bluuebunny/crossref_metadata_2025 huggingface dataset:
Right Ventricular Infarction
Authors: Murphy Joseph G. , Jentzer Jacob C.
Published: January 2025

Isolated right ventricular myocardial infarction is rarely seen in clinical practice, but an estimated 30% to 50% of patients with acute inferior myocardial infarction have clinical, electrocardiographic, and/or echocardiographic evidence of right ventricular dysfunction or infarction. Right ventricular infarction is frequently underdiagnosed, which is clinically important, as right ventricular myocardial infarction complicating inferior wall myocardial infarction is associated with increased in-hospital mortality compared with inferior wall myocardial infarction in patients with preserved right ventricular function. Many studies have shown that patients with right ventricular infarction are a unique subgroup of patients with a distinctive clinical presentation, treatment, and prognosis.
Cardiogenic Shock
Authors: Waterbury Thomas M. , Anavekar Nandan S.
Published: January 2025

Shock is defined as a physiologic state of inadequate blood flow to vital organs that leads to a global reduction in tissue perfusion with subsequent widespread cellular hypoxia and dysfunction. Four distinct types of shock are recognized: 1) hypovolemic shock, 2) distributive shock, 3) obstructive shock, and 4) cardiogenic shock.
Cardiac Emergencies,
Authors: Vallabhajosyula Saraschandra , Jentzer Jacob C.
Published: January 2025

Shock defines a state of circulatory failure in which inadequate tissue oxygen delivery results in organ dysfunction. The therapeutic approach to acute coronary syndrome can encompass numerous aspects because the syndrome has a broad spectrum of manifestations. The important therapeutic goals for this spectrum are revascularization, antithrombotic treatment, anti-ischemic treatment, administration of disease-modifying agents, and supplemental therapy. Hemodynamically unstable cardiac arrhythmias may occur in the clinical setting of almost any serious underlying cardiac disease. Acute heart failure can be divided into 4 distinct clinical phenotypes or syndromes, each of which can be caused by acute coronary syndrome. Hypertensive urgency or severe uncontrolled hypertension is considered asymptomatic severe hypertension without acute end-organ injury.
Systemic Disease and the Heart
Authors: Lin Grace , Mankad Rekha
Published: January 2025

Although uncommon, it is important to recognize that many systemic diseases can affect the heart. Cardiac involvement may in fact be the first sign of an underlying systemic disease. The presence or absence of a concomitant cardiac abnormality in the setting of a systemic disease may affect treatment options and prognosis.
Systolic Heart Function
Authors: Miller Wayne L. , Olson Lyle J.
Published: January 2025

Contractile sarcomeres occupy about 50% of the mass of cardiac myocytes. The key element in the initiation of cardiac contraction is the release of sarcoplasmic calcium. The transmembrane calcium current does not directly cause cardiac contraction but promotes release of sarcoplasmic calcium. The ability to augment preload provides a functional reserve to the heart in situations of acute stress or exercise. The most commonly applied and clinically available measure of systolic performance or contraction is ejection fraction.
Pharmacologic and Nonpharmacologic  Therapy for Systolic Ventricular Dysfunction  and Heart Failure
Authors: Rodeheffer Richard J. , Redfield Margaret M. , Boilson Barry A.
Published: January 2025

All patients with systolic ventricular dysfunction, or heart failure with reduced ejection fraction, should be considered for aggressive treatment of the underlying coronary artery disease, valvular heart disease, or hypertension. The current 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America Guideline for the Management of Heart Failure includes important updates on guideline-directed medical therapy that should be started to reduce morbidity and death, concurrent with the evaluation and management of the underlying cause of ventricular dysfunction. Treatment strategies for all patients with heart failure with reduced ejection fraction, regardless of the underlying myocardial disorder, are described according to the stage of heart failure. Therapies that have been proved to decrease morbidity and death should be used for all patients with decreased systolic function.
Myocarditis,
Authors: Lyle Melissa A. , Cooper Leslie T.
Published: January 2025

Myocarditis refers to inflammation of the myocardium and incorporates a broad spectrum of clinical and histopathologic presentations. Myocarditis classically results from either an external antigen, such as viruses, bacteria, parasites, drugs, or toxins, or an endogenous trigger, such as autoimmune activation against self-antigens. Although viral infection remains the most common cause of myocarditis, drug hypersensitivity, toxic drug reactions, and peripartum cardiomyopathy are being increasingly recognized as possible etiologies of myocarditis. The clinical presentation can be variable, ranging from subclinical disease to fulminant myocarditis, requiring inotropic therapy or mechanical circulatory support.
Restrictive Cardiomyopathy
Authors: Kushwaha Sudhir S.
Published: January 2025

Restrictive cardiomyopathy is defined as myocardial disease that results in impaired ventricular filling with 1) normal or reduced diastolic volume of either or both ventricles and 2) normal or near-normal systolic function and wall thickness. The condition usually results from increased stiffness of the myocardium, which causes pressure within the ventricles to increase precipitously with only small increases in volume. Affecting either or both ventricles, restrictive cardiomyopathy may cause symptoms or signs of right ventricular or left ventricular failure. Often, right-sided findings predominate, with elevated jugular venous pressure, peripheral edema, and ascites. When the left ventricle is affected, breathlessness and evidence of pulmonary edema are present, usually with normal cardiac dimensions. The diagnosis should therefore be considered when a patient has heart failure but no evidence of cardiomegaly or systolic dysfunction.
Cardiac Transplantation
Authors: Boilson Barry A. , Daly Richard C. , Kushwaha Sudhir S.
Published: January 2025

