bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment response lowers tumor symptom burden in recurrent and/or metastatic head and neck cancer
Authors: Hecht Markus , Hahn Dennis , Wolber Philipp , Hautmann Matthias G. , Reichert Dietmar , Weniger Steffi , Belka Claus , Bergmann Tobias , Göhler Thomas , Welslau Manfred , Große-Thie Christina , Guntinas-Lichius Orlando , Gruen Jens von der , Balermpas Panagiotis , Orlowski Katrin , Messinger Diethelm , Stenzel Karsten G. , Fietkau Rainer 
Published: September 2020

Abstract
Background: Head and neck squamous cell cancer (HNSCC) frequently causes severe symptoms that may be reduced, when the tumor is successfully treated. The SOCCER trial studied the association of treatment response with patient reported tumor symptom burden in first line treatment of recurrent and/or metastatic HNSCC.Methods: In this prospective, multi-center, non-interventional trial patients were treated either with platinum-based chemotherapy and cetuximab or radiotherapy and cetuximab. Tumor symptom burden was assessed every four weeks with a questionnaire containing ten visual analogue scales (VAS, range 0-100), which were summarized to the overall VAS score.Results: 470 patients were registered in 97 German centers. A total of 315 patients with at least the baseline and one subsequent questionnaire were available for analysis. Changes in the VAS score were rated as absolute differences from baseline. Negative values indicate improvement of symptoms. The overall VAS score improved significantly at the first post-baseline assessment in responders (-2.13 vs. non-responders +1.15, p=0.048), and even more for the best post-baseline assessment (-7.82 vs. non-responders -1.97, p=0.0005). The VAS for pain (-16.37 vs. non-responders -8.89, p=0.001) and swallowing of solid food (-16.67 vs. non-responders -5.06, p=0.002) improved significantly more in responders (best post-baseline assessment). In the multivariable Cox regression analysis, worse overall VAS scores were associated with worse overall survival (hazard ratio for death 1.12 per 10 points increment on the overall VAS scale, 95% CI 1.05-1.20, p=0.0009)Conclusion: In unselected patients beyond randomized controlled trials, treatment response lowers tumor symptom burden in recurrent and/or metastatic HNSCC.Trial registration: ClinicalTrials.gov, NCT00122460. Registered 22 Juli 2005, https://clinicaltrials.gov/ct2/show/NCT00122460
Enhanced differentiation of human pluripotent stem cells into pancreatic endocrine cells in 3D culture by inhibition of focal adhesion kinase
Authors: Liu Xiaofang , Qin Jinhua , Chang Mingyang , Wang Shuyong , Li Yali , Pei Xuetao , Wang Yunfang 
Published: September 2020

Abstract
Background: Generation of insulin-producing cells from human pluripotent stem cells (hPSCs) in vitro would be useful for drug discovery and cell therapy in diabetes. Three-dimensional (3D) culture is important for the acquisition of mature insulin-producing cells from hPSCs, but the mechanism by which it promotes β cell maturation is poorly understood.Methods: We established a stepwise method to induce high-efficiency differentiation of human embryonic stem cells (hESCs) into mature monohormonal pancreatic endocrine cells (PECs), with the last maturation stage in 3D culture. To comprehensively compare two-dimensional (2D) and 3D culture, we examined gene expression, pancreas-specific markers and functional characteristics in 2D culture-induced PECs and 3D culture-induced PECs. The mechanisms were considered from the perspectives of cell-cell and cell-extracellular matrix interactions which are fundamentally different between 2D and 3D culture.Results: The expression of the pancreatic endocrine-specific transcription factors PDX1, NKX6.1, NGN3, ISL1, and PAX6 and the hormones INS, GCG, and SST was significantly increased in 3D culture-induced PECs. 3D culture yielded monohormonal endocrine cells, while 2D culture-induced PECs co-expressed INS and GCG or INS and SST or even expressed all three hormones. We found that focal adhesion kinase (FAK) phosphorylation was significantly downregulated in 3D culture-induced PECs, and treatment with the selective FAK inhibitor PF-228 improved the expression of β cell-specific transcription factors in 2D culture-induced PECs. We further demonstrated that 3D culture may promote endocrine commitment by limiting FAK-dependent activation of the SMAD2/3 pathway. Moreover, the expression of the gap junction protein Connexin 36 was much higher in 3D culture-induced PECs than in 2D culture-induced PECs, and inhibition of the FAK pathway in 2D culture increased Connexin 36 expression. Conclusion: We developed a strategy to induce differentiation of monohormonal mature PECs from hPSCs and found limited FAK-dependent activation of the SMAD2/3 pathway and unregulated expression of Connexin 36 in 3D culture-induced PECs. This study has important implications for the generation of mature, functional β cells for drug discovery and cell transplantation therapy for diabetes, and sheds new light on the signalling events that regulate endocrine specification.
Exploring the experiences of stroke patients treated with transcranial magnetic stimulation for upper limb recovery: a qualitative study
Authors: Lieshout Eline CC van , Jacobs Lilliane D , Pelsma Maaike , Dijkhuizen Rick M , Visser-Meily Johanna MA 
Published: September 2020

