bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterochromatin protein 1 alpha (HP1α) undergoes a monomer to dimer transition that opens and compacts live cell genome architecture
Authors: Lou Jieqiong , Deng Qiji , Zhang Xiaomeng , Bell Charles C , Das Andrew B , Bediaga Naiara G , Zlatic Courtney O , Johanson Timothy M , Allan Rhys S , Griffin Michael D W , Paradkar PrasadN , Harvey Kieran F , Dawson Mark A , Hinde Elizabeth
Published: August 2024

Our understanding of heterochromatin nanostructure and its capacity to mediate gene silencing in a living cell has been prevented by the diffraction limit of optical microscopy. Thus, here to overcome this technical hurdle, and directly measure the nucleosome arrangement that underpins this dense chromatin state, we coupled fluorescence lifetime imaging microscopy (FLIM) of Förster resonance energy transfer (FRET) between histones core to the nucleosome, with molecular editing of heterochromatin protein 1 alpha (HP1α). Intriguingly, this super-resolved readout of nanoscale chromatin structure, alongside fluorescence fluctuation spectroscopy (FFS) and FLIM-FRET analysis of HP1α protein-protein interaction, revealed nucleosome arrangement to be differentially regulated by HP1α oligomeric state. Specifically, we found HP1α monomers to impart a previously undescribed global nucleosome spacing throughout genome architecture that is mediated by trimethylation on lysine 9 of histone H3 (H3K9me3) and locally reduced upon HP1α dimerisation. Collectively, these results demonstrate HP1α to impart a dual action on chromatin that increases the dynamic range of nucleosome proximity. We anticipate that this finding will have important implications for our understanding of how live cell heterochromatin structure regulates genome function.
Kidney thrombotic microangiopathy with concurrent monoclonal gammopathy
Authors: Tan Meng , Jia Changhao , Liu Xiaotian , Wu Daoxu , Yu Xiaojuan , Zhao Minghui , Tan Ying
Published: August 2024

Background

The concurrence of monoclonal gammopathy and thrombotic microangiopathy (TMA) has been suggested in a few studies. However, the complement activation was not fully studied in previous cases. In this study, we aimed to determine the complement activation in these group of patients and the association with clinical, laboratory and pathological features.

Methods

Between 2007 and 2020, 20 patients with biopsy-proven renal TMA and monoclonal gammopathy in Peking University First Hospital were included in the study. Complement activation was tested by enzyme-linked immunosorbent assay. Associations with clinical features, pathological data and laboratory findings were further investigated.

Results

Among renal TMA patients beyond 50 years of age, the prevalence of monoclonal gammopathy was 16.51% (18/109) which is almost 4-fold greater than the expected rate in population (4.2%). Eleven patients had acute kidney injury, and two patients required dialysis. Hematological diagnosis was consistent with monoclonal gammopathy of undetermined significance (MGUS) (n = 10), unconfirmed MGUS (n = 3), POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) syndromes (n = 4), Castleman's disease (n = 2) and chronic lymphocytic leukemia (n = 1). A majority of patients (84.2%) showed the activation of complement classical pathway. Fifteen percent (3/20) of patients received conservative therapy, 5% (1/20) received steroid only, 30% (6/20) with immunosuppression and 50% (10/20) received clone-targeted chemotherapy. During a median 56 months of follow-up, end-stage renal disease developed in two patients, and five patients died mainly because of hematological progression.

Conclusion

This study found the dysregulation of complement activation, especially the classical pathway, involved in the pathogenesis of biopsy-proven renal TMA and monoclonal gammopathy.
Genomic landscape of malignant phyllodes tumors reveals multiple targetable opportunities
Authors: Rosenberger Laura H , Riedel Richard F , Diego Emilia J , Nash Amanda L , Grilley-Olson Juneko E , Danziger Natalie A , Sokol Ethan S , Ross Jeffrey S , Sammons Sarah L
Published: August 2024

Background

Malignant phyllodes tumors (MPT) are rare fibroepithelial breast cancers with no known effective systemic therapy; metastatic progression portends a dismal prognosis. We sought to describe the genomic landscape of MPTs through genomic profiling and immunotherapeutic biomarker analysis.

Materials and methods

Cases of sequenced MPT were identified from a Clinical Laboratory Improvement Amendments-certified, College of American Pathologists-accredited laboratory (Foundation Medicine). All cases underwent genomic profiling using adaptor ligation-based, next-generation sequencing assay of 324 genes. Tumor agnostic immunotherapy biomarkers, microsatellite instability, tumor mutational burden (TMB), and programmed death-ligand 1 (PD-L1) expression were evaluated. Fisher’s Exact Tests and analysis of variance were used to test for differences between groups and for continuous variables as appropriate.

Results

Of 135 MPT cases identified; 94 (69.6%) were localized/locally recurrent and 41 (30.4%) were metastatic. Median age was 54 years (range 14-86). The median TMB was 2.5 mut/Mb and 3 were TMB-high (≥10 mut/Mb). 21.4% were PD-L1+ via Dako 22C3 assay (CPS ≥1). Most commonly altered genes included TERT-promoter (69.7%), CDKN2A (45.9%), TP53 (37.8%), NF1 (35.6%), CDKN2B (33.3%), MED12 (28.9%), MTAP (27.7%), KMT2D (22.2%), PIK3CA (20.0%), PTEN (18.5%), and RB1 (18.5%). Several tumors harboring genomic alterations with US Food and Drug Administration-approved indications in other tumor types were found including NF1, PIK3CA, EGFR Exon 19/20 insertions, and BRAF V600E mutations.

