bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating auditory brainstem response to a level-dependent chirp designed based on derived-band latencies
Authors: Huang Hsuan , Chen Yu-Fu , Hsu Chien-Yeh , Cheng Yen-Fu , Yang Tzong-Hann
Published: April 2022

The best cochlear–neural delay model for designing a chirp that can produce the largest auditory brainstem response (ABR) has not been established. This study comprised two experiments. Experiment I aimed to estimate the delay model by measuring derived-band ABR latencies at different levels. The results demonstrated that, as the level decreased, the delay between the center frequencies of 0.7 and 5.7 kHz increased. The aim of experiment II was to compare ABRs generated by three stimuli: (1) a level-dependent derived-band (DB)-Chirp, designed based on the model in experiment I; (2) a level-dependent level specific (LS)-Chirp from Kristensen and Elberling [(2012). J. Am. Acad. Audiol. 23, 712–721]; and (3) a click. The results demonstrated that the DB-Chirp produced significantly larger wave V than the LS-Chirp at 45 dB normal hearing level (nHL); however, no differences were observed at other levels. The wave I generated by the DB-Chirp and LS-Chirp were significantly larger than those evoked by the click at 45 and 60 dB nHL and at 30 and 45 dB nHL, respectively; however, at all levels, no differences between these two chirps were observed. The DB-Chirp may be a valuable stimulus for producing ABRs for clinical applications such as assessing cochlear synaptopathy and estimating hearing sensitivity.
Customer Engagement in Sport: An Updated Review and Research Agenda
Authors: McDonald Heath , Biscaia Rui , Yoshida Masayuki , Conduit Jodie , Doyle Jason P.
Published: April 2022

Customer engagement (CE) is an emerging perspective that provides a holistic view of the ways in which customers’ interactive experiences with organizations create value for both the parties. Central to this, is the need to develop an understanding of why a customer would choose to invest their resources (cognitive, emotional, and behavioral) with an organization, to be able to better facilitate this engagement and properly value the outcomes from it. Sport, with its inherently strong interactions for both participants and fans, would seem an ideal setting to study CE. To date, however, the CE work in sport domains has largely followed established paths. Given CE’s potential to unify many disparate areas of sport research, this paper presents a comprehensive review of the CE work to date and highlights several ways sport can leverage and advance this work through both academic research and management practice.
Surface warming–induced global acceleration of upper ocean currents
Authors: Peng Qihua , Xie Shang-Ping , Wang Dongxiao , Huang Rui Xin , Chen Gengxin , Shu Yeqiang , Shi Jia-Rui , Liu Wei
Published: April 2022

How the ocean circulation changes in a warming climate is an important but poorly understood problem. Using a global ocean model, we decompose the problem into distinct responses to changes in sea surface temperature, salinity, and wind. Our results show that the surface warming effect, a robust feature of anthropogenic climate change, dominates and accelerates the upper ocean currents in 77% of the global ocean. Specifically, the increased vertical stratification intensifies the upper subtropical gyres and equatorial currents by shoaling these systems, while the differential warming between the Southern Ocean upwelling zone and the region to the north accelerates surface zonal currents in the Southern Ocean. In comparison, the wind stress and surface salinity changes affect regional current systems. Our study points a way forward for investigating ocean circulation change and evaluating the uncertainty.
On vasa vasorum: A history of advances in understanding the vessels of vessels
Authors: Phillippi Julie A.
Published: April 2022

The vasa vasorum are a vital microvascular network supporting the outer wall of larger blood vessels. Although these dynamic microvessels have been studied for centuries, the importance and impact of their functions in vascular health and disease are not yet fully realized. There is now rich knowledge regarding what local progenitor cell populations comprise and cohabitate with the vasa vasorum and how they might contribute to physiological and pathological changes in the network or its expansion via angiogenesis or vasculogenesis. Evidence of whether vasa vasorum remodeling incites or governs disease progression or is a consequence of cardiovascular pathologies remains limited. Recent advances in vasa vasorum imaging for understanding cardiovascular disease severity and pathophysiology open the door for theranostic opportunities. Approaches that strive to control angiogenesis and vasculogenesis potentiate mitigation of vasa vasorum–mediated contributions to cardiovascular diseases and emerging diseases involving the microcirculation.
Epac1 activation by cAMP regulates cellular SUMOylation and promotes the formation of biomolecular condensates
Authors: Yang Wenli , Robichaux William G. , Mei Fang C. , Lin Wei , Li Li , Pan Sheng , White Mark A. , Chen Yuan , Cheng Xiaodong
Published: April 2022

Protein SUMOylation plays an essential role in maintaining cellular homeostasis when cells are under stress. However, precisely how SUMOylation is regulated, and a molecular mechanism linking cellular stress to SUMOylation, remains elusive. Here, we report that cAMP, a major stress-response second messenger, acts through Epac1 as a regulator of cellular SUMOylation. The Epac1-associated proteome is highly enriched with components of the SUMOylation pathway. Activation of Epac1 by intracellular cAMP triggers phase separation and the formation of nuclear condensates containing Epac1 and general components of the SUMOylation machinery to promote cellular SUMOylation. Furthermore, genetic knockout of Epac1 obliterates oxidized low-density lipoprotein–induced cellular SUMOylation in macrophages, leading to suppression of foam cell formation. These results provide a direct nexus connecting two major cellular stress responses to define a molecular mechanism in which cAMP regulates the dynamics of cellular condensates to modulate protein SUMOylation.
Efficacy and specificity of inhibitors of BCL-2 family protein interactions assessed by affinity measurements in live cells
Authors: Osterlund Elizabeth J. , Hirmiz Nehad , Pemberton James M. , Nougarède Adrien , Liu Qian , Leber Brian , Fang Qiyin , Andrews David W.
Published: April 2022

