bluuebunny/crossref_metadata_2025 huggingface dataset:
The association between sarcopenia and incident of depressive symptoms: a prospective cohort study
Authors: Li Zhenzhen , Liu Bingqing , Tong Xiang , Ma Yao , Bao Ting , Yue Jirong , Wu Chenkai
Published: January 2024

Background

Epidemiological studies have shown that sarcopenia was associated with depression among older adults. However, most of these investigations used a cross-sectional design, limiting the ability to establish a causal relation, the present study examined whether sarcopenia was associated with incident depressive symptoms.

Methods

This is a prospective cohort study with participants from the Western China Health and Aging Trends (WCHAT) study. Participants could complete anthropometric measurements and questionnaires were included. The exposure was sarcopenia, defined according to the Asian Working Group for Sarcopenia in 2019, the outcome was depressive symptoms, evaluated by GDS-15. We excluded depression and depressive symptoms at baseline and calculated the risk of incident depressive symptoms during the follow-up year.

Results

A total of 2612 participants (mean age of 62.14 ± 8.08 years) were included, of which 493 with sarcopenia. 78 (15.82%) participants with sarcopenia had onset depressive symptoms within the next year. After multivariable adjustment, sarcopenia increased the risk of depressive symptoms (RR = 1.651, 95%CI = 1.087–2.507, P = 0.0187) in overall participants. Such relationship still exists in gender and sarcopenia severity subgroups. Low muscle mass increased the risk of depressive symptoms (RR = 1.600, 95%CI = 1.150–2.228, P = 0.0053), but low muscle strength had no effect (RR = 1.250, 95%CI = 0.946–1.653, P = 0.117).

Conclusions

Sarcopenia is an independent risk factor for depressive symptoms, Precautions to early detect and targeted intervene for sarcopenia should continue to be employed in adult with sarcopenia to achieve early prevention for depression and reduce the incidence of adverse clinical outcomes.
Strategies to prevent, diagnose and treat kidney disease related to systemic arterial hypertension: a narrative review from the Mexican Group of Experts on Arterial Hypertension
Authors: Palomo-Piñón Silvia , Enciso-Muñoz José Manuel , Meaney Eduardo , Díaz-Domínguez Ernesto , Cardona-Muller David , Pérez Fabiola Pazos , Cantoral-Farfán Emilia , Anda-Garay Juan Carlos , Mijangos-Chavez Janet , Antonio-Villa Neftali Eduardo ,   on behalf of the Mexican Group of Experts on Arterial Hypertension, Alcocer Luis , Álvarez-López Humberto , Cardona-Muñoz Ernesto G. , Chávez-Mendoza Adolfo , Díaz-Díaz Enrique , Galván-Oseguera Héctor , Rosas-Peralta Martin , Coronado Vidal José González
Published: January 2024

This narrative review highlights strategies proposed by the Mexican Group of Experts on Arterial Hypertension endorsed to prevent, diagnose, and treat chronic kidney disease (CKD) related to systemic arterial hypertension (SAH). Given the growing prevalence of CKD in Mexico and Latin America caused by SAH, there is a need for context-specific approaches to address the effects of SAH, given the diverse population and unique challenges faced by the region. This narrative review provides clinical strategies for healthcare providers on preventing, diagnosing, and treating kidney disease related to SAH, focusing on primary prevention, early detection, evidence-based diagnostic approaches, and selecting pharmacological treatments. Key-strategies are focused on six fundamental areas: 1) Strategies to mitigate kidney disease in SAH, 2) early detection of CKD in SAH, 3) diagnosis and monitoring of SAH, 4) blood pressure targets in patients living with CKD, 5) hypertensive treatment in patients with CKD and 6) diuretics and Non-Steroidal Mineralocorticoid Receptor Inhibitors in Patients with CKD. This review aims to provide relevant strategies for the Mexican and Latin American clinical context, highlight the importance of a multidisciplinary approach to managing SAH, and the role of community-based programs in improving the quality of life for affected individuals. This position paper seeks to contribute to reducing the burden of SAH-related CKD and its complications in Mexico and Latin America.
Discovery of a small molecule that inhibits Bcl-3-mediated cyclin D1 expression in melanoma cells
Authors: Saamarthy Karunakar , Ahlqvist Kristofer , Daams Renée , Balagunaseelan Navisraj , Rinaldo-Matthis Agnes , Kazi Julhash U. , Sime Wondossen , Massoumi Ramin
Published: January 2024

