bluuebunny/crossref_metadata_2025_split huggingface dataset:
C3AR1 mRNA as a Potential Therapeutic Target Associates With Clinical Outcomes and Tumor Microenvironment in Osteosarcoma
Authors: Zou Tiannan , Liu Weibing , Wang Zeyu , Chen Jiayu , Lu Sheng , Huang Kun , Li Weichao 
Published: March 2021

Objective: Targeting cancer-specific messenger RNAs (mRNAs) may offer novel insights into therapeutic strategies in osteosarcoma. This study aimed to discover possible osteosarcoma-specific mRNA and probe its biological functions.Methods: Based on mRNA-seq data from the TARGET database, stromal and immune scores were estimated for each osteosarcoma sample via the ESTIMATE algorithm. Stromal and immune mRNAs were obtained via integration of differentially expressed mRNAs between high and low stromal / immune score groups. Among hub and prognostic mRNAs, C3AR1 mRNA was focused and its prognostic value was assessed. The associations between C3AR1 mRNA and immune cells were analyzed via the CIBERSORT algorithm. Its expression was verified in osteosarcoma tissues and cells by RT-qPCR and western blot. The functions of C3AR1 were investigated by a series of experiments.Results: Low stromal and immune scores were both indicative of unfavorable outcomes for osteosarcoma patients. Eighty-eight up-regulated and seven down-regulated stromal and immune mRNAs were identified. Among 30 hub mRNAs, low expression of C3AR1 mRNA indicated worse outcomes than its high expression. There was a lower mRNA expression of C3AR1 in metastatic than non-metastatic osteosarcoma. C3AR1 mRNA was closely correlated to various immune cells such as macrophages. C3AR1 was verified to be down-regulated in osteosarcoma tissues and cells. Its overexpression suppressed proliferation, migration and invasion and induced apoptosis in osteosarcoma cells.Conclusion: C3AR1 mRNA could be a promising therapeutic target for osteosarcoma, linked with prognosis and tumor microenvironment.
Comprehensive Analysis Identifies Potential Ferroptosis-Associated mRNA Therapeutic Targets in Ovarian Cancer
Authors: Zhang Jiyan , Xi Jie , Huang Ping , Zeng Saitian 
Published: March 2021

Objective: This study aimed to explore ferroptosis-related mRNAs as potential therapeutic targets for ovarian cancer treatment.Methods: Molecular subtypes were classified based on ferroptosis-related mRNAs via ConsensusClusterPlus package. The differences in prognosis, stromal score, immune score, immune function, and immune checkpoints were assessed between subtypes. Small molecular drugs were predicted via the CMap database. The sensitivity to chemotherapy drugs was estimated through the GDSC. A LASSO Cox regression model was conducted via the glmnet package, followed by a nomogram model.Results: Based on ferroptosis mRNA expression profile, two molecular subtypes (C1 and C2) were classified, with distinct clinical outcomes. C1 subtype exhibited higher stromal score, immune cell score (T helper, Treg, neutrophil) and immune function (APC co-inhibition, parainflammation and Type II IFN response). Higher mRNA expression levels of immune checkpoints (like PDCD1) were found in C1 than C2. Potential small molecular drugs (PI3K and mTOR inhibitors) were found for treatment of ovarian cancer. C1 was more sensitive to eight chemotherapy drugs (A.443654, AZD.0530, AZD6482, AZD7762, AZD8055, BAY.61.3606, Bicalutamide, and CGP.60474). A 15-ferroptosis-related mRNA signature was developed, which could robustly and independently predict the outcomes. Moreover, a nomogram was established combining the signature and age, which could intuitively and accurately predict the 5-year overall survival probability.Conclusion: Our study characterized two ferroptosis-related subtypes with distinct prognosis and tumor immune features, which could assist clinicians make decisions and individual therapy. Moreover, 15 ferroptosis-related mRNAs were identified, which could become potential therapeutic targets for ovarian cancer.
Case Report: Deep Cerebellar Stimulation for Tremor and Dystonia
Authors: Horisawa Shiro , Kohara Kotaro , Nonaka Taku , Mochizuki Tatsuki , Kawamata Takakazu , Taira Takaomi 
Published: March 2021

