bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ketogenic diet and fasting diet as Nutritional Approaches in Multiple Sclerosis (NAMS): protocol of a randomized controlled study
Authors: Bahr Lina Samira , Bock Markus , Liebscher Daniela , Bellmann-Strobl Judith , Franz Liane , Prüß Alexandra , Schumann Dania , Piper Sophie K. , Kessler Christian S. , Steckhan Nico , Michalsen Andreas , Paul Friedemann , Mähler Anja 
Published: January 2020

Abstract
Background
Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adults that may lead to progressive disability. Since pharmacological treatments may have substantial side effects, there is a need for complementary treatment options such as specific dietary approaches. Ketone bodies that are produced during fasting diets (FDs) and ketogenic diets (KDs) are an alternative and presumably more efficient energy source for the brain. Studies on mice with experimental autoimmune encephalomyelitis showed beneficial effects of KDs and FDs on disease progression, disability, cognition and inflammatory markers. However, clinical evidence on these diets is scarce. In the clinical study protocol presented here, we investigate whether a KD and a FD are superior to a standard diet (SD) in terms of therapeutic effects and disease progression.

Methods
This study is a single-center, randomized, controlled, parallel-group study. One hundred and eleven patients with relapsing–remitting MS with current disease activity and stable immunomodulatory therapy or no disease-modifying therapy will be randomized to one of three 18-month dietary interventions: a KD with a restricted carbohydrate intake of 20–40 g/day; a FD with a 7-day fast every 6 months and 14-h daily intermittent fasting in between; and a fat-modified SD as recommended by the German Nutrition Society. The primary outcome measure is the number of new T2-weighted MRI lesions after 18 months. Secondary endpoints are safety, changes in relapse rate, disability progression, fatigue, depression, cognition, quality of life, changes of gut microbiome as well as markers of inflammation, oxidative stress and autophagy. Safety and feasibility will also be assessed.

Discussion
Preclinical data suggest that a KD and a FD may modulate immunity, reduce disease severity and promote remyelination in the mouse model of MS. However, clinical evidence is lacking. This study is the first clinical study investigating the effects of a KD and a FD on disease progression of MS.

Trial registration
ClinicalTrials.gov, NCT03508414. Retrospectively registered on 25 April 2018.
Corticosteroid injection plus exercise versus exercise, beyond advice and a heel cup for patients with plantar fasciopathy: protocol for a randomised clinical superiority trial (the FIX-Heel trial)
Authors: Riel Henrik , Vicenzino Bill , Olesen Jens Lykkegaard , Jensen Martin Bach , Ehlers Lars Holger , Rathleff Michael Skovdal 
Published: January 2020

Abstract
Background
Plantar fasciopathy has a lifetime prevalence of 10%. Patients experience sharp pain under the heel, often for several months or years. Multiple treatments are available, but no single treatment appears superior to the others. A corticosteroid injection offers short-term pain relief but is no better than placebo in the longer term (> 8 weeks). Heavy-slow resistance training has shown potentially positive effects on long-term outcomes (> 3 months), and combining exercises with an injection may prove to be superior to exercises alone. However, the effect of heavy-slow resistance training compared with a simpler approach of patient advice (e.g., load management) and insoles is currently unknown. This trial compares the efficacy of patient advice with patient advice plus heavy-slow resistance training and with patient advice plus heavy-slow resistance training plus a corticosteroid injection in improving the Foot Health Status Questionnaire pain score after 12 weeks in patients with plantar fasciopathy.

Methods
In this randomised superiority trial, we will recruit 180 patients with ultrasound-confirmed plantar fasciopathy and randomly allocate them to one of three groups: (1) patient advice and an insole (n = 60); (2) patient advice, an insole, and self-dosed heavy-slow resistance training consisting of heel raises (n = 60); or (3) patient advice, an insole, heavy-slow resistance training, and an ultrasound-guided corticosteroid injection (n = 60). All participants will be followed for 1 year, with the 12-week follow-up considered the primary endpoint. The primary outcome is the Foot Health Status questionnaire pain domain score. Secondary outcomes include the remaining three domains of the Foot Health Status Questionnaire, a 7-point Global Rating of Change, the Pain Self-Efficacy Questionnaire, physical activity level, health-related quality of life measured by the EQ-5D-5L, and Patient Acceptable Symptom State, which is the point at which participants feel no further need for treatment. Additionally, a health economic evaluation of the treatments will be carried out.

