bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating individual tree species classification performance across diverse environments
Authors: Seeley M M , Vaughn N R , Asner G A
Published: January 2024

Vegetation species mapping using airborne imaging spectroscopy yields accurate results and is important for advancing conservation objectives and biogeographic studies. As these data become more readily available owing to the upcoming launch of spaceborne imaging spectrometers, it is necessary to understand how these data can be used to consistently classify species across large geographic scales. However, few studies have attempted to map species across multiple ecosystems; therefore, little is known regarding the effect of intra-specific variation on the mapping of a single species across a wide range of environments and among varying backgrounds of other non-target species. To explore this effect, we developed and tested species classification models for Metrosideros polymorpha, a highly polymorphic canopy species endemic to Hawai’i, which is found in a diverse array of ecosystems. We compared the accuracies of support vector machine (SVM) and random forest models trained on canopy reflectance data from each of eight distinct ecosystems (ecosystem-specific) and a universal model trained on data from all ecosystems. When applied to ecosystem-specific test datasets, the ecosystem-specific models outperformed the universal model; however, the universal model retained high (>81%) accuracies across all ecosystems. Additionally, we found that models from ecosystems with broad variation in M. polymorpha canopy traits, as estimated using chemometric equations applied to canopy spectra, accurately predicted M. polymorpha in other ecosystems. While species classifications across ecosystems can yield accurate results, these results will require sampling procedures that capture the intra-specific variation of the target species.
Health and Safety Executive research on wood dust exposure controls in British manufacturing
Authors: Simpson Andrew T , Beattie Helen , Lekka Chrysanthi , Keen Chris
Published: January 2024

To generate new intelligence on occupational exposure to wood dust in woodworking manufacturing activities in Britain, the Health and Safety Executive (HSE) performed 22 occupational hygiene site visits to assess exposure and exposure controls between 2014 and 2017. The work aimed to characterise good practice and therefore sites with a poor health and safety record, as identified from HSE inspection records, were not invited to participate. Sites selected covered furniture production, joinery, saw milling, and boat building and repair. Twenty-three follow-up telephone interviews were also carried out across 15 of the companies with supervisors and managers to explore how they tried to promote good practice among the workforce, and if there are any potential challenges encountered. The aim of the interviews was to gain a better understanding of how to enable organisations to improve the management of wood dust exposure.

This study found that 6.0% of all wood dust exposure measurements (15 out of 252) were above 5 mg/m³, and 17.6% of exposures to hardwood dust or mixtures of hardwood and softwood dust (38 out of 216) were above 3 mg/m³ (the then current and future workplace exposure limits). Sanding, cleaning, and maintenance activities were of particular concern. Improvements to exposure controls are required, in particular, improvements to local exhaust ventilation controls for hand-held power tools and hand sanding. The management, selection, and use of respiratory protective equipment were poor.

All the managers and supervisors recognised that exposure to wood dust can pose serious health risks, and that controls were crucial to protecting workers’ health. The findings from the telephone interviews suggest that supervision and provision of information about the health effects of exposure to wood dust were common approaches that organisations used to raise awareness and promote good practice, in relation to managing wood dust exposure. Worker attitudes towards controls, such as perceptions that they hinder task completion and habitual ways of working, were identified as factors influencing the use of controls. Risk communication approaches that focus on increasing workers’ awareness of their susceptibility to ill-health using credible sources, such as peers, can help enhance the uptake of messages on the use of controls. Financial constraints were identified as a challenge to improving the control of wood dust, particularly for small companies.
Constricted rights and imagined identities: Peace and accountability processes and constitution-making in Bosnia and Herzegovina
Authors: Begicevic Alma , Balint Jennifer
Published: January 2024

This article takes an interdisciplinary law-in-context approach to examine the nature of constitutionalism in Bosnia and Herzegovina. We argue that while the new constitution was necessary for implementing the postwar democratic transition and rebuilding processes, its fixed ethno-religious collective political identities achieved between 1992 and 1995 by forceful means have further reinforced ethno-territorial divisions in a multicultural society. As a consequence,the individual and state accountability for mass atrocities and genocide before the ad hoc International Criminal Tribunal for Former Yugoslavia and theInternational Court of Justice have become secondary to the postwar power-sharing arrangement, thus perpetuating inter-ethnic tensions. The dominant focus on a social order that reasserts citizenship and constitutional rights based on ethnic identities has created an enduring deadlock for the Bosnian transition. This article reimagines a citizen-based constitution generated by political participation for those in and outside of Bosnia and Herzegovina that safeguards the principles of non-discrimination and equal civil, political, socio-economic, and cultural rights, and encourages citizens’ education and democratic participation to shape the future of democracy.
Spatial organization of a soil cyanobacterium and its cyanosphere through GABA/Glu signaling to optimize mutualistic nitrogen fixation
Authors: Nelson Corey , Dadi Pavani , Shah Dhara D , Garcia-Pichel Ferran
Published: January 2024

