bluuebunny/crossref_metadata_2025 huggingface dataset:
The short continuance of friendship amongst the vicious, which is coeval only with mutual satisfaction
Authors: Goldsmith Oliver
Published: February 2022

My son’s account was too long to be delivered at once, the first part of it was begun that night, and he was concluding the rest after dinner the next day, when the appearance of Mr. Thornhill’s equipage at the door seemed to make a pause in the general satisfaction. The butler, who was now become my friend in the family, informed me with a whisper, that the ‘Squire had already made some overtures to Miss Wilmot, and that her aunt and uncle seemed highly to approve the match. Upon Mr. Thornhill’s entering, he seemed, at seeing my son and me, to start back; but I readily imputed that to surprize, and not displeasure. However, upon our advancing to salute him, he returned our greeting with the most apparent candour; and after a short time, his presence served only to encrease the general good humour.
A reformation in the gaol. To make laws complete, they should reward as well as punish
Authors: Goldsmith Oliver
Published: February 2022

The next morning early I was awakened by my family, whom I found in tears at my bed-side. The gloomy strength of every thing about us, it seems, had daunted them. I gently rebuked their sorrow, assuring them I had never slept with greater tranquility, and next enquired after my eldest daughter, who was not among them. They informed me that yesterday’s uneasiness and fatigue had encreased her fever, and it was judged proper to leave her behind. My next care was to send my son to procure a room or two to lodge the family in, as near the prison as conveniently could be found. He obeyed; but could only find one apartment, which was hired at a small expence, for his mother and sisters, the gaoler with humanity consenting to let him and his two little brothers lie in the prison with me. A bed was therefore prepared for them in a corner of the room, which I thought answered very conveniently. I was willing however previously to know whether my little children chose to lie in a place which seemed to fright them upon entrance.
Former benevolence now repaid with unexpected interest
Authors: Goldsmith Oliver
Published: February 2022

Mr. Thornhill made his entrance with a smile, which he seldom wanted, and was going to embrace his uncle, which the other repulsed with an air of disdain. ‘No fawning, Sir, at present,’ cried the Baronet, with a look of severity, ‘the only way to my heart is by the road of honour; but here I only see complicated instances of falsehood, cowardice, and oppression. How is it, Sir, that this poor man, for whom I know you professed a friendship, is used thus hardly? His daughter vilely seduced, as a recompence for his hospitality, and he himself thrown into a prison perhaps but for resenting the insult? His son too, whom you feared to face as a man—’
Mr. Kean’s Shylock
Authors: Hazlitt William
Published: February 2022

Mr. Kean (of whom report had spoken highly) made his appearance at this Theatre in the character of Shylock. For voice, eye, action, and expression, no actor has come out for many years at all equal to him. The applause, from the first scene to the last, was general, loud, and uninterrupted. Indeed, the very first scene in which he comes on with Bassanio and Anthonio, shewed the master in his art, and at once decided the opinion of the audience. Perhaps it was the most perfect of any. Notwithstanding the complete success of Mr. Kean in the part of Shylock, we question whether he will not become a greater favourite in other parts. There was a lightness and vigour in his tread, a buoyancy and elasticity of spirit, a fire and animation, which would accord better with almost any other character than with the morose, sullen, inward, inveterate, inflexible malignity of Shylock. The character of Shylock is that of a man brooding over one idea, that of its wrongs, and bent on one unalterable purpose, that of revenge.
Minor Theatres
Authors: Hazlitt William
Published: February 2022

This is a subject on which we shall treat, with satisfaction to ourselves, and, we hope, to the edification of the reader. Indeed, we are not a little vain of the article we propose to write on this occasion; and we feel the pen in our hands flutter its feathered down with more than its usual specific levity, at the thought of the idle, careless career before it. No Theatre-Royal* oppresses the imagination, and entombs it in a mausoleum of massy pride; no manager’s pompous pretensions choak up the lively current of our blood: no long-announced performance, big with expectation, comes to nothing, and yet compels us gravely to record its failure, and compose its epitaph.
The Fight
Authors: Hazlitt William
Published: February 2022

Where there’s
a will, there’s a way. — I said so to myself, as I walked down Chancery-lane, about half-past six o’clock on Monday the 10th of December, to inquire at Jack Randall’s* where the fight the next day was to be;* and I found ‘the proverb’ nothing ‘musty’* in the present instance. I was determined to see this fight, come what would, and see it I did, in great style. It was my first fight, yet it more than answered my expectations. Ladies! it is to you I dedicate this description; nor let it seem out of character for the fair to notice the exploits of the brave.
On Familiar Style
Authors: Hazlitt William
Published: February 2022

It is not easy to write a familiar style. Many people mistake a familiar for a vulgar style, and suppose that to write without affectation is to write at random. On the contrary, there is nothing that requires more precision, and, if I may so say, purity of expression, than the style I am speaking of. It utterly rejects not only all unmeaning pomp, but all low, cant phrases, and loose, unconnected, slipshod allusions. It is not to take the first word that offers, but the best word in common use; it is not to throw words together in any combinations we please, but to follow and avail ourselves of the true idiom of the language. To write a genuine familiar or truly English style, is to write as any one would speak in common conversation, who had a thorough command and choice of words, or who could discourse with ease, force, and perspicuity, setting aside all pedantic and oratorical flourishes. Or to give another illustration, to write naturally is the same thing in regard to common conversation, as to read naturally is in regard to common speech. It does not follow that it is an easy thing to give the true accent and inflection to the words you utter, because you do not attempt to rise above the level of ordinary life and colloquial speaking.
Lord Byron
Authors: Hazlitt William
Published: February 2022