Cytoplasmic and membrane-bound BCL-2 family proteins regulate apoptosis, a form of programmed cell death, via dozens of binary protein interactions confounding measurement of the effects of inhibitors in live cells. In cancer, apoptosis is frequently dysregulated, and cell survival depends on antiapoptotic proteins binding to and inhibiting proapoptotic BH3 proteins. The clinical success of BH3 mimetic inhibitors of antiapoptotic proteins has spawned major efforts by the pharmaceutical industry to develop molecules with different specificities and higher affinities. Here, quantitative fast fluorescence lifetime imaging microscopy enabled comparison of BH3 mimetic drugs in trials and preclinical development by measuring drug effects on binding affinities of interacting protein pairs in live cells. Both selectivity and efficacy were assessed for 15 inhibitors of four antiapoptotic proteins for each of six BH3 protein ligands. While many drugs target the designed interaction, most also have unexpected selectivity and poor efficacy in cells.
Blood-brain barrier–penetrating single CRISPR-Cas9 nanocapsules for effective and safe glioblastoma gene therapy
Authors: Zou Yan , Sun Xinhong , Yang Qingshan , Zheng Meng , Shimoni Olga , Ruan Weimin , Wang Yibin , Zhang Dongya , Yin Jinlong , Huang Xiangang , Tao Wei , Park Jong Bae , Liang Xing-Jie , Leong Kam W. , Shi Bingyang
Published: April 2022

We designed a unique nanocapsule for efficient single CRISPR-Cas9 capsuling, noninvasive brain delivery and tumor cell targeting, demonstrating an effective and safe strategy for glioblastoma gene therapy. Our CRISPR-Cas9 nanocapsules can be simply fabricated by encapsulating the single Cas9/sgRNA complex within a glutathione-sensitive polymer shell incorporating a dual-action ligand that facilitates BBB penetration, tumor cell targeting, and Cas9/sgRNA selective release. Our encapsulating nanocapsules evidenced promising glioblastoma tissue targeting that led to high PLK1 gene editing efficiency in a brain tumor (up to 38.1%) with negligible (less than 0.5%) off-target gene editing in high-risk tissues. Treatment with nanocapsules extended median survival time (68 days versus 24 days in nonfunctional sgRNA-treated mice). Our new CRISPR-Cas9 delivery system thus addresses various delivery challenges to demonstrate safe and tumor-specific delivery of gene editing Cas9 ribonucleoprotein for improved glioblastoma treatment that may potentially be therapeutically useful in other brain diseases.
In-person schooling and associated COVID-19 risk in the United States over spring semester 2021
Authors: Wiens Kirsten E. , Smith Claire P. , Badillo-Goicoechea Elena , Grantz Kyra H. , Grabowski M. Kate , Azman Andrew S. , Stuart Elizabeth A. , Lessler Justin
Published: April 2022

Because of the importance of schools to childhood development, the relationship between in-person schooling and COVID-19 risk has been one of the most important questions of this pandemic. Previous work in the United States during winter 2020–2021 showed that in-person schooling carried some risk for household members and that mitigation measures reduced this risk. Schooling and the COVID-19 landscape changed radically over spring semester 2021. Here, we use data from a massive online survey to characterize changes in in-person schooling behavior and associated risks over that period. We find increases in in-person schooling and reductions in mitigations over time. In-person schooling is associated with increased reporting of COVID-19 outcomes even among vaccinated individuals (although the absolute risk among the vaccinated is greatly reduced). Vaccinated teachers working outside the home were less likely to report COVID-19–related outcomes than unvaccinated teachers working exclusively from home. Adequate mitigation measures appear to eliminate the excess risk associated with in-person schooling.
Structural insight into UV-B–activated UVR8 bound to COP1
Authors: Wang Yidong , Wang Lixia , Guan Zeyuan , Chang Hongfei , Ma Ling , Shen Cuicui , Qiu Liang , Yan Junjie , Zhang Delin , Li Jian , Deng Xing Wang , Yin Ping
Published: April 2022

The CONSTITUTIVE PHOTOMORPHOGENIC 1-SUPPRESSOR OF PHYA-105 (COP1-SPA) complex is a central repressor of photomorphogenesis. This complex acts as an E3 ubiquitin ligase downstream of various light signaling transduced from multiple photoreceptors in plants. How the COP1-SPA activity is regulated by divergent light-signaling pathways remains largely elusive. Here, we reproduced the regulation pathway of COP1-SPA in ultraviolet-B (UV-B) signaling in vitro and determined the cryo-electron microscopy structure of UV-B receptor UVR8 in complex with COP1. The complex formation is mediated by two-interface interactions between UV-B-activated UVR8 and COP1. Both interfaces are essential for the competitive binding of UVR8 against the signaling hub component HY5 to the COP1-SPA complex. We also show that RUP2 dissociates UVR8 from the COP1-SPA4
1–464
-UVR8 complex and facilitates its redimerization. Our results support a UV-B signaling model that the COP1-SPA activity is repressed by UV-B-activated UVR8 and derepressed by RUP2, owing to competitive binding, and provide a framework for studying the regulatory roles of distinct photoreceptors on photomorphogenesis.
The developmental origin and the specification of the adrenal cortex in humans and cynomolgus monkeys
Authors: Cheng Keren , Seita Yasunari , Moriwaki Taku , Noshiro Kiwamu , Sakata Yuka , Hwang Young Sun , Torigoe Toshihiko , Saitou Mitinori , Tsuchiya Hideaki , Iwatani Chizuru , Hosaka Masayoshi , Ohkouchi Toshihiro , Watari Hidemichi , Umazume Takeshi , Sasaki Kotaro
Published: April 2022

