risks of inter-person contact. To help administrators respond to the COVID-19 pandemic and better understand its impacts, we surveyed SARS-CoV-2 seroprevalence among NOVA University employees and assessed community mental health.

Methods: Data were collected from voluntary participants at six NOVA University locations, in the Lisbon metropolitan area, from June 15–30, 2020. All subjects provided written informed consent. Of 1,627 recruited participants (mean age 42.0 ± 12.3 years), 1,624 were tested. Prior to blood collection, participants completed a questionnaire that assessed: COVID-19 symptoms during the previous 14 days, chronic non-communicable diseases, chronic medication, anxiety, and depression symptoms. SARS-CoV-2 serology tests were then performed, and results communicated approximately 4 days after blood draw. Participants with positive serology tests were contacted to assess COVID-19 symptoms since February.

Results: Estimated prevalence of SARS-CoV-2 IgG antibodies was 3.1% (n = 50), of which 43.5% reported symptoms in the previous 4 months. The Medical School had the highest seroprevalence (6.2%). Participants reported having at least one chronic disease (63.7%), depression-like symptoms (2.1%), and anxiety symptoms (8.1%). Rates of depression and anxiety symptoms were significantly higher in women, with sleep hours and occasional alcohol consumption negatively associated with depression. Male gender, older age, and sleep hours negatively associated with anxiety symptoms. School of employment and presence of comorbidities positively associated with anxiety.

Conclusion: By measuring seroprevalence of SARS-CoV-2 antibodies among NOVA employees and assessing subjects' mental health, we aim to help administrators at European public universities in urban areas, such as Lisbon, Portugal, better understand the needs of their communities. This study resulted in implementation of a stricter contingency plan in the Medical School, while other schools continued to follow Government mitigation guidelines. These findings may also guide the development of tailored strategies to ensure physical and mental health of the academic community during this pandemic crisis. We conclude that, together with COVID-19 contingency plans, psychological support services and facilities to help people effectively face pandemic-associated challenges and minimise anxiety and depression should be implemented.
A Comparison of the Simulations and Observations for a Nearby Spiral Arm
Authors: Piecka Martin , Paunzen Ernst
Published: June 2021

The analysis is focused on the ability of galactic open clusters to trace the spiral arms, based on the recent data releases from Gaia. For this, a simple 1D description of the motion of spiral arms and clusters is introduced. As next step, results are verified using a widely accepted kinematic model of the motion in spiral galaxies. As expected, both approaches show that open clusters older than about 100 Myr are bad tracers of spiral arms. The younger clusters (ideally < 30 Myr) should be used instead. This agrees with the most recent observational evidence. The latest maps of the diffuse interstellar bands are compared with the spiral structure of the Milky Way and the Antennae Galaxies. The idea of these bands being useful for studying a galactic structure cannot be supported based on the current data.
Thrombolytic Therapy During ex-vivo Normothermic Machine Perfusion of Human Livers Reduces Peribiliary Vascular Plexus Injury
Authors: Haque Omar , Raigani Siavash , Rosales Ivy , Carroll Cailah , Coe Taylor M. , Baptista Sofia , Yeh Heidi , Uygun Korkut , Delmonico Francis L. , Markmann James F.
Published: June 2021

Background: A major limitation in expanding the use of donation after circulatory death (DCD) livers in transplantation is the increased risk of graft failure secondary to ischemic cholangiopathy. Warm ischemia causes thrombosis and injury to the peribiliary vascular plexus (PVP), which is supplied by branches of the hepatic artery, causing higher rates of biliary complications in DCD allografts.

Aims/Objectives: We aimed to recondition discarded DCD livers with tissue plasminogen activator (tPA) while on normothermic machine perfusion (NMP) to improve PVP blood flow and reduce biliary injury.

Methods: Five discarded DCD human livers underwent 12 h of NMP. Plasminogen was circulated in the base perfusate prior to initiation of perfusion and 1 mg/kg of tPA was administered through the hepatic artery at T = 0.5 h. Two livers were split prior to perfusion (S1, S2), with tPA administered in one lobe, while the other served as a control. The remaining three whole livers (W1-W3) were compared to seven DCD control liver perfusions (C1-C7) with similar hepatocellular and biliary viability criteria. D-dimer levels were measured at T = 1 h to verify efficacy of tPA. Lactate, total bile production, bile pH, and difference in biliary injury scores before and after perfusion were compared between tPA and non-tPA groups using unpaired, Mann-Whitney tests.

Results: Average weight-adjusted D-dimer levels were higher in tPA livers in the split and whole-liver model, verifying drug function. There were no differences in perfusion hepatic artery resistance, portal vein resistance, and arterial lactate between tPA livers and non-tPA livers in both the split and whole-liver model. However, when comparing biliary injury between hepatocellular and biliary non-viable whole livers, tPA livers had significantly lower PVP injury scores (0.67 vs. 2.0) and mural stroma (MS) injury scores (1.3 vs. 2.7).

