bluuebunny/crossref_metadata_2025 huggingface dataset:
Coexisting patterns and significance of serum HBV RNA and HBV DNA in patients with treatment-naïve chronic hepatitis B virus infection
Authors: Hao Kun-yan , Fan Ye , Zhang Yi-qing , Yu Yue-cheng
Published: January 2025

Aim

The study aimed to explore the coexisting patterns and assess the significance of serum hepatitis B virus (HBV) RNA and traditional virological biomarkers in patients with antiviral treatment-naïve chronic hepatitis B virus (HBV) infection.

Methods

Serum HBV RNA, HBV DNA, hepatitis B surface antigen (HBsAg), and hepatitis B envelope antigen (HBeAg) levels were measured and compared in patients with chronic hepatitis B virus infection. The HBV RNA levels were determined using a simultaneous amplification and testing assay.

Results

In the HBeAg-negative (HBeAg [−]) patients, the serum HBV RNA detectable (HBV RNA [+]) rate (33.33%, 14/42) was significantly lower than the serum HBV DNA detectable (HBV DNA [+]) rate (95.24%, 40/42; p < 0.001). However, there was no significant difference in the HBeAg-positive (HBeAg [+]) patients (p > 0.05). The HBV RNA (+) rate (33.33%, 14/42) was lower in the HBeAg-negative patients than in the HBeAg-positive patients (100%, 17/17, p < 0.001), while the HBV DNA (+) rate (95.24%, 40/42 vs. 94.12%, 16/17) showed no significant difference (p > 0.05). The HBV RNA (+) rates showed a significant difference (p < 0.001) among the different HBsAg levels (10.00, 65.00, 84.21%, p < 0.001), while the HBV DNA (+) rate showed no significant difference (p > 0.05). In all patients, serum HBV RNA correlated well with HBV DNA (r = 0.72, p < 0.001), HBeAg (r = 0.68, p < 0.001), and HBsAg (r = 0.66, p < 0.001). However, the correlations between HBV RNA and other biomarkers varied across the different HBsAg and HBeAg levels.

Conclusion

The coexisting patterns of serum HBV RNA and HBV DNA varied with the levels of HBeAg and HBsAg in the patients with treatment-naïve chronic HBV infection. This further suggests that serum HBV RNA should be included in the key index panel to accurately evaluate the natural history of HBV infection and the effects of antiviral treatment.
Phenotypic and genotypic characterization of Mycobacterium tuberculosis pyrazinamide resistance—India, 2018–2020
Authors: Tamilzhalagan Sembulingam , Justin Evanslin Santus , Selvaraj Ashok , Venkateswaran Karthick , Sivakumar Arun Kumar , Chittibabu Suganthi , McLaughlin Heather P. , Moonan Patrick K. , Smith Jonathan P. , Suba Sakthi , Sathya Narayanan Mukesh Kumar , Ho Christine S. , Kumar Nishant , Tripathy Srikanth P. , Shanmugam Siva K. , Hall-Eidson Patricia J. , Ranganathan Uma Devi
Published: January 2025

Pyrazinamide (PZA) is a key first-line antituberculosis drug that plays an important role in eradicating persister Mycobacterium tuberculosis (TB) bacilli and shortening the duration of tuberculosis treatment. However, PZA-resistance is on the rise, particularly among persons with multidrug-resistant (MDR) tuberculosis. This nationwide study was conducted to explore the prevalence of mutations conferring PZA resistance, catalogue mutation diversity, investigate the associations of PZA resistance with specific lineages, examine co-resistance to 13 first- and second-line drugs, and evaluate the diagnostic accuracy of sequencing pncA and panD genes for predicting PZA resistance. Whole genome sequencing was performed on 2,207 M. tuberculosis isolates from 25 States and 4 Union Territories of India. The majority of phenotypically PZA-resistant isolates (77%) harbored 171 distinct mutations in pncA; however, a small number of mutations in panD, rpsA and clpC1 were also observed. A set of novel mutations associated PZA resistance was uncovered, along with an additional 143 PZA resistance-conferring mutations in pncA based on application of WHO-endorsed grading rules. PZA resistance was predominately observed in Lineage 2 and eight lineage-specific resistance markers were identified. Mutations distributed across pncA correlate to 94% of PZA resistance and were the predominant drivers of phenotypic resistance; evidence generated herein substantiates sequencing the entire gene and promoter for comprehensive genotypic-based prediction of PZA resistance. This work provides key insights into the scope of PZA-resistance in India, a high drug-resistant TB burden country, and can support the effectiveness of TB prevention and control efforts.
Evaluation of autophagic and apoptotic markers during infection with animal virus causing hemorrhagic fever in rabbits
Authors: Bębnowska Dominika , Rzeszotek Sylwia , Kolasa Agnieszka , Wiśniewska Karolina , Żabińska Magdalena , Szulc Aneta , Cyske Zuzanna , Pierzynowska Karolina , Wilk Aleksandra , Niedźwiedzka-Rystwej Paulina
Published: January 2025

Introduction

Lagovirus europaeus/GI.1 and GI.2 cause severe Rabbit Haemorrhagic Disease, and immune processes are among the important pathomechanisms of the disease. Autophagy and apoptosis are two key mechanisms involved in the host antiviral response. Both of these processes have been characterized in infection with GI.1 strains, while data on infection with GI.2 strains still need to be studied. This is particularly important because infection with different strains is associated with a different host immune response profile.

