bluuebunny/crossref_metadata_2025 huggingface dataset:
Machinability and parametric optimization of aluminum silicon carbide metal matrix composite (Al-SiC MMC) machined through µ-EDM
Authors: Kotlapati Aruna , Hiremath Somashekhar S.
Published: November 2022

Aluminum silicon carbide metal matrix composite (Al-SiC MMC) is widely used because of its exceptional mechanical and thermal properties. Some engineering applications include aerospace, automobile, electronics, and medical devices. In the present investigation, aluminum 7075 alloy (Al-7075) as a matrix material with reinforcement particles of 10% silicon carbide (SiC) is fabricated using stir casting. The developed Al-SiC MMC is machined using an in-house developed micro-electro discharge machine (µ-EDM) setup. Experiments are carried out with input parameters—voltage (V), capacitance (µF), and pulse-on time (µs)—to analyze the responses such as hole depth (HD), material removal rate (MRR), tool wear rate (TWR), surface roughness (SR), and circularity error (CE). Taguchi L16 orthogonal array is adopted to conduct 16 experiments with varying process parameters for 5 minutes’ duration with a copper tool electrode of Ø720 µm on the Al-SiC MMC workpiece of size 20 mm × 20 mm × 2.5 mm. The dielectric medium used for all experimentation is EDM oil. The resultant blind holes are characterized using scanning electron microscopy (SEM) images and a 3D profilometer. Later, the signal-to-noise ( S/N) ratio technique is used to optimize the process parameters to enhance individual output responses. The obtained results are discussed in the article. Further, analysis of variance (ANOVA) is performed to find out the contribution of each parameter to the output responses. Grey relational analysis (GRA) is also used for multiobjective optimization to get quality blind holes. The best parametric combination obtained through GRA are at 28 V, 100 µF, and 100 µs, resulting in 823 µm of HD, 0.38 mg/min of MRR, 0.10 mg/min of TWR, 8.98 µm of SR, and 48.37 µm of CE.
Overlaps between obstructive sleep apnoea and other respiratory diseases, including COPD, asthma and interstitial lung disease
Authors: Bouloukaki Izolde , Fanaridis Michail , Testelmans Dries , Pataka Athanasia , Schiza Sophia
Published: November 2022

In the past, there was limited research relating to the role of sleep in respiratory diseases. Physicians treating these patients tended to focus mainly on the daily disabling symptoms, overlooking the possible significant role of coexisting sleep disorders such as obstructive sleep apnoea (OSA).

Nowadays, OSA has been recognised as an important, highly prevalent comorbidity for respiratory diseases such as COPD, asthma and interstitial lung diseases (ILDs). Overlap syndrome refers to the coexistence of chronic respiratory disease and OSA in the same patient. Although, in the past, overlap syndromes have been poorly studied, recent data underline that they result in increased morbidity and mortality compared with either underlying disorder alone. OSA and respiratory disease may be of different severity, and this, along with the existence of various clinical phenotypes, points to the necessity of an individualised therapeutic plan. Early recognition and OSA management could offer key benefits, such as improved sleep, quality of life and disease outcomes.

Educational aims

Describe pathophysiological aspects of OSA in chronic respiratory diseases such as COPD, asthma and ILDs.

Understand the bidirectional clinical importance when OSA coexists in chronic respiratory diseases.

Review current knowledge of treatment strategies towards an individualised therapeutic plan resulting in patient-centric outcomes.
Comparison of intact protein and digested peptide techniques for high throughput proteotyping of ApoE
Authors: Maus Anthony , Figdore Dan , Milosevic Dragana , Algeciras-Schimnich Alicia , Bornhorst Joshua
Published: November 2022

Introduction

Apolipoprotein E (ApoE) genotyping has been shown to have diagnostic value in the evaluation of cardiovascular diseases and neurodegenerative disorders such as Alzheimer’s disease. Although genetic testing is well established for this application, liquid chromatography-mass spectrometry (LC–MS) has the potential to provide a high throughput, low-cost alternative for ApoE evaluation.

Methods

Serum samples were analyzed by peptide, intact protein, and genomic techniques. For peptide analysis, samples were digested with trypsin followed by liquid chromatography-tandem mass spectrometry analysis (LC–MS/MS) using a high-throughput multichannel LC system coupled to a Sciex 7500 mass spectrometer. For intact protein analysis, ApoE was immuno-purified using a monoclonal antibody immobilized on magnetic beads followed by high-resolution LC–MS analysis using an Exploris 480. DNA was extracted and evaluated using Sanger sequencing as a reference method.

Results and discussion

The peptide measurement method produced one discrepant result when compared to genomic sequencing (out of 38 sequenced samples), whereas the intact protein analysis followed by deconvolution resulted in two discrepant results and when the intact protein data was processed with chromatographic integration there were three discrepant results. Therefore, the intact protein method proved slightly less accurate, required longer analysis time, and is substantially more costly, while providing only a 30 min improvement in sample preparation time.

Conclusions

With current MS technology clinical laboratories appear to be better served to utilize trypsin digest sample preparation and LC–MS/MS as opposed to high-resolution LC–MS intact protein analysis techniques for evaluation of ApoE proteotype. Peptide analysis methods are capable of producing accurate results with high throughput and minimal cost.
Determination of temporal reproducibility and variability of cancer biomarkers in serum and EDTA plasma samples using a proximity extension assay
Authors: Christensen Troels D. , Maag Emil , Madsen Kasper , Lindgaard Sidsel Christy , Nielsen Dorte L. , Johansen Julia S.
Published: November 2022

Background

Proximity extension assay (PEA) is a novel antibody-based proteomic technology. Sparse data have been published concerning the matrix effect of serum vs. ethylenediamine tetraacetic acid (EDTA) plasma and the reproducibility of results obtained using PEA technology.