Background: The cerebellum plays an important role in the pathogenesis and pathophysiology of movement disorders, including tremor and dystonia. To date, there have been few reports on deep cerebellar stimulation.Case Report: The patient was a 35-year-old previously healthy man with no history of movement disorders. He developed a tremor and stiffness in his left hand at the age of 27 years, which was diagnosed as a dystonic tremor. We performed right thalamotomy, which resulted in a complete resolution of the tremor; however, the dystonia persisted. Subsequently, the patient developed left foot dystonia with inversion and a newly developed tremor in the right hand and foot. The patient underwent left ventralis intermedius (VIM) deep brain stimulation (VIM-DBS) and left pallidothalamic tract DBS (PTT-DBS). Left VIM-DBS completely resolved the right hand and foot tremor, and PTT-DBS significantly improved the left hand and foot dystonia. Three months postoperatively, the patient developed an infection and wound disruption at the surgical site. We performed palliative surgery for deep cerebellar stimulation via the posterior cranial region, which was not infected. The surgery was performed under general anesthesia with the patient lying in the prone position. Eight contact DBS electrodes were used. The placement of electrodes extended from the superior cerebellar peduncle to the dentate nucleus. Both the right hand and foot tremor improved with right cerebellar stimulation. Further, both the left hand and foot dystonia improved with left cerebellar stimulation. Right and left cerebellar stimulation led to no improvement in the left hand and foot dystonia and right hand and foot tremor, respectively. Stimulation-induced complications observed in the patient included dizziness, dysphagia, and dysarthria. After the surgery, the patient developed hypersalivation and hyperhidrosis in the left side of the body, both of which did not improve with adjustments of stimulation parameters. At the 6-month follow-up, the tremor and dystonia had almost completely resolved.Conclusion: Deep cerebellar stimulation deserves consideration as a potential treatment for tremor and dystonia.
Case Report: Management of a Patient With Chylomicronemia Syndrome During Pregnancy With Medical Nutrition Therapy
Authors: Zahedi Maryam , Asghari Golaleh , Mirmiran Parvin , Hosseinpanah Farhad 
Published: March 2021

Background: Hypertriglyceridemia (HTG) during pregnancy may be accompanied by acute pancreatitis, hyperviscosity syndrome, and preeclampsia. HTG during pregnancy should be managed by a multidisciplinary team; however, no clinical guidelines exist for severe gestational HTG.Case Presentation: We herein present a case of a 36-year-old in the first pregnancy (G1P0Ab0), with a history of severe HTG-induced necrotizing pancreatitis 9 years earlier. There was no family history of HTG. During these years, she did not follow any appropriate diet or medical therapy for HTG. She became pregnant in May 2019, without preconception counseling. Eruptive and tuberoeruptive xanthomas appeared in the 27th week of pregnancy. Serum triglycerides (TGs) and fasting blood sugar (FBS) were 6,620 and 124 mg/dL, respectively, indicating HTG and gestational diabetes (GDM). After admission for the management of severe HTG, she was put on parenteral nutrition with dextrose water 5% and infusion insulin therapy without receiving any enteral carbohydrate for 2 days. Following that, a very low-fat diet and omega-3 fatty acids (1,200 mg/day) were started. After 4 weeks, TG levels reached 1,000 mg/dL, and her self-monitoring blood glucose levels showed appropriate blood glucose for pregnancy. She underwent a successful elective cesarean section in the 39th of pregnancy.Conclusion: This case report demonstrates that HTG during pregnancy could be managed by medical nutrition therapy (MNT).
Characterization of Tumor Microenvironment in Lung Adenocarcinoma Identifies Immune Signatures to Predict Clinical Outcomes and Therapeutic Responses
Authors: Chen Donglai , Wang Yifei , Zhang Xi , Ding Qifeng , Wang Xiaofan , Xue Yuhang , Wang Wei , Mao Yiming , Chen Chang , Chen Yongbing 
Published: March 2021