Molecular targeted therapy using a drug that suppresses the growth and spread of cancer cells via inhibition of a specific protein is a foundation of precision medicine and treatment. High expression of the proto-oncogene Bcl-3 promotes the proliferation and metastasis of cancer cells originating from tissues such as the colon, prostate, breast, and skin. The development of novel drugs targeting Bcl-3 alone or in combination with other therapies can cure these patients or prolong their survival. As a proof of concept, in the present study, we focused on metastatic melanoma as a model system. High-throughput screening and in vitro experiments identified BCL3ANT as a lead molecule that could interfere with Bcl-3-mediated cyclin D1 expression and cell proliferation and migration in melanoma. In experimental animal models of melanoma, it was demonstrated that the use of a Bcl-3 inhibitor can influence the survival of melanoma cells. Since there are no other inhibitors against Bcl-3 in the clinical pipeline for cancer treatment, this presents a unique opportunity to develop a highly specific drug against malignant melanoma to meet an urgent clinical need.
Enrichment of colibactin-associated mutational signatures in unexplained colorectal polyposis patients
Authors: Terlouw Diantha , Boot Arnoud , Ducarmon Quinten R. , Nooij Sam , Suerink Manon , van Leerdam Monique E. , van Egmond Demi , Tops Carli M. , Zwittink Romy D. , Ruano Dina , Langers Alexandra M. J. , Nielsen Maartje , van Wezel Tom , Morreau Hans
Published: January 2024

Background

Colibactin, a genotoxin produced by polyketide synthase harboring (pks+) bacteria, induces double-strand breaks and chromosome aberrations. Consequently, enrichment of pks+Escherichia coli in colorectal cancer and polyposis suggests a possible carcinogenic effect in the large intestine. Additionally, specific colibactin-associated mutational signatures; SBS88 and ID18 in the Catalogue of Somatic Mutations in Cancer database, are detected in colorectal carcinomas. Previous research showed that a recurrent APC splice variant perfectly fits SBS88.

Methods

In this study, we explore the presence of colibactin-associated signatures and fecal pks in an unexplained polyposis cohort. Somatic targeted Next-Generation Sequencing (NGS) was performed for 379 patients. Additionally, for a subset of 29 patients, metagenomics was performed on feces and mutational signature analyses using Whole-Genome Sequencing (WGS) on Formalin-Fixed Paraffin Embedded (FFPE) colorectal tissue blocks.

Results

NGS showed somatic APC variants fitting SBS88 or ID18 in at least one colorectal adenoma or carcinoma in 29% of patients. Fecal metagenomic analyses revealed enriched presence of pks genes in patients with somatic variants fitting colibactin-associated signatures compared to patients without variants fitting colibactin-associated signatures. Also, mutational signature analyses showed enrichment of SBS88 and ID18 in patients with variants fitting these signatures in NGS compared to patients without.

Conclusions

These findings further support colibactins ability to mutagenize colorectal mucosa and contribute to the development of colorectal adenomas and carcinomas explaining a relevant part of patients with unexplained polyposis.
Assessment and determinants of depression and anxiety on a global sample of sexual and gender diverse people at high risk of HIV: a public health approach
Authors: Lamontagne Erik , Leroy Vincent , Yakusik Anna , Parker Warren , Howell Sean , Ventelou Bruno
Published: January 2024

Background

Sexual and gender diverse people face intersecting factors affecting their well-being and livelihood. These include homophobic reactions, stigma or discrimination at the workplace and in healthcare facilities, economic vulnerability, lack of social support, and HIV. This study aimed to examine the association between such factors and symptoms of anxiety and depression among sexual and gender diverse people.

Methods

This study is based on a sample of 108,389 gay, bisexual, queer and questioning men, and transfeminine people from 161 countries collected through a cross-sectional internet survey. We developed a multinomial logistic regression for each group to study the associations of the above factors at different severity scores for anxiety and depression symptoms.

Results

Almost a third (30.3%) of the participants reported experiencing moderate to severe symptoms of anxiety and depression. Higher severity scores were found for transfeminine people (39%), and queer or questioning people (34.8%). Severe symptoms of anxiety and depression were strongly correlated with economic hardship for all groups. Compared to those who are HIV-negative, those living with HIV were more likely to report severe symptoms of anxiety and depression, and the highest score was among those who do not know their HIV status. Transfeminine people were the most exposed group, with more than 80% higher risk for those living with HIV suffering from anxiety and depression. Finally, homophobic reactions were strongly associated with anxiety and depression. The relative risk of severe anxiety and depression was 3.47 times higher for transfeminine people facing transphobic reactions than those with no symptoms. Moreover, anxiety and depression correlate with stigma or discrimination in the workplace and healthcare facilities.

Conclusions

The strong association between the severity of anxiety and depression, and socioeconomic inequality and HIV status highlights the need for concrete actions to meet the United Nations' pledge to end inequalities faced by communities and people affected by HIV. Moreover, the association between stigma or discrimination and anxiety and depression among sexual and gender diverse people is alarming. There is a need for bold structural public health interventions, particularly for transfeminine, queer and questioning people who represent three communities under the radar of national HIV programmes.
Modifiable risk factors for cancer in the middle East and North Africa: a scoping review
Authors: Mansour Razan , Al-Ani Abdallah , Al-Hussaini Maysa , Abdel-Razeq Hikmat , Al-Ibraheem Akram , Mansour Asem H.
Published: January 2024

Purpose

This scoping review examines controllable predisposing factors attributable to cancer in the Middle East and North Africa (MENA) region’s adult population, highlighting opportunities to enhance cancer prevention programs.

Design

We systematically searched the PubMed, Science Direct, and CINAHL, EMBASE, and Cochrane Library databases from 1997 to 2022 for articles reporting on the impact of modifiable risk factors on adult patients with cancer in the MENA region.

