bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomised clinical trial: efficacy and safety of vonoprazan vs. lansoprazole in patients with gastric or duodenal ulcers – results from two phase 3, non‐inferiority randomised controlled trials
Authors: Miwa H. , Uedo N. , Watari J. , Mori Y. , Sakurai Y. , Takanami Y. , Nishimura A. , Tatsumi T. , Sakaki N. 
Published: November 2016

SummaryBackgroundVonoprazan is a new potassium‐competitive acid blocker for treatment of acid‐related diseases.AimTo conduct two randomised‐controlled trials, to evaluate the non‐inferiority of vonoprazan vs. lansoprazole, a proton pump inhibitor, for treatment of gastric ulcer (GU) or duodenal ulcer (DU).MethodsPatients aged ≥20 years with ≥1 endoscopically‐confirmed GU or DU (≥5 mm white coating) were randomised 1:1 using double‐dummy blinding to receive lansoprazole (30 mg) or vonoprazan (20 mg) for 8 (GU study) or 6 (DU study) weeks. The primary endpoint was the proportion of patients with endoscopically confirmed healed GU or DU.ResultsFor GU, 93.5% (216/231) of vonoprazan‐treated patients and 93.8% (211/225) of lansoprazole‐treated patients achieved healed GU; non‐inferiority of vonoprazan to lansoprazole was confirmed [difference = −0.3% (95% CI −4.750, 4.208); P = 0.0011]. For DU, 95.5% (170/178) of vonoprazan‐treated patients and 98.3% (177/180) of lansoprazole‐treated patients achieved healed DU; non‐inferiority to lansoprazole was not confirmed [difference = −2.8% (95% CI −6.400, 0.745); P = 0.0654]. The incidences of treatment‐emergent adverse events were slightly lower for GU and slightly higher for DU with vonoprazan than with lansoprazole. There was one death (subarachnoid haemorrhage) in the vonoprazan group (DU). The possibility of a relationship between this unexpected patient death and the study drug could not be ruled out. In both studies, increases in serum gastrin levels were greater in vonoprazan‐treated vs. lansoprazole‐treated patients; levels returned to baseline after treatment in both groups.ConclusionsVonoprazan 20 mg has a similar tolerability profile to lansoprazole 30 mg and is non‐inferior with respect to GU healing and has similar efficacy for DU healing.
Effects of oils on feed mildew and quality
Authors: Liu Jie , Qi Ming , Huang Yakuan , Guo Jiao , Zhang Jiacai , Li Chong , Zhang Niya , Sun Lvhui , Qi Desheng 
Published: November 2016

AbstractThis study was performed to determine the effects of oils on feed mildew and feed quality. Under different moisture content conditions (10%, 13% and 16%), the basal feeds were supplemented with 4%, 6%, 8%, 10% and 12% soybean oil. In addition, at different moisture content levels (10%, 13% and 16%), the basal feed was supplemented with 12% of various types of oil (soybean, peanut, corn and fish). Subsequently, a mixed mold spore suspension was added. The feed samples were incubated at 28°C, and the total mold, water activity (Aw), moisture, acid value, crude protein (CP), crude lipid (CL), crude ash (CA) and nitrogen‐free extract (NFE) levels were determined at 15, 30, 45 and 60 days. The results showed no significant variations in the feed moisture, CP, CL, CA and NEF contents. However, the acid value gradually increased in the feed samples with an extended incubation time and increasing initial moisture. The feed moisture content was a critical factor controlling feed mildew, and high levels of oil supplementation caused an elevated Aw. Additionally, peanut oil promoted mold growth in feed. These results provide a reference for the production and scientific management of formulated feed.
A systematic review of the outcomes reported in trials of medication review in older patients: the need for a core outcome set
Authors: Beuscart Jean‐Baptiste , Pont Lisa G. , Thevelin Stefanie , Boland Benoit , Dalleur Olivia , Rutjes Anne W. S. , Westbrook Johanna I. , Spinewine Anne 
Published: November 2016

