bluuebunny/crossref_metadata_2025_split huggingface dataset:
An innovative method for manufacturing the Tuebingen palatal plate for infants with Robin sequence
Authors: Müller-Hagedorn Silvia , Arand Jörg , Scholz Thilo , Poets Christian F. , Wiechers Cornelia 
Published: March 2020

AbstractBackgroundRobin sequence (RS) is characterized by mandibular micro- and retrognathia, glossoptosis, upper airway obstruction and optionally a cleft palate. With an incidence of 1:8000, it belongs to the so-called rare diseases; 30–50% of patients have RS as part of a syndrome. A comparatively well-studied treatment option is the Tuebingen Palatal Plate (TPP), which has proven effective in both, isolated and syndromic RS, but often requires multiple endoscopies for perfect fit and effectiveness. We report on a new method for fitting the TPP with only one session of nasopharyngeal endoscopy resulting in the plate being finished in one day.Methods and resultsFirst, a prototype is produced, consisting of a traditional acrylic palatal part and a velar extension made of thermoplastic resin, usually measuring 10x40mm. Using polymerization, a scale is added to the posterior part of the extension to help with determining its optimal length during endoscopic evaluation. The extension is pre-bent in the dental laboratory to achieve an approximate shape. During endoscopy, the prototype can be adjusted to the infant’s anatomy: first, the angulation is customized by controlled heating, bending and cooling of the thermoplastic spur. Second, the length of the spur is adapted by grinding its tip. Then the prototype is returned to the dental laboratory for completion; the final plate can be delivered to the patient on the same day. It acts by shifting the tongue into a more anterior position, thereby opening the airway and releasing upper airway obstruction, as well as by acting as a functional orthodontic appliance that stimulates mandibular growth through exerting pressure on the base of the tongue.ConclusionsWith the thermoplastic spur presented here, a TPP can be produced within one day, requiring only one endoscopy. This approach may facilitate fabricating the TPP.
Content and system development of a digital patient-provider communication tool to support shared decision making in chronic health care: InvolveMe
Authors: Seljelid Berit , Varsi Cecilie , Solberg Nes Lise , Stenehjem Aud-E , Bollerslev Jens , Børøsund Elin 
Published: March 2020

Abstract
Background
Chronic conditions present major health problems, affecting an increasing number of individuals who experience a variety of symptoms that impact their health related quality of life. Digital tools can be of support in chronic conditions, potentially improving patient-provider communication, promoting shared decision making for treatment and care, and possibly even improving patient outcomes. This study aimed to develop a digital tool for patient-provider communication in chronic health care settings and describes the data collection and subsequent content and software development of the InvolveMe tool. InvolveMe will provide patients with the opportunity to report symptoms and preferences to their health care providers (HCP), and to use secure messaging to interact with the HCPs.

Method
The study employed a combination of interviews with patients with chronic conditions and focus groups with HCPs, examining experiences with chronic conditions and the potential use of a digital tool for support. Participants were recruited from two outpatient clinics at a university hospital. Data collected from interviews and focus groups were analysed using thematic analysis. Content and software development was informed by the data collection and by tool development workshops.

Results
Analyses from interviews with patients (n = 14) and focus groups with HCPs (n = 11) generated three main themes: 1) Making symptoms and challenges visible, 2) Mastering a new life, and 3) Digital opportunities for follow-up. Each main theme generated separate subthemes. Theme 1 and 2 gave input for content development of the symptom and needs assessment part of the tool, while theme 3 provided ideas for the software development of the InvolveMe tool. Tool development workshops with patients (n = 6) and HCPs (n = 6) supplemented the development.

Conclusions
A digital tool such as InvolveMe has the potential to support shared decision making for patients with chronic health conditions. Through integration with an existing patient portal such a tool can provide opportunities for meaningful interactions and communication between patients and HCP’s, particularly with regards to symptoms, needs and preferences for care.
Challenges with scale-up of GeneXpert MTB/RIF® in Uganda: a health systems perspective
Authors: Nalugwa Talemwa , Shete Priya B. , Nantale Mariam , Farr Katherine , Ojok Christopher , Ochom Emma , Mugabe Frank , Joloba Moses , Dowdy David W. , Moore David A. J. , Davis J. Lucian , Cattamanchi Adithya , Katamba Achilles 
Published: March 2020

Abstract
Background
Many high burden countries are scaling-up GeneXpert® MTB/RIF (Xpert) testing for tuberculosis (TB) using a hub-and-spoke model. However, the effect of scale up on reducing TB has been limited. We sought to characterize variation in implementation of referral-based Xpert TB testing across Uganda, and to identify health system factors that may enhance or prevent high-quality implementation of Xpert testing services.

