bluuebunny/crossref_metadata_2025 huggingface dataset:
The severity of corneal nerve loss differentiates motor subtypes in patients with Parkinson’s disease
Authors: Che Ning-Ning , Jiang Qiu-Huan , Chen Shuai , Chen Si-Yuan , Zhao Zhen-Xiang , Li Xue , Ma Jian-Jun , Zhang Jie-Wen , Malik Rayaz A. , Yang Hong-Qi
Published: April 2023

Background:

Parkinson’s disease (PD) is a heterogeneous movement disorder with patients manifesting with either tremor-dominant (TD) or postural instability and gait disturbance (PIGD) motor subtypes. Small nerve fiber damage occurs in patients with PD and may predict motor progression, but it is not known whether it differs between patients with different motor subtypes.

Objective:

The aim of this study was to explore whether there was an association between the extent of corneal nerve loss and different motor subtypes.

Methods:

Patients with PD classified as TD, PIGD, or mixed subtype underwent detailed clinical and neurological evaluation and corneal confocal microscopy (CCM). Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) were compared between groups, and the association between corneal nerve fiber loss and motor subtypes was investigated.

Results:

Of the 73 patients studied, 29 (40%) had TD, 34 (46%) had PIGD, and 10 (14%) had a mixed subtype. CNFD (no./mm2, 24.09 ± 4.58 versus 28.66 ± 4.27; p < 0.001), CNBD (no./mm2, 28.22 ± 11.11 versus 37.37 ± 12.76; p = 0.015), and CNFL (mm/mm2, 13.11 ± 2.79 versus 16.17 ± 2.37; p < 0.001) were significantly lower in the PIGD group compared with the TD group. Multivariate logistic regression showed that higher CNFD (OR = 1.265, p = 0.019) and CNFL (OR = 1.7060, p = 0.003) were significantly associated with the TD motor subtype. The receiver operating characteristic (ROC) analysis demonstrated that combined corneal nerve metrics showed excellent discrimination between TD and PIGD, with an area under the curve (AUC) of 0.832.

Conclusion:

Greater corneal nerve loss occurs in patients with PIGD compared with TD, and patients with a higher CNFD or CNFL were more likely to have the TD subtype. CCM may have clinical utility in differentiating different motor subtypes in PD.
Correlation of preclinical and clinical biomarkers with efficacy and toxicity of cancer immunotherapy
Authors: Zheng Lin-Peng , Yang Jing , Chen Xie-Wan , Li Ling-Chen , Sun Jian-Guo
Published: April 2023

Immune checkpoint inhibitors (ICIs) have revealed significant clinical values in different solid tumors and hematological malignancy, changing the landscape for the treatment of multiple types of cancer. However, only a subpopulation of patients has obvious tumor response and long-term survival after ICIs treatment, and many patients may experience other undesirable clinical features. Therefore, biomarkers are critical for patients to choose exact optimum therapy. Here, we reviewed existing preclinical and clinical biomarkers of immunotherapeutic efficacy and immune-related adverse events (irAEs). Based on efficacy prediction, pseudoprogression, hyperprogressive disease, or irAEs, these biomarkers were divided into cancer cell-derived biomarkers, tumor microenvironment-derived biomarkers, host-derived biomarkers, peripheral blood biomarkers, and multi-modal model and artificial intelligence assessment-based biomarkers. Furthermore, we describe the relation between ICIs efficacy and irAEs. This review provides the overall perspective of biomarkers of immunotherapeutic outcome and irAEs prediction during ICIs treatment.
Characteristics of Coronial Autopsy Cases in the London Area of the United Kingdom, Pre and Post COVID-19 Lockdown
Authors: Bates Alan W. H.
Published: April 2023

Introduction:

In order to reduce transmission of COVID-19, in March 2020 the UK national and devolved governments imposed restrictions including spatial distancing, stay-at-home orders, and travel restrictions. The aim of this study is to compare the characteristics of cases referred to the Coronial system for autopsy in the months before and during the lockdown period.

Methods:

In all, 580 autopsy cases, performed in the London area between January and June 2020 were included in the study.

Results:

In the postlockdown period, there was an increase in the proportion of black individuals referred for autopsy, which just attained statistical significance ( p = 0.047). The proportion of decomposed bodies submitted for examination was significantly increased ( p = 0.011). The study did not show a significant increase in the proportion of out-of-hospital (community) deaths, traumatic deaths, or deaths due to alcohol or drug abuse or overdose.

Conclusion:

The study shows no evidence that COVID-19 preventative measures led to a change in the causes of death referred to the Coroner, except, of course, for COVID-related deaths. The proportion of black people among subjects for autopsy increased, probably because of a relatively higher incidence of COVID deaths among this group. Decomposed subjects were more common, probably due to social isolation.
Whose Preferred Future Is This? On Possibility, Potential, and Plurality in Visions of the Future
Authors: Joshi Viraj
Published: April 2023

What do the images of our futures tell us about the world we live in? Whose preferred future do we often imagine? That of the people, the planet, or solely made for profits of a few masters? If it is for the benefit of the people, who are they, how much do they benefit, and how will their lives be better? What unforeseen implications might this have for the planet? Speculation is famously a provocative medium that allows us to start crucial conversations without explicitly referring to sensitive anecdotes. In an increasingly polarised and fragmented world, these images hope to spark empathy, and promote a holistic, considerate discourse.
Total Knee Arthroplasty (TKA): When Do the Risks of TKA Overcome the Benefits? Double Risk of Failure in Patients up to 65 Years Old
Authors: Perdisa Francesco , Bordini Barbara , Salerno Manuela , Traina Francesco , Zaffagnini Stefano , Filardo Giuseppe
Published: April 2023

Objective

The aim of this study was to document the survival rate in the middle-aged patient group up to 65 years old and to compare it with other age groups of patients undergoing total knee arthroplasty (TKA) for knee osteoarthritis (OA).

