bluuebunny/crossref_metadata_2025 huggingface dataset:
Study protocol for a Randomized Controlled Trial of Supportive Parents – Coping Kids (SPARCK) - a Transdiagnostic and Personalized Parent Training Intervention to Prevent Childhood Mental Health Problems
Authors: Tømmerås Truls , Backer-Grøndahl Agathe , Høstmælingen Andreas , Laland Hanne , Gomez Maria Begonã , Apeland Anett , Karlsson Line Ragna Aakre , Grønlie Anette Arnesen , Torsvik Sissel , Bringedal Görel Eriksson , Aas Monica , Fisher Phillip Andrew , Gardner Frances , Kjøbli John , Malmberg-Heimonen Ira , Nissen-Lie Helene Amundsen
Published: February 2024

Background: To meet the scientific and political call for effective prevention of child and youth mental health problems and associated long-term consequences, we have co-created, tested, and optimized a transdiagnostic preventive parent-training intervention, Supportive parents – coping kids (SPARCK), together with and for the municipal preventive frontline services. The target group of SPARCK is parents of children between 4 and 12 years who display symptoms of anxiety, depression, and/or behavioral problems, that is, indicated prevention. The intervention consists of components from various empirically supported interventions representing different theorical models on parent-child interactions and child behavior and psychopathology (i.e., behavioral management interventions, attachment theory, emotion socialization theory, cognitive-behavioral therapy, and family accommodation intervention). The content and target strategies of SPARCK are tailored to the needs of the families and children, and the manual suggests how the target strategies may be personalized and combined throughout the maximum 12 sessions of the intervention. The aim of this project is to investigate the effectiveness of SPARCK on child symptoms, parenting practices, and parent and child stress hormone levels, in addition to later use of specialized services compared with usual care (UC; eg. active comparison group).
Methods: We describe a randomized controlled effectiveness trial in the frontline services of child welfare, health, school health and school psychological counselling services in 24 Norwegian municipalities. It is a two-armed parallel group randomized controlled effectiveness and superiority trial with assessment of key variables at pre-, post-, and six-month follow-up. 252 families will be included, and randomly allocated to SPARCK or UC.
Discussion: The current study will contribute with knowledge on potential effects of a preventive transdiagnostic parent-training intervention when compared with UC. Our primary objective is to innovate frontline services with a usable, flexible, and effective intervention for prevention of childhood mental health problems to promote equity in access to care for families and children across a heterogeneous service landscape characterized by variations in available resources, personnel, and end user symptomatology.
Trial registration: ClinicalTrials.gov ID: NTCT05800522
Analysis of the current situation of the utilization of medical resources and factors influencing the health-seeking behaviors of patients with chronic diseases
Authors: Chang Yujiao , Lu Yingjun , Liu Nian , Zeng Aizhong
Published: February 2024

Background
In the face of the increasing rate of population aging, the prevalence of chronic diseases among middle-aged and elderly people is also rapidly increasing. The aim of this study was to analyze the relationship between factors influencing outpatient and hospitalization health-seeking behaviors among middle-aged and elderly people with chronic diseases.
Methods
The study population was consecutive patients with chronic diseases who participated in the China Health and Retirement Longitudinal Study (CHARLS) baseline and follow-up surveys in 2018. Multilevel logistic regression models were used to analyze the independent and common factors affecting outpatient visits and hospitalization visits.
Results
A total of 14,036 chronic disease patients aged 45 years and older were included as survey respondents in this study, only 18.87% had outpatient visits in the past month and 19.24% had hospitalization visits in the past year. The adjusted model showed that age, sex, education level, type of residence, and self-reported health level were factors influencing the outpatient health-seeking behavior of chronic disease patients (p < 0.05), and age, sex, type of residence, hukou type, monthly income, type of health insurance, and self-reported health level were factors influencing hospitalization health-seeking behavior of chronic diseases (p < 0.05). Age, sex, and self-reported health level were common influences on outpatient and hospitalization health-seeking behaviors of patients with chronic diseases. Education level was a separate influencing factor for outpatient visits, and hukou type, monthly income, and health insurance were separate influencing factors for hospitalization visits. Type of residence was a multi-categorical variable with differential effects on different health-seeking behaviors.
Conclusions
The chronic disease patients have lower health-seeking behaviors, and this study suggests that there are similarities and differences in the factors affecting outpatient and inpatient health-seeking behaviors of chronic disease patients. In order to improve patients' health-seeking behavior, it is important to identify and take appropriate measures to intervene on the influencing factors in time.
Twenty-four-hour activity-count behavior patterns associated with depressive symptoms: Cross-sectional study by a big data-machine learning approach
Authors: Nawrin Saida Salima , Inada Hitoshi , Momma Haruki , Nagatomi Ryoichi
Published: February 2024