Methods

We analyzed samples with the PEA-based 92-plex Olink® immuno-oncology (I-O) assay. To estimate the matrix effect, we analyzed paired serum and EDTA plasma samples from 12 patients with biliary tract cancer. To evaluate the reproducibility, we used data from 7 studies, where 6–8 serum samples from patients with pancreatic cancer were used as bridging samples on 3 versions of the panel over a 2.5-years period.

Results

For the study of serum vs. plasma, 80 proteins were evaluable. The mean serum to EDTA plasma ratio ranged from 0.41–3.01. For 36 proteins, the serum and plasma values were not comparable due to high variability of the ratio, poor correlation, or possible concentration effect. For the bridging samples, the mean intra-study inter-assay coefficient of variation (CV) ranged from 11.3% to 26.1%. The mean inter-study CV was 42.0% before normalization and 26.2% after normalization. Inter-study results were well correlated (r ≥ 0.93), especially for studies using the same version of the panel (r ≥ 0.99).

Conclusion

For 44 of 92 proteins included in the Olink® I-O panel, the variation between results obtained using serum and EDTA plasma was constant and results were well correlated. Furthermore, samples could be stored for several years and used on different versions of the same PEA panel without it effecting results.
Hiring in border regions: experimental and qualitative evidence from a recruiter survey in Luxembourg
Authors: Gutfleisch Tamara , Samuel Robin
Published: November 2022

Firms in border regions typically deal with heterogeneous applicant pools that include both (foreign) domestic workers and cross-border commuters. However, we know little about recruiters’ workforce needs and hiring practices in cross-border labour markets. Based on a survey of real recruiters in Luxembourg, this study presents experimental and qualitative findings on the role of country of residence in recruiters’ hiring intentions against foreigners. Luxembourg presents a rarely studied but highly relevant case for hiring practices owing to a combination of a strong economy, strict labour market regulations, and a transnational workforce. Drawing on data from a factorial survey experiment, we found no discrimination against Portuguese and French applicants living in Luxembourg. Yet, (highly skilled) cross-border workers from France and Germany faced disadvantages regarding recruiters’ hiring intentions. However, differences in effect sizes between foreigners and cross-border workers were small and not statistically significant. When further asked about the potential challenges of recruiting in Luxembourg’s cross-border labour market, respondents expressed concerns about flexibility, poor social fit, and cultural differences in hiring foreign and cross-border employees. Overall, our study provides further points of reference for studies on hiring intentions in cross-border labour markets across Europe.
Chronic constriction injury-induced changes in circular RNA expression profiling of the dorsal root ganglion in a rat model of neuropathic pain
Authors: Xiong Wanxia , Wei Min , Zhang Li , Wang Jie , Liu Fan , Wang Zhiyao
Published: November 2022

Background

The pathogenesis of neuropathic pain (NP) has not been fully elucidated. Gene changes in dorsal root ganglia (DRG) may contribute to the development of NP. Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that form covalently closed loop structures and are crucial for genetic and epigenetic regulation. However, little is known about circRNA changes in DRG neurons after peripheral nerve injury.

Methods

A sciatic nerve chronic constriction injury (CCI) model was established to induce neuropathic pain. We performed genome-wide circRNA analysis of four paired dorsal root ganglion (DRG) samples (L4–L5) from CCI and negative control (NC) rats using next-generation sequencing technology. The differentially expressed circRNAs (DEcircRNAs) were identified by differential expression analysis, and the expression profile of circRNAs was validated by quantitative PCR. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to predict the function of DEcircRNAs.

Results

A total of 374 DEcircRNAs were identified between CCI and NC rats using circRNA high-throughput sequencing. Among them, 290 were upregulated and 84 were downregulated in the CCI group. The expression levels of nine DEcircRNAs were validated by qPCR. Functional annotation analysis showed that the DEcircRNAs were mainly enriched in pathways and functions, including ‘dopaminergic synapse,’ ‘renin secretion,’ ‘mitogen-activated protein kinase signaling pathway,’ and ‘neurogenesis.’ Competing endogenous RNA analysis showed that the top 50 circRNAs exhibited interactions with four pain-related microRNAs (miRNAs). Circ:chr2:33950934–33955969 was the largest node in the circRNA–miRNA interaction network.

Conclusions

Peripheral nerve injury-induced neuropathic pain led to changes in the comprehensive expression profile of circRNAs in the DRG of rats. DEcircRNAs may advance our understanding of the molecular mechanisms underlying neuropathic pain.
Novel insights on association and reactivity of Bispectral Index, frontal electromyogram, and autonomic responses in nociception-sedation monitoring of critical care patients
Authors: Stewart Juhani A. , Särkelä Mika O. K. , Wennervirta Johanna , Vakkuri Anne P.
Published: November 2022

Background

Assessing nociception and sedation in mechanically ventilated patients in the ICU is challenging, with few reliable methods available for continuous monitoring. Measurable cardiovascular and neurophysiological signals, such as frontal EEG, frontal EMG, heart rate, and blood pressure, have potential in sedation and nociception monitoring. The hypothesis of this explorative study is that derived variables from the aforementioned signals predict the level of sedation, as described by the Richmond Agitation-Sedation score (RASS), and respond to painful stimuli during critical care.

