bluuebunny/crossref_metadata_2025 huggingface dataset:
CHAPTER VIII
Authors: Austen Jane , Mullan John
Published: February 2023

Harriet slept at Hartfield that night. For some weeks past she had been spending more than half her time there, and gradually getting to have a bed-room appropriated to herself; and Emma judged it best in every respect, safest and kindest, to keep her...
CHAPTER IX
Authors: Austen Jane , Mullan John
Published: February 2023

Mr. Knightley might quarrel with her, but Emma could not quarrel with herself. He was so much displeased, that it was longer than usual before he came to Hartfield again; and when they did meet, his grave looks shewed that she was not forgiven....
CHAPTER XIII
Authors: Austen Jane , Mullan John
Published: February 2023

There could hardly be an happier creature in the world, than Mrs. John Knightley, in this short visit to Hartfield, going about every morning among her old acquaintance with her five children, and talking over what she had done every evening with her father...
CHAPTER XVIII
Authors: Austen Jane , Mullan John
Published: February 2023

Mr. Frank Churchill did not come. When the time proposed drew near, Mrs. Weston’s fears were justified in the arrival of a letter of excuse. For the present, he could not be spared, to his ‘very great mortification and regret; but still he looked...
CHAPTER IV
Authors: Austen Jane , Mullan John
Published: February 2023

Human nature is so well disposed towards those who are in interesting situations, that a young person, who either marries or dies, is sure of being kindly spoken of.

A week had not passed since Miss Hawkins’s name was first mentioned in Highbury, before she...
CHAPTER V
Authors: Austen Jane , Mullan John
Published: February 2023

Small heart had Harriet for visiting. Only half an hour before her friend called for her at Mrs. Goddard’s, her evil stars had led her to the very spot where, at that moment, a trunk, directed to The Rev. Philip Elton, White-Hart, Bath,...
CHAPTER VI
Authors: Austen Jane , Mullan John
Published: February 2023

The next morning brought Mr. Frank Churchill again. He came with Mrs. Weston, to whom and to Highbury he seemed to take very cordially. He had been sitting with her, it appeared, most companionably at home, till her usual hour of exercise; and on...
CHAPTER VII
Authors: Austen Jane , Mullan John
Published: February 2023

Emma’s very good opinion of Frank Churchill was a little shaken the following day, by hearing that he was gone off to London, merely to have his hair cut.* A sudden freak seemed to have seized him at breakfast, and he had...
CHAPTER IX
Authors: Austen Jane , Mullan John
Published: February 2023

Emma did not repent her condescension* in going to the Coles. The visit afforded her many pleasant recollections the next day; and all that she might be supposed to have lost on the side of dignified seclusion, must be amply repaid in...
CHAPTER X
Authors: Austen Jane , Mullan John
Published: February 2023

The appearance of the little sitting-room as they entered, was tranquillity itself; Mrs. Bates, deprived of her usual employment, slumbering on one side of the fire, Frank Churchill, at a table near her, most deedily* occupied about her spectacles, and Jane Fairfax,...
CHAPTER XII
Authors: Austen Jane , Mullan John
Published: February 2023

One thing only was wanting to make the prospect of the ball completely satisfactory to Emma — its being fixed for a day within the granted term of Frank Churchill’s stay in Surry; for, in spite of Mr. Weston’s confidence, she could not think...
CHAPTER XV
Authors: Austen Jane , Mullan John
Published: February 2023

Emma was not required, by any subsequent discovery, to retract her ill opinion of Mrs. Elton. Her observation had been pretty correct. Such as Mrs. Elton appeared to her on this second interview, such she appeared whenever they met again, — self-important, presuming, familiar, ignorant, and...
CHAPTER I
Authors: Austen Jane , Mullan John
Published: February 2023

A very little quiet reflection was enough to satisfy Emma as to the nature of her agitation on hearing this news of Frank Churchill. She was soon convinced that it was not for herself she was feeling at all apprehensive or embarrassed; it...
CHAPTER VIII
Authors: Austen Jane , Mullan John
Published: February 2023

The wretchedness of a scheme to Box Hill was in Emma’s thoughts all the evening. How it might be considered by the rest of the party, she could not tell. They, in their different homes, and their different ways, might be looking back on...
CHAPTER IX
Authors: Austen Jane , Mullan John
Published: February 2023

Emma’s pensive meditations, as she walked home, were not interrupted; but on entering the parlour, she found those who must rouse her. Mr. Knightley and Harriet had arrived during her absence, and were sitting with her father. — Mr. Knightley immediately got up, and in a...
CHAPTER X
Authors: Austen Jane , Mullan John
Published: February 2023

One morning, about ten days after Mrs. Churchill’s decease, Emma was called down stairs to Mr. Weston, who ‘could not stay five minutes, and wanted particularly to speak with her.’ — He met her at the parlour door, and hardly asking her how she did, in...
CHAPTER XII
Authors: Austen Jane , Mullan John
Published: February 2023

Till now that she was threatened with its loss, Emma had never known how much of her happiness depended on being first with Mr. Knightley, first in interest and affection. — Satisfied that it was so, and feeling it her due, she...
Directions and Information for the Tourist
Authors: Wordsworth William
Published: February 2023

In preparing this Manual, it was the Author’s principal wish to furnish a Guide or Companion for the Minds of Persons of taste, and feeling for Landscape, who might be inclined to explore the District of the Lakes with that degree of...
ODE
Authors: Wordsworth William
Published: February 2023

Within the mind strong fancies work,
A deep delight the bosom thrills,
Oft as I pass along the fork
Of these fraternal hills:
Where, save the rugged road, we find
No appanage of human kind;
Nor hint of man, if stone or rock
Seem...
Breakfast
Authors: Melville Herman , Blum Hester
Published: February 2023

I quickly followed suit, and descending into the bar-room accosted the grinning landlord very pleasantly. I cherished no malice towards him, though he had been skylarking with me not a little in the matter of my bed-fellow.

