bluuebunny/crossref_metadata_2025 huggingface dataset:
Rising incidence of late stage breast cancer after COVID-19 outbreak. Real-world data from the Italian COVID-DELAY Study
Authors: Mentrasti Giulia , Cantini Luca , Vici Patrizia , D’Ostilio Nicola , Verde Nicla La , Chiari Rita , Paolucci Vittorio , Crocetti Sonia , De Filippis Chiara , Pecci Federica , Lisa Francesca Sofia Di , Traisci Donatella , Cona Maria Silvia , Nicolardi Linda , Pizzuti Laura , Gildetti Simona , Oldani Simone , Mora Arianna Della , Rocchi Marco Luigi Bruno , Berardi Rossana
Published: April 2022

Purpose
Breast cancer (BC) patients’ (pts) management was affected by a global reorganization after Coronavirus disease 2019 (COVID-19). Our multicenter study aimed to assess the impact of COVID-19 on access to diagnosis, staging and treatment for BC pts compared to pre-pandemic.
Methods
Medical records of all consecutive newly diagnosed BC pts referred to 6 Italian Institutions between March and December 2020 were assessed. Monthly access rate and temporal intervals between date of symptoms onset, radiological, cytohistological diagnosis and treatment start were analyzed and compared with those of 2019.
Results
A reduction (25%) in newly diagnosed BC pts was observed compared to 2019 (666 vs 890). New BC pts in 2020 were less likely to be diagnosed with early stage (stage 0-I-II) BC (77% vs 83%, p<0.01), had a worse ECOG PS (19.8% had PS>0 in 2020 vs 16.5% in 2019, p<0.01) and fewer patients were asymptomatic at diagnosis in 2020 (54% vs 71%, p<0.01). COVID-19 did not negatively impact in terms of access to diagnosis, staging and treatment. Time intervals between symptom onset and radiological diagnosis, symptom onset and cytohistological diagnosis, cytohistological diagnosis and treatment start were maintained or even improved. However, less BC cases were discussed in multidisciplinary tumor meetings during 2020 (60% vs 73%, p<0.01).
Conclusions
Our data proved an alarming reduction of BC early stage diagnoses in 2020. Despite the upheaval generated by COVID-19, our study shed light on the effective performance delivered by Italian Oncology Departments to guarantee diagnostic-therapeutic pathways.
Application of Interval Type-2 Fuzzy Logic System and Ant Colony Optimization for Hydropower Dams Displacement Forecasting
Authors: MAI DINH SINH , Bui Kien-Trinh Thi , Doan Van-Chinh
Published: April 2022

The authors have requested that this preprint be removed from Research Square.
Dynamic Evaluation and Prediction of the Ecological Environment Quality of the Urban Agglomeration on the Northern Slope of Tianshan Mountains
Authors: Yibo Yan , Ziyuan Chai , Zibibula Simayi , Haobo Yan , Xiaodong Yang , Shengtian Yang
Published: April 2022

In order to timely understand the dynamic changes of the ecological environment quality and future development laws of the urban agglomeration on the northern slope of the Tianshan Mountains, combined with the actual situation of the urban agglomeration, 11 indicators are selected from the three aspects of natural ecology, social ecology, and economic ecology. Based on RS and GIS technology methods, Principal component analysis, coefficient of variation and analytic hierarchy process are used to reduce the dimensions of the indicators, and the ecological environmental quality (EQI) from 2000 to 2018 is dynamically evaluated, and the CA-Markov model is introduced to simulate the development status in 2026 predict.The main results are as follows: the overall ecological environment of the area shows a gradually improving distribution change from southwest to northeast; the proportion of ecological environment classification shows a gradually decreasing change pattern; the spatial differentiation of ecological environment quality shows a significant spatial positive correlation; from the influencing factors It can be seen that natural ecological factors occupy a major position; the prediction accuracy verification shows that the CA-Markov model is suitable for the prediction of the ecological environment quality in the region and has high accuracy; the comprehensive regional ecological environment quality indexes are 5.7392, 6.1856 and 6.4366, respectively, and the forecast in 2026 The value is predicted to be 6.6285, indicating that the overall ecological environment quality of the region has been improved and developed well. The research reveals the law of dynamic changes and future development of the ecological environment quality in the region, which can be used as a theoretical reference for the formulation of ecological environmental protection measures in the region.
Incidence of Pulmonary Tuberculosis under the Normal State of COVID-19 Epidemic Prevention and Control
Authors: Wu Ziwei , Chen Ziyi , Long Siyu , Wu Aiping , Wang Hongsheng
Published: April 2022

Background: The COVID-19 pandemic has driven public health intervention strategies, including keeping social distance, wearing masks in crowded places, and having good health habits, to prevent the transmission of the novel coronavirus (SARS-CoV-2). However, it is unknown whether the use of these intervention strategies influences morbidity in other human infectious diseases, such as tuberculosis.Methods: In this study, three prediction models were constructed to compare variations in PTB incidences after January 2020 without or with intervention includes strict and normalized interventions, when the COVID-19 outbreak began in China. The non-interventional model was developed with an autoregressive integrated moving average (ARIMA) model that was trained with the monthly incidence of PTB in China from January 2005 to December 2019. The interventional model was established using an ARIMA model with a continuing intervention function that was trained with the monthly PTB incidence in China from January 2020 to December 2020.Results: Starting with the assumption that no COVID-19 outbreak had occurred in China, PTB incidence was predicted, and then the actual incidence was compared with the predicted incidence. A remarkable overall decline in PTB incidence from January 2020 to December 2020 was observed likely due to the influence of intervention policies for COVID-19. If the same intervention strategy is applied for the next 2 years, the monthly PTB incidence would reduce on average by about 1.03 per 100,000 people each month compared with the incidence predicted by the non-interventional model. The annual incidence estimated 59.15 under normalized intervention per 100,000 in 2021, and the value would decline to 50.65 with strict interventions.Conclusions: Our models quantified the knock-on effect on PTB incidence of the intervention strategy used to control the transmission of COVID-19 in China. Combined with the feasibility of the strategies, these results suggested that continuous normalized interventions would play important roles in the future prevention and control of PTB.
A method for determination of kinetic friction coefficient under dynamic loading conditions
Authors: Mitrovic Slobodan , Brzakovic Ljiljana , Kocovic Vladimir , Busarac Nina , Tadic Branko
Published: April 2022