Development of the adrenal cortex, a vital endocrine organ, originates in the adrenogonadal primordium, a common progenitor for both the adrenocortical and gonadal lineages in rodents. In contrast, we find that in humans and cynomolgus monkeys, the adrenocortical lineage originates in a temporally and spatially distinct fashion from the gonadal lineage, arising earlier and more anteriorly within the coelomic epithelium. The adrenal primordium arises from adrenogenic coelomic epithelium via an epithelial-to-mesenchymal transition, which then progresses into the steroidogenic fetal zone via both direct and indirect routes. Notably, we find that adrenocortical and gonadal lineages exhibit distinct HOX codes, suggesting distinct anterior-posterior regionalization. Together, our assessment of the early divergence of these lineages provides a molecular framework for understanding human adrenal and gonadal disorders.
In utero exposure to maternal anti–aquaporin-4 antibodies alters brain vasculature and neural dynamics in male mouse offspring
Authors: Mader Simone , Brimberg Lior , Vo An , Strohl Joshua J. , Crawford James M. , Bonnin Alexandre , Carrión Joseph , Campbell Delcora , Huerta Tomás S. , La Bella Andrea , Berlin Roseann , Dewey Stephen L. , Hellman Matthew , Eidelberg David , Dujmovic Irena , Drulovic Jelena , Bennett Jeffrey L. , Volpe Bruce T. , Huerta Patricio T. , Diamond Betty
Published: April 2022

The fetal brain is constantly exposed to maternal IgG before the formation of an effective blood-brain barrier (BBB). Here, we studied the consequences of fetal brain exposure to an antibody to the astrocytic protein aquaporin-4 (AQP4-IgG) in mice. AQP4-IgG was cloned from a patient with neuromyelitis optica spectrum disorder (NMOSD), an autoimmune disease that can affect women of childbearing age. We found that embryonic radial glia cells in neocortex express AQP4. These cells are critical for blood vessel and BBB formation through modulation of the WNT signaling pathway. Male fetuses exposed to AQP4-IgG had abnormal cortical vasculature and lower expression of WNT signaling molecules
Wnt
5a and
Wnt
7a. Positron emission tomography of adult male mice exposed in utero to AQP4-IgG revealed increased blood flow and BBB leakiness in the entorhinal cortex. Adult male mice exposed in utero to AQP4-IgG had abnormal cortical vessels, fewer dendritic spines in pyramidal and stellate neurons, and more S100β
+
astrocytes in the entorhinal cortex. Behaviorally, they showed impairments in the object-place memory task. Neural recordings indicated that their grid cell system, within the medial entorhinal cortex, did not map the local environment appropriately. Collectively, these data implicate in utero binding of AQP4-IgG to radial glia cells as a mechanism for alterations of the developing male brain and adds NMOSD to the conditions in which maternal IgG may cause persistent brain dysfunction in offspring.
Inhibition of the enzyme autotaxin reduces cortical excitability and ameliorates the outcome in stroke
Authors: Bitar Lynn , Uphaus Timo , Thalman Carine , Muthuraman Muthuraman , Gyr Luzia , Ji Haichao , Domingues Micaela , Endle Heiko , Groppa Sergiu , Steffen Falk , Koirala Nabin , Fan Wei , Ibanez Laura , Heitsch Laura , Cruchaga Carlos , Lee Jin-Moo , Kloss Florian , Bittner Stefan , Nitsch Robert , Zipp Frauke , Vogt Johannes
Published: April 2022

Stroke penumbra injury caused by excess glutamate is an important factor in determining stroke outcome; however, several therapeutic approaches aiming to rescue the penumbra have failed, likely due to unspecific targeting and persistent excitotoxicity, which continued far beyond the primary stroke event. Synaptic lipid signaling can modulate glutamatergic transmission via presynaptic lysophosphatidic acid (LPA) 2 receptors modulated by the LPA-synthesizing molecule autotaxin (ATX) present in astrocytic perisynaptic processes. Here, we detected long-lasting increases in brain ATX concentrations after experimental stroke. In humans, cerebrospinal fluid ATX concentration was increased up to 14 days after stroke. Using astrocyte-specific deletion and pharmacological inhibition of ATX at different time points after experimental stroke, we showed that inhibition of LPA-related cortical excitability improved stroke outcome. In transgenic mice and in individuals expressing a single-nucleotide polymorphism that increased LPA-related glutamatergic transmission, we found dysregulated synaptic LPA signaling and subsequent negative stroke outcome. Moreover, ATX inhibition in the animal model ameliorated stroke outcome, suggesting that this approach might have translational potential for improving the outcome after stroke.
The ArcAB Two-Component System: Function in Metabolism, Redox Control, and Infection
Authors: Brown Aric N. , Anderson Mark T. , Bachman Michael A. , Mobley Harry L. T.
Published: April 2022

