bluuebunny/crossref_metadata_2025 huggingface dataset:
Demographic and clinical characteristics associated with anxiety and depressive symptom outcomes in users of a digital mental health intervention incorporating a relational agent
Authors: Chiauzzi Emil , Williams Andre , Mariano Timothy Y. , Pajarito Sarah , Robinson Athena , Kirvin-Quamme Andrew , Forman-Hoffman Valerie
Published: January 2024

Background

Digital mental health interventions (DMHIs) may reduce treatment access issues for those experiencing depressive and/or anxiety symptoms. DMHIs that incorporate relational agents may offer unique ways to engage and respond to users and to potentially help reduce provider burden. This study tested Woebot for Mood & Anxiety (W-MA-02), a DMHI that employs Woebot, a relational agent that incorporates elements of several evidence-based psychotherapies, among those with baseline clinical levels of depressive or anxiety symptoms. Changes in self-reported depressive and anxiety symptoms over 8 weeks were measured, along with the association between each of these outcomes and demographic and clinical characteristics.

Methods

This exploratory, single-arm, 8-week study of 256 adults yielded non-mutually exclusive subsamples with either clinical levels of depressive or anxiety symptoms at baseline. Week 8 Patient Health Questionnaire-8 (PHQ-8) changes were measured in the depressive subsample (PHQ-8 ≥ 10). Week 8 Generalized Anxiety Disorder-7 (GAD-7) changes were measured in the anxiety subsample (GAD-7 ≥ 10). Demographic and clinical characteristics were examined in association with symptom changes via bivariate and multiple regression models adjusted for W-MA-02 utilization. Characteristics included age, sex at birth, race/ethnicity, marital status, education, sexual orientation, employment status, health insurance, baseline levels of depressive and anxiety symptoms, and concurrent psychotherapeutic or psychotropic medication treatments during the study.

Results

Both the depressive and anxiety subsamples were predominantly female, educated, non-Hispanic white, and averaged 38 and 37 years of age, respectively. The depressive subsample had significant reductions in depressive symptoms at Week 8 (mean change =—7.28, SD = 5.91, Cohen’s d = -1.23, p < 0.01); the anxiety subsample had significant reductions in anxiety symptoms at Week 8 (mean change = -7.45, SD = 5.99, Cohen’s d = -1.24, p < 0.01). No significant associations were found between sex at birth, age, employment status, educational background and Week 8 symptom changes. Significant associations between depressive and anxiety symptom outcomes and sexual orientation, marital status, concurrent mental health treatment, and baseline symptom severity were found.

Conclusions

The present study suggests early promise for W-MA-02 as an intervention for depression and/or anxiety symptoms. Although exploratory in nature, this study revealed potential user characteristics associated with outcomes that can be investigated in future studies.

Trial Registration

This study was retrospectively registered on ClinicalTrials.gov (#NCT05672745) on January 5th, 2023.
Canadians’ knowledge of cancer risk factors and belief in cancer myths
Authors: E Rydz , J Telfer , EK Quinn , SS Fazel , E Holmes , G Pennycook , CE Peters
Published: January 2024

Background

Many untrue statements about cancer prevention and risks are circulating. The objective of this study was to assess Canadians’ awareness of known cancer risk factors and cancer myths (untruths or statements that are not completely true), and to explore how awareness may vary by sociodemographic and cognitive factors.

Methods

Cancer myths were identified by conducting scans of published, grey literature, and social media. Intuitive-analytic thinking disposition scores included were actively open- and close-minded thinking, as well as preference for intuitive and effortful thinking. A survey was administered online to participants aged 18 years and older through Prolific. Results were summarized descriptively and analyzed using chi-square tests, as well as Spearman rank and Pearson correlations.

Results

Responses from 734 Canadians were received. Participants were better at identifying known cancer risk factors (70% of known risks) compared to cancer myths (49%). Bivariate analyses showed differential awareness of known cancer risk factors (p < 0.05) by population density and income, cancer myths by province, and for both by ethnicity, age, and all thinking disposition scores. Active open-minded thinking and preference for effortful thinking were associated with greater discernment. Tobacco-related risk factors were well-identified (> 90% correctly identified), but recognition of other known risk factors was poor (as low as 23% for low vegetable and fruit intake). Mythical cancer risk factors with high support were consuming additives (61%), feeling stressed (52%), and consuming artificial sweeteners (49%). High uncertainty of causation was observed for glyphosate (66% neither agreed or disagreed). For factors that reduce cancer risk, reasonable awareness was observed for HPV vaccination (60%), but there was a high prevalence in cancer myths, particularly that consuming antioxidants (65%) and organic foods (45%) are protective, and some uncertainty whether drinking red wine (41%), consuming vitamins (32%), and smoking cannabis (30%) reduces cancer risk.

Conclusions

While Canadians were able to identify tobacco-related cancer risk factors, many myths were believed and numerous risk factors were not recognized. Cancer myths can be harmful in themselves and can detract the public’s attention from and action on established risk factors.
Stress and suicide risk among adolescents: the role of problematic internet use, gaming disorder and emotional regulation
Authors: Chamarro Andrés , Díaz-Moreno Adrian , Bonilla Ivan , Cladellas Ramon , Griffiths Mark D. , Gómez-Romero Maria José , Limonero Joaquín T.
Published: January 2024

Background

Previous studies have associated videogame playing and social media use with suicidal behaviors together with lower stress coping or poor emotion regulation strategies. Due to the inconclusive evidence regarding the factors associated with suicidal behavior, the present study aimed to overcome the limitations of previous research and explored the relationship between adolescent stress, problematic internet use (PIU), gaming disorder (GD), and emotional regulation (ER) in a cross-section design. It was hypothesized that stress would have a direct effect on suicide risk (SR) as well as being mediated by PIU, GD, and ER.