Methods
We conducted a cross-sectional study triangulating quantitative and qualitative data sources at 23 community health centers linked to one of 15 Xpert testing sites between November 2016 and May 2017 to assess health systems infrastructure for hub-and-spoke Xpert testing. Data sources included a standardized site assessment survey, routine TB notification data, and field notes from site visits.

Results
Challenges with Xpert implementation occurred at every step of the diagnostic evaluation process, leading to low overall uptake of testing. Of 2192 patients eligible for TB testing, only 574 (26%) who initiated testing were referred for Xpert testing. Of those, 54 (9.4%) were Xpert confirmed positive just under half initiated treatment within 14 days (n = 25, 46%). Gaps in required infrastructure at 23 community health centers to support the hub-and-spoke system included lack of refrigeration (n = 14, 61%) for sputum testing and lack of telephone/mobile communication (n = 21, 91%). Motorcycle riders responsible for transporting sputum to Xpert sites operated variable with trips once, twice, or three times a week at 10 (43%), nine (39%) and four (17%) health centers, respectively. Staff recorded Xpert results in the TB laboratory register at only one health center and called patients with positive results at only two health centers. Of the 15 Xpert testing sites, five (33%) had at least one non-functioning module. The median number of tests per day was 3.57 (IQR 2.06–4.54), and 10 (67%) sites had error/invalid rates > 5%.

Conclusions
Although Xpert devices are now widely distributed throughout Uganda, health system factors across the continuum from test referral to results reporting and treatment initiation preclude effective implementation of Xpert testing for patients presenting to peripheral health centers. Support for scale up of innovative technologies should include support for communication, coordination and health systems integration.
Betaine attenuates LPS-induced downregulation of Occludin and Claudin-1 and restores intestinal barrier function
Authors: Wu Jingtao , He Caimei , Bu Jie , Luo Yue , Yang Shuyuan , Ye Chengyan , Yu Silei , He Binsheng , Yin Yulong , Yang Xiaoping 
Published: March 2020

Abstract
Background
The intestinal epithelial barrier, which works as the first line of defense between the luminal environment and the host, once destroyed, it will cause serious inflammation or other intestinal diseases. Tight junctions (TJs) play a vital role to maintain the integrity of the epithelial barrier. Lipopolysaccharide (LPS), one of the most important inflammatory factors will downregulate specific TJ proteins including Occludin and Claudin-1 and impair integrity of the epithelial barrier. Betaine has excellent anti-inflammatory activity but whether betaine has any effect on TJ proteins, particularly on LPS-induced dysfunction of epithelial barriers remains unknown. The purpose of this study is to explore the pharmacological effect of betaine on improving intestinal barrier function represented by TJ proteins. Intestinal porcine epithelial cells (IPEC-J2) were used as an in vitro model.

Results
The results demonstrated that betaine enhanced the expression of TJ proteins while LPS (1 μg/mL) downregulates the expression of these proteins. Furthermore, betaine attenuates LPS-induced decreases of TJ proteins both shown by Western blot (WB) and Reverse transcription-polymerase chain reaction (RT-PCR). The immunofluorescent images consistently revealed that LPS induced the disruption of TJ protein Claudin-1 and reduced its expression while betaine could reverse these alterations. Similar protective role of betaine on intestinal barrier function was observed by transepithelial electrical resistance (TEER) approach.

