bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pyrotinib combined with trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2-positive metastatic breast cancer: a single-arm exploratory phase II trial
Authors: Xie Xiao-Feng , Zhang Qiu-Yi , Huang Jia-Yi , Chen Li-Ping , Lan Xiao-Feng , Bai Xue , Song Lin , Xiong Shui-Ling , Guo Si-Jia , Du Cai-Wen 
Published: July 2022

Abstract
Purpose: A substantial need for effective and safe treatment options is still unmet for patients with heavily pre-treated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Herein, we assessed the efficacy and safety of pyrotinib plus trastuzumab and chemotherapy in patients with heavily treated HER2-positive MBC.Methods: In this single-arm exploratory phase II trial, patients with HER2-positive MBC previously treated with trastuzumab plus lapatinib or pertuzumab, received pyrotinib plus trastuzumab and chemotherapy. The primary end point was progression-free survival (PFS) in the total population (TP). Secondary end points included PFS in the subgroup with brain metastases (Sub-BrM), confirmed objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), exploration of predictive factors of PFS, and safety.Results: Between November 1, 2018, and March 31, 2021, 40 patients were eligible for this study. The median PFS reached 7.5 months (95% confidence interval [CI], 4.7 to 9.9 months) and 9.4 months (95% CI, 6.6 to 12.1 months) in the TP and Sub-BrM, respectively. ORR was 50.5% (20/40). CBR was 75.5% (30/40) and DCR reached 97.5% (39/40). Cox univariate and multivariate analyses demonstrated that liver or/and lung metastases was the significant adverse prognostic factor for PFS (p = 0.018; p = 0.026; respectively). The most frequent grade 3 or 4 treatment-related adverse events were diarrhea, neutropenia and leukopenia. No new safety signals were observed.Conclusion: Pyrotinib plus trastuzumab and chemotherapy offered a promising option with manageable safety profile for heavily pre-treated HER2-positive MBC, especially for those without liver or/and lung metastases.
What we have learnt from the past – would treament decicions for GEP- NET patients differ between 2012 to 2016 by the new recommendations in 2022?
Authors: Stiefel Rahel , Lehmann Kuno , Winder Thomas , Siebenhüner Alexander R. 
Published: July 2022

Abstract
Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of tumors with a broad range of local and systemic treatment options. Still a lack of data regarding treatment sequences exists. The aim of this study was to analyze outcomes in GEP-NETs depending on stage and treatment steps and compare our treatment decisions to the latest treatment recommendations of ESMO 2020 for GEP-NETs. Methods: Patients were included in this retrospective single-center analysis from 2012 - 2016. Patient outcomes and treatment lines were analyzed by uni- and multivariable analysis. Results: Overall, we identified 256 GEP-NETs , mostly staged at advaced stage (62%) and located in small intestine tract and pancreatic gland. Survial depended on stage, grade, primary site and duration of response for the early systemic treatment. On average patients underwent 2.6 different treatment modalities, mostly depending on stage and higher tumor grade. Surgery was performed either early but as well in advanced stages, ususally followed by Somatostatine-Antagonist modalities. According to these findings, we formed a suggested treatment algorithm for advanced GEP-NETs, which does not differ from the latest treatment recommendation by ESMO guidelines for GEP-NETs. Conclusion: The results of this project may define GEP-NET patients’ selection for upcoming clinical prosepctive studies.
Impact of Air Quality on COVID-19 Confirmed and Death Cases: Evidence from China
Authors: Wang Yifei , Jin Meiling , Zhu Chunyan , Lu Mingshan 
Published: July 2022

Abstract
Coronavirus disease 2019 (COVID-19) has triggered the most significant public health crisis in recent years. However, studies on the impact of air quality on COVID-19 confirmed cases and death cases are still limited. This study examines the impact of the air quality on daily COVID-19 confirmed cases and deaths in prefecture-level cities in China from January 22, 2020, to December 31, 2020. The zero-inflated Poisson regression is applied in this paper to explore the impact of air pollution levels on daily confirmed cases and daily death cases. We find significant evidence for air quality index (AQI) to impact daily confirmed COVID-19 cases positively. By further decomposing AQI to its components, we find a significant positive impact from SO2, NO2, O3, and CO on daily confirmed COVID-19 cases. Results also show a positively significant impact from PM10, SO2, NO2, O3, and CO on daily dead COVID-19 cases. This study provides new insights into the relationship between air quality on daily COVID-19 confirmed cases and death cases in China and has direct implications for COVID-19 epidemic prevention and control.
Effects of intrusion and retreat of deep cold waters on the causative species of red tides offshore in the South Sea of Korea
Authors: Ok Jin Hee , Jeong Hae Jin , Lim An Suk , You Ji Hyun , Du Yoo Yeong , Kang Hee Chang , Park Sang Ah , Lee Moo Joon , Eom Se Hee 
Published: July 2022

