bluuebunny/crossref_metadata_2025 huggingface dataset:
Complex interplay of neurodevelopmental disorders (NDDs), fractures, and osteoporosis: a mendelian randomization study
Authors: Li Zefang , Wu Xueqiang , Li Hanzheng , Bi Cong , Zhang Can , Sun Yiqing , Yan Zhaojun
Published: March 2024

Background

Neurodevelopmental disorders (NDDs), such as Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and Tourette Syndrome (TS), have been extensively studied for their multifaceted impacts on social and emotional well-being. Recently, there has been growing interest in their potential relationship with fracture risks in adulthood. This study aims to explore the associations between these disorders and fracture rates, in order to facilitate better prevention and treatment.

Methods

Employing a novel approach, this study utilized Mendelian randomization (MR) analysis to investigate the complex interplay between ADHD, ASD, TS, and fractures. The MR framework, leveraging extensive genomic datasets, facilitated a systematic examination of potential causal relationships and genetic predispositions.

Results

The findings unveil intriguing bidirectional causal links between ADHD, ASD, and specific types of fractures. Notably, ADHD is identified as a risk factor for fractures, with pronounced associations in various anatomical regions, including the skull, trunk, and lower limbs. Conversely, individuals with specific fractures, notably those affecting the femur and lumbar spine, exhibit an increased genetic predisposition to ADHD and ASD. In this research, no correlation was found between TS and fractures, or osteoporosis.These results provide a genetic perspective on the complex relationships between NDDs and fractures, emphasizing the importance of early diagnosis, intervention, and a holistic approach to healthcare.

Conclusion

This research sheds new light on the intricate connections between NDDs and fractures, offering valuable insights into potential risk factors and causal links. The bidirectional causal relationships between ADHD, ASD, and specific fractures highlight the need for comprehensive clinical approaches that consider both NDDs and physical well-being.
Coverage and determinants of HIV testing and counseling services among mothers attending antenatal care in sub-Saharan African countries: a multilevel analysis
Authors: Raru Temam Beshir , Merga Bedasa Taye , Deressa Alemayehu , Birhanu Abdi , Ayana Galana Mamo , Negash Belay , Gamachu Mulugeta , Alemu Addisu , Hassen Fila Ahmed , Mohammed Ahmed , Firdisa Dawit , Regassa Lemma Demissie
Published: March 2024

Background

HIV/AIDS is one of the top global public health threats that causes significant cases, deaths, and socioeconomic impact. Even though both HIV testing and counseling are identified as essential HIV interventions during pregnancy, large population-representative data shows that service coverage and determinants are limited. Therefore, this study aimed to assess the coverage and determinants of HIV testing and counseling services among pregnant mothers attending antenatal care services in sub-Saharan African countries using different nationwide data.

Methods

This study was conducted on large national-representative data from the Demographic Health Survey (DHS) using multilevel analysis. Data extraction, cleaning, coding, and statistical analysis were performed using STATA version 17. Weighting was used to ensure the representativeness of the sample and to obtain reliable estimates and standard errors. The multivariable multilevel logistic regression model was used to identify the determinants of HIV testing and counseling during the antenatal care visit. Adjusted odds ratios with 95% confidence intervals were used to measure statistical significance.

Results

A total of 83,584 women attending antenatal care were included in this study. HIV testing and counseling coverage in sub-Saharan Africa was found to be 62.87% with a 95% CI of 62.54–63.19%. The HIV testing and counseling determinants included being in the age group of 35–49 (AOR = 1.64; 95% CI: 1.46–1.83), secondary and above education levels (AOR = 1.50; 95% CI: 1.39–1.60), having at least four ANC visits (AOR = 1.85; 95% CI: 1.68–2.02), living in an urban area (AOR = 1.40; 95% CI: 1.30–1.52), and living in countries such as Rwanda (AOR = 6.19; 95% CI: 5.19–7.38) and Mauritania (AOR = 0.02; 95% CI: 0.01–0.03).

Conclusion

This study revealed that HIV testing and counseling coverage was 62.87% in sub-Saharan Africa. Factors affecting the HIV testing and counseling coverage were age, education, frequency of antenatal care visits, residence area, and living in Rwanda and Mauritania. Therefore, to increase HIV testing and counseling coverage in sub-Saharan Africa, policymakers on maternal health and other stakeholders should work with an integrated approach with other sectors and give prior attention to modifiable factors such as promoting women’s education and the comprehensiveness of antenatal care follow-up services during the follow-up.
Menstruating while homeless: navigating access to products, spaces, and services
Authors: DeMaria Andrea L. , Martinez Rebecca , Otten Emily , Schnolis Emma , Hrubiak Sofia , Frank Jaclyn , Cromer Risa , Ruiz Yumary , Rodriguez Natalia M.
Published: March 2024

Background

People experiencing homelessness (PEH) in the United States face substantial challenges related to menstruation, exacerbated by the COVID-19 pandemic. Limited access to period products, heightened stigma, and gynecological challenges contribute to increased hardships for PEH, highlighting the need for improved services and policies to address period equity and overall well-being for this vulnerable population.

