bluuebunny/crossref_metadata_2025 huggingface dataset:
Azacitidine as a rare cause of reactive arthritis in a patient with acute myeloid leukemia
Authors: Alsaadi Daniah , Low Lyndon , Zubairu Mustafa , Clesham Kevin , Rowan Fiachra
Published: June 2023

Introduction

Azacitidine (AZA), a demethylating agent, is one of the mainstay treatments for patients with myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) who are ineligible for curative allogeneic stem-cell transplantation and is recommended as first-line treatment in multiple countries. While arthralgia and myalgia have been commonly reported as side effects, the incidence of drug-induced reactive arthritis has only been reported twice so far.

Case report

We present a retrospective overview of a clinical case of a 71-year-old patient that developed new cytopenias on a background of Chronic Lymphocytic Leukaemia and was diagnosed with therapy-associated AML. His treatment included an indefinite course of AZA to induce remission and optimise long-term survival which resulted in a satisfactory haematological response. However, after his ninth AZA cycle, he presented to the emergency department with knee swelling and erythema and conjunctivitis.

Management and outcomes

Arthrocentesis of the knee revealed reactive arthritis with no crystal or organism growth. His symptoms were managed effectively with conservative management including NSAIDs, analgesia and temporary immobilization for joint rest. The adverse drug reaction probability score in our study was calculated as six and adverse drug reaction was thus assigned to the “probable” category.

Conclusion

We report a case that points to AZA as a probable cause of arthritis flares in MDS patients. The current limitation of this study is the lack of available data, future reviews and research will aid in providing stronger evidence of a correlation between arthritis and AZA treatment.
The electro-mechanics of piezoelectric coating structure under frictional contacts
Authors: Xiao Jin-Xin , Jiang Tian-Lin , Hou Peng-Fei , Zhang Wen-Hua
Published: June 2023

In papers of the piezoelectric coating/substrate system under smooth spherical contact (DOI: 10.1177/1081 286519 865773), conical contact (DOI: 10.1016/j.ijsolstr.2019.08.031), and cylinder flat head contact (DOI: 10.1007/s11012-019-01085-1), Green’s function method has been applied to solve the problem of piezoelectric friction contact. We deduced the analytical expression of piezoelectric coating structure, which is expressed by elementary functions. The numerical results highlight the best thickness to maintain a higher potential difference and a critical potential difference. This study has guiding significance for the future research and analysis of friction signals in intelligent manufacturing, such as piezoelectric tactile sensors.
Assessing Fear, Embarrassment, and Disgust in Colonoscopy: The Development of Measurement Instruments and Psychometric Evidence
Authors: Peng Wei , McKinnon-Crowley Jocelyn , Huang Qian , Mao Bingjing
Published: June 2023

Background

Avoidance of colonoscopy is often associated with fear, embarrassment, and disgust aroused in screening procedures. However, each emotion can be linked to different challenges faced by patients. More research is needed to evaluate and address the causes of these respective emotions.

Aim

The purpose of this study was to develop and assess the scales of three negative emotions (i.e., fear, embarrassment, and disgust) caused by specific issues in colonoscopy screening.

Method

The measurement items were developed based on multiple common barriers in colonoscopy screening procedures. An online sample of 232 adults aged 45-75 was recruited from Amazon Mechanical Turk to test the scales. Explorative and confirmatory factor analyses were conducted to validate the measurement models.

Results

Psychometric evidence demonstrated the factor structures of three negative emotions. Each emotional factor was caused by unique combinations of barriers in the preparation, screening, and recovery stages of colonoscopy. Most of the emotional factors were associated with attitudes and screening intention.

Conclusion

This study showed different dimensions of negative emotions and their underlying causes in colonoscopy. These findings will help assess specific causes of negative emotions in colonoscopy and develop effective interventions to improve screening uptake.
Value of 1-Hour Plasma Glucose During an Oral Glucose Tolerance Test in a Multiethnic Cohort of Obese Children and Adolescents
Authors: Brar Preneet Cheema , Mehta Shilpa , Brar Ajay , Pierce Kristyn A , Albano Alesandro , Bergman Michael
Published: June 2023

One hour plasma glucose (1-hr PG) concentration during an oral glucose tolerance test (OGTT) is steadily emerging as an independent predictor of type 2 diabetes (T2D).

Methods:

We applied the current cut off thresholds reported in the pediatric literature for the 1-hr PG, 132.5 (7.4 mmol/l) and 155 mg/dL (8.6 mmol/l) during an OGTT, to report abnormal glucose tolerance (AGT) using ROC curve analyses. We determined the empirical optimal cut point for 1-hr PG for our multi ethnic cohort using the Youden Index.

Results:

About 1-hour and 2-hours plasma glucose showed the highest predictive potential based on Areas under the curve (AUC) values of 0.91 [CI: 0.85, 0.97] and 1 [CI: 1, 1], respectively. Further comparison of the ROC curves of the 1-hour and 2-hour PG measurements as predictors of an abnormal OGTT showed that their associated AUCs differed significantly ( X2(1) = 9.25, P < .05). Using 132.5 mg/dL as the cutoff point for plasma glucose at 1-hour yielded a ROC curve with an AUC of 0.796, a sensitivity of 88%, and a specificity of 71.2%. Alternatively, the cutoff point of 155 mg/dL resulted in a ROC AUC of 0.852, a sensitivity of 80%, and a specificity of 90.4%.