Methods

Thirty adult postoperative ICU patients on mechanical ventilation and receiving intravenous sedation, excluding patients with primary neurological disorders, head injury, or need for continuous neuromuscular blockage. Bispectral Index (BIS), EMG power (EMG), EMG-derived Responsiveness Index (RI), and averaged blood pressure variability (ARV) were tested against RASS measurements. The aforementioned variables together with blood pressure and Surgical Pleth Index (SPI) were explored before and after painful stimuli (for example bronchoscopy, or pleural puncture) at varying RASS levels, to test variable responsiveness.

Results

BIS, EMG, and RI predicted RASS levels with a prediction probability (PK) of 0.776 for BIS, 0.761 for EMG, and 0.763 for RI. In addition, BIS, EMG, and ARV demonstrated responsiveness to painful stimuli during deep sedation (RASS score ≤ -3).

Conclusion

Variables derived from EEG and EMG are associated with sedation levels, as described by the RASS score. Furthermore, these variables, along with ARV, react with consistency to painful stimuli during deep sedation (RASS -5 to -3), offering novel tools for nociception-sedation monitoring of mechanically ventilated ICU patients requiring deep sedation.
A randomised controlled trial of acceptance and commitment therapy plus usual care compared to usual care alone for improving psychological health in people with motor neuron disease (COMMEND): study protocol
Authors: Gould Rebecca L. , Thompson Benjamin J. , Rawlinson Charlotte , Kumar Pavithra , White David , Serfaty Marc A. , Graham Christopher D. , McCracken Lance M. , Bursnall Matt , Bradburn Mike , Young Tracey , Howard Robert J. , Al-Chalabi Ammar , Goldstein Laura H. , Lawrence Vanessa , Cooper Cindy , Shaw Pamela J. , McDermott Christopher J.
Published: November 2022

Background

Motor neuron disease (MND) is a rapidly progressive, fatal neurodegenerative disease that predominantly affects motor neurons from the motor cortex to the spinal cord and causes progressive wasting and weakening of bulbar, limb, abdominal and thoracic muscles. Prognosis is poor and median survival is 2–3 years following symptom onset. Psychological distress is relatively common in people living with MND. However, formal psychotherapy is not routinely part of standard care within MND Care Centres/clinics in the UK, and clear evidence-based guidance on improving the psychological health of people living with MND is lacking. Previous research suggests that Acceptance and Commitment Therapy (ACT) may be particularly suitable for people living with MND and may help improve their psychological health.

Aims

To assess the clinical and cost-effectiveness of ACT modified for MND plus usual multidisciplinary care (UC) in comparison to UC alone for improving psychological health in people living with MND.

Methods

The COMMEND trial is a multi-centre, assessor-blind, parallel, two-arm RCT with a 10-month internal pilot phase. 188 individuals aged ≥ 18 years with a diagnosis of definite, laboratory-supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis, and additionally the progressive muscular atrophy and primary lateral sclerosis variants, will be recruited from approximately 14 UK-based MND Care Centres/clinics and via self-referral. Participants will be randomly allocated to receive up to eight 1:1 sessions of ACT plus UC or UC alone by an online randomisation system. Participants will complete outcome measures at baseline and at 6- and 9-months post-randomisation. The primary outcome will be quality of life at six months. Secondary outcomes will include depression, anxiety, psychological flexibility, health-related quality of life, adverse events, ALS functioning, survival at nine months, satisfaction with therapy, resource use and quality-adjusted life years. Primary analyses will be by intention to treat and data will be analysed using multi-level modelling.

Discussion

This trial will provide definitive evidence on the clinical and cost-effectiveness of ACT plus UC in comparison to UC alone for improving psychological health in people living with MND.

Trial registration

ISRCTN Registry, ISRCTN12655391. Registered 17 July 2017,https://www.isrctn.com/ISRCTN12655391.

Protocol version: 3.1 (10/06/2020).
The combination of arterial lactate level with GCS-pupils score to evaluate short term prognosis in traumatic brain injury: a retrospective study
Authors: Wang Yu-Mei , Zhu Ning , Zhou Yi-Min , Su Rui , Li Hong-Liang , Zhou Jian-Xin
Published: November 2022

Background

The aim of the study was to determine whether the combination of Glasgow Coma Scale (GCS) and Pupil responses score (GCSP) with arterial lactate level would be an index to predict the short term prognosis in patients with traumatic brain injury (TBI).

Methods

A retrospective study was performed enrolling all TBI patients admitted to intensive care unit (ICU) from 2019 to 2020. The demographics, clinical characteristics, and arterial lactate concentration were recorded. The GCSP and arterial blood analysis (ABG) with lactate was tested as soon as the patient was admitted to ICU. The Glasgow Outcome Scale (GOS) after discharge was regarded as the clinical outcome. A new index named GCSP-L was the combination of GCSP and lactate concentration. GCSP-L was the GCSP score (range 1-15) plus the lactate score (range 0-2). The lactate score was defined based on different lactate concentrations. If lactate was below 2 mmol/L, lactate score was 0, which above 5 mmol/L was 2 and between 2 and 5 mmol/L, the score was 1. As the range of GCSP was 1-15, the range of the GCSP-L was 1 to 17. The area under receiver operating characteristic curve (AUC) was calculated to evaluate the predictive ability of GCSP, lactate and GCSP-L. Statistical significance was set when p value < 0.05.

