bluuebunny/crossref_metadata_2025 huggingface dataset:
V994 Herculis: a unique triply eclipsing sextuple star system
Authors: Zasche P , Borkovits T , Jayaraman R , Rappaport S A , Brož M , Vokrouhlický D , Bíró I B , Hegedüs T , Kiss Z T , Uhlař R , Schwengeler H M , Pál A , Mašek M , Howell S B , Dallaporta S , Munari U , Gagliano R , Jacobs T , Kristiansen M H , LaCourse D , Omohundro M , Terentev I , Vanderburg A , Henzl Z , Powell B P , Kostov V B
Published: January 2023

We report the discovery with the Transiting Exoplanet Survey Satellite (TESS) of a third set of eclipses from V994 Herculis (V994 Her, TIC 424508303), previously only known as a doubly eclipsing system. The key implication of this discovery and our analyses is that V994 Her is the second fully characterized (2+2) + 2 sextuple system, in which all three binaries eclipse. In this work, we use a combination of ground-based observations and TESS data to analyse the eclipses of binaries A and B in order to update the parameters of the inner quadruple’s orbit (with a derived period of 1062 ± 2 d). The eclipses of binary C that were detected in the TESS data were also found in older ground-based observations, as well as in more recently obtained observations. The eclipse timing variations of all three pairs were studied in order to detect the mutual perturbations of their constituent stars, as well as those of the inner pairs in the (2 + 2) core. At the longest periods they arise from apsidal motion, which may help constraining parameters of the component stars’ internal structure. We also discuss the relative proximity of the periods of binaries A and B to a 3:2 mean motion resonance. This work represents a step forward in the development of techniques to better understand and characterize multiple star systems, especially those with multiple eclipsing components.
A method to enrich polypeptidyl-tRNAs to capture snapshots of translation in the cell
Authors: Yamakawa Ayako , Niwa Tatsuya , Chadani Yuhei , Kobo Akinao , Taguchi Hideki
Published: January 2023

Life depends on proteins, which all exist in nascent states when the growing polypeptide chain is covalently attached to a tRNA within the ribosome. Although the nascent chains, i.e. polypeptidyl-tRNAs (pep-tRNAs), are considered as merely transient intermediates during protein synthesis, recent advances have revealed that they are directly involved in a variety of cell functions, such as gene expression control. An increasing appreciation for fine-tuning at translational levels demands a general method to handle the pep-tRNAs on a large scale. Here, we developed a method termed peptidyl-tRNA enrichment using organic extraction and silica adsorption (PETEOS), and then identify their polypeptide moieties by mass spectrometry. As a proof-of-concept experiment using Escherichia coli, we identified ∼800 proteins derived from the pep-tRNAs, which were markedly biased towards the N-termini in the proteins, reflecting that PETEOS captured the intermediate pep-tRNA population during translation. Furthermore, we observed the changes in the pep-tRNA set in response to heat shock or antibiotic treatments. In summary, PETEOS will complement conventional methods to investigate nascent chains in the cell.
A novel RHH family transcription factor aCcr1 and its viral homologs dictate cell cycle progression in archaea
Authors: Yang Yunfeng , Liu Junfeng , Fu Xiaofei , Zhou Fan , Zhang Shuo , Zhang Xuemei , Huang Qihong , Krupovic Mart , She Qunxin , Ni Jinfeng , Shen Yulong
Published: January 2023

Cell cycle regulation is of paramount importance for all forms of life. Here, we report that a conserved and essential cell cycle-specific transcription factor (designated as aCcr1) and its viral homologs control cell division in Sulfolobales. We show that the transcription level of accr1 reaches peak during active cell division (D-phase) subsequent to the expression of CdvA, an archaea-specific cell division protein. Cells over-expressing the 58-aa-long RHH (ribbon-helix-helix) family cellular transcription factor as well as the homologs encoded by large spindle-shaped viruses Acidianus two-tailed virus (ATV) and Sulfolobus monocaudavirus 3 (SMV3) display significant growth retardation and cell division failure, manifesting as enlarged cells with multiple chromosomes. aCcr1 over-expression results in downregulation of 17 genes (>4-fold), including cdvA. A conserved motif, aCcr1-box, located between the TATA-binding box and the translation initiation site of 13 out of the 17 highly repressed genes, is critical for aCcr1 binding. The aCcr1-box is present in the promoters and 5′ UTRs of cdvA genes across Sulfolobales, suggesting that aCcr1-mediated cdvA repression is an evolutionarily conserved mechanism by which archaeal cells dictate cytokinesis progression, whereas their viruses take advantage of this mechanism to manipulate the host cell cycle.
Genome-wide mapping of protein–DNA damage interaction by PADD-seq
Authors: Zhu Yongchang , Tan Yuanqing , Li Lin , Xiang Yuening , Huang Yanchao , Zhang Xiping , Yin Jiayong , Li Jie , Lan Fei , Qian Maoxiang , Hu Jinchuan
Published: January 2023

