bluuebunny/crossref_metadata_2025 huggingface dataset:
The Game and the Nation—Act Second
Authors: Wister Owen
Published: June 2023

“That is the only step I have had to take this whole trip,” said the Virginian. He holstered his pistol with a jerk. “I have been fearing he would force it on me.” And he looked at empty, receding Dakota with disgust. “So...
The Game and the Nation—Last Act
Authors: Wister Owen
Published: June 2023

It has happened to you, has it not, to wake in the morning and wonder for a while where on earth you are? Thus I came half to life in the caboose, hearing voices, but not the actual words at first.

But presently, “Hathaway!” said...
Scipio Moralizes
Authors: Wister Owen
Published: June 2023

Into what mood was it that the Virginian now fell? Being less busy, did he begin to “grieve” about the girl on Bear Creek? I only know that after talking so lengthily he fell into a nine days’ silence. The talking part of him...
“Would you be a Parson?”
Authors: Wister Owen
Published: June 2023

After this I gave up my experiments in conversation. So that by the final afternoon of our journey, with Sunk Creek actually in sight, and the great grasshoppers slatting their dry song over the sagebrush, and the time at hand when the Virginian and...
“What is a Rustler?”
Authors: Wister Owen
Published: June 2023

We all know what birds of a feather do. And it may be safely surmised that if a bird of any particular feather has been for a long while unable to see other birds of its kind, it will flock with them all the...
A Stable on the Flat
Authors: Wister Owen
Published: June 2023

When the first landmark, the lone clump of cotton-woods, came at length in sight, dark and blurred in the gentle rain, standing out perhaps a mile beyond the distant buildings, my whole weary body hailed the approach of repose. Saving the noon hour, I...
The Cottonwoods
Authors: Wister Owen
Published: June 2023

I do not know how long I stayed there alone. It was the Virginian who came back, and as he stood at the foot of my blankets his eye, after meeting mine full for a moment, turned aside. I had never seen him look...
“To fit her Finger”
Authors: Wister Owen
Published: June 2023

It was two rings that the Virginian wrote for when next I heard from him.

After my dark sight of what the Cattle Land could be, I soon had journeyed home by way of Washakie and Rawlins. Steve and Shorty did not leave my memory,...
Chapter One
Authors: London Jack
Published: June 2023

I SCARCELY know where to begin, though I sometimes facetiously place the cause of it all to Charley Furuseth’s credit. He kept a summer cottage in Mill Valley,* under the shadow of Mount Tamalpais, and never occupied it except when he loafed through...
Chapter Three
Authors: London Jack
Published: June 2023

WOLF LARSEN ceased swearing as suddenly as he had begun. He relighted his cigar and glanced around. His eyes chanced upon the cook.

“Well, Cooky?” he began, with a suaveness that was cold and of the temper of steel.

“Yes, sir,” the cook eagerly interpolated,...
Chapter Six
Authors: London Jack
Published: June 2023

BY the following morning the storm had blown itself quite out and the Ghost was rolling slightly on a calm sea without a breath of wind. Occasional light airs were felt, however, and Wolf Larsen patrolled the poop constantly, his eyes ever searching...
Chapter Nine
Authors: London Jack
Published: June 2023

THREE days of rest, three blessed days of rest, are what I had with Wolf Larsen, eating at the cabin table and doing nothing but discuss life, literature, and the universe, the while Thomas Mugridge fumed and raged and did my work as well as...
Chapter Ten
Authors: London Jack
Published: June 2023

MY intimacy with Wolf Larsen increases—if by intimacy may be denoted those relations which exist between master and man, or, better yet, between king and jester. I am to him no more than a toy, and he values me no more than a child values...
Chapter Twelve
Authors: London Jack
Published: June 2023

THE last twenty-four hours have witnessed a carnival of brutality. From cabin to forecastle it seems to have broken out like a contagion. I scarcely know where to begin. Wolf Larsen was really the cause of it. The relations among the men, strained and made...
Chapter Fifteen
Authors: London Jack
Published: June 2023

THERE was a deal of cursing and groaning as the men at the bottom of the ladder crawled to their feet.

“Somebody strike a light, my thumb’s out of joint,” said one of the men, Parsons, a swarthy, saturnine man, boat-steerer in Standish’s boat, in...
Chapter Sixteen
Authors: London Jack
Published: June 2023

I CANNOT say that the position of mate carried with it anything more joyful than that there were no more dishes to wash. I was ignorant of the simplest duties of mate, and would have fared badly indeed had the sailors not sympathized with me....
Chapter Nineteen
Authors: London Jack
Published: June 2023

I CAME on deck to find the Ghost heading up close on the port tack and cutting in to windward of a familiar spritsail close-hauled on the same tack ahead of us. All hands were on deck, for they knew that something was...
Chapter Twenty
Authors: London Jack
Published: June 2023

THE remainder of the day passed uneventfully. The young slip of a gale, having wetted our gills, proceeded to moderate. The fourth engineer and the three oilers, after a warm interview with Wolf Larsen, were furnished with outfits from the slop-chests, assigned places under the...
Chapter Twenty-One
Authors: London Jack
Published: June 2023

THE chagrin Wolf Larsen felt from being ignored by Maud Brewster and me in the conversation at table had to express itself in some fashion, and it fell to Thomas Mugridge to be the victim. He had not mended his ways nor his shirt, though...
Chapter Twenty-Six
Authors: London Jack
Published: June 2023