Methods

The participants comprised 430 adolescents (58.4% male) aged between 16 and 19 years. They completed an online survey including the Mobile-Related Experiences Questionnaire, Internet Gaming Disorder Scale-Short Form, Meta-Mood Trait Repair Scale, and Spanish version of the Suicidal Behaviors Questionnaire.

Results

A total of 34.2% of the adolescents (N = 147) were at risk for SR. Results also indicated that 30,7% had experienced suicidal ideation at some point in their life, 12.1% had at least one plan to die by suicide, and 5.1% had attempted suicide. Results of path analysis confirmed that stress appeared to be a risk factor for suicide, but that its effects were not mediated by PIU. However, ER and GD mediated the effect of stress on SR. The results suggest that stress is a main risk factor for suicide, especially among adolescents with poor emotional regulation or problematic gaming.

Conclusions

Considering the prevalence of suicide among adolescents, the results of the present study suggest that suicide prevention programs should include emotional regulation strategies, stress coping, and videogaming management skills in the early stages of high school. Providing these protective resources to adolescents will help them face the stressful and changing situations typical of adolescence and will help them to attain greater well-being and satisfaction with life.
Insufficient stem antetorsion and lower cup abduction is a combined risk factor for posterior hip dislocation in patients undergoing THA for femoral neck fractures: a retrospective analysis
Authors: Li Zhuokai , Yang Yang , Guo Shengyang , Liu Ju , Zhou Xiaoxiao , Ji Houlin
Published: January 2024

Background

The role of acetabular and femoral component positions with respect to the risk of post-operative instability and dislocation remains debated. In this study, we aimed to identify potential risk factors for early dislocation following primary total hip arthroplasty (THA) for displaced intracapsular femoral neck fractures (FNF) using radiological measurements.

Methods

We retrospectively analyzed data for patients who underwent cementless primary THA for FNF using a posterolateral approach between January 2018 and December 2021. Follow-up duration, age, sex, affected side, and mean time from THA to dislocation were recorded. Leg-length inequality, abductor lever arm, vertical and horizontal femoral offsets, vertical and horizontal hip centers of rotation, abduction, anteversion of the acetabulum and femoral prosthesis, and combined anteversion were measured.

Results

The study sample included 17 men and 34 women, with 21 and 30 patients undergoing left- and right-hip operations, respectively. The mean patient age was 70.18 ± 7.64 years, and the mean follow-up duration was 27.73 ± 13.52 months. The mean time between THA and dislocation was 1.58 ± 0.79 months. Seven patients (13.73%) sustained posterior dislocation of the hip. The abduction angle (36.05 ± 6.82° vs. 45.68 ± 8.78°) (p = 0.008) and anteversion of the femoral prosthesis (8.26 ± 4.47° vs. 19.47 ± 9.01°) (p = 0.002) were significantly lower in the dislocation group than in the control group. There were no significant differences in other parameters.

Conclusions

Insufficient stem antetorsion combined with lower abduction angle of the acetabular component were associated with a high risk of dislocation, especially in patients with deep flexion or internal rotation of the flexed hip joint and knees, or in patients with a stiff spine or anterior pelvic tilt, impingement may then occur in the neck of the prosthesis and cup component, ultimately resulting in posterior dislocation. These findings could remind surgeons to avoid simultaneous occurrence of both in THA surgery. These results provide new insight into risk factors for hip dislocation in patients undergoing primary THA for FNF and may aid in reducing the risk of instability and dislocation.

Level of evidence

Prospective comparative study Level II.
ENABLE-SG (Educate, Nurture, Advise, Before Life Ends for Singapore) as a proactive palliative care model: protocol for a hybrid type 1 effectiveness-implementation randomized wait-list controlled trial
Authors: Ke Yu , Cheung Yin Bun , Bakitas Marie , Odom J. Nicholas , Lum Elaine , Tan Daniel Shao Weng , Tan Tira J. , Finkelstein Eric , Oh Hong Choon , Zhou Siqin , Yang Grace Meijuan
Published: January 2024

Background

Specialist palliative care is often provided late in the patient’s disease trajectory in response to uncontrolled symptoms. Shifting from this reactionary illness-stress paradigm to a proactive health-wellness approach, the ENABLE (Educate, Nurture, Advise, Before Life Ends) telehealth model aims to enhance the coping, stress and symptom management, self-care, and advance care planning skills of patients with advanced cancers and their caregivers. The ENABLE model has been culturally adapted to Singapore (ENABLE-SG) and pilot-tested. A hybrid type 1 effectiveness-implementation design will be used to evaluate the effectiveness of ENABLE-SG while collecting real-world implementation data.