Methods

In this work, we analyzed the expression of selected genes and proteins involved in autophagic flux in the liver, spleen, kidney and peripheral blood, but also apoptotic cell death in the liver and peripheral blood of rabbits infected with the GI.2 strain.

Results

As a result, we showed that autophagy is strongly activated in the liver, spleen and kidney of infected rabbits, and confirmed the activation of apoptosis in the liver.

Discussion

This study highlights the role of apoptosis and autophagy in the immune response in rabbits infected with Lagovirus europaeus/GI.2.
Chlorfenapyr-related delayed rhabdomyolysis: a case series
Authors: Xu Lina , Zhou Qian , Li Yan , Ren Sisi , Hu Yubin , Wang Jieru
Published: January 2025

Introduction

Chlorfenapyr, a broad-spectrum insecticide and acaricide of the pyrrole-class pesticides, can induce dizziness, fatigue, profuse sweating, and altered consciousness by interfering with cell energy metabolism. However, chlorfenapyr-related rhabdomyolysis has rarely been reported.

Case presentations

Patient 1 was a healthy 26-year-old man who ingested approximately 30 mL of chlorfenapyr. After gastric lavage, rehydration, diuresis, liver protection, and symptomatic treatment, he was discharged. However, he was readmitted 11 days later with rhabdomyolysis and acute kidney injury, and his blood tralopyril level was 187 μg/mL. Patient 2 was a 43-year-old man who consumed approximately 50 mL of chlorfenapyr without seeking medical care for 6 days. On day 7, his blood chlorfenapyr and tralopyril levels were 42 μg/mL and 542 μg/mL, respectively. Subsequently, the patient was diagnosed with rhabdomyolysis and brainstem injury.

Discussion

Chlorfenapyr can disrupt cellular energy metabolism, leading to rhabdomyolysis and brainstem injury, and physical activity may trigger and accelerate rhabdomyolysis. The delayed damage caused by chlorfenapyr poisoning may be attributed to the gradual depletion of cellular energy and prolonged presence of its metabolites in the body.
An increase in flow-diverter oversizing values as an independent risk factor for developing more severe in-stent stenosis. A retrospective single-center study based on flow diversion of supraclinoid internal carotid artery aneurysms
Authors: Vladev Georgi , Sirakov Alexander , Matanov Svetozar , Sirakova Kristina , Ninov Kristian , Sirakov Stanimir
Published: January 2025

Introduction

In the past decade, flow diverters (FDs) have increasingly been used to treat cerebral aneurysms with unfavorable morphology in which other endovascular techniques fall short of being as effective. In-stent stenosis (ISS) is one of the most puzzling and frequent risks of flow diversion therapy observed on follow-ups. This complication, although mostly placid in its clinical course, can have dire consequences if patients become symptomatic. ISS is associated with many factors, none of which have been demonstrated to date to be solely responsible for the phenomenon.

Methods

This study was aimed at evaluating ISS incidence in patients in our clinic who were treated with flow-diverters for aneurysms, located on the supraclinoid segments of the internal carotid artery between September 2022 and May 2023. A retrospective analysis was conducted, which included 137 patients with a total of 142 aneurysms being treated. The main hypothesis was that oversizing of the implant might play a role in ISS development. The performed statistical analysis, aimed at finding a correlation between it and vessel lumen narrowing on the follow-ups. The effects of other known risk factors, such as sex, age, smoking, and hypertension, were also analyzed.

Results

Stent oversizing with respect to the parent artery was positively correlated with subsequent ISS occurrence and severity. Older age was a protective factor against ISS. Patients who actively smoked had diminished risk of developing severe ISS.

Discussion

Stent oversizing can lead to ISS development, which might be more pronounced with larger implant-to-vessel sizing discrepancies. To achieve optimal results, the choice of implant diameter should consider all segments of the vessel in which it will be implanted. In cases of severe symptomatic ISS, continuation of dual anti-platelet therapy is a reasonable and effective option to address this complication.
Metabolic changes of thalamus assessed by 1H-MRS spectroscopy in patients of cervical spondylotic myelopathy following decompression surgery
Authors: Zheng Jiangqin , Zhang Yujin , Zhao Baogen , Wang Ning , Gao Ting , Zhang Li
Published: January 2025

Objective

To assess the changes of thalamic metabolites before and after surgery in patients with Cervical Spondylotic Myelopathy (CSM) using Hydrogen Proton Magnetic Resonance Spectroscopy (1H-MRS) and to investigate its association with improvement in neurological function.

Methods

Forty-eight CSM patients who underwent cervical decompression surgery from December 2022 to June 2023 were included, and 33 healthy volunteers were recruited. All subjects underwent bilateral thalamic 1H-MRS scans before the surgical procedure, and subsequently again 6 months later. Neurological function was assessed pre-operatively and post-operatively (6 months) in all patients with CSM using the modified Japanese Orthopedic Association (mJOA). The changes of mJOA (ΔmJOA = postoperative mJOA–preoperative mJOA) were employed as an indicator of neurological improvement. The pre- and postoperative metabolic ratio of N-acetylaspartate/creatine (NAA/Cr), choline/creatine (Cho/Cr), myo-inositol/creatine (mI/Cr), glutamate and glutamine complex/creatine (Glx/Cr) were statistically compared in CSM patients and healthy controls (HCs). A correlation analysis was conducted to determine the relationship between alterations in pre- and postoperative metabolite ratios (ΔNAA/Cr, ΔCho/Cr, ΔmI/Cr, ΔGlx/Cr) and ΔmJOA.