In the United States, an estimated 5.7 million people carry a diagnosis of HF, and almost 300,000 people die of heart failure each year. The prevalence of heart failure is on the rise, and it increases with age. Advances in medical therapy have resulted in improved survival of patients with moderate or severe heart failure, but the prognosis for patients with end-stage heart failure remains poor. Orthotopic cardiac transplant is a highly successful procedure for the treatment of end-stage heart disease. Despite major advances since that first transplant, the number of procedures performed worldwide has plateaued, primarily because of the limited supply of donor organs. Cardiac transplantation is not appropriate for many patients due to advanced age and comorbidities. This has led to the development of new therapeutic avenues, including ventricular assist devices, the total artificial heart, cell therapy, and xenotransplantation.
Invasive Hemodynamics
Authors: Nishimura Rick A.
Published: January 2025

Measurement of volumetric flow rate (ie, stroke volume or cardiac output) is important for evaluating systolic performance of the heart. Stroke volume is the amount of blood that the heart can eject during systole, specifically during the systolic ejection period from aortic valve opening to aortic valve closure. This ejection phase index depends on the loading conditions of the heart (afterload and preload) and on the intrinsic contractility of the heart muscle. It provides an overall measurement of the ability of the heart to meet the metabolic demands of the body.
Atlas of Hemodynamic Tracings,
Authors: Nishimura Rick A. , Murphy Joseph G.
Published: January 2025

Double arterial pulses (Figures 93.1 through 93.5) can be divided into 2 main categories. In the first category, the double pulses span different cardiac cycles and include pulsus alternans and pulsus bigeminus. The other category of double pulses includes bifid, bisferiens, and dicrotic pulses. In this category, the split in the pulse is within 1 cardiac cycle.
Ninety-Nine Lessons in Critical Thinking
Authors: Friedland Robert P.
Published: January 2025

There is a danger that key factors in the development of young doctors and scientists are being lost because of the unremitting competition for their attention created by a continuous avalanche of information. The needs of the patient may be lost because of a focus on data and the electronic medical record. Key features of scientific problems may similarly be lost through extensive focus on methods and the monumental growth of the literature. Critically, medical and scientific insights are frequently lost because questions have not been properly identified and the many forms of bias have interfered with clinical and scientific judgment. This book presents 99 ways in which the capacity for observation, attention, understanding, and compassion can be enhanced. Using stories from the author’s experience and from the literature, methods for focusing attention and enhancing the awareness of preconceived ideas and other biases are presented. Young doctors and scientists face the difficult task of acquiring a vast amount of information. Attention to human evolution and how it has influenced the way the brain works provides valuable guidance in developing skills of selective attention and critical thinking. The needs of the patient and of the scientific matters at hand must not be lost in competition with the vast amount of data that the internet provides. Young doctors and scientists must learn how to be aware of how they think and how they can enhance their observational skills and judgment to become more effective professionals.
The Key Factor Which Determines What We Perceive Is Our Attention and How It Is Focused
Authors: Friedland Robert P.
Published: January 2025

Attention is not the same as experience. The focusing of attention is a critical factor in perception and judgment.
Which Is Older, Stories or Books?
Authors: Friedland Robert P.
Published: January 2025

Stories have been told by humans for thousands of years and books have been widely used only in the past few 100 years. The human brain evolved with an adaptive capacity for attention to and appreciation of stories.
Be Fierce, Nurture an Intense and Ferocious Aggressiveness in the Pursuit of Your Learning and the Benefit of Your Patients
Authors: Friedland Robert P.
Published: January 2025

It is important to be persistent and energetic in the pursuit of your learning and in the pursuit of the benefit of your patients.
Key Elements of the Patient Visit
Authors: Friedland Robert P.
Published: January 2025

Deep listening is listening to hear, not listening to prepare to speak.
Words Influence Thought
Authors: Friedland Robert P.
Published: January 2025

Although words are tools for expression of thoughts, they also influence thoughts.
The Physical Exam
Authors: Friedland Robert P.
Published: January 2025

The comprehensive physical exam is an important part of the medical interview
Touch Is Important
Authors: Friedland Robert P.
Published: January 2025

Touch can help to relieve the patient's anxiety and help establish good relations.
The Fundamental Three-Step Approach to Diagnosis
Authors: Friedland Robert P.
Published: January 2025

It is best to pursue diagnosis by first listening deeply to the patient to learn what they are telling you. After you consider the localization of the problem, then the etiology or cause can be considered. If you immediately consider the cause of a symptom or sign, you may miss other important features. It is critical to be able to recognize when you don't know something because understanding your level of ignorance is an important step in discovery. Attention to the patient is often more important than attention to the medical literature or the patients’ record. Family history and the possibility of toxic exposures are worth consideration. Salutogenesis, the production and maintenance of health, is just as relevant to patient care as pathogenesis, the production and maintenance of disease. Helping a patient enhance their fitness will be valuable in increasing their joy of living and ability to avoid disease.
Investigations
Authors: Friedland Robert P.
Published: January 2025