WOLF LARSEN took the distribution of the whiskey off my hands, and the bottles began to make their appearance while I worked over the fresh batch of wounded men in the forecastle. I had seen whiskey drunk, such as whiskey and soda by the men...
Chapter Twenty-Seven
Authors: London Jack
Published: June 2023

DAY broke, gray and chill. The boat was close-hauled on a fresh breeze and the compass indicated that we were just making the course which would bring us to Japan. Though stoutly mittened, my fingers were cold, and they pained from the grip on the...
Chapter Twenty-Eight
Authors: London Jack
Published: June 2023

THERE is no need of going into an extended recital of our suffering in the small boat during the many days we were driven and drifted, here and there, willy-nilly, across the ocean. The high wind blew from the northwest for twenty-four hours, when it...
Chapter Thirty-Two
Authors: London Jack
Published: June 2023

I AWOKE, oppressed by a mysterious sensation. There seemed something missing in my environment. But the mystery and oppressiveness vanished after the first few seconds of waking, when I identified the missing something as the wind. I had fallen asleep in that state of nerve...
Chapter Thirty-Nine
Authors: London Jack
Published: June 2023

THE day came for our departure. There was no longer anything to detain us on Endeavor Island. The Ghost’s stumpy masts were in place, her crazy sails bent. All my handiwork was strong, none of it beautiful; but I knew that it would...
III
Authors: Saunders Max
Published: June 2023

it was a very hot summer, in August, 1904; and Florence had already been taking the baths for a month. I don’t know how it feels to be a patient at one of those places. I never was a patient anywhere. I daresay the patients...
V
Authors: Saunders Max
Published: June 2023

Those words gave me the greatest relief that I have ever had in my life. They told me, I think, almost more than I have ever gathered at any one moment—about myself. I don’t think that before that day I had ever wanted anything very...
I
Authors: Saunders Max
Published: June 2023

The death of Mrs. Maidan occurred on the 4th of August, 1904. And then nothing happened until the 4th of August, 1913. There is the curious coincidence of dates, but I do not know whether that is one of those sinister, as if half-jocular and...
II
Authors: Saunders Max
Published: June 2023

Immediately after Florence’s death Leonora began to put the leash upon Nancy Rufford and Edward. She had guessed what had happened under the trees near the Casino. They stayed at Nauheim some weeks after I went, and Leonora has told me that that was the...
VI
Authors: Saunders Max
Published: June 2023

My coming on the scene certainly calmed things down—for the whole fortnight that intervened between my arrival and the girl’s departure. I don’t mean to say that the endless talking did not go on at night or that Leonora did not send me out with...
May Day
Authors: Bryer Jackson R.
Published: June 2023

There had been a war fought and won and the great city of the conquering people was crossed with triumphal arches and vivid with thrown flowers of white, red, and rose. All through the long spring days the returning soldiers marched up the chief...
The Curious Case of Benjamin Button
Authors: Bryer Jackson R.
Published: June 2023

As long ago as 1860 it was the proper thing to be born at home. At present, so I am told, the high gods of medicine have decreed that the first cries of the young shall be uttered upon the anesthetic air of a...
“O Russet Witch!”
Authors: Bryer Jackson R.
Published: June 2023

Merlin Grainger was employed by the Moonlight Quill Bookshop, which you may have visited, just around the corner from the Ritz-Carlton on Forty-seventh Street. The Moonlight Quill is, or rather was, a very romantic little store, considered radical and admitted dark. It was spotted...
Jemina, The Mountain Girl
Authors: Bryer Jackson R.
Published: June 2023

This don’t pretend to be “Literature.” This is just a tale for red-blooded folks who want a story and not just a lot of “psychological” stuff or “analysis.” Boy, you’ll love it! Read it here, see it in the movies, play it on...
Afterword
Authors: Freud Sigmund
Published: June 2023

While I have called this record the fragment of an analysis, the reader will have discovered that it is incomplete to a much wider extent than might be expected from that title. It is only right for me to try to explain the reasons...
Enhancing the activity of a monomeric alcohol dehydrogenase for site-specific applications by site-directed mutagenesis
Authors: Essert Arabella , Castiglione Kathrin
Published: June 2023

Gene fusion or co-immobilization are key tools to optimize enzymatic reaction cascades by modulating catalytic features, stability and applicability. Achieving a defined spatial organization between biocatalysts by site-specific applications is complicated by the involvement of oligomeric enzymes. It can lead to activity losses due to disturbances of the quaternary structures and difficulties in stoichiometric control. Thus, a toolkit of active and robust monomeric enzymes is desirable for such applications. In this study, we engineered one of the rare examples of monomeric alcohol dehydrogenases for improved catalytic characteristics by site-directed mutagenesis. The enzyme from the hyperthermophilic archaeon Thermococcus kodakarensis naturally exhibits high thermostability and a broad substrate spectrum, but only low activity at moderate temperatures. The best enzyme variants showed an ~5-fold (2-heptanol) and 9-fold (3-heptanol) higher activity while preserving enantioselectivity and good thermodynamic stability. These variants also exhibited modified kinetic characteristics regarding regioselectivity, pH dependence and activation by NaCl.
Validity of self-reported height, weight and BMI as applied to trends in malnutrition in Davao City, Philippines
Authors: Quianzon-Manuel Maria Fatima L , Fabian Noleen Marie C , Taduran Richard Jonathan O
Published: June 2023

Background

Self-reported height, weight and body mass index (BMI) data are widely used to monitor trends in malnutrition. However, several studies expressed concerns about its reliability—citing trends of over-reporting and underreporting anthropometric data. This study aims to: (1) identify the validity of self-reported height and weight and BMI as compared with measured values and (2) examine the potential recurrence of malnutrition in an urban-based population.