Results

The review identified 42 relevant articles, revealing that tobacco consumption, obesity, physical inactivity, and diet are significant modifiable risk factors for cancer in the region. Tobacco smoking is a leading cause of lung, bladder, squamous cell carcinoma, and colorectal cancer. A shift towards a westernized, calorie-dense diet has been observed, with some evidence suggesting that a Mediterranean diet may be protective against cancer. Obesity is a known risk factor for cancer, particularly breast malignancy, but further research is needed to determine its impact in the MENA region. Physical inactivity has been linked to colorectal cancer, but more studies are required to establish this relationship conclusively. Alcohol consumption, infections, and exposure to environmental carcinogens are additional risk factors, although the literature on these topics is limited.

Conclusion

The review emphasizes the need for further research and the development of targeted cancer prevention strategies in the MENA region.
M2 macrophages-derived exosomes regulate osteoclast differentiation by the CSF2/TNF-α axis
Authors: Zhou Yue , Hu Guangyao
Published: January 2024

Background

Osteoclast-mediated bone resorption cause bone loss in several bone diseases. Exosomes have been reported to regulate osteoclast differentiation. M2-polarized macrophages exhibit anti-inflammatory activity. This study aimed to explore the effect of exosomes from M2 polarized macrophages (M2-exos) on osteoclastogenesis and molecular mechanisms.

Methods

M2-exos were isolated from IL-4-induced Raw264.7 cells (M2 macrophages) and used to treat osteoclasts (RANKL-induced Raw264.7 cells). Osteoclast differentiation was visualized using tartrate resistant acid phosphatase staining. Quantitative real-time PCR (qPCR) was conducted to measure the levels of osteoclastogenesis-related genes. The underlying mechanisms of M2-exos were evaluated using qPCR and western blotting.

Results

M2-exos suppressed osteoclast differentiation induced by RANKL. Additionally, CSF2 was highly expressed in M2 macrophages, and knockdown of CSF2 further enhanced the effects of M2-exos on osteoclast differentiation. Moreover, CSF2 positively regulated TNF-α signaling, which inhibition promoted differentiation of M2-exo-treated osteoclasts.

Conclusion

M2-exos inhibited RANKL-induced osteoclast differentiation by downregulating the CSF2 expression through inactivating the TNF-α signaling, suggesting the potential application of exosomes in bone disease therapy.
Prevalence of Bruxism in alcohol abusers: a systematic review conducted according to PRISMA guidelines and the cochrane handbook for systematic reviews of interventions
Authors: Ronsivalle Vincenzo , Marrapodi Maria Maddalena , Siurkel Yuliia , Cicciù Marco , Minervini Giuseppe
Published: January 2024

Background

Bruxism, a common oral parafunctional behavior characterized by the grinding or clenching of teeth, is a multifactorial condition with potentially detrimental effects on oral health and overall well-being. In recent years, there has been growing interest in understanding the relationship between bruxism and alcohol abuse, as both are prevalent issues that may share underlying factors and exacerbate each other. This systematic review, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, aims to evaluate the frequency of bruxism among individuals with alcohol abuse.

Methods

A comprehensive search of electronic databases, including PubMed, Lilacs, Scopus and Web of Science, will be conducted to identify relevant studies published up to the knowledge cutoff date in January 2023. The search strategy will include keywords related to bruxism, alcohol abuse, and their synonyms. Inclusion criteria will encompass original research studies, such as observational, cross-sectional, cohort, and case-control studies, as well as clinical trials, that examine the relationship between bruxism and alcohol abuse. Two independent reviewers will perform the study selection, data extraction, and quality assessment, with discrepancies resolved by consensus.

Results

The systematic review will present a summary of the identified studies, including the study design, characteristics of the study populations, and key findings related to the association between bruxism and alcohol abuse. The potential mechanisms underlying this relationship will also be explored. Subgroup analyses and the quality of evidence will be assessed. Finally, the implications of this association for clinical practice and further research will be discussed.

Conclusions

This systematic review will contribute to a better understanding of the interplay between bruxism and alcohol abuse, shedding light on potential risk factors, mechanisms, and clinical implications. The findings may have significant implications for the prevention, management, and treatment of bruxism, particularly in individuals with a history of alcohol abuse.
Prevalence of anxiety and depression among Lebanese women using oral contraceptives: a cross-sectional study
Authors: Jaafar Kamel , Nabhan Elias , Daoud Rama , Nasser Zeina
Published: January 2024

Background

Oral contraceptives (OCs) are used worldwide, including Lebanese women. However, the association between OCs use and anxiety or depression remains unclear. This study aims to assess the prevalence of anxiety and depression among Lebanese women using oral contraceptive pills and investigate the differential impact of combined oral contraceptives (COCs) versus progestogen-only pills (POPs) on mental health outcomes.

Methods

A cross-sectional study was conducted among a sample of Lebanese women using OCs between January and March 2023. Nine hundred nighty seven out of the 2051 women who took part in the survey met our criteria and were included in this study. Data on anxiety and depression were collected using validated and reliable scales, the Arabic versions of the Generalized Anxiety Disorder-7 Questionnaire (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9). Statistical analyses, including multivariate analysis, were performed to assess the association between OCs type (COC vs. POP) and anxiety/depression.

