bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical outcome 5 years after Dynamic Intraligamentary Stabilization of acute ACL ruptures
Authors: Kösters Clemens , Glasbrenner Johannes , Raschke Michael J. , Lenschow Simon , Herbort Mirco , Schliemann Benedikt 
Published: June 2019

Aims and Objectives: Dynamic Intraligamentary Stabilisation (DIS) is an anterior cruciate ligament (ACL) preserving surgical procedure for acute ACL injuries. A braided suture and a threaded sleeve containing a preloaded spring fixed into the proximal tibia provides continuous biomechanical stability. In combination with mircofracturing, self-healing of the ACL is promoted. Materials and Methods: Between January and November 2013 65 patients with an acute ACL rupture treated by Dynamic Intraligamentary Stabilisation (DIS) were included in this prospective study. Inclusion criteria were acute ACL injury, a positive Lachman test compared to the healthy contralateral side and closed growth plates. The following demographic patient data was preoperatively recorded: age, gender, weight, activity scores (Tegner, Lysholm, IKDC), type of injury, ap-translation of both knees measured by KT-1000 or Rolimeter, knee function and prior surgeries to the knees. Furthermore pivot shift test, acl rupture type, days until surgery, operating time, pre-existing pathologies and concomitant injuries were detected during surgery. The result of the reconstruction was assessed by rating it as anatomical, almost anatomical or non-anatomical. Patients were followed-up at 6 weeks, 6 months, 1 year, 2 years and 5 years after surgery. Patient satisfaction was detected recorded on a visual analog scale (VAS) scale from 0-10. Results: 34 men and 31 women were included. Mean age was 32.6 years (range 15 to 62 years). More than 70% of the injuries were soccer or handball associated. In 24 patients meniscal tears had to be repaired and in 4 patients cartilage damages had to be treated. All patients could be examinated 5 years after surgery. Within the follow up period 8 reruptures occured which were treated by one-step ACL reconstruction using an ipsilateral semitendinosus autograft. 4 patients had to be revised performing an arthrolysis due to extension deficit. At 5 years, Tegner Score averaged at 4.9 (compared to 5.5 pre-operatively). IKDC had an average of 90 (98). Lysholm score was at 95 (99). Patient satisfaction was 8.5. Conclusion: With the use of DIS, ACL preserving restoration of knee joint kinematics and mid-term survival of the repaired ACL after acute acl rupture can be achieved. Perioperative morbidity is reduced since harvesting of tendon grafts is not required. In case of recurrent instability or rerupture, conventional ACL reconstruction can still be performed. Knee function scores have shown a good rehabilitation and return to pre-trauma activity levels. However, long-term results are required to confirm safety and effectivity of the presented technique.
The “Apple-Bite-Fracture”: ACL rupture combined with posterolateral tibia plateau fracture
Authors: Menzdorf Leif , Drenck Tobias , Preiss Achim , Akoto Ralph , Krause Matthias , Frosch Karl-Heinz 
Published: June 2019