Background
Depression is a global burden with profound personal and economic consequences. Previous studies have reported that the amount of physical activity is associated with depression. However, the relationship between the temporal patterns of physical activity and depressive symptoms is poorly understood. We hypothesize that the temporal patterns of daily physical activity could better explain the association of physical activity with depressive symptoms.
Methods
To address the hypothesis, we investigated the association between depressive symptoms and daily dominant activity behaviors based on 24-hour temporal patterns of physical activity. We conducted a cross-sectional study on NHANES 2011–2012 data where the data is collected from the noninstitutionalized civilian resident population of the United States. The number of participants that had the whole set of physical activity data collected by the accelerometer is 6613. Among 6613 participants 4242 participants had complete demography and Patient Health Questionnaire-9 (PHQ-9) questionnaire, a tool to quantify depressive symptoms.
Results
We identified four physical activity-count behaviors based on five physical activity-counting patterns classified by unsupervised machine learning. Regarding PHQ-9 scores, we found that evening dominant behavior was positively associated with depressive symptoms compared to morning dominant behavior as the control group.
Conclusions
Our results might contribute to monitoring and identifying individuals with latent depressive symptoms, emphasizing the importance of nuanced activity patterns and their probability of assessing depressive symptoms effectively.
MicroRNA-204-5p attenuates oxidative stress, apoptosis and inflammation by targeting TXNIP in diabetic cataract
Authors: Cao Xiang , Jiang Zhixin , Bu Xiaofei , Li Qingyu , Tian Ye , Xu Zijiao , Zhang Boyang , Yuan Xiaoyong
Published: February 2024

Diabetic cataract (DC) is a major cause of blindness in diabetic patients and it is characterized by early onset and rapid progression. MiR-204-5p was previously identified as one of the top five down-regulated miRNAs in human DC lens tissues. We aimed to determine the expression of miR-204-5p in human lens epithelial cells (HLECs) and explore its effects and mechanisms in regulating the progression of DC. The expression of miR-204-5p in the anterior capsules of DC patients and HLECs was examined by RT-qPCR. Bioinformatics tools were then used to identify the potential target of miR-204-5p. The relationship between miR-204-5p and the target gene was confirmed through a dual luciferase reporter assay. Additionally, the regulatory mechanism of oxidative stress, apoptosis, and inflammation in DC was investigated by overexpressing miR-204-5p using miR-204-5p agomir. The expression of miR-204-5p was downregulated in the anterior capsules of DC patients and HLECs. Overexpression of miR-204-5p reduced ROS levels, pro-apoptosis genes (Bid, Bax, caspase-3), and IL-1β production in HG-treated HLECs. TXNIP was the direct target of miR-204-5p by dual luciferase reporter assay. Therefore, This study demonstrated that miR-204-5p effectively reduced oxidative damage, apoptosis, and inflammation in HLECs under HG conditions by targeting TXNIP. Targeting miR-204-5p could be a promising therapeutic strategy for the potential treatment of DC.
Unilateral posterior scleral defects do not affect the clinical biomechanics of the eye: a case series
Authors: Oskam Joshua A , Wells Anthony P , Gale Jesse
Published: February 2024

Background
Modern advances in technology capable of measuring the biomechanics of the eye have brought about new ways of analysing and monitoring glaucoma and created means of further elucidating the pathophysiology of the disease. Optic pits or scleral defects could be expected to impact ocular biomechanics, potentially creating more viscous, energy dispersive behaviour.
Case presentation
In this case series we assessed the corneal and pressure biomechanics of three eyes with unilateral defects in the peripapillary sclera and compared them to the normal fellow eyes. Measurements obtained included corneal hysteresis, ocular pulse amplitude, deformation amplitude, changes in pressure with standing and lying, and response to a water-drinking test. Subtle differences between eyes were observed, but without consistency between participants or differences of clinical significance.
Conclusions
These findings suggest the current anterior measurements of ocular biomechanics do not detect posterior structural variations.
The Association between Statin Medication Use and Intracranial Aneurysm Risk: A Two- Way Mendelian Randomization Study
Authors: Chen Yao , Huang Jianhuang , Zhou Quanming , Kang Yuanbao
Published: February 2024

Background
Recent observational studies have identified a potential link between statin medication use and the risk of intracranial aneurysms (IAs). However, the causal relationship between these factors is not yet clear.
Methods
We used a two-way Mendelian randomization approach to examine the relationship between genetically predicted statin medication use and the risk of IAs, as well as the reverse association. We incorporated data from genome-wide association studies of statin medication and IAs in a European population. Our analysis relied on random-effects inverse variance weighted estimation as the primary statistical method.
Results
Neither statin medication use nor IA risk was significantly associated with the other, according to our findings. The odds ratio (OR) for statin medication was 1.551 (95% confidence interval [CI]: 0.895–2.685, P = 0.117), and the OR for IA risk was 1.020 (95% CI: 0.984–1.059, P = 0.281). Our results were consistent across different analytical methods, including MR-Egger regression and weighted median.
Conclusions
These findings suggest that there is no causal relationship between statin medication use and IA risk.
When Surrogates Choose Suffering A commentary
Authors: Al-Moussally Feras , Casey Edward
Published: February 2024