Background and ObjectiveIncreasing evidence has elucidated the clinicopathological significance of individual TME component in predicting outcomes and immunotherapeutic efficacy in lung adenocarcinoma (LUAD). Therefore, we aimed to investigate whether comprehensive TME-based signatures could predict patient survival and therapeutic responses in LUAD, and to assess the associations among TME signatures, single nucleotide variations and clinicopathological characteristics.MethodsIn this study, we comprehensively estimated the TME infiltration patterns of 493 LUAD patients and systematically correlated the TME phenotypes with genomic characteristics and clinicopathological features of LUADs using two proposed computational algorithms. A TMEscore was then developed based on the TME signature genes, and its prognostic value was validated in different datasets. Bioinformatics analysis was used to evaluate the efficacy of the TMEscore in predicting responses to immunotherapy and chemotherapy.ResultsThree TME subtypes were identified with no prognostic significance exhibited. Among them, naïve B cells accounted for the majority in TMEcluster1, while M2 TAMs and M0 TAMs took the largest proportion in TMEcluster2 and TMEcluster3, respectively. A total of 3395 DEGs among the three TME clusters were determined, among which 217 TME signature genes were identified. Interestingly, these signature genes were mainly involved in T cell activation, lymphocyte proliferation and mononuclear cell proliferation. With somatic variations and tumor mutation burden (TMB) of the LUAD samples characterized, a genomic landscape of the LUADs was thereby established to visualize the relationships among the TMEscore, mutation spectra and clinicopathological profiles. In addition, the TMEscore was identified as not only a prognosticator for long-term survival in different datasets, but also a predictive biomarker for the responses to immune checkpoint blockade (ICB) and chemotherapeutic agents. Furthermore, the TMEscore exhibited greater accuracy than other conventional biomarkers including TMB and microsatellite instability in predicting immunotherapeutic response (p &lt; 0.001).ConclusionIn conclusion, our present study depicted a comprehensive landscape of the TME signatures in LUADs. Meanwhile, the TMEscore was proved to be a promising predictor of patient survival and therapeutic responses in LUADs, which might be helpful to the future administration of personalized adjuvant therapy.
Daratumumab as Single Agent in Relapsed/Refractory Myeloma Patients: A Retrospective Real-Life Survey
Authors: Markovic Uros , Romano Alessandra , Del Fabro Vittorio , Bellofiore Claudia , Bulla Anna , Parisi Marina Silvia , Leotta Salvatore , Gentile Massimo , Cangialosi Clotilde , Vincelli Iolanda , Mineo Giuseppe , Rossi Marco , Poidomani Massimo , Uccello Giuseppina , Maugeri Cinzia , Mannina Donato , Innao Vanessa , Di Raimondo Francesco , Conticello Concetta 
Published: March 2021

BackgroundThe anti-CD38 monoclonal antibody daratumumab is approved as a single agent for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) who received at least three prior lines of therapy, including proteasome inhibitor and immunomodulatory agent. A retrospective multicentric study was designed to evaluate feasibility, tolerability, and efficacy of daratumumab in monotherapy in RRMM.MethodsThis study included 44 consecutive RRMM patients that underwent daratumumab monotherapy after a median number of four prior therapies (range 2–9). Patients were treated in seven Sicilian centers, as part of Sicilian Myeloma Network and three Calabrian centers outside of controlled clinical trials from August 2016 through July 2020.ResultsThe regimen was well tolerated with few grade 3–4 haematological and rare non-haematological adverse events, such as pneumonia. Definitive discontinuation was due to disease progression in 25 (57%) patients. Since three patients did not complete at least one full cycle, a total of 41 patients was evaluated for response. Overall response rate was 37%, and the disease control rate (stable disease or better) was high (73%). The best achieved responses within 6 months were very good partial remission or better (27%), partial remission (10%), minimal response (14%) and stable disease (22%). After a median follow up of 7.8 months, median progression free survival (PFS) was 7.2 months and overall survival (OS) 7.8 months. Univariate analysis showed that patients with PR or better after 6 months of therapy had longer median PFS and OS (respectively 29.5 vs 3.6 months, p=0.0001 and 30.6 vs 3.9 months p=0.0001), confirmed by multivariate analysis. Furthermore, standard cytogenetic risk and biochemical relapse type had prolonged median PFS, but not OS (respectively unreached vs 2.6, p=0.03 and 23.9 vs 6.2, p=0.05) in both univariate and multivariate analysis. Additionally, univariate analysis showed that patients treated with carfilzomib-lenalidomide-dexamethasone prior to daratumumab had significantly shorter PFS compared to pomalidomide-dexamethasone (3.4 months vs 9.3 months, p=0.03), that multivariate analysis failed to confirm.ConclusionsOur findings indicate that daratumumab as single agent is safe and well-tolerated regimen in real-life, associated to prolonged PFS and OS in responding patients. No new safety signals were identified.
West Syndrome Is an Exceptional Presentation of Pyridoxine- and Pyridoxal Phosphate-Dependent Epilepsy: Data From a French Cohort and Review of the Literature
Authors: Gibaud Marc , Barth Magalie , Lefranc Jérémie , Mention Karine , Villeneuve Nathalie , Schiff Manuel , Maurey Hélène , Barthez Marie-Anne , Caubel Isabelle , Chouchane Mondher , Doummar Diane , Kossorotoff Manoëlle , Lamblin Marie-Dominique , Roubertie Agathe , Nabbout Rima , Van Bogaert Patrick 
Published: March 2021