Conclusion:

Our cross-sectional study affirms that the 1-hr PG can identify obese children and adolescents at increased risk for prediabetes and/or T2D with almost the same accuracy as a 2-hr PG. In our multi-ethnic cohort, a 1-hr PG ⩾ 155 mg/dL (8.6 mmol/l) serves as an optimal cut-point, using the estimation of the Youden index with AUC of 0.86 and sensitivity of 80%.We support the petition to consider the 1-hr PG as integral during an OGTT, as this adds value to the interpretation of the OGTT beyond the fasting and 2-hr PG.
Clinical course of multiple sclerosis and patient experiences during breast cancer treatment
Authors: Nylander Alyssa N , Singh Jessica , Poole Shane , Anderson Annika , Marrie Ruth Ann , Rugo Hope , Bove Riley
Published: June 2023

Background:

Over one-third of multiple sclerosis (MS) patients are post-menopausal women, the primary demographic affected by breast cancer. After breast cancer diagnosis, there is little information about patients’ clinical experiences with both diseases.

Objective:

Utilize a case series of MS patients diagnosed with breast cancer to characterize oncologic and MS trajectories, and generate novel insights about clinical considerations using qualitative analysis.

Methods:

A single-center retrospective review was performed on medical record data of patients with MS and breast cancer. Thematic analysis was used to characterize experiences with the concurrent diagnoses.

Results:

For the 43 patients identified, mean age was 56.7 years at cancer diagnosis and MS duration was 16.5 years. Approximately half were treated with MS disease modifying therapy at cancer diagnosis, and half of these subsequently discontinued or changed therapy. Altogether 14% experienced MS relapse(s) during follow-up (with 2 relapses in the first 2 years), with mean annualized relapse rate of 0.03. Cohort Expanded Disability Status Scale (EDSS) scores remained stable during follow-up. Qualitative insights unique to this population were identified regarding immunosuppression use and neurologic symptoms.

Conclusions:

MS relapses were infrequent, and there was modest progression during breast cancer treatment. Oncologic outcomes were comparable to non-MS patients with similarly staged cancer.
Chronic stroke survivors’ perspective on the use of serious games to motivate upper limb rehabilitation – a qualitative study
Authors: Amorim Paula , Serra Helder , Sousa Beatriz Santos , Dias Paulo , Castelo-Branco Miguel , Martins Henrique
Published: June 2023

Upper limb paresis occurs quite commonly after stroke and may result in the affected limb’s disuse or learned non-use. As a result, its cortical representation may be suppressed, further inhibiting its spontaneous utilization, resulting in motor function deterioration, increase in spasticity, joint stiffness and pain.

The aim of this work was to involve stroke survivors in a qualitative study within a user centred design process to better understand the perspectives of stroke survivors on virtual reality - based serious games (SG) for upper limb rehabilitation during the chronic phase and use those insights to design a VR-based serious games which promotes activation of the affected cortical area.

A qualitative research method was performed using a multi professional focus group discussion, including a representative group of stroke survivors.

With the insights of this work, the authors initiated the design of a VR-based SG prototype for upper limb rehabilitation with two modes, one version to be played with any arm to pick a virtual hammer and hit targeted objects, and other version, a mirror version based on mirror therapy.
Welfare as flourishing social reproduction: Polish and Ukrainian migrant workers in a market-participation society
Authors: Plomien Ania , Schwartz Gregory
Published: June 2023

The historical link between labour and welfare is increasingly considered in the transnational register, largely because labour mobilities demand a rethinking of nation-based social protection systems. Transnational labour mobilities also illuminate other dimensions of boundary-crossing, including formality–informality, citizenship–non-citizenship and production–reproduction. These additional considerations call for going beyond the problem of transnational welfare access. We argue that the prism of social reproduction enables such a rethinking of the labour–welfare relationship. In this article, we conceptualise an expanded notion of welfare as flourishing social reproduction, in contradistinction to the principle of welfare deriving primarily from paid work and labour market participation. We apply this theorisation of welfare to our qualitative case study of the experiences and interests of Polish and Ukrainian migrant workers in Germany, Poland and the United Kingdom employed in care provision, food production and housing construction sectors. In the geopolitical setting of uneven and combined Europe, embodying high levels of differentiation together with advanced transnational social protection, we explore the role of differentiation of migrants in labour markets (along work, migration and citizenship axes) and the extent to which transnational mobility facilitates the improvement of social reproduction. While the low-waged labour of Polish and Ukrainian men and women working in care, food and housing furnishes their own and local workers’ social reproduction needs, we find that migrant workers’ welfare as flourishing social reproduction remains wanting, even for those with already privileged access to the current ‘gold-standard’ transnational social protection offered by the EUs freedoms of movement framework. Welfare remains centred on individualised paid work logic, leaving a vast range of needs unmet and work and workers excluded, bearing implications for prevalent transnational social protection efforts.
MHD micropolar fluid flow in porous media
Authors: Kocić Miloš , Stamenković Živojin , Petrović Jelena , Bogdanović-Jovanović Jasmina
Published: June 2023

