bluuebunny/crossref_metadata_2025 huggingface dataset:
The antioxidant and antimicrobial activity of ethanolic extract in roots, stems, and leaves of three commercial Cymbopogon species
Authors: Wahyuni Dwi Kusuma , Kharisma Viol Dhea , Murtadlo Ahmad Affan Ali , Rahmawati Cici Tya , Syukriya Alvi Jauharotus , Prasongsuk Sehanat , Subramaniam Sreeramanan , Wibowo Anjar Tri , Purnobasuki Hery
Published: July 2024

Background

Cymbopogon is a member of the family Poaceae and has been explored for its phytochemicals and bioactivities. Although the antimicrobial activities of Cymbopogon spp. extracts have been extensively studied, comprehensive analyses are required to identify promising compounds for the treatment of antimicrobial resistance. Therefore, this study investigated the antioxidant and antimicrobial properties of Cymbopogon spp. ethanolic extracts in every single organ.

Methods

Ethanolic extracts were obtained from three Indonesian commercial species of Cymbopogon spp., namely Cymbopogon citratus (L.) Rendle, Cymbopogon nardus (DC.) Spatf., and Cymbopogon winterianus Jowitt. The leaf, stem, and root extracts were evaluated via metabolite profiling using gas chromatography-mass spectrometry (GC–MS). In silico and in vitro analyses were used to evaluate the antioxidant and antimicrobial properties of the Cymbopogon spp. ethanolic extracts. In addition, bioactivity was measured using cytotoxicity assays. Antioxidant assays were performed using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azino-bis [3-ethylbenzothiazoline-6-sulfonic acid (ABTS) to determine toxicity to Huh7it-1 cells using a tetrazolium bromide (MTT) assay. Finally, the antimicrobial activity of these extracts was evaluated against Candida albicans, Bacillus subtilis, Staphylococcus aureus, and Escherichia coli using a well diffusion assay.

Results

GC–MS analysis revealed 53 metabolites. Of these, 2,5-bis(1,1-dimethylethyl)- phenol (27.87%), alpha-cadinol (26.76%), and 1,2-dimethoxy-4-(1-propenyl)-benzene (20.56%) were the predominant compounds. C. winterianus and C. nardus leaves exhibited the highest antioxidant activity against DPPH and ABTS, respectively. Contrastingly, the MTT assay showed low cytotoxicity. C. nardus leaf extract exhibited the highest antimicrobial activity against E. coli and S. aureus, whereas C. winterianus stem extract showed the highest activity against B. substilis. Furthermore, computational pathway analysis predicted that antimicrobial activity mechanisms were related to antioxidant activity.

Conclusions

These findings demonstrate that the leaves had strong antioxidant activity, whereas both the leaves and stems showed great antimicrobial activity. Furthermore, all Cymbopogon spp. ethanolic extracts showed low toxicity. These findings provide a foundation for future studies that assess the clinical safety of Cymbopogon spp. as novel drug candidates.
Hybridized deep learning goniometry for improved precision in Ehlers-Danlos Syndrome (EDS) evaluation
Authors: Kudithi Thirumalesu , Balajee J. , Sivakami R. , Mahesh T. R. , Mohan E. , Guluwadi Suresh
Published: July 2024

Background

Generalized Joint Hyper-mobility (GJH) can aid in the diagnosis of Ehlers-Danlos Syndrome (EDS), a complex genetic connective tissue disorder with clinical features that can mimic other disease processes. Our study focuses on developing a unique image-based goniometry system, the HybridPoseNet, which utilizes a hybrid deep learning model.

Objective

The proposed model is designed to provide the most accurate joint angle measurements in EDS appraisals. Using a hybrid of CNNs and HyperLSTMs in the pose estimation module of HybridPoseNet offers superior generalization and time consistency properties, setting it apart from existing complex libraries.

Methodology

HybridPoseNet integrates the spatial pattern recognition prowess of MobileNet-V2 with the sequential data processing capability of HyperLSTM units. The system captures the dynamic nature of joint motion by creating a model that learns from individual frames and the sequence of movements. The CNN module of HybridPoseNet was trained on a large and diverse data set before the fine-tuning of video data involving 50 individuals visiting the EDS clinic, focusing on joints that can hyperextend. HyperLSTMs have been incorporated in video frames to avoid any time breakage in joint angle estimation in consecutive frames. The model performance was evaluated using Spearman’s coefficient correlation versus manual goniometry measurements, as well as by the human labeling of joint position, the second validation step.

Outcome

Preliminary findings demonstrate HybridPoseNet achieving a remarkable correlation with manual Goniometric measurements: thumb (rho = 0.847), elbows (rho = 0.822), knees (rho = 0.839), and fifth fingers (rho = 0.896), indicating that the newest model is considerably better. The model manifested a consistent performance in all joint assessments, hence not requiring selecting a variety of pose-measuring libraries for every joint. The presentation of HybridPoseNet contributes to achieving a combined and normalized approach to reviewing the mobility of joints, which has an overall enhancement of approximately 20% in accuracy compared to the regular pose estimation libraries. This innovation is very valuable to the field of medical diagnostics of connective tissue diseases and a vast improvement to its understanding.
Implementing nursing interventions based on stress system theory alongside painting therapy for pediatric post-traumatic stress disorder following accidental injury
Authors: Yuan Xing , Xu Bing , Cai Bao , Huang Shan , Jiang Kai-Li
Published: July 2024

Objective

The aim of this study is to examine the impact of a nursing intervention based on stress system theory, coupled with painting therapy, on children experiencing post-traumatic stress disorder (PTSD) subsequent to an accidental injury.