Soil biocrusts are characterized by the spatial self-organization of resident microbial populations at small scales. The cyanobacterium Microcoleus vaginatus, a prominent primary producer and pioneer biocrust former, relies on a mutualistic carbon (C) for nitrogen (N) exchange with its heterotrophic cyanosphere microbiome, a mutualism that may be optimized through the ability of the cyanobacterium to aggregate into bundles of trichomes. Testing both environmental populations and representative isolates, we show that the proximity of mutualistic diazotroph populations results in M. vaginatus bundle formation orchestrated through chemophobic and chemokinetic responses to gamma-aminobutyric acid (GABA) /glutamate (Glu) signals. The signaling system is characterized by: a high GABA sensitivity (nM range) and low Glu sensitivity (μM to mM), the fact that GABA and Glu are produced by the cyanobacterium as an autoinduction response to N deficiency, and by the presence of interspecific signaling by heterotrophs in response to C limitation. Further, it crucially switches from a positive to a negative feedback loop with increasing GABA concentration, thus setting maximal bundle sizes. The unprecedented use of GABA/Glu as an intra- and interspecific signal in the spatial organization of microbiomes highlights the pair as truly universal infochemicals.
Comparative molecular profiling of multidrug-resistant Pseudomonas aeruginosa identifies novel mutations in regional clinical isolates from South India
Authors: Menon Nitasha D , Somanath Priyanka , Jossart Jennifer , Vijayakumar Gayathri , Shetty Kavya , Baswe Manasi , Chatterjee Meghna , Hari Malavika B , Nair Samitha , Kumar V Anil , Nair Bipin G , Nizet Victor , Perry J Jefferson P , Kumar Geetha B
Published: January 2024

Objectives

We sought to analyse the antibiotic susceptibility profiles and molecular epidemiology of MDR clinical Pseudomonas aeruginosa isolates from South India using non-MDR isolates as a reference.

Methods

We established a comprehensive clinical strain library consisting of 58 isolates collected from patients across the South Indian state of Kerala from March 2017 to July 2019. The strains were subject to antibiotic susceptibility testing, modified carbapenem inactivation method assay for carbapenemase production, PCR sequencing, comparative sequence analysis and quantitative PCR of MDR determinants associated with antibiotic efflux pump systems, fluoroquinolone resistance and carbapenem resistance. We performed in silico modelling of MDR-specific SNPs.

Results

Of our collection of South Indian P. aeruginosa clinical isolates, 74.1% were MDR and 55.8% were resistant to the entire panel of antibiotics tested. All MDR isolates were resistant to levofloxacin and 93% were resistant to meropenem. We identified seven distinct, MDR-specific mutations in nalD, three of which are novel. mexA was significantly overexpressed in strains that were resistant to the entire test antibiotic panel while gyrA and gyrB were overexpressed in MDR isolates. Mutations in fluoroquinolone determinants were significantly associated with MDR phenotype and a novel GyrA Y100C substitution was observed. Carbapenem resistance in MDR isolates was associated with loss-of-function mutations in oprD and high prevalence of NDM (blaNDM-1) within our sample.

Conclusions

This study provides insight into MDR mechanisms adopted by P. aeruginosa clinical isolates, which may guide the potential development of therapeutic regimens to improve clinical outcomes.
Autonomy, rationality, and religious initiation: replies to Hand, Wareham, Gheaus, Lewin, and Clayton
Authors: Tillson John
Published: January 2024

John Tillson concludes the symposium on his Children, Religion and the Ethics of Influence by replying to his five respondents. The reply focusses on Michael Hand’s defence of parental rights to raise their children in their faith; Ruth Wareham’s suggestion that the value of autonomy rules out a wider range of impermissible religious influences than Tillson’s account is able to; David Lewin’s alternative criteria for ethical influence and scepticism about rationality’s objectivity; Anca Gheaus’ proposal that initiation into multiple contradictory religious faiths is permissible; and Matthew Clayton’s rejection of the book’s perfectionist political morality.
An untimely vocation: Gadamer’s ‘Wissenschaft als Beruf. Über den Ruf und Beruf der Wissenschaft in unserer Zeit’ (1943)
Authors: Bey Facundo Norberto
Published: January 2024

On 27 September 1943, Hans-Georg Gadamer published a brief but significant article in the conservative newspaper Leipziger Neueste Nachrichten und Handels-Zeitung, entitled ‘Wissenschaft als Beruf. Über den Ruf und Beruf der Wissenschaft in unserer Zeit’ (Science as Vocation: On the Calling and Profession of Science in Our Time). The article, which addressed the problem of the value and status of science and philosophy in the midst of the Second World War, was never reprinted in Gadamer’s work, neither in the ten volumes of his collected writings published by Mohr Siebeck, nor separately in books or journals. I offer here a critical introduction to the context and main contents of this text due to its philosophical, political, and historical relevance. In particular, the introduction analyses Gadamer’s confrontation with his own time through explicit and implicit references to Max Weber’s 1917 lecture, ‘Wissenschaft als Beruf’ (Science as Vocation), and traces echoes in Gadamer’s later works that bear on contemporary challenges. Following that, I present the first English translation of Gadamer’s original German text.
Statistics did not prove that the Huanan Seafood Wholesale Market was the early epicentre of the COVID-19 pandemic
Authors: Stoyan Dietrich , Chiu Sung Nok
Published: January 2024

In a recent prominent study, Worobey et al. (2022. The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic. Science, 377(6609), 951–959) purported to demonstrate statistically that the Huanan Seafood Wholesale Market was the epicentre of the early COVID-19 epidemic. We show that this statistical conclusion is invalid on two grounds: (a) The assumption that a centroid of early case locations or another simply constructed point is the origin of an epidemic is unproved. (b) A Monte Carlo test used to conclude that no other location than the seafood market can be the origin is flawed. Hence, the question of the origin of the pandemic has not been answered by their statistical analysis.
Divergent Selection in Low Recombination Regions Shapes the Genomic Islands in Two Incipient Shorebird Species
Authors: Zhou Wenjun , Zhang Nan , Huang Kaichi , Lin Hongzhou , Tu Jie , Zheng Chenqing , Que Pinjia , Chiang Chung-Yu , Martinez Jonathan , Naerhulan Halimubieke , Székely Tamás , Zhang Zhengwang , Liu Yang
Published: January 2024

