bluuebunny/crossref_metadata_2025 huggingface dataset:
Today and Tomorrow in Ireland
Authors: Joyce James
Published: June 2023

In this book, the latest addition to the already formidable mass of modern Anglo-Irish literature, Mr Gwynn has collected ten essays from various reviews and journals, essays differing widely in interest, but for all of which he would claim a unity of subject. All the...
A Suave Philosophy
Authors: Joyce James
Published: June 2023

In this book one reads about a people whose life is ordered according to beliefs and sympathies which will seem strange to us. The writer has very properly begun his account of that life by a brief exposition of Buddhism, and he sets forth so...
Colonial Verses
Authors: Joyce James
Published: June 2023

These are colonial verses. The colonial Esau is asked on page 3 would he change his pottage for Jacob’s birthright—a question which evidently expects the answer, No.1 One piece is named ‘Is Canada Loyal?’ and Mr Wolley proclaims that it is loyal. His...
The Soul of Ireland
Authors: Joyce James
Published: June 2023

Aristotle finds at the beginning of all speculation the feeling of wonder,1 a feeling proper to childhood, and if speculation be proper to the middle period of life it is natural that one should look to the crowning period of life for the...
The Motor Derby
Authors: Joyce James
Published: June 2023

Interview with the French Champion

(from a correspondent)

Paris, Sunday.

In the Rue d’ Anjou, not far from the Church of the Madeleine, is M. Henri Fournier’s place of business. ‘Paris-Automobile’—a company of which M. Fournier is the manager—has its headquarters there. Inside the gateway...
New Fiction
Authors: Joyce James
Published: June 2023

This little volume is a collection of stories dealing chiefly with Indian life. The reader will find the first five stories—the adventures of Prince Aga Mirza—the most entertaining part of the book, if he is to any extent interested in tales of Indian magic. The...
A French Religious Novel
Authors: Joyce James
Published: June 2023

This novel, reprinted from the pages of one of the leading French reviews, and now very successfully translated into English, seems to have attracted more attention in London than in Paris. It deals with the problem of an uncompromising orthodoxy, beset by a peculiarly modern,...
Humanism
Authors: Joyce James
Published: June 2023

Barbarism, says Professor Schiller, may show itself in philosophy in two guises, as barbarism of style and as barbarism of temper, and what is opposed to barbarism is Professor Schiller’s philosophical creed: Humanism, or, as he sometimes names it, Pragmatism.1 One, therefore, who...
Shakespeare Explained
Authors: Joyce James
Published: June 2023

In a short prefatory note the writer of this book states that he has not written it for Shakespearian scholars, who are well provided with volumes of research and criticism, but has sought to render the eight plays more interesting and intelligible to the general...
Empire-Building
Authors: Joyce James
Published: June 2023

Empire-building does not appear to be as successful in Northern, as it has been in Southern, Africa. While his cousins are astonishing the Parisian public by excursions in the air M Jacques Lebaudy, the new Emperor of the Sahara, is preparing to venture into the...
Ireland: Island of Saints and Sages
Authors: Joyce James
Published: June 2023

Nations, like individuals, have their egos.1 It is not unusual for a race to wish to attribute to itself qualities or glories unknown in other races—from the time when our forefathers called themselves Aryans and nobles to the Greeks who were wont to...
Home Rule Comes of Age
Authors: Joyce James
Published: June 2023

Twenty-one years ago, on the evening of 9 April 1886,1 the laneway leading to the offices of the nationalist newspaper of Dublin was crammed with people. From time to time a bulletin printed in block letters appeared on the wall and in this...
Oscar Wilde: the Poet of ‘Salomé’
Authors: Joyce James
Published: June 2023

Oscar Fingal O’Flahertie Wills Wilde. Such were the high-sounding titles that with juvenile vanity he wanted to have printed on the titlepage of his first collection of poetry.1 By this vain gesture which he believed would lend him dignity, he sculpted, perhaps symbolically,...
Realism and Idealism in English Literature (Daniel Defoe—William Blake)
Authors: Joyce James
Published: June 2023

Daniel Defoe1 (I)

In the year of grace, 1660, the exiled, fugitive, and dispossessed Charles Stuart landed on English soil at Dover and, escorted by the fanfare and torches of a jubilant people, headed towards the capital to assume the crown that his father,...
The Universal Literary Influence of the Renaissance
Authors: Joyce James
Published: June 2023

The doctrine of evolution in the light of which our civilization basks teaches us that when we were small, we were not yet grown up.1 Accordingly, if we take the European Renaissance as a point of division, we must conclude that, until that...
The City of the Tribes: Italian Memories in an Irish Port
Authors: Joyce James
Published: June 2023

Galway, August The lazy Dubliner who does not travel much and knows his country only by hearsay thinks that the inhabitants of Galway are of Spanish stock, and that it is impossible to walk through the gloomy laneways of the city of the...
The Mirage of the Fisherman of Aran: England’s Safety Valve in Case of War
Authors: Joyce James
Published: June 2023

Galway, 2 September

The steamboat, carrying a small load of day-trippers, pulls away from the quays under the watchful eyes of the Scottish director who is absorbed in a dream of mental arithmetic. It goes out from the small port of Galway and takes to...
From A Banned Writer to a Banned Singer
Authors: Joyce James
Published: June 2023

He strides, booted with anger, along the spurs of Monte Rossini, accompanied solely by Fidelion, his mastiff’s voice. They quarrel consonantly about the vocality of the wind, calling each and its other clamant names.1

Just out of kerryosity howlike is a Sullivan? It has...
Author’s Note
Authors: Conrad Joseph
Published: June 2023

The last word of this novel was written on the 29th of May 1914. And that last word was the single word of the title.

