bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autophagy-dependent cell cycle arrest in esophageal cancer cells exposed to dihydroartemisinin
Authors: Ma Qiang , Liao Hebin , Xu Lei , Li Qingrong , Zou Jiang , Sun Ru , Xiao Dan , Liu Chang , Pu Wenjie , Cheng Jibing , Zhou Xi , Huang Guangcheng , Yao Lihua , Zhong Xiaowu , Guo Xiaolan 
Published: April 2020

Abstract
Background
Dihydroartemisinin (DHA), a derivate of artemisinin, is an effective antimalarial agent. DHA has been shown to exert anticancer activities to numerous cancer cells in the past few years, while the exact molecular mechanisms remain to be elucidated, especially in esophageal cancer.

Methods
Crystal violet assay was conducted to determine the cell viability of human esophageal cancer cell line Eca109 treated with DHA. Tumor-bearing nude mice were employed to evaluate the anticancer effect of DHA in vivo. Soft agar and crystal violet assays were used to measure the tumorigenicity of Eca109 cells. Flow cytometry was performed to evaluate ROS or cell cycle distribution. GFP-LC3 plasmids were delivered into Eca109 cells to visualize autophagy induced by DHA under a fluorescence microscope. The mRNA and protein levels of each gene were tested by qRT-PCR and western blot, respectively.

Results
Our results proved that DHA significantly reduced the viability of Eca109 cells in a dose- and time-dependent manner. Further investigation showed that DHA evidently induced cell cycle arrest at the G2/M phase in Eca109 cells. Mechanistically, DHA induced intracellular ROS generation and autophagy in Eca109 cells, while blocking ROS by an antioxidant NAC obviously inhibited autophagy. Furthermore, we found that telomere shelterin component TRF2 was down-regulated in Eca109 cells exposed to DHA through autophagy-dependent degradation, which could be rescued after autophagy was blocked by ROS inhibition. Moreover, the DNA damage response (DDR) was induced obviously in DHA treated cells. To further explore whether ROS or autophagy played a vital role in DHA induced cell cycle arrest, the cell cycle distribution of Eca109 cells was evaluated after ROS or autophagy blocking, and the results showed that autophagy, but not ROS, was essential for cell cycle arrest in DHA treated cells.

Conclusion
Taken together, DHA showed anticancer effect on esophageal cancer cells through autophagy-dependent cell cycle arrest at the G2/M phase, which unveiled a novel mechanism of DHA as a chemotherapeutic agent, and the degradation of TRF2 followed by DDR might be responsible for this cell phenotype.
Treatment outcomes following continuous miglustat therapy in patients with Niemann-Pick disease Type C: a final report of the NPC Registry
Authors: Patterson Marc C. , Mengel Eugen , Vanier Marie T. , Moneuse Patrick , Rosenberg Daniel , Pineda Mercedes 
Published: April 2020

Abstract
Background
Niemann-Pick disease Type C (NP-C) is a rare, progressive neurodegenerative disorder characterized by progressive neurodegeneration and premature death. We report data at closure of the NPC Registry that describes the natural history, disease course and treatment experience of NP-C patients in a real-world setting.

Methods
The NPC Registry was a prospective observational cohort study that ran between September 2009 and October 2017. Patients with a confirmed diagnosis of NP-C were enrolled regardless of treatment status. All patients underwent clinical assessments and medical care as determined by their physicians; data were collected through a secure internet-based portal.

Results
At closure on October 19, 2017, 472 patients from 22 countries were enrolled in the NPC Registry. Mean (standard deviation) age at enrollment was 21.2 (15.0) years, and 51.9% of patients were male. First neurological symptom onset occurred during the early-infantile (< 2 years), late-infantile (2 to < 6 years), juvenile (6 to < 15 years), or adolescent/adult (≥ 15 years) periods in 13.5, 25.6, 31.8, and 29.1% of cases, respectively. The most frequent neurological manifestations prior to enrollment included ataxia (67.9%), vertical supranuclear gaze palsy (67.4%), dysarthria (64.7%), cognitive impairment (62.7%), dysphagia (49.1%), and dystonia (40.2%). During infancy, splenomegaly and hepatomegaly were frequent (n = 199/398 [50%] and n = 147/397 [37.0%], respectively) and persisted in most affected patients. Of the 472 enrolled patients, 241 were continuously treated with miglustat during the NPC Registry observation period, of whom 172 of these 241 patients were treated continuously for ≥12 months. A composite disability score that assesses impairment of ambulation, manipulation, language, and swallowing was highest in the early-infantile population and lowest in the adolescent/adult population. Among the continuous miglustat therapy population, 70.5% of patients had improved or had stable disease (at least 3 of the 4 domains having a decreased or unchanged score between enrollment and last follow-up). The NPC Registry did not identify any new safety signals associated with miglustat therapy.