Conclusion: This study demonstrates that administration of tPA into DCD livers during NMP can reduce PVP and MS injury. Further studies are necessary to assess the effect of tPA administration on long term biliary complications.
Advances in drug release investigations: Trends and developments for dissolution test media
Authors: Kakuk Melinda , Farkas Dóra , Antal István , Kállai-Szabó Nikolett
Published: June 2021

Dissolution research started more than a century ago in the field of physical chemistry and went through several significant developments since. Yet, the explicit attention in drug-related dissolution has only started growing in the 1950s, after the researchers realized that drug release from orally administered solid pharmaceutical formulations significantly influences the bioavailability. Researches show that solubility and permeability of the drugs are key factors in the correlation between the in vitro examination and the in vivo determinations (IVIVC). This review aims to summarize the most relevant developments in chronological order, ranging from simple disintegration studies to biorelevant methods. Biorelevant methods can be used to recognize the effects of food on dissolution, as well as to identify solubility limitations and stability issues. The development of a biologically relevant dissolution method for oral dosage forms needs to take the physiological conditions of the gastrointestinal (GI) tract into account that may influence the drug dissolution. This review presents the simplest dissolution media, the composition of biorelevant media simulating gastrointestinal fluids, and the latest updates of the field.
Patient expectations and regulatory needs in the risk-based drug development of cystic fibrosis
Authors: Pallagi Edina , Csóka Ildikó
Published: June 2021

Aims: Cystic Fibrosis (CF) is a rare, chronic, progressive, multi-organ disease. It needs life-long, complex therapy with many difficulties for patients to follow. New therapy development also has difficulties owing to regulatory and economic challenges. Methods: This study evaluates the intervention possibilities of therapy management in CF, taking into consideration the aspects of patient adherence and Quality of Life (QoL), regulatory and economic backgrounds. It presents a Quality by Design (QbD)-based knowledge and Risk Assessment (RA)-based evaluation method. Results: The RA-based evaluation showed that the most highly critical intervention points in the CF therapy-management with greatest positive estimated impact are: increasing of the social support, increasing of the level of patient education and improvement of the potentials of therapy monitoring. The degree of adherence in CF depends mainly on the degree of progression and the complexity of the therapy. New drug combination and new medicine development were found as they have lower critical effect of the patient’s QoL. Conclusion: The risk-based exploration of the therapy interventions can help in finding the factors which have the highest effect on the therapy success and patient adherence. They can be the alternative of a time and cost consuming new medicinal research and development.
Optimized Voltage-Induced Control of Magnetic Domain-Wall Propagation in Hybrid Piezoelectric/Magnetostrictive Devices
Authors: Consolo Giancarlo , Valenti Giovanna
Published: June 2021

A theory of voltage-induced control of magnetic domain walls propagating along the major axis of a magnetostrictive nanostrip, tightly coupled with a ceramic piezoelectric, is developed in the framework of the Landau–Lifshitz–Gilbert equation. It is assumed that the strains undergone by the piezoelectric actuator, subject to an electric field generated by a dc bias voltage applied through a couple of lateral electrodes, are fully transferred to the magnetostrictive layer. Taking into account these piezo-induced strains and considering a magnetostrictive linear elastic material belonging to the cubic crystal class, the magnetoelastic field is analytically determined. Therefore, by using the classical traveling-wave formalism, the explicit expressions of the most important features characterizing the two dynamical regimes of domain-wall propagation have been deduced, and their dependence on the electric field strength has been highlighted. Moreover, some strategies to optimize such a voltage-induced control, based on the choice of the ceramic piezoelectric material and the orientation of dielectric poling and electric field with respect to the reference axes, have been proposed.
Online Model-Based Remaining-Useful-Life Prognostics for Aircraft Cooling Units Using Time-Warping Degradation Clustering
Authors: Mitici Mihaela , de Pater Ingeborg
Published: June 2021

Remaining-useful-life prognostics for aircraft components are central for efficient and robust aircraft maintenance. In this paper, we propose an end-to-end approach to obtain online, model-based remaining-useful-life prognostics by learning from clusters of components with similar degradation trends. Time-series degradation measurements are first clustered using dynamic time-warping. For each cluster, a degradation model and a corresponding failure threshold are proposed. These cluster-specific degradation models, together with a particle filtering algorithm, are further used to obtain online remaining-useful-life prognostics. As a case study, we consider the operational data of several cooling units originating from a fleet of aircraft. The cooling units are clustered based on their degradation trends and remaining-useful-life prognostics are obtained in an online manner. In general, this approach provides support for intelligent aircraft maintenance where the analysis of cluster-specific component degradation models is integrated into the predictive maintenance process.
Are Chilean Pasture Seed End-Users Adopting New Species? Trends and Joinpoint Regression Analysis of the Last 19 Years of Seed Imports
Authors: Moscoso Cristian J. , Ortega-Klose Fernando , Acuña Alejandra
Published: June 2021