Aims and Objectives: Anterior cruciate ligament (ACL) ruptures are often concomitated by posterolateral bone bruise in the MRI. This is caused by a ventral subluxation of the tibia and impact of the femur in the posterolateral tibia plateau. In some cases, this impact causes a fracture of the posterolateral tibia plateau, the so-called Apple-Bite-Fracture. The increased posterior slope can cause additional instability and has to be considered as a risk factor for ACL failure. In this study we investigated the short term clinical outcomes of patients with this combined injury. Materials and Methods: Retrospective study of 14 patients (mean age 46 ± 12,3) (8 male, 6 female) with a mean follow up of 23,75 months. Different treatment strategies were analyzed. The clinical evaluation included visual analog score (VAS) increasing from 0-10 for Pain, IKDC Score, Rasmussen score as well as a clinical evaluation. Results: First analysis of the treatment options revealed a non-uniformed therapy strategy. In three patients the ACL tear was treated nonsurgical. In 11 patients the ACL tear was addressed surgical: six times the ACL was reconstructed with hamstring tendon graft, two times the ACL was sutured. Two patients treated with a non-reconstructive technique to promote healing (“healing response”). In one patient a tibial eminence fracture was fixated with a screw. The fracture of the posterolateral tibia plateau was in nine cases minimally invasive reduced and fixated with a screw osteosynthesis in jail technique. Two patients needed posterior buttress plate. Three times the large bone defect has been augmented with autologous bone graft from the pelvis. The postoperative clinical testing did not reveal any persisting knee instabilities. All patient had a non-limited ROM. No significant differences in ROM in comparison to the contralateral knee was seen. One patient reported persisting knee pain (VAS 3). All other patients reported no pain (VAS 0). Subjective IKDC score was 78,18 (71,3 - 83,9; ± 5,68). Clinical Rasmussen scores ranged from 27 to 30 (mean 27, ± 3,0). Rasmussen radiological results ranged from 16 to 18, mean 16,67 (± 1,15). Conclusion: Despite a very small patient number and leck of statistical power the new patient-spedific mini-metal implant seems to be a good options fort he treatment of middle-aged patients who already underwent frustane cartilage surgery. In these relatively rare caes early unicompartimental arthroplasty can be prevented. Further clinical studies with larger patient collectives have to prove the effectiveness of this new technique.
Prevalence of BTK and PLCG2 mutations in a real-life CLL cohort still on ibrutinib after 3 years: a FILO group study
Authors: Quinquenel Anne , Fornecker Luc-Matthieu , Letestu Rémi , Ysebaert Loïc , Fleury Carole , Lazarian Grégory , Dilhuydy Marie-Sarah , Nollet Delphine , Guieze Romain , Feugier Pierre , Roos-Weil Damien , Willems Lise , Michallet Anne-Sophie , Delmer Alain , Hormigos Katia , Levy Vincent , Cymbalista Florence , Baran-Marszak Fanny 
Published: June 2019

Abstract
Mutational analyses performed following acquired ibrutinib resistance have suggested that chronic lymphocytic leukemia (CLL) progression on ibrutinib is linked to mutations in Bruton tyrosine kinase (BTK) and/or phospholipase Cγ2 (PLCG2) genes. Mutational information for patients still on ibrutinib is limited. We report a study aimed to provide a “snapshot” of the prevalence of mutations in a real-life CLL cohort still on ibrutinib after at least 3 years of treatment. Of 204 patients who initiated ibrutinib via an early-access program at 29 French Innovative Leukemia Organization (FILO) centers, 63 (31%) were still on ibrutinib after 3 years and 57 provided a fresh blood sample. Thirty patients had a CLL clone ≥0.5 × 109/L, enabling next-generation sequencing (NGS); BTK and PLCG2 mutations were detected in 57% and 13% of the NGS samples, respectively. After median follow-up of 8.5 months from sample collection, the presence of a BTK mutation was significantly associated with subsequent CLL progression (P = .0005 vs no BTK mutation). Our findings support that mutational analysis should be considered in patients receiving ibrutinib who have residual clonal lymphocytosis, and that clinical trials are needed to evaluate whether patients with a BTK mutation may benefit from an early switch to another treatment.
Activated protein C ameliorates chronic graft-versus-host disease by PAR1-dependent biased cell signaling on T cells
Authors: Sinha Ranjeet K. , Flynn Ryan , Zaiken Michael , Paz Katelyn , Gavin Amanda L. , Nemazee David , Fernández José A. , Xu Xiao , Griffin John H. , Blazar Bruce R. 
Published: June 2019