The analysis of mass and heat transfer in magnetohydrodynamic (MHD) flows has significant applications in heat exchangers, cooling nuclear reactors, designing energy systems and casting and injection processes of different types of fluids. On the other hand, extraction of crude oil, the flow of human or animal blood, as well as other polymer fluids or liquid crystals are just some examples of micropolar fluid flows. Due to the broad application spectrum of the theory of micropolar fluid flows, and the significance the impact the external magnetic field has on the flow of these fluids, this paper considers the stationary flow of a micropolar fluid between two plates under the influence of an external magnetic field which is perpendicular to the direction of the flow. Stationary plates are maintained at constant and different temperatures, while the whole problem is considered in the non-inductive approximation. The equation system used to define the physical problem under consideration is reduced to the system of differential equations that have been solved analytically and the solutions of which are of general nature. In addition to the solutions for velocity, microrotation and temperature, the paper gives solutions for shear stress at plates, the Nusselt number and flow rate. The provided solutions have been applied in order to reach some general conclusions about the influence of the magnetic field and physical characteristics of a micropolar fluid and the characteristics of porous media on the nature of micropolar fluid flows in porous media by means of chart analysis. General conclusions, obtained in the result analysis in this paper, give us the opportunity to understand the flows of micropolar fluids and highlight their significance.
Lightweight design of temporary support device of rectangular shield for the robot system of coal mine roadway excavation
Authors: Ma Hongwei , Wang Jianke , Wang Chuanwei , Zhang Heng , Xue Xusheng , Liu Peng , Tian Haibo
Published: June 2023

Owing to the existing problems of the temporary shield support device in a coal mine, such as considerable component weight, difficult disassembly, and large chamber installation, the design of the temporary rectangular shield support device was optimized. A module division method combining the functional analysis method and a similar feature clustering method was proposed, which completes the division of the functional module and establishes the structural module. A structural optimization method of “variable density topology optimization, parameter sensitivity analysis and Optimal Space-Filling Design (OSF)” was proposed. A variable-density topology optimization model of the device was established using the variable-density topology optimization method. The key variables of the device were determined using a parameter sensitivity analysis. The sample points of the critical variables were generated using the optimal space-filling design method, the approximate response surface models of mass, displacement, and stress were constructed, and the optimal solution of the device’s weight was obtained under the constraint conditions of pressure and displacement. A lightweight matching method of modularization based on transportability, disassembly, maintainability, and reliability was proposed, and the optimal matching scheme for the volume and mass of the device was determined. As a result, the weight of the temporary shield support device was reduced by 11.2%, and the maximum stress was reduced by 13.4%, under the premise of ensuring reliability. It realizes the convenience of transportation and high efficiency of assembly and disassembly in different design requirements, which is of great significance to accelerate the intelligent construction of coal mine.
Ecological Momentary Assessment and Personalized Networks in Cognitive Bias Modification Studies on Addiction: Advances and Challenges
Authors: Mansueto Alessandra C. , Pan Ting , van Dessel Pieter , Wiers Reinout W.
Published: June 2023

Adding cognitive bias modification (CBM) to treatment as usual for alcohol use disorders has been found to reduce relapse rates. However, CBM has not yielded effects as a stand-alone intervention. One possible reason may be that this is due to CBM effects being underpinned by inferential rather than associative mental mechanisms. This change in perspective has led to a proposed improved version of CBM: Inference-based ABC training. In ABC training, participants learn to relate the antecedents (A) of their addiction behavior to alternative behaviors (B) and to their expected consequences (C) in relation to their long-term goals. Mechanisms triggering and maintaining addiction, such as those targeted during ABC training, can differ between people. Ecological Momentary Assessment (EMA) and derived personalized statistics, including models depicting relationships between variables (i.e., personalized networks), are therefore promising tools to help to optimally personalize this training. In this paper, we (1) explain the theoretical background and first implementations of ABC training; (2) present novel approaches to personalize treatment based on EMA; (3) propose ways forward to integrate improved CBM approaches and EMA to potentially advance addiction treatment; and (4) discuss promises and challenges of these proposed new approaches.
Surgical Versus Non-Surgical Treatment for Thoracolumbar Burst Fractures Without Neurological Deficit: A Systematic Review and Meta-Analysis
Authors: Chou Tzu-Yi , Tsuang Fon-Yih , Hsu Yu-Lun , Chai Chung Liang
Published: June 2023

Study Design

A systematic review and meta-analysis.

Objective

To update the systematic review comparing the outcomes between surgical and non-surgical treatment for thoracolumbar burst fractures without neurological deficit.

Methods

We registered a protocol in PROSPERO (ID: CRD42021291769) and searched Medline, Embase, Web of Science, and Google Scholar databases. Surgical and non-surgical treatments were compared in patients with thoracolumbar burst fractures without neurological deficits. Predefined outcomes at ≥6 months included pain (defined as a visual analog scale [VAS] of 0-100), functional outcomes (Oswestry Disability Index [ODI] of 0-50 and Roland-Morris Disability Questionnaire [RMDQ] of 0-24), and kyphotic angulation.