Methods

The clinical data of 100 children diagnosed with PTSD following accidental injuries were retrospectively analyzed for the period spanning April 2021 to May 2023. There were 48 children who received standard nursing care between April 2021 and April 2022 in the control group, and 52 children who received nursing intervention based on stress system theory combined with painting therapy between May 2022 and May 2023 in the observation group. Scores of PTSD Self-evaluation Scale (PTSD-SS), post-traumatic growth, coping style, quality of life, and family satisfaction were compared between the two groups.

Results

Prior to nursing care, the scores of each dimension in the PTSD-SS, post-traumatic growth, coping style, and quality of life were similar between the two groups (P > 0.05). Following nursing intervention, the observation group exhibited lower scores in each dimension of the PTSD-SS compared to the control group. Moreover, the scores in each dimension of the children’s version of the Post-Traumatic Growth Inventory (PTGI) were higher in the observation group than in the control group. Additionally, the Confrontation scores in the Medical Coping Modes Questionnaire (MCMQ) were higher in the observation group than in the control group, while the scores of Avoidance and Resignation were lower in the observation group than in the control group. The scores of each dimension in the Pediatric Quality of Life Inventory Measurement Models (PedsQL4.0) were higher than those in the control group (P < 0.05), and the family satisfaction in the observation group (96.15%) was higher than that in the control group (81.25%), with P < 0.05.

Conclusion

The implementation of nursing intervention based on stress system theory combined with painting therapy in children with PTSD following an accidental injury can alleviate stress, help them actively cope with the condition, promote post-traumatic growth, and improve the quality of life and family satisfaction.
Associations of sugar intake, high-sugar dietary pattern, and the risk of dementia: a prospective cohort study of 210,832 participants
Authors: Zhang Sirui , Xiao Yi , Cheng Yangfan , Ma Yuanzheng , Liu Jiyong , Li Chunyu , Shang Huifang
Published: July 2024

Background

Limited evidence demonstrated the potential relationship between dietary sugar intake and dementia. This association demands further clarification in a large-scale population.

Methods

A total of 210,832 participants from the UK Biobank cohort were included in this prospective cohort study. Absolute and relative sugar intake and high-sugar dietary scores were utilized to reflect dietary sugar intake. Absolute sugar intake was identified by the Oxford WebQ in the UK Biobank. Relative sugar intake was calculated by dividing the absolute sugar intake by total diet energy. High-sugar dietary pattern was identified using the method of reduced rank regression. Cox proportional hazards regression analyses and restricted cubic splines were performed to examine the longitudinal associations between dietary sugar intake and all-cause dementia and its main subtype, Alzheimer’s disease. Explorative mediation analyses were conducted to explore underlying mechanisms.

Results

Increased absolute sugar intake (g/day) was significantly associated with a higher risk of all-cause dementia (HR = 1.003, [95%CI: 1.002–1.004], p < 0.001) and Alzheimer’s disease (1.002, [1.001–1.004], 0.005). Relative sugar intake (%g/kJ/day) also demonstrated significant associations with all-cause dementia (1.317, [1.173–1.480], p < 0.001) and Alzheimer’s disease (1.249, [1.041–1.500], 0.017), while the high-sugar dietary score was only significantly associated with a higher risk of all-cause dementia (1.090, [1.045–1.136], p < 0.001). In addition, both sugar intake and high-sugar dietary score demonstrated significant non-linear relationships with all-cause dementia and Alzheimer’s disease (all p values for non-linearity < 0.05).

Conclusions

Our study provided evidence that excessive sugar intake was associated with dementia. Controlling the excess consumption of dietary sugar may be of great public health implications for preventing dementia.
Towards genomic medicine: a tailored next-generation sequencing panel for hydroxyurea pharmacogenomics in Tanzania
Authors: Nkya Siana , Nzunda Collin , Saukiwa Emmanuel , Kaywanga Frida , Buberwa Eliud , Solomon David , Christopher Heavenlight , Ngowi Doreen , Johansen Julieth , Urio Florence , Mgaya Josephine , Karim Salman , Alimohamed Mohamed Zahir , Sangeda Raphael Z. , Chamba Clara , Chimusa Emile R. , Novelli Enrico , Makani Julie
Published: July 2024

Background

Pharmacogenomics of hydroxyurea is an important aspect in the management of sickle cell disease (SCD), especially in the era of genomic medicine. Genetic variations in loci associated with HbF induction and drug metabolism are prime targets for hydroxyurea (HU) pharmacogenomics, as these can significantly impact the therapeutic efficacy and safety of HU in SCD patients.

Methods

This study involved designing of a custom panel targeting BCL11A, ARG2, HBB, HBG1, WAC, HBG2, HAO2, MYB, SAR1A, KLF10, CYP2C9, CYP2E1 and NOS1 as potential HU pharmacogenomics targets. These genes were selected based on their known roles in HbF induction and HU metabolism. The panel was designed using the Illumina Design Studio (Illumina, San Diego, CA, USA) and achieved a total coverage of 96% of all genomic targets over a span of 51.6 kilobases (kb). This custom panel was then sequenced using the Illumina MiSeq platform to ensure high coverage and accuracy.

Results

We are reporting a successfully designed Illumina (MiSeq) HU pharmacogenomics custom panel encompassing 51.6 kilobases. The designed panel achieved greater than 1000x amplicon coverage which is sufficient for genomic analysis.

