bluuebunny/crossref_metadata_2025_split huggingface dataset:
The SPC manufacturing waiver: Good for patients, good for jobs, good for Europe
Authors: Shillingford Tomos 
Published: May 2018

The European Commission is currently considering an important legislative proposal which is supported by the generic pharmaceutical industry. Following the introduction of supplementary protection certificates in the 1990s, an unintended consequence has been felt by European generic manufacturers, whom are very often the last group to be able to commence commercial production, due to earlier expiry of rights in other parts of the world. This puts European pharmaceutical manufacturers at a competitive disadvantage, seeing as they are not able to manufacture product for export to countries in which no patent rights exist, or in readiness for day 1 launches in Europe. The supplementary protection certificate manufacturing waiver has been independently assessed to represent €7.3–9.5b of revenue to European industry by 2025, to generate 20,000–25,000 jobs, to lead to €1.6–3.1b in healthcare cost-savings and to improve patient access to healthcare. However, the European Federation of Pharmaceutical Industries and Associations (EFPIA) and other innovator pharmaceutical groups have been lobbying against the proposal. In this paper, I examine the arguments against the supplementary protection certificate manufacturing waiver, particularly those set out in EFPIA’s White Paper that was published in 2017. The conclusions of the White Paper are found to be unsupported. It is hoped that the supplementary protection certificate manufacturing waiver will be implemented, and provide a valuable stimulus for the manufacture of pharmaceuticals in Europe.
Assessing pressure injury risk using a single mobility scale in hospitalised patients: a comparative study using case-control design
Authors: Mordiffi Siti Zubaidah , Kent Bridie , Phillips Nicole M. , Choon Huat Gerald Koh 
Published: May 2018

Background Pressure injury is known to cause not only debilitating physical effects, but also substantial psychological and financial burdens. A variety of pressure injury risk assessment tools are in use worldwide, which include a number of factors. Evidence now suggests that assessment of a single factor, mobility, may be a viable alternative for assessing pressure injury risk. Aims The aim of this study was to ascertain whether using the Braden mobility subscale alone is comparable to the full Braden scale for predicting the development of pressure injury. Methods This study, a retrospective case-control design, was conducted in a large tertiary acute care hospital in Singapore. Medical records of 100 patients with hospital-acquired pressure injury were matched with 100 medical records of patients who had no pressure injury at a 1:1 ratio. Results Patients who were assessed using the Braden mobility subscale as having ‘very limited mobility’ or worse were 5.23 (95% confidence interval (CI) 2.66–10.20) times more likely to develop pressure injury compared with those assessed as having ‘slightly limited’ mobility or ‘no limitation’. Conversely, patients assessed using the Braden scale as having ‘low risk’ or higher were 3.35 (95% CI 1.77–6.33) times more likely to develop pressure injury compared with those assessed as ‘no risk’. Using full model logistic regression analysis, the Braden mobility subscale was the only factor that was a significant predictor of pressure injury and it remained significant when analysed for the most parsimonious model using backward logistic regression. Conclusions These findings provide the empirical evidence that using the Braden mobility subscale alone as an assessment tool for predicting pressure injury development is comparable to using the full Braden scale. Use of this single factor would simplify pressure injury risk assessment and support its use within busy clinical settings.
The benefit of EXtending oral antiCOAgulation treatment (EXCOA) after acute cerebral vein thrombosis (CVT): EXCOA-CVT cluster randomized trial protocol
Authors: Miranda Bruno , Aaron Sanjith , Arauz Antonio , Barinagarrementeria Fernando , Borhani-Haghighi Afshin , Carvalho Marta , Conforto Adriana B , Coutinho Jonathan M , Stam Jan , Canhão Patrícia , Ferro José M 
Published: May 2018

