Objectives: We investigated the molecular underpinnings of miR-205-3p in driving the proliferative behavior of endothelial cells originating from hepatocellular carcinoma (HCC). Methods: In our study, reverse transcription quantitative PCR analysis identified a significant upregulation of miR-205-3p in endothelial cells from HCC. This upregulation was consistently observed across various HCC cell lines and tissue samples. Further investigation highlighted the regulatory effect of miR-205-3p on the HINT1 gene. The interaction between miR-205-3p and the 3’ untranslated region of HINT1 was confirmed using a dual-luciferase reporter assay. Additionally, experiments involving MTT assays and flow cytometry demonstrated that lentivirus-mediated suppression of HINT1 enhanced cellular proliferation and reduced apoptotic activity in HCC cell models. Results: This study reveals that miR-205-3p contributes to the progression of endothelial cells from HCC by targeting and inhibiting HINT1, a tumor suppressor. Conclusions: This study provides a theoretical foundation suggesting that miR-205-3p may serve as a viable molecular target for gene therapy interventions in clinical settings.

Purpose: Hypertension (HT), dyslipidemia (DL), and diabetes mellitus (DM) are major risk factors for cardiovascular diseases. Despite the wide availability of medications to reduce this risk, poor adherence to medications remains an issue. The aim of this study is to evaluate medication adherence of prevalent users in these disease medications (HT, DL, DM) using claims data. Factors associated with non-adherence were also examined. Methods: Of 7,538 participants of the Tsuruoka Metabolomics Cohort Study, 3,737（HT: 2,724, DL: 2,137, DM: 665) were identified as prevalent users of these disease medications. Information on lifestyle was collected through a questionnaire. Adherence was assessed by a proportion of days covered (PDC) and participants with PDC ≥ 0.8 were defined as adherent. Predictors of non-adherence were determined by performing multivariable logistic regression. Results: Medication adherence differed by medication groups. Those with DL-only showed the lowest adherence (79.6%), followed by those with DM-only (81.7%) and those with HT-only (89.8%). The associations were observed especially among those with no comorbidities. Determinants associated with non-adherence in each medication group were skipping breakfast and poor understanding of medications among those with HT, females, having comorbidities, having the medical history of stroke, and drinking habit among those with DL, and skipping breakfast among those with DM. Conclusion: While participants showed high medication adherence, differences were observed across medication groups. The identified predictors of non-adherence could help target those in need of adherence support.

Case report: Actinomyces in Hand: An Unusual Cause of OsteomyelitisAlireza Khosravi 1, Alireza Ghanadan2, Alireza Hadizadeh 3, Mohammadsadegh Talebi Kahdouei 4, Fatemeh Aghaei5, Faezeh Salahshour6, Zahra Saffarian7*1. Mycology Research Center, Faculty of Veterinary Medicine, University of Tehran, Tehran, [email protected]. Professor of pathology department of dermatopathology, Razi hospital, department of pathology, cancer institute, Imam Khomeini Hospital Complex, Tehran University of Medical Science, Tehran, [email protected]. Female Pelvic Medicine and Reconstructive Surgery (FPMRS), Division of Urogynecology, University of Chicago, Northshore University HealthSystem, Skokie, IL, USA4. Medical School, Tehran University of Medical Science, Tehran, [email protected]. Medical School, Tehran University of Medical Science, Tehran, [email protected].  Department of Radiology, Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences and Liver Transplantation Research Center, Imam Khomeini Hospital complex, Tehran University of Medical Sciences (TUMS), Tehran, [email protected] [email protected] [email protected]. Assistant professor of dermatology, Dermatology Department of Imam Khomeini Hospital Complex, Tehran University of Medical Science, Tehran, [email protected]*Co-responder author:Assistant professor of dermatology, Dermatology Department of Imam Khomeini Hospital Complex, Tehran University of Medical Science, Tehran, [email protected]

