bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perturbation of gut microbiota decreases susceptibility but does not modulate ongoing autoimmune neurological disease
Authors: Gödel Clemens , Kunkel Birgit , Kashani Alireza , Lassmann Hans , Arumugam Manimozhiyan , Krishnamoorthy Gurumoorthy 
Published: March 2020

AbstractThe gut microbiota regulates the host immune and nervous systems and plays an important role in the pathogenesis of autoimmune neurological disease multiple sclerosis (MS). There are considerable efforts currently being undertaken to develop therapies for MS based on the modulation of microbiota. Evidence from experimental models suggests that the manipulation of microbiota through diet or antibiotics prior to the disease development limits disease susceptibility. However, it is currently unclear if microbiota manipulation therapies would also have an impact on ongoing neurological disease. Here, we examined the effect of antibiotic-based microbiota modulation in spontaneous experimental autoimmune encephalomyelitis (EAE) mouse models of MS before and after the onset of autoimmune disease. Prophylactic antibiotic treatment led to a significant reduction of susceptibility to spontaneous EAE. In contrast, antibiotic treatment after the onset of spontaneous EAE did not show a significant amelioration. These results reveal that the perturbation of gut bacteria alters disease susceptibility but has minimal impact on the ongoing neurological disease.
A double-blind, randomized controlled trial to explore oral tranexamic acid as adjunct for the treatment for postpartum hemorrhage
Authors: Diop Ayisha , Abbas Dina , Ngoc Nguyen thi Nhu , Martin Roxanne , Razafi Ange , Tuyet Hoang Thi Diem , Winikoff Beverly 
Published: March 2020

Abstract
Background
Oral tranexamic acid (TXA), if effective in reducing blood loss after delivery for women experiencing primary PPH, could be administered where parenteral administration is not feasible. This trial assessed the efficacy, safety, and acceptability of oral TXA when used as an adjunct to sublingual misoprostol to treat postpartum hemorrhage (PPH) following vaginal delivery.

Methods
From October 2016 to January 2018, women presenting at four hospitals in Senegal and Vietnam for vaginal delivery were screened for enrollment in the trial. Women diagnosed with postpartum hemorrhage (defined as blood loss ≥700 ml) were randomized to receive either oral TXA (1950 mg) or placebo in addition to 800 mcg sublingual misoprostol. Postpartum blood loss was measured using a calibrated drape. Blood loss for all PPH cases was recorded for 2 h after administration of the drugs. The primary outcome measure was the proportion of women with bleeding controlled with the trial regimen without recourse to further treatment. Secondary outcomes including the rate of severe PPH, mean/median blood loss, use of additional uterotonics and/or interventions side effects, and acceptability were also recorded.

Results
Of the 258 women who received treatment for PPH, 128 received placebo and misoprostol and 130 received TXA and misoprostol. The proportion of women who had active bleeding controlled with trial drugs alone and no additional interventions was similar in both groups: 77(60.2%) placebo; 74 (56.9%) TXA, p = 0.59). Use of other interventions to control bleeding, including uterotonics, did not differ significantly between groups. Median blood loss at PPH diagnosis was 700 ml in both groups. Uterine atony alone or in addition to another cause contributed to over 90% of PPH cases reported (92.2% placebo vs. 91.5% TXA), other causes included perineal and cervical lacerations and retained placenta. Reports of side effects and acceptability were similar in the two groups.

Conclusion
Adjunct use of oral TXA with misoprostol to treat PPH resulted in similar clinical and acceptability outcomes when compared to treatment with misoprostol alone.

Trial registration
This trial was registered with ClinicalTrials.gov, number NCT02805426. Registered on 3 September 2016.
Differential expression of human papillomavirus 16-, 18-, 52-, and 58-derived transcripts in cervical intraepithelial neoplasia
Authors: Baba Satoshi , Taguchi Ayumi , Kawata Akira , Hara Konan , Eguchi Satoko , Mori Mayuyo , Adachi Katsuyuki , Mori Seiichiro , Iwata Takashi , Mitsuhashi Akira , Maeda Daichi , Komatsu Atsushi , Nagamatsu Takeshi , Oda Katsutoshi , Kukimoto Iwao , Osuga Yutaka , Fujii Tomoyuki , Kawana Kei 
Published: March 2020

Abstract
Background
Human papillomavirus (HPV) infection is a primary cause of cervical cancer. Although epidemiologic study revealed that carcinogenic risk differs according to HPV genotypes, the expression patterns of HPV-derived transcripts and their dependence on HPV genotypes have not yet been fully elucidated.