Speciation in the face of gene flow is usually associated with a heterogeneous genomic landscape of divergence in nascent species pairs. However, multiple factors, such as divergent selection and local recombination rate variation, can influence the formation of these genomic islands. Examination of the genomic landscapes of species pairs that are still in the early stages of speciation provides an insight into this conundrum. In this study, population genomic analyses were undertaken using a wide range of sampling and whole-genome resequencing data from 96 unrelated individuals of Kentish plover (Charadrius alexandrinus) and white-faced plover (Charadrius dealbatus). We suggest that the two species exhibit varying levels of population admixture along the Chinese coast and on the Taiwan Island. Genome-wide analyses for introgression indicate that ancient introgression had occurred in Taiwan population, and gene flow is still ongoing in mainland coastal populations. Furthermore, we identified a few genomic regions with significant levels of interspecific differentiation and local recombination suppression, which contain several genes potentially associated with disease resistance, coloration, and regulation of plumage molting and thus may be relevant to the phenotypic and ecological divergence of the two nascent species. Overall, our findings suggest that divergent selection in low recombination regions may be a main force in shaping the genomic islands in two incipient shorebird species.
The Dividends of Democracy’s Destruction: Surplus, Ideology, and Militarism in the Turn to Empire in Du Bois’s Black Reconstruction
Authors: Valdez Inés
Published: January 2024

This paper offers an original reading of Du Bois’s Black Reconstruction that highlights how the knock down effects from Reconstruction’s failures contributed to the U.S. imperial trajectory. The coalition between the industrial North, Southern landowners, and white workers ended the promise of racial emancipation advanced by Black freedmen and the Freedmen’s Bureau. The gains from the resubjection of Black freedmen and women; the development of a national identity based racial hierarchy and an attachment to material wealth, and the racialized militarism of the South, Du Bois argues, underpinned the imperial pursuit of material wealth through violent means. The consolidation of white identity around technological ideals and militarism led Du Bois to revise his account of democratic education (redirecting it to critique capitalism and soulless technology) and to reach transnationally for emancipatory solidarity.
Multifaceted roles of t6A biogenesis in efficiency and fidelity of mitochondrial gene expression
Authors: Zhang Yong , Zhou Jing-Bo , Yin Yue , Wang En-Duo , Zhou Xiao-Long
Published: January 2024

N 6-Threonylcarbamoyladenosine at A37 (t6A37) of ANN-decoding transfer RNAs (tRNAs) is a universal modification whose functions have been well documented in bacteria and lower eukaryotes; however, its role in organellar translation is not completely understood. In this study, we deleted the mitochondrial t6A37-modifying enzyme OSGEPL1 in HEK293T cells. OSGEPL1 is dispensable for cell viability. t6A37 hypomodification selectively stimulated N1-methyladenosine at A9 (m1A9) and N2-methylguanosine at G10 (m2G10) modifications and caused a substantial reduction in the aminoacylation of mitochondrial tRNAThr and tRNALys, resulting in impaired translation efficiency. Multiple types of amino acid misincorporation due to the misreading of near-cognate codons by t6A37-unmodified tRNAs were detected, indicating a triggered translational infidelity. Accordingly, the alterations in mitochondrial structure, function, and the activated mitochondrial unfolded protein response were observed. Mitochondrial function was efficiently restored by wild-type, but not by tRNA-binding-defective OSGEPL1. Lastly, in Osgepl1 deletion mice, disruption to mitochondrial translation was evident but resulted in no observable deficiency under physiological conditions in heart, which displays the highest Osgepl1 expression. Taken together, our data delineate the multifaceted roles of mitochondrial t6A37 modification in translation efficiency and quality control in mitochondria.
Guidance for the Interpretation of Long-Acting Cabotegravir and Rilpivirine Concentrations Based on Real-World Therapeutic Drug Monitoring Data and Documented Failures
Authors: Thoueille Paul , Cavassini Matthias , Guidi Monia , Buclin Thierry , Girardin François R , Decosterd Laurent A , Marzolini Catia
Published: January 2024

The interpretation of long-acting cabotegravir and rilpivirine concentrations is complicated by the lack of consensus on the threshold to consider. Building on real-world therapeutic drug monitoring data and documented virologic failures, this article provides a reappraisal of the existing thresholds and guidance for the interpretation of cabotegravir and rilpivirine concentrations.
Increased Tuberculosis Reactivation Risk in Patients Receiving Immune Checkpoint Inhibitor-Based Therapy
Authors: Chen Hsing-Wu , Kuo Yao-Wen , Chen Chung-Yu , Chang Chin-Hao , Wang Su-Mei , Chien Ying-Chun , Lu Wei-Chen , Chen Jo-Pai , Chang Cheng-Yu , Wei Yu-Feng , Chang Shih-Chieh , Shu Chin-Chung , Wang Jann-Yuan , Liao Wei-Yu , Wang Hao-Chien , Yu Chong-Jen
Published: January 2024

Objective

Reports of tuberculosis (TB) during anticancer treatment with immune checkpoint inhibitors (ICIs) are increasing. However, it is not clear whether the use of ICIs is a significant risk factor for TB, including reactivation or latent TB infection (LTBI).

