bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stem cell therapy combined with core decompression versus core decompression alone in the treatment of avascular necrosis of the femoral head: a systematic review and meta-analysis
Authors: Li Mengyuan , Chen Duanyong , Ma Yuanchen , Zheng Minghao , Zheng Qiujian 
Published: August 2023

Abstract
Introduction
Accumulated clinical trials had been focused on stem cell therapy in combination of core decompression (CD) in the treatment of avascular necrosis of the femoral head (ANFH). Nonetheless, the results were inconclusive. Here, we performed a systematic review and meta-analysis of previous randomized controlled trials (RCTs) and retrospective studies to assess whether combined stem cell augmentation with CD improved the outcomes of ANFH compared with CD alone.

Methods
The current study included 11 RCTs and 7 retrospective studies reporting the clinical outcomes of a total of 916 patients and 1257 hips. 557 and 700 hips received CD and CD plus stem cell therapy, respectively. To compare CD with CD plus stem cell therapy, we examined the clinical evaluating scores, the occurrence of the femoral head, radiologic progression and conversion to total hip arthroplasty (THA).

Results
Only 10 studies reported significantly greater improvement in hip functions while combining stem cell procedure with CD. The pooled results in subgroup analysis indicated that stem cell group had a lower collapse rate on a mid-term basis (P = 0.001), when combined with mechanical support (P < 0.00001), and with extracted stem cells (P = 0.0002). Likewise, stem cell group had a lower radiographic progression rate at 2- to 5-year follow-up [P = 0.003], when combined with structural grafting (P < 0.00001), and with extracted stem cells (P = 0.004). Stem cell therapy resulted in an overall lower THA conversion rate (P < 0.0001) except that at a follow-up longer than 5 years.

Conclusion
Stem cell therapy combined with core decompression was more effective in preventing collapse, radiographic progression and conversion to THA.
Trial Registration The current protocol has been registered in PROSPERO with the registration number: CRD42023417248.
Potential mechanism of Taohong Siwu Decoction in uterine fibroid treatment based on integrated strategy of network pharmacology and experimental verification
Authors: Shi Shasha , Luo Li , Peng Fu , Yu Chenghao 
Published: August 2023

Abstract
Background
Taohong Siwu Decoction (THSWD) is a widely prescribed Traditional Chinese Medicine (TCM) for treating gynecological diseases. It is used to treat uterine fibroids (UF) in China, while its potential therapeutic effects and mechanism are unknown.

Methods
The present study used network pharmacology to identify PI3K/AKT as one of the main THSWD signaling pathways that can be targeted to treat UF. The potential binding sites of miR-21-5p to PTEN were predicted using online databases. We were able to establish a UF rat model successfully. We selected the 15% THSWD serum after preparing THSWD drug-containing serum to culture tumor tissue-derived cells. These studies enabled us to assess the role of THSWD in UF improvement.

Results
In vivo, we observed that low, medium, and high doses of THSWD improved histological changes in UF rats by increasing the expression levels of PTEN and miR-21-5p in their uterus while decreasing the expression levels of p-PI3K, p-AKT, and miR-21-5p. Treatment with THSWD medicated serum (15%) effectively inhibited the proliferation of cells derived from human UF and promoted apoptosis in vitro. PI3K phosphorylation, Akt phosphorylation, and miR-21-5p expression were decreased, while PTEN and cleaved caspase-3 were increased. These findings were reversed by administering 740 Y-P (a PI3K/Akt pathway agonist) and a miR-21-5p mimic. In addition, the double luciferase reporter gene assay confirmed the targeted binding relationship between miR-21-5p and PTEN.

Conclusions
THSWD inhibited the expression and activation of the PI3K/AKT and miR-21-5p/PTEN pathways, resulting in anti-UF activity in leiomyoma cell models. Our findings suggest that THSWD could be used to treat UF.
Identification of a novel isolated 4q35.2 microdeletion in a Chinese pediatric patient using chromosomal microarray analysis: a case report and literature review
Authors: Zhuang Jianlong , Liu Shufen , Chen Xinying , Jiang Yuying , Chen Chunnuan 
Published: August 2023

Abstract
Background
Isolated terminal 4q35.2 microdeletion is an extremely rare copy number variant affecting people all over the world. To date, researchers still have controversial opinions and results on its pathogenicity. Here, we aim to present a Chinese pediatric patient with terminal 4q35.2 microdeletion and use this case to clarify the underlying genotype–phenotype correlation.

