bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Study of Anlotinib as Third-Line or Above Therapy in Patients With Advanced or Metastatic Gastric Cancer: A Multicenter Retrospective Study
Authors: Nie Caiyun , He Yunduan , Lv Huifang , Gao Ming , Gao Xiaohui , Chen Beibei , Xu Weifeng , Wang Jianzheng , Liu Yingjun , Zhao Jing , Chen Xiaobing 
Published: July 2022

BackgroundThe present study was conducted to evaluate the efficacy and safety of anlotinib as third-line or above therapy for patients with advanced or metastatic gastric cancer.MethodsPatients with advanced or metastatic gastric cancer who have failed from second-line treatment and treated with anlotinib monotherapy or combined with chemotherapy or immunotherapy from June 2019 to January 2021 in 3 institutions across China were retrospectively analyzed. The primary end point was progression free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety.Results43 patients with advanced or metastatic gastric cancer who have failed prior treatment received anlotinib monotherapy or combination therapy as third-line or above therapy. In the general population, 4 patients achieved PR, 21 patients had SD and 18 patients had PD. The overall ORR and DCR were 9.3% (4/43) and 58.1% (25/43), respectively. Median PFS and OS were 3.0 months (95% CI=2.5-3.5) and 6.0 months (95% CI=4.4-7.6), respectively. The incidence of Grade 3-4 adverse events(AEs) was 34.9%. Subgroup analysis suggested that the ORR of anlotinib combination therapy was superior than anlotinib monotherapy, but with similar PFS and OS. The clinical benefit of anlotinib was not associated with previously anti-angiogenesis therapy with apatinib.ConclusionsAnlotinib monotherapy or combination therapy provide a feasible third-line or above therapeutic strategy in patients with advanced or metastatic gastric cancer a median PFS of 3.0 months and median OS of 6.0 months was obtained with well tolerated toxicity.
RAD21 Confers Poor Prognosis and Affects Ovarian Cancer Sensitivity to Poly(ADP-Ribose)Polymerase Inhibitors Through DNA Damage Repair
Authors: Gou Rui , Li Xiao , Dong Hui , Hu Yuexin , Liu Ouxuan , Liu Juanjuan , Lin Bei 
Published: July 2022

BackgroundPoly(ADP-ribose)polymerase (PARP) inhibitors are a class of molecular-targeted cancer drugs. Synthetic lethality is a phenomenon that renders homologous recombination repair defective cells more sensitive to PARP inhibitors. As a component of the cohesin complex, RAD21 regulates DNA damage repair. However, the biological roles of RAD21 in ovarian cancer and their underlying mechanisms remain unclear.MethodsAn immunohistochemical assay was used to validate the expression of RAD21 in ovarian cancer and its correlation with prognosis. The effects of RAD21 were evaluated through Cell Counting Kit-8 (CCK8), wound-healing, and invasion assays in vitro and the tumor growth in vivo. Furthermore, CCK8 assay and immunofluorescence assay were used to detect the effect of RAD21 on cell sensitivity to PARP inhibitors and their mechanism. The pathway changes were detected by Western blotting.ResultsRAD21 was markedly upregulated in ovarian cancer samples. High RAD21 expression was correlated with poor differentiation and poor prognosis in patients with ovarian cancer. Functionally, RAD21 overexpression promoted cancer cell proliferation, migration, and invasion. Moreover, RAD21 knockdown increased the sensitivity of ovarian cancer cells to three kinds of PARP inhibitors by affecting DNA damage repair. In vivo experiments indicated that RAD21 promoted tumor growth. Mechanistically, the overexpression of RAD21 led to increased phosphorylation levels of Akt and mTOR. Blocking the Akt/mTOR signaling pathway reversed RAD21 overexpression-induced cancer progression and drug resistance.ConclusionsRAD21 can serve as a valuable prognostic marker for ovarian cancer and has the potential as a therapeutic target that can expand the utility of PARP inhibitors.
Efficacy and Safety of Lenvatinib Combined With PD-1 Inhibitors Plus TACE for Unresectable Hepatocellular Carcinoma Patients in China Real-World
Authors: Li Xiaowei , Fu Zhigang , Chen Xiaoxia , Cao Kunkun , Zhong Jiaming , Liu Li , Ding Ning , Zhang Xiaoli , Zhai Jian , Qu Zengqiang 
Published: July 2022

