bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of interventions aiming to reduce inappropriate drug prescribing: an overview of interventions
Authors: Kroon Daniëlle , Steutel Nina F , Vermeulen Hester , Tabbers Merit M , Benninga Marc A , Langendam Miranda W , van Dulmen Simone A 
Published: June 2021

Abstract

Objective
Inappropriate prescribing of drugs is associated with unnecessary harms for patients and healthcare costs. Interventions to reduce these prescriptions are widely studied, yet the effectiveness of different types of interventions remains unclear. Therefore, we provide an overview regarding the effectiveness of intervention types that aim to reduce inappropriate drug prescriptions, unrestricted by target drugs, population or setting.

Methods
For this overview, systematic reviews (SRs) were used as the source for original studies. EMBASE and MEDLINE were searched from inception to August 2018. All SRs aiming to evaluate the effectiveness of interventions to reduce inappropriate prescribing of drugs were eligible for inclusion. The SRs and their original studies were screened for eligibility. Interventions of the original studies were categorized by type of intervention. The percentage of interventions showing a significant reduction of inappropriate prescribing were reported per intervention category.

Key findings
Thirty-two SRs were included, which provided 319 unique interventions. Overall, 61.4% of these interventions showed a significant reduction in inappropriate prescribing of drugs. Strategies that were most frequently effective in reducing inappropriate prescribing were multifaceted interventions (73.2%), followed by interventions containing additional diagnostic tests (antibiotics) (70.4%), computer interventions (69.2%), audit and feedback (66.7%), patient-mediated interventions (62.5%) and multidisciplinary (team) approach (57.1%). The least frequently effective intervention was an education for healthcare professionals (50.0%).

Conclusion
The majority of the interventions were effective in reducing inappropriate prescribing of drugs. Multifaceted interventions most frequently showed a significant reduction of inappropriate prescribing. Education for healthcare professionals is the most frequently included intervention in this overview, yet this category is least frequently effective.
Clostridioides difficile Infection in Children: The Role of Infection Prevention and Antimicrobial Stewardship
Authors: Savage Timothy J , Sandora Thomas J 
Published: June 2021

Abstract
There are 2 primary approaches to prevent Clostridioides difficile infection (CDI) in children: prevent transmission and acquisition of the organism and prevent the progression from colonization to disease. The most important interventions to reduce the risk of transmission include contact precautions, hand hygiene, and environmental disinfection. Glove use minimizes contamination of the hands by spores and is associated with reductions in CDI incidence. Hand hygiene with soap and water and disinfection with a sporicidal agent are recommended as the best approaches in hyperendemic settings. Because antibiotic exposure is the most important modifiable risk factor for CDI, antimicrobial stewardship focused on identified high-risk antibiotic classes (including clindamycin, fluoroquinolones, and third- and fourth-generation cephalosporins) is critical to preventing progression from colonization to infection. Despite clear evidence that antimicrobial stewardship programs (ASPs) are associated with reduced CDI rates in adults, data demonstrating the ASP impact on pediatric CDI are lacking.
A Normative Framework for the Reconciliation of EU Data Protection Law and Medical Research Ethics
Authors: Hallinan Dara 
Published: June 2021

Abstract
EU data protection law and medical research ethics overlap in scope and content in numerous instances in which personal data are processed in medical research. It is not always the case, however, that the conditions outlined by the two rule-sets precisely coincide. In the past few years, this lack of confluence has led to confusion as to how the two rule-sets should best relate to one another. This confusion has led to different approaches to the relationship being taken, on occasion leading to counter-intuitive conclusions. Unfortunately, there has hitherto been little effort to provide clarity to this confusion. In this regard, this article attempts to provide a general normative framework aimed at facilitating optimally cogent and just reconciliations of EU data protection law and medical research ethics.
Optimizing Visualization in Endoscopic Spine Surgery
Authors: Basil Gregory W , Kumar Vignessh , Wang Michael Y 
Published: June 2021