Abstract
Soluble thrombomodulin plasma concentrations are elevated in steroid-resistant graft-versus-host disease (GVHD), implying endothelial hypofunctioning for thrombomodulin-dependent generation of activated protein C’s (APC) anticoagulant, anti-inflammatory, and antiapoptotic functions. Recombinant thrombomodulin or APC administration decreases acute GVHD, manifested by intense inflammation and tissue destruction. Here, we administered recombinant murine wild-type (WT) APC to mice with established chronic GVHD (cGVHD), a less-inflammatory autoimmune-like disease. WT APC normalized bronchiolitis obliterans–induced pulmonary dysfunction. Signaling-selective APC variants (3A-APC [APC with lysine 191-193 replaced with 3 alanines] or 5A-APC [APC with lysine 191-193 replaced with 3 alanines and arginine 229/230 replaced with 2 alanines]) with normal cytoprotective properties, but greatly reduced anticoagulant activity, provided similar results. Mechanistically, WT APC and signaling-selective variants reduced T follicular helper cells, germinal center formation, immunoglobulin, and collagen deposition. WT APC can potentially cleave protease-activated receptor 1 (PAR1) at Arg41 or Arg46, the latter causing anti-inflammatory signaling. cGVHD was reduced in recipients of T cells from WT PAR1 or mutated Gln41-PAR1 donors but not from mutated Gln46-PAR1 donors. These data implicate donor T-cell APC-induced noncanonical cleavage at Arg46-PAR1, which is known to confer cytoprotective and anti-inflammatory activities. Together, these data indicate that APC anticoagulant activity is dispensable, whereas anti-inflammatory signaling and cytoprotective cell signaling by APC are essential. Because a phase 2 ischemic stroke clinical trial did not raise any safety issues for 3A-APC treatment, our studies provide a foundational platform for testing in clinical cGVHD therapy.
Availability of FLT3 inhibitors: how do we use them?
Authors: Perl Alexander E. 
Published: June 2019

Abstract
The natural history of FLT3-mutated AML is changing after the approval of midostaurin for frontline therapy and gilteritinib for relapsed or refractory patients. Recently reported, positive randomized trials of the drugs gilteritinib, quizartinib, and sorafenib predict even wider use of FLT3 inhibitors going forward. FLT3 inhibitors now emerge as an important, if not indispensable, part of therapy for a large subset of high-risk patients.
Bedtime Salivary Cortisol and Cortisone by LC-MS/MS in Healthy Adult Subjects: Evaluation of Sampling Time
Authors: Raff Hershel , Phillips Jonathan M 
Published: June 2019

AbstractThe measurement of late-night salivary cortisol is a mainstay in the diagnosis of Cushing syndrome. Furthermore, the measurement of salivary cortisol is useful in assessing the cortisol awakening response. Because the salivary glands express 11-β-hydroxysteroid dehydrogenase, the measurement of salivary cortisone may improve the performance of salivary corticosteroid measurements. We measured salivary cortisol by enzyme immunoassay (EIA) and salivary cortisol and cortisone by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in only 50 µL of saliva sampled from 54 healthy subjects (aged 20 to 64 years). We allowed patients to sample at their normal bedtime (2025 to 2400 hours) to answer a common question as to whether sampling at the normal bedtime is equivalent to the standard required sampling at 2300 to 2400 hours. We found that the salivary cortisol and cortisone results by LC-MS/MS correlated well with salivary cortisol measured with the US Food and Drug Administration-cleared EIA. Furthermore, the upper limit of normal of salivary cortisol by EIA for bedtime samples was lower than the previously published upper limit of normal with sampling required at 2300 to 2400 hours. There were no significant effects of age or sex on any of the salivary steroid measurements. We conclude that (i) salivary cortisol and cortisone can be reliably measured by LC-MS/MS in small volumes of saliva and (ii) that patients can be evaluated using saliva sampled at their normal bedtime, rather than being required to stay awake until 2300 to 2400 hours.
Different functional roles for K+ channel subtypes in regulating small intestinal glucose and ion transport
Authors: Du Chao , Chen Siyuan , Wan Hanxing , Chen Lihong , Li Lingyu , Guo Hong , Tuo Biguang , Dong Hui 
Published: June 2019