Consider all investigations with the question: what difference will the answer make in the life of the patient?
Don’t Be Afraid To Say You Don’t Know
Authors: Friedland Robert P.
Published: January 2025

Saying that you don't know something is a very important step in your knowledge.
Information Toxicity
Authors: Friedland Robert P.
Published: January 2025

Excessive information can have negative effects on thinking, perception and judgment.
It’s Good To Be Knowledgeable, but It Is Necessary to Also Be Attentive to the Patient
Authors: Friedland Robert P.
Published: January 2025

Do not allow knowledge coming from journals and books to interfere with your understanding and evaluation of what is happening to the patient.
Rare Presentations of Common Events Are More Common Than Common Presentations of Rare Events
Authors: Friedland Robert P.
Published: January 2025

Rare complications of common diseases may occur commonly Incidence, prevalence, epidemiology, complications, presentations
Symptoms and Signs Have Important Significance
Authors: Friedland Robert P.
Published: January 2025

Signs on physical exam may help with diagnosis. The absence of a sign is often less significant than its presence.
Salutogenesis
Authors: Friedland Robert P.
Published: January 2025

The absence of disease is not the same thing as the presence of health.
You Are Primarily Responsible for Caring for the Patient, Not the Family
Authors: Friedland Robert P.
Published: January 2025

Your care should be focused on the patient and not on the family.
Denial of Illness and Disability Can Be Shared by the Patient, the Family, and the Doctor
Authors: Friedland Robert P.
Published: January 2025

Denial of illness may be shared by the patient, family, doctor and society.
How Often Do Rare Events Occur?
Authors: Friedland Robert P.
Published: January 2025

Individual rare events occur rarely but everything that happens is a rare event.
Do Not Depend on Logic Alone
Authors: Friedland Robert P.
Published: January 2025

Be open to ways of thought that are not logical.
All Models Are Wrong
Authors: Friedland Robert P.
Published: January 2025

Models may be helpful but their assumptions must be remembered and reconsidered often.
Absence of Evidence Is Not Evidence of Absence
Authors: Friedland Robert P.
Published: January 2025

Decisions must be made on available evidence. The absence of evidence does not mean that a therapy is either safe or unsafe or effective or not effective.
Being Wrong (at Times) Is OK
Authors: Friedland Robert P.
Published: January 2025

“Theories are not true or false, they are fertile or sterile” (Claude Bernard).
Do Not Assume That Your Ideas Are Not Novel and Important Just Because They Appear To Be Obvious
Authors: Friedland Robert P.
Published: January 2025

Ideas which are obvious to you may not be obvious to others.
Consider the Evolutionary Aspects of Disease
Authors: Friedland Robert P.
Published: January 2025

Evolution provides valuable perspectives in understanding our cognitive capacities.
Live in “Day-Tight Compartments”
Authors: Friedland Robert P.
Published: January 2025

It is valuable to understanding how one learns best and where one finds meaning. These issues can only be resolved through a diverse range of experiences. Regardless of what area of specialization is chosen, the individual will need to recognize that they will be teaching and that they need to recognize the importance of salesmanship. The meaning of the disciplines and the need to avoid overspecialization it is important. Moreover, the capacity to look beyond the narrow confines of a chosen subspecialty will be rewarding (trespassing). Opportunities for collaboration, both locally and internationally, should be considered. In searching for educational and research opportunities, consider the best possible prospects. Attention to one’s own health in terms of physical exercise, diet, and mental health is important.
Neurology and Cardiology (Etc.) Don’t Exist
Authors: Friedland Robert P.
Published: January 2025

All disciplines are artificial and do not come in little baskets.
Pay Attention to Your Own Health and Learn How To Deal with Stress
Authors: Friedland Robert P.
Published: January 2025

Stress is a constant force which we must all learn to deal with.
Remember Pierre Curie, Carl Wernicke, and Others
Authors: Friedland Robert P.
Published: January 2025

Physicians and scientists may be at high risk of accidents because of failure to concentrate on what they're doing at the moment.
What Is Science?
Authors: Friedland Robert P.
Published: January 2025

Science involves attending to the world with an open mind, one capable of thinking without restriction by bias or prior information that may be wrong. Progress in science involves creating new paradigms and fundamentally changing understanding. All of the disciplines are metaphors because they do not actually exist. The most important feature of success in science is hard work (tenacity) and not brilliance. Experimentation and not contemplation is the best way to make progress. Technology is often vital to discovery but should generally not be your primary focus. Statistical analysis may be helpful but may also be considerably misleading. Assumptions of your methods must not be overlooked, and a new idea does not need to be supported by all available evidence.
There Is Only One Kind of Science, and That Is the Study of Everything with All Possible Methods
Authors: Friedland Robert P.
Published: January 2025

There are no rules concerning the border between biology and chemistry or between neurology and psychiatry, as all disciplines are artificial.
You Don’t Need To Be Brilliant To Be a Researcher
Authors: Friedland Robert P.
Published: January 2025