ArcAB, also known as the Arc system, is a member of the two-component system family of bacterial transcriptional regulators and is composed of sensor kinase ArcB and response regulator ArcA. In this review, we describe the structure and function of these proteins and assess the state of the literature regarding ArcAB as a sensor of oxygen consumption.
Mycobacterium tuberculosis Lineages Associated with Mutations and Drug Resistance in Isolates from India
Authors: Shanmugam Siva Kumar , Kumar Narender , Sembulingam Tamilzhalagan , Ramalingam Suresh Babu , Selvaraj Ashok , Rajendhiran Udhayakumar , Solaiyappan Sudha , Tripathy Srikanth P. , Natrajan Mohan , Chandrasekaran Padmapriyadarsini , Swaminathan Soumya , Parkhill Julian , Peacock Sharon J. , Ranganathan Uma Devi K.
Published: April 2022

Current knowledge on resistance-conferring determinants in
Mycobacterium tuberculosis
is biased toward globally dominant lineages 2 and 4. In contrast, lineages 1 and 3 are predominant in India.
Symbiont-Induced Phagosome Changes Rather than Extracellular Discrimination Contribute to the Formation of Social Amoeba Farming Symbiosis
Authors: Tian Yuehui , Peng Tao , He Zhenzhen , Wang Luting , Zhang Xurui , He Zhili , Shu Longfei
Published: April 2022

Protists are single-celled, extremely diverse eukaryotic microbes. Like animals and plants, they live with bacterial symbionts and have complex relationships.
Bacterial but Not Fungal Rhizosphere Community Composition Differ among Perennial Grass Ecotypes under Abiotic Environmental Stress
Authors: Sarkar Soumyadev , Kamke Abigail , Ward Kaitlyn , Rudick Aoesta K. , Baer Sara G. , Ran QingHong , Feehan Brandi , Thapa Shiva , Anderson Lauren , Galliart Matthew , Jumpponen Ari , Johnson Loretta , Lee Sonny T. M.
Published: April 2022

In this study, we used a 10-year long reciprocal garden system, and reports that different ecotypes (dry, mesic, and wet) of dominant prairie grass,Andropogon gerardiican maintain or recruit distinct bacterial but not fungal rhizobiomes after 10 years in an arid environment. We used both 16S rRNA and ITS2 amplicons to analyze the bacterial and fungal communities in the rhizospheres of the respective ecotypes.
(U-Th)/He chronology: Part 1. Data, uncertainty, and reporting
Authors: Flowers R.M. , Zeitler P.K. , Danišík M. , Reiners P.W. , Gautheron C. , Ketcham R.A. , Metcalf J.R. , Stockli D.F. , Enkelmann E. , Brown R.W.
Published: April 2022

The field of (U-Th)/He geochronology and thermochronology has grown enormously over the past ∼25 years. The tool is applicable across much of geologic time, new (U-Th)/He chronometers are under continuous development, and the method is used in a diverse array of studies. Consequently, the technique has a rapidly expanding user base, and new labs are being established worldwide. This presents both opportunities and challenges. Currently there are no universally agreedupon protocols for reporting measured (U-Th)/He data or data derivatives. Nor are there standardized practices for reporting He diffusion kinetic, 4He/3He, or continuous ramped heating data. Approaches for reporting uncertainties associated with all types of data also vary widely. Here, we address these issues. We review the fundamentals of the methods, the types of materials that can be dated, how data are acquired, the process and choices associated with data reduction, and make recommendations for data and uncertainty reporting. We advocate that both the primary measured and derived data be reported, along with statements of assumptions, appropriate references, and clear descriptions of the methods used to compute derived data from measured values. The adoption of more comprehensive and uniform approaches to data and uncertainty reporting will enable data to be re-reduced in the future with different interpretative contexts and data reduction methods, and will facilitate inter-comparison of data sets generated by different laboratories. Together, this will enhance the value, cross-disciplinary use, reliability, and ongoing development of (U-Th)/He chronology.
(U-Th)/He chronology: Part 2. Considerations for evaluating, integrating, and interpreting conventional individual aliquot data
Authors: Flowers R.M. , Ketcham R.A. , Enkelmann E. , Gautheron C. , Reiners P.W. , Metcalf J.R. , Danišík M. , Stockli D.F. , Brown R.W.
Published: April 2022

The (U-Th)/He dating technique is an essential tool in Earth science research with diverse thermochronologic, geochronologic, and detrital applications. It is now used in a wide range of tectonic, structural, petrological, sedimentary, geomorphic, volcanological, and planetary studies. While in some circumstances the interpretation of (U-Th)/He data is relatively straightforward, in other cases it is less so. In some geologic contexts, individual analyses of the same mineral from a single sample are expected to yield dates that differ well beyond their analytical uncertainty owing to variable He diffusion kinetics. Although much potential exists to exploit this phenomenon to decipher more detailed thermal history information, distinguishing interpretable intra-sample data variation caused by kinetic differences between crystals from uninterpretable overdispersion caused by other factors can be challenging. Nor is it always simple to determine under what circumstances it is appropriate to integrate multiple individual analyses using a summary statistic such as a mean sample date or to decide on the best approach for incorporating data into the interpretive process of thermal history modeling. Here we offer some suggestions for evaluating data, attempt to summarize the current state of thinking on the statistical characterization of data sets, and describe the practical choices (e.g., model structure, path complexity, data input, weighting of different geologic and chronologic information) that must be made when setting up thermal history models. We emphasize that there are no hard and fast rules in any of these realms, which continue to be an important focus of improvement and community discussion, and no single interpretational and modeling philosophy should be forced on data sets. The guiding principle behind all suggestions made here is for transparency in reporting the steps and assumptions associated with evaluating, integrating, and interpreting data, which will promote the continued development of (U-Th)/He chronology.
P09 Management of aggressive systemic mastocytosis in a 4kg infant
Authors: Forster Abbey
Published: April 2022

