bluuebunny/crossref_metadata_2025 huggingface dataset:
Adverse cardiovascular outcomes associated with proton pump inhibitor use after percutaneous coronary intervention: a systematic review and meta-analysis
Authors: Padhi Bijaya K. , Khatib Mahalaqua Nazli , Zahiruddin Quazi Syed , Rustagi Sarvesh , Sharma Rakesh Kumar , Sah Ranjit , Satapathy Prakasini , Rao Arathi P.
Published: July 2024

Background

Proton pump inhibitors (PPIs) are commonly prescribed for gastroprotection in patients undergoing percutaneous coronary intervention (PCI), who are at increased risk of gastrointestinal bleeding due to antiplatelet therapy. However, emerging evidence suggests that PPIs may adversely impact cardiovascular outcomes. This systematic review and meta-analysis sought to assess the relationship between using PPIs and cardiovascular outcomes in patients following PCI.

Methods

We searched various databases up to March 15, 2024, for observational studies and randomized controlled trials (RCTs) assessing the cardiovascular effects of PPIs in PCI patients. Data were extracted on study characteristics, patient demographics, PPI use, and cardiovascular outcomes. The Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool 2 assessed study quality. Meta-analyses were conducted using a random-effects model using R software version 4.3.

Results

A total of 21 studies involving diverse populations and study designs were included. Observational studies suggested a moderate increase in risk for composite cardiovascular diseases (CVD), myocardial infarction (MI), and major adverse cardiac events (MACE) associated with PPI use, with pooled hazard ratios (HRs) of 1.20 (95% CI: 1.093–1.308) for CVD, 1.186 (95% CI: 1.069–1.303) for MI, and 1.155 (95% CI: 1.001–1.309) for MACE. However, RCTs showed no significant link between PPI therapy and negative cardiovascular events (Relative Risk: 1.016, 95% CI: 0.878–1.175). Substantial heterogeneity was observed among observational studies but not RCTs.

Conclusion

The findings indicate that while observational studies suggest a potential risk of adverse cardiovascular events with post-PCI use of PPI, RCTs do not support this association. Further large-scale, high-quality studies are required to understand the cardiovascular implications of individual PPIs better and optimize patient management post-PCI. This analysis shows the complexity of PPI use in patients with coronary artery diseases and the necessity to balance gastroprotective benefits against potential cardiovascular risks.
Addressing researcher degrees of freedom through minP adjustment
Authors: Mandl Maximilian M. , Becker-Pennrich Andrea S. , Hinske Ludwig C. , Hoffmann Sabine , Boulesteix Anne-Laure
Published: July 2024

When different researchers study the same research question using the same dataset they may obtain different and potentially even conflicting results. This is because there is often substantial flexibility in researchers’ analytical choices, an issue also referred to as “researcher degrees of freedom”. Combined with selective reporting of the smallest p-value or largest effect, researcher degrees of freedom may lead to an increased rate of false positive and overoptimistic results. In this paper, we address this issue by formalizing the multiplicity of analysis strategies as a multiple testing problem. As the test statistics of different analysis strategies are usually highly dependent, a naive approach such as the Bonferroni correction is inappropriate because it leads to an unacceptable loss of power. Instead, we propose using the “minP” adjustment method, which takes potential test dependencies into account and approximates the underlying null distribution of the minimal p-value through a permutation-based procedure. This procedure is known to achieve more power than simpler approaches while ensuring a weak control of the family-wise error rate. We illustrate our approach for addressing researcher degrees of freedom by applying it to a study on the impact of perioperative $$paO_2$$

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a

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2

on post-operative complications after neurosurgery. A total of 48 analysis strategies are considered and adjusted using the minP procedure. This approach allows to selectively report the result of the analysis strategy yielding the most convincing evidence, while controlling the type 1 error—and thus the risk of publishing false positive results that may not be replicable.
Barriers faced by primary healthcare providers in addressing emergencies in the Northern region of Palestine before and during the Gaza war
Authors: Hamshari Suha , Hamadneh Sondos , Ghneem Mukaram , Khalaf Raghad , Daqqa Sara , Alwafa Rola Abu , Ktaifan Mahfouz
Published: July 2024

Introduction

Physicians working in primary health care (PHC) centers are the first contact for patients and expected to deal with emergencies. Emergency care training in PHC settings has been neglected globally, especially in low to middle income countries. Adequate preparation becomes especially important during periods of conflict. The study objectives are to identify the barriers facing PHC physicians when dealing with emergency cases in the northern region of Palestine during the current conflict.

Methods

A cross-sectional study was conducted with 179 physicians working in the 10 PHC centers distributed among 5 northern governances in Palestine. The study period was from July through December 2023. Data were collected electronically using a self-administered questionnaire, which was adapted from a comprehensive literature review. The questionnaire’s internal validity was confirmed by a Cronbach’s alpha coefficient of [0.85], indicating high reliability.

Results

The ages of the physicians ranged from 25 to 60 years, with a mean ± SD of 35.3 ± 8.15 years. A significant majority (91.6%) were not boarded in any specialty. Most physicians (85.5%) had attended Basic Life Support (BLS) courses, whereas 45.2% and 72% had never attended Advanced Cardiovascular Life Support (ACLS) or Advanced Trauma Life Support (ATLS) courses, respectively. Physicians with emergency department experience (P = 0.002) and those who had attended ACLS courses (P < 0.001) reported significantly higher perceived competence in managing emergency cases.