S-Adenosyl-L-methionine (SAM) is a substrate for many enzyme-catalyzed reactions and provides methyl groups in numerous biological methylations, and thus has vast applications in the agriculture and medical field. Saccharomyces cerevisiae has been engineered as a platform with significant potential for producing SAM, although the current production has room for improvement. Thus, a method that consists of a series of metabolic engineering strategies was established this study. These strategies included enhancing SAM synthesis, increasing ATP supply, and down-regulating SAM metabolism and downregulating competing pathway. After combinatorial metabolic engineering, Bayesian optimization was conducted on the obtained strain C262P6 to optimize the fermentation medium. A final yield of 2972.8 mg/L at 36 h with 29.7% of the L-Met conversion rate in the shake flask was achieved, which was 26.3 times higher than that of its parent strain and the highest reported production in the shake flask to date. This paper establishes a feasible foundation for the construction of SAM-producing strains using metabolic engineering strategies and demonstrates the effectiveness of Bayesian optimization in optimizing fermentation medium to enhance the generation of SAM.

Background: Major screening abnormalities in pre-colposcopic stage are tests results that imply direct referral to colposcopy (and/or expedited treatment) without performing additional high-grade squamous intraepithelial lesions or worse (HSIL+) risk selection testing. Currently, both clinically validated HSIL+ risk selection tests, reflex cytology and reflex p16/Ki67 dual staining (DS), are being compared for use in primary HPV-based screening to avoid possible overtreatment, but there is still no sufficient data available for their performance. Methods: Among 30,066 liquid-based cervical cancer screening tests results, a group of 332 women was selected with available HRHPV tests results with 16/18 limited genotyping, liquid-based cytology, DS, and histology results from standardized colposcopy with biopsy. In HPV 16/18+ cases, three triage approaches were retrospectively analyzed. Predictive values for detection of HSIL+ were calculated and number of colposcopies required in each strategy. Results: Both triage models with DS used (reflex cytology followed by DS, and reflex DS alone in all cases) had significantly higher PPV for HSIL+ than strategy with reflex cytology alone (44.2%/45.7% vs. 28.3%; p<0.0001). In models with DS, less colposcopies were required (95/92 vs. 152) and less colposcopies were needed per HSIL+ detection (2,26/2,19 vs. 3,54). Only 1 HSIL+ case was missed in both triage models with DS incorporation. Conclusions: p16/Ki67 dual-stain may be an effective, alone or combined with cytology, triage test to detect HSIL+ in patients with major screening abnormalities in primary HPV-based cervical cancer screening. Performing cytology as the first triage test improves the strategy by enabling referrals to expedited treatment in selected cases.

Rationale:Pesticide isomers are widely available in agricultural production and may vary widely in biological activity, potency, and toxicity. Chromatographic and mass spectrometric analysis of pesticide isomers is challenging due to structural similarities. Methods:Based on liquid chromatography-time of flight mass spectrometry (LC-Q-TOF/MS), identification of cis-trans isomeric pesticides was achieved through retention time, characteristic fragment ions, and relative abundance ratio. The cleavage pathways of six cis-trans isomers were elucidated through collision-induced dissociation (CID) to explain the origins of different fragment ions. The energy-resolved mass spectrometry combined with computational chemical density functional theory in terms of kinetics, thermodynamics, and bond lengths, the specific process of fragments were simulated to explain the reasons for the differences in characteristic fragment ions and abundance ratios. Results:Based on the above study, a high-resolution mass spectrometry method was developed for the separation and analysis of cis-trans isomers of pesticides in traditional Chinese medicine Radix Codonopsis, and six pesticide isomers were distinguished by retention time, product ions, and relative abundance ratios. The limits of quantification of the six pesticides were up to 10 μg/kg, and the linear ranges of them were 10-200 μg/kg, with the coefficients of determination (R 2)＞0.99, which demonstrated the good linearity of the six pesticides. The recoveries of the pesticides at the spiked concentrations of 10 μg/kg, 20 μg/kg, and 100 μg/kg reached 70-120% with the RSDs ≤20%. Conclusions:It was demonstrated that the application of the method was well-suited for accurate qualitative and quantitative analysis for each isomers with different structures which could avoid false negative results caused by ignoring another isomers effectively.