Backgound

Aggressive systemic mastocytosis is a very rare life-threatening diagnosis whereby mast cells accumulate in internal tissues and organs. There are limited case reports of this condition, particularly in children, and is associated with poor prognosis.

Situation

We present a case report of a child who was diagnosed as a neonate with cutaneous mastocytosis and subsequently developed massive hepatosplenomegaly, cytopenia and failure to thrive. Genetic testing was carried out, confirming somatic changes in the KIT proto-oncogene receptor tyrosine kinase, which controls important cellular processes. Her twin was unaffected. Treatment goal was to reduce disease burden and if clinically fit enough, to proceed with allogenic stem cell transplantation.

Contribution of the Pharmacy Team

This case presented numerous pharmaceutical challenges. Drug reactions can be severe and life-threatening resulting in anaphylaxis. Therefore, management of paediatric systemic mastocytosis includes strict avoidance of triggers of histamine; including: drugs, infection, allergens and physical stimuli. The pharmacy team advised on the most appropriate analgesia, infection prophylaxis, anti-mediator therapy and mast-cell targeted treatment options.

First line therapy for adult patients with this condition is midostaurin. This is formulated as a 25mg capsule, which is the only licensed preparation. Due to the rarity of this condition in paediatrics, only case reports were available. Suggested initial dosing of 30mg/m2 twice daily would provide a dose of 7.8mg twice daily in a 4kg infant. The manufacturer was contacted to request supply of an alternative formulation if available on a compassionate access basis to meet the clinical need to this patient. Initially the manufacturer was unable to support this request in a timely manner which led us to pursue second line therapy with cladrabine.

Pharmacist advised on cladrabine dosing based on chemotherapy protocols, liaised with procurement to source drug and facilitated set up of drug using electronic prescribing system, supported consultant to prescribe and nursing staff to administer drug.

Without the contribution of the pharmacy team, it is likely that this patient would not have received treatment in a timely manner and drugs may have been inadvertently prescribed and administered that could trigger histamine release.

Outcome

Patient received three cycles of cladribine using doses described in LCH-IV protocol. Hepato-splenomegaly was reduced and counts normalised. There was no visible improvement of skin lesions. The manufacturer of midostaurin responded several weeks later granting the supply of a trial stock liquid formulation on a compassionate basis.

Lessons Learnt

Medicines governance around compassionate access schemes are lengthy and therefore second line treatment was required. Consideration of most appropriate analgesia and infection prophylaxis was researched and prescribed for patient.
P11 Using novel technology to improve communication to and between pharmacy staff
Authors: Turner Paul
Published: April 2022

Aim

To explore possible alternatives to the current radio-pager communication system following the department of health’s order for their removal by the end of 2021. To analyse the feasibility and practicality of these systems and implement the most appropriate choice into practice.

Method

Analytical tools including driver diagrams and process maps were constructed and examined to identify possible alternatives to the current radio-pager system. Systems such as Microsoft Teams® and Whatsapp ® were considered but were discredited due to concerns surrounding information governance. CareFlow, a system already implemented in the adult services at the Trust, was consistently identified as fulfilling criteria to enable its utilisation as an alternative to radio-pager. These criteria being: ease of use (task raising), accessibility and maintaining information governance standards.

The utilisation of radio-pager and CareFlow data were retrospectively collected and analysed for the 10-weeks before and after the implementation of CareFlow. Comparison of this data involved 2-sided T-tests and ANOVA statistical tests, comparing mean data of radio pager against CareFlow tasks, the comparison of workload and efficiency of the pharmacy teams after rollout. CareFlow tasks raised were analysed for time to completion as the accepted limit for radio-pager response is 15 minutes.

Results

A statistically significant increase (P = 0.004) of 69.5% in the weekly average number of CareFlow tasks in the 10 weeks post-intervention (71) compared to the weekly average number of bleeps in the 10 weeks prior (42). Additionally, a statistically significant 45% decrease (P = 0.0002) in the number of bleeps in the 10 weeks post-change implementation (23). The median average response times of all three pharmacy teams were shown to be within the 15-minute time limit. Mean average response times were higher. Pharmacy team response times remained below the 15minute limit. ANOVA (F=7.1 fcrit = 3.3) and T-tests showed there were no significant differences in the mean average response times of pharmacy teams (p=0.7).