Conclusions

In the largest genomic evaluation of MPT to date, multiple clinically actionable mutations were found. Routine sequencing of metastatic MPT may provide additional information to guide treatment decisions and clinical trial enrollment.
Regulating programmed cell death in plant cells: Intracellular acidification plays a pivotal role together with calcium signaling
Authors: Bosch Maurice , Franklin-Tong Vernonica
Published: August 2024

Programmed cell death (PCD) occurs in different tissues in response to a number of different signals in plant cells. Drawing from work in several different contexts, including root-cap cell differentiation, plant response to biotic and abiotic stress, and some self-incompatibility (SI) systems, the data suggest that, despite differences, there are underlying commonalities in the early decision-making stages of PCD. Here, we focus on how 2 cellular events, increased [Ca2+]cyt levels and cytosolic acidification, appear to act as early signals involved in regulating both developmental and stimulus-induced PCD in plant cells.
Allele-specific expression of AP2-like ABA repressor 1 regulates iron uptake by modulating rhizosphere pH in apple
Authors: Ma Huaying , Fu Mengmeng , Xu Zhen , Chu Zicheng , Tian Ji , Wang Yi , Zhang Xinzhong , Han Zhenhai , Wu Ting
Published: August 2024

Genetic variation within a species can result in allelic expression for natural selection or breeding efforts. Here, we identified an iron (Fe) deficiency-inducible gene, AP2-like ABA repressor 1 (MdABR1), in apple (Malus domestica). MdABR1 exhibited differential expression at the allelic level (MdABR131A and MdABR131G) in response to Fe deficiency. The W-box insertion in the promoter of MdABR131A is essential for its induced expression and its positive role under Fe deficiency stress. MdABR1 binds to the promoter of basic helix–loop–helix 105 (MdbHLH105), participating in the Fe deficiency response, and activates its transcription. MdABR131A exerts a more pronounced transcriptional activation effect on MdbHLH105. Suppression of MdABR1 expression leads to reduced rhizosphere acidification in apple, and MdABR131A exhibits allelic expression under Fe deficiency stress, which is substantially upregulated and then activates the expression of MdbHLH105, promoting the accumulation of plasma membrane proton ATPase 8 (MdAHA8) transcripts in response to proton extrusion, thereby promoting rhizosphere acidification. Therefore, variation in the ABR1 alleles results in variable gene expression and enables apple plants to exhibit a wider tolerance capability and Fe deficiency response. These findings also shed light on the molecular mechanisms of allele-specific expression in woody plants.
Telomere biology disorders: from dyskeratosis congenita and beyond
Authors: Roka Kleoniki , Solomou Elena , Kattamis Antonis , Stiakaki Eftychia
Published: August 2024

Defective telomerase function or telomere maintenance causes genomic instability. Alterations in telomere length and/or attrition are the primary features of rare diseases known as telomere biology disorders or telomeropathies. Recent advances in the molecular basis of these disorders and cutting-edge methods assessing telomere length have increased our understanding of this topic. Multiorgan manifestations and different phenotypes have been reported even in carriers within the same family. In this context, apart from dyskeratosis congenita, disorders formerly considered idiopathic (i.e. pulmonary fibrosis, liver cirrhosis) frequently correlate with underlying defective telomere maintenance mechanisms. Moreover, these patients are prone to developing specific cancer types and exhibit exceptional sensitivity and toxicity in standard chemotherapy regimens. The current review describes the diverse spectrum of clinical manifestations of telomere biology disorders in pediatric and adult patients, their correlation with pathogenic variants, and considerations during their management to increase awareness and improve a multidisciplinary approach.
Relationships Between Socioecological Factors and Self-Efficacy to Participate in Physical Activity for Adults With Chronic Musculoskeletal Pain: An Integrative Review
Authors: Vorensky Mark , Orstad Stephanie L , Squires Allison , Parraga Susan , Byrne Katherine , Merriwether Ericka N
Published: August 2024

Objective

Self-efficacy for leisure-time or health-promoting physical activity (SEPA) is a psychosocial determinant of physical activity. The socioecological model can provide a robust perspective of SEPA. The objective of this study was to synthesize the evidence on multilevel correlates of SEPA among individuals with chronic musculoskeletal pain. The second aim examined the extent to which socioecological disparities are associated with SEPA among individuals with chronic musculoskeletal pain.

Methods

An integrative review was conducted. Included studies needed to investigate the relationship between SEPA and socioecological factors at the interpersonal, institutional, community, and/or macrosystem level among adults with chronic musculoskeletal pain (≥3 months). Searches in PubMed, EMBASE, PsycINFO, and CINAHL were performed (December 30, 2020, and October 12, 2022), yielding 4047 records after duplicates were removed. Two independent reviewers completed screening, full-text reviews, and data extraction. After title and abstract screening and full-text reviews, 17 studies were included. The constant comparison method included: data reduction, data display, data comparison, and conclusion drawing/verification. Quality of evidence was assessed using the Joanna Briggs Institute appraisal tools.

Results

Five themes emerged with respect to relationships between SEPA and socioecological factors: social relations, social comparisons, patient–provider relationship, organizational resources, and accessibility to physical activity. Relationships between interpersonal factors and SEPA were most prominently studied. One study examined and addressed potential disparities in SEPA at the macrosystem level.