Conclusions

This study provides a valuable tool for research in HU pharmacogenomics, especially in Africa where SCD is highly prevalent, and personalized medicine approaches are crucial for improving patient outcomes. The custom-designed Illumina (MiSeq) panel, with its extensive coverage and high sequencing depth, provides a robust platform for studying genetic variations associated with HU response. This panel can contribute to the development of tailored therapeutic strategies, ultimately enhancing the management of SCD through more effective and safer use of hydroxyurea.
The association between serum phosphate and length of hospital stay and all-cause mortality in adult patients: a cross-sectional study
Authors: Zhou Yiquan , Zhang Shuyi , Chen Zhiqi , Zhang Xiaomin , Feng Yi , Xu Renying
Published: July 2024

Background

Data is limited on the prevalence of hypophosphatemia in general hospitalized patients, and its association with length of hospital stay (LOS) and mortality remained unclear. We aimed to investigate the prevalence of admission phosphate abnormality and the association between serum phosphate level and length of hospital stay and all-cause mortality in adult patients.

Methods

This was a multi-center retrospective study based on real-world data. Participants were classified into five groups according to serum phosphate level (inorganic phosphorus, iP) within 48 h after admission: G1, iP < 0.64 mmol/L; G2, iP 0.64–0.8 mmol/L; G3, iP 0.8–1.16 mmol/L; G4, iP 1.16–1.45 mmol/L; and G5, iP ≥ 1.45 mmol/L, respectively. Both LOS and in-hospital mortality were considered as outcomes. Clinical information, including age, sex, primary diagnosis, co-morbidity, and phosphate-metabolism related parameters, were also abstracted from medical records.

Results

A total number of 23,479 adult patients (14,073 males and 9,406 females, aged 57.7 ± 16.8 y) were included in the study. The prevalence of hypophosphatemia was 4.74%. An “L-shaped” non-linear association was determined between serum phosphate level and LOS and the inflection point was 1.16 mmol/L in serum phosphate level. Compared with patients in G4, patients in G1, G2 or G3 were significantly associated with longer LOS after full adjustment of covariates. Each 0.1 mmol/L decrease in serum phosphate level to the left side of the inflection point led to 0.64 days increase in LOS [95% confidence interval (CI): 0.46, 0.81; p for trend < 0.001]. But there was no association between serum phosphate and LOS where serum levels of phosphate ≥ 1.16 mmol/L. Multivariable logistic regression analysis showed that adjusted all-cause in-hospital mortality was 3.08-fold greater in patients in G1 than those in G4 (95% CI: 1.52, 6.25; p for trend = 0.001). Similarly, no significant association with either LOS or mortality were found in patients in G5, comparing with G4.

Conclusions

Hypophosphatemia, but not hyperphosphatemia, was associated with LOS and all-cause mortality in adult inpatients. It is meaningful to monitor serum levels of phosphate to facilitate early diagnosis and intervention.
Bone marrow fibrosis in newly diagnosed multiple myeloma and its correlation with clinicopathological factors
Authors: Hu Xiumei , Dai Xiangyang , Guo Xinmeng , Jiang Xingran , Li Yunlong , Zhao Hongying , Lu Jun , Li Xue , Jin Mulan
Published: July 2024

Background

Bone marrow fibrosis (BMF) severely impacts both the quality of life and the efficacy of diagnostic procedures. However, the correlation between BMF and clinicopathological features, cytogenetic changes, and prognosis of newly diagnosed multiple myeloma (NDMM) remains unclear. This study determined the incidence, patient characteristics, and clinical outcomes of patients with NDMM with BMF.

Methods

The clinical data, histological features, and clinical outcomes of patients with NDMM were collected. Reticular fiber staining was performed on the enrolled cases, and the degree of reticular fiber overgrowth was graded. Patients with MF-2 and MF-3 were classified as the BMF+ group, and those with MF-0 and MF-1 were classified as the BMF- group, and BMF incidence was calculated. The differences in clinical data, histological features, and clinical outcomes between the BMF+ group and the BMF– group were compared.

Results

A consecutive series of 146 patients with NDMM were included. The incidence of MF-0, MF-1, MF-2, and MF-3 was 7.53% (11/146), 34.93% (51/146), 51.37% (75/146), and 6.16% (9/146), respectively. The incidence of BMF—MF-2 and MF-3—was 57.53% (84/146). A significant correlation was identified between the pattern of infiltration and BMF (P < 0.001). In the BMF- group, the distribution of cases with interstitial, nodular, and diffuse infiltration of plasma cells was 16 (25.8%), 21 (33.9%), and 25 (40.3%), respectively. Conversely, in the BMF+ group, these values for interstitial, nodular, and diffuse tumor cells were 9 (10.7%), 15 (17.9%), and 60 (71.4%). Furthermore, BMF was associated with a diffuse infiltration pattern. The overall survival (OS) of the BMF+ group (39.1 months; 95% confidence interval [CI]: 34.0–44.3) was lower than that of the BMF- group (45.4 months; 95% CI: 39.5–51.3), but there was no significant difference between the two groups (P = 0.221). Univariate and multivariate analyses showed that the BMF+ status was not associated with OS in patients with NDMM (P = 0.381 and P = 0.748, respectively).