Methods

This single-centre, assessor-blind, wait-list (immediately vs. 6 months) randomized controlled trial will recruit 300 adult patients within 60 days of an advanced cancer diagnosis and their family caregivers from the National Cancer Centre of Singapore. ENABLE-SG comprises structured psychoeducational sessions with a telehealth coach, covering essential topics of early palliative care. Participants will be assessed at baseline and every 3 months until patient’s death, 12 months (caregivers), or end of study (patients). The primary outcome is patient quality of life 6 months after baseline. Secondary patient-reported outcomes include mood, coping, palliative care concerns, and health status. Secondary caregiver-reported outcomes include caregiver quality of life, mood, coping, and care satisfaction. Mixed-effects regression modelling for repeated measurements will be used. To assess the effectiveness of ENABLE-SG versus usual care, patient and caregiver outcomes at 6 months will be compared. To compare earlier versus delayed ENABLE-SG, patient and caregiver outcomes at 12 months will be compared. Within the hybrid type 1 effectiveness-implementation design, implementation outcomes will be evaluated in both the early and delayed groups. Acceptability, adoption, appropriateness, and feasibility will be assessed using a feedback survey and semi-structured interviews with a purposive sample of patients, caregivers, and healthcare providers. Transcribed interviews will be analysed thematically. Other implementation outcomes of penetration, fidelity, and cost will be assessed using records of study-related processes and summarized using descriptive statistics. A cost-effectiveness analysis will also be conducted.

Discussion

This study will assess both effectiveness and implementation of ENABLE-SG. Insights into implementation processes can facilitate model expansion and upscaling.

Trial registration

Registered prospectively on ClinicalTrials.gov, NCT06044441. Registered on 21/09/2023.
Utilization of modern menstrual methods and related unmet needs among college going women in Coimbatore district: a descriptive cross-sectional study
Authors: Durairaj Thavansree , Aparnavi Periasamy , Narayanan Seetharaman , Mahantshetti Sushmitha , Dhandapani Srihari , Shanmugam Jeevithan , Rathinamoorthy Ramesh , Kumar Mohan
Published: January 2024

Objectives

The primary objectives were to determine the proportion of modern menstrual method (MMM) users among college going women in Coimbatore district, Tamil Nadu; and to estimate the unmet needs associated with use of MMMs in comparison with other menstrual hygiene methods (MHMs). We also assessed the factors that determine MMM use among college going women.

Methods

This was a descriptive cross-sectional study conducted among college going women in Coimbatore district, Tamil Nadu, India between October 2022 and January 2023 using a purpose predesigned, pretested, semi-structured proforma that included validated Menstrual Practice Needs Scale (MPNS-36).

Results

Only 1.4% of the study participants used MMMs – menstrual cups (1.3%) and tampons (0.1%). Sanitary pads were the most common MHM of choice (96.3%); of which majority (98.6%) used disposable pads and more than half (50.4%) used non-biodegradable pads. Importantly, one in six (16.5%) were not aware of nature of sanitary pads (biodegradable or nonbiodegradable) used. The unmet needs associated with MMMs (menstrual cups and tampons) were significantly lower than that for other MHMs (including sanitary pads), in particular, the unmet material and home environment needs, unmet material reliability concerns, unmet reuse needs and unmet reuse insecurity. However, we found no significant difference between MMMs, sanitary pads and other MHMs in terms of unmet transport, college environment, change and disposal insecurity needs. The significant predictors of use of MMMs were age (more than 21 years of age), residence (urban), type of stay (off campus including home), socioeconomic status (upper), fathers’ and mothers’ education (high school and above), and presence of personal income. Discussions with friends (or peers) both before and after menarche regarding menstruation resulted in higher adoption of modern menstrual methods.

Conclusion

MMMs provided comparative advantage with lesser unmet needs for material reliability and reuse insecurity concerns, particularly in home environment. However, none of the MHMs fulfilled the user expectations for transport and disposal insecurity concerns, particularly outdoors.
Synergistic effect of potential alpha-amylase inhibitors from Egyptian propolis with acarbose using in silico and in vitro combination analysis
Authors: Nada Ahmed A. , Metwally Aly M. , Asaad Aya M. , Celik Ismail , Ibrahim Reham S. , Eldin Safa M. Shams
Published: January 2024

Background

Type 2 Diabetes mellitus (DM) is an affliction impacting the quality of life of millions of people worldwide. An approach used in the management of Type 2 DM involves the use of the carbohydrate-hydrolyzing enzyme inhibitor, acarbose. Although acarbose has long been the go-to drug in this key approach, it has become apparent that its side effects negatively impact patient adherence and subsequently, therapeutic outcomes. Similar to acarbose in its mechanism of action, bee propolis, a unique natural adhesive biomass consisting of biologically active metabolites, has been found to have antidiabetic potential through its inhibition of α-amylase. To minimize the need for ultimately novel agents while simultaneously aiming to decrease the side effects of acarbose and enhance its efficacy, combination drug therapy has become a promising pharmacotherapeutic strategy and a focal point of this study.

Methods

Computer-aided molecular docking and molecular dynamics (MD) simulations accompanied by in vitro testing were used to mine novel, pharmacologically active chemical entities from Egyptian propolis to combat Type 2 DM. Glide docking was utilized for a structure-based virtual screening of the largest in-house library of Egyptian propolis metabolites gathered from literature, in addition to GC–MS analysis of the propolis sample under investigation. Thereafter, combination analysis by means of fixed-ratio combinations of acarbose with propolis and the top chosen propolis-derived phytoligand was implemented.