Those were the times of peace. Now that the moment of publication approaches I have been considering the discretion of...
III
Authors: Conrad Joseph
Published: June 2023

Human nature being what it is, having a silly side to it as well as a mean side, there were not a few who pretended to be indignant on no better authority than a general propensity to believe every evil report; and a good...
IV
Authors: Conrad Joseph
Published: June 2023

A few of us who were sufficiently interested went to Davidson for details. These were not many. He told us that he passed to the north of Samburan on purpose to see what was going on. At first, it looked as if that...
V
Authors: Conrad Joseph
Published: June 2023

Davidson happened to be two days late on his return trip; no great matter, certainly, but he made a point of going ashore at once, during the hottest hour of the afternoon, to look for Heyst. Schomberg’s hotel stood back in an extensive enclosure...
VI
Authors: Conrad Joseph
Published: June 2023

We said no more about Heyst on that occasion, and it so happened that I did not meet Davidson again for some three months. When we did come together, almost the first thing he said to me was:

“I’ve seen him.”

Before I could exclaim,...
VII
Authors: Conrad Joseph
Published: June 2023

“A common thief!”

Schomberg bit his tongue just too late, and woke up completely as he saw Ricardo retract his lips in a cat-like grin; but the companion of “plain Mr. Jones” didn’t alter his comfortable, gossiping attitude.

“Garn! What if he did want to...
Enter the Woman
Authors: Wister Owen
Published: June 2023

“We are taking steps,” said Mr. Taylor. “Bear Creek ain’t going to be hasty about a schoolmarm.”

“Sure,” assented the Virginian. “The children wouldn’t want yu’ to hurry.”

But Mr. Taylor was, as I have indicated, a serious family man. The problem of educating...
The Sincere Spinster
Authors: Wister Owen
Published: June 2023

I do not know with which of the two estimates—Mr. Taylor’s or the Virginian’s—you agreed. Did you think that Miss Mary Stark Wood of Bennington, Vermont, was forty years of age? That would have been an error. At the time she wrote the letter...
Where Fancy was Bred
Authors: Wister Owen
Published: June 2023

Two camps in the open, and the Virginian’s Monte horse, untired, brought him to the Swintons’ in good time for the barbecue. The horse received good food at length, while his rider was welcomed with good whiskey. Good whiskey—for had not steers...
“You’re going to love me before we get through”
Authors: Wister Owen
Published: June 2023

The Swinton barbecue was over. The fiddles were silent, the steer was eaten, the barrel emptied, or largely so, and the tapers extinguished; round the house and sunken fire all movement of guests was quiet, the families had long departed homeward, and after their...
Between the Acts
Authors: Wister Owen
Published: June 2023

My road to Sunk Creek lay in no straight line. By rail I diverged northwest to Fort Meade and thence, after some stay with the kind military people, I made my way on a horse. Up here in the Black Hills it sluiced rain...
In a State of Sin
Authors: Wister Owen
Published: June 2023

Thunder sat imminent upon the missionary’s brow. Many were to be at his mercy soon. But for us he had sunshine still. “I am truly sorry to be turning you upside down,” he said importantly. “But it seems the best place for my service.”...
A Letter with a Moral
Authors: Wister Owen
Published: June 2023

The letter which the Virginian wrote to Molly Wood was, as has been stated, the first that he had ever addressed to her. I think, perhaps, he may have been a little shy as to his skill in the epistolary art, a little anxious...
Progress of the Lost Dog
Authors: Wister Owen
Published: June 2023

It was not even an hour’s visit that the Virginian was able to pay his lady love. But neither had he come a hundred miles to see her. The necessities of his wandering work had chanced to bring him close enough for a glimpse...
Balaam and Pedro
Authors: Wister Owen
Published: June 2023

Resigned to wait for the Judge’s horses, Balaam went into his office this dry, bright morning and read nine accumulated newspapers; for he was behindhand. Then he rode out on the ditches, and met his man returning with the troublesome animals at last. He...
No Dream to Wake From
Authors: Wister Owen
Published: June 2023

For a long while after she had left him, he lay still, stretched in his chair. His eyes were fixed steadily upon the open window and the sunshine outside. There he watched the movement of the leaves upon the green cottonwoods. What had she...
Superstition Trail
Authors: Wister Owen
Published: June 2023

We did not make thirty-five miles that day, nor yet twenty-five, for he had let me sleep. We made an early camp and tried some unsuccessful fishing, over which he was cheerful, promising trout to-morrow when we should be higher among the mountains. He...
The Spinster Loses Some Sleep
Authors: Wister Owen
Published: June 2023

Somewhere at the eastern base of the Tetons did those hoofprints disappear into a mountain sanctuary where many crooked paths have led. He that took another man’s possessions, or he that took another man’s life, could always run here if the law or popular...
With Malice Aforethought
Authors: Wister Owen
Published: June 2023

Town lay twelve straight miles before the lover and his sweetheart, when they came to the brow of the last long hill. All beneath them was like a map: neither man nor beast distinguishable, but the veined and tinted image of a country, knobs...
Chapter Four
Authors: London Jack
Published: June 2023

WHAT HAPPENED to me next on the sealing-schooner Ghost, as I strove to fit into my new environment, are matters of humiliation and pain. The cook, who was called “the doctor” by the crew, “Tommy” by the hunters, and “Cooky” by Wolf Larsen,...
Chapter Eight
Authors: London Jack
Published: June 2023

SOMETIMES I think Wolf Larsen mad, or half-mad at least, what of his strange moods and vagaries. At other times I take him for a great man, a genius who has never arrived. And, finally, I am convinced that he is the perfect type of...
Chapter Thirteen
Authors: London Jack
Published: June 2023

FOR three days I did my own work and Thomas Mugridge’s too; and I flatter myself that I did his work well. I know that it won Wolf Larsen’s approval, while the sailors beamed with satisfaction during the brief time my régime lasted.