Methods

We conducted semi-structured qualitative interviews with PEH (n = 12) and community healthcare and social service providers (e.g., case managers, shelter directors, community health workers, and nurses, n = 12) in Lafayette, Indiana, a city located between Indianapolis and Chicago in the United States. We used thematic analysis techniques for data analysis.

Results

PEH’s limited access to products, services, and safe spaces hindered effective menstruation management within restrictive community contexts. Although community healthcare and service providers offered some support, complex interactions with the healthcare system, stigma, and limited access to spaces exacerbated barriers. The COVID-19 pandemic further intensified these difficulties by closing public spaces, worsening economic conditions, and straining service provider resources.

Conclusions

Results highlight critical organizational and policy gaps in the United States for menstruation management resources and services, emphasizing the need for better integration into health and well-being programs for PEH. These insights will advance reproductive and public health research, shedding light on the disparities faced by PEH in managing menstruation in Indiana and contributing to the national discourse on addressing these barriers. Amid the complex landscape of public health, particularly during and after the pandemic, prioritizing menstrual health remains essential for all individuals’ overall well-being, including those experiencing homelessness.
Cyberchondria severity and utilization of health services in Polish society: a cross-sectional study
Authors: Kobryn Mateusz , Duplaga Mariusz
Published: March 2024

Background

It has been suggested that cyberchondria leads to increased utilization of healthcare services. Unfortunately, not many studies have analyzed this effect comprehensively. The aim of this study was to analyze the relationship between cyberchondria severity and the utilization of healthcare services among adult Internet users after adjusting for sociodemographic characteristics and the health status of respondents.

Methods

The analysis detailed in this paper examined data from a computer-based, web-based interviewing survey performed among a representative sample of 1613 Polish Internet users. Cyberchondria severity was assessed with the Cyberchondria Severity Scale (CSS). The variables reflecting the use of healthcare services were based on the frequency of visits to family physicians and specialists, diagnostic procedures, hospital admissions, and emergency services, and finally being vaccinated against COVID-19. The effect of cyberchondria severity on the utilization of healthcare services and alternative medicine was adjusted for key sociodemographic variables, the presence of chronic diseases, disability, and unspecific symptoms. For variables reflecting the use of services, ordinal logistic regression and multivariable logistic regression models were developed.

Results

Cyberchondria severity was a significant predictor of the utilization of all but one of the analyzed healthcare services and alternative medicine. The odds of being in a higher category of the utilization of visits to family physicians and specialists, hospital admissions, emergency services and alternative medicine services increased by a factor of 1.01–1.02 for every unit increase of the cyberchondria score. The cyberchondria score was a negative predictor of COVID-19 vaccine uptake. The effect of cyberchondria on outcome variables was independent of the level of health anxiety, sociodemographic variables, and variables reflecting the health status of respondents.

Conclusions

Cyberchondria leads to more intensive use of nearly all healthcare services, but in the case of vaccination against COVID-19, cyberchondria severity was a negative predictor. Cyberchondria’s effect extends beyond health anxiety.
A novel homozygous variant (c.5876T > C: p. Leu1959Pro) in DYSF segregates with limb-girdle muscular dystrophy: a case report
Authors: Hesami Hamed , Ghasemi Serwa , Houshmand Golnaz , Nilipour Yalda , Hesami Mahshid , Biglari Alireza , Nafissi Shahriar , Maleki Majid , Kalayinia Samira
Published: March 2024

Background

Limb girdle muscular dystrophies (LGMDs) constitute a heterogeneous group of neuromuscular disorders with a very variable clinical presentation and overlapping traits. The clinical symptoms of LGMD typically appear in adolescence or early adulthood. Genetic variation in the dysferlin gene (DYSF) has been associated with LGMD.

Methods

We characterized a recessive LGMD in a young adult from consanguineous Irani families using whole-exome sequencing (WES) technology. Sanger sequencing was performed to verify the identified variant. Computational modeling and protein-protein docking were used to investigate the impact of the variant on the structure and function of the DYSF protein.

Results

By WES, we identified a novel homozygous missense variant in DYSF (NM_003494.4: c.5876T > C: p. Leu1959Pro) previously been associated with LGMD phenotypes.

Conclusions

The identification and validation of new pathogenic DYSF variant in the present study further highlight the importance of this gene in LGMD.
Immediate implant placement in the anterior mandible: a cone beam computed tomography study
Authors: Kanewoff Emmy , Alhallak Reem , de Carvalho Machado Vinícius , Chrcanovic Bruno Ramos
Published: March 2024

Background

The placement of implants into the alveolar socket right after tooth extraction is called immediate implant placement (IIP). This approach has its particularities depending on which region of the jaws is involved. The anterior mandible region is peculiar due to the presence of mandibular incisors, which have the shortest roots among all permanent teeth.

Purpose

This study aimed to investigate the factors that could be associated with the risk of either cortical bone wall perforation or invasion of the 2 mm secure distance from the surrounding anatomical structures (defined as unsafe implant placement), with IIP in the maxillary aesthetic zone, in a cone-beam computed tomography (CBCT) virtual study.

Materials and methods

CBCT exams from 239 eligible subjects were investigated. Implants were virtually placed in two distinct positions: prosthetically-driven (along the long axis of the existing tooth) and bone-driven position (according to the available bone and with regard to nearby anatomical structures). Correlation between several variables was tested, and binary logistic regression analysis in order to assess of the possible associations between covariates and unsafe placement was performed.