Results

Nineteen studies involving 1056 patients were included in the analyses. For outcomes at ≥6 months, little to no difference was found in pain VAS score (mean difference, .95 [95% confidence interval {CI}, -6.02 to 7.92]; 827 participants; 15 studies; I2 = 92%), ODI (mean difference, -1.40 [95% CI, -5.11 to 2.31]; 446 participants; 7 studies; I2 = 79%), and RMDQ (mean difference, -.73 [95% CI, -5.13 to 3.66]; 216 participants; 5 studies; I2 = 77%). The kyphotic angulation in the surgery group was 6.35° lower than that in the non-surgery group (mean difference, -6.56° [95% CI, -10.26° to -2.87°]; 527 participants; ten studies; I2 = 86%). The trial sequential analysis indicated all outcomes reached adequate statistical power. The certainty of the evidence for all 4 outcomes was very low. For the analysis of minimally invasive procedures compared to traditional open surgeries, a statistically significant subgroup difference was found for VAS and ODI ( P < .01 and P < .04, respectively).

Conclusion

Surgical and non-surgical treatments showed little or no difference in outcomes at ≥6 months. This review provides a conclusion with adequate statistical power by including non-randomized studies. However, non-randomized studies also lowered the certainty of the evidence to a very low level.
Predicting the Symmetric and Asymmetric Volatility of Energy Market: Evidence from COVID Outbreak in India and USA
Authors: Panwar Kajal , Yadav Miklesh Prasad , Puri Neha
Published: June 2023

The COVID-19 pandemic had a tremendous impact on the energy sector because of demand factor. Volatility has emerged as a major concern in the energy industry and COVID-19 has cast a dark shadow over this characteristic. We predict the symmetrical and asymmetric volatility of energy market in India and USA during COVID-19 outbreak tenure. The energy market is proxied by crude oil and natural gas of these two countries. For an empirical estimation, standard generalized autoregressive conditional heteroscedasticity (s-GARCH) and exponential GARCH (e-GARCH) are employed based on daily observations spanning from March 25, 2020 to January 31, 2022. The result reveals that new information is captured and there is volatility persistence in both Indian and US energy markets. The conditional volatility decays over the time of these markets since it is backed by mean reversion and Indian energy market decays fast comparatively. Additionally, it depicts that there is no leverage effect in both Indian and US energy markets. This study furnishes an insight to the investors and portfolio managers with respect to risk prediction considering impact of good and bad news.
The Relationship Between Board Structure and Human Resource Disclosure Practices: A Study of Indian Companies
Authors: Aggarwal Kirti
Published: June 2023

The objective of the present study is to examine the effect of board structure on human resource disclosure index (HRDI) in Indian listed companies. The present study is based on companies listed on NSE-200 Index. The final sample includes 126 companies for the period of ranging from F.Y. 2012–2013 to 2018–2019. The data of variables are collected from annual reports of the sample companies. In the analysis part, the descriptive statistics are used to check the level of human resource disclosures. After that, Pearson’s correlation matrix is applied for checking the correlation between board variables and HRDI. At last, to check the effect of board structure on HRDI, the one-way least square dummy variable (LSDV) regression model is applied. The outcomes of descriptive statistics show that the mean percentage of HRDI is 43.86. It lies on moderate side. Further, the outcomes of one-way LSDV regression model show that there is significant positive effect of board size, board meeting and audit committee on HRDI. In contrast, there is insignificant but positive effect of board independence, CEO duality on the level of human resource disclosure of the sample companies. Overall, it can be said that the human resource disclosure practice of the Indian companies is fairly good.
Pandemic Job Separation and Psychological Distress: Modeling Chains of Adversity
Authors: Hill Terrence D. , Leppard Tom R. , Miller Michael V. , Davis Andrew P. , Zapata Veronica R.
Published: June 2023

Although recent studies have linked pandemic unemployment with poorer mental health, the mechanisms underlying this association remain understudied. In this paper, we develop a mediation model to explain why pandemic job separation might undermine mental health. Using national data from the 2021 Crime, Health, and Politics Survey (n = 1,258), we test the indirect effects of pandemic job separation on psychological distress through several mechanisms. Mediation analyses reveal compound indirect effects of pandemic job separation on psychological distress through the primary pathway of financial strain and the secondary pathways of social support, self-esteem, mastery, religious struggles, and sleep disturbance. Absent the indirect effect of pandemic job separation through financial strain, we would have failed to observe any simple indirect effects through the other proposed mechanisms. Formal moderated mediation analyses also indicate that our observed indirect effects are invariant to subgroup differences in current employment status, education, and household income. In short, our indirect effects are observed for those respondents who were able to regain employment, those with college degrees, and those with the most financial resources. Our results suggest that the temporary expansion of public assistance has been insufficient to offset widespread unemployment and financial hardship during a global pandemic.
Willingness of Older Adults From Culturally Diverse Populations to Participate in COVID-19 Related Treatment Trials and Associated Factors
Authors: Brown Ellen Leslie , Paul-Ward Amy , Felber Neff Donna , Webb Fern J. , Vieira Edgar Ramos , Gaillard Trudy
Published: June 2023

This survey study aimed to assess the willingness of culturally diverse older adults to participate in COVID-19 research. The majority of the 276 participants were women (81%, n = 223) and Black/African American (62%, n = 172) or White Hispanic (20%, n = 56). A key finding from the survey was less than 1 of 10 respondents would be likely to participate in COVID-19 related research if given the opportunity. There were no differences observed by gender, race or ethnicity. Implications of these findings are considered. These study findings indicate continued effort and better messaging strategies are required to increase awareness that COVID-19 related research needs to include culturally diverse older adults to ensure vaccines and treatments are efficacious in different populations.
Status and Educational Effects of Practical Nursing Training for Medical Students as Part of Interprofessional Education
Authors: Igarashi Ryoko
Published: June 2023

Objectives

The WHO has recognized the importance of multidisciplinary education and recommended its promotion worldwide. In our medical school, students experience practical nursing training in their first year to promote multidisciplinary education. Herein, we clarified the learning experiences of medical students during a practical nursing training for enhancing multidisciplinary collaborative education.