Abstract
Given the inherent limitations of spinal endoscopic surgery, proper lighting and visualization are of tremendous importance. These limitations include a small field of view, significant potential for disorientation, and small working cannulas. While modern endoscopic surgery has evolved in spite of these shortcomings, further progress in improving and enhancing visualization must be made to improve the safety and efficacy of endoscopic surgery. However, in order to understand potential avenues for improvement, a strong basis in the physical principles behind modern endoscopic surgery is first required. Having established these principles, novel techniques for enhanced visualization can be considered. Most compelling are technologies that leverage the concepts of light transformation, tissue manipulation, and image processing. These broad categories of enhanced visualization are well established in other surgical subspecialties and include techniques such as optical chromoendoscopy, fluorescence imaging, and 3-dimensional endoscopy. These techniques have clear applications to spinal endoscopy and represent important avenues for future research.
Regulation of antibody responses against self and foreign antigens by Tfr cells: implications for vaccine development
Authors: Basto Afonso P , Graca Luis 
Published: June 2021

Abstract
The production of antibodies can constitute a powerful protective mechanism against infection, but antibodies can also participate in autoimmunity and allergic responses. Recent advances in the understanding of the regulation of germinal centres (GC), the sites where B cells acquire the ability to produce high-affinity antibodies, offered new prospects for the modulation of antibody production in autoimmunity and vaccination. The process of B cell affinity maturation and isotype switching requires signals from T follicular helper (Tfh) cells. In addition, Foxp3+ T follicular regulatory (Tfr) cells represent the regulatory counterpart of Tfh in the GC reaction. Tfr cells were identified one decade ago and since then it has become clear their role in controlling the emergence of autoreactive B cell clones following infection and immunization. At the same time, Tfr cells are essential for fine-tuning important features of the humoral response directed to foreign antigens that are critical in vaccination. However, this regulation is complex and several aspects of Tfr cell biology are yet to be disclosed. Here, we review the current knowledge about the regulation of antibody responses against self and foreign antigens by Tfr cells and its implications for the future rational design of safer and more effective vaccines.
A roadmap of plant membrane transporters in arbuscular mycorrhizal and legume–rhizobium symbioses
Authors: Banasiak Joanna , Jamruszka Tomasz , Murray Jeremy D , Jasiński Michał 
Published: June 2021

AbstractMost land plants live in close contact with beneficial soil microbes: the majority of land plant species establish symbiosis with arbuscular mycorrhizal fungi, while most legumes, the third largest plant family, can form a symbiosis with nitrogen-fixing rhizobia. These microbes contribute to plant nutrition via endosymbiotic processes that require modulating the expression and function of plant transporter systems. The efficient contribution of these symbionts involves precisely controlled integration of transport, which is enabled by the adaptability and plasticity of their transporters. Advances in our understanding of these systems, driven by functional genomics research, are rapidly filling the gap in knowledge about plant membrane transport involved in these plant–microbe interactions. In this review, we synthesize recent findings associated with different stages of these symbioses, from the pre-symbiotic stage to nutrient exchange, and describe the role of host transport systems in both mycorrhizal and legume–rhizobia symbioses.
Investor Rewards to Climate Responsibility: Stock-Price Responses to the Opposite Shocks of the 2016 and 2020 U.S. Elections
Authors: Ramelli Stefano , Wagner Alexander F , Zeckhauser Richard J , Ziegler Alexandre 
Published: June 2021

Abstract
Donald Trump’s 2016 election and his nomination of climate skeptic Scott Pruitt to head the Environmental Protection Agency drastically downshifted expectations about U.S. policy toward climate change. Joseph Biden’s 2020 election shifted them dramatically upward. We study firms’ stock-price movements in reaction to these changes. As expected, the 2016 election boosted carbon-intensive firms. Surprisingly, firms with climate-responsible strategies also gained, especially those firms held by long-run investors. Such investors appear to have bet on a “boomerang” in climate policy. Harbingers of a boomerang appeared during Trump’s term. The 2020 election marked its arrival. (JEL G14, G38, G41)
Lipidomic analysis reveals disturbances in glycerophospholipid and sphingolipid metabolic pathways in benzene-exposed mice
Authors: Yu Linling , Sun Rongli , Xu Kai , Pu Yunqiu , Huang Jiawei , Liu Manman , Chen Minjian , Zhang Juan , Yin Lihong , Pu Yuepu 
Published: June 2021

