bluuebunny/crossref_metadata_2025 huggingface dataset:
Arthroscopic capsular release is more effective in pain relief than conservative treatment in patients with frozen shoulder
Authors: Skaliczki Gábor , Kovács Krisztián , Antal Imre , Sallai Imre , Kovács Beáta , Nyőgér Zoltán , Géresi Áron , Kiss Balázs , Várnagy Anna
Published: February 2024

Background

Frozen shoulder is a common medical condition, but the ideal therapeutic method is yet to be determined. Our aim was to analyze the pain-relieving effect of different treatment options used for the management of this disease.

Methods

Medical records of 59 patients (22 male, 37 female, average age: 55.5 years ±9.9) with early stage primary frozen shoulder were evaluated, their demographic data, physical examination, concomitant diseases and treatment specific data were registered. Life quality and the level of pain were assessed using the Oxford Shoulder Score (OSS) and Numeric Rating Scale (NRS). Different treatment modalities and their effect on pain relief were recorded. Any existing correlation between life quality, pain and demographic data, concomitant diseases or the therapeutic method used was investigated.

Results

The level of pain measured on NRS improved from 7.9 ± 1.6 to 1.9 ± 2.2. The most effective therapeutic method in terms of pain relief was surgery, followed by physiotherapy and intraarticular steroid injection (NRS score after treatment: 2 - p < 0.0001; 3.3 - p < 0.0001; 4.9 - p < 0.0001, respectively). Non-steroidal anti-inflammatory drugs (NSAIDs) did not reduce pain significantly. OSS improved from 24 to 43.6 and was not affected by the investigated variables, time to recovery was not influenced by the demographic data, the type of treatment or concomitant diseases.

Conclusions

Arthroscopic capsular release, physiotherapy and intraarticular steroid injection outperformed physical therapy and NSAID treatment in terms of pain relief. Despite of slight but persistent post-therapeutic pain found in half of the cases, treatment was considered satisfactory by the patients. Nor patient specific neither therapy specific data had a significant effect on the course of the disease.
Values of multiparametric and biparametric MRI in diagnosing clinically significant prostate cancer: a multivariate analysis
Authors: Feng Xiao , Chen Xin , Peng Peng , Zhou He , Hong Yi , Zhu Chunxia , Lu Libing , Xie Siyu , Zhang Sijun , Long Liling
Published: February 2024

Background

To investigate the value of semi-quantitative and quantitative parameters (PI-RADS score, T2WI score, ADC, Ktrans, and Kep) based on multiparametric MRI (mpMRI) or biparametric MRI (bpMRI) combined with prostate specific antigen density (PSAD) in detecting clinically significant prostate cancer (csPCa).

Methods

A total of 561 patients (276 with csPCa; 285 with non-csPCa) with biopsy-confirmed prostate diseases who underwent preoperative mpMRI were included. Prostate volume was measured for calculation of PSAD. Prostate index lesions were scored on a five-point scale on T2WI images (T2WI score) and mpMRI images (PI-RADS score) according to the PI-RADS v2.1 scoring standard. DWI and DCE-MRI images were processed to measure the quantitative parameters of the index lesion, including ADC, Kep, and Ktrans values. The predictors of csPCa were screened by logistics regression analysis. Predictive models of bpMRI and mpMRI were established. ROC curves were used to evaluate the efficacy of parameters and the model in diagnosing csPCa.

Results

The independent diagnostic accuracy of PSA density, PI-RADS score, T2WI score, ADCrec, Ktrans, and Kep for csPCa were 80.2%, 89.5%, 88.3%, 84.6%, 58.5% and 61.6%, respectively. The diagnostic accuracy of bpMRI T2WI score and ADC value combined with PSAD was higher than that of PI-RADS score. The combination of mpMRI PI‑RADS score, ADC value with PSAD had the highest diagnostic accuracy.

Conclusions

PI-RADS score according to the PI-RADS v2.1 scoring standard was the most accurate independent diagnostic index. The predictive value of bpMRI model for csPCa was slightly lower than that of mpMRI model, but higher than that of PI-RADS score.
Cervical cancer screening program in Indonesia: is it time for HPV-DNA tests? Results of a qualitative study exploring the stakeholders’ perspectives
Authors: Ekawati Fitriana Murriya , Listiani Putri , Idaiani Sri , Thobari Jarir At , Hafidz Firdaus
Published: February 2024

Objectives

Cervical cancer is a significant public health concern in Indonesia, and effective screening methods are necessary to improve the detection and reduce mortality. This study aimed to explore the perspectives of high-level stakeholders involved in cervical cancer screening in Indonesia and whether the use of human papillomavirus-deoxyribonucleic acid (HPV-DNA) methods for cervical cancer screening is acceptable in Indonesian settings.

Methods

A qualitative research approach guided by realist evaluation was applied using focus group discussions (FGDs) between December 2021 and February 2022, conducted with stakeholders involved in cervical cancer screening in Indonesia. They were representatives of practitioners and policymakers involved in the screening, and were recruited through purposive recruitment. The data were analysed using inductive approach of thematic analysis.

Results

The analysis of two FGDs with 29 participants identified four main themes: (i) Visual inspection with acetic acid (VIA) method as the most common modality used for cervical cancer screening, (ii) the applied screening programs in the community, (iii) the perceived challenges on the screening program, such as limitations of the National Health Insurance benefits package and a lack of regulations regarding screening procedures, and (iv) the possibilities of HPV-DNA testing as another modality for cervical cancer screening. Incorporating HPV-DNA testing also needs to ensure the capacity of the workers and the readiness of healthcare facilities.