AimMedication review has been advocated as one of the measures to tackle the challenge of polypharmacy in older patients, yet there is no consensus on how best to evaluate its efficacy. This study aimed to assess outcome reporting in trials of medication review in older patients.MethodsRandomized controlled trials (RCTs), prospective studies and RCT protocols involving medication review performed in patients aged 65 years or older in any setting of care were identified from: (1) a recent systematic review; (2) RCT registries of ongoing studies; (3) the Cochrane library. The type, definition, and frequency of all outcomes reported were extracted independently by two researchers.ResultsForty‐seven RCTs or prospective published studies and 32 RCT protocols were identified. A total of 327 distinct outcomes were identified in the 47 published studies. Only one fifth (21%) of the studies evaluated the impact of medication reviews on adverse events such as drug reactions or drug‐related hospital admissions. Most of the outcomes were related to medication use (n = 114, 35%) and healthcare use (n = 74, 23%). Very few outcomes were patient‐related (n = 24, 7%). A total of 248 distinct outcomes were identified in the 32 RCT protocols. Overall, the number of outcomes and the number and type of health domains covered by the outcomes varied largely.ConclusionOutcome reporting from RCTs concerning medication review in older patients is heterogeneous. This review highlights the need for a standardized core outcome set for medication review in older patients, to improve outcome reporting and evidence synthesis.
Characterization of adverse drug reactions causing admission to an intensive care unit
Authors: Rojas‐Velandia Camilo , Ruiz‐Garzón Jair , Moscoso‐Alcina Juan‐Carlos , Vallejos‐Narvaéz Álvaro , Castro‐Canoa Jenny , Bustos‐Martínez Yuri , Flórez‐Cutiva Max , Contreras‐Muñoz Mabel , Gómez‐Gil Jully‐Carolina , Calderón‐Ospina Carlos‐Alberto 
Published: December 2016

AimsThis study aimed to determine the occurrence of adverse drug reactions (ADRs) that caused admission to the intensive care unit (ICU) of a university hospital.MethodsClinical records were reviewed for patients meeting the inclusion criteria who were admitted to the ICU between September and December 2012. Suspected cases of ADRs were documented. Nine researchers later evaluated causality using the Naranjo Algorithm, preventability using the Schumock and Thornton criteria, and clinical classification based on the dose–time–susceptibility system.ResultsIn total, 96 patients presented 108 cases of ADR (13.8%, 95% confidence interval 11.2–16.4%) as the cause of admission. The most frequent ADRs were bradyarrhythmias and upper gastrointestinal bleeding (12%). Therapeutic failure accounted for 20%. The most commonly associated medications were acetylsalicylic acid (16%) and losartan (10%). Forty‐six cases were categorized as possible, and only one as definite. According to the dose–time–susceptibility classification, in 82% of the cases, the dosage was collateral (within the therapeutic range), and 90% were independent of time; the factors most associated with susceptibility to ADRs were comorbidities (42%) and age (49%). Forty‐four percent of the ADRs were considered possibly preventable.ConclusionsADRs contribute significantly to ICU admissions, and a significant number of ADRs are preventable. National studies are needed to assess their incidence and to establish classification standards to reduce their clinical impact.
The use of anthracyclines in the treatment of endemic Burkitt lymphoma
Authors: Molyneux Elizabeth , Schwalbe Ed , Chagaluka George , Banda Kondwani , Israels Trijn , Depani Sarita , Mittermayer‐Vassallo Kirstin , Windebank Kevin , Mvula Jessie , Njiram'madzi Jenala , O'Brien Stephen , Carey Peter , Bailey Simon 
Published: November 2016

SummaryBurkitt lymphoma is the most common malignancy in children in Malawi, the world's poorest country, where there is a long history of treating this disease using a 28‐day cyclophosphamide‐based protocol. Stage III/IV disease has had poor outcomes. In an attempt to improve the outcome for higher stage disease, anthracyclines were added to the existing protocol. The disease‐free (DFS) and overall survival (OS) of 58 children with cytologically confirmed Burkitt lymphoma admitted during 2012–2014 and treated using this protocol were calculated. Six (10%) children had stage I disease, ten (17%) stage II and 42 stage III or IV (73%). Overall 12‐month DFS (OS) was 68·5% (72·9%); for stage I disease 100% (100%), stage II 56·2% (60%), stage III/IV 66·3% (72·2%). The DFS was significantly improved from the previous protocol (P = 8 × 10−4). The addition of doxorubicin to stage III and IV disease resulted in a markedly improved DFS. Anthracyclines are deliverable in resource‐poor settings and possibly improve the survival of children with Burkitt lymphoma.
DEFINING RELEVANT MARKETS FOR PHARMACEUTICALS
Authors: Mihaescu Oana , Rudholm Niklas 
Published: November 2016