Conclusion

A spectrum of relationships from supporting to straining SEPA were found at the interpersonal level. Relationships between institutional, community, and macrosystem factors and SEPA were comparably sparse. Gaps in the literature were identified regarding how health disparities present across the socioecological model with respect to SEPA.

Impact

Clinicians can use this review to evaluate how SEPA can be supported or threatened by factors across the socioecological model. This may be a preliminary step towards examining and addressing health disparities in SEPA.
Challenging Identity Conflict: How Queer, Trans, and Nonbinary Muslim Organizations Incite Activism
Authors: Golriz Golshan
Published: August 2024

This article synthesizes new directions taken in the sociology of religion and social movement studies and examines Queer, Trans, and Nonbinary (QTN) Muslim activism in Toronto, Canada. The author argues that Queer Trans and Nonbinary Muslim Organizations (QTNMOs) do more than help reconcile their members’ conflicting identities. Instead, QTNMOs use intersectional frameworks to help QTN Muslims resist intracommunity marginalization in mainstream queer and religious organizations. Findings show that QTNMOs can be considered Social Movement Organizations in three ways: these groups defy culturally embedded institutional norms that are harmful to QTN Muslims, they aim to foster oppositional consciousness, and they incite collective action from their constituents. The article provides a case study of multi-institutional LGBTQ religious activism. The intersectional perspectives of QTN Muslims allow interested sociology of religion and social movements scholars to strengthen the insights gained from each of these fields.
Preoperative Symptom Duration and the Effect on Clinical Outcomes and PROMIS-PF in Patients Undergoing Lumbar Fusion Surgery
Authors: Johnson Andrea H. , Brennan Jane C. , Rana Parimal , Hall Sarah , Turcotte Justin J. , Patton Chad
Published: August 2024

Study Design.

Retrospective Review

Objective.

The purpose of this study is to examine the effect of preoperative symptom duration on postoperative clinical outcomes for patients undergoing lumbar fusion surgery.

Summary of Background Data.

Lumbar fusion surgery can be significantly beneficial for lumbar spondylolisthesis and spinal stenosis. Surgical treatment is typically preceded by some amount of non-operative intervention and there isn’t a consensus on the optimal timing between symptom onset and surgical intervention.

Methods.

A retrospective review of 144 patients undergoing a 1-3 level lumbar fusion from June 2020 to December 2023 was performed. Demographics, preoperative symptom onset, primary diagnosis, and surgical procedure were compared between patients with less than or greater than 2 years of symptoms. Postoperative outcomes and PROMIS-PF were compared between groups. Univariate and multivariate analyses were performed.

Results.

52 (36.1%) had symptoms for 2 years or longer while 92 (63.9%) had symptoms for less than 2 years. There was no difference in demographics, procedure type, primary diagnosis, or preoperative symptoms between those who had symptoms for greater than or less than 2 years. Those who had symptoms for 2+ years had a significantly lower change in PF (4.7±7.1 vs. 7.7±9.0; P=0.029) and lower rate of MCID achievement (44.2% vs. 65.2%; P=0.023). There was no difference in outcomes by symptom duration. On multivariate analysis those with symptoms of 2 years or more were 2.4 times less likely to achieve an MCID (OR: 0.42, 95% CI: 0.19 to 0.92; P=0.031).

Conclusion.

Patients undergoing lumbar fusion with greater than 2 years of symptoms prior to surgery have a smaller increase in PROMIS-PF and are less likely to achieve MCID on PROMIS-PF. Further study is needed in order to determine the optimal timing for lumbar fusion surgery following symptom onset.
Association between Paraspinal Muscle Parameters and single-segment Degenerative Lumbar Spondylolisthesis
Authors: Liu Shuang , Shi Qi , Da Wei-Wei , Xue Chun-Chun , Chen Lin , Li Yu-Nan , Xue Yong-Peng , Du Wen-Lan , Li Xiao-Feng
Published: August 2024

Study Design.

A retrospective, cross-sectional cohort study.

Objective.

This study aims to investigate the association between paraspinal muscle parameters and single-segment degenerative lumbar spondylolisthesis (DLS).

Summary of Background Data.

The relationship between lumbar paraspinal muscles morphology and single-segment DLS remains unclear.

Methods.

A retrospective review was conducted on 115 patients with L4/5 single-segment DLS and 105 subjects without DLS. Two independent investigators assessed the relative cross-sectional area and fat infiltration rate of the multifidus, erector spinae, and psoas major at L3/4, L4/5, and L5/S1 levels, comparing these measurements between the two groups. Additionally, binary logistic regression analysis was performed with DLS as the dependent variable to analyze the relative cross-sectional area and fat infiltration rate of different paraspinal muscles. Within the DLS group, the correlation between paraspinal muscle characteristics and the anteroposterior diameter of the spinal canal was examined.

Results.

The fat infiltration rate of multifidus, erector spinae, and psoas major were higher in the DLS group than in the control group, while the relative cross-sectional area of multifidus and psoas major were lower in the DLS group. Binary logistic regression analysis revealed a significant correlation between fat infiltration rate of multifidus and psoas major and DLS. The relative cross-sectional area of multifidus and erector spinae was significantly smaller below the affected segment in the DLS group compared to the control group. A significant positive correlation was observed between the relative cross-sectional area of multifidus and erector spinae and the anteroposterior diameter of the spinal canal.

Conclusion.