Protein–DNA damage interactions are critical for understanding the mechanism of DNA repair and damage response. However, due to the relatively random distributions of UV-induced damage and other DNA bulky adducts, it is challenging to measure the interactions between proteins and these lesions across the genome. To address this issue, we developed a new method named Protein-Associated DNA Damage Sequencing (PADD-seq) that uses Damage-seq to detect damage distribution in chromatin immunoprecipitation-enriched DNA fragments. It is possible to delineate genome-wide protein–DNA damage interactions at base resolution with this strategy. Using PADD-seq, we observed that RNA polymerase II (Pol II) was blocked by UV-induced damage on template strands, and the interaction declined within 2 h in transcription-coupled repair-proficient cells. On the other hand, Pol II was clearly restrained at damage sites in the absence of the transcription–repair coupling factor CSB during the same time course. Furthermore, we used PADD-seq to examine local changes in H3 acetylation at lysine 9 (H3K9ac) around cisplatin-induced damage, demonstrating the method's broad utility. In conclusion, this new method provides a powerful tool for monitoring the dynamics of protein–DNA damage interaction at the genomic level, and it encourages comprehensive research into DNA repair and damage response.
Structure and functional determinants of Rad6–Bre1 subunits in the histone H2B ubiquitin-conjugating complex
Authors: Shukla Prakash K , Bissell Jesse E , Kumar Sanjit , Pokhrel Srijana , Palani Sowmiya , Radmall Kaitlin S , Obidi Onyeka , Parnell Timothy J , Brasch Julia , Shrieve Dennis C , Chandrasekharan Mahesh B
Published: January 2023

The conserved complex of the Rad6 E2 ubiquitin-conjugating enzyme and the Bre1 E3 ubiquitin ligase catalyzes histone H2B monoubiquitination (H2Bub1), which regulates chromatin dynamics during transcription and other nuclear processes. Here, we report a crystal structure of Rad6 and the non-RING domain N-terminal region of Bre1, which shows an asymmetric homodimer of Bre1 contacting a conserved loop on the Rad6 ‘backside’. This contact is distant from the Rad6 catalytic site and is the location of mutations that impair telomeric silencing in yeast. Mutational analyses validated the importance of this contact for the Rad6–Bre1 interaction, chromatin-binding dynamics, H2Bub1 formation and gene expression. Moreover, the non-RING N-terminal region of Bre1 is sufficient to confer nucleosome binding ability to Rad6 in vitro. Interestingly, Rad6 P43L protein, an interaction interface mutant and equivalent to a cancer mutation in the human homolog, bound Bre1 5-fold more tightly than native Rad6 in vitro, but showed reduced chromatin association of Bre1 and reduced levels of H2Bub1 in vivo. These surprising observations imply conformational transitions of the Rad6–Bre1 complex during its chromatin-associated functional cycle, and reveal the differential effects of specific disease-relevant mutations on the chromatin-bound and unbound states. Overall, our study provides structural insights into Rad6–Bre1 interaction through a novel interface that is important for their biochemical and biological responses.
Unexpected moves: a conformational change in MutSα enables high-affinity DNA mismatch binding
Authors: Bruekner Susanne R , Pieters Wietske , Fish Alexander , Liaci A Manuel , Scheffers Serge , Rayner Emily , Kaldenbach Daphne , Drost Lisa , Dekker Marleen , van Hees-Stuivenberg Sandrine , Delzenne-Goette Elly , de Konink Charlotte , Houlleberghs Hellen , Dubbink Hendrikus Jan , AlSaegh Abeer , de Wind Niels , Förster Friedrich , te Riele Hein , Sixma Titia K
Published: January 2023

The DNA mismatch repair protein MutSα recognizes wrongly incorporated DNA bases and initiates their correction during DNA replication. Dysfunctions in mismatch repair lead to a predisposition to cancer. Here, we study the homozygous mutation V63E in MSH2 that was found in the germline of a patient with suspected constitutional mismatch repair deficiency syndrome who developed colorectal cancer before the age of 30. Characterization of the mutant in mouse models, as well as slippage and repair assays, shows a mildly pathogenic phenotype. Using cryogenic electron microscopy and surface plasmon resonance, we explored the mechanistic effect of this mutation on MutSα function. We discovered that V63E disrupts a previously unappreciated interface between the mismatch binding domains (MBDs) of MSH2 and MSH6 and leads to reduced DNA binding. Our research identifies this interface as a ‘safety lock’ that ensures high-affinity DNA binding to increase replication fidelity. Our mechanistic model explains the hypomorphic phenotype of the V63E patient mutation and other variants in the MBD interface.
Association between β-carotene supplementation and risk of cancer: a meta-analysis of randomized controlled trials
Authors: Zhang Yulin , Yang Jiaqi , Na Xiaona , Zhao Ai
Published: January 2023

Context

β-Carotene, which is derived from most fruits and vegetables, is the most common type of carotenes. Existing studies have demonstrated that β-carotene is associated with some positive health outcomes. However, results about the effects of supplemental β-carotene on cancer are inconsistent.

Objective

To determine the association between supplemental β-carotene intake and the risk of cancers.

Data sources

Eight databases (PubMed, Web of Science, Embase, Cochrane, China National Knowledge Infrastructure, Wangfang, China Science and Technology Journal Database, and Chinese Biomedical Literature Database) were systematically searched until September 2022.

Data extraction

Only reports from randomized controlled trials in which an association between supplemental β-carotene intake and the risk of cancer was found were included in the meta-analysis.

Data analysis

A total of 18 eligible studies based on 8 different randomized controlled trials were included in the meta-analysis, with varying sample sizes from 391 to 39 876 participants. There was no significant association between supplemental β-carotene intake and overall cancer incidence rate after synthesizing all the results (risk ratio [RR]: 1.02; 95% confidence interval [CI], 0.99–1.05). Results from subgroup analysis indicated that intake of supplemental β-carotene significantly increased the risk of lung cancer (RR: 1.19; 95%CI: 1.08–1.32), whereas no significant associations were observed for other site-specific cancers. In addition, smokers and the subgroup of participants with only low-dose β-carotene intake had a risk increment of cancer if they took supplemental β-carotene (RR: 1.16; 95%CI: 1.05–1.29).