Conclusion

Although HPV-DNA testing is a promising modality, challenges on the cervical cancer screening in Indonesia remain on the coverage, accessibility of the tools in practice and the women’s awareness towards the screening. Ultimately, the findings of this study would help inform policies to improve cervical cancer screening programs in Indonesia.
Sequential embryo transfer combined with intrauterine perfusion improved pregnancy outcomes in patients with recurrent implantation failure
Authors: Zou Wenda , Liu Dan , Peng Juan , Tang Zhijing , Li Yukun , Zhang Juan , Liu Ziwei
Published: February 2024

Objective

To compare the application of sequential embryo transfer, cleavage embryo transfer, and blastocyst transfer combined with intrauterine perfusion in frozen–thawed embryo transfer cycles in patients with recurrent implantation failure to provide a reference for reproductive clinicians.

Methods

The 166 patients who underwent frozen–thawed embryo transfer due to recurrent implantation failure in the reproductive center from January 2021 to March 2022 were retrospectively analyzed. According to the different embryos transferred, they were divided into cleavage embryo transfer groups (72 cases in Group A), blastocyst transfer group (29 cases in Group B), and sequential transfer group (65 cases in Group C). All three groups were treated with intrauterine perfusion 5 days before embryo transfer. The general data and clinical pregnancy outcome indicators, such as embryo implantation rate, clinical pregnancy rate, ongoing pregnancy rate, live birth rate, twin rate, were compared among the three groups.

Results

The embryo implantation rate (53.1%), clinical pregnancy rate (76.9%), ongoing pregnancy rate (67.7%) and live birth rate(66.15%) in the sequential transfer group were significantly higher than those in the other two groups (P < 0.05), and the ectopic pregnancy rate was lower in the sequential transfer group.

Conclusion

Sequential transfer combined with intrauterine perfusion partially improves clinical pregnancy outcomes and reduces the risk of ectopic pregnancy in frozen embryo cycle transfers in patients with recurrent implantation failure, which may be a favourable transfer reference strategy for patients with recurrent implantation failure.
Exploring the understanding and experience of women with rheumatic diseases regarding fertility intention- a qualitative content analysis
Authors: Manouchehri Elham , Larki Mona , Sahebari Maryam
Published: February 2024

Background

Patients with rheumatic diseases (RDs) have a lower desire to have children, fewer children, and a longer interval between their pregnancies, which can be due to the patient’s personal choice, the physician’s advice, changes in sexual activity, changes in fertility, and pregnancy failure. This study aimed to explore the understanding and experience of women with RDs regarding pregnancy intention.

Method

In Mashhad, Northeast Iran, between December 2022 and March 2023, this qualitative inquiry was carried out. Purposive sampling was used to select thirty women with RDs. Semi-structured interviews were used to collect the data. Graneheim and Lundman’s conventional content analysis method was used to analyze the data. The data organization was done using MAXQDA 12 software. Credibility, dependability, confirmability, and transferability have been considered as elements of trustworthiness.

Results

The participants’ data analysis revealed the following main theme: “duality of desire and fear in childbearing”. Five main categories were identified, including “Individual health concerns following pregnancy”, “motherhood and womanhood perceptions”, “concerns about child harm”, “contradictory beliefs and attitudes of significant family members and clinicians about pregnancy”, and “lack of social support for fertility”.

Conclusion

In order to improve the outcomes of pregnancy for women with RDs, the medical professionals who manage them must actively and frequently inquire about their intentions to childbearing and offer them individualized guidance on how to be in the best possible health at the time of conception. Rheumatologists, gynecologists, and reproductive health specialists can better address the sexual and reproductive health needs of this population by enhancing their collaboration in the care of women with RDs.
HPLC analysis, genotoxic and antioxidant potential of Achillea millefolium L. and Chaerophyllum villosum Wall ex. Dc
Authors: Adil Muhammad , Dastagir Ghulam , Quddoos Atifa , Naseer Muhammad , Filimban Faten Zubair
Published: February 2024

Background

Methanolic and chloroformic extract of Achillea millefolium and Chaerophyllum villosum were evaluated for HPLC analysis, genotoxic and antioxidant potential.

Materials and methods

Genotoxic activity was carried out on human blood lymphocytes via comet assay and antioxidant activity was studied through DPPH method.

