bluuebunny/crossref_metadata_2025 huggingface dataset:
Empowering patients in primary care: a qualitative exploration of the usability and utility of an online diabetes self-management tool
Authors: Choo Jeremy Wei Song , Moosa Aminath Shiwaza , Koh Jeremy Wei Mei , Ng Chirk Jenn , Tan Ngiap Chuan
Published: April 2024

Background

Despite the potential advantages of Internet-based diabetes self-management education, its adoption was not widespread among Singapore’s public primary care clinics (polyclinics). An interactive online tool was thus developed to help educate patients with Type 2 diabetes mellitus (T2DM), and was now ready for user testing before implementation.

Aim

To explore the perceived utility and usability of the educational tool in patients with suboptimally-controlled T2DM in a Singapore primary care setting.

Methods

In-depth interviews were used to gather qualitative data from multi-ethnic Asian adults who had suboptimally-controlled T2DM. A total of 17 IDIs were conducted between April 2022 to March 2023, audio-recorded, transcribed, and analyzed to identify emergent themes via thematic analysis.

Results

Regarding utility, users found the educational tool useful because it provided them with information that was comprehensive, accessible, reliable, and manageable. Regarding usability, the majority of users reported that the educational tool was easy to use, and suggested ways to improve navigational cues, visual clarity, readability and user engagement.

Conclusion

Participants generally found the educational tool useful and easy to use. A revised educational tool will be developed based on their feedback and implemented in clinical practice.
Association of 8-hydroxy-2’-deoxyguanosine with motoric cognitive risk in elderly Chinese people: RUGAO longevity and aging cross-sectional study
Authors: Dai Qingqing , Ma Yajun , Liu Chang , Zhao Ruixue , Chen Qi , Chen Weijia , Wang Xiaofeng , Jiang Xiaoyan , Li Shujuan
Published: April 2024

Background

Motor cognitive risk syndrome (MCR) represents a critical pre-dementia and disability state characterized by a combination of objectively measured slow walking speed and subjective memory complaints (SMCs). This study aims to identify risk factors for MCR and investigate the relationship between plasma levels of 8-hydroxy-2’-deoxyguanosine (8-OHdG) and MCR among Chinese community-dwelling elderly populations.

Methods

A total of 1312 participants were involved in this study based on the data of the Rugao Longevity and Aging Study (RuLAS). The MCR was characterized by SMCs and slow walking speed. The SCCs were defined as a positive answer to the question ‘Do you feel you have more problems with memory than most?’ in a 15-item Geriatric Depression Scale. Slow walking speed was determined by one standard deviation or more below the mean value of the patient’s age and gender group. The plasma of 8-OHdG were measured by a technician in the biochemistry laboratory of the Rugao People’s Hospital during the morning of the survey.

Results

The prevalence of MCR was found to be 7.9%. After adjusting for covariates, significant associations with MCR were observed in older age (OR 1.057; p = 0.018), history of cerebrovascular disease (OR 2.155; p = 0.010), and elevated 8-OHdG levels (OR 1.007; p = 0.003).

Conclusions

This study indicated the elevated plasma 8-OHdG is significantly associated with increased MCR risk in the elderly, suggesting its potential as a biomarker for early detection and intervention in MCR. This finding underscores the importance of monitoring oxidative DNA damage markers in predicting cognitive and motor function declines, offering new avenues for research and preventive strategies in aging populations.
Willingness to receive COVID-19 vaccines, associated factors and reasons for not taking a vaccine: a cross sectional study among persons aged 13–80 years in Wakiso, Central Uganda
Authors: Daama Alex , Rashid Naziru , Asani Kasango , Nalwoga Grace Kigozi , Nalugoda Fred , Bulamba Robert , Kyasanku Emmanuel , Nakigozi Gertrude , Kigozi Godfrey , Kagaayi Joseph , Mugamba Stephen
Published: April 2024

Background

Vaccination has been recommended as one of the approaches for the control of COVID-19 pandemic. However, adequate vaccine coverage is critical to the effectiveness of the vaccine at population level. Data on acceptability of the vaccine in Ugandan urban areas are limited. This study examined the prevalence, factors associated with willingness to accept COVID-19 vaccine including reasons for not taking COVID-19 vaccine in a predominantly urban population of Wakiso, central Uganda.

Methods

Data were obtained from a cross-sectional study conducted between March 1st, 2021 and September 30th, 2021 in the urban population-based cohort of the Africa Medical and behavioral Sciences Organization (AMBSO). A Multivariable modified Poisson regression analysis was used to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals of willingness to accept the COVID-19 vaccine.

Results

A total of 1,903 participants were enrolled in this study; 61% of whom were females. About 63% of participants indicated their willingness to accept the COVID-19 vaccine. Persons aged 13–19 years (aPR = 0.79; [95% CI: 0.74, 0.84]) or 20-29years (aPR = 0.93; [95% CI: 0.88, 0.98]) were less likely to accept the vaccine compared to persons aged 40–49 years. Persons with post-primary level of education (aPR = 1.05; [95% CI: 1.02, 1.09]) were more likely to accept the vaccine compared to persons with primary level of education. Additionally, students or individuals working in government (aPR = 1.13; [95% CI: 1.04, 1.23]) were more likely to accept the vaccine compared to individuals doing construction and Mechanic work as their main occupation. Reported reasons for not taking a COVID-19 vaccine included; concerns about side effects of the vaccine 154(57.0%), 64(23.7%) did not think the vaccines were effective, while 32(11.9%) did not like the vaccines.

