bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID‐19: legal implications for critical care
Authors: Coghlan N. , Archard D. , Sipanoun P. , Hayes T. , Baharlo B. 
Published: May 2020

SummaryThe COVID‐19 pandemic has caused an unprecedented challenge for the provision of critical care. Anticipating an unsustainable burden on the health service, the UK Government introduced numerous legislative measures culminating in the Coronavirus Act, which interfere with existing legislation and rights. However, the existing standards and legal frameworks relevant to critical care clinicians are not extinguished, but anticipated to adapt to a new context. This new context influences the standard of care that can be reasonably provided and yields many human rights considerations, for example, in the use of restraints, or the restrictions placed on patients and visitors under the Infection Prevention and Control guidance. The changing landscape has also highlighted previously unrecognised legal dilemmas. The perceived difficulties in the provision of personal protective equipment for employees pose a legal risk for Trusts and a regulatory risk for clinicians. The spectre of rationing critical care poses a number of legal issues. Notably, the flux between clinical decisions based on best interests towards decisions explicitly based on resource considerations should be underpinned by an authoritative public policy decision to preserve legitimacy and lawfulness. Such a policy should be medically coherent, legally robust and ethically justified. The current crisis poses numerous challenges for clinicians aspiring to remain faithful to medicolegal and human rights principles developed over many decades, especially when such principles could easily be dismissed. However, it is exactly at such times that these principles are needed the most and clinicians play a disproportionate role in safeguarding them for the most vulnerable.
Testicular ultrasound score: A new proposal for a scoring system to predict testicular function
Authors: Pozza Carlotta , Kanakis George , Carlomagno Francesco , Lemma Andrea , Pofi Riccardo , Tenuta Marta , Minnetti Marianna , Tarsitano Maria G. , Sesti Franz , Paoli Donatella , Anzuini Antonella , Lenzi Andrea , Isidori Andrea M. , Gianfrilli Daniele 
Published: May 2020

AbstractBackgroundTesticular ultrasound (US) is routinely employed in the evaluation of reproductive and sexual function. However, its use for characteristics other than testicular volume is hampered by a lack of information on the prognostic value of its findings, which to date have only been incorporated in a score proposed by Lenz et al in 1993.ObjectivesWe sought to explore whether testicular US examination can predict the quality of spermatogenesis and provide information on testicular endocrine function.Materials and methodsWe retrospectively reviewed 6210 testicular US examinations, finally selecting examinations from 2230 unique men. The following variables were considered: bitesticular volume and testicular asymmetry, parenchymal echotexture, echogenicity and presence of microlithiasis, solid lesions and varicocoele. Concurrent fasting hormonal data were available for 1160 men, while 979 had a semen sample available from the same day as the US examination.ResultsWe derived a new US score, termed TU score, that can predict both impaired spermatogenesis (AUC 0.73, sensitivity 72%, specificity 61%, P < .001) and hypogonadism (AUC 0.71, sensitivity 71%, specificity 53%, P < .001) more accurately than the Lenz's score. In a multivariate analysis, a reduced sperm composite index (defined as total spermatozoa × total motility × normal forms) was independently predicted by bitesticular volume and by inhomogeneous echotexture, while hypogonadism was independently predicted also by reduced echogenicity and presence of microlithiasis.Discussion and conclusionsWe describe the testicular US characteristics that are independently associated with impaired spermatogenesis and hypogonadism and propose the TU score as a simple screening method for use in subjects referred for testicular US.
Prevention of nosocomial Acinetobacter baumannii infections with a conserved immunogenic fimbrial protein
Authors: Mahmoudi Zeinab , Rasooli Iraj , Jahangiri Abolfazl , Darvish Alipour Astaneh Shakiba 
Published: May 2020