Results

The genotoxic potential of A. millefolium and C. villosum’s methanolic and chloroformic extract was analysed using comet assay technique. Comet shaped human lymphocytes cells were observed when treated with different concentrations (50 mg/mL, 75 mg/mL, 100 mg/mL) of methanolic and chloroformic extract of both plants. Reading was taken on the basis of damaged DNA head and tail length. Greater the length of tail as compared to head, greater will be the damage and vice versa. Total comet score was obtained from A. millefolium subjected to different concentrations. After a time interval of 24 h both the extract showed dose dependant genoprotection with maximum genoprotectivity at 98.7 ± 12.7 and 116 ± 5.3 at 50 mg/100 mL for methanolic and chloroformic extract respectively. Similarly Total Comet score was obtained from C. villosum subjected to different concentrations of methanolic and chloroformic extract. After 24 h exhibited dose dependent genoprotection with maximum protectivity at 85.7 ± 22.0 and 101.7 ± 8.6 at 50 mg/100 mL for methanolic and chloroformic extract were determined. The antioxidant activity revealed that methanolic extract of A. millefolium showed highest antioxidant activity (84.21%) at 300 mg/ml after 90 min while the chloroformic extract of C. villosum exhibited highest (68.46%) antioxidant activity (59.69%) at 300 µg/ml after 90 min but less than the standard drug ascorbic acid (88.72%). Quantitative phytochemical screening revealed high percentage of alkaloids (27.4%), Phenols (34.5%), Flavonoids (32.4%) as compared to Tannins (12%) in methanolic extract of A.millefolium. While high percentage of alkaloids (31.4), Phenols (19.3%), Flavonoids (35.5%) as compared to Tannins (16.6%) in chloroformic extract of C. villosum.

Conclusion

The present results showed that A. millefolium and C. villosum possess a number of important compounds and revealed genoprotective property which may be used to treat several genetic disorders such as alzeimer’s disease in future (Grodzicki W, Dziendzikowska K, Antioxidants 9(3):229, 2020).
Development of propolis, hyaluronic acid, and vitamin K nano-emulsion for the treatment of second-degree burns in albino rats
Authors: Elsamman Marwan , El-borady Ola M. , Nasr Mohanad M. , Al-Amgad Zeinab , Metwally Asmaa A.
Published: February 2024

Burns are the fourth most common type of injury worldwide. Many patients also suffer numerous infections and complications that impair the burn healing process, which makes the treatment of burns a challenge. This study aimed to prepare and characterize nano-emulsion (NE) of propolis, hyaluronic acid, and vitamin K for treatment of second-degree burns. High-Pressure Liquid Chromatography (HPLC) was used for the qualitative assessment of the phenolic and flavonoid contents in crude propolis. The structural, optical, and morphological characterization, besides the antimicrobial, antioxidant, cytotoxicity, in-vitro, and in-vivo wound healing activities were evaluated. For in-vivo study, 30 adult male albino rats were divided randomly into control and treated groups, which were treated with normal saline (0.9%), and NE, respectively. The wounds were examined clinicopathologically on the 3rd, 7th, and 14th days. The NE revealed the formation of a mesh-like structure with a size range of 80–180 nm and a 21.6 ± 6.22 mV zeta potential. The IC50 of NE was 22.29 μg/ml. Also, the NE showed antioxidant and antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. The in-vitro investigation of the NE on normal human skin fibroblasts using scratch assay proved an acceleration for wound healing. The treated rats showed improved wound healing clinically and pathologically and wound contraction percent (WC %) was 98.13% at 14th day, also increased epithelization, fibrous tissue formation, collagen deposition, and angiogenesis compared to the control. It could be concluded that the prepared NE possesses antimicrobial, antioxidant, and healing effect in the treatment of second-degree burns.
Chemical composition, anticancer, antimicrobial activity of Aloysia citriodora Palau essential oils from four different locations in Palestine
Authors: Al-Maharik Nawaf , Salama Yousef , Al-Hajj Nisreen , Jaradat Nidal , Jobran Naji Thaer , Warad Ismael , Hamdan Lina , Alrob Moataz Abo , Sawafta Asil , Hidmi Adel
Published: February 2024

The primary aim of this investigation was to determine the anticancer and antimicrobial properties of essential oils (EOs) extracted from the leaves of Aloysia citriodora Palau, which were procured from four separate locations in Palestine, in addition to analyzing their chemical composition. These areas include Jericho, which has the distinction of being the lowest location on Earth, at 260 m below sea level. The EOs were acquired by hydrodistillation, and their chemical composition was examined utilizing gas chromatography-mass spectrometry (GC-MS). The minimum inhibitory concentration (MIC) of EOs was assessed against six bacterial strains and one fungal species using 96-well microtiter plates. The primary components found in these oils are geranial (26.32–37.22%), neral (18.38–29.00%), and α-curcumene (7.76–16.91%) in three regions. α-Curcumene (26.94%), spathulenol (13.69%), geranial (10.79%), caryophyllene oxide (8.66%), and neral (7.59%) were found to be the most common of the 32 chemical components in the EO from Jericho. The EOs exhibited bactericidal properties, particularly against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and showed highly effective fungicidal activity. Nevertheless, the antifungal efficacy of the EO was found to surpass its antibacterial activity when administered at lower dosages. The EOs exhibited anticancer activities against melanoma cancer cells, as indicated by their IC50 values, which ranged from 4.65 to 7.96 μg/mL. A. citriodora EO possesses substantial antifungal and anticancer characteristics, rendering it appropriate for utilization in food-related contexts, hence potentially enhancing the sustainability of the food sector.
Advanced patient-specific microglia cell models for pre-clinical studies in Alzheimer’s disease
Authors: Cuní-López Carla , Stewart Romal , Oikari Lotta E. , Nguyen Tam Hong , Roberts Tara L. , Sun Yifan , Guo Christine C. , Lupton Michelle K. , White Anthony R. , Quek Hazel
Published: February 2024

Background

Alzheimer’s disease (AD) is an incurable neurodegenerative disorder with a rapidly increasing prevalence worldwide. Current approaches targeting hallmark pathological features of AD have had no consistent clinical benefit. Neuroinflammation is a major contributor to neurodegeneration and hence, microglia, the brain’s resident immune cells, are an attractive target for potentially more effective therapeutic strategies. However, there is no current in vitro model system that captures AD patient-specific microglial characteristics using physiologically relevant and experimentally flexible culture conditions.