Conclusion

Data and practical use has shown that the transfer of pharmacy communications away from radio-pagers to the CareFlow notification system has been a success. We have shown pharmacy to be more accessible and efficient in their completion of tasks assigned by other members of staff. With noted benefits of receiving tasks out of hours for completion in the morning. Response times remain within the 15minute limit, showing the majority of their tasks are responded to efficiently. However, mean responses were relatively higher. This may indicate tasks that are not responded to within these 15minutes may have been missed, and therefore have far longer waiting periods. This is likely a contributory factor for the continued low-level use of the radio-pagers through the 10 weeks post-change implementation.
Development of the Get Active Questionnaire for Pregnancy: breaking down barriers to prenatal exercise
Authors: Davenport Margie H. , Neil-Sztramko Sarah , Lett Bridget , Duggan Mary , Mottola Michelle F. , Ruchat Stephanie-May , Adamo Kristi B. , Andrews Kate , Artal Raul , Beamish Nicole , Chari Radha , Forte Milena , Lane Kirstin N. , May Linda , Maclaren Kaleigh , Zahavich Ashley
Published: April 2022

Evidence-based guidelines represent the highest level of scientific evidence to identify best practices for clinical/public health. However, the availability of guidelines do not guarantee their use, targeted knowledge translation strategies and tools are necessary to help promote uptake. Following publication of the 2019 Canadian Guideline for Physical Activity throughout Pregnancy, the Get Active Questionnaire for Pregnancy, and an associated Health Care Provider Consultation Form for Prenatal Physical Activity were developed to promote guideline adoption and use amongst pregnant individuals and health care providers. This paper describes the process of developing these tools. First, a survey was administered to qualified exercise professionals to identify the barriers and facilitators in using existing prenatal exercise screening tools. A Working Group of researchers and stakeholders then convened to develop an evidence-informed exercise pre-participation screening tool for pregnant individuals, building from previous tool and survey findings. Finally, end-user feedback was solicited through a survey and key informant interviews to ensure tools are feasible and acceptable to use in practice. The uptake and use of these documents by pregnant individuals, exercise, and health care professionals will be assessed in future studies.

Novelty:

Evidence supports the safety/benefits of exercise for most pregnant individuals; however, exercise is not recommended for a small number of individuals with specific medical conditions. The Get Active Questionnaire for Pregnancy and Health Care Provider Consultation Form for Physical Activity during Pregnancy identify individuals where prenatal exercise may pose a risk, while reducing barriers to physical activity participation for the majority of pregnant individuals.
Bone marrow granulocytes downregulate IL-1β and TNF production and the microbicidal activity of inflammatory macrophages
Authors: Novaes Renata , Costa Tatiana F.R. , Goundry Amy L. , Verçoza Brunno R.F. , Rodrigues Juliany C.F. , Godinho Joseane Lima P. , Reis Flavia C.G. , Morrot Alexandre , Lima Ana Paula C.A.
Published: April 2022

Macrophages play critical roles in inflammation and defense against pathogens, as well as in the return to tissue homeostasis. Macrophage subpopulations displaying antagonistic phenotypes are generally classified as proinflammatory M1, implicated in antipathogen and antitumoral activities, or as anti-inflammatory M2, associated with tissue repair. Granulocytic and monocytic myeloid-derived suppressor cells recruited from the bone marrow to tissues and phagocytosis of apoptotic neutrophils can attenuate macrophage microbicidal activity. Here, we showed that bone marrow neutrophils, but not thioglycollate-recruited neutrophils, directly suppress the responses of macrophages that were previously committed to an inflammatory phenotype. Cocultures of inflammatory macrophages with bone marrow CD11b+Ly6Ghi granulocytes led to reduced release of IL-1β, TNF-α, and IL-6 by macrophages after lipopolysaccharide stimulation. The suppressive activity was unrelated to granulocyte apoptosis or to secreted factors and required cell-to-cell contact. The suppressive effect was paralleled by reduction in the nuclear levels of the NF-κB p65 subunit, but not of the p50 subunit. Furthermore, bone marrow granulocytes decreased the phagocytic activity of macrophages and their capacity to kill intracellular Escherichia coli. Taken together, these results show that bone marrow granulocytes can function as suppressors of the proinflammatory activity and microbial-killing responses of macrophages.
Prediction of driven pile resistances in shales considering weathering and time effects
Authors: Islam Md Shafiqul , Ng Kam W. , Wulff Shaun S.
Published: April 2022

The difficulty with shale sampling and testing and the lack of pile load tests in shales have created challenges with shale classification, pile resistance prediction, and understanding time-dependent pile responses. Treating shale as soil can yield a conservative pile design. Shales were classified into soil-based and rock-based depending on their weathering conditions, mechanical properties, and measured pile resistances. Failure behaviors of soil- and rock-based shales are discussed. Prediction equations were developed to account for predicting shale properties. Properties of rock-based shales decrease with the increase in weathering. New static analysis (SA) methods were proposed to predict unit shaft resistance ( qs) and unit end bearing ( qb) of piles in shales and validated. Our study yields higher resistance and efficiency factors for the proposed SA methods and piles in shales than existing SA methods developed for piles in soils. The qs in the soil-based shale exhibits pile setup, while the qs in rock-based shales experience both setup and relaxation. The qb in both soil-based and highly weathered shales is likely to experience pile setup. However, the qb in the moderately and slightly weathered shales experience both setup and relaxation.
Porphyromonas gingivalis infection upregulates the endothelin (ET) system in brain microvascular endothelial cells
Authors: Karakaya Eda , Abdul Yasir , Chowdhury Nityananda , Wellslager Bridgette , Jamil Sarah , Albayram Onder , Yilmaz Özlem , Ergul Adviye
Published: April 2022