Results

The prevalence of anxiety and depression among Lebanese women taking OCs was found to be 39.9% and 64.3%, respectively. Furthermore, the study revealed that POP users had 2.8 times higher odds of developing anxiety (adjusted odds ratio ORadj = 2.8 with 95% confidence interval CI of 1.770 to 4.435) p-value < 0.001 and 9.2 times higher odds of developing depression (adjusted odds ratio ORadj = 9.2 with 95% confidence interval CI of 5.790 to 14.506) p-value < 0.001 compared to COC users.

Conclusion

The results of this study shed light on the elevated prevalence of anxiety and depression among Lebanese women using OCs and emphasized the varying effects of COCs and POPs on their mental health outcomes. Further research is needed to comprehensively understand this association, considering both the dosage and specific type of oral contraceptive to improve the overall well-being of women using these contraceptives.
A retrospective observational study of vCare: a virtual emergency clinical advisory and transfer service in rural and remote Australia
Authors: Dean Kimberley , Chang Cynthia , McKenna Erin , Nott Shannon , Hunter Amanda , Tall Julie A. , Setterfield Madeline , Addis Bridget , Webster Emma
Published: January 2024

Background

Provision of critical care in rural areas is challenging due to geographic distance, smaller facilities, generalist skill mix and population characteristics. Internationally, the amalgamation telemedicine and retrieval medicine services are developing to overcome these challenges. Virtual emergency clinical advisory and transfer service (vCare) is one of these novel services based in New South Wales, Australia. We aim to describe patient encounters with vCare from call initiation at the referring site to definitive care at the accepting site.

Methods

This retrospective observational study reviewed all patients using vCare in rural and remote Australia for clinical advice and/or inter-hospital transfer for higher level of care between February and March 2021. Data were extracted from electronic medical records and included remoteness of sites, presenting complaint, triage category, camera use, patient characteristics, transfer information, escalation of therapeutic intervention and outcomes. Data were summarised using cross tabulation.

Results

1,678 critical care patients were supported by vCare, with children (12.5%), adults (50.6%) and older people (36.9%) evenly split between sexes. Clinicians mainly referred to vCare for trauma (15.1%), cardiac (16.1%) and gastroenterological (14.8%) presentations. A referral to vCare led to an escalation of invasive intervention, skill, and resources for patient care. vCare cameras were used in 19.8% of cases. Overall, 70.5% (n = 1,139) of patients required transfer. Of those, 95.1% were transferred to major regional hospitals and 11.7% required secondary transfer to higher acuity hospitals. Of high-urgency referrals, 42.6% did not receive high priority transport. Imaging most requested included CT and MRI scans (37.2%). Admissions were for physician (33.1%) and surgical care (23.3%). The survival rate was 98.6%.

Conclusion

vCare was used by staff in rural and remote facilities to support decision making and care of patients in a critical condition. Issues were identified including low utilisation of equipment, heavy reliance on regional sites and high rates of secondary transfer. However, these models are addressing a key gap in the health workforce and supporting rural and remote communities to receive care.
A mixed methods evaluation assessing the feasibility of implementing a PrEP data dashboard in the Southeastern United States
Authors: Burgan Kaylee , McCollum C. Greer , Guzman Alfredo , Penney Brooke , Hill Samantha V. , Kudroff Kachina , Thorn Shey , Burton Toya , Turner Kelly , Mugavero Michael J. , Rana Aadia , Elopre Latesha
Published: January 2024

Background

Alabama is one of seven priority states for the National Ending the HIV Epidemic Initiative due to a disproportionate burden of rural infections. To reverse growing infection rates, the state must increase its focus on prevention efforts, including novel strategies. One such approach is to utilize dashboards that visualize real-time data on the pre-exposure prophylaxis (PrEP) care continuum to assist in prioritizing evidence-based preventative care for those most vulnerable for HIV infection.

Methods

We conducted a mixed methods evaluation to ascertain stakeholders’ perceptions on the acceptability, feasibility, appropriateness, and usability of a PrEP care continuum dashboard, as well as gain insight on ways to improve the activities necessary to sustain it. Clinicians, administrators, and data personnel from participating sites in Alabama completed surveys (n = 9) and participated in key informant interviews (n = 10) to better understand their experiences with the prototype data dashboard and to share feedback on how it can be modified to best fit their needs.

Results

Surveys and interviews revealed that all participants find the pilot data dashboard to be an acceptable, feasible, and appropriate intervention for clinic use. Overall, stakeholders find the pilot dashboard to be usable and helpful in administrative efforts, such as report and grant writing; however, additional refining is needed in order to reduce burden and optimize usefulness. Participants voiced concerns about their site’s abilities to sustain the dashboard, including the lack of systematized PrEP protocols and limited funds and staff time dedicated to PrEP data collection, cleaning, and upload.

