bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary CNS diffuse large B-cell lymphoma
Authors: Grommes Christian , Giulino-Roth Lisa , Gupta Tejpal , Ferreri Andrés José María
Published: July 2024

Primary central nervous system lymphomas (PCNSLs) are rare, extranodal, aggressive non-Hodgkin lymphomas confined to the brain, eyes, cerebrospinal fluid (CSF), and spinal cord, without systemic, non-central nervous system involvement. Clinical presentation, imaging characteristics, diagnostic evaluation, novel pathophysiological insights, and treatment of immunocompetent PCNSL patients are reviewed in this chapter. The prognosis of PCNSLs has improved over the past few decades, due to the introduction and widespread use of high-dose methotrexate, which now forms the backbone of all first-line polychemotherapy treatments. Despite this progress, durable remission is still only observed in approximately 50% of patients. Novel insights into the pathophysiology of PCNSLs have identified the B-cell receptor pathway, as well as the immunosuppressed tumour microenvironment and immune evasion, as key mechanisms in the pathogenesis of PCNSLs. Novel small molecules and agents targeting these aberrant pathways have been introduced into clinical trials of refractory and relapsed PCNSLs. Newer agents, such as the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib, or immunomodulatory drugs, such as lenalidomide and pomalidomide, have shown promising response rates in the relapsed setting. The diagnosis of PCNSL requires a high level of suspicion because clinical symptoms and signs are variable and depend upon the involved neuroanatomical structures. Rapid initiation of therapy is essential for recovery and prognosis. The optimal treatment regimen has not been defined, but methotrexate-based chemotherapy regimens are considered the standard of care for induction treatment. Novel targeted agents have recently been introduced into the therapeutic arsenal.
Neurological complications of red blood cell disorders
Authors: Klein Joshua P. , Archer Natasha M.
Published: July 2024

Abnormalities in erythrocyte structure and function result from a variety of genetic, metabolic, and infectious causes. Such abnormalities impair the ability of the erythrocyte to carry and deliver oxygen and other nutrients to tissues of the body. Consequently, many of the major medical and neurological complications of erythrocyte dysfunction are due to hypoxaemic or ischaemic tissue injury. This chapter reviews the neurological complications caused by disorders of the erythrocyte, focusing on hypoproliferative anaemias, megaloblastic anaemias, disorders of haemoglobin, and infections of the erythrocyte. Four distinctive neurological conditions are highlighted: restless legs syndrome in iron deficiency anaemia; subacute combined degeneration in cobalamin deficiency, moyamoya syndrome in sickle cell disease, and cerebral involvement in Plasmodium falciparum infection.
Addressing the consequences of the corporatization of reproductive medicine
Authors: Attinger Sara A , Jackson Emily , Karpin Isabel , Kerridge Ian , Newson Ainsley J , Stewart Cameron , van de Wiel Lucy , Lipworth Wendy
Published: July 2024

In Australia and the UK, commercialization and corporatization of assisted reproductive technologies have created a marketplace of clinics, products, and services. While this has arguably increased choice for patients, ‘choice’, shaped by commercial imperatives may not mean better-quality care. At present, regulation of clinics (including clinic–corporations) and clinicians focuses on the doctor–patient dyad and the clinic–consumer dyad. Scant attention has been paid to the conflicts between the clinic–corporation’s duty to its shareholders and investors, the medical profession’s duty to the corporations within which they practice, and the obligations of both clinicians and corporations to patients and to health systems. Frameworks of regulation based in corporate governance and business ethics, such as stakeholder models and ‘corporate social responsibility’, have well-recognized limits and may not translate well into healthcare settings. This means that existing governance frameworks may not meet the needs of patients or health systems. We argue for the development of novel regulatory approaches that more explicitly characterize the obligations that both corporations and clinicians in corporate environments have to patients and to society, and that promote fulfilment of these obligations. We consider mechanisms for application in the multi-jurisdictional setting of Australia, and the single jurisdictional settings of the UK.
The sherlock pipeline: new exoplanet candidates in the WASP-16, HAT-P-27, HAT-P-26, and TOI-2411 systems
Authors: Dévora-Pajares Martín , Pozuelos Francisco J , Thuillier Antoine , Timmermans Mathilde , Van Grootel Valérie , Bonidie Victoria , Mota Luis Cerdeño , Suárez Juan C
Published: July 2024

The launches of NASA Kepler and Transiting Exoplanet Survey Satellite (TESS) missions have significantly enhanced the interest in the exoplanet field during the last 15 yr, providing a vast amount of public data that are being exploited by the community thanks to the continuous development of new analysis tools. However, using these tools is not straightforward, and users must dive into different codes, input–output formats, and methodologies, hindering an efficient and robust exploration of the available data. We present the sherlock pipeline, an end-to-end public software that allows the users to easily explore observations from space-based missions such as TESS or Kepler to recover known planets and candidates issued by the official pipelines and search for new planetary candidates that remained unnoticed. The pipeline incorporates all the steps to search for transit-like features, vet potential candidates, provide statistical validation, conduct a Bayesian fitting, and compute observational windows from ground-based observatories. Its performance is tested against a catalogue of known and confirmed planets from the TESS mission, trying to recover the official TESS Objects of Interest (TOIs), explore the existence of companions that have been missed, and release them as new planetary candidates. sherlock demonstrated an excellent performance, recovering 98 per cent of the TOIs and confirmed planets in our test sample and finding new candidates. Specifically, we release four new planetary candidates around the systems WASP-16 (with P $\sim$ 10.46 d and R $\sim$ 2.20 $\mathrm{ R}_{\oplus }$), HAT-P-27 (with P $\sim$ 1.20 d and R $\sim$ 4.33 $\mathrm{ R}_{\oplus }$), HAT-P-26 (with P $\sim$ 6.59 d and R $\sim$ 1.97 $\mathrm{ R}_{\oplus }$), and TOI-2411 (with P $\sim$ 18.75 d and R $\sim$ 2.88 $\mathrm{ R}_{\oplus }$).
Linear operator theory of phase mixing
Authors: Darling Keir , Widrow Lawrence M
Published: July 2024