Results

A total of 192 TBI patients were included in the study. Based on GCSP, mild, moderate, and severe TBI were 13.02, 14.06 and 72.92%, respectively. There were 103 (53.65%) patients with the lactate concentration below 2 mmol/L (1.23 ± 0.37 mmol/l), 63 (32.81%) of the range from 2 to 5 (3.04 ± 2.43 mmol/l) and 26 (13.54%) were above 5 mmol/l (7.70 ± 2.43 mmol/l). The AUC was 0.866 (95% CI 0.827-0.904) for GCSP-L, 0.812 (95% CI 0.765-0.858) for GCSP and 0.629 (95% CI 0.570—0.0.688) for lactate. The AUC of GCSP-L was higher than the other two, GCSP and lactate alone.

Conclusions

The combination of GCSP and lactate concentration can be used to predict the short term prognosis in TBI patients.
Magnitude of husbands’ involvement in skilled birth attendant service utilization in Deder town, Oromiya, Ethiopia
Authors: Mohammed Abdusamed , Kifle Gizaw , Beshir Furo , Mume Abas , Abdullahi Yasin , Abdulwehab Remzia
Published: November 2022

Background

Husbands’ involvement strategies are employed to support their wives to access care, address the influence of gender inequality on maternal and newborn health, and promote husbands’ positive involvement as fathers. Yet, evidence of the husbands’ involvement in skilled birth attendant service utilization in Ethiopia is scarce, which limits the facility to improve institutional delivery services. Therefore, this study aimed to assess the magnitude of husbands’ involvement in skilled birth attendant service utilization among fathers of children of less than one year in Deder town, Oromiya, Ethiopia.

Methods

A community-based cross-sectional study was conducted using a structured questionnaire among 399 fathers selected by a simple random sampling technique. Data were collected through face-to-face interview from March 24 to April 20, 2021. Data entry was done by Epi-data version-4.2 and analyzed with SPSS version-21. Descriptive statistics used frequency, mean and median and presented by tables and figures. The level of significance was set at p-value ≤0.05 for multivariable logistic regression and an adjusted odds ratio with a 95% confidence interval was used to measure the degree of statistical significance of dependent and independent variables.

Result

The prevalence of husbands’ involvement in skilled birth attendant service utilization was 84.2%. The age group of 25 to 29 years (AOR = 2.63, CI: 1.124–6.142), prior knowledge of skilled-delivery attendants (AOR = 2.75, CI: 1.456–5.205) and good attitude towards skilled birth attendants (AOR =2.46, CI: 1.227–4.948) were statistically significant determinants of husbands’ involvement in skilled birth attendants service utilization.

Conclusion and recommendation

This study revealed that the husbands’ involvement in skilled birth attendants was high. Age, level of knowledge and attitude were the significant determinants of husbands’ involvement in promoting skilled-delivery attendants. Therefore, improving husbands’ level of knowledge and attitude towards skilled birth attendants is needed.
A single center analysis of first-line treatment in advanced KRAS mutant non-small cell lung cancer: real-world practice
Authors: Liu Yanxia , Gao Yuan , Wang Ying , Zhao Cong , Zhang Zhiyun , Li Baolan , Zhang Tongmei
Published: November 2022

Purpose

For the first-line treatment of KRAS mutant non-small cell lung cancer (NSCLC) patients, immunotherapy or platinum-based chemotherapy are the main treatment method. Here, we investigated the clinical efficacy and prognosis those two regimens as first-line treatment in real-world practice.

Methods

KRAS mutant NSCLC patients received chemotherapy or immunotherapy as first-line treatment from September 2014 to March 2022 were enrolled. Clinical characteristics, treatment scheme, clinical curative effect and follow-up data of enrolled patients were collected for analysis.

Results

Fifty patients received immunotherapy and 115 patients received chemotherapy were enrolled. Patients who received immunotherapy (HR = 0.350, 95%CI 0.156–0.781, P = 0.010), or pemetrexed-based regimen (HR = 0.486, 95%CI 0.255–0.928, P = 0.029), or antiangiogenic therapy (HR = 0.355, 95%CI 0.159–0.790, P = 0.011) were at a low risk of disease progression. And patients received antiangiogenic therapy had lower risk of death than those not (HR = 0.333, 95%CI 0.120–0.926, P = 0.035). Subgroup analysis revealed the immunotherapy compared to chemotherapy alone had lower risk of disease progression (HR = 0.377, 95%CI 0.166–0.856, P = 0.020) in PD-L1 expression ≥1% subgroup. And in non-G12C KRAS subgroup, but not in G12C KRAS subgroup, patients who received antiangiogenic therapy had lower risk of disease progression (HR = 0.254, 95%CI 0.098–0.656, P = 0.005) and death than those not (HR = 0.197, 95%CI 0.056–0.692, P = 0.011). In terms of different chemotherapy regimen, platinum-paclitaxel combined with antiangiogenic therapy achieved the highest ORR and DCR (P < 0.05), while the platinum-pemetrexed combined with antiangiogenic therapy had the longest PFS and OS (P < 0.001).

