bluuebunny/crossref_metadata_2025_split huggingface dataset:
Streamlining the KOOS Activities of Daily Living Subscale Using Machine Learning
Authors: Gupta Ashim , Potty Ajish S.R. , Ganta Deepak , Mistovich R. Justin , Penna Sreeram , Cady Craig , Potty Anish G. 
Published: March 2020

Background: Functional outcome scores provide valuable data, yet they can be burdensome to patients and require significant resources to administer. The Knee injury and Osteoarthritis Outcome Score (KOOS) is a knee-specific patient-reported outcome measure (PROM) and is validated for anterior cruciate ligament (ACL) reconstruction outcomes. The KOOS requires 42 questions in 5 subscales. We utilized a machine learning (ML) algorithm to determine whether the number of questions and the resultant burden to complete the survey can be lowered in a subset (activities of daily living; ADL) of KOOS, yet still provide identical data. Hypothesis: Fewer questions than the 17 currently provided are actually needed to predict KOOS ADL subscale scores with high accuracy. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: Pre- and postoperative patient-reported KOOS ADL scores were obtained from the Surgical Outcome System (SOS) data registry for patients who had ACL reconstruction. Categorical Boosting (CatBoost) ML models were built to analyze each question and its value in predicting the patient’s actual functional outcome (ie, KOOS ADL score). A streamlined set of minimal essential questions were then identified. Results: The SOS registry contained 6185 patients who underwent ACL reconstruction. A total of 2525 patients between the age of 16 and 50 years had completed KOOS ADL scores presurgically and 3 months postoperatively. The data set consisted of 51.84% male patients and 48.16% female patients, with a mean age of 29 years. The CatBoost model predicted KOOS ADL scores with high accuracy when only 6 questions were asked ( R2 = 0.95), similar to when all 17 questions of the subscale were asked ( R2 = 0.99). Conclusion: ML algorithms successfully identified the essential questions in the KOOS ADL questionnaire. Only 35% (6/17) of KOOS ADL questions (descending stairs, ascending stairs, standing, walking on flat surface, putting on socks/stockings, and getting on/off toilet) are needed to predict KOOS ADL scores with high accuracy after ACL reconstruction. ML can be utilized successfully to streamline the burden of patient data collection. This, in turn, can potentially lead to improved patient reporting, increased compliance, and increased utilization of PROMs while still providing quality data.
Relationship Between Demographic and Radiographic Characteristics and Second Ray Pathology in Hallux Valgus Patients
Authors: Cronin Samantha , Conti Matthew , Williams Nicholas , Ellis Scott J. 
Published: March 2020

Background: Hallux valgus can alter load bearing in the foot leading to abnormal forces on the second toe. The purpose of this study was to determine demographic and radiographic factors associated with second ray hammertoes in hallux valgus using 3-dimensional weightbearing CT scans. Methods: Seventy-one patients who underwent a modified Lapidus procedure for hallux valgus with preoperative weightbearing CT scans were separated into 2 groups: (1) hallux valgus only (47 feet) and (2) hallux valgus with second ray hammertoe (29 feet). Preoperative age, body mass index (BMI), sex, hallux valgus angle (HVA), intermetatarsal angle (IMA), absolute and effective metatarsal (MT) lengths, ratios between metatarsal lengths, Meary angle, metatarsus adductus angle (MAA), and pronation were measured. Mean values of continuous variables were compared and both simple and multivariable logistic regression models were used to evaluate associations between variables and hammertoe occurrence. Results: Patients in the hammertoe group were found to be significantly older and have higher BMIs, HVAs, effective second MT lengths, IMAs, and more apex plantar Meary angles (all P < .05). The multivariable analysis demonstrated that a higher IMA and a more apex plantar Meary angle were the only significant predictors of second ray hammertoe risk ( P = .03 and P = .01, respectively) once corrected for age and BMI. Conclusion: Significant associations were found between older age, higher BMI, and more severe deformity and the occurrence of hammertoe in hallux valgus patients. These results may help clinicians counsel hallux valgus patients about the risk of developing an advanced hammertoe deformity. Level of Evidence: Level III, retrospective comparative series
A human SIRPA knock-in xenograft mouse model to study human hematopoietic and cancer stem cells
Authors: Jinnouchi Fumiaki , Yamauchi Takuji , Yurino Ayano , Nunomura Takuya , Nakano Michitaka , Iwamoto Chika , Obara Teppei , Miyawaki Kohta , Kikushige Yoshikane , Kato Koji , Maeda Takahiro , Miyamoto Toshihiro , Baba Eishi , Akashi Koichi , Takenaka Katsuto 
Published: March 2020