Methods

A questionnaire about nursing practice was conducted after training completion. Regarding attitudes during the training, the nurses in charge of shadowing evaluated the students, and the students also evaluated themselves. The survey results were analyzed qualitatively, and the attitude evaluation results quantitatively.

Results

There were 76 students who provided informed consent, of whom 55 completed the survey. Three main learning areas were extracted from survey: Nursing treatment, support, and communication activities (7 categories), Nursing care for hospitalized patients (3 categories), Multidisciplinary collaboration through effective communication and coordination (2 categories). On the first training day, the scores of evaluation by others were higher than those of self-evaluation in 6 items. On the second day, the scores of self-evaluation were higher than those of evaluation by others in “Actively learning” and “Communicating appropriately with medical staff and patients.”

Conclusion

Through the training, students learned about Nursing treatment, support, and communication activities; Nursing care for hospitalized patients; and Multidisciplinary collaboration through effective communication and coordination. The training enabled the students to understand the doctors’ roles in the clinical setting, and to reflect on what doctors should be. Leaning from nursing training is highly beneficial for medical students.
Morphology and Variant Anatomy of the Mandibular Canal in a Kenyan Population: A Cone-Beam Computed Tomography Study
Authors: Okiriamu Andrew , Butt Fawzia , Opondo Florence , Onyango Fredrick
Published: June 2023

Study Design

Descriptive cross-sectional study.

Objective

The mandibular canal (MC) exhibits surgically significant anatomical variations in its course and terminal segment among different ethnic groups. The aim of this study was to document a surgically relevant position of the MC, its variants, and related anatomical structures in dentate patients from a select Kenyan population.

Methods

351 hemi mandibular cone-beam computed tomography (CBCT) scans from 202 patients were used to evaluate the MC and mental foramen (MF) for normal morphology, anatomical variations, and their linear relationship to various reference points.

Results

The most frequently encountered course of the MC was the progressive descent type seen in 241 (68.7%) scans. Accessory MC were observed in 15 (4.3%) scans. Accessory MF were observed in 29 (8.3%) scans. The mean diameter of the MC was 3.36 ± .39 mm. The orientation of the MC was more lingual towards the angle of the mandible and more buccal towards the MF. The most frequent position of the main MF in relation to the second premolar was anterior (53.3%). The average distance from the MF to the inferior border of the mandible was 12.17 ± 1.91 mm. The anterior loop of the mental nerve was observed in 18 (5.1%) scans and its mean length was 4.83 ± .89 mm.

Conclusions

Our study revealed significant variations in the position, size, and course of the MC and MF. This knowledge should assist oral surgeons to avoid inadvertent injury to the inferior alveolar neurovascular bundle in the local population.
Infectious neutrophil deployment is regulated by resolvin D4
Authors: Libreros Stephania , Nshimiyimana Robert , Lee Brendon , Serhan Charles N.
Published: June 2023

Neutrophils reside in the bone marrow (BM), ready for deployment to sites of injury/infection, initiating inflammation and its resolution. Here, we report that distal infections signal to the BM via resolvins to regulate granulopoiesis and BM neutrophil deployment. Emergency granulopoiesis during peritonitis evoked changes in BM resolvin D1 (RvD1) and BM RvD4. We found that leukotriene B4 stimulates neutrophil deployment. RvD1 and RvD4 each limited neutrophilic infiltration to infections, and differently regulated BM myeloid populations: RvD1 increased reparative monocytes, and RvD4 regulated granulocytes. RvD4 disengaged emergency granulopoiesis, prevented excess BM neutrophil deployment, and acted on granulocyte progenitors. RvD4 also stimulated exudate neutrophil, monocyte, and macrophage phagocytosis, and enhanced bacterial clearance. This mediator accelerated both neutrophil apoptosis and clearance by macrophages, thus expediting the resolution phase of inflammation. RvD4 stimulated phosphorylation of ERK1/2 and STAT3 in human BM-aspirate–derived granulocytes. RvD4 in the 1 to 100 nM range stimulated whole-blood neutrophil phagocytosis of Escherichia coli. RvD4 increased BM macrophage efferocytosis of neutrophils. Together, these results demonstrate the novel functions of resolvins in granulopoiesis and neutrophil deployment, contributing to the resolution of infectious inflammation.
Lipid nanoparticles allow efficient and harmless ex vivo gene editing of human hematopoietic cells
Authors: Vavassori Valentina , Ferrari Samuele , Beretta Stefano , Asperti Claudia , Albano Luisa , Annoni Andrea , Gaddoni Chiara , Varesi Angelica , Soldi Monica , Cuomo Alessandro , Bonaldi Tiziana , Radrizzani Marina , Merelli Ivan , Naldini Luigi
Published: June 2023