Lord Byron and Sir Walter Scott are among writers now living1 the two, who would carry away a majority of suffrages as the greatest geniuses of the age. The former would, perhaps, obtain the preference with the fine gentlemen and ladies (squeamishness apart) — the latter with the critics and the vulgar. We shall treat of them in the same connection, partly on account of their distinguished pre-eminence, and partly because they afford a complete contrast to each other. In their poetry, in their prose, in their politics, and in their tempers no two men can be more unlike.
The Shipwreck
Authors: Dickens Charles
Published: February 2022

Never had I seen a year going out, or going on, under quieter circumstances. Eighteen hundred and fifty–nine had but another day to live, and truly its end was Peace* on that sea–shore that morning.
Poor Mercantile Jack
Authors: Dickens Charles
Published: February 2022

Is the sweet little cherub* who sits smiling aloft and keeps watch on the life of Poor Jack, commissioned to take charge of Mercantile Jack, as well as Jack of the national navy? If not, who is? What is the cherub about, and what are we all about, when Poor Mercantile Jack is having his brains slowly knocked out by pennyweights, aboard the brig Beelzebub, or the bark Bowie–knife—when he looks his last at that infernal craft, with the first officer’s iron boot–heel in his remaining eye, or with his dying body towed overboard in the ship’s wake, while the cruel wounds in it do “the multitudinous seas incarnadine”?*
The Great Tasmania's Cargo
Authors: Dickens Charles
Published: February 2022

I travel constantly, up and down a certain line of railway that has a terminus in London. It is the railway for a large military depôt, and for other large barracks.* To the best of my serious belief, I have never been on that railway by daylight, without seeing some handcuffed deserters in the train.
Shy Neighbourhoods
Authors: Dickens Charles
Published: February 2022

So much of my travelling is done on foot, that if I cherished betting propensities, I should probably be found registered in sporting newspapers under some such title as the Elastic Novice, challenging all eleven–stone mankind to competition in walking. My last special feat was turning out of bed at two, after a hard day, pedestrian and otherwise, and walking thirty miles into the country to breakfast. The road was so lonely in the night, that I fell asleep to the monotonous sound of my own feet, doing their regular four miles an hour. Mile after mile I walked, without the slightest sense of exertion, dozing heavily and dreaming constantly. It was only when I made a stumble like a drunken man, or struck out into the road to avoid a horseman close upon me on the path—who had no existence—that I came to myself and looked about.
Night Walks
Authors: Dickens Charles
Published: February 2022

some years ago, a temporary inability to sleep, referable to a distressing impression, caused me to walk about the streets all night, for a series of several nights. The disorder might have taken a long time to conquer, if it had been faintly experimented on in bed; but it was soon defeated by the brisk treatment of getting up directly after lying down, and going out, and coming home tired at sunrise.
The Calais Night Mail
Authors: Dickens Charles
Published: February 2022

It is an unsettled question with me whether I shall leave Calais something handsome in my will, or whether I shall leave it my malediction. I hate it so much, and yet I am always so very glad to see it, that I am in a state of constant indecision on this subject.
Some Recollections of Mortality
Authors: Dickens Charles
Published: February 2022

I had parted from the small bird at somewhere about four o’clock in the morning, when he had got out at Arras, and had been received by two shovel-hats in waiting at the station, who presented an appropriately ornithological and crow-like appearance. My compatriot and I had gone on to Paris; my compatriot enlightening me occasionally with a long list of the enormous grievances of French railway travelling: every one of which, as I am a sinner, was perfectly new to me, though I have as much experience of French railways as most uncommercials.
Birthday Celebrations
Authors: Dickens Charles
Published: February 2022

It came into my mind that I would recal in these notes a few of the many hostelries I have rested at in the course of my journeys; and, indeed, I had taken up my pen for the purpose, when I was baffled by an accidental circumstance. It was the having to leave off, to wish the owner of a certain bright face that looked in at my door, “many happy returns of the day.” Thereupon a new thought came into my mind, driving its predecessor out, and I began to recal—instead of Inns—the birthdays that I have put up at, on my way to this present sheet of paper.
The Boiled Beef Of New England
Authors: Dickens Charles
Published: February 2022

The shabbiness of our English capital, as compared with Paris, Bordeaux, Frankfort, Milan, Geneva—almost any important town on the continent of Europe—I find very striking after an absence of any duration in foreign parts. London is shabby in contrast with Edinburgh, with Aberdeen, with Exeter, with Liverpool, with a bright little town like Bury St. Edmunds. London is shabby in contrast with New York, with Boston, with Philadelphia. In detail, one would say it can rarely fail to be a disappointing piece of shabbiness, to a stranger from any of those places. There is nothing shabbier than Drury-lane, in Rome itself. The meanness of Regent-street, set against the great line of Boulevarts in Paris, is as striking as the abortive ugliness of Trafalgar-square, set against the gallant beauty of the Place de la Concorde.
In The French-Flemish Country
Authors: Dickens Charles
Published: February 2022