In modern era medicine, patient’s autonomy is held in the epitome of medical decision making. When patients lose decision making capacity, providers try to the best of their ability to uphold patient’s pre-expressed wishes, often using substituted judgment. The goal is to answer: What is in the patient’s best interest and what would the patient want if they could speak for themselves? But what happens when providers feel that patient’s best interests are not being put front and center? In addition, substituted judgment is considered a basic guiding principle when making decisions for incapacitated patients; but literature illustrates that this framework is not free of fault. We present a case of a 70-year-old male with a diagnosis of terminal colon cancer with metastasis to the brain, lung, and bones who presented with complaints of weakness and altered mental status. Although the patient could not speak, he exhibited signs and symptoms of severe pain. The surrogate refused to provide the patient with analgesics. The ethics committee was consulted to help navigate the situation and facilitate a solution. Though the pursuit of substituted judgment is well-intended, it is not infallible. It is important to recognize this when having discussions with surrogate decision makers and understanding that alternative models could be a better fit in certain situations. All while trying to the best of the provider’s ability to uphold patient’s wishes and best interests.
New score models for predicting bleeding and ischemic of ticagrelor therapy in patients with diabetes mellitus
Authors: Xia Xiaotong , Chen Shu , Cao Chang , Ye YanRong , Shen Yun
Published: February 2024

Purpose
Ticagrelor is an antiplatelet drug, and its use increases the risk of bleeding. Coronary artery disease is significantly influenced by the widespread occurrence of diabetes mellitus. In order to decrease the incidence of clinical adverse events, a novel bleeding and thrombosis score is developed in this research.
Methods
We conducted a retrospective analysis of patient data from two medical centers who were diagnosed with diabetes mellitus and treated with ticagrelor.We gathered information on every patient from the electronic database of the hospital and follow-up.The collected data were statistically analyzed to obtain risk factors for bleeding and ischemic events.
Results
A total of 851 patients with diabetes mellitus who have been administered ticagrelor are included in our investigation. A total of 76 patients have bleeding events and 80 patients have ischemic events. The analysis of multiple variables indicates that characteristics like the age of > 65, having a previous occurrence of bleeding, experiencing anemia, using aspirin, and taking atorvastatin are linked to a higher likelihood of bleeding. Additionally, the age of > 65, smoking, having a history of blood clots, and having a BMI ≥ 30 are found to increase the risk of ischemia.
Conclusion
The A4B score has been created by considering five risk factors. The A4B score outperforms the HAS-BLED score(AUC 0.714 vs 0.570).The ABST score has been created by considering four risk factors. The ABST score outperforms the CHA2DS-VASc score(AUC 0.708 vs 0.540). The novel risk-assessment model can potentially detect patients with a substantial likelihood of experiencing bleeding and ischemic events.(2023-09-11,ChiCTR2300075627)
Application of the FRAME-IS to a Multifaceted Implementation Strategy
Authors: EdD Antoinette Schoenthaler , Calle Franze De La , Leon Elaine , Garcia Masiel , Colella Doreen , RN Jacalyn Nay , Dapkins Isaac
Published: February 2024

Background: Research demonstrates the importance of documenting adaptations to implementation strategies that support integration of evidence-based interventions into practice. While studies have utilized the FRAME-IS [Framework for Reporting Adaptations and Modifications for Implementation Strategies] to collect structured adaptation data, they are limited by a focus on discrete implementation strategies (e.g., training), which do not reflect the complexity of multifaceted strategies like practice facilitation (PF). In this paper, we apply the FRAME-IS to our trial evaluating the effectiveness of PF on implementation fidelity of an evidence-based technology-facilitated team care model for improved hypertension control within a federally qualified health center (FQHC).
Methods: Three data sources are used to document adaptations: (1) implementation committee meeting minutes, (2) narrative reports completed by practice facilitators, and (3) structured notes captured on root cause analysis and Plan-Do-Study-Act worksheets. Text was extracted from the data sources according to the FRAME-IS modules and inputted into a master matrix for content analysis by two authors; a third author conducted member checking and code validation.
Results: We modified the FRAME-IS to include part 2 of module 2 (what is modified) to add greater detail of the modified strategy, and a numbering system to track adaptations across the modules. This resulted in identification of 27 adaptations, of which 88.9% focused on supporting practices in identifying eligible patients and referring them to the intervention. About half (52.9%) of the adaptations were made to modify the context of the PF strategy to include a group-based format, add community health workers to the strategy, and to shift the implementation target to nurses. The adaptations were often widespread (83.9%), affecting all practices within the FQHC. While most adaptations were reactive (84.6%), they resulted from a systematic process of reviewing data captured by multiple sources. All adaptations included the FQHC in the decision-making process.
Conclusion: With modifications, we demonstrate the ability to document our adaptation data across the FRAME-IS modules, attesting to its applicability and value for a range of implementation strategies. Based on our experiences, we recommend refinement of tracking systems to support more nimble and practical documentation of iterative, ongoing, and multifaceted adaptations.
Trial Registration: clinicaltrials.gov NCT03713515, Registration date: October 19, 2018
Association between lumbar, renal, and gonadal vein diameters and varicocele in people with left-sided nephrectomy: An observational study
Authors: Rahimi Mohsen Mohammad , Ghavshough Mahdi Hemmati , Zomorodi Afshar , Rezaei Mona , Kakaei Farzad , Bageri Amin
Published: February 2024