Design

The Register of Orthopaedic Prosthetic Implants (RIPO) regional registry was used to analyze the results of patients <80 years old affected by primary OA and treated with TKA from 2000 to 2019. The database was investigated according to the age group: younger than 50 years, 50-65 years, or 66-79 years, with the aim to estimate revision surgeries and implant survivorship.

Results

A total of 45,488 TKAs for primary OA were included in the analysis (M: 11,388; F: 27,846). The percentage of patients <65 years old increased from 13.5% to 24.8% between 2000 and 2019 ( P < 0.0001). The survival analysis showed an overall influence of age on the implant revision rate ( P < 0.0001), with an estimated survival rate of 78.7%, 89.4%, and 94.8% at 15 years in the 3 groups, respectively. Compared with the older-aged group, the relative risk of failure was 3.1 (95% confidence interval [CI] = 2.2-4.3; P < 0.001) higher in patients <50 years old and 1.8 (95% CI = 1.6-2.0; P < 0.001) higher in patients 50-65 years old.

Conclusions

TKA use in the middle-aged patient population up to 65 years old increased significantly over time. These patients present a double risk of failure with respect to older patients. This is particularly important considering the increasing life expectancy and the emergence of new joint preserving strategies, which could postpone the need for TKA to an older age.
Gender-affirming hormone therapy, mental health, and surgical considerations for aging transgender and gender diverse adults
Authors: Iwamoto Sean J. , Defreyne Justine , Kaoutzanis Christodoulos , Davies Robert D. , Moreau Kerrie L. , Rothman Micol S.
Published: April 2023

As the transgender and gender diverse (TGD) population ages, more transfeminine and transmasculine individuals present to clinic to initiate or continue their gender-affirming care at older ages. Currently available guidelines on gender-affirming care are excellent resources for the provision of gender-affirming hormone therapy (GAHT), primary care, surgery, and mental health care but are limited in their scope as to whether recommendations require tailoring to older TGD adults. Data that inform guideline-recommended management considerations, while informative and increasingly evidence-based, mainly come from studies of younger TGD populations. Whether results from these studies, and therefore recommendations, can or should be extrapolated to aging TGD adults remains to be determined. In this perspective review, we acknowledge the lack of data in older TGD adults and discuss considerations for evaluating cardiovascular disease, hormone-sensitive cancers, bone health and cognitive health, gender-affirming surgery, and mental health in the older TGD population on GAHT.
Variegated Roles of and Relationships Between Private Tutoring and Schooling: Insights From the State of Maharashtra, India
Authors: Bhorkar Shalini
Published: April 2023

Purpose

The relationship between private tutoring (PT) and mainstream education is among the complex themes characterizing PT discourses in the literature. This study examined the complications of practices and processes in tutoring and schooling to elucidate different roles played by PT and its relationship with mainstream education.

Design/Approach/Methods

This study used qualitative data from a diverse set of 37 PT providers from the State of Maharashtra, India, to delineate their roles and explore their relationship with schooling in this context.

Findings

The classification of PT providers’ roles into complementary, accommodating, competing, and substitutive ones demonstrated a diverse range of relationships between PT and mainstream education. Further analysis showed that these relationships are dynamic in nature, and the boundaries between them are blurred.

Originality/Value

Research in the field of PT has been consistently pointing toward a perplexing mixture of positive and negative outcomes resulting from its relationship with mainstream education. This study transcended the positive vis-à-vis negative binary approach by contributing to the deeper understanding of PT relationships. Furthermore, it exemplified how future studies can disentangle the complexities of such relationships by deploying flexible, context-specific theoretical approaches.
Identifying and Decreasing Sharps Injuries Through Root Cause Analysis in a Large Urban Hospital System
Authors: Stallard Christopher , Heaton Karen , Montgomery Aoyjai P. , Trimble Roseann , Hammond Stephanie
Published: April 2023

Background:

Despite safety mandates and interventions, sharps injuries remain an occupational risk for registered nurses (RNs). Sharps and needlestick injuries increase the risk of exposure to blood-borne pathogens. Post-exposure direct and indirect costs of these percutaneous injuries have been estimated at about US$700 per incident. The goal of this quality improvement project was to identify root causes of sharps injuries for RNs at a large urban hospital system.

Methods:

A retrospective evaluation of sharps injuries sustained by RNs, identification epsication of themes or root causes, and the development of a fishbone diagram to sort the causes into categories to identify workable solutions were conducted. Fisher’s exact tests were performed to identify association between variables and root causes.

Findings:

A total of 47 sharps injuries were reported from January 2020 through June 2020. Among sharps injuries sustained by nurses, 68.1% were among nurses 19 to 25 years of age and 57.4% reported job tenure of 1 to 2 years. There was a statistically significant association between root causes and tenure range, gender, and procedure type ( p < .05) with moderate effect size (Cramer’s V = 0.35-0.60). Technique also was a primary cause of sharps injuries for blood draw (77%), discontinuing line (75%), injection (46%), intravenous (IV) start (100%), and suturing (50%).