Conclusion

β-Carotene supplementation has no beneficial or harmful effect on cancer incidence; moreover, it might have potentially harmful effects on lung cancer, especially for people who smoke. On the basis of the evidence from this study, supplemental intake of β-carotene is not recommended for preventing cancer, and the establishment of a tolerable upper intake level of β-carotene should be considered.
Greek Death Rituals and Lament
Authors: Holst-Warhaft Gail
Published: January 2023

Research into Greek death rituals and laments was begun in the nineteenth century in an attempt to establish continuity between modern and ancient Greece. Despite valuable insights, the approach biased understanding of laments and other death rituals. Later anthropological studies of Greek regions and villages built up a detailed picture of customs and beliefs about death, showing that, despite regional variations and modernization, they follow predictable patterns from village to village and are observed in immigrant communities in the cities. Revivals of lament and lament therapy indicate new trends in lament research but are far removed from the ritual and religious context that created them. Comparative studies of Balkan lament are rare and would benefit the field.
Receiving the Vision of Vatican II in Oceania
Authors: Rush Ormond
Published: January 2023

This chapter will explore the reception of Vatican II in the widely diverse geographical, cultural, and ecclesiastical region called Oceania. It will be demonstrated that an understanding of the reception of Vatican II throughout the local churches of Oceania can be conceived as taking place on three levels, based on Alois Grillmeier’s framework of conciliar reception in the early Church: official reception (by the hierarchy); theological reception (by theologians); and spiritual reception (by the baptized faithful). These three levels are important, since the hierarchy, theologians, and lay faithful have distinct but complementary roles in the Church. This chapter will also consider the council’s communio ecclesiology as another useful criterion for evaluating and assessing how deeply the conciliar vision has been received at these three levels.
The History of Conciliar Reception
Authors: Pié-Ninot Salvador
Published: January 2023

This chapter frames the reception of Vatican II in three different macro-periods: from the conclusion of the council until the Extraordinary Bishops’ Synod of 1985 (1965–85); the period of the ‘hermeneutic of reform’ (1986–2012); and what can be termed the ‘Francis effect’ (2013– ). The first stage, from conciliar euphoria to the harmonizing of interpretations of Vatican II at the Synod of Bishops of 1985, led the bishops to issue a final statement under four general principles which will be examined in the first section. The second stage can be characterized as a battle for meaning between the continuity and discontinuity of Vatican II. Benedict XVI’s ‘hermeneutic of reform’ serves as a helpful ‘Formula of Concord’ between the different positive proposals. The third stage, beginning with the pontificate of Francis, can be seen as the beginning of a new phase of reception of the council. His teaching, especially in Evangelii Gaudium (2013), provides an original interpretation of Vatican II. The ‘Francis effect’ moves the Church towards a living experience of the Second Vatican Council through the new experience of Synodality in the Church.
Transcription factor WOX11 regulates protein translation via ribosome protein acetylation in rice roots
Authors: Xu Qiutao , Wang Yijie , Yue Yaping , Chen Zhengting , Zhou Dao-Xiu , Zhao Yu
Published: January 2023

WUSCHEL-related Homeobox 11 regulates protein translation via lysine acetylation of ribosome protein mediated by ROS in rice root meristem.
U-box E3 ubiquitin ligase PUB8 attenuates abscisic acid responses during early seedling growth
Authors: Li Zhipeng , Li Shaoqin , Jin Dongjie , Yang Yongping , Pu Zhengyan , Han Xiao , Hu Yanru , Jiang Yanjuan
Published: January 2023

ABSCISIC ACID-INSENSITIVE3 (ABI3) and ABI5 are 2 crucial transcription factors in abscisic acid (ABA) signaling, and their homeostasis at the protein level plays a decisive role in seed germination and subsequent seedling growth. Here, we found that PLANT U-BOX 8 (PUB8), a U-box E3 ubiquitin ligase, physically interacts with ABI3 and ABI5 and negatively regulates ABA responses during early Arabidopsis (Arabidopsis thaliana) seedling growth. Loss-of-function pub8 mutants were hypersensitive to ABA-inhibited cotyledon greening, while lines overexpressing PUB8 with low levels of ABI5 protein abundance were insensitive to ABA. Genetic analyses showed that ABI3 and ABI5 were required for the ABA-sensitive phenotype of pub8, indicating that PUB8 functions upstream of ABI3 and ABI5 to regulate ABA responses. Biochemical analyses showed that PUB8 can associate with ABI3 and ABI5 for degradation through the ubiquitin-mediated 26S proteasome pathway. Correspondingly, loss-of-function of PUB8 led to enhanced ABI3 and ABI5 stability, while overexpression of PUB8 impaired accumulation of ABI3 and ABI5 in planta. Further phenotypic analysis indicated that PUB8 compromised the function of ABI5 during early seedling growth. Taken together, our results reveal the regulatory role of PUB8 in modulating the early seedling growth by controlling the homeostasis of ABI3 and ABI5.
Resting cytosol Ca2+ level maintained by Ca2+ pumps affects environmental responses in Arabidopsis
Authors: Li Zhan , Harper Jeffrey F , Weigand Chrystle , Hua Jian
Published: January 2023

