bluuebunny/crossref_metadata_2025_split huggingface dataset:
FVIII half-life extension by coadministration of a D′D3 albumin fusion protein in mice, rabbits, rats, and monkeys
Authors: Pestel Sabine , Beltz Hans-Wilhelm , Claar Philipp , Lind Holger , Mischnik Marcel , Raquet Elmar , Andrews Arna , Simmonds Jason , Tomasetig Vesna , Dower Steven K. , Tjärnlund-Wolf Anna , Schulte Stefan , Schmidt Peter M. , Weimer Thomas 
Published: May 2020

AbstractA novel mechanism for extending the circulatory half-life of coagulation factor VIII (FVIII) has been established and evaluated preclinically. The FVIII binding domain of von Willebrand factor (D′D3) fused to human albumin (rD′D3-FP) dose dependently improved pharmacokinetics parameters of coadministered FVIII in all animal species tested, from mouse to cynomolgus monkey, after IV injection. At higher doses, the half-life of recombinant FVIII (rVIII-SingleChain) was calculated to be increased 2.6-fold to fivefold compared with rVIII-SingleChain administered alone in rats, rabbits, and cynomolgus monkeys, and it was increased 3.1-fold to 9.1-fold in mice. Sustained pharmacodynamics effects were observed (ie, activated partial thromboplastin time and thrombin generation measured ex vivo). No increased risk of thrombosis was observed with coadministration of rVIII-SingleChain and rD′D3-FP compared with rVIII-SingleChain alone. At concentrations beyond the anticipated therapeutic range, rD′D3-FP reduced the hemostatic efficacy of coadministered rVIII-SingleChain. This finding might be due to scavenging of activated FVIII by the excessive amount of rD′D3-FP which, in turn, might result in a reduced probability of the formation of the tenase complex. This observation underlines the importance of a fine-tuned balance between FVIII and its binding partner, von Willebrand factor, for hemostasis in general.
BK virus–specific T-cell immune reconstitution after allogeneic hematopoietic cell transplantation
Authors: Espada Eduardo , Cheng Matthew P. , Kim Haesook T. , Woolley Ann E. , Avigan Jason I. , Forcade Edouard , Soares Maria V. D. , Lacerda João F. , Nikiforow Sarah , Gooptu Mahasweta , Romee Rizwan , Alyea Edwin P. , Armand Philippe , Cutler Corey S. , Ho Vincent T. , Koreth John , Antin Joseph H. , Soiffer Robert J. , Marty Francisco M. , Ritz Jerome 
Published: May 2020

AbstractClinical disease caused by BK virus reactivation is a frequent complication of allogeneic hematopoietic cell transplantation (HCT). Because of the lack of effective antiviral agents, BK virus–specific T cells are emerging as a potential therapy for BK virus disease, but the immune response to BK virus after allogeneic HCT has not been well characterized. Our study describes reconstitution of BK virus–specific T-cell immunity in 77 adult patients after HCT. All patients had urinary symptoms, and urine was tested for BK virus replication; 33 patients were positive for BK virus (cases), and 44 were negative (controls). In BK virus cases, the median time to first positive test was 75 days (range, 2-511). BK virus cases had lower CD4 T-cell counts 3 to 9 months after transplant, but CD8 T-cell counts were similar in cases and controls. BK virus–specific T cells were identified by cytokine flow cytometry in cryopreserved samples collected prospectively. BK virus–specific CD4 T cells producing T helper 1 (Th1) cytokines recovered quickly after HCT. BK virus–specific T cells were detected more frequently in patients with BK virus reactivation at most time points, and CD4 T cells producing Th1 cytokines were more frequent than BK virus–specific cytolytic CD8 T cells. Early detection of interferon-γ+ and cytolytic BK virus–specific CD4 T cells was associated with lower rates of hematuria among cases. Overall, our study describes recovery of BK virus–specific T cells after HCT and the distinct roles for BK virus–specific T cells in the development and resolution of clinical symptoms.
Upregulation of miR-215 attenuates propofol-induced apoptosis and oxidative stress in developing neurons by targeting LATS2
Authors: Tang Fang , Zhao Lili , Yu Qi , Liu Tianyin , Gong Hongyan , Liu Zhiyi , Li Qing 
Published: May 2020