Methods
A 17-year-old boy from Quanzhou, South China, was recruited as the main subject in this study. Karyotype and single-nucleotide polymorphism (SNP) based microarray analysis were carried out to detect chromosomal abnormalities and copy number variants in this family. Trio whole exome sequencing (Trio-WES) was performed to investigate the potential pathogenic variant in this family.

Results
During observation, we identified abnormal clinical phenotypes including upper eyelid ptosis, motor developmental delay, abnormal posturing, abnormality of coordination, attention deficit hyperactivity disorder, and involuntary movements in the patient. SNP array analysis results confirmed a case of 2.0 Mb 4q35.2 microdeletion and parental SNP array verification results indicated that the terminal 4q35.2 microdeletion was inherited from his mother. No copy number variants were detected in his father. In addition, the trio-WES results demonstrated none of pathogenic or likely pathogenic variants in the patient.

Conclusions
This study brings a novel analysis of a case of 2.0 Mb terminal 4q35.2 microdeletion affecting a Chinese individual. In addition, additional clinical symptoms such as upper eyelid ptosis and involuntary movements were first reported to affect a patient with terminal 4q35.2 microdeletion, which may broaden the phenotype spectrum of the condition.
Macular microvasculature in patients with thyroid-associated orbitopathy: a cross-sectional study
Authors: Abrishami Mojtaba , Sabermoghaddam Aliakbar , Salahi Zeinab , Bakhtiari Elham , Motamed Shariati Mehrdad 
Published: August 2023

Abstract
Purpose
The aim of this study was to evaluate macular blood flow in patients with thyroid-associated orbitopathy (TAO) as compared to healthy subjects. The inflammatory nature of the disease, as well as the vascular congestion caused by the increase in the volume of orbital soft tissue and extraocular muscles, rationalize the assessment of retinal blood flow changes in these patients.

Methods
This is a cross-sectional study with the convenience sampling method. Macular flow density was assessed using optical coherence tomography angiography (OCTA) and compared between patients with TAO and healthy individuals. We also compared macular flow density in two subgroups of patients based on clinical activity score (CAS).

Results
Eighty–five cases, including 30 healthy individuals and 55 patients with TAO, participated. The foveal avascular zone (FAZ) area was significantly larger in the patient group than in the control. Patients with active TAO with CAS 3 or more had significantly larger FAZ areas than those with CAS less than 3 (p = 0.04).

Conclusion
We showed that the FAZ area is larger in active TAO patients and can be considered a possible candidate feature for monitoring disease activity and thyroid-associated vasculopathy.
Effect of 12-week intermittent calorie restriction compared to standard of care in patients with nonalcoholic fatty liver disease: a randomized controlled trial
Authors: Lee Han Ah , Moon Hyeyoung , Kim Yuri , Lee Hye Ah , Kim Hwi Young 
Published: August 2023

Abstract
Background
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. NAFLD can result in various complications. Owing to the lack of effective pharmacological therapies, lifestyle modifications are the cornerstone treatment for NAFLD. However, there has been no recommendation for a specific dietary therapy. Because no significant effects have been observed in previous studies. Intermittent calorie restriction (ICR) consists of alternating phases of extreme energy restriction and regular energy intake. Recent studies have demonstrated a significantly higher reduction in liver fat content in the ICR group than in the standard of care (SOC) or continuous calorie restriction groups in patients with NAFLD. However, critical weaknesses limit the broader application of ICR in clinical practice; those are a lack of appropriate assessment tools, different cutoffs of body mass index (BMI) used to define obesity, and different food portions. Thus, we report a protocol for a prospective, randomized controlled trial. The trial will evaluate the effect of 12-week ICR on improving liver fat content in NAFLD patients (Nonalcoholic Fatty Liver Disease-Intermittent Calorie Restriction [FLICR]).