“It is neither a bold nor a diversified country,” said I to myself, “this country which is three–quarters Flemish, and a quarter French; yet it has its attractions too. Though great lines of railway traverse it, the trains leave it behind, and go puffing off to Paris and the South, to Belgium and Germany, to the Northern Sea–Coast of France, and to England, and merely smoke it a little in passing. Then I don’t know it, and that is a good reason for being here: and I can’t pronounce half the long queer names I see inscribed over the shops, and that is another good reason for being here, since I surely ought to learn how.” In short, I was “here,” and I wanted an excuse for not going away from here, and I made it to my satisfaction, and stayed here.
Educating Future Police Professionals Amid Covid-19 a UAE Perspective
Authors: Davies Amanda , Al Sharefeen Rami
Published: February 2022

In 2020, as the world focused efforts to address the humanitarian challenges presented by the Covid-19 pandemic, the global education community was similarly challenged to demonstrate resilience and innovation to support a level of ‘normality’ for students at all levels and professions. The research presented in this article offers insight into the preparation and deployment of transitioning education of police students from face-to-face delivery to online delivery in an environment historically unfamiliar with online learning delivery. The results indicate the critical attention placed on the preparation for transition beyond only subject matter delivery, for both students and faculty was pivotal in the resultant positive student learning outcomes. The approach to transitioning to the online learning delivery environment, the early trending data for which indicate minimal impact on achievement of learning for students, contributes to the decision making for education institutions centred on developing resilience professionals such as police officers.
Enhancing the policing response to COVID-19 with media engagement: The United Arab Emirates experience
Authors: Alam Edris
Published: February 2022

Global evaluations of response to the COVID-19 pandemic, the Global Clinical Practice (a network of 12,942 clinicians from 151 countries), and the Global Response to Infections Disease have consistently rated the United Arab Emirates (UAE) as one of the most effective medical responses to the COVID-19 pandemic. In parallel, according to the 2020 Edelman Trust Barometer, public trust in the UAE government is 81%—a leading score in the Middle East. While widespread miscommunication rumours, and lack of coordination was observed in the early phases of COVID-19 globally, the UAE case demonstrates a comprehensive positive approach and experience. The research reported in this paper aimed to understand the role of media in the police response in relation to COVID-19 risk management in the UAE. Content analysis of documentary and data sources was conducted from public COVID-19-related meta-data sources. The findings suggest pre-defined conducive legislative and institutional structure, professionalism of media and police, and collaborative approaches among implementing agencies contributed to the success of the early phase COVID-19 risk management in the UAE. This research contributes to the body of knowledge in pandemic and infodemic risk management through analysis of the UAE experience.
The Marketing Capability Premium
Authors: Ang Tze Chuan (Chewie) , Chordia Tarun , Mai Vivian Van-Anh , Singh Harminder
Published: February 2022

Marketing capability refers to a firm’s ability to optimally deploy and integrate different marketing inputs to achieve high sales at low cost. This paper examines whether the value of marketing capability is incorporated into stock returns. High-level marketing capability predicts better future operating performance and stock returns. A marketing capability-based long-short portfolio strategy earns an average annual return of 5.16%, a substantial portion of which is earned over subsequent earnings announcements. The return predictability is stronger in stocks with higher valuation uncertainty and lower investor attention. Investors underreact to the value-relevant, but difficult to process, information embedded in marketing capability. (JEL G12, G14, G10, M30)

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Preparation of multigradient hydroxyapatite scaffolds and evaluation of their osteoinduction properties
Authors: Huang Hao , Yang Anchun , Li Jinsheng , Sun Tong , Yu Shangke , Lu Xiong , Guo Tailin , Duan Ke , Zheng Pengfei , Weng Jie
Published: February 2022

Porous hydroxyapatite (HA) scaffolds are often used as bone repair materials, owing to their good biocompatibility, osteoconductivity and low cost. Vascularization and osteoinductivity of porous HA scaffolds were limited in clinical application, and these disadvantages were need to be improved urgently. We used water-in-oil gelation and pore former methods to prepare HA spheres and a porous cylindrical HA container, respectively. The prepared HA spheres were filled in container to assemble into composite scaffold. By adjusting the solid content of the slurry (solid mixture of chitin sol and HA powder) and the sintering temperature, the porosity and crystallinity of the HA spheres could be significantly improved; and mineralization of the HA spheres significantly improved the biological activity of the composite scaffold. The multigradient (porosity, crystallinity and mineralization) scaffold (HA-700) filled with the mineralized HA spheres exhibited a lower compressive strength; however, in vivo results showed that their vascularization ability were higher than those of other groups, and their osteogenic Gini index (Go: an index of bone mass, and inversely proportional to bone mass) showed a continuous decrease with the implantation time. This study provides a new method to improve porous HA scaffolds and meet the demands of bone tissue engineering applications.
Central Oxidative Stress and Early Vocational Outcomes in First Episode Psychosis: A 7-Tesla Magnetic Resonance Spectroscopy Study of Glutathione
Authors: MacKinley Michael , Ford Sabrina D , Jeon Peter , Théberge Jean , Palaniyappan Lena
Published: February 2022

Background and hypothesis

Following the first episode of psychosis, some patients develop poor social and occupational outcomes, while others display a pattern of preserved functioning. Evidence from preclinical, genetic, and biochemical studies suggest a role for high oxidative stress in poor functional outcomes among patients. The measurement of intracortical glutathione (GSH) using magnetic resonance spectroscopy (MRS) enables investigating the relationship between central antioxidant tone and functional outcomes at the time of first-episode psychosis (FEP). We hypothesized that patients with higher central antioxidant tone at first presentation will have better functional outcomes in early stages of illness.