Conclusion

For the first-line treatment of KRAS mutant NSCLC patients, immunotherapy, antiangiogenic therapy, and pemetrexed-based regimen could obtain more benefits. Subgroup analysis revealed the benefits of immunotherapy compared to chemotherapy were applicable in PD-L1 expression≥1% subgroup, and antiangiogenic therapy could benefit non-G12C KRAS subgroup, but not G12C KRAS subgroup. In terms of different chemotherapy regimen, platinum-pemetrexed combined with antiangiogenic therapy may be the preferred chemotherapy regimen.
Attitudes of European students towards family decision-making and the harmonisation of consent systems in deceased organ donation: a cross-national survey
Authors: Molina-Pérez Alberto , Werner-Felmayer Gabriele , Van Assche Kristof , Jensen Anja M. B. , Delgado Janet , Flatscher-Thöni Magdalena , Hannikainen Ivar R. , Rodriguez-Arias David , Schicktanz Silke , Wöhlke Sabine
Published: November 2022

Background

European countries are increasingly harmonising their organ donation and transplantation policies. Although a growing number of nations are moving to presumed consent to deceased organ donation, no attempts have been made to harmonise policies on individual consent and the role of the family in the decision-making process. Little is known about public awareness of and attitudes towards the role of the family in their own country and European harmonisation on these health policy dimensions. To improve understanding of these issues, we examined what university students think about the role of the family in decision-making in deceased organ donation and about harmonising consent policies within Europe.

Methods

Using LimeSurvey© software, we conducted a comparative cross-sectional international survey of 2193 university students of health sciences and humanities/social sciences from Austria (339), Belgium (439), Denmark (230), Germany (424), Greece (159), Romania (190), Slovenia (190), and Spain (222).

Results

Participants from opt-in countries may have a better awareness of the family’s legal role than those from opt-out countries. Most respondents opposed the family veto, but they were more ambivalent towards the role of the family as a surrogate decision-maker. The majority of participants were satisfied with the family’s legal role. However, those who were unsatisfied preferred to limit family involvement. Overall, participants were opposed to the idea of national sovereignty over consent policies. They favoured an opt-out policy harmonisation and were divided over opt-in. Their views on harmonisation of family involvement were consistent with their personal preferences.

Conclusions

There is overall division on whether families should have a surrogate role, and substantial opposition to granting them sole authority over decision-making. If European countries were to harmonise their policies on consent for organ donation, an opt-out system that grants families a surrogate decision-making role may enjoy the widest public support.
Concurrent use of opioids and stimulants and risk of fatal overdose: A cohort study
Authors: Palis Heather , Xavier Chloé , Dobrer Sabina , Desai Roshni , Sedgemore Kali-olt , Scow Marnie , Lock Kurt , Gan Wenqi , Slaunwhite Amanda
Published: November 2022

Background

Stimulant use has been rising among people with opioid use disorder in recent years in North America, alongside a parallel rise in illicit drug toxicity (overdose) deaths. This study aimed to examine the association between stimulant use and overdose mortality.

Methods

Data from a universal health insurance client roster were used to identify a 20% random general population sample (aged ≥12) in British Columbia, Canada (N = 1,089,682). Provincial health records were used to identify people who used opioids and/or stimulants. Fatal overdose observed during follow-up (January 1 2015-December 31 2018) was retrieved from Vital Statistics Death Registry and BC Coroners Service Data. Potential confounders including age, sex, health region, comorbidities and prescribed medications were retrieved from the provincial client roster and health records.

Results

We identified 7460 people who used stimulants and or opioids. During follow-up there were 272 fatal overdose events. People who used both opioids and stimulants had more than twice the hazard of fatal overdose (HR: 2.02, 95% CI: 1.47-2.78, p < 0.001) compared to people who used opioids only. The hazard of death increased over time among people who used both opioids and stimulants.

Conclusions

There is an urgent need to prioritize the service needs of people who use stimulants to reduce overdose mortality in British Columbia. Findings have relevance more broadly in other North American settings, where similar trends in opioid and stimulant polysubstance use have been observed.
Advances in novel therapeutic approaches for periodontal diseases
Authors: Haque Md Mahamudul , Yerex Katherine , Kelekis-Cholakis Anastasia , Duan Kangmin
Published: November 2022

Periodontal diseases are pathological processes resulting from infections and inflammation affecting the periodontium or the tissue surrounding and supporting the teeth. Pathogenic bacteria living in complex biofilms initiate and perpetuate this disease in susceptible hosts. In some cases, broad-spectrum antibiotic therapy has been a treatment of choice to control bacterial infection. However, increasing antibiotic resistance among periodontal pathogens has become a significant challenge when treating periodontal diseases. Thanks to the improved understanding of the pathogenesis of periodontal disease, which involves the host immune response, and the importance of the human microbiome, the primary goal of periodontal therapy has shifted, in recent years, to the restoration of homeostasis in oral microbiota and its harmonious balance with the host periodontal tissues. This shift in therapeutic goals and the drug resistance challenge call for alternative approaches to antibiotic therapy that indiscriminately eliminate harmful or beneficial bacteria. In this review, we summarize the recent advancement of alternative methods and new compounds that offer promising potential for the treatment and prevention of periodontal disease. Agents that target biofilm formation, bacterial quorum-sensing systems and other virulence factors have been reviewed. New and exciting microbiome approaches, such as oral microbiota replacement therapy and probiotic therapy for periodontal disease, are also discussed.
A study of the factors associated with emergency department visits in advanced cancer patients receiving palliative care
Authors: Dumnui Netsakao , Nagaviroj Kittiphon , Anothaisintawee Thunyarat
Published: November 2022

Purpose

Several studies demonstrated that cancer patients visited the emergency department (ED) frequently. This indicates unmet needs and poor-quality palliative care. We aimed to investigate the factors that contribute to ED visits among patients with advanced cancer in order to identify strategies for reducing unnecessary ED visits among these patients.