Background
Varicocele, which is defined as varicose veins in the scrotum, is associated with different complications, in particular infertility. However, the definite etiologies have not determined yet. Our objective was to investigate the association between left lumbar, renal, and gonadal veins diameters and varicocele occurrence and grading in kidney donors underwent left-sided nephrectomy. Also, the frequency of varicocele were evaluated three months after the surgery.
Methods
In this observational study, male kidney donors aged 18 to 65, who underwent open nephrectomy were included between 2022 and 2023. Baseline data on age, body mass index (BMI), and the presence or grade of varicocele were collected through medical records and physical examinations. During the procedure, the diameter of the left lumbar, renal, and gonadal veins were measured using a graded ruler on the back table. Three months after the nephrectomy, the patients were re-evaluated for varicocele recurrence.
Results
We included 30 kidney donor with a mean age of 38.2 years and BMI of 23.5 kg/m2. The renal vein diameter decreased with higher grading (p = 0.05) and the gonadal vein diameter increased with higher grading (p = 0.04). However, there was no significant association between varicocele grading and left lumbar vein diameter. Following three months of nephrectomy, the frequency of varicocele increased from 33.4–50.0%.
Conclusions
The diameter of the left lumbar vein was almost unchanged in varicocele, while the size of the left renal vein decreased, and the size of the left gonadal vein increased. Furthermore, occurrence of varicocele increased after three months of left-sided nephrectomy. Therefore, people undergoing nephrectomy are at a higher risk of developing varicocele which should be considered in follow-up visits.
Protocol: Prospective cohort study investigating the impact of muscle degeneration on low back pain after lumbar decompression
Authors: Gotfryd Alberto Ofenhejm , Antonioli Eliane , Couri Pedro Henrique Cortat Proba , Castro Adham Amaral e , Machado Luciana Pereira Magalhaes , Gomes Amanda Maradini Narciso , Miranda Frederico Celestino , Baptista Eduardo , Barros Durval Carmo Santos , Rosemberg Laercio Alberto , Lenza Mario
Published: February 2024

Background
The main reason for surgical procedures in the lumbar spine is nerve compression associated with radiculopathy or neurogenic claudication. Lumbar surgical decompression is effective in relieving neurogenic pain and restoring walking ability. However, the presence of associated preoperative low back pain (LBP) in patients with neurological symptoms is not uncommon, and its management is still controversial. Chronic dysfunctions, such as atrophy and muscle fat replacement of the main spine muscles, are related to pain intensity. These dysfunctions can be identified and measured by means of magnetic resonance imaging (MRI) as muscle fat infiltration and reduction of muscular cross-sectional area. The primary objective of this study was to correlate the degree of muscle degeneration with the presence of LBP before lumbar decompression surgery. The secondary objectives are evaluations of the impact of different surgical techniques in muscle degeneration, as well as of the association of pain, disability, quality life and psychosocial factors during recovery after lumbar decompression surgery.
Methods
This prospective cohort will include individuals older than 18 years who underwent surgical lumbar decompression. Radiographic exams and MRI examinations will be performed before the surgical procedure. Changes in scores of pain, kinesiophobia, psychosocial risk prognosis, perception of improvement, anxiety, depression, disability and quality of life will be measured at baseline and at 3, 6, 12 and 24 months of follow-up. The primary outcome will be the intensity of LBP.
Study status
Protocol Trial version: 02 Date: Feb 10, 2021
Recruitment Start Date: January 2020
Recruitment Estimated End Date: December/2025
Status: Recruiting
Trial registration number: NCT04273828
Detachment-activated FAK-STAT3-NNMT inhibits anoikis by enhancing fatty acid oxidation in breast cancer
Authors: Tong Qingchao , Ma Yilei , Gao Yuzhen , Zhou Lin , Fang Qiang , Fang Sining , Zhao Ru , Zeng Jin , Li Guoli , Xie Xinyou , Wang Yanzhong , Zhang Jun
Published: February 2024

Purpose: Breast cancer metastasis claims the majority of breast cancer-related deaths. Anoikis resistance is a key prerequisite for tumor metastasis. Possible mechanism of evading anoikis in breast cancer remains unclear. Our previous research demonstrated that Nicotinamide N-methyltransferase (NNMT) has essential functions in cancer development and metastasis. However, the spercific functional mechanisms of NNMT in breast cancer anoikisp remain to be explored
Method: Immunofluorescence staining, confocal microscopy analysis, immunoblotting and qPCR were used to analyze NNMT expression. Flow cytometry and soft agar assay were used to analyze the proportion of breast cancer cells undergoing anoikis. ChIP assay and detached cell model were used to confirm the presence of FAK-STAT3-NNMT in detached breast cancer cells. BODIPY staining was used to visualize lipid deposit in the cytoplasm, and Seahorse analysis was used to directly measure FAO rate of attached and detached breast cancer cells.
Results: Detachment of breast cancer cells activates the FAK-STAT3 axis to increase the transcription of NNMT, which then protects breast cancer cells from anoikis by enhancing fatty acid oxidation (FAO). Mechanistically, NNMT promotes the expression of CPT1A, a FAO rate-limiting gene, by suppressing PP2A methylation. Furthermore, NNMT-induced FAO accelerates the clearance of reactive oxygen species (ROS), which triggers anoikis and hinders cancer metastasis, by maintaining NADP+/NADPH balance. In vivo experiments show that NNMT-knockdown breast cancer cells colonize the lung much less than that of NNMT high expression cells. Additionally, inhibitors of NNMT or FAO suppressed breast cancer cell metastasis, suggesting that NNMT-mediated FAO enhances the metastatic potential of breast cancer.
Conclusion: Our study identifies that NNMT, an enzyme upregulated during detachment via the FAK-STAT3 axis, activates the FAO pathway to resist anoikis of breast cancer cells.
The Effect of Constipation on Quality of Life in Child Patients Receiving Chemotherapy: Descriptive Cross-Sectional Study
Authors: BULUT Hacer KOBYA , YETIMOGLU Merve , Bahadır Aysenur
Published: February 2024