Conclusion

Emergency services at PHC centers in northern Palestine are operational but require significant enhancements. There is a critical need for increased availability of essential equipment, supplies, and medications. Additionally, implementing comprehensive training programs in emergency management, particularly ACLS, is essential to improve the competence and performance of PHC physicians in emergency situations.
The symbiotic experiences of residents with and without dementia co-living in Taiwan’s long-term care facilities: a phenomenological study
Authors: Fang Chan-Chuan , Liu Yi-Hsun , Huang Shu-He
Published: July 2024

Background

In Taiwan, residents with and without dementia mostly co-live in long-term care facilities. The behavioral and psychiatric symptoms of dementia residents often pose challenges for others living together. This study explored the symbiotic experiences of residents without dementia co-living with those with dementia in long-term care facilities in Taiwan to present their experiences of living together.

Methods

This was a cross-sectional descriptive study with a phenomenological design. Semi-structured face-to-face interviews were conducted with 30 residents without dementia from three long-term care institutions in Taiwan. Colaizzi’s data processing steps were used for analysis.

Results

The analysis of interview transcripts revealed that the experiences of residents who lived with those with dementia were that of a “symbiosis.” Three core themes were found: “the impact of co-living,” “facing difficulties and coping,” and “companionship and reciprocity.” This study showed that residents without dementia may be affected by the behavioral and psychiatric symptoms of residents with dementia when co-living in long-term care facilities. However, there are also positive and mutually beneficial interactions between them. By helping people with dementia in their daily lives, residents without dementia feel happy and accomplished and their self-worth is enhanced. Furthermore, residents with dementia have more opportunities for social engagement and co-living interactions.

Conclusion

These results can guide long-term care facilities without special care dementia units to support residents without dementia, reduce the interference of the behavioral and psychiatric symptoms of residents with dementia, and promote mutual benefits. However, these findings warrant further investigation.
High silent prevalence of human herpesvirus 1 (HSV-1) infection affecting the indigenous reservation of the municipality of Dourados, Central-West Brazil
Authors: de Oliveira Bonfim Flávia Freitas , Villar Livia Melo , Croda Julio , Pereira Jéssica Gonçalves , Guimarães Ana Carolina Silva , da Silva Solange Rodrigues , Maymone Gonçalves Crhistinne Cavalheiro , Leonardo Lucas Fernando Tinoco , de Rezende Romeira Grazielli Rocha , Cesar Gabriela Alves , Weis-Torres Sabrina , de Oliveira Landgraf de Castro Vivianne , Horta Marco Aurélio , Simionatto Simone , Motta-Castro Ana Rita Coimbra , de Paula Vanessa Salete
Published: July 2024

Background

The indigenous population located in the central region of Brazil, is the second largest in terms of population size in the country. The Indigenous Reserve of Dourados has risk factors that increase the vulnerability of the indigenous population to infectious diseases, especiallyHuman alphaherpesvirus(HSV-1), a neglected disease with high prevalence in priority populations in developing countries. The virus can also cause many more severe diseases, including widespread neonatal infections, herpetic keratitis, and herpes encephalitis, which can be fatal if left untreated. We estimated the prevalence of anti-HSV-1 antibodies and correlated it with the demographic and behavioral characteristics of the Indigenous population of the Jaguapirú and Bororó villages (Dourados, Mato Grosso do Sul (MS), Brazil).

Methods

Our approach was cross-sectional. From March 2017 to November 2018. Using anti-HSV-1 (Gg1) IgM and anti-HSV-1 (gG1) IgG Euroimmun and the detection and quantification of HSV-1 viral load in plasma samples, through real-time PCR. The maps were constructed using QGIS and the statistical analyses using R Studio software.

Results

A total of 1138 individuals (> 18 years old) were enrolled. The prevalence of anti-HSV-1 IgM and IgG were 20% and 97.5%, respectively. The prevalence of anti-HSV-1 antibodies for IgG was higher in both sexes. Anti-HSV-1 IgM antibodies were present in 17.1%, 21.2%, 12.5%, and 22% of the participants with urinary problems, genital wounds, genital warts, and urethral discharge, respectively. Real-time PCR was used for confirmatory testing; HSV-1 DNA was detected in 25.6% (54/211) of anti-HSV1 IgM-positive samples. Viral loads ranged from 5.99E + 02 to 3.36E + 13.

Conclusions

The seroprevalence of HSV-1 IgM and detection of HSV-1 DNA in the Indigenous population confirmed high silent prevalence. Furthermore, the seroprevalence of HSV-1 in the Indigenous population was higher than that reported in the general adult Brazilian population. Various socioeconomic factors, drug use, and health and sexual behaviors could contribute to the facilitation of HSV-1 transmission in the Indigenous population. Our results may help develop culturally appropriate intervention programs that eliminate health access barriers and improve the implementation of public health policies aimed at promoting information regarding the prevention, treatment, and control of HSV-1 infection in Brazilian Indigenous populations.
Neurological manifestations of ehrlichiosis among a cohort of patients: prevalence and clinical symptoms
Authors: Iyamu Osahon , Ciccone Emily J. , Schulz Abigail , Sung Julia , Abernathy Haley , Alejo Aidin , Tyrlik Katherine , Arahirwa Victor , Mansour Odai , Giandomenico Dana , Diaz Monica M. , Boyce Ross M.
Published: July 2024

Background

Ehrlichiosis is a potentially fatal tick-borne disease that can progress to involve the central nervous system (CNS) (i.e., neuro-ehrlichiosis), particularly in cases where diagnosis and treatment are delayed. Despite a six-fold national increase in the incidence of ehrlichiosis over the past 20 years, recent data on the prevalence and manifestations of neuro-ehrlichiosis are lacking.