Ex vivo gene editing in T cells and hematopoietic stem/progenitor cells (HSPCs) holds promise for treating diseases. Gene editing encompasses the delivery of a programmable editor RNA or ribonucleoprotein, often achieved ex vivo via electroporation, and when aiming for homology-driven correction of a DNA template, often provided by viral vectors together with a nuclease editor. Although HSPCs activate a robust p53-dependent DNA damage response upon nuclease-based editing, the responses triggered in T cells remain poorly characterized. Here, we performed comprehensive multiomics analyses and found that electroporation is the main culprit of cytotoxicity in T cells, causing death and cell cycle delay, perturbing metabolism, and inducing an inflammatory response. Nuclease RNA delivery using lipid nanoparticles (LNPs) nearly abolished cell death and ameliorated cell growth, improving tolerance to the procedure and yielding a higher number of edited cells compared with using electroporation. Transient transcriptomic changes upon LNP treatment were mostly caused by cellular loading with exogenous cholesterol, whose potentially detrimental impact could be overcome by limiting exposure. Notably, LNP-based HSPC editing dampened p53 pathway induction and supported higher clonogenic activity and similar or higher reconstitution by long-term repopulating HSPCs compared with electroporation, reaching comparable editing efficiencies. Overall, LNPs may allow efficient and harmless ex vivo gene editing in hematopoietic cells for the treatment of human diseases.
Exploring the experiences of people living with dementia in Dementia Friendly Communities (DFCs) in Northern Ireland: a realist evaluation protocol
Authors: Craig Stephanie , Mitchell Gary , Halloran Peter O’ , Stark Patrick , Wilson Christine Brown
Published: June 2023

Background

The aim of this study is to 1) explore the experiences of people living with dementia interacting with DFCs and 2) identify factors that influence empower and support people living with dementia to live successfully in DFCs. The main elements of a DFC are related to people; communities; organisations and partnerships. There are over 200 organisations recognised as dementia-friendly in Northern Ireland (NI). This realist evaluation is to understand how DFCs work for people living with dementia, how positive outcomes are achieved, for whom and in what contexts do DFCs work best.

Methods

A realist evaluation using case study methodology. The process evaluation includes a realist review of the literature, non-participant observation of people living with dementia in their local communities, semi-structured interviews to explore the facilitators and barriers to living well in DFCs and focus groups comprised of people living with dementia, family caregivers and people working in DFCs to support Context- Mechanisms and Outcomes (CMOs). This four-stage realist assessment cycle is used, including iterative rounds of theory development, data gathering, and theory testing. In the end, analysis will reveal context mechanisms that influence how dementia-friendly communities operate and present an initial theory of how people think, which, if adopted, may be able to alter current contexts so that "key" mechanisms are activated to generate desired outcomes.

Discussion

To give confidence in moving from hypothetical constructions about how DFCs could function to explanations of possible or observable causal mechanisms, the realist evaluation of a complex intervention incorporates a variety of evidence and perspectives. Despite playing a significant role in a person with dementia's everyday life, it appears that little is known about how communities function to achieve intended results. Even though there has been a lot of work to pinpoint the fundamentals and crucial phases of building DFCs, it is still unclear how people living with dementia benefit the most from these communities. This study intends to advance our understanding of how outcomes are produced for people living with dementia by contributing to the underlying theory of DFCs as well as addressing the primary research objectives.
Adding epitope compatibility to deceased donor kidney allocation criteria: recommendations from a pan-Canadian online public deliberation
Authors: Edwards Louisa , Bentley Colene , Burgess Michael , Sapir-Pichhadze Ruth , Hartell David , Keown Paul , Bryan Stirling
Published: June 2023

Background

The widening supply–demand imbalance for kidneys necessitates finding ways to reduce rejection and improve transplant outcomes. Human leukocyte antigen (HLA) epitope compatibility between donor and recipient may minimize premature graft loss and prolong survival, but incorporating this strategy to deceased donor allocation criteria prioritizes transplant outcomes over wait times. An online public deliberation was held to identify acceptable trade-offs when implementing epitope compatibility to guide Canadian policymakers and health professionals in deciding how best to allocate kidneys fairly.

Methods

Invitations were mailed to 35,000 randomly-selected Canadian households, with over-sampling of rural/remote locations. Participants were selected for socio-demographic diversity and geographic representation. Five two-hour online sessions were held from November–December 2021. Participants received an information booklet and heard from expert speakers prior to deliberating on how to fairly implement epitope compatibility for transplant candidates and governance issues. Participants collectively generated and voted on recommendations. In the final session, kidney donation and allocation policymakers engaged with participants. Sessions were recorded and transcribed.

Results

Thirty-two individuals participated and generated nine recommendations. There was consensus on adding epitope compatibility to the existing deceased donor kidney allocation criteria. However, participants recommended including safeguards/flexibility around this (e.g., mitigating declining health). They called for a transition period to epitope compatibility, including an ongoing comprehensive public education program. Participants unanimously recommended regular monitoring and public sharing of epitope-based transplant outcomes.