Calcium ion transporting systems control cytosol Ca2+ levels ([Ca2+]cyt) and generate transient calcium (Ca2+) signatures that are key to environmental responses. Here, we report an impact of resting [Ca2+]cyt on plants from the functional study of calmodulin-regulated Ca2+ pumps or Ca2+-ATPases in Arabidopsis (Arabidopsis thaliana). The plasma membrane-localized pumps ACA8 (autoinhibited Ca2+-ATPase) and ACA10, as well as the vacuole-localized pumps ACA4 and ACA11, were critical in maintaining low resting [Ca2+]cyt and essential for plant survival under chilling and heat-stress conditions. Their loss-of-function mutants aca8 aca10 and aca4 aca11 had autoimmunity at normal temperatures, and this deregulated immune activation was enhanced by low temperature, leading to chilling lethality. Furthermore, these mutants showed an elevated resting [Ca2+]cyt, and a reduction of external Ca2+ lowered [Ca2+]cyt and repressed their autoimmunity and cold susceptibility. The aca8 aca10 and the aca4 aca11 mutants were also susceptible to heat, likely resulting from more closed stomata and higher leaf surface temperature than the wild type. These observations support a model in which the regulation of resting [Ca2+]cyt is critical to how plants regulate biotic and abiotic responses.
A 4-week morning light treatment with stable sleep timing for individuals with fibromyalgia: a randomized controlled trial
Authors: Burgess Helen J , Bahl Sonal , Wilensky Katelyn , Spence Emily , Jouppi Riley J , Rizvydeen Muneer , Goldstein Cathy , Kim Hyungjin Myra , Williams David A , Burns John W
Published: January 2023

Objectives

Fibromyalgia is characterized by chronic widespread pain, mood, and sleep disturbance. Pharmacological treatments have modest efficacy and are associated with negative side effects, and alternative approaches are needed. Morning bright light treatment may assist in the management of fibromyalgia as it can reduce depressive symptoms, improve sleep, and advance circadian timing.

Methods

Sixty people with fibromyalgia (58 women, mean age 41.8 ± 13.3 years) were enrolled in a study comparing 4 weeks of a 1-hour daily morning bright light treatment (active treatment) to a morning dim light treatment (comparison treatment). Both light treatments included behavioral procedures to stabilize sleep timing. The morning bright light treatment was expected to produce larger improvements in pain and function than the dim light treatment and larger improvements in potential mediators (mood, sleep, and circadian timing).

Results

Both the bright and dim light treatment groups achieved significant but similar levels of improvement in pain intensity, pain interference, physical function, depressive symptoms, and sleep disturbance. Overall, the sample on average displayed a clinically meaningful improvement in the Fibromyalgia Impact Questionnaire-Revised score (mean reduction of 11.2 points), comparable to that reported following physical exercise treatments. Minimal side effects were observed.

Conclusions

Findings indicate that the effects of a morning bright light treatment did not exceed those of a comparison dim light treatment; yet the changes on average in both conditions revealed clinically meaningful improvements. Future research is warranted to identify what elements of this trial may have contributed to the observed effects.
Shoulder Performance Activity Test (SPAT) for People With Shoulder Pain: Feasibility, Reliability, and Validity
Authors: Sousa Catarina O , Nascimento José Diego S , Pozzi Federico , Kardouni Joseph R , Michener Lori A
Published: January 2023

Objective

The purpose of this study was to assess feasibility, reliability, and validity of a new performance-based test, the Shoulder Performance Activity Test (SPAT).

Methods

People with shoulder pain (n = 93) and without shoulder pain (n = 43) were included. The SPAT consists of overhead reach, hand behind head, and hand behind back tasks, each performed with 20 repetitions and rated by time, pain, and effort. The SPAT scores were summed for time, pain, and effort, and a total score across the 3 tasks. Feasibility was assessed by the percentage of SPAT task completion, test–retest reliability by intraclass correlation coefficient (ICC), standard error measurement, minimal detectable change, and known-groups construct validity by comparing between groups (shoulder pain and no pain) and between shoulders in those with pain.

Results

All participants performed the 3 SPAT tasks. The ICC was 0.74–0.91, and the minimal detectable change was 3.1–4.7 for task scores and 10.0 points for the total score. Individuals with pain presented higher tasks and total scores compared with those without pain. The moderate/severe pain group had higher scores than the low pain and no shoulder pain groups, and the low pain group had higher scores than the no pain group. Scores were higher in the involved shoulder compared with the uninvolved shoulder.

Conclusion

The SPAT is a feasible and reliable performance-based test for use in patients with shoulder pain and can differentiate between individuals with and without pain, among different levels of pain, and between involved and uninvolved shoulders.

Impact

The SPAT provides a standardized method for clinicians to assess shoulder functional performance tasks, which can enable a comprehensive assessment of shoulder disability and clinical decision making. The error metrics can be used to determine meaningful changes in performance.
Learning Health Systems Research Competencies: A Survey of the Rehabilitation Research Community
Authors: McDonough Christine M , Poploski Kathleen M , Anderson Catherine A , Annaswamy Thiru M , Clark Melissa A , Douglas Natalie F , Flores Ann Marie , Freburger Janet K , Hafner Brian J , Hoffman Jeanne M , Kinney Adam R , Ressel Kristin , Sánchez Jennifer , Whitten Margarite J , Resnik Linda
Published: January 2023

Objective

The Learning Health Systems Rehabilitation Research Network (LeaRRn), an NIH-funded rehabilitation research resource center, aims to advance the research capacity of learning health systems (LHSs) within the rehabilitation community. A needs assessment survey was administered to inform development of educational resources.

Methods

The online survey included 55 items addressing interest in and knowledge of 33 LHS research core competencies in 7 domains and additional items on respondent characteristics. Recruitment targeting rehabilitation researchers and health system collaborators was conducted by LeaRRn, LeaRRn health system partners, rehabilitation professional organizations, and research university program directors using email, listservs, and social media announcements.