Methods

We conducted a retrospective chart review of all patients tested for ehrlichiosis at University of North Carolina Health facilities between 2018 and 2021 and identified patients who met epidemiological criteria for ehrlichiosis as established by the Council of State and Territorial Epidemiologists and employed by the Centers for Disease Control and Prevention. We estimated the prevalence of neurological symptoms and described the spectrum of neurological manifestations in acute ehrlichiosis, documenting select patient cases in more detail in a case series.

Results

Out of 55 patients with confirmed or probable ehrlichiosis, five patients (9.1%) had neurologic symptoms, which is notably lower than previous estimates. Neurological presentations were highly variable and included confusion, amnesia, seizures, focal neurological deficits mimicking ischemic vascular events, and an isolated cranial nerve palsy, though all patients had unremarkable neuroimaging at time of presentation. All but one patient had risk factors for severe ehrlichiosis (i.e., older age, immunosuppression).

Conclusions

Neuro-ehrlichiosis may lack unifying patterns in clinical presentation that would otherwise aid in diagnosis. Clinicians should maintain a high index of suspicion for neuro-ehrlichiosis in patients with acute febrile illness, diverse neurological symptoms, and negative neuroimaging in lone star tick endemic regions.
Maternal health service utilization in the Jimma Zone, Ethiopia: results from a baseline study for mobile phone messaging interventions
Authors: Bulcha Gebeyehu , Gutema Hordofa , Amenu Demisew , Birhanu Zewdie
Published: July 2024

Background

Over the last 20 years, global healthcare has placed a major focus on improving the survival rates of mothers and children, recognizing the potential to prevent a significant number of deaths resulting from pregnancy and childbirth. Nevertheless, there remains an ongoing obstacle to the insufficient utilization of critical obstetric services to achieve optimal health outcomes for pregnant women. This study aimed to assess the magnitude and determinants of maternal healthcare use in the Jimma Zone, Ethiopia.

Methods

Data were obtained from a household survey as part of the baseline assessment of a cluster randomized controlled trial. The study participants comprised 588 women in early pregnancy, specifically those with a gestational age of less than 20 weeks. Logistic regression analysis was employed to identify factors associated with the use of maternal health services. Adjusted odds ratios (AORs) were used to assess the strength of the associations, with significance level set at a p-value ≤ 0.05.

Results

The overall prevalence of maternal health service utilization was 87.9% (CI: 85.1, 90.4) for antenatal care, 74.7% (CI: 73.2, 79.9) for health facility delivery, and 60.4% (CI: 56.4, 64.3) for postnatal care. Multivariable logistic analysis revealed that maternal health service use was significantly influenced by access to health facilities (AOR: 6.6; 95% CI: 2.39, 18.16), financial hardship (AOR: 3; 95% CI: 1.97, 4.61), perceived respectful care (AOR: 2.3; 95% CI: 1.07, 5.11), perceived privacy of service provisions (AOR: 2.4; 95% CI: 1.47, 4.06), and attitudes toward maternal service use (AOR: 2.2; 95% CI: 1.48, 3.24).

Conclusions

The study revealed slightly higher rates of antenatal care, facility delivery, and postpartum care utilization. However, there was a low proportion of early antenatal care initiation, and high rates of antenatal care dropout. Mobile phone-based messaging intervention may enhance maternal health service use by addressing factors such as lack of access, economic challenges, disrespectful care, no privacy of procedures, and unfavorable attitudes.
Associations between left-behind children’s characteristics and psychological symptoms: a cross-sectional study from China
Authors: Liu Cong , Xu Yan , Sun Hao , Yuan Yan , Lu Jinkui , Jiang Jing , Liu Ningling
Published: July 2024

Background

Parent-child separation poses a significant challenge for left-behind children (LBC). However, limited empirical evidence exists regarding the correlation between left-behind characteristics and the psychological symptoms of LBC. This study investigated psychological symptoms among LBC and explored associations between left-behind characteristics and those symptoms.

Methods

Using stratified cluster sampling, 1,832 LBC aged 13–18 years from three cities in East China were selected for analysis. Participants’ depression and anxiety symptoms were assessed with the Patient Health Questionnaire 9 and the General Anxiety Disorder 7, respectively. Chi-square tests were used to compare differences in detection rates of psychological symptoms among LBC in different groups. Binary logistic regression analysis was used to infer associations between left-behind characteristics and psychological symptoms.

Results

Depression and anxiety symptoms were detected in 32.86% and 33.24%, respectively, of participating LBC. Univariate analysis showed statistically significant differences in detection rates of depression symptoms by sex, grade, and timing of parent-child separation. Statistically significant differences were observed in anxiety symptom rates by sex, grade, type of caregiver, and timing of mother-child separation. Multivariate analysis indicated a positive association between LBC’s anxiety symptoms and mother-child separation that occurred during post-primary school, and type of caregiver (father only or mother only). Our findings confirm a positive association between left-behind characteristics and anxiety symptoms among LBC.