Methods

To determine the risk of TB reactivation in patients with lung cancer who use ICIs or tyrosine kinase inhibitors (TKIs), we conducted a retrospective study using a hospital-based cancer registry. In addition, we monitored patients with cancer using ICI or TKI in a multicenter prospective study to check the incidence of LTBI.

Results

In the retrospective study, several demographic factors were imbalanced between the ICI and TKI groups: the ICI group was younger, had more males, exhibited more squamous cell carcinoma in histology rather than adenocarcinoma, had fewer EGFR mutations, and received more chemotherapy. Propensity score matching was used to control for confounding factors, and we found that the incidence of TB was higher among patients with lung cancer who received ICIs than among those who received TKIs (2298 vs 412 per 100 000 person-years, P = .0165). Through multivariable analysis, group (ICI vs TKI) was the independent risk factor for TB development (adjusted hazard ratio (aHR): 6.29, 95% CI, 1.23-32.09, P = .0269). In the prospective cohort, which included 72 patients receiving ICIs and 50 receiving TKIs, we found that the incidence of positive seroconversion of LTBI by interferon gamma release assay (IGRA) was significantly higher in patients receiving ICIs (18% vs 0%, aHR: 9.88, P = 0.035) under multivariable Cox regression.

Conclusion

The use of ICIs may be linked to a higher likelihood of TB reactivation and LTBI than individuals solely receiving TKIs as anticancer therapy. Consequently, the implementation of a screening program for TB reactivation and LTBI among patients undergoing ICI treatment could prove advantageous by enabling early detection and prompt treatment of the infection.
Neoadjuvant Intra-arterial Cytoreductive Chemotherapy Improves Outcomes in Lacrimal Gland Adenoid Cystic Carcinoma
Authors: Costa Philippos Apolinario , Tse David T , Benedetto Pasquale
Published: January 2024

Background

Lacrimal gland adenoid cystic carcinoma (LGACC) has historically been associated with a poor prognosis even with localized disease, with a survival of 56% at 5 years. In 1988, we treated the first patient with neoadjuvant intra-arterial cytoreductive chemotherapy (IACC). Since then, we have used this protocol as the standard approach. We aim to analyze the outcomes of patients with LGACC treated with the protocol and compare them to a population-based cohort to assess if IACC can improve survival.

Methods

We prospectively assessed all non-metastatic patients with LGACC treated with IACC at a single institution between 1988 and 2021. For a comparison group, we identified all non-metastatic patients with LGACC treated with excision from the Surveillance, Epidemiology, and End Results (SEER) registry. We calculated disease-specific survival using the Kaplan-Meier and Cox proportional-hazards modeling methods.

Results

Thirty-five non-metastatic patients with LGACC treated with IACC were identified at a single institution, and 64 patients with non-metastatic LGACC treated with excision were identified in the SEER database. The 5- and 10-year disease-specific survival rates for patients treated with IACC were 84% (95%CI 71-97) and 76% (95%CI 60-92), respectively. While the 5- and 10-year disease-specific survival rates for the population-based cohort were 72% (95%CI 62-82) and 46% (95%CI 32-60). The survival analysis favored IACC, with a 60% lower risk of death (HR: 0.4; 95%CI 0.2-0.9).

Conclusion

IACC improves disease-specific survival in comparison to a population-based cohort treated with excision. Additional patients treated with IACC at multiple institutions are required to provide further external validity.
ACC SYNTHASE4 inhibits gibberellin biosynthesis and FLOWERING LOCUS T expression during citrus flowering
Authors: Chu Le-Le , Zheng Wei-Xuan , Liu Hai-Qiang , Sheng Xing-Xing , Wang Qing-Ye , Wang Yue , Hu Chun-Gen , Zhang Jin-Zhi
Published: January 2024

Flowering is an essential process in fruit trees. Flower number and timing have a substantial impact on the yield and maturity of fruit. Ethylene and gibberellin (GA) play vital roles in flowering, but the mechanism of coordinated regulation of flowering in woody plants by GA and ethylene is still unclear. In this study, a lemon (Citrus limon L. Burm) 1-aminocyclopropane-1-carboxylic acid synthase gene (CiACS4) was overexpressed in Nicotiana tabacum and resulted in late flowering and increased flower number. Further transformation of citrus revealed that ethylene and starch content increased, and soluble sugar content decreased in 35S:CiACS4 lemon. Inhibition of CiACS4 in lemon resulted in effects opposite to that of 35S:CiACS4 in transgenic plants. Overexpression of the CiACS4-interacting protein ETHYLENE RESPONSE FACTOR3 (CiERF3) in N. tabacum resulted in delayed flowering and more flowers. Further experiments revealed that the CiACS4–CiERF3 complex can bind the promoters of FLOWERING LOCUS T (CiFT) and GOLDEN2-LIKE (CiFE) and suppress their expression. Moreover, overexpression of CiFE in N. tabacum led to early flowering and decreased flowers, and ethylene, starch, and soluble sugar contents were opposite to those in 35S:CiACS4 transgenic plants. Interestingly, CiFE also bound the promoter of CiFT. Additionally, GA3 and 1-aminocyclopropanecarboxylic acid (ACC) treatments delayed flowering in adult citrus, and treatment with GA and ethylene inhibitors increased flower number. ACC treatment also inhibited the expression of CiFT and CiFE. This study provides a theoretical basis for the application of ethylene to regulate flower number and mitigate the impacts of extreme weather on citrus yield due to delayed flowering.
Value Distribution of Logarithmic Derivatives of Quadratic Twists of Automorphic L-functions
Authors: Akbary Amir , Hamieh Alia
Published: January 2024