Results

Of the 650 people who initiated the survey, 410 respondents constituted the study sample. Respondents indicated interest in LHS research and responded to at least 1 competency item and/or demographic question. Two-thirds of the study sample had doctoral research degrees, and one-third reported research as their profession. The most common clinical disciplines were physical therapy (38%), communication sciences and disorders (22%), and occupational therapy (10%). Across all 55 competency items, 95% of respondents expressed “a lot” or “some” interest in learning more, but only 19% reported “a lot” of knowledge. Respondents reported “a lot” of interest in a range of topics, including selecting outcome measures that are meaningful to patients (78%) and implementing research evidence in health systems (75%). “None” or “some” knowledge was reported most often in Systems Science areas such as understanding the interrelationships between financing, organization, delivery, and rehabilitation outcomes (93%) and assessing the extent to which research activities will improve the equity of health systems (93%).

Conclusion

Results from this large survey of the rehabilitation research community indicate strong interest in LHS research competencies and opportunities to advance skills and training.

Impact

Competencies where respondents indicated high interest and limited knowledge can inform development of LHS educational content that is most needed.
The incidence of Kawasaki disease using hospital admissions data for England 2006–2021
Authors: Odingo Myron , Rutter Megan , Bowley Jonathan , Peach Emily J , Lanyon Peter C , Grainge Matthew J , Stillwell Peter , McPhail Sean , Bythell Mary , Aston Jeanette , Stevens Sarah , McCormack Rachael , Brogan Paul , Pearce Fiona A
Published: January 2023

Objective

To describe the incidence of Kawasaki Disease (kDa) between 2006 and 2021 in England.

Methods

We identified all cases in hospital episode statistics with an ICD-10 diagnostic code M303 (for kDa) between 1 April 2006 and 31 March 2021. We validated 83 diagnoses using hospital medical records and found >97% accuracy. We calculated incidence rate ratios (IRRs) using Poisson regression and assessed the influence of age, sex, ethnicity and index of multiple deprivation (IMD). We used Office for National Statistics population estimates for England as the denominator.

Results

We identified a total of 5908 cases of kDa in all children under the age of 16 (mean age 3.8, s.d.=3.2, 95% CI: 3.7, 3.9). Incidence in children aged <5 years was 8.9 (95% CI: 8.6, 9.2)/100 000 person-years; in children aged 5–9, 2.4 (95% CI: 2.3, 2.6)/100 000 person-years; and in children aged 10–15, 0.6 (95% CI: 0.6, 0.7). Male : female ratio was 1.5 : 1. Incidence was higher among non-White than White ethnicities [adjusted IRR 2.1 (2.0–2.2) for Asian, 3.0 (2.8–3.3) for Black and 4.5 (4.2–4.8) for other ethnicities]. The incidence increased with socioeconomic deprivation; the adjusted IRR of the least deprived IMD quintile compared with the most deprived quintile was 0.81 (0.77–0.84).

Conclusions

Incidence rates of kDa derived from hospital admission data in England were higher than in studies relying on clinician reporting. We confirm previous findings on the influence of sex and ethnicity on kDa incidence and observe that there was a higher incidence of kDa within more deprived socioeconomic groups.
Ableism in Health Care
Authors: Graff Joyce Carolyn , Russell Jennifer H.
Published: January 2023

Improving our knowledge of disability can reduce stereotypes and stigma.
Carotid body tumors
Authors: Ratliff Catherine R. , Strider David V.
Published: January 2023

Background:

Carotid body tumors (CBTs) are uncommon neuroendocrine tumors located near the carotid bifurcation within the carotid body. CBTs are slow-growing; affected individuals may remain asymptomatic for years and are often diagnosed incidentally following imaging studies. When present, symptoms are nonspecific. Because incidence is low, retrospective review of CBT case series is an ideal study design for investigating common symptomology, identifying successful diagnostic tools, and evaluating treatment outcomes.

Methods:

This article describes a case series of 11 patients treated for CBTs at an academic medical center in the Southeastern US. A retrospective chart review of 11 patients who had been discharged from the hospital following treatment for CBTs between 2017 and 2021 was conducted. Descriptive statistics were used to delineate the case series.

Results:

There were four males (36%) and seven females (64%) included in the retrospective case series. The age range was 34 to 79 with a mean of 56.73 (standard deviation 16.038). Three patients were found to have a neck mass on physical exam. Additional symptoms included vocal cord paralysis, facial paralysis, ischemic stroke, Bell palsy, dysphonia, and dizziness. Two patients had familial CBTs. Ten patients underwent surgical excision.

Conclusion:

This case series showed that patients with CBTs should be assessed with a combination of history and physical exams along with imaging studies to confirm the diagnosis. Because CBTs may become malignant and metastasize, it is important for NPs to be knowledgeable about presenting symptoms and appropriate diagnostic studies to be able to refer patients to vascular surgeons early to prevent complications.
Inpatient Low-dose Transitions From Full Agonist Opioids Including Methadone Onto Long-acting Depot Buprenorphine: Case Series From a Multicenter Clinical Trial
Authors: Seval Nikhil , Nunez Johnathan , Roth Prerana , Schade Meredith , Strong Michelle , Frank Cynthia A. , Litwin Alain H. , Levin Frances R. , Brady Kathleen T. , Nunes Edward V. , Springer Sandra A.
Published: January 2023

Objectives

Persons with opioid use disorder (OUD) suffer disproportionately from morbidity and mortality related to serious addiction-related infections requiring hospitalization. Long-acting buprenorphine (LAB) is an underused medication for OUD that may facilitate linkage to care and treatment retention when administered before hospital discharge. Transition onto buprenorphine in the inpatient setting is often complicated by pain, active infection management, potential surgical interventions, and risk of opioid withdrawal in transition from full agonists to a partial agonist.