Conclusion

A substantial proportion of individuals were not willing to accept the COVID-19 vaccine. Health education campaigns on vaccination within urban communities could help reduce COVID-19 vaccine misconceptions in the urban populations more especially the young and persons with low levels of formal education.
The effect of ascending- descending ultrafiltration and sodium profiles on blood pressure in hemodialysis patients: a randomized cross-over study
Authors: Arasnezhad Morteza , Namazinia Mohammad , Mazlum Seyyed Reza , Miri Kheizaran
Published: April 2024

Background

Considering no previous research into the utilization of ascending/descending ultrafiltration and linear sodium profiles in improving blood pressure among hemodialysis patients, the present study aimed to explore the effect of the A/D-UF along with linear sodium profiles on HD patients with hypotension.

Methods

Applying a crossover design, this clinical trial was fulfilled between December 2022 and June 2023 on 20 patients undergoing HD, randomized into two groups, each one receiving two intervention protocols, viz., (a) an intervention protocol in which the liquid sodium in the dialysis solution was linear and the UF profiling was A/D, and (b) a routine protocol or HD, wherein both liquid sodium and UF in the dialysis solution remained constant. The HD patients’ BP was then checked and recorded at six intervals, namely, before HD, one, two, three, and four hours after it, and following its completion, within each session. The data were further statistically analyzed using the IBM SPSS Statistics 20 and the related tests.

Results

In total, 20 patients, including 12 men (60%) and 8 women (40%), with the mean age of 58.00 ± 14.54 on HD for an average of 54 months, were recruited in this study. No statistically significant difference was observed in the mean systolic and diastolic BP levels in the group receiving the A/D-UF profile all through the desired hours (p > 0.05), indicating that the patients did not face many changes in these two numbers during HD. Our cross-over clinical trial demonstrated a statistically significant reduction in symptomatic IDH episodes from 55 to 15% with the application of the A/D-UF profile (p < 0.05).

Conclusion

The study demonstrated that the A/D-UF profile could contribute to the stability of blood pressure levels among HD patients, with no significant fluctuations observed during treatment sessions.

Trial Registration

This study was registered in the Iranian Registry of Clinical Trials (no. IRCT20180429039463N5) on 07/01/2023.
Binimetinib in combination with nivolumab or nivolumab and ipilimumab in patients with previously treated microsatellite-stable metastatic colorectal cancer with RAS mutations in an open-label phase 1b/2 study
Authors: Elez Elena , Cubillo Antonio , Alfonso Pilar Garcia , Middleton Mark R. , Chau Ian , Alkuzweny Baha , Alcasid Ann , Zhang Xiaosong , Van Cutsem Eric
Published: April 2024

Background

In patients with previously treated RAS-mutated microsatellite-stable (MSS) metastatic colorectal cancer (mCRC), a multicenter open-label phase 1b/2 trial was conducted to define the safety and efficacy of the MEK1/MEK2 inhibitor binimetinib in combination with the immune checkpoint inhibitor (ICI) nivolumab (anti–PD-1) or nivolumab and another ICI, ipilimumab (anti-CTLA4).

Methods

In phase 1b, participants were randomly assigned to Arm 1A (binimetinib 45 mg twice daily [BID] plus nivolumab 480 mg once every 4 weeks [Q4W]) or Arm 1B (binimetinib 45 mg BID plus nivolumab 480 mg Q4W and ipilimumab 1 mg/kg once every 8 weeks [Q8W]) to determine the maximum tolerable dose (MTD) and recommended phase 2 dose (RP2D) of binimetinib. The MTD/RP2D was defined as the highest dosage combination that did not cause medically unacceptable dose-limiting toxicities in more than 35% of treated participants in Cycle 1. During phase 2, participants were randomly assigned to Arm 2A (binimetinib MTD/RP2D plus nivolumab) or Arm 2B (binimetinib MTD/RP2D plus nivolumab and ipilimumab) to assess the safety and clinical activity of these combinations.

Results

In phase 1b, 21 participants were randomized to Arm 1A or Arm 1B; during phase 2, 54 participants were randomized to Arm 2A or Arm 2B. The binimetinib MTD/RP2D was determined to be 45 mg BID. In phase 2, no participants receiving binimetinib plus nivolumab achieved a response. Of the 27 participants receiving binimetinib, nivolumab, and ipilimumab, the overall response rate was 7.4% (90% CI: 1.3, 21.5). Out of 75 participants overall, 74 (98.7%) reported treatment-related adverse events (AEs), of whom 17 (22.7%) reported treatment-related serious AEs.

Conclusions

The RP2D binimetinib regimen had a safety profile similar to previous binimetinib studies or nivolumab and ipilimumab combination studies. There was a lack of clinical benefit with either drug combination. Therefore, these data do not support further development of binimetinib in combination with nivolumab or nivolumab and ipilimumab in RAS-mutated MSS mCRC.

Trial registration

NCT03271047 (09/01/2017).
The effect of individuals' oral hygiene habits and knowledge levels on peri-implant health and disease: a questionnaire-based observational study
Authors: Şahin Tuğba
Published: April 2024

Background

Peri-implant disease and health are associated with microbial dental plaque. Therefore, oral hygiene plays a role in preventing and treating these diseases. This study aimed to determine the relationships among knowledge of peri-implant status, oral hygiene habits, and peri-implant disease and health.