Conclusions

Our findings suggest that BMF is linked to a diffuse infiltration pattern, and its occurrence is not related to the prognosis of patients with NDMM, providing a basis for further exploring the BMF value in NDMM diagnosis and treatment.
FIFA 11+ KIDS in the prevention of soccer injuries in children: a systematic review
Authors: Ramos Ana Paula , de Mesquita Raphael Schmidt , Migliorini Filippo , Maffulli Nicola , Okubo Rodrigo
Published: July 2024

Background

The “FIFA 11+” is an injury prevention program conceived for soccer athletes aged over 14. The use of FIFA 11+ Kids in soccer was associated with a reduction of the overall risk of injuries in children by 48%, and of 74% for serious injuries. However, to the best of our knowledge, a systematic review of the literature on the effects of FIFA 11+ Kids is still missing. Therefore, a systematic review was conducted to ascertain the benefits of the “FIFA 11+ KIDS” program in children who practice soccer.

Methods

This systematic review was conducted according to the PRISMA recommendations and prospectively registered in PROSPERO. The electronic search was conducted in the following databases: Web of Science, PubMed, Medline via Ovid, EMBASE and SportDiscuss via EBSCO. Database searches were performed in January 2024. This review included studies that evaluated the effects of the “FIFA 11+ KIDS” program. Eligible studies had to describe program implementation and the mean age of the children.

Results

A total of 11 articles were included in this systematic review from a pool of 8513 articles screened across various databases. These articles involved over 10,000 young participants from 8 countries, primarily aged 7–14 years, with the majority being soccer athletes. Study quality varied, with four categorized as high, four as good, and three as fair quality. Objectives varied across studies, with four focusing on FIFA 11+ Kids' efficacy in injury prevention, five examining its impact on performance and physical abilities, and two assessing its effects on children's focus and attention skills. Notably, injury prevention studies reported around a 50% reduction in overall injuries and nearly 60% in severe injuries, with a dose–response relationship observed with increased weekly sessions. Significant improvements were noted in physical and functional tests such as the Y balance, jump tests, and various soccer skills, along with positive effects on children's focus and attention, as indicated by 13–18% improvements in Attention Scale for Elementary School Children (ASESC) scores.

Conclusion

The FIFA 11+ KIDS injury prevention program appears to be effective in reducing injuries in young football players. This can positively influence player and team overall performance and might support the long-term athlete development of these young athletes. These findings highlight the importance and necessity of injury prevention in young athletes.
Osteointegration of functionalised high-performance oxide ceramics: imaging from micro-computed tomography
Authors: Migliorini Filippo , Eschweiler Jörg , Betsch Marcel , Maffulli Nicola , Tingart Markus , Hildebrand Frank , Lecouturier Sophie , Rath Björn , Schenker Hanno
Published: July 2024

Background

This study evaluated the osseointegration potential of functionalised high-performance oxide ceramics (HPOC) in isolation or coated with BMP-2 or RGD peptides in 36 New Zeeland female rabbits using micro-computed tomography (micro CT). The primary outcomes of interest were to assess the amount of ossification evaluating the improvement in the bone volume/ total volume (BV/TV) ratio and trabecular thickness at 6 and 12 weeks. The second outcome of interest was to investigate possible differences in osteointegration between the functionalised silanised HPOC in isolation or coated with Bone Morphogenetic Protein 2 (BMP-2) or RGD peptides.

Methods

36 adult female New Zealand white rabbits with a minimum weight of three kg were used. One-third of HPOCs were functionalised with silicon suboxide (SiOx), a third with BMP-2 (sHPOC-BMP2), and another third with RGD (sHPOC-RGD). All samples were scanned with a high-resolution micro CT (U-CTHR, MILabs B.V., Houten, The Netherlands) with a reconstructed voxel resolution of 10 µm. MicroCT scans were reconstructed in three planes and processed using Imalytics Preclinical version 2.1 (Gremse-IT GmbH, Aachen, Germany) software. The total volume (TV), bone volume (BV) and ratio BV/TV were calculated within the coating area.

Results

BV/TV increased significantly from 6 to 12 weeks in all HPOCs: silanised (P = 0.01), BMP-2 (P < 0.0001), and RGD (P < 0.0001) groups. At 12 weeks, the BMP-2 groups demonstrated greater ossification in the RGD (P < 0.0001) and silanised (P = 0.008) groups. Trabecular thickness increased significantly from 6 to 12 weeks (P < 0.0001). At 12 weeks, BMP-2 promoted greater trabecular thickness compared to the silanised group (P = 0.07), although no difference was found with the RGD (P = 0.1) group.

Conclusion

Sinalised HPOC in isolation or functionalised with BMP-2 or RGD promotes in vivo osteointegration. The sinalised HOPC functionalised with BMP-2 demonstrated the greatest osseointegration.
Global health diplomacy in humanitarian action
Authors: Falqui Luca , Li Fangfang , Xue Yufeng
Published: July 2024