However, a good laugh is a mighty good...
The Chapel
Authors: Melville Herman , Blum Hester
Published: February 2023

In the same New Bedford there stands a Whaleman’s Chapel, and few are the moody fishermen, shortly bound for the Indian Ocean or the Pacific, who fail to make a Sunday visit to the spot. I am sure that I did not....

Returning from...
The Pulpit
Authors: Melville Herman , Blum Hester
Published: February 2023

I had not been seated very long ere a man of a certain venerable robustness entered; immediately as the storm-pelted door flew back upon admitting him, a quick regardful eyeing of him by all the congregation, sufficiently attested that this fine...
The Sermon
Authors: Melville Herman , Blum Hester
Published: February 2023

Father Mapple rose, and in a mild voice of unassuming authority ordered the scattered people to condense. “Starboard gangway, there! side away to larboard — larboard gangway to starboard! Midships! midships!”

There was a low rumbling of heavy sea-boots among the benches, and a still slighter shuffling...
A Bosom Friend
Authors: Melville Herman , Blum Hester
Published: February 2023

Returning to the Spouter-Inn from the Chapel, I found Queequeg there quite alone; he having left the Chapel before the benediction some time. He was sitting on a bench before the fire, with his feet on the stove hearth, and in one hand was...
Nantucket
Authors: Melville Herman , Blum Hester
Published: February 2023

Nothing more happened on the passage worthy the mentioning; so, after a fine run, we safely arrived in Nantucket.

Nantucket! Take out your map and look at it. See what a real corner of the world it occupies; how it stands there, away off shore,...
Chowder
Authors: Melville Herman , Blum Hester
Published: February 2023

It was quite late in the evening when the little Moss came snugly to anchor, and Queequeg and I went ashore; so we could attend to no business that day, at least none but a supper and a bed. The landlord of the Spouter-Inn...
The Ship
Authors: Melville Herman , Blum Hester
Published: February 2023

In bed we concocted our plans for the morrow. But to my surprise and no small concern, Queequeg now gave me to understand, that he had been diligently consulting Yojo — the name of his black little god — and Yojo had told him two or three times...
Knights and Squires
Authors: Melville Herman , Blum Hester
Published: February 2023

The chief mate of the Pequod was Starbuck, a native of Nantucket, and a Quaker by descent. He was a long, earnest man, and though born on an icy coast, seemed well adapted to endure hot latitudes, his flesh being hard as twice-baked biscuit....
The Quarter-Deck
Authors: Melville Herman , Blum Hester
Published: February 2023

(Enter Ahab: Then, all.)

It was not a great while after the affair of the pipe, that one morning shortly after breakfast, Ahab, as was his wont, ascended the cabin-gangway to the deck. There most sea-captains usually walk at that hour, as...
Dusk
Authors: Melville Herman , Blum Hester
Published: February 2023

By the Mainmast; Starbuck leaning against it.

My soul is more than matched; she’s overmanned; and by a madman! Insufferable sting, that sanity should ground arms on such a field! But he drilled deep down, and blasted all my reason out of me! I...
First Night-Watch
Authors: Melville Herman , Blum Hester
Published: February 2023

(Stubb solus, and mending a brace.)
Hark!
Authors: Melville Herman , Blum Hester
Published: February 2023

“Hist! Did you hear that noise, Cabaco?”

It was the middle-watch: a fair moonlight; the seamen were standing in a cordon, extending from one of the fresh-water butts in the waist, to the scuttle-butt near the taffrail. In this manner, they passed the...
The Mat-Maker
Authors: Melville Herman , Blum Hester
Published: February 2023

It was a cloudy, sultry afternoon; the seamen were lazily lounging about the decks, or vacantly gazing over into the lead-colored waters. Queequeg and I were mildly employed weaving what is called a sword-mat, for an additional lashing to our boat. So still and...
The First Lowering
Authors: Melville Herman , Blum Hester
Published: February 2023

The phantoms, for so they then seemed, were flitting on the other side of the deck, and, with a noiseless celerity, were casting loose the tackles and bands of the boat which swung there. This boat had always been deemed one of the spare...
The Hyena
Authors: Melville Herman , Blum Hester
Published: February 2023

There are certain queer times and occasions in this strange mixed affair we call life when a man takes this whole universe for a vast practical joke, though the wit thereof he but dimly discerns, and more than suspects that the joke is at...
Ahab’s Boat and Crew. Fedallah
Authors: Melville Herman , Blum Hester
Published: February 2023

“Who would have thought it, Flask!” cried Stubb; “if I had but one leg you would not catch me in a boat, unless maybe to stop the plughole with my timber toe. Oh! he’s a wonderful old man!”