In general, the kinetic friction coefficient can, under any contact loading condition, be determined using methods completely different from the existing methods based on the measurements of contact load and friction force. The proposed method refers to the determination of kinetic friction coefficient using the dynamic equation of motion for a rotating body, where the active force acts on the rotating body only at the initial moment of motion, while body masses, which are concentrically and eccentrically distributed in relation to the axis of rotation, provide a static and dynamic component of a desired 'sleeve-bearing' contact load. If the body angle of rotation change is experimentally determined as a function of time, then, based on the dynamic equation of motion, it is possible to determine the current friction coefficient values for the entire time period from the start of the motion to the rotation stop. It can be said that acceleration is a physical and energy indicator for friction and energy dissipation in tribomechanical systems, and that it defines the complete dynamics of the friction process itself.
Assessment of knowledge of surgical and clinical skills among medical students and residents in Syria: A cross-sectional study.
Authors: Ataya Jamal , Ismail Abdullah Ismail , Kousa Alyamama , Shahoud Zein Shahoud , Alhalabi Rawan Alhalabi , Ghanem Rita , Zaitouna Mazen
Published: April 2022

Background:Based on the importance of surgical and clinical skills for any doctor, regardless of his specialty, it was necessary to assess the knowledge and familiarity of medical students and recent graduates with these skills, perhaps this assessment would be a constructive step towards improving the professional reality of all doctors in our country.Methods:We surveyed medical students in Syrian Universities by a questionnare which was published via online students platforms. Main topics of the questionnaire concerned basic surgical and clinical skills by twenty questions that were taken from international references.Results:The final sample was 500 questionnaires and 77% of the students had an intermediate assessment. A relationship was noted with the University where they studied and the gender of participants. The percentage of correct answers ranged from 29% to 76.8% for surgical skills and from 9% to 98.4% for clinical skills.Conclusions:We have noticed a defect in many students in applying their theoretical knowledge in a good practical way, so we suggested that these faculties adopt systematic plans to develop the teaching of these skills and provide efficient scientific expertise in addition to improving training methods by reducing the number of Students and placing them in an appropriate environment with securing the necessary laboratories and equipment.
The effect of monochromatic, combined, and mixed light-emitting diode light regimes on growth traits, fear responses and slaughter-carcass characteristics in broiler chickens
Authors: Sayin Yunus , Kaplan Onur , Karaduman Esra , Haqyar Dost Mohammad , Narinç Doğan
Published: April 2022

This study aims to determine the effects of blue and green monochromatic, blue-green combination, and blue-green mixed led lighting systems on growth, fear, and carcass characteristics of broilers reared in an extensive indoor system. Experimental groups were formed as follows; 1-conventional (incandescent), 2-blue, 3-green, 4-blue-green combined (blue for the first ten days, then green), 5-green-blue combined (green for the first ten days, then blue), and 6-blue-green intermittent (alternating every 5 minutes) monochromatic lightings. It was detected that the average values of the body weight of chickens at 42 and 56 days of age in the green-blue group were higher than those of the other treatment groups (both P<0.05). It was determined that the broilers in the green and green-blue groups had higher means of the β0 parameter of Gompertz model. The tonic immobility, emergence test, home cage avoidance test, a looming human test, and box-plus experimenter test were applied to determine the fear responses. It was determined that the worst results for fear responses of broilers were in the intermittent lighting group and green-blue combined group. As a result, it was determined that the application of green monochromatic lighting in the first ten days of the fattening period and blue monochromatic lighting in the following period positively affected growth and slaughter-carcass characteristics. However, it was found that broilers reared under green-blue combined lighting had high fear levels.
Plants control the structure of pathogenic and saprotrophic fungal communities in soil in a 50-year maize monoculture experiment
Authors: Wachowska Urszula , Rychcik Bogumił
Published: April 2022