Results

Aucubin, identified for the first time in propolis worldwide and kaempferol were the most promising virtual hits. Subsequent in vitro α-amylase inhibitory assay demonstrated the ability of these hits to significantly inhibit the enzyme in a dose-dependent manner with an IC50 of 2.37 ± 0.02 mM and 4.84 ± 0.14 mM, respectively. The binary combination of acarbose with each of propolis and kaempferol displayed maximal synergy at lower effect levels. Molecular docking and MD simulations revealed a cooperative binding mode between kaempferol and acarbose within the active site.

Conclusion

The suggested strategy seems imperative to ensure a steady supply of new therapeutic entities sourced from Egyptian propolis to regress the development of DM. Further pharmacological in vivo investigations are required to confirm the potent antidiabetic potential of the studied combination.
Behavioral variant frontotemporal dementia associated with GRN and ErbB4 gene mutations: a case report and literature review
Authors: Cai Youde , Peng Zhongyong , He Qiansong , Sun Ping
Published: January 2024

Objective

To report the clinical manifestation and genetic characteristics of a patient having frontotemporal dementia (FTD) with abnormal behavior and unstable walking.

Methods

The clinical and imaging features of a patient who was eventually diagnosed with FTD were analyzed. The patient’s neuropsychological, PET-CT, electromyography, and genetic data were collected. Furthermore, the patient’s blood samples were examined for FTD-related genes.

Results

The patient was a 52-year-old man with hidden onset. The symptoms progressed gradually, presenting with abnormal behaviors, including repeated shopping, taking away other people’s things, constantly eating snacks, and frequently calling friends at night. The patient also exhibited executive dysfunction, such as the inability to cook and multiple driving problems, e.g., constantly deviates from his lane while driving. In addition, the patient showed personality changes such as irritability, indifference, and withdrawal, as well as motor symptoms, including unstable walking and frequent falls when walking. Brain magnetic resonance imaging revealed hippocampal sclerosis along with widening and deepening of the bilateral temporal lobe sulcus. Brain metabolic imaging via PET-CT demonstrated decreased metabolism in the bilateral prefrontal lobe, with the abnormal energy metabolism indicating FTD. Lastly, blood sample analysis detected mutations in the amyotrophic lateral sclerosis (ALS)-related GRN gene c.1352C > T (p.P451L) and ErbB4 gene c.256 T > C (p.Y86H).

Conclusion

This is the first case of heterozygous mutations in the GRN and ErbB4 genes in FTD alone. The GRN and ErbB4 genes are likely to be important in the pathogenesis of FTD, expanding the common genetic profile of ALS and FTD.
Role and intervention of PAD4 in NETs in acute respiratory distress syndrome
Authors: Liu Xiaojie , Li Tianjun , Chen Huailong , Yuan Li , Ao Hushan
Published: January 2024

Background

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Acute respiratory distress syndrome (ARDS) is a common sepsis-associated injury that can increase postoperative mortality but the mechanism is still unclear.

Main text

The role of neutrophils in the pathophysiology of sepsis was deeply challenged after the discovery of NETosis, a process resulting in neutrophil extracellular traps (NETs) release. NETs can support thrombin generation and the concept of immunothrombosis has emerged as a new innate response to infection. Immunothrombosis leads to thrombosis in microvessels and supports immune cells together with specific thrombus-related molecules. ARDS is a common sepsis-associated organ injury. Immunothrombosis participates in thrombosis in pulmonary capillaries. Intervention regarding immunothrombosis in ARDS is a key scientific problem. PAD4 is the key enzyme regulating the NET skeleton protein histone H3 to citrulline histone to form NETs in immune thrombosis. This review summarizes NETosis and immunohaemostasis, ARDS and therapeutic opportunities targeting PAD4 via PAD4 inhibitors and lncRNAs potentially, providing future therapies.

Conclusions

We identified and summarized the fundamental definition of ARDS and the concept of immune thrombosis and its composition. NETs activation has become particularly relevant in the formation of immune thrombosis. The taskforce highlighted the intervention targets of PAD4, including noncoding RNAs, potentially providing future therapeutic targets to confront the high postoperative mortality of ARDS.
Forest-goers as a heterogeneous population at high-risk for malaria: a case–control study in Aceh Province, Indonesia
Authors: Gallalee Sarah , Zarlinda Iska , Silaen Martha G. , Cotter Chris , Cueto Carmen , Elyazar Iqbal R. F. , Jacobson Jerry O. , Gosling Roly , Hsiang Michelle S. , Bennett Adam , Coutrier Farah N. , Smith Jennifer L.
Published: January 2024

Background

A major challenge to malaria elimination is identifying and targeting populations that are harbouring residual infections and contributing to persistent transmission. In many near-elimination settings in Southeast Asia, it is known that forest-goers are at higher risk for malaria infection, but detailed information on their behaviours and exposures is not available.