“I don’t think it so strange,...
The Spirit-Spout
Authors: Melville Herman , Blum Hester
Published: February 2023

Days, weeks passed, and under easy sail, the ivory Pequod had slowly swept across four several cruising-grounds; that off the Azores; off the Cape de Verdes; on the Plate (so called), being off the mouth of the Rio de la Plata; and...
The Gam
Authors: Melville Herman , Blum Hester
Published: February 2023

The ostensible reason why Ahab did not go on board of the whaler we had spoken was this: the wind and sea betokened storms. But even had this not been the case, he would not after all, perhaps, have boarded her — judging by his subsequent...
Of the Less Erroneous Pictures of Whales, and the True Pictures of Whaling Scenes
Authors: Melville Herman , Blum Hester
Published: February 2023

In connexion with the monstrous pictures of whales, I am strongly tempted here to enter upon those still more monstrous stories of them which are to be found in certain books, both ancient and modern, especially in Pliny, Purchas, Hackluyt, Harris, Cuvier,...
Brit
Authors: Melville Herman , Blum Hester
Published: February 2023

Steering north-eastward from the Crozetts, we fell in with vast meadows of brit, the minute, yellow substance, upon which the Right Whale largely feeds. For leagues and leagues it undulated round us, so that we seemed to be sailing through boundless fields of ripe...
Squid
Authors: Melville Herman , Blum Hester
Published: February 2023

Slowly wading through the meadows of brit, the Pequod still held on her way north-eastward towards the island of Java; a gentle air impelling her keel, so that in the surrounding serenity her three tall tapering masts mildly waved to that languid breeze, as...
The Dart
Authors: Melville Herman , Blum Hester
Published: February 2023

A word concerning an incident in the last chapter.

According to the invariable usage of the fishery, the whale-boat pushes off from the ship, with the headsman or whale-killer as temporary steersman, and the harpooneer or whale-fastener pulling the foremost oar, the one...
The Crotch
Authors: Melville Herman , Blum Hester
Published: February 2023

Out of the trunk, the branches grow; out of them, the twigs. So, in productive subjects, grow the chapters.

The crotch alluded to on a previous page deserves independent mention. It is a notched stick of a peculiar form, some two feet in length, which...
Stubb’s Supper
Authors: Melville Herman , Blum Hester
Published: February 2023

Stubb’s whale had been killed some distance from the ship. It was a calm; so, forming a tandem of three boats, we commenced the slow business of towing the trophy to the Pequod. And now, as we eighteen men with our thirty-six arms, and...
The Jeroboam’s Story
Authors: Melville Herman , Blum Hester
Published: February 2023

Hand in hand, ship and breeze blew on; but the breeze came faster than the ship, and soon the Pequod began to rock.

By and by, through the glass the stranger’s boats and manned mast-heads proved her a whale-ship. But as she was so far...
Stubb and Flask Kill a Right Whale; and then Have a Talk Over Him
Authors: Melville Herman , Blum Hester
Published: February 2023

It must be borne in mind that all this time we have a Sperm Whale’s prodigious head hanging to the Pequod’s side. But we must let it continue hanging there a while till we can get a chance to attend to it. For the...
The Sperm Whale’s Head.—Contrasted View
Authors: Melville Herman , Blum Hester
Published: February 2023

Here, now, are two great whales, laying their heads together; let us join them, and lay together our own.

Of the grand order of folio leviathans, the Sperm Whale and the Right Whale are by far the most noteworthy. They are the only whales...
Jonah Historically Regarded
Authors: Melville Herman , Blum Hester
Published: February 2023

Reference was made to the historical story of Jonah and the whale in the preceding chapter. Now some Nantucketers rather distrust this historical story of Jonah and the whale. But then there were some sceptical Greeks and Romans, who, standing out from the orthodox...
The Fountain
Authors: Melville Herman , Blum Hester
Published: February 2023

That for six thousand years — and no one knows how many millions of ages before — the great whales should have been spouting all over the sea, and sprinkling and mistifying the gardens of the deep, as with so many sprinkling or mistifying pots; and that for...
The Grand Armada
Authors: Melville Herman , Blum Hester
Published: February 2023

The long and narrow peninsula of Malacca, extending southeastward from the territories of Birmah, forms the most southerly point of all Asia. In a continuous line from that peninsula stretch the long islands of Sumatra, Java, Bally, and Timor; which, with many others, form...
Schools and Schoolmasters
Authors: Melville Herman , Blum Hester
Published: February 2023

The previous chapter gave account of an immense body or herd of Sperm Whales, and there was also then given the probable cause inducing those vast aggregations.

Now, though such great bodies are at times encountered, yet, as must have been seen, even at...
Fast-Fish and Loose-Fish
Authors: Melville Herman , Blum Hester
Published: February 2023

The allusion to the waifs and waif-poles in the last chapter but one, necessitates some account of the laws and regulations of the whale fishery, of which the waif may be deemed the grand symbol and badge.

It frequently happens that when several ships...
Heads or Tails
Authors: Melville Herman , Blum Hester
Published: February 2023

“De balena vero sufficit, si rex habeat caput, et regina caudam.”*

Bracton, l. 3, c. 3.
The Pequod Meets the Rose-Bud
Authors: Melville Herman , Blum Hester
Published: February 2023

“In vain it was to rake for Ambergriese in the paunch of this

Leviathan, insufferable fetor denying that inquiry.”