Purpose
This study was conducted to evaluate the effect of constipation on quality of life in paediatric patients receiving chemotherapy.
Methods
This study was carried out in a descriptive cross-sectional research design with 60 children and their parents in the outpatient chemotherapy unit of a university hospital. Data were collected face-to-face by means of questionnaires.
Results
It was determined that 70% of the children receiving chemotherapy experienced constipation. A significant correlation was found between having a female gender and experiencing constipation (p˂0.05). The quality of life of parents of children with constipation was low. At the same time, there is significance between experiencing constipation and parental quality of life (p˂0.05). Among children with constipation, 61.9% reported that they perceived constipation as a very important problem.
Evidence that chronic lymphocytic leukemia arises from a multiclonal selection process
Authors: Bagnara Davide , Cardente Niccolò , Vergani Stefano , Kasar Siddha , Fernandes Stacey , Mazzarello Andrea , Ferrer Gerardo , Ghiotto Fabio , Barrientos Jacqueline , Rai Kanti , Kolitz Jonathan , Allen Steven , Fais Franco , Brown Jennifer , Ferrarini Manlio , Chiorazzi Nicholas
Published: February 2024

Although chronic lymphocytic leukemia (CLL) is diagnosed by identifying in a patient’s blood a B-cell clone that exceeds 5x106/µL, additional clones have on occasion been identified. To characterize such clones in patients with CLL, we analyzed by NGS the IGHV-IGHD-IGHJ gene rearrangements in circulating CD5+ B cells from 57 untreated patients. In every patient, we identified additional distinct clonotypes (ADCs) from the clinically relevant clone (CRC). Even when defining clonal expansion using a rigorous threshold, 68% of patients had at least one expanded ADC. The predominant ADC (pADC) reached numbers qualifying as a CLL clone in two patients and qualifying as low/high-count monoclonal B-cell lymphocytosis in each other case. Over time, pADCs enlarged or shrank, suggesting an ongoing selection process. Stereotyped IGHV-D-J rearrangements were enriched in ADCs and IGHV usage and mutations revealed similarities specifically between pADCs and CRCs, while minor ADCs more closely resembled normal CD5+ B-cells. Thus, finding multiple expanded clones within the CD5+ B-cell population of patients with CLL is more the rule rather than the exception. Thus, leukemogenesis involves a competitive selection for dominance of more than one B-cell clone, with the process being influenced to some degree by the structure of the B-cell receptor.
Landing Style Influences Peak ‘ground’ Reaction Forces During Repeated Jumping Using a Supine Jump Sled in Microgravity
Authors: Price Phil DB , Kennett John E , Scott Jonathan PR , Green David A , Cleather Daniel J
Published: February 2024

Repeated jumping has been demonstrated as a feasible exercise countermeasure in microgravity and has been shown to reduce deconditioning in head down bed rest studies. However, varying landing stiffness may provide greater contribution of both axial and medio-lateral bone strain and muscle loading at greater muscle lengths, which may help minimize bone and muscle deconditioning. Therefore, this study investigated the effect of different landing styles on the force profile and ground contact time during repeated jumping using HIFIm in microgravity. Two participants performed repeated jumping on the HIFIm jump sled in microgravity during a parabolic flight campaign. ‘Ground’ forces and ground contact time were compared between landing styles where increased landing stiffness was instructed to the jumper, and increased spring resistance. The results show that the forces experienced when performing repeated jumps in microgravity are sensitive to the landing style employed. As greater stiffness was instructed, peak forces increased, and ground contact time decreased significantly. Peak forces and ground contact time also significantly increased when spring resistance increased. These results highlight that landing instructions and spring configurations could be used as training variables when developing an astronaut training program, which can use different jump styles to minimize bone and muscle deconditioning. Further research using bed rest analogs and repeated jumping using HIFIm is needed to demonstrate varied repeated jumping interventions as an effective exercise method for minimizing deconditioning in astronauts.
Therapeutic efficacy of artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria treatment in Metehara, Central-east Ethiopia
Authors: Tesfaye Mahelet , Assefa Ashenafi , Mamo Hassen
Published: February 2024