Results

Safe placing implants was significantly higher for the bone-driven in comparison to the prosthetically-driven position (22.2% vs. 3.3%, respectively), and the 2-mm secure distance from anatomical structures was not possible to respect in the majority of cases (77.6% vs. 82.9%, respectively). Covariates associated with a higher risk of unsafe placement were tooth region (CI in relation to IL and CA), decrease of labial concavity angle (LCA), decrease of mandible basal bone height (MBBH), and decrease in mandibular bone thickness at the tooth apex level (MBT0).

Conclusion

The possibility of safely placing immediate implants in the anterior mandible is significantly higher for bone-driven than in prosthetically driven position. Presurgical virtual planning with CBCT is a great tool for minimizing the risk of implant unsafe placement with regards to the anatomical conditions in the mandible.
Decellularized human amniotic membrane scaffolds: influence on the biological behavior of dental pulp stem cells
Authors: Zhang Zonghao , Lu Bingling , Zou Luning , Huang Xinhui , Yang Fan , Lv Hongbing
Published: March 2024

Objective

The objective of this study was to assess the characterization of human acellular amniotic membrane (HAAM) using various decellularization methods and their impact on the proliferation and differentiation of human dental pulp stem cells (DPSCs). The goal was to identify scaffold materials that are better suited for pulp regeneration.

Methods

Six different decellularization methods were used to generate the amniotic membranes. The characteristics of these scaffolds were examined through hematoxylin and eosin (H&E) staining, scanning electron microscopy (SEM), and immunohistofluorescence staining (IHF). The DPSCs were isolated, cultured, and their capacity for multidirectional differentiation was verified. The third generation (P3) DPSCs, were then combined with HAAM to form the decellularized amniotic scaffold-dental pulp stem cell complex (HAAM-DPSCs complex). Subsequently, the osteogenic capacity of the HAAM-DPSCs complex was evaluated using CCK8 assay, live-dead cell staining, alizarin red and alkaline phosphatase staining, and real-time quantitative PCR (RT-PCR).

Results

Out of the assessed decellularization methods, the freeze-thaw + DNase method and the use of ionic detergent (CHAPS) showed minimal changes in structure after decellularization, making it the most effective method. The HAAM-DPSCs complexes produced using this method demonstrated enhanced biological properties, as indicated by CCK8, alizarin red, alkaline phosphatase staining, and RT-PCR.

Conclusion

The HAAM prepared using the freeze-thaw + DNase method and CHAPS methods exhibited improved surface characteristics and significantly enhanced the proliferation and differentiation capacity of DPSCs when applied to them. The findings, therefore demonstrate the capacity for enhanced pulp regeneration therapy.
Tetrastigma hemsleyanum (Sanyeqing) root extracts evoke S phase arrest while inhibiting the migration and invasion of human pancreatic cancer PANC-1 cells
Authors: Sun Yifan , Qin Haiyan , Zhang Chunchun , Xu Jian , Zhang Ting
Published: March 2024

Background

Ethyl acetate extracts from Tetrastigma hemsleyanum (Sanyeqing) (EFT), a member of the Vitaceae plant family, have been shown to exhibit efficacy against a variety of cancers. In this light, our current study seeks to examine the mechanism of efficacy between EFT extracts and human pancreatic cancer PANC-1 cells.

Methods

The chemical components of EFT were analyzed by gas chromatography–mass spectrometry. The cytotoxicity of EFT on PANC-1 cells was measured using an MTT assay. In order to investigate EFT induction of cell cycle arrest, changes in cell-cycle distribution were monitored by flow cytometry. Wound healing and transwell assays were employed to investigate whether migration and invasion of PANC-1 cells were inhibited by EFT. Relative protein expression was detected using Western blot.

Results

GC-MS analysis of the chemical composition of EFT revealed that the majority of constituents were organic acids and their corresponding esters. EFT exhibits measurable cytotoxicity and inhibition of PANC-1 invasion. Growth inhibition was primarily attributed to downregulation of CDK2 which induces cell cycle arrest in the S-phase. Inhibition of metastasis is achieved through downregulation of mesenchymal-associated genes/activators, including ZEB1, N-cadherin, Vimentin, and Fibronectin. Meanwhile, the expression of E-cadherin was significantly increased by EFT treatment. Furthermore, downregulation of MMP-2 and MMP-9 were observed.

Conclusion

Treatment of PANC-1 with EFT demonstrated measurable cytotoxic effects. Furthermore, EFT evoked S phase arrest while inhibiting the migration and invasion of PANC-1 cells. Additionally, EFT inhibited the epithelial to mesenchymal transition and MMPs expression in PANC-1 cells. This study serves to confirm the strong therapeutic potential of EFT while identifying the mechanisms of action.
Needs assessment for direct ophthalmoscopy training in neurology residency
Authors: Saroya Jasmeet , Chahal Noor , Jiang Alice , Pet Douglas , Rasool Nailyn , Terrelonge Mark , Yung Madeline
Published: March 2024

Background

Assessment of the ocular fundus, traditionally by direct ophthalmoscopy (DO), is essential to evaluate many neurologic diseases. However, the status of DO training in neurology residencies is unknown. We conducted a needs assessment to determine current attitudes, curricula, and gaps in DO training.