Methods

To address this shortcoming, we developed novel 3D Matrigel-based monocyte-derived microglia-like cell (MDMi) mono-cultures and co-cultures with neuro-glial cells (ReNcell VM). We used single-cell RNA sequencing (scRNAseq) analysis to compare the transcriptomic signatures of MDMi between model systems (2D, 3D and 3D co-culture) and against published human microglia datasets. To demonstrate the potential of MDMi for use in personalized pre-clinical strategies, we generated and characterized MDMi models from sixteen AD patients and matched healthy controls, and profiled cytokine responses upon treatment with anti-inflammatory drugs (dasatinib and spiperone).

Results

MDMi in 3D exhibited a more branched morphology and longer survival in culture compared to 2D. scRNAseq uncovered distinct MDMi subpopulations that exhibit higher functional heterogeneity and best resemble human microglia in 3D co-culture. AD MDMi in 3D co-culture showed altered cell-to-cell interactions, growth factor and cytokine secretion profiles and responses to amyloid-β. Drug testing assays revealed patient- and model-specific cytokine responses.

Conclusion

Our study presents a novel, physiologically relevant and AD patient-specific 3D microglia cell model that opens avenues towards improving personalized drug development strategies in AD.
Association between preoperative hemoglobin with length of hospital stay among non-cardiac and non-obstetric surgery patients: a secondary analysis of a retrospective cohort study
Authors: Wang Zhaopeng , Liu Min , Men Hengtong , Lyu Chunfeng , Zheng Ning
Published: February 2024

Background

Previous studies concerning the association between preoperative Hemoglobin (HB) level and the Length Of hospital Stay (LOS) in patients with non-cardiac surgery and non-obstetric surgery remain inconclusive. Herein, the objective of this study was to analyze whether and to what extent the preoperative HB level was connected with the LOS in non-cardiac and non-obstetric surgery patients.

Methods

This retrospective cohort study was performed at a single institution, involving patients who underwent elective non-cardiac, non-obstetric surgery from April 2007 to September 2013. Clinical characteristics of patients such as demographics, comorbidities, preoperative HB level, LOS, mortality, procedure length, and pulmonary hypertension (PHTN) Severity Class data were collected. A univariate analysis was used to determine the association between clinical characteristics and LOS. Multivariate regression analysis was conducted to investigate the relationship between preoperative HB level and LOS.

Results and discussion

In this study, 311 patients were included. We observed that compared with the LOS > 7 days group, the average HB level of patients in the LOS ≤ 7 days group was higher (12.04 ± 2.20 g/dl vs. 10.92 ± 2.22 g/dl, p < 0.001). In addition, there were fewer patients with moderate-to-severe anemia in LOS ≤ 7 days group than the LOS > 7 days group (32.74% vs 58.82%, p < 0.001). In addition, we found that patients with LOS ≤ 7 days were accompanied with lower mortality (0.44% vs. 7.06%, p < 0.001) and lower mean combined pulmonary artery systolic pressure (PASP) and right ventricular systolic pressure (RVSP) than that in patients with LOS > 7 days (42.56 ± 11.97 vs. 46.00 ± 12.37, p < 0.05). After controlling for relevant confounders, we discovered a nonlinear association between preoperative HB level and LOS as well as a threshold effect based on LOS. Specifically, when preoperative HB level was less than 11.9 g/dL, LOS decreased by 2 days for each 1 g/dL increase in HB level. However, LOS did not alter substantially with the rise of preoperative HB level when it was higher than 11.9 g/dL.

Conclusion

Our study showed a close non-linear association between preoperative HB level and LOS in patients with non-cardiac surgery and non-obstetric surgery. In particular, for patients with preoperative HB less than 11.9 g/dL, increasing the preoperative HB level can help shorten the LOS after operation.
Assessing the diagnostic utility of the Gaucher Earlier Diagnosis Consensus (GED-C) scoring system using real-world data
Authors: Revel-Vilk Shoshana , Shalev Varda , Gill Aidan , Paltiel Ora , Manor Orly , Tenenbaum Avraham , Azani Liat , Chodick Gabriel
Published: February 2024

Background

Gaucher disease (GD) is a rare autosomal recessive condition associated with clinical features such as splenomegaly, hepatomegaly, anemia, thrombocytopenia, and bone abnormalities. Three clinical forms of GD have been defined based on the absence (type 1, GD1) or presence (types 2 and 3) of neurological signs. Early diagnosis can reduce the likelihood of severe, often irreversible complications. The aim of this study was to validate the ability of factors from the Gaucher Earlier Diagnosis Consensus (GED-C) scoring system to discriminate between patients with GD1 and controls using real-world data from electronic patient medical records from Maccabi Healthcare Services, Israel’s second-largest state-mandated healthcare provider.

Methods

We applied the GED-C scoring system to 265 confirmed cases of GD and 3445 non-GD controls matched for year of birth, sex, and socioeconomic status identified from 1998 to 2022. The analyses were based on two databases: (1) all available data and (2) all data except free-text notes. Features from the GED-C scoring system applicable to GD1 were extracted for each individual. Patients and controls were compared for the proportion of the specific features and overall GED-C scores. Decision tree and random forest models were trained to identify the main features distinguishing GD from non-GD controls.