Methods

A retrospective study was conducted between January and December, 2019. Eligible patients were previously enrolled in the comprehensive palliative care program prior to their ED visit. All patients older than 18 were included. Patients were excluded if they had died at the initial consultation, were referred to other programs at the initial consultation, or had an incomplete record. The trial ended when the patients died, were referred to other palliative programs, or the study ended. The time between the initial palliative consultation and study endpoints was categorized into three groups: 16 days, 16–100 days, and > 100 days, based on the literature review. To investigate the factors associated with ED visits, a logistic regression analysis was conducted. The variables with a P value < 0.15 from the univariate logistic regression analysis were included in the multiple logistic regression analysis.

Results

Among a total of 227 patients, 93 visited the ED and 134 did not. Mean age was 65.5 years. Most prevalent cancers were colorectal (18.5%), lung (16.3%), and hepatobiliary (11.9%). At the end, 146 patients died, 45 were alive, nine were referred to other programs, and 27 were lost to follow-up. In univariate logistic regression analysis, patients with > 100 days from palliative consultation (OR 0.23; 95%CI 0.08, 0.66; p-value 0.01) were less likely to attend the ED. In contrast, PPS 50–90% (OR 2.02; 95%CI 1.18, 3.47; p-value 0.01) increased the ED visits. In the multiple logistic regression analysis, these two factors remained associated with ED visits:> 100 days from the palliative consultation (OR 0.18; 95%CI 0.06, 0.55; p-value 0.01) and PPS 50–90% (OR 2.62; 95%CI 1.44, 4.79; p-value 0.01).

Conclusions

There was reduced ED utilization among cancer patients with > 100 days of palliative care. Patients having a lower PPS were associated with a lower risk of ED visits.
Assessment during Covid-19: quality assurance of an online open book formative examination for undergraduate medical students
Authors: Rehman Javeria , Ali Rahila , Afzal Azam , Shakil Sara , Sultan Amber Shamim , Idrees Romana , Fatima Syeda Sadia
Published: November 2022

Background

The spread of COVID-19 pandemic in early 2020 compelled all the educational activities, including medical education to be shifted from face-to-face interaction to a virtual platform. This shift provided opportunities for exploring online assessment modalities. One such assessment method is an online open book exam which is a unique concept in medical education of Pakistan. Limited information is available in literature regarding open book exam for the basic science subjects. Hence, the objective of the study was to determine the quality of the open book exam administered as a pilot project to the first-year medical students.

Methods

It was a cross-sectional analytical study that included 99 students of first year MBBS. The students were administered an online unrestricted type of open book exam as a formative assessment. The exam consisted of 30 open-ended, short answer type questions. The scores of the exam were analyzed for psychometric quality.

Results

The mean score was 47.24 ± 15.30 SD %. The reliability of the exam was 0.79. The majority (66.6%) of items were found to be moderately difficult with their difficulty index ranging from 31 to 80%. The majority (86.6%) items were in the range of moderate to high discrimination. There were no questions with negative discrimination.

Conclusions

The exam was found to be reliable and can be implemented with training of faculty and students. Online open book exam provides a good format for remote and formative assessment of students with minimum proctoring during times of constraints such as COVID-19 pandemic.
Provider reported value and use of virtual resources in extended primary care prior to and during COVID-19
Authors: Haun Jolie N. , Panaite Vanessa , Cotner Bridget A. , Melillo Christine , Venkatachalam Hari H. , Fowler Christopher A. , Zilka Brian , Messina William
Published: November 2022

Background

A proactive approach to delivering care using virtual resources, while reducing in-person contact, is needed during the COVID-19 pandemic.

Objective

In the current study we describe pre- to post- COVID-19 pandemic onset related changes in electronic delivery of primary care.

Methods

A longitudinal, pre-post within-subjects design was used. Patient-aligned care team providers from one VA medical center, a primary care annex, and four affiliated community-based outpatient clinics completed both a baseline and follow up survey (N = 62) or the follow-up survey only (N = 85). The follow-up survey contained questions about COVID-19.

Results

The majority of providers (88%) reported they would continue virtual care once pandemic restrictions were lifted. Most (83%) felt prepared to transition to virtual care when pandemic restrictions began. Use of My HealtheVet, Telehealth, and mobile apps showed a significant increase (22.7%; 31.1%; 48.5%). Barriers to virtual care included (1) internet connectivity; (2) patients’ lack of technology comfort and skills; and (3) technical issues. Main supports to provide virtual care to patients were (1) peers/ colleagues; (2) technology support through help desk; (3) equipment such as laptops and dual screens; (4) being able to use doximety and virtual care manager, and (5) training.

Conclusions

Overall, provider-use and perceptions related to using virtual care improved over time. Providers adapted quickly to providing virtual care during COVID-19 and planned to provide virtual care long-term.
Gravidity and malaria trends interact to modify P. falciparum densities and detectability in pregnancy: a 3-year prospective multi-site observational study
Authors: Matambisso Glória , Brokhattingen Nanna , Maculuve Sónia , Cisteró Pau , Mbeve Henriques , Escoda Anna , Miguel Judice , Buetas Elena , de Jong Ianthe , Cuna Boaventura , Melembe Cardoso , Ndimande Nelo , Porras Gemma , Chen Haily , Tetteh Kevin K. A. , Drakeley Chris , Gamain Benoit , Chitnis Chetan , Chauhan Virander , Quintó Llorenç , Galatas Beatriz , Macete Eusébio , Mayor Alfredo
Published: November 2022

Background

Low-density Plasmodium falciparum infections prevail in low transmission settings, where immunity is expected to be minimal, suggesting an immune-independent effect on parasite densities. We aimed to describe parasite densities in pregnancy, and determine how gravidity and antibody-mediated immunity affect these, during a period of declining malaria transmission in southern Mozambique.