We study solutions of the collisionless Boltzmann equation (CBE) in a functional Koopman representation. This facilitates the use of linear spectral techniques characteristic of the analysis of Schrödinger-type equations. For illustrative purposes, we consider the classical phase mixing of a non-interacting distribution function in a quartic potential. Solutions are determined perturbatively relative to a harmonic oscillator. We impose a form of coarse-graining by choosing a finite-dimensional basis to represent the distribution function and time evolution operators, which sets a minimum length-scale on phase space structure. We observe a relationship between the dimension of the representation and the multiplicity of the harmonic oscillator eigenvalues. System dynamics are understood in terms of degenerate subspaces of the linear operator spectra. Each subspace is associated with a mode of the harmonic oscillator, the first two being bending and breathing structures. The quartic potential splits the degenerate eigenvalues within each subspace. This facilitates the formation of spiral structure as deformations from the harmonic oscillator modes. We ultimately argue that this construction provides a promising avenue for study of self-interacting systems experiencing phase mixing, which is an outstanding problem in the context of the Gaia DR2 vertical phase space spirals.
Closing the gap: secular evolution of bar-induced dark gaps in the presence of thick discs
Authors: Ghosh Soumavo , Gadotti Dimitri A , Fragkoudi Francesca , Nagpal Vighnesh , Di Matteo Paola , Cuomo Virginia
Published: July 2024

The presence of dark gaps, a preferential light deficit along the bar minor axis, is observationally well known. The properties of dark gaps are thought to be associated with the properties of bars, and their spatial locations are often associated with bar resonances. However, a systematic study, testing the robustness and universality of these assumptions, is still largely missing. Here, we investigate the formation and evolution of bar-induced dark gaps using a suite of N-body models of (kinematically cold) thin and (kinematically hot) thick discs with varying thick disc mass fractions and different thin-to-thick disc geometries. We find that dark gaps are a natural consequence of the trapping of disc stars by the bar. The properties of dark gaps (such as strength and extent) are well correlated with the properties of bars. For stronger dark gaps, the fractional mass-loss along the bar minor axis can reach up to ${\sim} 60\!-\!80$ per cent of the initial mass contained, which is redistributed within the bar. These trends hold true irrespective of the mass fraction in the thick disc and the assumed disc geometry. In all our models harbouring slow bars, none of the resonances (corotation, inner Lindblad resonance, and 4:1 ultraharmonic resonance) associated with the bar correspond to the location of dark gaps, thereby suggesting that the location of dark gaps is not a universal proxy for these bar resonances, in contrast with earlier studies.
The Great Rift Valley is a more pronounced biogeographic barrier than the Blue Nile Valley for six Ethiopian Highland passerines in the eastern Afromontane biodiversity hotspot
Authors: Behrends Garrett J , Meheretu Yonas , Manthey Joseph D
Published: July 2024

The Ethiopian Highlands are divided by lowland biogeographic barriers, including the Blue Nile Valley (BNV) and Great Rift Valley (GRV). We show that the GRV is a more pronounced phylogeographic break than the BNV for 6 focal passerines. Previous research suggests that the BNV greatly shaped phylogeographic patterns in relatively sedentary montane taxa such as frogs and rodents, whereas the GRV shaped phylogeographic patterns in volant taxa such as birds. However, no previous research simultaneously compares the impact of each valley on phylogeographic patterns in birds, and as these barriers vary in geographic extent and topography, the relative extent of their effects on gene flow is unclear. Using whole-genome resequencing, we quantified genetic variation in 6 montane forest passerines in the Ethiopian Highlands and found that their phylogeographic patterns varied, with general trends distinct from those of taxa that were previously studied across the same barriers. Genetic variation was assessed by estimating genome-wide genetic diversity (HO), demographic history, phylogeographic structure, and phylogeographic concordance among taxa. Population pairs flanking the GRV showed higher FST and more distinct population clusters in principal component analysis than those separated by the BNV. HO was broadly consistent across populations, excluding noticeable reductions in 2 populations (1 population each in 2 separate species). The overall phylogenetic signature and concordance across study taxa supported populations separated by the BNV as sister and populations southeast of the GRV as most distinct.
On Artin’s Primitive Root Conjecture for Function Fields over 𝔽q
Authors: Hochfilzer Leonhard , Waxman Ezra
Published: July 2024

In 1927, E. Artin proposed a conjecture for the natural density of primes p for which g generates $(\mathbb{Z}/p\mathbb{Z})^\times$. By carefully observing numerical deviations from Artin’s originally predicted asymptotic, Derrick and Emma Lehmer (1957) identified the need for an additional correction factor, leading to a modified conjecture which was eventually proved to be correct by Hooley (1967) under the assumption of the generalized Riemann hypothesis. An appropriate analogue of Artin’s primitive root conjecture may moreover be formulated for an algebraic function field K of r variables over $\mathbb{F}_{q}$. Relying on a soon to be established theorem of Weil (1948), Bilharz (1937) provided a proof in the particular case that K is a global function field (that is, r = 1), which is correct under the assumption that $g \in K$ is a geometric element. Under the same assumptions, Pappalardi and Shparlinski (1995) established a quantitative version of Bilharz’s result. In this paper we build upon these works by both generalizing to function fields in r variables over $\mathbb{F}_{q}$ and removing the assumption that $g \in K$ is geometric, thereby completing a proof of Artin’s primitive root conjecture for function fields over $\mathbb{F}_{q}$. In doing so, we moreover identify an interesting correction factor which emerges when g is not geometric. A crucial feature of our work is an exponential sum estimate over varieties that we derive from Weil’s Theorem.
Tax Policy and Abnormal Investment Behavior
Authors: Xu Qiping , Zwick Eric
Published: July 2024