Methods
We will include adult (19–75 years) NAFLD patients. NAFLD will be diagnosed by histologic assessment or magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥ 8%. A total of 72 patients will be classified according to BMI (obese group: BMI ≥ 25 kg/m2 [n = 36] and non-obese group: BMI < 25 kg/m2 [n = 36]). Participants will be followed up for 24 weeks. Participants will be randomly assigned to one of the two groups: the SOC or ICR group. The primary objective will be the change in liver fat content measured using MRI-PDFF from baseline to 12 weeks.

Discussion
This FLICR study may provide clinical evidence on ICR in the treatment of NAFLD in both obese and non-obese patients. The use of ICR in patients with NAFLD will improve the clinical outcomes of patients facing a shortage of effective medical therapy.

Trial registration
This trial was registered at the United States National Library of Medicine (NLM) at the National Institutes of Health. ClinicalTrials.gov NCT05309642. Registered on April 4, 2022.
Efficacy and safety of pentoxifylline for chronic venous leg ulcers: study protocol for a multicenter randomized controlled trial in China (ESPECT study)
Authors: Chen Lihong , Gao Yun , Liu Ming , Li Qiu , Han Chunmao , Zhao Yue , Li Binghui , Xu Jun , Dai Yan , Li Pei , Li Jianli , Li Yuanyuan , Ran Xingwu 
Published: August 2023

Abstract
Background
Venous leg ulcers (VLUs) are the most severe manifestation of chronic venous disease, with long healing time and a high recurrence rate. It imposes a heavy burden on patients, their families, and the health care system. Chronic inflammation triggered by sustained venous hypertension is now recognized as the hallmark of chronic venous disease. The anti-inflammatory effect of pentoxifylline may offer a promising avenue to treat VLUs. However, current evidence of pentoxifylline for VLUs is relatively small and of low quality. The aim of this study is to evaluate the efficacy and safety of pentoxifylline for VLUs in the Chinese population.

Methods
This is a randomized, double-blinded, double-dummy, multi-center, placebo-controlled clinical trial. A total of 240 patients will be randomized to receive pentoxifylline (400 mg, twice daily) or placebo for 24 weeks. All participants will receive diosmin treatment and standard care of VLUs and other comorbidities. The primary outcome is the difference in the wound healing rate within 12 weeks between pentoxifylline and placebo. Secondary outcomes include (1) percent wound size changes at 12 weeks, (2) the levels of TNF-α and IL-6, (3) venous clinical severity score and chronic venous insufficiency quality of life score, and (4) ulcer recurrence within 24 weeks.

Discussion
This study would evaluate the efficacy and safety of pentoxifylline for VLUs in the Chinese population. If confirmed, it wound offer another effective and safe therapeutic option for treatment of VLUs.

Trial registration
The trial was registered at the Chinese Clinical Trial Registry (No. ChiCTR-2100053053). Registered on 10 November, 2021, https://www.chictr.org.cn/showproj.aspx?proj=137010
Hydro-organic mobile phase and factorial design application to attain green HPLC method for simultaneous assay of paracetamol and dantrolene sodium in combined capsules
Authors: Abdallah Nora A. , Tolba Manar M. , El-Brashy Amina M. , Ibrahim Fawzia A. , Fathy Mona E. 
Published: August 2023