Results

Compared to the HCs, patients with CSM showed significantly lower pre- and post-operative NAA/Cr (Z = −4.235, p < 0.001; Z = −3.184, p = 0.001), Cho/Cr (Z = −5.050, p < 0.001; (Z = −2.624, p = 0.007) and mI/Cr (Z = −3.739, p = 0.001; Z = −2.014, p = 0.044). There was no difference in Glx/Cr between patients in patients with CSM, either preoperatively or postoperatively, compared to HCs. Post-operative NAA/Cr (Z  = −2.285, p = 0.041) and mI/Cr (Z = −2.925, p = 0.021) were increased in CSM patients compared to pre-operative NAA/Cr and mI/Cr. In CSM patients, ΔmI/Cr correlated significantly with ΔmJOA (r = 0.507, p < 0.001).

Conclusion

The preliminary findings indicate that metabolites in the thalamus of CSM patients exhibit changes following surgery. Additionally, it has been demonstrated that elevated postoperative mI correlates with improvements in neurological function.
Insight into interplay between PANoptosis and autophagy: novel therapeutics in ischemic stroke
Authors: Tian He-Yan , Lei Yun-Xing , Zhou Jing-Tao , Liu Long-Jun , Yang Tong , Zhou Yue , Ge Jin-Wen , Xu Chen , Mei Zhi-Gang
Published: January 2025

PANoptosis is a novelly defined mode of programmed cell death that involves the activation of multiple cellular death pathways, including pyroptosis, apoptosis, and necroptosis, triggering robust inflammatory reactions. Autophagy is a crucial cellular process that maintains cellular homeostasis and protects cells from various stresses. PANoptosis and autophagy, both vital players in the intricate pathological progression of ischemic stroke (IS), a brain ailment governed by intricate cell death cascades, have garnered attention in recent years for their potential interplay. While mounting evidence hints at a crosstalk between these two processes in IS, the underlying mechanisms remain elusive. Therefore, this review delves into and dissects the intricate mechanisms that underpin the intersection of PANoptosis and autophagy in this devastating condition. In conclusion, the crosstalk between PANoptosis and autophagy in IS presents a promising target for the development of novel stroke therapies. Understanding the interplay between these two pathways offers a much-needed insight into the underlying mechanisms of IS and opens the possibility for new therapeutic strategies.
Optimizing oral 3-hydroxybutyrate dosage using pharmacokinetic model to improve cognitive function and mood in healthy subjects
Authors: Nishioka Kentaro , Ishimoto Takahiro , Sato Mariko , Yasuda Ruki , Nakamura Yumi , Watanabe Hiroshi , Suzuki Toshihide , Araragi Yudai , Kato Yukio , Yoshida Ken-ichi , Murayama Norihito
Published: January 2025

Introduction

The brain uses ketones, mainly 3-hydroxybutyrate (3-HB), as an alternative energy source. Therefore, oral intake of 3-HB may help maintain brain health. Previous studies indicated that achieving a maximum concentration (Cmax) of 3-HB in plasma at 0.28 mM could initiate ketone metabolism in the brain; we hypothesized that attaining this Cmax would improve brain health.

Methods

We aimed to demonstrate the efficacy of an optimized single oral dose of 3-HB on cognitive function and mood through two clinical studies: a pharmacokinetic study and an efficacy study. In the pharmacokinetic study, healthy subjects were ingested 2 and 4 g of 3-HB to construct a compartment model to predict the minimum oral dose of 3-HB needed to achieve the target Cmax. In the efficacy study, a randomized, double-blinded, and placebo-controlled crossover trial, the effects of 3-HB at the predicted doses on cognitive function and mood in healthy subjects were assessed by a serial arithmetic test (SAT), the cognitrax, the profile of mood states 2nd edition (POMS2), and fatigue visual analog scale (VAS).

Results

In the pharmacokinetic study, a one-compartment model that includes saturable and non-saturable absorption pathways, constant biosynthesis, and the linear elimination of 3-HB after oral administration were constructed. The model principally reflected the observed serum 3-HB concentrations profiles and predicted a minimum dose of 3.5 g needed to achieve the target Cmax. In the efficacy study, although no significant difference was observed in any cognitive domains assessed by the Cognitrax, total responses and correct answers in the SAT were significantly improved in the active group receiving 3.5 g of 3-HB compared to the placebo group. Regarding the POMS2, confusion–bewilderment, fatigue–inertia, vigor-activity, and total mood disturbance scales were significantly improved in the active group compared to the placebo group. Additionally, fatigue VAS were also significantly improved in the active group compared to the placebo group.

Discussion

We successfully established a one-compartment model for oral 3-HB intake and demonstrated partial efficacy on cognitive function and broad efficacy on mood in healthy subjects with a single oral dose of 3.5 g of 3-HB optimized by the model.