Langerhans cell histiocytosis (LCH) is a rare hematologic neoplasm characterized by the clonal proliferation of Langerhans-like cells. Colony-stimulating Factor 1 receptor (CSF1R) is a membrane-bound receptor that is highly expressed in LCH cells and tumor-associated macrophages. In this study, a soluble form of CSF1R protein (sCSF1R) was identified by plasma proteome profiling, and its role in evaluating LCH prognosis was explored. We prospectively measured plasma sCSF1R levels in 104 LCH patients and 10 healthy children using ELISA. Plasma sCSF1R levels were greater in LCH patients than in healthy controls ( P < 0.001) and significantly differed among the three disease extents, with the highest level in MS RO+ LCH patients ( P < 0.001). Accordingly, immunofluorescence showed the highest level of membrane-bound CSF1R in MS RO+ patients. Furthermore, the plasma sCSF1R concentration at diagnosis could efficiently predict the prognosis of LCH patients treated with standard first-line treatment (AUC =0.782, P < 0.001). Notably, dynamic monitoring of sCSF1R levels could predict relapse early in patients receiving BRAF inhibitor treatment. In vitro drug sensitivity data showed that sCSF1R increased resistance to Ara-C in THP-1 cells expressing ectopic BRAF-V600E. Overall, the plasma sCSF1R level at diagnosis and during follow-up is of great clinical importance in pediatric LCH patients.

Right heart failure after pericardiectomy: a case report

In this paper, we consider the matrix-weighted consensus problems with disturbances. To this end, we firstly propose a new disturbance observer design for systems with unknown matched or mismatched disturbances representable as a linear combination of time-varying basis functions. Under some assumptions on the boundedness and persistent excitation of the regression matrix, the disturbances can be precisely estimated at an exponential rate and thus, can be compensated by a suitable compensation input. Next, disturbance-observer based consensus algorithms are proposed for matrix-weighted networks of single- and double-integrators with matched or mismatched disturbances. We show that both matched and mismatched disturbances can be estimated and actively compensated, and the system globally asymptotically converges to a fixed point in the kernel of the matrix-weighted Laplacian. Depending on the network connectivity, the system can asymptotically achieve a consensus or a cluster configuration. The disturbance-observer based consensus design is further extended for higher-order integrators with disturbances. Finally, simulation results are provided to support the mathematical analysis.

The objective of this study was to assess the effect of different soil acidity levels, determined by base-cation saturation (BCS) levels, on the anatomical, and morphological analyses of the roots, the nutritional status of the plants, as well as the root and shoot biomass production. A 107-days greenhouse experiment was carried out, employing a randomized block design with a 2x4 factorial arrangement. The factors included two propagation methods (seeds and stem cuttings) and four BCS levels (19%, 39%, 52%, and 63%). There was no observed interaction between propagation methods and BCS levels regarding root and shoot biomass production. This indicates that T. diversifolia’s tolerance to acidic soils is not affected by the propagation method. However, stem-propagated plants exhibited significantly greater root (31% increase) and shoot (26% increase) biomass production compared to seed-propagated plants. Regardless of the propagation method, T. diversifolia plants grown in soil with a 19% BCS level showed a substantial reduction in root (45% decrease) and shoot (31% decrease) biomass compared to the 63% BCS level treatment. The root anatomy and morphology of T. diversifolia are affected when cultivated in acidic soils with a 19% BCS level. Nevertheless, the PAS test detected some mucilage in T. diversifolia roots, suggesting a potential defense mechanism for Al 3+. The shoot biomass of T. diversifolia plants cultivated in soil with a 19% BCS level exhibited greater nutritional values compared to the 63% BCS level. In conclusion, propagation methods have a limited impact on the tolerance of T. diversifolia to acidic soils. Despite the negative effects on root and shoot biomass production, T. diversifolia effectively maintains nutrient uptake even under acidic soil conditions with Al 3+ availability of 5 mmol c dm -3.