Sir T. Browne, V. E.
The Castaway
Authors: Melville Herman , Blum Hester
Published: February 2023

It was but some few days after encountering the Frenchman, that a most significant event befell the most insignificant of the Pequod’s crew; an event most lamentable; and which ended in providing the sometimes madly merry and predestinated craft with a living and ever...
The Try-Works
Authors: Melville Herman , Blum Hester
Published: February 2023

Besides her hoisted boats, an American whaler is outwardly distinguished by her try-works. She presents the curious anomaly of the most solid masonry joining with oak and hemp in constituting the completed ship. It is as if from the open field a brick-kiln were...
A Bower in the Arsacides
Authors: Melville Herman , Blum Hester
Published: February 2023

Hitherto, in descriptively treating of the Sperm Whale, I have chiefly dwelt upon the marvels of his outer aspect; or separately and in detail upon some few interior structural features. But to a large and thorough sweeping comprehension of him, it behoves me now...
Ahab and the Carpenter
Authors: Melville Herman , Blum Hester
Published: February 2023

(Carpenter standing before his vice-bench, and by the light of two lanterns busily filing the ivory joist for the leg, which joist is firmly fixed in the vice. Slabs of ivory, leather straps, pads, screws, and various tools of all sorts lying about the bench....
Ahab and Starbuck in the Cabin
Authors: Melville Herman , Blum Hester
Published: February 2023

According to usage they were pumping the ship next morning; and lo! no inconsiderable oil came up with the water; the casks below must have sprung a bad leak. Much concern was shown; and Starbuck went down into the cabin to report this unfavorable...
Midnight Aloft.—Thunder and lightning
Authors: Melville Herman , Blum Hester
Published: February 2023

The Main-top-sail yard. — Tashtego passing new lashings around it

“Um, um, um. Stop that thunder! Plenty too much thunder up here. What’s the use of thunder? Um, um, um. We don’t want thunder; we want rum; give us a glass of rum. Um, um,...
The Life-Buoy
Authors: Melville Herman , Blum Hester
Published: February 2023

Steering now south-eastward by Ahab’s levelled steel, and her progress solely determined by Ahab’s level log and line; the Pequod held on her path towards the Equator. Making so long a passage through such unfrequented waters, descrying no ships, and ere long, sideways impelled...
The Chase — Second Day
Authors: Melville Herman , Blum Hester
Published: February 2023

At day-break, the three mast-heads were punctually manned afresh.

“D’ye see him?” cried Ahab, after allowing a little space for the light to spread.

“See nothing, sir.”

“Turn up all hands and make sail! he travels faster than I thought for; — the top-gallant sails! — aye, they should...
The Chase — Third Day
Authors: Melville Herman , Blum Hester
Published: February 2023

The morning of the third day dawned fair and fresh, and once more the solitary night-man at the fore-mast-head was relieved by crowds of the daylight look-outs, who dotted every mast and almost every spar.

“D’ye see him?” cried Ahab; but the whale was not...
The Tail
Authors: Melville Herman , Blum Hester
Published: February 2023

Other poets have warbled the praises of the soft eye of the antelope, and the lovely plumage of the bird that never alights; less celestial, I celebrate a tail.

Reckoning the largest sized Sperm Whale’s tail to begin at that point of the trunk...
Looking-Glass House
Authors: Carroll Lewis , Jaques Zoe
Published: February 2023

one thing was certain,* that the white kitten had had nothing to do with it: — it was the black kitten’s* fault entirely. For the white kitten had been having its face washed by the old cat*...
Humpty Dumpty
Authors: Carroll Lewis , Jaques Zoe
Published: February 2023

however, the egg only got larger and larger, and more and more human: when she had come within a few yards of it, she saw that it had eyes and a nose and mouth; and when she had come close to it, she saw...
Utero-placental expression and functional implications of HSD11B1 and HSD11B2 in canine pregnancy
Authors: Tavares Pereira Miguel , Schuler Gerhard , Aslan Selim , Payan-Carreira Rita , Reichler Iris M , Reynaud Karine , Kowalewski Mariusz P
Published: February 2023

Glucocorticoids modulate the feto-maternal interface during the induction of parturition. In the dog, the prepartum rise of cortisol in the maternal circulation appears to be erratic, and information about its contribution to the prepartum luteolytic cascade is scarce. However, the local placental upregulation of glucocorticoid receptor (GR/NR3C1) at term led to the hypothesis that species-specific regulatory mechanisms might apply to the involvement of cortisol in canine parturition. Therefore, here, we assessed the canine uterine/utero-placental spatio-temporal expression of hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1; reduces cortisone to cortisol), and -2 (HSD11B2; oxidizes cortisol to the inactive cortisone). Both enzymes were detectable throughout pregnancy. Their transcriptional levels were elevated following implantation, with a strong increase in HSD11B2 post-implantation (days 18–25 of pregnancy), and in HSD11B1 at mid-gestation (days 35–40) (P < 0.05). Interestingly, when compared pairwise, HSD11B2 transcripts were higher during post-implantation, whereas HSD11B1 dominated during mid-gestation and luteolysis (P < 0.05). A custom-made species-specific antibody generated against HSD11B2 confirmed its decreased expression at prepartum luteolysis. Moreover, in mid-pregnant dogs treated with aglepristone, HSD11B1 was significantly higher than −2 (P < 0.05). HSD11B2 (protein and transcript) was localized mostly in the syncytiotrophoblast, whereas HSD11B1 mRNA was mainly localized in cytotrophoblast cells. Finally, in a functional approach using placental microsomes, a reduced conversion capacity to deactivate cortisol into cortisone was observed during prepartum luteolysis, fitting well with the diminished HSD11B2 levels. In particular, the latter findings support the presence of local increased cortisol availability at term in the dog, contrasting with an enhanced inactivation of cortisol during early pregnancy.
iCre recombinase expressed in the anti-Müllerian hormone receptor 2 gene causes global genetic modification in the mouse
Authors: Dickson Mackenzie J , Gruzdev Artiom , DeMayo Francesco J
Published: February 2023