Methods

A total of 144 implants in nonsmokers with controlled systemic disease were included in the study. Peri-implant disease and the conditions of the implants were determined with periodontal indices and radiographs based on the 2017 World Workshop on the Classification of Periodontal and Peri-implant Diseases and Conditions and The EFP S3 level clinical practice guideline. Individuals were asked 66 questions regarding demographic information, oral hygiene habits and history, and knowledge of peri-implant diseases. One-way ANOVA was used to compare the three peri-implant disease and condition categories.

Results

There was a significant difference between groups regarding toothpaste type (p < 0.05). Gum protection toothpaste was greater in the peri-implant health group. Patients' use of interdental products was very low; often, no products were used for implant prosthesis. There was no significant difference among the groups regarding oral hygiene product use or oral hygiene habits (p > 0.05). There was a significant difference between groups regarding frequency of visit (p < 0.05). The frequency of visits to the dentist for pain was greater for individuals with peri-implantitis. There is a significant difference between the groups' answers for the causative and initiating factors of peri-implant disease (p < 0.05). The peri-implant health group answered that microbial dental plaque is the most crucial initiating factor of peri-implant diseases, and bleeding on probing is the most critical determinant of peri-implant diseases at a higher rate than the other groups.

Conclusions

Patients' oral hygiene habits and knowledge levels are almost similar according to peri-implant status. Knowledge does not reflect a patient's oral hygiene behavior. Clinicians should ensure that individuals' oral hygiene practices align with their increased awareness regarding peri-implant illnesses.
The cost-effectiveness of school-based interventions for chronic diseases: a systematic review
Authors: Lin George , Werner Kalin , Alqunaiebet Ada , Hamza Mariam M. , Alkanhal Norah , Alsukait Reem F. , Alruwaily Amaal , Rakic Severin , Cetinkaya Volkan , Herbst Christopher H. , Lin Tracy Kuo
Published: April 2024

Background

Chronic diseases, or non-communicable diseases (NCD), are conditions of long duration and often influenced and contributed by complex interactions of several variables, including genetic, physiological, environmental, and behavioral factors. These conditions contribute to death, disability, and subsequent health care costs. Primary and secondary school settings provide an opportunity to deliver relatively low cost and effective interventions to improve public health outcomes. However, there lacks systematic evidence on the cost-effectiveness of these interventions.

Methods

We systematically searched four databases (PubMed/Medline, Cochrane, Embase, and Web of Science) for published studies on the cost-effectiveness of chronic-disease interventions in school settings. Studies were eligible for inclusion if they assessed interventions of any chronic or non-communicable disease, were conducted in a school setting, undertook a full cost-effectiveness analysis and were available in English, Spanish, or French.

Results

Our review identified 1029 articles during our initial search of the databases, and after screening, 33 studies were included in our final analysis. The most used effectiveness outcome measures were summary effectiveness units such as quality-adjusted life years (QALYs) (22 articles; 67%) or disability-adjusted life years (DALYs) (4 articles; 12%). The most common health condition for which an intervention targets is overweight and obesity. Almost all school-based interventions were found to be cost-effective (30 articles; 81%).

Conclusion

Our review found evidence to support a number of cost-effective school-based interventions targeting NCDs focused on vaccination, routine physical activity, and supplement delivery interventions. Conversely, many classroom-based cognitive behavioral therapy for mental health and certain multi-component interventions for obesity were not found to be cost-effective.
THOC7-AS1/OCT1/FSTL1 axis promotes EMT and serves as a therapeutic target in cutaneous squamous cell carcinoma
Authors: Yu Site , Cui Xu , Zhou Situo , Li Yun , Feng Wenjie , Zhang Xiangjun , Zhong Yuhui , Zhang Pihong
Published: April 2024

Background

THOC7-AS1 and FSTL1 expression are frequently upregulated in cutaneous squamous cell carcinoma (cSCC). However, their molecular biological mechanisms remain elusive and their potential as therapeutic targets needs urgent exploration.

Methods

Human tissue samples were used to evaluate clinical parameters. In vitro and in vivo experiments assessed biological functions. Quantitative PCR, western blot, immunohistochemistry, immunocytochemistry, immunoprecipitation, RNA fluorescence in situ hybridization, RNA pull-down, RNA immunoprecipitation, silver staining, chromatin immunoprecipitation, dual luciferase reporter assays etc. were utilized to explore the molecular biological mechanisms.

Results

We found FSTL1 is an oncogene in cSCC, with high expression in tumor tissues and cells. Its elevated expression closely associates with tumor size and local tissue infiltration. In vitro and in vivo, high FSTL1 expression promotes cSCC proliferation, migration and invasion, facilitating malignant behaviors. Mechanistically, FSTL1 interacts with ZEB1 to promote epithelial-to-mesenchymal transition (EMT) in cSCC cells. Exploring upstream regulation, we found THOC7-AS1 can interact with OCT1, which binds the FSTL1 promoter region and promotes FSTL1 expression, facilitating cSCC progression. Finally, treating tumors with THOC7-AS1 antisense oligonucleotides inhibited cSCC proliferative and migratory abilities, delaying tumor progression.

Conclusions

The THOC7-AS1/OCT1/FSTL1 axis regulates EMT and promotes tumor progression in cSCC. This study provides clues and ideas for cSCC targeted therapy.
The integration of single-cell and bulk RNA-seq atlas reveals ERS-mediated acinar cell damage in acute pancreatitis
Authors: Yang Kaige , Xie Rongli , Xiao Guohui , Zhao Zhifeng , Ding Min , Lin Tingyu , Tsang Yiu Sing , Chen Ying , Xu Dan , Fei Jian
Published: April 2024

Background

Acute pancreatitis (AP) is a clinically common acute abdominal disease, whose pathogenesis remains unclear. The severe patients usually have multiple complications and lack specific drugs, leading to a high mortality and poor outcome. Acinar cells are recognized as the initial site of AP. However, there are no precise single-cell transcriptomic profiles to decipher the landscape of acinar cells during AP, which are the missing pieces of jigsaw we aimed to complete in this study.