Abstract
The key nutrient sources for red-tide species are freshwater and deep cold waters. However, a lack of data on their growth rates at different depths limits our understanding of the effects of deep cold waters on red-tide formation. Offshore water was collected from 0, 20, and 40 m in the South Sea of Korea and the growth rates of major red-tide species were measured after their addition to these waters. The growth rates of Margalefidinium polykrikoides in the waters from 0, 20, and 40 m (0.25, 0.25, and 0.21 d-1) were similar. The growth rates of Prorocentrum donghaiense, Tripos furca, and Alexandrium fraterculus in the water from 20 m (0.30, 0.37, and 0.42 d-1) were similar to those from 40 m but higher than those from 0 m (0.16, 0.04, and 0.21 d-1). The ability of P. donghaiense, T. furca, and A. fraterculus to reach deep waters is therefore a critical factor affecting red-tide formation. Considering their vertical migration depths and growth rates at different depths, P. donghaiense, T. furca, or A. fraterculus can dominate when deep waters are intruded to 10 m, while A. fraterculus or M. polykrikoides can dominate when deep waters retreat to 20 m. Only M. polykrikoides can dominate when deep waters retreat to 30 m. These scenarios are supported by the results recorded in the red-tide events of 2014. Red-tide species can thus be predicted using data on their growth rates at different depths, their vertical migration depths, and the position of deep cold waters.
Environmental, Ecological, and Health Risks Assessment of Olive Orchard Soils in Izmir Province of Turkey
Authors: Deliboran Aise 
Published: July 2022

Abstract
Soil contamination with TEs become a severe concern, however, the evaluation of ecological and human health problems in intensive agricultural areas remained limited. In this study, Pb, Cr, Ni, Al, Fe, Co, Mn, Cu, Cd, and Zn content of olive orchard soils in Izmir province of Turkey were investigated to the state of pollution, environmental, ecological, and health hazards. Soil samples were taken from 129 olive orchards at 0-30 cm depth. Air-dried samples were eliminated by a 0.5 mm sieve and digested in HNO3 and HCl (3: 1) at a microwave digestion device. TheTEs concentrations are determined by ICP-OES. Cr and Ni levels were advanced at the limit level. In terms of EF, the soils are significantly contaminated by Cd (7.18), moderately contaminated by Ni (2.94), and Cu (2.56). In terms of Cf, soils were moderately contaminated by Cd (1.96), and in terms of Er moderate by Cd (58.83). Co, Fe, Al, and Mn are the lithogenic origin, and Pb, Zn, Al, Cd, Cu, and Ni are anthropogenic. The HQ, HI, and THI in terms of adults and children were below 1, all TEs via ingestion, skin contact, and inhalation pathways had no serious non-carcinogenic hazards. The harmful health consequences of TEs were accentuated in children. This study may serve as a method for managing the contamination-related risk of olive cultivation areas where agrochemicals are widely employed. Additional studies are recommended about TEs contamination risk and the potential health dangers in olive fruits.
Cytotoxic flavokawain B inhibits the growth and metastasis of hepatocellular carcinoma through the suppression of UCK2-mediated downregulation of the STAT3/Hif-1α/VEGF signalling pathway
Authors: Malami Ibrahim , Alhasan Alhasan Muhammad , Adamu Adamu Ahmed , Bello Muhammad Bashir , Muhammad Aliyu , Imam Mustapha Umar 
Published: July 2022