Let $d\in\mathbb{N}$ and π be a fixed cuspidal automorphic representation of $\mathrm{GL}_{d}(\mathbb{A}_{\mathbb{Q}})$ with unitary central character. We determine the limiting distribution of the family of values $-\frac{L^{\prime}}{L}(1+it,\pi\otimes\chi_D)$ as D varies over fundamental discriminants. Here, t is a fixed real number and χD is the real character associated with D. We establish an upper bound on the discrepancy in the convergence of this family to its limiting distribution. As an application of this result, we obtain an upper bound on the small values of $\left|\frac{L^{\prime}}{L}(1,\pi\otimes\chi_D)\right|$ when π is self-dual.
Lactate accumulation induced by Akt2‐PDK1 signaling promotes pulmonary fibrosis
Authors: Sun Zhiheng , Ji Zhihua , He Wanyu , Duan Ruoyu , Qu Junxing , Yu Guoying
Published: January 2024

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with an abnormal accumulation of fibrotic tissue in the lung parenchyma and elevated glycolysis level in associated cells without effective therapy options. Lactate accumulation in pulmonary fibrotic tissue is a significant factor aggravating IPF development, but the main mechanism regulating glycolysis needs further investigation. In this study, lung fibrosis model was induced by bleomycin (BLM) intratracheally in female C57BL/6 mice. The changes of lactate level and fibrotic markers were detected. For in vitro studies, cell lines of alveolar epithelial cell and lung fibroblast cell were stimulated with TGF‐β1 and BLM respectively, to detect changes in their fibrotic properties. The function of lactate accumulation on facilitating fibrosis was verified. We demonstrated that BLM‐induced pulmonary fibrosis is accompanied by lactate accumulation owing to glycolysis upregulation. Significantly high PDK1 expression in lung fibrotic tissue promotes glycolysis. Moreover, PDK1 stimulated trans‐differentiation of lung fibroblasts and epithelial‐mesenchymal transition (EMT) of alveolar epithelial cells. Furthermore, phosphorylated Akt2 activated PDK1 to cause pulmonary fibrosis and inhibitors of Akt2 and PDK1 could suppress fibrotic process. This study is the first to consider PDK1 facilitated lactate accumulation through glycolysis as a vital factor in pulmonary fibrosis and could be initiated by Akt2. We concluded that the pro‐fibrotic properties of PDK1 are associated with Akt2 phosphorylation and thus provide new potential therapeutic targets for pulmonary fibrosis.
Mentoring in Academic Nursing From the Perspectives of Faculty Mentors
Authors: Busby Katie Ruth , Draucker Claire Burke
Published: January 2024

AIM

The aim of this study was to create a theoretical framework that describes how mentoring relationships in academic nursing unfold from the perspectives of nurse faculty mentors.

BACKGROUND

Mentoring is a strategy that can promote the satisfaction and retention of nurse faculty. Although research has focused on the experiences of protégés in mentoring relationships, little is known about mentoring from the perspectives of nurse faculty mentors.

METHOD

Constructivist grounded theory was used to interview 24 experienced nurse faculty about their mentoring experiences.

RESULTS

The theoretical framework Growing Together: Mentors’ Perspectives on Mentoring included four phases (getting together, getting going, going together, going beyond) and three strands (relationship with protégé, work of mentoring, emotional impact of mentoring).

CONCLUSION

Participants experienced a variety of benefits from mentoring while also experiencing a variety of challenges. Findings suggest that more resources are needed for experienced faculty who mentor novice nurse faculty.
Immune checkpoint expression patterns on T cell subsets in light-chain amyloidosis: VISTA, PD-1, and TIGIT as potential therapeutic targets
Authors: Wang Jinghua , Zhao Yujie , Liao Pengjun , Huang Shuxin , Huang Youxue , Chen Shaohua , Li Yangqiu , Zhong Liye
Published: January 2024

Amyloid light chain (AL) amyloidosis is a rare plasma cell dyscrasia with dismal prognosis. This study aims to investigate the T-cell immune checkpoint expression patterns in systemic AL amyloidosis and its relationship with clinicobiological traits. We examined the frequencies of V-domain immunoglobulin suppressor of T cell activation+ (VISTA+), programmed cell death 1+ (PD-1+), T cell immunoglobulin and mucin-domain-containing-3+ (Tim-3+), T cell immunoreceptor with Ig and ITIM domains+ (TIGIT+) T cells in peripheral blood (PB) and bone marrow (BM) from 19 patients with newly diagnosed AL amyloidosis. Patients with AL amyloidosis had significantly higher percentages of VISTA+ and PD-1+ T cells in PB than healthy individuals (HIs), with no statistical differences in BM. The percentages of some double-positive T cells in PB were also considerably higher in AL amyloidosis than those in HIs. Additionally, the patients with renal involvement had more PD-1+ and TIGIT+ T cells than the patients without, and PD-1+CD3+%, PD-1+CD4+%, PD-1+Treg% were positively correlated with 24-hour proteinuria levels. Furthermore, the AL amyloidosis patients had higher counts of PD-1+ Treg in PB than multiple myeloma (MM) patients, while the MM patients had higher counts of TIGIT+ T cells than AL amyloidosis patients. Collectively, this is the first report of elevated proportions of VISTA+ and PD-1+ T cells in PB of AL amyloidosis patients, indicating an immunosuppressive milieu, and the increased PD-1+ and TIGIT+ T cells were associated with renal damage. VISTA, PD-1, and TIGIT may be potential targets for reversing T-cell exhaustion in AL amyloidosis.
Narrative bias (“spin”) is common in randomised trials and systematic reviews of cannabinoids for pain
Authors: Moore Andrew , Karadag Paige , Fisher Emma , Crombez Geert , Straube Sebastian , Eccleston Christopher
Published: January 2024