Methods

The COMMIT Trial is a randomized controlled trial evaluating LAB administered by infectious disease physicians and hospitalists compared with treatment as usual for persons with OUD hospitalized with infections. We report a case series of participants on full agonist opioids including methadone who were transitioned to sublingual buprenorphine using low-dose (microdosing) strategies followed by LAB injection.

Results

Seven participants with current opioid use disorder and life-threatening infections, all with significant concurrent pain and many requiring surgical intervention, underwent low-dose transitions starting at buccal buprenorphine doses ranging from 225 μg to 300 μg 3 times a day on the first day. All were well tolerated with average time to LAB injection of 7.5 days (range, 5–10 days).

Conclusions

Inpatient low-dose buprenorphine transition from full agonist opioids including methadone onto LAB is feasible even in those with complex hospitalizations for concurrent infections and/or surgery. This strategy facilitates dosing of LAB before hospital discharge when risk of opioid relapse and overdose are significant.
Aspects of Patient Experience Associated With Improved Scoliosis Research Society-22 Revised (SRS-22R) and European Quality of Life Five-Dimension Five-Level (EQ-5D-5L) Scores in Patients With Adolescent Idiopathic Scoliosis Managed With Observation or Bracing
Authors: Chua Yi Ling , Toh Alyssa Jia Ning , Tan Xavier Yeow Boon , Pan Daryl Chen Yi , Lee Nicole Kim Luan , Lim Kevin Boon Leong
Published: January 2023

Study Design.

Prospective cohort study.

Objective.

The purpose of this study was to evaluate the relationship between patient-reported experience measures (PREMs) and patient-reported outcome measures (PROMs) in adolescent idiopathic scoliosis (AIS) managed nonsurgically with bracing or observation.

Summary of Background Data.

PREMs and PROMs are increasingly used to assess the effectiveness of patient-centered health care provision. To date, no study has attempted to study the relationship between PREMs and PROMs in AIS.

Methods.

All patients who visited our one-stop, tertiary center for AIS between 2020 and 2021, were asked to complete pairs of PREMs and PROMs questionnaires. PREMs were evaluated using our institution’s outpatient experience survey adapted from Hospital Consumer Assessment of Healthcare Providers and Systems survey. PROMs were determined via the Scoliosis Research Society-22 revised (SRS-22r) and European Quality of Life Five-Dimension Five-Level (EQ-5D-5L) forms.

Results.

In total, we included 730 patients who completed pairs of PREMs and PROMs questionnaires. 451 patients were treated by observation and 279 were braced. In the observation group, there was no association between patient experience and SRS-22r or EQ-5D-5L scores. In the brace group, improved SRS-22r were associated with higher PREM scores. In particular, having confidence and trust in treating physicians (r=0.34), reporting that their worries and concerns were addressed during treatment (r=0.34) and being taught self-care (r=0.33, P<0.0001 for all) were most highly correlated with better SRS-22r scores.

Conclusions.

In patients with AIS treated with bracing, improved patient experience was positively correlated with better patient reported outcomes, especially if patients' concerns were addressed during treatment and they received supportive care and education on self-care. In contrast, patient experience did not correlate with PROMs in children and adolescents with AIS who were under observation.
Patient, Operator, and Procedural Characteristics of Guidewire Retention as a Complication of Vascular Catheter Insertion
Authors: Kassis Nicholas , Alkukhun Laith , Kravitz Kathleen , Miclea Carolyn , Gill Amanjit , Udeh Chiedozie I. , Mathur Piyush , Hamilton Aaron C. , Lyden Sean P. , Kapadia Samir R. , Khot Umesh N.
Published: January 2023

OBJECTIVES:

Guidewire retention after intravascular catheter insertion is considered a “never event.” Prior reports attribute this complication to various characteristics including uncooperative patients, operator inexperience, off-hour or emergent insertion, and underutilization of ultrasound guidance. In this descriptive analysis of consecutive events, we assessed the frequency of patient, operator, and procedural factors in guidewire retention.

DESIGN:

Pre-specified observational analysis as part of a quality improvement study of consecutive guidewire retention events across a multihospital health system from August 2007 to October 2015.

SETTING:

Ten hospitals within the Cleveland Clinic Health System in Ohio, United States.

PATIENTS:

Consecutive all-comers who experienced guidewire retention after vascular catheter insertion.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Data were manually obtained from the electronic medical records and reviewed for potential contributing factors for guidewire retention, stratified into patient, operator, and procedural characteristics. A total of 24 events were identified. Overall, the median age was 74 years, 58% were males, and the median body mass index was 26.5 kg/m2. A total of 12 (50%) individuals were sedated during the procedure. Most incidents (10 [42%]) occurred in internal jugular venous access sites. The majority of cases (13 [54%]) were performed or supervised by an attending. Among all cases, three (12%) were performed by first-year trainees, seven (29%) by residents, three (12%) by fellows, and four (17%) by certified nurse practitioners. Overall, 16 (67%) events occurred during regular working hours (8 amto 5 pm). In total, 22 (92%) guidewires were inserted nonemergently, with two (8%) during a cardiac arrest. Ultrasound guidance was used in all but one case.

CONCLUSIONS:

Guidewire retention can occur even in the presence of optimal patient, operator, and procedural circumstances, highlighting the need for constant awareness of this risk. Efforts to eliminate this important complication will require attention to issues surrounding the technical performance of the procedure.
Relationship Between Skeletal Muscle Quality and Hospital-Acquired Disability in Patients With Sepsis Admitted to the ICU: A Pilot Study
Authors: Takahashi Yuta , Morisawa Tomoyuki , Okamoto Hiroshi , Matsumoto Noriko , Saitoh Masakazu , Takahashi Tetsuya , Fujiwara Toshiyuki
Published: January 2023

IMPORTANCE:

Early risk assessment of functional decline in patients with sepsis is clinically challenging. Recently, there is increasing interest in the nonvolitional evaluation of skeletal muscle quality.