Methods
In this study, 382 patients with abnormal cervical cytology were enrolled to assess the associations between HPV-derived transcripts and cervical intraepithelial neoplasia (CIN) grades and/or HPV genotypes. Specifically, four HPV-derived transcripts, namely, oncogenes E6 and E6*, E1^E4, and viral capsid protein L1 in four major HPV genotypes—HPV 16, 18, 52, and 58—were investigated.

Results
The detection rate of E6/E6* increased with CIN progression, whereas there was no significant change in the detection rate of E1^E4 or L1 among CIN grades. In addition, we found that L1 gene expression was HPV type-dependent. Almost all HPV 52-positive specimens, approximately 50% of HPV 58-positive specimens, around 33% of HPV 16-positive specimens, and only one HPV18-positive specimen expressed L1.

Conclusions
We demonstrated that HPV-derived transcripts are HPV genotype-dependent. Especially, expression patterns of L1 gene expression might reflect HPV genotype-dependent patterns of carcinogenesis.
Molecular karyotypes of loquat (Eriobotrya japonica) aneuploids can be detected by using SSR markers combined with quantitative PCR irrespective of heterozygosity
Authors: Wen Guo , Dang Jiangbo , Xie Zhongyi , Wang Jinying , Jiang Pengfei , Guo Qigao , Liang Guolu 
Published: March 2020

Abstract
Background
Aneuploidy, a condition caused by an imbalance between the relative dosages of chromosomes, generally produces a novel phenotype specific to the molecular karyotype. Few techniques are currently available for detecting the molecular karyotypes of aneuploids in plants.

Results
Based on this imbalance in chromosome dosage, a new approach (referred to as ‘SSR-qPCR’) combining simple sequence repeat (SSR) markers and quantitative real-time PCR (qPCR) has been developed and utilized to detect some common aneuploids irrespective of heterozygosity. We screened 17 specific SSR markers covering all loquat linkage groups and redesigned 6 pairs of primers for SSR markers that can detect loquat chromosome aneuploidies. The SSR-qPCR detection results obtained for hybrid progeny and open-pollination progeny of triploid loquat showed diagnostic accuracies of 88.9% and 62.5%, respectively, compared with the chromosome preparation results.

Conclusion
SSR-qPCR can detect loquat aneuploids and be used to construct the entire molecular karyotypes of aneuploid individuals. Therefore, this method offers a novel alternative for the detection of chromosome aneuploidies.
A qualitative study of design stakeholders’ views of developing and implementing a registry-based learning health system
Authors: Dixon-Woods Mary , Campbell Anne , Chang Trillium , Martin Graham , Georgiadis Alexandros , Heney Veronica , Chew Sarah , Van Citters Aricca , Sabadosa Kathryn A. , Nelson Eugene C. 
Published: March 2020

Abstract
Background
New opportunities to record, collate, and analyze routine patient data have prompted optimism about the potential of learning health systems. However, real-life examples of such systems remain rare and few have been exposed to study. We aimed to examine the views of design stakeholders on designing and implementing a US-based registry-enabled care and learning system for cystic fibrosis (RCLS-CF).

Methods
We conducted a two-phase qualitative study with stakeholders involved in designing, implementing, and using the RCLS-CF. First, we conducted semi-structured interviews with 19 program personnels involved in design and delivery of the program. We then undertook 11 follow-up interviews. Analysis of interviews was based on the constant comparative method, supported by NVivo software.