Abstract
Benzene, a known occupational and environmental contaminant, has been recognized as the hematotoxin and human carcinogen. Lipids have a variety of important physiological functions and the abnormal lipid metabolism has been reported to be closely related to the occurrence and development of many diseases. In the present study, we aim to utilize LC–MS/MS lipidomic platform to identify novel biomarkers and provide scientific clues for mechanism study of benzene hematotoxicity. Results showed that a total of 294 differential metabolites were obtained from the comparison of benzene-treated group and control group. The glycerophospholipid pathway was altered involving the down-regulation of the levels of phosphatidylcholine and phosphatidylserine. In addition, phosphatidylethanolamine (PE) and 1-Acyl-sn-glycero-3-phosphocholine levels were increased in benzene-treated group. Based on the relationship between PE and autophagy, we then found that effective biomarker of autophagy, Beclin1 and LC3B, were increased remarkably. Furthermore, following benzene treatment, significant decreases in glucosylceramide (GlcCer) and phytosphingosine (PHS) levels in sphingolipid pathway were observed. Simultaneously, the levels of proliferation marker (PCNA and Ki67) and apoptosis regulator (Bax and Caspase-3) showed clear increases in benzene-exposed group. Based on our results, we speculate that disturbances in glycerophospholipid pathway play an important role in the process of benzene-induced hematopoietic toxicity by affecting autophagy, while sphingolipid pathway may also serve as a vital role in benzene-caused toxicity by regulating proliferation and apoptosis. Our study provides basic study information for the future biomarker and mechanism research underlying the development of benzene-induced blood toxicity.
Recombinant SARS-CoV-2 genomes circulated at low levels over the first year of the pandemic
Authors: VanInsberghe David , Neish Andrew S , Lowen Anice C , Koelle Katia 
Published: June 2021

Abstract
Viral recombination can generate novel genotypes with unique phenotypic characteristics, including transmissibility and virulence. Although the capacity for recombination among betacoronaviruses is well documented, recombination between strains of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has not been characterized in detail. Here, we present a lightweight approach for detecting genomes that are potentially recombinant. This approach relies on identifying the mutations that primarily determine SARS-CoV-2 clade structure and then screening genomes for ones that contain multiple mutational markers from distinct clades. Among the over 537,000 genomes queried that were deposited on GISAID.org prior to 16 February 2021, we detected 1,175 potential recombinant sequences. Using a highly conservative criteria to exclude sequences that may have originated through de novo mutation, we find that at least 30 per cent (n = 358) are likely of recombinant origin. An analysis of deep-sequencing data for these putative recombinants, where available, indicated that the majority are high quality. Additional phylogenetic analysis and the observed co-circulation of predicted parent clades in the geographic regions of exposure further support the feasibility of recombination in this subset of potential recombinants. An analysis of these genomes did not reveal evidence for recombination hotspots in the SARS-CoV-2 genome. While most of the putative recombinant sequences we detected were genetic singletons, a small number of genetically identical or highly similar recombinant sequences were identified in the same geographic region, indicative of locally circulating lineages. Recombinant genomes were also found to have originated from parental lineages with substitutions of concern, including D614G, N501Y, E484K, and L452R. Adjusting for an unequal probability of detecting recombinants derived from different parent clades and for geographic variation in clade abundance, we estimate that at most 0.2–2.5 per cent of circulating viruses in the USA and UK are recombinant. Our identification of a small number of putative recombinants within the first year of SARS-CoV-2 circulation underscores the need to sustain efforts to monitor the emergence of new genotypes generated through recombination.
Stimulation of the Hepatic Toll‐like Receptor Signaling Pathway after Induction of Equine Laminitis Using Gastrointestinal Models
Authors: Stokes Ashley Michelle , McGeachy Matthew , Carlisle Katherine , Keowen Michael L , Garza Frank 
Published: June 2021