Methods

A survey was developed and administered to residents and program directors (PDs) at ACGME accredited neurology residencies in the United States. The survey assessed factors such as current DO curricula, perceived importance of DO, confidence of skills, and need for improvement. Data analysis was performed using the Mann Whitney U test and Fisher Exact Test.

Results

Nineteen PDs (11.6%) and 74 (41.1%) residents responded to the survey. 97.1% of residents and 100.0% of PDs believe DO is an important skill to learn. 29.4% of PDs expected graduating residents to have completed > 10 supervised DO exams, while 0.0% of graduating fourth year residents reported doing so (p = 0.03). 35.7% of graduating residents had never correctly identified an abnormal finding on DO. The number of times residents practiced DO unsupervised correlated with increasing confidence in all components of the DO exam (p < 0.05). Residents who felt their program emphasized DO were more likely to perform DO at least once a week compared to residents who did not perceive program emphasis (61.9% vs. 35.0%, p = 0.02) and were more confident in DO (p < 0.05). 66.7% of residents and 42.1% of PDs were not satisfied with current levels of DO training. 96.7% of residents and 78.9% of PDs felt it was important to improve curriculum for DO training. Supervised practice and practice skills sessions were identified as the most helpful interventions to improve DO training.

Conclusions

The vast majority of neurology PDs and residents believe DO is an important skill to learn, are unsatisfied with the current level of DO training, and advocate for improvement in DO curricula. Current DO curricula have limited formal didactic training and supervised practice. The bulk of DO learning occurs through unsupervised practice, which is influenced by motivational factors such as perceived residency emphasis on DO learning.
Exploring health and disease concepts in healthcare practice: an empirical philosophy of medicine study
Authors: van der Linden Rik R. , Schermer Maartje H.N.
Published: March 2024

In line with recent proposals for experimental philosophy and philosophy of science in practice, we propose that the philosophy of medicine could benefit from incorporating empirical research, just as bioethics has. In this paper, we therefore take first steps towards the development of an empirical philosophy of medicine, that includes investigating practical and moral dimensions. This qualitative study gives insight into the views and experiences of a group of various medical professionals and patient representatives regarding the conceptualization of health and disease concepts in practice and the possible problems that surround them. This includes clinical, epistemological, and ethical issues. We have conducted qualitative interviews with a broad range of participants (n = 17), working in various health-related disciplines, fields and organizations. From the interviews, we highlight several different practical functions of definitions of health and disease. Furthermore, we discuss 5 types of problematic situations that emerged from the interviews and analyze the underlying conceptual issues. By providing theoretical frameworks and conceptual tools, and by suggesting conceptual changes or adaptations, philosophers might be able to help solve some of these problems. This empirical-philosophical study contributes to a more pragmatic way of understanding the relevance of conceptualizing health and disease by connecting the participants’ views and experiences to the theoretical debate. Going back and forth between theory and practice will likely result in a more complex but hopefully also better and more fruitful understanding of health and disease concepts.
A multi-country mixed-method study identifying the association between perceived ethical work climate and problems among critical care nurses
Authors: Ahmed Fatma Refaat , Al-Yateem Nabeel , Hisham Hijji Farha , Al Dweik Ghadeer , Alkawaldeh Mohammad , Subu Muhammad Arsyad , Dias Jacqueline Maria , Aburuz Mohannad Eid , Farghaly Sally Mohammed
Published: March 2024

Background

Given the grave ethical tension and dilemmas posed continuously which are aggravated in the intensive care unit context and its related caregiving provision, combined with their impact on critical care nurses’ job satisfaction and work-related risks, exploring and analyzing these tensions and conflicts is crucial. This study was conducted to examine the relationship between perceived ethical work climate and problems among critical care nurses in addition to exploring their perspectives on the ethical work climates while caring for patients with infectious diseases.

Design and method

A mixed-method research design was used to conduct this study among 635 participants, comprising 170 from Egypt, 144 from Jordan, 161 from Saudi Arabia, and 160 from the United Arab Emirates. Online or paper-based survey forms were distributed to all eligible critical care nurses who agreed to take part in the study. The survey contained both quantitative and qualitative data that were analyzed separately and integrated during the discussion. The study was reported following the STROBE guidelines.

Findings

The overall ethical work climate was fairly good and was significantly associated with ICU nurses’ personal and professional characteristics. The findings also identified three main themes: (1) an ethical sense of failure, (2) environmental condemnation, and (3) an instant action plan for resolving ethical conflicts.

Conclusions

ICU nurses perceived that ICU ethical climate was fairly good. The results indicated that ICU nurses generally had a relatively fair perception of the ethical work climate, with implications for addressing ethical issues and conflicts in various settings.

Impact

Mentorship and/or close supervision concerning ethical resilience, consultation, and decision-making is crucial in the ICU milieu. Metacognitive strategies to reinforce problem-solving and decision-making ICU nurses’ skills could help them overcome the different ethical challenges. Adequate resources, teamwork, and organizational support are promising tactics to improve ICU nurses’ ethical skills.