This paper studies tax-minimizing investment, whereby firms tilt capital purchases toward year-end to reduce taxes. We use this pattern to characterize how taxes affect investment behavior. We exploit variation in firm tax positions from administrative data to confirm that tax minimization causes spikes. Spikes increase when firms face financial constraints or higher option values of waiting. Cumulative investment does not completely reverse after spikes. We develop an investment model with tax asymmetries to rationalize these patterns. Both depreciation motives (later investments face lower effective tax rates) and option value motives (tax asymmetry implies time-varying opportunities to minimize taxes) are necessary to fit the data. (JEL G31, G38, H25)
Poor sleep and inflammatory gene expression among care partners of persons living with dementia: a pilot trial of a behavioral sleep intervention
Authors: Song Yeonsu , Martin Jennifer L , McCurry Susan M , Kelly Monica R , Teng Edmond , Alessi Cathy A , Irwin Michael R , Cole Steve
Published: July 2024

Objective

Poor sleep is associated with increased inflammation, thereby increasing the risk of chronic diseases and mortality. However, the effects of behavioral sleep interventions on the upstream inflammatory system are unknown among family care partners (CP). The present study explored the role of a behavioral sleep intervention program on inflammatory gene expression.

Methods

This was part of a randomized controlled trial of a sleep intervention for dementia care dyads with sleep problems. Thirty dyads were randomized to sleep intervention or control groups. Sleep outcomes for CP were assessed with 1 week of actigraphy and sleep diary, and the Pittsburgh Sleep Quality Index. Other information included CP demographics, body mass index, and intensity of caregiving tasks. All outcomes were collected at baseline, post-treatment, and 3-month follow-up.

Results

Neither group showed any significant differential changes in gene expression from baseline to post-treatment or 3-month follow-up. A decrease in inflammatory gene expression was significantly associated with more nights of good sleep (i.e. nights without trouble falling or staying asleep at night). This finding remained significant after controlling for group (intervention/control), timepoint (baseline, post-treatment, and 3-month follow-up), and CP characteristics (e.g. age and ethnicity).

Conclusions

Although better sleep was associated with decreased inflammatory gene expression, this study did not demonstrate any benefits of a behavioral sleep intervention over control, most likely due to a small sample. Studies with larger sample sizes are needed to test the specific aspects of disturbed sleep that relate to inflammatory biology among CP of persons living with dementia.
Muscle cell‐derived Ccl8 is a negative regulator of skeletal muscle regeneration
Authors: Boss‐Kennedy A. , Kim D. , Barai P. , Maldonado C. , Reyes‐Ordoñez A. , Chen J.
Published: July 2024

Skeletal muscles undergo robust regeneration upon injury, and infiltrating immune cells play a major role in not only clearing damaged tissues but also regulating the myogenic process through secreted cytokines. Chemokine C‐C motif ligand 8 (Ccl8), along with Ccl2 and Ccl7, has been reported to mediate inflammatory responses to suppress muscle regeneration. Ccl8 is also expressed by muscle cells, but a role of the muscle cell‐derived Ccl8 in myogenesis has not been reported. In this study, we found that knockdown of Ccl8, but not Ccl2 or Ccl7, led to increased differentiation of C2C12 myoblasts. Analysis of existing single‐cell transcriptomic datasets revealed that both immune cells and muscle stem cells (MuSCs) in regenerating muscles express Ccl8, with the expression by MuSCs at a much lower level, and that the temporal patterns of Ccl8 expression were different in MuSCs and macrophages. To probe a function of muscle cell‐derived Ccl8 in vivo, we utilized a mouse system in which Cas9 was expressed in Pax7+ myogenic progenitor cells (MPCs) and Ccl8 gene editing was induced by AAV9‐delivered sgRNA. Depletion of Ccl8 in Pax7+ MPCs resulted in accelerated muscle regeneration after barium chloride‐induced injury in both young and middle‐aged mice, and intramuscular administration of a recombinant Ccl8 reversed the phenotype. Accelerated regeneration was also observed when Ccl8 was depleted in Myf5+ or MyoD+ MPCs by similar approaches. Our results suggest that muscle cell‐derived Ccl8 plays a unique role in regulating the initiation of myogenic differentiation during injury‐induced muscle regeneration.
Certified Registered Nurse First Assistant
Authors: Barraza Bobbie
Published: July 2024

These nurses assist in surgical procedures.
Short-Term Antibiotic Therapy Is Noninferior to Usual Care for VAP
Authors: Rosenberg Karen
Published: July 2024

According to this study:

In adults with ventilator-associated pneumonia, individualized shortened antibiotic therapy based on clinical response was noninferior to usual care and reduced antibiotic side effects.