Methods

A single-cell sequencing dataset was used to identify the cell types in pancreas of AP mice and to depict the transcriptomic maps in acinar cells. The pathways’ activities were evaluated by gene sets enrichment analysis (GSEA) and single-cell gene sets variation analysis (GSVA). Pseudotime analysis was performed to describe the development trajectories of acinar cells. We also constructed the protein–protein interaction (PPI) network and identified the hub genes. Another independent single-cell sequencing dataset of pancreas samples from AP mice and a bulk RNA sequencing dataset of peripheral blood samples from AP patients were also analyzed.

Results

In this study, we identified genetic markers of each cell type in the pancreas of AP mice based on single-cell sequencing datasets and analyzed the transcription changes in acinar cells. We found that acinar cells featured acinar-ductal metaplasia (ADM), as well as increased endocytosis and vesicle transport activity during AP. Notably, the endoplasmic reticulum stress (ERS) and ER-associated degradation (ERAD) pathways activated by accumulation of unfolded/misfolded proteins in acinar cells could be pivotal for the development of AP.

Conclusion

We deciphered the distinct roadmap of acinar cells in the early stage of AP at single-cell level. ERS and ERAD pathways are crucially important for acinar homeostasis and the pathogenesis of AP.
C9ORF72 patient-derived endothelial cells drive blood-brain barrier disruption and contribute to neurotoxicity
Authors: Aragón-González Ana , Shaw Allan C , Kok Jannigje R , Roussel Florence S , Santos Souza Cleide dos , Granger Sarah M , Vetter Tatyana , de Diego Yolanda , Meyer Kathrin C , Beal Selina N , Shaw Pamela J , Ferraiuolo Laura
Published: April 2024

The blood-brain barrier (BBB) serves as a highly intricate and dynamic interface connecting the brain and the bloodstream, playing a vital role in maintaining brain homeostasis. BBB dysfunction has been associated with multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS); however, the role of the BBB in neurodegeneration is understudied. We developed an ALS patient-derived model of the BBB by using cells derived from 5 patient donors carrying C9ORF72 mutations. Brain microvascular endothelial-like cells (BMEC-like cells) derived from C9ORF72-ALS patients showed altered gene expression, compromised barrier integrity, and increased P-glycoprotein transporter activity. In addition, mitochondrial metabolic tests demonstrated that C9ORF72-ALS BMECs display a significant decrease in basal glycolysis accompanied by increased basal and ATP-linked respiration. Moreover, our study reveals that C9-ALS derived astrocytes can further affect BMECs function and affect the expression of the glucose transporter Glut-1. Finally, C9ORF72 patient-derived BMECs form leaky barriers through a cell-autonomous mechanism and have neurotoxic properties towards motor neurons.

Graphical Abstract
Patient-reported experience with Fabry disease and its management in the real-world setting: results from a double-blind, cross-sectional survey of 280 respondents
Authors: Berry Lisa , Walter Jerry , Johnson Jack , Alton Julia , Powers Janet , Llòria Xavier , Koulinska Irene , McGee Meghan , Laney Dawn
Published: April 2024

Background

Fabry disease (FD) is a rare X-linked lysosomal storage disorder with a heterogeneous clinical presentation. Patients with FD may exhibit early signs/symptoms including neuropathic pain, gastrointestinal complaints, and dermatologic manifestations. FD may ultimately progress to renal, neurologic, and cardiac dysfunction. Current treatments for FD have significantly improved the management and outcomes for patients with FD, but important clinical and convenience limitations still exist.

Methods

To illuminate the impact of FD on daily life from the patient’s perspective, we asked adult patients (≥ 18 years old) with FD in the United States and Canada to complete a 33-question online survey to assess patient-reported disease severity, management, and treatment outcomes.

Results

A total of 280 respondents with FD completed the survey; they had a mean age of 47 years, and 68% (191/280) were women. Most were currently receiving FD treatment (84%, 234/280) with enzyme replacement therapy (ERT) (89%, 208/234) or chaperone therapy (11%, 26/234). Common symptoms included low energy/fatigue (72%, 201/280), tingling (62%, 174/280) or pain in the hands/feet (60%, 168/280), ringing in ears/hearing loss (54%, 151/280), general body pains/pain crises (51%, 143/280), and abdominal/stomach pain (50%, 140/280). More than half (51%, 144/280) of respondents reported their symptoms as bothersome (38%, 106/280) or difficult to control (14%, 38/280). Temporary symptom worsening between infusions was reported by about half of respondents: 51% (108/211) currently receiving ERT and 48% (14/29) previously receiving ERT. Only 48% (59/122) of respondents reported their symptom worsening to their physician. Of those who reported it, 41% (24/59) said that their physician prescribed medication to manage their symptoms or changed their treatment regimen.