Conclusions
The profiles of clinical manifestations in the final NPC Registry dataset agreed with previous clinical descriptions. Miglustat therapy was associated with a stabilization of neurological manifestations in most patients. The safety and tolerability of miglustat therapy was consistent with previous reports.
Validity and reliability of the Australian Therapy Outcome Measures – Physiotherapy, for podiatry (AusTOMs‐PT for use in podiatry)
Authors: Williams Cylie M. , Davies Nina , Kolic Jessica , Caserta Antoni , James Alicia M. , Unsworth Carolyn 
Published: April 2020

AbstractBackgroundValid and reliable outcome measure enable measurement of health care service impact. There are limited valid and reliable outcome measures for use in podiatry practice to measure the impact of treatment. This research aimed to test the face validity of the AusTOMs for Physiotherapy (AusTOMs‐PT), it's adaptability to podiatry clinical practice and the reliability of its use with podiatrists.MethodsStage 1 used a nominal group technique with podiatrists who worked in public and/or private settings. All podiatrists underwent self‐directed training in the AusTOMs framework and measures prior to interviews or focus group discussion. Discussion was centred about transferability of the core scales of the AusTOMs‐PT and an adjunct measure, AusTOMs for Occupational Therapy (AusTOMs‐OT) to podiatry practice.Stage 2 used 10 case studies representative of people who had foot or ankle concerns. Podiatrists were recruited and trained in the use of the relevant AusTOMs‐PT scales. Podiatrists individually scored the cases at two timepoints (1 month apart) using the six scales from the AusTOMs‐PT deemed by stage 1 as relevant to podiatry. Intra and inter‐rater reliability of scales were determined using intraclass correlation coefficients (ICCs).ResultsThirteen podiatrists participated in individual or focus group interviews in Stage 1. Consensus was gained on six of the nine core scales adopted from the AusTOMs‐PT. These were 1. Balance and Postural Control, 3. Musculoskeletal Movement Related Functions, 4. Neurological Movement Related Functions, 5. Pain, 7. Sensory Functions, 8. Skin Functions. Each core scale rated the functional domains of Impairment, Activity Limitation, Participation Restriction and Wellbeing/Distress relating to that presentation of goals of the person in the case study.There were 22 podiatrists complete training and scored two rounds of case studies using the six scales in Stage 2. There were 91%(n = 20) participants with an intra‐rater ICC > 0.5 (moderate or greater). Each domain had an inter‐rater reliability of > 0.9 (excellent) during the first round.ConclusionsThe AusTOMs‐PT for use in podiatry may be implemented to record change in impairment, function, participation and wellbeing of people receiving podiatry treatment. Podiatry specific training and mentoring, together with repeated use could be expected to improve intra‐reliability.
Ovarian endometrioma infiltrating neutrophils orchestrate immunosuppressive microenvironment
Authors: Xu Hua , Zhao Jing , Lu Jiaqi , Sun Xiaoxi 
Published: April 2020

Abstract
Background
Ovarian endometrioma (EM) lesions not only have overwhelmed the amount of infiltrating immune cells but also display immunosuppressive phenotype. The close relationship between neutrophils and the pathogenesis of endometriosis has been demonstrated. The present study aims to elucidate whether or not neutrophils are involved in the regulation of immunosuppressive microenvironment in ovarian endometrioma.