There was no increased risk of mortality or pneumonia recurrence.
Studies Needed of Thick vs. Thin Liquids in Patients with Dementia and Dysphagia
Authors: Rosenberg Karen
Published: July 2024

According to this study:
Addressing Compassion Fatigue
Authors: Harper Robin , Ortelli Tracy A.
Published: July 2024

Resources to improve nurses' well-being
Opening a Donor Management Center
Authors: Max Emma , MacKenzie-Greenle Meredith , Acero-Webb Jamie Ann , Lambe Leah , Martin Niels D. , Vail Emily
Published: July 2024

In the United States alone, more than 100,000 people are waiting for a lifesaving organ transplant. In response to the growing need for viable organs to transplant, donor management centers have opened to provide care to brain-dead organ donors prior to the organ procurement operation. This article describes donor management center operations, details the opening of one such unit, and describes the results and lessons learned. More research is needed on the impact of nursing care on the specialized organ donor population.
Escaping the Closed World of Intimate Partner Violence
Authors: Brooks Andrea Nicole
Published: July 2024

A nurse colleague's nonjudgmental support proves crucial.
Perinatal depression and anxiety
Authors: Scrandis Debra A. , Scrandis Kayla S.
Published: July 2024

Perinatal depression (PND) and perinatal anxiety are common conditions that can arise during or after pregnancy and can have a major impact on patients and their families. A potential outcome of PND includes death by suicide, a leading cause of maternal mortality. This article provides an overview of these conditions, including discussion of neurobiology, risk factors, warning signs for individuals at risk for suicide and/or infant harm, and relevant screening tools. Considerations for psychotherapy and pharmacotherapy are highlighted, and an overview of neuroactive steroid gamma-aminobutyric acid A receptor positive allosteric modulators, a newer pharmacologic treatment option for postpartum depression, is provided.
Testosterone replacement therapy for hypogonadism
Authors: Gallegos Julian L.
Published: July 2024

Testosterone replacement therapy (TRT) is a crucial intervention for men diagnosed with hypogonadism, a condition characterized by inadequate testosterone production. As primary care NPs play an essential role in managing patients with hypogonadism, they must comprehensively understand TRT. This article serves as a primer for primary care NPs, based on current guidelines, to provide evidence-based care for men with hypogonadism. It offers an overview of the etiology, clinical presentation, diagnostic criteria, and treatment options for hypogonadism, focusing on using TRT appropriately in primary care settings.
Restrictive versus Decision Support Guided Fluid Therapy During Major Hepatic Resection Surgery
Authors: Coeckelenbergh Sean , Proux-Soucy Maxim , Van der Linden Philippe , Roullet Stephanie , Moussa Maya , Kato Hiromi , Toubal Leila , Naili Salima , Rinehart Joseph , Grogan Tristan , Cannesson Maxime , Duranteau Jacques , Joosten Alexandre
Published: July 2024

Background:

Fluid therapy during major hepatic resection aims at minimizing fluids during the dissection phase to reduce central venous pressure (CVP), retrograde liver blood flow, and venous bleeding. This strategy, however, may lead to hyperlactatemia. The Acumen™ Assisted Fluid Management system uses novel decision support software whose algorithm helps clinicians optimize fluid therapy. We tested the hypothesis that using this decision support system could decrease arterial lactate at the end of major hepatic resection when compared to a more restrictive fluid strategy.

Methods:

This two-arm, prospective, randomized controlled, assessor-and patient-blinded superiority study included consecutive patients undergoing major liver surgery equipped with an arterial catheter linked to an uncalibrated stroke volume monitor. In the decision support group, fluid therapy was guided throughout the entire procedure using the assisted fluid management software. In the restrictive fluid group, clinicians were recommended to restrict fluid infusion to 1-2 ml.kg-1.h-1 until the completion of hepatectomy. They then administered fluids based on advanced hemodynamic variables. Noradrenaline was titrated in all patients to maintain a mean arterial pressure >65mmHg. The primary outcome was arterial lactate level upon completion of surgery (i.e., skin closure).

Results:

Ninety patients were enrolled over a 7-month period. The primary outcome was lower in the decision support group than in the restrictive group (median[Q1-Q3] 2.5[1.9-3.7]mmol.L-1 vs 4.6[3.1-5.4]mmol.L-1, median difference -2.1, 95%CI(-2.7,-1.2), p<0.001). Among secondary exploratory outcomes, there was no difference in blood loss (median[Q1-Q3] 450[300-600]ml vs 500[300-800]ml, p=0.727) although CVP was higher in the decision support group (mean (SD) of 7.7(2.0)mmHg vs 6.6(1.1)mmHg, p<0.002).

Conclusion:

Patients managed using a clinical decision support system to guide fluid administration during major hepatic resection had a lower arterial lactate concentration at the end of surgery when compared to a more restrictive fluid strategy. Future trials are necessary to make conclusive recommendations that will change clinical practice.
Cell-Free DNA Analysis for the Determination of Fetal Red Blood Cell Antigen Genotype in Individuals With Alloimmunized Pregnancies
Authors: Rego Shannon , Ashimi Balogun Olaide , Emanuel Kirsten , Overcash Rachael , Gonzalez Juan M. , Denomme Gregory A. , Hoskovec Jennifer , King Haley , Wilson Ashley , Wynn Julia , Moise Kenneth J.
Published: July 2024

OBJECTIVE:

To evaluate the accuracy of next-generation sequencing–based quantitative cell-free DNA analysis for fetal antigen genotyping in individuals with alloimmunized pregnancies undergoing clinical testing in practices across the United States as early as 10 weeks of gestation, with the objective of identifying individuals with pregnancies at risk for hemolytic disease of the fetus and newborn and guiding management.