“The first...
Chapter Fourteen
Authors: London Jack
Published: June 2023

IT has dawned upon me that I have never placed a proper valuation upon womankind. For that matter, though not amative to any considerable degree so far as I have discovered, I was never outside the atmosphere of women until now. My mother and sisters...
Chapter Eighteen
Authors: London Jack
Published: June 2023

THE next day, while the storm was blowing itself out, Wolf Larsen and I crammed anatomy and surgery and set Mugridge’s ribs. Then, when the storm broke, Wolf Larsen cruised back and forth over that portion of the ocean where we had encountered it, and...
Chapter Twenty-Five
Authors: London Jack
Published: June 2023

YOU’VE been on deck, Mr. Van Weyden,” Wolf Larsen said, the following morning at the breakfast table. “How do things look?”

“Clear enough,” I answered, glancing at the sunshine which streamed down the open companionway. “Fair westerly breeze, with a promise of stiffening, if Louis...
Chapter Thirty-Six
Authors: London Jack
Published: June 2023

FOR two days Maud and I ranged the sea and explored the beaches in search of the missing masts. But it was not till the third day that we found them, all of them, the shears included, and, of all perilous places, in the pounding...
Chapter Thirty-Seven
Authors: London Jack
Published: June 2023

AT once we moved aboard the Ghost, occupying our old state-rooms and cooking in the galley. The imprisonment of Wolf Larsen had happened most opportunely, for what must have been the Indian summer of this high latitude was gone and drizzling stormy weather...
DEDICATORY LETTER To STELLA FORD
Authors: Saunders Max
Published: June 2023

My dear Stella,

I have always regarded this as my best book*—at any rate as the best book of mine of a pre-war period; and between its writing and the appearance of my next novel nearly ten years must have elapsed, so that...
IV
Authors: Saunders Max
Published: June 2023

So began those nine years of uninterrupted tranquillity. They were characterised by an extraordinary want of any communicativeness on the part of the Ashburnhams to which, we on our part replied by leaving out quite as extraordinarily, and nearly as completely, the personal note. Indeed,...
VI
Authors: Saunders Max
Published: June 2023

I remember laughing at the phrase, “accept the situation”, which she seemed to repeat with a gravity too intense. I said to her something like:

“It’s hardly as much as that. I mean, that I must claim the liberty of a free American citizen to...
II
Authors: Saunders Max
Published: June 2023

Let me think where we were. Oh, yes . . . that conversation took place on the fourth of August, 1913. I remember saying to her that, on that day, exactly nine years before, I had made their acquaintance, so that it had seemed quite...
III
Authors: Saunders Max
Published: June 2023

And then Leonora completely broke down—on the day that they returned to Branshaw Teleragh. It is the infliction of our miserable minds—it is the scourge of atrocious but probably just destiny that no grief comes by itself. No, any great grief, though the grief itself...
V
Authors: Saunders Max
Published: June 2023

I call this the Saddest Story, rather than “The Ashburnham Tra­gedy,” just because it is so sad, just because there was no current to draw things along to a swift and inevitable end. There is about it none of the elevation that accompanies tragedy; there...
II
Authors: Saunders Max
Published: June 2023

Well, that about brings me up to the date of my receiving, in Waterbury, the laconic cable from Edward to the effect that he wanted me to go to Branshaw and have a chat. I was pretty busy at the time and I was half...
III
Authors: Saunders Max
Published: June 2023

Nancy had, in fact, been thinking ever since Leonora had made that comment over the giving of the horse to young Selmes. She had been thinking and thinking, because she had had to sit for many days silent beside her aunt’s bed. (She had always...
V
Authors: Saunders Max
Published: June 2023

It is this part of the story that makes me saddest of all. For I ask myself unceasingly, my mind going round and round in a weary, baffled space of pain—what should these people have done? What, in the name of God, should they have...
The Jelly-Bean
Authors: Bryer Jackson R.
Published: June 2023

Jim Powell was a Jelly-bean. Much as I desire to make him an appealing character, I feel that it would be unscrupulous to deceive you on that point. He was a bred-in-the-bone, dyed-in-the-wool, ninety-nine three-quarters per cent Jelly-bean and he grew lazily all during...
The Diamond as Big as the Ritz
Authors: Bryer Jackson R.
Published: June 2023

I

John T. Unger came from a family that had been well known in Hades — a small town on the Mississippi River — for several generations. John’s father had held the amateur golf championship through many a heated contest; Mrs. Unger was known “from hot-box to hot-bed,”...
A Table of Contents
Authors: Bryer Jackson R.
Published: June 2023