Results
The organizing principle for the RCLS-CF was a shift to more partnership-based relationships between patients and clinicians, founded in values of co-production, and facilitated by technology-enabled data sharing. Participants proposed that, for the system to be successful, the data it collects must be both clinically useful and meaningful to patients and clinicians. They suggested that the prerequisites included a technological infrastructure capable of supporting data entry and joint decision-making in an accessible way, and a set of social conditions, including willingness from patients and clinicians alike to work together in new ways that build on the expertise of both parties. Follow-up interviews highlighted some of the obstacles, including technical challenges and practical constraints on refiguring relationships between clinicians and patients.

Conclusions
The values and vision underlying the RCLS-CF were shared and clearly and consistently articulated by design stakeholders. The challenges to realization were often not at the level of principle, but were both practical and social in character. Lessons from this study may be useful to other systems looking to harness the power of “big data” registries, including patient-reported data, for care, research, and quality improvement.
Sickle cell disease induces resistance to cutaneous carcinogenesis
Authors: Soutou Boutros , Senet Patricia , Lionnet François , Habibi Anoosha , Aractingi Sélim 
Published: March 2020

Abstract
Background
While skin carcinomas are reported in chronic ulcers and in patients treated with hydroxyurea (HU) for myeloproliferative neoplasms, no skin carcinoma has been reported in patients with sickle cell disease (SCD), presenting chronic skin ulcers or treated with HU. The objective was to estimate the risk of cutaneous malignant transformation in SCD patients with prolonged leg ulcers or under HU therapy.

Results
In this cross-sectional study, the cohort consisted of 1543 patients. In the first series, 29 patients presented a total of 53 ulcers lasting more than two years. The median age was 35 ± 8.4 years old. The median duration for a single ulcer was 9.2 ± 7 years. None of the examined ulcers showed any suspicious area of malignant transformation. In the second series, 187 patients treated with HU for more than two years were identified. The median age was 31.3 ± 9.9 years old. The median duration of treatment with HU was 6 ± 3.2 years. No skin carcinoma or actinic keratosis was recorded.

Conclusions
This study showed that skin carcinogenesis did not occur in our series of SCD patients exposed to transforming events such as long term HU treatment or prolonged leg ulcers.
Sinomenine inhibits amyloid beta-induced astrocyte activation and protects neurons against indirect toxicity
Authors: Singh Deepali , Agrawal Apurva , Singal Chitra Mohinder Singh , Pandey Hriday Shanker , Seth Pankaj , Sharma Shiv Kumar 
Published: March 2020

AbstractAmyloid beta is a major constituent of the plaques found in the brains of patients suffering from Alzheimer’s disease (AD). A growing body of research work suggests that neuroinflammation plays important roles in the development of AD. Thus, considerable efforts are directed towards identification of compounds that can reduce or inhibit neuroinflammation. Here, we show that sinomenine, a compound present in a Chinese medicinal plant, Sinomenium acutum, inhibits oligomeric amyloid beta-induced production of reactive oxygen species (ROS), nitric oxide (NO) and inflammation-related molecules from astrocytic cells. The conditioned medium from oligomeric amyloid beta-treated astrocytic cells induces cell death in the hippocampal neuronal cells. Importantly, sinomenine inhibits this cell death. In addition, this compound has inhibitory effects on the production of ROS, NO and inflammation-related factors from oligomeric amyloid-beta treated human astrocytes. Finally, the conditioned medium from oligomeric amyloid beta-treated human astrocytes induces cell death in the primary culture of human neurons, which is inhibited by sinomenine. Thus, sinomenine inhibits amyloid beta-induced production of toxic factors from astrocytes, and confers protection to hippocampal neuronal cells as well as human neurons against indirect toxicity. The results suggest that this compound could provide beneficial effects in AD and other neurodegenerative conditions by reducing inflammation and neuronal cell death.
Rescue under ongoing CPR from an upper floor: evaluation of three different evacuation routes and mechanical and manual chest compressions: a manikin trial
Authors: Drinhaus Hendrik , Nüsgen Sebastian , Adams Niels , Wetsch Wolfgang A. , Annecke Thorsten 
Published: March 2020

Abstract
Background
If transport under ongoing cardiopulmonary resuscitation (CPR) from an upper floor is indicated, the ideal CPR-method and evacuation route is unknown hitherto. We aimed to elaborate a strategy for evacuation of patients under ongoing CPR from an upper floor, comparing three different evacuation routes and manual and mechanical chest compressions.