This commentary explores the intersection of Global Health Diplomacy (GHD) and humanitarian action within Fragility, Conflict, and Violence (FCV) contexts. It aims at addressing the multifaceted challenges faced by communities living in these environments, where a convergence of multiple factors, including over 110 active armed conflicts, creates complex emergencies impact on large populations globally. This commentary holds three primary significances: 1) it scrutinizes the profound and enduring health consequences of major humanitarian crises on last-mile populations, highlighting the pivotal role of health diplomacy for better navigating humanitarian challenges; 2) it advocates for a paradigm shift in humanitarian approaches, recognizing GHD’s potential in shaping international cooperation, building consensus on inclusive global health policies, and enabling more effective interventions; 3) it underscores the operational impact of health diplomacy, both at diplomatic tables and on the frontlines of humanitarian efforts. Through real-world cases such as the cholera outbreak in Yemen and the response to Ebola outbreaks in DRC, the paper illustrates how diplomatic dialogue can impact health outcomes in fragile settings.
The cross-talk between the macro and micro-environment in precursor lesions of pancreatic cancer leads to new and promising circulating biomarkers
Authors: Mottini Carla , Auciello Francesca Romana , Manni Isabella , Pilarsky Christian , Caputo Damiano , Caracciolo Giulio , Rossetta Alessandro , Di Gennaro Elena , Budillon Alfredo , Blandino Giovanni , Roca Maria Serena , Piaggio Giulia
Published: July 2024

Pancreatic cancer (PC) is a clinically challenging tumor to combat due to its advanced stage at diagnosis as well as its resistance to currently available therapies. The absence of early symptoms and known detectable biomarkers renders this disease incredibly difficult to detect/manage. Recent advances in the understanding of PC biology have highlighted the importance of cancer-immune cell interactions, not only in the tumor micro-environment but also in distant systemic sites, like the bone marrow, spleen and circulating immune cells, the so-called macro-environment. The response of the macro-environment is emerging as a determining factor in tumor development by contributing to the formation of an increasingly immunogenic micro-environment promoting tumor homeostasis and progression. We will summarize the key events associated with the feedback loop between thetumorimmunemicro-environment (TIME) and thetumorimmunemacroenvironment (TIMaE) in pancreatic precancerous lesions along with how it regulates disease development and progression. In addition, liquid biopsy biomarkers capable of diagnosing PC at an early stage of onset will also be discussed. A clearer understanding of the early crosstalk between micro-environment and macro-environment could contribute to identifying new molecular therapeutic targets and biomarkers, consequently improving early PC diagnosis and treatment.
Enzymatic hydrolysis of waste streams originating from wastewater treatment plants
Authors: Zarina Ruta , Mezule Linda
Published: July 2024

Background

Achieving climate neutrality is a goal that calls for action in all sectors. The requirements for improving waste management and reducing carbon emissions from the energy sector present an opportunity for wastewater treatment plants (WWTPs) to introduce sustainable waste treatment practices. A common biotechnological approach for waste valorization is the production of sugars from lignocellulosic waste biomass via biological hydrolysis. WWTPs produce waste streams such as sewage sludge and screenings which have not yet been fully explored as feedstocks for sugar production yet are promising because of their carbohydrate content and the lack of lignin structures. This study aims to explore the enzymatic hydrolysis of various waste streams originating from WWTPs by using a laboratory-made and a commercial cellulolytic enzyme cocktail for the production of sugars. Additionally, the impact of lipid and protein recovery from sewage sludge prior to the hydrolysis was assessed.

Results

Treatment with a laboratory-made enzyme cocktail produced by Irpex lacteus (IL) produced 31.2 mg sugar per g dry wastewater screenings. A commercial enzyme formulation released 101 mg sugar per g dry screenings, corresponding to 90% degree of saccharification. There was an increase in sugar levels for all sewage substrates during the hydrolysis with IL enzyme. Lipid and protein recovery from primary and secondary sludge prior to the hydrolysis with IL enzyme was not advantageous in terms of sugar production.

Conclusions

The laboratory-made fungal IL enzyme showed its versatility and possible application beyond the typical lignocellulosic biomass. Wastewater screenings are well suited for valorization through sugar production by enzymatic hydrolysis. Saccharification of screenings represents a viable strategy to divert this waste stream from landfill and achieve the waste treatment and renewable energy targets set by the European Union. The investigation of lipid and protein recovery from sewage sludge showed the challenges of integrating resource recovery and saccharification processes.
A new magnetic resonance imaging-based PUMCH classification system for congenital cervical malformations: devising a standardised diagnosis pathway
Authors: Yuan Zhi-Lin , Ren Jing , Huang Meng-Lin , Qi Ya-Fei , Gao Xin , Sun Yi-Ying , He Yong-Lan , Zhu Lan , Xue Hua-Dan
Published: July 2024

Objectives

To develop an innovative magnetic resonance imaging (MRI)-based PUMCH (Peking Union Medical College Hospital) classification system aimed at standardising the diagnosis of congenital cervical malformations (CCMs) by identifying their distinctive MRI features.

Methods

Seventy-nine consecutive patients with CCM underwent pre-treatment pelvic MRI; three experienced gynaecological radiologists retrospectively analysed these images. Qualitative assessments included Rock et al’s classification; PUMCH classification; haematometra; cervical signal features; ovarian endometriosis; haematosalpinx; and uterine, vaginal, urinary, and musculoskeletal malformations. Quantitative assessments involved the uterine volume, sagittal cervical length, and maximum ovarian cross-sectional area. The surgical treatment types were also recorded. Statistical methods were used to incorporate differences in clinical features and surgical methods into our classification.

Results

Morphologically, CCMs were categorised into three types: type I (53%) was characterised by the presence of a cervix with visible cervical canals; type II (23%) featured an existing cervix with concealed cervical canals; and type III (24%) indicated cervical aplasia, which involves a blind end in the lower part of the uterine corpus. Haematometra was significantly more prevalent in patients with type I CCM than in those with type II (p < 0.001). There were three cervical signal patterns: no signal (27%), no evident layer differentiation (21%), and multi-layer differentiation with haematocele (52%). Most patients (94%) had complete vaginal atresia. Type I CCM patients had a higher likelihood of regaining normal uterovaginal anatomy compared to types II and III.