Aims
Saprotrophic soil fungi participate in biomass mineralization, inhibit pathogen development and promote plant growth. Pathogens accumulate in soil and decrease crop yields. The structure of fungal communities is determined mainly by the organic matter content and pH of soil. Little is known about the influence of crop rotation and long-term monoculture on saprotrophic fungi that decompose plant roots and crop residues as sources of soil biomass.
Methods
Fungal communities that promote plant growth (arbuscular mycorrhizal fungi (AMF), yeasts, Trichoderma spp.), cellulolytic fungi and pathogenic species were analyzed in a 6-year crop rotation system (maize – spring barley – peas – winter rapeseed – winter wheat – sugar beets) and in 50-year maize monoculture. Fungal DNA was extracted from the rhizosphere and plant roots, and the ITS2 region of fungal rDNA was analyzed by high-throughput sequencing. In both treatments, weeds were controlled chemically (terbuthylazine + mesotrione + s-metolachlor) or mechanically.
Results
A total of 311 fungal species were identified. The biodiversity of soil fungi, in particular AMF and yeasts, was higher in monoculture than in crop rotation. Maize pathogens were more frequently identified in monoculture, whereas species of the genus Trichoderma were more prevalent in crop rotation. Herbicides clearly increased the abundance of cellulolytic fungi of the phyla Mucoromycota and Mortierellomycota, Mortierella spp. and Minimedusa polyspora. The abiotic properties of soil were affected by the cropping sequence. The content of organic carbon (Corg) and the availability of P and Mg decreased in monoculture. Maize yields were bound by a strong positive correlation with the availability of macronutrients and Corg in soil, as well as a weak positive correlation with the abundance of Trichoderma spp., Mucoromycota and Mortierellomycota.
Conclusions
Fungi exert a complex and ambiguous effect on maize biomass yields, whereas a decrease in the macronutrient content of soil in monoculture strongly decreases maize yields. In the long term, the cropping sequence considerably influences the structure of the soil microbiome which can be a reservoir of unique species and species that minimize the negative effects of monoculture in agroecosystems.
Menthol carbonates as potent antiparasitic agents: synthesis and in vitro studies along with computer-aided approaches
Authors: Clemente Camila M. , Robledo Sara M. , Ravetti Soledad
Published: April 2022

Background: Despite the number of deaths and the significant economic and social costs associated with Chagas, Leishmaniasis and Malaria diseases worldwide, available drugs are limited and have serious side effects and high toxicity for the patient. Therefore, there is an urgent need for safe, low-cost, and effective treatments. Natural products are an important source of bioactive compounds and there is current interest in finding natural bioactive molecules that can be used for treating these parasitic diseases. In the present study we proposed to evaluate the in vitro antiparasitic activity of new menthol derivatives against Trypanosoma cruzi, Leishmania braziliensis and Plasmodium falciparum; moreover, we propose to explore their mode of action through in silico approaches.Methods: A series of carbonate prodrugs (1-9) were synthesized from menthol with different aliphatic alcohols. Spectroscopic techniques were used to confirm the structures of the synthesized compounds. The cytotoxicity of the compounds was assessed using U-937 cells. In vitro trypanocidal, leishmanicidal and antiplasmodial activity were evaluated using a T. cruzi, L. braziliensis and P. falciparum organism, respectively. In addition, in silico studies were also performed through molecular dynamics simulations and MM-PBSA analysis.Results: The assay revealed that most of the compounds were highly active against intracellular amastigotes of T. cruzi and L. braziliensis, and had moderate activity against the total forms of P. falciparum. Compound 2 was one of the drugs that showed a high selectivity index (SI) for the three organisms evaluated. The prediction of the ADME properties suggests that all the compounds have drug-like molecular properties and the probability to be lead candidates. Finally, molecular dynamics simulations, and MM-PBSA studies indicate that menthol at the substrate binding site of TcDHODH, LbDHODH and PfDHODH is structurally stable in the same order as the natural substrate; also, interactions of menthol with residues involved in the inhibition of TcDHODH and PfDHODH proteins were predicted.Conclusions: The present study demonstrates that menthol prodrugs are promising antiparasitic agents; however, the mechanisms of action proposed in this study need to be experimentally verified by future enzymatic assays.
Significance of Tumor Heterogeneity of p-Smad2 and c-Met in HER2-positive Gastric Carcinoma with Lymph Node Metastasis
Authors: Tsujio Gen , Maruo Koji , Yamamoto Yurie , Sera Tomohiro , Sugimoto Atsushi , Kasashima Hiroaki , Miki Yuichiro , Yoshii Mami , Tamura Tatsuro , Toyokawa Takahiro , Tanaka Hiroaki , Muguruma Kazuya , Ohira Masaichi , Yashiro Masakazu
Published: April 2022

Background: Tumor heterogeneity has frequently been observed in gastric cancer (GC), but the correlation between patients' clinico-pathologic features and the tumoral heterogeneity of GC-associated molecules has not been clarified. We investigated the correlation between lymph node metastasis and the tumoral heterogeneity of driver molecules in GC.Materials and Methods: We retrospectively analyzed the case of 504 patients who underwent a gastrectomy at the department of Gastroenterological Surgery Osaka City University and 389 cases of The Cancer Genome Atlas (TGCA) data. The clustering analysis was performed based on eight cancer-associated molecules including HER2, c-Met, and p-Smad2, using the protein expression revealed by our immunohistochemical study of the patients and TGCA cases. We determined the correlations between HER2 expression and the other molecules based on the degree of lymph node metastasis.Results: Immunohistochemical staining data showed that a 43 of the 504 patients with GC (8.5%) were HER2-positive. In the HER2-positive cases, the expressions of c-Met and p-Smad2 were increased in accord with the lymph-node metastatic level. The overall survival of the HER2-positive GC patients with both p-Smad2 and c-Met expression was significantly (p=0.030) poorer than that of the patients with p-Smad2-negative and/or c-Met-negative expression. The results of the TCGA data analysis revealed that 58 of the 389 GC cases (14.9%) were ERBB2-positive. MET expression was more frequent in the N1 metastasis group than the N0 group. In the high lymph-node metastasis (N2 and N3) group, SMAD2 expression was more frequent in addition to ERBB2 and MET expression.Conclusion: p-Smad2 and c-Met signaling might play important roles in lymph node metastasis in HER2-positive GC.
Tubo-Ovarian Mass with raised CA-125 in 21-year-old female
Authors: Purwar Roli , Soni Kishan , Tilak Ragini , Verma Ashish , Pandey Manoj
Published: April 2022