Conclusions

Our analysis highlights the gap between current standard-of-care in disease monitoring and patient perception of disease progression among patients with FD. This information may be helpful for healthcare providers and drug developers seeking to improve the care of patients with FD by addressing unmet needs of high relevance.
Clinical spectrum, over 12-year follow-up and experience of SGLT2 inhibitors treatment on patients with glycogen storage disease type Ib: a single-center retrospective study
Authors: Shao Yong-Xian , Liang Cui-Li , Su Ya-Ying , Lin Yun-Ting , Lu Zhi-Kun , Lin Rui-Zhu , Zhou Zhi-Zi , Zeng Chun-Hua , Tao Chun-Yan , Liu Zong-Cai , Zhang Wen , Liu Li
Published: April 2024

Background

Glycogen storage disease type Ib (GSD Ib) is a rare disorder characterized by impaired glucose homeostasis caused by mutations in the SLC37A4 gene. It is a severe inherited metabolic disease associated with hypoglycemia, hyperlipidemia, lactic acidosis, hepatomegaly, and neutropenia. Traditional treatment consists of feeding raw cornstarch which can help to adjust energy metabolism but has no positive effect on neutropenia, which is fatal for these patients. Recently, the pathophysiologic mechanism of the neutrophil dysfunction and neutropenia in GSD Ib has been found, and the treatment with the SGLT2 inhibitor empaglifozin is now well established. In 2020, SGLT2 inhibitor empagliflozin started to be used as a promising efficient remover of 1,5AG6P in neutrophil of GSD Ib patients worldwide. However, it is necessary to consider long-term utility and safety of a novel treatment.

Results

In this study, we retrospectively examined the clinical manifestations, biochemical examination results, genotypes, long-term outcomes and follow-up of thirty-five GSD Ib children who visited our department since 2009. Fourteen patients among them underwent empagliflozin treatment since 2020. This study is the largest cohort of pediatric GSD Ib patients in China as well as the largest cohort of pediatric GSD Ib patients treated with empagliflozin in a single center to date. The study also discussed the experience of long-term management on pediatric GSD Ib patients.

Conclusion

Empagliflozin treatment for pediatric GSD Ib patients is efficient and safe. Increase of urine glucose is a signal for pharmaceutical effect, however attention to urinary infection and hypoglycemia is suggested.
METTL3 recruiting M2-type immunosuppressed macrophages by targeting m6A-SNAIL-CXCL2 axis to promote colorectal cancer pulmonary metastasis
Authors: Ouyang Peng , Li Kang , Xu Wei , Chen Caiyun , Shi Yangdong , Tian Yao , Gong Jin , Bao Zhen
Published: April 2024

Background

The regulatory role of N6-methyladenosine (m6A) modification in the onset and progression of cancer has garnered increasing attention in recent years. However, the specific role of m6A modification in pulmonary metastasis of colorectal cancer remains unclear.

Methods

This study identified differential m6A gene expression between  primary colorectal cancer and its pulmonary metastases using transcriptome sequencing and immunohistochemistry. We investigated the biological function of METTL3 gene both in vitro and in vivo using assays such as CCK-8, colony formation, wound healing, EDU, transwell, and apoptosis, along with a BALB/c nude mouse model. The regulatory mechanisms of METTL3 in colorectal cancer pulmonary metastasis were studied using methods like methylated RNA immunoprecipitation quantitative reverse transcription PCR, RNA stability analysis, luciferase reporter gene assay, Enzyme-Linked Immunosorbent Assay, and quantitative reverse transcription PCR.

Results

The study revealed high expression of METTL3 and YTHDF1 in the tumors of patients with pulmonary metastasis of colorectal cancer. METTL3 promotes epithelial-mesenchymal transition in colorectal cancer by m6A modification of SNAIL mRNA, where SNAIL enhances the secretion of CXCL2 through the NF-κB pathway. Additionally, colorectal cancer cells expressing METTL3 recruit M2-type macrophages by secreting CXCL2.

Conclusion

METTL3 facilitates pulmonary metastasis of colorectal cancer by targeting the m6A-Snail-CXCL2 axis to recruit M2-type immunosuppressive macrophages. This finding offers new research directions and potential therapeutic targets for colorectal cancer treatment.
Effects of task-based mirror therapy on upper limb motor function in hemiplegia: study protocol for a randomized controlled clinical trial
Authors: Liu Hongzhen , Xu Yangjie , Jiang Wei , Hu Fangchao , Zhou Yi , Pan Lu , Zhou Feng , Yin Ying , Tan Botao
Published: April 2024

Background and purpose

Research to date has lacked definitive evidence to determine whether mirror therapy promotes the recovery of upper extremity function after stroke. Considering that previous studies did not stratify patients based on structural retention, this may be one of the reasons for the negative results obtained in many trials. The goal evaluates the efficacy of TBMT (utilizing an innovatively designed mirror) versus standard occupational therapy for stroke patient’s upper limb functionality.

Methods and analysis

This single-center randomized controlled trial will involve 50 patients with stroke. All patients will be randomly assigned to either the task-based mirror therapy or the control group. The interventions will be performed 5 days per week for 4 weeks. The primary outcomes will be the mean change in scores on both the FMA-UE and modified Barthel Index (MBI) from baseline to 4 weeks intervention and at 12 weeks follow-up between the two groups and within groups. The other outcomes will include the Action Research Arm Test (ARAT), the Nine Hole Peg Test (9HPT), the Functional Independence Measure, and MRI.

Discussion

This trial will not only to establish that task-based mirror therapy (TBMT) could improve the recovery of hand function after stroke but also to explore the underlying mechanisms. We expect that this finding will clarify the brain activation and brain network mechanisms underlying the improvement of hand function with task-oriented mirror therapy and lead to new ideas for stroke hand function rehabilitation.