Conclusion

The timing of mother-child separation and type of caregiver are potential risk factors for the development of anxiety symptoms in this population.
‘Life became harder with COVID-19’: exploring the experiences of the COVID-19 pandemic among youth living in eThekwini district, South Africa
Authors: Closson Kalysha , Dong Erica , Zulu Bongiwe , Dietrich Janan J. , Zharima Campion , Jesson Julie , Pakhomova Tatiana , Beksinska Mags , Kaida Angela
Published: July 2024

Background

In South Africa, pervasive age and gender inequities have been exacerbated by the COVID-19 pandemic and public health response. We aimed to explore experiences of the COVID-19 pandemic among youth in eThekwini district, South Africa.

Methods

Between December 2021-May 2022 we explored experiences of the COVID-19 pandemic on youth aged 16–24 residing in eThekwini, South Africa. We collated responses to the open-ended question “Has the COVID-19 pandemic affected you in any other way you want to tell us about?” in an online survey focused on understanding the pandemic’s multi-levelled health and social effects. We used a thematic analysis to summarise the responses.

Results

Of 2,068 respondents, 256 (12.4%, median age = 22, 60.9% women) completed the open-ended survey question (11% in isiZulu). Results were organized into three main themes encompassing (1) COVID-19-related loss, fear, grief, and exacerbated mental and physical health concerns; (2) COVID-19-related intensified hardships, which contributed to financial, employment, food, education, and relationship insecurities for individuals and households; and (3) positive effects of the pandemic response, including the benefits of government policies and silver linings to government restrictions.

Conclusions

We found that South African youth experienced significant grief and multiple losses (e.g., death, income, job, and educational) during the COVID-19 pandemic. Trauma-aware interventions that provide economic and educational opportunities must be included in post-COVID recovery efforts.
Effect of wildfire on the prevalence of opioid misuse through anxiety among young adults in the United States: a modeling study
Authors: Maya Sigal , Mirzazadeh Ali , Kahn James G.
Published: July 2024

Background

Exposure to climate change events like wildfires can lead to health and mental health problems. While conceptual frameworks have been hypothesized describing the potential relationship between disaster exposure and substance use, the association remains under-researched and unquantified.

Methods

We constructed a quantitative portrayal of one proposed conceptual framework that focuses on the intermediary role of anxiety. We used the Monte Carlo simulation to estimate the impact of wildfire exposure on opioid misuse outcomes through increased anxiety. We searched for and extracted prior empirical evidence on the associations between wildfire anxiety and anxiety-opioid misuse. Three scenarios were devised: in S1 the impact of wildfire on opioid misuse was limited to increasing anxiety incidence; in S2 we also considered the additive role of altered anxiety phenotype; and in S3 we further considered the role of increased opioid-related consequences of pre-existing anxiety due to wildfire exposure.

Results

Models show that the prevalence of opioid misuse post-wildfire may rise to 6.0%-7.2% from a baseline of 5.3%. In S1, the opioid misuse prevalence ratio was 1.12 (95% uncertainty interval [UI]: 1.00 – 1.27). The two exploratory scenarios, with less stringent assumptions, yielded prevalence ratios of 1.23 (95% UI: 1.00 – 1.51) and 1.34 (95% UI: 1.11 – 1.63).

Conclusions

Our modeling study suggests that exposure to wildfires may elevate opioid misuse through increasing anxiety incidence and severity. This can lead to substantial health burdens, possibly beyond the duration of the wildfire event, which may offset recent gains in opioid misuse prevention.
National trends and ecological factors of physical activity engagement among U.S youth before and during the COVID-19 pandemic: A cohort study from 2019 to 2021
Authors: Zhu Yuxin , Chan Derwin K.C. , Pan Qianqian , Rhodes Ryan E. , Tao Sisi
Published: July 2024

Background

This study aims to investigate the trends and ecological determinants of physical activity among U.S. children and adolescents during the 2019–2021 period, encompassing the COVID-19 pandemic’s onset and subsequent years.

Methods

Utilizing data from the National Survey of Children’s Health over three years, this cohort study analyzed physical activity levels and ecological determinants among 82,068 participants aged 6–17. The sample included 36,133 children (44%) and 45,935 adolescents (56%), with variables assessed by caregiver reports.

Results

The analysis revealed a significant decline in physical activity among children from 2019 to 2020, followed by a recovery in 2021, whereas adolescents showed a continued decrease without recovery. Over the study period, children were consistently more active than adolescents. Better health status, normal weight, less screen time, stronger peer relationships, higher parental involvement, better family resilience and greater school participation were consistently correlated with increased physical activity in both age groups. Sleep duration was a predictor of activity only in children, while mental health status was solely a predictor in adolescents. Neighborhood environment consistently predicted children’s activity levels but was a significant factor for adolescents only in 2020.