We define narrative bias as a tendency to interpret information as part of a larger story or pattern, regardless of whether the facts support the full narrative. Narrative bias in title and abstract means that results reported in the title and abstract of an article are done so in a way that could distort their interpretation and mislead readers who had not read the whole article. Narrative bias is often referred to as “spin.” It is prevalent in abstracts of scientific papers and is impactful because abstracts are often the only part of an article read. We found no extant narrative bias instrument suitable for exploring both efficacy and safety statements in randomized trials and systematic reviews of pain. We constructed a 6-point instrument with clear instructions and tested it on randomised trials and systematic reviews of cannabinoids and cannabis-based medicines for pain, with updated searches to April 2021. The instrument detected moderate or severe narrative bias in the title and abstract of 24% (8 of 34) of randomised controlled trials and 17% (11 of 64) of systematic reviews; narrative bias for efficacy and safety occurred equally. There was no significant or meaningful association between narrative bias and study characteristics in correlation or cluster analyses. Bias was always in favour of the experimental cannabinoid or cannabis-based medicine. Put simply, reading title and abstract only could give an incorrect impression of efficacy or safety in about 1 in 5 papers reporting on these products.
An experimental model for primary neuropathic corneal pain induced by long ciliary nerve ligation in rats
Authors: Wu Jinhong , Yuan Tianjie , Fu Danyun , Xu Rui , Zhang Wenna , Li Shuangshuang , Ding Jiahui , Feng Lili , Xia Ying , Wang Jijiang , Li Wenxian , Han Yuan
Published: January 2024

Neuropathic corneal pain (NCP) is a new and ill-defined disease characterized by pain, discomfort, aching, burning sensation, irritation, dryness, and grittiness. However, the mechanism underlying NCP remain unclear. Here, we reported a novel rat model of primary NCP induced by long ciliary nerve (LCN) ligation. After sustained LCN ligation, the rats developed increased corneal mechanical and chemical sensitivity, spontaneous blinking, and photophobia, which were ameliorated by intraperitoneal injection of morphine or gabapentin. However, neither tear reduction nor corneal injury was observed in LCN-ligated rats. Furthermore, after LCN ligation, the rats displayed a significant reduction in corneal nerve density, as well as increased tortuosity and beading nerve ending. Long ciliary nerve ligation also notably elevated corneal responsiveness under resting or menthol-stimulated conditions. At a cellular level, we observed that LCN ligation increased calcitonin gene–related peptide (neuropeptide)–positive cells in the trigeminal ganglion (TG). At a molecular level, upregulated mRNA levels of ion channels Piezo2, TRPM8, and TRPV1, as well as inflammatory factors TNF-α, IL-1β, and IL-6, were also detected in the TG after LCN ligation. Meanwhile, consecutive oral gabapentin attenuated LCN ligation–induced corneal hyperalgesia and increased levels of ion channels and inflammation factors in TG. This study provides a reliable primary NCP model induced by LCN ligation in rats using a simple, minimally invasive surgery technique, which may help shed light on the underlying cellular and molecular bases of NCP and aid in developing a new treatment for the disease.
Effect of Intensive Nurse-Led Optimization of Heart Failure Medications in Patients With Heart Failure
Authors: Driscoll Andrea , Meagher Sharon , Kennedy Rhoda , Currey Judy
Published: January 2024

Background

Prescribing of recommended medications for heart failure (HF) is suboptimal, leaving patients at a high risk of death or rehospitalization post discharge. Nurse-led titration (NLT) clinics are one strategy that could potentially improve the prescription of these medications.

Objective

The aim of this article was to determine the effect of NLT clinics on all-cause mortality, all-cause or HF rehospitalizations, and adverse effects in patients with HF.

Methods

We searched MEDLINE, EMBASE, Cochrane CENTRAL, International Clinical Trials Registry Platform, and ClinicalTrials.gov to identify randomized controlled trials comparing NLT of β-blocking agents, angiotensin receptor–neprilysin inhibitors, angiotensin-converting enzyme inhibitors, and/or angiotensin receptor blockers to optimization by another health professional in patients with HF. We used the fixed-effects Mantel-Haenszel method or meta-analyses. We assessed heterogeneity between studies using χ2 and I
2.

Results

Eight studies with 2025 participants were included. Participants in the NLT group experienced a lower rate of all-cause rehospitalizations (relative risk, 0.76, 95% confidence interval, 0.68–0.85; moderate quality of evidence) and less HF-related rehospitalizations (relative risk, 0.47; 95% confidence interval, 0.33–0.66; high quality of evidence) compared with the usual care group. All-cause mortality was lower in the NLT group (relative risk, 0.67; 95% confidence interval, 0.48–0.92; moderate quality of evidence) compared with the usual care group. Authors of one study reported no adverse events, and another study found one adverse event.