Introduction: Peritonitis associated with fungal species Curvularia lunata seldom occurs with only five cases reported in literature, all in middle age patients with comorbidities undergoing dialysis. Case Report: A 21-year-old female who was referred to surgical oncology OPD with a diagnosis of ovarian malignancy, based on raised cancer antigen 125 (CA 125) and suspected tubo-ovarian mass (TOM) on MRI. Review of the MRI showed pelvic collection with TOM, suggestive of infective pathology. Ultrasound guided aspiration of the cystic collection identified the presence of Curvularia lunata. She was treated with oral Itraconazole which showed symptomatic improvement and radiological response. In the follow-up period the patient developed chest wall swelling, aspiration and geneXpert® revealed MDR tuberculosis and treatment was started. Conclusions: Unusual causes of TOM and raised CA 125 should be kept in mind when dealing with young patients, as the possibility of epithelial ovarian cancer in this age is very low.
Comparison between Q-M type B and C2 abdominal radical hysterectomy for FIGO 2018 stage IB1 cervical cancer:a multicentre retrospective study
Authors: Liu Pan , Li Pengfei , Liu Ping , Liu Chang , Xu Yan , Ma Ben , Lin Lihong , Zhao Weidong , Lu Anwei , Yao Jilong , Wang Zhonghai , Bin Xiaonong , Lang Jinghe , Chen Chunlin
Published: April 2022

Objective: To compare the oncological results and surgical outcomes of abdominal Q-M type B and type C2 radical hysterectomy (RH) for patients with FIGO 2018 stage IB1 cervical cancer.Methods: We retrospectively compared the oncological results and surgical outcomes of 1158 cervical cancer patients treated with Q-M type B (n=775) or type C2 (n=383) RH between January 2004 and December 2018 at 47 hospitals in mainland China.Results: The type B group and type C2 group showed similar 5-year DFS and OS rates (OS: 98.5% vs 98.0%, P=0.461; DFS: 94.3% vs 93.3%, p=0.461) in the total study population. Multivariable analysis revealed that Q-M type B RH was not associated with a worse 5-year OS rate (hazard ratio [HR]=1.493; 95% CI=0.522-4.269, P=0.455 95% CI: 0.522-4.269;p=0.455) or DFS rate (HR=1.169;95%CI: 0.650-2.101;p=0.603). Compared with type C2, type C resulted in a significantly shorter operating time (215 min vs. 188 min, P＜0.001). The defecation time and atherization time were less in the type B group than in the type C2 RH group (3.04 d vs. 2.81 d, P<0.001; 10.59 d vs. 8.97 d, P<0.001). Additionally, intraoperative complications occurred with Q-M type C2 RH compared with Q-M type B RH (OR = 11.287, 95% CI= 4.667-27.300, P＜0.001). Conclusion: Among cervical cancer patients with FIGO 2018 stage IB1 disease, the oncological outcomes of Q-M type B RH and Q-M type C2 RH were similar, and Q-M type B RH was associated with a shorter operation time, less intraoperative blood loss and fewer intraoperative complications. This suggests that Q-M type B RH might be an rational option for FIGO 2018 stage IB1 cervical cancer.
Interactions between invasive and native harvestmen
Authors: Toft Søren , Brodersen Karen Eva , Hansen Thomas Hagen , Vo Tuyen
Published: April 2022

The harvestman Opilio canestrinii arrived in Denmark around 1980 and quickly became a dominant species in urban habitats. This was followed by nearly complete disappearance of the formerly co-dominant Leiobunum gracile . A second invasive species, Dicranopalpus ramosus , arrived in 2007 and is still under population increase. Old forests have been a refuge for L. gracile , but both invasive species are now invading this habitat. We investigated the possible presence of exploitative and interference competition in relation to limited food resources between the three species in the laboratory using pairs of individuals, either heterospecific ( O. canestrinii/L. gracile ; D. ramosus/L. gracile ) or conspecific ( L. gracile/L. gracile ) and offered food resources that were insufficient for both individuals. O. canestrinii gained significantly more weight than other species. L. gracile exhibited less startle behaviour and a higher contact time with its partner in the conspecific than in the heterospecific treatment. Overall, O. canestrinii performed better than L. gracile , when faced with food scarcity and restricted space, whereas D. ramosus did not. Thus, competition (both exploitative and interference) is a possible mechanism for explaining the disappearance of L. gracile from urban habitats following the successful establishment of O. canestrinii in Denmark; additionally, O. canestrinii may be a potential future threat to L .gracile in forests.
The structure characterized of Nostoc commune polysaccharide and antioxidant activity of Gansu Nostoc commune
Authors: Xinjian Wang , Zhen Yang , Xuehong Wang , Yu Liu , Hongjuan Zhang , Ruofeng Shang , Cidan Laba , Cuomu Wujin , Baocheng Hao
Published: April 2022