Background: Although K+ channels are important in mediating the driving force for colonic ion transport, their role in the small intestinal transport is poorly understood.Methods: Small intestinal short circuit currents (Isc) and HCO3− secretion were measured in mice, and intracellular pH (pHi) was measured in small intestinal epithelial SCBN cells. The expression and location of Kv subtypes were verified by RT-PCR, Western blotting and immunohistochemistry. Diabetic mice were also used to investigate the role of Kv subtypes in regulating intestinal glucose absorption.Results: KV7.1 is not involved in duodenal ion transport, while KCa3.1 selectively regulates duodenal Isc and HCO3− secretion in a Ca2+-mediated but not cAMP-mediated manner. Blockade of KCa3.1 increased the rate of HCO3− fluxes via CFTR channels in SCBN cells. Jejunal Isc was significantly stimulated by glucose, but markedly inhibited by 4-AP and TEA. Moreover, both Kv1.1 and Kv1.3 were expressed in jejunal mucosae. Finally, 4-AP significantly attenuated weight gain of normal and diabetic mice, and both 4-AP and TEA significantly lowered blood glucose of diabetic mice.Conclusions: This study not only examines the contribution of various K+ channel subtypes to small intestinal epithelial ion transport and glucose absorption, but also proposes a novel concept for developing specific K+ channel blockers to reduce weight gain and lower blood glucose in diabetes mellitus.
Sumoylation regulates protein dynamics during meiotic chromosome segregation in C. elegans oocytes
Authors: Pelisch Federico , Bel Borja Laura , Jaffray Ellis G. , Hay Ronald T. 
Published: June 2019

ABSTRACT
Oocyte meiotic spindles in most species lack centrosomes and the mechanisms that underlie faithful chromosome segregation in acentrosomal meiotic spindles are not well understood. In C. elegans oocytes, spindle microtubules exert a poleward force on chromosomes that is dependent on the microtubule-stabilising protein CLS-2, the orthologue of the mammalian CLASP proteins. The checkpoint kinase BUB-1 and CLS-2 localise in the central spindle and display a dynamic localisation pattern throughout anaphase, but the signals regulating their anaphase-specific localisation remains unknown. We have shown previously that SUMO regulates BUB-1 localisation during metaphase I. Here, we found that SUMO modification of BUB-1 is regulated by the SUMO E3 ligase GEI-17 and the SUMO protease ULP-1. SUMO and GEI-17 are required for BUB-1 localisation between segregating chromosomes during early anaphase I. We also show that CLS-2 is subject to SUMO-mediated regulation; CLS-2 precociously localises in the midbivalent when either SUMO or GEI-17 are depleted. Overall, we provide evidence for a novel, SUMO-mediated control of protein dynamics during early anaphase I in oocytes.
Climate change in the UAE: Modeling air temperature using ARIMA and STI across four bio-climatic zones
Authors: Ksiksi Taoufik Saleh , Al-Blooshi Latifa Saeed 
Published: June 2019

Background: Standardizing climate-related indices and models across spatial and temporal scales presents a challenge. Especially when predicting climatic conditions in the era of climate change. The present work aims to assess the use of ARIMA (Auto Regressive Integrated Moving Average) modeling approach coupled with STI (Standardized Temperature Index) to predict temperature anomalies across four bio-climatic regions within the United Arab Emirates (UAE). Methods: We used monthly temperature data from NOAA Land-Based Station Data for Abu Dhabi, Al-Ain, Dubai and Sharjah. ARIMA modeling and STI assessment of climatic events were used to predict and study the dynamics of climate of the four zones. The use of such forecasting powers was intended for an ultimate aim to study the impact of climate change on land use and land cover changes. Results: Data were not auto-correlated as shown by the Box-Ljung test. Additionally, the box-plots showed that Abu Dhabi had the highest median temperature. The ARIMA forecasting suggested that Dubai is predicted to have increasing trend of average temperatures until 2030. "Extremely hot" events were highest for Al-Ain (i.e. 9), followed by Abu Dhabi, Dubai and Sharjah. Dubai had the highest occurrences of "Moderately hot" events, when compared to all other studied zones. Further, events classified as "very cold" were in the order of 20, 10, and 8, for Dubai, Sharjah, and for each of Abu Dhabi and Al-Ain, respectively. Conclusions: The temperature is predicted to increase in Dubai and Sharjah, with each representing a different bio-climatic zone. This was also reflected in the STI assessment of the historical temperature. "Moderately hot" and "very cold" events for Dubai were the highest as compared to the other studied zones in the UAE. It is therefore believed that ARIMA, coupled with STI, may be a valid approach to forecast temperature and analyse extreme events.
Preprints and Scholarly Communication: Adoption, Practices, Drivers and Barriers
Authors: Chiarelli Andrea , Johnson Rob , Pinfield Stephen , Richens Emma 
Published: June 2019