OBJECTIVES:

The aim of this study was to assess the relationship between skeletal muscle quality and functional decline after intensive care.

DESIGN, SETTING, AND PARTICIPANTS:

This pilot study was a single-center prospective observational study conducted from March 2021 to February 2022. We included consecutive patients with sepsis who were admitted to our ICU.

MAIN OUTCOMES AND MEASURES:

The primary outcome was hospital-acquired disability (HAD), which is defined as a decrease in the Barthel index score of at least 5 points from pre-hospital to hospital discharge. Muscle quality was assessed by: 1) muscle echogenicity with ultrasound and 2) phase angle (PhA) with bioelectrical impedance analysis, both of which were measured on ICU days less than 3, 3–5, 5–7, 7–10, and 10–14. We compared longitudinal changes in muscle echogenicity and PhA between the HAD and non-HAD groups using two-way repeated measures analysis of variance with mixed models.

RESULTS:

Among the 22 patients, 7 (31.8%) had HAD. Muscle echogenicity was higher in the HAD group than in the non-HAD group (p < 0.001); however, no interaction effects were found between the two groups (p = 0.189). PhA showed a main effect on each evaluation day in patients (p = 0.040) and a significant interaction effect between the groups, including an early decreased pattern in the HAD group (p = 0.036).

CONCLUSIONS AND RELEVANCE:

Higher muscle echogenicity and a decreased PhA pattern are related to HAD. Noninvasive assessment of muscle quality using ultrasound and bioelectrical impedance analysis may be useful in predicting the functional prognosis of patients with sepsis.
Longitudinal Validation of Right Ventricular Pressure Monitoring for the Assessment of Right Ventricular Systolic Dysfunction in a Large Animal Ischemic Model
Authors: Couture Etienne J. , Moses Kevin , Monge García Manuel Ignacio , Potes Cristhian , Haddad Francois , Grønlykke Lars , Garcia Fernando , Paster Eden , Pibarot Philippe , Denault André Y.
Published: January 2023

CONTEXT:

Right ventricular (RV) dysfunction is a major cause of morbidity and mortality in intensive care and cardiac surgery. Early detection of RV dysfunction may be facilitated by continuous monitoring of RV waveform obtained from a pulmonary artery catheter. The objective is to evaluate the extent to which RV pressure monitoring can detect changes in RV systolic performance assess by RV end-systolic elastance (Ees) following the development of an acute RV ischemic in a porcine model.

HYPOTHESIS:

RV pressure monitoring can detect changes in RV systolic performance assess by RV Ees following the development of an acute RV ischemic model.

METHODS AND MODELS:

Acute ischemic RV dysfunction was induced by progressive embolization of microsphere in the right coronary artery to mimic RV dysfunction clinically experienced during cardiopulmonary bypass separation caused by air microemboli. RV hemodynamic performance was assessed using RV pressure waveform-derived parameters and RV Ees obtained using a conductance catheter during inferior vena cava occlusions.

RESULTS:

Acute ischemia resulted in a significant reduction in RV Ees from 0.26 mm Hg/mL (interquartile range, 0.16–0.32 mm Hg/mL) to 0.14 mm Hg/mL (0.11–0.19 mm Hg/mL; p < 0.010), cardiac output from 6.3 L/min (5.7–7 L/min) to 4.5 (3.9–5.2 L/min; p = 0.007), mean systemic arterial pressure from 72 mm Hg (66–74 mm Hg) to 51 mm Hg (46–56 mm Hg; p < 0.001), and mixed venous oxygen saturation from 65% (57–72%) to 41% (35–45%; p < 0.001). Linear mixed-effect model analysis was used to assess the relationship between Ees and RV pressure-derived parameters. The reduction in RV Ees best correlated with a reduction in RV maximum first derivative of pressure during isovolumetric contraction (dP/dtmax) and single-beat RV Ees. Adjusting RV dP/dtmax for heart rate resulted in an improved surrogate of RV Ees.

INTERPRETATION AND CONCLUSIONS:

Stepwise decreases in RV Ees during acute ischemic RV dysfunction were accurately tracked by RV dP/dtmax derived from the RV pressure waveform.
Partial Identification of Personalized Treatment Response with Trial-reported Analyses of Binary Subgroups
Authors: Li Sheyu , Litvin Valentyn , Manski Charles F.
Published: January 2023

Medical journals have adhered to a reporting practice that seriously limits the usefulness of published trial findings. Medical decision makers commonly observe many patient covariates and seek to use this information to personalize treatment choices. Yet standard summaries of trial findings only partition subjects into broad subgroups, typically binary categories. Given this reporting practice, we study the problem of inference on long mean treatment outcomes E[y(t)|x], where t is a treatment, y(t) is a treatment outcome, and the covariate vector x has length K, each component being a binary variable. The available data are estimates of {E[y(t)|xk = 0], E[y(t)|xk = 1], P(xk)}, k = 1,..., K reported in journal articles. We show that reported trial findings partially identify {E[y(t)|x], P(x)}. Illustrative computations demonstrate that the summaries of trial findings in journal articles may imply only wide bounds on long mean outcomes. One can realistically tighten inferences if one can combine reported trial findings with credible assumptions having identifying power, such as bounded-variation assumptions.
Prevalence of Obstructive Sleep Apnea With Floppy Eyelid Syndrome: A Systematic Review and Meta-analysis
Authors: Bulloch Gabriella , Seth Ishith , Alphonse Stephen , Sathe Aditya , Jennings Matthew , Sultan Dana , Rahmeh Rami , McNab Alan A.
Published: January 2023

Purpose:

This study investigated the prevalence of obstructive sleep apnea (OSA) in floppy eyelid syndrome (FES) patients and evaluated the severity of OSA with FES prevalence.

