bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization and small-molecule stabilization of the multisite tandem binding between 14-3-3 and the R domain of CFTR
Authors: Stevers Loes M. , Lam Chan V. , Leysen Seppe F. R. , Meijer Femke A. , van Scheppingen Daphne S. , de Vries Rens M. J. M. , Carlile Graeme W. , Milroy Lech G. , Thomas David Y. , Brunsveld Luc , Ottmann Christian 
Published: February 2016

Significance
It has been shown that 14-3-3 proteins increase trafficking of cystic fibrosis transmembrane conductance regulator (CFTR) to the plasma membrane by binding to its regulatory (R) domain. This paper contains a detailed characterization of the 14-3-3/CFTR interaction, showing that multiple phosphorylated binding sites in the CFTR R-domain are necessary for significant binding with 14-3-3. We find that one of these binding sites serves as an anchor, while surrounding weaker sites enhance the interaction. Furthermore, we show the druggability of this interaction using natural-product fusicoccin-A, which stabilizes the 14-3-3/CFTR interaction by selectively modifying a weaker binding site. This mechanism of action can serve as a model for the development of new trafficking corrector molecules to treat cystic fibrosis.
Expression of factor H binding protein in meningococcal strains can vary at least 15-fold and is genetically determined
Authors: Biagini Massimiliano , Spinsanti Marco , De Angelis Gabriella , Tomei Sara , Ferlenghi Ilaria , Scarselli Maria , Rigat Fabio , Messuti Nicola , Biolchi Alessia , Muzzi Alessandro , Anderloni Giulia , Brunelli Brunella , Cartocci Elena , Buricchi Francesca , Tani Chiara , Stella Maria , Moschioni Monica , Del Tordello Elena , Colaprico Annalisa , Savino Silvana , Giuliani Marzia M. , Delany Isabel , Pizza Mariagrazia , Costantino Paolo , Norais Nathalie , Rappuoli Rino , Masignani Vega 
Published: February 2016

Significance
Complement is the main line of defense against bacterial pathogens; however, the molecular mechanisms triggering killing are largely unknown. Factor H binding protein (fHbp) is a component of two licensed vaccines against serogroup B meningococcus and a key target of complement-mediated bacterial killing. Selected reaction monitoring was used for the absolute quantification of fHbp on invasive meningococcal strains, showing that expression among strains can vary at least 15-fold and a minimum of 757 molecules separated by not more than 130 nm are required to engage C1q and kill the bacteria. Furthermore, the amount of fHbp is genetically determined by the sequence of the promoter region and correlated with the bactericidal activity. These findings increase the understanding of complement-mediated killing and vaccine protection.
Acute Cryptococcal Immune Reconstitution Inflammatory Syndrome in a Patient on Natalizumab
Authors: Gundacker Nathan D. , Jordan Stephen J. , Jones Benjamin A. , Drwiega Joseph C. , Pappas Peter G. 
Published: February 2016

Abstract
Presented is the first case of acute immune reconstitution inflammatory syndrome (IRIS)-associated cryptococcal meningoencephalitis in a patient on natalizumab for multiple sclerosis. The patient developed acute cerebral edema after initiation of amphotericin B. We propose several mechanisms that explain the acuity of IRIS in this specific patient population and suggest possible therapies.
A Missed Summer Wave of the 1918–1919 Influenza Pandemic: Evidence From Household Surveys in the United States and Norway
Authors: Mamelund Svenn-Erik , Haneberg Bjørn , Mjaaland Siri 
Published: February 2016

Abstract
Background.  Reanalysis of influenza survey data from 1918 to 1919 was done to obtain new insights into the geographic and host factors responsible for the various waves.
Methods.  We analyzed the age- and sex-specific influenza morbidity, fatality, and mortality for the city of Baltimore and smaller towns and rural areas of Maryland and the city of Bergen (Norway), using survey data. The Maryland surveys captured the 1918 fall wave, whereas the Bergen survey captured 3 waves during 1918–1919.
Results.  Morbidity in rural areas of Maryland was higher than in the city of Baltimore during the fall of 1918, that was almost equal to that in Bergen during the summer of 1918. In Bergen, the morbidity in the fall was only half of that in the summer, with more females than males just above the age of 20 falling ill, as seen in both regions of Maryland. In contrast, more males than females fell ill during the summer wave in Bergen. Individuals &lt;40 years had the highest morbidity, whereas school-aged children had the lowest fatality and mortality.
Conclusion.  A previously unrecognized pandemic summer wave may have hit the 2 regions of Maryland in 1918.
Randomized Sham-controlled Double-Blind Multicenter Clinical Trial to Ascertain the Effect of Percutaneous Radiofrequency Treatment for Sacroiliac Joint Pain
Authors: van Tilburg Cornelis W.J. , Schuurmans Fleur A. , Stronks Dirk L. , Groeneweg Johannes G. , Huygen Frank J.P.M. 
Published: February 2016

Objectives:
To investigate the effect of a percutaneous radiofrequency (RF) heat lesion compared with a sham procedure, applied to the lateral branches of L5, S1, S2, S3, and S4 nerve roots.