Conclusions/Applications to Practice:

Technique and patient behavior were primary root causes of sharps injuries in this study. More sharps injuries caused by technique occurred among nurses with job tenure of 1 to 10 years, female, blood draw, discontinuing line, injection, IV start, and suturing procedures. The root cause analysis identified tenure, technique, and behavior as potential root causes of sharps injuries specifically occurring most during blood draw and injections at a large urban hospital system. These findings will inform nurses, especially new nurses in the proper use of safety devices and behaviors to prevent injury.
Health Status, Health Care Access, and Health Information Sources Among Latino Immigrant Cattle Feedyard Workers in the Midwest
Authors: Rowland Sheri A. , Ramos Athena K. , Maiya Sahitya , Carlo Gustavo
Published: April 2023

Background:

Cattle production in the United States is heavily supported by Latino/a workers. Beyond injury rates, our understanding of the health status of cattle feedyard workers is limited. The purpose of this study was to describe the health status and health care access among Latino immigrant cattle feedyard workers in the Midwest.

Methods:

A cross-sectional design using face-to-face structured interviews with Latino immigrant cattle feedyard workers in Kansas and Nebraska was conducted between May 2017 and February 2020.

Findings:

A total of 243 workers completed interviews; 91% were men. Over half (58%) had health insurance but few (36%) had a regular health care provider. Few chronic health conditions were reported despite most being overweight (53%) or obese (37%). The sample mean of sleep hours/24 hours was 7.1 ± 1.1. Problem drinking was moderate (42%), cigarette smoking was low (14%), and drug use was extremely low (<1%). Receiving health information from work was associated with less problem drinking, less obesity, lower blood pressure, and better sleep.

Conclusions:

Although few workers reported having a chronic health condition, most workers had chronic disease risk (i.e., elevated body mass index, problem drinking) and few had a regular health care provider. Receiving health information at work may have protective health effects.

Applications to Practice:

Occupational health professionals can partner with feedyard employers to expand current health and safety training programs beyond injury prevention to focus on health more broadly and to connect workers with local health care resources.
Inspirational and Worthy of Charity: (Mis)Representations of Disability in Sport Media
Authors: Holland Katherine , Holland Steven K. , Haegele Justin A.
Published: April 2023

This study explored how one United States-based sports media company (SMC) represents disability through their Twitter account. A directed content analysis approach was utilized to analyze the tweets of the SMC for calendar year 2019. Of 6080 tweets reviewed, 126 (2.1%) were determined to represent disabled athletes or individuals. 43 (34.1%) tweets represented disabled athletes or individuals in participant roles while 83 (65.9%) represented disabled individuals in spectator or nonathlete roles. The tweets were coded into one of four categories of disability portrayal (Garland-Thomson, 2002): wonderous ( n = 73), sentimental ( n = 43), realistic ( n = 7), and exotic ( n = 3). They were then open coded into relevant subcategories to provide more context. Findings demonstrate that despite the flexibility and opportunity to feature more diverse sports and athletes through one of their social media platforms (Twitter), the SMC chooses to continue the hegemonic practices deployed in their traditional outlets that focus on nondisabled athletes, popular sports, and representing disabled athletes and individuals through ableist and charity-focused narratives. By drawing attention to these inequities, we may be able to promote change and more equitable opportunities for disabled athletes as sports journalism is cemented in digital platforms.
Job Crafting for Workplace Happiness: A Study of Millennials Across Indian Service Sectors
Authors: Moulik Mimi , Giri V. N.
Published: April 2023

The article examines the relationship between proactive job crafting and workplace happiness in the context of millennials associated with the Indian service sector. This study was conducted with 310 millennial employees associated with IT and ITES, telecom, and banking services. The study used self-reporting questionnaires, and the hypotheses were tested using structural equation modeling. The study highlights the nature of job crafting in a hitherto under-researched sector of the Indian economy. The findings suggest that job crafting has a positive influence on driving employee happiness. Crafting structural job resources predicted millennials’ job satisfaction and work engagement. Crafting by seeking social resources and challenging demands was positively associated with commitment and engagement. The study is relevant in the wake of the coronavirus pandemic when organizations are keen to address employee happiness at work. It provides evidence from the Indian service organizations for the implications of adopting job crafting behavior at work to test the adoption of theories developed in the Anglo-Saxon cultures.
Life Satisfaction in a Clinical and a Nonclinical Group of Older People: The Role of Self-Compassion and Social Support
Authors: Yotsidi Vasiliki , Gournellis Rossetos , Alexopoulos Panagiotis , Richardson Clive
Published: April 2023

Despite the health-promoting role of life satisfaction, little is known about its determining factors in older people with mental health problems compared to nonclinical participants. This study provides preliminary data into the role of social support, self-compassion, and meaning in life on older people’s life satisfaction within both clinical and non-clinical populations. In total, 153 older adults (age ≥60) completed the Satisfaction With Life Scale (SWLS), the Self-Compassion Scale (SCS), the Meaning in Life Questionnaire (MLQ), and questions for relational variables. Hierarchical logistic regression analysis revealed that determinants of life satisfaction were self-kindness ( B = 2.036, p = .001) and intimate friends’ network ( B = 2.725, p = .021), while family relationships were found to be significant among the clinical group ( B = 4.556, p = .024). Findings are discussed in relation to incorporating self-kindness and rapport with family in clinical work with older adults to better promote their well-being.
Lessons From The Office: Mismanaged Motivation
Authors: Smith Sockbeson Caitlin E. , Hartman Leigh R. , Shaw John C.
Published: April 2023