Conclusions

Participants supported adding epitope compatibility to kidney allocation criteria, but advised safeguards and flexibility around implementation. These recommendations provide guidance to policymakers about incorporating epitope-based deceased donor allocation criteria.
COVID-19 vaccine hesitancy and attitudes in Pakistan: a cross-sectional phone survey of major urban cities
Authors: Khan Adnan Ahmad , Abdullah Mujahid , Aliani Razia , Mohiuddin Amal Fatima , Sultan Faisal
Published: June 2023

Background

COVID-19 mass vaccination is the only hopeful savior to curb the pandemic. Vaccine distribution to achieve herd immunity is hindered by hesitance and negative attitude of the public against COVID-19 vaccination. This study aims to evaluate the vaccine hesitancy and attitudes in major cities in Pakistan as well as their determinants.

Methods

A cross-sectional telephonic survey was conducted in June 2021 in major cities of Pakistan including Karachi, Lahore, Islamabad, Peshawar, and Gilgit, from unvaccinated urban population aged 18 years or older. Random Digit Dialing through multi-stage stratified random sampling was used to ensure representation of each target city and socio-economic classes. Questionnaire collected information on socio-demographics, COVID-19-related experiences, risk perception of infection, and receptivity of COVID-19 vaccination. Multivariate logistic regression analyses were performed to identify key determinants of vaccine hesitancy and acceptance.

Results

The prevalence of vaccinated population in this survey was 15%. Of the 2270 respondents, 65% respondents were willing to vaccinate, while only 19% were registered for vaccination. Factors significantly associated with vaccine willingness were older age (aOR: 6.48, 95% CI: 1.94–21.58), tertiary education (aOR: 2.02, 95% CI: 1.36, 3.01), being employed (aOR: 1.34, 95% CI: 1.01, 1.78), perceived risk of COVID-19 (aOR: 4.38, 95% CI: 2.70, 7.12), and higher compliance with standard operating procedures (aOR: 1.72, 95% CI: 1.26, 2.35). The most common vaccine hesitancy reasons were ‘no need’ (n = 284, 36%) and concerns with ‘vaccine safety and side effects’ (n = 251, 31%), while most reported vaccine motivation reasons were ‘health safety’ (n = 1029, 70%) and ‘to end the pandemic’ (n = 357, 24%).

Conclusions

Although our study found 35% hesitancy rate of COVID-19 vaccine, there were noticeable demographic differences that suggest tailored communication strategy to address concerns held by most hesitant subpopulation. Use of mobile vaccination facilities particularly for less mobile and disadvantaged, and implementation and evaluation of social mobilization strategy should be considered to increase overall COVID-19 vaccination acceptance and coverage.
Lipoprotein (a) and myocardial infarction: impact on long-term mortality
Authors: Zhang Jian , Jia Lin , Yang Yu , Xiao Ai , Lin Xianhe
Published: June 2023

Background and aims

Lipoprotein (a) [Lp(a)] is a genetically regulated lipoprotein particle that is an independent risk factor for coronary atherosclerotic heart disease. However, the correlation between Lp(a) and left ventricular ejection fraction (LVEF) in patients with myocardial infarction (MI) has been poorly studied. The present study investigated the correlation between Lp(a) and LVEF, as well as the impact of Lp(a) on long-term mortality in patients with MI.

Methods

Patients who underwent coronary angiography resulting in MI diagnosis between May 2018 and March 2020 at the First Affiliated Hospital of Anhui Medical University were included in this study. The patients were divided into groups based on the Lp(a) concentration and LVEF (reduced ejection fraction group: < 50%; normal ejection fraction group: ≥ 50%). Then, correlations between the Lp(a) level and LVEF, as well as the impact of Lp(a) on mortality, were assessed.

Results

This study included 436 patients with MI. The Lp(a) level and LVEF were significantly and negatively correlated (r = -0.407, β = -0.349, P < 0.001). The area under the receiver operating characteristic curve (ROC) indicated that an Lp(a) concentration > 455 mg/L was the best predictive value for reduced ejection fraction (AUC: 0.7694, P < 0.0001). The clinical endpoints did not differ based on the Lp(a) concentration. However, all-cause mortality and cardiac mortality differed based on LVEF.

Conclusions

These results suggest that an elevated Lp(a) concentration predicts reduced ejection fraction and that LVEF predicts all-cause mortality and cardiac mortality in patients with MI.
High preoperative CEA and systemic inflammation response index (C-SIRI) predict unfavorable survival of resectable colorectal cancer
Authors: Cai Hao , Chen Yu , Zhang Qiao , Liu Yang , Jia HouJun
Published: June 2023

Background

CEA and systemic inflammation were reported to correlate with proliferation, invasion, and metastasis of colorectal cancer. This study investigated the prognostic significance of the preoperative CEA and systemic inflammation response index (C-SIRI) in patients with resectable colorectal cancer.

Methods

Two hundred seventeen CRC patients were recruited from Chongqing Medical University, the first affiliated hospital, between January 2015 and December 2017. Baseline characteristics, preoperative CEA level, and peripheral monocyte, neutrophil, and lymphocyte counts were retrospectively reviewed. The optimal cutoff value for SIRI was defined as 1.1, and for CEA, the best cutoff values were 4.1 ng/l and 13.0 ng/l. Patients with low levels of CEA (< 4.1 ng/l) and SIRI (< 1.1) were assigned a value of 0, those with high levels of CEA (≥ 13.0 ng/l) and SIRI (≥ 1.1) were assigned a value of 3, and those with CEA (4.1–13.0 ng/l) and SIRI (≥ 1.1), CEA (≥ 13.0 ng/l), and SIRI (< 1.1) were assigned a value of 2. Those with CEA (< 4.1 ng/l) and SIRI (≥ 1.1) and CEA (4.1–13.0 ng/l) and SIRI (< 1.1) were assigned a value of 1. The prognostic value was assessed based on univariate and multivariate survival analysis.