In this paper，Nostoc commune crude polysaccharide was extracted by hot water and Ultrasonic-assisted extraction, then purified by DEAE-cellulose52 cellulose column chromatography and Sephacryl G-100 gel column chromatography. Homogeneous polysaccharide HNCP3 extracted with hot water and UNCP4 extracted by ultrasound were obtained. The structures of HNCP3 and UNCP4 were characterized by molecular weight determination, infrared spectroscopy, DSC detection, sodium periodate oxidation, smith degradation reaction and methylation analysis. The conformation of the solution was studied by SEM and AFM. The results showed that the Ultrasonic-assisted extraction had an effect on the molecular weight, monosaccharide composition molar ratio and configuration of Nostoc commune. The main chains of HNCP3 and UNCP4 were mainly →6) -D-Glcp (1→ and →2,6) -D -Glcp, but there are 1,2,6-galactose branches and 2,3-Me2-D-Ara in UNCP4 and there is no HNCP3. The results of the composition of monosaccharides showed that both HNCP3 and UNCP4 have the presence of mannose. SEM and AFM showed that the structure of UNCP4 was helical, and the solution conformation of HNCP3 and UNCP4 was different in different solution environments. In experiments on the antioxidant activity and hypoglycemic effect of HNCP3 and UNCP4 in vitro, it was shown that UNCP4 has higher antioxidant activity scavenging ability and UNCP4 is stronger than HNCP3 inhibitory activity. Therefore, UAE increases the NCP extraction rate while also increasing the biological activity in NCP.
Positive effect of manipulated virtual kinematic intervention in individuals with traumatic stiff shoulder: Pilot study
Authors: Schwartz Isabella , Safran Ori , Karniel Naama , Abel Michal , Berko Adina , Seyres Martin , Tsoar Tamir , Portnoy Sigal
Published: April 2022

Virtual Reality allows to manipulate the patient’s perception, thereby providing a motivational addition to real-time biofeedback exercises. We aimed to test the effect of manipulated virtual kinematic intervention on measures of active and passive Range of Motion (ROM), pain, and disability level in individuals with traumatic stiff shoulder. In a double-blinded study, patients with stiff shoulder following proximal humerus fracture and non-operative treatment were randomly divided into a non-manipulated feedback group (NM-group; N = 6) and a manipulated feedback group (M-group; N = 7). The shoulder ROM, pain, and the Disabilities of the Arm, Shoulder and Hand (DASH) scores were tested at baseline and after the 6 sessions, during which the subjects performed shoulder flexion and abduction in front of a graphic visualization of the shoulder angle. The biofeedback provided to the NM-group was the actual shoulder angle and the feedback provided to the M-group was manipulated so that 10° were constantly subtracted from the actual angle detected by the motion capture system. The M-group showed greater improvement in the active flexion ROM (p = .046) and the DASH scores (p = .022). Manipulated intervention is beneficial in individuals with traumatic stiff shoulder and should be further tested for other populations with orthopedic injuries.
Association of JAK/STAT pathway gene polymorphisms with EGFR-TKIs adverse drug reactions in patients with advanced NSCLC
Authors: Wang Yan , Qi Huijie , Wang Tianxiao , Zhang Wenxin , Shi Xiaojin , Zhan Qiong , Li Qunyi , Zhong Mingkang
Published: April 2022

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been confirmed as an effective therapy for advanced non-small cell lung cancer (NSCLC) patients with EGFR-positive. However, various adverse drug reactions (ADRs) are frequently occurred in patients treated with EGFR-TKIs. Genetic polymorphisms may predict EGFR-TKI-induced ADRs. We attempted to explored the potential association between the genetic polymorphisms of the JAK-STAT pathway and EGFR-TKIs related ADRs in non-small cell lung cancer (NSCLC) patients. In addition, we also researched the correlation between single nucleotide polymorphisms (SNPs) of Janus Kinase- Signal Transducer and Activator of Transcription (JAK-STAT) pathway and clinical survival outcomes of NSCLC patients treated with EGFR-TKIs.Methods: We recruited 162 Han Chinese patients with advanced non-small cell lung cancer. We analyzed the relationship between the adverse reactions of EGFR-TKIs and JAK-STAT signaling pathway by single factor and multi-factor logistic regression analysis. Kaplan–Meier test was used to evaluate the association of SNPs with progression-free survival of advanced NSCLC patients.Results: In the discovery group, we found the following: There were significantly associations between the severity of adverse drug reactions caused by EGFR-TKIs and rs1053023 (P=0.016), rs1053005 (P = 0.016) in STAT3, rs324011 (P= 0.019) in STAT6. Furthermore, patients with AA genotype had a prolonged progression-free survival (PFS) (P= 0.012) compared with AT and TT genotype of rs7043371. Besides, validation experiments showed that STAT3 rs1053023 (P=0.021), rs1053005 (P = 0.021), STAT6 rs324011 (P=0.002) were all significantly associated with the severity of ADRs induced by EGFR-TKIs by multivariable regression, which consistent with the study in the discovery group.Conclusions: STAT3 rs1053023, rs1053005 and STAT6 rs324011 might be potential predictors of the severity of ADRs in EGFR-TKIs treated NSCLC patients and their variants play important roles in predicting the adverse reactions of non-small cell lung cancer patients with EGFR-TKIs.
Differentially private federated deep learning for multi-site medical image segmentation
Authors: Ziller Alexander , Usynin Dmitrii , Remerscheid Nicolas W. , Knolle Moritz , Braren Rickmer F. , Rueckert Daniel , Kaissis Georgios
Published: April 2022

Collaborative machine learning techniques such as federated learning (FL) enable the training of models on effectively larger datasets without data transfer. Recent initiatives have demonstrated that segmentation models trained with FL can achieve performance similar to locally trained models. However, FL is not a fully privacy-preserving technique and privacy-centred attacks can disclose confidential patient data. Thus, supplementing FL with privacy-enhancing technologies (PETs) such as differential privacy (DP) is a requirement for clinical applications in a multi-institutional setting. The application of PETs to FL in medical imaging and the trade-offs between privacy guarantees and model utility, the ramifications on training performance and the susceptibility of the final models to attacks have not yet been conclusively investigated. Here we demonstrate the first application of differentially private gradient descent-based FL on the task of semantic segmentation in computed tomography. We find that high segmentation performance is possible under strong privacy guarantees with an acceptable training time penalty. We furthermore demonstrate the first successful gradient-based model inversion attack on a semantic segmentation model and show that the application of DP prevents it from divulging sensitive image features. Our code is available at https://github.com/TUM-AIMED/PrivateSegmentation.
Moxibustion exhibits an anti-inflammatory effect on rheumatoid arthritis rats by promoting the polarization of M2 macrophage
Authors: Zhong Yu-mei , Guo Yan-ding , Luo Kun , Hu Dan-hui , Yang Xin , Zhu Jun , Gao Xiu-hua , Yu Shu-guang , Wintermark Max , Zhou Hai-yan
Published: April 2022