Study design

We scanned 57 patients with FEP and 30 matched healthy controls and estimated GSH resonance using 7-Tesla MRS. We minimized the confounding effects of illness chronicity, long-term treatment exposure, and metabolic complications by recruiting patients with <2 weeks of lifetime antipsychotic exposure on average and followed up this cohort for the next 1 year to determine functional outcomes.

Study results

Patients who achieved employment/education or training status (EET) in the first year, had higher GSH at the baseline than healthy controls. Social and occupational functioning assessment scale (SOFAS) scores were also significantly higher in patients with higher GSH levels at the outset, after adjusting for various confounds including baseline SOFAS. Patients who were not in EET did not differ from healthy subjects in their GSH levels.

Conclusion

Our observations support a key role for the central antioxidant tone in the functional outcomes of early psychosis.
Diversification and species limits in scale-backed antbirds (Willisornis: Thamnophilidae), an Amazonian endemic lineage
Authors: Quaresma Tânia Fontes , Cronemberger Áurea A , Batista Romina , Aleixo Alexandre
Published: February 2022

The genus Willisornis is endemic to the Amazon Basin, inhabiting upland terra firme forest, with two species and seven subspecies currently recognized. Despite numerous systematic studies, a taxonomically-dense sampled phylogeny for Willisornis is still lacking, which, combined with evidence of paraphyly and gene flow between its recognized species, underscores the uncertainty concerning species limits and evolutionary history of the genus. Here we present phylogenies and population genetic analyses, including all currently recognized Willisornis taxa, relating them to patterns of plumage variation, and reconstructing the spatiotemporal context of diversification in the genus. Our analyses have uncovered 13 independent genetic lineages in the genus, and the monophyly of all currently named taxa, which also showed robust plumage diagnoses. However, deeply coalesced genetic lineages were also found within most Willisornis taxa, for which no consistent variation in plumage was found. The diversification of the genus Willisornis is related to hydrographic and climate change cycles across Amazonia since the Plio-Pleistocene, with most genetic lineages originating in the past one million years. Based on our findings, we recommend the recognition of a total of six species in Willisornis (one of which polytypic) based on the congruency between deeply coalesced lineages and consistent plumage diagnoses.
A new lineage of deep-reef gobies from the Caribbean, including two new species and one new genus (Teleostei: Gobiidae: Gobiosomatini)
Authors: Tornabene Luke , Manning Rachel , Robertson D Ross , Van Tassell James L , Baldwin Carole C
Published: February 2022

Fish communities on tropical deep reefs are dominated by species that belong to families primarily composed of shallow-water species. Collections of deep-reef fishes via submersibles have allowed us to include these deep-reef species in molecular phylogenies, providing insights into the timing and frequency of invasions from shallow to deep reefs. Here we provide evidence of a new deep-reef invasion in the tribe Gobiosomatini in the family Gobiidae (gobies). We describe two new species, one of which belongs to a new genus, and incorporate these taxa into a time-calibrated molecular phylogeny of Gobiosomatini to show that, collectively, these two genera represent a previously unreported independent invasion on to deep reefs that occurred approximately 20–30 million years ago. These new taxa are readily distinguished from related genera and species by a combination of live coloration, pelvic-fin morphology, meristic characters, head-pore patterns and other osteological characters. We discuss the relevance of these two new species to the systematics of the tribe Gobiosomatini and include a comparison to all known genera in the tribe.
mRNA Decapping Factors LSM1 and PAT Paralogs Are Involved in Turnip Mosaic Virus Viral Infection
Authors: Zuo Zhangli , Roux Milena , Rodriguez Eleazar , Petersen Morten
Published: February 2022

Turnip mosaic virus is a devastating potyvirus infecting many economically important brassica crops. In response to this, the plant host engages its RNA silencing machinery, involving AGO proteins, as a prominent strategy to restrain turnip mosaic virus (TuMV) infection. It has also been shown that the mRNA decay components DCP2 and VCS partake in viral infection suppression. Here, we report that the mRNA decapping components LSM1, PAT1, PATH1, and PATH2 are essential for TuMV infection. More specifically, lsm1a/lsm1b double mutants and pat1/path1/path2 triple mutants in summ2 background exhibit resistance to TuMV. Concurrently, we observed that TuMV interferes with the decapping function of LSM1 and PAT proteins as the mRNA-decay target genes UGT87A2 and ASL9 accumulate during TuMV infection. Moreover, as TuMV coat protein can be specifically found in complexes with PAT proteins but not LSM1, this suggests that TuMV “hijacks” decapping components via PAT proteins to support viral infection.