Acinetobacter baumannii, one of the most life‐threatening nosocomial drug‐resistant pathogens, imposes high morbidity and mortality rates, thus highlighting immunization‐based treatments or prevention measures. The selection of appropriate antigens can elicit protective immunity. The gene encoding a fimbrial protein introduced via reverse vaccinology was cloned, expressed and evaluated for immunogenicity in a murine model. Mice immunized with the recombinant protein were challenged with A. baumannii ATCC 19606. Adherence to A549 cell line of specific anti‐sera treated A. baumannii was also assessed. Passive immunity was evaluated in a murine pneumonia model. Indirect ELISA showed a high specific antibody titre. Adherence of A. baumannii to A549 cell line decreased by 40% after incubation with 1:250 dilution of specific anti‐sera. All the actively immunized mice survived. Bacterial load in the spleen and liver of the immunized mice was 3‐fold lower than those of the control. The number of bacteria in the lungs of passively immunized mice was about 6‐fold lower than the control mice. The fimbrial protein could be considered as a promising protective immunogen against A. baumannii.
Clonal relationship in multisited mucosa‐associated lymphoid tissue lymphomas: a single‐centre experience
Authors: Condom Maria , Climent Fina , Fernández Davinia , Colomer Dolors , Lopez‐Guerra Mónica , Varela Mar , Carro Itziar , Maluquer Clara , Mercadal Santiago , Oliveira Ana Carla , Pané Maria , Matias‐Guiu Xavier , González‐Barca Eva , Sureda Anna , Domingo‐Domenech Eva 
Published: May 2020

SummaryClonal heterogeneity in multisited or recurrent lymphoid neoplasms is a phenomenon that has been increasingly studied in recent years. However, in mucosa‐associated lymphoid tissue (MALT) lymphomas it remains largely unexplored. Patients diagnosed at our institution with multisited MALT lymphoma, from January 2009 to October 2018, were studied. Molecular studies were performed for the detection of clonally rearranged immunoglobulin by polymerase chain reaction.In all, 91 patients were included. Of those, 28 had a multisited disease and in 16 clonality studies were done. In eight cases, multifocal involvement was synchronous and in eight metachronous. Patients with non‐gastric gastrointestinal tract involvement tended to disseminate within the same tract, without observing other specific dissemination patterns. Four cases (25%) had clonal heterogeneity at the different organs involved. All patients with late relapses (two patients) had different clones. The majority of patients with multisited MALT lymphomas presented with the same clone in the different involved organs, identifying a different clone in those with late relapses. These patients could represent de novo neoplasms, rather than a relapse. This could mean that some individuals might have a genetic predisposition to develop this type of lymphoma and it could also have clinical implications regarding therapeutic decisions.
AMP‐activated protein kinase (AMPK) regulates autophagy, inflammation and immunity and contributes to osteoclast differentiation and functionabs
Authors: Tong Xishuai , Ganta Roman R. , Liu Zongping 
Published: May 2020

AbstractOsteoclasts are multinucleated giant cells, responsible for bone resorption. Osteoclast differentiation and function requires a series of cytokines to remove the old bone, which coordinates with the induction of bone remodelling by osteoblast‐mediated bone formation. Studies have demonstrated that AMP‐activated protein kinase (AMPK) play a negative regulatory role in osteoclast differentiation and function. Research involving AMPK, a nutrient and energy sensor, has primarily focused on osteoclast differentiation and function; thus, its role in autophagy, inflammation and immunity remains poorly understood. Autophagy is a conservative homoeostatic mechanism of eukaryotic cells, and response to osteoclast differentiation and function; however, how it interacts with inflammation remains unclear. Additionally, based on the regulatory function of different AMPK subunits for osteoclast differentiation and function, its activation is regulated by upstream factors to perform bone metabolism. This review summarises the critical role of AMPK‐mediated autophagy, inflammation and immunity by upstream and downstream signalling during receptor activator of nuclear factor kappa‐B ligand‐induced osteoclast differentiation and function. This pathway may provide therapeutic targets for bone‐related diseases, as well as function as a biomarker for bone homoeostasis.
Could FiLaC™ be effective in the treatment of anal fistulas? A systematic review of observational studies and proportional meta‐analysis
Authors: Frountzas M. , Stergios K. , Nikolaou C. , Bellos I. , Schizas D. , Linardoutsos D. , Kontzoglou K. , Vaos G. , Williams A. B. , Toutouzas K. 
Published: May 2020