Conclusion

This meta-analysis indicates that NLT clinics may improve optimization of guideline-recommended medications with the potential to reduce rehospitalization and improve survival in a cohort of patients known for their poor outcomes.
Depressive Symptoms and Sleep Quality Mediate the Relationship Between Race and Quality of Life Among Patients With Heart Failure
Authors: Wu Jia-Rong , Moser Debra K. , Lin Chin-Yen , Chiang Ambrose A. , Riegel Barbara
Published: January 2024

Background

Black patients with heart failure (HF) report worse quality of life (QoL) than White patients. Few investigators have examined mediators of the association between race and QoL, but depressive symptoms and sleep quality are associated with QoL.

Objective

The aim of this study was to determine whether depressive symptoms and sleep quality are mediators of the relationship between race and QoL among patients with HF.

Methods

This was a cross-sectional study. We included 271 outpatients with HF. Self-reported race (White/Black), depressive symptoms (Patient Health Questionnaire), sleep quality (Pittsburgh Sleep Quality Index), and QoL (Kansas City Cardiomyopathy Questionnaire) were collected at baseline. A serial multiple mediator analysis was conducted using the PROCESS macro for SPSS.

Results

Ninety-six patients (35.4%) were Black. Black participants reported higher levels of depressive symptoms and poorer sleep quality than White participants. Race was not directly associated with QoL but indirectly associated with QoL through depressive symptoms and poorer sleep quality. Because of higher levels of depressive symptoms and poorer sleep quality, Black participants reported poorer QoL than White participants.

Conclusions

Depressive symptoms and sleep quality together mediated the relationship between race and QoL. These findings suggest that screening for depressive symptoms and sleep quality could identify patients at risk for poor QoL, especially in Black patients.
Efficacy of Long-Acting Injectable Antipsychotics Versus Oral Antipsychotics in Preventing Psychiatric Rehospitalizations
Authors: Thaman Pragya , Kulig Caitlin E. , Greer Daniel
Published: January 2024

Purpose/Background

Schizophrenia is a chronic, debilitating mental illness that incurs a large economic burden. Decreasing hospital readmissions is a priority in health care to improve patient quality of life and decrease health care costs. Determining ways to prevent readmissions such as improving access to long-acting injectable (LAI) antipsychotics is important to assess.

Methods/Procedures

A single-center retrospective review was conducted comparing readmission rates of patients diagnosed with schizophrenia or schizoaffective disorder discharged on LAI or oral antipsychotics between August 1, 2019, and June 30, 2022. The primary outcome was the 30-day psychiatric readmission rate. Secondary outcomes included chlorpromazine equivalent doses and use of anticholinergic medications.

Findings/Results

The 30-day readmission rate was 1.9% for the LAI antipsychotic group and 8.3% for the oral antipsychotic group (P = 0.03; 95% confidence interval, 1.05–20.02). The average chlorpromazine equivalent antipsychotic dose of patients discharged on LAI versus oral antipsychotic medications was 477.3 and 278.6 mg/d, respectively (P < 0.001). In addition, the prevalence of medications used to treat extrapyramidal symptom was 22.3% (n = 23) for the LAI antipsychotic group and 30.8% (n = 74) for the oral antipsychotic group (P = 0.12). Sixty-four percent of LAI antipsychotics utilized were obtained from pharmaceutical company hospital inpatient free trial programs.

Implications/Conclusions

Long-acting injectable antipsychotics showed a statistically significant reduction in 30-day rehospitalizations as compared with oral antipsychotics and hospital inpatient free trial programs aided in LAI antipsychotic acquisition.
Quality Indicator Development for the Approach to Ineffective Esophageal Motility
Authors: Kamal Afrin N. , Kathpalia Priya , Leiman David A. , Bredenoord Albert J. , Clarke John O. , Gyawali C. Prakash , Katzka David A. , Lazarescu Adriana , Pandolfino John E. , Penagini Roberto , Roman Sabine , Savarino Edoardo , Vela Marcelo F. , Otaki Fouad
Published: January 2024

Goals:

Develop quality indicators for ineffective esophageal motility (IEM).

Background:

IEM is identified in up to 20% of patients undergoing esophageal high-resolution manometry (HRM) based on the Chicago Classification. The clinical significance of this pattern is not established and management remains challenging.

Study:

Using RAND/University of California, Los Angeles Appropriateness Methods, we employed a modified-Delphi approach for quality indicator statement development. Quality indicators were proposed based on prior literature. Experts independently and blindly scored proposed quality statements on importance, scientific acceptability, usability, and feasibility in a 3-round iterative process.

Results:

All 10 of the invited esophageal experts in the management of esophageal diseases invited to participate rated 12 proposed quality indicator statements. In round 1, 7 quality indicators were rated with mixed agreement, on the majority of categories. Statements were modified based on panel suggestion, modified further following round 2’s virtual discussion, and in round 3 voting identified 2 quality indicators with comprehensive agreement, 4 with partial agreement, and 1 without any agreement. The panel agreed on the concept of determining if IEM is clinically relevant to the patient’s presentation and managing gastroesophageal reflux disease rather than the IEM pattern; they disagreed in all 4 domains on the use of promotility agents in IEM; and had mixed agreement on the value of a finding of IEM during anti-reflux surgical planning.