Methods
A CPR-training manikin recording CPR-quality was placed on the fifth floor and was evacuated to an ambulance via lift, turntable ladder, or staircase. Chest compressions were performed manually or with a mechanical CPR-device. Efficiency endpoints were compression depth and frequency, sufficiency of chest release, compared with European Resuscitation Council (ERC) Guidelines, and duration of the evacuation. Adverse outcomes were disconnection/dislocation of devices and hazards/accidents to the personnel.

Results
For all evacuation routes, compression depth and frequency were significantly more compliant with ERC-guidelines under mechanical CPR. Manual CPR was associated with considerable deviations from correct compression depth and frequency. Chest release only slightly differed between groups. Evacuation via lift under mechanical CPR was fastest and evacuation via turntable ladder under manual CPR was slowest. No device disconnections or accidents occurred, but hazard to personnel was perceived during evacuation via ladder under manual CPR.

Conclusions
In this study, a mechanical CPR-device proved to deliver better CPR-quality during evacuation from an upper floor. If a lift accessible with a stretcher is available, this route should be preferred, regardless of manual or mechanical CPR. Turntable ladders can only be meaningfully used with mechanical CPR, otherwise CPR-quality is poor and hazard to the personnel is increased. Not all evacuation routes may be useable in a specific real-life scenario.

Trial registration
German Clinical Trials Registry, www.drks.de, registration number DRKS00012885, registration date 17.08.2017.
Designs for adding a treatment arm to an ongoing clinical trial
Authors: Bennett Maxine , Mander Adrian P. 
Published: March 2020

AbstractBackgroundFor many disease areas, there are often treatments in different stages of the development process. We consider the design of a two-arm parallel group trial where it is planned to add a new experimental treatment arm during the trial. This could potentially save money, patients, time and resources; however, the addition of a treatment arm creates a multiple comparison problem. Current practice in trials when a new treatment arm has been added is to compare the new treatment only to controls randomised concurrently, and this is the setting we consider here. Furthermore, for standard multi-arm trials, optimal allocation randomises a larger number of patients to the control arm than to each experimental treatment arm.MethodsIn this paper we propose an adaptive design, the aim of which is to adapt the sample size of the trial when the new treatment arm is added to control the family-wise error rate (FWER) in the strong sense, whilst maintaining the marginal power of each treatment-to-control comparison at the level of the original study. We explore optimal allocation for designs where a treatment arm is added with the aim of increasing the overall power of the study, where we define the overall power to be the probability of detecting all treatments that are better than the control.Results and conclusionsAn increase in sample size is required to maintain the marginal power for each pairwise comparison when adding a treatment arm if control of the FWER is required at the level of the type I error in the original study. When control of the FWER is required in a single trial which adds an additional experimental treatment arm, but control of the FWER is not required in separate trials, depending on the design characteristics, it may be better to run a separate trial for each experimental treatment, in terms of the number of patients required. An increase in overall power can be achieved when optimal allocation is used once a treatment arm has been added to the trial, rather than continuing with equal allocation to all treatment arms.
Patient experience of the informed consent process during acute myocardial infarction: a sub-study of the VALIDATE-SWEDEHEART trial
Authors: Olsson Anneli , Ring Camilla , Josefsson Johan , Eriksson Annika , Rylance Rebecca , Fröbert Ole , James Stefan , Sparv David , Erlinge David 
Published: March 2020

Abstract
Objective
We aimed to assess the patient experience of informed consent (IC) during acute myocardial infarction (AMI) in a sub-study of the VALIDATE-SWEDEHEART trial. The original trial compared two anticoagulant agents in patients undergoing coronary intervention. A witnessed oral IC was required prior to randomization in patients with ST-segment elevation myocardial infarction, which was subsequently complemented with a written IC after percutaneous coronary intervention. Written consent was obtained before angiography in patients with non-ST-segment elevation myocardial infarction.