Trial registration

URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2300068855. Registered on March 1, 2023
A first report of Pseudosuccinea columella (Say, 1817), an alien intermediate host for liver fluke, in Malawi
Authors: Jones S. , Juhász A. , Makaula P. , Cunningham L. J. , Archer J. , Nkolokosa C. , Namacha G. , Kambewa E. , Lally D. , Kapira D. R. , Chammudzi P. , Kayuni S. A. , Musaya J. , Stothard J. Russell
Published: April 2024

Starting in October 2021, quarterly malacological surveys have been undertaken in Malawi, with the sampling of 12 specified freshwater habitats throughout a calendar year. Each survey monitors the presence of aquatic intermediate snail hosts of medical and veterinary importance. In March 2023, the alien lymnaeid species Pseudosuccinea columella was encountered for the first time in the surveys, in Nsanje District. This species identity was later confirmed upon DNA analysis of mitochondrial ribosomal 16S sequences. In July 2023, P. columella was also noted at single sites within Mangochi and Chikwawa Districts, and again in Nsanje District, with an additional location observed. Of particular importance, our sampled location in Mangochi District was directly connected to Lake Malawi, which expands the species list of invasive molluscs in this lake. While P. columella is a well-known intermediate snail host for human and animal fascioliasis, screening collected snails for trematode cercariae, alongside molecular xenomonitoring, did not yield equivocal evidence of active fluke infection. However, the newly recognized presence of this alien intermediate snail host within Lake Malawi, and along the Shire River Valley, flags a new concern in altered local transmission potential for human and animal fascioliasis.

Graphical Abstract
Single cell lineage tracing reveals clonal dynamics of anti-EGFR therapy resistance in triple negative breast cancer
Authors: Pellecchia Simona , Franchini Melania , Viscido Gaetano , Arnese Riccardo , Gambardella Gennaro
Published: April 2024

Background

Most primary Triple Negative Breast Cancers (TNBCs) show amplification of the Epidermal Growth Factor Receptor (EGFR) gene, leading to increased protein expression. However, unlike other EGFR-driven cancers, targeting this receptor in TNBC yields inconsistent therapeutic responses.

Methods

To elucidate the underlying mechanisms of this variability, we employ cellular barcoding and single-cell transcriptomics to reconstruct the subclonal dynamics of EGFR-amplified TNBC cells in response to afatinib, a tyrosine kinase inhibitor (TKI) that irreversibly inhibits EGFR.

Results

Integrated lineage tracing analysis revealed a rare pre-existing subpopulation of cells with distinct biological signature, including elevated expression levels of Insulin-Like Growth Factor Binding Protein 2 (IGFBP2). We show that IGFBP2 overexpression is sufficient to render TNBC cells tolerant to afatinib treatment by activating the compensatory insulin-like growth factor I receptor (IGF1-R) signalling pathway. Finally, based on reconstructed mechanisms of resistance, we employ deep learning techniques to predict the afatinib sensitivity of TNBC cells.

Conclusions

Our strategy proved effective in reconstructing the complex signalling network driving EGFR-targeted therapy resistance, offering new insights for the development of individualized treatment strategies in TNBC.
The inhibitory effects of carvacrol, nystatin, and their combination on oral candidiasis isolates
Authors: Balef Seyed Saeed Hosseini , Hosseini Seyed Sedigheh , Asgari Negar , Sohrabi Ahmad , Mortazavi Nazanin
Published: April 2024

Background

Candida, a common oral microbiota, can cause opportunistic fungal infections. With rising Candida infections and limited effective antifungals, new treatments are needed. This study investigates carvacrol essential oil’s effect on oral candidiasis, alone and with nystatin, compared to nystatin alone.

Materials and methods

In this study, oral samples were collected from dental clinic patients, especially denture users. The presence of Candida was confirmed and cultured from these samples. Candidiasis was detected by observing Candida colonies. Drug sensitivity was tested on 100 positive samples. The minimum concentration of inhibition and lethality of each isolate was evaluated using nystatin and carvacrol. The results were compared using two-way analysis of variance. Finally, the minimum inhibitory concentration (MIC) of nystatin and carvacrol was calculated individually and in combination.

Results

The present study found that Candida albicans and non-albicans species were equally prevalent. Carvacrol showed significant biological activity against all Candida species, with an average MTT of 50.01%. The average MIC value of carvacrol was 24.96 µg/ml, indicating its potential to inhibit Candida growth. The mean Minimum Fungicidal Concentration (MFC) value of carvacrol was 23.48 µg/ml, suggesting its effectiveness in killing the fungi.

Conclusion

The study’s findings reveal that the MIC of carvacrol was significantly lower than that of nystatin and the combination of nystatin and carvacrol. This suggests that carvacrol holds potential as an effective herbal remedy for candidiasis.
Finite-time blowup for the 3-D viscous primitive equations of oceanic and atmospheric dynamics
Authors: Zheng Lin
Published: April 2024