Trial registration

Not applicable.
Evaluation of a peer-support, ‘mentor mother’ program in Gaza, Mozambique; a qualitative study
Authors: Katirayi Leila , Ndima Sozinho , Farah Amgad , Ludwig Whitney , Mabote Atanásio , Chiposse Ismail , Muteerwa Ana , Cowan Jessica Greenberg , Meque Ivete
Published: March 2024

Background

Retention in prevention of mother-to-child transmission of HIV programs is critical to reduce vertical transmission. To addresses challenges with retention, Mozambique launched a peer-support program in 2018, in which HIV-positive mothers provide adherence support as mentor mothers (MMs) for HIV-positive pregnant and lactating women and HIV-exposed and infected children.

Methods

A descriptive qualitative evaluation was conducted across nine facilities in Gaza Province to assess the acceptability and barriers to implementation of the mentor mother program (MMP) among those receiving services and providing services. In-depth interviews and focus group discussions were conducted with MMs, MM supervisors, health care workers (HCWs), HIV-positive mothers enrolled in the MMP, HIV-positive mothers who declined MMP enrollment, and key informants involved in the implementation of the program. Thematic analysis identified emerging recurrent themes and patterns across the participants’ responses. Data were collected between November-December 2020.

Results

There were initial challenges with acceptability of the MMP, especially regarding confidentiality concerns and MM roles. Sharing additional information about MMs and making small changes during the beginning of the MMP resulted in generally high acceptance of the MMP. HIV-positive mothers reported that counseling from MMs improved their understanding of the importance of anti-retroviral treatment (ART) and how to take and administer ART. HIV-positive mothers reported having reduced guilt and shame about their HIV-status, feeling less alone, and having more control over their health. MMs shared that their work made them feel valued and decreased their self-stigmatization. However, MMs also reported feeling that they had inadequate resources to perform optimal job functions; they listed inadequate transportation, insufficient stipends, and false addresses of clients among their constraints. Overall, HCWs felt that their workload was significantly reduced with MM support and wanted more MMs in the community and health facility.

Conclusions

This study found that the MMP was considered a substantive and highly valued support to HIV-positive mothers, resulting in increased ART literacy among patients, improved self-reported well-being and sense of community and reduced feelings of isolation. Recommendations include strengthening MM training, increasing financial and materiel resources, additional information provided to newly enrolled mothers and support for the male partners.
Association of pharmacogenomic, clinical and behavioural factors with oral levothyroxine (LT-4) dose of hypothyroid patients in Sri Lanka: a matched case control study
Authors: Dalugodage S. S. , Bowatte Gayan , Antonypillai Charles , Rajapakse S. , Tennakoon T. M. I. U. K.
Published: March 2024

Background

Hypothyroidism is a common endocrine disorder that exerts a substantial influence on people all over the world. Levothyroxine (LT-4) is the drug of choice for the treatment of hypothyroidism and the starting oral dose is typically ranging from 1.5 to 1.7 µg/kg/day. The target is to achieve an optimum serum TSH level of 0.4-4.0 mIU/L; hence, the dose is titrated accordingly. Once the LT-4 dose is adjusted to obtain the target TSH level, it usually remains stable for a long period of time in most cases. However, some of the patients require frequent dose adjustments and some of them require unusually high doses. Therefore, the aim of this study is to determine the association of pharmacogenomic, clinical and behavioural factors with the oral levothyroxine (LT-4) dose requirement of hypothyroid patients in Sri Lanka.

Method

This study will be conducted as a matched case-control study and will involve primary hypothyroid patients who visit the diabetes and endocrinology clinic at the National Hospital, Kandy, Sri Lanka. We will recruit a total of 292 cases and select 292 controls from the clinic who are matched in terms of age, sex and Body Mass Index (BMI). An interviewer-administered questionnaire will be used to collect data from the participants (n = 584). Of the 584 patients, blood samples will be collected from a sub-sample (n = 150) for DNA extraction. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) will be performed for single nucleotide polymorphisms (SNP) analysis.

Discussion

Frequent dose adjustments of levothyroxine cause a serious economic burden to the healthcare system. By identifying the root causes of the variations in LT-4 dosage, a more comprehensive comprehension of hypothyroidism and its management can be attained in Sri Lanka. Furthermore, upon identification of a positive association/correlation between genetic polymorphisms and the LT-4 dose, SNP profiles can be used as a possible genetic marker for dose adjustment determination in future patients.
Exosomal long non-coding RNA TRPM2-AS promotes angiogenesis in gallbladder cancer through interacting with PABPC1 to activate NOTCH1 signaling pathway
Authors: He Zhiqiang , Zhong Yuhan , Regmi Parbatraj , Lv Tianrun , Ma Wenjie , Wang Junke , Liu Fei , Yang Siqi , Zhong Yanjie , Zhou Rongxing , Jin Yanwen , Cheng Nansheng , Shi Yujun , Hu Haijie , Li Fuyu
Published: March 2024

Background

Abnormal angiogenesis is crucial for gallbladder cancer (GBC) tumor growth and invasion, highlighting the importance of elucidating the mechanisms underlying this process. LncRNA (long non-coding RNA) is widely involved in the malignancy of GBC. However, conclusive evidence confirming the correlation between lncRNAs and angiogenesis in GBC is lacking.

