bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing Femoral Rotation: A Survey Comparison of Techniques
Authors: Marchand Lucas S. , Jacobson Lance G. , Stuart Ami R. , Haller Justin M. , Higgins Thomas F. , Rothberg David L. 
Published: September 2019

Objectives:
To compare 3 common techniques for assessing femoral malrotation through a response analysis.

Methods:
Ten intact human cadaveric pelvis-to-knee specimens were used to create a fracture model. A mobile C-arm x-ray system was used to capture images of an intact control femur and a contralateral test femur on each specimen. A midshaft femoral osteotomy was created on the test femur and it was then internally and externally rotated in 5-degree intervals up to 20 degrees. Images were obtained and stored at each increment of malrotation. Eight surveys of 20-paired images each were generated and presented for surgeon review. Accuracy of predicting femoral malrotation using the true lateral technique (TLT), neck horizontal angle (NHA) method, and lesser trochanter profile (LTP) was measured.

Results:
Eighty-five surgeons completed a survey with 80 surgeons (94%) acknowledging the use of a described fluoroscopic method for assisting with rotational alignment. Surgeons correctly accepted a fracture rotated less than 20 degrees and rejected a fracture rotated 20 degrees or more 63% of the time. The ability to correctly identify 20 degrees of malrotation varied per technique used to assess rotation. With the LTP and NHA method, 67% of surgeons responded correctly. Surgeons performed significantly worse when using the TLT with only 53% providing correct responses (P < 0.0001).

Conclusions:
Surgeons using described fluoroscopic methods to identify acceptable rotation in femoral shaft fractures are correct 63% of the time. The LTP and NHA techniques are equally reliable and more effective than the TLT at detecting clinically significant femoral malrotation.
Aluminum Chloride–Induced Apoptosis Leads to Keratinization Arrest and Granular Parakeratosis
Authors: Fujii Mizue , Kishibe Mari , Honma Masaru , Anan Takashi , Ishida-Yamamoto Akemi 
Published: September 2019

Abstract:
Aluminum chloride (AlCl3) is the main active ingredient in commonly used antiperspirant. Antiperspirant use may cause a rare keratinization disease, granular parakeratosis (GP), then AlCl3 may be associated with the etiology of GP. The objective of this study is to elucidate the skin effect of topical aluminum application using a mouse model. We sprayed 20% aluminum chloride every day on the depilated mice skin and analyzed the skin clinically, histopathologically, and immunohistologically. We have succeeded in the histological replication of GP on mouse skin. The basophilic granules in the stratum corneum contained filaggrin, and processing of profilaggrin to filaggrin was disrupted in aluminum-treated mouse skin (Al-mouse). In Al-mouse, cytochrome c and cleaved-caspase 3 were upregulated mainly in the granular layer, and caspase 3 p20 subunit was upregulated. TUNEL-positive cells increased significantly in the Al-mouse from the granular to the horny layer. Caspase 3 inhibitor inhibited granular parakeratotic change of Al-mouse. Our results indicated that aluminum-induced apoptosis leads to keratinization arrest and acceleration of nuclear degradation before completion of profilaggrin processing. This could lead to retention of the basophilic granules composed of underprocessed profilaggrin in the horny layer of Al-mouse skin, the hallmark of GP.
Clinical outcome of open surgery versus laparoscopic surgery for cirrhotic hepatocellular carcinoma patients: a meta-analysis
Authors: Xing Li , Guo Huai-Bin , Kan Jin-Long , Liu San-Guang , Lv Hai-Tao , Liu Jian-Hua , Bian Wei 
Published: September 2019

Background and aim
Open surgery remains the major approach to treat hepatocellular carcinoma, and laparoscopy-assisted liver resection has been recommended as a superior treatment. However, the efficacy of laparoscopic surgery versus open surgery for cirrhotic patients is under debate. Therefore, the aim of this meta-analysis was to compare the clinical outcomes of laparoscopic and open resection of hepatocellular carcinoma in patients with cirrhosis.

Methods
Electronic databases were searched for eligible literature updated on November 2018. After rigorous review of quality, the data were extracted from eligible trials. All the data were pooled with the corresponding 95% confidence interval using RevMan software. Sensitivity analyses and heterogeneity were quantitatively evaluated.

