bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

AbstractPeriodontal 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractThis 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

Abstract
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

Abstract
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

Abstract
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.