Popular culture references have demonstrated usefulness as a pedagogical tool as they enhance student engagement and information retention. Use of the American version of the hit mockumentary TV series The Office has demonstrated pedagogical effectiveness in management, organizational behavior, and human resources courses. The show uses satire to exemplify ineffective management that demonstrates “what not to do.” This resource review suggests the use of video clips from The Office to illustrate equity, expectancy, and goal-setting motivational theories, particularly in undergraduate management courses. Students often struggle with the volume of motivational theories, and the use of humorous clips can help them understand and retain key information. This article includes an overview of the show’s premise, specific scenes that include motivational concepts, motivational theoretical background, and suggested discussion questions and answers.
Noncoding RNAs in asthmatic airway smooth muscle cells
Authors: Xiao Bo , Li Liangxian , Yao Dong , Mo Biwen
Published: April 2023

Asthma is a complex and heterogeneous airway disease caused by genetic, environmental and epigenetic factors treated with hormones and biologics. Irreversible pathological changes to airway smooth muscle cells (ASMCs) such as hyperplasia and hypertrophy can occur in asthmatic patients. Determining the mechanisms responsible is vital for preventing such changes. In recent years, noncoding RNAs (ncRNAs), especially microRNAs, long noncoding RNAs and circular RNAs, have been found to be associated with abnormalities of the ASMCs. This review highlights recent ncRNA research into ASMC pathologies. We present a schematic that illustrates the role of ncRNAs in pathophysiological changes to ASMCs that may be useful in future research in diagnostic and treatment strategies for patients with asthma.
Effective combination of biocompatible zinc oxide nanocrystals and high-energy shock waves for the treatment of colorectal cancer
Authors: Racca Luisa , Rosso Giada , Carofiglio Marco , Fagoonee Sharmila , Mesiano Giulia , Altruda Fiorella , Cauda Valentina
Published: April 2023

Background

Colorectal cancer (CRC) is the third most diagnosed tumor worldwide, with a very high mortality rate, second only to lung cancer. Current treatments, such as surgery, chemotherapy or radiotherapy, are not effective enough and show several limitations. Among the emerging strategies, nanomedicine offers very powerful tools in cancer treatment. Recently, the combination of nanoparticle antitumor effect with a triggering external stimulation was formulated to boost up the cytotoxic activity.

Results

In this work, we show the synergistic effect of oleic acid-capped zinc oxide nanocrystals (ZnO NCs) and mechanical high-energy shock waves (SW) in the treatment for CRC cells, in vitro. We tested two different types of ZnO NCs synthetized in our laboratory, the basal undoped ZnO NCs and the iron-doped ones (Fe:ZnO NCs). The presence of the oleic acid capping and the further amino-propyl functionalization guarantee a high colloidal stability to both NCs, while the iron doping confers to Fe:ZnO NCs interesting magnetic properties useful for imaging applications in a clinical perspective. Thus, the iron-doped ZnO NCs are very attractive as potentially theranostic nanoparticles, allowing both stimuli-responsive therapy and magnetic resonance imaging.

Importantly, two colon adenocarcinoma cell lines, the HT-29 and the Dukes’ type C Colo 320DM cells were tested, both showing a good bio-tolerance and internalization rates of NCs. With the aim of eradicating the CRC cells, the possible synergism between the undoped/iron-doped ZnO NCs and an external physical stimulus, i.e., high-energy SW, was then here investigated in vitro. We demonstrated that the combined treatment resulted in an augmentation of the antitumor activity, especially for Colo 320DM cells, when compared to controls. Moreover, a repeated and sequenced SW treatment (three times/day, 3SW) after ZnO NCs exposure resulted in a further increased mortality of CRC cells.

Conclusion

Our work proposes the combination of the cytotoxic activity of ZnO NCs with the SW external stimulation to obtain a booster of the antitumor activity, which warrants further investigation in vivo on CRC as well as on other tumors.

Graphical Abstract
Reintroducing genetic diversity in populations from cryopreserved material: the case of Abondance, a French local dairy cattle breed
Authors: Jacques Alicia , Leroy Grégoire , Rognon Xavier , Verrier Etienne , Tixier-Boichard Michèle , Restoux Gwendal
Published: April 2023

Background

Genetic diversity is a necessary condition for populations to evolve under natural adaptation, artificial selection, or both. However, genetic diversity is often threatened, in particular in domestic animal populations where artificial selection, genetic drift and inbreeding are strong. In this context, cryopreserved genetic resources are a promising option to reintroduce lost variants and to limit inbreeding. However, while the use of ancient genetic resources is more common in plant breeding, it is less documented in animals due to a longer generation interval, making it difficult to fill the gap in performance due to continuous selection. This study investigates one of the only concrete cases available in animals, for which cryopreserved semen from a bull born in 1977 in a lost lineage was introduced into the breeding scheme of a French local dairy cattle breed, the Abondance breed, more than 20 years later.