Methods

LncRNA sequencing was performed to identify the differentially expressed lncRNAs. RT-qPCR, western blot, FISH, and immunofluorescence were used to measure TRPM2-AS and NOTCH1 signaling pathway expression in vitro. Mouse xenograft and lung metastasis models were used to evaluate the biological function of TRPM2-AS during angiogenesis in vivo. EDU, transwell, and tube formation assays were used to detect the angiogenic ability of HUVECs. RIP, RAP, RNA pull-down, dual-luciferase reporter system, and mass spectrometry were used to confirm the interaction between TRPM2-AS, IGF2BP2, NUMB, and PABPC1.

Results

TRPM2-AS was upregulated in GBC tissues and was closely related to angiogenesis and poor prognosis in patients with GBC. The high expression level and stability of TRPM2-AS benefited from m6A modification, which is recognized by IGF2BP2. In terms of exerting pro-angiogenic effects, TRPM2-AS loaded with exosomes transported from GBC cells to HUVECs enhanced PABPC1-mediated NUMB expression inhibition, ultimately promoting the activation of the NOTCH1 signaling pathway. PABPC1 inhibited NUMB mRNA expression through interacting with AGO2 and promoted miR-31-5p and miR-146a-5p-mediated the degradation of NUMB mRNA. The NOTCH signaling pathway inhibitor DAPT inhibited GBC tumor angiogenesis, and TRPM2-AS knockdown enhanced this effect.

Conclusions

TRPM2-AS is a novel and promising biomarker for GBC angiogenesis that promotes angiogenesis by facilitating the activation of the NOTCH1 signaling pathway. Targeting TRPM2-AS opens further opportunities for future GBC treatments.
Knowledge and perception of HPV vaccination among Lebanese mothers of children between nine and 17 years old
Authors: Elissa Nassif , Charbel Hadchity , Marly Azzi , Ingrid Nader , Nadine Saleh , Rachel Abdo
Published: March 2024

Background

The human papillomavirus (HPV), a prevalent sexually transmitted infection, is linked to a wide range of diseases, with cervical cancer being the most common and serious one. HPV vaccination is crucial for preventing cervical cancer and other HPV-related problems. The low acceptability of HPV vaccination among teenagers globally is largely due to a lack of understanding and information about HPV among parents. Our study aimed to evaluate the level of knowledge, attitude, intention, and HPV vaccination among parents in Lebanon as well as the variables influencing Lebanese mothers' intentions to vaccinate their children.

Methods

A cross-sectional survey-based study involving 392 participants was conducted between May and June 2022. The study assessed parents' intention to vaccinate their children against HPV, their knowledge about HPV, and the HPV vaccine. The data was collected through an anonymous electronic questionnaire. A bivariate analysis was conducted using Student t-test and ANOVA to examine the relationship between the dependent variable “Intention to vaccination” and the secondary variables. The level of statistical significance was set at 0.05 for all data.

Results

Our findings showed that only 63% of the 392 participants claimed they would give their child the HPV vaccination. A positive significant association was demonstrated between "Intention to vaccinate against HPV" and mother's nationality, father's educational level, family income per month, information received about the HPV vaccine, parents' HPV vaccination, insurance coverage of the HPV vaccine, children's vaccinations with all required vaccines, knowledge of HPV, and knowledge of the HPV vaccine. Furthermore, when parents know about HPV, their desire to vaccinate their child increases by a factor of 1.832 times, and by 1.207 times when their knowledge level increases by one point.

Conclusion

The majority of parents lacked a general understanding of most HPV-related statements, which highlights the requirement for educational interventions to raise parental awareness, understanding, and attitudes toward HPV and, as a result, increase parental acceptance of vaccinating their children. To increase the vaccination rate among adolescents, government authorities should ensure that the HPV vaccine is available in all hospitals and clinics and should be provided free of charge.
Dysphoric milk ejection reflex among Japanese mothers: a self-administered survey
Authors: Moriyama Yukako , Nakao Yuko , Yamamoto Naoko , Oki Toshimichi
Published: March 2024

Background

The dysphoric milk ejection reflex (D-MER) is a reflex that causes temporary discomfort during milk ejection. D-MER develops due to the effects of hormones involved in lactation, and it has been reported that it is a physiological symptom different from postpartum depression, but the actual situation is unknown in Japan.

Methods

This study was conducted using a self-administered, anonymous survey of mothers of children who had undergone health checkups at three years of age at five health centers in Kagoshima city and aimed to clarify the reality and perceptions of mothers regarding D-MER. The survey period was from May to September, 2022. The questionnaires were distributed to 389 mothers, and 216 (55.5% recovery rate) responses were received, of which 202 (valid response rate 93.5%) were included in the analysis.