Advances in science are often made because of powers of observation and not because of brilliance
Appreciate a Diversity of Approaches
Authors: Friedland Robert P.
Published: January 2025

Studies with animals can be valuable, but the limitations of animal models must be appreciated.
Why Think When You Can Experiment?
Authors: Friedland Robert P.
Published: January 2025

Reading is an important step in preparing for experimentation, but there is a time when experimentation must begin.
Do Not Be Obsessed with Technology and Methods
Authors: Friedland Robert P.
Published: January 2025

Focus on technology should not extinguish your attention to scientific questions.
Pay Attention to Study Design, Data Analysis, and Statistics
Authors: Friedland Robert P.
Published: January 2025

Look at all the data and remember the assumptions of all methods used.
Pay Attention to the Assumptions of Diagnostic Testing and Research Evaluations
Authors: Friedland Robert P.
Published: January 2025

All methods involve assumptions which should be remembered.
It Is Possible To Be Productive from a Distance
Authors: Friedland Robert P.
Published: January 2025

Important discoveries can be made without access to advanced technologies.
The Myth of Progress
Authors: Friedland Robert P.
Published: January 2025

The idea that improvements in the human condition are happening and will continue is a myth.
Don’t Be Ageist
Authors: Friedland Robert P.
Published: January 2025

Age discrimination is widespread and should be challenged.
Can tidal evolution lead to close-in planetary bodies around white dwarfs – I. Orbital period distribution
Authors: Li Yuqi , Bonsor Amy , Shorttle Oliver , Rogers Laura K
Published: January 2025

The evolution of planetary systems around white dwarfs is crucial to understanding the presence of planetary material in the atmospheres of white dwarfs. These systems uniquely probe exoplanetary compositions. Periodic signals in the photometry of a handful of white dwarfs suggest material blocking the star, potentially from disintegrating planetesimals. Tidal evolution followed by scattering can bring planetesimals on to close-in orbits that would have been within the envelope of the white dwarf progenitor. The orbital period distribution of planetesimals undergoing tidal evolution will peak at short-period (nearly) circularized orbits (∼10 h–1 d), with a rising tail towards long-period highly eccentric orbits (∼100 d). This prediction is generally consistent with the observed white dwarf transiting systems. In order for the planetesimal on the 4.5 h period around WD 1145+017 to be explained by the tidal evolution of a planetesimal, that planetesimal must have an ultimate tensile strength comparable to that of iron meteorites.
Cold fronts in galaxy clusters – I. A case for the large-scale global eigenmodes in unmagnetized and weakly magnetized cluster core
Authors: Choudhury Prakriti Pal , Reynolds Christopher S
Published: January 2025

Galaxy clusters show large-scale azimuthal X-ray surface brightness fluctuations known as cold fronts. Cold fronts are argued to originate due to sloshing driven by sub-halo passage at close proximity to the cluster centre. While this causes large-scale perturbations, the physical mechanisms that can sustain spiral density structures are not clear. In this work, we explore whether long-wavelength thermal instability is an explanation for cold front formation in a cluster core that is perturbed by sub-haloes or active galactic nuclei activity. Using global linear perturbation analysis, we show that unstable internal gravity waves form large-scale 3D spirals, akin to observed cold fronts. We explore if the presence of magnetic field (along spherical $\hat{\phi }$) may support such structures (by suppressing small-scale Kelvin–Helmholtz modes) or disrupt them (by promoting additional thermal instability). We find that latter happens at shorter wavelengths and above characteristic Brunt–Väisälä frequency ($\gt N_{\rm BV}$). Our work implies that large-scale spirals are sustained over a long time-scale ($\gt N^{-1}_{\rm BV}$) even in presence of aligned magnetic fields that is otherwise supportive against mixing at the interface. Secondly, short-wavelength (but relatively longer along the field) unstable compressive modes may form within or in the vicinity of such spirals. The instability is an overstable slow wave, and grows in 2D at time-scales $\gtrsim 2{\small --}3$ times longer than the spiral growth time-scale (via thermal instability). Thus this instability cannot destroy the large-scale coherence.
Survival, Quality of Life, and Motor Function in Brain Metastases Surgery - The Role of Complete Resection
Authors: Winther Rebecca R , Hjermstad Marianne J , Yri Olav Erich , Skovlund Eva , Aass Nina , Astrup Guro L , Kaasa Stein , Saxhaug Cathrine , Vik-Mo Einar Osland
Published: January 2025

Background

One in three patients with advanced cancer develops brain metastases. Surgical resection of brain metastases is done in 15-20% of these patients. While gross total resection (GTR) is believed to extend overall survival (OS), concerns exist regarding increased morbidity. This study examines the impact of surgical resection, particularly GTR, on self-reported symptoms, focusing on quality of life (QoL) and motor dysfunction.

Methods

We conducted a prospective cohort study involving adult patients undergoing surgical resection for brain metastases from solid tumors in a defined region of Norway between 2017 and 2021. Clinical data were collected at inclusion prior to surgery and every three months the first year. Patients completed monthly questionnaires assessing QoL and motor dysfunction. QoL was measured using the EORTC QLQ-C15-PAL, while motor dysfunction was evaluated using the EORTC QLQ-BN20.