Conclusions

These findings highlight the differing impacts of the pandemic on physical activity between children and adolescents, emphasizing the need for targeted public health interventions, particularly for adolescents whose activity levels have not recovered from the pandemic period. Age-specific physical activity interventions should consider sleep duration and neighborhood environmental factors when targeting children and mental health factors when focused on adolescents.
Prevalence of diabetes and hospitalization due to poor glycemic control in people with bladder cancer or renal cell carcinoma in Sweden
Authors: Andersson Emelie , Brådvik Gunnar , Nilsson Fredrik O. L. , Arpegård Johannes , Strambi Angela , Kollberg Petter , Carlsson Katarina Steen
Published: July 2024

Background

Bladder cancer (BC) and Renal cell carcinoma (RCC) are the most common urogenital cancers among both sexes, with a yearly global incidence of around 500 000 each. Both BC and RCC have been linked to diabetes. Poor glycemic control (malglycemia) is a serious consequence of diabetes and a possible consequence of systemic treatments used in BC and RCC. The objective of this study was to investigate the prevalence of diabetes and use of hospital-based care for malglycemia in people with BC or RCC.

Methods

This Swedish retrospective population-based register study used national health-data registers for longitudinal data on cancer incidence covering 15 years, use of hospital-based health care, and filled prescriptions of outpatient medications. Study endpoints included co-prevalence of diabetes in individuals with BC/RCC, healthcare resource utilization due to malglycemia, use of systemic corticosteroids, and changes in diabetes management for people with concomitant type 2 diabetes.

Results

We identified 36,620 and 15,581 individuals diagnosed with BC and RCC, respectively, between 2006 and 2019. The proportion of individuals registered with diabetes was 24% in BC and 23% in RCC. An association between BC/RCC and poor glycemic control was found, although the number of malglycemic events in hospital-based care were few (65/59 per 1000 individuals with diabetes and BC/RCC respectively with at least one event). An earlier switch to insulin-based diabetes management was observed in BC/RCC compared to matched individuals with type 2 diabetes but no cancer. The results also indicated an association between steroid treatment and poor glycemic control, and that systemic corticosteroids were more common among people with BC/RCC compared to diabetes controls.

Conclusion

The high prevalence of diabetes and increased use of systemic corticosteroid treatment observed in this large national study highlights the need for specific clinical management, risk-assessment, and monitoring of individuals with BC/RCC and diabetes.
Correlation between serum sex hormone-binding globulin levels and nutrition indicators and malnutrition exposure risk in men and postmenopausal women with type 2 diabetes
Authors: Lin Jinxin , Wu Weiming , Weng Yifu , Lan Yingru , Wen Yuqiong , Lai Shuiqing , Fu Xiaoying , Kuang Jian , Guan Haixia , Chen Hongmei
Published: July 2024

Background

This study sought to investigate the correlation between serum sex hormone-binding globulin (SHBG) levels and nutrition indicators and the malnutrition exposure risk in men and postmenopausal women with type 2 diabetes mellitus (T2DM).

Methods

A cross-sectional analysis was conducted, involving patients diagnosed with T2DM at the Guangdong Provincial People’s Hospital between May 2018 and December 2019.

Results

The study comprised 551 participants (363 men, mean age of 55.55 ± 11.57 years), among whom 167 (30.31%) were classified as with malnutrition exposure risk (GNRI ≤ 98). Multivariable logistic regression analysis revealed that SHBG (OR = 1.04, 95% CI: 1.02–1.05, P < 0.001), glycated hemoglobin (OR = 1.36, 95% CI: 1.22–1.51, P < 0.001), hemoglobin (OR = 0.96, 95% CI: 0.94–0.97, P < 0.001), and non-alcoholic fatty liver disease (OR = 0.41, 95% CI: 0.23–0.73, P < 0.003) were independently associated with the malnutrition exposure risk. SHBG was inversely correlated with body mass index (males: r = -0.34; postmenopausal females: r = -0.22), albumin (males: r = -0.30; postmenopausal females: r = -0.20), transferrin (males: r = -0.28; postmenopausal females: r = -0.19), and prealbumin (males: r = -0.35; postmenopausal females: r = -0.30) (all P < 0.05).

Conclusions

Serum SHBG levels are correlated with nutritional indicators and the risk of malnutrition in men and postmenopausal women with T2DM. A multicenter prospective study is imperative to verify this result in the future.
Mental health care use and quality among Medicaid adults with serious mental illness receiving care at Federally Qualified Health Centers vs. other settings
Authors: Myong Catherine , Yang Zhiyou , Behr Caroline , Fung Vicki
Published: July 2024

Background

Federally Qualified Health Centers (FQHCs) are a critical source of care for medically underserved populations and often serve as medical homes for individuals with serious mental illness (SMI). Many FQHCs provide mental health services and could facilitate access to mental health treatment within and outside of FQHCs. This study compared mental health care utilization and acute care events for adult Medicaid enrollees with SMI who receive care at Federally Qualified Health Centers (FQHCs) vs. other settings.

Methods

This study used the 2015–2016 Massachusetts All-Payer Claims Database to examine outpatient mental health care and acute care events for 32,330 Medicaid adults, ages 18–64 and with major depressive, bipolar, or schizophrenia spectrum disorders (SSD), who resided in FQHC service areas and received care from FQHCs vs. other settings in 2015. Multivariable linear regressions assessed associations between receiving care at FQHCs and outpatient mental health visits, psychotropic medication fills, and acute care events in 2016.

Results

There were 8,887 (27.5%) adults in the study population (N = 32,330) who had at least one FQHC visit in 2015. Those who received care at FQHCs were more likely to have outpatient mental health visits (73.3% vs. 71.2%) and psychotropic medication fills (73.2% vs. 69.0%, both p < .05), including antidepressants among those with depressive disorders and antipsychotics among those with SSD. They were more likely to have ED visits (74.0% vs. 68.7%), but less likely to be hospitalized (27.8% vs. 31.9%, both p < .05). However, there was no significant difference in the likelihood of having an acute psychiatric hospitalization (9.5% vs. 9.8%, p = .35).

