bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of beneficial populations for targeted-immunotherapy combinations: tailoring later-line care for patients with pMMR/MSS metastatic colorectal cancer
Authors: Li Dan , Jin Hui , Liu Yan , Liu Jiayin , Zhang Xue , Wang Long , Fan Zhisong , Feng Li , Zuo Jing , Han Jing , Wang Yudong
Published: October 2024

Objective

This study explores the benefits of targeted-immunotherapy combination in third-line or beyond treatment for microsatellite stable (MSS) metastatic colorectal cancer (mCRC) in a real-world setting.

Methods

Patients with MSS mCRC who were treated with either a targeted-immunotherapy combination or targeted therapy alone in the third-line or beyond setting at our hospital from August 2018 to August 2022 were included in the study. Inclusion criteria comprised patients treated with targeted therapy alone or in combination with immunotherapy. Effectiveness was compared between treatments, and patients with the potential to benefit from targeted-immunotherapy combination were identified.

Results

Among 71 patients, 31 received targeted therapies alone (TT group) and 40 received a combination of targeted therapy and immunotherapy (TI group). The TI group had higher objective response rates (20% vs 3.2%) and disease control rates (82.5% vs 58.1%). The median progression-free survival was significantly better in the TI group (4.6 vs 4.1 months, P = 0.027). Liver metastasis was associated with poor prognosis, while patients with only lung metastases had the longest median progression-free survival of 12.3 months with combination therapy.

Conclusion

The study indicates that targeted-immunotherapy combination offers more benefits than targeted therapy alone for MSS mCRC in the third-line or beyond setting.
Tumor-related IGF2BP1-derived molecular subtypes to predict prognosis and immune microenvironment in head and neck squamous cell carcinoma
Authors: Ding Qin , Liu Mingzhu , Pan Yuhui , Wu Ziyi , Wang Jing , Li Yi , Liu Xiaoyong , Lai Jinghua , Hu Dan , Qiu Sufang
Published: October 2024

Background

Recent studies have underscored the biological significance of RNA modifications in tumorigenicity and progression. However, the potential roles of RNA modifications in immune regulation and the formation of the tumor microenvironment (TME) in head and neck squamous carcinoma (HNSC) remain unclear.

Methods

We collected 199 untreated HNSC samples and clinicopathological data from Fujian Provincial Cancer Hospital. MeRIP-seq and RNA-seq were performed to generate methylation and gene expression profiles, respectively. Consensus molecular subtyping was employed to identify prognosis-related genes and RNA modification patterns in HNSC. Experiments confirmed the potential oncogenic behavior influenced by key genes. Molecular subtypes were identified through consensus clustering and validated using external cohort validation sets.

Results

Among the RNA modification-related genes, IGF2BP1 emerged as the most prognostic. HNSC patients were categorized into high and low IGF2BP1 expression groups. High-expressing patients exhibited poorer survival and reduced chemosensitivity, coupled with increased tumor mutational burden, low PD-L1 expression, and limited immune cell infiltration, indicative of aggressive disease. Analysis revealed two distinct RNA modification patterns associated with IGF2BP1 expression: biosynthetically intense type (BIT) and oncogenically active type (OAT), each characterized by distinct clinical features, outcomes, and biological pathways. In an independent immunotherapy cohort, BIT patients displayed enhanced immune responses and sustained clinical benefits.

Conclusions

This study highlights the crucial link between RNA modification and TME diversity. Evaluating RNA modification in tumors improves our understanding of TME features and supports the development of effective immunotherapy strategies.
Chronic pain management in fibromyalgia: the INTEGRO (INTEGRated Psychotherapeutic InterventiOn) protocol and its application on two case studies
Authors: Pasini Ilenia , Donisi Valeria , Veneziani Elisa , Perlini Cinzia , Nizzero Marta , Lippolis Irma , Polati Enrico , Schweiger Vittorio , Del Piccolo Lidia
Published: October 2024

Objectives

To present an innovative integrated manualized psychotherapeutic intervention for fibromyalgia (FM) based on cognitive and behavioral therapy, acceptance and commitment therapy, and somatic experiential techniques (namely the INTEGRated Psychotherapeutic InterventiOn, INTEGRO) and illustrate its application on two case studies.

Methods

INTEGRO is composed of 12 individual sessions. The main objectives of the intervention were psychoeducation of chronic pain mechanisms, understanding the role of cognitive and emotional variables in one’s pain perception, teaching patient-tailored skills to increase pain awareness and its management, and learning how to live with pain experience. A 57-year-old woman (patient A) and a 26-year-old woman (patient B) with FM have been selected to describe their care pathways connected to the INTEGRO protocol. Data related to assessment variables and clinical processes have been reported, focusing on the mechanisms that contribute to the maintenance (i.e., avoidance or overcompensation) of chronic pain in FM, on the role of patients’ naïf theories, and on the implications that all these aspects may have on the burden related to pain management.

Results

Both patients showed a reduction in FM burden and an increase in self-efficacy in pain management: patient A reported an improvement in emotional regulation ability; patient B showed a decrease in pain interference in work activities and on emotional dimension.