The attention network test (ANT), developed based on the triple-network taxonomy by Posner and colleagues, has been widely used to examine the efficacy of alerting, orienting, and executive control in clinical and developmental neuroscience studies. Recent research suggests the imperfect reliability of the behavioral ANT and its variants. However, the classical ANT fMRI task’s test-retest reliability has received little attention. Moreover, it remains ambiguous whether the attention-related intrinsic network components, especially the dorsal attention, ventral attention, and frontoparietal network, manifest acceptable reliability. The present study approaches these issues by utilizing an openly available ANT fMRI dataset for participants with Parkinson’s disease and healthy elderly. The reproducibility of group-level activations across sessions and participant groups and the test-retest reliability at the individual level were examined at the voxel, region, and network levels. The intrinsic network was defined using the Yeo-Schaefer atlas. Our results reveal three critical facets: (1) The overlapping of the group-level contrast map between sessions and between participant groups was unsatisfactory; (2) The reliability of alerting, orienting, and executive, defined as contrast between conditions, was worse than estimates of specific conditions. (3) Dorsal attention, ventral attention, visual, and somatomotor networks showed acceptable reliability for the congruent and incongruent conditions. Our results suggest that specific condition estimates might be used instead of the contrast map for individual or group-difference studies.

Background: Given the enormous impact that the software industry has on so many facets of our lives today, software projects are extremely important. Digital transformation is driven across industries by software developments. They facilitate the utilisation of technology by organisations to optimise operations, augment productivity, and provide inventive products and services. To be competitive and adjust to the quickly changing market dynamics of today’s world, companies must undergo digital transformation by making full use of software projects. Objectives: The main aim of the current study is to determine the main causes of project delay and cost overrun in software projects, identify the effects of project delay and cost overrun on software projects, and define the role of cost estimation models in overcoming project delays and cost overruns in these projects. Results and conclusions:The researcher reviews the literature on causes behind delay and cost overrun and describes the role that can be played by cost estimation models in that process. In light of the reviewed literature, the researcher reaches certain recommendations for the software industry.

Affective Touch plays a pivotal role in regulating emotions, fostering social bonds, and nurturing affiliations with others. Its emotional and arousing dimensions rely on specific features of tactile stimulations characterizing gentle human caresses, such as touch velocity and the nature of the stroking source. While previous research has examined the physiological responses to these individual features of Affective Touch, no study has explored how they interact to shape autonomic activity. In this study, we investigated whether and how both the nature of the touching effector (Human hand vs. Artificial hand) and touch type (Dynamic vs. Static) influenced the participants’ pupil dilation and their subjective experience during tactile stimulation. We observed that when participants received a dynamic touch, they displayed an increase in pupil dilation when the touch was promoted by a human compared to an artificial hand, and that such discrimination was absent for static touch. Also, dynamic touch promoted by a human hand invoked a supralinear enhancement of pupil dilation indicating that the combination of these two features induced a significantly stronger autonomic activation than the summed effects of each separately. Moreover, this specific type of touch was perceived as the most pleasant compared to all other tactile stimulations. Overall, our results suggest that pupil dilation could map the pleasant experience of human-to-human tactile interactions, supporting the notion that the autonomic nervous system encodes the emotional and hedonic aspects associated with Affective Touch as a complex and holistic social experience, rather than solely responding to its low-level sensory properties.

IntroductionCoccidioidomycosis, known as Valley Fever, is the disease caused by the inhalation of arthroconidia from the soil-dwelling dimorphic fungi,Coccidioides immitis and Coccidioides posadasii [1]. In the United States, coccidioidomycosis is endemic to the southwestern part of the country, with most cases located in the San Joaquin Valley of California and Southern Arizona. The incidence of coccidioidomycosis is approximately 10,000 cases reported annually [1,2]. Coccidioidomycosis may affect any demographic, but primarily affects those aged 40-60 years old and has a slight male predominance. Clinical manifestations range from asymptomatic to disseminated infection depending on the patient’s immune status.Cutaneous manifestations in coccidioidomycosis can be classified as reactive or organism-containing lesions in secondary or primary cutaneous infection [3]. Sweet syndrome, or acute febrile neutrophilic dermatosis, is an inflammatory, non-infectious skin reaction rarely observed as one of the reactive skin manifestations of coccidioidomycosis. Patients with Sweet syndrome clinically present with fever, leukocytosis with neutrophilia, and painful erythematous papules, plaques, pustules, and nodules commonly appearing on the upper limbs, trunk, head, and neck [4]. Here, we present a case of coccidioidomycosis associated with Sweet’s syndrome.