In this paper, we prove that for certain class of initial data, the corresponding solutions to the 3-D viscous primitive equations blow up in finite time. Specifically, we find a special solution to simplify the 3-D systems, assuming that the pressure function $p(x,y,t)$
p
(
x
,
y
,
t
)
is a concave function. We also consider the equations on the line $x=0$
x
=
0
, $y=0$
y
=
0
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Level of implementation of multimodal strategies for infection prevention and control interventions and prevalence of healthcare-associated infections in Northern Italy
Authors: Vicentini Costanza , Bussolino Roberta , Gastaldo Claudia , Castagnotto Marta , D’Ancona Fortunato “Paolo” , Zotti Carla Maria ,   on behalf of the Working group “Unità Prevenzione Rischio Infettivo (UPRI), Regione Piemonte”, Bert Fabrizio , Bolla Cesare , Broda Roberta , D’Aloia Francesco , De Gregorio Francesco , Di Nardo Francesco , Fenu Piero , Ferrauto Gerolamo , Franco Mauro , Gatti Scipione , Gremo Franca , Maiello Agostino , Morabito Domenica , Muca Aida , Palladino Roberta , Paudice Alessandro , Pellegrino Paolo , Plazzotta Claudio , Porretto Simone , Ripamonti Giorgio , Salvatico Maurizio , Silvaplana Paola , Silvestre Carlo , Tangolo Domenico , Venturino Valentina , Viroletti Maria Rita
Published: April 2024

Background

In November 2022, Italy participated in the third edition of the European Centre for disease prevention and control (ECDC) point prevalence survey (PPS) of healthcare-associated infections (HAIs) in acute-care hospitals. A questionnaire based on the WHO infection prevention and control assessment framework (IPCAF) was included, which aims to investigate multimodal strategies for the implementation of IPC interventions.

Methods

A PPS was conducted using the ECDC PPS protocol version 6.0. The Regional health authority of the region of Piedmont, in north-western Italy, chose to enlist all public acute-care hospitals. Data were collected within one day per each ward, within 3 weeks in each hospital, at hospital, ward and patient level. A score between 0–1 or 0–2 was assigned to each of the 9 items in the IPCAF questionnaire, with 14 points representing the best possible score. HAI prevalence was calculated at the hospital-level as the percentage of patients with at least one HAI over all included patients. Relations between HAI prevalence, IPCAF score, and other hospital-level variables were assessed using Spearman's Rho coefficient.

Results

In total, 42 acute-care hospitals of the region of Piedmont were involved, with a total of 6865 included patients. All participant hospitals reported they employed multimodal strategies to implement IPC interventions. The median IPCAF overall score was 11/14 (interquartile range, IQR: 9.25–12). The multimodal strategy with the highest level of adherence was education and training, followed by communication and reminders. Strategies with the lowest level of adherence were safety climate and culture of change, and system change. Overall HAI prevalence was 8.06%. A weak to moderate inverse relation was found between IPCAF score and HAI prevalence (Spearman’s Rho -0.340, p 0.034). No other significant correlation was found.

Conclusions

This study found a high self-reported overall level of implementation of multimodal strategies for IPC in the region. Results of this study suggest the relevance of the multimodal approach and the validity of the IPCAF score in measuring IPC programs, in terms of effectiveness of preventing HAI transmission.
Enhancing Structural Resilience: Microbial-Based Self-Healing in High-Strength Concrete
Authors: Mohammed Tesfaye Alemu , Kasie Yonathan Muche , Assefa Eleyas , Getu Yiglet Mebrat , Tufa Dereje Hailu
Published: April 2024

Concrete’s weak tensile strength renders it susceptible to cracking under prolonged loads, leading to reduced load-bearing capacity and reinforcing bar corrosion. This study investigates the effectiveness of microbial-based self-healing in high-strength concrete, focusing on two bacterial strains: Sporosarcina koreensis and Bacillus. Results demonstrate significant enhancements in micro- and macro-physical properties of high-strength bacterial concrete with Bacillus flexus and S. koreensis, surpassing the control. Bacillus flexus-infused concrete exhibits a remarkable 21.8% increase in compressive strength at 7 days and 11.7% at 56 days. Similarly, S. koreensis-treated concrete shows 12.2% and 7.4% increases at 7 and 56 days, respectively. Enhanced crack healing occurs due to calcite precipitation, confirmed by X-ray diffraction and scanning electron microscopy. Both bacterial strains achieve crack closure within 42 days, with widths of 259.7 µm and 288.7 µm, respectively. Moreover, bacterial concrete from these strains excels in durability against water, acid, and salt exposure, surpassing control concrete. These findings emphasize microbial-based self-healing’s potential in high-strength concrete, providing a practical strategy to enhance structural resilience and extend concrete infrastructure lifespan.
Injury and fatality risks for child pedestrians and cyclists on public roads
Authors: Swedler David I. , Ali Bina , Hoffman Rebecca , Leonardo Jennifer , Romano Eduardo , Miller Ted R.
Published: April 2024

Background

Pedestrians and cyclists are often referred to as “vulnerable road users,” yet most research is focused on fatal crashes. We used fatal and nonfatal crash data to examine risk factors (i.e., relationship to an intersection, urbanicity, crash circumstances, and vehicle type) for police-reported pedestrian and cyclist injuries on public roads among children aged 0–9 and aged 10–19. We also compared risk factors among these two age groups with adults aged 20–29 and aged 30–39.

Methods

Crash data were obtained for 2016–2020 from the National Highway Traffic Safety Administration’s Fatality Analysis Reporting System for fatal crash injuries and Crash Report Sampling System for nonfatal crash injuries. We collected data on victim demographics, roadway, and vehicle- and driver-related factors. Descriptive analyses were conducted between and within pedestrian and cyclist victims.

Results

We analyzed 206,429 pedestrian injuries (36% in children aged 0–19) and 148,828 cyclist injuries (41% in children aged 0–19) from 2016 to 2020. Overall, child pedestrians had lower injury rates than adults, but children aged 10–19 had greater cycling crash rates than adults. Almost half of the pedestrian injuries in children aged 0–9 were “dart-out” injuries (43%). In the majority of the cyclist injuries, children in both age groups failed to yield to vehicles (aged 0–9 = 40% and aged 10–19 = 24%). For children and all ages included in the study, the fatality risk ratio was highest when pedestrians and cyclists were struck by larger vehicles, such as trucks and buses. Further exploration of roadway factors is presented across ages and transportation mode.