Rationale After a cerebral vein thrombosis, there is an increased risk of further venous thromboembolic events. The optimal duration of anticoagulation after cerebral vein thrombosis is unknown. Aim To compare efficacy and safety of a policy of short- (3–6 months) versus long-term (12 months) anticoagulation (any type venous thromboembolic events) after cerebral vein thrombosis for the prevention of venous thromboembolic events. Sample size estimates A sample of 1428 patients (749 per arm) allows detecting a reduction from 10 to 5% in the risk of venous thromboembolic event recurrence with 80% power at 5% significance, with 3% dropout rate. Methods and design An international multicenter, prospective cluster-randomized trial with equal allocation between both interventions (ISRCTN25644448). Each cluster is a participating center, which accepted to be randomly allocated to one of the anticoagulation policies. Eligible patients are adults with radiologically confirmed cerebral vein thrombosis within 30 days, and stable to initiate post-acute anticoagulation. Patients judged by the investigator to be an absolute indication for permanent anticoagulation are excluded. Follow-up is at 6, 12 and 24 months. Study outcomes Primary efficacy outcome is any symptomatic and confirmed fatal/nonfatal venous thromboembolic event (recurrent-cerebral vein thrombosis or non-cerebral venous thromboembolic event). Primary safety outcomes include bleeding events during treatment periods and death from any cause. Discussion This study responds to a knowledge gap in the post-acute management of cerebral vein thrombosis patients by comparing short- versus long-term anticoagulation for the prevention of venous thromboembolic event recurrence.
Synchronous endometrial adenocarcinoma and carcinosarcoma in endometrial polyp
Authors: Alnimer Yanal , Zaghmout Osama , Azher Qazi 
Published: May 2018

Introduction: Carcinosarcoma is a rare gynecological malignancy and it usually follows an aggressive clinical course. Rarely, it can be confined to an endometrial polyp or be synchronous with another gynecological malignancy. Herein, we report a rare case of synchronous carcinosarcoma confined to an endometrial polyp and endometrioid endometrial adenocarcinoma arising from a distinct uterine wall site. Case presentation: A 57-year-old female patient presented with heavy vaginal bleeding. She underwent hysterectomy with bilateral salpingo-oophorectomy for endometrioid endometrial adenocarcinoma that was diagnosed preoperatively through dilation and curettage. Full histopathological examination of the uterine specimen revealed carcinosarcoma confined to a 4 cm endometrial polyp in addition to a stage IA endometrioid endometrial adenocarcinoma which arose from a distinct uterine wall. Conclusion: Having an endometrioid endometrial cancer diagnosis preoperatively through dilation and curettage and at examination of the frozen section specimen following surgical resection should not preclude the standard full histopathological examination of the uterine specimen, since this could reveal an additional uterine malignancy, such as carcinosarcoma. Such a finding would alter the post-operative management, prognosis, and outcome even if it is confined to an endometrial polyp.
Long‐term health and treatment outcomes in adult coeliac disease patients diagnosed by screening in childhood
Authors: Kivelä Laura , Popp Alina , Arvola Taina , Huhtala Heini , Kaukinen Katri , Kurppa Kalle 
Published: May 2018

BackgroundThe diagnostic yield of coeliac disease could be improved by screening in at‐risk groups, but long‐term benefits of this approach are obscure.ObjectiveTo investigate health, quality of life and dietary adherence in adult coeliac patients diagnosed in childhood by screening.MethodsAfter thorough evaluation of medical history, follow‐up questionnaires were sent to 559 adults with a childhood coeliac disease diagnosis. The results were compared between screen‐detected and clinically‐detected patients, and also between originally asymptomatic and symptomatic screen‐detected patients.ResultsIn total, 236 (42%) patients completed the questionnaires a median of 18.5 years after childhood diagnosis. Screen‐detected patients (n = 48) had coeliac disease in the family and type 1 diabetes more often, and were less often smokers and members of coeliac societies compared to clinically‐detected patients, whereas the groups did not differ in current self‐experienced health or health concerns, quality of life or dietary adherence. Screen‐detected, originally asymptomatic patients had more anxiety than those presenting with symptoms, whereas the subgroups were comparable in other current characteristics.ConclusionComparable long‐term outcomes between screen‐detected and clinically‐detected patients support risk‐group screening for coeliac disease. However, asymptomatic patients may require special attention.
Post‐infectious IBS: Defining its clinical features and prognosis using an internet‐based survey
Authors: Card Tim , Enck Paul , Barbara Giovanni , Boeckxstaens Guy EE , Santos Javier , Azpiroz Fernando , Mearin Fermin , Aziz Qasim , Marshall John , Spiller Robin 
Published: May 2018