Malaria drug resistance presents a significant challenge to malaria control and elimination efforts. Therefore, it is crucial to conduct regular surveillance to assess the therapeutic efficacy of first-line antimalarial drugs, which informs policy decisions to manage this threat. This study aimed to evaluate the therapeutic efficacy of artemether-lumefantrine (AL), which is the first-line treatment for uncomplicated malaria in Ethiopia since 2004, for uncomplicated Plasmodium falciparum malaria in Metehara, central-east Ethiopia. Using a one-arm prospective evaluation design, the study assessed the clinical and parasitological responses of patients with uncomplicated P. falciparum malaria. Initially, 80 patients (50 males and 30 females) were screened, and a total of 73 participants (44 males, 29 females) successfully completed the follow-up. The results indicated rapid parasite clearance and resolution of clinical symptoms, with all patients achieving complete recovery from asexual parasitemia and fever by day 3. The prevalence of gametocytes decreased from 6.3% on day zero to 2.5% on days two, three, seven, and ultimately achieving complete clearance afterwards. The overall cure rate for AL treatment, without a polymerase chain reaction correction, was 100%, demonstrating its high efficacy in effectively eliminating the malaria parasite in patients. Importantly, no serious adverse events related to AL treatment were reported during the study, suggesting its safety and tolerability among the participants. These findings confirm that, even 20 years after its introduction in Ethiopia, AL remains an effective treatment for uncomplicated P. falciparum malaria in the study site.
Exploring the link between particulate matter pollution and type II Diabetes in Italy and Lombardy using clinical longitudinal data: a comparative analysis
Authors: Abbafati Cristiana , Nieddu Luciano
Published: February 2024

Background:
The association between particulate ambient air pollution and an increased risk of type II Diabetes (T2DM) is well-established. Air pollution, a significant public health concern globally, affects various non-communicable diseases, including T2DM. Italy faces significant challenges with both particulate air pollution and T2DM. No studies in Italy exist assessing the association of particulate and T2DM on a large dataset regarding clinically diagnosed T2DM.
Methods:
This study aims to assess the association between particulate matter (PM2.5 and PM10) and T2DM prevalence, and incidence rate in Lombardy compared to the rest of Italy from 2006 to 2019. The association with Years lived with disability (YLDs) rates has been assessed on data from 2006 to 2016. Data is obtained from the AMD dataset, a comprehensive outpatient longitudinal dataset, while particulate matter data is sourced from European Environment Agency and ARPA Lombardy. The association has been assessed via mixed-effects models.
Results:
The mixed-effects model revealed a significant positive association between particulate matter and T2DM incidence rates in Italy, with notable variations over time and between regions (Lombardy vs the rest of Italy). While no significant effect was observed of particulate on prevalence rates and YLDs rates, there is a positive significant connection between particulate and Incidence rate for Italy. The effect increases with time. The opposite tendency has been observed for Lombardy with a negative association of particulate and incidence. Said effect decreases with time opposing the trend for Italy.
Conclusions:
Particulate matter pollution, specifically PM2.5 and PM10, seems to be significantly associated with T2DM incidence rates in Italy. However, the impact varies between regions, with Lombardy exhibiting a complex relationship influenced by socioeconomic factors. This study underscores the importance of addressing air pollution as a public health priority, particularly in regions with high pollution levels like Lombardy, to mitigate the risk of T2DM and its associated burden.
MiR-223 Enhances Lipophagy by Suppressing CTSB in Microglia Following Lysolecithin-Induced Demyelination in Mice
Authors: Ma Hao , Ou Zhilin , Alaeiilkhchi Nima , Cheng Yongquan , Chen Kai , Chen Jiayu , Guo Ruqin , He Minyue , Tang Shiyi , Zhang Xin , Huang Zhiping , Liu Jie , Zhu Qinan , Huang Zu-cheng , Jiang Hui
Published: February 2024

Background
Lipid droplet (LD)-laden microglia are key pathological hallmarks of multiple sclerosis. The recent discovery of a novel microglial subtype, lipid-droplet-accumulating microglia (LDAM), is notable for increased inflammatory factor secretion and diminished phagocytic capability. Lipophagy, the autophagy-mediated selective degradation of LDs, plays a critical role in this context. This study investigates microRNA (miRNA) involvement in lipophagy during demyelinating diseases, assesses their capacity to modulate LDAM subtypes, and elucidates potential underlying mechanisms.
Methods
We conducted in vivo experiments using C57BL/6 mice. Two weeks post-demyelination induction at the cervical level 4 (C4), we performed histological assessments and confocal imaging to examine LD accumulation in microglia within the lesion site. Autophagic changes were observed using transmission electron microscopy. MiRNA and mRNA multi-omics analyses identified differentially expressed miRNAs and mRNAs under demyelinating conditions and the related autophagy target genes. We specifically explored the role of miR-223 in lipophagy in these conditions. In vitro studies, including miR-223 upregulation in BV2 cells via lentiviral transfection, validated bioinformatics findings. Immunofluorescence staining measured LD accumulation, autophagy levels, target gene expression, and inflammatory mediators, elucidating miR-223's mechanisms in LDAM.
Results
Oil Red O staining and confocal imaging revealed substantial LD accumulation in the demyelinated spinal cord. Transmission electron microscopy showed increased autophagic vacuoles at the injury site. Multi-omics analysis pinpointed miR-223 as a crucial regulatory gene in lipophagy during demyelination. Integrating miRNA, mRNA, and autophagy gene databases identified Cathepsin B (CTSB) as a miR-223 target in autophagy. In vitro, miR-223 upregulation suppressed CTSB expression in BV2 cells, augmented autophagy, alleviated LD accumulation, and decreased IL-1β, an inflammatory mediator.
Conclusion
These findings indicate miR-223's pivotal role in lipophagy during demyelinating conditions. By inhibiting CTSB, miR-223 promotes selective LD degradation, thereby reducing the lipid burden and inflammatory phenotype in LDAM. This study broadens our understanding of lipophagy's molecular mechanisms and proposes lipophagy induction as a potential therapeutic approach to mitigate inflammatory responses in demyelinating diseases.
TAG Synthesis and Oxidation Activated by YAP/TEAD Confers ROS Resistance in Cancer Stem Cells
Authors: Lin Jiun-Han , Hsu Tien-Wei , Cheng Wei-Chung , Liu Chen-Chi , Li Anna Fen-Yau , Hung Mien-Chie , Hsu Han-Shui , Hung Shih-Chieh
Published: February 2024