There is a close association between paraspinal muscle degeneration and single-segment DLS, with increased relative cross-sectional area of the multifidus and psoas major possibly being risk factors for single-segment DLS. The restoration or enhancement of paraspinal muscle function could potentially serve as a pivotal target for the prevention and treatment of single-segment DLS.

Level of Evidence.

III
Preventing perinatal HIV acquisition; current gaps and future perspectives
Authors: Cockbain Beatrice , Fidler Sarah , Lyall Hermione
Published: August 2024

Purpose of review

Although current treatment could eradicate vertical transmission, in 2022, 130 000 infants acquired HIV globally. HIV suppression with antiretroviral therapy (ART) transforms survival for people living with HIV (PLWH), and prevents transmission, including vertical. International guidelines recommend lifelong ART for PLWH, consequently perinatal HIV acquisition reflects implementation gaps in the HIV care cascade. We summarize these gaps, exploring potential novel approaches and therapeutic innovations towards eliminating vertical HIV transmission.

Recent findings

Multifactorial challenges continue to underpin gaps in the HIV care cascade, including accessibility, availability and sustainability of HIV testing, prevention and treatment, alongside stigma, gender-based violence and poverty. Long-acting ART may be important in preventing perinatal HIV acquisition, with early data demonstrating tolerability and efficacy of injectable ART throughout pregnancy, both as HIV treatment and prevention. Carefully selected long-acting broadly neutralizing antibodies (bNAbs) matching circulating, exposing viral envelope sequences have demonstrated safety, clinical trials are ongoing to demonstrate efficacy.

Emerging clinical studies should prioritize pregnant/lactating people and infants to ensure such therapies are well tolerated and efficacious. Alongside therapeutic innovation, programmatic strategies must address social and economic challenges, ensuring sustainable HIV treatment/prevention programmes and facilitating global elimination of blood-borne viruses.
Post Hoc Analysis Comparing the Safety and Efficacy of PrabotulinumtoxinA in Millennials and Nonmillennials With Moderate to Severe Glabellar Lines
Authors: Avelar Rui
Published: August 2024

BACKGROUND

Millennials accept and invest in aesthetic procedures more than older generations.

OBJECTIVE

To compare efficacy outcomes between millennial and nonmillennial patients after treatment of glabellar lines with prabotulinumtoxinA.

MATERIALS AND METHODS

This was a post hoc analysis of 3 Phase III studies of 20 U prabotulinumtoxinA for the treatment of moderate to severe glabellar lines. Investigator- and/or subject-assessed positive responder rates in the Glabellar Line Scale, Global Aesthetic Improvement Scale, and Subject Satisfaction Scale were compared between millennials (born 1982–2000) and nonmillennials (born ≤1981).

RESULTS

Aesthetic outcomes and subject satisfaction of prabotulinumtoxinA treatment were high in nonmillennials (n= 65) and even higher in millennials (n= 668) at all time points. At Days 7, 14, and 30 post-treatment, positive responder rates were >85% and >97% across all scales in nonmillennials and millennials, respectively, with statistical superiority observed in millennials at multiple time points in virtually all scales. The incidence of treatment-related adverse events was similar between groups.

CONCLUSION

PrabotulinumtoxinA was highly effective in treating moderate to severe glabellar lines. The greater efficacy seen in millennials may reflect physiological differences related to aging as well as botulinum toxin-mediated effects on mood. The results align well with their aesthetic expectations.
Clinical Benefits of DaxibotulinumtoxinA for Injection: Beyond Glabellar Line Effacement?
Authors: Mariwalla Kavita , Shamban Ava , Green Jeremy B. , Gross Todd M. , Brown Jessica , Gallagher Conor J.
Published: August 2024

BACKGROUND

Botulinum toxin type A (BoNTA) is standard of care for glabellar lines ameliorization. DaxibotulinumtoxinA for Injection (DAXI) is a new BoNTA with a unique formulation representing the latest advancement in BoNTA technology. There is an unmet need for patients to understand the full potential of BoNTA treatment and new technologies.

OBJECTIVE

To update clinical data supporting the use of DAXI for glabellar lines within the context of clinical experience.

MATERIALS AND METHODS

A narrative review of the literature and summary of clinical experience with DAXI.

RESULTS

The DAXI clinical trial program reflects clinical experience post-FDA approval, with DAXI demonstrating rapid onset, high patient response rates, and extended treatment duration versus conventional BoNTAs. Clinical observations suggest that DAXI has limited diffusion from the injection site, enabling more localized control of muscle activity and greater improvements in wrinkle severity. DAXI enables practitioners to exert greater finesse in their injections and in predicting changes to eyebrow shape and position and achieve improvement in skin quality.

CONCLUSION

Advances in BoNTA technology can provide patients with greater options for treatment outcomes. The potential for enhanced localized effects with DAXI may contribute to more precise and targeted effects on muscle activity and additional aesthetic benefits to patients.
Advances in Topical Botulinum Therapy
Authors: Edelson Jonathan T.
Published: August 2024

BACKGROUND

A successfully developed topical botulinum toxin product would overcome the disadvantages of injectable administration commonly seen with all available botulinum products, including the potential pain, bleeding, and bruising associated with injection.

OBJECTIVE

Identify the disadvantages of injectable administration of botulinum products and advantages of topical administration. Identify previous attempts to develop topical products and review the only topical product candidate (ET-01, abbreviated EMX) under clinical development.