Conclusion

Study participants from clinics providing HIV prevention services, including PrEP, in Alabama voiced interest in sustaining and refining a data dashboard that tracks clients across the PrEP care continuum. Despite viewing the platform itself as an acceptable, feasible, and appropriate intervention, participants agreed that efforts need to be focused on standardizing PrEP data collection protocols in order to ensure consistent, accurate data capture and that limited funds and staff time are barriers to the sustained implementation of the dashboard in practice.
Employees’ experiences of a large-scale implementation in a public care setting: a novel mixed-method approach to content analysis
Authors: Säfström My , Löfkvist Ulrika
Published: January 2024

Background

Research for evidence-based interventions and strategies for implementation continues. Yet there is a continued shortage of qualified health care staff while stress and burnout are common. Health care professionals’ individual perceptions towards change needs to be considered to succeed in organisational change. It is therefore relevant to investigate how implementation processes affect employees within the health care sector. Challenges to implementation are especially large in the field of disability care. The present study aims to investigate employees’ experiences of an ongoing large-scale implementation, and what they perceived as important to succeed in a complex clinical setting.

Methods

Semi-structured focus group interviews were conducted with a self-selected sample of employees from a large and complex health care organisation responsible for public disability care in a centrally located Swedish region. A mixed-method approach adapted to content analysis was performed in a three-step process. In the first round, each unit of analysis was selected and then colour coded. In a second round, the coloured units were coded according to content analysis, and categories and concepts were compared and adjusted until the two researchers reached consensus. Finally, to further complement the content analysis, a quantitative analysis of the colour categories was made.

Results

In general, employees experienced the implementation as being insufficient, yet opinions of the process of implementation were mixed. Most positive experiences were found in relation to the outcomes that the new method had on work effectiveness and patient care. Closely related topics like time constraints, uncertainties concerning the method and the need for supportive functions reoccurred in several concepts suggesting a relationship between differing contextual factors, implementation activities and fidelity. Also evident in the results were the strain on organisational and social work environment and the importance of managers’ active leadership.

Conclusions

Implementation processes are experienced as challenging for employees. Key facilitators are available support functions, clear leadership and time that is sufficient and kept sacrosanct. Leaders need to communicate how and why employees may experience implementation processes differently. The impact that organisational change has on work environment should be considered.
Evaluation of the implementation of a community health worker-led COVID-19 contact tracing intervention in Chiapas, Mexico, from March 2020 to December 2021
Authors: Aranda Zeus , Vázquez Sandra , Gopaluni Anuraag , Martínez Laura , Ramírez Mayra , Jiménez Ariwame , Bernal Daniel , Rodríguez Ana L. , Chacón Selene , Vargas Bruno , Fulcher Isabel R. , Barnhart Dale A. ,   The Partners In Health Cross-Site COVID-19 Cohort Technical Working Group
Published: January 2024

Background

Mexico is one of the countries with the greatest excess death due to COVID-19. Chiapas, the poorest state in the country, has been particularly affected. Faced with an exacerbated shortage of health professionals, medical supplies, and infrastructure to respond to the pandemic, the non-governmental organization Compañeros En Salud (CES) implemented a COVID-19 infection prevention and control program to limit the impact of the pandemic in the region. We evaluated CES’s implementation of a community health worker (CHW)-led contact tracing intervention in eight rural communities in Chiapas.

Methods

Our retrospective observational study used operational data collected during the contract tracing intervention from March 2020 to December 2021. We evaluated three outcomes: contact tracing coverage, defined as the proportion of named contacts that were located by CHWs, successful completion of contact tracing, and incidence of suspected COVID-19 among contacts. We described how these outcomes changed over time as the intervention evolved. In addition, we assessed associations between these three main outcomes and demographic characteristics of contacts and intervention period (pre vs. post March 2021) using univariate and multivariate logistic regression.

Results

From a roster of 2,177 named contacts, 1,187 (54.5%) received at least one home visit by a CHW and 560 (25.7%) had successful completion of contact tracing according to intervention guidelines. Of 560 contacts with complete contact tracing, 93 (16.6%) became suspected COVID-19 cases. We observed significant associations between sex and coverage (p = 0.006), sex and complete contact tracing (p = 0.049), community of residence and both coverage and complete contact tracing (p < 0.001), and intervention period and both coverage and complete contact tracing (p < 0.001).

Conclusions

Our analysis highlights the promises and the challenges of implementing CHW-led COVID-19 contact tracing programs. To optimize implementation, we recommend using digital tools for data collection with a human-centered design, conducting regular data quality assessments, providing CHWs with sufficient technical knowledge of the data collection system, supervising CHWs to ensure contact tracing guidelines are followed, involving communities in the design and implementation of the intervention, and addressing community member needs and concerns surrounding stigmatization arising from lack of privacy.
Cell-free DNA levels associate with COPD exacerbations and mortality
Authors: Ware Sarah A. , Kliment Corrine R. , Giordano Luca , Redding Kevin M. , Rumsey William L. , Bates Stewart , Zhang Yingze , Sciurba Frank C. , Nouraie S. Mehdi , Kaufman Brett A.
Published: January 2024

The question addressed by the study

Good biological indicators capable of predicting chronic obstructive pulmonary disease (COPD) phenotypes and clinical trajectories are lacking. Because nuclear and mitochondrial genomes are damaged and released by cigarette smoke exposure, plasma cell-free mitochondrial and nuclear DNA (cf-mtDNA and cf-nDNA) levels could potentially integrate disease physiology and clinical phenotypes in COPD. This study aimed to determine whether plasma cf-mtDNA and cf-nDNA levels are associated with COPD disease severity, exacerbations, and mortality risk.