METHODS:

This prospective cohort study included patients with alloimmunized pregnancies undergoing clinical fetal antigen cell-free DNA analysis between 10 0/7 and 37 0/7 weeks of gestation at 120 clinical sites. Both the pregnant person with the alloimmunized pregnancy and the neonates resulting from the pregnancies were included. The laboratory issued the cell-free DNA results prospectively as a part of clinical care. After delivery, neonatal buccal swabs collected between 0 and 270 days of life were sent to an outside independent laboratory for antigen genotyping. The outside laboratory was blinded to the fetal cell-free DNA results, and the results were compared. Concordance was reported for the fetal antigen cell-free DNA analysis for antigens to which the pregnant person was alloimmunized and for all antigens for which the pregnant person was genotype negative.

RESULTS:

A total of 156 pregnant people who received clinically ordered cell-free DNA fetal antigen testing provided neonatal buccal swabs for genotyping after delivery. Overall, 15.4% of participants were Hispanic, 9.0% were non-Hispanic Black, 65.4% were non-Hispanic White, 4.5% were Asian, 1.3% were more than one race or ethnicity, and 4.5% were unknown. The median gestational age at the time of testing was 16.4 weeks with a median fetal fraction of 11.1%. Concordance between cell-free DNA analysis results and neonatal genotype was determined for 465 antigen calls for the following antigens: K1 (n=143), E (124), C (60), Fya (50), c (47), and D(RhD) (41). These 465 calls included 145 in which the fetus was antigen positive and 320 in which the fetus was antigen negative. We observed complete concordance between prenatal fetal antigen cell-free DNA analysis results and neonatal genotypes for the 465 calls, resulting in 100% sensitivity, specificity, and accuracy.

CONCLUSION:

In a diverse multicenter cohort, cell-free DNA analysis was highly sensitive and specific for determining fetal antigen genotype as early as 10 weeks of gestation in individuals with alloimmunized pregnancies. Taken together with previously published evidence, this study supports the implementation of cell-free DNA testing to manage individuals with alloimmunized pregnancies in the United States.
Differences at Index Surgery in Operative Complexity and Residual Disease for Earlier and Later Repeat Lumbar Surgery
Authors: Duculan Roland , Mancuso Carol A. , Cammisa Frank P. , Sama Andrew A. , Hughes Alexander P. , Lebl Darren R. , Girardi Federico P.
Published: July 2024

Study Design.

Retrospective review, single-institution cohort studies.

Objective.

To compare patients with earlier (i.e. <1.5 yr) and later (i.e. >1.5 yr) repeat lumbar surgery to patients with no repeat surgery according to clinical characteristics at index surgery.

Background.

Grouping patients as earlier or later repeat surgery may reveal different associations when compared with patients with no repeat surgery.

Patients and Methods.

Patients undergoing index surgery for diverse conditions reported preoperative demographic/clinical variables, including comorbidity and depressive symptoms. Extent (i.e. complexity) of surgery was assigned based on a valid index that included decompression, fusion, and instrumentation. Co-existing disease at nonoperated levels was ascertained from imaging reports. Postoperative records of all medical visits up to the time of this study (12 yr) were reviewed for repeat surgery. Patients were grouped as earlier (<1.5 yr) or later surgery (≥1.5 yr) and compared with patients with no repeat surgery in separate multivariable analyses.

Results.

Among 1334 patients (51% men, mean age 59), 82% did not have repeat surgery, 7% had earlier and 11% had later repeat surgery. Compared with no surgery, earlier surgery was associated with more comorbidity (OR: 1.7, CI: 1.1–2.6, P=0.02), positive depression screen (OR: 1.9, CI: 1.2–2.9, P=0.006), opioid use (OR: 1.8, CI: 1.2–2.8, P=0.008), and greater extent of index surgery (OR: 1.1, CI: 1.0–1.1, P=0.0009). Compared with no surgery, later surgery was associated with preindex lumbar surgery (OR: 1.9, CI: 1.3–2.8, P=0.0005) and disease at nonoperated levels at index surgery (OR: 1.6, CI: 1.0–2.4, P=0.05). Earlier surgeries were more likely to involve only the same vertebra as index surgery (51% vs. 16%) and later surgeries were more likely to involve only other levels (5% vs. 36%, P=0.01).

Conclusions.

Earlier and later repeat lumbar surgeries differed in complexity and residual disease compared with no repeat surgery. These findings have implications for patient counseling regarding short-term and long-term postoperative spine health.
A comparison of pediatric nail disorders between the years with and without the COVID-19 pandemic
Authors: Chen Wenting , Zhong Xinni , Sun Qi , Li Wei
Published: July 2024

Background:

Coronavirus disease 2019 (COVID-19) pandemic between 2020 to 2022 considerably impacted public health in China. Nail disorders account for the majority of pediatric dermatology. We investigated outpatient nail disease diagnosed at the dermatology clinic to determine the effect of the outbreak of the COVID-19 pandemic on these patients.

Methods:

We gathered information from the outpatient department of the Dermatology clinic at Children’s Hospital of Soochow University from January 2018 to December 2022. We distinguish between pre-epidemic (January 1, 2018 to December 31, 2019) and post-epidemic (January 1, 2020 to December 31, 2022).

Results:

8666 outpatients were included in the pre-epidemic group and 13,885 were included in the post-epidemic group. The percentage of outpatient nail disorders in the top 7 slightly differs from 2018 to 2022, while the first place is always Paronychia. The percentage of nail dystrophy, onycholysis, and onychomadesis decreased during the COVID-19 pandemic years and the percentage of paronychia, onychomycosis, longitudinal melanonychia, and psychosomatic nail disorders increased during the COVID-19 pandemic years.