MATERIALS AND METHODS

A literature review regarding injectable botulinum products and topical botulinum product candidates and an analysis of data regarding EMX development were performed.

RESULTS

Multiple disadvantages of injectable administration and advantages of topical administration of botulinum toxin were identified. If available, topical botulinum products are expected to expand the clinical use of botulinum toxin. Several previous attempts to develop topical products were identified. EMX has been studied for lateral canthal line treatment in multiple controlled phase 2 clinical trials including over 700 subjects. EMX has demonstrated statistically significant positive results.

CONCLUSION

The development of a topical botulinum toxin is appealing because it overcomes multiple disadvantages observed with injectable administration and would likely result in increased clinical use of botulinum toxin. The development of EMX shows promise and merits further study.
Using Neuromodulators to Improve Scar Formation, Keloids, Rosacea, and Antiaging
Authors: Rosales Santillan Monica , Ozog David , Wu Woffles
Published: August 2024

BACKGROUND

Botulinum toxin A (BoNT-A) treatment has many uses in dermatology. Its mechanism of action and long-term effects for scar formation, rosacea, and antiaging are still being investigated.

OBJECTIVE

To conduct a literature review on BoNT-A to further investigate its use in scar formation, rosacea, and antiaging.

METHODS

A literature review was conducted using PubMed on botulinum toxin treatment for scar formation, rosacea, and antiaging. Studies discussing the toxin mechanism of action and treatment algorithm were included. The authors also provided their personal experience in BoNT-A use for these 3 conditions.

RESULTS

The mechanism of action of Botulinum toxin A in improving scar formation, rosacea, and antiaging is now better understood. While it is effective in the short term, little is still known about how frequently treatment needs to be repeated and if there are any long-term effects.

CONCLUSION

While in vitro studies have supporting evidence on the mechanism of action of BoNT-A on scar formation, rosacea, and antiaging, further studies are needed to identify long-term treatment effects.
Lifting With Neuromodulators
Authors: Kaufman-Janette Joely , Trindade de Almeida Ada
Published: August 2024

BACKGROUND

The use of botulinum toxins for facial rejuvenation and improvement of dynamic wrinkles has become a mainstay in the aesthetic treatment armamentarium. However, using these same neuromodulators (NMs) for lifting the structures of the face, is a newer addition to antiaging protocols. The muscles of facial animation all interplay with each other. Lifting can be accomplished by treating those muscles that are responsible for depression, leaving the elevators unopposed and resulting in a rejuvenated, lifted outcome. Brow lifting, cheek lifting, and even contouring of the lower face and jawline are all possibilities using NMs.

OBJECTIVE

To review the literature and current practices in techniques for lifting the different anatomic facial zones.

METHODS

The authors present and discuss the published data and personal experiences of using NM for lifting and retraining of the facial musculature. This article will discuss the effects and approaches to lifting with botulinum toxin injections, including the potential success and side effects associated with these off-label injections.

RESULTS/CONCLUSIONS

The use of botulinum toxins has expanded beyond its traditional use as a reducer of dynamic wrinkles. A significant amount of published data now exists for the off-label use of botulinum toxins for lifting and shaping the face. These can be considered advanced techniques as each region has its own anatomic intricacies and side effects can occur. More placebo-controlled objective data would also help elucidate exact dosing strategies for each region.
Influence of pairing in examiner leniency and stringency (‘hawk-dove effect’) in part II of the European Diploma of Anaesthesiology and Intensive Care
Authors: Sciberras Stephen , Klimek Markus , Ateleanu Bazil , Scipioni Hugues , Di Loreto Rodolphe , Berger-Estilita Joana
Published: August 2024

BACKGROUND

The European Diploma of Anaesthesiology and Intensive Care (EDAIC) Part II examination is a supranational examination for anaesthesiologists.

OBJECTIVE(S)

We explore the impact of examiner pairing on leniency and stringency, commonly referred to as the ‘hawk-dove effect’. We investigate the potential variations in grading approaches, resulting from different examiner pairs and their implications for candidate performance.

DESIGN

Retrospective cohort, observational design.

SETTING

EDAIC Part II examination data from 2021 to 2023.

PARTICIPANTS

Three hundred and twenty-five examiners across 122 EDAIC Part II single-day examination sessions.

INTERVENTION(S)

We analysed the influence of examiner leniency and examiner pairing on candidate performance in the EDAIC Part II using many-facet Rasch modelling.

MAIN OUTCOME MEASURES

The study's main outcome measure was determining a leniency score among the examiner population. The study also aimed to assess how examiner pairing influenced candidate performance, as measured by their scores in the examination.

RESULTS

During the study period, the number of examiners who participated in 2021, 2022 and 2023 were 253, 242 and 247, respectively. The median [IQR] single-day sessions attended were 7.0 [3 to 10]. The examination data revealed a mean leniency score of 0 (95% confidence interval (CI) −0.046 to 0.046), with the standard deviation being one-third that of the candidates’ ability scores. There were 1424 different pairs of examiners, with most pairs (97%) having only a one-point difference in marking. The mean leniency score for the pair of examiners was −0.053 (95% CI −0.069 to −0.037).

CONCLUSION

The variations in grading approaches associated with different pairings emphasise the potential for the ‘hawk-dove effect’ to influence candidate performance and outcomes. Understanding these variations can guide curriculum development, examiner training and coupling, ensuring a balanced and equitable assessment process.