BackgroundGastrointestinal infection is an important risk factor for developing irritable bowel syndrome (IBS). Our aim was to characterise post‐infectious IBS (PI‐IBS) compared to other IBS patients.MethodsAn internet survey of IBS patients using Rome III diagnostic questionnaire, Hospital Anxiety and Depression Scale (HADS) and Patient Health Questionnaire‐12 Somatic Symptom (PHQ12‐SS) scale score documenting the mode of onset was conducted.ResultsA total of 7811 participants (63.2% female), of whom 1004 (13.3%) met criteria for PI‐IBS, were studied. Seventy per cent of PI‐IBS patients described sudden onset, 35% onset while travelling, 49.6% vomiting, 49.9% fever and 20.3% bloody diarrhoea. Compared to other IBS individuals, PI‐IBS was significantly associated with living in Northern Europe and North America, having a hysterectomy, not having an appendicectomy, higher PHQ12‐SS score and having more than one toilet in the family home. PI‐IBS patients had more frequent stools. At one year recovery rate in the PI‐IBS and non‐PI‐IBS group was 19.7% and 22.2%, p = 0.15. Recovery rates were lower for females (20.7%) vs males (38.8%), those with somatisation (23.0%) vs those without (33.2%) and those living in North America or Northern Europe (21.1%) vs living elsewhere (33.9%) p ≤ 0.001.ConclusionPI‐IBS accounts for around 13% of all IBS in this internet sample, with some distinctive features but a similar prognosis to the remainder.
Evaluating touchless capacitive gesture recognition as an assistive device for upper extremity mobility impairment
Authors: Nelson Alexander , McCombe Waller Sandy , Robucci Ryan , Patel Chintan , Banerjee Nilanjan 
Published: May 2018

Introduction This paper explores the feasibility of using touchless textile sensors as an input to environmental control for individuals with upper-extremity mobility impairments. These sensors are capacitive textile sensors embedded into clothing and act as proximity sensors. Methods We present results from five individuals with spinal cord injury as they perform gestures that mimic an alphanumeric gesture set. The gestures are used for controlling appliances in a home setting. Our setup included a custom visualization that provides feedback to the individual on how the system is tracking the movement and the type of gesture being recognized. Our study included a two-stage session at a medical school with five subjects with upper extremity mobility impairment. Results The experimenting sessions derived binary gesture classification accuracies greater than 90% on average. The sessions also revealed intricate details in participant’s motions, from which we draw two key insights on the design of the wearable sensor system. Conclusion First, we provide evidence that personalization is a critical ingredient to the success of wearable sensing in this population group. The sensor hardware, the gesture set, and the underlying gesture recognition algorithm must be personalized to the individual’s need and injury level. Secondly, we show that explicit feedback to the user is useful when the user is being trained on the system. Moreover, being able to see the end goal of controlling appliances using the system is a key motivation to properly learn gestures.
Learning From Failure in Cartilage Repair Surgery: An Analysis of the Mode of Failure of Primary Procedures in Consecutive Cases at a Tertiary Referral Center
Authors: Krych Aaron J. , Hevesi Mario , Desai Vishal S. , Camp Christopher L. , Stuart Michael J. , Saris Daniel B.F. 
Published: May 2018

Background: As the number of cartilage restoration procedures is increasing, so is the number of revision procedures. However, there remains limited information on the reasons for failure of primary cartilage restoration procedures. Purpose: To determine the common modes of failure in primary cartilage restoration procedures to improve surgical decision making and patient outcomes. Study Design: Case series; Level of evidence, 4. Methods: Patients who presented for revision after failed cartilage repair surgery were evaluated for factors contributing to failure of the primary procedure. All revision cases performed by a single surgeon at a tertiary center for failed cartilage restoration over a 6-year time frame were identified. In all cases, the medical records, preoperative radiographs, and magnetic resonance imaging scans were reviewed by 2 experienced cartilage surgeons. The cause for failure was categorized as malalignment, meniscal deficiency, graft or biologic failure, or instability. Univariate and descriptive statistics regarding patient demographics, index procedure, lesion location and size, and mechanism of failure were analyzed. Results: A total of 59 cases in 53 patients (32 male, 21 female) met the inclusion criteria. The mean patient age at the time of revision was 27.6 years, and the mean body mass index was 28.4 kg/m2. Failed index surgical procedures included 35 microfractures (59%), 12 osteochondral allograft transplantations (20%), 10 osteochondral autograft transfers (17%), 2 nonviable osteochondral allografts (3%), and 2 particulated juvenile chondral allografts (3%). The mean lesion size was 4.4 cm2. Reasons for failure included 33 cases with untreated malalignment (56%), 16 with graft failure (27%), 11 with untreated meniscal deficiency (19%), and 3 with untreated instability (5%); 4 cases demonstrated multiple reasons for failure. Conclusion: The most commonly recognized reason for failure was untreated malalignment. While biologic and graft failures will occur, the majority of failures were attributed to untreated background factors such as malalignment, meniscal deficiency, and instability. The stepwise approach of considering and addressing alignment, meniscal volume, and stability remains essential in cartilage restoration surgery.
The new mineral novograblenovite, (NH4,K)MgCl3·6H2O from the Tolbachik volcano, Kamchatka, Russia: mineral description and crystal structure
Authors: Okrugin Viktor M. , Kudaeva Sharapat S. , Karimova Oxana V. , Yakubovich Olga V. , Belakovskiy Dmitry I. , Chukanov Nikita V. , Zolotarev Andrey A. , Gurzhiy Vladislav V. , Zinovieva Nina G. , Shiryaev Andrey A. , Kartashov Pavel M. 
Published: May 2018