AbstractThe greenness of any analytical method has become a very important aspect of a good analytical method. However, most chromatographic methods depend on the usage of relatively large amounts of lethal and un-decaying chemicals and solvents. So, a green approach based on the full factorial design was employed to develop a simple and rapid HPLC technique for concurrent determination of paracetamol and dantrolene sodium in their combined capsules. Both drugs are highly recommended to be administered together in patients with severe musculoskeletal disorders. Avoiding the routine methodology and resorting to the modern technology represented in the usage of experimental design allows rapid determination of the studied drugs using the optimum quantity of chemicals to avoid any waste of resources. Simultaneous separation of a binary mixture of paracetamol and dantrolene sodium was accomplished using a reversed phase Hypersil C18 column using an eco-friendly isocratic eluent. The used mobile phase consisted simply of ethanol: water (40:60, v/v). Orthophosphoric acid was used to adjust the pH of the mobile phase to 4.5. Triethanolamine (0.2%) was added aiming to reduce the peak tailing. The assay was completed within less than 6 min adopting 0.8 mL/min as a flow rate. The detection was carried out using a UV-detector at 290 nm. The suggested technique shows a linear correlation over concentration ranges of 1.0–200 and 1.0–40 µg/mL for paracetamol and dantrolene sodium, respectively. The suggested technique allowed the simultaneous analysis of the two co-formulated drugs in their synthetic mixture and combined capsule. The suggested technique is considered a greener substitute for the other reported HPLC techniques through the usage of safer solvents and chemicals, along with decreasing both waste output and analysis time. The method is accurate with recoveries between 97.85 and 101.27%, precise, as %RSD for the intraday and interday precision were between 0.39 and 1.72% and very sensitive with limits of detection (LOD)’s 0.15 and 0.18 µg/ml and limits of quantification (LOQ)’s 0.48 and 0.61 µg/ml for paracetamol and dantrolene sodium, respectively. The method greenness was ensured through its assessment by four greenness metrics. It is also validated following the International Conference on Harmonization Guidelines. The recommended technique could be a good alternative to traditional methods in the routine quality control analysis of the studied drugs due to its minimum harm to the planet or human beings.
Comparison of Mini-FLOTAC, Flukefinder® and sedimentation techniques for detection and quantification of Fasciola hepatica and Calicophoron daubneyi eggs using spiked and naturally infected bovine faecal samples
Authors: Bosco Antonio , Ciuca Lavinia , Maurelli Maria Paola , Vitiello Paola , Cringoli Giuseppe , Prada Joaquin M. , Rinaldi Laura 
Published: August 2023

Abstract
Background
Fasciolosis (Fasciola hepatica) and paramphistomosis (Calicophoron daubneyi) are two important infections of livestock. Calicophoron daubneyi is the predominant Paramphistomidae species in Europe, and its prevalence has increased in the last 10–15 years. In Italy, evidence suggests that the prevalence of F. hepatica in ruminants is low in the southern part, but C. daubneyi has been recently reported at high prevalence in the same area. Given the importance of reliable tools for liver and rumen fluke diagnosis in ruminants, this study evaluated the diagnostic performance of the Mini-FLOTAC (MF), Flukefinder® (FF) and sedimentation (SED) techniques to detect and quantify F. hepatica and C. daubneyi eggs using spiked and naturally infected cattle faecal samples.

Methods
Briefly, negative bovine faecal samples were artificially spiked with either F. hepatica or C. daubneyi eggs to achieve different egg count levels: 10, 50 and 100 eggs per gram (EPG) of faeces. Moreover, ten naturally infected cattle farms from southern Italy with either F. hepatica and/or C. daubneyi were selected. For each farm, the samples were analysed individually only with MF technique and as pools using MF, FF and SED techniques. Bayesian latent class analysis (LCA) was used to estimate sensitivity and accuracy of the predicted intensity of infection as well as the infection rate in the naturally infected farms.

Results
The outcome of this study showed that the highest number of eggs (F. hepatica and C. daubneyi) recovered was obtained with MF, followed by FF and SED in spiked infected samples at 50 and 100 EPG, while at lower infection levels of 10 EPG, FF gave the best results. Moreover, the sensitivity for all the techniques included in the study was estimated at > 90% at infection levels > 20 EPG for both F. hepatica and C. daubneyi eggs. However, MF was the most accurate of the three techniques evaluated to estimate fluke infection intensity. Nevertheless, all three techniques can potentially estimate infection rate at farm level accurately.

Conclusions
Optimization and standardization of techniques are needed to improve the FEC of fluke eggs.

Graphical Abstract
Depressive symptoms are associated with fatigue, poorer functional status and less engagement in sports in axSpA and PsA: an analysis from the RABBIT-SpA cohort
Authors: Reich Andreas , Weiß Anja , Lindner Lisa , Baraliakos Xenofon , Poddubnyy Denis , Zinke Silke , Stille Carsten , Strangfeld Anja , Regierer Anne C. 
Published: August 2023

Abstract
Background
In patients with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA), concomitant depression might have a negative impact on the course of disease and treatment outcomes. The aims of this analysis are to determine the prevalence of depressive symptoms in axSpA and PsA patients in a real-world cohort study and to identify sociodemographic and clinical associated factors for moderate or severe depressive symptoms in both diseases.

