bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of buccal and palatal bone thickness on post-surgical marginal bone changes around implants placed in posterior maxilla: a multi-centre prospective study
Authors: Cicciù Marco , Pratella Umberto , Fiorillo Luca , Bernardello Fabio , Perillo Francesco , Rapani Antonio , Stacchi Claudio , Lombardi Teresa 
Published: May 2023

Abstract
Background
Numerous clinical variables may influence early marginal bone loss (EMBL), including surgical, prosthetic and host-related factors. Among them, bone crest width plays a crucial role: an adequate peri-implant bone envelope has a protective effect against the influence of the aforementioned factors on marginal bone stability. The aim of the present study was to investigate the influence of buccal and palatal bone thickness at the time of implant placement on EMBL during the submerged healing period.

Methods
Patients presenting a single edentulism in the upper premolar area and requiring implant-supported rehabilitation were enrolled following inclusion and exclusion criteria. Internal connection implants (Twinfit, Dentaurum, Ispringen, Germany) were inserted after piezoelectric implant site preparation. Mid-facial and mid-palatal thickness and height of the peri-implant bone were measured immediately after implant placement (T0) with a periodontal probe and recorded to the nearest 0.5 mm. After 3 months of submerged healing (T1), implants were uncovered and measurements were repeated with the same protocol. Kruskal-Wallis test for independent samples was used to compare bone changes from T0 to T1. Multivariate linear regression models were built to assess the influence of different variables on buccal and palatal EMBL.

Results
Ninety patients (50 females, 40 males, mean age 42.9 ± 15.1 years), treated with the insertion of 90 implants in maxillary premolar area, were included in the final analysis. Mean buccal and palatal bone thickness at T0 were 2.42 ± 0.64 mm and 1.31 ± 0.38 mm, respectively. Mean buccal and palatal bone thickness at T1 were 1.92 ± 0.71 mm and 0.87 ± 0.49 mm, respectively. Changes in both buccal and palatal thickness from T0 to T1 resulted statistically significant (p = 0.000). Changes in vertical bone levels from T0 to T1 resulted not significant both on buccal (mean vertical resorption 0.04 ± 0.14 mm; p = 0.479) and palatal side (mean vertical resorption 0.03 ± 0.11 mm; p = 0.737). Multivariate linear regression analysis showed a significant negative correlation between vertical bone resorption and bone thickness at T0 on both buccal and palatal side.

Conclusion
The present findings suggest that a bone envelope > 2 mm on the buccal side and > 1 mm on the palatal side may effectively prevent peri-implant vertical bone resorption following surgical trauma.

Trial Registration
The present study was retrospectively recorded in a public register of clinical trials (www.clinicaltrials.gov - NCT05632172) on 30/11/2022.
Evaluation of registered nurses’ interprofessional emergency care competence through the gamification of cardiopulmonary resuscitation training: a cross-sectional study
Authors: Chen Tzu-Sang , Hsieh Pei-Lun , Tung Chien Chien , Wu Chao-Hsin , Cheng Yu-Chieh 
Published: May 2023

Abstract
Backgrounds
Cardiopulmonary resuscitation (CPR) training is generally led by instructors in a classroom; thus, conventional teaching materials used in CPR training are often constrained by spatiotemporal factors, limiting learners’ interest and sense of achievement in learning and preventing them from effectively applying what they learn in practice. For greater effectiveness and more flexible application, clinical nursing education has increasingly emphasized contextualization, individualization, and interprofessional learning. This study determined the self-assessed emergency care competencies of nurses who received gamified emergency care training and explored the factors associated with those competencies.

Methods
Quota sampling of nurses working at a certain regional hospital in central Taiwan was conducted, and a structured questionnaire was administered to the recruited nurses. A total of 194 valid responses were collected. The research tool was a scale measuring the participants’ emergency care competencies after they received gamified emergency care training. The data were analyzed using descriptive and inferential statistics and multiple regression.

Results
Of the recruited participants, 50.52% were ≤ 30 years old; 48.45% worked in the internal medicine department; 54.64% graduated from 2-year university technical programs; 54.12% were N2 registered nurses; 35.57% and 21.13% had ≥ 10 and 1–3 years of work experience, respectively; and 48.45% worked in general wards. User need (r = 0.52, p = 0.000), perceived usefulness (r = 0.54, p = 0.000), perceived ease of use (r = 0.51, p = 0.000), and usage attitude (r = 0.41, p = 0.000) were positively correlated with emergency care competencies. Furthermore, the multiple regression analysis revealed that perceived usefulness was the primary factor associated with the participants’ emergency care competencies.