AbstractThe new mineral novograblenovite, (NH4,K)MgCl3·6H2O, was found on basaltic lava from the 2012–2013 Tolbachik fissure eruption at the Plosky Tolbachik volcano, Kamchatka Peninsula, Russia. It occurs as prismatic, needle-like transparent crystals together with gypsum and halite. Novograblenovite was formed due to the exposure of the host rocks to eruptive gas exhalations enriched in HCl and NH3. Basalt was the source of potassium and magnesium for the mineral formation. Novograblenovite crystallises in the monoclinic space groupC2/c, with unit-cell parametersa= 9.2734(3) Å,b= 9.5176(3) Å,c= 13.2439(4) Å, β = 90.187(2)°,V= 1168.91(2) Å3andZ= 4. The five strongest reflections in the powder X-ray diffraction pattern [dobs, Å (I, %) (h k l)] are: 3.330 (100) (2 2 0), 2.976 (45) ($\bar{1}\; 1\; 4$), 2.353 (29) ($\bar {2}\; 2\; 4$), 3.825 (26) (2 0 2), 1.997 (25) ($\overline {4\; 2} $2). The density calculated from the empirical formula and the X-ray data is 1.504 g cm–3. The mineral is biaxial (+) with α = 1.469(2), β = 1.479(2) and γ = 1.496(2) (λ = 589 nm); 2Vmeas.= 80(10)° and 2Vcalc.= 75.7°. The crystal structure (solved and refined using single-crystal X-ray diffraction data,R1= 0.0423) is based on the perovskite-like network of (NH4,K)Cl6-octahedra sharing chlorine vertices, and comprises [Mg(H2O)6]2+groups in framework channels. The positions of all independent H atoms were obtained by difference-Fourier techniques and refined isotropically. All oxygen, nitrogen and chlorine atoms are involved in the system of hydrogen bonding, acting as donors or acceptors. The formula resulting from the structure refinement is [(NH4)0.7K0.3]MgCl3·6H2O. The mineral is named after Prokopiy Trifonovich Novograblenov, one of the researchers of Kamchatka Peninsula, a teacher, naturalist, geographer and geologist.
Hemostatic efficacy of pathogen-inactivated vs untreated platelets: a randomized controlled trial
Authors: van der Meer Pieter F. , Ypma Paula F. , van Geloven Nan , van Hilten Joost A. , van Wordragen-Vlaswinkel Rinie J. , Eissen Okke , Zwaginga Jaap J. , Trus Michael , Beckers Erik A. M. , te Boekhorst Peter , Tinmouth Alan , Lin Yulia , Hsia Cyrus , Lee David , Norris Philip J. , Goodrich Raymond P. , Brand Anneke , Hervig Tor , Heddle Nancy M. , van der Bom Johanna G. , Kerkhoffs Jean-Louis H. 
Published: May 2018