[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Multivariate analysis of the predictive value of asymmetric skin creases in diagnosis of decentralized developmental dysplasia of the hip
Authors: Sevencan Ahmet , Ucpunar Hanifi , Ozyalvac Osman Nuri , Akpinar Evren , Bayhan Avni Ilhan , Yildirim Timur
Published: February 2022

The aim of this study was to investigate the relationship of developmental dysplasia of the hip (DDH) with asymmetrical skin crease (ASC) in the inguinal, gluteal and thigh regions and to determine which ASC has the most predictive value for the diagnosis of hip dislocation in infants. This study was planned as a prospective, observational study and conducted between 1 October 2020 and 1 June 2021. Asymmetric distribution of skin creases was evaluated separately in three regions (inguinal, gluteal and thigh). Then, hip ultrasonography (USG) was performed and the Graf method was used to classify the cases as ‘centralized’ [Graf types I, IIa (-), IIb and IIc] and ‘decentralized’ (Graf types IId, III and IV). The relationship between the groups was evaluated using univariate and then multivariate analyses. A total of 241 patients were included in the study. The number of patients with ASC was 49 (21%). While 36 of these 49 patients had centralized hips, 13 had decentralized hips (P < 0.001). Sixty-five percent (13/20) of 20 infants with decentralized hips had ASC in at least one of the inguinal, gluteal or thigh regions. The presence of ASC in the inguinal (P < 0.001) and gluteal (P < 0.014) regions increased the risk of the decentralized hip in the child, whereas the presence of ASC in the isolated thigh region did not increase the risk of the dislocated hip (P = 0.534). Inguinal ASC and gluteal ASC are reliable findings in DDH screening, but the relationship of isolated thigh ASC with DDH could not be demonstrated statistically. Level of Evidence: Level II – diagnostic study.
Association of Histamine-2 Blockers and Proton-Pump Inhibitors With Delirium Development in Critically Ill Adults: A Retrospective Cohort Study
Authors: Shiddapur Ami , Kistler Christine E. , Busby-Whitehead Jan , Austin C. Adrian
Published: February 2022

OBJECTIVES:

Histamine-2 receptor antagonists are commonly administered for stress ulcer prophylaxis in critically ill adults and may be associated with delirium development. We aimed to determine differential associations of histamine-2 receptor antagonist or proton-pump inhibitor administration with delirium development in patients admitted to a medical ICU.

DESIGN:

Retrospective observational study using a deidentified database sourced from the University of North Carolina Health Care system. Participants were identified as having delirium utilizing an International Classification of Diseases-based algorithm. Associations among histamine-2 receptor antagonist, proton-pump inhibitor, or no medication administration and delirium were identified using relative risk. Multiple logistic regression was used to control for potential confounders including mechanical ventilation and age.

SETTING:

Academic tertiary care medical ICU in the United States.

PATIENTS:

Adults admitted to the University of North Carolina medical ICU from January 2015 to December 2019, excluding those on concurrent histamine-2 receptor antagonists and proton-pump inhibitors in the same encounter.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We identified 6,645 critically ill patients, of whom 29% (n = 1,899) received mechanical ventilation, 45% (n = 3,022) were 65 or older, and 22% (n = 1,487) died during their medical ICU encounter. Of the 6,645 patients, 31% (n = 2,057) received an histamine-2 receptor antagonist and no proton-pump inhibitors, 40% (n = 2,648) received a proton-pump inhibitor and no histamine-2 receptor antagonists, and 46% (n = 3,076) had delirium. The histamine-2 receptor antagonist group had a greater association with delirium than the proton-pump inhibitor group compared with controls receiving neither medication, after controlling for mechanical ventilation and age (risk ratio, 1.36; 1.25–1.47; p < 0.001) and (risk ratio, 1.15; 1.07–1.24; p < 0.001, respectively).

CONCLUSIONS:

Histamine-2 receptor antagonists are more strongly associated with increased delirium than proton-pump inhibitors. Prospective studies are necessary to further elucidate this association and to determine if replacement of histamine-2 receptor antagonists with proton-pump inhibitors in ICUs decreases the burden of delirium in critically ill patients.
PHarmacist Avoidance or Reductions in Medical Costs in CRITically Ill Adults: PHARM-CRIT Study
Authors: Rech Megan A. , Gurnani Payal K. , Peppard William J. , Smetana Keaton S. , Van Berkel Megan A. , Hammond Drayton A. , Flannery Alexander H. ,   For PHARM-CRIT Investigators, on behalf of the Society of Critical Care Medicine Clinical Pharmacy and Pharmacology Section and endorsed by the Discovery Network
Published: February 2022

OBJECTIVES:

To comprehensively classify interventions performed by ICU clinical pharmacists and quantify cost avoidance generated through their accepted interventions.

DESIGN:

A multicenter, prospective, observational study was performed between August 2018 and January 2019.

SETTING:

Community hospitals and academic medical centers in the United States.

PARTICIPANTS:

ICU clinical pharmacists.

INTERVENTIONS:

Recommendations classified into one of 38 intervention categories (divided into six unique sections) associated with cost avoidance.