Results
Fourteen trials met the inclusion criteria. According to the pooled result of surgery duration, laparoscopic surgery was associated with significantly shorter hospital stay [STD mean difference (SMD) = −0.61, 95% confidence interval −0.89 to −0.32; P < 0.0001], lower intraoperative blood loss (SMD = −0.56, 95% confidence interval −0.99 to −0.12; P = 0.01), fewer complications (odds ratio = 0.38, 95% confidence interval 0.28 to 0.52; P < 0.00001) and lower transfusion rate (odds ratio = 0.58, 95% confidence interval 0.36–0.93; P = 0.02). Nevertheless, there was no remarkable difference in operative time (SMD = 0.17, 95% confidence interval −0.25 to −0.59; P = 0.42) between the two groups. The pooled analysis of overall survival showed that laparoscopic surgery did not achieve benefit compared with open surgery (P = 0.02). Moreover, the pooled results of three subgroups indicated that laparoscopic surgery was associated with significantly better disease-free survival (P < 0.05).

Conclusion
The current analysis indicates that laparoscopic liver resection for hepatocellular carcinoma improved intraoperative and disease-free survival, with similar overall survival compared to the open procedure. Laparoscopic surgery may serve as a safe and feasible alternative for selected hepatocellular carcinoma patients with cirrhosis.
Population-Based Epidemiology and Outcomes of Acute Kidney Injury in Critically Ill Children*
Authors: Alobaidi Rashid , Morgan Catherine , Goldstein Stuart L. , Bagshaw Sean M. 
Published: September 2019

Objectives:
We describe the epidemiology, characteristics, risk factors, and incremental risks associated with acute kidney injury in critically ill children at a population-level.

Design:
Population-based retrospective cohort study.

Setting:
PICUs in Alberta, Canada.

Patients:
All children admitted to PICUs in Alberta, Canada between January 1, 2015, and December 31, 2015.

Interventions:
None.

Measurements and Main Results:
A total of 1,017 patients were included. Acute kidney injury developed in 308 patients (30.3%; 95% CI, 28.1–33.8%) and severe acute kidney injury (Kidney Disease: Improving Global Outcomes stage 2 and 3) developed in 124 patients (12.2%; 95% CI, 10.3–14.4%). Incidence rates for critical illness-associated acute kidney injury and severe acute kidney injury were 34 (95% CI, 30.3–38.0) and 14 (95% CI, 11.38–16.38) per 100,000 children-year, respectively. Severe acute kidney injury incidence rates were greater in males (incidence rate ratio, 1.55; 95% CI, 1.08–2.33) and infants younger than 1 year old (incidence rate ratio, 14.77; 95% CI, 10.36–21.07). Thirty-two patients (3.1%) did not survive to PICU discharge. The acute kidney injury-associated PICU mortality rate was 2.3 (95% CI, 1.4–3.5) per 100,000 children-year. In multivariate analysis, severe acute kidney injury was associated with greater PICU mortality (odds ratio, 11.93; 95% CI, 4.68–30.42) and 1-year mortality (odds ratio, 5.50; 95% CI, 2.76–10.96). Severe acute kidney injury was further associated with greater duration of mechanical ventilation, duration of vasoactive support, and lengths of PICU and hospital stay.

Conclusions:
The population-level burden of acute kidney injury and its attributable risks are considerable among critically ill children. These findings emphasize the need for enhanced surveillance for acute kidney injury, identification of modifiable risks, and evaluation of interventional strategies.
Offspring Versus Nonoffspring to Parent Living Donor Liver Transplantation: Does Donor Relationship Matter?
Authors: Dagan Amir , Choudhury Rashikh A. , Yaffe Hillary , Yoeli Dor , Moore Hunter B. , Conzen Kendra D. , Adams Megan , Wachs Michael , Pomposelli James J. , Pomfret Elizabeth A. , Nydam Trevor L. 
Published: September 2019

Background.
Offspring (donor) to parent (recipient) transplant is the most common form of living donor liver transplant in the United States. In kidney transplantation, it has been suggested that female recipients of offspring living donor kidney allografts have inferior outcomes. It is unknown whether such a phenomenon also occurs following living donor liver transplantation.

Methods.
A retrospective analysis was completed of recipients of a living donor liver transplant from January 1998 to January 2018 in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Patients were grouped as having received a living donor liver allograft from either an offspring or a nonoffspring, with exactly 3 HLA matches, as would be expected between an offspring and parent. Graft and patient survival were analyzed using Cox proportional hazards modeling.