Clinical trial registration

https://www.umin.ac.jp/ctr/index-j.htm, identifier [UMIN000042095, UMIN000046666].
Therapeutic potential of short-chain fatty acids for acute lung injury: a systematic review and meta-analysis of preclinical animal studies
Authors: Xie Liying , Wang Linyan , Liao Yongxin , Yao Miaoen , Mai Tong , Fan Rongrong , Han Yun , Zhou Gengbiao
Published: January 2025

Background

Short-chain fatty acids (SCFAs), derived from the fermentation of dietary fiber by intestinal commensal bacteria, have demonstrated protective effects against acute lung injury (ALI) in animal models. However, the findings have shown variability across different studies. It is necessary to conduct a comprehensive evaluation of the efficacy of these treatments and their consistency.

Objective

This systematic review and meta-analysis aimed to explore the effects of SCFAs on ALI based on preclinical research evidence, in order to provide new treatment strategies for ALI.

Methods

We included studies that tested the effects of SCFAs on ALI in animal models. This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search for relevant studies was conducted in the PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases up to February 2024. The data were extracted in accordance with the established selection criteria, and the risk of bias was evaluated for each study.

Results

A total of 16 articles were finally included in the meta-analysis. The results indicated that the SCFAs significantly reduced lung wet-to-dry weight (SMD = −2.75, 95% CI = −3.46 to −2.03, p < 0.00001), lung injury scores (SMD = −5.07, 95% CI = −6.25 to −3.89, p < 0.00001), myeloperoxidase (SMD = −3.37, 95% CI = −4.05 to −2.70, p < 0.00001), tumor necrosis factor-alpha (SMD = −3.31, 95% CI = −4.45 to −2.16, p < 0.00001) and malondialdehyde (SMD = −3.91, 95% CI = −5.37 to −2.44, p < 0.00001) levels in animal models of ALI. The results of the subgroup analysis indicated that the efficacy of SCFAs varies significantly with dosage and duration of treatment.

Conclusion

SCFAs can reduce inflammation and oxidative stress in animal models of ALI. The clinical efficacy of SCFAs for ALI deserves further in-depth research.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=584008, CRD42024584008.
Bilateral chylothorax following total thyroidectomy with neck lymph node dissection for thyroid cancer: a case report and literature review
Authors: Wang Yunsheng , Liu Xudong , Wang Xingyue , Tian Youxin , Liu Qinjiang , Wang Jun , Xue Jincai
Published: January 2025

Purpose

Investigating the diagnosis and treatment of bilateral Chylothorax after neck lymph node dissection for thyroid cancer.

Methods

The clinical data of a patient with bilateral chylothorax after neck lymph node dissection for thyroid cancer were retrospectively analyzed, and the relevant literature was reviewed.

Results

The patient underwent a total thyroidectomy and left neck lymph node dissection, with no evidence of lymph fluid leakage observed during the operation. The patient experienced chest tightness, shortness of breath, dyspnea, and decreased lung auscultation breath sounds on the 7th day after the surgery. The chest X-ray examination revealed the presence of bilateral pleural effusion. Under ultrasound guidance, bilateral thoracic closed drainage tube was implanted, and a small sample of the milky white fluid was tested for chylothorax, yielded positive results. The patient is diagnosed with bilateral chylothorax. After received conservative treatment, the patient’s drainage flow gradually decreased. Subsequent review of a chest X-ray showed no signs of chest hydrops, and as a result, the thoracic drainage tube was removed. The patient eventually recovered and was subsequently discharged.

Conclusion

Bilateral chylothorax is a rare complication following neck lymph node dissection for thyroid cancer. It is deemed safe and effective to administer active conservative treatment upon early detection.
Case report: Illustrating associated malignancies in Paget’s disease using contrast-enhanced mammography
Authors: Mariano Luciano , Nicosia Luca , Bozzini Anna , Pesapane Filippo , Magnoni Francesca , Mazzarol Giovanni , Meneghetti Lorenza , Sorce Adriana , Cassano Enrico
Published: January 2025

Introduction

The following presentation explores the diagnostic potential of Contrast-Enhanced Mammography (CEM) in evaluating and managing Paget’s Disease (PD) of the breast, particularly as an alternative or complementary tool to Magnetic Resonance Imaging (MRI) in cases where MRI is contraindicated or inconclusive.

Clinical cases

Two clinical cases of PD diagnosed at our Breast Imaging Division between January and May 2024 were analyzed using CEM. These cases involved imaging techniques, including Digital Mammography (DM), Breast Ultrasound (US), MRI and CEM, alongside histopathological confirmation through nipple-areolar complex (NAC) punch biopsies. CEM identified disease extensions and NAC involvement that was not evident in conventional imaging in both cases. CEM findings influenced surgical decisions, leading to total mastectomies with reconstruction instead of conservative approaches. The cases highlighted CEM’s sensitivity and ability to delineate the disease extent comparable to MRI.

Discussion and conclusions

PD often presents diagnostic challenges due to frequent associations with underlying malignancies that are undetectable by standard imaging. While MRI is the gold standard, its limitations, such as costs, contraindications, and false positives, warrant alternative methods. CEM demonstrated utility in diagnosing and staging PD, offering benefits in patient acceptability, cost, and sensitivity comparable to MRI. CEM is a promising diagnostic and planning tool for PD management, especially in MRI-infeasible cases. More extensive multicentric studies will be needed to validate CEM’s role in this context. CEM could enhance PD diagnostic workflows and treatment strategies, significantly impacting clinical outcomes.
The optimization and application of photodynamic diagnosis and autofluorescence imaging in tumor diagnosis and guided surgery: current status and future prospects
Authors: Wan Wei , Liu Huiquan , Zou Junrong , Xie Tianpeng , Zhang Guoxi , Ying Weihai , Zou Xiaofeng
Published: January 2025