Conclusion:

Using a robust methodology, 2 IEM quality indicators were identified. These quality indicators can track performance when physicians identify this manometric pattern on HRM. This study further highlights the challenges met with IEM and the need for additional research to better understand the clinical importance of this manometric pattern.
Management of Irritable Bowel Syndrome With Diarrhea
Authors: Marasco Giovanni , Cremon Cesare , Barbaro Maria Raffaella , Stanghellini Vincenzo , Barbara Giovanni
Published: January 2024

Irritable bowel syndrome (IBS) with diarrhea (IBS-D) affects ~1% of the general population and is characterized by abdominal pain associated with diarrhea. IBS-D symptoms significantly impact the quality of life of patients. Major uncertainties remain regarding the optimal management of these patients. Several therapies have been investigated over the years for the treatment of IBS-D. In the initial management, commonly prescribed approaches with an effect on global IBS symptoms include a low Fermentable Oligo-, Di-, Mono-Saccharides and Polyols diet and probiotics, while antispasmodics are used for targeting abdominal pain and loperamide for diarrhea only. Additional therapeutic options for the relief of global IBS symptoms include rifaximin, 5-HT3 antagonists, gut-directed psychological therapies, and eluxadoline, while tricyclic antidepressants can target abdominal pain and bile acid sequestrants diarrhea. Promising evidence exists for the use of mesalazine and fecal microbiota transplantation in IBS-D, although further evidence is needed for definitive conclusions regarding their efficacy.
Can Medication be a Factor that Can Negatively Affect the Effect of Transcranial Magnetic Stimulation in Depression?
Authors: Constantin Dan A. , Monescu Vlad , Cioriceanu Ionut H. , Leaşu Florin Gabriel , Rogozea Liliana M.
Published: January 2024

Background:

This study aims to evaluate the efficacy of transcranial magnetic stimulation (TMS) in patients with depression and whether concurrent psychotropic medication use negatively affects the treatment outcome of TMS. Patients' characteristics, predictors of treatment response, the relationship between demographics, and the selection of TMS as a treatment modality were also analyzed.

Study Question:

Can psychotropic medication be a factor that can negatively affect the efficacy of TMS in patients with depression?

Study Design:

This pilot-controlled study included 40 subjects from Romanian clinical practice who were treated with pharmacological treatment and TMS for major depressive disorder. The severity of depression and anxiety symptoms was measured using validated scales at baseline (day 1) and follow-up (day 30).

Data Sources:

All patients' characteristics and information were collected manually from the clinic's medical records, deidentified, and then introduced into an electronic database for analysis.

Limitations:

Conducting the study in a clinical routine practice, it was not possible to include an active and/or sham control group. In addition, because TMS is not used as a monotherapy in this type of practice, we could not evaluate its safety and efficacy without concomitant pharmacological treatment. The study sample is small; therefore, the results cannot be generalized.

Results:

Sixty percentage of patients (n = 24) included in this study obtained a clinical response, and 30% of patients (n = 12) obtained remission of depression. The group with pharmacological treatment obtained clinical responses in 80% of patients (n = 16) and remission of depression in 45% of patients (n = 9). The group with pharmacological treatment and TMS obtained clinical responses in 40% of patients (n = 8) and remission of depression in 15% (n = 3) of cases.

Conclusions:

The study results show a lack of efficacy for TMS as an adjunctive therapy to pharmacological treatment for patients with depression. In addition, a negative impact of psychotropic medication on TMS efficacy is observed in our study sample.
Risk Factors for Post–Endoscopic Retrograde Cholangio-Pancreatography Pancreatitis in Children With Chronic Pancreatitis and Its Prediction Using 4-Hour Postprocedure Serum Amylase and Lipase Levels
Authors: Samanta Arghya , Vadlapudi Srinivas Srinidhi , Srivastava Anshu , Mohindra Samir , Sen Sarma Moinak , Poddar Ujjal , Saraswat Vivek Anand , Mishra Prabhakar
Published: January 2024

Background

Post–endoscopic retrograde cholangio-pancreatography pancreatitis (PEP) is seen in 3% to 16% of children undergoing therapeutic endoscopic retrograde cholangio-pancreatography (ERCP). We evaluated the risk factors of PEP and utility of 4-hour post-ERCP amylase and lipase for early prediction of PEP in children with chronic pancreatitis (CP).

Materials and Methods

Thirty children with CP (boys 20, 14.3 [interquartile range, 9.3–16] years) who underwent 62 ERCP procedures were studied. Clinical and procedural details with outcome were noted. Serum amylase and lipase were measured before, 4 hours, and 24 hours after ERCP. Multivariate analysis was done to identify risk factors for PEP. Cutoff scores of 4-hour amylase and lipase were identified.

Results

PEP occurred in 14.5% (9/62) of ERCP procedures (mild, 8; moderate, 1) with no mortality. On univariate analysis, endoscopic sphincterotomy (P = 0.04), difficult cannulation (P = 0.004), and prior PEP (P = 0.036) were risk factors, while prior ERCP (P = 0.04) was protective. Difficult cannulation (odds ratio, 5.83; 95% confidence interval, 1.329–25.592) was the independent risk factor on multivariate analysis overall and for first ERCP session alone. Amylase >3.3 times upper limit of normal (ULN) and lipase of >5 times ULN at 4 hours had best sensitivity and specificity for diagnosis of PEP. All cases with PEP were symptomatic by 6 hours and none had amylase/lipase <3 ULN at 4 hours. Amylase/lipase of <3 ULN at 4 hours could exclude PEP with good sensitivity (100%) and specificity (76% and 81%, respectively).

Conclusions

PEP occurred in 14.5% of procedures in children with CP, with difficult cannulation being the independent risk factor. Asymptomatic patients with 4-hour amylase/lipase <3 times ULN can be safely discharged.