Conclusions

Our proposed PUMCH classification system has a high potential for enhancing the efficiency of clinical diagnosis among patients with CCM.

Critical relevance statement

The proposed new PUMCH classification promised to elevate the conventional diagnostic trajectory for congenital cervical malformations, offering a valuable framework to refine the selection and planning of surgical interventions, thereby enhancing overall clinical efficacy.

Key Points

Effective classification of congenital cervical malformations is desirable to optimise the diagnostic process.

We presented a PUMCH classification of congenital cervical malformations using pelvic MRI.

The new classification significantly aids clinical triage for congenital cervical malformations.

Graphical Abstract
Benign and malignant focal liver lesions displaying rim arterial phase hyperenhancement on CT and MRI
Authors: Matteini Francesco , Cannella Roberto , Garzelli Lorenzo , Dioguardi Burgio Marco , Sartoris Riccardo , Brancatelli Giuseppe , Vilgrain Valérie , Ronot Maxime , Vernuccio Federica
Published: July 2024

Rim arterial phase hyperenhancement is an imaging feature commonly encountered on contrast-enhanced CT and MRI in focal liver lesions. Rim arterial phase hyperenhancement is a subtype of arterial phase hyperenhancement mainly present at the periphery of lesions on the arterial phase. It is caused by a relative arterialization of the periphery compared with the center of the lesion and needs to be differentiated from other patterns of peripheral enhancement, including the peripheral discontinuous nodular enhancement and the corona enhancement. Rim arterial phase hyperenhancement may be a typical or an atypical imaging presentation of many benign and malignant focal liver lesions, challenging the radiologists during imaging interpretation. Benign focal liver lesions that may show rim arterial phase hyperenhancement may have a vascular, infectious, or inflammatory origin. Malignant focal liver lesions displaying rim arterial phase hyperenhancement may have a vascular, hepatocellular, biliary, lymphoid, or secondary origin. The differences in imaging characteristics on contrast-enhanced CT may be subtle, and a multiparametric approach on MRI may be helpful to narrow the list of differentials. This article aims to review the broad spectrum of focal liver lesions that may show rim arterial phase hyperenhancement, using an approach based on the benign and malignant nature of lesions and their histologic origin.

Critical relevance statement

Rim arterial phase hyperenhancement may be an imaging feature encountered in benign and malignant focal liver lesions and the diagnostic algorithm approach provided in this educational review may guide toward the final diagnosis.

Key Points

Several focal liver lesions may demonstrate rim arterial phase hyperenhancement.

Rim arterial phase hyperenhancement may occur in vascular, inflammatory, and neoplastic lesions.

Rim arterial phase hyperenhancement may challenge radiologists during image interpretation.

Graphical Abstract
Optimization strategies for mesenchymal stem cell-based analgesia therapy: a promising therapy for pain management
Authors: Zhang Jing , Wu Ping , Wen Qingping
Published: July 2024

Pain is a very common and complex medical problem that has a serious impact on individuals’ physical and mental health as well as society. Non-steroidal anti-inflammatory drugs and opioids are currently the main drugs used for pain management, but they are not effective in controlling all types of pain, and their long-term use can cause adverse effects that significantly impair patients’ quality of life. Mesenchymal stem cells (MSCs) have shown great potential in pain treatment. However, limitations such as the low proliferation rate of MSCs in vitro and low survival rate in vivo restrict their analgesic efficacy and clinical translation. In recent years, researchers have explored various innovative approaches to improve the therapeutic effectiveness of MSCs in pain treatment. This article reviews the latest research progress of MSCs in pain treatment, with a focus on methods to enhance the analgesic efficacy of MSCs, including engineering strategies to optimize the in vitro culture environment of MSCs and to improve the in vivo delivery efficiency of MSCs. We also discuss the unresolved issues to be explored in future MSCs and pain research and the challenges faced by the clinical translation of MSC therapy, aiming to promote the optimization and clinical translation of MSC-based analgesia therapy.

Graphical Abstract
Mesenchymal stem cells-derived extracellular vesicles ameliorate lupus nephritis by regulating T and B cell responses
Authors: Li Cuifang , Wu Feifeng , Mao Jueyi , Wang Yang , Zhu Junquan , Hong Kimsor , Xie Haotian , Zhou Xin , Tian Jidong , Wen Chuan
Published: July 2024

Background

Human umbilical cord mesenchymal stem cells-derived extracellular vesicles (hUCMSC-EVs) have potent immunomodulatory properties similar to parent cells. This study investigated the therapeutic effects and immunomodulatory mechanisms of hUCMSC-EVs in an experimental lupus nephritis model.

Methods

The hUCMSC-EVs were isolated by using differential ultracentrifugation. In vivo, the therapeutic effects of hUCMSC-EVs in lupus-prone MRL/lpr mice were investigated, and the mechanisms of treatment were explored according to the abnormal T and B cell responses among both the spleen and kidney.

Results

MRL/lpr mice treated with hUCMSC-EVs reduced proteinuria extent, serum creatinine and renal pathological damage; decreased splenic index and serum anti-dsDNA IgG level; and improved survival rate. hUCMSC-EVs lowered the percentage of T helper (Th)1 cells, double-negative T (DNT) cells, and plasma cells among splenocytes; inhibited the infiltration of Th17 cells but promoted regulatory T (Treg) cells in the kidney, followed by a reduction in pro-inflammatory cytokine levels(IFN-γ, IL-2, IL-6, IL-21, and IL-17 A). In addition, hUCMSC-EVs inhibited the activation of STAT3 and down-regulated IL-17 A protein levels in the kidney.