Endothelin-1 (ET-1), the most potent vasoconstrictor identified to date, contributes to cerebrovascular dysfunction and brain ET-1 levels were shown to be related to Alzheimer's disease and related dementias (ADRD) progression. ET-1 also contributes to neuroinflammation, especially in infections of the central nervous system. Recent studies causally linked chronic periodontal infection with an opportunistic anaerobic bacterium Porphyromonas gingivalis (Coykendall et al.) Shah & Collins to AD development. Thus, the goal of the study was to determine the impact of P. gingivalis infection on the ET system and cell senescence in brain microvascular endothelial cells. Cells were infected with a multiplicity of infection 50 P. gingivalis with and without extracellular ATP-induced oxidative stress for 24 h. Cell lysates were collected for analysis of endothelin A receptor (ETA)/endothelin B receptor (ETB) receptor as well as senescence markers. ET-1 levels in cell culture media were measured with enzyme-linked immunosorbent assay. P. gingivalis infection increased ET-1 (pg/mL) secretion, as well as the ETA receptor expression, whereas decreased lamin A/C expression compared to control. Tight junction protein claudin-5 was also decreased under these conditions. ETA or ETB receptor blockade during infection did not affect ET-1 secretion or the expression of cell senescence markers. Current findings suggest that P. gingivalis infection may compromise endothelial integrity and activate the ET system.
Electromagnetic influence on hyperbolically symmetric sources in f(T) gravity
Authors: Bhatti M. Z. , Yousaf Z. , Hanif S.
Published: April 2022

The present study aims to see how gravitational modification, specifically, the f(T) gravitational field, where T is torsion scalar, impacts static fluid content with hyperbolic symmetry and electromagnetic field. We enlarge Herrera’s strategy (Herrera et al. in Phys Rev D 103:024037, 2021) to analyze the impact of electromagnetic field on f(T) gravity. We distinguish the stress–energy tensor by considering the ingredients of the tetrad field in the Minkowski co-ordinate frame, commencing with modified field equations. With the advent of negative density, this sort of fluid is supposed to surpass extreme physical conditions, enabling quantum impacts to be detected. We calculate a viable formulation of mass utilizing the Tolman mass from the viewpoint of f(T) gravity along with the electromagnetic field. The gravitational interference is repulsive, as made evident by the negative value of the Tolman mass. Also, we explored the structure scalars in f(T) gravity and found significant solutions in presence of electric charge.
Ultraviolet properties of Lifshitz-type scalar field theories
Authors: Zappalà Dario
Published: April 2022

We consider Lifshitz-type scalar field theories that exhibit anisotropic scaling laws near the ultraviolet fixed point, with explicit breaking of Lorentz symmetry. It is shown that, when all momentum dependent vertex operators are discarded, actions with anisotropy parameter $$z=3$$

z
=
3

in 3+1 dimensions generate Lorentz symmetry violating quantum corrections that are suppressed by inverse powers of the momentum, so that the symmetry is sensibly restored in the infrared region. In the ultraviolet region, the singular behavior of the corrections is strongly smoothened: only logarithmic divergences show up, producing very small changes of the couplings over a range of momentum of many orders of magnitude. In the particular case where all couplings are equal, the theory shows a Liouville-like potential and quantum corrections are exactly summable, giving an asymptotically free theory. However, the observed weakening of the divergences is not sufficient to avoid a residual fine tuning of the mass parameter at a very high energy scale, in order to recover a physically acceptable mass in the infrared region.
Ridge Estimation for Uncertain Moving Average Model Under Imprecise Observations
Authors: Gao Xin , Xue Chun
Published: April 2022

By observing and studying the time series, looking for the law of its change and development, and predicting its future trend is time series analysis. The observation data in traditional time series are accurate, but the statistical data we get in actual observations such as carbon emissions and temperature are often inaccurate. We regard this type of imprecise observation as uncertain variables, model it with the uncertain moving average model (UMA), and estimate the parameters in the UMA model with the ridge method. Then through the residual analysis of the fitted model, we acquire the forecast value and the confidence interval. Finally, numerical examples are used to prove the feasibility of the method.
Development of a Novel CNN Architecture for Improved Diagnosis from Liver Ultrasound Tumor Images
Authors: Sivanandan Revathy , Jayakumari J.
Published: April 2022

Malignant liver tumors are considered as one of the most common cancers and a leading cause of cancer death worldwide. While using convolutional neural networks (CNNs) for feature extraction from ultrasound (US) images and tasks thereafter, most works focus on pre-trained architectures using transfer learning which can sometimes cause negative transfer and reduced performance in medical domain. A new method based on Pascal’s Triangle was developed for feature extraction using CNN. The convolutions and the kernels in Pascal’s Triangle based CNN (PT-CNN) are according to the coefficients at each level of Pascal’s Triangle. Due to the fuzzy nature of US images, the input layer takes a combination of the image and its neutrosophically pre-processed components as a single unit to improve noise robustness. The proposed CNN when implemented as a backbone for feature extraction for binary classification, gave validation accuracy > 90% and test accuracy >95% than other state-of-the-art CNN architectures. For tumor segmentation using Mask R-CNN framework, the aggregated feature maps from all convolutional layers were given as the input to the region proposal network for multiscale region proposals and to facilitate the detection of tumors of varying sizes. This gave an F1 score > 0.95 when compared with other architectures as backbone on Mask R-CNN framework and simple U-Net based segmentation. It is suggested that the promising results of PT-CNN as a feature extraction backbone could be further investigated in other domains.
A Comparison of Formulations and Approximations for the Nonlinear Analysis of Steel Frames under Thermal Loading
Authors: Petrolito J. , Ionescu D. , Sim A. , Lougoon T.
Published: April 2022