AbstractAimFistula Laser Closure (FiLaC™) is a novel sphincter‐preserving technique that is based on new technologies and shows promising results in repairing anal fistulas whilst maintaining external sphincter function. The aim of the present meta‐analysis is to present the efficacy and the safety of FiLaC™ in the management of anal fistula disease.MethodThe present proportional meta‐analysis was designed using the PRISMA and AMSTAR guidelines. We searched MEDLINE, Scopus, clinicaltrials.gov, Embase, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases from inception until November 2019.ResultsOverall, eight studies were included that recruited 476 patients. The pooled success rate of the technique was 63% (95% CI 50%–75%). The pooled complication rate was 8% (95% CI 1%–18%). Sixty‐six per cent of patients had a transsphincteric fistula and 60% had undergone a previous surgical intervention, mainly the insertion of a seton (54%). The majority had a cryptoglandular fistula. Operation time and follow‐up period were described for each study.ConclusionFiLaC™ seems to be an efficient therapeutic option for perianal fistula disease with an adequate level of safety that preserves quality of life. Nevertheless, randomized trials need to be designed to compare FiLaC™ with other procedures for the management of anal fistulas such as ligation of intersphincteric fistula tract, anal advancement flaps, fibrin glue, collagen paste, autologous adipose tissue, fistula plug and video‐assisted anal fistula treatment.
Comparative clinical study on microwave ablation combined with gemcitabine and cisplatin or combined with pemetrexed and cisplatin in treatment of advanced NSCLC
Authors: Zhang YingQing , Feng Yan , Wu YongLei , Zhou YingXin , Wang LinLan 
Published: May 2020

AbstractObjectiveSolving the limitations of single chemotherapy in the treatment of non‐small cell lung cancer (NSCLC).MethodsAbout 100 patients with NSCLC treated in First Hospital of Jiaxing, Zhejiang from June 2016 to June 2018 were selected and randomly divided into MPC group and MGC group, with 50 cases in each group. The patients in MPC group were treated with microwave ablation (MWA) combined with PC while patients in MGC group were given MWA combined with gemcitabine plus cisplatin (GC). The therapeutic effects of the two groups as well as the complications and adverse reactions (ADRs) were observed and recorded.ResultsThere was no significant difference in disease response rate (MPC group 33.3% vs MGC group 32.0%), disease control rate (MPC group 86.4% vs MGC group 78.0%) and overall survival (1‐, 2‐ and 3‐year survival, MPC group 65%, 59%, 32.7% vs MGC group 58%, 46%, 30%) between the two groups. In addition, the ADR myelosuppression was slighter in MPC group. There were 12 cases (23%) developed myelosuppression in the MPC group and 20 cases (42%) in MGC group, with a significant difference between the two groups (P < 0.05). The treatment was interrupted for 0 case (0%) in MPC group because of myelosuppression while 4 cases (8.3%) in MGC group.ConclusionThe two therapeutic regimens have similar efficacy in treatment of advanced NSCLC, but MPC causes slighter myelosuppression and can be the first‐line therapy for advanced NSCLC.
The Protected Area Paradox and refugee species: The giant panda and baselines shifted towards conserving species in marginal habitats
Authors: Kerley Graham I. H. , te Beest Mariska , Cromsigt Joris P. G. M. , Pauly Daniel , Shultz Susanne 
Published: May 2020