TRIAL REGISTRATION

None
Bedside-focused transthoracic echocardiography in acute atraumatic thoracic aortic syndrome: a systematic review and meta-analysis of diagnostic accuracy
Authors: Mani Nick , Cherian Nishant , Burkert Julia , Jarman Robert David
Published: August 2024

The objective of this review was to assess the diagnostic accuracy of bedside-focused transthoracic echocardiography (TTE) in acute atraumatic thoracic aortic syndrome in adults. We performed a systematic review and meta-analysis of publications that described the use of bedside-focused TTE on adults presenting to emergency care settings with suspected atraumatic thoracic aortic syndrome. Studies were identified using keyword and MeSH on relevant databases as well as grey literature, followed by abstract screening and study selection by two independent reviewers. Sixteen studies over six decades were included in the meta-analysis (n = 4569 patients). The prevalence of type A thoracic aortic dissection was 11% (range 1.4–45.7%) and type B dissection was 7% (range 1.8–30.55%). Pooled sensitivity and specificity for type A dissection (through direct TTE visualisation of an intimal flap) were 89% [95% confidence interval (CI), 82–94%] and 92% (95% CI, 88–95%), respectively. For type B dissection, pooled sensitivity was 65% (95% CI, 45–80%) and specificity was 100% (95% CI, 0.69–100%). Regarding indirect TTE signs, pooled sensitivities and specificities were 64% (5.2–98.2%) and 94% (92–96.1%), respectively for aortic valve regurgitation, 92% (54–99.2%) and 87% (62–97%) for thoracic aortic aneurysm and 39% (33.8–45%) and 94% (92–95%) for pericardial effusion. In this systematic review and meta-analysis, bedside-focused TTE has high specificity for type A and B dissection, a moderate to high sensitivity for type A but poor for type B, and unclear diagnostic accuracy for intramural haematoma and penetrating aortic ulcer.
Pragmatic Trial of Palliative Care Support Using Extension for Community Healthcare Outcomes Mentoring
Authors: Kupershmidt Sabina , Pithan Anne , Fischbach Cheryl , Pudwill Katie , Berke Charlene , Kroeze Visser Angela , Snyders Michele , Kullerd Deborah
Published: August 2024

Increasing rates of chronic diseases and an aging population have placed palliative care at the forefront of public health efforts. The major goal of palliative care is to achieve the best possible quality of life for patients and their families or caregivers. To reduce barriers and improve palliative care, the From Advance Care Planning Toward Palliative Care coalition was first formed in South Dakota in 2017. It comprises an interprofessional, multi-institutional group of health care professionals who aim to promote palliative care through education, research, and advocacy. The project’s purpose was to increase awareness and knowledge of best palliative care practices and to improve access to resources and networking among stakeholders. In 2021 and 2022, the coalition implemented the Extension for Community Healthcare Outcomes model. The objective was to provide a centralized structure for distant providers to obtain mentoring in palliative care through case-based learning according to a standardized communication and mentoring strategy, thereby increasing access to palliative care networking opportunities in rural and underserved regions.
Psycho-oncology interventions from research to practice: the case of mindfulness-based interventions
Authors: Carlson Linda E.
Published: August 2024

As a past recipient of the International Psycho-Oncology Society (IPOS) Bernard Fox Memorial Award, on the occasion of IPOS' 40th anniversary, Dr. Carlson reflects on the development, evaluation, and uptake of mindfulness-based interventions (MBIs) over the past 25 years as an example of a psychosocial oncology intervention that has moved from a complementary therapy generally outside of conventional medicine to a therapy endorsed in mainstream clinical practice guidelines. She summarizes the literature on MBIs for people with cancer and her team's contributions to the body of science now supporting the use of MBIs and reviews recent clinical practice guidelines from the American Society of Clinical Oncology and the National Comprehensive Cancer Network, which include recommendations for the use of MBIs for treating common symptoms in people with cancer including anxiety, depression, and fatigue as an example of a process that IPOS may support for other promising programs.
Development and Psychometric Analysis of a Patient-Reported Measure of Diagnostic Excellence for Emergency and Urgent Care Settings
Authors: Gleason Kelly T. , Dukhanin Vadim , Peterson Susan K. , Gonzalez Natalia , Austin J.M. , McDonald K.M.
Published: August 2024

Background

Emergency and urgent care settings face challenges with routinely obtaining performance feedback related to diagnostic care. Patients and their care partners provide an important perspective on the diagnostic process and outcome of care in these settings. We sought to develop and test psychometric properties of Patient-Report to IMprove Diagnostic Excellence in Emergency Department settings (PRIME-ED), a measure of patient-reported diagnostic excellence in these care settings.

Methods

We developed PRIME-ED based on literature review, expert feedback, and cognitive testing. To assess psychometric properties, we surveyed AmeriSpeak, a probability-based panel that provides sample coverage of approximately 97% of the U.S. household population, in February 2022 to adult patients, or their care partners, who had presented to an emergency department or urgent care facility within the last 30 days. Respondents rated their agreement on a 5-point Likert scale with each of 17 statements across multiple domains of patient-reported diagnostic excellence. Demographics, visit characteristics, and a subset of the Emergency Department Consumer Assessment of Healthcare Providers & Systems were also collected. We conducted psychometric testing for reliability and validity.