Methods

In Aceh Province, Indonesia, a near-elimination setting where a growing proportion of malaria is due to Plasmodium knowlesi, a case–control study was conducted to identify risk factors for symptomatic malaria, characteristics of forest-goers, and key intervention points. From April 2017 to September 2018, cases and controls were recruited and enrolled in a 1:3 ratio. Cases had confirmed malaria infection by rapid diagnostic test or microscopy detected at a health facility (HF). Gender-matched controls were recruited from passive case detection among individuals with suspected malaria who tested negative at a health facility (HF controls), and community-matched controls were recruited among those testing negative during active case detection. Multivariable logistic regression (unconditional for HF controls and conditional for community controls) was used to identify risk factors for symptomatic malaria infection.

Results

There were 45 cases, of which 27 were P. knowlesi, 17 were Plasmodium vivax, and one was not determined. For controls, 509 and 599 participants were recruited from health facilities and the community, respectively. Forest exposures were associated with high odds of malaria; in particular, working and sleeping in the forest (HF controls: adjusted odds ratio (aOR) 21.66, 95% CI 5.09–92.26; community controls: aOR 16.78, 95% CI 2.19–128.7) and having a second residence in the forest (aOR 6.29, 95% CI 2.29–17.31 and 13.53, 95% CI 2.10–87.12). Male forest-goers were a diverse population employed in a variety of occupations including logging, farming, and mining, sleeping in settings, such as huts, tents, and barracks, and working in a wide range of group sizes. Reported use of protective measures, such as nets, hammock nets, mosquito coils, and repellents was low among forest-goers and interventions at forest residences were absent.

Conclusions

Second residences in the forest and gaps in use of protective measures point to key malaria interventions to improve coverage in forest-going populations at risk for P. knowlesi and P. vivax in Aceh, Indonesia. Intensified strategies tailored to specific sub-populations will be essential to achieve elimination.
Magnetic resonance imaging with upconversion nanoprobes capable of crossing the blood-cerebrospinal fluid barrier
Authors: Han Fang , Gao Jiahao , Lv Guanglei , Liu Tao , Hu Qingfeng , Zhu Meilin , Du Zunguo , Yang Jing , Yao Zhenwei , Fang Xiangming , Ni Dalong , Zhang Jiawen
Published: January 2024

The central nervous system (CNS) maintains homeostasis with its surrounding environment by restricting the ingress of large hydrophilic molecules, immune cells, pathogens, and other external harmful substances to the brain. This function relies heavily on the blood-cerebrospinal fluid (B-CSF) and blood-brain barrier (BBB). Although considerable research has examined the structure and function of the BBB, the B-CSF barrier has received little attention. Therapies for disorders associated with the central nervous system have the potential to benefit from targeting the B-CSF barrier to enhance medication penetration into the brain. In this study, we synthesized a nanoprobe ANG-PEG-UCNP capable of crossing the B-CSF barrier with high targeting specificity using a hydrocephalus model for noninvasive magnetic resonance ventriculography to understand the mechanism by which the CSF barrier may be crossed and identify therapeutic targets of CNS diseases. This magnetic resonance nanoprobe ANG-PEG-UCNP holds promising potential as a safe and effective means for accurately defining the ventricular anatomy and correctly locating sites of CSF obstruction.
Recommendations from people who use drugs in Philadelphia, PA about structuring point-of-care drug checking
Authors: Reed Megan K. , Borne Elias , Esteves Camacho Tracy , Kelly Morgan , Rising Kristin L.
Published: January 2024

Background

Adulterants, such as fentanyl and xylazine, among others, are present in a high percentage of the illicit drug supply, increasing the risk for overdose and other adverse health events among people who use drugs (PWUD). Point-of-care drug checking identifies components of a drug sample and delivers results consumers. To successfully meet the diverse needs of PWUD, more information is needed about the utility of drug checking, motivations for using services contextualized in broader comments on the drug supply, hypothesized actions to be taken after receiving drug checking results, and the ideal structure of a program.

Methods

In December 2021, semi-structured interviews were conducted with 40 PWUD who were accessing harm reduction services in Philadelphia, PA. Participants were asked about opinions and preferences for a future drug checking program. Interviews were audio recorded, transcribed and coded using content analysis to identify themes.

Results

Participants were primarily White (52.5%) and male (60%). Heroin/fentanyl was the most frequently reported drug used (72.5%, n = 29), followed by crack cocaine (60.0%, n = 24) and powder cocaine (47.5%, n = 19). Emerging themes from potential drug checking consumers included universal interest in using a drug checking program, intentions to change drug use actions based on drug checking results, deep concern about the unpredictability of the drug supply, engaging in multiple harm reduction practices, and concerns about privacy while accessing a service.

Conclusions

We offer recommendations for sites considering point-of-care drug checking regarding staffing, safety, logistics, and cultural competency. Programs should leverage pre-existing relationships with organizations serving PWUD and hire people with lived experiences of drug use. They should work with local or state government to issue protections to people accessing drug checking programs and ensure the service is anonymous and that data collection is minimized to keep the program low-threshold. Programs will ideally operate in multiple locations and span “atmosphere” (e.g., from clinical to a drop-in culture), offer in-depth education to participants about results, engage with a community advisory board, and not partner with law enforcement.
Preferences as fairness judgments: a critical review of normative frameworks of preference elicitation and development of an alternative based on constitutional economics
Authors: Rogowski Wolf , John Jürgen
Published: January 2024