Results

The GED-C scoring distinguished individuals with GD from controls using both databases. Decision tree models for the databases showed good accuracy (0.96 [95% CI 0.95–0.97] for Database 1; 0.95 [95% CI 0.94–0.96] for Database 2), high specificity (0.99 [95% CI 0.99–1]) for Database 1; 1.0 [95% CI 0.99–1] for Database 2), but relatively low sensitivity (0.53 [95% CI 0.46–0.59] for Database 1; 0.32 [95% CI 0.25–0.38]) for Database 2). The clinical features of splenomegaly, thrombocytopenia (< 50 × 109/L), and hyperferritinemia (300–1000 ng/mL) were found to be the three most accurate classifiers of GD in both databases.

Conclusion

In this analysis of real-world patient data, certain individual features of the GED-C score discriminate more successfully between patients with GD and controls than the overall score. An enhanced diagnostic model may lead to earlier, reliable diagnoses of Gaucher disease, aiming to minimize the severe complications associated with this disease.
Epidemiology and economic burden of Von Hippel-Lindau Disease-associated central nervous system hemangioblastomas and pancreatic neuroendocrine tumors in the United States
Authors: Jonasch Eric , Song Yan , Freimark Jonathan , Berman Richard , Nguyen Ha , Signorovitch James , Sundaram Murali
Published: February 2024

Background

To date, real-world evidence around the clinical and economic burden related to von Hippel-Lindau (VHL) disease is limited. Therefore, this study characterized the prevalence, healthcare resource utilization (HRU), and economic burden of von Hippel-Lindau–associated central nervous system hemangioblastoma (VHL-CNS-Hb) and pancreatic neuroendocrine tumors (VHL-pNET) in the United States (US).

Methods

Patients with VHL-CNS-Hb or VHL-pNET were identified from Optum’s de-identified Clinformatics® Data Mart Database (2007–2020) and matched 1:5 to control patients without VHL disease or CNS-Hb/pNET. Prevalence rates of VHL-CNS-Hb and VHL-pNET (standardized by age and sex) in 2019 were estimated. HRU and healthcare costs (2020 US dollars) were compared between the VHL-CNS-Hb/VHL-pNET and control cohorts.

Results

In 2019, US prevalence rates of VHL-CNS-Hb and VHL-pNET were estimated to be 1.12 cases per 100,000 (3,678 patients) and 0.12 cases per 100,000 (389 patients), respectively. Patients with VHL-CNS-Hb (N = 220) had more inpatient, outpatient, and emergency department visits and $49,645 higher annual healthcare costs than controls (N = 1,100). Patients with VHL-pNET (N = 20) had more inpatient and outpatient visits and $56,580 higher annual healthcare costs than controls (N = 100). Costs associated with surgical removal of CNS-Hb and pNET were particularly high.

Conclusions

In this retrospective, claims-based study, both VHL-CNS-Hb and VHL-pNET were associated with substantial HRU and healthcare costs, particularly tumor reduction surgery–related costs. These findings provide important insight for healthcare payers regarding the expected real-world costs that enrollees with VHL-CNS-Hb and VHL-pNET may incur over the course of their disease.
Tissue-specific roles of peroxisomes revealed by expression meta-analysis
Authors: Plessner Matthias , Thiele Leonie , Hofhuis Julia , Thoms Sven
Published: February 2024

Peroxisomes are primarily studied in the brain, kidney, and liver due to the conspicuous tissue-specific pathology of peroxisomal biogenesis disorders. In contrast, little is known about the role of peroxisomes in other tissues such as the heart. In this meta-analysis, we explore mitochondrial and peroxisomal gene expression on RNA and protein levels in the brain, heart, kidney, and liver, focusing on lipid metabolism. Further, we evaluate a potential developmental and heart region-dependent specificity of our gene set. We find marginal expression of the enzymes for peroxisomal fatty acid oxidation in cardiac tissue in comparison to the liver or cardiac mitochondrial β-oxidation. However, the expression of peroxisome biogenesis proteins in the heart is similar to other tissues despite low levels of peroxisomal fatty acid oxidation. Strikingly, peroxisomal targeting signal type 2-containing factors and plasmalogen biosynthesis appear to play a fundamental role in explaining the essential protective and supporting functions of cardiac peroxisomes.
The analysis of continuous data from n-of-1 trials using paired cycles: a simple tutorial
Authors: Senn Stephen
Published: February 2024

N-of-1 trials are defined and the popular paired cycle design is introduced, together with an explanation as to how suitable sequences may be constructed.

Various approaches to analysing such trials are explained and illustrated using a simulated data set. It is explained how choosing an appropriate analysis depends on the question one wishes to answer. It is also shown that for a given question, various equivalent approaches to analysis can be found, a fact which may be exploited to expand the possible software routines that may be used.