AbstractIn human-to-mouse xenogeneic transplantation, polymorphisms of signal-regulatory protein α (SIRPA) that decide their binding affinity for human CD47 are critical for engraftment efficiency of human cells. In this study, we generated a new C57BL/6.Rag2nullIl2rgnull (BRG) mouse line with Sirpahuman/human (BRGShuman) mice, in which mouse Sirpa was replaced by human SIRPA encompassing all 8 exons. Macrophages from C57BL/6 mice harboring Sirpahuman/human had a significantly stronger affinity for human CD47 than those harboring SirpaNOD/NOD and did not show detectable phagocytosis against human hematopoietic stem cells. In turn, Sirpahuman/human macrophages had a moderate affinity for mouse CD47, and BRGShuman mice did not exhibit the blood cytopenia that was seen in Sirpa−/− mice. In human to mouse xenograft experiments, BRGShuman mice showed significantly greater engraftment and maintenance of human hematopoiesis with a high level of myeloid reconstitution, as well as improved reconstitution in peripheral tissues, compared with BRG mice harboring SirpaNOD/NOD (BRGSNOD). BRGShuman mice also showed significantly enhanced engraftment and growth of acute myeloid leukemia and subcutaneously transplanted human colon cancer cells compared with BRGSNOD mice. BRGShuman mice should be a useful basic line for establishing a more authentic xenotransplantation model to study normal and malignant human stem cells.
Prognostic and predictive impact of genetic markers in patients with CLL treated with obinutuzumab and venetoclax
Authors: Tausch Eugen , Schneider Christof , Robrecht Sandra , Zhang Can , Dolnik Anna , Bloehdorn Johannes , Bahlo Jasmin , Al-Sawaf Othman , Ritgen Matthias , Fink Anna-Maria , Eichhorst Barbara , Kreuzer Karl-Anton , Tandon Maneesh , Humphrey Kathryn , Jiang Yanwen , Schary William , Bullinger Lars , Mertens Daniel , Lurà Michele Porro , Kneba Michael , Döhner Hartmut , Fischer Kirsten , Hallek Michael , Stilgenbauer Stephan 
Published: March 2020

Abstract
Genetic parameters are established prognostic factors in chronic lymphocytic leukemia (CLL) treated with chemoimmunotherapy, but are less well studied with novel compounds. We assessed immunoglobulin heavy variable chain (IGHV) mutation status, common genomic aberrations, and gene mutations in 421 untreated patients within the CLL14 trial (NCT02242942), comparing obinutuzumab+chlorambucil (GClb) vs obinutuzumab+venetoclax (VenG). The incidences of genomic aberrations considering the hierarchical model were del(17p) 7%, del(11q) 18%, +12 18%, and del(13q) 35%, whereas IGHV was unmutated in 60% of patients. NOTCH1 mutations were most common (23%), followed by SF3B1 (16%), ATM (13%), and TP53 (10%). Although the overall response rate (ORR) for GClb was lower in patients with del(17p), del(11q), mutated TP53, ATM, and BIRC3, none of these parameters reduced complete remission (CR) rate and ORR with VenG. At a median follow-up of 28 months, del(17p) and mutated TP53 were the only abnormalities with an effect on progression-free survival (PFS) for both treatment groups: GClb (hazard ratio [HR], 4.6 [P &lt; .01]; HR, 2.7 [P &lt; .01], respectively) and VenG (HR, 4.4 [P &lt; .01]; HR, 3.1 [P &lt; .01], respectively). No other factors affected outcome with VenG, whereas for GClb del(11q), BIRC3, NOTCH1, and unmutated IGHV were associated with shorter PFS. Multivariable analysis identified del(17p), del(11q), unmutated IGHV, and mutated TP53, BIRC3, and SF3B1 as independent prognostic factors for PFS with GClb, whereas for VenG, only del(17p) was significant. VenG was superior to GClb across most genetic subgroups. Patients with adverse genetic markers had the strongest benefit from VenG, particularly subjects with unmutated IGHV, which was identified as a predictive factor in a multivariable treatment-interaction analysis.
Phase 2 trial of montelukast for prevention of pain in sickle cell disease
Authors: Field Joshua J. , Kassim Adetola , Brandow Amanda , Embury Stephen H. , Matsui Neil , Wilkerson Karina , Bryant Valencia , Zhang Liyun , Simpson Pippa , DeBaun Michael R. 
Published: March 2020