Materials and methods

We quantified mtDNA and nDNA copy numbers in plasma from participants enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE, n = 2,702) study and determined associations with relevant clinical parameters.

Results

Of the 2,128 participants with COPD, 65% were male and the median age was 64 (interquartile range, 59–69) years. During the baseline visit, cf-mtDNA levels positively correlated with future exacerbation rates in subjects with mild/moderate and severe disease (Global Initiative for Obstructive Lung Disease [GOLD] I/II and III, respectively) or with high eosinophil count (≥ 300). cf-nDNA positively associated with an increased mortality risk (hazard ratio, 1.33 [95% confidence interval, 1.01–1.74] per each natural log of cf-nDNA copy number). Additional analysis revealed that individuals with low cf-mtDNA and high cf-nDNA abundance further increased the mortality risk (hazard ratio, 1.62 [95% confidence interval, 1.16–2.25] per each natural log of cf-nDNA copy number).

Answer to the question

Plasma cf-mtDNA and cf-nDNA, when integrated into quantitative clinical measurements, may aid in improving COPD severity and progression assessment.
Integrative study of pulmonary microbiome, transcriptome and clinical outcomes in Mycoplasma pneumoniae pneumonia
Authors: Huang Xia , Luo Yingying , Wang Jing , Zhang Xuefang , Chen Lei , Wu Ruxi , Xue Zhengyang , Gu Haiyan , Li Daiying , Tang Heng , Qin Houbing , Zhao Deyu , Liu Feng
Published: January 2024

Background

This study aimed to investigate the interactions among three core elements of respiratory infection—pathogen, lung microbiome, and host response—and their avocation with the severity and outcomes of Mycoplasma pneumoniae pneumonia (MPP) in children.

Methods

We prospectively collected bronchoalveolar lavage fluid from a cohort of 41 children with MPP, including general MPP (GMPP) and complicated MPP (CMPP), followed by microbiome and transcriptomic analyses to characterize the association among pathogen, lung microbiome, and host response and correlate it with the clinical features and outcomes.

Results

The lung microbiome of patients with CMPP had an increased relative abundance of Mycoplasma pneumoniae (MP) and reduced alpha diversity, with 76 differentially expressed species. Host gene analysis revealed a key module associated with neutrophil function and several inflammatory response pathways. Patients with a high relative abundance of MP, manifested by a specific lung microbiome and host response type, were more prone to CMPP and had a long imaging recovery time.

Conclusion

Patients with CMPP have a more disrupted lung microbiome than those with GMPP. MP, lung microbiome, and host response interacts with each other and are closely related to disease severity and outcomes in children with MPP.

Graphical Abstract
Establishment of tumor microenvironment-preserving organoid model from patients with intracranial meningioma
Authors: Kim Dokyeong , Park Junseong , Park Hyeon-Chun , Zhang Songzi , Park Minyoung , Park Soon A. , Lee Sug Hyung , Lee Youn Soo , Park Jae-Sung , Jeun Sin-Soo , Chung Yeun-Jun , Ahn Stephen
Published: January 2024

Background

Although meningioma is the most common primary brain tumor, treatments rely on surgery and radiotherapy, and recurrent meningiomas have no standard therapeutic options due to a lack of clinically relevant research models. Current meningioma cell lines or organoids cannot reflect biological features of patient tumors since they undergo transformation along culture and consist of only tumor cells without microenvironment. We aim to establish patient-derived meningioma organoids (MNOs) preserving diverse cell types representative of the tumor microenvironment.

Methods

The biological features of MNOs were evaluated using WST, LDH, and collagen-based 3D invasion assays. Cellular identities in MNOs were confirmed by immunohistochemistry (IHC). Genetic alteration profiles of MNOs and their corresponding parental tumors were obtained by whole-exome sequencing.

Results

MNOs were established from four patients with meningioma (two grade 1 and two grade 2) at a 100% succession rate. Exclusion of enzymatic dissociation-reaggregation steps endowed MNOs with original histology and tumor microenvironment. In addition, we used a liquid media culture system instead of embedding samples into Matrigel, resulting in an easy-to-handle, cost-efficient, and time-saving system. MNOs maintained their functionality and morphology after long-term culture (> 9 wk) and repeated cryopreserving-recovery cycles. The similarities between MNOs and their corresponding parental tumors were confirmed by both IHC and whole-exome sequencing. As a representative application, we utilized MNOs in drug screening, and mifepristone, an antagonist of progesterone receptor, showed prominent antitumor efficacy with respect to viability, invasiveness, and protein expression.