Discussion
This trial will test if adding heavy-slow resistance training to fundamental patient advice and an insole improves outcomes and if a corticosteroid injection adds even further to that effect in patients with plantar fasciopathy.

Trial registration
ClinicalTrials.gov, NCT03804008. Prospectively registered on January 15, 2019.
Effects of lutein supplementation on inflammatory biomarkers and metabolic risk factors in adults with central obesity: study protocol for a randomised controlled study
Authors: Zhou Juan , Zhao Dan , Wang Ning , Zeng Zhiwei , Wang Changyi , Hao Liping , Peng Xiaolin 
Published: January 2020

Abstract
Background
The prevalence of central obesity is constantly increasing, and visceral fat is associated with increased production of inflammatory factors and metabolic risk factors. Lutein might retard the development of metabolic disease through its antioxidant and anti-inflammatory properties. Furthermore, epidemiological studies have associated higher dietary intake and serum levels of lutein with decreased adiposity. However, few randomised controlled trials have shown the effects of lutein supplementation on inflammatory biomarkers and metabolic risk factors, especially in adults with central obesity.

Methods
This study will be conducted as a double-blind, parallel placebo-controlled clinical trial in which 120 people who have central obesity, are 18 to 60 years old and are willing to provide informed consent will be randomly assigned to the intervention or placebo group in a 1:1 ratio according to sex, age and waist circumference. The intervention group will receive 10 mg daily lutein supplementation for 12 weeks to explore the effect of lutein supplementation on serum lutein, glycaemic and lipid profiles, inflammatory factors and body composition. Two populations (intention-to-treat population and per-protocol population) will be used in the data analyses.

Discussion
Our findings from this trial will contribute to the knowledge of the association between lutein supplementation and inflammatory biomarkers and metabolic risk factors in people with central obesity and will offer a possibility for the prevention of inflammatory diseases.

Trial registration
Chinese Clinical Trial Registry: ChiCTR1800018098. Registered on 30 August 2018.
A traffic data collection and analysis method based on wireless sensor network
Authors: Wang Huan , Ouyang Min , Meng Qingyuan , Kong Qian 
Published: January 2020

AbstractWith the rapid development of urbanization, collecting and analyzing traffic flow data are of great significance to build intelligent cities. The paper proposes a novel traffic data collection method based on wireless sensor network (WSN), which cannot only collect traffic flow data, but also record the speed and position of vehicles. On this basis, the paper proposes a data analysis method based on incremental noise addition for traffic flow data, which provides a criterion for chaotic identification. The method adds noise of different intensities to the signal incrementally by an improved surrogate data method and uses the delayed mutual information to measure the complexity of signals. Based on these steps, the trend of complexity change of mixed signal can be used to identify signal characteristics. The numerical experiments show that, based on incremental noise addition, the complexity trends of periodic data, random data, and chaotic data are different. The application of the method opens a new way for traffic flow data collection and analysis.
Multiple positive solutions to singular fractional differential equations with integral boundary conditions involving $p-q$-order derivatives
Authors: Wang Han , Jiang Jiqiang 
Published: January 2020

AbstractIn this paper, we investigate the existence for a class of higher-order fractional differential equations with integral boundary value conditions involving$p-q$p−q-order derivatives. As an application of the height functions on some special bounded sets, we obtain the existence of two positive solutions by means of the Leray–Schauder nonlinear alternative and cone expansion and cone compression fixed point theory. The nonlinearity may take negative infinity, and there may appear a singular phenomenon on both time and space variables.
The SMAC mimetic LCL-161 selectively targets JAK2V617F mutant cells
Authors: Craver Brianna M. , Nguyen Thanh Kim , Nguyen Jenny , Nguyen Hellen , Huynh Christy , Morse Sarah J. , Fleischman Angela G. 
Published: January 2020

Abstract
Background
Evasion from programmed cell death is a hallmark of cancer and can be achieved in cancer cells by overexpression of inhibitor of apoptosis proteins (IAPs). Second mitochondria-derived activator of caspases (SMAC) directly bind to IAPs and promote apoptosis; thus, SMAC mimetics have been investigated in a variety of cancer types. particularly in diseases with high inflammation and NFĸB activation. Given that elevated TNFα levels and NFĸB activation is a characteristic feature of myeloproliferative neoplasms (MPN), we investigated the effect of the SMAC mimetic LCL-161 on MPN cell survival in vitro and disease development in vivo.