The analysis of building frames under thermal loading is an important task in structural engineering. Linear analysis is generally inadequate for large temperature changes, and nonlinear analysis is essential to correctly model the behavior of the structure. Various nonlinear models are used in practice and these models usually involve some form of approximation of the nonlinear effects. In this case, it is not often clear what effects the approximations have on the analysis. This paper discusses a general approach for the nonlinear analysis of steel frames under thermal loading. In particular, we consider the role of approximations in the governing equations of the structure and the effects of the changes in material properties at high temperatures. Several examples are given in the paper that demonstrate the various effects of the approximations and assumptions on the results.
Simulation of magnetic field effect on heat transfer enhancement of swirling nanofluid
Authors: Mahfoud Brahim
Published: April 2022

In this paper, the swirling nanofluid flow which is driven by a rotating bottom disk of a cylindrical container under magnetic field effect and temperature gradient is considered. Effects of electrical conductivity of cylindrical walls on heat transfer enhancement are numerically analyzed. The governing equations that describe the combined problem (magnetohydrodynamics and mixed convection) under the adoptive assumptions are solved numerically by the finite volume technique. Calculations were made for fixed Reynolds number (Re[Formula: see text]1000), Richardson number (0[Formula: see text]Ri[Formula: see text]2), aspect ratio ([Formula: see text]), Hartmann number (0[Formula: see text]Ha[Formula: see text]60), and solid nanoparticle (copper) with volume fraction ([Formula: see text]). Five cases are considered in this study: (EI-Walls), (EC-Walls), (EC-Bottom), (EC-Top), and (EC-Sidewall). A decrease in the mean Nusselt number was found with the increase of the Richardson number due to stratification layers. These latter limits the heat transfers between the hot and cold zones of the cylinder. The results indicate that the Nusselt number gets bigger within a certain range of Hartmann numbers, and especially when the rotating lid is electrically conducting. Indeed, average Nusselt number decreases while the Hartmann number increase after it exceeds a critical value. Finally, the electrical conductivity of the rotating lid plays an important role in heat transfer enhancement in nanofluid swirling flow.
A Cost-Effective Built-In Self-Test Mechanism for Post-Manufacturing TSV Defects in 3D ICs
Authors: Maity Dilip Kumar , Roy Surajit Kumar , Giri Chandan
Published: April 2022

Three-Dimensional Integrated Circuit (3D IC) based on Through-Silicon-Via (TSV) has brought a drastic change in IC technology. Since TSVs connect different layers of 3D stacks, their proper functioning is an essential prerequisite for system operation. Therefore, testing of TSV is essential for 3D IC. In this article, we propose a cost-effective Built-In Self-Test (BIST) method to test the TSVs of a 3D IC. The test method aims at identifying single and multiple defective TSVs using low test time with small hardware overhead. Further, we introduce a BIST partitioning scheme to reduce the test time and hardware overhead for many TSVs. We also present EBIST, an extended-BIST, to enhance BIST reliability with the least hardware cost. The time cycle needed for testing is calculated and compared with previously proposed methods. The simulation result shows that the proposed BIST reduces the test time by 87% compared to prior works. Moreover, the approach yields reduced area as compared to existing test architecture.
Syntactic Completeness of Proper Display Calculi
Authors: Chen Jinsheng , Greco Giuseppe , Palmigiano Alessandra , Tzimoulis Apostolos
Published: April 2022

A recent strand of research in structural proof theory aims at exploring the notion of
analytic calculi
(i.e., those calculi that support general and modular proof-strategies for cut elimination) and at identifying classes of logics that can be captured in terms of these calculi. In this context, Wansing introduced the notion of
proper display calculi
as one possible design framework for proof calculi in which the analyticity desiderata are realized in a particularly transparent way. Recently, the theory of
properly displayable
logics (i.e., those logics that can be equivalently presented with some proper display calculus) has been developed in connection with generalized Sahlqvist theory (a.k.a. unified correspondence). Specifically, properly displayable logics have been syntactically characterized as those axiomatized by
analytic inductive axioms
, which can be equivalently and algorithmically transformed into analytic structural rules so the resulting proper display calculi enjoy a set of basic properties: soundness, completeness, conservativity, cut elimination, and the subformula property. In this context, the proof that the given calculus is
complete
w.r.t. the original logic is usually carried out
syntactically
, i.e., by showing that a (cut-free) derivation exists of each given axiom of the logic in the basic system to which the analytic structural rules algorithmically generated from the given axiom have been added. However, so far, this proof strategy for
syntactic completeness
has been implemented on a case-by-case base and not in general. In this article, we address this gap by proving syntactic completeness for properly displayable logics in any normal (distributive) lattice expansion signature. Specifically, we show that for every analytic inductive axiom a cut-free derivation can be effectively generated that has a specific shape, referred to as
pre-normal form
.