Results

A total of 155 patients were included and median OS was 13 months. GTR was achieved in 69 (44%) patients and was associated with longer median OS compared to subtotal resection (17.7 vs. 10.9 months, p=0.04). Mean QoL remained stable throughout the follow-up period. Improved motor dysfunction one month after surgery was reported by 23% of the patients, while 25% reported worse motor dysfunction. Factors associated with a high motor dysfunction score at one month were age >70 years, higher baseline motor dysfunction, and multiple brain metastases. Neither GTR nor location of metastases in motor associated areas were associated with worsened motor dysfunction.

Conclusion

Self-reported QoL is maintained after surgery for brain metastases. Complete resection is associated with extended OS without compromising self-reported motor function.
Barnacles dominate the winter diet of Calidris maritima (Purple Sandpiper) in Maine: A bona fide dietary shift or molecular techniques revealing an unknown diet composition?
Authors: Johnston Elliot M , Mittelhauser Glen H , Foster Jeffrey T , Mau Rebecca L , Gibson Alexandra A , Gillece John D , Klemmer Amanda J , Olsen Brian J
Published: January 2025

At temperate latitudes, the overwintering period for birds is often longer than subsequent periods, and lower daily foraging success during this period may produce population-level impacts that are similar to or larger than those reported during shorter periods of the annual cycle. In this study, we use DNA metabarcoding of fecal samples to reveal previously undocumented characteristics of the winter diet of Calidris maritima (Purple Sandpiper) in Maine (USA), with potential implications for this population’s local overwintering declines during a recent 10-yr period. Of the 24 taxonomic groups detected, barnacles were the dominant prey item while mussels—a common diet item in previous studies—were rare. In addition, we identified both expected prey taxa (e.g., marine snails) and several less-expected taxa (e.g., terrestrial insects). Our study is the first to employ molecular techniques to describe C. maritima diet, and as a result, may have uncovered an unknown diet composition that was difficult to detect with morphological techniques. Alternatively, our results may be at least in part due to a recent dietary shift during a period of increased environmental warming in the Gulf of Maine, which has previously been correlated with declines of marine invertebrates that are known C. maritima prey items. This period of accelerated warming coincided with a steep decline in Maine’s C. maritima overwintering population that occurred from 2004 to 2014. The relationship between a putative dietary shift in our study and the recent declines in overwintering C. maritima in Maine is intriguing, but unclear and requires further tests of winter food limitation. Regardless, utilizing a novel technique to understand C. maritima diet has shed light on this species’ food resources during the long overwintering period.
Linking plant genes to arthropod community dynamics: Current progress and future challenges
Authors: Barbour Matthew A , Pérez-López Cintia Beatriz
Published: January 2025

Plant genetic variation can play a key role in shaping ecological communities. Prior work investigated the effects of coarse-grain variation among plant genotypes on their diverse arthropod communities. Several recent studies, however, have leveraged the boom of genomic resources to study how genome-wide plant variation influences associated communities. These studies have demonstrated that the effects of plant genomic variation are not just detectable but can be important drivers of arthropod communities in natural ecosystems. Field common gardens and lab-based mesocosm experiments are also revealing candidate genes that have large effects on arthropod communities. While we highlight these exciting results, we also discuss key challenges to address in future research. We argue that a major hurdle lies in the integration of genomic tools with hierarchical models of species communities (HMSC). HMSC are generative models that provide the opportunity to not only better understand the processes underlying community change, but to also predict community dynamics. We also advocate for future research to apply models of genomic prediction to explore the genetic architecture of arthropod community phenotypes. We hypothesize that this genetic architecture will follow an exponential distribution, where a few genes of large effect, but also many genes of small effect, contribute to variation in arthropod communities. The next generation of studies linking plant genes to community dynamics will require interdisciplinary collaborations to build truly predictive models of plant genetic and arthropod community change.
Proving research misconduct
Authors: Leclerc Olivier
Published: January 2025

Detecting and punishing violations of research integrity requires first having to prove them. However, establishing proof of research misconduct presents a number of challenges. Firstly, it has to be conducted in a variety of contexts, including before research integrity officers, university disciplinary committees, civil courts, criminal courts, at first instance and on appeal. In each of these instances, the rules of evidence have their own specific features. Secondly, it may be necessary to prove not only material facts, but also circumstances that are more difficult to grasp, such as intention or negligence. In addition, not all evidence is admissible, as it may breach a duty of fairness or protected secrets. Consequently, research integrity officers and judges may be unable to consider all relevant evidence when assessing allegations of misconduct. This article examines the legal issues pertaining to the proof of research misconduct, based on French law and the law of the European Convention on Human Rights. This article examines the burden of proof, the object of proof, the admissibility of evidence and the exclusion of evidence. It identifies the differences in evidence that exist depending on whether investigations into research misconduct are conducted before research integrity officers or before the courts. It analyses the justifications for these differences and concludes that the role of research integrity officers should not be confused with that of judges, even if this leads to differences in the proving of research misconduct.
A phase 2 randomized trial of safety and pharmacokinetics of IgPro20 and IgPro10 in patients with diffuse cutaneous systemic sclerosis
Authors: Denton Christopher P , Kowal-Bielecka Otylia , Proudman Susanna M , Olesińska Marzena , Worm Margitta , Del Papa Nicoletta , Matucci-Cerinic Marco , Radewonuk Jana , Jochems Jeanine , Panaite Adrian , Shebl Amgad , Krupa Anna , Allanore Yannick , Hofmann Jutta H , Gasior Maria J
Published: January 2025

Objectives

The primary objective was the safety of s.c. immunoglobulin, IgPro20 (Hizentra, CSL Behring) in adults with dcSSc. Secondary objectives included pharmacokinetics and relative bioavailability of IgPro20, and safety and pharmacokinetics of IVIG, IgPro10 (Privigen, CSL Behring).