Results

Regarding the experience of D-MER, 202 mothers in the study population had given birth to a total of 403 children and experienced D-MER when breastfeeding 62 children (15.4%). Of the 202 mothers included in the analysis, 47 (23.3%) answered that they had experienced D-MER with at least one child while breastfeeding. Sixty-six mothers (32.7%) knew about D-MER. Compared to those who had not experienced D-MER, those who had experienced D-MER had significantly higher scores on the items related to having had trouble breastfeeding (odds ratio (OR]: 3.78; 95% confidence interval (CI]: 1.57, 9.09) and knowing about D-MER (OR 2.41; 95% CI 1.20, 4.84). Regarding symptoms, irritability (n = 24, 51.1%), anxiety (n = 22, 46.8%), and sadness (n = 18, 38.3%) ranked high. Coping strategies included distraction, focusing on the child, and, in some cases, cessation of breastfeeding. Thirty mothers (63.8%) answered that they did not consult anyone, citing reasons such as a belief that no one would be likely to understand their symptoms, and that they could not sufficiently explain their symptoms.

Conclusion

The low level of awareness of D-MER suggests that it is necessary to inform and educate mothers and the public about the physiological symptoms of D-MER. Moreover, it is necessary to listen to the feelings of mothers with D-MER and support them in coping with their symptoms.
Multiparametric MRI-based intratumoral and peritumoral radiomics for predicting the pathological differentiation of hepatocellular carcinoma
Authors: Liu Hai-Feng , Wang Min , Wang Qing , Lu Yang , Lu Yu-Jie , Sheng Ye , Xing Fei , Zhang Ji-Lei , Yu Sheng-Nan , Xing Wei
Published: March 2024

Purpose

To explore the predictive potential of intratumoral and multiregion peritumoral radiomics features extracted from multiparametric MRI for predicting pathological differentiation in hepatocellular carcinoma (HCC) patients.

Methods

A total of 265 patients with 277 HCCs (training cohort n = 193, validation cohort n = 84) who underwent preoperative MRI were retrospectively analyzed. The risk factors identified through stepwise regression analysis were utilized to construct a clinical model. Radiomics models based on MRI (arterial phase, portal venous phase, delayed phase) across various regions (entire tumor, Peri_5mm, Peri_10mm, Peri_20mm) were developed using the LASSO approach. The features obtained from the intratumoral region and the optimal peritumoral region were combined to design the IntraPeri fusion model. Model performance was assessed using the area under the curve (AUC).

Results

Larger size, non-smooth margins, and mosaic architecture were risk factors for poorly differentiated HCC (pHCC). The clinical model achieved AUCs of 0.77 and 0.73 in the training and validation cohorts, respectively, while the intratumoral model achieved corresponding AUC values of 0.92 and 0.82. The Peri_10mm model demonstrated superior performance to the Peri_5mm and Peri_20mm models, with AUC values of 0.87 vs. 0.84 vs. 0.73 in the training cohort and 0.80 vs. 0.77 vs. 0.68 in the validation cohort, respectively. The IntraPeri model exhibited remarkable AUC values of 0.95 and 0.86 in predicting pHCC in the training and validation cohorts, respectively.

Conclusions

Our study highlights the potential of a multiparametric MRI-based radiomic model that integrates intratumoral and peritumoral features as a tool for predicting HCC differentiation.

Critical relevance statement

Both clinical and multiparametric MRI-based radiomic models, particularly the intratumoral radiomic model, are non-invasive tools for predicting HCC differentiation. Importantly, the IntraPeri fusion model exhibited remarkable predictiveness for individualized HCC differentiation.

Key points

• Both the intratumoral radiomics model and clinical features were useful for predicting HCC differentiation.

• The Peri_10mm radiomics model demonstrated better diagnostic ability than other peritumoral region-based models.

• The IntraPeri radiomics fusion model outperformed the other models for predicting HCC differentiation.

Graphical Abstract
Diagnostic performance of ultrasound in the assessment of gastric contents: a meta-analysis and systematic review
Authors: Pan Xuanyuan , Chai Jun , Gao Xin , Li Si , Liu Jie , Li Linxing , Li Yanjing , Li Zhichao
Published: March 2024

Objective

To systematically analyze the accuracy of ultrasonic techniques in assessing the nature of gastric contents and their volume.

Methods

English-language articles that used ultrasonic techniques to assess the nature of gastric contents and their volume in patients were selected. In eligible studies, data were recalculated and analyzed for forest plots and subject summary curves of operating characteristics (SROC). Study quality was assessed using the diagnostic accuracy study quality assessment tool QUADAS-2. Publication bias was tested using funnel plots.

Results

Nine articles with a total of 523 study subjects were identified for this review. All studies were feasibility studies. The sensitivity of ultrasound assessment of gastric contents ranged from 53 to 100% and the specificity from 48 to 99%. The combined analysis yielded an area under the working characteristic curve for subjects of 97% (95% confidence interval (CI), 95–98%), a sensitivity of 95% (95% CI, 84–99%), and a specificity of 88% (95% CI, 72–95%). There was a high degree of heterogeneity among the studies due to inter-operator differences and small sample sizes.

Conclusion

Ultrasound techniques have high diagnostic accuracy in assessing the nature of gastric contents and their volume in patients. However, most of the studies were feasibility studies with small sample sizes, lacked standardization, and had high risk of bias. More studies are needed in the future to investigate the diagnostic performance of gastric ultrasound assessment techniques.

Critical relevance statement

Ultrasonography can be used to assess gastric contents, but standardized data integration and reporting are needed to account for the diagnostic capabilities of this technology.