Conclusion

The results of this study demonstrated that hUCMSC-EVs had therapeutic effects on experimental lupus nephritis (LN) by regulating Th1/Th17/Treg imbalance and inhibiting DNT and plasma cells. Additionally, hUCMSC-EVs inhibited Th17 cell differentiation in kidney by regulating the IL-6/STAT3/IL-17 signal pathway, which might be an important mechanism for alleviating renal injury. Taken together, we demonstrated that hUCMSC-EVs regulating T and B cell immune responses might represent a novel mechanism of hUCMSCs in treating LN, thus providing a new strategy for treating LN.
[68Ga]Ga-FAPI versus 2-[18F]FDG PET/CT in patients with autoimmune thyroiditis: a case control study
Authors: Pabst Kim M. , Kessler Lukas , Ferdinandus Justin , Hamacher Rainer , Bartel Timo , Siveke Jens T. , Nader Michael , Brandenburg Tim , Desaulniers Mélanie , Herrmann Ken , Fendler Wolfgang P.
Published: July 2024

Purpose

Radiolabelled fibroblast activation protein inhibitors (FAPIs) are becoming increasingly important for imaging various tumour diseases. However, it is essential to be aware of potential pitfalls. Here, we investigate FAP expression in the thyroid gland in autoimmune thyroiditis (AIT).

Methods

AIT patients with pathological thyroid uptake on [68Ga]Ga-FAPI PET were compared with glucose metabolism on 2-[18F]FDG PET in terms of SUVmax/SUVpeak/SUVmean/tissue-to-background ratio (TBR), and with a healthy control group.

Results

Between September 2019 and July 2021, 6 patients presented with a visually increased thyroid uptake and TBR on [68Ga]Ga-FAPI PET. In the retrospective clinical work-up, all patients had known or newly diagnosed AIT. Compared to a matched healthy control group, FAP expression and glucose metabolism were significantly increased ([68Ga]Ga-FAPI (SUVpeak): 7.0 vs. 1.7; p = 0.004/(TBRbloodpool): 6.8 vs. 1.7; p = 0.002; 2-[18F]FDG (SUVpeak): 3.9 vs. 1.4; p = 0.004/(TBRbloodpool): 4.0 vs. 1.2; p = 0.041). However, there was no significant difference in median uptake between [68Ga]Ga-FAPI and 2-[18F]FDG PET (SUVpeak: 7.3 vs. 5.6; p = 0.104).

Conclusion

Patients with AIT show higher thyroid uptake on [68Ga]Ga-FAPI and 2-[18F]FDG PET. Incidental thyroid uptake is another pitfall in the interpretation of [68Ga]Ga-FAPI PET and should prompt a clinical work-up.
Has China’s hierarchical medical system improved doctor-patient relationships?
Authors: Gao Yang , Yang Yang , Wang Shoupeng , Zhang Wenqian , Lu Jiao
Published: July 2024

Background and objective

Developing harmonious doctor-patient relationships is a powerful way to promote the construction of a new pattern of medical reform in developing countries. We aim to analyze the effects of China’s hierarchical medical system on doctor-patient relationships, thus contributing to China’s medical and health system reform.

Methods

With panel data on prefectural-level cities in China from 2012 to 2019, we used a time-varying difference-in-differences model to evaluate the effect of hierarchical medical treatment policy.

Results

Hierarchical medical treatment policies can significantly improve doctor-patient relationships, and this conclusion is supported by various robustness tests. And improving doctor-patient relationships can be indirectly realized by the optimization of resource allocation and saving of medical costs. In addition, the marginal effect of the pilot policy on doctor-patient relationships decreased with age within the city population. In focal cities and cities with high levels of fiscal spending on health care, the effect of the pilot policy on doctor-patient relationships was stronger.

Conclusion

While reinforcing the literature on the doctor-patient relationship, this study also provides a reference for further exploration of the pilot policy of hierarchical medical treatment and the development of new medical and health system reform in developing countries.
Integrative analysis of bulk and single-cell RNA sequencing reveals the gene expression profile and the critical signaling pathways of type II CPAM
Authors: Li Fengxia , Tan Zheng , Chen Hongyu , Gao Yue , Xia Jie , Huang Ting , Liang Liang , Zhang Jian , Zhang Xianghong , Shi Xucong , Chen Qiang , Shu Qiang , Yu Lan
Published: July 2024

Backgroud

Type II congenital pulmonary airway malformation (CPAM) is a rare pulmonary microcystic developmental malformation. Surgical excision is the primary treatment for CPAM, although maternal steroids and betamethasone have proven effective in reducing microcystic CPAM. Disturbed intercellular communication may contribute to the development of CPAM. This study aims to investigate the expression profile and analyze intercellular communication networks to identify genes potentially associated with type II CPAM pathogenesis and therapeutic targets.

Methods

RNA sequencing (RNA-seq) was performed on samples extracted from both the cystic area and the adjacent normal tissue post-surgery in CPAM patients. Iterative weighted gene correlation network analysis (iWGCNA) was used to identify genes specifically expressed in type II CPAM. Single-cell RNA-seq (scRNA-seq) was integrated to unveil the heterogeneity in cell populations and analyze the communication and interaction within epithelial cell sub-populations.