Materials and Methods:
Sixty patients aged 18 years and above with a medical history and physical examination suggestive for sacroiliac joint pain and a reduction of 2 or more on a numerical rating scale (NRS, 0 to 10) after a sacroiliac joint test block were included in this study. Treatment group: percutaneous RF heat lesion at the lateral branches of S1, S2, S3, and S4 nerve roots and the posterior ramus dorsalis of L5; sham group: same procedure as the treatment group except for the RF heat lesion. Primary outcome measure: pain reduction (NRS). Secondary outcome measure: Global Perceived Effect.

Results:
No statistically significant differences in pain level over time between the groups (Group×Period) (F
1,58=0.353; P=0.56) nor within the treatment Group (F
1,58=0.212; P=0.65) were found. The Period factor, however, yielded a significant difference (F
1,58=61.67; P<0.001), that is, when pooled together the mean pain level of the patients was significantly reduced at T1 compared with T0. In the crossover group, 42.1% experienced a reduction in NRS of 2 or more at 1 month (P=0.65). No statistically significant difference in satisfaction over time between the groups was found (F
1,50=2.1; P=0.15). The independent factors Group (F
1,50=2.02; P=0.16) and Period (F
1,50=0.95; P=0.33) also showed no statistically significant difference. The same applies to recovery: no statistically significant Group×Period effect (F
1,51=0.09; P=0.77) was found, neither an effect of Group (F
1,51=0.004; P=0.95) nor of Period (F
1,51=0.27; P=0.60).

Discussion:
The hypothesis of no difference in pain reduction or in Global Perceived Effect between the treatment and sham group cannot be rejected.

Level of Evidence:
Level 1A.
Efficacy of Cabbage Leaf Wraps in the Treatment of Symptomatic Osteoarthritis of the Knee
Authors: Lauche Romy , Gräf Nadine , Cramer Holger , Al-Abtah Jallal , Dobos Gustav , Saha Felix J. 
Published: February 2016

Objectives:
Osteoarthritis (OA) of the knee is one of the most common chronic diseases among older adults. This study aimed to test the effects of cabbage leaf wraps (CLWs) in the treatment of symptomatic OA.

Methods:
Patients with OA of the knee at stages II to III (Kellgren-Lawrence) were randomly assigned to 4 weeks of treatment with CLWs (daily for at least 2h), topical pain gel (TPG) (10 mg diclofenac/g, at least once daily), or usual care (UC). The primary outcome measure was pain intensity (VAS) after 4 weeks. Secondary outcomes included functional disability Western Ontario and McMaster Universities Arthritis Index (WOMAC), quality of life (SF-36), self-efficacy (Arthritis Self-Efficacy Scale-D), physical function (30 s Chair Stand Test), pressure pain sensitivity (PPT), satisfaction, and safety after 4 and 12 weeks.

Results:
In total, 81 patients were included in this study (42 women, 65.9±10.3 y). After 4 weeks patients in the CLW group reported significantly less pain compared with those in the UC group (difference, −12.1; 95% [confidence interval] CI, −23.1, −1.0; P=0.033) but not when compared with the TPG group (difference, −8.6; 95% CI, −21.5, 4.4; P=0.190). Significant effects were also found in WOMAC, SF-36, 30-second Chair Stand Test, and PPT scores in the CLW group compared with the UC group. Compared with TPG, effects from CLW were found for WOMAC after 4 weeks and for quality of life after 12 weeks. Patients were satisfied with both active interventions, and except for 2 adverse events in both groups the applications were well tolerated.

Conclusions:
CLWs are more effective for knee OA than UC, but not compared with diclofenac gel. Therefore, they might be recommended for patients with OA of the knee. Further research is warranted.
Differing Psychologically Derived Clusters in People With Chronic Low Back Pain are Associated With Different Multidimensional Profiles
Authors: Rabey Martin , Smith Anne , Beales Darren , Slater Helen , O’Sullivan Peter 
Published: February 2016

Objectives:
To explore the existence of subgroups in a cohort with chronic low back pain (n=294) based upon data from multiple psychological questionnaires, and profile subgroups on data from multiple dimensions.