Conclusion

Examining each phase of the clinical protocol through the lens of its clinical application, the paper provides insights into the relationship among crucial psychosocial mechanisms, pain perception, management in FM treatment, and how all these aspects have been dealt with during psychotherapeutic treatment.
Distribution and diversity of cultured endophytic fungi in Gentiana straminea Maxim. at different altitudes on the northeastern Qinghai-Tibetan Plateau
Authors: Cheng Tingfeng , Lin Pengcheng , Zhou Dangwei , Wang Huan , Zheng Kun , Shen Jianwei , Shi Shengbo , Hu Xingqiang , Ye Xing , Cao Xueye
Published: October 2024

Endophytic fungi are a crucial microbial resource that can influence plant growth and development through their interactions with host plants. Gentiana straminea Maxim. is an important traditional Tibetan herb used to treat a range of diseases in the Qinghai-Tibetan region. However, the diversity and community structure of endophytic fungi in the species remain poorly understood. In this study, a total of 944 strains of endophytic fungi were isolated from the roots, stems, and leaves of G. straminea from four different altitudes. A total of 87 OTUs were identified through sequence alignment, comprising 6 classes, 15 orders, 25 families, and 44 genera. The colonization rate and diversity of endophytic fungi were affected by tissue type and altitude. With the exception of Xining, the endophytic fungi colonization rate of tissues was roots>leaves>stems. Moreover, the α-diversity of endophytic fungi among different tissues was leaves>stems>roots. Notably, the phylogenetic diversity index in leaves was significantly higher than that in roots. In addition, the colonization rate and diversity of endophytic fungi in leaves and stems demonstrated a decline with the increasing altitude. The β-diversity analysis revealed significant differences in the endophytic fungi of G. straminea at varying altitudes. In roots, geographical factors, such as latitude and longitude, were the primary drivers of variation, whereas environmental factors, including temperature and precipitation, had a greater influence on endophytes in leaves and stems. In addition, the results of the endophytic fungi association preference, linear discriminant analysis effect size (LEfSe), and co-network analysis indicated that these differential endophytic fungi may play a significant role in the authenticity and stress resistance of G. straminea.
Effects of cropland-to-orchard conversion on soil multifunctionality, particularly nitrogen cycling in the eastern Loess Plateau
Authors: Fan Zhuanzhuan , Wang Jiali , Lv Dandan , Li Shangbin , Miao Yuan , Hu Mengjun , Wu Donghui , Liu Fengying , Wang Dong
Published: October 2024

The conversion of cropland to orchards is one of the main measures of the Grain for Green Program for soil and water conservation and ecosystem function maintenance in the eastern Loess Plateau, China. However, the patterns and influencing forces of soil multifunctionality during the conversion from cropland to orchard remain unclear. This study evaluated the responses and regulating factors of soil multifunctionality following the conversion of cropland to pomegranate (Punica granatum L.) orchard along a 10-year chronosequence. Results showed that the conversion of cropland to pomegranate trees significantly increased the L-leucine aminopeptidase enzyme activity from 4.77 to 17.69 nmol g−1 h−1. The 10-year pomegranate stand exhibited the highest nitrogen (N) cycle multifunctionality. The N cycle multifunctionality was positively correlated with soil dissolved organic carbon (C) content, soil available phosphorus content, microbial biomass C content, phospholipid fatty acid, and soil feature index (All p < 0.05). Structural equation modeling suggested that the increased N cycle multifunctionality was attributed to soil feature index rather than soil microbial C content and phospholipid fatty acid. Land-use change did not affect soil C cycle, phosphorus cycle, or soil multifunctionality. Overall, our findings reveal that cropland conversion to orchards significantly enhances soil N cycle multifunctionality, highlighting the soil feature index’s role in maintaining soil function. The conversion from cropland to orchards, which has economic benefits and increases soil N cycle multifunctionality, is an effective approach of the Grain for Green Program in the Loess Plateau.
Response of soil microbial community structure to temperature and nitrogen fertilizer in three different provenances of Pennisetum alopecuroides
Authors: Deng Niandong , Nian Lili , Zhang Shuolun , Liang Yixuan , Shang Huiying , Li Yang , Mao Zhuxin
Published: October 2024

Soil microorganisms are key indicators of soil health, and it is crucial to investigate the structure and interactions of soil microbial communities among three different provenances of Pennisetum alopecuroides under varying nitrogen fertilizer and temperature levels in Northwest China. This study aims to provide theoretical support for the sustainable use of artificial grassland in this region. Employing a two-factor pot-control experiment with three nitrogen fertilizer treatments and three temperature treatments, a total of all treatments was utilized to examine the composition and abundance of soil microbial communities associated with Pennisetum alopecuroides using high-throughput sequencing, PCR technology, and molecular ecological network analysis. The results revealed that Proteobacteria was the dominant bacterial phylum while Ascomycota was the dominant fungal phylum in the soil samples from three provenances of Pennisetum. Specifically, Proteobacteria exhibited higher abundance in the N3T2 treatment compared to other treatments under N3T2 (25–30°C, 3 g/pot) treatment conditions in Shaanxi and Gansu provinces; similarly, Proteobacteria was more abundant in the N1T2 (25–30°C, 1 g/pot) treatment in Inner Mongolia under N1T2. Moreover, Ascomycota displayed higher abundance than other treatments in both Inner Mongolia and Gansu provinces. Additionally, Pennisetum Ascomycota demonstrated greater prevalence under (25–30°C, 3 g/pot) treatment compared to other treatments; furthermore, Shaanxi’s Pennisetum Ascomycota exhibited increased prevalence under N3T1 (18–23°C, 3 g/pot) treatment compared to other treatments. The richness and diversity of soil microbial communities were significantly influenced by nitrogen fertilizer and temperature changes, leading to notable alterations in their structure. Molecular ecological network analyses revealed strong collaborative relationships among microbial species in Shaanxi Pennisetum and Inner Mongolia Pennisetum under high nitrogen and high temperature treatments, while competitive relationships were observed among microbial species in Gansu Pennisetum under similar conditions. Redundancy analysis indicated that soil pH, total potassium, and total phosphorus were the primary environmental factors influencing microorganisms. In summary, this study offers a theoretical foundation for assessing the sustainable utilization of Pennisetum artificial grasslands in Northwest China by investigating the shifts in soil microbial communities and the driving factors under varying nitrogen fertilizer and temperature levels.
Associations between environmental perchlorate, nitrate, and thiocyanate exposure and severe headache or migraine: a cross-sectional, population-based analysis
Authors: Mao Jiesheng , Zhou Mi , Yanjun Li , Zhao Yunhan , Hu Haoxiang , Yang Xiaokai
Published: October 2024