Abstract
Background: Transcranial magnetic stimulation (TMS) treatments have shown promise in improving arm recovery in stroke patients. Currently, little is known about patients’ experiences with TMS treatment, and this lack of knowledge may affect optimal implementation in clinical practice. The aim of this explorative study was to gain insight in the perceived effects and experiences of the design and delivery of a TMS treatment for upper limb recovery from the perspectives of stroke patients.Methods: This qualitative study was conducted as part of a randomized controlled trial (RCT) in a specialized rehabilitation center. Data were collected through face-to-face semi-structured interviews with 13 stroke patients who completed a 10-day TMS intervention for upper limb recovery. The interviews were recorded, transcribed verbatim and analyzed using thematic analysis.Results: The major themes that emerged from the patients’ feedback were the following: positive experiences of the treatment (experienced physical effects, comfort, therapeutic relationship, receiving information, learning about the brain, no burden of added rTMS treatment session, no unpleasant aspects), concerns (effects of stimulation of the brain, equipment, logistics), general experience of recovery, experienced psychological effects (grateful, sense of purpose, recovery as extra motivation to exercise, disappointment and hope of group allocation), and motivation to participate (personal benefit and cognitions, altruism). Important components related to the positive experience of the design and delivery of the treatment included comfort (i.e. moment of relaxation) and the sensation of a painless treatment without side-effects. Key concerns included uncertainty and anxiety about possible negative consequences and group allocation.Conclusions: This study demonstrates that TMS is well accepted by stroke patients with an upper limb paresis. Besides the expectation of a therapeutic benefit, the patients reported various psychological effects. Positive experiences, such as the provision of a short moment of relaxation each day, could have practical implications for clinical stroke rehabilitation settings aimed at improving patient satisfaction. Explanation about and feedback from routine motor recovery progression monitoring at fixed times post-stroke is also valued by patients. Negative emotions may be limited or avoided by transparent and recurrent information delivery in future trials.
Clinical Phenotypes and Heath-Related Quality of Life of COPD Patients in a Rural Setting in Malaysia – A Cross-Sectional Study
Authors: Chai Chee-Shee , Mos Sumastika Bt , Ng Diana-Leh-Ching , Goh Greta-Miranda-Kim-Choo , Su Anselm-Ting , Ibrahim Muhammad Amin Bin , Musa Aisya Natasya Bt , Tan Seng-Beng , Pang Yong-Kek , Liam Chong-Kim 
Published: September 2020

Abstract
Background

The Spanish chronic obstructive pulmonary disease (COPD) guideline phenotypes patients according to the exacerbation frequency and COPD subtypes. In this study, we compared the patients’ health-related quality of life (HRQoL) according to their COPD phenotypes.

Methods

This was a cross-sectional study of COPD patients who attended the outpatient clinic of the Serian Divisional Hospital and Bau District Hospital from 23 th January 2018 to 22 th January 2019. The HRQoL was assessed using modified Medical Research Council (mMRC), COPD Assessment Test (CAT), and St George's Respiratory Questionnaire for COPD (SGRQ-c).

Results

Of 185 patients, 108 (58.4%) were non-exacerbators (NON-AE), 51 (27.6%) were frequent exacerbators (AE), and the remaining 26 (14.1%) had asthma-COPD overlap (ACO). Of AE patients, 42 (82.4%) had chronic bronchitis and only 9 (17.6%) had emphysema. Of the COPD patients, 65.9% had exposure to biomass fuel.