AbstractCysteinyl leukotrienes (CysLTs) are lipid mediators of inflammation. In patients with sickle cell disease (SCD), levels of CysLTs are increased compared with controls and associated with a higher rate of hospitalization for pain. We tested the hypothesis that administration of the CysLT receptor antagonist montelukast would improve SCD-related comorbidities, including pain, in adolescents and adults with SCD. In a phase 2 randomized trial, we administered montelukast or placebo for 8 weeks. The primary outcome measure was a &gt;30% reduction in soluble vascular cell adhesion molecule 1 (sVCAM), a marker of vascular injury. Secondary outcome measures were reduction in daily pain, improvement in pulmonary function, and improvement in microvascular blood flow, as measured by laser Doppler velocimetry. Forty-two participants with SCD were randomized to receive montelukast or placebo for 8 weeks. We found no difference between the montelukast and placebo groups with regard to the levels of sVCAM, reported pain, pulmonary function, or microvascular blood flow. Although montelukast is an effective treatment for asthma, we did not find benefit for SCD-related outcomes. This clinical trial was registered at www.clinicaltrials.gov as #NCT01960413.
Interferon-complement loop in transplant-associated thrombotic microangiopathy
Authors: Jodele Sonata , Medvedovic Mario , Luebbering Nathan , Chen Jenny , Dandoy Christopher E. , Laskin Benjamin L. , Davies Stella M. 
Published: March 2020

AbstractTransplant-associated thrombotic microangiopathy (TA-TMA) is an important cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). The complement inhibitor eculizumab improves TA-TMA, but not all patients respond to therapy, prompting a search for additional targetable pathways of endothelial injury. TA-TMA is relatively common after HSCT and can serve as a model to study mechanisms of tissue injury in other thrombotic microangiopathies. In this work, we performed transcriptome analyses of peripheral blood mononuclear cells collected before HSCT, at onset of TA-TMA, and after resolution of TA-TMA in children with and without TA-TMA after HSCT. We observed significant upregulation of the classical, alternative, and lectin complement pathways during active TA-TMA. Essentially all upregulated genes and pathways returned to baseline expression levels at resolution of TA-TMA after eculizumab therapy, supporting the clinical practice of discontinuing complement blockade after resolution of TA-TMA. Further analysis of the global transcriptional regulatory network showed a notable interferon signature associated with TA-TMA with increased STAT1 and STAT2 signaling that resolved after complement blockade. In summary, we observed activation of multiple complement pathways in TA-TMA, in contrast to atypical hemolytic uremic syndrome (aHUS), where complement activation occurs largely via the alternative pathway. Our data also suggest a key relationship between increased interferon signaling, complement activation, and TA-TMA. We propose a model of an “interferon-complement loop” that can perpetuate endothelial injury and thrombotic microangiopathy. These findings open opportunities to study novel complement blockers and combined anti-complement and anti-interferon therapies in patients with TA-TMA and other microangiopathies like aHUS and lupus-associated TMAs.
Reducing turnover intention: perceived organizational support for frontline employees
Authors: Wang Qiang , Wang Chao 
Published: March 2020