Results.
A total of 279 offspring to parent and 241 nonoffspring donor liver transplants were included in the analysis. Female recipients of offspring liver allografts had both inferior 10-year graft (52% versus 72%; P < 0.001) and patient survival (52% versus 81%; P < 0.001) compared with female recipients of nonoffspring allografts. No such difference in outcomes was discovered among male recipients. A stratified analysis of sex of offspring donors to female recipients demonstrated that donor male gender was associated with graft failure (HR = 2.87; P = 0.04) and mortality (hazard ratio = 3.89; P = 0.03). Again, this association was not seen with male recipients.

Conclusions.
Among female recipients, offspring to parent living donor liver transplantation yields inferior long-term graft and patient survival. Furthermore, among offspring donors, male sex was strongly associated with inferior outcomes. These findings have significant implications for donor selection.
Predicting Cost-Effectiveness of Generic Versus Brand Dabigatran Using Pharmacometric Estimates among Patients with Atrial Fibrillation in the United States
Authors: Wang Ching-Yu , Pham Phuong N. , Kim Sarah , Lingineni Karthik , Schmidt Stephan , Diaby Vakaramoko , Brown Joshua 
Published: September 2019

ABSTRACTGeneric entry of newer anticoagulants is expected to decrease the costs of atrial fibrillation management. However, when making switches between brand and generic medications, bioequivalence failures are possible. The objectives of this study were to predict and compare the lifetime cost-effectiveness of brand dabigatran with hypothetical future generics. Markov micro-simulations were modified to predict the lifetime costs and quality-adjusted life years of patients on either brand or generic dabigatran from a U.S. private payer perspective. Event rates for generics were predicted using previously developed pharmacokinetic-pharmacodynamic models. The analyses showed that generic dabigatran with lower-than-brand systemic exposure was dominant. Meanwhile, generic dabigatran with extremely high systemic exposure was not cost-effective compared to the brand reference. Cost-effectiveness of generic medications cannot always be assumed as shown in this example. Combined use of pharmacometric and pharmacoeconomic models can assist in decision making between brand and generic pharmacotherapies.
A polygenic predictor of treatment-resistant depression using whole exome sequencing and genome-wide genotyping
Authors: Fabbri Chiara , Kasper Siegfried , Kautzky Alexander , Zohar Joseph , Souery Daniel , Montgomery Stuart , Albani Diego , Forloni Gianluigi , Ferentinos Panagiotis , Rujescu Dan , Mendlewicz Julien , Uher Rudolf , Lewis Cathryn M. , Serretti Alessandro 
Published: September 2019

AbstractTreatment-resistant depression (TRD) occurs in ∼30% of patients with major depressive disorder (MDD) but the genetics of TRD was previously poorly investigated.Whole exome sequencing and genome-wide genotyping were performed in 1320 MDD patients. Response to the first pharmacological treatment was compared to non-response to one treatment and non-response to two or more treatments (TRD). Differences in the risk of carrying damaging variants were tested. A score expressing the burden of variants in genes and pathways was calculated weighting each variant for its functional (Eigen) score and frequency, considering rare variants only and rare + common variants. Gene- and pathway-based scores were used to develop predictive models of TRD and non-response using gradient boosting in 70% of the sample (training) which were tested in the remaining 30% (testing), evaluating also the addition of clinical predictors. Independent replication was tested in STAR*D and GENDEP using exome array-based data.After quality control 1209 subjects were included. TRD and non-responders did not show higher risk to carry damaging variants compared to responders. Genes/pathways associated with TRD included those modulating cell survival and proliferation, neurodegeneration and immune response. Significant prediction of TRD vs. response was observed in the testing sample which was improved by the addition of clinical factors. Some models were replicated, with a weaker prediction, in STAR*D and GENDEP when considering also clinical factors and in the extremes of the genetic score distribution.These results suggested relevant biological mechanisms implicated in TRD and a new methodological approach to the prediction of TRD.
Mutations in the SPTLC1 gene are a cause of juvenile amyotrophic lateral sclerosis that may be amenable to serine supplementation
Authors: Johnson J. O. , Chia R. , Miller D. E. , Li R. , Abramzon Y. , Kumaran R. , Alahmady N. , Faghri F. , Renton A. E. , Topp S. D. , Pliner H. A. , Gibbs J. R. , Ding J. , Smith N. , Landeck N. , Nalls M. A. , Cookson M. R. , Pletnikova O. , Troncoso J. , Scholz S. W. , Sabir M. S. , Ahmed S. , Dalgard C. L. , Troakes C. , Jones A. R. , Shatunov A. , Iacoangeli A. , Al Khleifat A. , Ticozzi N. , Silani V. , Gellera C. , Blair I. P. , Dobson-Stone C. , Kwok J. B. , England B. K. , Bonkowski E. S. ,   The International ALS Genomics Consortium,   The ITALSGEN Consortium,   The FALS Sequencing Consortium,   The American Genome Center, Tienari P. J. , Stone D. J. , Morrison K. E. , Shaw P. J. , Al-Chalabi A. , Brown R. H. , Brunetti M. , Calvo A. , Mora G. , Al-Saif H. , Gotkine M. , Leigh F. , Chang I. J. , Perlman S. J. , Glass I. , Shaw C. E. , Landers J. E. , Chiò A. , Crawford T. O. , Smith B. N. , Traynor B. J. 
Published: September 2019

