bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.
Does it matter for health if steps are taken during work or leisure? A prospective accelerometer study using register-based long-term sickness absence
Authors: Christensen Marie Raunkjær , Nabe-Nielsen Kirsten , Holtermann Andreas , Gupta Nidhi 
Published: June 2023

AbstractBackgroundWalking is known to be good for health. However, it is unknown whether it matters if steps are taken during work or leisure. Therefore, we aimed to examine the prospective association between accelerometer-measured steps taken during work or leisure and register-based long-term sickness absence (LTSA).MethodsWe included 937 blue- and white-collar workers from the PODESA cohort who wore a thigh-based accelerometer over four days to measure number of steps during work and leisure. Steps were divided into domain based on diary data. First event of LTSA was retrieved from a national register with four years’ follow-up. We used Cox proportional hazard models to analyze the association between domain-specific and total daily steps and LTSA, adjusted for age, sex, job type, smoking, and steps in the other domain (e.g., work/leisure).ResultsWe found more steps at work to be associated with a higher LTSA risk [Hazard Ratio (HR):1.04; 95% CI: 1.00–1.08 per 1000 steps]. No significant association was found between steps during leisure and LTSA (HR: 0.97; 95% CI: 0.91–1.02), nor between total daily steps and LTSA (HR: 1.01; CI 95% 0.99–1.04).ConclusionsMore steps at work were associated with higher risk of LTSA, while steps during leisure was not clearly associated with LTSA risk. These findings partly support ‘the physical activity paradox’ stating that the association between physical activity and health depends on the domain.