The scores of mMRC, CAT, and SGRQ-c were significantly different between COPD phenotypes (p < 0.001). There were significantly more patients with mMRC 2 – 4 among AE (68.6%) (p < 0.001), compared to those with ACO (38.5%) and NON-AE (16.7%). AE patients had significantly higher total CAT (p = 0.003; p < 0.001) and SGRQ-c (both p < 0.001) scores than those with ACO and NON-AE. Patients with ACO also had significantly higher total CAT and SGRQ-c (both p < 0.001) scores than those with NON-AE.

AE patients had significantly higher score in each item of CAT and component of SGRQ-c compared to those with NON-AE (all p < 0.001), and ACO [(p = 0.003 – 0.016; p = < 0.001 – 0.005) except CAT 1, 2 and 7. ACO patients had significantly higher score in each item of CAT and component of SGRQ-c (p = < 0.001 – 0.040; p < 0.001) except CAT 2 and activity components of SGRQ-c.

Conclusions

The HRQoL of COPD patients was significantly different across COPD phenotypes. HRQoL was worst in AE, followed by ACO and NON-AE. This study supports phenotyping COPD patients based on their exacerbation frequency and COPD subtypes. The treatment of COPD should be personalised according to these two factors.
Evaluation of the standard procedure for the treatment of periprosthetic joint infections (PJI) in Germany - Results of a survey within the EndoCert initiative
Authors: Rimke Christina , Enz Andreas , Bail Hermann Josef , Heppt Peter , Kladny Bernd , von Lewinski Gabriela , Lohmann Christoph H. , Osmanski-Zenk Katrin , Haas Holger , Mittelmeier Wolfram 
Published: September 2020

Abstract
Background: The periprosthetic joint infection (PJI) is a severe complication in the field of arthroplasty. Despite the rising number of primary joint replacements, no unified therapeutic standard has been established for the treatment of PJI yet.Methods: A survey on the principles of treatment of PJI in Germany wasconducted. A total of 515 EndoProthetikZentren (EPZ) were included, resulting in a response rate of 100%.Results: For early infections 97.6% of the centers use prosthesis-preserving procedures (DAIR). A one-stage exchange was implemented by less than 50% of the centers. If implemented, this treatment entails a prior selection of patients for a successful treatment. The two-stage exchange is performed in all centers, and most centers proceed with the implantation of a cemented spacer between stages. 75% of the centers proceed with a center-based concept for the treatment of PJI.Conclusion: The aim of a uniform PJI standard at the centers has not yet been fully achieved. Further improvements within the certification were initiated. The most relevant treatment options in Germany are displayed. The two-stage revision with a cemented spacer is the most widely implemented treatment. This exposition of principles could help for the further development of standardized treatment guidelines and definitions.
Genetic analysis reveals unique characteristics of Plasmodium falciparum parasite populations in Haiti
Authors: Daniels Rachel , Chenet Stella , Rogier Eric , Lucchi Naomi , Herman Camelia , Pierre Baby , Lemoine Jean Frantz , Boncy Jacques , Wirth Dyann , Chang Michelle , Udhayakumar Venkatachalam , Volkman Sarah 
Published: September 2020

Abstract
Background: With increasing interest in eliminating malaria from the Caribbean region, Haiti is one of the two countries on the island of Hispaniola with continued malaria transmission. While the Haitian populace remains at risk for malaria, there are a limited number of cases annually, making conventional epidemiological measures such as case incidence and prevalence of potentially limited value for fine-scale resolution of transmission patterns and trends. In this context, genetic signatures may be useful for the identification and characterization of the Plasmodium falciparum parasite population in order to identify foci of transmission, detect outbreaks, and track parasite movement to potentially inform malaria control and elimination strategies. Methods: This study evaluated the genetic signals based on analysis of 21 single-nucleotide polymorphisms (SNPs) from 462 monogenomic (single-genome) P. falciparum DNA samples extracted from dried blood spots collected from malaria-positive patients reporting to health facilities in three southwestern Haitian departments (Nippes, Grand’Anse, and Sud) in 2016. Results: Assessment of the parasite genetic relatedness revealed evidence of clonal expansion within Nippes and the exchange of parasite lineages between Nippes, Sud, and Grand'Anse. Furthermore, 437 of the 462 samples shared high levels of genetic similarity­­—at least 20 of 21 SNPS—with at least one other sample in the dataset. Conclusions: These results revealed patterns of relatedness suggestive of the repeated recombination of a limited number of founding parasite types without significant outcrossing. These genetic signals offer clues to the underlying relatedness of parasite populations and may be useful for the identification of the foci of transmission and tracking of parasite movement in Haiti for malaria elimination.
Cutaneous Anthrax Outbreak Associated with Handling Dead Animals, Rhino Camp Sub-county: Arua District, Uganda, January-May2018
Authors: Ntono Vivian , Eurien Daniel , Bulage Lilian , Kadobera Daniel , Harris Julie , Ario Alex Riolexus 
Published: September 2020