Results

We found that this re-introduced bull was genetically distinct with respect to the current population and thus allowed part of the genetic diversity lost over time to be restored. The expected negative gap in milk production due to continuous selection was absorbed in a few years by preferential mating with elite cows. Moreover, the re-use of this bull more than two decades later did not increase the level of inbreeding, and even tended to reduce it by avoiding mating with relatives. Finally, the reintroduction of a bull from a lost lineage in the breeding scheme allowed for improved performance for reproductive abilities, a trait that was less subject to selection in the past.

Conclusions

The use of cryopreserved material is an efficient way to manage the genetic diversity of an animal population, by mitigating the effects of both inbreeding and strong selection. However, attention should be paid to mating of animals to limit the disadvantages associated with incorporating original genetic material, notably a discrepancy in the breeding values for selected traits or an increase in inbreeding. Therefore, careful characterization of the genetic resources available in cryobanks could help to ensure the sustainable management of populations, in particular local or small populations. These results could also be transferred to the conservation of wild threatened populations.
Identifying altered developmental pathways in human globoid cell leukodystrophy iPSCs-derived NSCs using transcriptome profiling
Authors: Lv Yafeng , Qin Yu , Wang Jing , Tian Guoshuai , Wang Wei , Cao Chunyu , Zhang Ye
Published: April 2023

Background

Globoid cell leukodystrophy (GLD) is a devastating neurodegenerative disease characterized by widespread demyelination caused by galactocerebrosidase defects. Changes in GLD pathogenesis occurring at the molecular level have been poorly studied in human-derived neural cells. Patient-derived induced pluripotent stem cells (iPSCs) are a novel disease model for studying disease mechanisms and allow the generation of patient-derived neuronal cells in a dish.

Results

In this study, we identified gene-expression changes in iPSCs and iPSC-derived neural stem cells (NSCs) from a patient with GLD (K-iPSCs/NSCs) and normal control (AF-iPSCs/NSCs), in order to investigate the potential mechanism underlying GLD pathogenesis. We identified 194 (K-iPSCs vs. AF-iPSCs) and 702 (K-NSCs vs. AF-NSCs) significantly dysregulated mRNAs when comparing the indicated groups. We also identified dozens of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway terms that were enriched for the differentially expressed genes. Among them, 25 differentially expressed genes identified by RNA-sequencing analysis were validated using real-time quantitative polymerase chain reaction analysis. Dozens of pathways involved in neuroactive ligand–receptor interactions, synaptic vesicle cycle signaling, serotonergic synapse signaling, phosphatidylinositol–protein kinase B signaling, and cyclic AMP signaling were identified as potential contributors to GLD pathogenesis.

Conclusions

Our results correspond to the fact that mutations in the galactosylceramidase gene may disrupt the identified signaling pathways during neural development, suggesting that alterations in signaling pathways contribute to GLD pathogenesis. At the same time, our results demonstrates that the model based on K-iPSCs is a novel tool that can be used to study the underlying molecular basis of GLD.
Genome-environment associations along elevation gradients in two snowbed species of the North-Eastern Calcareous Alps
Authors: Felkel Sabine , Tremetsberger Karin , Moser Dietmar , Dohm Juliane C. , Himmelbauer Heinz , Winkler Manuela
Published: April 2023

Background

Anthropogenic climate change leads to increasing temperatures and altered precipitation and snowmelt patterns, especially in alpine ecosystems. To understand species’ responses to climate change, assessment of genetic structure and diversity is crucial as the basis for the evaluation of migration patterns, genetic adaptation potential as well as the identification of adaptive alleles.

Results

We studied genetic structure, diversity and genome-environment associations of two snowbed species endemic to the Eastern Alps with a large elevational range, Achillea clusiana Tausch and Campanula pulla L. Genotyping-by-sequencing was employed to assemble loci de novo, call variants and perform population genetic analyses. Populations of either species were distinguishable by mountain, and to some extent by elevation. We found evidence for gene flow between elevations. Results of genome-environment associations suggested similar selective pressures acting on both species, emanating mainly from precipitation and exposition rather than temperature.

Conclusions

Given their genetic structure and amount of gene flow among populations the two study species are suitable to serve as a model for genetic monitoring of climate change adaptation along an elevation gradient. Consequences of climate change will predominantly manifest via changes in precipitation and, thus, duration of snow cover in the snowbeds and indirectly via shrub encroachment accompanied by increasing shading of snowbeds at lower range margins. Assembling genomes of the study species and studying larger sample sizes and time series will be necessary to functionally characterize and validate the herein identified genomic loci putatively involved in adaptive processes.
Median effective dose of esketamine for intranasal premedication in children with congenital heart disease
Authors: Huang Jiajia , Liu Daoqing , Bai Jie , Gu Hongbin
Published: April 2023

Background

Esketamine is commonly used as a premedication for its sedation effect. However, the proper dosage for intranasal use in children with congenital heart disease (CHD) has not been determined. This study aimed to estimate the median effective dose (ED50) of esketamine for intranasal premedication in children with CHD.

Methods

Thirty-four children with CHD who needed premedication in March 2021 were enrolled. Intranasal esketamine was initiated at a dose of 1 mg/kg. Based on the outcome of sedation in the previous patient, the dose for the subsequent patient was either increased or reduced by 0.1 mg/kg, which was adjusted between each child. Successful sedation was defined as a Ramsay Sedation Scale score ≥ 3 and Parental Separation Anxiety Scale score ≤ 2. The required ED50 of esketamine was calculated using the modified sequential method. Non-invasive blood pressure, heart rate, saturation of peripheral oxygen, sedation onset time, and adverse reactions were recorded at 5 min intervals after drug administration.