Background
Cancer stem cells (CSCs) are characterized by lower levels of reactive oxygen species (ROS), which contribute to radioresistance through mechanisms that remain unidentified.
Methods
Our study employed lipidomic analyses to investigate the lipid composition of lung CSCs, while concurrently utilizing RNA-seq analysis to assess the expression profile of CSCs. Gain and loss of functional studies were conducted to decipher the underlying molecular pathways. In addition, we performed immunohistochemical staining on clinical samples from human lung cancer patients and utilized transcriptome data to identify potential biomarkers for prognosis prediction.
Results
Lipidomic analyses unveiled that the predominant lipid in lung CSCs was triacylglycerol (TAG), which localized to peri-mitochondria lipid droplets. TAG acted as mitochondria-derived ROS scavengers, displaying higher oxidation levels compared to other lipids when exposed to H2O2. RNA-seq analysis revealed an upregulation of TAG synthesis enzymes (ACSL1/4, LPIN2, DGAT1/2, and PNPLA3) and the anti-ferroptosis arsenal GPX4 in CSCs. These molecular alterations were found to be relevant to CSC radioresistance, sphere formation, and tumor initiation. Furthermore, a six-gene TAG synthesis signature was identified, effectively predicting the prognosis and survival of lung cancer patients. Mechanistically, lung CSCs activated the YAP/TEAD pathway, enhancing the transcription of TAG synthesis genes, thereby playing a crucial role in both TAG synthesis and oxidation, ultimately conferring ROS resistance.
Conclusions
This comprehensive study enhances our understanding of the intricate mechanisms underlying CSC radioresistance. The identified pathways and signatures provide a promising foundation for the development of targeted therapies aimed at overcoming radioresistance in CSCs, with the potential to significantly improve patient outcomes in lung cancer treatment.
Graphic Abstract
Abscisic acid improves the phytoremediation ability of the aquatic accumulator plant Nasturtium officinale R. Br. in cadmium-contaminated soil
Authors: Peng Xuemei , Xiao Yunying , Tang Wanjia , Dai Zhen , Zhang Dilian , Zheng Yangxia , Lin Lijin
Published: February 2024

Previous studies report significant contamination of farmland soil by cadmium (Cd). Cadmium contamination increases the risk of diseases after consumption of grain crops with high Cd levels. Hyperaccumulators or accumulators have been widely used to bioremediate Cd-contaminated farmland soil. Studies report that aquatic hyperaccumulators or accumulators are rarely used in phytoremediation, or their phytoremediation efficiencies are low. A pot experiment was carried out to explore the effects of abscisic acid (ABA) on the cadmium (Cd) accumulation (phytoremediation) of emerged aquatic accumulator plant Nasturtium officinale R. Br. ABA application increased the shoot biomass, peroxidase (POD) activity, superoxide dismutase (SOD) activity, catalase (CAT) activity, and soluble protein content of N. officinale under Cd-contamination condition. The application of ABA at 5, 10, and 20 µmol/L increased the chlorophyll and carotenoid contents in N. officinale. The application of ABA also increased the shoot Cd content and shoot Cd extraction of N. officinale. The application of ABA at 1, 5, 10, and 20 µmol/L increased the shoot Cd extraction by 11.65, 25.27, 37.91, and 58.52%, respectively, compared with the control. In addition, ABA concentration had a linear regression relationship with the root biomass, shoot biomass, root Cd extraction, and shoot Cd extraction. Correlation, grey relational, and path analyses showed that the root biomass, shoot biomass, root Cd extraction, root Cd content, POD activity, SOD activity, and soluble protein content were significantly associated with the shoot Cd extraction. These findings indicate that ABA application can improve the phytoremediation ability of N. officinale under Cd-contaminated flooded fields.
Transcultural Adaptation and Psychometric Evaluation of the Serbian Ankylosing Spondylitis Quality of Life (Asqol) Questionnaire and Its Correlations With Disease Activity (Asdas, Basdai) and Functional Status Indexes
Authors: Mirjana Zlatkovic-Svenda , Dejan Dudok , Jeanette Thorpe , Jelena Milicevic , Dejana Petrovic , Marija Zdravkovic , Goran Radunovic
Published: February 2024