Results

A total of 2,618 differentially expressed genes were identified, primarily enriched in cilium-related biological process and inflammatory response process. Key genes such as EDN1, GPR17, FPR2, and CHRM1, involved in the G protein-coupled receptor (GPCR) signaling pathway and playing roles in cell differentiation, apoptosis, calcium homeostasis, and the immune response, were highlighted based on the protein-protein interaction network. Type II CPAM-associated modules, including ciliary function-related genes, were identified using iWGCNA. By integrating scRNA-seq data, AGR3 (related to calcium homeostasis) and SLC11A1 (immune related) were identified as the only two differently expressed genes in epithelial cells of CPAM. Cell communication analysis revealed that alveolar type 1 (AT1) and alveolar type 2 (AT2) cells were the predominant communication cells for outgoing and incoming signals in epithelial cells. The ligands and receptors between epithelial cell subtypes included COLLAGEN genes enriched in PI3K-AKT singaling and involved in epithelial to mesenchymal transition.

Conclusions

In summary, by integrating bulk RNA-seq data of type II CPAM with scRNA-seq data, the gene expression profile and critical signaling pathways such as GPCR signaling and PI3K-AKT signaling pathways were revealed. Abnormally expressed genes in these pathways may disrupt epithelial-mesenchymal transition and contribute to the development of CPAM. Given the effectiveness of prenatal treatments of microcystic CPAM using maternal steroids and maternal betamethasone administration, targeting the genes and signaling pathways involved in the development of CPAM presents a promising therapeutic strategy.
A qualitative, multi-centre approach to the current state of digitalisation and automation of surveillance in infection prevention and control in German hospitals
Authors: Eisenmann Michael , Spreckelsen Cord , Rauschenberger Vera , Krone Manuel , Kampmeier Stefanie
Published: July 2024

Background

Healthcare associated infections (HAI) pose a major threat to healthcare systems resulting in an increased burden of disease. Surveillance plays a key role in rapidly identifying these infections and preventing further transmissions. Alas, in German hospitals, the majority of surveillance efforts have been heavily relying on labour intensive processes like manual chart review. In order to be able to identify further starting points for future digital tools and interventions to aid the surveillance of HAI we aimed to gain an understanding of the current state of digitalisation in the context of the general surveillance organisation in German clinics across all care-levels. The end user perspective of infection prevention and control (IPC) professionals was chosen to identify digital interventions that have the biggest impact on the daily surveillance work routines of IPC professionals. Perceived impediments in the advancement of surveillance digitalisation should be explored.

Methods

Following the development of an interview guideline, eight IPC professionals from seven German hospitals of different care levels were questioned in semi- structured interviews between December 2022 and January 2023. These included questions about general surveillance organisation, access to digital data sources, software to aid the surveillance process as well as current issues in the surveillance process and implementation of software systems. Subsequently, after full transcription, the interview sections were categorized in code categories (first deductive then inductive coding) and analysed qualitatively.

Results

Results were characterised by high heterogeneity in terms of general surveillance organisation and access to digital data sources. Software configuration of hospital and laboratory information systems (HIS/LIS) as well as patient data management systems (PDMS) varied not only between hospitals of different care levels but also between hospitals of the same care level. Outside research projects, neither fully automatic software nor solutions utilising artificial intelligence have currently been implemented in clinical routine in any of the hospitals.

Conclusions

Access to digital data sources and software is increasingly available to aid surveillance of HAI. Nevertheless, surveillance processes in hospitals analysed in this study still heavily rely on manual processes. In the analysed hospitals, there is an implementation and funding gap of (semi-) automatic surveillance solutions in clinical practice, especially in healthcare facilities of lower care levels.
Longitudinal associations between family functioning and generalized anxiety among adolescents: the mediating role of self-identity and cognitive flexibility
Authors: Ma Ran , Zhang Qian , Zhang Chunyang , Xu Wei
Published: July 2024

Background

Generalized anxiety (GA) is showing a high prevalence among adolescents nowadays; investigations on influencing factors and potential mechanisms are important to inform intervention development. The present two-wave study investigated the ways in which family functioning predicted GA six months later among adolescents, by considering the mediating role of self-identity and cognitive flexibility.

Methods

Adolescents were recruited from 27 randomly selected classes in two secondary schools in Chongqing and Fujian Province, China. Survey questionnaires assessing family functioning, self-identity, cognitive flexibility and GA were obtained from 1223 adolescents (Mage = 13.14, SD = 1.35) at two time points of the 6-month interval.

Results

The association between family functioning (T1) and GA (T2) was significant (r= -0.152, p < 0.01). Self-identity and cognitive flexibility sequentially mediated the relationship between family functioning (T1) and GA (T2) (with the indirect effect = -0.005, 95% CI = -0.007~ -0.002) after controlling for age, gender, and GA at baseline. Cognitive flexibility also showed a significant and direct mediating effect (with the indirect effect = -0.008, 95% CI = -0.012 ~ -0.005).

Conclusion

Findings indicated that family functioning can be a protective factor of GA, and self-identity and cognitive flexibility act as a crucial role in the association between family functioning and GA. Future studies should adopt more time points and long-term follow-up assessments using more robust approaches to improve the reliability of the study findings. Findings may offer some implications that building a harmonious, open and warm family and guiding adolescents to develop self-identity as well as more flexible cognitive style could be helpful to prevent and cope with anxious emotion.