AbstractBackgroundPropofol is an intravenous anesthetic agent that commonly induces significant neuroapoptosis. MicroRNAs (miRNAs) have been reported to participate in the regulation of propofol exposure-mediated neurotoxicity. MiR-215, as one of miRNAs, was found to regulate nerve cell survival. However, the mechanism through which miRNAs regulate propofol exposure-mediated neurotoxicity is still unclear.MethodsReal-time PCR was used to detect miR-215 expression level. Cell viability was measured using MTT assay. Cell apoptosis was examined via flow cytometry analysis. ROS, MDA, LDH and SOD levels were assayed through ELISA kits. Dual luciferase reporter assay identified the interaction between miR-215 and large tumor suppressor 2 (LATS2). Protein level was detected using western blot analysis.ResultsMiR-215 expression was downregulated in propofol-treated rat hippocampal neurons. MiR-215 mimics promoted cell viability and reduced apoptosis in propofol-treated neonatal rat hippocampal neuron. MiR-215 mimics also caused inhibition of oxidative stress as evidenced by suppression of ROS, MDA and LDH levels as well as increase of SOD level. In addition, we found that large tumor suppressor 2 (LATS2) is a target of miR-215 and miR-215 mimics decreased LATS2 level in propofol-treated neonatal rat hippocampal neuron. Further, LATS2 overexpression suppressed the effect of miR-215 on propofol-induced apoptosis and oxidative stress in neonatal rat hippocampal neuron.ConclusionTaken together, we demonstrate that miR-215 attenuates propofol-induced apoptosis and oxidative stress in neonatal rat hippocampal neuron by targeting LATS2, suggesting that miR-215 may provide a new candidate for the treatment of propofol exposure-induced neurotoxicity.
Predictors of pain in general ageing populations: results from a multi-country analysis based on ATHLOS harmonized database
Authors: Raggi Alberto , Leonardi Matilde , Mellor-Marsá Blanca , Moneta Maria V. , Sanchez-Niubo Albert , Tyrovolas Stefanos , Giné-Vázquez Iago , Haro Josep M. , Chatterji Somnath , Bobak Martin , Ayuso-Mateos Jose L. , Arndt Holger , Hossin Muhammad Z. , Bickenbach Jerome , Koskinen Seppo , Tobiasz-Adamczyk Beata , Panagiotakos Demosthenes , Corso Barbara 
Published: May 2020

Abstract
Background
Pain is a common symptom, often associated with neurological and musculoskeletal conditions, and experienced especially by females and by older people, and with increasing trends in general populations. Different risk factors for pain have been identified, but generally from studies with limited samples and a limited number of candidate predictors. The aim of this study is to evaluate the predictors of pain from a large set of variables and respondents.

Methods
We used part of the harmonized dataset of ATHLOS project, selecting studies and waves with a longitudinal course, and in which pain was absent at baseline and with no missing at follow-up. Predictors were selected based on missing distribution and univariable association with pain, and were selected from the following domains: Socio-demographic and economic characteristics, Lifestyle and health behaviours, Health status and functional limitations, Diseases, Physical measures, Cognition, personality and other psychological measures, and Social environment. Hierarchical logistic regression models were then applied to identify significant predictors.

Results
A total of 13,545 subjects were included of whom 5348 (39.5%) developed pain between baseline and the average 5.2 years’ follow-up. Baseline risk factors for pain were female gender (OR 1.34), engaging in vigorous exercise (OR 2.51), being obese (OR 1.36) and suffering from the loss of a close person (OR 1.88) whereas follow-up risk factors were low energy levels/fatigue (1.93), difficulties with walking (1.69), self-rated health referred as poor (OR 2.20) or average to moderate (OR 1.57) and presence of sleep problems (1.80).

Conclusions
Our results showed that 39.5% of respondents developed pain over a five-year follow-up period, that there are proximal and distal risk factors for pain, and that part of them are directly modifiable. Actions aimed at improving sleep, reducing weight among obese people and treating fatigue would positively impact on pain onset, and avoiding vigorous exercise should be advised to people aged 60 or over, in particular if female or obese.
Localized biphasic malignant mesothelioma presenting as a giant pelvic wall mass: a rare case report and literature review
Authors: Liu Yunsong , Wu Jingjun , Zhao Ying , Zhang Pengxin , Hua Zhengyu , Dong Wan , Lin Tao , Liu Ailian 
Published: May 2020

Abstract
Background
Localized biphasic MPeM is rare in clinical practice, we reviewed 8 cases of localized biphasic MPeM (including our present case), and summarized the clinical and imaging features of the disease.