Methods
Patients from the RABBIT-SpA cohort with an axSpA or PsA diagnosis and a valid WHO-5 Well-Being Index score at baseline were included. A descriptive analysis of baseline and outcome parameters by category of depressive symptoms was performed and factors associated with the presence of depressive symptoms (moderate or severe) were examined in a logistic regression.

Results
Two thousand four hundred seventy patients (1,245 axSpA; 1,225 PsA) were included in the analysis. In both diagnoses, the proportion of patients with moderate depressive symptoms was 8% and 21% with severe symptoms.
Patients with moderate or severe depressive symptoms were less likely to engage in sports than those with no or mild depressive symptoms, had more comorbidities and higher scores for disease activity, functional limitations, fatigue, and pain and took more analgesics.
In axSpA, patients with a higher disease activity, a greater functional impairment and more severe fatigue were more likely to experience depressive symptoms, while patients with more years in education and engaging in sports for at least 1 h/week were less likely to experience depressive symptoms. PsA patients with a greater functional impairment and more severe fatigue were more likely to experience depressive symptoms while those engaging in sports for at least 1 h/week were less likely to experience depressive symptoms.

Conclusion
We confirmed a high prevalence of depressive symptoms in both PsA and axSpA. Factors negatively associated with the presence of depressive symptoms were fatigue, not engaging in sports, and greater functional limitations. Depressive symptoms may affect the perception of disease activity / severity by patients. Thus, depressive symptoms are an important condition in axSpA and PsA that should be considered when evaluating disease activity and treatment outcomes.
Endobronchial obstruction in connective tissue diseases: an uncommon but life threatening complication: two case reports
Authors: Shah Rushab , Lim Lisa , Nikpour Mandana 
Published: August 2023

Abstract
Background
Granulomatosis with polyangiitis and relapsing polychondritis are rare, multisystemic and potentially life-threatening connective tissue diseases. We present two cases of severe endobronchial obstruction in the aforementioned conditions and discuss difficulties with detection and treatment. Despite differing underlying pathophysiologies, endobronchial disease is a less frequently reported but serious complication of both conditions.

Case presentation
Case 1, a 31-year-old South Asian woman with relapsing polychondritis, required partial tracheal resection and reconstruction in combination with immunosuppressive therapy to achieve respiratory recovery following collapse of her right main bronchus and a stricture in her left main bronchus. Case 2, a 22-year-old Caucasian male with granulomatosis with polyangiitis, underwent surgical resection of an endobronchial growth causing occlusion of his right main bronchus. Although his respiratory status was initially stabilised with increased immunosuppression, he continues to have disease progression in spite of this.

Conclusions
Our cases highlight the importance of a multidisciplinary approach combining immunosuppression with supportive care and judicious use of surgical interventions in select cases. A further review of the literature shows endobronchial obstruction is potentially under-reported due to overlap in connective tissue disease symptomatology and there is no consensus on best practice.
Mitral regurgitation in the critically ill: the devil is in the detail
Authors: Duncan Chris F. , Bowcock Emma , Pathan Faraz , Orde Sam R. 
Published: August 2023

AbstractMitral regurgitation (MR) is common in the critically unwell and encompasses a heterogenous group of conditions with diverging therapeutic strategies. MR may present acutely with haemodynamic instability or more insidiously with failure to wean from mechanical ventilation. Critical illness is associated with marked physiological stress and haemodynamic changes that dynamically influence the severity and implication of MR. The expanding role of critical care echocardiography uniquely positions the intensivist to apply advanced bedside valvular assessment to recognise haemodynanically significant MR, manipulate and optimise cardiopulmonary physiology and identify patients requiring urgent cardiology and surgical referral. This review will consider common clinical scenarios, therapeutic strategies and the pearls and pitfalls of echocardiographic assessment and quantification in the critically unwell.