Preference elicitation is widely used within health economic evaluations to inform coverage decisions. However, coverage decisions involve questions of social justice and it is unclear what role empirical evidence about preferences can play here. This study reviews the prevalent normative frameworks for using population-based preference elicitation and the criticisms they face, and proposes an alternative based on constitutional economics. The frameworks reviewed include a supposedly value-neutral framework of preferences as predictors of choice, preference utilitarian frameworks that aim to maximize preference satisfaction, and substantive consequentialist frameworks that aim to maximize happiness, health, or capabilities. The proposed alternative implements the idea that indices of social value are tools for conflict resolution, rather than tools for maximization. Preference elicitation is used for validating values generated by multi-criteria decision analysis results within representative processes of stakeholder deliberation.
Tumorous IRE1α facilitates CD8+T cells-dependent anti-tumor immunity and improves immunotherapy efficacy in melanoma
Authors: Yang Yuqi , Wang Sijia , Wang Xiang-xu , Guo Sen , Wang Huina , Shi Qiong , Tian Yangzi , Wang Hao , Zhao Tao , Zhang Hengxiang , Zhang Baolu , Gao Tianwen , Li Chunying , Yi Xiuli , Guo Weinan
Published: January 2024

Background

Tumor cells frequently suffer from endoplasmic reticulum (ER) stress. Previous studies have extensively elucidated the role of tumorous unfolded protein response in melanoma cells, whereas the effect on tumor immunology and the underlying mechanism remain elusive.

Methods

Bioinformatics, biochemical assays and pre-clinical mice model were employed to demonstrate the role of tumorous inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α) in anti-tumor immunity and the underlying mechanism.

Results

We firstly found that IRE1α signaling activation was positively associated with the feature of tumor-infiltrating lymphocytes. Then, pharmacological ER stress induction by HA15 exerted prominent anti-tumor effect in immunocompetent mice and was highly dependent on CD8+T cells, paralleled with the reshape of immune cells in tumor microenvironment via tumorous IRE1α-XBP1 signal. Subsequently, tumorous IRE1α facilitated the expression and secretion of multiple chemokines and cytokines via XBP1-NF-κB axis, leading to increased infiltration and anti-tumor capacity of CD8+T cells. Ultimately, pharmacological induction of tumorous ER stress by HA15 brought potentiated therapeutic effect along with anti-PD-1 antibody on melanoma in vivo.

Conclusions

Tumorous IRE1α facilitates CD8+T cells-dependent anti-tumor immunity and improves immunotherapy efficacy by regulating chemokines and cytokines via XBP1-NF-κB axis. The combination of ER stress inducer and anti-PD-1 antibody could be promising for increasing the efficacy of melanoma immunotherapy.
K-Ras(V12) differentially affects the three Akt isoforms in lung and pancreatic carcinoma cells and upregulates E-cadherin and NCAM via Akt3
Authors: Geißert Rebekka , Lammert Angela , Wirth Stefanie , Hönig Rabea , Lohfink Dirk , Unger Monika , Pek Denis , Schlüter Konstantin , Scheftschik Theresa , Smit Daniel J. , Jücker Manfred , Menke Andre , Giehl Klaudia
Published: January 2024

K-Ras is the most frequently mutated Ras variant in pancreatic, colon and non-small cell lung adenocarcinoma. Activating mutations in K-Ras result in increased amounts of active Ras-GTP and subsequently a hyperactivation of effector proteins and downstream signaling pathways. Here, we demonstrate that oncogenic K-Ras(V12) regulates tumor cell migration by activating the phosphatidylinositol 3-kinases (PI3-K)/Akt pathway and induces the expression of E-cadherin and neural cell adhesion molecule (NCAM) by upregulation of Akt3. In vitro interaction and co-precipitation assays identified PI3-Kα as a bona fide effector of active K-Ras4B but not of H-Ras or N-Ras, resulting in enhanced Akt phosphorylation. Moreover, K-Ras(V12)-induced PI3-K/Akt activation enhanced migration in all analyzed cell lines. Interestingly, Western blot analyses with Akt isoform-specific antibodies as well as qPCR studies revealed, that the amount and the activity of Akt3 was markedly increased whereas the amount of Akt1 and Akt2 was downregulated in EGFP-K-Ras(V12)-expressing cell clones. To investigate the functional role of each Akt isoform and a possible crosstalk of the isoforms in more detail, each isoform was stably depleted in PANC-1 pancreatic and H23 lung carcinoma cells. Akt3, the least expressed Akt isoform in most cell lines, is especially upregulated and active in Akt2-depleted cells. Since expression of EGFP-K-Ras(V12) reduced E-cadherin-mediated cell-cell adhesion by induction of polysialylated NCAM, Akt3 was analyzed as regulator of E-cadherin and NCAM. Western blot analyses revealed pronounced reduction of E-cadherin and NCAM in the Akt3-kd cells, whereas Akt1 and Akt2 depletion upregulated E-cadherin, especially in H23 lung carcinoma cells. In summary, we identified oncogenic K-Ras4B as a key regulator of PI3-Kα-Akt signaling and Akt3 as a crucial regulator of K-Ras4B-induced modulation of E-cadherin and NCAM expression and localization.
MyD88 in myofibroblasts enhances nonalcoholic fatty liver disease-related hepatocarcinogenesis via promoting macrophage M2 polarization
Authors: Liu Yu , Chen Haiqiang , Yan Xuanxuan , Zhang Jie , Deng Zhenzhong , Huang Maosheng , Gu Jianchun , Zhang Jinhua
Published: January 2024

Background

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver diseases and has emerged as the leading factor in the pathogenesis of hepatocellular carcinoma (HCC). MyD88 contributes to the development of HCC. However, the underlying mechanism by which MyD88 in myofibroblasts regulates NAFLD-associated liver cancer development remains unknown.