Methods

In this prospective, multicentre, randomized, open-label, crossover phase 2 study (NCT04137224), patients (aged ≥18 years) with dcSSc were assigned to 16 weeks of IgPro20 (0.5 g/kg/week) followed by 16 weeks of IgPro10 (2 g/kg/4 weeks over two to five sessions), or vice versa. Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), infusion site reactions (ISRs), clinical tests, pharmacokinetic and bioavailability were assessed.

Results

Twenty-seven patients were randomized from 9 October 2019 to 31 August 2021. In total, 22 patients (81.5%) experienced 107 TEAEs (IgPro20, 49; IgPro10, 58); most were mild/moderate. Six patients (22.2%) experienced 10 SAEs (IgPro20, 6; IgPro10, 4); no treatment-related SAEs and no deaths were reported. IgPro20 ISR rate was low (2 per 100 infusions). Maximum IgG concentration [mean (s.d.)] was numerically lower following IgPro20 [23.7 (1.2) g/l] vs IgPro10 [46.1 (1.2) g/l], as was the geometric mean dose-normalized, baseline-corrected area under the concentration–time curve from time point 0 to tau [IgPro20, 44.8 (1.4) h*g/l; IgPro10, 60.2 (1.4) h*g/l]. The bioavailability of IgPro20 relative to IgPro10 was 76.1%.

Conclusion

This study shows that in patients with dcSSc, safety, pharmacokinetic and bioavailability profiles of IgPro20, and safety and pharmacokinetics of IgPro10, are similar to those observed in other approved indications.

Trial registration

ClinicalTrials.gov, https://clinicaltrials.gov, NCT04137224
Associations between objectively measured sleep characteristics and six-minute walk distance in older adults: the Disparities in Sleep and Cognitive Outcomes (DISCO) study
Authors: Chapagai Swaty , Harrington Katharine , Alexandria Shaina J , Vu Thanh-Huyen T , Khan Sadiya S , Carnethon Mercedes R , Knutson Kristen L
Published: January 2025

Study Objectives

A decline in physical functioning in older adults has been associated with a higher risk of chronic diseases. Subjective sleep disturbances have been associated with declines in physical functioning with aging. We examined the association between objectively measured sleep characteristics and 6-minute walk distance, a marker of functional capacity, in a sample of older adults.

Methods

This analysis included 199 participants who were enrolled in the Disparities in Sleep and Cognitive Outcomes (DISCO) study, a longitudinal cohort of older adults aged ≥55 years. Exposures included: sleep duration, sleep percentage, sleep fragmentation, and sleep regularity index measured using 7 days of wrist actigraphy; sleep stages including non-rapid eye movement (REM) stage 3 (N3) and REM, and apnea–hypopnea index (AHI) measured using an overnight type 2 home polysomnography. The primary outcome was the total distance walked in 6 minutes (6MWD). Multiple linear regression was used for analysis.

Results

The mean age of participants was 67.6 (SD = 6.3) years (range 55–84 years), 69.3% were women, 62.3% were white and 84.4% were non-Hispanic. The average 6 MWD was 476.0 (SD = 95.6) meters. In adjusted models (B [95% CI]), higher sleep percentage (2.65 [0.22, 5.08] percent) and greater sleep regularity (1.03 [0.0047, 2.05] units) were associated with higher 6 MWD. Greater sleep fragmentation was associated with lower 6 MWD (−2.56 [−4.02, −1.10] percent). Sleep duration, N3, REM, and AHI were not associated with 6 MWD.

Conclusions

Poorer objective sleep quality and irregular sleep were associated with poorer functional capacity in older adults. Future work should test whether improving sleep quality and regularity improves physical functioning and overall health in older adults.
Patient-reported quality of life outcomes with mandibular advancement versus continuous positive airway pressure: insights from the CRESCENT trial
Authors: Colpani Juliana Tereza , Ou Yi-Hui , Thakumar Annushiah Vasan , Cheong Crystal S , Loke Weiqiang , Sia Ching-Hui , Teo Yao-Hao , Chan Siew-Pang , Chin Calvin W , Kojodjojo Pipin , Chan Mark Y , Cistulli Peter A , Luo Nan , Lee Chi-Hang
Published: January 2025

Study Objectives

We compared mandibular advancement device (MAD) versus continuous positive airway pressure (CPAP) on quality-of-life (QoL) in a prespecified analysis of the CRESCENT trial.