Conclusion
In conclusion, our research demonstrated that betaine attenuated LPS-induced downregulation of Occludin and Claudin-1 and restored the intestinal barrier function.
Novel therapeutic strategies and perspectives for metastatic pancreatic cancer: vaccine therapy is more than just a theory
Authors: Luo Wenhao , Yang Gang , Luo Wentao , Cao Zhe , Liu Yueze , Qiu Jiangdong , Chen Guangyu , You Lei , Zhao Fangyu , Zheng Lianfang , Zhang Taiping 
Published: March 2020

AbstractPancreatic cancer is an aggressive and malignant tumor with an exceedingly high mortality rate. The quality of life and survival rates of pancreatic cancer patients with metastasis are poor compared with those without metastasis. Thus far, no effective treatment strategy has been established for metastatic pancreatic cancer patients. Therefore, an appropriate therapeutic method based on the elimination of metastatic pancreatic cancer is critical to improve patient outcome. Tumor-targeted vaccines have been widely discussed in recent studies and enabled important breakthroughs in the treatment of pancreatic cancer by preventing the escape of tumor cells from immune surveillance and activating the immune system to eliminate cancer cells. T cells can be activated by the stimulation of tumor-targeted vaccines, but to mount an effective immune response, both immune checkpoint inhibitors and positive costimulatory molecules are required. In this review, we discuss potential tumor-targeted vaccines that can target pancreatic cancer, elaborate the probably appropriate combination of vaccines therapy and evaluate the underlying benefits as well as obstacles in the current therapy for metastatic pancreatic cancer.
Quality of life in subjects with upper- and lower-limb spasticity treated with incobotulinumtoxinA
Authors: Fheodoroff Klemens , Rekand Tiina , Medeiros Luisa , Koßmehl Peter , Wissel Jörg , Bensmail Djamel , Scheschonka Astrid , Flatau-Baqué Birgit , Simon Olivier , Dressler Dirk , Simpson David M. 
Published: March 2020

Abstract
Background
We evaluated quality of life among subjects with upper- and lower-limb spasticity who received escalating doses of incobotulinumtoxinA (total body doses up to 800 U) in the prospective, single-arm, dose-titration TOWER study.

Methods
In this exploratory trial, subjects (N = 155; 18–80 years of age) with upper- and lower-limb spasticity due to cerebral causes who were deemed to require total body doses of up to 800 U incobotulinumtoxinA received three consecutive injection cycles of incobotulinumtoxinA (400, 600, and up to 800 U), each with 12 to 16 weeks’ follow-up. QoL was assessed using the EuroQol 5-dimensions questionnaire, three-level (EQ-5D), before and 4 weeks post-injection in each injection cycle and at the end of injection cycle 3.

Results
The mean EQ-5D visual analog scale scores of 155 participants continuously improved from study baseline to 4 weeks post-injection in all injection cycles (mean [standard deviation] change 6.7 [14.1], 9.6 [16.3], and 8.6 [17.0] for injection cycles 1, 2, and 3, respectively; p < 0.0001 for all, paired sample t-test). In general, among those with a change in the EQ-5D rating of their condition, the proportion of subjects with ‘improvement’ was greater than that with ‘worsening’ for individual EQ-5D dimensions across all injection cycles. At the end of injection cycle 3, the proportion of subjects rating their condition as ‘normal’ increased from study baseline for all dimensions, and there was a ≥ 46% reduction in the proportion of subjects with a rating of ‘severe impairment’.

Conclusion
These preliminary results suggest that escalating incobotulinumtoxinA doses up to 800 U are associated with improvement in quality of life ratings in subjects with multifocal upper- and lower-limb spasticity, and form a basis for future comparator studies.

Trial registration
ClinicalTrials.gov, NCT01603459. Date of registration: May 22, 2012.
Mobile phone support to sustain exclusive breastfeeding in the community after hospital delivery and counseling: a quasi-experimental study
Authors: Jerin Iftia , Akter Monira , Talukder Khurshid , Talukder Muhammad Qudrat e Khuda , Rahman Mohammad Abdur 
Published: March 2020

Abstract
Background
Rapid increases in hospital and cesarean deliveries threaten an already falling exclusive breastfeeding rate (EBR) in Bangladesh. There is neither a sustained Baby-Friendly Hospital Initiative (BFHI) nor any community support for breastfeeding mothers. Our aim was to find out whether breastfeeding support after hospital delivery and subsequently by mobile phone at home is effective in improving EBR in infants under six-months of age.