Results

Preoperative C-SIRI was statistically correlated with gender, site, stage, CEA, OPNI, NLR, PLR, and MLR. However, no difference was observed between C-SIRI and age, BMI, family history of cancer, adjuvant therapy, and AGR groups. Among these indicators, the correlation between PLR and NLR is the strongest. In addition, high preoperative C-SIRI was significantly correlated with poorer overall survival (OS) (HR: 2.782, 95% CI: 1.630–4.746, P < 0.001) based on univariate survival analysis. Moreover, it remained an independent predictor for OS (HR: 2.563, 95% CI: 1.419–4.628, p = 0.002) in multivariate Cox regression analysis.

Conclusion

Our study showed that preoperative C-SIRI could serve as a significant prognostic biomarker in patients with resectable colorectal cancer.
Testis cell pyroptosis mediated by CASP1 and CASP4: possible sertoli cell-only syndrome pathogenesis
Authors: Liu Wantao , Li Xinan , Ma Qiang , Zhu Yongtong , Zhao Wenzhong , Yang Yisheng , Xiao Weiqiang , Huang Daxiong , Cai Fengbo , Chan David Yiu Leung , Zhao Shanchao , Chu Qingjun
Published: June 2023

Background

Sertoli cell-only syndrome (SCOS) is the most serious pathological type of non-obstructive azoospermia. Recently, several genes related to SCOS have been identified, including FANCM, TEX14, NR5A1, NANOS2, PLK4, WNK3, and FANCA, but they cannot fully explain the pathogenesis of SCOS. This study attempted to explain spermatogenesis dysfunction in SCOS through testicular tissue RNA sequencing and to provide new targets for SCOS diagnosis and therapy.

Methods

We analyzed differentially expressed genes (DEGs) based on RNA sequencing of nine patients with SCOS and three patients with obstructive azoospermia and normal spermatogenesis. We further explored the identified genes using ELISA and immunohistochemistry.

Results

In total, 9406 DEGs were expressed (Log2|FC|≥ 1; adjusted P value < 0.05) in SCOS samples, and 21 hub genes were identified. Three upregulated core genes were found, including CASP4, CASP1, and PLA2G4A. Thus, we hypothesized that testis cell pyroptosis mediated by CASP1 and CASP4 might be involved in SCOS occurrence and development. ELISA verified that CASP1 and CASP4 activities in the testes of patients with SCOS were significantly higher than those in patients with normal spermatogenesis. Immunohistochemical results showed that CASP1 and CASP4 in the normal spermatogenesis group were mainly expressed in the nuclei of spermatogenic, Sertoli, and interstitial cells. CASP1 and CASP4 in the SCOS group were mainly expressed in the nuclei of Sertoli and interstitial cells because of the loss of spermatogonia and spermatocytes. CASP1 and CASP4 expression levels in the testes of patients with SCOS were significantly higher than those in patients with normal spermatogenisis. Furthermore, the pyroptosis-related proteins GSDMD and GSDME in the testes of patients with SCOS were also significantly higher than those in control patients. ELISA also showed that inflammatory factors (IL-1 β, IL-18, LDH, and ROS) were significantly increased in the SCOS group.

Conclusions

For the first time, we found that cell pyroptosis-related genes and key markers were significantly increased in the testes of patients with SCOS. We also observed many inflammatory and oxidative stress reactions in SCOS. Thus, we propose that testis cell pyroptosis mediated by CASP1 and CASP4 could participate in SCOS occurrence and development.
Use it or lose it? Identifying reasons for the low use of psychosocial support by hospital staff
Authors: van de Baan Frank , Poesen Lieze , Westra Daan , Fleuren Bram , Ruwaard Dirk , Zijlstra Fred , Gifford Rachel
Published: June 2023

Background

Psychosocial support programs are a way for hospitals to support the mental health of their staff. However, while support is needed, utilization of support by hospital staff remains low. This study aims to identify reasons for non-use and elements that are important to consider when offering psychosocial support.

Methods

This mixed-method, multiple case study used survey data and in-depth interviews to assess the extent of psychosocial support use, reasons for non-use and perceived important elements regarding the offering of psychosocial support among Dutch hospital staff. The study focused on a time of especially high need, namely the COVID-19 pandemic. Descriptive statistics were used to assess frequency of use among 1514 staff. The constant comparative method was used to analyze answers provided to two open-ended survey questions (n = 274 respondents) and in-depth interviews (n = 37 interviewees).

Results

The use of psychosocial support decreased from 8.4% in December 2020 to 3.6% by September 2021. We identified four main reasons for non-use of support: deeming support unnecessary, deeming support unsuitable, being unaware of the availability, or feeling undeserving of support. Furthermore, we uncovered four important elements: offer support structurally after the crisis, adjust support to diverse needs, ensure accessibility and awareness, and an active role for supervisors.

Conclusions

Our results show that the low use of psychosocial support by hospital staff is shaped by individual, organizational, and support-specific factors. These factors can be targeted to increase use of psychosocial support, whereby it is important to also focus on the wider hospital workforce in addition to frontline staff.