Methods
To investigate the effect of the SMAC mimetic LCL-161 in vitro, we utilized murine and human cell lines to perform cell viability assays as well as primary bone marrow from mice or humans with JAK2V617F–driven MPN to interrogate myeloid colony formation. To elucidate the effect of the SMAC mimetic LCL-161 in vivo, we treated a JAK2V617F–driven mouse model of MPN with LCL-161 then assessed blood counts, splenomegaly, and myelofibrosis.

Results
We found that JAK2V617F-mutated cells are hypersensitive to the SMAC mimetic LCL-161 in the absence of exogenous TNFα. JAK2 kinase activity and NFĸB activation is required for JAK2V617F-mediated sensitivity to LCL-161, as JAK or NFĸB inhibitors diminished the differential sensitivity of JAK2V617F mutant cells to IAP inhibition. Finally, LCL-161 reduces splenomegaly and may reduce fibrosis in a mouse model of JAK2V617F-driven MPN.

Conclusion
LCL-161 may be therapeutically useful in MPN, in particular when exogenous TNFα signaling is blocked. NFĸB activation is a characteristic feature of JAK2V617F mutant cells and this sensitizes them to SMAC mimetic induced killing even in the absence of TNFα. However, when exogenous TNFα is added, NFĸB is activated in both mutant and wild-type cells, abolishing the differential sensitivity. Moreover, JAK kinase activity is required for the differential sensitivity of JAK2V617F mutant cells, suggesting that the addition of JAK2 inhibitors to SMAC mimetics would detract from the ability of SMAC mimetics to selectively target JAK2V617F mutant cells. Instead, combination therapy with other agents that reduce inflammatory cytokines but preserve JAK2 signaling in mutant cells may be a more beneficial combination therapy in MPN.
Gravity analysis of the offset between crustal structure and topography in the Liupan Shan, northeast Tibetan Plateau
Authors: Wang Zhenyu , Fu Guangyu 
Published: January 2020

AbstractDense gravity/GPS measurements collected around the southwest margin of the Ordos Block in 2014 and 2017 were used to obtain three gravity anomaly profiles across the Liupan Shan Mountains. The Liupan Shan is located in a Bouguer gravity anomaly (BGA) transitional zone; however, low BGAs to the west do not correspond to the topography of the Liupan Shan in that region, with a maximum offset of approximately 34 km. This offset is also found in inverted crustal density structures whereby the interface between the upper and lower crust is notably concave to the west of the Liupan Shan. Flexural analysis indicates that the effective elastic thickness is 5 km and the uplift is caused by oblique subduction of surface materials. According to this uplift mechanism, the offset suggests that Liupan Shan migrated eastward following partial isostatic compensation. Therefore, we suggest that Liupan Shan has experienced an uplift–compensation–uplift tectonic process.
Laceration of the transverse mesocolon in an old man with a habit of abdominal massage for constipation: a case report
Authors: Mori Shusuke , Ai Tomohiko , Otomo Yasuhiro 
Published: January 2020

Abstract
Background
Abdominal massage for the resolution of constipation has been reported to be safe and recommended in some studies. It is conventionally performed for the elderly suffering from intractable constipation. Meantime, isolated mesenteric injury after blunt abdominal trauma is uncommon. Here, we report a case of isolated mesenteric injury following self-abdominal massage for constipation.

Case presentation
A 68-year-old man consulted a local hospital due to a sudden abdominal pain. He had a history of prostate cancer treated with radiation therapy 3 years ago, and he had been suffering from chronic constipation for many years. A plain computed tomography (CT) revealed a fist-sized homogeneous mass-like lesion located in the left upper abdomen and a moderate amount of ascites. With the initial diagnosis of a malignant tumor accompanied by peritonitis carcinomatosa, he was hospitalized for further examinations. On the next day, his hemoglobin concentration dropped from 11.6 to 6.6 g/dl, and diagnostic paracentesis showed bloody ascites. He was urgently transferred to our tertiary emergency center. An enhanced CT demonstrated a non-enhanced, homogeneous, 8.5 cm in diameter, mass lesion located to the posterior of the stomach with massive bloody ascites. He underwent an emergency exploratory laparotomy, and it showed a 5 cm of laceration in the transverse mesocolon adjacent to Treitz’s ligament and approximately 1.5 l of intraabdominal hemorrhage. Hemostasis of the bleeding from the laceration was achieved by suture ligations, but the gap of the laceration could not be closed by suturing because the tissue was too fragile. Blood transfusion with 4 units of packed red blood cells and 10 units of fresh frozen plasma was performed during operation. He was discharged without any significant complications except for postoperative paralytic ileus. Later on, it turned out that he had a habit of massaging his abdomen for the resolution of intractable constipation and did it hard 1 day before the onset.