Light exposure has been proven to significantly impact human health, and as a result, researchers are increasingly exploring its potential benefits and drawbacks. With the advancements in understanding light and the manufacturing of light sources, modern health lighting has become widely utilized in daily life and plays a critical role in the prevention and treatment of various illnesses. The use of light in healthcare is a global trend, and many countries are actively promoting the development and application of relevant scientific research and medical technology. This field has gained worldwide attention and support from scientists and doctors alike. In this review, we examine the application of lighting in human health and recent breakthroughs in light exposure related to pathology, therapeutic strategies, molecular changes, and more. Finally, we also discuss potential future developments and areas of application.

INTRODUCTIONPleural effusion is an abnormal collection of fluid within pleural space usually resulting from excess fluid production and or decreased lymphatic absorption. Pleural effusion is rare during neonatal period with the estimated prevalence of 0.06%1. Neonatal pleural effusion may be due to antenatal congenital causes or postnatal acquired causes. Antenatal pleural effusion may be due to hydrops fetalis, congenital chylothorax, congenital heart disease (CHD), chromosomal anomalies, pulmonary anomalies or infection like congenital herpes simplex viral (HSV) and Paro virus infection. Postnatal acquired causes include extravasation of peripherally inserted central catheters, parapneumonic effusion or traumatic chylothorax.As neonatal pleural effusion can cause significant respiratory distress, vigilant delivery room management is required. Identifying the underlying cause is important as it leads to specific therapeutic measures. Diagnostic chests tap for pleural fluid analysis is important for diagnosis and its consequent management.2Similarly, echocardiography, karyotyping and other investigations are also indicated for identifying subsequent etiology.Here, we report a case of neonatal pleural effusion; which on evaluation; pulmonary sequestration-extra lobar type was found as the cause of effusion. Extra lobar pulmonary sequestration associated with pulmonary effusion is a very rare entity.3 The purpose of this case report is to familiarize clinician regarding lung sequestration as the cause of neonatal pleural effusion and prevent subsequent morbidity and mortality.

Sydenham’s chorea in a female child with rheumatic fever in Bhutan: a case reportTshering Penjor1, Thinley Dorji1, Sangay Wangchuk11Department of Internal Medicine, Central Regional Referral Hospital, Gelephu, BhutanAddress of corresponding author: Dr Tshering Penjor, MD. Department of Internal Medicine, Central Regional Referral Hospital, Gelephu, Bhutan.

In recent years, with the updating and iterating of new global technologies, digital twins (DTs) originated in the aerospace industry has been widely used in smart manufacturing, smart construction, and smart management as a new type of informatization management tool. It is therefore important for scholars to understand the current state of research on DTs to conduct more targeted research in the future. Based on Scopus, 7384 publications related to DTs were found from 1951 to 2023 in this study. With VOSviewers, the major countries, authors, and institutions researching DTs globally were analyzed and discussed. In conclusion, the study found that since 2018, increasing numbers of scholars around the globe, especially in China and the United States, have conducted relevant research in relation to DTs. Manufacturing and construction are the most common application areas for DTs. Over the past three years, the integration of AI, IoT, cloud, and digital technologies has developed into a hotpot of research. Additionally, communication technologies such as 5G and 6G contribute to the development of DTs. In the future, it can be predicted that DTs will be utilizing machine learning, blockchain and other technologies as a result of advancements in becoming smarter and more secure over the years.