MY LAST FLAPPERS

THE JELLY-BEAN Page 11

This is a Southern story, with the scene laid in the small city of Tarleton, Georgia. I have a profound affection for Tarleton, but somehow whenever I write a story about it I receive letters from all over...
A Case of Hysteria
Authors: Freud Sigmund
Published: June 2023

A Case of Hysteria, popularly known as the Dora Case, affords a rare insight into how Freud dealt with patients and interpreted what they told him. The 18-year-old ‘Dora’ was sent for psychoanalysis by her father after threatening suicide; as Freud’s enquiries deepened, he uncovered a remarkably unhappy and conflict-ridden family, with several competing versions of their story. The narrative became a crucial text in the evolution of his theories, combining his studies on hysteria and his new theory of dream-interpretation with early insights into the development of sexuality. The unwitting preconceptions and prejudices with which Freud approached his patient reveal his blindness and the broader attitudes of turn-of-the-century Viennese society, while his account of ‘Dora’s’ emotional travails is as gripping as a modern novel.

This new translation is accompanied by a substantial introduction which sets the work in its biographical, historical, and intellectual context, and offers a close and critical analysis of the text itself.
The Concept and Measurement of Legislative Backsliding
Authors: Sebők Miklós , Kiss Rebeka , Kovács Ádám
Published: June 2023

The article examines the concept of legislative backsliding and offers a measurement strategy for its empirical analysis. Legislative backsliding is defined as a move away from liberal democracy in four critical dimensions of legislative quality, its public policy; legal-constitutional-formal; procedural; and stability aspects. We operationalise each of these dimensions with their separate indices relying on components such as stakeholder consultations, time passed between bill introduction and passing the law as well as results of constitutional reviews. We use qualitative mini case studies from Hungary, widely considered from 2010 on to be a poster child for democratic backsliding, to illustrate the viability of the proposed measurement strategy. We find that laws which show deficiencies in terms of legislative quality exhibit them in not just but several dimensions. Based on the case studies we offer insights into scaling up the law-level analysis to the level of legislative cycles and show how the legislative quality index can be used to measure macro-level legislative backsliding.
Geminivirus C5 proteins mediate formation of virus complexes at plasmodesmata for viral intercellular movement
Authors: Zhao Siwen , Gong Pan , Liu Jie , Liu Hui , Lozano-Durán Rosa , Zhou Xueping , Li Fangfang
Published: June 2023

Movement proteins (MPs) encoded by plant viruses deliver viral genomes to plasmodesmata (PD) to ensure intracellular and intercellular transport. However, how the MPs encoded by monopartite geminiviruses are targeted to PD is obscure. Here, we demonstrate that the C5 protein of tomato yellow leaf curl virus (TYLCV) anchors to PD during the viral infection following trafficking from the nucleus along microfilaments in Nicotiana benthamiana. C5 could move between cells and partially complement the traffic of a movement-deficient turnip mosaic virus (TuMV) mutant (TuMV-GFP-P3N-PIPO-m1) into adjacent cells. The TYLCV-C5 null mutant (TYLCV-mC5) attenuates viral pathogenicity and decreases viral DNA and protein accumulation, and ectopic overexpression of C5 enhances viral DNA accumulation. Interaction assays between TYLCV-C5 and the other eight viral proteins described in TYLCV reveal that C5 associates with C2 in the nucleus and with V2 in the cytoplasm and at PD. The V2 protein is mainly localized in the nucleus and cytoplasmic granules when expressed alone; in contrast, V2 forms small punctate granules at PD when co-expressed with C5 or in TYLCV-infected cells. The interaction of V2 and C5 also facilitates their nuclear export. Furthermore, C5-mediated PD localization of V2 is conserved in two other geminiviruses. Therefore, this study solves a long-sought-after functional connection between PD and the geminivirus movement and improves our understanding of geminivirus-encoded MPs and their potential cellular and molecular mechanisms.
Cardiovascular Burden of Narcolepsy Disease (CV-BOND): a real-world evidence study
Authors: Ben-Joseph Rami H , Saad Ragy , Black Jed , Dabrowski Elizabeth C , Taylor Ben , Gallucci Sophia , Somers Virend K
Published: June 2023

Study Objectives

Narcolepsy is associated with cardiovascular risk factors; however, the risk of new-onset cardiovascular events in this population is unknown. This real-world study evaluated the excess risk of new-onset cardiovascular events in U.S. adults with narcolepsy.

Methods

A retrospective cohort study using IBM MarketScan administrative claims data (2014–2019) was conducted. A narcolepsy cohort, comprising adults (≥18 years) with at least two outpatient claims containing a narcolepsy diagnosis, of which at least one was non-diagnostic, was matched to a non-narcolepsy control cohort (1:3) based on cohort entry date, age, sex, geographic region, and insurance type. The relative risk of new-onset cardiovascular events was estimated using a multivariable Cox proportional hazards model to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

The narcolepsy and matched non-narcolepsy control cohorts included 12 816 and 38 441 individuals, respectively. At baseline, cohort demographics were generally similar; however, patients with narcolepsy had more comorbidities. In adjusted analyses, the risk of new-onset cardiovascular events was higher in the narcolepsy cohort compared with the control cohort: any stroke (HR [95% CI], 1.71 [1.24, 2.34]); heart failure (1.35 [1.03, 1.76]); ischemic stroke (1.67 [1.19, 2.34]); major adverse cardiac event (1.45 [1.20, 1.74]); grouped instances of stroke, atrial fibrillation, or edema (1.48 [1.25, 1.74]); and cardiovascular disease (1.30 [1.08, 1.56]).