Abstract
Hepatocellular carcinoma (HCC) is currently the third most common cancer-related death worldwide. HCC is associated with a high mortality rate due to early recurrence and its distant metastasis to the nearby organs. Current treatment options include surgical removal and transplantation as well as chemotherapy, which remains a major challenge to patient treatment. Flavokawain B (FKB) is a natural bioactive molecule capable of providing effective therapy against this life-threatening disease. This study investigates the effects of Flavokawain B (FKB) on the growth and development of metastatic hepatocellular carcinoma. HepG2 cells were used in this study and a neutral red assay was performed to determine the anti-proliferation effects of FKB at varying concentrations. Cell scratch and exclusion zone assays were performed to assess the inhibitory effects of FKB on cell migration and invasion and relative mRNA levels were quantified using the RT-qPCR. FKB inhibited the proliferation of HepG2 cells at an IC50 value of 28 µM, which conforms to its apoptosis-inducing effects. Cell migration and invasion were significantly inhibited at 7, 14, and 28 µM of FBK. UCK2 expression was significantly downregulated after FKB treatments. Inhibition of STAT3 expression subsequently induced the downregulation of VEGF and HIF-1α expressions. Our data suggest that FKB inhibits HepG2 proliferation and suppresses its metastasis abilities, thus providing a potential alternative and viable strategy against HCC.
Statistical study on the regional characteristics of seismic activity in and around Japan: frequency-magnitude distribution and tidal correlation
Authors: Nagata Kohei , Tamaribuchi Koji , Hirose Fuyuki , Noda Akemi 
Published: July 2022

Abstract
We propose a statistical analysis method to identify common features of seismic activity that are indistinguishable from most other seismicity, and to find anomalous activity that differs from these common features. Using the hypocenter catalogue of earthquakes which occurs in and around Japan during the past 20 years, we apply this method for the parameters of the frequency-magnitude distribution and a parameter that expresses the correlation of seismicity with tides as indices, with a focus on objectively understanding the regional characteristics of seismicity. As a result, we extracted a "typical" probability density distribution of each index value common to the most analysis regions and "anomalous" regions with index-value distributions that differ significantly from the typical distributions. In terms of the frequency-magnitude distribution, most estimated values of indices in the anomalous activity areas can be explained as variations corresponding to the effects of fluids, interplate coupling, and stress fields that control faulting styles that have been pointed out in previous studies. By extracting typical index values for the frequency-magnitude distribution, common features of the frequency-magnitude distribution that depend on the earthquake occurrence interval were identified. Although seismicity showed no clear correlation with tides, the index value for tidal correlation changes to reflect the proportion of earthquakes occurring in a series of periods shorter than the tidal period; it is therefore useful as an index to capture the characteristics of such earthquake occurrence intervals. We also show that the typical probability density distribution of these index values can be represented by existing models or their extensions. By using the proposed models as a reference, it is possible to quantify the degree of anomaly using the same concept as that of the method presented here; hence, such a method should be applicable to monitor seismic activity.
The role and Mechanism of Endophilin A1 in LPS-induced Parkinson's disease model mice
Authors: Han Junhui , Liu Mengqing , Ling Yi , Oiu Yue , Ren Yubo , Liu Yi , Yin Yanyan 
Published: July 2022

Abstract
Background: Neuroinflammation and oxidative stress are closely related to the pathogenesis of Parkinson's disease (PD), and PD is pathologically characterized by progressive loss of dopaminergic neurons in the SN pars compacta and excessive accumulation of α-synuclein. Endophilin A1(EPA1) is a cytoplasmic protein that is widely expressed in presynaptic nerve terminals in the brain and regulates synaptic vesicle cycling. EPA1 is encoded by the SH3GL2 gene, and SH3GL2 was designated as a PD risk locus by genome-wide association analysis, suggesting that EPA1 may be involved in the occurrence and development of PD. However, the role of EPA1 in PD remains unclear.Methods: The mice PD model was prepared by injecting LPS into the SN, and the changes in the behavioral data of mice in each group were observed through grasping force and open-field behavioral experiments. The damage of DA neurons, activation of microglia, and reactive oxygen species (ROS) generation were detected by immunofluorescence method; calcium ion concentration was detected by calcium content detection kit; EPA1 and inflammation and its related indicators (NLRP1, ASC, Caspase-1, IL-1β, IL-18, IL-6, TNF-α) were detected by Western blot method. EPA1 knockdown was performed by an adeno-associated virus (AAV) vector containing EPA1-shRNA-eGFP infusion.Results: LPS-induced PD model mice developed behavioral dysfunction, SN dopaminergic nerve damage, significantly increased calcium ion, calpain 1, and ROS production, activated NLRP1 inflammasome and promoted pro-inflammatory cell release, and SN EPA1 knockdown improves behavioral disorders, alleviates dopaminergic neuron damage, reduces calcium, calpain 1, ROS generation, and blocks NLRP1 inflammasome-driven inflammatory responses.Conclusions: The expression of EPA1 in the SN of LPS-induced PD model mice was increased, and it played a role in promoting the occurrence and development of PD. EPA1 activates the NLRP1 inflammasome to promote the release of inflammatory factors by regulating calcium ion homeostasis and ROS generation, and induces DA neuron damage through an inflammatory mechanism, thereby participating in the occurrence and development of PD.
A homozygous PIWIL2 frameshift variant affects the formation and maintenance of human induced pluripotent stem cell-derived spermatogonial stem cells and causes Sertoli cell only-syndrome
Authors: Wang Xiaotong , Li Zili , Qu Mengyuan , Xiong Chengliang , Li Honggang 
Published: July 2022