MEASUREMENTS AND MAIN RESULTS:

Two-hundred fifteen ICU pharmacists at 85 centers performed 55,926 interventions during 3,148 shifts that were accepted on 27,681 adult patient days and generated $23,404,089 of cost avoidance. The quantity of accepted interventions and cost avoidance generated in six established sections was adverse drug event prevention (5,777 interventions; $5,822,539 CA), resource utilization (12,630 interventions; $4,491,318), individualization of patient care (29,284 interventions; $9,680,036 cost avoidance), prophylaxis (1,639 interventions; $1,414,465 cost avoidance), hands-on care (1,828 interventions; $1,339,621 cost avoidance), and administrative/supportive tasks (4,768 interventions; $656,110 cost avoidance). Mean cost avoidance was $418 per intervention, $845 per patient day, and $7,435 per ICU pharmacist shift. The annualized cost avoidance from an ICU pharmacist is $1,784,302. The potential monetary cost avoidance to pharmacist salary ratio was between $3.3:1 and $9.6:1.

CONCLUSIONS:

Pharmacist involvement in the care of critically ill patients results in significant avoidance of healthcare costs, particularly in the areas of individualization of patient care, adverse drug event prevention, and resource utilization. The potential monetary cost avoidance to pharmacist salary ratio employing an ICU clinical pharmacist is between $3.3:1 and $9.6:1.
Inflammation and Conception in a Prospective Time-to-Pregnancy Cohort
Authors: Jukic Anne Marie Z. , Weinberg Clarice R. , Mumford Sunni L. , Steiner Anne Z.
Published: February 2022

Background:

Inflammation may contribute to subfertility but this has not been well-explored in large prospective cohort studies.

Methods:

We conducted a prospective 12-month cohort study of time to pregnancy in North Carolina, the Time to Conceive study (2010–2016). Participants were 30–44 years old, without a history of infertility (N = 727). We analyzed blood samples with a high sensitivity assay for C-reactive protein (CRP). Women reported their weight, height, and other covariates. We natural log-transformed CRP and examined it (1) linearly, after exploration using restricted cubic splines and (2) in categories based on American Heart Association criteria. We estimated fecundability ratios (FRs) with log-binomial discrete-time-to-pregnancy models. Separate models included an interaction term with body mass index (BMI).

Results:

The adjusted estimated FR per natural log-unit increase in CRP level was 0.97 (confidence interval [CI] = 0.91, 1.0). The FR (CI) for high CRP (>10 mg/L) compared with low CRP (<1 mg/L) was 0.78 (0.52, 1.2). Compared with normal-weight women with low CRP, women with obesity and high CRP had lower estimated fecundability, but the confidence interval was wide (FR = 0.63; CI = 0.35, 1.1). There was no pattern in the estimated fecundability across levels of CRP within categories of BMI.

Conclusions:

There was no evidence of an association between CRP and fecundability either alone or within levels of BMI. Further studies of CRP and fecundability should include higher levels of CRP and additional markers of inflammation.
Declining serum bone turnover markers are associated with the short-term positive change of lumbar spine bone mineral density in postmenopausal women
Authors: Zhao Shengli , Mo Xiaoyi , Wen Zhenxing , Liu Ming , Chen Zhipeng , Lin Wei , Huang Zifang , Chen Bailing
Published: February 2022

Objective:

While serum bone turnover markers (BTMs) and bone mineral density (BMD) have been confirmed as useable risk assessment tools for postmenopausal osteoporosis, the associations between BTMs and BMD changes are still ambiguous. The aim of this study was to explore the underlying associations between BTMs and BMD changes in postmenopausal women.

Methods:

Between January 2015 and October 2020, 135 postmenopausal women were retrospectively enrolled. They were divided into two groups according to lumbar spine (LS) 1-4 BMD change (1 y T-score minus baseline T-score, Group 1 [n = 36] < 0 and Group 2 [n = 99] ≥ 0). The changes of BTMs (N-terminal middle segment osteocalcin [N-MID], propeptide of type I procollagen [P1NP], and β-C-terminal telopeptide of type I collagen [β-CTX]) and their associations with LS 1-4 BMD change were analyzed. The biochemical indices and clinical parameters related with LS 1-4 BMD change were also evaluated.

Results:

The 1 year N-MID, P1NP, β-CTX and Phosphorus in Group 2 were lower than those in Group 1 (P < 0.05), their changes within 1 year were significantly negatively correlated with LS 1-4 BMD change (R
2 = –0.200, P < 0.001; R
2 = –0.230, P < 0.001; R
2 = –0.186, P < 0.001; R
2 = –0.044, P = 0.015; respectively). Except for the Phosphorus change (area under the curve [AUC] = 0.623), the changes of N-MID, P1NP, and β-CTX and their 1 year levels had similar AUC to diagnose the short-term LS 1-4 BMD change (AUC > 0.7 for all, with the AUC of 1 y P1NP being the largest at 0.803). Binary logistic regression analysis showed that the physical activity and drug intervention were the determinant factors for the LS 1-4 BMD change (odds ratio = 6.856, 95% confidence interval: 2.058-22.839, P = 0.002; odds ratio  = 5.114, 95% confidence interval: 1.551-16.864, P = 0.007; respectively).