Case presentation
We reported a 79-year-old man with chief complaint of a narrowing in the caliber of the stool for one year. A soft tissue shadow was occasionally found by CT examination in the right pelvic wall, and it was diagnosed as localized biphasic malignant peritoneal mesothelioma (MPeM) by postoperative pathology. Radical excision was performed and no radio-chemotherapy was applied. Nearly six years after surgery, the mass was significantly enlarged, and the neighboring tissues including rectum, prostate, seminal vesicle, and right ischial ramus were all infiltrated. The patient was in the end stage of cancer with poor prognosis.

Conclusions
The localized biphasic MPeM may show following characteristics: (1) with heterogeneous low-density and obscure margin; (2) with low incidence rate of ascites; (3) with few central hemorrhage and necrosis; (4) with few calcified structures; (5) with mild to moderate heterogeneous delayed enhancement on contrast-enhanced CT. The imaging characteristics can provide further information for the diagnosis of localized biphasic MPeM in the future.
Stability of the gross motor function classification system in children with cerebral palsy for two years
Authors: Park Eun-Young 
Published: May 2020

Abstract
Background
The prognosis of gross motor function is a major concern for therapy and intervention in children with cerebral palsy (CP). The classification system for gross motor function, the Gross Motor Function Classification System (GMFCS), is actively studied because it could be useful in the communication between professionals and families. This study aimed to verify the stability of GMFCS over 2 years in children with CP aged 2–12 years.

Methods
The GMFCS level of 100 children with CP who underwent rehabilitation therapy in hospitals or who attended special elementary schools in South Korea were collected in the study. The agreements across three measurement points were analyzed in these children.

Results
The weighted kappa coefficients were statistically significant (p < .05). The coefficients ranged from 0.690 to 0.789 in children with CP aged 2–12 years. The lowest coefficient of 0.557 was observed in children with CP aged 2–4 years between the first and third measurements points.

Conclusions

The results provided evidence of GMFCS stability for the first year and change of the GMFCS during the two-year study period in children aged 2–4 years. Moreover, the findings indicate that the stability of GMFCS varies with time, duration, and age. It is recommended that GMFCS assessments be performed periodically, which are even more necessary for children with CP aged 2–4 years.
Visual rehabilitation of patients with corneal diseases
Authors: Oeverhaus Michael , Dekowski Dirk , Hirche Herbert , Esser Joachim , Schaperdoth-Gerlings Barbara , Eckstein Anja 
Published: May 2020

Abstract
Background
Although most patients with visual impairment due to corneal diseases can be treated successfully with surgery, some require visual rehabilitation to restore reading ability. To evaluate the best LVAs especially in terms of reading speed and characterize this specific patient group we performed a prospective, randomized cross-over trial.

Methods
All 34 patients underwent a detailed examination (slit-lamp, funduscopy, SD-OCT, ETDRS) as screening. Only patients with corneal diseases without other ocular diseases were included. Reading-speed was assessed with International-Reading-Speed-Texts (IReST) consecutively with five different LVAs (low vision aids) during one day in a randomized cross-over design. Corneal haze was quantified with corneal densitometry (Pentacam).

Results
Patients were either visually impaired (n = 28), severely impaired (n = 4) or legally blind (n = 2). Patients read significantly faster with LVAs (p < 0.0001). Fastest reading speed could be achieved with video magnifier (CCTV). Optical magnifier and portable-electronic magnifier enabled significantly lower reading speeds (p < 0.01). In a subgroup of patients (VA < 3/60,n = 6) black background enabled patients to read significantly faster compared to white background (p = 0.03).

Conclusion
Patients with low magnification requirement can be treated successfully with optical LVAs and portable-electronic magnifiers. More severely afflicted patients need a CCTV. Black background enables fastest reading-speeds, probably due to less blinding. Visual impairment can be estimated with corneal densitometry. Our trial confirms the capability of LVAs to successfully restore the reading ability in patients with corneal diseases, which is a crucial part of visual rehabilitation.

Trial registration
This trial was registered at the German Clinical Trials Register as DRKS00010887 at 09.08.2016.
Higher prevalence of obesity among children with functional abdominal pain disorders
Authors: Galai Tut , Moran-Lev Hadar , Cohen Shlomi , Ben-Tov Amir , Levy Dina , Weintraub Yael , Amir Achiya , Segev Or , Yerushalmy-Feler Anat 
Published: May 2020

Abstract
Background
Functional abdominal pain (FAP) disorders are one of the most common gastrointestinal disorders in children. We aimed to define the association between obesity and functional abdominal pain (FAP) disorders and to assess differences between overweight/obese children and normal weight children with FAP disorders.