AbstractFrontline employees are generally under great pressure, and carry out repetitive and mundane daily tasks, leading to burnout and a high turnover intention among them. To identify ways to reduce this turnover intention, this study examines the effect of perceived organizational support (POS) on burnout and turnover intention in the Chinese context and adds to the literature on frontline employee burnout. Using data from a survey of the frontline employees of a gas station in Beijing, we examine the mediating effects of frontline employee burnout on their POS and turnover intention. This study shows that POS has a significant negative impact on burnout and turnover intention, and that job resources cannot substitute POS.
The energy impact of adaptive cruise control in real-world highway multiple-car-following scenarios
Authors: He Yinglong , Makridis Michail , Fontaras Georgios , Mattas Konstantinos , Xu Hongming , Ciuffo Biagio 
Published: March 2020

Abstract
Background
Surging acceptance of adaptive cruise control (ACC) across the globe is further escalating concerns over its energy impact. Two questions have directed much of this project: how to distinguish ACC driving behaviour from that of the human driver and how to identify the ACC energy impact. As opposed to simulations or test-track experiments as described in previous studies, this work is unique because it was performed in real-world car-following scenarios with a variety of vehicle specifications, propulsion systems, drivers, and road and traffic conditions.

Methods
Tractive energy consumption serves as the energy impact indicator, ruling out the effect of the propulsion system. To further isolate the driving behaviour as the only possible contributor to tractive energy differences, two techniques are offered to normalize heterogeneous vehicle specifications and road and traffic conditions. Finally, ACC driving behaviour is compared with that of the human driver from transient and statistical perspectives. Its impact on tractive energy consumption is then evaluated from individual and platoon perspectives.

Results
Our data suggest that unlike human drivers, ACC followers lead to string instability. Their inability to absorb the speed overshoots may partly be explained by their high responsiveness from a control theory perspective. Statistical results might imply the followers in the automated or mixed traffic flow generally perform worse in reproducing the driving style of the preceding vehicle. On the individual level, ACC followers have tractive energy consumption 2.7–20.5% higher than those of human counterparts. On the platoon level, the tractive energy values of ACC followers tend to consecutively increase (11.2–17.3%).

Conclusions
In general, therefore, ACC impacts negatively on tractive energy efficiency. This research provides a feasible path for evaluating the energy impact of ACC in real-world applications. Moreover, the findings have significant implications for ACC safety design when handling the stability-responsiveness trade-off.
Internal versus external European air market realities: the competitive divide
Authors: Ellis Darren 
Published: March 2020

AbstractBackgroundThis paper looks at how ongoing attempts to improve air market competitiveness in Europe are challenged by the differing internal and external realities that exist. Europe’s internal multilateral single air market has encouraged the proliferation of pan-European airlines unhindered by national borders, which have stimulated increased competition and driven down airfare prices. Meanwhile, externally the bilateral system continues to dominate the wider global airline industry and a number of countries still prefer to negotiate air access with individual European countries.MethodsData from a five stage mixed-method Delphi study underpin the paper. Qualitative data, collected at a first stage brainstorming workshop and during final stage in-depth interviews, were thematically analysed to locate key and sub-themes. Quantitative survey data were collected across the remaining stages and were statistically analysed with mostly t-tests and chi-square tests of association to a 95% confidence level.ResultsThe key themetransferabilityof the European regional single air market emerged from the study data; supported by the three sub-themesEU regional model, extraterritorialityandNorth Atlantic single air market.ConclusionsEurope remains the multilateral exception to the general rule in international aviation that bilateralism is the norm. Despite efforts to address this competitive divide, aeropowers like China and Russia are reluctant to embrace extensive change, while major European flag carriers resist unfettered competition from outside the bloc.
Infectious pseudo-aneurysm of the left ventricle: a case report and a review of the literature
Authors: Juliana Amadu E. , van ’t Kruys Kevin H. , Voigt Pieter G. , Blom Nico A. 
Published: March 2020

Abstract
Background
In the workup of a pediatric patient with pericarditis we found evidence of a pseudo-aneurysm of the left ventricle, which is a rare complication of purulent pericarditis.