Conclusion

Individuals with narcolepsy are at increased risk of new-onset cardiovascular events compared with individuals without narcolepsy. Physicians should consider cardiovascular risk in patients with narcolepsy when weighing treatment options.
Single-session bilateral reduced-settings photodynamic therapy for bilateral chronic central serous chorioretinopathy
Authors: Pauleikhoff Laurenz J.B. , Diederen Roselie M.H. , Feenstra Helena , Schlingemann Reinier O. , van Dijk Elon H.C. , Boon Camiel J.F.
Published: June 2023

Purpose:

We performed a multicenter, retrospective study on patients with bilateral chronic central serous chorioretinopathy (cCSC) that received single-session bilateral reduced-settings photodynamic therapy (ssbPDT) and assessed anatomical (resolution of subretinal fluid (SRF)) and functional (best-corrected visual acuity (BCVA)) outcomes as well as safety.

Methods:

Patients that underwent ssbPDT between 01/01/2011 and 30/09/2022 were included. The resolution of SRF at first, second, and final follow-up was assessed on optical coherence tomography (OCT) and BCVA measurements were collected at these visits. When fovea-involving ssbPDT was performed, ellipsoid zone (EZ) and external limiting membrane (ELM) integrity was graded pre- and post-treatment.

Results:

Fifty-five patients were included in this study. Sixty two out of 108 eyes (56%) showed a complete resolution of SRF at first follow-up, which increased to 73/110 (66%) at final follow-up. Mean LogMAR BCVA improved by -0.047 (p = 0.02) over follow-up. EZ integrity increased from 14/21 (67%) to 24/30 (80%), while ELM integrity increased from 22/30 (73%) to 29/30 (97%).

Conclusion:

cCSC patients with bilateral SRF at baseline showed significant anatomical and functional improvement after ssbPDT, both at short-term and long-term follow-up. No relevant adverse events were noted.
Accuracy of New Intraocular Lens Calculation Formulae in eyes undergoing Silicone Oil Removal/Pars Plana Vitrectomy-cataract surgery
Authors: Chen Xu , Zhao He , Xu Yufei , Qin Zuoxin , Ren Jiayun , Wang Lu , Wan Junli , Wang Ziran , Liu Bo , Wu Nan , Liu Xi , Liu Yong
Published: June 2023

Purpose:

To investigate the performance of novel intraocular lens (IOL) calculation formulae (Barrett Universal II [BUII], Emmetropia Verifying Optical [EVO], and Kane) and conventional formulae (Haigis, Hoffer Q, Holladay 1, and SRK/T) in patients who underwent pars plana vitrectomy (PPV) or silicone oil removal (SOR) combined with cataract surgery.

Methods:

In total, 301 eyes from 301 patients underwent PPV/SOR with concomitant cataract surgery were enrolled and divided into four groups according to preoperative diagnosis: silicone oil-filled eyes after PPV, epiretinal membrane, primary retinal detachment (RD), and macular hole.

Results:

BUII exhibited the smallest mean absolute error (MAE) (0.65 diopters [D]) and median absolute error (MedAE) (0.39 D) in total. In patients with RD, each formula exhibited the worst refractive outcomes in diverse vitreoretinal pathologies (P<.01), and no difference in accuracy between the seven formulas was observed (P=.075). For long eyes, the second linear (WK2) version of the Wang-Koch adjustment significantly reduced the MedAE for Holladay 1 and SRK/T (P<.001 and P=.019).

Conclusion:

In combined surgery, both new and conventional formulas using WK2 adjustment demonstrated satisfactory performance, with BUII exhibiting the best overall performance. However, in patients with RD, all seven formulas showed less favorable performance.
Testosterone immunomodulation in free-living and captive
Rhinella icterica
male toads
Authors: Titon Stefanny Christie Monteiro , Junior Braz Titon , Assis Vania Regina , Cobo de Figueiredo Aymam , Floreste Felipe Rangel , Lima Alan Siqueira , Gomes Fernando Ribeiro
Published: June 2023

Testosterone (T) regulates immune function, with both immunostimulatory and immunosuppressive effects on several vertebrates. We investigated the covariation between plasma T and corticosterone (CORT) levels and immunity (plasma bacterial killing ability (BKA), and neutrophil to lymphocyte ratio (NLR)) in free-living
Rhinella icterica
male toads inside and outside the reproductive season. We found an overall positive correlation between steroids and immune traits, with toads during the reproductive season displaying increased T, CORT and BKA. We also investigated the T transdermal application effects on T, CORT, phagocytosis of blood cells, BKA and NLR in captive toads. Toads were treated with T (1, 10 or 100 µg) or vehicle (sesame oil) for eight consecutive days. Animals were bled on the first and eighth days of treatment. Increased plasma T was observed on the first and last day of T-treatment, while increased BKA was observed following all T doses on the last day, with a positive correlation between T and BKA. Plasma CORT, NLR and phagocytosis increased on the last day for all T-treated and vehicle groups. Overall, we demonstrated a positive covariation between T and immune traits in the field and T-induced augmented BKA in captive toads, indicating a T immunoenhancing effect in
R. icterica
males.