Genetically engineered mice are widely used to study the impact of altered gene expression in vivo. Within the reproductive tract, the Amhr2-IRES-Cre(Bhr) mouse model is used to ablate genes in ovarian granulosa and uterine stromal cells. There are reports of Amhr2-IRES-Cre(Bhr) inducing recombination in non-target tissues. We hypothesized the inefficiency or off-target Cre action in Amhr2-IRES-Cre(Bhr) mice is due to lack of recombination in every cell that expresses Amhr2. To investigate, we created a new targeted knock-in mouse model, Amhr2-iCre(Fjd), by inserting a codon-optimized improved Cre (iCre) into exon 1 of the Amhr2 gene. Amhr2-iCre(Fjd)/+ males were mated with females that contain a lox-stop-lox cassette in the Sun1 gene so when DNA recombination occurs, SUN1-sfGFP fusion protein is expressed in a peri-nuclear pattern. In adult Amhr2-iCre(Fjd)/+ Sun1LsL/+ mice, Amhr2-iCre(Fjd)-mediated genetic recombination was apparent in uterine epithelial, stromal, and myometrial cells, while Amhr2-IRES-Cre(Bhr)/+ Sun1LsL/+ females demonstrated inter-mouse variability of Amhr2-IRES-Cre(Bhr) activity in uterine cells. Fluorescence was observed in Amhr2-iCre(Fjd)-positive mice at post-natal Day 1, indicating global genetic recombination, while fluorescence of individual Amhr2-IRES-Cre(Bhr)-positive pups varied. To determine the developmental stage that genetic recombination first occurs, Sun1LsL/LsL females were super-ovulated and mated with Amhr2-IRES-Cre(Bhr)/+ or Amhr2(iCre/+)Fjd males, then putative zygotes were collected and cultured. In the four-cell embryo, Amhr2-iCre(Fjd) and Amhr2-IRES-Cre(Bhr) activities were apparent in 100% and 25–100% of cells, respectively. In conclusion, Amhr2-IRES-Cre(Bhr) or Amhr2-iCre(Fjd) driven by the Amhr2 promoter is active in the early embryo and can lead to global genetic modification, rendering this transgenic mouse model ineffective.
Karyotypic diversity: a neglected trait to explain angiosperm diversification?
Authors: Carta Angelino , Escudero Marcial
Published: February 2023

Evolutionary changes in karyotype provide genetic support to organisms’ differentiation and adaptation; however, the association between karyotype diversity and species diversification in flowering plants (angiosperms) remains to be fully elucidated. We sought evidence for this association within a phylogenetic framework using a dataset comprising > 413,000 worldwide chromosome counts of 66,000 angiosperms species. Karyotypic diversity (e.g., number of distinct chromosome numbers) explains species richness and diversification rates at both family and genus levels highlighting that chromosome evolution has probably played, at least, an important role in reinforcing speciation that was already initiated or completed by other geographical or ecological drivers. Thus, research programs investigating chromosome variation as a direct or indirect driver of diversification should be encouraged.
Transcriptomic analysis provides insight into the mechanism of IKKβ-mediated suppression of HPV18E6-induced cellular abnormalities
Authors: Collins Quincy P , Grunsted Michael J , Arcila Dahiana , Xiong Yi , Padash Barmchi Mojgan
Published: February 2023

High-risk human papillomaviruses (HPVs) 16 and 18 are responsible for more than 70% of cervical cancers and majority of other HPV-associated cancers world-wide. Current treatments for these cancers have limited efficacy, which in turn has resulted in disease recurrence and poor survival rates in advanced disease stages. Hence, there is a significant need for development of novel molecularly-targeted therapeutics. This can only be achieved through improved understanding of disease mechanism. Recently, we developed a Drosophila model of HPV18E6 plus human E3 ubiquitin ligase (hUBE3A) and demonstrated that the E6-induced cellular abnormalities are conserved between humans and flies. Subsequently, we demonstrated that reduced level and activity of IKKβ, a regulator of NF-κB, suppresses the cellular abnormalities induced by E6 oncoprotein and that the interaction of IKKβ and E6 is conserved in human cells. In this study, we performed transcriptomic analysis to identify differentially expressed genes that play a role in IKKβ-mediated suppression of E6-induced defects. Transcriptome analysis identified 215 genes whose expression was altered due to reduced levels of IKKβ. Of these 215 genes, 151 genes showed annotations. These analyses were followed by functional genetic interaction screen using RNAi, overexpression, and mutant fly strains for identified genes. The screen identified several genes including genes involved in Hippo and Toll pathways as well as junctional complexes whose downregulation or upregulation resulted in alterations of E6-induced defects. Subsequently, RT-PCR analysis was performed for validation of altered gene expression level for a few representative genes. Our results indicate an involvement for Hippo and Toll pathways in IKKβ-mediated suppression of E6 + hUBE3A-induced cellular abnormalities. Therefore, this study enhances our understanding of the mechanisms underlying HPV-induced cancer and can potentially lead to identification of novel drug targets for cancers associated with HPV.
Application of Dried Urine Spots for Non-Targeted Quadrupole Time-of-Flight Drug Screening
Authors: Stöth Frederike , Martin Fabritius Marie , Weinmann Wolfgang , Luginbühl Marc , Gaugler Stefan , König Stefan
Published: February 2023