PurposeTo evaluate the efficacy and safety of lenvatinib combined with programmed death receptor-1 signaling inhibitors plus transarterial chemoembolization (LePD1-TACE) for treatment of unresectable hepatocellular carcinoma (uHCC) in a real-world setting in China.MethodsThis was a retrospective study involving consecutive patients with uHCC (n =114) receiving LePD1-TACE treatment from June 2019 to May 2021. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were calculated to evaluate the antitumor efficacy. Treatment-related adverse events (TRAEs) were analyzed to assess the safety profiles. In addition, we also evaluated prognostic factors related to survival and disease progression.ResultsA total of 114 patients with a median age of 53 years were analyzed during a median follow-up duration of 10.6 months (95% confidence interval [CI]: 8.5 -12.8). The Kaplan-Meier analysis showed that the median OS was 18.0 months (95% CI: 14.1 - Not reached), the median PFS was 10.4 months (95% CI: 6.6 - 12.4). Based on modified Response Evaluation Criteria in Solid Tumors, the best ORR was 69.3% and DCR was 80.7%. Almost all patients suffered from TRAEs, the most common grade 3-4 TRAEs were hypertension (8.8%), proteinuria (3.6%), hyperbilirubinemia (1.8%), leukopenia (4.4%) and alanine aminotransferase elevation (3.6%) across all patients. The independent treatment factors associated with OS and PFS were tumor number, neutrophil-to-lymphocyte ratio (NLR) and the early tumor response. In the early tumor response (CR+PR) patients, median OS and PFS were 25.1 months (95% CI: 13.8 - Not reached) and 15.2 months (95% CI: 10.5 - 19.1). The patients with tumor number &lt; 3 had a superior median OS and PFS (25.1, 16.4 months) compared to patients with tumor number ≥ 3 (14.1 months, P = 0.012; 6.6 months, P = 0.007). The patients with NLR ≤ 2.165 had a longer median OS and PFS (Not reached, 15.2 months) than those with NLR &gt; 2.165 (17.7 months, P = 0.003; 7.5 months, P = 0.047).ConclusionIn this real-world study, LePD1-TACE triple therapy showed encouraging efficiency and manageable safety in patients with uHCC. The tumor number (&lt; 3), NLR (≤ 2.165) and early tumor response (CR+PR) could be one of the prognostic markers.
Epimedin C Alleviates Glucocorticoid-Induced Suppression of Osteogenic Differentiation by Modulating PI3K/AKT/RUNX2 Signaling Pathway
Authors: Xu Yongxiang , Chen Shichun , Huang Linxuan , Han Weichao , Shao Yingying , Chen Minyi , Zhang Yusheng , He Ruirong , Xie Baocheng 
Published: July 2022