Results

The 34 children enrolled had a mean age of 22.5 ± 16.4 (4–54) months and a mean weight of 11.2 ± 3.6 (5.5–20.5) kg; American Society of Anesthesiologists classification I–III. The ED50 of intranasal S(+)-ketamine (esketamine) required for preoperative sedation in pediatric patients with CHD was 0.7 (95% confidence interval: 0.54–0.86) mg/kg, and the mean sedation onset time was 16.39 ± 7.24 min. No serious adverse events, such as respiratory distress, nausea, and vomiting were observed.

Conclusions

The ED50 of intranasal esketamine was 0.7 mg/kg, which was safe and effective for preoperative sedation in pediatric patients with CHD.

Trial registration

: The trial was registered in the Chinese Clinical Trial Registry Network (ChiCTR2100044551) on 24/03/2021.
Predicting cholangiocarcinoma in primary sclerosing cholangitis: using artificial intelligence, clinical and laboratory data
Authors: Hu Chang , Iyer Ravishankar K. , Juran Brian D. , McCauley Bryan M. , Atkinson Elizabeth J. , Eaton John E. , Ali Ahmad H. , Lazaridis Konstantinos N.
Published: April 2023

Background

Primary sclerosing cholangitis (PSC) patients have a risk of developing cholangiocarcinoma (CCA). Establishing predictive models for CCA in PSC is important.

Methods

In a large cohort of 1,459 PSC patients seen at Mayo Clinic (1993–2020), we quantified the impact of clinical/laboratory variables on CCA development using univariate and multivariate Cox models and predicted CCA using statistical and artificial intelligence (AI) approaches. We explored plasma bile acid (BA) levels’ predictive power of CCA (subset of 300 patients, BA cohort).

Results

Eight significant risk factors (false discovery rate: 20%) were identified with univariate analysis; prolonged inflammatory bowel disease (IBD) was the most important one. IBD duration, PSC duration, and total bilirubin remained significant (p < 0.05) with multivariate analysis. Clinical/laboratory variables predicted CCA with cross-validated C-indexes of 0.68–0.71 at different time points of disease, significantly better compared to commonly used PSC risk scores. Lower chenodeoxycholic acid, higher conjugated fraction of lithocholic acid and hyodeoxycholic acid, and higher ratio of cholic acid to chenodeoxycholic acid were predictive of CCA. BAs predicted CCA with a cross-validated C-index of 0.66 (std: 0.11, BA cohort), similar to clinical/laboratory variables (C-index = 0.64, std: 0.11, BA cohort). Combining BAs with clinical/laboratory variables leads to the best average C-index of 0.67 (std: 0.13, BA cohort).

Conclusions

In a large PSC cohort, we identified clinical and laboratory risk factors for CCA development and demonstrated the first AI based predictive models that performed significantly better than commonly used PSC risk scores. More predictive data modalities are needed for clinical adoption of these models.
Association between infant birthweight and pelvic floor muscle strength: a population-based cohort study
Authors: Zhu Junyan , Si Junwen , Zhao Lu , Liu Wei
Published: April 2023

Background

To assess the relationship between infant birthweight and pelvic floor muscle (PFM) strength in China.

Methods

We performed a retrospective, single-center cohort study of 1575 women delivering vaginally between January 2017 and May 2020. All participants completed pelvic floor examinations within 5–10 weeks after delivery and were evaluated for PFM strength, which was estimated by vaginal pressure. Data were collected from electronic records. We evaluated the association between infant birthweight and vaginal pressure through multivariable-adjusted linear regression analysis. We also performed subgroup analyses stratified by potential confounders.

Results

Vaginal pressure decreased as the quartile of birthweight increased (P for trend < 0.001). Beta coefficients were -5.04 (95%CI -7.98 to -2.1), -5.53 (95%CI -8.5 to -2.57), -6.07 (95%CI -9.08 to -3.07) for birthweight quartile 2–4, respectively (P for trend < 0.001), independent of age, postpartum hemorrhage, and the number of vaginal deliveries. In addition, the results of subgroup analyses showed the same patterns across strata.

Conclusions

This study demonstrates that infant birthweight was associated with decreased vaginal pressure in women after vaginal delivery and could be considered a risk factor for decreased PFM strength in the population with vaginal delivery. This association may provide an extra basis for appropriate fetal weight control during pregnancy, and for earlier pelvic floor rehabilitation of postpartum women delivering babies with larger birthweight.
Improved uptake and survival with systemic treatments for metastatic non-small cell lung cancer: younger versus older adults
Authors: Leung Bonnie , Shokoohi Aria , Al-Hashami Zamzam , Moore Sara , Pender Alexandra , Wong Selina K. , Wang Ying , Wu Jonn , Ho Cheryl
Published: April 2023

Background

Over the past decade, there has been increasing availability of novel therapeutics with improved tolerability and efficacy for advanced non-small cell lung cancer (NSCLC). The study goals were: to compare the uptake of systemic therapy (ST) before and after the availability of targeted tyrosine kinase inhibitors (TKI) and immunotherapy and to examine the changes in overall survival (OS) over time between younger and older adults with advanced NSCLC.