Methods
Immunochemistry (IHC) and flow cytometry analysis (FACS) were conducted to measure CD66b expression in ovarian endometrioma samples from EM patients. The correlation between percentage of CD66b and PD1 + CD8+, TIM3 + CD8+, CTLA4 + CD8+, IFN-γ + CD8+ of CD45+ cells were analyzed. Neutrophil survival and PD-L1 expression were determined under the stimulations of ovarian endometrioma conditional supernatants (OECS). Finally, CD8+ T cell’s proliferation and IFN-γ expression were detected under co-cultured with OECS cultured neutrophils stimulated with the α-CD3/α-CD28 antibody.

Results
IHC and FACS results revealed correlation between the counts of neutrophils and the severity of ovarian endometrioma. The percentage of CD66b + cells was positively correlated with PD1 + CD8+, TIM3 + CD8+ and CTLA4 + CD8+ of CD45+ cells in ovarian endometrioma. OECS promoted neutrophils’ survival and enhanced PD-L1 expression. OECS cultured neutrophils inhibited proliferation and activity of autologous T cells.

Conclusions
Neutrophils play a crucial role in the progression of ovarian endometrioma by orchestrated the immunosuppressive microenvironment under the PD-1/PD-L1 axis.
Comparison of the predictive performance of risk of malignancy indexes 1–4, HE4 and risk of malignancy algorithm in the triage of adnexal masses
Authors: Hada Abha , Han Li-ping , Chen Yanyan , Hu Qing-hong , Yuan Yidan , Liu Liya 
Published: April 2020

Abstract
Objectives
For patients presenting with adnexal mass, it is important to correctly distinguish whether the mass is benign or malignant for the purpose of precise and timely referral and implication of correct line of management. The objective of this study was to evaluate the performance of Risk of malignancy Indexes (RMI) 1–4, Human Epididymis Protein 4 (HE4) and Risk of Malignancy Algorithm (ROMA) in differentiating the adnexal mass into benign and malignant.

Methods
A retrospective study using 155 patients diagnosed with adnexal mass between January 2014 to December 2014 in The First Affiliated Hospital of Zhengzhou University was conducted. The patient records were assessed for age, menopausal status, serum CA125 and HE4 levels, ultrasound characteristics of the pelvic mass and the final pathological diagnosis of the mass. RMI1, RMI2, RMI3, RMI4, ROMA were calculated for each patient and the sensitivity, specificity and the Receiver Operating Characteristics (ROC) curves were determined for each test to evaluate their performance.

Results
Among 155 patients with adnexal masses meeting inclusion criteria, 120 (77.4%) were benign, 8 (5.2%) borderline and 27 (17.4%) were malignant. RMI2 and RMI4 had the highest sensitivity (66.7%) while HE4 had the highest specificity (96.9%).Although ROMA had the highest area under the curve (AUC) of 0.886 it was not found to be statistically superior to the other tests. For epithelial ovarian cancers, ROMA (80%), HE4 (96.9%) and RMI 4 (0.868) had the highest sensitivity, specificity and AUC respectively however, the AUC characteristics were not statistically significant between any groups. Compared to the postmenopausal group (sensitivity 72.2–77.8%) all the tests showed lower sensitivity (42.9%) for the premenopausal group of patients.

Conclusions
RMI 1–4, ROMA and HE4 were all found to be useful for differentiating benign/borderline adnexal masses from malignant ones for deciding optimal therapy, however no test was found to be significantly better than the other. None were able to differentiate between benign and borderline tumors. All of the tests demonstrated increased sensitivity when borderline tumors were considered low-risk, and when only epithelial ovarian cancers were considered.
Novel Coronavirus disease (COVID-19) in newborns and infants: what we know so far
Authors:   The Study Group of Neonatal Infectious Diseases of The Italian Society of Neonatology (SIN), De Rose Domenico Umberto , Piersigilli Fiammetta , Ronchetti Maria Paola , Santisi Alessandra , Bersani Iliana , Dotta Andrea , Danhaive Olivier , Auriti Cinzia 
Published: April 2020