Secondary osteoporosis is triggered mostly by glucocorticoid (GC) therapy. Dexamethasone (DEX) was reported to inhibit osteogenic differentiation in zebrafish larvae and MC3T3-E1 cells in prior research. In this research, we primarily examined the protective impacts of epimedin C on the osteogenic inhibition impact of MC3T3-E1 cells and zebrafish larvae mediated by DEX. The findings illustrated no apparent toxicity for MC3T3-E1 cells after administering epimedin C at increasing dosages from 1 to 60 μM and no remarkable proliferation in MC3T3-E1 cells treated using DEX. In MC3T3-E1 cells that had been treated using DEX, we discovered that epimedin C enhanced alkaline phosphatase activities and mineralization. Epimedin C could substantially enhance the protein expression of osterix (OSX), Runt-related transcription factor 2 (RUNX2), and alkaline phosphatase (ALPL) in MC3T3-E1 cells subjected to DEX treatment. Additionally, epimedin C stimulated PI3K and AKT signaling pathways in MC3T3-E1 cells that had been treated using DEX. Furthermore, in a zebrafish larvae model, epimedin C was shown to enhance bone mineralization in DEX-mediated bone impairment. We also found that epimedin C enhanced ALPL activity and mineralization in MC3T3-E1 cells treated using DEX, which may be reversed by PI3K inhibitor (LY294002). LY294002 can also reverse the protective impact of epimedin C on DEX-mediated bone impairment in zebrafish larval. These findings suggested that epimedin C alleviated the suppressive impact of DEX on the osteogenesis of zebrafish larval and MC3T3-E1 cells via triggering the PI3K and AKT signaling pathways. Epimedin C has significant potential in the development of innovative drugs for the treatment of glucocorticoid-mediated osteoporosis.
Femtosecond Third-Order Non-Linear Optical Properties of Unconstrained Green Fluorescence Protein Chromophores
Authors: Ahmed Md Soif , Biswas Chinmoy , Banerjee Dipanjan , Chetti Prabhakar , Yang Jye-Shane , Soma Venugopal Rao , Raavi Sai Santosh Kumar 
Published: July 2022

We report herein results on the third-order non-linear optical (NLO) properties of four structurally unconstrained green fluorescence protein (GFP) chromophores, namely, 1, 2, 3, and 4. Using experimental techniques and theoretical calculations such as UV–visible spectroscopy, density functional theory (DFT), time-dependent density functional theory (TDDFT), and Z-scan techniques, we have investigated the linear absorption, ultrafast non-resonant third-order optical non-linearities, and the onset of optical-limiting thresholds of these benzylidenedimethylimidazolinone (BDI) dyes. The Z-scan measurements were performed at a wavelength of 800 nm with ∼70 femtosecond (fs) pulses. We have witnessed a strong reverse saturable absorption (fitted to three-photon absorption) for all of the molecules with fs pulse excitation. The valley–peak curves obtained from the closed-aperture Z-scan technique revealed the positive non-linear refractive index (self-focusing) nature of these molecules. We have evaluated the various third-order NLO coefficients (second hyperpolarizability, γ ∼10–33 esu), which were found to be larger than those of similar molecules reported in the recent literature.
Percutaneous Auricular Vagus Nerve Stimulation Reduces Inflammation in Critical Covid-19 Patients
Authors: Seitz Tamara , Szeles József Constantin , Kitzberger Reinhard , Holbik Johannes , Grieb Alexander , Wolf Hermann , Akyaman Hüseyin , Lucny Felix , Tychera Alexander , Neuhold Stephanie , Zoufaly Alexander , Wenisch Christoph , Kaniusas Eugenijus 
Published: July 2022

Covid-19 is an infectious disease associated with cytokine storms and derailed sympatho-vagal balance leading to respiratory distress, hypoxemia and cardiovascular damage. We applied the auricular vagus nerve stimulation to modulate the parasympathetic nervous system, activate the associated anti-inflammatory pathways, and reestablish the abnormal sympatho-vagal balance. aVNS is performed percutaneously using miniature needle electrodes in ear regions innervated by the auricular vagus nerve. In terms of a randomized prospective study, chronic aVNS is started in critical, but not yet ventilated Covid-19 patients during their stay at the intensive care unit. The results show decreased pro-inflammatory parameters, e.g. a reduction of CRP levels by 32% after 1 day of aVNS and 80% over 7 days (from the mean 151.9 mg/dl to 31.5 mg/dl) or similarly a reduction of TNFalpha levels by 58.1% over 7 days (from a mean 19.3 pg/ml to 8.1 pg/ml) and coagulation parameters, e.g. reduction of DDIMER levels by 66% over 7 days (from a mean 4.5 μg/ml to 1.5 μg/ml) and increased anti-inflammatory parameters, e.g. an increase of IL-10 levels by 66% over 7 days (from the mean 2.7 pg/ml to 7 pg/ml) over the aVNS duration without collateral effects. aVNS proved to be a safe clinical procedure and could effectively supplement treatment of critical Covid-19 patients while preventing devastating over-inflammation.
Regional Differences in Carbon-14 Data of the 993 CE Cosmic Ray Event
Authors: Miyake Fusa , Hakozaki Masataka , Kimura Katsuhiko , Tokanai Fuyuki , Nakamura Toshio , Takeyama Mirei , Moriya Toru 
Published: July 2022