Sets of N-of-1 trials are analogous to sets of parallel group trials. This means that software for carrying out meta-analysis can be used to combine results from N-of-1 trials. In doing so, it is necessary to make one important change, however. Because degrees of freedom for estimating variances for individual subjects will be scarce, it is advisable to estimate local standard errors using pooled variances. How this may be done is explained and fixed and random effect approaches to combining results are illustrated.
Important nutrient sources and carbohydrate metabolism patterns in the growth and development of spargana
Authors: Liang Pei , Liang Peng , Chen Kemin , Chen Zhengxin , Liu Yamei , Lin Yujin , Li Jin , Fu Ruijia , Lu Gang , Wang Dayong
Published: February 2024

Background

Sparganosis is a worldwide food-borne parasitic disease caused by spargana infection, which infects the muscle of frogs and snakes as well as many tissues and organs in humans. There are currently no viable treatments for sparganosis. Understanding spargana’s nutrition source and carbohydrate metabolism may be crucial for identifying its energy supply and establishing methods of treatment for sparganosis.

Methods

Using an amino acid analyzer and nutrient concentration detection kits, we assessed nutrient concentrations in the muscles of Fejervarya limnocharis and Pelophylax plancyi infected or not infected with spargana. Quantitative polymerase chain reaction (PCR) was used to quantify the major enzymes involved in five glucose metabolism pathways of spargana developing in vivo. We also used quantitative PCR to assess key enzymes and transcriptome sequencing to explore the regulation of carbohydrate metabolic pathways in vitro in response to different 24-h food treatments.

Results

Infected muscle tissues had considerably higher concentrations of glucogenic and/or ketogenic amino acids, glucose, and glycogen than non-infected muscle tissues. We discovered that the number of differentially expressed genes in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was larger in low-glucose than in other dietary groups. We examined differences in the expression of genes producing amino acid transporters, glucose transporters, and cathepsins in spargana grown in various nutritional environments. In the normal saline group, only the major enzymes in the tricarboxylic acid cycle (TCA), glycogenesis, and glycogenolysis pathways were expressed. The l-glutamine group had the greatest transcriptional levels of critical rate-limiting enzymes of gluconeogenesis and glycogenesis. Furthermore, the low-glucose group had the highest transcriptional levels of critical rate-limiting enzymes involved in the TCA, glycolytic, and glycogenolysis pathways. Surprisingly, when compared to the in vitro culturing groups, spargana developing in vivo exhibited higher expression of these critical rate-limiting enzymes in these pathways, with the exception of the pentose phosphate pathway.

Conclusions

Spargana have a variety of nutritional sources, and there is a close relationship between nutrients and the carbohydrate metabolism pathways. It takes a multi-site approach to block nutrient absorption and carbohydrate metabolism pathways to provide energy to kill them.

Graphical Abstract
Assessment of intestinal luminal stenosis and prediction of endoscopy passage in Crohn’s disease patients using MRI
Authors: Wu Wenjuan , Jin Yan , Zhu Dongyang , Wang Junqing , Cheng Yue , Zhang Lei
Published: February 2024

Background

Crohn’s disease (CD) is an inflammatory disease of the gastrointestinal tract. The disease behavior changes over time, and endoscopy is crucial in evaluating and monitoring the course of CD. To reduce the economic burden of patients and alleviate the discomfort associated with ineffective examination, it is necessary to fully understand the location, extent, and severity of intestinal stenosis in patients with CD before endoscopy. This study aimed to utilize imaging features of magnetic resonance enterography (MRE) to evaluate intestinal stenosis in patients with CD and to predict whether endoscopy could be passed.

Methods

MRE data of patients with CD were collected, while age, gender, disease duration, and laboratory test parameters were also gathered. Two radiologists analyzed the images and assessed whether endoscopy could be passed based on the imaging performance. Imaging features of MRE were analyzed in groups based on endoscopy results.

Results

The readers evaluated the imaging performance for 86 patients to determine if endoscopy could be passed and performed a consistency test (compared between two readers k = 0.812, p = 0.000). In the univariate analysis, statistical differences were observed in the degree of T1WI enhancement, thickness of the intestine wall at the stenosis, and diameter of the upstream intestine between the two groups of whether endoscopy was passed. In multivariate logistic regression, the diameter of the upstream intestine was identified to be an independent factor in predicting whether endoscopy was passed or not (OR = 3.260, p = 0.046).

Conclusions

The utilization of MRE signs for assessing the passage of an endoscope through the narrow segment revealed that the diameter of the upstream intestine emerged as an independent predictor of endoscopic passage. Before performing an endoscopy, MRE can aid in evaluating the passage of the endoscope.

Critical relevance statement

This retrospective study explored the imaging features of MRE to evaluate intestinal stenosis in patients with Crohn’s disease and determined that the diameter of the upstream intestine of the stenotic segment was an independent predictor in assessing endoscopic passage.

Key points

• Endoscopy is crucial in evaluating and monitoring the course of Crohn’s disease.

• The diameter of the upstream intestine of the stenotic segment was an independent predictor in assessing endoscopic passage.

• MRE can aid in evaluating the passage of the endoscope in stenotic segments of Crohn’s disease.

Graphical Abstract
Superolateral Hoffa fat pad edema in adolescent competitive alpine skiers: temporal evolution over 4 years and risk factors
Authors: Feuerriegel Georg C. , Marth Adrian A. , Fröhlich Stefan , Scherr Johannes , Spörri Jörg , Sutter Reto
Published: February 2024

Objectives

To longitudinally assess and correlate the prevalence of superolateral Hoffa fat pad (SHFP) edema with changes in features of the knee extensor mechanism in adolescent competitive alpine skiers over 48 months.