Key PointsPathogen-inactivated platelets were noninferior in preventing bleeding only in intention-to-treat analysis. In contrast to animal models, alloimmunization could not be prevented when using pathogen-inactivated platelets.
Effects of linagliptin on endothelial function and postprandial lipids in coronary artery disease patients with early diabetes: a randomized, placebo-controlled, double-blind trial
Authors: Tripolt Norbert J. , Aberer Felix , Riedl Regina , Url Jasmin , Dimsity Gudrun , Meinitzer Andreas , Stojakovic Tatjana , Aziz Faisal , Hödl Ronald , Brachtl Gabriele , Strunk Dirk , Brodmann Marianne , Hafner Franz , Sourij Harald 
Published: May 2018

Abstract
Background
Early glucose lowering intervention in subjects with type 2 diabetes mellitus was demonstrated to be beneficial in terms of micro- and macrovascular risk reduction. However, most of currently ongoing cardiovascular outcome trials are performed in subjects with manifest atherosclerosis and long-standing diabetes. Therefore, the aim of this study is to investigate the effects of the dipeptidylpeptidase-4 inhibitor linagliptin in subjects with coronary artery disease (CAD) but early type 2 diabetes mellitus (T2DM) on a set of cardiovascular surrogate measurements.

Methods
In this randomized, placebo-controlled, double-blind, single-center study, we included subjects with early diabetes (postchallenge diabetes (2 h glucose > 200 mg/dl) or T2DM treated with diet only or on a stable dose of metformin monotherapy and an HbA1c < 75 mmol/mol) and established CAD. Participants were randomized to receive either linagliptin (5 mg) once daily orally or placebo for 12 weeks. The primary outcome was the change in flow mediated dilatation (FMD). The secondary objective was to investigate the effect of linagliptin treatment on arginine bioavailability ratios [Global arginine bioavailability ratio (GABR) and arginine to ornithine ratio (AOR)]. Arginine, ornithine and citrulline were measured in serum samples with a conventional usual amino acid analysis technique, involving separation of amino acids by ion exchange chromatography followed by postcolumn continuous reaction with ninhydrin. GABR was calculated by l-arginine divided by the sum of (l-ornithine plus l-citrulline). The AOR was calculated by dividing l-arginine by l-ornithine levels. Group comparisons were calculated by using a two-sample t-test with Satterthwaite adjustment for unequal variances.

Results
We investigated 43 patients (21% female) with a mean age of 63.3 ± 8.2 years. FMD at baseline was 3.5 ± 3.1% in the linagliptin group vs. 4.0 ± 2.9% in the placebo group. The change in mean FMD in the linagliptin group was not significantly different compared to the change in the placebo group (0.43 ± 4.84% vs. − 0.45 ± 3.01%; p = 0.486). No significant improvements were seen in the arginine bioavailability ratios (GABR; p = 0.608 and AOR; p = 0.549).

Conclusion
Linagliptin treatment in subjects with CAD and early T2DM did not improve endothelial function or the arginine bioavailability ratios.
Trial registration ClinicalTrials.gov, NCT02350478 (https://clinicaltrials.gov/ct2/show/NCT02350478)
Assembly and maintenance of GABAergic and Glycinergic circuits in the mammalian nervous system
Authors: Gamlin Clare R. , Yu Wan-Qing , Wong Rachel O. L. , Hoon Mrinalini 
Published: May 2018

AbstractInhibition in the central nervous systems (CNS) is mediated by two neurotransmitters: gamma-aminobutyric acid (GABA) and glycine. Inhibitory synapses are generally GABAergic or glycinergic, although there are synapses that co-release both neurotransmitter types. Compared to excitatory circuits, much less is known about the cellular and molecular mechanisms that regulate synaptic partner selection and wiring patterns of inhibitory circuits. Recent work, however, has begun to fill this gap in knowledge, providing deeper insight into whether GABAergic and glycinergic circuit assembly and maintenance rely on common or distinct mechanisms. Here we summarize and contrast the developmental mechanisms that regulate the selection of synaptic partners, and that promote the formation, refinement, maturation and maintenance of GABAergic and glycinergic synapses and their respective wiring patterns. We highlight how some parts of the CNS demonstrate developmental changes in the type of inhibitory transmitter or receptor composition at their inhibitory synapses. We also consider how perturbation of the development or maintenance of one type of inhibitory connection affects other inhibitory synapse types in the same circuit. Mechanistic insight into the development and maintenance of GABAergic and glycinergic inputs, and inputs that co-release both these neurotransmitters could help formulate comprehensive therapeutic strategies for treating disorders of synaptic inhibition.