AbstractRecently, an outbreak of viral pneumonitis in Wuhan, Hubei, China successively spread as a global pandemia, led to the identification of a novel betacoronavirus species, the 2019 novel coronavirus, successively designated 2019-nCoV then SARS-CoV-2). The SARS-CoV-2 causes a clinical syndrome designated coronavirus disease 2019 (COVID19) with a spectrum of manifestations ranging from mild upper respiratory tract infection to severe pneumonitis, acute respiratory distress syndrome (ARDS) and death. Few cases have been observed in children and adolescents who seem to have a more favorable clinical course than other age groups, and even fewer in newborn babies. This review provides an overview of the knowledge on SARS-CoV-2 epidemiology, transmission, the associated clinical presentation and outcomes in newborns and infants up to 6 months of life.
CEOP/IVE/GDP alternating regimen compared with CEOP as the first-line therapy for newly diagnosed patients with peripheral T cell lymphoma: results from a phase 2, multicenter, randomized, controlled clinical trial
Authors: Cai Ming-Ci , Cheng Shu , Wang Xin , Hu Jian-Da , Song Yong-Ping , Huang Yao-Hui , Yan Zi-Xun , Jiang Yu-Jie , Fang Xiao-Sheng , Zheng Xiao-Yun , Dong Li-Hua , Ji Meng-Meng , Wang Li , Xu Peng-Peng , Zhao Wei-Li 
Published: April 2020

Abstract
Background
Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)/CHOP-like chemotherapy is widely used in peripheral T cell lymphoma (PTCL). Here we conducted a phase 2, multicenter, randomized, controlled trial, comparing the efficacy and safety of CEOP/IVE/GDP alternating regimen with CEOP in newly diagnosed PTCL.

Methods
PTCL patients, except for anaplastic large cell lymphoma-anaplastic lymphoma kinase positive, were 1:1 randomly assigned to receive CEOP/IVE/GDP (CEOP, cyclophosphamide 750 mg/m2, epirubicin 70 mg/m2, vincristine 1.4 mg/m2 [maximum 2 mg] on day 1, and prednisone 60 mg/m2 [maximum 100 mg] on days 1–5 every 21 days, at the first and fourth cycle; IVE, ifosfamide 2000 mg/m2 on days 1–3, epirubicin 70 mg/m2 on day 1, and etoposide 100 mg/m2 on days 1–3 every 21 days, at the second and fifth cycle; and GDP, gemcitabine 1000 mg/m2 on days 1 and 8, cisplatin 25 mg/m2 on days 1–3, and dexamethasone 40 mg on days 1–4 every 21 days, at the third and sixth cycle) and CEOP (every 21 days for 6 cycles). Analysis of efficacy and safety was of the intent-to-treatment population. The primary endpoint was a complete response rate at the end of treatment. Meanwhile, whole exome sequencing and targeted sequencing were performed in 62 patients with available tumor samples to explore prognostic biomarkers in this cohort as an exploratory post hoc analysis.

Results
Among 106 patients, 53 each were enrolled to CEOP/IVE/GDP and CEOP. With 51 evaluable patients each in two groups, a complete response rate of the CEOP/IVE/GDP group was similar to that of the CEOP group (37.3% vs. 31.4%, p = 0.532). There was no difference in median progression-free survival (PFS; 15.4 months vs. 9.2 months, p = 0.122) or overall survival (OS; 24.3 months vs. 21.9 months, p = 0.178). Grade 3–4 hematological and non-hematological adverse events were comparable. Histone modification genes were most frequently mutated (25/62, 40.3%), namely KMT2D, KMT2A, SETD2, EP300, and CREBBP. Multivariate analysis indicated that CREBBP and IDH2 mutations were independent factors predicting poor PFS and OS (all p < 0.001), while KMT2D predicting poor PFS (p = 0.002).

Conclusions
CEOP/IVE/GDP alternating regimen showed no remission or survival advantage to standard chemotherapy. Future clinical trials should aim to develop alternative regimen targeting disease biology as demonstrated by recurrent mutations in epigenetic factors.

Trial registration
The study was registered on ClinicalTrial.gov (NCT02533700) on August 27, 2015.
Obstructive sleep apnea and the risk of gout: a population-based case-control study
Authors: van Durme Caroline , Spaetgens Bart , Driessen Johanna , Nielen Johannes , Sastry Manuel , Boonen Annelies , de Vries Frank 
Published: April 2020

Abstract
Background
Patients with obstructive sleep apnea (OSA) might be at risk of gout because of pathophysiological mechanisms that can lead to hyperuricemia and eventually gout or because of shared risk factors between both diseases. The objective of the present study was to investigate the risk of gout in patients with OSA.