Abstract
Background
The most serious condition of male infertility is complete Sertoli cell-only syndrome (SCOS), referring to lack of all spermatogenic cells in testes. Genetic cause of SCOS remains to be explored. We aimed to investigate the genetic cause of SCOS and assess the effects of the identified causative variant on human male germ cells.
Methods
Whole-exome sequencing was performed to identify potentially pathogenic variants in a man with complete SCOS and Sanger sequencing was performed to verify the causative variant in this man and his father and brother. The pathogenic mechanisms of the causative variant were investigated by in vitro differentiation of human induced pluripotent stem cells (hiPSCs) into germ cell-like cells.
Results
The homozygous loss-of function (LoF) variant p.His244ArgfsTer31 (c.731_732delAT) in PIWIL2 was identified as the causative variant in the man with complete SCOS, and the same variant in heterozygosis was confirmed in his father and brother. This variant resulted in a truncated PIWIL2 protein lacking of all functional domains, and no PIWIL2 expression was detected in the patient’s testes. The patient and PIWIL2−/− hiPSCs could be differentiated into primordial germ cell-like cells and spermatogonial stem cell-like cells (SSCLCs) in vitro, but the formation and maintenance of SSCLCs were severely impaired. RNA-seq analyses proposed inactivation of the Wnt signaling pathway in the process of SSCLC induction in the PIWIL2−/− group, which was validated in the patient group by RT-qPCR. The Wnt signaling pathway inhibitor hindered the formation and maintenance of SSCLCs during the differentiation of normal hiPSCs.
Conclusions
Our study revealed the pivotal role of PIWIL2 in the formation and maintenance of human spermatogonial stem cells. We provided clinical and functional evidence that the LoF variant in PIWIL2 is a genetic cause of SCOS, which supported the potential role of PIWIL2 in genetic diagnosis. Furthermore, our results highlighted the applicability of in vitro differentiation models to function validation experiments.
Characteristics and Outcomes of Neonatal Opioid Withdrawal Syndrome in Preterm Infants: A retrospective cohort study in the current era
Authors: Heyward Alicia , Minich Nori Mercuri , Hoffman Adriana , Hibbs Anna Maria , Zhao Lulu , Crowley Moira 
Published: July 2022

Abstract
OBJECTIVE: Compare Neonatal Opioid Withdrawal Syndrome (NOWS) in preterm and term infants. STUDY DESIGN: Single center, retrospective chart review of all in-utero opioid exposed infants born between 2014 and 2019. Withdrawal symptoms were assessed using Modified Finnegan Assessment Tool. RESULTS: Thirteen preterm (PT), 72 late preterm (LPT), and 178 term infants were included. Preterm and LPT compared to term infants had lower peak Finnegan scores (9/9 vs. 12) and received less pharmacologic treatment (23.1/22.4 vs. 66.3%). Similar onset, peak symptoms, and treatment duration was observed in LPT and term infants. CONCLUSIONS: Preterm and LPT infants have lower Finnegan scores and require less pharmacologic therapy for NOWS. It is unclear if this is because our current assessment tool does not capture their symptoms or if they truly have less withdrawal. Onset of NOWS is similar in LPT and term infant, thus LPT infants do not require prolonged hospital monitoring for NOWS.
Analysis of catch-up growth in 87 premature infants within corrected age of 12 months:a retrospective single-center study
Authors: Yang Tingting , Shen Qianqian , Li Chunlei , Liang Liang , Xu Fan , Wang Siyu , Dong Tianfang , He Youfang , Luo Fang , Liang Jiahong , Xiao Shasha , Ma Xiaoxue , Yin Xuerong , Yan Jiacong , Yang Jinghui 
Published: July 2022