ABSTRACTTo identify the relevant product markets for Swedish pharmaceuticals, a spatial econometrics approach is employed. First, we calculate Moran's Is for different market definitions and then we use a spatial Durbin model to determine the effect of price changes on quantity sold of own and competing products. As expected, the results show that competition is strongest between close substitutes; however, the relevant product markets for Swedish pharmaceuticals extend beyond close substitutes down to products included in the same class on the four‐digit level of the Anatomic Therapeutic Chemical system as defined by the World Health Organization. The spatial regression model further indicates that increases in the price of a product significantly lower quantity sold of that product and in the same time increase the quantity sold of competing products. For close substitutes (products belonging to the same class on the seven‐digit level of the Anatomic Therapeutic Chemical system), as well as for products that, without being close substitutes, belong to the same therapeutic/pharmacological/chemical subgroup (the same class on the five‐digit level of the Anatomic Therapeutic Chemical system), increased competition is also visible after 1 July 2009 when the latest policy changes with regards to pharmaceuticals have been implemented in Sweden.
OSLsignal resetting in young deposits determined with a pulsed photon‐stimulated luminescence (PPSL) unit
Authors: Muñoz‐Salinas Esperanza , Castillo Miguel , Arce José Luis 
Published: December 2016

Optical Stimulated Luminescence (OSL) is a technique that can be used for dating geological materials deposited within the last half‐million years, including sediments transported by air, water or gravity, as well as rocks heated at high temperatures. Recently, several studies have shown thatOSLcan also provide information on sediment transport. The pulsed photon‐stimulated luminescence (PPSL) unit (also known as a portableOSLreader) developed by the Scottish Universities Environmental Research Centre is an instrument designed to read luminescence signals from bulk (untreated) sediment samples comprising poly‐mineral and poly‐grain fractions. In this contribution, we evaluate the potential of thePPSLunit to assess the degree ofOSLsignal resetting in 27 young deposits (<2 ka) transported by different geomorphic agents in volcanic, coastal and fluvial depositional settings located in Mexico. Our results are in agreement with previous findings that used the RisøTL/OSLreader, confirming that sediments transported by debrisflows contain the highest inherited luminesce signals. Infrared stimulation (IRSL) values in volcanic ash, lavas, and sand beach and dune deposits exhibit low scatter. However, with blue stimulation (BLSL) these samples reveal a large degree of scattering, attributed to charge transfer in the case of the coastal deposits and to the low sensitivity of quartz in the case of volcanic material. The luminescence signals of fluvial sediments exhibit a highly scattered distribution in bothIRSLandBLSL. We conclude that the use of aPPSLunit is a simple approach to assess the degree ofOSLsignal resetting in deposits sourced from different geological environments. This research contributes to previous studies that have investigated new applications of thePPSLunit to assist inOSLdating of geological materials.
Critical roles of conventional dendritic cells in promoting T cell-dependent hepatitis through regulating natural killer T cells
Authors: Wang J , Cao X , Zhao J , Zhao H , Wei J , Li Q , Qi X , Yang Z , Wang L , Zhang H , Bai L , Wu Z , Zhao L , Hong Z , Yin Z 
Published: November 2016

SummaryDendritic cells (DCs) play critical roles in initiating and regulating innate immunity as well as adaptive immune responses. However, the role of conventional dendritic cells (cDCs) in concanavalin A (ConA)-induced fulminant hepatitis is unknown. In this study, we demonstrated that depletion of cDCs using either CD11c-diphtheria toxin receptor transgenic mice (DTR Tg) mice or anti-CD11c antibody reduced the severity of liver injury significantly, indicating a detrimental role of cDCs in ConA-induced hepatitis. We elucidated further the pathological role of cDCs as being the critical source of interleukin (IL)-12, which induced the secretion of interferon (IFN)-γ by natural killer (NK) T cells. Reconstitution of cDCs-depleted mice with IL-12 restored ConA-induced hepatitis significantly. Furthermore, we determined that NK T cells were the target of DC-derived IL-12, and NK T cells contributed to liver inflammation and injury through production of IFN-γ. In summary, our study demonstrated a novel function of cDCs in mediating ConA-induced hepatitis through regulating IFN-γ secretion of NK T cells in an IL-12-dependent fashion. Targeting cDCs might provide potentially therapeutic applications in treating autoimmune related liver diseases.
Sorafenib and azacitidine as salvage therapy for relapse of FLT3‐ITD mutated AML after allo‐SCT
Authors: Rautenberg Christina , Nachtkamp Kathrin , Dienst Ariane , Schmidt Pia Verena , Heyn Claudia , Kondakci Mustafa , Germing Ulrich , Haas Rainer , Kobbe Guido , Schroeder Thomas 
Published: November 2016