Methods
A quasi-experimental study was carried out in 2010 at the Centre for Woman and Child Health (CWCH), Savar, Bangladesh. A total of 129 mothers delivered at CWCH were recruited in pre-intervention phase and their infants followed up between 0 and 5 months of age in the community for exclusive breastfeeding (EBF), anthropometry and illness. An intervention package was then implemented with postpartum support for first hour breastfeeding initiation, correction of position and attachment and face-to-face counseling in hospital followed by mobile phone support by two trained Research Assistants once every 15 days after discharge up to six months of age. During the intervention phase, 164 pregnant women delivered at CWCH were recruited and followed up as in the pre-intervention phase.

Results
In the pre-intervention phase among 114 infants, 66 (58%) were found to be exclusively breastfed. In the intervention phase among 151 infants, 118 (78%) were exclusively breastfed (p = 0.000). In the pre-intervention phase EBR at less than one month and five months were 85 and 42% as in the intervention phase these EBR were 89 and 71% respectively. Wasting (weight-for-height Z-score < − 2.00), stunting (height-for-age Z-score < − 2.00), and underweight (weight-for-age Z-score < − 2.00) was 17 (15%), 7 (6%), and 14 (13%) respectively in the pre-intervention phase. In the intervention phase wasting, stunting, and underweight was 16 (11%), 16 (11%), and 15 (10%) respectively. Therefore, there was no statistically significant differences in nutritional status of the infants in the two phases. There was also no significant differences in child morbidity (pneumonia and diarrhea) between the two phases.

Conclusion
A combination of hospital support and mobile phone counseling in the community sustained higher rates of EBF in the community after hospital delivery.
The JNK pathway represents a novel target in the treatment of rheumatoid arthritis through the suppression of MMP-3
Authors: Kanai Tomotake , Kondo Naoki , Okada Masayasu , Sano Hiroshige , Okumura Go , Kijima Yasufumi , Ogose Akira , Kawashima Hiroyuki , Endo Naoto 
Published: March 2020

Abstract
Background and aim
The pathophysiology of rheumatoid arthritis (RA) is characterized by excess production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) by neutrophils and macrophages in synovium. Additionally, these cytokines promote the production of reactive oxygen species (ROS), and increased production of matrix metalloproteinases (MMPs), including MMP-3, in synoviocytes that result in joint destruction. There is limited information on how proteolytic enzymes such as MMP-3 can be regulated. We evaluated the effect of the antioxidant N-acetylcysteine (NAC) on RA and identified the relationship between the c-Jun N terminal kinase (JNK) pathway and MMP-3. We hypothesized that elucidating this relationship would lead to novel therapeutic approaches to RA treatment and management.

Methods
We investigated the effect of administering a low dose (1000 μM or less) of an antioxidant (NAC) to human rheumatoid fibroblast-like synoviocytes (MH7A cells). We also investigated the response of antioxidant genes such as nuclear factor erythroid -derived 2-related factor 2 (Nrf2) and Sequestosome 1 (p62). The influence of MMP-3 expression on the JNK pathway leading to joint destruction and the mechanisms underlying this relationship were investigated through primary dispersion culture cells collected from the synovial membranes of RA patients, consisting of rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLS).

Results
Low-dose NAC (1000 μM) increased the expression of Nrf2 and phospho-p62 in MH7A cells, activating antioxidant genes, suppressing the expression of MMP-3, and inhibiting the phosphorylation of JNK. ROS, MMP-3 expression, and IL-6 was suppressed by administering 30 μM of SP600125 (a JNK inhibitor) in MH7A cells. Furthermore, the administration of SP600125 (30 μM) to RA-FLS suppressed MMP-3.

Conclusions
We demonstrated the existence of an MMP-3 suppression mechanism that utilizes the JNK pathway in RA-FLS. We consider that the JNK pathway could be a target for future RA therapies.
Quality indicators for patients with traumatic brain injury in European intensive care units: a CENTER-TBI study
Authors:   the CENTER-TBI investigators and participants for the ICU stratum, Huijben Jilske A. , Wiegers Eveline J. A. , Ercole Ari , de Keizer Nicolette F. , Maas Andrew I. R. , Steyerberg Ewout W. , Citerio Giuseppe , Wilson Lindsay , Polinder Suzanne , Nieboer Daan , Menon David , Lingsma Hester F. , van der Jagt Mathieu 
Published: March 2020

Abstract
Background
The aim of this study is to validate a previously published consensus-based quality indicator set for the management of patients with traumatic brain injury (TBI) at intensive care units (ICUs) in Europe and to study its potential for quality measurement and improvement.