Background

Environmental contaminants may play a significant role in the development of migraine. Perchlorate, nitrate, and thiocyanate were selected for this study due to their known impact on thyroid function, which is closely linked to neurological processes. Disruptions in thyroid function have been associated with various neurological disorders, including migraines. However, there is currently no evidence linking exposure to these specific chemicals to migraine. The study aims to evaluate the association between urinary concentrations of perchlorate, nitrate, and thiocyanate with the prevalence of severe headache or migraine in U.S. adults.

Methods

A cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2001–2004. Utilizing electrospray tandem mass spectrometry in conjunction with ion chromatography, urinary concentrations of perchlorate, nitrate, and thiocyanate urine were measured. Multiple logistic regression models were employed to evaluate the linear correlation between perchlorate, nitrate, and thiocyanate exposure and severe headache or migraine. The non-linear relationship is described analytically using a fitted smoothing curve and a two-piecewise regression model. Subgroup analyses were used to further clarify the stability of this relationship across different populations.

Results

There were 1,446 participants in this population-based study, ranging in age from 20 to 85. After adjusting for potential confounding variables, the multiple logistic regression findings demonstrated that thiocyanate was significantly positively associated with the prevalence of migraine (odds ratio [OR] = 1.18; [1.06, 1.30]; p < 0.001). There was consistency in this connection across different subgroups (p for interaction >0.05). Furthermore, there was a non-linear correlation between urinary thiocyanate and migraine. Using a fitted smoothing curve and a two-piecewise regression model, it was found that the correlation between urinary thiocyanate and migraine was U-shaped (p for Log-likelihood ratio = 0.002). According to the findings of the multiple regression analysis, there was no significant correlation between urinary perchlorate and nitrate and migraine (both p > 0.05).

Conclusion

We should limit our exposure to thiocyanate by keeping it within a reasonable range, as indicated by the U-shaped correlation between urinary thiocyanate and migraine.
Serum glial cell line-derived neurotrophic factor: a potential biomarker for white matter alteration in Parkinson’s disease with mild cognitive impairment
Authors: Liu Yi , Xu Yan , Tong SuYan
Published: October 2024

Objective

Mild cognitive impairment (MCI) is a common non-motor manifestation of Parkinson’s disease, commonly referred to as PD-MCI. However, there is a lack of comprehensive data regarding the role of glial cell line-derived neurotrophic factor (GDNF) and cerebral white matter damage in the pathogenesis of PD-MCI. The objective of this study is to investigate the association between alterations in GDNF levels and cerebral white matter damage in individuals diagnosed with PD-MCI, as well as to explore their potential involvement in cognitive progression.

Methods

Neuropsychological assessments were conducted on 105 patients with Parkinson’s disease and 45 healthy volunteers to examine various cognitive domains. An enzyme-linked immunosorbent assay (ELISA) was employed to measure serum levels of GDNF. Additionally, all participants underwent 3.0T magnetic resonance imaging (MRI) to acquire diffusion tensor images (DTI), and a voxel-based analysis (VBA) approach was utilized to compare the fractional anisotropy (FA) values of white matter in the brain.

Results

There was a significant correlation between the right corpus callosum, right cingulate gyrus, and the Digit Span Backward Test (DSB-T) as well as the Trail Making Test A (TMT-A), both of which assess attention and working memory functions. The left internal capsule exhibited a significant correlation with the Trail Making Test B (TMT-B) and the Clock Drawing Test (CDT), which evaluate executive function. Additionally, the right cingulate gyrus showed a significant association with scores on the Auditory Verbal Learning Test-HuaShan (AVLT-H), assessing memory function. Abnormal fiber structures that demonstrated significant correlations with serum GDNF levels included the left internal capsule, left corticospinal tract, right corpus callosum, and right cingulate gyrus.