Conclusions
This is the first report of life-threatening mesenteric injury caused by self-abdominal massage to resolve constipation, though other etiologies such as rupture of small aneurysms could not perfectly be excluded. Abdominal massage is reported to be effective and safe for the resolution of constipation; however, this case demonstrated it could be detrimental.
Overbaked: assessing and predicting acute adverse reactions to Cannabis
Authors: LaFrance Emily M. , Stueber Amanda , Glodosky Nicholas C. , Mauzay Dakota , Cuttler Carrie 
Published: January 2020

Abstract
Background
Trends toward legalizing cannabis may increase experimentation with the drug among less experienced users with limited knowledge of possible adverse reactions. This study explores the prevalence, frequency, and levels of distress produced by various acute adverse reactions to cannabis, as well as predictors of these reactions.

Methods
The Adverse Reactions Scale (ARS) was created and administered to a large sample of undergraduate college students (n = 999) who were predominantly white (> 70%), female (> 70%), recreational (> 90%) cannabis users. The ARS was administered in an anonymous online survey measuring demographics, cannabis use patterns, cannabis use motives, personality, and negative affect.

Results
The most prevalent adverse reactions to cannabis were coughing fits, anxiety, and paranoia, which > 50% of the sample reported experiencing. The most frequently occurring reactions were coughing fits, chest/lung discomfort, and body humming, which occurred on approximately 30–40% of cannabis use sessions. Panic attacks, fainting, and vomiting were rated as the most distressing, with mean ratings falling between “moderately” and “quite” distressing. Multiple regression analyses revealed that lower frequency of cannabis use predicted increased frequency of adverse reactions. Symptoms of cannabis use disorder, conformity motives, and anxiety sensitivity were significant predictors of both the prevalence of, and distress caused by, adverse reactions.

Conclusions
Relative to past research, this study provides a more comprehensive account of possible adverse reactions to cannabis, and individual difference variables that predict these reactions. This study has implications for inexperienced cannabis users, as well as medical professionals and budtenders who provide information about cannabis use.
Anti–B-Cell Maturation Antigen BiTE Molecule AMG 420 Induces Responses in Multiple Myeloma
Authors: Topp Max S. , Duell Johannes , Zugmaier Gerhard , Attal Michel , Moreau Philippe , Langer Christian , Krönke Jan , Facon Thierry , Salnikov Alexey V. , Lesley Robin , Beutner Karl , Kalabus James , Rasmussen Erik , Riemann Kathrin , Minella Alex C. , Munzert Gerd , Einsele Hermann 
Published: January 2020

PURPOSE The anti–B-cell maturation antigen BiTE molecule AMG 420 was assessed in patients with relapsed/refractory multiple myeloma. PATIENTS AND METHODS In this first-in-human study, up to 10 cycles of AMG 420 were given (4-week infusions/6-week cycles). Patients had progression after ≥ 2 lines of prior therapy and no extramedullary disease. Minimal residual disease (MRD) response was defined as < 1 tumor cell/104 bone marrow cells by flow cytometry. RESULTS Forty-two patients received AMG 420 at 0.2-800 μg/d. Median age was 65 years, and median disease duration was 5.2 years. Median exposure was 1 cycle (range, 1-10 cycles) and 7 cycles (range, 1-10 cycles) for responders. Patients discontinued for disease progression (n = 25), adverse events (AEs; n = 7), death (n = 4), completion of 10 cycles (n = 3), and consent withdrawal (n = 1). Two patients remain on treatment. There were 2 nontreatment-related deaths from AEs, influenza/aspergillosis and adenovirus-related hepatitis. Serious AEs (n = 20; 48%) included infections (n = 14) and polyneuropathy (n = 2); treatment-related serious AEs included 2 grade 3 polyneuropathies and 1 grade 3 edema. There were no grade ≥ 3 CNS toxicities or anti-AMG 420 antibodies. In this study, 800 μg/d was considered to not be tolerable because of 1 instance each of grade 3 cytokine release syndrome and grade 3 polyneuropathy, both of which resolved. The overall response rate was 31% (n = 13 of 42). At the maximum tolerated dose (MTD) of 400 μg/d, the response rate was 70% (n = 7 of 10). Of these, five patients experienced MRD-negative complete responses, and 1 had a partial response, and 1 had a very good partial response; all 7 patients responded during the first cycle, and some responses lasted > 1 year. CONCLUSION In this study of AMG 420 in patients with relapsed/refractory multiple myeloma, the response rate was 70%, including 50% MRD-negative complete responses, at 400 μg/d, the MTD for this study.
Increasing Cervical Cancer Incidence in Rural Eastern Cape Province of South Africa From 1998 to 2012: A Population-Based Cancer Registry Study
Authors: Somdyala Nontuthuzelo I.M. , Bradshaw Debbie , Dhansay Muhammad A. , Stefan Daniela C. 
Published: January 2020