Cosmogenic nuclides such as 14C from tree rings and 10Be and 36Cl from ice cores are excellent proxies for the past extremely large solar energetic particle (SEP) events, which are dozens of times larger than the largest SEP event in the history of observation. So far, several rapid 14C increases have been discovered, which are considered to have originated from extreme SEP events (or set of successive SEP events) from verifications using multiple cosmogenic nuclide analyses in natural archives. Although these events are characterized by a rapid increase in cosmogenic nuclide concentrations, 14C data recorded worldwide do not always show similar variations, especially during the 993 CE event, where a rapid increase was recorded in either 992–993 CE or 993–994 CE in several records. We present new 14C data of the Japanese cedar sample for the 993 CE event. Although the latest data show no significant increase in 1 year, an overall increase pattern is consistent with the previously reported 14C data of the Japanese cedar, which supports that a significant 14C increase occurred from 993 to 994 CE in the Japanese sample. Given the dominant 14C production in high latitudes by SEPs, the difference in timing of increase may be a transport effect in the atmosphere. Moreover, the difference in the timing of the 14C increase can cause a 1-year age-determination error using the 993 CE radiocarbon spike. Compared with the 14C data between tree samples from high latitude and midlatitude, including Japan, high-latitude data can capture 14C changes originating from SEP events more quickly and clearly and may be more suitable for a SEP event exploration in the past.
Is It Necessary to Remove the Implants After Fixation of Thoracolumbar and Lumbar Burst Fractures Without Fusion? A Retrospective Cohort Study of Elderly Patients
Authors: Xu Xiangyu , Cao Yuan , Fan JiXing , Lv Yang , Zhou Fang , Tian Yun , Ji Hongquan , Zhang Zhishan , Guo Yan , Yang Zhongwei , Hou Guojin 
Published: July 2022

ObjectiveFractures of the thoracolumbar spine are the most common fractures of the spinal column. This retrospective cohort study aimed to determine whether it is necessary to remove implants of patients aged over 65 years after the fixation of thoracolumbar and lumbar burst fractures without fusion.MethodsThis retrospective cohort study included 107 consecutive patients aged ≥65 years without neurological deficits, who underwent non-fusion short posterior segmental fixation for thoracolumbar or lumbar burst fractures. Outcome measures included the visual analog score (VAS), Oswestry Disability Index (ODI), residual symptoms, complications, and imaging parameters. Patients were divided into groups A (underwent implant removal) and B (implant retention) and were examined clinically at 1, 3, 6, and 12 months postoperatively and annually thereafter, with a final follow-up at 48.5 months.ResultsOverall, 96 patients with a mean age of 69.4 (range, 65–77) years were analyzed. At the latest follow-up, no significant differences were observed in functional outcomes and radiological parameters between both groups, except in the local motion range (LMR) (P = 0.006). Similarly, between preimplant removal and the latest follow-up in group A, significant differences were found only in LMR (P &lt; 0.001). Two patients experienced screw breakage without clinical symptoms. Significant differences were only found in operation time, blood loss, ODI, and fracture type between minimally invasive group and open group.ConclusionsSimilar radiological and functional outcomes were observed in elderly patients, regardless of implant removal. Implant removal may not be necessary after weighing the risks and benefits for elderly patients. Patients should be informed about the possibility of implant breakage and accelerating degeneration of adjacent segments in advance.
Gastric-type Mucinous Carcinoma with an Abnormal Increase of CA199: A Case Report and Literature Review
Authors: Qian Xue-qian , Wang Fen-fen , Liang Yun , Chen Li-Li , Wan Xiao-yun 
Published: July 2022