Conclusion

The decrease in serum GDNF levels among PD-MCI patients exhibiting impairments in attention and working memory function was significantly correlated with alterations in the corpus callosum (knee) and posterior cingulate gyrus. Furthermore, the reduction of serum GDNF levels in PD-MCI patients with impaired executive function is associated with changes in the internal capsule (forelimb) projection fibers. Additionally, the decline of serum GDNF levels in PD-MCI patients experiencing memory function impairment is related to alterations in the right cingulate gyrus.
A combined radiomics and anatomical features model enhances MRI-based recognition of symptomatic nerves in primary trigeminal neuralgia
Authors: Li Hongjian , Li Bing , Zhang Chuan , Xiao Ruhui , He Libing , Li Shaojie , Yang Yu-Xin , He Shipei , Sun Baijintao , Qiu Zhiqiang , Yang Maojiang , Wei Yan , Xu Xiaoxue , Yang Hanfeng
Published: October 2024

Background

The diagnosis of primary trigeminal neuralgia (PTN) in radiology lacks the gold standard and largely depends on the identification of neurovascular compression (NVC) using magnetic resonance imaging (MRI) water imaging sequences. However, relying on this imaging sign alone often fails to accurately distinguish the symptomatic side of the nerve from asymptomatic nerves, and may even lead to incorrect diagnoses. Therefore, it is essential to develop a more effective diagnostic tool to aid radiologists in the diagnosis of TN.

Purpose

This study aims to establish a radiomics-based machine learning model integrating multi-region of interest (multiple-ROI) MRI and anatomical data, to improve the accuracy in differentiating symptomatic from asymptomatic nerves in PTN.

Methods

A retrospective analysis of MRI data and clinical anatomical data was conducted on 140 patients with clinically confirmed PTN. Symptomatic nerves of TN patients were defined as the positive group, while asymptomatic nerves served as the negative group. The ipsilateral Meckel’s cavity (MC) was included in both groups. Through dimensionality reduction analysis, four radiomics features were selected from the MC and 24 radiomics features were selected from the trigeminal cisternal segment. Thirteen anatomical features relevant to TN were identified from the literature, and analyzed using univariate logistic regression and multivariate logistic regression. Four features were confirmed as independent risk factors for TN. Logistic regression (LR) models were constructed for radiomics model and clinical anatomy, and a combined model was developed by integrating the radiomics score (Rad-Score) with the clinical anatomy model. The models’ performance was evaluated using receiver operating characteristic curve (ROC) curves, calibration curves, and decision curve analysis (DCA).

Results

The four independent clinical anatomical factors identified were: degree of neurovascular compression, site of neurovascular compression site, thickness of the trigeminal nerve root, and trigeminal pons angle (TPA). The final combined model, incorporating radiomics and clinical anatomy, achieved an area under the curve (AUC) of 0.91/0.90 (95% CI: 0.87–0.95/0.81–0.96) and an accuracy of approximately 82% in recognizing symptomatic and normal nerves.

Conclusion

The combined radiomics and anatomical model provides superior recognition efficiency for the symptomatic nerves in PTN, offering valuable support for radiologists in diagnosing TN.
Glaucoma and dietary links: insights from high-salt intake, the Mediterranean diet, and specific nutrients
Authors: Yang Yuqi , Zhou Hongyan , Hong Zhang
Published: October 2024

Glaucoma, a prevalent and potentially blinding eye disease, is linked to a variety of factors, including elevated intraocular pressure, optic nerve damage, and oxidative stress. In recent years, dietary habits, as a controllable lifestyle factor, have received increasing attention in the prevention and treatment of glaucoma. The purpose of this review was to investigate the effects of dietary factors on glaucoma, with a particular emphasis on two common dietary patterns: the high-salt diet and the Mediterranean diet. In addition, we investigated the association between many particular nutrients (including omega-3 fatty acids, vitamins, caffeine, and minerals) and glaucoma to fully assess the potential involvement of dietary variables in glaucoma pathogenesis, prevention, and treatment. This article reveals the importance of dietary components in glaucoma prevention and explores prospective possibilities for future research by conducting a comprehensive review of previous scientific studies.
Tislelizumab plus chemotherapy in metastatic extramammary Paget disease after surgery: a case report
Authors: Wang Dongxing , Huang Chuang , Wang Dongming , Chang Dehui
Published: October 2024

Extramammary Paget disease (EMPD) is a rare epithelial adenocarcinoma in apocrine-gland rich skin, involving the vulva, the scrotum, and the penis. with distant metastases and a poor prognosis. Local EMPD patients generally have a good prognosis, with expected 5-year survival of 60%–92%, but distant metastasis represents poor prognosis and 5-year survival of 10%. Treatment approaches for advanced EMPD are chemotherapy and biological agents, which carry limited efficacy. We report the case of a 57-year-old man diagnosed with metastatic EMPD, who showed a long-term disease control with a combination therapy (an immune checkpoint inhibitor - tislelizumab plus chemotherapy – paclitaxel albumin and cisplatin). This patient underwent a wide penile scrotal lesion excision and six cycles of tislelizumab plus chemotherapy. The patient achieved partial response for the metastatic lesions according to the Response Evaluation Criteria in Solid Tumors (version 1.1). This case report supports further investigation of the combination treatment of chemotherapy and immune checkpoint inhibitors in the management of metastatic EMPD, which currently has an abysmal prognosis and no standardized treatment.
Case report: Combinations of immune checkpoint inhibitor, chemotherapy, and hyperthermia therapy avoid lymphatic recurrence in cholangiocarcinoma
Authors: Chang Heng-Jui , Ke Chiao-Hsu , Wang Yu-Shan
Published: October 2024