AbstractJuvenile amyotrophic lateral sclerosis (ALS) is a rare form of childhood motor disorder with a heterogeneous clinical presentation. The underlying causes of this condition are poorly understood, hindering the development of effective therapies. In a whole-exome sequencing trio-family study of three unrelated juvenile patients diagnosed with ALS and failure to thrive, we identified de-novo mutations in SPTLC1 (p.Ala20Ser in two patients and p.Ser331Tyr) not present in their healthy parents or siblings. SPTLC1 encodes a subunit of the serine palmitoyltransferase complex, a key enzyme in sphingolipid biosynthesis. Mutations in this gene are known to cause hereditary sensory autonomic neuropathy, type 1A, with a characteristic increase in plasma levels of neurotoxic deoxymethyl-sphinganine. We found an increase of this metabolite in one of our patients carrying the p.Ala20Ser mutation. Treatment of one of the patients with high dose, oral L-serine led to an increase in body weight, suggesting that serine supplementation may be beneficial among patients carrying mutations in this gene.
Network effects of the neuropsychiatric 15q13.3 microdeletion on the transcriptome and epigenome in human induced neurons
Authors: Zhang Siming , Zhang Xianglong , Ma Shining , Purmann Carolin , Davis Kasey , Wong Wing Hung , Bernstein Jonathan , Hallmayer Joachim , Urban Alexander E 
Published: September 2019

AbstractHeterozygous deletions in the 15q13.3 region are associated with several neuropsychiatric disorders including autism, schizophrenia, and attention deficit hyperactivity disorder. Several genes within the 15q13.3 deletion region may play a role in neuronal dysfunction, based on association studies in humans and functional studies in mice, but the intermediate molecular mechanisms remain unknown. We analyzed the genome-wide effects of the 15q13.3 microdeletion on the transcriptome and epigenome. Induced pluripotent stem cell (iPSC) lines from three patients with the typical heterozygous 15q13.3 microdeletion and three sex-matched controls were generated and converted into induced neurons (iNs) using the neurogenin-2 induction method. We analyzed genome-wide gene expression using RNA-Seq, genome-wide DNA methylation using SeqCap-Epi, and genome-wide chromatin accessibility using ATAC-Seq, in both iPSCs and iNs. In both cell types, gene copy number change within the 15q13.3 microdeletion was accompanied by significantly decreased gene expression and no compensatory changes in DNA methylation or chromatin accessibility, supporting the model that haploinsufficiency of genes within the deleted region drives the disorder. Further, we observed global effects of the deletion on the transcriptome and epigenome, with the effects being cell type specific and occurring at discrete loci. Several genes and pathways associated with neuropsychiatric disorders and neuronal development were significantly altered, including Wnt signaling, ribosome biogenesis, DNA binding, and clustered protocadherins. This molecular systems analysis of a large neuropsychiatric microdeletion can also be applied to other brain relevant chromosomal aberrations to further our etiological understanding of neuropsychiatric disorders.
Feedback adaptation to unpredictable force fields in 250ms
Authors: Crevecoeur Frédéric , Mathew James , Bastin Marie , Lefevre Philippe 
Published: September 2019