ObjectiveGastric-type mucinous carcinoma (GAS), as a rare subtype of mucinous adenocarcinoma, accounts for approximately 1%–3% of cervical adenocarcinoma. It was considered as a new type of cervical mucinous adenocarcinoma by the World Health Organization (WHO) in 2014. GAS represents more aggressive disease than does usual type endocervical adenocarcinoma (UEA).Case reportA case of cervical adenocarcinoma with an abnormal increase of CA199 in a 50-year-old Chinese woman was reported. Our patient presented with abnormal vaginal discharge and combined with elevated Ca199 at the value of 2,729 U/mL. Imaging examinations showed no abnormalities. Diagnostic conical resection suggested cervical adenocarcinoma in situ. Post-operative pathology confirmed mucinous cervical adenocarcinoma (considering gastric type), infiltrating cervical interstitial &gt;2/3, involving the deep myometrium, accompanied by vascular carcinoma infiltration and lymph node metastasis.The patients received an extensive hysterectomy and post-operative adjuvant chemoradiotherapy. The chemotherapy regimen was paclitaxel, combined with platinum. After 20 months of follow-up, the patient showed no signs of recurrence.ConclusionPreoperative diagnosis of cervical adenocarcinoma is insidious and can be easily misdiagnosed. For patients with high preoperative Ca199, the possibility of GAS should be kept open.
Contributions of Plant Litter Decomposition to Soil Nutrients in Ecological Tea Gardens
Authors: Liu Shaqian , Yang Rui , Peng Xudong , Hou Chunlan , Ma Juebing , Guo Jiarui 
Published: July 2022

Plant litter decomposition and its effect on soil nutrients are important parts of the ecosystem material cycle, and understanding these processes is key for species selection and allocation to promote the effective use of litter in ecological tea gardens. In this study, the in situ litter decomposition method was used to examine the decomposition characteristics of leaf litter of Cinnamomum glanduliferum, Betula luminifera, Cunninghamia lanceolata, Pinus massoniana, and Camellia sinensis prunings in the Jiu’an ecological tea garden in Guizhou and their effects on soil nutrients. The results showed that the litter decomposition rate of broad-leaved tree species was higher than that of coniferous tree species, with a half-life of 1.11–1.75a and a turnover period of 4.79–7.57a. There are two release modes of nutrient release from litter: direct release and leaching–enrichment–release. Different litters make different contributions to soil nutrients; Betula luminifera and Cinnamomum glanduliferum litter increased the contents of soil organic carbon, soil total nitrogen, and soil hydrolyzed nitrogen. Betula luminifera litter increased the content of soil total phosphorus, soil available phosphorus, and soil available potassium, and Pinus massoniana litter increased the content of soil total potassium and soil available potassium; therefore, it is concluded that the decomposition of Betula luminifera litter had a positive effect on soil nutrient content. Thus, Betula luminifera is a good choice for inclusion in ecological tea gardens to increase their nutrient return capacity, maintain fertility, and generally promote the ecological development of tea gardens.
Diagnosis of Scrotal Mass in Children
Authors: Lumi Axel P. , Lampus Harsali , Pali Nathaniel 
Published: July 2022