Cholangiocarcinoma is a malignancy known for its aggressiveness and limited treatment options. The malignant tumor behaviors include intrahepatic recurrence, regional lymph node (LN) metastasis, peritoneal carcinomatosis, and lung metastasis. Herein, we reported a case of lymphatic recurrence in an intrahepatic cholangiocarcinoma patient after surgery, adjuvant concurrent chemoradiotherapy (CCRT), who experienced a remarkable response to a combination therapy. However, the patient failed to undergo radiotherapy or other invasive local therapy and therefore received Opdivo (nivolumab) in combination with chemotherapy (FOLFOX) and modulated electro-hyperthermia. Notably, after these medical interventions, this patient had a complete response (CR) to treatments, in which no lymph node metastasis occurred, and a significantly decreased tumor marker, CA 19-9, level was found. This case highlights the potential of multiple anti-tumor therapies, including immune checkpoint inhibitors, chemotherapy, and hyperthermia, in managing challenging cholangiocarcinoma cases.
Clinical utility of circulating tumor DNA profiling in detecting targetable fusions in non-small cell lung cancer
Authors: Kim Young-gon , Lee Boram , Ha Changhee , Lee Cheonghwa , Jung Hyun Ae , Sun Jong-Mu , Lee Se-Hoon , Ahn Myung-Ju , Choi Yoon-La , Park Sehhoon , Kim Jong-Won
Published: October 2024

Introduction

Numerous studies have suggested high concordance between tissue and circulating tumor DNA (ctDNA) comprehensive genomic profiling (CGP) tests but only few of them focused on fusions. In addition, atypical breakpoints occasionally detected from DNA-based fusion detection make interpretation difficult, and their clinical significance remains unclear. This study evaluated the clinical utility of ctDNA CGP for fusion detection.

Methods

The results of ctDNA CGP tests performed on patients with stage IV non-small cell lung cancer during routine clinical care were retrospectively reviewed. The concordance between ctDNA CGP and combined tissue test results was analyzed using CGP, immunohistochemistry, fluorescence in situ hybridization, and reverse transcription polymerase chain reaction. The clinical significance of fusions detected by ctDNA CGP, including those with atypical breakpoints at the DNA level, was assessed.

Results

In total, 264 patients were tested with ctDNA CGP. Fusions were detected in 27 patients (10.2%), and the fusion drivers were RET (n=12, 4.6%), ALK (n=9, 3.4%), ROS1 (n=4, 1.5%), and FGFR2 (n=2, 0.8%). The overall prevalence of fusion in tissue CGP was comparable to that in ctDNA CGP. A total of 371 ctDNA-tissue test pairs were available, and the overall positive and negative percent agreement rates were 92.9% (13/14) and 100.0% (357/357), respectively. One ALK IHC-positive and ctDNA CGP-negative case did not respond to ALK-targeted therapy. Response to targeted therapy was assessed in 16 patients, and a partial response was achieved in all patients, including four with atypical breakpoints.

Conclusion

Fusion detection using ctDNA CGP showed high concordance with tissue tests and accuracy in predicting therapeutic responses in patients with non-small cell lung cancer. ctDNA CGP may provide an important diagnostic tool for fusion detection.
Analysis of risk factors associated with cervical HPV infection and their effects on female sexual function and anxiety: a multicenter cross-sectional study based on Chinese women
Authors: Wang Haoye , Nie Keyi , Liu Zixuan , Zhao Yumeng , Ha Yingxin , Zhang Huanyan , Mao Dongwei
Published: October 2024

Introduction

This research aimed to explore the determinants of cervical HPV infection and evaluate how cervical cancer screening outcomes influence sexual functioning and anxiety among women across three provinces in China.

Methods

Study participants were categorized into HPV-positive or HPV-negative groups, after which they completed the General Characteristics Questionnaire and the SAS Anxiety Scale. The HPV-positive cohort was further divided into four subgroups: Subgroup 1 consisted of individuals with HPV types 16 or 18 but no cytological abnormalities. Subgroup 2 included those with cytological abnormalities and infections with HPV types 16 or 18. Subgroup 3 included participants infected with high-risk HPV types other than 16 and 18, who did not show cytological abnormalities, while Subgroup 4 encompassed individuals with both cytological abnormalities and infections with high-risk HPV types other than 16 and 18. All participants were assessed using the Female Sexual Function Index Scale (FSFI), which measures sexual function across these subgroups.

Results

A total of 531 questionnaires were analyzed. Logistic regression identified several risk factors for HPV infection, including manual labor, service occupations, other occupations, low- and middle-income groups, and cervical columnar epithelial ectasia, as well as an increase in the number of previous sexual partners. Conversely, protective factors included condom use during sexual activity and mutual genital hygiene prior to intercourse. The incidence of lower genital tract infections was significantly higher in the HPV-positive group compared to the HPV-negative group, with rates of chlamydia (13.3% versus 4.6%, P<0.001), gonococcal infections (5.2% versus 0.4%, P<0.001), and mycobacterial diseases (38.9% versus 23.4%, P<0.001). Additionally, anxiety levels were significantly higher in the HPVpositive group compared to the HPV-negative group (p<0.005). Anxiety levels and cytological outcomes were significantly correlated across the four HPV-positive subgroups (p<0.05), with type 16/18 infections being associated with notably lower FSFI scores compared to other high-risk HPV types (p<0.05).