Pastures are important for the agricultural sector as forage, recreational and sports systems. The Chilean pasture seed market is highly dependent on introduced genetics; however, the effect of climate change and market conditions can modify pasture options. The objective of this study was to quantify changes of the pasture seeds sown by Chilean end-users, as metric tons (Mt) or proportion of the total (PT), based on 19 years of imported seed. The Mann–Kendall test and joinpoint regression analysis were used to estimate the overall trends and the average annual percent change (AAPC) for the whole period, respectively. The total imported Mt had an increasing trend and AAPC (+5.7%), wherein a large PT corresponded to ryegrasses (Lolium spp.) (0.681), with increasing trends for Mt and PT. Clovers (Trifolium spp.) had decreasing trends and AAPC (−2.9% for Mt and −9.6% for PT). For PT, the main species was perennial ryegrass (L. perenne L.) (0.357), with increasing trends for Mt. As Mt, a positive AAPC was found for plantain (P. lanceolata L.) (+17.4%) and chicory (C. intybus L.) (+63.2%). Over a period of 19 years, based on Mt but not PT, Chilean end-users have been adopting new pasture species with a decreasing use of Trifolium spp.
Efficiency of Recycled Biogas Digestates as Phosphorus Fertilizers for Maize
Authors: Bach Inga-Mareike , Essich Lisa , Müller Torsten
Published: June 2021

Despite phosphorus resources on Earth being limited, over fertilization in many agricultural situations causes significant resource consumption. Phosphorus-recycling within agricultural production can reduce global dilution into the environment and is thus essential to secure sustainable future supply. This study investigated the fertilization efficacy of phosphorus fertilizers recycled from biogas digestates in maize shoots grown under controlled greenhouse conditions, in two soils, in a pot experiment. Variables investigated were plant-available phosphorus in soil, plant biomass production, and concentration of phosphorus, calcium, and magnesium in shoots. Soils were treated with three different fertilizer fractions, separated from biogas digestates, at equivalent phosphorus concentrations, using different combinations and application techniques, isolated or in combination, and compared to triple superphosphate (TSP) as a reference. One of the fractions (P-Salt) had effects on biomass production and plant phosphorus concentration equivalent to TSP in agricultural surface soil. In the second soil (with less active soil life and nutrient content), equivalence to TSP was achieved with combinations of two recycled fractions (P-Salt and dried solids). The enhancement of the phosphorus fertilizing effect by the solids was synergistic, indicating that the solids had a soil conditioning effect. The results show that biogas digestates are a valuable source for phosphorus recycling of fractions that have equivalent or even superior fertilizing properties compared to TSP.
Canadian Greenhouse Operations and Their Potential to Enhance Domestic Food Security
Authors: LaPlante Gabriel , Andrekovic Sonja , Young Robert G. , Kelly Jocelyn M. , Bennett Niki , Currie Elliott J. , Hanner Robert H.
Published: June 2021

Food security is a growing societal challenge. The pressure to feed a projected global population of 9.6 billion by 2050 will continue to be limited by decreasing arable land. The recent disruptions in international trade resulting from responses to the COVID-19 pandemic have highlighted the importance of regional self-reliance in food production. While Canada is highly self-reliant in food categories such as meat and dairy, the nation relies heavily on international imports to fulfill fresh vegetable demands. In potential future scenarios where international trade faces disruptions, Canadian food security could be at risk. By providing local sources of fresh foods year-round, the greenhouse vegetable industry holds strong potential to overcome future food supply shortages and could become a critical contributor to self-sustainable food production in Canada. Many challenges, however, surround the Canadian greenhouse industry. Some challenges include the persistence and spread of infectious plant pathogens and forecasted labour shortages. Opportunities to alleviate such challenges include introducing more diverse commodity groups and integrating innovative technologies to accelerate efficiency within the industry. In this commentary, we examine the current state of the Canadian greenhouse industry, explore potential challenges, and highlight opportunities that could promote food security across the nation.
Plant Antioxidants for Food Safety and Quality: Exploring New Trends of Research
Authors: Loi Martina , Paciolla Costantino
Published: June 2021

Antioxidants are an heterogeneous group of compounds able to counteract cell oxidation by acting as reducing agents, as free radical scavengers, and quenchers of radical species and other pro-oxidants, such as metals [...]