Background
Rheumatoid arthritis (RA) is a refractory autoimmune disease characterized by chronic synovitis. Moxibustion is a natural therapy that possesses anti-inflammatory bioactivity. However, the anti-inflammatory mechanism of moxibustion for the treatment of RA has not yet been clarified. Macrophage infiltration is a prominent characteristic in the pathological process of RA synovitis.
Objective
The aim of the present research is to investigate the effect of moxibustion on the polarization of macrophage.
Methods
The rats' right hind paws were injected with freundʼs complete adjuvant (FCA) to establish the model of RA. Seven days after the injection of FCA, moxibustion therapy was performed on the acupoints of Shenshu (BL23) and Zusanli (ST36) once a day for three weeks. The Immunofluorescence, Western bolt and Elisa were used to analyze the influence of moxibustion on the expression of STAT1/miR-155/SOCS1 signaling pathway and macrophage's marker.
Results
We observed that moxibustion decreased the thickness of foot pad and arthritis scores. Moxibustion up-regulated the exression of Tim-3, promoted the polarization of macrophages to M2 type and inhibited the polarization of macrophages to M1 type. Treatment with moxibustion decreased the level of interleukin (IL)-23 and increased the level of IL-4, IL-10 and Argininase (Arg)-1. Moreover, moxibustion blocked the activation of STAT1/miR-155/SOCS1 signaling pathway and promoted the polarization of macrophages to M2 type. Furthermore, when Tim-3 was knocked down, the anti-inflammatory effect of moxibustion was reduced and the effect of regulating macrophage polarization was inhibited.
Conclusion
moxibustion may regulate the expression of related molecules in the STAT1/miR-155/SOCS1 signaling pathway through Tim-3, promote the polarization of macrophages M2, and exhibit anti-inflammatory effects.
Development of China's first space-borne high-spectral-resolution lidar: retrieval algorithm and airborne demonstration
Authors: Ke Ju , Sun Yingshan , Dong Changzhe , Zhang Xingying , Wang Zijun , Lyu Liqing , Zhu Wei , Ansmann Albert , Su Lin , Bu Lingbing , Xiao Da , Wang Shuaibo , Chen Sijie , Liu Jiqiao , Chen Weibiao , Liu Dong
Published: April 2022

Aerosols and clouds greatly affect the Earth's radiation budget and global climate. Light detection and ranging (lidar) has been recognized as a promising active remote sensing technique for the vertical profiles of aerosols and clouds. China is developing its first space-borne aerosol-cloud high-spectral-resolution lidar (ACHSRL) for global high accuracy observations of aerosols/clouds profiles. This study presents a retrieval algorithm for aerosol and cloud optical properties from ACHSRL which was compared with the end-to-end Monte-Carlo simulations and validated with the data from an airborne flight with the ACHSRL prototype (A2P) instrument. Using imaging denoising, threshold discrimination, and iterative reconstruction methods, this algorithm was developed for calibration, feature detection, and extinction coefficient retrievals. The simulation results show that 95.4% of the backscatter coefficient have an error less than 12% while 95.4% of extinction coefficient have an error less than 24%. Cirrus and marine and urban aerosols were identified based on the airborne measurements over different surface types. Then, comparisons were made with U.S. Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) profiles, Moderate-resolution Imaging Spectroradiometer (MODIS), and the ground-based sun photometers. High correlations (R > 0.79) were found between backscatter (extinction) coefficient profiles of A2P and CALIOP over forest and town cover; the aerosol optical depth retrievals have correlation coefficient of 0.71 with MODIS data and show spatial variations consistent with those from the sun photometers. The algorithm developed for ACHSRL in this study can be directly employed for future space-borne high-spectral-resolution lidar (HSRL) and its data products will also supplement CALIOP data coverage for global observations of aerosol and cloud properties.
In Vivo Qualification of Human Aqueous Veins by EDI-OCT and OCTA Images
Authors: Chen Zhiqi , Chen Wei , Deng Chaohua , Guo Jingmin , Zhang Hong , Wang Junming
Published: April 2022