Methods

Competitive alpine skiers were prospectively enrolled in 2018 and underwent bilateral knee MRI at baseline and after 48 months. MRI was assessed for the prevalence of SHFP edema. Features of the knee extensor mechanism were assessed by measuring the trochlear sulcus angle and depth, lateral and medial trochlear inclination, trochlear angle, patella tilt, Insall‒Salvati ratio (ISR), and patellar ligament to lateral trochlear facet (PL-T) distance. Separate logistic regression models were used to calculate the odds ratios between each measurement and the presence of SHFP edema at both time points.

Results

Sixty-three athletes were included in the study (mean age 15.3 ± 1.3 years, 25 women). At baseline, 23 knees had SHFP edema, increasing to 34 knees at the 48-month follow-up. At baseline, knees with measurements in the highest quartile for ISR and lowest quartile for trochlear depth and PL-T were 9.3, 5.1, and 7.7 times more likely to show SHFP edema, respectively. At follow-up, these correlations were confirmed and additionally, knees with measurements in the highest quartile for trochlear sulcus angle and the lowest quartile for lateral trochlear inclination were 4.1 and 3.4 times more likely to show SHFP edema.

Conclusion

An increased prevalence of SHFP edema in competitive alpine skiers during adolescence was associated with persistent high-riding patella, reduced patellar ligament to trochlear distance, and flattened lateral trochlear facet.

Critical relevance statement

In clinical routine, assessment of the mechanical properties of the knee extensor mechanism, together with anatomical developments during adolescence, may improve the understanding and management of patellofemoral instability.

Key points

• Superolateral Hoffa fat pad (SHFP) edema is a frequent cause of anterolateral knee pain but the role of predisposing factors is still debated.

• A higher prevalence of SHFP edema was associated with high-riding patella, reduced patellar ligament to trochlear distance, and flattened lateral trochlear facet.

• Understanding of the mechanical interaction and the anatomical development of the knee during adolescence provides further insight into the development of SHFP edema.

Graphical Abstract
TC14012 enhances the anti-fibrosis effects of UC-MSCs on the liver by reducing collagen accumulation and ameliorating inflammation
Authors: Ding Fan , Liu Yuting , Li Jia , Wei Xiao , Zhao Jiangdong , Liu Xiaojing , Zhang Liqiang
Published: February 2024

Background

Mesenchymal stem cells (MSCs) are attracting attention as a promising cell-based therapy for the treatment of liver fibrosis or cirrhosis. However, the strategies and potential mechanisms of MSCs therapy need further investigation. The CXCL12/CXCR4/CXCR7 chemokine axis is well known to regulate cell migration and is involved in the regulation of liver fibrosis. This study aims to treat MSCs with a CXCR7-specific agonist to evaluate its therapeutic effects on hepatic fibrosis and potential mechanisms.

Methods

TC14012, a potent agonist of CXCR7, has been used to pretreat human umbilical cord-derived MSCs (UC-MSCs) and assess its effect on proliferation, apoptosis, migration, immunoregulation, and gene regulatory network. Then, CCl4-induced liver fibrosis mice models were used to evaluate the therapeutic effect and mechanism of TC14012-treated UC-MSCs for treating hepatic fibrosis.

Results

TC14012 increased CXCR7 expression in UC-MSCs. Notably, co-culture of liver sinusoidal endothelial cells (LSEC) with TC14012-pretreated UC-MSCs increased CXCR7 expression in LSEC. Additionally, TC14012 promoted cell migration and mediated the immunoregulation of UC-MSCs. Compared to UC-MSCs without TC14012 pretreatment, UC-MSCs treated with TC14012 ameliorated live fibrosis by restoring CXCR7 expression, reducing collagen fibril accumulation, inhibiting hepatic stellate cells activation, and attenuating the inflammatory response.

Conclusion

This study suggests that TC14012 pretreatment can enhance the therapeutic effects of UC-MSCs on liver fibrosis, mainly by promoting the migration and immunoregulation of MSCs.
The m6A methylation and expression profiles of mouse neural stem cells after hypoxia/reoxygenation
Authors: Zhang Shaoqiong , Cui Kaile , Li Yuanyuan , Fan Yiting , Wang Dongxu , Yao Xingen , Fang Bo
Published: February 2024

Background

Ischemia–reperfusion injury to the central nervous system often causes severe complications. The activation of endogenous neural stem cells (NSCs) is considered a promising therapeutic strategy for nerve repair. However, the specific biological processes and molecular mechanisms of NSC activation remain unclear, and the role of N6-methyladenosine (m6A) methylation modification in this process has not been explored.

Methods

NSCs were subjected to hypoxia/reoxygenation (H/R) to simulate ischemia–reperfusion in vivo. m6A RNA methylation quantitative kit was used to measure the total RNA m6A methylation level. Quantitative real-time PCR was used to detect methyltransferase and demethylase mRNA expression levels. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were conducted for NSCs in control and H/R groups, and the sequencing results were analyzed using bioinformatics. Finally, the migration ability of NSCs was identified by wound healing assays, and the proliferative capacity of NSCs was assessed using the cell counting kit-8, EdU assays and cell spheroidization assays.