Results

Over a thousand (n = 1116) national panelists completed the PRIME-ED survey, of which 58.7% were patients and 40.9% were care partners; 49.6% received care at an emergency department and 49.9% at an urgent care facility. Responses had high internal consistency within 3 patient-reported diagnostic excellence domain groupings: diagnostic process (Cronbach’s alpha 0.94), accuracy of diagnosis (0.93), and communication of diagnosis (0.94). Domain groupings were significantly correlated with concurrent Emergency Department Consumer Assessment of Healthcare Providers & Systems items. Factor analyses substantiated 3 domain groupings.

Conclusions

PRIME-ED has potential as a tool for capturing patient-reported diagnostic excellence in emergency and urgent care.
68Ga-FAPI-04 PET/CT Imaging in a Patient With Psoriatic Arthritis
Authors: Zhang Zitong , Yang Lixiang , Jiang Lisha , Tian Rong , Li Qianrui
Published: August 2024

We described the findings of 68Ga-FAPI-04 PET/CT of psoriatic arthritis in a 56-year-old man. Intense FAPI uptake was observed alongside the spine and in the joints of bilateral feet and the right hip. 68Ga-FAPI PET/CT is potentially valuable for the evaluation of join involvement and disease activity in patients with psoriasis.
Diagnosing the Recent Decrease in Utilization of Deceased Donor Kidneys
Authors: Wood Nicholas L. , VanDerwerken Douglas N. , Massie Allan B. , Segev Dorry L. , Snyder Jon J. , Gentry Sommer E.
Published: August 2024

Background.

The number of deceased donor kidney transplants has been increasing and is at a record high, yet nonuse of kidneys recovered for transplantation has risen to 25.8% following circular kidney allocation system based on 250–nautical-mile circles implemented on March 15, 2021 (KAS250).

Methods.

Using Scientific Registry of Transplant Recipients data, we studied all deceased donor kidneys recovered for transplant from March 15, 2019, to January 31, 2023. We calculated the association of multiple factors with kidney nonuse, including increasing recovery of kidneys from nonideal donors, delays in offer acceptance observed under KAS250, and impacts of COVID-19.

Results.

In the 2 y before KAS250, the nonuse rate was 21.2%. Had this rate continued, 2334 more kidneys would have been transplanted through January 2023. We estimated that about 769 of these nonused kidneys (33%) were associated with offer acceptance delays under KAS250; about 994 of these nonused kidneys (43%) were associated with increased prevalence of nonideal donors: donation after circulatory death donors, older donors, and donors with elevated peak serum creatinine; and about 542 of these nonused kidneys (23%) were associated with an otherwise unexplained gradual upward trend in nonuse of recovered kidneys across the pre-KAS250 and KAS250 eras. The overall impact of COVID-19 on the nonuse rate was not significant.

Conclusions.

The rise in kidney nonuse rate was significantly associated with both increased recovery of nonideal donors, and with KAS250 allocation complexity and delays. Increasing recovery of kidneys from nonideal donors benefits patients because recovering more kidneys increases the number of kidneys available for transplant.
Investigating Cardiac Temperature During Heart Transplantation Using the Static Cold Storage Paradigm
Authors: Paez Juan Rodriguez , White Ruth E. , Dunn Kaitlyn , Gopagani Lasya , Pham Si , Pahinkar Darshan , Chivukula Venkat Keshav
Published: August 2024

Background.

Static cold storage is a mainstay of the heart transplantation (HTx) process. However, the temperature distribution within the organ at each stage of HTx is unknown. In this study, we aimed to quantify how long it took for the heart to warm up and cool down and the nature of temperature distribution with the organ at each stage of HTx.

Methods.

We used high-fidelity computational time-varying biothermal modeling on an anatomical human heart model to model the HTx process in 5 interdependent stages, including cardioplegia, back-table preparation, static cold storage ice box storage and transport, back-table preparation at the recipient institution and warm-up within the recipient body before cross-clamp release.

Results.

Results indicate that the heart experiences roller-coaster-like temperature changes in stage, including rapid cool down from body temperature to <10 °C within 15 min in stage 1 with a maximum cooling rate of 5 °C/min. This was followed by cooling and extended duration of temperatures <2 °C in the ice box and rapid warming up to body temperature within 10 min at rates of 2 °C/min and 4 °C/min for the left and right sides, respectively, during implantation. Temperature distribution throughout the heart was heterogeneous, with right-sided temperature change occurring nearly 2× faster than on the left side.

Conclusions.

We present, for the first time, detailed temperature distributions and evolution at each stage of HTx. Quantification of the rapid and heterogeneous temperature changes is crucial to optimize HTx and improve organ viability.
Kidney Transplant Outcomes in Amyloidosis: US National Database Study
Authors: Yamauchi Junji , Raghavan Divya , Jweehan Duha , Oygen Suayp , Marineci Silviana , Hall Isaac E. , Molnar Miklos Z.
Published: August 2024

Background.

We aimed to assess contemporary transplant outcomes among kidney recipients with amyloidosis, as the treatment and prognosis of amyloidosis have shown improvement over time.

Methods.

Using the US Organ Procurement and Transplantation Network database, we initially evaluated the changes in patient and graft survival among kidney recipients with amyloidosis from 2002 to 2021. We then compared transplant outcomes between recipients with amyloidosis versus those with diabetic and nondiabetic causes of kidney failure, creating 1:4 matches with highly similar characteristics separately for deceased donor kidney transplant (DDKT) and living donor kidney transplant (LDKT) during the last decade (2012–2021).

Results.