AbstractObjectivePatients with acute myeloid leukemia (AML) carrying FLT3‐ITD mutations (FLT3‐ITD+) who relapse after allogeneic transplantation (allo‐SCT) have a very dismal prognosis with the currently available treatment options.MethodsWe treated eight patients with FLT3‐ITD+ AML who had relapsed in median 91 d (range, 28–249) following allo‐SCT with a combination of the multikinase inhibitor sorafenib and the DNA methyltransferase inhibitor azacitidine (Aza).ResultsPatients received a median of five cycles of Aza (range, 2–9) and sorafenib with a median daily dosage of 750 mg (range 400–800) for 129 d (range, 61–221). Six of eight patients received donor lymphocyte infusions (DLI) with a median number of two DLI per patient (range, 1–4). Following this treatment, four patients (50%) achieved a complete remission and three of them a complete molecular remission. Median duration of CR was 182 d (range, 158–406), and two patients remain in ongoing remission for 406 and 168 d. Median overall survival was 322 d (range, 108–574 d) with three patients being currently alive.ConclusionTaken together, the combination of sorafenib, Aza, and DLI shows promising efficacy and deserves further evaluation in larger patient groups.
Salvage therapy in first relapse: a retrospective study in a large patient population with multiple myeloma
Authors: Offidani Massimo , Corvatta Laura , Bringhen Sara , Gentili Silvia , Troia Rossella , Maracci Laura , Larocca Alessandra , Gay Francesca , Leoni Pietro , Boccadoro Mario 
Published: November 2016

AbstractObjectiveThere is no strong evidence to guide therapeutic approach to multiple myeloma (MM) patients who experience first relapse. The treatment choice can be difficult since currently all patients are exposed to novel agents as thalidomide, bortezomib and lenalidomide.MethodsIn this retrospective analysis, we evaluated the best therapeutic sequence, the role of retreatment, and the most beneficial cutoff of first remission in order to choose retreatment, analyzing 476 patients relapsed after first‐line therapy.ResultsBortezomib‐based regimens upfront followed by lenalidomide‐based regimens at first relapse resulted in significantly better second progression‐free survival (2ndPFS), PFS2, and overall survival (OS) compared to the opposite sequence. Changing therapy resulted in significantly better 2ndPFS in the whole population, whereas PFS2 was significantly longer only in patients who underwent maintenance therapy. Moreover, until PFS1 was shorter than 27 months, changing therapy at first relapse significantly extended 2ndPFS and PFS2 compared to retreatment, whereas similar outcomes were observed between the two strategies, when PFS1 was longer than 27 months.ConclusionLacking randomized trials, our study could help to choose the most appropriate therapy algorithm in patients with MM.
Spectral summation and facilitation in on‐ and off‐responses for optimized representation of communication calls in mouse inferior colliculus
Authors: Akimov Alexander G. , Egorova Marina A. , Ehret Günter 
Published: November 2016

AbstractSelectivity for processing of species‐specific vocalizations and communication sounds has often been associated with the auditory cortex. The midbrain inferior colliculus, however, is the first center in the auditory pathways of mammals integrating acoustic information processed in separate nuclei and channels in the brainstem and, therefore, could significantly contribute to enhance the perception of species’ communication sounds. Here, we used natural wriggling calls of mouse pups, which communicate need for maternal care to adult females, and further 15 synthesized sounds to test the hypothesis that neurons in the central nucleus of the inferior colliculus of adult females optimize their response rates for reproduction of the three main harmonics (formants) of wriggling calls. The results confirmed the hypothesis showing that average response rates, as recorded extracellularly from single units, were highest and spectral facilitation most effective for both onset and offset responses to the call and call models with three resolved frequencies according to critical bands in perception. In addition, the general on‐ and/or off‐response enhancement in almost half the investigated 122 neurons favors not only perception of single calls but also of vocalization rhythm. In summary, our study provides strong evidence that critical‐band resolved frequency components within a communication sound increase the probability of its perception by boosting the signal‐to‐noise ratio of neural response rates within the inferior colliculus for at least 20% (our criterion for facilitation). These mechanisms, including enhancement of rhythm coding, are generally favorable to processing of other animal and human vocalizations, including formants of speech sounds.
Toxic effects of human and rodent variants of alpha‐synuclein in vivo
Authors: Landeck Natalie , Buck Kerstin , Kirik Deniz 
Published: November 2016