Photodynamic diagnosis (PDD) and autofluorescence imaging (AFI) are emerging cancer diagnostic technologies that offer significant advantages over traditional white-light endoscopy in detecting precancerous lesions and early-stage cancers; moreover, they hold promising potential in fluorescence-guided surgery (FGS) for tumors. However, their shortcomings have somewhat hindered the clinical application of PDD and AFI. Therefore, it is imperative to enhance the efficacy of PDD and AFI, thereby maximizing their potential for practical clinical use. This article reviews the principles, characteristics, current research status, and advancements of PDD and AFI, focusing on analyzing and discussing the optimization strategies of PDD and AFI in tumor diagnosis and FGS scenarios. Considering the practical and technical feasibility, optimizing PDD and AFI may result in an effective real-time diagnostic tool to guide clinicians in tumor diagnosis and surgical guidance to achieve the best results.
Mapping the intellectual structure and emerging trends on nanomaterials in colorectal cancer: a bibliometric analysis from 2003 to 2024
Authors: Lu Man , Liu Yi , Zhu Jin , Shang Jiarong , Bai Lu , Jin Zhichao , Li Wenting , Hu Yue , Zheng Xia , Qian Jun
Published: January 2025

Background

Colorectal cancer (CRC) is one of thes most prevalent malignant tumors worldwide. Current therapeutic strategies for CRC have limitations, while nanomaterials show significant potential for diagnosing and treating CRC. This study utilizes bibliometric analysis to evaluate the current status and trends in this field.

Methods

Research on nanomaterials in CRC from 2003 to 2024 was retrieved from the Web of Science Core Collection (WOSCC). Tools such as CiteSpace, VOSviewer, RStudio, GraphPad Prism, and Excel were used to analyze trends and hotspots, covering publication trends, countries, institutions, authors, journals, co-citation analysis, and keywords. Visual maps were created to forecast future developments.

Results

The analysis includes 3,683 publications by 17,261 authors from 3,721 institutions across 100 countries/regions, published in 840 journals. Global publications have steadily increased, particularly since 2018. China leads in publication volume and citations, with six of the top ten research institutions and seven of the ten most cited authors, while the United States excels in citation impact and academic centrality. Both countries currently dominate the field, underscoring the urgent need for enhanced international collaboration. Ramezani M and Abnous K lead in publication volume and H-index, while Siegel RL is highly cited. The International Journal of Nanomedicine has the highest publication volume, while the Journal of Controlled Release is the most cited. In addition to “colorectal cancer” and “nanoparticles,” the most common keyword is “drug delivery.” Emerging research areas such as “metal-organic frameworks (MOFs)” and “green synthesis” are gaining attention as leading hotspots.

Conclusion

This study offers an in-depth analysis of the application of nanomaterials in CRC, promoting interdisciplinary collaboration and advancing scientific progress in this field.
Achieving reliable patient reported outcomes collection to measure health care improvement in a learning health network: lessons from pediatric rheumatology care and outcomes improvement network
Authors: Pan Nancy , Morgan Esi M. , Ryan Meghan , Gottlieb Beth , Harris Julia G. , Lee Tzielan , Goh Y. Ingrid
Published: January 2025

Introduction

Data from the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) registry suggests that reliable collection of patient-reported outcomes (PROs) varies across sites. The objective of this study was to better understand the practices of collecting PROs at PR-COIN sites.

Methods

A REDCap survey was sent to the lead representative for each PR-COIN site. Registry data were analyzed to better understand the completion rates of PROs. Interviews of physician leaders of high performing sites were conducted by videoconference, audiotranscribed and themes were summarized. Quantitative data were analyzed using descriptive statistics and qualitative data were thematically analyzed.

Results

All 23 PR-COIN sites responded to the survey. PROs were collected by 21/23 (91%) sites. Arthritis-related pain intensity, morning stiffness, and physical function were the top three collected PROs (
Supplementary 3 and 4). PROs were collected using paper, electronically or in combination, with most sites collecting PROs only on paper. PROs were manually scored at most sites. Among sites with electronic PRO collection, 42% did not have automatic transfer of scores into the electronic medical record. Facilitators to successful collection of PROs included availability of staff, training, and culture. Barriers to PRO collection cited were limited time, lack of infrastructure, and lack of staff. Completion rates of PROs in the registry in top 4 performing centers for morning stiffness was 100%, overall well-being and pain intensity scores ranged from 93%–98%, and for physical function 69%–94%. Interviews with physician leaders indicated that their site overcame barriers through: integration of PRO collection into workflow, gaining buy-in of stakeholders (clinicians and patients), and automating PRO collection. Interviewees endorsed automation of data collection (e.g., self-completion on tablets) and automated transfer to electronic medical record (EMR) as key components enabling reliable PRO collection.

Conclusions

Through understanding our current ability to systematically collect PROs across all sites in PR-COIN and exploring successful implementation of PRO collection both within and outside our learning health network, we share lessons learned and identify the most influential factors for successful PRO collection in pediatric rheumatology.
Case Report: Nephrotic syndrome as the primary manifestation of Alport syndrome in a Chinese pediatric patient
Authors: Song Yue , Li Yifei , Lu Liqun , Yang Changqiang , Lu Jing
Published: January 2025

Background

Alport syndrome (AS) is a genetically heterogeneous disorder resulting from variants in genes coding for the alpha-3/4/5 chains of Collagen IV, leading to defective basement membranes in the kidney, cochlea, and eye. The clinical manifestations of AS vary in patients. Cases of childhood AS caused by COL4A3 presenting primarily with nephrotic syndrome (NS) are rarely reported. Here, we report a pediatric case presenting initially with NS attributed to AS caused by COL4A3.