Methods

Paired t-tests and Pearson’s correlation coefficients were conducted to identify potential discrepancies between self-reported and measured anthropometric data. These values were collected among 255 male and 400 female participants in the Davao City.

Results

Height overestimation in females and underestimation in males were observed to be statistically significant (P < 0.05). Researchers also note an alarming rise in malnutrition cases when the Asia-Pacific Index was applied to the BMI study data. A 40.79 and 22% increase in obese cases among male and female respondents were recorded.

Conclusion

Modifying participant-gathered height and weight values is likely to result in discrepancies between self-reported and measured values. Identifying a person’s height and weight status is crucial to understanding who among the population experience malnutrition. Thus, policymakers are called to strengthen educational support that trains respondents to report reliable and valid health data.
AI am a rheumatologist: a practical primer to large language models for rheumatologists
Authors: Venerito Vincenzo , Bilgin Emre , Iannone Florenzo , Kiraz Sedat
Published: June 2023

Natural language processing (NLP), a subclass of artificial intelligence, large language models (LLMs), and its latest applications, such as Generative Pre-trained Transformers (GPT), ChatGPT, or LLAMA, have recently become one of the most discussed topics. Up to now, artificial intelligence and NLP ultimately impacted several areas, such as finance, economics and diagnostic/scoring systems in healthcare. Another area that artificial intelligence has affected and will continue to affect increasingly is academic life. This narrative review will define NLP, LLMs and their applications, discuss the opportunities and challenges that components of academic society will experience in rheumatology, and discuss the impact of NLP and LLMs in rheumatology healthcare.
SECRETARY OF STATE FOR HEALTH v SERVIER LABORATORIES LTD
Authors:   Supreme Court
Published: June 2023

H1 Patents — European patents — Pharmaceuticals — Generic products — Economic torts — Unlawful means — Strike out application — Necessary elements of the tort — Whether the unlawful means had to interfere with claimant’s liberty to deal with third party against whom the unlawful act relied upon had been committed — Invalid patents — Proceedings for patent infringement — Interim injunctions — Market entry of third party generic product delayed — Prices thereby maintained — Patent later invalidated — Claim struck out at first instance and decision upheld by Court of Appeal — Appeal to Supreme Court
The Potential Role of Exosomes in Aesthetic Plastic Surgery: A Review of Current Literature
Authors: Ku Ying C. , Omer Sulaiman Hafsa , Anderson Spencer R. , Abtahi Ali R.
Published: June 2023

Background:

Despite an increasing surge of exosome use throughout the aesthetic arena, a paucity of published exosome-based literature exists. Exosomes are membrane-bound extracellular vesicles derived from various cell types, exerting effects via intercellular communication and regulation of several signaling pathways. The purpose of this review was to summarize published articles elucidating mechanisms and potential applications, report available products and clinical techniques, and prompt further investigation of this emerging treatment within the plastic surgery community.

Methods:

A literature review was performed using PubMed with keywords exosomes, secretomes, extracellular vesicles, plastic surgery, skin rejuvenation, scar revision, hair growth, body contouring, and breast augmentation. Publications from 2010 to 2021 were analyzed for relevance and level of evidence. A Google search identified exosome distributors, where manufacturing/procurement details, price, efficacy, and clinical indications for use were obtained by direct contact and summarized in table format.

Results:

Exosomes are currently derived from bone marrow, placental, adipose, and umbilical cord tissue. Laboratory-based exosome studies demonstrate enhanced outcomes in skin rejuvenation, scar revision, hair restoration, and fat graft survival on the macro and micro levels. Clinical studies are limited to anecdotal results. Prices vary considerably from $60 to nearly $5000 based on company, source tissue, and exosome concentration. No exosome-based products are currently Food and Drug Administration–approved.

Conclusions:

Administered alone or as an adjunct, current reports show promise in several areas of aesthetic plastic surgery. However, ongoing investigation is warranted to further delineate concentration, application, safety profile, and overall outcome efficacy.
Red Breast Syndrome and Acellular Dermal Matrix
Authors: Podsednik Gardner Allison , Nunez Aidee , De la Garza Mauricio
Published: June 2023