Conclusions

Among Medicaid enrollees with SMIs who had access to care at FQHCs, those receiving care at FQHCs were more likely to have outpatient mental health visits and psychotropic medication fills, with lower rates of hospitalization, suggesting potentially improved quality of outpatient care. Higher ED visit rates among those receiving care at FQHCs warrant additional investigation.
Roughness affects the response of human fibroblasts and macrophages to sandblasted abutments
Authors: Romero-Gavilán Francisco , Arias-Mainer Carlos , Cerqueira Andreia , Peñarrocha-Oltra David , Bernabeu-Mira Juan Carlos , García-Arnáez Iñaki , Elortza Félix , Muriach María , Gurruchaga Mariló , Goñi Isabel , Suay Julio
Published: July 2024

Background

A strong seal of soft-tissue around dental implants is essential to block pathogens from entering the peri-implant interface and prevent infections. Therefore, the integration of soft-tissue poses a challenge in implant-prosthetic procedures, prompting a focus on the interface between peri-implant soft-tissues and the transmucosal component. The aim of this study was to analyse the effects of sandblasted roughness levels on in vitro soft-tissue healing around dental implant abutments. In parallel, proteomic techniques were applied to study the interaction of these surfaces with human serum proteins to evaluate their potential to promote soft-tissue regeneration.

Results

Grade-5 machined titanium discs (MC) underwent sandblasting with alumina particles of two sizes (4 and 8 μm), resulting in two different surface types: MC04 and MC08. Surface morphology and roughness were characterised employing scanning electron microscopy and optical profilometry. Cell adhesion and collagen synthesis, as well as immune responses, were assessed using human gingival fibroblasts (hGF) and macrophages (THP-1), respectively. The profiles of protein adsorption to the surfaces were characterised using proteomics; samples were incubated with human serum, and the adsorbed proteins analysed employing nLC–MS/MS. hGFs exposed to MC04 showed decreased cell area compared to MC, while no differences were found for MC08. hGF collagen synthesis increased after 7 days for MC08. THP-1 macrophages cultured on MC04 and MC08 showed a reduced TNF-α and increased IL-4 secretion. Thus, the sandblasted topography led a reduction in the immune/inflammatory response. One hundred seventy-six distinct proteins adsorbed on the surfaces were identified. Differentially adsorbed proteins were associated with immune response, blood coagulation, angiogenesis, fibrinolysis and tissue regeneration.

Conclusions

Increased roughness through MC08 treatment resulted in increased collagen synthesis in hGF and resulted in a reduction in the surface immune response in human macrophages. These results correlate with the changes in protein adsorption on the surfaces observed through proteomics.
Modulating cell stiffness for improved vascularization: leveraging the MIL-53(fe) for improved interaction of titanium implant and endothelial cell
Authors: Wu Jie , Liu Leyi , Du Weidong , Lu Yunyang , Li Runze , Wang Chao , Xu Duoling , Ku Weili , Li Shujun , Hou Wentao , Yu Dongsheng , Zhao Wei
Published: July 2024

Vascularization plays a significant role in promoting the expedited process of bone regeneration while also enhancing the stability and viability of artificial bone implants. Although titanium alloy scaffolds were designed to mimic the porous structure of human bone tissues to facilitate vascularization in bone repair, their biological inertness restricted their broader utilization. The unique attribute of Metal-organic framework (MOF) MIL-53(Fe), known as “breathing”, can facilitate the efficient adsorption of extracellular matrix proteins and thus provide the possibility for efficient interaction between scaffolds and cell adhesion molecules, which helps improve the bioactivity of the titanium alloy scaffolds. In this study, MIL-53(Fe) was synthesized in situ on the scaffold after hydrothermal treatment. The MIL-53(Fe) endowed the scaffold with superior protein absorption ability and preferable biocompatibility. The scaffolds have been shown to possess favorable osteogenesis and angiogenesis inducibility. It was indicated that MIL-53(Fe) modulated the mechanotransduction process of endothelial cells and induced increased cell stiffness by promoting the adsorption of adhesion-mediating extracellular matrix proteins to the scaffold, such as laminin, fibronectin, and perlecan et al., which contributed to the activation of the endothelial tip cell phenotype at sprouting angiogenesis. Therefore, this study effectively leveraged the intrinsic “breathing” properties of MIL-53 (Fe) to enhance the interaction between titanium alloy scaffolds and vascular endothelial cells, thereby facilitating the vascularization inducibility of the scaffold, particularly during the sprouting angiogenesis phase. This study indicates that MIL-53(Fe) coating represents a promising strategy to facilitate accelerated and sufficient vascularization and uncovers the scaffold-vessel interaction from a biomechanical perspective.