Methods:
Psychological questionnaires considered as indicator variables entered into latent class analysis included: Depression, Anxiety, Stress scales, Thought Suppression and Behavioural Endurance subscales (Avoidance Endurance questionnaire), Chronic Pain Acceptance Questionnaire (short-form), Pain Catastrophising Scale, Pain Self-Efficacy Questionnaire, and Fear-Avoidance Beliefs Questionnaire. Multidimensional profiling of derived clusters included: demographics, pain characteristics, pain responses to movement, behaviors associated with pain, body perception, pain sensitivity, and health and lifestyle factors.

Results:
Three clusters were derived. Cluster 1 (23.5%) was characterized by low Cognitive and Affective Questionnaire scores, with the exception of fear-avoidance beliefs. Cluster 2 (58.8%) was characterized by relatively elevated thought suppression, catastrophizing, and fear-avoidance beliefs, but lower pain self-efficacy, depression, anxiety, and stress. Cluster 3 (17.7%) had the highest scores across cognitive and affective questionnaires.
Cluster 1 reported significantly lower pain intensity and bothersomeness than other clusters. Disability, stressful life events, and low back region perceptual distortion increased progressively from cluster 1 to cluster 3, whereas mindfulness progressively decreased. Clusters 2 and 3 had more people with an increase in pain following repeated forward and backward spinal bending, and more people with increasing pain following bending, than cluster 1. Cluster 3 had significantly greater lumbar pressure pain sensitivity, more undiagnosed comorbid symptoms, and more widespread pain than other clusters.

Discussion:
Clinical implications relating to presentations of each cluster are postulated.
The Effect of Medicinal Cannabis on Pain and Quality-of-Life Outcomes in Chronic Pain
Authors: Haroutounian Simon , Ratz Yael , Ginosar Yehuda , Furmanov Karina , Saifi Fayez , Meidan Ronit , Davidson Elyad 
Published: February 2016

Objectives:
The objective of this prospective, open-label study was to determine the long-term effect of medicinal cannabis treatment on pain and functional outcomes in participants with treatment-resistant chronic pain.

Patients and Methods:
The primary outcome was the change in the pain symptom score on the S-TOPS (Treatment Outcomes in Pain Survey—Short Form) questionnaire at the 6-month follow-up in an intent-to-treat population. Secondary outcomes included the change in S-TOPS physical, social, and emotional disability scales, the pain severity, and pain interference on the Brief Pain Inventory, sleep problems, and the change in opioid consumption.

Results:
A total of 274 participants were approved for treatment; complete baseline data were available for 206 (intent-to-treat), and complete follow-up data for 176 participants. At follow-up, the pain symptom score improved from median 83.3 (95% confidence interval [CI], 79.2-87.5) to 75.0 (95% CI, 70.8-79.2) (P<0.001). The pain severity score (7.50 [95% CI, 6.75-7.75] to 6.25 [95% CI, 5.75-6.75]) and the pain interference score (8.14 [95% CI, 7.28-8.43] to 6.71 [95% CI, 6.14-7.14]) improved (both P<0.001), together with most social and emotional disability scores. Opioid consumption at follow-up decreased by 44% (P<0.001). Serious adverse effects led to treatment discontinuation in 2 participants.

Discussion:
The treatment of chronic pain with medicinal cannabis in this open-label, prospective cohort resulted in improved pain and functional outcomes, and a significant reduction in opioid use. Results suggest long-term benefit of cannabis treatment in this group of patients, but the study’s noncontrolled nature should be considered when extrapolating the results.
Movement Along the Spine Induced by Transcranial Electrical Stimulation Related Electrode Positioning
Authors: Hoebink Eric A. , Journée Henricus L. , de Kleuver Marinus , Berends Hanneke , Racz Ilona , van Hal Chantal 
Published: February 2016

Study Design.
A prospective, nonrandomized cohort study.

Objective.
To describe a technique quantifying movement induced by transcranial electrical stimulation (TES) induced movement in relation to the positioning of electrodes during spinal deformity surgery.

Summary of Background Data.
TES induced movement may cause injuries and delay surgical procedures. When TES movements are evoked, muscles other than those being monitored any adjustments in stimulation protocols and electrode positioning may be expected to minimize movement whereas preserving quality of monitoring. In this study, seismic evoked responses (SER) induced through TES were studied at different electrode positions.