Conclusions
The results of this study may serve as a reference for acute care facility authorities in designing advanced nursing competency standards and emergency care training programs for nurses.
Evaluation of a dementia awareness game for undergraduate nursing students in Northern Ireland: a Pre-/Post-Test study
Authors: Craig Stephanie , Stark Patrick , Wilson Christine Brown , Carter Gillian , Clarke Sonya , Mitchell Gary 
Published: May 2023

Abstract
Introduction
Although it is possible to live well with dementia and many individuals with dementia lead active lives with the help of family, friends, and communities, the general impression of dementia is frequently negative. Dementia is a global health issue. Despite this, little research has been done on the effects of innovative dementia education strategies among undergraduate nursing students. The aim of this study was therefore to assess if this serious digital game, originally intended for the public, could increase knowledge about dementia in first-year nursing students.

Methods
The intervention was a digital serious game called “The Dementia Game”, which was available to students throughout February 2021, to a convenience sample of first-year undergraduate nursing students (n = 560) completing a BSc Honours Nursing Degree programme in one university in Northern Ireland. The game was evaluated using a pretest-posttest design. The questionnaire comprised of a 30- item true- false Alzheimer’s Disease Knowledge Scale (ADKS), which covers risk factors, assessment and diagnosis, symptoms, course, life impact, caregiving and treatment and management. Data were analysed using paired t-tests and descriptive statistics.

Results
Overall dementia knowledge increased significantly after playing the game. Pre-test to post-test increases were observed across a range of seven categories of dementia knowledge (life impact, risk factors, symptoms, treatment, assessment, caregiving and trajectory), with particularly large increases in knowledge of trajectory and risk factors, as shown using paired t-tests. All pre-test to post-test comparisons were significant at the p < 0.001 level.

Conclusions
A short serious digital game on dementia improved first-year student’s knowledge about dementia. Undergraduate students also expressed that this approach to dementia education was effective in improving their knowledge about the disease.
Chinese Intelligence Prescription System improves prescription accuracy while decreasing labor and drug costs
Authors: Huang Ting-Yu , Huang Wei-Te , Lin Yu-Chuan , Hung Hao-Hsiu , Ou Shi-Chen , Chang Chin-Wei , Lin Hung-En , Lin Ting-Yen , Chang Ching-Wen , Hung Hui-Chun , Huang Sheng-Teng 
Published: May 2023

Abstract
Background and Aim
The traditional method of taking Chinese Medicine involves creating a decoction by cooking medicinal Chinese herbs. However, this method has become less popular, being replaced by the more convenient method of consuming concentrated Chinese herbal extracts, which creates challenges related to the complexity of stacking multiple formulas.

Methods
We developed the Chinese Intelligence Prescription System (CIPS) to simplify the prescription process. In this study, we used data from our institutions pharmacy to calculate the number of reductions, average dispensing time, and resulting cost savings.

Results
The mean number of prescriptions was reduced from 8.19 ± 3.65 to 7.37 ± 3.34 ($$p=2.46\;\times10^{-8}$$

p
=
2.46

×

10

-
8

). The reduction in the number of prescriptions directly resulted in decreased dispensing time, reducing it from 1.79 ± 0.25 to 1.63 ± 0.66 min ($$p=1.88\;\times10^{-14}$$

p
=
1.88

×

10

-
14

). The reduced dispensing time totaled 3.75 h per month per pharmacist, equivalent to an annual labor cost savings of $15,488 NTD per pharmacist. In addition, drug loss was reduced during the prescription process, with a mean savings of $4,517 NTD per year. The combined savings adds up to a not insignificant $20,005 NTD per year per pharmacist. When taking all TCM clinics/hospitals in Taiwan into account, the total annual savings would be $77 million NTD.

Conclusion
CIPS assists clinicians and pharmacists to formulate precise prescriptions in a clinical setting to simplify the dispensing process while reducing medical resource waste and labor costs.
Familial 5.29 Mb deletion in chromosome Xq22.1–q22.3 with a normal phenotype: a rare pedigree and literature review
Authors: Xu Hui-Hui , Zhang Yang , He Zhe-Hang , Di Xing-Hong , Pan Fei-Yan , Shi Wei-Wu 
Published: May 2023

Abstract
Background
Xq22.1–q22.3 deletion is a rare chromosome aberration. The purpose of this study was to identify the correlation between the phenotype and genotype of chromosome Xq22.1–q22.3 deletions.