AbstractParadoxically, despite the growth in protected areas globally, many species remain threatened and continue to decline. Attempts to conserve species in suboptimal habitats (i.e., as refugee species) may in part explain this Protected Area Paradox. Refugee species yield poor conservation outcomes as they suffer lower densities and fitness. We suggest that the giant panda may serve as an iconic example, reflecting the contraction and shift in the giant panda's range, diet and habitat use over the past 3,500 years, coinciding with increasing human pressure, and now maintained by conservation efforts, this due to shifted baselines. The global bias of protected area location to less productive habitats indicates that this problem may be widespread. We urgently need efforts to identify victims of refugee species status to allow improved conservation management globally, reducing the paradoxical outcomes of our conservation efforts.
Cholesterol lowering with EVOLocumab to prevent cardiac allograft Vasculopathy in De‐novo heart transplant recipients: Design of the randomized controlled EVOLVD trial
Authors: Broch Kaspar , Gude Einar , Karason Kristjan , Dellgren Göran , Rådegran Göran , Gjesdal Grunde , Gustafsson Finn , Eiskjær Hans , Lommi Jyri , Pentikäinen Markku , Lemström Karl B. , Andreassen Arne K. , Gullestad Lars 
Published: May 2020

AbstractBackgroundCardiac allograft vasculopathy (CAV) is characterized by diffuse thickening of the arterial intima. Statins reduce the incidence of CAV, but despite the use of statins, CAV remains one of the leading causes of long‐term death after heart transplant. Inhibitors of proprotein convertase subtilisin‐kexin type 9 (PCSK9) substantially reduce cholesterol levels but have not been tested in heart transplant recipients.MethodsThe Cholesterol lowering with EVOLocumab to prevent cardiac allograft Vasculopathy in De‐novo heart transplant recipients (EVOLVD) trial (ClinicalTrials.gov Identifier: NCT03734211) is a randomized, double‐blind trial designed to test the effect of the PCSK9 inhibitor evolocumab on coronary intima thickness in heart transplant recipients. Adults who have received a cardiac transplant within the past 4‐8 weeks are eligible. Exclusion criteria include an estimated glomerular filtration rate < 20 mL/min/1.73 m2, renal replacement therapy, or contraindications to coronary angiography with intravascular ultrasound. 130 patients will be randomized (1:1) to 12‐month treatment with evolocumab or matching placebo. The primary endpoint is the coronary artery intima thickness as measured by intravascular ultrasound.ConclusionThe EVOLVD trial is a randomized clinical trial designed to show whether treatment with the PCSK9 inhibitor evolocumab can ameliorate CAV over the first year after heart transplant.
What solid organ transplant healthcare providers should know about renin‐angiotensin‐aldosterone system inhibitors and COVID‐19
Authors: Wong Sunnie Y. , Brubaker Aleah L. , Wang Aileen X. , Taiwo Adetokunbo A. , Melcher Marc L. 
Published: May 2020

AbstractThe data on the outcomes of solid organ transplant recipients who have contracted coronavirus disease 2019 (COVID‐19) are still emerging. Kidney transplant recipients are commonly prescribed renin‐angiotensin‐aldosterone system (AAS) inhibitors given the prevalence of hypertension, diabetes, and cardiovascular disease. As the angiotensin‐converting enzyme 2 (ACE2) facilitates the entry of coronaviruses into target cells, there have been hypotheses that preexisting use of renin‐angiotensin‐aldosterone system (RAAS) inhibitors may increase the risk of developing severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. Given the common use of RAAS inhibitors among solid organ transplant recipients, we sought to review the RAAS cascade, the mechanism of SARS‐CoV‐2 entry, and pertinent data related to the effect of RAAS inhibitors on ACE2 to guide management of solid organ transplant recipients during the COVID‐19 pandemic. At present, there is no clear evidence to support the discontinuation of RAAS inhibitors in solid organ transplant recipients during the COVID‐19 pandemic.
Technical Note: Mean Lead‐Time as a Real‐Time Key Performance Indicator
Authors: Niemi Tapio , Gallay Olivier , Hameri Ari‐Pekka 
Published: May 2020