This article is part of the theme issue ‘Amphibian immunity: stress, disease and ecoimmunology’.
Inter-species diversity and functional genomic analyses of closed genome assemblies of clinically isolated, megaplasmid-containing Enterococcus raffinosus Er676 and ATCC49464
Authors: Sharon Belle M. , Hulyalkar Neha V. , Zimmern Philippe E. , Palmer Kelli L. , De Nisco Nicole J.
Published: June 2023

Enterococcus raffinosus

is an understudied member of its genus possessing a characteristic megaplasmid contributing to a large genome size. Although less commonly associated with human infection compared to other enterococci, this species can cause disease and persist in diverse niches such as the gut, urinary tract, blood and environment. Few complete genome assemblies have been published to date for

E. raffinosus

. In this study, we report the complete assembly of the first clinical urinary

E. raffinosus

strain, Er676, isolated from a postmenopausal woman with history of recurrent urinary tract infection. We additionally completed the assembly of clinical type strain ATCC49464. Comparative genomic analyses reveal inter-species diversity driven by large accessory genomes. The presence of a conserved megaplasmid indicates it is a ubiquitous and vital genetic feature of

E. raffinosus

. We find that the

E. raffinosus

chromosome is enriched for DNA replication and protein biosynthesis genes while the megaplasmid is enriched for transcription and carbohydrate metabolism genes. Prophage analysis suggests that diversity in the chromosome and megaplasmid sequences arises, in part, from horizontal gene transfer. Er676 demonstrated the largest genome size reported to date for

E. raffinosus

and the highest probability of human pathogenicity. Er676 also possesses multiple antimicrobial resistance genes, of which all but one are encoded on the chromosome, and has the most complete prophage sequences. Complete assembly and comparative analyses of the Er676 and ATCC49464 genomes provide important insight into the inter-species diversity of

E. raffinosus

that gives it its ability to colonize and persist in the human body. Investigating genetic factors that contribute to the pathogenicity of this species will provide valuable tools to combat diseases caused by this opportunistic pathogen.
The UK Divide: Does having a Pembrolizumab-Chemotherapy option in head and neck cancer matter? Real-world experience of first-line palliative pembrolizumab monotherapy and pembrolizumab-chemotherapy combination in Scotland
Authors: Thapa Alekh , Cowell Anna , Peters Adam , Noble David J , James Allan , Lamb Carolynn , Grose Derek , Vohra Saurabh , Schipani Stefano , Mactier Karen , Mackenzie Joanna , Srinivasan Devraj , Laws Kirsten , Moleron Rafael , Niblock Paddy , Soh Feng Yi , Paterson Claire , Wilson Christina
Published: June 2023

Objectives

The Scottish Medical Consortium recently approved first-line pembrolizumab monotherapy or in combination with chemotherapy for head and neck squamous cell carcinoma (HNSCC) in the palliative setting, contrasting with the decision made by the National Institute for Health and Care Excellence who approved monotherapy alone in England and Wales. We aimed to provide real-world performance data for first-line pembrolizumab-containing treatments for head and neck squamous cell carcinoma (HNSCC) in the palliative setting in Scotland.

Materials and Methods

We analysed the electronic records of patients who initiated pembrolizumab-containing treatment between 01/03/2020–30/09/2021. Outcomes included overall survival (OS), progression-free survival (PFS), duration of response (DOR), disease control rate (DCR). Data were compared with the KEYNOTE-048 study and clinical factors were evaluated for association with survival.

Results

Our cohort included 91 patients (median follow-up 10.8 months). Patient characteristics were similar to the KEYNOTE-048 study though our cohort had a higher proportion of patients with newly diagnosed, non-metastatic disease.

For patients receiving monotherapy (n=76), 12-month and 24-month OS was 45% and 27%, respectively. For patients receiving pembrolizumab-chemotherapy (n=15), 12-month OS was 60% (24-month OS had not yet been reached). Experiencing ≥1 irAE (versus no irAEs), of any grade, was associated with favourable OS and PFS for patients receiving monotherapy in both univariable log-rank analysis (median OS 17.4 months versus 8.6 months, respectively, P=0.0033; median PFS 10.9 months versus 3.0 months, respectively, P<0.0001) and multivariable analysis (Cox proportional hazards regression: OS HR: 0.31, P=0.0009; PFS HR: 0.17, P<0.0001).

Conclusion

Our real-world data support the KEYNOTE-048 study findings and the value of combination treatment options. Additionally, our data show irAEs of any grade, as reported in routine clinical records, are associated with better outcomes in this patient group, adding to the growing body of evidence showing irAEs are generally a positive marker of PD-L1 inhibitor response.
Genomic insights into the 2022–2023Vibrio choleraeoutbreak in Malawi
Authors: Chaguza Chrispin , Chibwe Innocent , Chaima David , Musicha Patrick , Ndeketa Latif , Kasambara Watipaso , Mhango Chimwemwe , Mseka Upendo L. , Bitilinyu-Bangoh Joseph , Mvula Bernard , Kipandula Wakisa , Bonongwe Patrick , Munthali Richard J. , Ngwira Selemani , Mwendera Chikondi A. , Kalizang’oma Akuzike , Jambo Kondwani C. , Kambalame Dzinkambani , Kamng’ona Arox W. , Steele A Duncan , Chauma-Mwale Annie , Hungerford Daniel , Kagoli Matthew , Nyaga Martin M. , Dube Queen , French Neil , Msefula Chisomo L. , Cunliffe Nigel A. , Jere Khuzwayo C.
Published: June 2023