Background: The Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire gauges the impact of ankylosing spondylitis on individuals' overall well-being, shedding light on the quality of life challenges associated with this condition. The main goal of this study was to translate and adapt a Serbian version of the ASQoL questionnaire and to validate it with Serbian speaking AS patients.
Methods: Three stages were accomplished in this study. First, the ASQoL questionnaire was translated using transcultural adaptation and its linguistic intelligibility and naturalness were assessed by a bilingual and a lay panel. Second, cognitive debriefing interviews were implemented to determine face and content validity. Third, psychometric properties of the ASQoL were assessed by construct validity (convergent validity by using NHP as a comparator scale, and known group validity by correlating with disease activity and overall health state), and reliability through the internal consistency and test-retest reliability. Finally, correlations of the ASQoL were evaluated with disease activity and functional status indexes.
Results: The bilingual panel consisted of one male and five female Serbian professionals fluent in English, aged 25 to 35 years. The lay panel comprised two males and three females aged 28 to 65 years. Both panels were led by the same moderator. Cognitive debriefing interviews were conducted with 10 patients with a range of demographic backgrounds. The newly adapted questionnaire was evaluated as clear, precise and easy to understand and complete, and all of the questions were found to be valid and appropriate. Psychometric properties were tested on 60 randomly selected patients. Convergent validity was assessed by correlations of ASQoL and NHP domains of the pain (r =0.79), emotional reactions (r=0.78), physical activity (r=0.77) and energy (r=0.75) scales. Internal reliability measured by Cronbach’s alpha coefficient was 0.95 (1st administration) and 0.91 (2nd administration), test-retest reliability was 0.84, showing high correlations of the 1st and 2nd ASQoL administrations. Three independent regression analyses have shown significant relations (p<0.001) between ASQoL and ASDAS (R²=0.40), BASDAI (R²=0.56) and BASFI (R²=0.44).
Conclusion: The Serbian ASQoL has demonstrated excellent psychometric properties, indicating that it is a valid and veracious instrument for use both in clinical studies and clinical practice.
Neonatal ECMO in Severe Bronchiolitis: Our Experience in the Last 10 Years.
Authors: Merino-Hernández Amaia , Muñoz-Cutillas Agustín , Zeballos-Sarrato Susana , Bernardo-Atienza Belén , Sánchez-Luna Manuel
Published: February 2024

Introduction:
Bronchiolitis is the most common lower respiratory tract infection in infants less than 1 year of age, and the leading cause of hospitalization in this age group in developed countries. Neonates with bronchiolitis usually have a favorable prognosis, but preterm infants due their immaturity sometimes they undergo progressive and rapid deterioration with failure of the standard respiratory support and may require rescue treatment with extracorporeal membrane oxygenation (ECMO).
Materials and Methods
Observational, retrospective and single-center study conducted in the neonatology department of a high-complexity hospital (Level IIIC). The study included patients admitted to the Neonatal Intensive Care Unit who required ECMO for severe respiratory failure due to acute bronchiolitis between 2013 and 2022.
Results
6 patients were included, 83.3% preterm with a median gestational age of 28.6 weeks (IQR 27.1–29.6)). 3 patients (50%) presented with community bronchiolitis, and 3 (50%) with nosocomial bronchiolitis. RSV was isolated in 4 patients, rhinovirus in one and influenza A in another. The median duration of mechanical ventilation before ECMO was 2.5 days (IQR 1–4). At the beginning of ECMO support, the median age was 48.5 days (IQR 34–120), with a median postmenstrual age of 38 weeks (IQR 35-41.8) and a median weight of 2490 grams (IQR 1800–2900). The median duration of ECMO therapy was 14 days (IQR 9–24). 2 patients (33%) died, one from cardiac arrest due to hemopericardium and the other from liver failure with severe coagulopathy. All surviving patients were followed up by pulmonology and neurology. 2 (33.3%) required home oxygen therapy, and both had a respiratory admission in the first year of life. One required bronchodilator treatment, and the other has had a good evolution. One patient was diagnosed with attention deficit hyperactivity disorder, one with autism spectrum disorder and another with mild cognitive retardation and deafness.
Conclusion
Small infants are at high risk of developing severe bronchiolitis. Although they usually have good outcomes, some cases with the most severe respiratory failure may require rescue treatment with ECMO. When ECMO was needed, an increased mortality rate of 33% was observed, and it was associated with RSV-Bronchiolitis, prematurity, and prolonged ECMO .
Brain tumor patients’ experiences and psychological needs in peri-operative environment
Authors: Gabrijolavičiūtė Diana , Pranckevičienė Aistė , Deltuva Vytenis Pranas , Tamašauskas Arimantas
Published: February 2024

Purpose.
Brain tumor (BT) diagnosis and treatment is a lifechanging experience that might lead to impaired physical, cognitive, emotional, and social functioning. An acute stage of BT treatment often starts with neurosurgery. The aim of this study is to reveal and describe the experiences of primary BT patients during peri-operative period and discuss emerging psychological needs and possible support options during this time.
Methods
. Five primary brain tumor patients − 3 men and 2 women - participated in this study. Data was collected through semi-structured in-depth interviews and analyzed using J. A. Smith’s interpretative phenomenological analysis.
Results.
Analysis revealed five overarching themes: 1) A need to control one’s situation; 2) Futile wishing to escape from the depressive hospital environment; 3) Increased dependency and fears for the future; 4) Experiences of solidarity and isolation; 5) Confusion about changes in the head.
Conclusions.
Results indicates that empowering patients with information and sense of control, reducing environmental stressors and individualizing care, providing specialized mental health care in the process of grieving the old life and adjusting to the new one, as well as providing support and information to the caregivers of the patients might be beneficial for brain tumor patients and their transition to further treatment phases.