Background: Since 2013, there has been a dramatic increase in the number of preprint servers available online. To date, little is known about the position of researchers, funders, research performing organisations and other stakeholders with respect to this fast-paced landscape. In this article, we explore the benefits and challenges of preprint posting, along with issues such as infrastructure and financial sustainability. We also discuss the definition of a ‘preprint’ in different communities, and the impact this has on further uptake. Methods: This study is based on 38 detailed semi-structured interviews of key stakeholders based on a purposive heterogeneous sampling approach. Interviews were undertaken between October 2018 and January 2019. These were recorded, transcribed and subjected to thematic analysis to identify trends. Interview questions were designed based on Innovation Diffusion Theory, which is also used to interpret the results of this study. Results: Our study is the first using empirical data to understand the new wave of preprint servers and found that early and fast dissemination is the most appealing feature of the practice. The main concerns are related to the lack of quality assurance and the ‘Ingelfinger rule’. We identified trust as an essential enabler of preprint posting and stress the enabling role of Twitter in showcasing preprints and enabling comments on these. Conclusions: The preprints landscape is evolving fast and disciplinary communities are at different stages in the innovation diffusion process. The landscape is characterised by significant experimentation, which leads to the conclusion that a one-size-fits-all approach to preprints is not feasible. Cooperation and active engagement between the stakeholders involved will play an important role in the future. In our paper, we share questions for the further development of the preprints landscape, with the most important being whether preprint posting will develop as a publisher- or researcher-centric practice.
Identifying ‘hard-to-reach’ groups and strategies to engage them in biomedical research: perspectives from engagement practitioners in Southeast Asia
Authors: Nguyen Thanh Ha , Cheah Phaik Yeong , Chambers Mary 
Published: June 2019

Public or community engagement (PE/CE) is an increasingly important component of biomedical research. However, PE/CE projects have been criticized for focusing on the ‘convenient sample’ populations that are more accessible and more likely to respond, thus missing out the less-socially visible groups. In January 2018, engagement practitioners from across Southeast Asia, attending a regional workshop, undertook a discussion about the ‘hard-to-reach’ populations in the region, and how PE projects can better engage them. This paper is a summary of that discussion. After an initial brainstorming exercise the hard-to-reach populations identified by workshop participants were broadly categorised into three groups: urban poor, ethnic minority groups and children in rural primary schools. Delegates identified common characteristics of the populations and possible interventions to reach them. Notes of the discussions were used as data for the report. Four common issues that become barriers for engagement were identified: (1) financial instability; (2) mobility in residency and work; (3) discrimination and isolation; and (4) limitations in local resources. It is important to recognise that a group might be more disadvantaged by one factor than the others, but often these issues inter-relate to restrict outreach. In order to engage these populations, a tailor-made programme, that suits the local context, should be created. This can be done through four strategies that have the acronym ‘FIND’: (1) Formative research to improve understanding of the population; (2) Integrating into local life; (3) Networking with relevant stakeholders; and (4) Developing local resources. Our discussion highlights the importance of a deep understanding of the local contexts in order to implement relevant and acceptable engagement projects. Findings from this report may be useful for planning public engagement projects in similar settings.
Living with Parkinson's—past, present and future: a qualitative study of the subjective perspective
Authors: Maffoni Marina , Pierobon Antonia , Frazzitta Giuseppe , Callegari Simona , Giardini Anna 
Published: June 2019

Background: the social impact of Parkinson's is difficult to capture in quantitative research given the condition's variable presentation, so qualitative research is needed to support a person-centred approach. Aims: to describe how people with Parkinson's experience living with their condition over time. Methods: 27 audio-recorded verbatim-transcribed interviews were analysed through the grounded theory method. Findings: past, present and future were the core categories that emerged. Past is the dimension of regretted memories of past life overturned by the communication of diagnosis. Present is the time dimension in which patients concretely experience the hindrances associated with the condition (loss of autonomy, submissive acceptance and social embarrassment), and the resources (search for autonomy, serene or in-progress acceptance, and social support). Future is characterised by both positive visions of tomorrow and negative ones (worry, resignation, denial). Conclusion: these results, highlighting what living with Parkinson's means over time, may contribute to a better tailoring of nursing practice to the person's needs and rhythm, in a perspective of continuous adaptation.