Increasingly popular for use in breast reconstruction, acellular dermal matrix (ADM) can provide support and protection to implants. However, use of ADM may be associated with infection and complications, including red breast syndrome (RBS). RBS is an inflammatory event that typically presents with cutaneous erythema over the domain where the ADM is surgically implanted. As ADM use increases, presumably, more cases of RBS will occur. Thus, techniques and tools to mitigate or manage RBS are needed to improve patient outcomes. Here, we describe a case where RBS was diagnosed and interestingly resolved after exchange for a different brand of dermal matrix. This surgical resolution maintained excellent reconstructive results with no recurrent erythema over a follow-up period of 7 months. Although we cannot rule out RBS due to other variables, RBS due to patient hypersensitivity to certain ADMs has been documented in the literature. In this instance, our results suggest that revision with an alternate ADM brand may serve as a potential solution.
Requirements for design and function of blood pressure measuring devices used for the management of hypertension: Consensus Statement by the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability and STRIDE BP
Authors: Stergiou George S. , Parati Gianfranco , Kollias Anastasios , Schutte Aletta E. , Asayama Kei , Asmar Roland , Bilo Grzegorz , de la Sierra Alejandro , Dolan Eamon , Filipovsky Jan , Head Geoffrey , Kario Kazuomi , Kyriakoulis Konstantinos G. , Mancia Giuseppe , Manios Efstathios , Menti Ariadni , McManus Richard J. , Mihailidou Anastasia S. , Muntner Paul , Niiranen Teemu , Ohkubo Takayoshi , Omboni Stefano , Protogerou Athanasios , Saladini Francesca , Sharman James , Shennan Andrew , Shimbo Daichi , Topouchian Jirar , Wang Jiguang , O’Brien Eoin , Palatini Paolo
Published: June 2023

Objective:

To develop scientific consensus recommendations for the optimal design and functions of different types of blood pressure (BP) measuring devices used in clinical practice for the detection, management, and long-term follow-up of hypertension.

Methods:

A scientific consensus meeting was performed by the European Society of Hypertension (ESH) Working Group on BP Monitoring and Cardiovascular Variability and STRIDE BP (Science and Technology for Regional Innovation and Development in Europe) during the 2022 Scientific Meeting of the ESH in Athens, Greece. Manufacturers were also invited to provide their feedback on BP device design and development. Thirty-one international experts in clinical hypertension and BP monitoring contributed to the development of consensus recommendations on the optimal design of BP devices.

Statement:

International consensus was reached on the requirements for the design and features of five types of BP monitors, including office (or clinic) BP monitors, ambulatory BP monitors, home BP monitors, home BP telemonitors, and kiosk BP monitors for public spaces. For each device type “essential” requirements (must have), and “optional” ones (may have) are presented, as well as additional comments on the optimal device design and features.

Conclusions:

These consensus recommendations aim at providing manufacturers of BP devices with the requirements that are considered mandatory, or optional, by clinical experts involved in the detection and management of hypertension. They are also directed to administrative healthcare personnel involved in the provision and purchase of BP devices so that they can recommend the most appropriate ones.
MULTIPLYING BROWN SPOTS
Authors: Alsoudi Amer F. , Parvus Matthew N. , Pulido Jose , Chevez-Barrios Patricia , Teh Bin S. , Bernicker Eric , Miles Sarah , Schefler Amy
Published: June 2023

Background/Purpose:

Bilateral diffuse uveal melanocytic proliferation is a paraneoplastic syndrome affecting the eye that is a sign of poor prognosis of underlying malignancy. This is the first documented case to show serial and sustained improvement of bilateral diffuse uveal melanocytic proliferation after immunotherapy in the setting of primary non–small-cell carcinoma of the lung.

Methods:

Single-center, case report.

Results:

A 65-year-old man reported a gradual decrease in vision and floaters in the right eye after cataract surgery. Fundus examination demonstrated diffuse multiple brown subretinal lesions bilaterally. Next-generation sequencing of melanocytic tissue of the patient described in this case revealed a specific RB1c.411A>T (p.Glu137Asp) variant with an allele frequency of 44.8%, consistent with heterozygosity. Plasma samples from the patient and a control patient with no history of cancer and/or paraneoplastic syndrome were cultured with neonatal melanocytes, which revealed a >180% increase in proliferation of normal neonatal melanocytes compared with the control. Pembrolizumab therapy was initiated, which resulted in shrinkage and stabilization of the lesions documented in serial diagnostic testing.

Conclusion:

In conclusion, we report a cytologically and serologically confirmed case of bilateral diffuse uveal melanocytic proliferation in a patient with a primary non–small-cell carcinoma of the lung. Next-generation sequencing of melanocytic tissue of the patient described in this case revealed a specific RB1 c.411A>T (p.Glu137Asp) variant with an allele frequency of 44.8%, consistent with heterozygosity. Furthermore, we show documented serial improvement in the patient's ocular and systemic disease with treatment. This case as one of the longest surviving confirmed cases of a patient with bilateral diffuse uveal melanocytic proliferation.
Nutrition and autophagy deficiency in critical illness
Authors: Vanhorebeek Ilse , Casaer Michaël , Gunst Jan
Published: June 2023

Purpose of review

Critical illness imposes a severe insult on the body, with various stressors triggering pronounced cell damage. This compromises cellular function, leading to a high risk of multiple organ failure. Autophagy can remove damaged molecules and organelles but appears insufficiently activated during critical illness. This review discusses insight into the role of autophagy in critical illness and the involvement of artificial feeding in insufficient autophagy activation in critical illness.

Recent findings

Animal studies manipulating autophagy have shown its protective effects against kidney, lung, liver, and intestinal injury after several critical insults. Autophagy activation also protected peripheral, respiratory, and cardiac muscle function, despite aggravated muscle atrophy. Its role in acute brain injury is more equivocal. Animal and patient studies showed that artificial feeding suppressed autophagy activation in critical illness, particularly with high protein/amino acid doses. Feeding-suppressed autophagy may explain short and long-term harm by early enhanced calorie/protein feeding in large randomized controlled trials.