Conclusion:

Although the impact of the COVID-19 pandemic on outpatients in the dermatology department was minimal, the spectrum of nail disorders was affected. A significant increase in infectious and psychosomatic nail disorders during the COVID-19 pandemic was an important finding in this study. Knowing the pattern of nail diseases may help hospitals to better prepare for future pandemics.
Antidepressant effect of PT-31, an α₂-adrenoceptor agonist, on lipopolysaccharide-induced depressive-like behavior in mice
Authors: Machado Kayser Juliana , Petry Fernanda , Alijar Souza Maryelen , Santin Zanatta Schindler Monica , Vidor Morgan Letícia , Zimmermann Prado Rodrigues Gabriela , Mazon Samara Cristina , Silva Aguiar Gean Pablo , Galdino da Rocha Pitta Marina , da Rocha Pitta Ivan , Leal Xavier Léder , Girardi Müller Liz , Gehlen Günther , Heemann Betti Andresa
Published: July 2024

Increasing evidence indicates that neuroinflammation, oxidative stress, and neurotrophic factors play a key role in the pathophysiology of major depressive disorder (MDD). In addition, the attenuation of inflammatory response has been considered a putative mechanism for MDD treatment. PT-31 is an imidazolidine derivative and a putative α₂-adrenoceptor agonist that has previously demonstrated antinociceptive activity. The present study aimed to investigate the effect of PT-31 on depressive-like behavior and lipopolysaccharide-induced neurochemical changes. To this end, mice received intraperitoneally saline or lipopolysaccharide (600 µg/kg), and 5 h postinjection animals were orally treated with saline, PT-31 (3, 10, and 30 mg/kg), or fluoxetine (30 mg/kg). Mice were subjected to the open field test (OFT) 6 and 24 h after lipopolysaccharide administration and to the tail suspension test (TST) 24 h postlipopolysaccharide. Subsequently, animals were euthanized, and brains were dissected for neurochemical analyses. The administration of lipopolysaccharide-induced sickness- and depressive-like behaviors, besides promoting an increase in myeloperoxidase activity and a reduction in brain-derived neurotrophic factor (BDNF) levels. Noteworthy, PT-31 3 mg/kg attenuated lipopolysaccharide-induced decreased locomotor activity 6 h after lipopolysaccharide in the OFT. All tested doses of PT-31 significantly reduced the immobility time of animals in the TST and attenuated lipopolysaccharide-induced increased myeloperoxidase activity in the cortex of mice. Our results demonstrate that PT-31 ameliorates behavioral changes promoted by lipopolysaccharide in OFT and TST, which is possibly mediated by attenuation of the inflammatory response.
Evaluation of potential punishing effects of 2,5-dimethoxy-4-methylamphetamine (DOM) in rhesus monkeys responding under a choice procedure
Authors: Maguire David R.
Published: July 2024

Objectives

There has been substantial and growing interest in the therapeutic utility of drugs acting at serotonin 2A subtype (5-HT2A) receptors, increasing the need for characterization of potential beneficial and adverse effects of such compounds. Although numerous studies have evaluated the possible rewarding and reinforcing effects of 5-HT2A receptor agonists, there have been relatively few studies on potential aversive effects.

Methods

The current study investigated punishing effects of 2,5-dimethoxy-4-methylamphetamine (DOM) in four rhesus monkeys responding under a choice procedure in which responding on one lever delivered a sucrose pellet alone and responding on the other lever delivered a sucrose pellet plus an intravenous infusion of a range of doses of fentanyl (0.1–3.2 µg/kg/infusion), histamine (3.2–100 µg/kg/infusion), or DOM (3.2–100 µg/kg/infusion).

Results

When fentanyl was available, responding for a pellet plus an infusion increased dose dependently in all subjects, indicating a positive reinforcing effect of fentanyl. When histamine was available, responding for a pellet plus an infusion decreased in three of four subjects, indicating a punishing effect of histamine. Whether available before or after histamine, DOM did not systematically alter choice across the range of doses tested.

Conclusion

These results suggest that the 5-HT2A receptor agonist DOM has neither positive reinforcing nor punishing effects under a choice procedure that is sensitive to both processes.
Asymptomatic hyperuricemia: to treat or not a threat? A clinical and evidence-based approach to the management of hyperuricemia in the context of cardiovascular diseases
Authors: Fiori Emiliano , De Fazio Ludovica , Pidone Chiara , Perone Francesco , Tocci Giuliano , Battistoni Allegra , Barbato Emanuele , Volpe Massimo , Gallo Giovanna ,   the Young Group of The Italian Society of Cardiovascular Prevention (SIPREC)
Published: July 2024

Asymptomatic hyperuricemia is defined by serum uric acid levels above 6.2 mg/dl in women and 7 mg/dl in men. In the presence of monosodium urate crystal formation and articular inflammation, hyperuricemia may become symptomatic (namely nephrolithiasis and gout). Uric acid results from purine catabolism and is at the centre of a complex metabolic interplay that involves oxidative stress, inflammation, renin–angiotensin–aldosterone system (RAAS) activation and insulin resistance. Uric acid levels present a continuous relation with conditions like hypertension and chronic kidney disease (CKD) and are reported to have an impact on risk of cardiovascular events. However, whether elevated uric acid is a causal agent and thus a possible therapeutic target is still uncertain and matter of further investigation. Treating symptomatic hyperuricemia involves lowering uric acid drugs and controlling inflammation. Urate-lowering agents are well tolerated but show minimal impact on cardiovascular events in patients with gout. Use of direct-acting urate-lowering agents in asymptomatic hyperuricemia associated with cardiovascular diseases does not warrant a clear benefit, whereas addressing cardiovascular issues with guideline-recommended therapies lowers uric acid and reduces the occurrence of cardiovascular events. Regular assessment of uric acid and clinical symptoms is advised before starting and renewing a urate-lowering treatment.
Gender Differences in Letters of Recommendations and Personal Statements for Neurotology Fellowship over 10 Years: A Deep Learning Linguistic Analysis
Authors: Vasan Vikram , Cheng Christopher P. , Fan Caleb J. , Lerner David K. , Pascual Karen , Iloreta Alfred Marc , Babu Seilesh C. , Cosetti Maura K.
Published: July 2024

Objective

Personal statements (PSs) and letters of recommendation (LORs) are critical components of the neurotology fellowship application process but can be subject to implicit biases. This study evaluated general and deep learning linguistic differences between the applicant genders over a 10-year span.