Conclusion

Taken together, our MNO model overcame limitations of previous meningioma models and showed superior resemblance to parental tumors. Thus, our model could facilitate translational research identifying and selecting drugs for meningioma in the era of precision medicine.
Presence and abundance of malaria vector species in Miami-Dade County, Florida
Authors: Wilke André B. B. , Vasquez Chalmers , Medina Johana , Unlu Isik , Beier John C. , Ajelli Marco
Published: January 2024

Background

Malaria outbreaks have sporadically occurred in the United States, with Anopheles quadrimaculatus serving as the primary vector in the eastern region. Anopheles crucians, while considered a competent vector, has not been directly implicated in human transmission. Considering the locally acquired Plasmodium vivax cases in Sarasota County, Florida (7 confirmed cases), Cameron County, Texas (one confirmed case), and Maryland (one confirmed case) in the summer of 2023. The hypothesis of this study is that major cities in the United States harbour sufficient natural populations of Anopheles species vectors of malaria, that overlap with human populations that could support local transmission to humans. The objective of this study is to profile the most abundant Anopheles vector species in Miami-Dade County, Florida—An. crucians and An. quadrimaculatus.

Methods

This study was based on high-resolution mosquito surveillance data from 2020 to 2022 in Miami-Dade County, Florida. Variations on the relative abundance of An. crucians and An. quadrimaculatus was assessed by dividing the total number of mosquitoes collected by each individual trap in 2022 by the number of mosquitoes collected by the same trap in 2020. In order to identify influential traps, the linear distance in meters between all traps in the surveillance system from 2020 to 2022 was calculated and used to create a 4 km buffer radius around each trap in the surveillance system.

Results

A total of 36,589 An. crucians and 9943 An. quadrimaculatus were collected during this study by the surveillance system, consisting of 322 CO2-based traps. The findings reveal a highly heterogeneous spatiotemporal distribution of An. crucians and An. quadrimaculatus in Miami-Dade County, highlighting the presence of highly conducive environments in transition zones between natural/rural and urban areas. Anopheles quadrimaculatus, and to a lesser extent An. crucians, pose a considerable risk of malaria transmission during an outbreak, given their high abundance and proximity to humans.

Conclusions

Understanding the factors driving the proliferation, population dynamics, and spatial distribution of Anopheles vector species is vital for implementing effective mosquito control and reducing the risk of malaria outbreaks in the United States.
Adipo-oncology: adipocyte-derived factors govern engraftment, survival, and progression of metastatic cancers
Authors: Sato Shinya
Published: January 2024

Conventional therapies for metastatic cancers have limited efficacy. Recently, cancer therapies targeting noncancerous cells in tumor microenvironments have shown improved clinical outcomes in patients. However, further advances in our understanding of the metastatic tumor microenvironment are required to improve treatment outcomes. Adipocytes are distributed throughout the body, and as a part of the metastatic tumor microenvironment, they interact with cancer cells in almost all organs. Adipocytes secrete various factors that are reported to exert clinical effects on cancer progression, including engraftment, survival, and expansion at the metastatic sites. However, only a few studies have comprehensively examined their impact on cancer cells. In this review, we examined the impact of adipocytes on cancer by describing the adipocyte-secreted factors that are involved in controlling metastatic cancer, focusing on adipokines, such as adiponectin, leptin, visfatin, chemerin, resistin, apelin, and omentin. Adipocyte-secreted factors promote cancer metastasis and contribute to various biological functions of cancer cells, including migration, invasion, proliferation, immune evasion, and drug resistance at the metastatic sites. We propose the establishment and expansion of “adipo-oncology” as a research field to enhance the comprehensive understanding of the role of adipocytes in metastatic cancers and the development of more robust metastatic cancer treatments.
Mitochondria-derived methylmalonic acid aggravates ischemia–reperfusion injury by activating reactive oxygen species-dependent ferroptosis
Authors: Guo Junchen , Wang Shanjie , Wan Xin , Liu Xiaoxuan , Wang Zeng , Liang Chenchen , Zhang Zhenming , Wang Ye , Yan Miao , Wu Pengyan , Fang Shaohong , Yu Bo
Published: January 2024

Ferroptosis is a regulatory cell death process pivotal in myocardial ischemia–reperfusion (I/R) injury. However, the precise mechanism underlying myocardial ferroptosis remains less known. In this study, we investigated the pathophysiological mechanisms of methylmalonic acid (MMA) associated with ferroptosis activation in cardiomyocytes after I/R. We found an increase level of MMA in patients with acute myocardial injury after reperfusion and AC16 cells under hypoxia/reoxygenation (H/R) condition. MMA treatment was found to be associated with excessive oxidative stress in cardiomyocytes, leading to ferroptosis-related myocardial injury. In mice with I/R injury, MMA treatment aggravated myocardial oxidative stress and ferroptosis, which amplified the myocardial infarct size and cardiac dysfunction. Mechanistically, MMA promoted NOX2/4 expression to increase reactive oxygen species (ROS) production in cardiomyocytes, aggravating myocardial injury. Notably, the increased ROS further activated ferroptosis by inhibiting solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression. In addition, MMA decreased the ectopic nuclear distribution of nuclear factor E2-related factor 2 (NRF2) by increasing the interaction between NRF2 and kelch-like ECH-associated protein 1 (KEAP1). This impeded the activation of GPX4/SLC7A11, downstream of NRF2, activating ferroptosis and aggravating myocardial cell injury. Collectively, our study indicates that MMA activates oxidative stress and ROS generation, which induces ferroptosis to exacerbate cardiomyocyte injury in an I/R model. These findings may provide a new perspective for the clinical treatment of I/R injury and warrant further investigation.
New advances of the androgen receptor in prostate cancer: report from the 1st International Androgen Receptor Symposium
Authors: Mehralivand Sherif , Thomas Christian , Puhr Martin , Claessens Frank , van de Merbel Arjanneke F. , Dubrovska Anna , Jenster Guido , Bernemann Christof , Sommer Ulrich , Erb Holger H. H.
Published: January 2024