Methods.
Intraoperative TES-motor evoked potentials were carried out in 12 patients undergoing corrective spine surgery. Accelerometer transducers recorded SER in two directions at four different locations of the spine for TES-electrode montage groups Cz-Fz and C3-C4. A paired t test was used to compare the means of SER and the relationship between movement and TES electrode positioning.

Results.
SERs were strongest in the upper body. All mean SERs values for the Cz-Fz group were up to five times larger when compared with the C3-C4 group. However, there were no differences between the C3-C4 and Cz-Fz groups in the lower body locations. Both electrode montage groups showed a gradual stepwise reduction in all mean SER values along the spine from the cranial to caudal region. For the upper body locations, there were no significant associations between SER and both montages; in contrast, a significant association SER was demonstrated in the lumbar region.

Conclusion.
At supramaximum levels, movements resulting from multipulse TES are likely caused by relatively strong contractions from muscles in the neck resulting from direct extracranial stimulation. When interchanging electrode montages in individual cases, the movement in the neck may become reduced. At lumbar levels transcranial evoked muscle contractions dominate movement in the surgically exposed areas.

Level of Evidence: 4
How Effective is Physical Therapy for Common Low Back Pain Diagnoses?
Authors: Eleswarapu Ananth S. , Divi Srikanth N. , Dirschl Douglas R. , Mok James M. , Stout Christopher , Lee Michael J. 
Published: February 2016

Study Design.
A retrospective review.

Objective.
The aim of this study is to evaluate whether the treatment of low back pain with physical therapy results in clinically significant improvements in patient-reported pain and functional outcomes.

Summary of Background Data.
Low back pain is a major cause of morbidity and disability in health care. Previous studies have found poor efficacy for surgery in the absence of specific indications. A variety of nonoperative treatments are available; however, there is scant evidence to guide the practitioner as to the efficacy of these treatments.

Methods.
Four thousand five hundred ninety-seven patients who underwent physical therapy for the nonoperative treatment of low back pain were included. The primary outcome measures were pre-and post-treatment scores on the Oswestry Disability Index (ODI), Numeric Pain Rating Scale (NPRS) during activity, and NPRS during rest. Previously published thresholds for minimal clinically important difference (MCID) were used to determine the proportion of patients meeting MCID for each of our outcomes. Patients with starting values below the MCID for each variable were excluded from analysis. Logistic regression analysis was used to determine patient risk factors predictive of treatment failure.

Results.
About 28.5% of patients met the MCID for improvement in ODI. Presence of night symptoms, obesity, and smoking were predictors of treatment failure for ODI. Fifty-nine percent of patients met the MCID for improvement in resting NPRS, with a history of venous thromboembolism, night symptoms, psychiatric disease, workers’ compensation status, smoking, and obesity predictive of treatment failure. Sixty percent of patients met the MCID for improvement in activity NPRS, with night symptoms, workers’ compensation status, and smoking predictive of treatment failure.

Conclusion.
We observed that a substantial percentage of the population did not meet MCID for pain and function following treatment of low back pain with physical therapy. Common risk factors for treatment failure included smoking and presence of night symptoms.

Level of Evidence: 4
Surgical Outcomes and Prognostic Factors in Patients With Diffuse Large B-cell Lymphoma-associated Metastatic Spinal Cord Compression
Authors: Han Shuai , Yang Xinghai , Jiang Dongjie , Zhou Wang , Liu Tielong , Yan Wangjun , Wang Ting , Cheng Li , Xiao Jianru 
Published: February 2016

Study Design.
A retrospective study.

Objective.
The aim of this study was to discuss the factors that may affect surgical outcomes of patient with diffuse large B-cell lymphoma (DLBCL)-associated metastatic spinal cord compression (MSCC).

Summary of Background Data.
DLBCL in the spine is rare and minimal information has been published in the literature regarding this subject. Although DLBCL is highly sensitive to both chemotherapy and radiotherapy, surgical decompression is recommended in the treatment of DLBCL-associated MSCC. However, the prognostic factors affecting surgical outcomes of patients with DLBCL-associated MSCC remain unknown.

Methods.
We conducted a retrospective study to investigate the impact of surgical decompression on recovery from neurological deficit caused by DLBCL-associated MSCC. Univariate and multivariate analyses were performed to identify prognostic factors for overall survival of spinal DLBCL. The survival rate was estimated by the Kaplan-Meier method, and differences were analyzed by the log-rank test. Factors with P values of 0.1 or less were subjected to multivariate analysis for survival rate by multivariate Cox proportional hazards analysis.