PURPOSE.
To investigate the aqueous vein in vivo by using enhanced depth imaging optical coherence tomography (EDI-OCT) and optical coherence tomography angiography (OCTA).
METHODS.
In this cross-sectional comparative study, 30 healthy participants were enrolled. Images of the aqueous and conjunctival veins were captured by EDI-OCT and OCTA during the static state and after water loading. The area, height, width, depth and blood flow of the aqueous vein and conjunctival vein were measured by ImageJ software.
RESULTS.
In the static state, the area of the aqueous vein was 8166.7 ± 3272.7µm2, which was smaller than that of the conjunctival vein (13690 ± 7457 µm2). The mean vessel density of the aqueous vein was 35.3 ± 12.6%, which was significantly less than that of the conjunctival vein (51.5 ± 10.6%). After water loading, the area of the aqueous vein decreased significantly from 8725.8 ± 779.4 µm2 (baseline) to 7005.2 ± 566.2 µm2 after 45 min but returned to 7863.0 ± 703.2 µm2 after 60 min. The vessel density of the aqueous vein decreased significantly from 41.2 ± 4.5% (baseline) to 35.4 ± 3.2% after 30 min but returned to 45.6 ± 3.6% after 60 min.
CONCLUSIONS.
The structure and vessel density of the aqueous vein can be effectively evaluated by OCT and OCTA, which might provide a biological indicator to evaluate aqueous vein changes and aqueous outflow resistance under different interventions in glaucoma patients.
Contrasted concentrations of neonicotinoids in human hair and urine suggest long-term vs short-term exposure in two observational studies, international academics and rural population of the Philippines.
Authors: Taira Kumiko , Fujioka Kazutoshi , Aebi Alexandre , Glauser Gaétan , Mitchell Edward A. D. , Ikenaka Yoshinori , Sanchez-Bayo Francisco , Tapparo Andrea , Lumawig-Heitzmann Elizabeth , Bonmatin Jean-Marc , Safer Anton , Lexmond Maarten Bijleveld van , Claveria Florencia , Aoyama Yoshiko , Miyabara Yuichi , Komori Makiko
Published: April 2022

Neonicotinoid insecticides, the most widely used category of insecticides for 20 years and candidate risk of neurodevelopment, have been detected in human urine and in hair. If the former reflecting dietary contamination over short periods and the latter total exposure over longer periods is not known. We quantified and compared the concentrations in spot urine by LC-MS/MS and in hair by UHPLC-MS/MS.In the first study, samples from an international group of scientists in Italy in 2016 (M/F=12/7),detection rate in urine and in hair was 0% vs 85.0% for imidacloprid; 0% vs 52.5% for thiacloprid; 0% vs 45.0% for acetamiprid; 0% vs 25.0% for thiamethoxam; and 0% vs 17.5% for clothianidin.In the second study, samples from 99 volunteers in three islands of the Philippines in 2017,detection rate in urine and in hair was 48.5% vs 60.6% for imidacloprid; 1.0% vs 8.1% for thiacloprid; 10.1% vs 13.1% for acetamiprid; 31.3% vs 30.3% for thiamethoxam; and 14.1% vs 45.5% for clothianidin. In the Philippine, concentrations were negatively correlated between urine and hair for thiamethoxam (r = -0.70, p = 0.016), but not for clothianidin or imidacloprid. Both analyses of urine and hair are complementary to assess human neonicotinoid exposure.
Clinical Profiles, Risk Factors and In-hospital Outcomes of Stroke in the Medical Ward of Dessie Comprehensive Specialized Hospital, Northeast Ethiopia; A retrospective study
Authors: Abdu Hussen , Seyoum Girma , Tadese Fentaw
Published: April 2022

Background: Stroke is undoubtedly becoming a worldwide public health problem. Stroke-related deaths are attributable to modifiable risk factors. In Ethiopia, a demographic shift increased the prevalence of stroke risk factors. Besides, there is limited critical information regarding stroke. Therefore, this study aimed to carefully assess clinical presentations, possible risk factors, and outcomes of stroke in the medical ward of Dessie comprehensive specialized hospital.Methods: A retrospective cross-sectional study design was properly employed among stroke patients. Medical records appropriately containing complete patient information and confirmed diagnosis of stroke using imaging techniques were included in the study. The necessary data were attentively entered into SPSS version 24.0 for comprehensive analysis. Results with P-value < 0.05 were considered statistically significant. Results: Most (51.9%) of the study participants were female. The average age of the patients was 59.2 ± 14.6 years. Many 163 (52.2%) of stroke patients lost sensation and developed weakness in their body parts. One hundred forty (44.9%) patients presented with hemiplegia/hemiparesis and 79 (25.3%) patients were unconscious. Hypertension 197 (63.1%), atrial fibrillation 47 (15.1%), chat chewing 46 (14.7%), and structural heart diseases 39 (12.5%) were the most traditional risk factors for stroke. The mortality rate of stroke was 21.8%, where 67 compliant patients conveniently died. Having a previous history of stroke, atrial fibrillation, and structural heart diseases was a predictor of risk factors for stroke-related mortality. Conclusion: Elders are more affected by stroke. Hypertension, atrial fibrillation, structural heart diseases, and family history of stroke are recognized risk factors for stroke. There is a high rate of stroke mortality in the hospital. Thus, establishing promotive, preventive, curative, and rehabilitative strategies are indispensable.
Effects of acute or chronic administration gold nanospheres on testicular functions in male rats
Authors: Mansour Doaa , Orabi Sahar , Fathalla Said , Gadallah Shaaban , Din Amina Gamal el , Abdoon Ahmed
Published: April 2022

This study investigated the effect of gold nanospheres (AuNPs) administration on the rat male reproductive function. Experiment 1: Fifty-four rats were assigned into three groups (n=18/group). Group І (control), Group ІІ (50 nm AuNPs) and Group ІІІ (10 nm AuNPs), in which rats were intramuscular (i.m) injected with a single dose of 75μg AuNPs/kg/bwt. Experiment 2: Eighteen rats were randomly assigned to three groups (n=6/group). Group І (control), Group ІІ (50nm AuNPs) and Group ІІІ (10 nm AuNPs): rats were injected repeated doses of 75μg AuNPs /kg/bwt for 5 weeks followed by 3 weeks washout period. Blood, testes and epididymis samples were collected on Days-3, 7, and 60 in experiment 1 and on Day-60 in the 2nd experiment. Results indicated that acute or chronic administration of 10nm AuNPs caused significantly increased serum testosterone level on day-60. Chronic administration of 50nm AuNPs has an antioxidant effect. Acute or chronic study induced no histopathological changes and no changes in Proliferating Cell Nuclear Antigen (PCNA) and caspase-3 in testicular tissues. Acute or chronic administration of 10nm AuNPs significantly increased the spermatozoa in epididymal ducts and testicular tissue on Day-60 post-treatment. In conclusion, the administration of AuNPs (10nm and 50nm size) is safe on the male reproductive function.
Curcumin induces Mitochondrial Apoptosis in Human Hepatoma Cells through BCLAF1-mediated Modulation of PI3K/AKT/GSK-3β Signaling
Authors: Bai Chunhua , Zhao Jiaqi , Su Jielin , Chen Jiaxin , Cui Xinmu , Sun Manqing , Zhang Xuewu
Published: April 2022