Conclusions:

Declining N-MID, P1NP, β-CTX, and Phosphorus are associated with the short-term increase of LS 1-4 BMD within 1 year. Physical activity and drug intervention are factors significantly influencing the change of LS 1-4 BMD in postmenopausal women.
A 16-week multicomponent exercise training program improves menopause-related symptoms in middle-aged women. The FLAMENCO project randomized control trial
Authors: Baena-García Laura , Flor-Alemany Marta , Marín-Jiménez Nuria , Aranda Pilar , Aparicio Virginia A.
Published: February 2022

Objective:

To investigate the influence of a supervised multicomponent exercise training program on menopause-related symptoms, particularly vasomotor symptoms (VMS), in middle-aged women.

Methods:

A total of 112 middle-aged women (mean age 52 ± 4 y old, age range 45-60 y) from the FLAMENCO project (exercise [n = 59] and counseling [n = 53] groups) participated in this randomized controlled trial (perprotocol basis). The exercise group followed a multicomponent exercise program composed of 60-minute sessions 3 days per week for 16 weeks. The 15-item Cervantes Menopause and Health Subscale was used to assess the frequency of menopause-related symptoms.

Results:

After adjusting for body mass index and Mediterranean diet adherence, the subscales measuring menopause-related symptoms and VMSs decreased 4.6 more in the exercise group compared to the counseling group (between-group differences [B]: 95% CI: -8.8 to -0.2; P 
= 0.040). The exercise group also showed significant improvements in the subscales of couple relationships (between-group differences [B]: -1.87: 95% CI: -3.29 to - 0.45; P 
= 0.010), psychological state (between-group differences [B]: -2.3: 95% CI: -5 to -0.2; P 
= 0.035), and VMSs (between-group differences [B]: -4.5: 95% CI: -8.8 to -0.2; p 
= 0.040) in the Cervantes Menopause and Health Subscale compared with the counseling group.

Conclusions:

A 16-week multicomponent physical exercise program showed a positive effect on menopause- related symptoms especially in couple relationships, psychological state, and VMS, among 45 to 60 year old women.
Association of urinary angiotensinogen with renal arteriolar remodeling in chronic kidney disease
Authors: Kanamitsu Takafumi , Kohagura Kentaro , Zamami Ryo , Nakamura Takuto , Oshiro Nanako , Miyagi Tsuyoshi , Nakamura Koshi , Ohya Yusuke
Published: February 2022

Objective:

Renin–angiotensin system (RAS) might be associated with arteriolar remodeling. The present study aimed to explore the hitherto unknown relationship between renal RAS and renal arteriolar remodeling and to elucidate whether altered renal RAS subsequently affects renal function in patients with chronic kidney disease (CKD).

Methods:

In this retrospective study, patients with various CKDs not using RAS inhibitors who underwent renal biopsy were included in cross-sectional and longitudinal analyses. Urinary angiotensinogen (UAGT) levels and wall/lumen ratio (WLR) were determined to evaluate renal RAS and renal arteriolar remodeling, respectively. The association between ln(UAGT) and ln(WLR) was cross-sectionally examined using a liner regression model. Furthermore, the association of ln(UAGT) with subsequent changes in estimated glomerular filtration rate (eGFR) per year were longitudinally examined in the largest subgroup of patients who were diagnosed with IgA nephropathy.

Results:

In the overall cohort (n = 54), the median age, blood pressures, eGFR, and WLR were 37 years, 120/73 mmHg, 85 ml/min per 1.73 m2, and 0.93, respectively. Ln(UAGT) was significantly and positively associated with ln(WLR) even after adjusting for classical and nonclassical clinical renal risk factors. In patients with IgA nephropathy, higher ln(UAGT) was associated with higher ln(WLR). Ln(UAGT) also tended to be associated with a greater decline in eGFR per year over a median period of 8.7 years, even after adjusting for potential confounding factors.

Conclusion:

In patients with CKD, renal RAS might be associated with renal arteriolar remodeling and future decline in eGFR, independent of potential risk factors.
Stage 1 hypertension and risk of cardiovascular disease mortality in United States adults with or without diabetes
Authors: Wang Yutang
Published: February 2022

Objective:

This study aimed to investigate the association of S1 hypertension, classified according to the 2017 American College of Cardiology/American Heart Association blood pressure (BP) guideline, with cardiovascular disease (CVD) mortality in adults with or without diabetes from the general United States population.

Methods:

This cohort study included 40 518 United States adults (including 3555 with diabetes) naive to antihypertensive drugs who attended the National Health and Nutrition Examination Surveys from 1988 to 2014.

Results:

Participants were followed up for 489 679 person-years (mean follow-up, 12.1 years) with 1569 CVD deaths being recorded. S1 hypertension was neither associated with an increased CVD mortality risk in the whole cohort nor in participants with or without diabetes after full adjustment. In age-stratified analyses, compared with normal BP, S1 hypertension was associated with increased CVD mortality in young adults, unrelated to CVD mortality in midlife, and associated with lower CVD mortality in the elderly. In older participants (≥70 years), people with S1 hypertension had a 23% lower multivariate-adjusted CVD mortality risk compared with those with normal BP (hazard ratio 0.77; 95% confidence interval 0.61–0.98). In younger (<70 years) adults without diabetes, people with normal BP had the lowest CVD mortality risk; however, in younger adults with diabetes, it was people with elevated BP who had the lowest CVD mortality risk.