Insufficient autophagy during critical illness is at least partly explained by feeding-induced suppression. This may explain why early enhanced nutrition failed to benefit critically ill patients or even induced harm. Safe, specific activation of autophagy avoiding prolonged starvation opens perspectives for improving outcomes of critical illness.
An update on essential micronutrients in critical illness
Authors: Koekkoek Kristine W.A. , Berger Mette M.
Published: June 2023

Purpose of review

Numerous micronutrients are involved in antioxidant and immune defence, while their blood concentrations are frequently low in critically ill patients: this has fuelled many supplementation trials. Numerous observational, randomized studies have been published, which are presented herein.

Recent findings

Micronutrient concentrations must be analysed considering the context of the inflammatory response in critical illness. Low levels do not always indicate a deficiency without objective micronutrients losses with biological fluids. Nevertheless, higher needs and deficiencies are frequent for some micronutrients, such as thiamine, vitamins C and D, selenium, zinc and iron, and have been acknowledged with identifying patients at risk, such as those requiring continuous renal replacement therapy (CRRT). The most important trials and progress in understanding have occurred with vitamin D (25(OH)D), iron and carnitine. Vitamin D blood levels less than 12 ng/ml are associated with poor clinical outcomes: supplementation in deficient ICU patients generates favourable metabolic changes and decreases mortality. Single high-dose 25(OH)D should not be delivered anymore, as boluses induce a negative feedback mechanism causing inhibition of this vitamin. Iron-deficient anaemia is frequent and can be treated safely with high-dose intravenous iron under the guidance of hepcidin to confirm deficiency diagnosis.

The needs in critical illness are higher than those of healthy individuals and must be covered to support immunity. Monitoring selected micronutrients is justified in patients requiring more prolonged ICU therapy. Actual results point towards combinations of essential micronutrients at doses below upper tolerable levels. Finally, the time of high-dose micronutrient monotherapy is probably over.
Defining the Incidence of the Impostor Phenomenon in Academic Plastic Surgery: A Multi-Institutional Survey Study
Authors: Sergesketter Amanda R. , Butler Paris D. , Gosman Amanda A. , Leis Amber , Baynosa Richard C. , Momeni Arash , Greives Matthew R. , Sears Erika D. , Park Julie E. , Butterworth James A. , Janis Jeffrey E. , Rezak Kristen , Patel Ashit
Published: June 2023

BACKGROUND:

Impostor phenomenon occurs when high-achieving individuals have persistent self-doubt despite objective measures of competence and success, and has been associated with professional burnout and attenuated career advancement in medical specialties. This study aimed to define the incidence and severity of the impostor phenomenon in academic plastic surgery.

METHODS:

A cross-sectional survey containing the Clance Impostor Phenomenon Scale (0-100; higher scores indicating greater severity of impostor phenomenon) was distributed to residents and faculty from 12 academic plastic surgery institutions across the United States. Generalized linear regression was used to assess demographic and academic predictors of impostor scores.

RESULTS:

From a total of 136 resident and faculty respondents (response rate, 37.5%), the mean impostor score was 64 (SD 14), indicating frequent impostor phenomenon characteristics. On univariate analysis, mean impostor scores varied by gender (Female: 67.3 vs. Male: 62.0; p=0.03) and academic position (Residents: 66.5 vs. Attendings: 61.6; p=0.03), but did not vary by race/ethnicity, post-graduate year of training among residents, or academic rank, years in practice, or fellowship training among faculty (all p>0.05). After multivariable adjustment, female gender was the only factor associated with higher impostor scores among plastic surgery residents and faculty (Estimate 2.3; 95% Confidence Interval 0.03-4.6; p=0.049).

CONCLUSION:

The prevalence of the impostor phenomenon may be high among residents and faculty in academic plastic surgery. Impostor characteristics appear to be tied more to intrinsic characteristics, including gender, rather than years in residency or practice. Further research is needed to understand the influence of impostor characteristics on career advancement in plastic surgery.
Inappropriate Indexing of Case Reports to the “Papilledema” Subject Heading: A Systematic Review
Authors: Tao Brendan K. , Vosoughi Amir R. , Pandya Bhadra U. , Ishaq Junaid , Margolin Edward A. , Micieli Jonathan A.
Published: June 2023

Background:

Papilledema must be managed distinctly from other causes of optic disc edema (ODE) due to its basis in raised intracranial pressure (ICP). However, evidence indicates that the term “papilledema” is widely misused across specialties to describe ODE without raised ICP. Sources of this misconception remain undiscerned. Because all physicians consult medical databases, our objective was to evaluate whether nonspecific “papilledema” subject heading definitions misleadingly associate articles on other conditions with papilledema proper.

Methods:

Systematic review of case reports, prospectively registered on PROSPERO (CRD42022363651). MEDLINE and Embase were searched to July 2022 for any full-length case report indexed to the “papilledema” subject heading. Studies were graded for incorrect indexing, defined as cases lacking evidence for raised ICP. Nonpapilledema diagnoses were assigned to a predefined set of diseases and pathophysiological mechanisms for subsequent comparison.

Results:

Incorrect indexing occurred in 40.67% of 949 included reports. Embase-derived studies were misindexed significantly less than MEDLINE-derived studies (P < 0.01). There was also significant heterogeneity in incorrect indexing among specific diseases (P = 0.0015) and mechanisms (P = 0.0003). The most commonly misindexed diseases were uveitis (21.24% of errors), optic neuritis (13.47%), and instances with no mention of ODE (13.99%). The most commonly misindexed mechanisms were inflammation (34.97%), other mechanism (e.g., genetic; 25.91%), and ischemia (20.47%).