Methods

We documented P. falciparum infections at first antenatal care visits (n = 6471) between November 2016 and October 2019 in Ilha Josina (high-to-moderate transmission area), Manhiça (low transmission area), and Magude (pre-elimination area). Two-way interactions in mixed-effects regression models were used to assess gravidity-dependent differences in quantitative PCR-determined P. falciparum positivity rates (PfPRqPCR) and densities, in the relative proportion of detectable infections (pDi) with current diagnostic tests (≥ 100 parasites/μL) and in antimalarial antibodies.

Results

PfPRqPCR declined from 28 to 13% in Ilha Josina and from 5–7 to 2% in Magude and Manhiça. In primigravidae, pDi was highest in Ilha Josina at the first study year (p = 0.048), which declined with falling PfPRqPCR (relative change/year: 0.41, 95% CI [0.08; 0.73], p = 0.029), with no differences in antibody levels. Higher parasite densities in primigravidae from Ilha Josina during the first year were accompanied by a larger reduction of maternal hemoglobin levels (− 1.60, 95% CI [− 2.49; − 0.72; p < 0.001), than in Magude (− 0.76, 95% CI [− 1.51; − 0.01]; p = 0.047) and Manhiça (− 0.44, 95% CI [− 0.99; 0.10; p = 0.112). In contrast, multigravidae during the transmission peak in Ilha Josina carried the lowest pDi (p = 0.049). As PfPRqPCR declined, geometric mean of parasite densities increased (4.63, 95% CI [1.28; 16.82], p = 0.020), and antibody levels declined among secundigravidae from Ilha Josina.

Conclusions

The proportion of detectable and clinically relevant infections is the highest in primigravid women from high-to-moderate transmission settings and decreases with declining malaria. In contrast, the falling malaria trends are accompanied by increased parasite densities and reduced humoral immunity among secundigravidae. Factors other than acquired immunity thus emerge as potentially important for producing less detectable infections among primigravidae during marked declines in malaria transmission.
The effects of aging and gestational month on uteroplacental vascular perfusion, and umbilical artery hemodynamics in pregnant jennies
Authors: Abdelnaby Elshymaa A. , Emam Ibrahim A. , El-Sherbiny Hossam R. , Fadl Aya M.
Published: November 2022

This study aimed to correlate the pulsed wave spectral indices of the middle uterine artery at both sides with placental development in jenny within mid-late pregnancies, and establish umbilical Doppler values for different ages and different gestational months. Twenty Equus Asinus pregnant jennies 260–450 kg (average, 320 ± 10 kg) were examined from 5 to 9 months of pregnancy with different ages (4–14 years). Monthly B-mode ultrasound examination was performed on both the combined thickness of the uterus and placenta (CTUP; mm) and umbilical artery cross-sectional diameter, and Doppler mode examination was performed on both the middle uterine (MUA at right [R] and left [L] sides) and umbilical arteries to measure both Doppler indices that expressed by resistance (RI) and pulsatility indices (PI), and blood flow rate. CTUP was elevated within pregnancy time at different ages (P < 0.05). L. PI was significantly declined throughout different ages (P < 0.05), but this declining trend was not observed in L. RI. The L. blood flow rate (R; bpm) was elevated among different ages and different months (P < 0.05). Both RI and PI were significantly decreased from 5 to 9 month of gestation period in jennies (P < 0.05).. The umbilical arteries cross-sectional diameter (Umb A; mm), was elevated among different ages and different months, while both Doppler indices were declined. A positive correlation was found (between both Doppler indices of both umbilical and uterine arteries P < 0.001). There was elevated vascular perfusion in uterine and umbilical arteries associated with reduced both Doppler indices along the course of pregnancy at different ages.
IL-11 system participates in pulmonary artery remodeling and hypertension in pulmonary fibrosis
Authors: Milara Javier , Roger Inés , Montero Paula , Artigues Enrique , Escrivá Juan , Cortijo Julio
Published: November 2022

Background

Pulmonary hypertension (PH) associated to idiopathic pulmonary fibrosis (IPF) portends a poor prognosis. IL-11 has been implicated in fibrotic diseases, but their role on pulmonary vessels is unknown. Here we analyzed the contribution of IL-11 to PH in patients with IPF and the potential mechanism implicated.

Methods

Pulmonary arteries, lung tissue and serum of control subjects (n = 20), IPF (n = 20) and PH associated to IPF (n = 20) were used to study the expression and localization of IL-11 and IL-11Rα. Two models of IL-11 and bleomycin-induced lung fibrosis associated to PH were used in Tie2-GFP transgenic mice to evaluate the contribution of IL-11 and endothelial cells to pulmonary artery remodeling. The effect of IL-11 and soluble IL-11Rα on human pulmonary artery endothelial cells and smooth muscle cell transformations and proliferation were analyzed.