Conclusions

The findings suggest that infections with HPV type 16/18, especially when accompanied by abnormal cytological findings,significantly elevate anxiety and distress in women and are associated with reduced FSFI scores. These results highlight the complex impact of HPV infection on women’s sexual health and psychological well-being with HPV type 16/.
Investigating conditioned pain modulation in horses: can the lip-twitch be used as a conditioning stimulus?
Authors: Blum Severin , Gisler Jana , Dalla Costa Emanuela , Montavon Stéphane , Spadavecchia Claudia
Published: October 2024

Study objective was to evaluate whether the application of a lip twitch could be proposed as conditioning stimulus in the context of a novel Conditioned Pain Modulation (CPM) assessment paradigm for use in horses. The study was a prospective, experimental, randomized trial. Twelve healthy horses were evaluated in two experimental sessions. The lip twitch was used as the conditioning stimulus in both sessions; electrical stimulation was used as the test stimulus in one session, while mechanical and thermal stimulations were used in the other. Differences between thresholds recorded before and during twitching (Δ) as well as their percent (%) change were computed for each stimulation modality as a measure of CPM. Heart rate and respiratory rate were recorded throughout the experiments to monitor physiological reactions, while the general level of stress and aversiveness toward twitching were scored using ad hoc behavioural scales. Based on these scores, interruption criteria were defined. Ten and seven horses completed the electrical and mechanical/thermal experimental sessions respectively. For electrical stimulation, median (IQR) Δ was −2.8 (−3.9, −1.1) mA and% change 87.9 (65.7–118.2)%; for mechanical stimulation, Δ was −18.2 (−6.4, −21.4) N and% change 343.5 (140, 365.3)%; for thermal stimulation, Δ was −3.1 (−9.2, −2.1)°C, while% change was not calculated. Heart rate and respiratory rates varied significantly over time, with higher values recorded during twitching. Median stress and aversion scores did not differ between the two sessions. As lip twitching consistently affected thresholds to all stimulation modalities, it can be proposed as effective conditioning method for CPM assessment in horses. The exclusion of subjects due to severe aversion shows that this paradigm cannot be indistinctively applied to all horses and that stringent interruption criteria are necessary to guarantee adequate welfare during testing.
Pediatric kidney transplantation in Europe, a clinical snapshot pilot
Authors: Oomen Loes , Bootsma-Robroeks Charlotte M. H. H. T. , Bouts Antonia H. M. , Carbonell Pradas Mar , Gander Romy , Kienzl-Wagner Katrin , König Paul , Pereira Pedro Lopez , Dunand Olivier , Mosca Sara M. F. S. , Pac Michal , Podracka Ludmila , Prytula Agnieszka A. , Sangermano Maria , Vitkevic Renata , Zieg Jakub , van der Zanden Loes F. M. , Feitz Wout F. J. , de Wall Liesbeth L.
Published: October 2024

Background

Pediatric kidney transplantations are rarely performed, and there is limited knowledge about the diversity in current clinical practices across Europe. This study aims to explore the utility of clinical snapshot studies in identifying these disparities, establishing a foundation for future snapshot studies and standardization efforts.

Methods

A pilot clinical snapshot study was conducted, with invitations extended to all 109 pediatric kidney transplant centres in Europe. Each participating centre provided pre-, peri-, and postoperative data concerning their most recent thirty transplantations. The primary outcomes encompassed the evaluation of disparities in donor-recipient selection, surgical techniques, post-operative drainage procedures, and immunosuppressive therapy protocols. Secondary outcomes involved the analysis of rejection rates, incidence of infections, and graft survival.

Results

The study involved 439 patients from fifteen centres (14%) in twelve countries, with varying transplant volumes (range 1–29 transplantations per year) and follow-up periods. Significant differences were found among centres in terms of donor types, cold and warm ischemia time, pre-emptive transplant rates, and kidney transplant drainage methods. The rate of living donors varied between 3% and 90% and the median duration of cold ischemia ranged was 770 min after deceased donation and 147 min after living donation. Basiliximab was the dominant induction therapy, yet steroid withdrawal varied widely. Infection, rejection, and graft survival rates also varied significantly between centres.

Conclusion

This study revealed substantial variation in clinical practices among European centres performing pediatric kidney transplantations. These findings could serve as a stimulus for international dialogue and collaboration.
Synergistic anti-osteoporosis effects of Anemarrhena asphodeloides bunge–Phellodendron chinense C.K. Schneid herb pair via ferroptosis suppression in ovariectomized mice
Authors: Deng Xuehui , Xiao Wenlong , Lin Bingfeng , Wang Fang , Song Li , Wang Nani
Published: October 2024

Introduction

Ferroptosis plays a crucial role in the progression of postmenopausal osteoporosis. Anemarrhena asphodeloides Bunge/Phellodendron chinense C.K. Schneid (AA/PC) is the core herb pair in traditional Chinese medicines formulae for postmenopausal osteoporosis treatment. However, the synergistic effects, and mechanisms, of AA/PC on alleviating ferroptosis and postmenopausal osteoporosis remain unclear.

Methods

The goal herein was to analyze the effective ingredients and molecular mechanisms of AA/PC in the treatment of osteoporosis through serum pharmacochemistry, network pharmacology, metabolomics analysis, and pharmacodynamics evaluation. A bilateral ovariectomized (OVX) mouse model was established.