Conclusions:

Database subject headings, especially from MEDLINE, do not adequately distinguish between true papilledema and other causes of ODE. Inflammatory diseases were most often incorrectly indexed among other diseases and mechanisms. Current “papilledema” subject headings should be revised to reduce the probability of misinformation.
Social Media in Neuro-Ophthalmology: Paradigms, Opportunities, and Strategies
Authors: Lai Kevin E. , Antonio Aileen A. , Ko Melissa W. , Epling Joel P. , Nguyen Anne X. , Carey Andrew R.
Published: June 2023

Background:

Social media (SoMe) is an integral part of life in the 21st century. Its potential for rapid dissemination and amplification of information offers opportunities for neuro-ophthalmologists to have an outsized voice to share expert-level knowledge with the public, other medical professionals, policymakers, and trainees. However, there are also potential pitfalls, because SoMe may spread incorrect or misleading information. Understanding and using SoMe enables neuro-ophthalmologists to influence and educate that would otherwise be limited by workforce shortages.

Evidence Acquisition:

A PubMed search for the terms “social media” AND “neuro-ophthalmology,” “social media” AND “ophthalmology,” and “social media” AND “neurology” was performed.

Results:

Seventy-two neurology articles, 70 ophthalmology articles, and 3 neuro-ophthalmology articles were analyzed. A large proportion of the articles were published in the last 3 years (2020, 2021, 2022). Most articles were analyses of SoMe content; other domains included engagement analysis such as Altmetric analysis, utilization survey, advisory opinion/commentary, literature review, and other. SoMe has been used in medicine to share and recruit for scientific research, medical education, advocacy, mentorship and medical professional networking, and branding, marketing, practice building, and influencing. The American Academy of Neurology, American Academy of Ophthalmology, and North American Neuro-Ophthalmology Society have developed guidelines on the use of SoMe.

Conclusions:

Neuro-ophthalmologists may benefit greatly from harnessing SoMe for the purposes of academics, advocacy, networking, and marketing. Regularly creating appropriate professional SoMe content can enable the neuro-ophthalmologist to make a global impact.
Blinking Parameters Do Not Normalize After Botulinum Toxin Therapy in Blepharospasm and Hemifacial Spasm Patients
Authors: Gameiro Gustavo R. , Osaki Midori H. , Yabumoto Cristina , Osaki Teissy , Garcia Denny M. , Belfort Rubens , Cruz Antonio Augusto V. , Osaki Tammy H.
Published: June 2023

Background:

Little is known regarding changes induced by botulinum toxin injections on blinking parameters in blepharospasm (BSP) and hemifacial spasm (HFS) patients. The purpose of this study was to investigate objective changes induced by botulinum toxin (BoNT) injections on blinking parameters in BSP and HFS patients.

Methods:

Thirty-seven patients with BSP and HFS were evaluated before and 30 days after receiving onabotulinumtoxinA injections. Twelve age-matched control subjects were also assessed. Pretreatment and post-treatment parameters were assessed and compared with normal controls. A high-speed camera and microlight-emitting diodes were used to register the blinking in patients and control groups. Outcomes were blinking frequency, amplitude, and maximum velocity of eyelid closure.

Results:

BoNT injections led to a significant reduction in all parameters, compared with baseline, in BSP and on the affected side in HFS, respectively: 22% (P < 0.001) and 20% (P = 0.015) in amplitude; 21% (P = 0.04) and 39% in frequency (P = 0.002); and 41% (P < 0.001) and 26% (P = 0.005) in maximum closing velocity. Blinking amplitude (P = 0.017 and P = 0.019) and velocity (P < 0.001 for both groups) were significantly lower at 30 days on BSP and on the affected HFS side, when compared with controls. BSP and HFS patients presented a significantly lower velocity of eyelid closure, even before BoNT, compared with controls (P = 0.004. and P < 0.001, respectively).

Conclusions:

Although blinking frequency became close to normal, amplitude and velocity after BoNT applications were significantly lower in BSP and on the affected side of HFS patients when compared with age-matched normal controls, demonstrating that blinking parameters do not normalize after treatment. The velocity of eyelid closure was shown to be significantly lower, even before BoNT treatment, when compared with control subjects.
Metabolic perturbations and key pathways associated with the bacteriostatic activity of Clitoria ternatea flower anthocyanin fraction against Escherichia coli
Authors: Jeyaraj Ethel Jeyaseela , Han Mei-Ling , Li Jian , Choo Wee Sim
Published: June 2023

Clitoria ternatea flowers are rich in anthocyanins and possess various biological activities. Specifically, the antibacterial mechanism of action of C. ternatea anthocyanins remains unknown and was investigated in Escherichia coli. Time-kill assay was used to assess the antibacterial activity and the metabolic perturbations in E. coli were investigated utilising LC-MS-based metabolomics. Pathway analyses were carried out for metabolites showing ≥ 2-fold changes. The anthocyanin fraction remarkably reduced the growth of E. coli at 4 h by 95.8 and 99.9% at minimum inhibitory concentration (MIC) and 2 × MIC, respectively. The antibacterial activity of the anthocyanin fraction (MIC) was shown to have perturbed glycerophospholipids (1-Acyl-sn-glycero-3-phosphoethanolamine, phosphatidylglycerol, diacylglycerol and cardiolipin), amino acids (valine, tyrosine and isoleucine) and energy (ubiquinone and NAD) metabolites at 1 and 4 h. This study demonstrated significant metabolic perturbations of the glycerophospholipid, amino acid and energy metabolism being the key pathways involved in the antibacterial activity of anthocyanins from C. ternatea and has promising potential as antibacterial agents for E. coli-related infections.
Streptococcus parasanguinis: An emerging pathogen causing neonatal endocarditis: A case report
Authors: Shrimali Twishi , Malhotra Shikhir , Relhan Nidhi , Tak Vibhor , Choudhary Sushil Kumar , Gupta Neeraj , Singh Arun Kumarendu
Published: June 2023