Abstract
Background: On the 9 February 2018, Arua District notified Uganda Ministry of Health of a confirmed anthrax outbreak among humans in Rhino Camp sub-county. Many persons fell ill after reported contact with livestock that died suddenly. We investigated to determine the scope, mode of transmission and exposures associated with identified anthrax, to guide control and prevention measures. Methods: We defined a suspected cutaneous anthrax case as onset of skin lesions (e.g., papule, vesicle, or eschar) in a person residing in Rhino Camp sub-county, Arua District from 25 December, 2017 to 31 May, 2018. A confirmed case was a suspected case with PCR-positivity for Bacillus anthracis from a clinical sample. We identified cases by reviewing medical records at Rhino Camp Health Centre. We also conducted additional case searches in the affected community with support from Community Health Workers. In a retrospective cohort study, we interviewed all members of households in which at least one person had contact with the carcasses of or meat from animals suspected to have died of anthrax. We collected and tested hides of implicated animals using an anthrax rapid diagnostic test.Results: We identified 14 case-patients (1 confirmed, 13 suspected); none died. Only males were affected (AR: 12/10,000). Mean age of case-persons was 33years (SD: 22).The epidemic curve shows that the outbreak lasted for 5 months, from January 2018-May 2018, peaking in February.Skinning(RR=2.7, 95%CI=1.1-6.7), dissecting (RR=3.0, 95%CI=1.2-7.6), and carrying the dead animals (RR=2.7, 95%CI=1.1-6.7) were associated with increased risk of illness, as were carrying dissected parts of the animal (RR=2.9, 95%CI 1.3-6.5) and preparing and cooking the meat (RR=2.3, 95%CI 2.7-8.1). We found evidence of animal remains on pastureland.Conclusion: Multiple exposures to the hides and meat of animals that died suddenly were associated with this cutaneous anthrax outbreak in Arua District. We recommended public education about safe disposal of carcasses of livestock that die suddenly.
Development and validation of an RNA binding protein-associated prognostic model for hepatocellular carcinoma
Authors: wang Min , Huang Shan , Chen Zefeng , Han Zhiwei , Li Kezhi , Chen Chuang , Wu Guobin , Zhao Yinnong 
Published: September 2020

Abstract
Background: Hepatocellular carcinoma (HCC) is among the deadliest forms of cancer. While RNA-binding proteins (RBPs) have been shown to be key regulators of oncogenesis and tumor progression, their dysregulation in the context of HCC remains to be fully characterized.Methods: Data from the Cancer Genome Atlas - liver HCC (TCGA-LIHC) database were downloaded and analyzed in order to identify RBPs that were differentially expressed in HCC tumors relative to healthy normal tissues. Functional enrichment analyses of these RBPs were then conducted using the GO and KEGG databases to understand their mechanistic roles. Central hub RBPs associated with HCC patient prognosis were then detected through Cox regression analyses, and were incorporated into a prognostic model. The prognostic value of this model was then assessed through the use of Kaplan-Meier curves, time-related ROC analyses, univariate and multivariate Cox regression analyses, and nomograms. Lastly, the relationship between individual hub RBPs and HCC patient overall survival (OS) was evaluated using Kaplan-Meier curves. Finally, find protein-coding genes (PCGs) related to hub RBPs were used to construct a hub RBP-PCG co-expression network.Results: In total, we identified 81 RBPs that were differentially expressed in HCC tumors relative to healthy tissues (54 upregulated, 27 downregulated). Seven prognostically-relevant hub RBPs (SMG5, BOP1, LIN28B, RNF17, ANG, LARP1B, and NR0B1) were then used to generate a prognostic model, after which HCC patients were separated into high- and low-risk groups based upon resultant risk score values. In both the training and test datasets, we found that high-risk HCC patients exhibited decreased OS relative to low-risk patients, with time-dependent area under the ROC curve values of 0.801 and 0.676, respectively. This model thus exhibited good prognostic performance. We additionally generated a prognostic nomogram based upon these seven hub RBPs and found that four other genes were significantly correlated with OS.Conclusion: We herein identified a seven RBP signature that can reliably be used to predict HCC patient OS, underscoring the prognostic relevance of these genes.
Impact of emphysema on sputum culture conversion in male patients with pulmonary tuberculosis: a retrospective analysis
Authors: Takasaka Naoki , Seki Yoshitaka , Fujisaki Ikumi , Uchiyama Shota , Matsubayashi Sachi , Sato Akihito , Yamanaka Yumie , Odashima Kyuto , Kazuyori Taisuke , Seki Aya , Takeda Hiroshi , Ishikawa Takeo , Kuwano Kazuyoshi 
Published: September 2020