The use of dried urine spots (DUS) can simplify sample handling, shipment and storage when compared to liquid urine samples. To prepare DUS, a small amount of urine is pipetted on a filter paper card. The subsequent drying of the specimen can prevent the post-sampling formation or degradation of substances (e.g., caused by bacteria). To evaluate the potential of DUS screening, 17 authentic urine samples, containing a broad range of substances, were extracted and analyzed on a Sciex TripleTOF® 5600+ System using a non-targeted screening and library searching approach. The screening results were compared to the analysis of the same urine sample in liquid form, using the same high-resolution liquid chromatography--quadrupole time-of-flight mass spectrometry method. More than 65 different legal and illegal drugs were successfully identified within the investigated 17 urine samples using the DUS screening approach. When compared to the analysis of liquid urine, the following compounds could not be identified: 1x ecgonine methyl ester, 1x nicotine, 1x promazine and 1x 11-nor-9-carboxy-∆9-tetrahydrocannabinol. Overall, 95.2% of the target substances that have been detected in liquid urine were identified correctly using the DUS approach. In conclusion, DUS screening offers a simple, cost-effective and easier sample handling alternative to the traditional use of liquid urine and provides the detection of the most important substances for forensic requirements. Furthermore, the DUS sample preparation can be fully automated (sample documentation, internal standard application and extraction).
Benign osteonecrosis of the external ear canal: case series
Authors: Chandler Kiyoshi , Hawthorne McKenna , Georgolios Alexandros
Published: February 2023

Benign osteonecrosis of the external ear canal is a rare pathology that commonly gets misdiagnosed as cholesteatoma of the external ear canal, keratosis obturans and malignant otitis externa. Each pathology has characteristics that allow for differentiation between them. Careful analysis is required to diagnose properly and determine the best modality of management. This case series presents two patients that were diagnosed with benign osteonecrosis of the external ear canal and is being managed conservatively with serial debridement. Response to conservative treatment has resulted in adequate control of symptoms in both patients.
Single-port laparoscopic surgery for parasitic cystic teratoma of the greater omentum and bilateral ovarian teratomas: a case report
Authors: Misawa Akihiko , Kimura Eizo , Oka Aiko , Osanai Kiyono , Suzuki Atsushi
Published: February 2023

Teratomas of extragonadal origin are extremely rare. The most common extragonadal site is the greater omentum. A 36-year-old woman was referred to our department for treatment of bilateral ovarian tumors. A 3- to 4-cm mass was observed in each ovary; bilateral ovarian mature cystic teratoma was diagnosed through imaging studies. The patient underwent single-port laparoscopic surgery, during which we found not only bilateral ovarian mature cystic teratomas but also an omental tumor macroscopically similar to the ovarian teratomas. The ovarian and omental teratomas were successfully removed through single-port laparoscopic surgery. The histopathological diagnosis of the omental tumor was parasitic mature cystic teratoma.
Efficacy of Conservative Interventions for Musculoskeletal Conditions on Pain and Disability in Active Serving Military Personnel—A Systematic Review
Authors: Bounds Courtney L , Coppieters Michel W , Thomson Hayley W , Larsen Brianna , Evans Kerrie
Published: February 2023

Introduction

Musculoskeletal (MSK) injuries and associated pain disorders are one of the leading causes for soldiers not being medically fit for deployment, impacting force capability and readiness. Musculoskeletal pain continues to be a leading cause of disability within military services and is associated with a substantial financial burden. A better understanding of the effectiveness of MSK pain management strategies is required. This review was designed to determine the efficacy of nonsurgical interventions, such as physiotherapy, exercise, pharmacology, and multidisciplinary programs, to manage MSK conditions in active serving military populations.

Materials and Methods

MEDLINE, Embase, CINAHL, and SPORTDiscus were searched to identify relevant randomized clinical trials. Recommended methods were used for article identification, selection, and data extraction. The Cochrane Risk of Bias tool and the Grade of Recommendation, Assessment, Development, and Evaluation were used to appraise the studies. Where possible, meta-analyses were performed. The review was conducted according to the PRISMA guidelines.

Results

Nineteen articles (1,408 participants) met the eligibility criteria. Low back pain (LBP) was the most frequently investigated condition, followed by knee pain, neck pain, and shoulder pain. Early physiotherapy, exercise and adjunct chiropractic manipulation (for LBP), and multidisciplinary pain programs (physiotherapy, occupational therapy, and psychology) (for chronic MSK pain) improved pain (standardized mean difference ranged from −0.39 to −1.34; low strength of evidence). Participation in multidisciplinary pain programs, adjunct chiropractic manipulation, and early physiotherapy improved disability (for LBP) (standardized mean difference ranged from −0.45 to −0.86; low to very low strength of evidence). No studies evaluated pain medication. Dietary supplements (glucosamine, chondroitin sulfate, and manganese ascorbate), electrotherapy, isolated lumbar muscle exercises, home cervical traction, or training in virtual reality showed no benefit. The studies had a high risk of bias, were typically underpowered, and demonstrated high clinical heterogeneity.