Abstract
BackgroundThe aim of this study was to explore the physical development law and the factors affecting catch-up growth of premature infants within 12 months of corrected age.MethodsA retrospective analysis was made on the catch-up growth of premature infants. ResultsCatch-up growth was been seen in both reaching catch-up growth group (group 1) and non-reaching catch-up growth group (group 2). The physical development indexes catch up quickly within the 6 months of corrected age, and then slowdown. The peak of physical development indexes in group 1 appeared before the corrected age of 1 month, and that in group 2 appeared between the corrected age of 1 month and 2 months. The catch-up growth gradually deceleration after 2 months of corrected age in group 2. There was no significant difference in the developmental quotients of the five functional areas in Gesell scale between two groups in present study (P≥0.05).None of the factors included were protective or risk factors for catch-up growth.ConclusionAdequate nutrition, regular monitoring, scientific guidance, and individualized intervention programmes are necessary for catch-up growth in premature infants.Trial registration Retrospectively registered.
Magnetically Responsive Nanoplatform Targeting circRNA circ_0058051 Inhibits Hepatocellular Carcinoma Progression
Authors: You Song , Luo Zijin , Cheng Niangmei , Wu Ming , Lai Yongping , Wang Fei , Zheng Xiaoyuan , Wang Yingchao , Liu Xiaolong , Liu Jingfeng , Zhao Bixing 
Published: July 2022

Abstract
Circular RNAs (circRNAs) are a kind of highly stable and closed-loop non-coding RNA, which is involved in the occurrence and development of hepatocellular carcinoma (HCC). However, little is known about the therapeutic role of circRNAs in HCC. We found that high circ_0058051 expression was negatively correlated with the prognosis of HCC patients. Circ_0058051 Knockdown attenuated the proliferation and clone formation, meanwhile inhibited migration of HCC cells. Circ_0058051 may be used as a target for HCC gene therapy. We synthesized a novel small interfering RNA (siRNA) delivery system PEG-PCL-PEI-C14-SPIONs (PPPCSs) based on Superparamagnetic iron oxide nanoparticles (SPIONs). PPPCSs protected siRNA of circ_0058051 from degradation in serum, and effectively deliver siRNA into SMMC-7721 cells. Meanwhile, intravenous injection of the PPPCSs/siRNA complex could inhibit tumor growth in the subcutaneous tumor model. In addition, the nanocomposite is not toxic to the organs of nude mice. The above results show that PPPCSs/si-circ_0058051 complex may provide a novel and promising method of HCC treatment.
Study on the correlation mechanism between the living vegetation volume of urban road plantings and PM2.5 concentrations
Authors: Sheng Qianqian , Dai Anqi , Zhang Huihui , Zhu Zunling 
Published: July 2022

Abstract
To study the effects of species diversity of different urban road green space on PM2.5 reduction, and to provide a theoretical basis for the optimal design of urban road plantings. Different combinations of road plantings in Xianlin Avenue of Nanjing were used as sample areas, and 3–6 PM2.5 monitoring points were set up in each sample area. The monitoring points were setup at 10, 20, 30, 40, 50, and 60 m from the roadbed for detecting PM2.5 concentrations in different sample areas. Moreover, the living vegetation volume of each sample area was calculated. The coupling relationship between the living vegetation volumes and PM2.5 concentrations in different sample areas was evaluated by regression fitting and other methods. PM2.5 concentrations among different sample areas were significantly different. PM2.5 concentrations were higher in the morning than in the afternoon, while the differences were not significant. The living vegetation volumes of the eight sample areas varied from 2038.73 m3 to 15032.55 m3. Affected by different plant configurations, the living vegetation volumes in the sample areas showed obvious differences with an order of S7 > S2 > S3 > S1 > S5 > S6 > S8 > S4. The S2 sample area, which was considered as control, was inside a residential area. The fitting curve of living vegetation volumes and PM2.5 concentrations in sample areas of S1 and S3–S8 can explain 76.4% of the change in PM2.5 concentrations, which showed significant fitting. The fitting relationship between living vegetation volumes and PM2.5 concentrations in different road green space is different owing to different compositions of plantings. With the increase in living vegetation volumes, their fitting functions first increase and then decrease in a certain range. It is speculated that only when the living vegetation volume exceeds a certain range, it will promote PM2.5 reduction.