Graphical Abstract
Targeting CCL2-CCR2 signaling pathway alleviates macrophage dysfunction in COPD via PI3K-AKT axis
Authors: Dong Yue , Dong Ying , Zhu Chengyue , Yang Lan , Wang Hanlin , Li Junqing , Zheng Zixuan , Zhao Hanwei , Xie Wanji , Chen Meiting , Jie Zhijun , Li Jia , Zang Yi , Shi Jindong
Published: July 2024

Background

Chronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality worldwide, characterized by persistent respiratory symptoms and airflow limitation. The involvement of C–C motif chemokine ligand 2 (CCL2) in COPD pathogenesis, particularly in macrophage regulation and activation, is poorly understood despite its recognized role in chronic inflammation. Our study aims to elucidate the regulatory role and molecular mechanisms of CCL2 in the pathogenesis of COPD, providing new insights for therapeutic strategies.

Methods

This study focused on the CCL2-CCR2 signaling pathway, exploring its role in COPD pathogenesis using bothCcl2knockout (KO) mice and pharmacological inhibitors. To dissect the underlying mechanisms, we employed various in vitro and in vivo methods to analyze the secretion patterns and pathogenic effects of CCL2 and its downstream molecular signaling through the CCL2-CCR2 axis.

Results

Elevated Ccl2 expression was confirmed in the lungs of COPD mice and was associated with enhanced recruitment and activation of macrophages. Deletion ofCcl2in knockout mice, as well as treatment with a Ccr2 inhibitor, resulted in protection against CS- and LPS-induced alveolar injury and airway remodeling. Mechanistically, CCL2 was predominantly secreted by bronchial epithelial cells in a process dependent on STAT1 phosphorylation and acted through the CCR2 receptor on macrophages. This interaction activated the PI3K-AKT signaling pathway, which was pivotal for macrophage activation and the secretion of inflammatory cytokines, further influencing the progression of COPD.

Conclusions

The study highlighted the crucial role of CCL2 in mediating inflammatory responses and remodeling in COPD. It enhanced our understanding of COPD's molecular mechanisms, particularly how CCL2's interaction with the CCR2 activates critical signaling pathways. Targeting the CCL2-CCR2 axis emerged as a promising strategy to alleviate COPD pathology.

Graphical Abstract
Regulation of brain fluid volumes and pressures: basic principles, intracranial hypertension, ventriculomegaly and hydrocephalus
Authors: Hladky Stephen B. , Barrand Margery A.
Published: July 2024

The principles of cerebrospinal fluid (CSF) production, circulation and outflow and regulation of fluid volumes and pressures in the normal brain are summarised. Abnormalities in these aspects in intracranial hypertension, ventriculomegaly and hydrocephalus are discussed. The brain parenchyma has a cellular framework with interstitial fluid (ISF) in the intervening spaces. Framework stress and interstitial fluid pressure (ISFP) combined provide the total stress which, after allowing for gravity, normally equals intracerebral pressure (ICP) with gradients of total stress too small to measure. Fluid pressure may differ from ICP in the parenchyma and collapsed subarachnoid spaces when the parenchyma presses against the meninges. Fluid pressure gradients determine fluid movements. In adults, restricting CSF outflow from subarachnoid spaces produces intracranial hypertension which, when CSF volumes change very little, is called idiopathic intracranial hypertension (iIH). Raised ICP in iIH is accompanied by increased venous sinus pressure, though which is cause and which effect is unclear. In infants with growing skulls, restriction in outflow leads to increased head and CSF volumes. In adults, ventriculomegaly can arise due to cerebral atrophy or, in hydrocephalus, to obstructions to intracranial CSF flow. In non-communicating hydrocephalus, flow through or out of the ventricles is somehow obstructed, whereas in communicating hydrocephalus, the obstruction is somewhere between the cisterna magna and cranial sites of outflow. When normal outflow routes are obstructed, continued CSF production in the ventricles may be partially balanced by outflow through the parenchyma via an oedematous periventricular layer and perivascular spaces. In adults, secondary hydrocephalus with raised ICP results from obvious obstructions to flow. By contrast, with the more subtly obstructed flow seen in normal pressure hydrocephalus (NPH), fluid pressure must be reduced elsewhere, e.g. in some subarachnoid spaces. In idiopathic NPH, where ventriculomegaly is accompanied by gait disturbance, dementia and/or urinary incontinence, the functional deficits can sometimes be reversed by shunting or third ventriculostomy. Parenchymal shrinkage is irreversible in late stage hydrocephalus with cellular framework loss but may not occur in early stages, whether by exclusion of fluid or otherwise. Further studies that are needed to explain the development of hydrocephalus are outlined.
Modelling the nicotine pharmacokinetic profile for e-cigarettes using real time monitoring of consumers’ physiological measurements and mouth level exposure
Authors: Prasad Krishna , Griffiths Allen , Agrawal Kavya , McEwan Michael , Macci Flavio , Ghisoni Marco , Stopher Matthew , Napleton Matthew , Strickland Joel , Keating David , Whitehead Thomas , Conduit Gareth , Murray Stacey , Edward Lauren
Published: July 2024

Pharmacokinetic (PK) studies can provide essential information on abuse liability of nicotine and tobacco products but are intrusive and must be conducted in a clinical environment. The objective of the study was to explore whether changes in plasma nicotine levels following use of an e-cigarette can be predicted from real time monitoring of physiological parameters and mouth level exposure (MLE) to nicotine before, during, and after e-cigarette vaping, using wearable devices. Such an approach would allow an -effective pre-screening process, reducing the number of clinical studies, reducing the number of products to be tested and the number of blood draws required in a clinical PK study Establishing such a prediction model might facilitate the longitudinal collection of data on product use and nicotine expression among consumers using nicotine products in their normal environments, thereby reducing the need for intrusive clinical studies while generating PK data related to product use in the real world.