Results

IL-11 and IL-11Rα were over-expressed in pulmonary arteries and serum of patients with PH associated to IPF vs IPF patients without PH. Recombinant mice (rm)IL-11 induced lung fibrosis and PH in Tie2-GFP mice, activating in vivo EnMT as a contributor of pulmonary artery remodeling and lung fibrosis. Transient transfection of siRNA-IL-11 reduced lung fibrosis and PH in Tie2-GFP bleomycin model. Human (h)rIL-11 and soluble hrIL-11Rα induced endothelial to mesenchymal transition (EnMT) and pulmonary artery smooth muscle cell to myofibroblast-like transformation, cell proliferation and senescence in vitro.

Conclusions

IL-11 and IL-11Rα are overexpressed in pulmonary arteries of PH associated to IPF patients, and contributes to pulmonary artery remodeling and PH.
Impact of diabetes mellitus on long-term clinical and graft outcomes after off-pump coronary artery bypass grafting with pure bilateral skeletonized internal thoracic artery grafts
Authors: Park Ilkun , Choi Kuk Bin , Ahn Joong Hyun , Kim Wook Sung , Lee Young Tak , Jeong Dong Seop
Published: November 2022

Background

The effect of diabetes mellitus (DM) on the long-term outcomes of coronary artery bypass graft (CABG) remained debatable and various strategies exist for CABG; hence, clarifying the effects of DM on CABG outcomes is difficult. The current study aimed to evaluate the effect of DM on clinical and graft-related outcomes after CABG with bilateral internal thoracic artery (BITA) grafts.

Methods

From January 2001 to December 2017, 3395 patients who underwent off-pump CABG (OPCAB) with BITA grafts were enrolled. The study population was stratified according to preoperative DM. The primary endpoint was cardiac death and the secondary endpoints were myocardial infarction (MI), revascularization, graft failure, stroke, postoperative wound infection, and a composite endpoint of cardiac death, MI, and revascularization. Multiple sensitivity analyses, including Cox proportional hazard regression and propensity-score matching analyses, were performed to adjust baseline differences.

Results

After CABG, the DM group showed similar rates of cardiac death, MI, or revascularization and lower rates of graft failure at 10 years (DM vs. non-DM, 19.0% vs. 24.3%, hazard ratio [HR] 0.711, 95% confidence interval [CI] 0.549–0.925; P = 0.009) compared to the non-DM group. These findings were consistent after multiple sensitivity analyses. In the subgroup analysis, the well-controlled DM group, which is defined as preoperative hemoglobin A1c (HbA1c) of < 7%, showed lower postoperative wound infection rates (well-controlled DM vs. poorly controlled DM, 3.7% vs. 7.3%, HR 0.411, 95% CI 0.225–0.751; P = 0.004) compared to the poorly controlled DM group, which was consistent after propensity-score matched analysis.

Conclusions

OPCAB with BITA grafts showed excellent and comparable long-term clinical outcomes in patients with and without DM. DM might have a protective effect on competition and graft failure of ITA. Strict preoperative hyperglycemia control with target HbA1c of < 7% might reduce postoperative wound infection and facilitate the use of BITA in CABG.
Potential use of EGFR-targeted molecular therapies for tumor suppressor CYLD-negative and poor prognosis oral squamous cell carcinoma with chemoresistance
Authors: Kanemaru Ayumi , Shinriki Satoru , Kai Mimi , Tsurekawa Kanae , Ozeki Kazuya , Uchino Shota , Suenaga Naoki , Yonemaru Kou , Miyake Shunsuke , Masuda Takeshi , Kariya Ryusho , Okada Seiji , Takeshita Hisashi , Seki Yuki , Yano Hiromu , Komohara Yoshihiro , Yoshida Ryoji , Nakayama Hideki , Li Jian-Dong , Saito Hideyuki , Jono Hirofumi
Published: November 2022

Background

Tumor suppressor CYLD dysfunction by loss of its expression, triggers malignant transformation, especially drug resistance and tumor invasion/metastasis. Although loss of CYLD expression is significantly associated with poor prognosis in a large variety of tumors, no clinically-effective treatment for CYLD-negative cancer patients is available.

Methods

We focused on oral squamous cell carcinoma (OSCC), and sought to develop novel therapeutic agents for CYLD-negative cancer patients with poor prognosis. CYLD-knockdown OSCC cells by using CYLD-specific siRNA, were used to elucidate and determine the efficacy of novel drug candidates by evaluating cell viability and epithelial-mesenchymal transition (EMT)-like change. Therapeutic effects of candidate drug on cell line-derived xenograft (CDX) model and usefulness of CYLD as a novel biomarker using patient-derived xenograft (PDX) model were further investigated.

Results

CYLD-knockdown OSCC cells were resistant for all currently-available cytotoxic chemotherapeutic agents for OSCC, such as, cisplatin, 5-FU, carboplatin, docetaxel, and paclitaxel. By using comprehensive proteome analysis approach, we identified epidermal growth factor receptor (EGFR), a receptor tyrosine kinase, played key roles in CYLD-knockdown OSCC cells. Indeed, cell survival rate in the cisplatin-resistant CYLD-knockdown OSCC cells was markedly inhibited by treatment with clinically available EGFR tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib. In addition, gefitinib was significantly effective for not only cell survival, but also EMT-like changes through inhibiting transforming growth factor-β (TGF-β) signaling in CYLD-knockdown OSCC cells. Thereby, overall survival of CYLD-knockdown CDX models was significantly prolonged by gefitinib treatment. Moreover, we found that CYLD expression was significantly associated with gefitinib response by using PDX models.

Conclusions

Our results first revealed that EGFR-targeted molecular therapies, such as EGFR-TKIs, could have potential to be novel therapeutic agents for the CYLD-negative OSCC patients with poor prognosis.