AbstractMotor learning and adaptation are important functions of the nervous system. Classical studies have characterized how humans adapt to changes in the environment during tasks such as reaching, and have documented improvements in behavior across movements. Yet little is known about how quickly the nervous system adapts to such disturbances. In particular, recent work has suggested that adaptation could be sufficiently fast to alter the control strategies of an ongoing movement. To further address the possibility that learning occurred within a single movement, we designed a series of human reaching experiments to extract in muscles recordings the latency of feedback adaptation. Our results confirmed that participants adapted their feedback responses to unanticipated force fields applied randomly. In addition, our analyses revealed that the feedback response was specifically and finely tuned to the ongoing perturbation not only across trials with the same force field, but also across different kinds of force fields. Finally, changes in muscle activity consistent with feedback adaptation occurred in about 250ms following reach onset. We submit this estimate as the latency of motor adaptation in the nervous system.
Evaluation of the anti-inflammatory effects of synthesised tanshinone I and isotanshinone I analogues in zebrafish
Authors: Foulkes Matthew J. , Henry Katherine M. , Renshaw Stephen A. , Jones Simon 
Published: September 2019

AbstractDuring inflammation, dysregulated neutrophil behaviour can play a major role in chronic inflammatory diseases such as chronic obstructive pulmonary disease, for which current treatments are generally ineffective. Recently, tanshinones have shown promising antiinflammatory effects by targeting neutrophilsin vivo, yet are still an underexplored general group of compounds. Here, an existing six step synthetic route was optimised and used to prepare a small family of substituted tanshinone and isomeric isotanshinone analogues, together with the synthesis of other structurally similar molecules. Evaluation of these using a transgenic zebrafish model of inflammation revealed that many of these compounds exhibit promising anti-inflammatory effectsin vivo. Several compounds affect neutrophil recruitment and/or resolution of neutrophilic inflammation, and broad structure-activity relationships were constructed. In particular, the methoxy-substituted tanshinone39specifically accelerates resolution of inflammation without affecting organism host defence, making this a particularly attractive candidate for potential pro-resolution therapeutics. On the other hand, β-lapachones exhibit effects on neutrophil recruitment yet not on resolution. Notable differences in toxicity profiles between compound classes were also observed.
Genome-wide association analyses identify variants inIRF4associated with acute myeloid leukemia and myelodysplastic syndrome susceptibility
Authors: Wang Junke , Clay-Gilmour Alyssa I. , Karaesmen Ezgi , Rizvi Abbas , Zhu Qianqian , Yan Li , Preus Leah , Liu Song , Wang Yiwen , Griffiths Elizabeth , Stram Daniel O. , Pooler Loreall , Sheng Xin , Haiman Christopher , Van Den Berg David , Webb Amy , Brock Guy , Spellman Stephen , Pasquini Marcelo , McCarthy Philip , Allan James , Stölzel Friedrich , Onel Kenan , Hahn Theresa , Sucheston-Campbell Lara E. 
Published: September 2019

ABSTRACTThe role of common genetic variation in susceptibility to acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS), a group of rare clonal hematologic disorders characterized by dysplastic hematopoiesis and high mortality, remains unclear. We performed AML and MDS genome-wide association studies (GWAS) in the DISCOVeRY-BMT cohorts (2309 cases and 2814 controls). Association analysis based on subsets (ASSET) was used to conduct a summary statistics SNP-based analysis of MDS and AML subtypes. For each AML and MDS case and control we used PrediXcan to estimate the component of gene expression determined by their genetic profile and correlate this imputed gene expression level with risk of developing disease in a transcriptome-wide association study (TWAS). ASSET identified an increased risk forde novoAML and MDS (OR=1.38, 95% CI, 1.26-1.51, Pmeta=2.8×10-12) in patients carrying the T allele at rs12203592 inInterferon Regulatory Factor 4(IRF4), a transcription factor which regulates myeloid and lymphoid hematopoietic differentiation. Our TWAS analyses showed increasedIRF4gene expression is associated with increased risk ofde novoAML and MDS (OR=3.90, 95% CI, 2.36-6.44, Pmeta=1.0×10-7). The identification ofIRF4by both GWAS and TWAS contributes valuable insight on the role of genetic variation in AML and MDS susceptibility.