An exploratory machine learning model was developed to predict changes in plasma nicotine levels following the use of an e-cigarette; from real time monitoring of physiological parameters and MLE to nicotine before, during, and after e-cigarette vaping. This preliminary study identified key parameters, such as heart rate (HR), heart rate variability (HRV), and physiological stress (PS) that may act as predictors for an individual’s plasma nicotine response (PK curve). Relative to baseline measurements (per participant), HR showed a significant increase for nicotine containing e-liquids and was consistent across sessions (intra-participant). Imputing missing values and training the model on all data resulted in 57% improvement from the original’learning’ data and achieved a median validation R2 of 0.70.

The study is in its exploratory phase, with limitations including a small and non-diverse sample size and reliance on data from a single e-cigarette product. These findings necessitate further research for validation and to enhance the model's generalisability and applicability in real-world settings. This study serves as a foundational step towards developing non-intrusive PK models for nicotine product use.
The RP11-417E7.1/THBS2 signaling pathway promotes colorectal cancer metastasis by activating the Wnt/β-catenin pathway and facilitating exosome-mediated M2 macrophage polarization
Authors: Liu Yunze , Lv Heng , Liu Xin , Xu Lei , Li Tiankang , Zhou Hui , Zhu Hongmei , Hao Chuanchuan , Lin Changwei , Zhang Yi
Published: July 2024

Background

Metastasis is the major cause of colorectal cancer (CRC) mortality. Emerging evidence suggests that long noncoding RNAs (lncRNAs) drive cancer metastasis and that their regulatory pathways could be targeted for preventing metastasis. However, the underlying mechanisms of lncRNAs in CRC metastasis remain poorly understood.

Methods

Microarray analysis was used to screen for differentially expressed lncRNAs. Transwell assays, fibronectin cell adhesion assays, and mouse metastasis models were utilized to evaluate the metastatic capacities of CRC in vitro and in vivo. Chromatin isolation by RNA purification, chromatin immunoprecipitation and chromosome conformation capture were applied to investigate the underlying mechanism involved. qRT‒PCR and transmission electron microscopy were performed to confirm macrophage polarization and the presence of cancer-derived exosomes.

Results

The lncRNA RP11-417E7.1 was screened and identified as a novel metastasis-associated lncRNA that was correlated with a poor prognosis. RP11-417E7.1 enhances the metastatic capacity of CRC cells in vivo and in vitro. Mechanistically, RP11-417E7.1 binding with High mobility group A1 (HMGA1) promotes neighboring thrombospondin 2 (THBS2) transcription via chromatin loop formation between its promoter and enhancer, which activates the Wnt/β-catenin signaling pathway and facilitates CRC metastasis. Furthermore, exosomes derived from CRC cells transport THBS2 into macrophages, thereby inducing the M2 polarization of macrophages to sustain the prometastatic microenvironment. Notably, netropsin, a DNA-binding drug, suppresses chromatin loop formation mediated by RP11-417E7.1 at the THBS2 locus and significantly inhibits CRC metastasis in vitro and in vivo.

Conclusions

This study revealed the novel prometastatic function and mechanism of the lncRNA RP11-417E7.1, which provides a potential prognostic indicator and therapeutic target in CRC.
Targeted proteomics of plasma extracellular vesicles uncovers MUC1 as combinatorial biomarker for the early detection of high-grade serous ovarian cancer
Authors: Cooper Tyler T. , Dieters-Castator Dylan Z. , Liu Jiahui , Siegers Gabrielle M. , Pink Desmond , Veliz Lorena , Lewis John D. , Lagugné-Labarthet François , Fu Yangxin , Steed Helen , Lajoie Gilles A. , Postovit Lynne-Marie
Published: July 2024

Background

The five-year prognosis for patients with late-stage high-grade serous carcinoma (HGSC) remains dismal, underscoring the critical need for identifying early-stage biomarkers. This study explores the potential of extracellular vesicles (EVs) circulating in blood, which are believed to harbor proteomic cargo reflective of the HGSC microenvironment, as a source for biomarker discovery.

Results

We conducted a comprehensive proteomic profiling of EVs isolated from blood plasma, ascites, and cell lines of patients, employing both data-dependent (DDA) and data-independent acquisition (DIA) methods to construct a spectral library tailored for targeted proteomics. Our investigation aimed at uncovering novel biomarkers for the early detection of HGSC by comparing the proteomic signatures of EVs from women with HGSC to those with benign gynecological conditions. The initial cohort, comprising 19 donors, utilized DDA proteomics for spectral library development. The subsequent cohort, involving 30 HGSC patients and 30 control subjects, employed DIA proteomics for a similar purpose. Support vector machine (SVM) classification was applied in both cohorts to identify combinatorial biomarkers with high specificity and sensitivity (ROC-AUC > 0.90). Notably, MUC1 emerged as a significant biomarker in both cohorts when used in combination with additional biomarkers. Validation through an ELISA assay on a subset of benign (n = 18), Stage I (n = 9), and stage II (n = 9) plasma samples corroborated the diagnostic utility of MUC1 in the early-stage detection of HGSC.

Conclusions

This study highlights the value of EV-based proteomic analysis in the discovery of combinatorial biomarkers for early ovarian cancer detection.