Results and Discussion

Micron-scale computed tomography analysis showed that AA/PC increased bone mineral density in OVX mice. The effects of AA/PC were better than AA or PC alone on inhibiting the bone resorption marker nuclear factor of activated T-cells 1. Furthermore, five absorbable compounds were detected in serum: mangiferin, magnoflorine, berberine, timosaponin BIII, and timosaponin AIII. Network pharmacology showed these compounds had close relationship with seven ferroptosis targets. Importantly, compared with AA or PC alone, the AA/PC herb pair exerted better effects on regulating crucial ferroptosis pathways, including the system xc-/glutathione/glutathione peroxidase 4, transferrin receptor/ferritin, and acyl-CoA synthetase long chain family member 4/polyunsaturated fatty acids signaling pathways. These results indicate that AA/PC exerts synergistic effects on regulating glutathione synthesis, iron homeostasis, and lipid metabolism in ferroptosis. This work lays the foundation for further development and use of AA/PC herb pair for preventing and treating postmenopausal osteoporosis.
Underlying mechanisms of ketotherapy in heart failure: current evidence for clinical implementations
Authors: Liu Kun , Yang Yang , Yang Jing-Hua
Published: October 2024

Heart failure (HF) is a life-threatening cardiac syndrome characterized by high morbidity and mortality, but current anti-heart failure therapies have limited efficacy, necessitating the urgent development of new treatment drugs. Exogenous ketone supplementation helps prevent heart failure development in HF models, but therapeutic ketosis in failing hearts has not been systematically elucidated, limiting the use of ketones to treat HF. Here, we summarize current evidence supporting ketotherapy in HF, emphasizing ketone metabolism in the failing heart, metabolic and non-metabolic therapeutic effects, and mechanisms of ketotherapy in HF, involving the dynamics within the mitochondria. We also discuss clinical strategies for therapeutic ketosis, aiming to deepen the understanding of the characteristics of ketone metabolism, including mitochondrial involvement, and its clinical therapeutic potential in HF.
Action potentials in vitro: theory and experiment
Authors: Pi Ziqi , Zocchi Giovanni
Published: October 2024

Action potential generation underlies some of the most consequential dynamical systems on Earth, from brains to hearts. It is therefore interesting to develop synthetic cell-free systems, based on the same molecular mechanisms, which may allow for the exploration of parameter regions and phenomena not attainable, or not apparent, in the live cell. We previously constructed such a synthetic system, based on biological components, which fires action potentials. We call it “Artificial Axon”. The system is minimal in that it relies on a single ion channel species for its dynamics. Here we characterize the Artificial Axon as a dynamical system in time, using a simplified Hodgkin-Huxley model adapted to our experimental context. We construct a phase diagram in parameter space identifying regions corresponding to different temporal behavior, such as Action Potential (AP) trains, single shot APs, or damped oscillations. The main new result is the finding that our system with a single ion channel species, with inactivation, is dynamically equivalent to the system of two channel species without inactivation (the Morris-Lecar system), which exists in nature. We discuss the transitions and bifurcations occurring crossing phase boundaries in the phase diagram, and obtain criteria for the channels’ properties necessary to obtain the desired dynamical behavior. In the second part of the paper we present new experimental results obtained with a system of two AAs connected by excitatory and/or inhibitory electronic “synapses”. We discuss the feasibility of constructing an autonomous oscillator with this system.
Personalised in silico biomechanical modelling towards the optimisation of high dose-rate brachytherapy planning and treatment against prostate cancer
Authors: Hadjicharalambous Myrianthi , Roussakis Yiannis , Bourantas George , Ioannou Eleftherios , Miller Karol , Doolan Paul , Strouthos Iosif , Zamboglou Constantinos , Vavourakis Vasileios
Published: October 2024

High dose-rate brachytherapy presents a promising therapeutic avenue for prostate cancer management, involving the temporary implantation of catheters which deliver radioactive sources to the cancerous site. However, as catheters puncture and penetrate the prostate, tissue deformation is evident which may affect the accuracy and efficiency of the treatment. In this work, a data-driven in silico modelling procedure is proposed to simulate brachytherapy while accounting for prostate biomechanics. Comprehensive magnetic resonance and transrectal ultrasound images acquired prior, during and post brachytherapy are employed for model personalisation, while the therapeutic procedure is simulated via sequential insertion of multiple catheters in the prostate gland. The medical imaging data are also employed for model evaluation, thus, demonstrating the potential of the proposed in silico procedure to be utilised pre- and intra-operatively in the clinical setting.
Strict biennial lifecycle and anthropogenic interventions affect temporal genetic differentiation in the endangered endemic plant, Pedicularis hallaisanensis
Authors: Kim Seongjun , Lee Byoung-Doo , Lee Chang Woo , Park Hwan-Joon , Hwang Jung Eun , Park Hyeong Bin , Kim Young-Joong , Jeon Daeyoung , Yoon Young-Jun
Published: October 2024