Malawi is experiencing its deadliestVibrio cholerae(Vc) outbreak following devastating cyclones, with >58,000 cases and >1,700 deaths reported between March 2022 and May 2023. Here, we use population genomics to investigate the attributes and origin of the Malawi 2022– 2023Vcoutbreak isolates. Our results demonstrate the predominance of ST69 seventh cholera pandemic El Tor (7PET) strains expressing O1 Ogawa (∼80%) serotype followed by Inaba (∼16%) and typical non-outbreak-associated non-O1/non-ST69 serotypes (∼4%). Phylogenetic reconstruction of the current and historicalVcisolates from Malawi, together with globalVcisolates, suggested the Malawi outbreak strains originated from Asia. The unique antimicrobial resistance and virulence profiles of the 2022–2023 isolates, notably the acquisition of ICEGEN/ICEVchHai1/ICEVchind5 SXT/R391-like integrative conjugative elements and a CTXφ prophage, which causedctxB3toctxB7genotype shift, support the importation hypothesis. These data suggest that the recent importation ofctxB7O1 strains, coupled with climatic changes, may explain the magnitude of the cholera outbreak in Malawi.
Deep-Learning Model for Personalized Prediction of Positive MRSA Culture Results Using Patient’s Time-Series Electronic Health Records
Authors: Nigo Masayuki , Rasmy Laila , Xie Ziqian , Kannadath Bijun Sai , Zhi Degui
Published: June 2023

Methicillin-resistant Staphylococcus aureus (MRSA) is a common bacterial cause of morbidity and mortality. Our deep-learning model (PyTorch_EHR) processes time-series structured electronic health record (EHR) data, including previous cultures and antimicrobial exposures, to predict the lab result of MRSA culture positivity over the next two weeks. After training and evaluation on data from 8,164 MRSA and 22,563 non-MRSA patient events from Memorial Hermann Hospital System, Houston, Texas, the PyTorch_EHR outperformed traditional machine learning methods logistic regression and light GBM (Area Under the Curve of Receiver Operating Curve [AUC]PyTorch_EHR=91.12%, AUCLR=85.91%, AUCLGBM=89.11%). External validation using the MIMIC-IV dataset of 393,713 patient events from a tertiary care center in Boston, Massachusetts, confirmed PyTorch_EHR’s accuracy (AUCPyTorch_EHR=85.50%, AUCLR=83.24%, AUCLGBM=82.48%). The model maintained its accuracy across most subgroup analyses based on infection type. The cumulative incidence curves based on our model successfully high-, medium-, and low-risk patients. This study demonstrates the potential of deep-learning models to predict the presence of MRSA-positive cultures to optimize MRSA antimicrobial therapy.
Lifespan of COVID-19 living guideline recommendations: a survival analysis
Authors: McFarlane Emma , Mercer Toby , Sharp Steve , Hunter Debra , Kelley Kate , Glen Fiona , Majeed Maria
Published: June 2023

Background

NICE has maintained a portfolio of COVID-19 living guidelines since March 2020. Recommendations within these living guidelines are subject to continuous surveillance and updates in response to triggers. However, the lifespan of individual living guideline recommendations and features that may impact on whether a recommendation becomes out of date sooner, is unknown.

Objectives

This study aimed to describe the length of time NICE COVID-19 living guideline recommendations have remained valid.

Methods

All guidelines within NICE’s COVID-19 portfolio were included to determine the lifespan of living guideline recommendations. Data were collected on all recommendations that had been developed, undergone surveillance or updated between 1 March 2020 and 31 August 2022. Information on initial publication date, decision to update, and update publication date was extracted. Updates were labelled as major changes in evidence synthesis or minor changes without a substantial change in evidence base. Any recommendation that had not been updated or withdrawn was censored. Survival analysis (Kaplan-Meier Curve) was carried out to determine the lifespan of recommendations.

Results

Overall, 26 COVID-19 living guidelines and 1182 recommendations were included in the analysis. Living recommendations had median survival time of 739 days (IQR: 332, 781). Based on recommendation type, intervention recommendations had a shorter survival time (354 days, IQR 312, 775) compared to diagnosis (368 days, IQR: 328, 795), patient experience (733 days, IQR: 345, 795) and service delivery (739 days, IQR: 643, 781). Within intervention type, pharmacological recommendations had shortest survival time versus non-pharmacological recommendations [335 days (IQR: 161, 775) vs 775 days (IQR: 354, 775)]. Updates were published an average of 29.12 days following a surveillance decision.

Conclusion

Within living guidelines, some recommendations need to be updated sooner than others. This study outlines the value of a flexible responsive approach to surveillance within the living mode according to pace of change and expectation of update triggers.

What is new?

Key findings

Within the context of a living guideline, some recommendations will become out of date sooner than others.

What this adds to what was known?

This study supports the concept of prioritising recommendations within a guideline to be living.

What is the implication and what should change now?

Guideline developers should consider which recommendations within a living guideline would have the most value in being maintained as living to optimise resources.
Assessment of fetal corpus callosum biometry by 3D super-resolution reconstructed T2-weighted MRI
Authors: Lamon Samuel , de Dumast Priscille , Dunet Vincent , Pomar Léo , Vial Yvan , Koob Mériam , Cuadra Meritxell Bach
Published: June 2023

Objective

To assess the accuracy of corpus callosum (CC) and its sub-segments’ biometry by super-resolution (SR) 3-dimensional fetal brain MRI in comparison to measurements in 2-dimensional or 3-dimensional ultrasonography (US) and clinical low-resolution T2-weighted MRI sequences (T2WS).