The toll‐like receptor (TLR) signaling pathway is important in orchestrating innate immunity in response to many factors including circulating bacterial components. In cases of GI disruption, portal blood flow may lead to strong stimulation of the hepatic TLR signaling pathway with the subsequent systemic release of inflammatory mediators known to play a role in laminitis.Our objectives were to evaluate key mediators of the TLR signaling pathway in hepatic tissues after the use of two GI models of laminitis induction (black walnut extract (BWE) or carbohydrate overload (CHO) models). We examined TLR4, cluster of differentiation 14 (CD‐14), TLR2, phosphatidylinositol‐3‐kinase regulatory subunit 1 (PIK3R1), inhibitor of NF‐êB (INFKB), cyclooxygenase 2 (COX2), and interleukin 8 (IL‐8). Liver tissues (normal, BWE‐induced, CHO‐induced, and naturally‐acquired) were used in TaqMan RT‐PCR.CD14, TLR2, PIK3R1 and INFKB were significantly (p<0.05) upregulated in all laminitic horses. TLR4 was significantly upregulated in both models of laminitis induction, especially those following CHO which closely mimics the clinical presentation of a high percentage of laminitis cases.These findings demonstrate that TLR mediators are upregulated in cases of laminitis following GI disruption and systemic therapeutic intervention for laminitis prevention in these cases is warranted.
Dynamic imaging of single microvilli in opossum kidney cells
Authors: Lanzano Luca , Fwu Peter , Giral Hector , Levi Moshe , Gratton Enrico 
Published: June 2021

Reabsorption of inorganic phosphate (Pi) in the renal proximal tubule is fundamental to overall Pi homeostasis. Its regulation occurs via the apical brush border membrane (BBM) sodium gradient‐dependent Pi (NaPi) cotransport proteins. Distinct families of NaPi cotransporters show differential regulation under dietary and hormonal stimuli, but how this is accomplished at a molecular level is not yet fully understood.The application of modern fluorescence correlation spectroscopies to the BBM of living cultured Opossum Kidney (OK) cells expressing NaPi cotransporters with different GFP constructs could provide useful information on the dynamics of the proteins, including diffusion, aggregation and interaction with other proteins. However, BBM microvilli show a relatively fast motion that makes the use of fluctuation spectroscopy difficult.We developed an optical imaging technique called Modulation Tracking (MT) in which we track the center of mass of the microvillus at an arbitrary point along its length via orbital scanning while the laser spot rapidly oscillates perpendicularly to the surface. Using this technique we obtained high resolution images of the microvilli and applied fluctuation correlation spectroscopies in order to study protein dynamics.Work supported in part by NIH RO1 DK066029‐01A2 (ML, EG), NIH‐P41 P41‐RRO3155 (EG, PF and LL) and P50‐GM076516 (EG, PF and LL).
TNF is a key mediator in sepsis‐induced intestinal barrier dysfunction but is independent of enterocyte NFκB
Authors: Samocha Alexandr J. , Coopersmith Craig M. , Dominguez Jessica A. 
Published: June 2021

Inhibition of enterocyte NFκB augments sepsis‐induced intestinal hyperpermeability, gut apoptosis, and TNF expression. We hypothesized that TNF is a key mediator of gut barrier dysfunction and apoptosis in sepsis.Mice lacking enterocyte IKKβ (resultant NFκB inhibition) were created via Cre/lox recombination under control of the villin promoter. Wildtype (WT) and Vil‐Cre/IkkβF/Ä (IKKβ−/−) mice were injected 3 hr pre‐operatively with monoclonal anti‐TNF antibody or isotype control followed by cecal ligation and puncture (n=5–12/group). At 24 hr, intestinal permeability was assessed in vivo using FD4. Apoptosis was evaluated in crypts by active caspase‐3 staining. Blood was harvested for bacterial cultures.Anti‐TNF decreased permeability in septic WT (1832±321 vs. 4678±421 ng/ml; p<0.001) and septic IKKβ −/− mice (2528±446 vs. 6650±951 ng/ml; p<0.01). Sepsis‐induced apoptosis was decreased in both anti‐TNF treated septic WT (13±1 vs. 4±2; p<0.05) and septic IKKβ −/− mice (20±2 vs. 4±1; p<0.001). Anti‐TNF decreased bacteremia in septic WT (4×103±2×103 vs. 4×105±3×105 CFU/ml; p<0.05) and septic IKKβ −/− mice (500±500 vs. 3×106±2×106 CFU/ml; p<0.01). There were no differences between anti‐TNF treated groups for any parameter.TNF appears to be a key mediator in sepsis‐induced intestinal barrier dysfunction. However, this mechanism is independent of enterocyte NFκB. NIH GM66202 & GM082008.
RhoA‐dependent tight junction regulation is associated with dysregulated Akt and ERK signaling and increased claudin‐2 expression
Authors: Gluth Markus , Pape Ulrich‐Frank , Theuring Franz , Fischer Andreas 
Published: June 2021