Methods
We conducted a retrospective study of children (2–18 years old) with a clinical diagnosis of FAP who were followed-up in our pediatric gastroenterology unit between 1/2016–10/2018. FAP disorders were defined according to the ROME IV criteria. Body mass index (BMI) percentiles were defined by CDC standards. Patients with BMIs ≥85th percentile were designated as being overweight/obese. A population control group was obtained from the 2015–2016 Israel national health survey.

Results
Data from 173 children with FAP disorders (median age 11.5 years, 114 females) were included. Seventy-one children (41%) were classified as having functional abdominal pain-NOS, 67 (38.7%) as having irritable bowel syndrome (IBS), and 35 (20.2%) has having functional dyspepsia. Fifty-three children (30.6%) were classified as being overweight/obese.
Adolescents with FAP disorders had a significantly higher prevalence of overweight/obesity compared to controls (39.5% vs. 30%, respectively, p = 0.04). Children with FAP and overweight were older [12.4 (range 9.8–15.3) vs. 10.8 (7.4–14.1) years, p = 0.04] and had more hospitalizations due to FAP (20.8% vs. 7.6%, p = 0.01) compared to Children with FAP and normal weight.

Conclusions
Adolescents with FAP had higher prevalence of overweight/obesity compared to controls. Future studies are warranted to raise awareness of weight issues in FAP and determine the effect of weight loss on FAP.
Promoting parent-child relationships and preventing violence via home-visiting: a pre-post cluster randomised trial among Rwandan families linked to social protection programmes
Authors: Betancourt Theresa S. , Jensen Sarah K. G. , Barnhart Dale A. , Brennan Robert T. , Murray Shauna M. , Yousafzai Aisha K. , Farrar Jordan , Godfroid Kalisa , Bazubagira Stephanie M. , Rawlings Laura B. , Wilson Briana , Sezibera Vincent , Kamurase Alex 
Published: May 2020

Abstract
Background
Sugira Muryango is a father-engaged early child development and violence-prevention home-visiting programme delivered by trained lay workers. This cluster-randomised trial evaluates whether families living in extreme poverty (Ubudehe 1, the poorest category in the Government of Rwanda’s wealth ranking) who receive Sugira Muryango in combination with a government-provided social protection programme demonstrate greater responsive, positive caregiving, nutrition, care seeking, hygiene, and father involvement compared with control families receiving usual care (UC).

Methods
Using detailed maps, we grouped closely spaced villages into 284 geographic clusters stratified by the type of social protection programmes operating in the village clusters; 198 clusters met all enrolment criteria. Sugira Muryango was delivered to n = 541 families in 100 treatment clusters with children aged 6–36 months living in extreme poverty. We assessed changes in outcomes in intervention and n = 508 UC control families using structured surveys and observation. Analyses were intent to treat using mixed models to accommodate clustering.

Results
Families receiving Sugira Muryango improved on core outcomes of parent-child relationships assessed using the Home Observation for Measurement of the Environment (Cohen’s d = 0.87, 95% CI: 0.74, 0.99) and the Observation of Mother-Child Interaction (Cohen’s d = 0.29, 95% CI: 0.17, 0.41). We also saw reductions in harsh discipline on items from the UNICEF MICS (OR = 0.30: 95% CI: 0.19, 0.47) and in violent victimisation of female caregivers by their partners (OR = 0.49, 95% CI: 0.24, 1.00) compared with UC. Moreover, children in families receiving SM had a 0.45 higher increase in food groups consumed in the past 24 h (Cohen’s d = 0.35, 95% CI: 0.22, 0.47), increased care seeking for diarrhoea (OR = 4.43, 95% CI: 1.95, 10.10) and fever (OR = 3.28, 95% CI: 1.82, 5.89), and improved hygiene behaviours such as proper treatment of water (OR = 3.39, 95% CI: 2.16, 5.30) compared with UC. Finally, Sugira Muryango was associated with decreased caregiver depression and anxiety (OR = 0.58, 95% CI: 0.38, 0.88).

Conclusions
Sugira Muryango led to improvements in caregiver behaviours linked to child development and health as well as reductions in violence.