Abstract: Scrotal mass is one of the diseases in the urology field with a moderately high prevalence. Problems with the contents of scrotum vary, ranging from infections, tumors, to fluid. Diagnosis of scrotal mass is based on detail ananmnesis, systematic physical examination, and other supporting examinations. Scrotal ultrasound can confirm the exact location of a mass and rule out the presence of an inguinal hernia. Scrotal masses in adults require a formal examination with serum tumor markers, scrotal ultrasound as needed, and immediate consultation with a urologist for staging and further intervention. Scrotal masses in children are much less common than in adults and should be evaluated by a urologist.Keywords: scrotal mass; children Abstrak: Massa skrotum merupakan salah satu penyakit di bidang urologi dengan prevalensi yang cukup tinggi. Masalah pada isi skrotum bervariasi, mulai dari infeksi, tumor, hingga cairan. Diagnosis massa skrotum ditegakkan melalui anamnesis yang cermat, pemeriksaan fisik terarah, dan pemeriksaan penunjang. Ultrasonografi (USG) skrotum dapat mengonfirmasi lokasi yang tepat dari suatu massa sekaligus menyingkirkan adanya hernia inguinalis. Massa testis pada dewasa memerlukan pemeriksaan formal, dengan penanda tumor serum, USG skrotum sesuai kebutuhan, dan konsultasi segera dengan ahli urologi untuk staging dan intervensi lebih lanjut. Massa skrotum pada anak jauh lebih jarang daripada dewasa dan harus dievaluasi oleh seorang ahli urologi.Kata kunci: massa skrotum; anak
Efektivitas Metode Reward And Punishment Pada Peningkatan Minat Belajar Dan Kemampuan Passing Bawah Siswa Kelas Xi Smk Negeri 1 Gabuswetan
Authors: Suwandi Suwandi 
Published: July 2022

Introduction: Pengamatan terhadap pelaksanaan proses pembelajaran permainan Bola Voli di beberapa sekolah, menunjukkan bahwa banyak ditemukan masalah, kurangnya penguasaan ketrampilan tehnik permainan bola voli, maka perlu diajarkan secara mendalam tentang tehnik permainan bola voli . Sehubungan dengan masalah itu terutama Passing, anak didik perlu diajarkan macam-macam pasing. Sesuai dengan perkembangannya, Pasing dalam permainan bola voli dibagi menjadi dua macam, yaitu: Passing bawah, dan Passing atas, akan tetapi Passing bawah yang memiliki tingkat kesulitan yang tinggi Objective: Sesuai tujuan pembelajaran PJOK siswa dituntut untuk menguasai gerakan pasing bawah dari pelajaran yang diajarkan tetapi pada akhinya banyak siswa yang tidak tertarik terhadap pembelajaran pasing bawah. Salah satu usaha untuk memperbaiki dan meningkatkan minat siswa dalam mengikuti pembelajaran pasing bawah perlu adanya modifikasih pembelajaran yang mengena yaitu dengan menggunakan metode pembelajaran reward dan punishment Method: Subjek dalam penelitian ini adalah siswa kelas XI SMK N 1 Gabuswetan sebanyak 34 siswa. Prosedur penelitian dilaksanakan dengan menggunakan siklus-siklus tindakan (daur ulang). Daur ulang dalam penelitian diawali dengan perencanaan (Planning), tindakan (Action), mengobservasi (Observation), dan melakukan refleksi (Reflection), dan seterusnya sampai adanya peningkatan yang diharapkan tercapai. Results: Berdasarkan hasil penelitian, diperoleh peningkatan minat dan hasil belajar siswa. Sebelum Penerapan (Pra Siklus) rata-rata minat belajar siswa adalah 35% pada kategori baik. Pada Siklus I, rata-rata minat belajar pelajaran bola voli pasing bawah meningkat diman minat belajar siswa naik menjadi 53% pada katagori cukup baik. Pada Siklus II, rata-rata minat belajar siswa meningkat menjadi 100% pada kategori sangat baik (SB). Conclusion: Selain itu, terdapat peningkatan kemampuan siswa dalam mengikuti pembelajaran pasing bawah pada pembelajaran bola voli. Pada tahap Pra Siklus, frekuensi katagori Cukup Baik sedangkan pada siklus I dan II setelah diterapkan model pembelajaran metode reward dan punishment , diperoleh hasil pada kategori baik.