Methods

Two hundred and twenty participants over age 40 with Obstructive sleep apnea (OSA), hypertension, and increased cardiovascular risk from three public hospitals were randomly assigned to MAD or CPAP (1:1). Multi-dimensional QoL questionnaires were administered at baseline, 6 months, and 12 months. Three sleep-related QoL questionnaires: Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), and Sleep Apnea Quality of Life Index (SAQLI). Two generic QoL questionnaires: EuroQoL 5-D (EQ-5D) and Short Form 36 Health Survey (SF36).

Results

MAD adherence was 5.5 (3.9–6.9) hours at 6 months and 5.0 (3.3–6.1) hours at 12 months. CPAP adherence was 4.9 (3.3–6.1) hours at 6 months and 4.8 (3.3–5.7) hours at 12 months. Both groups showed improvements in sleep-related QoL. ESS improved at 6 and 12 months (p < .001), with a between-group difference favoring CPAP at 6 months (Δ 1.45 [0.44 to 2.46], p = .005). FOSQ improved at 6 and 12 months (p < .001), with a between-group difference favoring CPAP at 12 months (Δ −0.91 [−1.77 to −0.05], p = .038). SAQLI improved at 6 and 12 months (p < .001) without between-group differences. For generic QoL questionnaires, SF-36 improved in most domains at 6 and 12 months, with the Social Functioning section favoring CPAP at 12 months (p = .013). EQ-5D improved at 12 months, with a trend favoring CPAP (p = .053).

Conclusions

MAD and CPAP effectively improved sleep-related QoL and some aspects of generic QoL. CPAP improved sleep-related QoL to a greater extent than MAD.

Clinical Trial Name

The Cardiosleep Research Program on OSA, Blood Pressure Control and Maladaptive Myocardial Remodeling—Non-inferiority Trial (CRESCENT). URL: https://clinicaltrials.gov/study/NCT04119999?locStr=Singapore&country=Singapore&cond=Obstructive%20Sleep%20Apnea&aggFilters=ages:adult%20older,studyType:int&rank=6

TRIAL REGISTRATION: NCT04119999.
Continuous positive airway pressure versus conventional oxygen therapy in meconium aspiration syndrome: a randomized controlled trial
Authors: Mustaqeem Arifa , Yadav Anita , Kumar Jogender , Debata Pradeep
Published: January 2025

Neonates with meconium aspiration syndrome (MAS) frequently require respiratory support. However, the initial mode of respiratory support in these patients remains unclear. We aimed to assess whether early nasal continuous positive airway pressure (nCPAP), compared to conventional oxygen therapy, reduces the need for invasive mechanical ventilation (IMV) in neonates with MAS. In this open-label randomized controlled trial, neonates born at >34 weeks of gestation who developed mild to moderate respiratory distress within the first 24 hours were randomly allocated to the nCPAP or oxygen hood (5–10 l/min) group. The primary outcome was the need for intubation and IMV during the first 72 hours of life. The secondary outcomes included all-cause mortality before discharge, air leaks, sepsis, pulmonary hypertension, duration of respiratory support, and hospital stay. We analyzed the data using the intention-to-treat method. Eighty neonates (40 in each group) were enrolled. There was no statistically significant difference in the need for IMV between the nCPAP and oxygen hood groups (4 [10%] vs. 5 [12.5%]; relative risk, 0.80; 95% CI: 0.23–2.76). Primary respiratory support failure rates, mortality, pulmonary hypertension, and other outcomes were comparable between the groups. In this trial, nCPAP therapy was not superior to conventional oxygen therapy for the treatment of mild to moderate MAS.

Trial registration

Clinical Trial Registry of India (CRTI/2020/02/023529)
Is Early and Recurrent Anemia in a Preterm Infant a Risk Factor for Neonatal Appendicitis?
Authors: Alvarado Socarras Jorge L. , Theurel Martín Delia E. , Franco Mateus Beatriz H. , Medina Medina Edwin A. , Orejarena Adriana P. , Parra Reyes Hernando
Published: January 2025

Background:

Neonatal appendicitis (NA) is a rare condition with an estimated incidence of 0.04% to 0.2%. It is more prevalent in male preterm infants, with a mortality rate of 20% to 25%. It is usually misdiagnosed as neonatal necrotizing enterocolitis (NEC) owing to its diverse diagnostic challenges. Poor perfusion, hypoxia, anemia, or any other condition that impairs intestinal blood supply is a risk factor for bowel injury, which could explain the physiopathology of NA.

Clinical Findings:

We describe an interesting case of a preterm infant with recurrent episodes of abdominal distension and persistent anemia who was finally diagnosed with NA.

Primary Diagnosis:

The patient was treated with exploratory laparotomy and appendicectomy, with further symptom resolution. The diagnosis was confirmed by pathological examination.

Interventions:

Surgery for acute abdomen secondary to perforated appendicitis.

Outcomes:

Improved recurrent abdominal distension and persistent anemia and achieved full enteral nutrition. Patients with other diseases such as Hirschsprung’s disease were ruled out.