Study Design

Retrospective cohort.

Setting

Two institutions.

Main Outcome Measures

PSs and LORs were collected from 2014 to 2023 from two institutions. The Valence Aware Dictionary and Sentiment Reasoner (VADER) natural language processing (NLP) package was used to compare the positive or negative sentiment in LORs and PSs. Next, the deep learning tool, Empath, categorized the text into scores, and Wilcoxon rank sum tests were performed for comparisons between applicant gender.

Results

Among 177 applicants over 10 years, 120 were males and 57 were females. There were no differences in word count or VADER sentiment scores between genders for both LORs and PSs. However, among Empath sentiment categories, male applicants had more words of trust (p = 0.03) and leadership (p = 0.002) in LORs. Temporally, the trends show a consistently higher VADER sentiment and Empath “trust” and “leader” in male LORs from 2014 to 2019, after which there was no statistical significance in sentiment scores between genders, and females even have higher scores of trust and leadership in 2023.

Conclusions

Linguistic content overall favored male applicants because they were more frequently described as trustworthy and leaders. However, the temporal analysis of linguistic differences between male and female applicants found an encouraging trend suggesting a reduction of gender bias in recent years, mirroring an increased composition of women in neurotology over time.
Mendelian Randomization Study Reveals a Predicted Relationship between Sensorineural Hearing Loss and Mitochondrial Proteins
Authors: Yan Jiangyu , Wu Linrong , Zheng Mengmeng , Lv Yuan , Jiang Feng , Gao Weibo , Pan Fangfang
Published: July 2024

Background

Mitochondrial proteins assume a pivotal role in the onset and progression of diverse diseases. Nonetheless, the causal interconnections with sensorineural hearing loss (SNHL) demand meticulous exploration. Mendelian randomization analysis is a method used in observational epidemiological studies to predict the relationship between exposure factors and outcomes using genetic variants as instrumental variables. In this study, we applied this analytical approach to two distinct samples to predict the causal impact of mitochondrial proteins on SNHL.

Methods

Two-sample Mendelian randomization analyses were executed to scrutinize the predicted associations between 63 mitochondrial proteins (nuclear-encoded) and SNHL, utilizing summary statistics derived from genome-wide association studies. Assessments of pleiotropy and heterogeneity were carried out to gauge the robustness of the obtained findings.

Results

Four mitochondrial proteins exhibited a suggestive causal relationship with the susceptibility to SNHL. Dihydrolipoamide dehydrogenase (DLD; OR = 0.9706, 95% CI = 0.9382–0.9953, p = 0.0230) was linked to a diminished risk of SNHL. Conversely, elevated levels of mitochondrial ribosomal protein L34 (MRPL34; OR = 1.0458, 95% CI = 1.0029–1.0906, p = 0.0362), single-pass membrane protein with aspartate-rich tail 1 (SMDT1; OR = 1.0619, 95% CI = 1.0142–1.1119, p = 0.0104), and superoxide dismutase 2 (SOD2; OR = 1.0323, 95% CI = 1.0020–1.0634, p = 0.0364) were associated with an elevated risk of SNHL.

Conclusion

This research utilized Mendelian randomization analysis to predict the relationship between mitochondrial proteins and SNHL. It provides a potential viewpoint on the etiology and diagnosis.
Intratympanic Lidocaine as a Potent Remedy for Tinnitus in Sudden Sensorineural Hearing Loss: A Double-Blind, Randomized Clinical Trial
Authors: Zhang Di , Li Daibo , Chen Ting , Feng Xuefei , Zhang Juan
Published: July 2024

Objective

This study evaluates intratympanic lidocaine's efficacy and safety for tinnitus relief in sudden sensorineural hearing loss (SSNHL) patients.

Methods

In a double-blind randomized controlled trial, 100 SSNHL patients with unilateral tinnitus received either intratympanic lidocaine or saline plus usual care. Treatment impact was assessed at 1 and 3 months using the Tinnitus Handicap Inventory, subjective visual analog scale, pure-tone audiometry.

Results

The lidocaine group demonstrated significant tinnitus relief according to the Tinnitus Handicap Inventory and visual analog scale, without pure-tone audiometry improvement or serious adverse events throughout the study period.