Conclusions

Currently available randomized clinical trials do not provide sufficient evidence to guide military organizations or health care professionals in making appropriate treatment decisions to manage MSK pain in active serving military personnel. Future research is essential to enable evidence-based recommendations for the effective management of MSK pain conditions in this unique population.
II
Authors: Conrad Joseph
Published: February 2023

There were ten station men who had been left by the Director. Those fellows, having engaged themselves to the Company for six months (without having any idea of a month in particular and only a very faint notion of time in general), had been...
III
Authors: Conrad Joseph
Published: February 2023

For two years at short intervals we visited him. We came to like him, to trust him, almost to admire him. He was plotting and preparing a war with patience, with foresight—with a fidelity to his purpose and with a steadfastness of which I...
VI
Authors: Conrad Joseph
Published: February 2023

Hollis looked smiling into the box. He had lately made a dash home through the Canal. He had been away six months, and only joined us again just in time for this last trip. We had never seen the box before. His hands hovered...
I
Authors: Conrad Joseph
Published: February 2023

The
Nellie, a cruising yawl, swung to her anchor without a flutter of the sails, and was at rest. The flood had made, the wind was nearly calm, and being bound down the river, the only thing for it was to come to and...
II
Authors: Conrad Joseph
Published: February 2023

“One evening as I was lying flat on the deck of my steamboat, I heard voices approaching—and there were the nephew and the uncle strolling along the bank. I laid my head on my arm again, and had nearly lost myself in a doze,...
Pecuniary Emulation
Authors: Veblen Thorstein
Published: February 2023

In the sequence of cultural evolution the emergence of a leisure class coincides with the beginning of ownership. This is necessarily the case, for these two institutions result from the same set of economic forces. In the inchoate phase of their development they are...
Conspicuous Consumption
Authors: Veblen Thorstein
Published: February 2023

In what has been said of the evolution of the vicarious leisure class and its differentiation from the general body of the working classes, reference has been made to a further division of labour,—that between the different servant classes. One portion of the servant...
Dress as an Expression of the Pecuniary Culture
Authors: Veblen Thorstein
Published: February 2023

It will be in place, by way of illustration, to show in some detail how the economic principles so far set forth apply to everyday facts in some one direction of the life process. For this purpose no line of consumption affords a more...
Industrial Exemption and Conservatism
Authors: Veblen Thorstein
Published: February 2023

The life of man in society, just like the life of other species, is a struggle for existence, and therefore it is a process of selective adaptation. The evolution of social structure has been a process of natural selection of institutions. The progress which...
Modern Survivals of Prowess
Authors: Veblen Thorstein
Published: February 2023

The leisure class lives by the industrial community rather than in it. Its relations to industry are of a pecuniary rather than an industrial kind. Admission to the class is gained by exercise of the pecuniary aptitudes—aptitudes for acquisition rather than for serviceability. There...
The Belief in Luck
Authors: Veblen Thorstein
Published: February 2023

The gambling propensity is another subsidiary trait of the barbarian temperament. It is a concomitant variation of character of almost universal prevalence among sporting men and among men given to warlike and emulative activities generally. This trait also has a direct economic value. It...
I
Authors: Norris Frank
Published: February 2023

It was Sunday, and, according to his custom on that day, McTeague took his dinner at two in the afternoon at the car conductors’ coffee-joint on Polk Street. He had a thick gray soup; heavy, underdone meat, very hot, on a cold plate; two...
II
Authors: Norris Frank
Published: February 2023

After his breakfast the following Monday morning, McTeague looked over the appointments he had written down in the book-slate that hung against the screen. His writing was immense, very clumsy, and very round, with huge, full-bellied l’s and h’s. He saw that he had...
III
Authors: Norris Frank
Published: February 2023

Once every two months Maria Macapa set the entire flat in commotion. She roamed the building from garret to cellar, searching each corner, ferreting through every old box and trunk and barrel, groping about on the top shelves of closets, peering into ragbags, exasperating...
VII
Authors: Norris Frank
Published: February 2023

‘What nonsense!’ answered Trina.

‘Ach Gott! What is ut?’ cried Mrs Sieppe, misunderstanding, supposing a calamity.

‘What—what—what,’ stammered the dentist, confused by the lights, the crowded stairway, the medley of voices. The party reached the landing. The others surrounded them. Marcus alone seemed to rise...
IX
Authors: Norris Frank
Published: February 2023

Trina and McTeague were married on the first day of June, in the photographer’s rooms that the dentist had rented. All through May the Sieppe household had been turned upside down. The little box of a house vibrated with excitement and confusion, for not...
X
Authors: Norris Frank
Published: February 2023

That summer passed, then the winter. The wet season began in the last days of September and continued all through October, November, and December. At long intervals would come a week of perfect days, the sky without a cloud, the air motionless, but touched...
XVII
Authors: Norris Frank
Published: February 2023

One day, about a fortnight after the coroner’s inquest had been held, and when the excitement of the terrible affair was calming down and Polk Street beginning to resume its monotonous routine, Old Grannis sat in his clean, well-kept little room, in his cushioned...
XXI
Authors: Norris Frank
Published: February 2023