Background
The IC process in patients with AMI is under debate. Earlier trials in this population have required prospective consent before randomization. A trial published some years ago used deferred consent, but the patient experience of this process is poorly studied.

Methods
A total of 414 patients who participated in the main trial were enrolled and asked the following questions: (1) Do you remember being asked to participate in a study? (2) How was your experience of being asked to participate; do you remember it being positive or negative? (3) Would you have liked more information about the study? (4) Do you think it would have been better if you were included in the study without being informed until a later time?

Results
Of these patients, 94% remembered being included; 85% of them experienced this positively, 12% were neutral and 3% negative. Regarding more information, 88% did not want further information, and 68% expressed that they wanted to be consulted before inclusion. Of the patients, 5% thought it would have been better to have study inclusion without consent, and 27% considered it of no importance.

Conclusion
It is reasonable to ask patients for verbal IC in the acute phase of AMI. Most patients felt positively about being asked to participate and had knowledge of being enrolled in a scientific study. In addition they objected to providing IC after randomization and treatment.

Trial registration
VALIDATE-SWEDEHEART European Union Clinical Trials Register: 2012-005260-10. ClinicalTrials.gov: NCT02311231. Registered on 8 Dec 2014.
A study of capecitabine metronomic chemotherapy is non-inferior to conventional chemotherapy as maintenance strategy in responders after induction therapy in metastatic colorectal cancer
Authors: Shi Min , Ma Tao , Xi Wenqi , Jiang Jinling , Wu Junwei , Zhou Chenfei , Yang Chen , Zhu Zhenggang , Zhang Jun 
Published: March 2020

Abstract
Background
The aim of this study is to demonstrate that capecitabine metronomic chemotherapy is non-inferior to capecitabine conventional chemotherapy as maintenance treatment, in patients who have responded to 16–18 weeks first-line chemotherapy in metastatic colorectal cancer (mCRC).

Methods
The study design is a prospective, randomized, open label, phase II clinical trial. Those patients with mCRC who respond well after 16–18 weeks of standard doublet chemotherapy as induction may be enrolled into this study, and randomly assigned to the capecitabine metronomic group or standard dosage group. The duration of disease control after randomization and progression-free survival after enrollment are the primary endpoints. Overall survival, safety, and quality of life are the secondary endpoints. The sample size required to achieve the research objectives of this project is 79 patients in each group. The study recently started on 1 January 2018, and will last for 36 months.

Discussion
This project is intended to study the efficacy and safety of capecitabine metronomic chemotherapy in the maintenance treatment of advanced colorectal cancer, and to explore the strategy of “low toxicity, high efficiency, economy, and individualization”, which is suitable for China’s national conditions and pharmacoeconomics. It has great prospects for clinical application and a clear socioeconomic value.

Trial registration
ClinicalTrials.gov: NCT03158610. Registered on 15 May 2017.
Pathway dissection, regulation, engineering and application: lessons learned from biobutanol production by solventogenic clostridia
Authors: Li Shubo , Huang Li , Ke Chengzhu , Pang Zongwen , Liu Liming 
Published: March 2020

AbstractThe global energy crisis and limited supply of petroleum fuels have rekindled the interest in utilizing a sustainable biomass to produce biofuel. Butanol, an advanced biofuel, is a superior renewable resource as it has a high energy content and is less hygroscopic than other candidates. At present, the biobutanol route, employing acetone–butanol–ethanol (ABE) fermentation inClostridiumspecies, is not economically competitive due to the high cost of feedstocks, low butanol titer, and product inhibition. Based on an analysis of the physiological characteristics of solventogenic clostridia, current advances that enhance ABE fermentation from strain improvement to product separation were systematically reviewed, focusing on: (1) elucidating the metabolic pathway and regulation mechanism of butanol synthesis; (2) enhancing cellular performance and robustness through metabolic engineering, and (3) optimizing the process of ABE fermentation. Finally, perspectives on engineering and exploiting clostridia as cell factories to efficiently produce various chemicals and materials are also discussed.