Methods

All patients with advanced NSCLC referred to British Columbia (BC) Cancer in 2009, 2011, 2015 and 2017 were included. One-year time points were based on molecular testing implementation and funded drug availability: baseline (2009), epidermal growth factor receptor TKI (2011), anaplastic lymphoma kinase TKI (2015) and Programed Death-1 (PD-1) inhibitors (2017). Age groups were <70years and ≥70years. Baseline demographics, simplified comorbidity scores (SCS), disease characteristics, and ST details were collected retrospectively. Variables were compared using X2, Fisher’s exact tests and logistic-regression analysis. OS was calculated using the Kaplan-Meier method and compared using the log-rank test.

Results

3325 patients were identified. Baseline characteristics were compared between ages < 70 years and ≥ 70 years for each time cohort with significant differences noted in baseline Eastern Cooperative Oncology Group (ECOG) performance status and SCS. The rate of ST delivery trended upwards over time with age <70 years: 2009 44%, 2011 53%, 2015 50% and 2017 52% and age ≥70 years: 22%, 25%, 28% and 29% respectively. Predictors for decreased use of ST for age <70 years: ECOG ≥2, SCS ≥9, year 2011, and smoking history; and age ≥70 years: ECOG ≥2, years 2011 and 2015, and smoking history. The median OS of patients who received ST improved from 2009 to 2017: age <70 years 9.1 m vs. 15.5 m and age ≥70 years 11.4 m vs. 15.0 m.

Conclusions

There was an increased uptake of ST for both age groups with the introduction of novel therapeutics. Although a smaller proportion of older adults received ST, those who received treatment had comparable OS to their young counterpart. The benefit of ST in both age groups was seen across the different types of treatments. With careful assessment and selection of appropriate candidates, older adults with advanced NSCLC appear to benefit from ST.
The association between schizophrenia and white blood cells count: a bidirectional two-sample Mendelian randomization study
Authors: Gao Zibo , Li Biao , Guo Xinru , Bai Wei , Kou Changgui
Published: April 2023

Background

Positive associations between the risk of schizophrenia and the level of white blood cells (WBC) count have been suggested by observational studies. However, the causality of this association is still unclear.

Methods

We used a group of bidirectional two-sample Mendelian randomization (MR) analyses to estimate the causal relationship between schizophrenia and WBC count traits (i.e., WBC count, lymphocyte count, neutrophil count, basophil count, eosinophil count, and monocyte count). The threshold of FDR-adjusted P < 0.05 was considered as showing potential evidence of a causal effect. Instrument variables were included based on the genome-wide significance threshold (P < 5 × 10− 8) and linkage disequilibrium (LD) clumping (r2 < 0.01). In total, 81, 95, 85, 87, 76, and 83 schizophrenia-related single nucleotide polymorphisms (SNPs) were used as genetic instruments from Psychiatric Genomics Consortium for six WBC count traits, respectively. And in reverse MR analysis, 458, 206, 408, 468, 473, and 390 variants extracted from six WBC count traits were utilized as genetic instruments, which were obtained from a recent large-scale Genome-Wide Association Study (GWAS).

Results

Genetically predicted schizophrenia was positively associated with the level of WBC count [odds ratio (OR) 1.017, 95% confidence interval (CI) 1.008–1.026; P = 7.53 × 10− 4], basophil count (OR 1.014, 95%CI 1.005–1.022; P = 0.002), eosinophil count (OR 1.021, 95%CI 1.011–1.031; P = 2.77 × 10− 4), monocyte count (OR 1.018, 95%CI 1.009–1.027; P = 4.60 × 10− 4), lymphocyte count (OR 1.021, 95%CI 1.012–1.030; P = 4.51 × 10− 5), and neutrophil count (OR 1.013, 95%CI 1.005–1.022; P = 0.004). WBC count traits are not associated with the risk of schizophrenia in our reverse MR results.

Conclusion

Schizophrenia is associated with elevated levels of WBC count (i.e., higher WBC count, lymphocyte count, neutrophil count, basophil count, eosinophil count, and monocyte count).
Alterations in inflammasome-related immunometabolites in individuals with severe psychiatric disorders
Authors: Hylén Ulrika , Särndahl Eva , Bejerot Susanne , Humble Mats B , Hyötyläinen Tuulia , Salihovic Samira , Eklund Daniel
Published: April 2023

Introduction

Psychiatric disorders are common and significantly impact the quality of life. Inflammatory processes are proposed to contribute to the emergence of psychiatric disorders. In addition to inflammation, disturbances in metabolic pathways have been observed in individuals with different psychiatric disorders. A suggested key player in the interaction between inflammation and metabolism is the Nod-like receptor 3 (NLRP3) inflammasome, and NLRP3 is known to react to a number of specific metabolites. However, little is known about the interplay between these immunometabolites and the NLRP3 inflammasome in mental health disorders.

Aim

To assess the interplay between immunometabolites and inflammasome function in a transdiagnostic cohort of individuals with severe mental disorders.

Methods

Mass spectrometry-based analysis of selected immunometabolites, previously known to affect inflammasome function, were performed in plasma from low-functioning individuals with severe mental disorders (n = 39) and sex and aged-matched healthy controls (n = 39) using a transdiagnostic approach. Mann Whitney U test was used to test differences in immunometabolites between psychiatric patients and controls. To assess the relationship between inflammasome parameters, disease severity, and the immunometabolites, Spearman’s rank-order correlation test was used. Conditional logistic regression was used to control for potential confounding variables. Principal component analysis was performed to explore immunometabolic patterns.