Conclusion

Intratympanic lidocaine provides a safe, efficacious treatment option for SSNHL tinnitus. Further studies should refine the dosage and delivery parameters because of SSNHL's heterogenous nature.
A Mock Circulatory Loop Analysis of Cardiorenal Hemodynamics With Intra-Aortic Mechanical Circulatory Support
Authors: Barua Sumita , Stevens Michael , Jain Pankaj , Matus Vazquez Gabriel , Boss Laurence , Muthiah Kavitha , Hayward Christopher
Published: July 2024

Type 1 cardiorenal syndrome is associated with significant excess morbidity and mortality in patients with severe acute decompensated heart failure. Previous trials of vasoactive drugs and ultrafiltration have not shown superiority over placebo or intravenous diuretics. Pilot data suggest short-term mechanical support devices may support diuresis in the cardiorenal syndrome. We evaluated the intra-aortic balloon pump (IABP) and a novel intra-aortic entrainment pump (IAEP) in a mock circulation loop (MCL) biventricular systolic heart failure model, to assess impact on renal flow and cardiac hemodynamics. Both devices produced similar and only modest increase in renal flow (IABP 3.3% vs. IAEP 4.3%) and cardiac output, with associated reduction in afterload elastance in the MCL. There were minor changes in coronary flow, increase with IABP and minor decrease with IAEP. Differences in device preload and afterload did not impact percentage change in renal flow with IABP therapy, however, there was a trend toward higher percentage flow change with IAEP in response to high baseline renal flow. The IAEP performed best in a smaller aorta and with more superior positioning within the descending aorta. Demonstrated changes in MCL flow during IAEP were of lower magnitude than previous animal studies, possibly due to lack of autoregulation and hormonal responses.
HLA Mismatches Identified by a Novel Algorithm Predict Risk of Antibody-mediated Rejection From De Novo Donor-specific Antibodies
Authors: Zhang Xiaohai , Reinsmoen Nancy L. , Kobashigawa Jon A.
Published: July 2024

Background.

The development of de novo donor-specific antibodies (dnDSA) and antibody-mediated rejection (AMR) remains a barrier to long-term graft and patient survival. Most dnDSA are directed against mismatched donor HLA-DQ antigens. Here, we describe a novel algorithm, which we have termed categorical amino acid mismatched epitope, to evaluate HLA-DQ mismatches.

Methods.

In this algorithm, amino acid residues of HLA-DQ protein were categorized into 4 groups based on their chemical characteristics. The likelihood of categorically mismatched peptides presented by the recipient’s HLA-DRB1 was expressed as a normalized value, %Rank score. Categorical HLA-DQ mismatches were analyzed in 386 heart transplant recipients who were mismatched with their donors at the HLA-DQB1 locus.

Results.

We found that the presence of DQB1 mismatches with %Rank score ≤1 was associated with the development of dnDSA (P = 0.002). Furthermore, dnDSA increased the risk of AMR only in recipients who had DQ mismatches with %Rank score ≤1 (hazard ratio = 5.8), but the freedom from AMR was comparable between recipients with dnDSA and those without dnDSA if %Rank scores of DQ mismatching were >1.

Conclusions.

These results suggest that HLA-DQ mismatches evaluated by the categorical amino acid mismatched epitope algorithm can stratify the risk of development of dnDSA and AMR in heart transplant recipients.
Clinical Management and Outcomes of Nontuberculous Mycobacterial Infections in Solid Organ Transplant Recipients: A Multinational Case-control Study
Authors: López-Medrano Francisco , Carver Peggy L. , Rutjanawech Sasinuch , Aranha-Camargo Luis F. , Fernandes Ruan , Belga Sara , Daniels Shay-Anne , Mueller Nicolas J. , Burkhard Sara , Theodoropoulos Nicole M. , Postma Douwe F. , van Duijn Pleun J. , Arnaiz de las Revillas Francisco , Pérez del Molino-Bernal Concepción , Hand Jonathan , Lowe Adam , Bodro Marta , Vanino Elisa , Fernández-Cruz Ana , Ramos-Martínez Antonio , Makek Mateja Jankovic , Bou Mjahed Ribal , Manuel Oriol , Kamar Nassim , Calvo-Cano Antonia , Rueda-Carrasco Laura , Muñoz Patricia , Álvarez-Uría Ana , Pérez-Recio Sandra , Sabé Núria , Rodríguez-Álvarez Regino , Silva José Tiago , Mularoni Alessandra , Vidal Elisa , Alonso-Titos Juana , del Rosal Teresa , Classen Annika Y. , Goss Charles W. , Agarwal Mansi , Mejía-Chew Carlos ,   on behalf of the EMOTE (Epidemiology, Management and Outcomes of Non-tuberculous Mycobacteria Infections in Transplant Recipients in Europe and America) study group
Published: July 2024

Background.

The management and outcomes of nontuberculous mycobacterial (NTM) infections in solid organ transplant (SOT) recipients are poorly characterized. We aimed to describe the management and 1-y mortality of these patients.

Methods.

Retrospective, multinational, 1:2 matched case-control study included SOT recipients aged 12 y old or older diagnosed with NTM infection between January 1, 2008, and December 31, 2018. Controls were matched on transplanted organs, NTM treatment center, and posttransplant survival at least equal to the time to NTM diagnosis. The primary aim was 1-y mortality after NTM diagnosis. Differences between cases and controls were compared using the log-rank test, and Cox regression models were used to identify factors associated with mortality at 12 mo among cases.

Results.

In 85 patients and 169 controls, the median age at the time of SOT was 54 y (interquartile range, 40–62 y), 59% were men, and the lungs were the most common site of infection after SOT (57.6%). One-year mortality was significantly higher in cases than in controls (20% versus 3%; P < 0.001), and higher mortality was associated with lung transplantation (hazard ratio 3.27; 95% confidence interval [1.1-9.77]; P = 0.034). Median time (interquartile range) from diagnosis to treatment initiation (20 [4–42] versus 11 [3–21] d) or the reduction of net immunosuppression (36% versus 45%, hazard ratio 1.35 [95% CI, 0.41-4.43], P = 0.618) did not differ between survivors and those who died.

Conclusions.

NTM disease in SOT recipients is associated with a higher mortality risk, especially among lung transplant recipients. Time to NTM treatment and reduction in net immunosuppression were not associated with mortality.