ABSTRACTMeasuring the average time that a process takes from start to finish, using observation time windows (OTWs) of different length, is required for numerous operational monitoring and control processes. We refer to this measure as the Mean Lead‐Time (MLT). This study is based on the fact that computing the MLT in an operational context is often misleading for two reasons: (1) the computed value directly depends on the length of the used OTW; and (2) some jobs are usually still running at the end of the OTW, and thus their final lead‐time is not known yet. To overcome these issues, we revisit the definition of the MLT as well as the way to measure it. We develop a method to take these two aspects into account and apply this method to four real‐life cases in different business contexts. Using these practical cases, we show that the proposed methodology makes it possible to compute a standardized measure of the MLT, allowing for a meaningful comparison when different OTW lengths are considered. These new results open the door for an efficient use of the MLT as a commensurable performance indicator and allow near real‐time monitoring and comparison across different process steps, departments, and factories.
The moment‐to‐moment pitch dynamics of child‐directed speech shape toddlers’ attention and learning
Authors: Nencheva Mira L. , Piazza Elise A. , Lew‐Williams Casey 
Published: May 2020

AbstractYoung children have an overall preference for child‐directed speech (CDS) over adult‐directed speech (ADS), and its structural features are thought to facilitate language learning. Many studies have supported these findings, but less is known about processing of CDS at short, sub‐second timescales. How do the moment‐to‐moment dynamics of CDS influence young children's attention and learning? In Study 1, we used hierarchical clustering to characterize patterns of pitch variability in a natural CDS corpus, which uncovered four main word‐level contour shapes: ‘fall’, ‘rise’, ‘hill’, and ‘valley’. In Study 2, we adapted a measure from adult attention research—pupil size synchrony—to quantify real‐time attention to speech across participants, and found that toddlers showed higher synchrony to the dynamics of CDS than to ADS. Importantly, there were consistent differences in toddlers’ attention when listening to the four word‐level contour types. In Study 3, we found that pupil size synchrony during exposure to novel words predicted toddlers’ learning at test. This suggests that the dynamics of pitch in CDS not only shape toddlers’ attention but guide their learning of new words. By revealing a physiological response to the real‐time dynamics of CDS, this investigation yields a new sub‐second framework for understanding young children's engagement with one of the most important signals in their environment.
Martin Luther and Philip Melanchthon on the care and feeding of [future] Pastors
Authors: Wengert Timothy J. 
Published: May 2020

AbstractThis article argues that humanist training was all‐encompassing, not just for Philip Melanchthon but also for Martin Luther. By reexamining the relationship between the two reformers in this area, the article shows how their substantial, overarching agreements, especially in matters of pedagogy, led to a single‐minded reform of Wittenberg's curriculum. Finally, it argues that their revolutionary approach to seminary training also addresses its collapse in our own day.
Oral antidiabetes agents for the management of inpatient hyperglycaemia: so far, yet so close
Authors: Koufakis T. , Mustafa O. G. , Zebekakis P. , Kotsa K. 
Published: May 2020

AbstractBackgroundHyperglycaemia is an ongoing challenge in hospital settings and is associated with poor outcomes. Current recommendations for the management of inpatient hyperglycaemia suggest insulin as the main glucose‐lowering treatment choice and limit the administration of oral antidiabetes agents to a small proportion of cases because of safety concerns.AimTo present and critically appraise the available evidence on the use of oral antidiabetes agents in the hospital setting and the risk–benefit balance of such an approach in the era of cardiovascular outcomes trials.MethodsPubMed, Embase and Google Scholar databases were searched to identify relevant published work. Available evidence on the efficacy and the safety profile of oral agents in the context of their use in hospitalized individuals are summarized and discussed in this narrative review.ResultsThere is no robust evidence to suggest the use of metformin, thiazolidinediones, sulfonylureas and sodium‐glucose co‐transporter‐2 inhibitors in the hospital setting, although some of their effects on acute outcomes deserve further evaluation in future studies. However, the use of dipeptidyl peptidase‐4 inhibitors in inpatients with type 2 diabetes is supported by a few, well‐designed, randomized controlled trials. These trials have demonstrated good safety and tolerability profiles, comparable to insulin glucose‐lowering efficacy, and a reduction in insulin dose when dipeptidyl peptidase‐4 inhibitors are co‐administered with insulin, in individuals with mild to moderate hyperglycaemia and a stable clinical condition.ConclusionThe administration of dipeptidyl peptidase‐4 inhibitors to specific groups of inpatients might be a safe and effective alternative to insulin.