Objective: To characterize the electro-clinical presentation of patients with pyridoxine-dependent epilepsy (PDE) and pyridoxal phosphate (PLP)-dependent epilepsy in order to determine whether some of them could be diagnosed as de novo West syndrome, i. e., West syndrome that starts after the age of 2 months without other types of seizures (focal seizures for instance) before the onset of epileptic spasms.Methods: We analyzed data from an unpublished cohort of 28 genetically confirmed cases of PDE with antiquitine (ATQ) deficiency and performed a review of the literature looking for description of West syndrome in patients with either PDE with ATQ deficiency or PLP-dependent epilepsy with Pyridox(am)ine phosphate oxidase (PNPO) deficiency.Results: Of the 28 cases from the ATQ deficiency French cohort, 5 had spasms. In four cases, spasms were associated with other types of seizures (myoclonus, focal seizures). In the last case, seizures started on the day of birth. None of these cases corresponded to de novo West syndrome. The review of the literature found only one case of PNPO deficiency presenting as de novo West syndrome and no case of ATQ deficiency.Significance: The presentation of PDE- and PLP-dependent epilepsy as de novo West syndrome is so exceptional that it probably does not justify a systematic trial of pyridoxine or PLP. We propose considering a therapeutic trial with these vitamins in West syndrome if spasms are associated with other seizure types or start before the age of 2 months.
The Effectiveness and Safety of Commonly Used Injectates for Ultrasound-Guided Hydrodissection Treatment of Peripheral Nerve Entrapment Syndromes: A Systematic Review
Authors: Buntragulpoontawee Montana , Chang Ke-Vin , Vitoonpong Timporn , Pornjaksawan Sineenard , Kitisak Kittipong , Saokaew Surasak , Kanchanasurakit Sukrit 
Published: March 2021

Background: Peripheral nerve entrapment syndromes commonly result in pain, discomfort, and ensuing sensory and motor impairment. Many conservative measures have been proposed as treatment, local injection being one of those measures. Now with high-resolution ultrasound, anatomical details can be visualized allowing diagnosis and more accurate injection treatment. Ultrasound-guided injection technique using a range of injectates to mechanically release and decompress the entrapped nerves has therefore developed called hydrodissection or perineural injection therapy. Several different injectates from normal saline, local anesthetics, corticosteroids, 5% dextrose in water (D5W), and platelet-rich plasma (PRP) are available and present clinical challenges when selecting agents regarding effectiveness and safety.Aims: To systematically search and summarize the clinical evidence and mechanism of different commonly used injectates for ultrasound-guided hydrodissection entrapment neuropathy treatment.Methods: Four databases, including PubMed, EMBASE, Scopus, and Cochrane were systematically searched from the inception of the database up to August 22, 2020. Studies evaluating the effectiveness and safety of different commonly used injectates for ultrasound-guided hydrodissection entrapment neuropathy treatment were included. Injectate efficacy presents clinical effects on pain intensity, clinical symptoms/function, and physical performance, electrodiagnostic findings, and nerve cross-sectional areas. Safety outcomes and mechanism of action of each injectate were also described.Results: From ten ultrasound-guided hydrodissection studies, nine studies were conducted in carpal tunnel syndrome and one study was performed in ulnar neuropathy at the elbow. All studies compared different interventions with different comparisons. Injectates included normal saline, D5W, corticosteroids, local anesthetics, hyaluronidase, and PRP. Five studies investigated PRP or PRP plus splinting comparisons. Both D5W and PRP showed a consistently favorable outcome than those in the control group or corticosteroids. The improved outcomes were also observed in comparison groups using injections with normal saline, local anesthetics, or corticosteroids, or splinting. No serious adverse events were reported. Local steroid injection side effects were reported in only one study.Conclusion: Ultrasound-guided hydrodissection is a safe and effective treatment for peripheral nerve entrapment. Injectate selection should be considered based on the injectate mechanism, effectiveness, and safety profile.
A Modified Version of the Transactional Stress Concept According to Lazarus and Folkman Was Confirmed in a Psychosomatic Inpatient Sample
Authors: Obbarius Nina , Fischer Felix , Liegl Gregor , Obbarius Alexander , Rose Matthias 
Published: March 2021