Abstract
Background Although cigarette smoking may have a negative impact on the clinical outcome of pulmonary tuberculosis (PTB), few studies have investigated the impact of smoking-associated lung diseases. Emphysema is a major pathological finding of smoking-related lung damage. We aimed to clarify the effect of emphysema on sputum culture conversion rate for Mycobacterium tuberculosis (MTB). Methods We retrospectively studied 79 male patients with PTB confirmed by acid-fast bacillus smear and culture at Jikei University Daisan Hospital between January 2015 and December 2018. We investigated the sputum culture conversion rates for MTB after starting standard anti-TB treatment in patients with or without emphysema. Emphysema was defined as Goddard score ≥1 based on low attenuation area < -950 Hounsfield Unit (HU) using computed tomography (CT). We also evaluated the effect on PTB-related CT findings prior to anti-TB treatment. Results Mycobacterial median time to culture conversion (TCC) in 38 PTB patients with emphysema was 52.0 days [ interquartile range (IQR) 29.0–66.0 days], which was significantly delayed compared with that in 41 patients without emphysema (28.0 days, IQR 14.0–42.0 days) (p<0.001, log-rank test). Multivariate Cox proportional hazards analysis showed that the following were associated with delayed TCC: emphysema [ hazard ratio (HR): 2.43; 95% confidence interval (CI): 1.18–4.97; p=0.015), cavities (HR: 2.15; 95% CI: 1.83–3.89; p=0.012) and baseline time to TB detection within 2 weeks (HR: 2.95; 95% CI: 1.64–5.31; p<0.0001). Cavities and consolidation were more often identified by CT in PTB patients with than without emphysema (71.05% vs 43.90%; p=0.015 and 84.21% vs 60.98%; p=0.021, respectively). Conclusions This study suggests that emphysema poses an increased risk of delayed TCC in PTB. Emphysema detection by CT might be a useful method for prediction of the duration of PTB treatment required for sputum negative conversion.
The predictive value of D-dimer test for venous thromboembolism during puerperium in women age 35 or older：A prospective cohort study
Authors: Hu Wen , Xu Dong , Li Juan , Chen Cheng , Chen Yuan , Xi Fangfang , Zhou Feifei , Guo Xiaohan , Zhao Baihui , Luo Qiong 
Published: September 2020

Abstract
Background: This study aimed to investigate the predictive value of the D-dimer level for venous thromboembolism (VTE) events during puerperium of women age at 35 years or older, as well as to identify other risk factors associated with the occurrence of VTE. Methods: It was a prospective observational cohort study, from January 2014 to December 2018, which involved 12451 women age 35 or older who delivered at least 28 weeks of gestation at Women’s Hospital of Zhejiang University, School of Medicine. The maternal and fetal demographic characteristics, pregnancy complications, imaging finding and results of laboratory test within postpartum 24 hours including D-dimer level, platelet counts and fibrinogen level were collected for analyses. Results: 30(2.4‰) women were identified as VTE, including 1 pulmonary embolism event and 29 deep venous thrombosis events. The receiver operating characteristic (ROC) curve analysis suggested the best cutoff point for D-dimer level within postpartum 24 hours of women age 35 or older was 5.545 mg/L, with a specificity of 70.0% and a sensitivity of 75.4%. Besides, there was no statistical correlation between platelet counts and VTE, as well as between fibrinogen level and VTE. On multivariate analysis, D-dimer≥5.50 mg/L (OR=5.874, 95%CI: 2.678-12.886) and emergency cesarean section (OR=11.965, 95%CI: 2.732-52.401) were independently associated with VTE in puerperium of women age 35 or older.Conclusions: We concluded that D-dimer≥5.50 mg/L was an independent predictor of VTE in puerperium with maternal age 35 or older and D-dimer testing was a necessary examination for perinatal women.