Conclusion

Our findings on child, driver, vehicle, and roadway factors related to fatal and nonfatal pedestrian and cyclist injuries may help to tailor prevention efforts for younger and older children.
A qualitative feasibility study of a prototype patient-centered video intervention to increase uptake of cancer genetic testing among Black Americans
Authors: Smith Katherine Clegg , Grob Rachel , McCullough Michelle , May Betty , Warne Emily , Matchette Amanda , Connor Avonne E. , Visvanathan Kala
Published: April 2024

Background

Health advances due to developments in genomic medicine are unequally experienced in the USA; racial differences in the uptake of genetic testing are one factor in this disparity. In collaboration with Black patients and diverse health care providers, we are developing a patient-centered video intervention to increase cancer genetic testing among eligible Black Americans. The objective of the pilot work is to explore the acceptability of and support for the intervention and key content components.

Methods

In order to create a patient-centered video intervention prototype, we conducted a targeted, secondary analysis of 47 coded transcripts from video-taped qualitative interviews with people with a known genetic or inherited cancer risk. The review focused on decision-making, testing experiences, and perceived value of genetic testing. We subsequently generated a 15-min video montage of content from 9 diverse (age, gender, race) participants. We used the prototype video as prompt material for semi-structured interviews with 10 Black patients who had undergone genetic testing in the last 2 years and 10 racially diverse providers (genetic counselors, a nurse, and medical oncologists) who provide management recommendations for high-risk patients. Interviews sought to understand the acceptability of a video intervention to enhance informed decision-making by Black patients and key elements for intervention efficacy.

Results

Study participants were generally positive about the prototype video and provided guidance for intervention development. Interviewed patients prioritized perceived authenticity and relatability of video participants. The presentation of patients’ perspectives on testing, their experiences of testing, and the benefits of having test results were all seen as useful. The benefits of testing for self and family were identified as important considerations. Privacy concerns and science skepticism were identified as germane issues, with guidance to present barriers to testing alongside possible solutions. The inclusion of clinicians was seen as potentially useful but with caution that clinicians are not universally trusted.

Conclusions

Study findings provided critical input for the creation of a professionally produced, tailored intervention video for a randomized clinical trial with Black Americans to evaluate the influence on uptake of genetic testing. The interviews suggest the acceptability and potential utility of an authentic, realistic, and tailored, patient-centered video intervention to increase consideration and uptake of genetic testing.
Evaluation of peripheral and autonomic nervous systems dysfunctions in patients with Parkinson’s disease
Authors: Ragab Osama A. , Mohamed Ehab S. , Nassar Mahmoud H.
Published: April 2024

Background

Peripheral neuropathy (PN) is increasingly recognized in Parkinson’s disease (PD). This study aimed to evaluate peripheral nerve and autonomic nervous system dysfunction in PD. Forty patients with PD (20 drug-naïve, 20 on treatment) and 20 controls underwent neurological examination, Toronto Clinical Neuropathy Score (TCNS), nerve conduction studies, autonomic function tests including (heart rate variability, Blood pressure changes with standing and sustained handgrip, and sudomotor pathways. The Ewing classification system scored each test to quantify autonomic failure severity). Laboratory tests (B12, homocysteine, methylmalonic acid).

Results

Treated patients with PD had higher MDS-UPDRS scores than drug-naïve (p = 0.001). TCNS indicated mild PN in some drug-naïve patients, and mild–moderate PN in treated patients. Nerve conduction studies showed significant sensory and motor neuropathy in treated versus drug-naïve PD and controls. Treated patients had lower B12, higher homocysteine/methylmalonic acid than other groups. Across autonomic tests, controls had the most normal results, followed by drug-naïve patients, with treated patients being most abnormal. Autonomic dysfunction correlated with disease duration, severity, L-dopa dose. Lower B12, higher homocysteine/methylmalonic acid levels were associated with greater neuropathy and disease severity.

Conclusion

Patients with PD show evidence of PN and autonomic dysfunction, which is milder in drug-naïve patients but worsens with disease progression and treatment. Peripheral nervous system assessments may help diagnose and monitor PD neuropathy and effects of interventions.
Removal method of a Supera interwoven stent invaginated during its implantation in endovascular procedure: a case report
Authors: Kozasa Tasuku , Fujihara Masahiko , Tsukizawa Tomofumi , Yazu Yuko , Abe Naoko , Doami Ryoki , Yokoi Yoshiaki
Published: April 2024

Background

Supera interwoven stents (IWS) have a unique interwoven structure; thus, precise stent placement can be challenging as they are prone to elongation, shortening, and invagination. Particularly, invagination limits long-term patency. This proposed method aims to remove invaginated IWS.

Case presentation

A 70-year-old man presented with intermittent claudication in his left lower limb. Endovascular therapy was conventionally performed, and a 5.5 × 40 mm IWS was placed after balloon dilatation; however, invagination occurred. The invaginated IWS was successfully removed by a threading 0.014" wire through the outside of the stent strut, and a snare catheter was used to hold it in place from the inside. Then, while still in place, the 0.014" wire and snare catheter were driven into the guiding sheath.

Conclusions

This practical and easy approach to remove invaginated IWS from the body relies on the particular structural characteristics.