Methods
Chromosome aberrations were identified by copy number variation sequencing (CNV-seq) technology and karyotype analysis. Furthermore, we reviewed patients with Xq22.1–q22.3 deletions or a deletion partially overlapping this region to highlight the rare condition and analyse the genotype–phenotype correlations.

Results
We described a female foetus who is the “proband” of a Chinese pedigree and carries a heterozygous 5.29 Mb deletion (GRCh37: chrX: 100,460,000–105,740,000) in chromosome Xq22.1–q22.3, which may affect 98 genes from DRP2 to NAP1L4P2. This deletion encompasses 7 known morbid genes: TIMM8A, BTK, GLA, HNRNPH2, GPRASP2, PLP1, and SERPINA7. In addition, the parents have a normal phenotype and are of normal intelligence. The paternal genotype is normal. The mother carries the same deletion in the X chromosome. These results indicate that the foetus inherited this CNV from her mother. Moreover, two more healthy female family members were identified to carry the same CNV deletion through pedigree analysis according to the next-generation sequencing (NGS) results. To our knowledge, this family is the first pedigree to have the largest reported deletion of Xq22.1–q22.3 but to have a normal phenotype with normal intelligence.

Conclusions
Our findings further improve the understanding of the genotype–phenotype correlations of chromosome Xq22.1–q22.3 deletions.This report may provide novel information for prenatal diagnosis and genetic counselling for patients who carry similar chromosome abnormalities.
Targeting unfolded protein response reverts ER stress and ER Ca2+ homeostasis in cardiomyocytes expressing the pathogenic variant of Lamin A/C R321X
Authors: Pietrafesa Giusy , De Zio Roberta , Scorza Simona Ida , Armentano Maria Francesca , Pepe Martino , Forleo Cinzia , Procino Giuseppe , Gerbino Andrea , Svelto Maria , Carmosino Monica 
Published: May 2023

Abstract
Background
We previously demonstrated that an Italian family affected by a severe dilated cardiomyopathy (DCM) with history of sudden deaths at young age, carried a mutation in the Lmna gene encoding for a truncated variant of the Lamin A/C protein (LMNA), R321X. When expressed in heterologous systems, such variant accumulates into the endoplasmic reticulum (ER), inducing the activation of the PERK-CHOP pathway of the unfolded protein response (UPR), ER dysfunction and increased rate of apoptosis. The aim of this work was to analyze whether targeting the UPR can be used to revert the ER dysfunction associated with LMNA R321X expression in HL-1 cardiac cells.

Methods
HL-1 cardiomyocytes stably expressing LMNA R321X were used to assess the ability of 3 different drugs targeting the UPR, salubrinal, guanabenz and empagliflozin to rescue ER stress and dysfunction. In these cells, the state of activation of both the UPR and the pro-apoptotic pathway were analyzed monitoring the expression levels of phospho-PERK, phospho-eIF2α, ATF4, CHOP and PARP-CL. In addition, we measured ER-dependent intracellular Ca2+ dynamics as indicator of proper ER functionality.

Results
We found that salubrinal and guanabenz increased the expression levels of phospho-eIF2α and downregulated the apoptosis markers CHOP and PARP-CL in LMNA R321X-cardiomyocytes, maintaining the so-called adaptive UPR. These drugs also restored ER ability to handle Ca2+ in these cardiomyocytes. Interestingly, we found that empagliflozin downregulated the apoptosis markers CHOP and PARP-CL shutting down the UPR itself through the inhibition of PERK phosphorylation in LMNA R321X-cardiomyocytes. Furthermore, upon empagliflozin treatment, ER homeostasis, in terms of ER ability to store and release intracellular Ca2+ was also restored in these cardiomyocytes.