AbstractIn Parkinson's disease, abnormal alpha‐synuclein (asyn) accumulation leads to the formation of soluble oligomeric species thought to be toxic to cells as well as intraneuronal inclusions. To date, the precise mechanisms leading to aggregation of asyn in the brain is not well‐understood. Previous studies in yeast, drosophila, and transgenic mice suggested that a non‐A beta component depleted version of human asyn [h‐asyn(D70‐83)] or human beta‐synuclein (h‐bsyn), naturally lacking this centrally located hydrophobic region, are less prone to form aggregates in vitro and are expected to be less toxic compared to h‐asyn in vivo, although not all experimental studies unequivocally support the latter view. To address this outstanding issue, we directly compared the neurotoxicity of human asyn against that of h‐asyn(D70‐83), h‐bsyn as well as rat asyn using an adeno‐associated viral vector to express these proteins in a dose‐response study where the vector load was varied over two orders of magnitude. By quantifying the neurodegeneration of rat substantia nigra dopamine neurons here we show that h‐asyn, h‐bsyn, and h‐asyn(D70‐83) display comparable neurotoxicity across the vector doses tested. On the other hand, rat asyn and GFP control vectors displayed a different profile, where no detectable neurodegeneration was seen except at the highest vector titer. Thus, the two main conclusions of our study are that (i) deletion of the central hydrophobic region in h‐asyn is not sufficient to alter its neurotoxic properties and (ii) expression of the widely used GFP control protein can cause measurable neurodegeneration at high titers.
A Comedy We Believe In: A Further Look at Sartre's Theory of Emotions
Authors: Hartmann Martin 
Published: December 2016

AbstractThis paper discusses recent interpretations of Jean‐Paul Sartre's early theory of emotions, in particular his Sketch for a Theory of the Emotions. Despite the great interest that Sartre's approach has generated, most interpretations assume that his approach fails because it appears to be focussed on ‘malformed’, ‘irrational’ or ‘distorted’ emotions. I argue that these criticisms adopt a rationalistic or epistemically biassed perspective on emotions that is wrongly applied to Sartre's text. In my defence of Sartre I show that the directional fit of emotions is not towards an evaluatively loaded world which is independently given and, at best, represented by emotions, but towards a world shaped through the impact of emotions themselves. Sartre's idea of emotions ‘magically transforming’ reality for the subject so that the latter is better able to cope with problematic aspects of practically relevant situations encapsulates the world‐shaping capacities of emotions, which are thus not reserved for a restricted class of emotions. Recognition of the transformative powers of emotions will also direct attention away from their seemingly representative elements to their normative and practical aspects and offer a new basis for delineating the criteria for judging them. The plausibility of this position is discussed with reference to some of Sartre's examples, such as fear, sadness and horror, but also with reference to Joan Didion's account of grief in The Year of Magical Thinking.
An advanced mouse model for human skin wound healing
Authors: Wen Jie , Li Xiangyong , Leng Xue , Xu Xin , Wu Xunwei 
Published: November 2016

AbstractHere, we report a model for studying wound repair based on skin regenerated from human tissue culture‐expanded cells. The reconstituted skin (hRSK) responds to injury similar to that of intact human skin, and its constituent cells contribute to the healing process. As we have demonstrated that hRSK composed of GFP‐labelled cells also heals “normally,” we believe this model will be useful in analysing the wound repair process using genetically modified human cells.
Crack propagation models: numerical and experimental results on Ti–6Al–4V notched specimens
Authors: Baragetti S , Villa F 
Published: December 2016

AbstractTo investigate on corrosion fatigue, a reliable crack propagation rate model has to be adopted, along with a suitable fracture mechanics model, to decouple the mechanical contribution from the environmental effects. In the present work, a numerical algorithm is proposed to characterize the mechanical behaviour of notched Ti–6Al–4V specimens for fatigue and corrosion fatigue tests. The method is based on theoretical crack propagation rate models, jointly with stress intensity factor range obtained from linear finite element models. Results are compared with experimental data for axial fatigue (R = 0.1) and theoretical models for fatigue crack growth, such as Paris, Walker and Kato.