Background
The microbial infection of the endocardium, popularly known as Infective Endocarditis (IE), is typically classified on the basis of anatomy, valve nativity and its associated microbiology. As per the associated microbiology, Staphylococcus aureus is the most common microorganism responsible for the cause of IE. Even though, Streptococcus group  accounts for a smaller percentage of IE, however this doesn’t give us the liberty of ignoring the high mortality and morbidity associated with this pathogen.
Case presentation
We report an unusual case of neonatal sepsis, complicated with endocarditis, caused by penicillin resistant Streptococcus parasanguinis. The neonate however died of the same despite all efforts. The said baby was given birth by a mother with gestational diabetes mellitus.  
Conclusion
High index of clinical suspicion and prompt diagnosis are the most important factors of patient management, especially in cases of life threatening neonatal infections. In such conditions a coordinated interdepartmental approach is very much needed.
SARS-CoV-2 infections among pregnant women, 2020, Finland – cross-testing of neutralization assays
Authors: Virtanen J , Korhonen EM , Salonen S , Vapalahti O , Sironen T , Jääskeläinen AJ
Published: June 2023

We studied the development of SARS-CoV-2 pandemic in Finland in 2020 and evaluated the performance of two surrogate immunoassays for detection of neutralizing antibodies (NAbs). The dataset consisted of 12000 retrospectively collected samples from pregnant women in their 1sttrimester throughout 2020. All the samples were initially screened for IgG with SARS-CoV-2 spike antibody assay (EIM-S1, Euroimmun, Lübeck, Germany) followed by confirmation with nucleocapsid antibody assay (Architect SARS-CoV-2, Abbott, Illinois, USA). Samples that were reactive (positive or borderline) with both assays were subjected to testing with commercial surrogate immunoassays of NeutraLISA (EIM) and cPassTM(GenScript Biotech Corporation, Rijswijk, Netherlands) by using pseudoneutralization assay (PNAbA) as a golden standard. No seropositive cases were detected between January and March. Between April and December, IgG (EIM-S1 and Abbott positive) and NAb (PNAbA positive) seroprevalences were between 0.4-1.4%. NeutraLISA showed 90% and cPass 55% concordant results with PNAbA among PNAbA negative samples and 49% and 92% among PNAbA positive samples giving NeutraLISA better specificity but lower sensitivity than cPass. To conclude, seroprevalence in pregnant women reflected that of the general population but the variability of the performance of serological protocols needs to be taken into account in inter-study comparison.
Declines in Influenza Vaccination Coverage in White and Black, Non-Hispanic Children from 2012-2019 to 2019-2022
Authors: Corle Abigail L.
Published: June 2023

Declines in routine influenza vaccination rates have become a cause for concern as influenza vaccine coverage rates have declined among Black, Non-Hispanic children compared to an increase in coverage among White, Non-Hispanic children ages 6 months to 17 years old. Influenza season years analyzed were 2012-2022 using data provided by the US Center for Disease Control’s FluVaxView database. Data for this database is sourced from the National Immunization Survey-Flu (NIS-Flu) and the Behavioral Risk Factor Surveillance System (BRFSS) survey. White, Non-Hispanic children saw an increase in vaccination coverage from 55.8% to 60.3%, whereas Black, Non-Hispanic children decreased from 58.2% to 52.9% coverage. Chi-squared tests with Yates correlation were performed to find statistical significance. Vaccination coverage rate changes for both demographics were found to be statistically significant at p < 0.00001. 70% influenza vaccination coverage rate remains the US Department of Health’sHealthyPeople 2030initiative’s goal for all demographics and may be achieved by utilizing interventional tools such as motivational interviewing, provider-patient dialogue, community-based vaccination clinics, or home visits. Evidence-based interventional provider-patient dialogue has had success in increasing vaccination rates among other vaccines. Continued research into the cause of influenza vaccination rate decline among vulnerable and medically underserved populations is needed to best implement vaccine-based interventions.
Quantitatively assessing early detection strategies for mitigating COVID-19 and future pandemics
Authors: Liu Andrew Bo , Lee Daniel , Jalihal Amogh Prabhav , Hanage William P. , Springer Michael
Published: June 2023