BackgroundStress is a major risk factor for the impairment of psychological well-being. The present study aimed to evaluate the empirical evidence of the Transactional Stress Model proposed by Lazarus and Folkman in patients with psychosomatic health conditions.MethodsA structural equation model was applied in two separate subsamples of inpatients from the Department of Psychosomatic Medicine (totaln= 2,216) for consecutive model building (sample 1,n= 1,129) and confirmatory analyses (sample 2,n= 1,087) using self-reported health status information about perceived stress, personal resources, coping mechanisms, stress response, and psychological well-being.ResultsThe initial model was created to reflect the theoretical assumptions by Lazarus and Folkman about their transactional stress concept. This model was modified until a sufficient model fit was reached (sample 1: CFI = 0.904, TLI = 0.898, RMSEA = 0.072 [0.071–0.074], SRMR = 0.061). The modified model was confirmed in a second sample (sample 2: CFI = 0.932, TLI = 0.928, RMSEA = 0.066 [0.065–0.068], SRMR = 0.052). Perceived external stressors and personal resources explained 91% of the variance of the stress response, which was closely related to symptoms of depression (63% variance explained). The attenuating effect of resources on stress response was higher (standardized β = -0.73,p&lt; 0.001) than the impact of perceived stressors on stress response (standardized β = 0.34,p&lt; 0.001).ConclusionThe empirical data largely confirmed the theoretical assumption of the Transactional Stress Model, which was first presented by Lazarus and Folkman, in patients with a wide range of psychosomatic conditions. However, data analyses were solely based on self-reported health status. Thus, proposed inner psychological mechanisms such as the appraisal process could not be included in this empirical validation. The operationalization and understanding of coping processes should be further improved.
IMPLEMENTASI IoT(Internet Of Things) MONITORING KUALITAS AIR DAN SISTEM ADMINISTRASI PADA PENGELOLA AIR BERSIH SKALA KECIL
Authors: Febrianti Fitri , Adi Wibowo Suryo , Vendyansyah Nurlaily 
Published: March 2021

Kebutuhan air bersih untuk masyarakat Indonesia sangatlah penting. Baik itu digunakan untuk air minum , memasak, mandi dan mencuci. Namun kebutuhan air bersih ini sangat sulit di penuhi di daerah yang jauh dari sumber mata air, terlebih lagi sumur-sumur milik pribadi. Kebanyakan sumber air yang diperoleh dari sumur sering sekali keruh dan pH airnya tidak sesuai dari batas nomal. Salah satunya di desa Pangkalan lada , Kalimantan Tengah. Masih banyak penduduknya menggunakan sumur tadah hujan yang kualitas airnya tidak selau baik. Dengan adanya masalah tersebut , solusi yang dapat di terapkan adalah monitoring kualitas air untuk menetukan baik buruknya kualitas air agar bisa digunakan oleh masyarakat.
Dikembangkan implementasi IoT(internet of things) monitoring kualitas air dan sistem administrasi pada pengelola air bersih skala kecil yang menampilkan keadaan secara visual pada fitur monitoring dapat dikendalikan secara efisien dengan media wireless melalui website. Disamping itu dengan ditambahkannya sebuah sensor untuk mendeteksi kadar pH air dan penyaringannya dapat membantu penduduk yang sulit mendapatkan air bersih maupun menetukan bahwa air tersebut layak tidaknya untuk di konsumsi. Serta menampilkan biaya penggunaan PDAM dalam kurun waktu bulanan pada website monitoring yang didapatkan dari data sensor flow meter. Pengembangan ini termasuk dalam pengelolaan smart city skala kecil, karena pengembangan alat ini membantu penduduk untuk lebih moderenisasi alat-alat dalam kehidupan sehari- hari .
Dari Implementasi IoT(internet of things) monitoring kualitas air dan sistem administrasi dilakukan pengujian pada Setiap alat yang dilakukan pada setiap sensor yang di gunakan pada tiap alat . Diperoleh Hasil pengujian menunjukkan bahwa sensor pH didapatkan nilai 7.00 untuk air mineral, air lemon 5.9, air sabun 10.4, dan dengan indikasi lakmus dalam penentuan asam basa pada air. Pengujian diperoleh pada sensor turbidity terhadap air bersih didapatkan nilai rata-rata error0.12%, teh 0.02%, dan air kopi 0.08%.