Method

We performed fetal brain biometry of the overall length of the CC, the heights of its sub-segments and its area by two observers (one junior observer, obs1, and one senior pediatric neuroradiologist, obs2) in a cohort of 57 subjects (between 21 and 35 weeks of gestational age (GA), including 11 cases of partial agenesis of CC). Obs1 made measures on US, T2WS, and SR, and obs2 in T2WS and SR. Regression curves of CC biometry with GA were done. Statistical analysis of inter-modality (US vs. T2WS, US vs. SR, and T2WS vs SR) agreement for single observer (obs1) and inter-modality (US vs. T2WS, and US vs. SR) between observers (obs1 vs obs2) were also conducted.

Results

Our study shows a high concordance through GA of CC measurements performed by SR in comparison with US, with a higher agreement than biometry based on T2WS clinical acquisitions. For obs1, SR measurements are highly concordant to US (except for the genu and the CC length) and helps visualizing the splenium. For obs2, SR measurements are highly concordant to US, except for the rostrum and the CC length. Rostrum and Genu (forming the anterior callosum) are the subsegments with larger variability. Regression curves by SR overlay more accurately those from the literature (by US) for the CC length, the splenium and the body than T2WS.

Conclusion

Super-resolution MRI could be used in the biometrical assessment of the CC, providing measurements close to US, except for the anterior part of the CC Thanks to its 3D-visualisation capacity and improved through plane spatial resolution, it allows to perform CC biometry more frequently than on T2WS.
Associations of longitudinal BMI percentile classification patterns in early childhood with neighborhood-level social determinants of health
Authors: Gupta Mehak , Phan Thao-Ly T. , Lê-Scherban Félice , Eckrich Daniel , Bunnell H. Timothy , Beheshti Rahmatollah
Published: June 2023

Background

Understanding social determinants of health (SDOH) that may be risk factors for childhood obesity is important to developing targeted interventions to prevent obesity. Prior studies have examined these risk factors, mostly examining obesity as a static outcome variable.

Methods

We extracted EHR data from 2012-2019 for a children’s health system that includes 2 hospitals and wide network of outpatient clinics spanning 5 East Coast states in the US. Using data-driven and algorithmic clustering, we have identified distinct BMI-percentile classification groups in children from 0 to 7 years of age. We used two separate algorithmic clustering methods to confirm the robustness of the identified clusters. We used multinomial logistic regression to examine the associations between clusters and 27 neighborhood SDOHs and compared positive and negative SDOH characteristics separately.

Results

From the cohort of 36,910 children, five BMI-percentile classification groups emerged: always having obesity (n=429; 1.16%), overweight most of the time (n=15,006; 40.65%), increasing BMI-percentile (n=9,060; 24.54%), decreasing BMI-percentile (n=5,058; 13.70%), and always normal weight (n=7,357; 19.89%). Compared to children in the decreasing BMI-percentile and always normal weight groups, children in the other three groups were more likely to live in neighborhoods with higher poverty, unemployment, crowded households, single-parent households, and lower preschool enrollment.

Conclusions

Neighborhood-level SDOH factors have significant associations with children’s BMI-percentile classification and changes in classification. This highlights the need to develop tailored obesity interventions for different groups to address the barriers faced by communities that can impact the weight and health of children living within them.

Impact Statement

This study demonstrates the association between longitudinal BMI-percentile patterns and SDOH in early childhood. Five distinct clusters with different BMI-percentile trajectories are found and a strong association between these clusters and SDOH is observed. Our findings highlight the importance of targeted prevention and treatment interventions based on children’s SDOH.
The Mediterranean Diet Scale (MDS): translation and validation of the Arabic version
Authors: Aljehani Raghdah , Aljehani Ghaidaa , Alharazi Hanaa , Horta Paula M , Duarte Camila Kümmel , Ghisi. Gabriela Lima de Melo
Published: June 2023

Objectives

The self-administered version of the Mediterranean Diet Scale (MDS) has been developed to test the inherent characteristics of this dietary pattern in a quick and simple way, due to the need of this assessment in the clinical and research setting. This study aimed to translate and psychometrically validate the self-administered MDS in Arabic (CRBS-A).

Methods

The original (English) version was originally translated to Arabic, followed by back-translation. Next, 10 healthcare providers, followed by 10 cardiovascular disease (CVD) patients rated the face and content validity (CV) of materials, providing input to improve cross-cultural applicability. Then, 200 patients from Saudi Arabia completed the questionnaire, of which factor structure, internal consistency, criterion and construct validity were assessed.

Results

Content and face validity was supported based on experts and patients’ reviews (ranges: CV scores 0.9-1.0/1.0 and clarity 3.5 to 4.5/5). Minor edits were made. Subsequent factor analysis revealed 4 factors consistent with the original version of the instrument, all internally consistent. Total CRBS-A α was 0.74. Criterion validity was confirmed by the significantly higher scores in patients who participated in CR. Construct validity was also established by significant associations between MDS scores and monthly family income, having the diagnosis of acute coronary syndrome or with a history of valve repair or replacement, being obese or having dyslipidemia.

Conclusions

Overall, these results confirm the validity and reliability of the MDS in Arabic-speaking patients.