Case presentation

An 11-year-old boy presented with hematuria and nephrotic range proteinuria. After excluding secondary causes, primary NS was considered. He was administered with prednisone (60 mg/day). The patient had not responded to treatment by the end of 4 weeks, so he was diagnosed with steroid-resistant NS. A renal biopsy showed granular and vacuolar degeneration of renal tubular epithelial cells, multifocal foam cell infiltration in the renal interstitium, and immunofluorescence indicated the absence of α3, α4, and α5 expression in the glomerular and tubular basement membrane, while Bowman's capsule expression was normal. Electron microscopy ultrastructural suggested variable basement membrane thickness, and partial tearing and web-like structures. Genetic testing revealed a heterozygous COL4A3 missense mutation c.3210 (exon 37)G>A(NM:000091). These findings are consistent with the diagnosis of AS. Prednisone was gradually tapered and enalapril maleate was initiated.

Conclusion

We have described a pediatric case of AS featuring NS as its primary manifestation. It is important to consider AS to be a diagnosis or differential diagnosis in patients who have NS with hematuria or steroid resistance.
Safety of combined drug use in patients with cardiovascular and cerebrovascular diseases: an analysis based on the spontaneous reporting database of adverse drug reactions in Hubei Province
Authors: Wang Jia , Zhao Yuhang , Chen Zherui , Huang Rui
Published: January 2025

Objective

There is a lack of studies investigating the safety of combination regimens specifically for cardiovascular and cerebrovascular diseases. This study aimed to evaluate the safety of combination drugs for cardiovascular and cerebrovascular diseases using real-world data.

Methods

We analyzed adverse drug reaction data received by the Hubei Adverse Drug Reaction Center from the first quarter of 2014 to the fourth quarter of 2022. The safety of combined drugs for cardiovascular and cerebrovascular diseases in different people was assessed using the association rule method and Ω shrinkage measurement.

Results

A total of 53,038 reports were included in this study, revealing 9 signals of adverse reactions caused by combination drugs. The strongest signal found in this study was jaundice caused by the combination of amlodipine and atorvastatin (Ω 0.025:3.08, lift: 1116.69, conviction: 1.75). Additionally, the combination of aspirin with other drugs was associated with hemorrhaging in various organs. Female patients showed a cold signal when taking vitamin C and vitamin B6 together compared to male patients (Ω 0.025:0.89, lift: 7.15, conviction: 1.12). Patients under 60 years old had a palpitations signal when combining eritrea bei sha Tanzania and felodipine (Ω 0.025:0.41, lift: 14.65, conviction: 3.8), and an erythema signal when combining nifedipine (Ω 0.025:0.23, lift: 8.17, conviction: 1.077).

Conclusion

Among the 9 signals identified in this study, 4 were off-label adverse drug reactions that require further clinical research for exploration and confirmation, in order to provide more scientifically informed drug labeling. Five adverse events associated with aspirin-induced bleeding were identified. Notably, different adverse drug reactions were observed in different populations, suggesting the need for future studies to expedite the development of personalized medicine.
Oral administration of ethanol extract from Gynura procumbens stems corrects kidney injury and renal anemia in chronic kidney disease
Authors: Li Ting-Ting , Wen Li-Ying , Meng Sha-Sha , Li Yu-Sang , Tang He-Bin
Published: January 2025

Background

Gynura procumbens (Lour.) Merr. is a plant used in traditional Chinese medicine that reduces hepatotoxicity, relieves kidney discomfort, and has anti-inflammatory and antioxidant properties.

Methods

We aimed to explore the mechanisms underlying the therapeutic effects of an ethanol extract from G. procumbens stems (EEGS) and selected metabolites on kidney injury and renal anemia associated with chronic kidney disease (CKD). An adenine-induced rat CKD model was used to elucidate the effective mechanism of EEGS and selected metabolites to correct renal anemia.

Results

The results showed that treatment with EEGS reversed abnormal changes in the blood indicators, including hemoglobin, red blood cells, serum erythropoietin (EPO), and creatinine levels. Moreover, EEGS inhibited xanthine oxidase (XOD) activity in vitro, significantly inhibited liver XOD activity, and reduced intrahepatic inflammatory infiltration. Analysis of the pathological changes revealed that EEGS treatments resulted in reduced renal tubular apoptosis, decreased a number of crystals, a narrowed tubular lumen, and attenuated tubular fibrosis. Immunohistochemical staining revealed that EEGS significantly ameliorated the adenine-induced abnormal changes in the expression of related proteins, including β-catenin, COX-2, HIF-2α, and EPO, in the rat kidney tissues. Among the selected EEGS metabolites, the combined effect of chlorogenic acid and trans-p-coumaric acid was superior to that of either compound alone.