Conclusions
We provided evidence that the different drugs, although interfering with different steps of the UPR, were able to counteract pro-apoptotic processes and to preserve the ER homeostasis in R321X LMNA-cardiomyocytes. Of note, two of the tested drugs, guanabenz and empagliflozin, are already used in the clinical practice, thus providing preclinical evidence for ready-to-use therapies in patients affected by the LMNA R321X associated cardiomyocytes.
Predicting response and toxicity to immune checkpoint inhibitors in lung cancer using antibodies to frameshift neoantigens
Authors: Shen Luhui , Brown Justin R. , Johnston Stephen Albert , Altan Mehmet , Sykes Kathryn F. 
Published: May 2023

Abstract
Purpose
To evaluate a new class of blood-based biomarkers, anti-frameshift peptide antibodies, for predicting both tumor responses and adverse immune events to immune checkpoint inhibitor (ICI) therapies in advanced lung cancer patients.

Experimental design
Serum samples were obtained from 74 lung cancer patients prior to palliative PD-(L)1 therapies with subsequently recorded tumor responses and immune adverse events (irAEs). Pretreatment samples were assayed on microarrays of frameshift peptides (FSPs), representing ~ 375,000 variant peptides that tumor cells can be informatically predicted to produce from translated mRNA processing errors. Serum-antibodies specifically recognizing these ligands were measured. Binding activities preferentially associated with best-response and adverse-event outcomes were determined. These antibody bound FSPs were used in iterative resampling analyses to develop predictive models of tumor response and immune toxicity.

Results
Lung cancer serum samples were classified based on predictive models of ICI treatment outcomes. Disease progression was predicted pretreatment with ~ 98% accuracy in the full cohort of all response categories, though ~ 30% of the samples were indeterminate. This model was built with a heterogeneous sample cohort from patients that (i) would show either clear response or stable outcomes, (ii) would be administered either single or combination therapies and (iii) were diagnosed with different lung cancer subtypes. Removing the stable disease, combination therapy or SCLC groups from model building increased the proportion of samples classified while performance remained high. Informatic analyses showed that several of the FSPs in the all-response model mapped to translations of variant mRNAs from the same genes. In the predictive model for treatment toxicities, binding to irAE-associated FSPs provided 90% accuracy pretreatment, with no indeterminates. Several of the classifying FSPs displayed sequence similarity to self-proteins.

Conclusions
Anti-FSP antibodies may serve as biomarkers for predicting ICI outcomes when tested against ligands corresponding to mRNA-error derived FSPs. Model performances suggest this approach might provide a single test to predict treatment response to ICI and identify patients at high risk for immunotherapy toxicities.
An ocular Th1 immune response promotes corneal nerve damage independently of the development of corneal epitheliopathy
Authors: Vereertbrugghen Alexia , Pizzano Manuela , Sabbione Florencia , Keitelman Irene Angelica , Shiromizu Carolina Maiumi , Aguilar Douglas Vera , Fuentes Federico , de Paiva Cintia S. , Giordano Mirta , Trevani Analía , Galletti Jeremías G. 
Published: May 2023

AbstractProper sight is not possible without a smooth, transparent cornea, which is highly exposed to environmental threats. The abundant corneal nerves are interspersed with epithelial cells in the anterior corneal surface and are instrumental to corneal integrity and immunoregulation. Conversely, corneal neuropathy is commonly observed in some immune-mediated corneal disorders but not in others, and its pathogenesis is poorly understood. Here we hypothesized that the type of adaptive immune response may influence the development of corneal neuropathy. To test this, we first immunized OT-II mice with different adjuvants that favor T helper (Th)1 or Th2 responses. Both Th1-skewed mice (measured by interferon-γ production) and Th2-skewed (measured by interleukin-4 production) developed comparable ocular surface inflammation and conjunctival CD4+ T cell recruitment but no appreciable corneal epithelial changes upon repeated local antigenic challenge. Th1-skewed mice showed decreased corneal mechanical sensitivity and altered corneal nerve morphology (signs of corneal neuropathy) upon antigenic challenge. However, Th2-skewed mice also developed milder corneal neuropathy immediately after immunization and independently of ocular challenge, suggestive of adjuvant-induced neurotoxicity. All these findings were confirmed in wild-type mice. To circumvent unwanted neurotoxicity, CD4+ T cells from immunized mice were adoptively transferred to T cell-deficient mice. In this setup, only Th1-transferred mice developed corneal neuropathy upon antigenic challenge. To further delineate the contribution of each profile, CD4+ T cells were polarized in vitro to either Th1, Th2, or Th17 cells and transferred to T cell-deficient mice. Upon local antigenic challenge, all groups had commensurate conjunctival CD4+ T cell recruitment and macroscopic ocular inflammation. However, none of the groups developed corneal epithelial changes and only Th1-transferred mice showed signs of corneal neuropathy. Altogether, the data show that corneal nerves, as opposed to corneal epithelial cells, are sensitive to immune-driven damage mediated by Th1 CD4+ T cells in the absence of other pathogenic factors. These findings have potential therapeutic implications for ocular surface disorders.
The BET PROTAC inhibitor dBET6 protects against retinal degeneration and inhibits the cGAS-STING in response to light damage
Authors: Zhu Xingfei , Liu Wei , Tang Xiangcheng , Chen Yulin , Ge Xiangyu , Ke Qin , Liang Xingmiao , Gan Yuwen , Zheng Yingfeng , Zou Ming , Deng Mi , Liu Yizhi , Li David Wan-Cheng , Gong Lili 
Published: May 2023