Methods
Our analysis was based on 2006 adult patients admitted to 54 ICUs between 2014 and 2018, enrolled in the CENTER-TBI study. Indicator scores were calculated as percentage adherence for structure and process indicators and as event rates or median scores for outcome indicators. Feasibility was quantified by the completeness of the variables. Discriminability was determined by the between-centre variation, estimated with a random effect regression model adjusted for case-mix severity and quantified by the median odds ratio (MOR). Statistical uncertainty of outcome indicators was determined by the median number of events per centre, using a cut-off of 10.

Results
A total of 26/42 indicators could be calculated from the CENTER-TBI database. Most quality indicators proved feasible to obtain with more than 70% completeness. Sub-optimal adherence was found for most quality indicators, ranging from 26 to 93% and 20 to 99% for structure and process indicators. Significant (p < 0.001) between-centre variation was found in seven process and five outcome indicators with MORs ranging from 1.51 to 4.14. Statistical uncertainty of outcome indicators was generally high; five out of seven had less than 10 events per centre.

Conclusions
Overall, nine structures, five processes, but none of the outcome indicators showed potential for quality improvement purposes for TBI patients in the ICU. Future research should focus on implementation efforts and continuous reevaluation of quality indicators.

Trial registration
The core study was registered with ClinicalTrials.gov, number NCT02210221, registered on August 06, 2014, with Resource Identification Portal (RRID: SCR_015582).
A multicenter randomized trial of personalized acupuncture, fixed acupuncture, letrozole, and placebo letrozole on live birth in infertile women with polycystic ovary syndrome
Authors: Huang Shiya , Hu Min , Ng Ernest Hung Yu , Stener-Victorin Elisabet , Zheng Yanhua , Wen Qidan , Wang Cong , Lai Maohua , Li Juan , Gao Xingcheng , Wang Xinhua , Hu Zhenxing , Xia Tian , Hu Rongkui , Liu Jianping , Wen Xiaohui , Li Shuna , Quan Kewei , Liang Xingyan , Shang Hongcai , Ma Hongxia , Qiao Jie 
Published: March 2020

Abstract
Background
Traditional Chinese medicine (TCM) usually involves syndrome differentiation and treatment. Acupuncture, one form of TCM, requires the selection of appropriate acupoints and needling techniques, but many clinical trials on acupuncture have used fixed acupuncture protocols without accounting for individual patient differences. We have designed a multicenter randomized controlled trial (RCT) to evaluate whether personalized or fixed acupuncture increases the likelihood of live births in infertile women with polycystic ovary syndrome (PCOS) compared with letrozole or placebo letrozole. We hypothesize that letrozole is more effective than personalized acupuncture, which in turn is more effective than fixed acupuncture, and that placebo letrozole is the least effective intervention. Moreover, we hypothesize that personalized acupuncture is more likely to reduce the miscarriage rate and the risk of pregnancy complications compared with letrozole.

Methods/design
The study is designed as an assessor-blinded RCT. A total of 1100 infertile women with PCOS will be recruited from 28 hospitals and randomly allocated to 4 groups: personalized acupuncture, fixed acupuncture, letrozole, or placebo letrozole. They will receive treatment for 16 weeks, and the primary outcome is live birth. Secondary outcomes include ovulation rate, conception rate, pregnancy rate, pregnancy loss rate, changes in hormonal and metabolic parameters, and changes in quality of life scores. Adverse events will be recorded throughout the trial. All statistical analyses will be performed using IBM SPSS Statistics version 21.0 software (IBM Corp., Armonk, NY, USA), and a P value < 0.05 will be considered statistically significant.

Discussion
This study will be the first multicenter RCT to compare the effect of personalized or fixed acupuncture with letrozole or placebo letrozole on live birth in infertile women with PCOS. The findings will inform whether personalized acupuncture therapy can be considered an alternative treatment to improve the live birth rate in infertile women with PCOS.

Trial registration
ClinicalTrials.gov, NCT03625531. Registered on July 13, 2018.
Chinese Clinical Trial Registry, ChiCTR1800017304. Registered on July 23, 2018.