Conclusion

These results suggest that EEGS and selected metabolites can effectively correct renal anemia in CKD rats by inhibiting XOD activity, reducing inflammation, and alleviating renal injury.
Normative and limit values of speed, endurance and power tests results of young football players
Authors: Nowak Michał , Szymanek-Pilarczyk Marta , Stolarczyk Artur , Oleksy Łukasz , Muracki Jarosław , Wąsik Jacek
Published: January 2025

Introduction

This study aimed to assess the development of speed, endurance and power in young football players and to create percentile charts and tables for standardized assessment.

Methods

Cross-sectional data were collected from 495 male players aged 12–16 years at RKS Raków Częstochowa Academy in 2018–2022. Players participated in a systematic training in which running time 5 m, 10 m, 30 m, lower limb power (standing long jump), and Maximum Aerobic Speed (MAS) were measured using the 30–15 Intermittent Fitness Test. All tests were performed under constant environmental conditions by qualified personnel. Statistical analysis included ANOVA and percentile distribution for P3, P10, P25, P50, P75, P90, P97.

Results

Results indicated that the most significant improvements occurred between the ages of 13 and 14, with increased speed over all distances and a significant increase in power. Percentile tables were developed, highlighting improvements in speed 5 m: 0.087–0.126 s; 10 m 0.162–0.215 s; 30 m: 0.438–0.719 s and power in the long jump test: 31–48 cm. Improvements in MAS ranged from 0.3 to 0.6 m/s across the percentiles.

Discussion

The results highlight the need for individual training programs tailored to the biological maturity of players. The developed percentile charts and tables offer a valuable tool for coaches and sports scientists to monitor progress, optimize training loads, and minimize the risk of injury, providing a frame of reference for assessing the physical development of young soccer players. Future research should focus on extending these charts and tables to other age groups and genders to refine training methodologies further.
Morphology, phylogeography, phylogeny, and taxonomy of Cyclorhiza (Apiaceae)
Authors: Song Bo-Ni , Aou Xueyimu , Tian Rong-Ming , Cai Jing , Tan Wei-Yan , Liu Chang-Kun , He Xing-Jin , Zhou Song-Dong
Published: January 2025

Background

The genus Cyclorhiza is endemic to China and belongs to the Apiaceae family, which is widely distributed in the Himalaya–Hengduan Mountains (HHM) region. However, its morphology, phylogeny, phylogeography, taxonomy, and evolutionary history were not investigated due to insufficient sampling and lack of population sampling and plastome data. Additionally, we found that Seseli purpureovaginatum was not similar to Seseli members but resembled Cyclorhiza species in morphology, indicating that the taxonomic position of S. purpureovaginatum needs to be re-evaluated.

Methods

First, we observed the morphology of the genus. Second, we newly sequenced four plastomes and conducted comparative analyses. Third, we used the newly sequenced internal transcribed spacer (ITS) and chloroplast DNA (cpDNA) (matK, trnQ-rps16, and trnD-trnT) from 27 populations totaling 244 individuals to explore the genetic diversity and structure. Finally, we performed the phylogenetic analyses based on three datasets (plastome data, ITS sequences, and haplotypes) and estimated the origin and divergence time of the genus.

Results and discussion

The morphology of Cyclorhiza plants and S. purpureovaginatum was highly similar, and their plastomes in structure and features were conserved. The genus possessed high genetic diversity and significant lineage geographic structure, which may be associated with the long-term evolutionary history, complex terrain and habitat, and its sexual reproduction mode. The genus Cyclorhiza originated in the late Eocene (36.03 Ma), which was closely related to the early uplift of the Qinghai–Tibetan Plateau (QTP) and Hengduan Mountains (HDM). The diversification of the genus occurred in the late Oligocene (25.43 Ma), which was largely influenced by the colonization of the newly available climate and terrain. The phylogenetic results showed that Cyclorhiza species clustered into a separate clade and S. purpureovaginatum nested within Cyclorhiza. Cyclorhiza waltonii was sister to Cyclorhiza peucedanifolia, and Cyclorhiza puana clustered with S. purpureovaginatum. Thus, based on the morphology, plastome analyses, and phylogenetic evidence, S. purpureovaginatum should be transferred to Cyclorhiza. All these evidences further supported the monophyly of the genus after including S. purpureovaginatum. Finally, we clarified the generic limits of Cyclorhiza and provided a species classification key index for the genus. In conclusion, the study comprehensively investigated the morphology, phylogeography, phylogeny, taxonomy, and evolution of the genus Cyclorhiza for the first time.
How can graduate students’ research pressure be transformed into motivation and innovative behavior? The role of graduate students’ mentorship homegate (or team) support
Authors: Li Qiming , Du Xian , Chen Hua , Zhou Xianli
Published: January 2025

Introduction

This study explores how graduate students’ mentorship homegate (or team) support (GSMTS) and challenging-hindering pressures impact their intrinsic motivation for research, identification with research roles, and innovative behaviors.

Methods

Data from 548 graduate students were collected using convenience sampling and analyzed using Amos and SPSS statistical software package via questionnaires distributed to universities in SiChuan province of China.

Result

The findings reveal that (1) research stress can not directly and positively predict innovative behaviors among graduate students, while intrinsic research motivation and research role identification mediate the relationship between research stress and graduate students’ innovative behavior; (2) hindering research pressure negatively impacts the intrinsic motivation for research, whereas challenging research pressure has a positive effect; (3) GSMTS directly fosters innovative behaviors among graduate students, with intrinsic motivation and roles’ identification for research as sequential mediators; and (4) GSMTS positively moderates the relationship between challenging research pressure and both the intrinsic motivation for research and role identity.