Practice Recommendations:

This case demonstrates that identifying the early signs and symptoms of NA requires a high index of suspicion. Anemia may play a significant role in the etiology of intestinal injury, increasing the risk of NA and NEC. Further studies are needed to explore the association between anemia and intestinal injury and its implications for neurodevelopment.
Voices from the frontline: Perspectives from certified nurse practitioners, clinical nurse specialists and physician assistants at an Academic Medical Center
Authors: Dickerman Katherine N. , Chao Cara A. , Rondinelli Nicole M. , Brackett Hareklia L. , Schulte Martina M. , Bowden Kasey R. , Burden Marisha A. , Chrastil Hillary J. , Morrison Katherine T. , Jensen Kristin M. , Seggelke Stacey A.
Published: January 2025

Background:

The COVID-19 pandemic has exacerbated already existing stressors within health care. In August 2020, a campus-wide COVID-19 well-being survey indicated high levels of burnout, stress, and mental health concerns among certified nurse practitioners (CNPs), clinical nurse specialists (CNSs), and physician assistants (PAs) within our Department of Medicine.

Purpose:

In response to this survey, an interdisciplinary task force was formed by CNPs, CNSs, and PAs across departmental specialty divisions to conduct focus groups to gain a deeper understanding of workplace experience both prepandemic and during the COVID-19 pandemic.

Methodology:

As part of a quality-improvement project, 14 focus groups involving 34 CNPs, CNSs, and PAs within our department were conducted to better understand their experiences before and during the COVID-19 pandemic. A rapid qualitative analysis was used to identify themes and subthemes. In this article, we explore these themes and review potential solutions solicited from the focus groups.

Results:

The following themes were identified: (1) the importance of being valued; (2) the need for career development opportunities; and (3) the significance of professional fulfillment.

Conclusions:

Each of these themes existed before, but was exacerbated by, the ongoing COVID-19 pandemic. The manifestation of these stressors is unique to the CNPs, CNSs, and PAs experience, although the larger themes may overlap with physician colleagues.

Implications:

To improve the professional experience and well-being of CNPs, CNSs, and PAs at our institution, it will be critical for leadership to acknowledge these differences and develop specific initiatives to address these concerns.
Health Care Utilization and Expenditure Associated With Musculoskeletal Disorders Among Adults With Type 2 Diabetes
Authors: Adesoba Taiwo P. , Brown Clare C. , Felix Holly C. , Baloh Jure , Lipschitz Riley , Goudie Anthony
Published: January 2025

Introduction:

Adults with type 2 diabetes (T2D) often experience musculoskeletal disorders (MSDs), which complicate health care provision and negatively impact their health and health care utilization and expenditure. The objective of this study was to estimate the incremental health care utilization and expenditure associated with MSD among adult T2D patients in the United States overall and by race/ethnicity.

Methods:

A sample (unweighted n=6205) of noninstitutionalized US adults with a T2D diagnosis was obtained from the Medical Expenditure Panel Survey (MEPS), panels 2015–2016 to 2019–2020. Propensity score matching (PSM) was used to reduce selection bias between participants with and without MSD. Differences in health care utilization were estimated using negative binomials, while expenditures were estimated using generalized linear models and 2-part models. Outcomes were estimated overall and by race and ethnicity.

Results:

Among the sample of patients with T2D before PSM, 52% had MSD. In the matched sample, increased utilization associated with MSD occurred across all health care service types, with prescription medications (13.31; 95% CI: 11.12, 15.50) having the largest increase. The increased total expenditure associated with MSD among T2D patients was $5712 (95% CI: $4278, $7147), and the major drivers were office and inpatient expenditures. Increased total expenditure associated with MSD was highest among Hispanic patients ($8490; 95% CI: $4744, $12,237).

Conclusions:

MSD is associated with increased utilization and expenditure among T2D patients, particularly Hispanics. Efforts targeting earlier recognition and management of MSD may reduce excess utilization and expenditure, and also racial/ethnic disparities.
Mesenchymal Stem Cells-Derived Exosomes Combined With Bone Grafts Ameliorate Bone Regeneration in Mandibular Defects
Authors: Gönen Zeynep Burçin , Kemaloğlu Cemal Alper , Gökdemir Nur Seda , Soylu Emrah , Bolat Demet , Yay Arzu
Published: January 2025

Although scaffold materials serve as effective bone substitutes for mandibular reconstruction, their high resorption and biodegradation rates decrease the success of the therapeutic effect. This study aims to explore the bone regenerative potential of bovine-derived osteoid matrix xenografts coupled with cell-free treatments. The study was conducted as a randomized in vivo experiment to repair critical-sized defects in rabbit mandibles. Two treatment groups were established with 10 rabbits: the right hemimandibles were reconstructed with xenograft (control), and the left hemimandibles were reconstructed with dental pulp stem cell (DPSCs)-derived exosomes soaked xenograft (experimental group) within the same rabbit. Micro-computed tomography and histologic analysis were performed at 4 weeks postoperatively. The histopathologic analysis revealed a significant difference in new bone formation scores between the experimental group (4.87±0.78) and the control group (2.87±0.41). Although the micro-computer tomography analysis did not show a statistically significant difference in new bone volume and surface between the groups, it did reveal that the experimental group had greater bone mineral density, trabecular thickness, and separation. The combination of DPSCs-derived exosomes and xenografts proved to be a promising strategy for enhancing new bone formation and regenerative scores in repairing critical-size defects in rabbit mandibles.