Strict biennials are among the least known lifecycles in plant ecology due to their rarity in nature, and their population genetics still remain unknown. The present study addressed the strict biennial lifecycle and associated population genetics of Pedicularis hallaisanensis, an endangered endemic plant in Korea. All P. hallaisanensis individuals were counted in August from 2021 to 2023 in the wild population of Gayasan National Park, and lifecycle and morphological changes were monitored monthly. A de novo draft genome and single nucleotide polymorphism (SNP) analysis were used to study the population’s genetic structure. P. hallaisanensis strictly requires a 2-year lifecycle per generation, including 8 and 10 months of growing periods as a first-year seedling and second-year adult, respectively. Facultative annual and perennial lifecycles were undetected, resulting in odd-year and even-year flowering cohorts. Permutational multivariate analysis of variance on the detected 3,716 SNPs demonstrated that the flowering group (p < 0.005), microhabitat (p < 0.001), and their interaction (p < 0.01) had a significant effect on genetic structure, which was differentiated between odd-year and even-year flowering cohorts. Other cluster analyses also showed that a microhabitat under historical anthropogenic interventions contained lowered genetic diversity due to a decreased genetic distance between odd-year and even-year flowering cohorts (p < 0.05). Overall, the findings suggest that excessive anthropogenic interventions should be avoided to preserve genetic diversity in the wild P. hallaisanensis population. Moreover, conservation programs for similar biennial plants should collect wild breeds from both odd-year and even-year flowering cohorts to improve the genetic diversity of artificially propagated individuals.
Reflective groundcovers promote anthocyanin content and advance fruit maturity of ‘Evercrisp’ apples grown in the Mid-Atlantic US
Authors: Miah Md Shipon , Farcuh Macarena
Published: October 2024

Enhanced skin blush is critical in many apple cultivars to ensure crop profitability and acceptability. Anthocyanin content is a crucial determinant of apple skin blush. Reflective groundcovers are a preharvest management strategy that can improve apple skin blush, but integrative studies assessing its effects at the environmental, physiological, gene, and metabolite levels are lacking. In the present study, we assessed the impact of reflective groundcovers on light environment, preharvest fruit drop, internal ethylene concentration (IEC), fruit-quality-related physicochemical parameters, skin coloration, expression levels of important anthocyanin biosynthesis-related structural genes and transcription factors, and total anthocyanin content of ‘Evercrisp’ fruit located in the canopy’s lower third during on-the-tree ripening, for 2 years, under mid-Atlantic US conditions. Fruit treated with reflective groundcovers displayed an enhanced red skin coloration, reaching >60% blush 1 week before commercial harvest and 2 weeks earlier than control fruit. This resulted from a significantly increased transcript accumulation of anthocyanin biosynthesis-assessed genes, which was promoted by an increased light reflectance (>5–25 times greater than control), which also led to a correspondingly higher total anthocyanin content. Additionally, reflective groundcover-treated ‘Evercrisp’ fruit also exhibited an increased IEC and an advanced maturity, but without differences in fruit drop, as compared to control fruit, during on-the-tree ripening. Reflective groundcovers deployment would allow for an earlier harvest (of at least one week) of ‘Evercrisp’ fruit, which would be packing out in the premium grades as compared to control, thus increasing fruit crop value.
Towards contextualized complex systems approaches to scaling-up hepatitis B birth-dose vaccination in the African region: a qualitative systematic review
Authors: Solomon-Rakiep Tasneem , Olivier Jill , Amponsah-Dacosta Edina
Published: October 2024

Background

Despite the longstanding implementation of universal hepatitis B infant vaccination programs, the World Health Organization African region (WHO AFRO) maintains the highest prevalence (2.5%) of chronic hepatitis B virus (HBV) infection among children ≤5 years of age. Scaling-up hepatitis B birth-dose (HepB BD) vaccination could avert mother-to-child transmission of HBV infection and advance regional progress towards eliminating viral hepatitis.

Objective

To describe whether – and how – complexities within the health system or intervention influence the performance of HepB BD vaccination programs in the WHO AFRO.

Methods

Using a complexity perspective, we conducted a qualitative systematic review of literature published between 2009–2022. A Boolean search strategy retrieved relevant literature indexed in PubMed, EBSCOhost databases, Scopus, and Web of Science, with supplementary searches conducted to identify any missed articles. No language restrictions were applied. Data extraction, synthesis and analysis were guided by a systems-based logic model tailored to systematic reviews of complex interventions.

Results

Our search yielded 672 published records. Of these, 28 (26 English, 2 French) were eligible for inclusion. Among the 12 WHO AFRO member states represented, the origin of evidence weighted highest in Nigeria (n = 12) and Senegal (n = 5). The performance of HepB BD vaccination programs across member states are influenced by underlying complexities across eight cross-cutting themes: (i) availability and interpretation of HepB BD vaccination policies, (ii) capacity of vaccine supply and cold chain systems, (iii) availability of equitable and sustainable financing, (iv) capacity and capability of health care workers (HCWs), (v) immunization monitoring systems and impaired feedback loops, (vi) influence of context vs system design on the timeliness of vaccination, (vii) maternal knowledge and socio-economic factors, and (viii) wider contextual factors (geography, climate, cultural practices).

Conclusion

Countries looking to introduce, or scale-up HepB BD vaccination programs will benefit from careful consideration of components of the intervention design that are dependent on the end-user’s context and capabilities in accessing the vaccine; the adherence and interpretation of essential components of the policy; the provision of adequate support of stakeholders specifically HCWs and government ministries; and the need for innovative approaches to underlying complexities. Lessons offered by these African experiences provide pragmatic approaches to successfully implementing HepB BD vaccination programs in the region.