Abstract
Background
Chronic inflammation significantly contributes to photoreceptor death in blinding retinal diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Bromodomain and extraterminal domain (BET) proteins are epigenetic readers that act as key proinflammatory factors. We recently found the first-generation BET inhibitor JQ1 alleviated sodium iodate-induced retinal degeneration by suppressing cGAS-STING innate immunity. Here, we investigated the effects and mechanism of dBET6, a proteolysis‑targeting chimera (PROTAC) small molecule that selectively degrades BET by the ubiquitin‒proteasome system, in light-induced retinal degeneration.

Methods
Mice were exposed to bright light to induce retinal degeneration, and the activation of cGAS-STING was determined by RNA-sequencing and molecular biology. Retinal function, morphology, photoreceptor viability and retinal inflammation were examined in the presence and absence of dBET6 treatment.

Results
Intraperitoneal injection of dBET6 led to the rapid degradation of BET protein in the retina without detectable toxicity. dBET6 improved retinal responsiveness and visual acuity after light damage (LD). dBET6 also repressed LD-induced retinal macrophages/microglia activation, Müller cell gliosis, photoreceptor death and retinal degeneration. Analysis of single-cell RNA-sequencing results revealed cGAS-STING components were expressed in retinal microglia. LD led to dramatic activation of the cGAS-STING pathway, whereas dBET6 suppressed LD-induced STING expression in reactive macrophages/microglia and the related inflammatory response.

Conclusions
This study indicates targeted degradation of BET by dBET6 exerts neuroprotective effects by inhibiting cGAS-STING in reactive retinal macrophages/microglia, and is expected to become a new strategy for treatment of retinal degeneration.
A Nano-QSTR model to predict nano-cytotoxicity: an approach using human lung cells data
Authors: Meneses João , González-Durruthy Michael , Fernandez-de-Gortari Eli , Toropova Alla P. , Toropov Andrey A. , Alfaro-Moreno Ernesto 
Published: May 2023

Abstract
Background
The widespread use of new engineered nanomaterials (ENMs) in industries such as cosmetics, electronics, and diagnostic nanodevices, has been revolutionizing our society. However, emerging studies suggest that ENMs present potentially toxic effects on the human lung. In this regard, we developed a machine learning (ML) nano-quantitative-structure-toxicity relationship (QSTR) model to predict the potential human lung nano-cytotoxicity induced by exposure to ENMs based on metal oxide nanoparticles.

Results
Tree-based learning algorithms (e.g., decision tree (DT), random forest (RF), and extra-trees (ET)) were able to predict ENMs’ cytotoxic risk in an efficient, robust, and interpretable way. The best-ranked ET nano-QSTR model showed excellent statistical performance with R2 and Q2-based metrics of 0.95, 0.80, and 0.79 for training, internal validation, and external validation subsets, respectively. Several nano-descriptors linked to the core-type and surface coating reactivity properties were identified as the most relevant characteristics to predict human lung nano-cytotoxicity.

Conclusions
The proposed model suggests that a decrease in the ENMs diameter could significantly increase their potential ability to access lung subcellular compartments (e.g., mitochondria and nuclei), promoting strong nano-cytotoxicity and epithelial barrier dysfunction. Additionally, the presence of polyethylene glycol (PEG) as a surface coating could prevent the potential release of cytotoxic metal ions, promoting lung cytoprotection. Overall, the current work could pave the way for efficient decision-making, prediction, and mitigation of the potential occupational and environmental ENMs risks.