Results

Among the selected immunometabolites (n = 9), serine, glutamine, and lactic acid were significantly higher in the patient group compared to the controls. After adjusting for confounders, the differences remained significant for all three immunometabolites. No significant correlations were found between immunometabolites and disease severity.

Conclusion

Previous research on metabolic changes in mental disorders has not been conclusive. This study shows that severely ill patients have common metabolic perturbations. The changes in serine, glutamine, and lactic acid could constitute a direct contribution to the low-grade inflammation observed in severe psychiatric disorders.
Eosinophilic granulomatosis with polyangiitis developed after dupilumab administration in patients with eosinophilic chronic rhinosinusitis and asthma: a case report
Authors: Suzaki Isao , Tanaka Akihiko , Yanai Ryo , Maruyama Yuki , Kamimura Sawa , Hirano Kojiro , Kobayashi Hitome
Published: April 2023

Background

Eosinophilic granulomatosis with polyangiitis (EGPA) is a form of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis characterized by eosinophil-rich granulomatous inflammation and small-to-medium vessel vasculitis associated with asthma, rhinosinusitis, and eosinophilia. EGPA is often difficult to distinguish from severe asthma and eosinophilic chronic rhinosinusitis (ECRS) in cases when there are no findings that suggest vasculitis. Dupilumab, an anti-IL-4Rα monoclonal antibody, is expected to be effective in eosinophilic airway inflammatory diseases, such as refractory asthma and chronic rhinosinusitis (CRS). Although transient eosinophilia and eosinophilic pneumoniae have been reported in patients with refractory asthma and CRS associated with dupilumab, few studies have examined the development of EGPA.

Case presentation

We report a case of a 61-year-old woman treated with dupilumab for refractory ECRS and eosinophilic otitis media (EOM) complicated by severe asthma. Although she had a previous history of eosinophilic pneumoniae and myeloperoxidase (MPO) ANCA positivity, there were no apparent findings of vasculitis before the initiation of dupilumab. After the second administration of dupilumab, several adverse events developed, including worsening of ECRS, EOM and asthma, and neuropathy. A blood test showed an eosoinophilia and re-elevation of MPO-ANCA levels after the administration of dupilumab. Therefore, dupilumab was discontinued owing to the development of EGPA, and prednisolone and azathioprine administration was initiated for a remission induction therapy.

Conclusion

To the best of our knowledge, this is the first case report that suggests that dupilumab may directly trigger the manifestation of vasculitis in patients who were previously MPO-ANCA-positive. Although the precise mechanism of how dupilumab could trigger the development of EGPA requires further elucidation, measuring MPO-ANCA in patients with multiple eosinophilic disorders before the initiation of dupilumab might be helpful when considering the possibility of a latent EGPA. When administering dupilumab to patients with a previous history of MPO-ANCA positivity, clinicians must carefully monitor and collaborate with other specialists in the pertinent fields of study for appropriate usage.
Concentrated growth factor combined with iRoot BP Plus promotes inflamed pulp repair: an in vitro and in vivo study
Authors: Zeng Qian , Zhou Can , Li Mengjie , Qiu Yu , Wei Xi , Liu Hongyan
Published: April 2023

Background

Platelet concentrates combined with calcium silicate cements may promote reparative dentin formation. However, few studies have reported their effect on dental pulp inflammation. This study aimed to evaluate the effects of concentrated growth factor (CGF) combined with iRoot BP Plus on inflammatory human dental pulp stem cells (hDPSCs) in vitro and inflamed pulp in rats in vivo.

Methods

The proliferation of LPS-stimulated hDPSCs treated with 50% CGF with/without 25% iRoot BP Plus was evaluated using Cell Counting Kit-8 on days 1, 4 and 7. The expression of genes associated with inflammation on day 1 and differentiation on day 14 was analysed by real-time polymerase chain reaction. The exposed pulp of rat maxillary molars was injected with 10 mg/mL LPS and directly capped with CGF membrane with/without iRoot BP Plus extract for 1, 7 and 28 days. The teeth were subjected to histologic analyses and immunohistochemistry.

Results

The proliferation rates of the inflammatory hDPSCs after the combination treatment were significantly higher than those after the other treatments on days 4 and 7 (P < 0.05). IL-1β, IL-6, and TNF-α levels were increased in inflammatory hDPSCs but decreased after treatment with CGF combined with iRoot BP Plus extract, whereas IL-4 and IL-10 showed the opposite expression patterns. Expression of the odontogenesis-related genes OCN, Runx2, and ALP was dramatically enhanced by combined treatment with CGF and iRoot BP Plus extract. In rat pulp, the average inflammation scores of the CGF and CGF-iRoot BP Plus groups significantly decreased in comparison with those of the LPS group (P < 0.05), and the CGF-iRoot BP Plus group had more reparative dentin than the CGF and BP groups. Immunohistochemical staining showed fewer M1 macrophages on day 1 and more M2 macrophages on day 7 in the CGF-iRoot BP Plus group than in the other groups.

Conclusions

The combination of CGF and iRoot BP Plus showed a synergistic effect on anti-inflammatory potential and promoted greater pulp healing than CGF or iRoot BP Plus alone.