Conclusion:

In this representative sample of United States adults not on BP-lowering medications, S1 hypertension was associated with elevated CVD mortality in younger adults and with lower CVD mortality in those 70 or more years of age.
AXL Inhibition Represents a Novel Therapeutic Approach in BCR-ABL Negative Myeloproliferative Neoplasms
Authors: Beitzen-Heineke Antonia , Berenbrok Nikolaus , Waizenegger Jonas , Paesler Sarina , Gensch Victoria , Udonta Florian , Vargas Delgado Maria Elena , Engelmann Janik , Hoffmann Friederike , Schafhausen Philippe , von Amsberg Gunhild , Riecken Kristoffer , Beumer Niklas , Imbusch Charles D. , Lorens James , Fischer Thomas , Pantel Klaus , Bokemeyer Carsten , Ben-Batalla Isabel , Loges Sonja
Published: February 2022

BCR-ABL negative myeloproliferative neoplasms (MPNs) consist of essential thrombocythemia, polycythemia vera, and myelofibrosis. The majority of patients harbor the JAK2-activating mutation V617F. JAK2 inhibitors were shown to reduce symptom burden and splenomegaly in MPN patients. However, treatment options are limited after failure of JAK2 inhibitors. AXL, a member of the TAM family of receptor tyrosine kinases, mediates survival and therapy resistance of different myeloid cancers including acute myeloid leukemia and chronic myeloid leukemia. We studied the relevance of AXL as a target in MPN using primary patient cells and preclinical disease models. We found that AXL is abundantly activated in MPN cells and that its ligand growth arrest-specific gene 6 is upregulated in MPN patients. Pharmacologic and genetic blockade of AXL impaired viability, decreased proliferation and increased apoptosis of MPN cells. Interestingly, ruxolitinib treatment induced increased phosphorylation of AXL indicating that activation of AXL might mediate resistance to ruxolitinib. Consistently, the AXL inhibitor bemcentinib exerted additive effects with ruxolitinib via impaired STAT3, STAT5, and AKT signaling. Both agents had activity when employed alone and exerted an additive effect on survival and splenomegaly in vivo. Moreover, bemcentinib treatment normalized red blood cell count and hemoglobin levels in vivo. Thus, our data indicate that AXL inhibition represents a novel treatment option in MPN warranting clinical investigation.
Restoration of Tc-99m methyl diphosphonate bone scan image using Richardson–Lucy algorithm
Authors: Pandey Anil Kumar , Sonker Damini , Chaudhary Jagrati , Jaleel Jasim , Baghel Vivek , Sharma Param D. , Patel Chetan , Kumar Rakesh
Published: February 2022

Introduction

In this study, the optimal input parameters point spread function (PSF) and the number of iterations of the Richardson–Lucy algorithm were experimentally determined to restore Tc-99 m methyl diphosphonate (MDP) whole-body bone scan images.

Materials and methods

The experiment was performed on 60 anonymized Tc-99 m MDP whole-body bone scan images. Ten images were used for estimating the optimum value of PSF and the number of iterations to restore scintigraphic images. The remaining 50 images were used for validation of estimated parameters. The image quality of observed and restored images was assessed objectively using blind/referenceless image spatial quality evaluator (BRISQUE), mean brightness (MB), discrete entropy (DE), and edge-based contrast measure (EBCM) image quality metrics. Image quality was subjectively assessed by two nuclear medicine physicians (NMPs) by comparing the restored image quality with observed image quality and assigning a score to each image on the scale of 0–5.

Results

Based on BRISQUE, MB, DE, and EBCM scores, the restored images were significantly sharper, less bright, had more detailed information, and had less contrast around edges compared to the input images. The restored images had improved resolution based on visual assessment as well; NMPs assigned an average image quality score of 4.00 to restored images. Maximum resolution enhancement was noticed at PSF (size: 11 pixels, sigma: 1.75 pixels) and the number of iterations = 10. With the increase in the number of iterations, noise also gets amplified along with resolution enhancement and affects the detectability of small lesions; in the case of relatively low noisy input images, the number of iterations = 5 gave better results.

Conclusion

Tc-99 m MDP bone scan images were restored to improve image quality using the Richardson–Lucy algorithm. The optimum value of the PSF parameter was found to be of size = 11 pixels and sigma = 1.75 pixels.
Biomarkers of rejection in liver transplantation
Authors: Perottino Giovanni , Harrington Claire , Levitsky Josh
Published: February 2022

Purpose of review

Liver transplantation is a lifesaving therapy for thousands of individuals with end-stage liver disease across the world. Allograft rejection, which is traditionally detected through an invasive graft biopsy, is a major complication for liver transplant recipients in the postoperative period. Biomarkers represent a relatively newer and safer means of detecting and predicting transplant rejection when compared with the current standard of care: liver biopsy. This review serves to compile recent progress in the field of biomarker discovery in liver allograft rejection.

Recent findings

Several promising biomarkers exist in the field of liver transplant rejection. Recent developments include blood genomic assays measuring miRNA, mRNA and donor-derived cell-free DNA. Additionally, serum levels of cytokines, proteoforms, donor-specific antibodies and immunophenotyping have shown promising results in predicting rejection pre and/or posttransplant.

Biomarkers represent a novel method of predicting the risk of developing allograft rejection. The findings discussed in the studies outlined in this review are promising in the potential to improve patient management, reduce complications from over- or under-immunosuppression, and ultimately enhance outcomes.