Curcumin is a yellow pigment extracted from the rhizome of turmeric, a traditional Chinese medicine. Here, we tested the hypothesis that curcumin-mediated downregulation of BCLAF1 triggers mitochondrial apoptosis in hepatoma cells by inhibiting PI3K/AKT/GSK-3β signaling. Treatment of the human hepatoma cell lines, HepG2 and SK-Hep-1, with various concentrations of curcumin revealed a time-dependent and concentration-dependent inhibition of cell proliferation, increased apoptosis, cell cycle arrest at the G0/G1 phase, reduced mitochondrial membrane potential, and reduced expression levels of PI3K, p-PI3K, AKT, p-AKT, GSK-3β, and p-GSK-3β. Additionally, curcumin suppressed the levels of apoptotic factors after treating the cells with LY294002, a PI3K inhibitor. Curcumin also suppressed the expression of BCLAF1. Treating stable BCLAF1 knockout HepG2 and SK-Hep-1 cells with curcumin further enhanced apoptosis and increased the number of cells in G0/G1 cell cycle arrest, while inhibiting the downregulation of PI3K/AKT/GSK-3β pathway-related proteins. Treatment of a nude mouse xenograft model bearing HepG2 cells with curcumin inhibited tumor growth, disrupted the cellular structure of the tumor tissue, and suppressed the expression of BCLAF1 and PI3K/AKT/GSK-3β proteins. In summary, our in vitro and in vivo analyses show that curcumin downregulates BCLAF1 expression, inhibits the activation of the PI3K/AKT/GSK-3β pathway, and triggers mitochondrial apoptosis in HCC. These findings uncover a potential therapeutic strategy leveraging the antitumor effects of curcumin against HCC.
A Caching-Enabled Permissioned Blockchain Framework for Industrial Internet of Things based on Deep Reinforcement Learning
Authors: Liu Peng , Yao Chuanjian , Li Chunpei , Zhang Shuyi , Li Xianxian
Published: April 2022

The integration of Industrial Internet of Things (IIoT) and blockchain has become a popular concept. Numerous IIoT nodes together form a decentralized network with rich location-aware computation resources, which can provide great data processing capability and offer low-latency services. However, we are still facing the challenges of how to efficiently process the massive IIoT data on resource-constrained IIoT nodes by blockchain smart contracts, as their storage only allows them to store limited blockchain data. This work aims to improve the smart contract execution efficiency on these IIoT nodes by caching based on Deep Reinforcement Learning. On the one hand, focusing on the characteristics of IIoT, the ledger structure, network architecture, and transaction flow are optimized. IIoT nodes are enabled to cache part of block data without affecting global data consistency. On the other hand, we formulated the blockchain caching problem as a Markov Decision Process and implemented a lightweight caching agent based on deep Q-learning. Proper features and a reward function are defined to minimize the execution delay of smart contracts. The extensive experiment results show that our proposed framework can effectively reduce the block dissemination costs and the agent can provide satisfactory caching performance.
Locating the precise sources of high-frequency microseisms using distributed acoustic sensing
Authors: Xiao Han , Tanimoto Toshiro , Spica Zack , Gaite Beatriz , Ruiz-Barajas Sandra , Pan Mohan , Viens Loïc
Published: April 2022

Although microseisms have been observed for more than 100 years, the precise locations of their excitation sources in the oceans are still elusive. Underwater Distributed Acoustic Sensing (DAS) brings new opportunities to study microseism generation mechanisms. Using DAS data off the coast of Valencia, Spain, and applying a cross-correlation approach, we show that the sources of high-frequency microseisms (0.5-2 Hz) are confined between 7 and 27 km offshore, where the water depth varies from 25 to 100 m. Over time, we observe that these sources move quickly along narrow areas, sometimes within a few kilometres. Our method with DAS data allows characterizing microseisms with a high spatiotemporal resolution, opening a new chapter in understanding these global and complex seismic phenomena happening in the oceans.
Correlation between Macroinvertebrates and Physicochemical Parameters in the Barna Basin of the Narmada River
Authors: Bhawsar Abhilasha , Vyas Vipin
Published: April 2022

The ecological assessment of Barna basin was done using physicochemical parameters and benthic macroinvertebrates collected from 6 streams of Barna basin of Narmada River basin. The methodology was followed from scientific manuals (Adoni et al., 1985; APHA, 1998). Principal component analysis (PCA) and correlation matrix were used to analyze the association between the physicochemical parameters and macroinvertebrate distribution. Nutrient levels were generally low however; significant differences existed between the values of physicochemical parameters as well as between the macroinvertebrate diversity at the different sampling sites. The results explained that the distribution and abundance of macroinvertebrates is governed by the physicochemical parameters of water quality of Barna basin hence, macroinvertebrates are good indicator of water quality and can be used for biomonitoring of water bodies which will help in making management and conservation strategies of the water resources.