Results

Overall of m6A modification level and Mettl14 mRNA expression increased in NSCs after H/R treatment. The m6A methylation and expression profiles of mRNAs in NSCs after H/R are described for the first time. Through the joint analysis of MeRIP-seq and RNA-seq results, we verified the proliferation of NSCs after H/R, which was regulated by m6A methylation modification. Seven hub genes were identified to play key roles in the regulatory process. Knockdown of Mettl14 significantly inhibited the proliferation of NSCs. In addition, separate analysis of the MeRIP-seq results suggested that m6A methylation regulates cell migration and differentiation in ways other than affecting mRNA expression. Subsequent experiments confirmed the migration ability of NSCs was suppressed by knockdown of Mettl14.

Conclusion

The biological behaviors of NSCs after H/R are closely related to m6A methylation of mRNAs, and Mettl14 was confirmed to be involved in cell proliferation and migration.
Modeling SO2 dispersion from future eruptions in the Auckland Volcanic Field, New Zealand
Authors: Brody-Heine Siena , Katurji Marwan , Stewart Carol , Wilson Thomas , Smid Elaine R. , Trancoso Rosa
Published: February 2024

Auckland city (pop. 1.7 M) is Aotearoa New Zealand’s largest city and an important economic hub. The city is built upon the active intraplate basaltic Auckland Volcanic Field (AVF). An AVF eruption would cause considerable impacts. An important component of volcanic risk management is assessing the likely volcanic hazards to help inform emergency planning and other preparedness activities. Previous volcanic hazard assessments for the AVF, particularly those for emergency planning scenarios, have modeled multiple volcanic hazards including lava flows, pyroclastic density currents, ballistic projectiles and tephra fall. Despite volcanic gas being an important and impactful hazard from intraplate basaltic field eruptions, there has been limited consideration of volcanic gas in AVF hazard assessment to date. This project is one of the first to quantitatively assess potential volcanic gas hazards for an explosive eruption scenario. For basaltic volcanism, sulfur dioxide (SO2) gas is typically the most consequential volcanic gas emitted. The aim of this exploratory study was to model SO2 dispersion from a high impact eruption during weather conditions conducive to high ground level pollutant concentrations. Since ground level SO2 concentrations are influenced by complex wind patterns resulting from interactions of locally driven flow circulations and topographically influenced weather, we modeled SO2 dispersion using the HYSPLIT model, a state-of-the art hybrid Eulerian and Lagrangian dispersion model widely used for volcanic gases, using high-resolution meteorological forcing fields given by the Weather Research and Forecasting (WRF) model.

Modeled air parcel trajectories and ground level SO2 concentrations illustrate the effect of the converging sea breeze winds on SO2 dispersion. Under worst-case dispersion conditions, extensive areas of up to hundreds of square kilometers to the north and northwest of the eruption location would exceed New Zealand short-term (24 h) air quality standards and guidelines for SO2, indicating heightened health risks to downwind communities. Using this numerical modeling approach, this work presents a methodology for future applications to other AVF eruption scenarios, with a wider range of meteorological conditions that can help in exploring consequences for health services such as anticipated emergency department respiratory admissions.
The impact of the first and the second wave of the COVID-19 pandemic on vascular surgery practice in the leading regional center: a comparative, retrospective study
Authors: Stadnik-Zawalska Katarzyna , Tomys-Składowska Julia , Zawalski Patryk , Buczkowski Krzysztof , Migdalski Arkadiusz
Published: February 2024

Background

We conducted an analysis of the vascular surgery regional center reorganization in response to the first and the second wave of the coronavirus disease-2019 (COVID-19) pandemic to see what lessons we learned from the first wave.

Methods

The study included a total of 632 patients admitted to the vascular surgery department in three periods: March–May 2020, October–December 2020, and October–December 2019 as a control period.

Results

In the pandemic periods the number of admitted patients decreased in relation to the control period. There was a reduction in performed procedures. We observed an increase in the ratio of less invasive procedures. There was a significant decline in hospitalization time in comparison to the control period.

Conclusions

The reduction of scheduled admissions and procedures affected vascular centers all over the world. Minimally invasive procedures were more willingly performed to shorten the hospitalization time and reduce the patient's exposure to hospital infection. It allowed us to treat more patients during the second wave. Nevertheless, an increased number of vascular patients should be expected in the future, which will result from the failure to perform elective procedures during the pandemic.
Flexible emotional regulation typology: associations with PTSD symptomology and trait resilience
Authors: Spikol Eric , McGlinchey Emily , Robinson Martin , Armour Cherie
Published: February 2024

Background

Multiple factors influence posttraumatic stress disorder (PTSD) risk in trauma exposed individuals. An established association exists between trait resilience and decreased PTSD distress and between emotion regulation (ER) ability/flexibility and trait resilience. Typologies in ER ability/flexibility, associated with trait resilience and PTSD experience, could explain the difference in risk. This study aimed to explore the relationship between ER ability, ER flexibility, context sensitivity, resilience, and PTSD.

Methods

Data from N = 563 trauma exposed UK residents was used in a latent profile analysis (LPA) and membership in the resultant profiles was explored in a logistic regression of sociodemographics, resilience, and PTSD symptomology.

Results

Analysis showed 2 latent profiles (High Flexibility, Low Flexibility) typified by emotion regulation ability and context sensitivity. Members of the Low Flexibility profile were more likely to be younger, male, endorsing less trait resilience, and experiencing negative cognition/mood and hyperarousal PTSD symptomology.

Conclusions

Difficulties in ER ability and flexibility could be improved with targeted learning in a therapeutic or home setting, potentially increasing trait resilience after trauma exposure and reducing PTSD distress.