‘Well,’ said one of the deputies, as he backed the horse into the shafts of the buggy in which the pursuers had driven over from the Hill, ‘we’ve about as good as got him. It isn’t hard to follow a man who carries...
Perspectives on Health With Spinal Cord Injury Now and in the Future: A Qualitative Descriptive Study
Authors: Baehr Laura A , Fisher Kathleen , Finley Margaret
Published: February 2023

Objective

Over the past half century, the landscape of life and aging with spinal cord injury (SCI) has changed drastically, in part due to medical advancements and the rapidly increasing aging population. With these changes comes a critical need for rehabilitation professionals to understand aging with SCI in relation to strategies that support health maintenance over time. The purpose of this study was to identify and describe the meaning of health maintenance and aging outlook from the perspectives of individuals living with SCI.

Methods

A qualitative descriptive approach using focus group interviews and thematic analysis was used to generate a rich understanding of shared experiences with SCI by allowing for discussion among participants.

Results

Participants were 24 individuals ranging in age from 22 to 76 years who were living with chronic SCI (>12 months), with injury duration ranging from 3 to 47 years. Health maintenance was connected to 3 themes: self-management routine to prevent secondary health conditions; importance of injury acceptance over time; and engagement with disability networks. Aging outlook was linked to fear of functional dependence and lack of evidence-based education on aging with SCI.

Conclusion

These findings suggest that individuals living with SCI would benefit from clinical support that acknowledges psychological and social aspects of health beyond physical routines.

Impact

These findings inform the development and implementation of SCI-related interventions to maximize healthy aging. It is crucial for clinicians and researchers to investigate issues beyond routine self-management and functional independence to support the emotional adjustment of life with SCI. Unique personal considerations based on life stage when injured warrant investigation. Education and advocacy for peer support is imperative at all life stages given its positive impact on health.
Small-molecule screening in aged Drosophila identifies mGluR as a regulator of age-related sleep impairment
Authors: Hou Xue , Hayashi Reina , Itoh Motoyuki , Tonoki Ayako
Published: February 2023

As a normal physiological phenomenon, aging has a significant impact on sleep. Aging leads to sleep impairment, including sleep loss, fragmented sleep, and a lower arousal threshold, leading to various diseases. Because sleep regulates memory consolidation, age-dependent sleep impairment also affects memory. However, the mechanisms underlying age-related sleep dysregulation and its impact on memory remain unclear. Using male and female Drosophila as a model, which possesses sleep characteristics similar to those of mammals and exhibits age-dependent sleep impairment, we performed small-molecule screening to identify novel regulators of age-dependent decline in sleep. The screening identified 3,3ʹ-difluorobenzaldazine (DFB), a positive allosteric modulator of the metabotropic glutamate receptor (mGluR) 5, as a novel sleep-promoting compound in aged flies. We found that mutant flies of mGluR, a single mGluR gene in Drosophila, and decreased mGluR expression had significant impairment in sleep and memory due to olfactory conditioning. The decreased sleep phenotype in the mGluR mutants was not promoted by DFB, suggesting that the effects of DFB on age-dependent sleep impairment are dependent on mGluR. Although aging decreases the expression of mGluR and the binding scaffold proteins Homer and Shank, the transient overexpression of mGluR in neurons improves sleep in both young and aged flies. Overall, these findings indicate that age-dependent decreased expression or function of mGluR impairs sleep and memory in flies, which could lead to age-related sleep and memory impairment.
Taurine protects against perfluorooctanoic acid-induced hepatotoxicity via inhibition of oxidative stress, inflammatory, and apoptotic pathways
Authors: Naderi Maloos , Seyedabadi Mohammad , Amiri Fereshteh Talebpour , Mohammadi Ebrahim , Akbari Sholeh , Shaki Fatemeh
Published: February 2023

We are constantly encountering with low doses of chemicals in everyday life rather than toxic doses at a time. So, ongoing low-dose exposures of environmental chemicals commonly encountered are very likely to cause an adverse health effects. Perfluorooctanoic acid (PFOA) is frequently used for production of an array of consumer products and industrial processes. The present study evaluated the underlying mechanisms of PFOA-induced liver damage and also potential protection by taurine. Male Wistar rats were exposed to PFOA alone and in combination with taurine (25, 50, and 100 mg/kg/day) by gavage for 4 weeks. Liver function tests as well as histopathological examinations were studied. Also, oxidative stress markers, mitochondrial function, and nitric oxide (NO) production in liver tissues were measured. In addition, the expression of apoptosis-related genes (caspase-3, Bax, and Bcl-2), inflammation-associated genes (TNF-α, IL-6, NF-B), and c-Jun-N-terminal kinase (JNK) were evaluated. Taurine significantly reversed serum biochemical and histopathological alterations in the liver tissue following exposure to PFOA (10 mg/kg/day). Similarly, taurine alleviated mitochondrial oxidative damage-induced by PFOA in the liver tissue. An increased Bcl2: Bax ratio with decrees in the expression level of caspase-3, and decreased expression of inflammatory markers (TNF-α and IL-6), NF-B, and JNK were also observed following the administration of taurine. These findings suggest a protective role of taurine against PFOA-induced hepatotoxicity via the inhibition of oxidative stress, inflammation, and apoptosis.