Results

Myofibroblast MyD88-deficient (SMAMyD88−/−) mice were protected from diet-induced obesity and developed fewer and smaller liver tumors. MyD88 deficiency in myofibroblasts attenuated macrophage M2 polarization and fat accumulation in HCC tissues. Mechanistically, MyD88 signaling in myofibroblasts enhanced CCL9 secretion, thereby promoting macrophage M2 polarization. This process may depend on the CCR1 receptor and STAT6/ PPARβ pathway. Furthermore, liver tumor growth was attenuated in mice treated with a CCR1 inhibitor. CCLl5 (homologous protein CCL9 in humans) expression was increased in myofibroblasts of HCC and was associated with shorter survival of patients with HCC. Thus, our results indicate that MyD88 in myofibroblasts promotes NAFLD-related HCC progression and may be a promising therapeutic target for HCC treatment.

Conclusion

This study demonstrates that MyD88 in myofibroblasts can promote nonalcoholic fatty liver disease-related hepatocarcinogenesis by enhancing macrophage M2 polarization, which might provide a potential molecular therapeutic target for HCC.

Graphical Abstract
Weight development from childhood to motherhood—embodied experiences in women with pre-pregnancy obesity: a qualitative study
Authors: Sandsæter Heidi L. , Eik-Nes Trine Tetlie , Getz Linn Okkenhaug , Haugdahl Hege S. , Magnussen Elisabeth Balstad , Rich-Edwards Janet W. , Horn Julie
Published: January 2024

Background

Pre-pregnancy obesity increases the risk of perinatal complications. Post-pregnancy is a time of preparation for the next pregnancy and lifestyle advice in antenatal care and postpartum follow-up is therefore recommended. However, behavioral changes are difficult to achieve, and a better understanding of pregnant women’s perspectives and experiences of pre-pregnancy weight development is crucial.

Methods

We used a qualitative design and conducted semi-structured interviews with 14 women in Norway with pre-pregnancy obesity 3–12 months postpartum. Data were analyzed using thematic analysis.

Results

Four themes addressing women’s experiences and understanding of their weight development were generated: (1) Unmet essential needs, (2) Genetic predisposition for obesity, challenging life course transitions and turning points, (3) Under a critical eye: an ever-present negative bodily awareness, and (4) Wrestling with food. Parents’ inability to meet children’s essential needs caused weight gain through an unbalanced diet, increased stress, and emotional eating patterns. Body criticism and a feeling of not belonging led to negative body awareness that influenced behavioral patterns and relationships. Participants reporting having had a good childhood more often described their weight development as a result of genetic predisposition, challenging life course transitions and turning points, such as illness and injuries. Nevertheless, these participants also described how eating patterns were influenced by stress and negative emotions.

Conclusions

Healthcare providers should pay attention to the insider perspectives of pre-pregnancy weight development. An open and shared understanding of the root causes of these women’s weight development can form a basis for more successful lifestyle guidance.
Perceptions in orthopedic surgery on the use of cannabis in treating pain: a survey of patients with spine pain (POSIT Spine)
Authors: Gjorgjievski Marko , Madden Kim , Bullen Conner , Koziarz Frank , Koziarz Alex , Cenic Aleksa , Li Silvia , Bhandari Mohit , Johal Herman
Published: January 2024

Background

Back pain is the leading cause of disability worldwide. Despite guidelines discouraging opioids as first-line treatment, opioids remain the most prescribed drugs for back pain. There is renewed interest in exploring the potential medical applications of cannabis, and with the recent changes in national legislation there is a unique opportunity to investigate the analgesic properties of cannabis.

Methods

This was a multi-center survey-based study examining patient perceptions regarding cannabis for spine pain. We included patients presenting with back or neck pain to one of three Orthopedic clinics in Ontario. Our primary outcome was perceived effect of cannabis on back pain, while secondary outcomes were perceptions regarding potential applications and barriers to cannabis use.

Results

259 patients participated in this study, 35.3% (90/255) stating they used cannabis medically. Average pain severity was 6.5/10 ± 0.3 (95% CI 6.2–6.8). Nearly three-quarters were prescribed opioids (73.6%, 148/201), with oxycodone/oxycontin (45.9% 68/148) being the most common, and almost half of (49.3%, 73/148) had used an opioid in the last week. Patients estimated cannabis could treat 54.3% ± 4.0 (95% CI 50.3–58.3%) of their spine pain and replace 46.2% ± 6. 6 (95% CI 39.6–52.8%) of their current analgesics. Age (β = − 0.3, CI − 0.6–0.0), higher pain severity (β = 0.4, CI 0.1–0.6) and previous cannabis use (β = 14.7, CI 5.1–24.4) were associated with a higher perceived effect of cannabis. Patients thought cannabis would be beneficial to treat pain (129/146, 88.4%), and reduce (116/146, 79.5%) or eliminate opioids (102/146, 69.9%). Not considering using cannabis for medical purposes (65/150, 43.3%) was the number one reported barrier.