PURPOSE In this study, we aimed to investigate trends in the age-standardized and age-specific incidence rates in two distinct regions (the northern and southern areas) of South Africa covered by a population-based cancer registry. In addition, trends in coverage of the cervical cancer screening program were assessed using routine health service data. METHODS Occurrences (topography C53.0-C53.9) for the period 1998-2012 were extracted from a cancer registry database from which basic descriptive statistics and frequencies were analyzed for all variables using CanReg4. Trends over time were estimated using a direct standardization method and world standard population as a reference. Screening coverage annualized figures for women age ≥ 30 years by sub–health district were extracted from the District Health Information System. RESULTS In the northern area, annual age-standardized incidence rates per 100,000 women increased from 24.0 (95% CI, 21.1 to 27.0) in 1998-2002 to 39.0 (95% CI, 35.6 to 42.5) in 2008-2012, with a screening coverage rate of 15% by 2012. In contrast, no increase was observed in incidence in the southern area, with rates of 20.0 (95% CI, 18.5 to 21.4) in 1998-2002 and 18.8 (95% CI, 16.2 to 21.4) in 2008-2012, and the southern area had a higher screening coverage of 41% in 2012. Overall, the percentage distribution of stage at diagnosis showed that 28.5% of occurrences were diagnosed at disease stages I and II and 35%, at III and IV; 36% had with missing stage information (2003-2012). In 77% of occurrences, a histologically verified diagnosis was made, compared with only 12.3% by cytology. CONCLUSION This study has demonstrated an almost two-fold increase in the incidence rate in the northern area but little change in the southern area of the cancer registry.
Least square fitting demodulation technique for the interrogation of an optical fiber Fabry–Perot sensor with arbitrary reflectivity
Authors: Liu Wenyi , Ren Qianyu , Jia Pinggang , Hong Yingping , Liang Ting , Liu Jia , Xiong Jijun 
Published: January 2020

A novel Fabry–Perot (F–P) demodulation technique based on least square fitting for arbitrary reflectivity F–P sensors is proposed. The demodulation method was simulated and analyzed to verify feasibility of the algorithm. Two different finesse F–P interferometers constructed with a reflector bracket were used to make the stability experiments and the stepping experiments. The results show that the demodulation technique can interrogate the cavity length of F–P interferometers with different fineness in a wide range, and the demodulation error is less than 12 nm.
Ultra compact Bragg grating devices with broadband selectivity
Authors: Li Ang , Davis Jordan , Fainman Yeshaiahu 
Published: January 2020

Current silicon waveguide Bragg gratings typically introduce perturbation to the optical mode in the form of modulation of the waveguide width or cladding. However, since such a perturbation approach is limited to weak perturbations to avoid intolerable scattering loss and higher-order modal coupling, it is difficult to produce ultra-wide stopbands. In this Letter, we report an ultra-compact Bragg grating device with strong perturbations by etching nanoholes in the waveguide core to enable an ultra-large stopband with apodization achieved by proper location of the nanoholes. With this approach, a 15 µm long device can generate a stopband as wide as 110 nm that covers the entire

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band with a 40 dB extinction ratio and over a 10 dB sidelobe suppression ratio (SSR). Similar structures can be further optimized to achieve higher SSR of

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for a stopband of about 80 nm.