Methods:

Cochrane CENTRAL, Medline, Science Direct, Google Scholar, and PubMed databases were searched for studies on FES patients and its association with OSA syndrome, of any design, published from January 1, 1997, to January 1, 2022. A random-effects model that weighted the studies was used when there was heterogeneity between studies (p < 0.10) and if I2 values were more than 50%. All p values were 2-tailed and considered statistically significant if <0.05.

Results:

A total of 12 studies comprising 511 patients were included in this meta-analysis. Of these, 368 were male (77.6%) and the average age was 55.10 years. The overall prevalence of OSA in FES patients was 57.1% (95% CI: 46.5–74.8%), M:F ratio was 48:1 (98% male), and 69.1% of patients received their OSA diagnosis at the time of the study. Of those with FES, tear film abnormalities were the most common ocular comorbidity (78.9%) followed by keratoconus (20.6%), glaucoma (9.8%), and lower eyelid ectropion (4.6%). Obesity was the most common systemic morbidity (43.7%) followed by hypertension (34.0%) and diabetes mellitus (17.9%).

Conclusion:

This meta-analysis demonstrates OSA is a common comorbidity in the FES population. Ophthalmologists are often the first to evaluate patients with FES, and considering this coincidence, routine screens for sleep apnea symptoms in at-risk FES patients should be undertaken. Large case-control studies are required to better elucidate the exact prevalence of OSA and other morbidities in patients with FES, and to better understand the etiology of FES.
Atypical Spindle Cell and Pleomorphic Lipomatous Tumor of the Ocular Adnexa: Two Cases of a Rare Entity
Authors: Ulloa-Padilla Jan P. , Rubio Raul Hernandez , Zhou Siwei , Carrasco Jacqueline , Watson Alison , Jiang Wei , Cooper Kumarasen , Morgenstern Kenneth , Milman Tatyana
Published: January 2023

Abstract: Atypical spindle cell and pleomorphic lipomatous tumor (ASCPLT) is a rare lipomatous neoplasm that was recently introduced into the World Health Organization Classification of Soft Tissue and Bone tumors as a distinct entity. ASCPLT has potential for local recurrence but does not metastasize. This biologic behavior separates ASCPLT from its morphologic mimics. Ocular adnexal ASCPLT has not been previously reported. Described herein are two patients with ASCPLT. The subcutaneous orbital rim lesion featured markedly pleomorphic spindle and multinucleated cells. The eyelid lesion was dominated by atypical spindle cells in a background of mature adipocytes. Both neoplasms demonstrated infiltrative margins, rare mitotic figures, immunoreactivity for CD34 and loss of Rb1, and the absence of MDM2 amplification by fluorescence in situ hybridization. Recognition of ASCPLT in the differential of ocular adnexal neoplasms may lead to a re-evaluation of morphologically similar tumors, which may have varied biologic behavior and warrant a different management approach.
Mirogabalin improves cancer-associated pain but increases the risk of malignancy in mice with pancreatic cancer
Authors: Itaya Tomoaki , Sano Makoto , Kajiwara Ichie , Oshima Yukino , Kuramochi Tomoya , Kim Jinsuk , Ichimaru Yoshimi , Kitajima Osamu , Masamune Atsushi , Ijichi Hideaki , Ishii Yukimoto , Suzuki Takahiro
Published: January 2023

Mirogabalin, a selective voltage-gated calcium channel α2δ ligand, improves peripheral neuropathic pain; however, its effects on patients with cancers including pancreatic ductal adenocarcinoma (PDAC) remain unknown. We analyzed the effects of mirogabalin on a KPPC (LSL-Kras

G12D/+

; Trp53

flox/flox

; Pdx-1

cre/+
) mouse model of PDAC. Six-week-old KPPC mice received oral mirogabalin (10 mg/kg/day) (n = 10) or vehicle water (n = 14) until the humane end point. Cancer-associated pain was evaluated using the scores of hunching and mouse grimace scale (MGS). Tumor status and plasma cytokine levels were determined using histopathological analysis and cytokine array, respectively. The effects of mirogabalin on the proliferative ability of PDAC cell lines were determined. The scores of the hunching and MGS improved after mirogabalin administration with a decrease in the plasma levels of inflammatory cytokines, such as tumor necrosis factor-α, interleukin-6, and interferon-γ. Although no significant difference in the survival rate was observed, mirogabalin significantly increased pancreatic tumor size and proliferative index of Ki-67 and cyclins. Local arginase-1+ M2-like tumor-associated macrophages and CD31+ tumor blood vessels increased after mirogabalin administration. By contrast, the number of α-smooth muscle actin+ cancer-associated fibroblasts, desmoplastic stroma, and CD8+ T cells decreased. Local myeloperoxidase+ tumor-associated neutrophils and CD45R+ B cells were unaltered. Mirogabalin enhanced the proliferative ability of PDAC cell lines with the upregulation of cyclins and cyclin-dependent kinases; however, it inhibited the potential of pancreatic stellate cells in vitro. Therefore, our results suggest that mirogabalin improves cancer-associated pain but enhances the proliferative potential of PDAC in vitro and in vivo.