Methods
A population-based case-control study using the UK Clinical Practice Research Datalink GOLD including all patients aged 40 years and older with a first diagnosis of gout between 1987 and 2014. Gout cases were matched by year of birth, sex, and practice to non-gout controls. Conditional logistic regression estimated the risk of gout with an earlier diagnosis of OSA. Analyses were adjusted for lifestyle factors, comorbidities, and recent drug use.

Results
One hundred eleven thousand five hundred nine cases were matched with 210,241 controls. Patients with OSA were at increased risk of gout (OR 1.86; 95%CI (1.71–2.02). However, this association disappeared (OR 1.05; 95% CI 0.96–1.16) after adjustment for smoking status, body mass index (BMI), alcohol use, a history of heart failure, diabetes mellitus, renal function, and recent use of diuretics and other medications. Among females with OSA and patients with OSA associated with heart failure, renal impairment, or higher BMI, the risk of gout was however still increased when compared to the total control population.

Conclusion
This study showed that the observed association between OSA and gout disappeared after adjustment.
The effect of a sand surface on physical performance responses of junior male handball players to plyometric training
Authors: Hammami Mehrez , Bragazzi Nicola Luigi , Hermassi Souhail , Gaamouri Nawel , Aouadi Ridha , Shephard Roy J. , Chelly Mohamed Souhaiel 
Published: April 2020

Abstract
Background
The effects of 7 weeks plyometric training on a stable surface and on sand were compared in junior male handball players.

Methods
A team of experienced players was divided randomly between three groups, undertaking a standard in-season regimen (C, n = 10), or supplementing this regimen by plyometric training on sand (PS, n = 11) or a stable surface (P, n = 10) for 7 weeks. Assessments included 20 m sprint times, change of direction tests (Modified change-of-direction T-test and Modified Illinois test), a repeated sprint T-test, jumping ability (squat, countermovement and five jump tests), and static and dynamic balance.

Results
After the intervention, PS showed significant increases of sprint speed relative to P and C. Change of direction scores were also improved for PS relative to P and C. Both PS and P increased vertical jump performance (squat jump, p = 0.005; ES = 0.170; counter-movement jump p < 0.001; ES = 0.247). Repeated sprint T-test scores improved in PS and P relative to C, with best times of PS > P (p < 0.05). Both plyometric groups improved their dynamic balance (p < 0.05), with three parameters of PS and only one of P being significantly greater than C. Static balance was also enhanced in both experimental groups (PS > P).

Conclusions
We conclude that for reasons that remain to be clarified, several performance measures in adolescent male handball players were increased more by 7 weeks of PS than by P.
Prevalence of trypanosomes associated with drug resistance in Shimba Hills, Kwale County, Kenya
Authors: Kulohoma Benard W. , Wamwenje Sarah A. O. , Wangwe Ibrahim I. , Masila Nicodemus , Mirieri Caroline K. , Wambua Lillian 
Published: April 2020

Abstract
Objective
Animal African trypanosomiasis (AAT) is a life-threatening vector-borne disease, caused by trypanosome parasites, which are principally transmitted by tsetse flies. In Kenya, the prevalence of drug-resistant trypanosomes in endemic regions remains poorly understood. The objective of this study was to establish AAT point prevalence, drug susceptibility of associated trypanosomes, and measure infectivity by multiple AAT mammalian hosts to tsetse flies in Shimba hills, a resource-poor region with high bovine trypanosomiasis prevalence and morbidity rates at the coast of Kenya. We collected tsetse flies using traps (1 Ngu and 2 biconical), and then sorted them on sex and species. Trypanosomes present in tsetse flies were detected by first extracting all genomic DNA, and then performing PCR reactions with established primers of the internal transcribed spacer regions. Polymorphisms associated with trypanocide resistance in the TbAT1 gene were also detected by performing PCR reactions with established primers.

Results
Our findings suggest low trypanosome prevalence (3.7%), low trypanocide resistance, and low infectivity by multiple mammalian hosts to tsetse flies in Shimba hills. We conclude that enhanced surveillance is crucial for informing disease management practices that help prevent the spread of drug-resistant trypanosomiasis.