We identified 643 kidney recipients with amyloidosis during 2002–2021. Patient and death-censored graft survival improved over time. In the matching analysis for 207 DDKT and 166 LDKT recipients with amyloidosis during 2012–2021, patient survival was not significantly different between amyloidosis and diabetes groups in both DDKT (log-rank, P = 0.057) and LDKT (P = 0.99). Compared with the nondiabetes group, patient survival in the amyloidosis group was not significantly different for DDKTs (P = 0.56) but was significantly lower for LDKTs (P = 0.04). Death-censored graft failure risk was not significantly different between amyloidosis and diabetes or nondiabetes groups for both DDKTs (P = 0.78 and 0.75) and LDKTs (P = 0.40 and 0.24).

Conclusions.

In this well-matched cohort study, we found no significant differences in patient and graft survival between kidney recipients with amyloidosis and those with diabetes. Similarly, these outcomes were not significantly different between those with amyloidosis versus nondiabetic causes, except for patient survival of LDKT recipients.
Donor and Recipient Age Influence Outcomes Following Orthotopic Heart Transplantation in the 2018 US Heart Allocation System
Authors: Iyanna Nidhi , Hong Yeahwa , Hess Nicholas R. , Ziegler Luke A. , Dorken-Gallastegi Ander , Hickey Gavin W. , Keebler Mary E. , Kaczorowski David J.
Published: August 2024

Background.

This study evaluates the interaction of donor and recipient age with outcomes following heart transplantation under the 2018 heart allocation system.

Methods.

The United Network for Organ Sharing registry was queried to analyze adult primary isolated orthotopic heart transplant recipients and associated donors from August 18, 2018, to June 30, 2021. Both recipient and donor cohorts were grouped according to age: <65 and ≥65 y for recipients and <50 and ≥50 y for donors. The primary outcome was survival. Subanalyses were performed to evaluate the impact of donor age.

Results.

A total of 7601 recipients and 7601 donors were analyzed. Of these, 1584 recipients (20.8%) were ≥65 y old and 560 donors (7.4%) were ≥50 y old. Compared with recipients <65, recipients ≥65 had decreased 1-y (88.8% versus 92.3%) and 2-y (85.1% versus 88.5%) survival rates (P < 0.001). The association of recipient age ≥65 with lower survival persisted after adjusting for potential cofounders (hazard ratio, 1.38; 95% confidence interval, 1.18-1.61; P < 0.001). Recipients <65 with donors ≥50 had comparable 1-y and 2-y survival rates to recipients <65 with donors <50 (P = 0.997). Conversely, transplantation of older allografts was associated with lower 1-y (84.2% versus 89.4%) and 2-y (79.5% versus 85.8%) survival rates in recipients ≥65 (P = 0.025).

Conclusions.

Recipient age ≥65 continues to be associated with worse survival following heart transplantation in the 2018 heart allocation system compared with younger recipients. Donors ≥50 may be acceptable among recipients <65 with comparable outcomes. However, careful donor age selection should be considered for recipients ≥65, as the use of younger donor allografts appears to improve posttransplantation survival.
Ideonella margarita sp. nov., Ideonella lacteola sp. nov., Pseudaquabacterium inlustre sp. nov. and Pseudaquabacterium rugosum sp. nov., isolated from streams in China and re-examining the taxonomic status of all the genera within the family Sphaerotilaceae
Authors: Lu Huibin , Chen Li
Published: August 2024

Four Gram-stain-negative, aerobic, rod-shaped and motile strains (LYT19WT, DXS22WT, DXS29WT and BYS139WT) were isolated from streams in China. All four strains showed highest 16S rRNA gene sequence similarities to the species of genus Ideonella. The calculated average nucleotide identity, digital DNA–DNA hybridization and average amino acid identity values among strains LYT19WT, DXS22WT, DXS29WT, BYS139WT and other closely related strains were less than 79.5, 22.5 and 74.0%, respectively, indicating that each of the four strains should represent an independent novel species. The further reconstructed phylogenomic tree showed that strains LYT19WT and DXS29WT clustered closely with Ideonella strains, but strains DXS22WT and BYS139WT formed an independent clade with Aquabacterium terrae and Aquabacterium pictum. Comparing with other Aquabacterium species, A. terrae and A. pictum harboured distinct physiological and genetic characteristics, so it was reasonable to propose a novel genus Pseudaquabacterium to accommodate A. terrae, A. pictum, DXS22WT and BYS139WT. The major fatty acids of the four strains contained C16 : 0, summed feature 3 (C16 : 1
 ω6c and/or C16 : 1
 ω7c) and summed feature 8 (C18 : 1
 ω6c and/or C18 : 1
 ω7c). The predominant polar lipids were phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol and one unidentified aminophospholipid. Combining above descriptions, strains LYT19WT and DXS29WT should represent two novel species of the genus Ideonella, for which the names Ideonella margarita sp. nov. (type strain LYT19WT=GDMCC 1.3205T=KCTC 92545T) and Ideonella lacteola sp. nov. (type strain DXS29WT=GDMCC 1.3207T=KCTC 92547T) are proposed, respectively. Strains DXS22WT and BYS139WT should represent two novel species of the new genus Pseudaquabacterium, for which the names Pseudaquabacterium inlustre sp. nov. (type strain DXS22WT=GDMCC 1.3206T=KCTC 92546T) and Pseudaquabacterium rugosum sp. nov. (type strain BYS139WT=GDMCC 1.3208T=KCTC 92548T) are proposed, respectively.