Previous studies have demonstrated that expression of either constitutively‐active (CA) or dominant negative (DN) RhoA reduced tight junction barrier function in cultured MDCK monolayers (Jou et al. 1998). However, the mechanisms by which RhoA disruption causes barrier loss have not been defined. The aims of this study were to determine whether RhoA regulates barrier function in mammary epithelia and to identify the molecular events responsible. V14 and N19 (CA and DN, respectively) RhoA were expressed in EpH4 mammary epithelial cells. RhoA (CA or DN) expression in confluent monolayers caused a dose‐dependent loss of transepithelial electrical resistance. Neither trafficking of ZO‐1 and occludin to the tight junction nor cell viability were affected by CA or DN RhoA expression, but western blots showed that ERK and Akt were phosphorylated (consistent with activation) after either CA or DN RhoA expression. Transcript content of several claudins was altered after CA or DN RhoA expression. Most notably, claudin‐2 mRNA and protein expression were increased following either CA or DN RhoA expression. These data demonstrate that RhoA regulates the barrier in mammary epithelia and suggest that increased claudin‐2 expression contributes to RhoA‐mediated tight junction regulation.Supported by Charite Universitaetsmedizin Berlin.
Down‐regulation of CFTR is required for epithelial‐mesenchymal transition in cancer development.
Authors: Zhang Jieting , Chung Hilda , Chan Hsiao Chang 
Published: June 2021

Epithelial‐mesenchymal transition (EMT) is an essential component of embryonic development, tissue remodeling, and wound repair. Many epithelial tumors also appear to undergo EMT to acquire a more invasive and metastatic phenotype. Subsequently, the metastasized tumor cells should undergo mesenchymal‐epithelial transition (MET) in order to form a new site. Using an EMT and MET colon carcinoma cell model LIM1863, we report that the cystic fibrosis transmembrane regulator (CFTR) was down‐regulated in cells undergoing EMT induced by TGF‐β alone in 5 days or by TGF‐β with TNF‐α in 24 hours. The down‐regulation of CFTR during EMT was time dependent. On the contrary, the expression of CFTR was upregulated during MET. A specific CFTR inhibitor CFTRinh‐172 induced EMT in the absence of TGF‐β or TNF‐α in the cell model, and the effect was dependent on inhibitor concentrations. MET was blocked by CFTRinh‐172 at similar concentrations. These results suggest that down‐regulation of CFTR is required for EMT, which is inhibitory for MET. Further studies along this line my reveal novel mechanism regulating the processes of EMT and MET.This project was supported by Focused Investments of the Chinese University of Hong Kong.
Plasticity of the noradrenergic response in gastric vagal circuits
Authors: Browning Kirsteen N , Travagli R. Alberto 
Published: June 2021

Catecholaminergic inputs from the nucleus tractus solitarius pars centralis (cNTS) to dorsal motor nucleus of the vagus (DMV) neurons exert profound, vagally mediated effects on gastrointestinal motility.We have shown that opioid and pancreatic polypeptides modulate glutamatergic, but not GABAergic, transmission between NTS and DMV. Elevation of cAMP levels within the brainstem, however, allows transient modulation by these peptides of the otherwise unresponsive GABAergic synapse.The aim of this study was to ascertain whether this short‐term plasticity is a generalized phenomenon also relevant to modulation by catecholamines.Whole cell recordings were made from identified gastric‐projecting rat DMV neurons. Electrical stimulation of the NTS evoked either paired IPSC or EPSC. Norepinephrine and/or the α2 agonist UK 14,304 decreased the amplitude of EPSC; these effects were blocked by yohimbine. The amplitude of the IPSC was, however, unaffected by either agonists unless the levels of cAMP were elevated by pretreatment with agents, such as forskolin, known to increase cAMP levels.These results suggest that, as with opioids and pancreatic polypeptides, the effects of catecholamines on GABAergic transmission depend upon the levels of cAMP within gastric vagal circuits. This short‐term plasticity appears to be a generalized phenomenon within the NTS to DMV GABAergic synapse.Supported by DK 55530