Results.
A total of 37 patients with spinal DLBCL from 2003 to 2014 were included in the study. International Prognostic Index (IPI) (0–1/2–5), duration of preoperative symptoms (≤2m/>2m), and lactate dehydrogenase (normal/abnormal) were suggested as the potential prognostic factors through univariate analysis. However, as they were submitted to the multivariate Cox regression model, only IPI and duration of preoperative symptoms were found as independent prognostic factors.

Conclusion.
Surgical decompression improves recovery from neurological deficit. Patient IPI score plays an important role in decision making for surgical intervention, as it affects the length of survival and functional outcome. Patients with duration of preoperative symptoms no more than 2 months confer a very poor prognosis.

Level of Evidence: 4
Cost Averted With Timely Fecal Microbiota Transplantation in the Management of Recurrent Clostridium difficile Infection in Alberta, Canada
Authors: Waye Arianna , Atkins Kerry , Kao Dina 
Published: February 2016

Background:
Fecal microbiota transplantation (FMT) is highly effective in treating recurrent Clostridium difficile infection (RCDI). However, the ideal timing for offering FMT remains to be determined. Furthermore, the direct medical costs averted with timely FMT have not been examined.

Methods:
A retrospective review of the Edmonton FMT program database included patients who received FMT for RCDI (October 2012 to September 2014). They were divided into 2 groups: those who received FMT after 2 recurrences (the timely FMT group) and those who received FMT after at least 3 recurrences (the delayed FMT group). The primary outcome was the difference in direct medical costs related to hospital admissions and emergency room visits due to CDI between the 2 groups. The secondary outcomes were RCDI cure rate and duration of RCDI in each group.

Results:
A total of 75 patients were included: 30 received timely FMT, whereas 45 received delayed FMT. The mean difference in hospital length of stay and emergency room visits related to CDI were 13.8 days shorter and 1.3 visits fewer with timely FMT, associated with a mean cost saving of $29,842 per patient. Sensitivity analysis was performed to examine the effect of outliers and comorbities on the differential costs, and it was found that the differences in average cost per patient were more pronounced in those with Charlson comorbidity index ≥3 compared with those with scores of 0 to 2. The cure rate was 94% (timely FMT group) and 93% (delayed FMT group). The mean duration of RCDI was 109 days (timely FMT group) and 281 days (delayed FMT group).

Conclusions:
Timely FMT can provide significant cost savings to health-care systems, especially for patients with multiple comorbidities.
Obstructive sleep apnea is associated with fatty liver index, the index of nonalcoholic fatty liver disease
Authors: Chen Xiao , Lin Xian , Chen Li-Da , Lin Qi-Chang , Chen Gong-Ping , Yu Yao-Hua , Huang Jian-Chai , Zhao Jian-Ming 
Published: February 2016

Background and objectives
The relationship between obstructive sleep apnea (OSA) and nonalcoholic fatty liver disease (NAFLD) is gaining increased attention. The aim of the present study was to examine the relationship of OSA with NAFLD defined by an elevated fatty liver index (FLI).

Materials and methods
A total of 319 consecutive patients who underwent standard polysomnography were enrolled. Fasting blood samples were obtained from all patients for biological profile measurements, and demographic data were collected. Values of FLI were determined and assessed as predictors of the presence of NAFLD, as measured by ultrasound. The discriminative ability of FLI was estimated on the basis of the area under the receiver operator characteristic curve.

Results
An FLI of 60 achieved the highest diagnostic accuracy and yielded an area under the receiver operator characteristic curve of 0.822 (95% confidence interval: 0.729–0.916) in the detection of NAFLD. Patients with an FLI of 60 or higher had a significantly lower lowest O2 saturation (73 vs. 83%, P<0.001), a lower mean nocturnal oxygen saturation (93 vs. 95%, P<0.001), a higher apnea–hypopnea index (39.7 vs. 18.4, P<0.001), a higher oxygen desaturation index (39 vs. 10.6, P<0.001), and a higher percentage of sleep time spent with SpO2 less than 90% (4.63 vs. 0.92%, P<0.001) compared with those with FLI less than 60. In multivariate analysis, the presence of OSA was independently associated with elevated FLI after adjusting for confounding factors (odds ratio: 5.141, 95% confidence interval: 1.414–18.696, P=0.013).

Conclusion
Our results suggest a positive association between the severity of OSA and NAFLD defined by an elevated FLI, which may serve as a good biomarker for detecting NAFLD in OSA patients.