Key points

• Ultrasound is a safe and feasible tool for assessing gastric contents.

• Ultrasound has good diagnostic performance for gastric contents.

• There is still a certain heterogeneity within our analysis process; more research is needed in the future to improve our results.

Graphical Abstract
Serial daily lactate levels association with 30-day outcome in cardiogenic shock patients treated with VA-ECMO: a post-hoc analysis of the HYPO-ECMO study
Authors: Levy Bruno , Girerd Nicolas , Baudry Guillaume , Duarte Kevin , Cuau Samuel , Bakker Jan , Kimmoun Antoine ,   for the HYPO-ECMO trial group and the International ECMO Network (ECMONet)
Published: March 2024

Background

Reliable predictors of outcomes in venoarterial extracorporeal membrane oxygenation (VA-ECMO) therapy are limited. While elevated lactate levels over time have been linked to outcomes in cardiogenic shock (CS), their significance in VA-ECMO-treated patients remains inconclusive.

Methods

We conducted a post hoc analysis of data from the HYPO-ECMO trial, which compared normothermia to moderate hypothermia in CS patients supported by VA-ECMO. We examined daily lactate levels collected over a week to assess their correlation with 30-day mortality.

Results

Among the 318 out of 334 patients (95%) with baseline lactate measurements, 66 had normal levels (< 2.2 mmol/l, 21%). No difference was found in lactate course between moderate hypothermia and normothermia groups. Lactate levels were consistently higher in non-survivors at each time point (p = 0.0002). Baseline hyperlactatemia was associated with an increased risk of death (Hazard Ratio [HR]: 1.85 (1.12–3.05), p = 0.016). When considering all time points, lactate levels during the ICU stay were significantly and gradually associated with a higher risk of death (p < 0.0001). In the overall population, a decrease in lactate levels was not linked to 30-day mortality. However, patients with baseline hyperlactatemia exhibited a more significant decrease in lactate levels from day one to seven (p < 0.0001). In this group, survivors had a significantly greater decrease in lactate levels at day 1 compared to non-survivors (63% (48–77) versus 57% (21–75), p = 0.026). Patients experiencing a secondary increase in lactate (24%) had a worse prognosis (Hazard Ratio: 1.78 (1.21–2.61), p = 0.004), regardless of both baseline lactate levels and the occurrence of severe ischemic adverse events (intestinal and/or limb ischemia).

Conclusions

The consistent and significant association between lactate levels, whether assessed at baseline or during ICU treatment, and the risk of mortality underscores the pivotal prognostic relevance of lactate levels in patients with CS undergoing VA-ECMO therapy. The study findings provide some novel insights, regarding the trend profile and the relevance of a second peak during the 7 day period after ECMO start.

Trial Registration identifier NCT02754193 registered on 2016–04–12.
Co-design workshops to develop evidence synthesis summary formats for use by clinical guideline development groups
Authors: Murray Ruairi , Magendran Erindaa , Chander Neya , Lynch Rosarie , O’Neill Michelle , Devane Declan , Smith Susan M. , Mahtani Kamal , Ryan Máirín , Clyne Barbara , Sharp Melissa K.
Published: March 2024

Background

Evidence synthesis is used by decision-makers in various ways, such as developing evidence-based recommendations for clinical guidelines. Clinical guideline development groups (GDGs) typically discuss evidence synthesis findings in a multidisciplinary group, including patients, healthcare providers, policymakers, etc. A recent mixed methods systematic review (MMSR) identified no gold standard format for optimally presenting evidence synthesis findings to these groups. However, it provided 94 recommendations to help produce more effective summary formats for general evidence syntheses (e.g., systematic reviews). To refine the MMSR recommendations to create more actionable guidance for summary producers, we aimed to explore these 94 recommendations with participants involved in evidence synthesis and guideline development.

Methods

We conducted a descriptive qualitative study using online focus group workshops in February and March 2023. These groups used a participatory co-design approach with interactive voting activities to identify preferences for a summary format's essential content and style. We created a topic guide focused on recommendations from the MMSR with mixed methods support, ≥ 3 supporting studies, and those prioritized by an expert advisory group via a pragmatic prioritization exercise using the MoSCoW method (Must, Should, Could, and Will not haves). Eligible participants must be/have been involved in GDGs and/or evidence synthesis. Groups were recorded and transcribed. Two independent researchers analyzed transcripts using directed content analysis with 94 pre-defined codes from the MMSR.

Results

Thirty individuals participated in six focus groups. We coded 79 of the 94 pre-defined codes. Participants suggested a “less is more” structured approach that minimizes methodological steps and statistical data, promoting accessibility to all audiences by judicious use of links to further information in the full report. They emphasized concise, consistently presented formats that highlight key messages, flag readers to indicators of trust in the producers (i.e., logos, websites, and conflict of interest statements), and highlight the certainty of evidence (without extenuating details).

Conclusions

This study identified guidance based on the preferences of guideline developers and evidence synthesis producers about the format of evidence synthesis summaries to support decision-making. The next steps involve developing and user-testing prototype formats through one-on-one semi-structured interviews to optimize evidence synthesis summaries and support decision-making.