Case presentation
We present a case of a six-year-old girl who was diagnosed with pericarditis and a fistula between the pericardial and the intra-luminal space of the left ventricle of the heart. She was successfully treated with antibiotics and cardio-thoracic surgery. We found 23 published cases (21 with follow-up) of infectious pseudo-aneurysm of the heart, of which 19 underwent surgery, 5 had fatal outcome, and 2 who refused surgery survived. The majority of cases were associated with Staphylococcus aureus. The exact mechanisms of this rare complication remain unknown.

Conclusions
A pseudo-aneurysm of the left ventricle is a rare and not well understood complication of a purulent pericarditis most commonly caused by Staphylococcus aureus infection. Because of risk of rupture, surgical intervention is advised.
Novel variants underlying autosomal recessive intellectual disability in Pakistani consanguineous families
Authors: Ilyas Muhammad , Efthymiou Stephanie , Salpietro Vincenzo , Noureen Nuzhat , Zafar Faisal , Rauf Sobiah , Mir Asif , Houlden Henry 
Published: March 2020

Abstract
Background
Intellectual disability (ID) is both a clinically diverse and genetically heterogeneous group of disorder, with an onset of cognitive impairment before the age of 18 years. ID is characterized by significant limitations in intellectual functioning and adaptive behaviour. The identification of genetic variants causing ID and neurodevelopmental disorders using whole-exome sequencing (WES) has proven to be successful. So far more than 1222 primary and 1127 candidate genes are associated with ID.

Methods
To determine pathogenic variants causative of ID in three unrelated consanguineous Pakistani families, we used a combination of WES, homozygosity-by-descent mapping, de-deoxy sequencing and bioinformatics analysis.

Results
Rare pathogenic single nucleotide variants identified by WES which passed our filtering strategy were confirmed by traditional Sanger sequencing and segregation analysis. Novel and deleterious variants in VPS53, GLB1, and MLC1, genes previously associated with variable neurodevelopmental anomalies, were found to segregate with the disease in the three families.

Conclusions
This study expands our knowledge on the molecular basis of ID as well as the clinical heterogeneity associated to different rare genetic causes of neurodevelopmental disorders. This genetic study could also provide additional knowledge to help genetic assessment as well as clinical and social management of ID in Pakistani families.
A novel variant of IHH in a Chinese family with brachydactyly type 1
Authors: Yang Qi , Wang Jin , Tian Xiaoxian , Shen Fei , Lan Jing , Zhang Qiang , Fan Xin , Yi Shang , Li Mengting , Shen Yiping 
Published: March 2020

AbstractBackgroundBrachydactyly type A1(BDA-1) is an autosomal dominant disorder which is caused by heterozygous pathogenic variants in a specific region of the N-terminal active fragment of Indian Hedgehog (IHH). The disorder is mainly characterized by shortening or missing of the middle phalanges. In this study, Our purpose is to identify the pathogenic variations associated with BDA-1 involved in a five-generation Chinese family.MethodsA BDA-1 family with 8 affected and 14 unaffected family members was recruited. Whole exome sequencing (WES) was performed to identify the pathogenic variant in the proband, and which was later confirmed and segregated by Sanger sequencing. The significance of variants were assessed using several molecular and bioinformatics analysis methods.ResultsWe uncovered a novel heterozygous missense variant c.299A > G (p.D100G) at the mutational hotspot ofIHHgene following whole-exome sequencing of a Chinese family with BDA-1. The variant co-segregated with BDA-1 in the pedigree, showed 100% penetrance for phalange phenotype with variable expressivity.ConclusionsIn conclusion, this study reports a five-generation Chinese family with BDA-1 due to a novel pathogenic variant (c.299A > G (p.D100G)) of IHH and expands the clinical and genetic spectrum of BDA-1.