The androgen receptor (AR) is a crucial player in various aspects of male reproduction and has been associated with the development and progression of prostate cancer (PCa). Therefore, the protein is the linchpin of current PCa therapies. Despite great research efforts, the AR signaling pathway has still not been deciphered, and the emergence of resistance is still the biggest problem in PCa treatment. To discuss the latest developments in AR research, the “1st International Androgen Receptor Symposium” offered a forum for the exchange of clinical and scientific innovations around the role of the AR in prostate cancer (PCa) and to stimulate new collaborative interactions among leading scientists from basic, translational, and clinical research. The symposium included three sessions covering preclinical studies, prognostic and diagnostic biomarkers, and ongoing prostate cancer clinical trials. In addition, a panel discussion about the future direction of androgen deprivation therapy and anti-AR therapy in PCa was conducted. Therefore, the newest insights and developments in therapeutic strategies and biomarkers are discussed in this report.
Monogenic systemic lupus erythematosus onset in a 13-year-old boy with Noonan like-syndrome: a case report and literature review
Authors: Morán-Álvarez Patricia , Gianviti Alessandra , Diomedi-Camassei Francesca , Ginevrino Monia , de Benedetti Fabrizio , Bracaglia Claudia
Published: January 2024

Background

Childhood systemic lupus erythematosus (cSLE) has been considered as a polygenic autoimmune disease; however, a monogenic lupus-like phenotype is emerging with the recent recognition of several related novel high-penetrance genetic variants. RASopathies, a group of disorders caused by mutations in the RAS/MAPK pathway, have been recently described as a cause of monogenic lupus.

Case presentation

We present a 13-year-old boy with Noonan-like syndrome with loose anagen hair who developed a monogenic lupus. The renal biopsy confirmed a class III lupus nephritis and identified the presence of zebra bodies.

Conclusions

RASopathies represent a cause of monogenic lupus. We report a new case of monogenic lupus in a child with Noonan-like syndrome with loose anagen hair. Lupus nephritis which has never been described in this context, may be part of the presentation. The presence of zebra bodies in SLE or RASopathies in unclear, but no other known conditions (Fabry disease or drugs) were identified as the cause of zebra bodies in our patient.
Wide-spread dispersal in a deep-sea brooding polychaete: the role of natural history collections in assessing the distribution in quill worms (Onuphidae, Annelida)
Authors: Budaeva Nataliya , Agne Stefanie , Ribeiro Pedro A. , Straube Nicolas , Preick Michaela , Hofreiter Michael
Published: January 2024

Background

Modern integrative taxonomy-based annelid species descriptions are detailed combining morphological data and, since the last decades, also molecular information. Historic species descriptions are often comparatively brief lacking such detail. Adoptions of species names from western literature in the past led to the assumption of cosmopolitan ranges for many species, which, in many cases, were later found to include cryptic or pseudocryptic lineages with subtle morphological differences. Natural history collections and databases can aid in assessing the geographic ranges of species but depend on correct species identification. Obtaining DNA sequence information from wet-collection museum specimens of marine annelids is often impeded by the use of  formaldehyde and/or long-term storage in ethanol resulting in DNA degradation and cross-linking.

Results

The application of ancient DNA extraction methodology in combination with single-stranded DNA library preparation and target gene capture resulted in successful sequencing of a 110-year-old collection specimen of quill worms. Furthermore, a 40-year-old specimen of quill worms was successfully sequenced using a standard extraction protocol for modern samples, PCR and Sanger sequencing. Our study presents the first molecular analysis of Hyalinoecia species including the previously known species Hyalinoecia robusta, H. tubicloa, H. artifex, and H. longibranchiata, and a potentially undescribed species from equatorial western Africa morphologically indistinguishable from H. tubicola. The study also investigates the distribution of these five Hyalinoecia species. Reassessing the distribution of H. robusta reveals a geographical range covering both the Atlantic and the Indian Oceans as indicated by molecular data obtained from recent and historical specimens.

Conclusion

Our results represent an example of a very wide geographical distribution of a brooding deep-sea annelid with a complex reproduction strategy and seemingly very limited dispersal capacity of its offspring, and highlights the importance of molecular information from museum specimens for integrative annelid taxonomy and biogeography.