Discussion

This suggests that higher education institutions should cultivate an optimal research and innovation environment for graduate students by increasing challenging research pressure and reducing hindering pressure. They should also emphasize the development of graduate students’ intrinsic motivation for research and identification with research roles. Concurrently, the role of GSMTS should be highlighted to facilitate both the direct and indirect development of graduate students’ innovative behaviors.
The mediating role of English learning motivation between socioeconomic status and pragmatic awareness
Authors: Hui Xiaomeng , Chen Yuqing
Published: January 2025

Socioeconomic status (SES) has received great attention in learning a second or foreign language (SL/FL). However, little research has investigated the association between SES and SL/FL pragmatic learning, let alone the influencing pathways of SES on SL/FL pragmatic awareness (PA). Therefore, this research aimed to address the link between learners’ SES and PA with the mediating effects of learning motivation based on the L2 motivation self-system (L2MSS) theory by surveying 292 Chinese EFL university students. Structural equation modeling analyses indicated that: (1) SES had no significant effect on ought-to L2 self and intended learning efforts; (2) ought-to L2 self and intended learning efforts had significant predictive effects on PA; (3) SES positively and directly predicted EFL learners’ PA; and (4) ideal L2 self, attitudes toward L2 community, and attitudes toward learning English mediated the relationship between SES and Chinese EFL learners’ PA significantly.
Remedies from nature: exploring the moderating mechanisms of natural landscape features on emotions and perceived restoration in urban parks
Authors: Li Yihe , Li Wenbo , Liu Yang
Published: January 2025

Urban parks are the primary places where urban residents reconnect with natural environments. Numerous studies have shown that natural landscape features benefit human mental health and promote perceived restoration. However, few studies have explored the extent to which natural landscape features in urban parks can mitigate or compensate for the negative effects of artificial landscape features on emotions and restoration. This study employed a field survey method, collecting questionnaire data from 599 participants in four urban parks in Hangzhou, China. The DeepLabV3+ semantic segmentation tool was employed to identify and extract landscape features from panoramic images. Data were statistically analyzed using Structural Equation Modeling (PLS-SEM) to explore the potential moderating effects of different natural landscape features in various environmental contexts on emotions and restoration. The results from the SEM model indicate that the R2 values for emotional state (ES) and perceived restorative scale (PRS) are 0.359 and 0.643, respectively, demonstrating an acceptable level of explanatory power and fit for the model. The results revealed that not all artificial landscape features negatively affect emotions and restoration. Although Pavement showed a significant negative impact on Perceived Restoration (β = −0.155, p = 0.004), their effect on emotions was not significant (β = 0.111, p = 0.115). Additionally, the study demonstrated that certain natural landscape features, such as the sky and trees, had a significant moderating effect in alleviating the negative emotions caused by artificial landscape features. However, for Perceived restoration, the moderating effect of these natural landscape features was not significant and, in some cases, even exhibited a negative moderating effect. These findings specifically explore how different natural landscape features can offset the adverse effects of artificial landscape features and, to varying degrees, enhance positive emotional responses and improve perceived restoration. The results contribute to understanding the complex dynamics between landscape features, emotions, and restoration in urban parks, offering strategic recommendations for planning, management, and design to create healthier and more restorative urban park environments.
Video-feedback intervention for promoting social engagement in children with neurodevelopmental disabilities
Authors: Montirosso Rosario , Micheletti Serena , Pisoni Camilla , Mascheroni Eleonora , Scarano Elisa , Naboni Cecilia , Rosa Elisa , Castagna Annalisa , Bonino Margherita , Fazzi Elisa , Orcesi Simona
Published: January 2025

Introduction

Children with neurodevelopmental disabilities (NDs) display several developmental impairments across various domains that impact parent–child interactions, emphasizing the need for effective early interventions. This multi-centric study aimed to evaluate the impact of video-feedback intervention (VFI) on enhancing maternal behavior (i.e., sensitivity) and socio-emotional skills (i.e., engagement and emotionality) in children with NDs during normal or stressful interactions (i.e., the Face-to-Face Still-Face, [FFSF]) paradigm.

Methods

A single-cohort design with pre-(T0) and post-(T1) intervention assessment was used to evaluate 37 mother–child dyads from three units in Northern Italy. The children, aged between 6 and 24 months, had a diagnosis of ND, including psychomotor delay (n = 26) and cerebral palsy (n = 5). The VFI was administered over 6 weeks, with each session focusing on improving parents’ developmental supporting behaviors and enhancing the quality of parent–child interactions. Using the Global Rating Scale coding system (GRS), child behaviors (engagement and emotionality) and maternal behavior (sensitivity) were assessed during the FFSF.

Results

Analyses of variance (ANOVA) indicated significant improvement post-intervention in child engagement in the Reunion episode, with an increase in mother-directed gaze communicative gestures and positive vocalization. A paired sample t-test revealed that the mother’s sensitivity significantly improves between T0 and T1 during the Reunion phase. Moreover, a higher increase in sensitive maternal behavior during the Reunion phase was associated with greater child engagement at T1 during the Reunion episode. No significant changes post-intervention were observed in the emotionality of the child.

Conclusion

The VFI effectively enhanced socio-emotional skills and maternal sensitivity during parent–child interactions, particularly in recovering from interactive disruptions.