Researchers and policymakers have proposed systems to detect novel pathogens earlier than existing surveillance systems by monitoring samples from hospital patients, wastewater, and air travel, in order to mitigate future pandemics. How much benefit would such systems offer? We developed, empirically validated, and mathematically characterized a quantitative model that simulates disease spread and detection time for any given disease and detection system. We find that hospital monitoring could have detected COVID-19 in Wuhan 0.4 weeks earlier than it was actually discovered, at 2,300 cases (standard error: 76 cases) compared to 3,400 (standard error: 161 cases). Wastewater monitoring would not have accelerated COVID-19 detection in Wuhan, but provides benefit in smaller catchments and for asymptomatic or long-incubation diseases like polio or HIV/AIDS. Monitoring of air travel provides little benefit in most scenarios we evaluated. In sum, early detection systems can substantially mitigate some future pandemics, but would not have changed the course of COVID-19.
Maternal pertussis immunization and the blunting of routine vaccine effectiveness: A meta-analysis and modeling study
Authors: Briga Michael , Goult Elizabeth , Brett Tobias S , Rohani Pejman , Domenech de Cellès Matthieu
Published: June 2023

Abstract

A key goal of pertussis control is to protect infants too young to be vaccinated, the age group most vulnerable to this highly contagious respiratory infection. In the last decade, maternal immunization has been deployed in many countries, successfully reducing pertussis in this age group. Because of immunological blunting, however, this strategy may erode the effectiveness of primary vaccination at later ages. Here, we systematically reviewed the literature on the relative risk (RR) of pertussis after primary immunization of infants born to vaccinated vs. unvaccinated mothers. The four studies identified had ≤6 years of follow-up and large statistical uncertainty (meta- analysis weighted mean RR: 0.71, 95% CI: 0.38–1.32). To interpret this evidence, we designed a new mathematical model with explicit blunting mechanisms and evaluated maternal immunization’s short- and long-term impact on pertussis transmission dynamics. We show that transient dynamics can mask blunting for at least a decade after rolling out maternal immunization. Hence, the current epidemiological evidence may be insufficient to rule out modest reductions in the effectiveness of primary vaccination. Irrespective of this potential collateral cost, we predict that maternal immunization will remain effective at protecting unvaccinated newborns, supporting current public health recommendations.
SARS-CoV-2 Spread Under the Controlled-Distancing Model of Rio Grande do Sul, Brazil
Authors: Rohweder Ricardo , Schüler-Faccini Lavínia , Ferraz Gonçalo
Published: June 2023

In early 2020, the government of Rio Grande do Sul established a public-health assessment-response framework to halt the spread of SARS-CoV-2, called ‘controlled-distancing model’ (CDM). This framework subdivided the state in 21 regions where it evaluated a composite index of disease transmission and health-service capacity. Updated on a weekly basis, the index placed regions on a color-coded scale of flags, which guided adoption of non-pharmaceutical interventions. We aim to evaluate the extent to which the CDM accurately assessed transmission and the effectiveness of its responses throughout 2020. We estimated the weekly effective reproduction number (Rt) of SARS-CoV-2, for each region, using a renewal-equation-based statistical model of notified COVID-19 deaths. UsingRtestimates, we explored whether flag colors assigned by the CDM either reflected or affected SARS-CoV-2 dissemination. Flag assignments did reflect variations inRt, to a limited extent, but we found no evidence that they affected Rtin the short term. Medium-term effects were apparent in only four regions after eight or more weeks of red-flag assignment. Analysis of Google movement metrics showed no evidence that people moved differently under different flags. The dissociation between flag colors and the propagation of SARS-CoV-2 does not support the claim that non-pharmaceutical interventions are ineffective. Our results show, however, that decisions made under the CDM framework were ineffective both for influencing the movement of people and for halting the spread of the virus.
Content-enriched fluorescence lifetime fluctuation spectroscopy to study bio-molecular condensate formation
Authors: Perego Eleonora , Zappone Sabrina , Castagnetti Francesco , Mariani Davide , Vitiello Erika , Rupert Jakob , Zacco Elsa , Tartaglia Gian Gaetano , Bozzoni Irene , Slenders Eli , Vicidomini Giuseppe
Published: June 2023

Quantitative fluorescence microscopy is experiencing an important revolution thanks to single-photon array detectors. These detectors provide users with so far inaccessible specimen information: The distribution of the specimen’s fluorescence emission at single-photon level and high spatiotemporal sampling. In laser-scanning microscopy, this photon-resolved measurement has enabled robust fluorescence lifetime imaging at sub-diffraction spatial resolution, thus opening new perspectives for structural and functional imaging. Despite these significant advances in imaging, studying the time evolution of biological processes remains a considerable challenge. Here we present a com-prehensive framework of live-cell spectroscopy methodologies – compatible with imaging – to investigate bio-molecular processes at various spatiotemporal scales. We use photon-resolved spatial and temporal measurements granted by a single-photon array detector to boost the information content of a unified fluorescence fluctuation spectroscopy and fluorescence lifetime experiment. To demonstrate the potential of this approach, we investigate the phase transition of liquid-like condensates during oxidative stress inside living cells. These condensates are generally found in several cellular processes and exhibit substantial variations in molecular composition, size, and kinetics, posing a significant challenge for quantifying their underlying molecular dynamics. This study demonstrates how the pro-posed approach reveals the mutual dynamics of different RNA-binding proteins involved in the stress granules formation – inaccessible to imaging alone. We observe condensate formation by performing time-lapse super-resolved imaging of the cellular macro-environment while simultaneously monitoring the molecular mobility, the sub-diffraction environment organization, interactions, and nano-environment properties through fluorescence lifetime fluctuation spectroscopy. We are confident that our framework offers a versatile toolkit for investigating a broad range of bio-molecular processes – not limited to liquid-liquid phase transition – and we anticipate their widespread application in future life-science research.