Conclusions

Patients estimated medical cannabis could treat more than half of their spine pain, with one in three patients already using medical cannabis. 79% of patients also believe cannabis could reduce opioid usage. This data will help support more research into cannabis for musculoskeletal pain.
Comparison of analgesic effects of percutaneous and transthoracic intercostal nerve block in video-assisted thoracic surgery: a propensity score-matched study
Authors: Hui Hongliang , Miao Haoran , Qiu Fan , Li Huaming , Lin Yangui , Jiang Bo , Zhang Yiqian
Published: January 2024

Background

This study aimed to compare the analgesic efficacy of transthoracic intercostal nerve block (TINB) and percutaneous intercostal nerve block (PINB) for video-assisted thoracic surgery (VATS) using a retrospective analysis.

Methods

A total of 336 patients who underwent VATS between January 2021 and June 2022 were reviewed retrospectively. Of the participants, 194 received TINB and were assigned to the T group, while 142 patients received PINB and were assigned to the P group. Both groups received 25 ml of ropivacaine via TINB or PINB at the end of the surgery. The study measured opioid consumption, pain scores, analgesic satisfaction, and safety. Propensity score matching (PSM) analysis was performed to minimize selection bias due to nonrandom assignment.

Results

After propensity score matching, 86 patients from each group were selected for analysis. The P group had significantly lower cumulative opioid consumption than the T group (p < 0.01). The Visual Analogue Scale (VAS) scores were lower for the P group than the T group at 6 and 12 h post-surgery (p < 0.01); however, there was no significant difference in the scores between the two groups at 3, 24, and 48 h (p > 0.05). The analgesic satisfaction in the P group was higher than in the T group (p < 0.05). The incidence of back pain, nausea or vomiting, pruritus, dizziness, and skin numbness between the two groups was statistically insignificant (p > 0.05).

Conclusion

The study suggests that PINB provides superior analgesia for patients undergoing thoracic surgery compared to TINB without any extra adverse effects.
Evaluation of a multi-component early warning system for pastoralist populations in Doolo zone, Ethiopia: mixed-methods study
Authors: Baertlein Luke , Dubad Bashir Ali , Sahelie Birhanu , Damulak Istifanus Chindong , Osman Mohammed , Stringer Beverley , Bestman Agatha , Kuehne Anna , van Boetzelaer Elburg , Keating Patrick
Published: January 2024

Background

This study evaluated an early warning, alert and response system for a crisis-affected population in Doolo zone, Somali Region, Ethiopia, in 2019–2021, with a history of epidemics of outbreak-prone diseases. To adequately cover an area populated by a semi-nomadic pastoralist, or livestock herding, population with sparse access to healthcare facilities, the surveillance system included four components: health facility indicator-based surveillance, community indicator- and event-based surveillance, and alerts from other actors in the area. This evaluation described the usefulness, acceptability, completeness, timeliness, positive predictive value, and representativeness of these components.

Methods

We carried out a mixed-methods study retrospectively analysing data from the surveillance system February 2019–January 2021 along with key informant interviews with system implementers, and focus group discussions with local communities. Transcripts were analyzed using a mixed deductive and inductive approach. Surveillance quality indicators assessed included completeness, timeliness, and positive predictive value, among others.

Results

1010 signals were analysed; these resulted in 168 verified events, 58 alerts, and 29 responses. Most of the alerts (46/58) and responses (22/29) were initiated through the community event-based branch of the surveillance system. In comparison, one alert and one response was initiated via the community indicator-based branch. Positive predictive value of signals received was about 6%. About 80% of signals were verified within 24 h of reports, and 40% were risk assessed within 48 h. System responses included new mobile clinic sites, measles vaccination catch-ups, and water and sanitation-related interventions. Focus group discussions emphasized that responses generated were an expected return by participant communities for their role in data collection and reporting. Participant communities found the system acceptable when it led to the responses they expected. Some event types, such as those around animal health, led to the community’s response expectations not being met.

Conclusions

Event-based surveillance can produce useful data for localized public health action for pastoralist populations. Improvements could include greater community involvement in the system design and potentially incorporating One Health approaches.
Chromosomal microarray analysis for prenatal diagnosis of uniparental disomy: a retrospective study
Authors: Xu Chenxia , Li Miaoyuan , Gu Tiancai , Xie Fenghua , Zhang Yanfang , Wang Degang , Peng Jianming
Published: January 2024

Background

Chromosomal microarray analysis (CMA) is a valuable tool in prenatal diagnosis for the detection of chromosome uniparental disomy (UPD). This retrospective study examines fetuses undergoing invasive prenatal diagnosis through Affymetrix CytoScan 750 K array analysis. We evaluated both chromosome G-banding karyotyping data and CMA results from 2007 cases subjected to amniocentesis.

Results

The detection rate of regions of homozygosity (ROH) ≥ 10 Mb was 1.8% (33/2007), with chromosome 11 being the most frequently implicated (17.1%, 6/33). There were three cases where UPD predicted an abnormal phenotype based on imprinted gene expression.

Conclusion

The integration of UPD detection by CMA offers a more precise approach to prenatal genetic diagnosis. CMA proves effective in identifying ROH and preventing the birth of children affected by imprinting diseases.