Trial registration
ClinicalTrials.gov number NCT02510313.
The predictive value of procalcitonin for postoperative early pancreatic fistula
Authors: Zhou Quanyu , Xia Yuxiao , Lei Zehua 
Published: May 2020

Abstract
Background
To investigate the early prediction value of procalcitonin (PCT) in pancreatic fistula (POPF) after pancreatoduodenectomy (PD).

Method
Retrospective analysis of clinical data of 67 patients undergoing pancreaticoduodenectomy (PD) and 19 patients undergoing distalpancreatectomy (DP) were performed in the Department of Hepatobiliary Surgery, Leshan People’s Hospital from January 2017 to December 2018. All patients were divided into POPF group and non-POPF group depending on the presence of pancreatic fistula. And fistulas were classified according to the ISGPF classification scheme. Plasma PCT levels, serum CRP concentration, and WBC counts were assessed preoperatively and on postoperative days (PODs) 1, 3, and 5. Statistical analyses were performed with statistical software. The ROC curve was used to analyze the efficacy of PCT and CRP in POPF prediction after surgery and determine their Cut-off value.

Result
There were no statistically significant differences identified in age, gender, BMI, diabetes, abdominal surgery history, preoperative laboratory data, operation time, intraoperative bleeding volume, tumor nature and medical expenses of PD patients between the two groups (P > 0.05). While the incidence of postoperative hyperglycemia, postoperative ICU rate and postoperative hospital stay were statistically significant (P < 0.05). The AUC for PCT diagnosis of pancreatic fistula 1 day after surgery was 0.77 (95% CI: 0.675 ~ 0.860). Compared with CRP [0.53 (95% CI: 0.420 ~ 0.639)] and WBC [0.60 (95% CI: 0.490 ~ 0.705)], the optimal cut-off value (cut-off) was 0.67 μg/L. At this time, the sensitivity and specificity of detecting pancreatic fistula were 73.68 and 76.12%, respectively. The results at 3 days after surgery were similar to those at 5 days after surgery. And DP patients had similar results as PD patients.

Conclusion
The PCT is valuable for early prediction of pancreatic fistula after Pancreaticoduodenectomy.
A unusual case of multifocal pyogenic abscess formation following ERCP procedure
Authors: Merei Fahed , Shapiro Galina , Abu Shakra Ibrahim , Bickel Amitai , Ganam Samer , Bez Maxim , Kakiashvili Eli 
Published: May 2020

Abstract
Background
Endoscopic retrograde cholangiopancreatography (ERCP) is essential for managing biliary and pancreatic disorders. Infection is the most morbid complication of ERCP and among the most common causes of ERCP-related death.

Case presentation
A 69-year-old man presented with right upper quadrant abdominal pain, obstructive jaundice and abnormal liver function tests. Ultrasound revealed cholelithiasis without bile duct dilation. After receiving intravenous antibiotics for acute cholecystitis, the patient was discharged. Two weeks later, an endoscopic ultrasound demonstrated gallstones and CBD dilation of up to 6.4 mm with 2 filling defects. An ERCP was performed with a papillotomy and stone extraction. Twenty-four hours post-ERCP the patient developed a fever, chills, bilirubinemia and elevated liver function tests. Ascending cholangitis was empirically treated using Ceftriaxone and Metronidazole. However, the patient remained febrile, with a diffusely tender abdomen and elevated inflammatory markers. A CT revealed a very small hypodense lesion in the seventh liver segment. Extended-spectrum beta-lactamase positive Klebsiella Pneumonia and Enterococcus Hirae were identified, and the antibiotics were switched to Imipenem and Cilastatin. The hypodense lesion in the liver increased to 1.85 cm and a new hypodense lesion was seen in the right psoas. At day 10 post-ERCP, the patient started having low back pain and difficulty walking. MRI revealed L4-L5 discitis with a large epidural abscess, spanning L1-S1 and compressing the spinal cord. Decompressive laminectomy of L5 was done and Klebsiella pneumonia was identified. Due to continued drainage from the wound, high fever, we performed a total body CT which revealed increased liver and iliopsoas abscess. Decompressive laminectomy was expanded to include L2-L4 and multiple irrigations were done. Gentamycin and Vancomycin containing polymethylmethacrylate beads were implanted locally and drainage catheters were placed before wound closure. Multidisciplinary panel discussion was performed, and it was decided to continue with a non invasive approach .

Conclusions
Early recognition of complications and individualized therapy by a multi-disciplined team is important for managing post-ERCP septic complications. Particular attention should be given to adequate coverage by empiric antibiotics.