bluuebunny/crossref_metadata_2025 huggingface dataset:
Post-Penetration Development, Pathogenicity and Histological Changes in Ridge gourd infected by Root-Knot Nematode (Meloidogyne incognita)
Authors: V BASAVARAJ , Bilebhavi Chaitra M , S Shraddha , Sharada M S , R Sampathkumar M , M Mahesh H
Published: April 2024

Ridge gourd (Luffa acutangula (L.) Roxb.) is a crucial warm-season vegetable crop cultivated extensively in India and tropical regions of Asia and Africa. Despite its medicinal significance and popularity in Indian cuisine, Ridge gourd faces numerous biotic stressors, with root-knot nematodes (Meloidogyne spp.) being one of the most prevalent. This study aimed to investigate the post-penetration development of Meloidogyne incognita on Ridge gourd, assessing its pathogenicity and histopathological changes induced in the host plants. Under controlled laboratory and glasshouse conditions, experiments were conducted to observe nematode penetration and development stages, as well as the impact of nematode inoculum levels on Ridge gourd growth parameters and chlorophyll content. Histopathological studies were performed to visualize anatomical changes in infected roots. Results demonstrated swift penetration and developmental progression of M. incognita within Ridge gourd roots, culminating in reproductive stages. Pathogenicity assessments revealed a dose-dependent relationship between nematode density and plant damage, with higher inoculum levels resulting in significant reductions in growth parameters and chlorophyll content. Histopathological analyses unveiled extensive damage to root tissues, including gall formation and anatomical abnormalities. This study enhances the understanding of M. incognita interactions with Ridge gourd, emphasizing the need for effective management strategies to mitigate nematode-induced losses in agricultural productivity.
Spatial Heterogeneity in Climate Change: Evidence from Brazilian Biomes
Authors: Rodarte Adriano Braga , Laurini Márcio Poletti
Published: April 2024

We present a methodology designed to study the spatial heterogeneity of climate change. Our approach involves decomposing the observed changes in temperature patterns into multiple trend, cycle, and seasonal components within spatio-temporal models. We apply this method to test the hypothesis of a global long-term temperature trend against multiple trends in distinct biomes. Applying this methodology, we delve into the examination of heterogeneity of climate change in Brazil — a country characterized by a spectrum of climate zones. The findings challenge the notion of a global trend, revealing the presence of distinct trends in warming effects, and more accelerated trends for the Amazon and Cerrado biomes, indicating a composition between global warming and deforestation in determining changes in permanent temperature patterns.
The protective effect of sildenafil on colon anastomosis in a rat model undergoing hypertermic intraperitoneal chemotherapy
Authors: Başak Ahmet , Aydın Mehmet Timuçin , Fersahoğlu Mehmet Mahir , Taşdelen İksan , Somay Adnan , Teke Emre , Durum Erdem , Memişoğlu Kemal
Published: April 2024

Aim: The aim of this study was to investigate the effects of sildenafil on colonic anastomosis healing in rats treated with hyperthermic intraperitoneal chemotherapy.
Method: In our study, 30 Wistar-albino rats were used. 30 rats were divided into 3 groups: the sildenafil, control and sham groups. Left colon anastomosis was performed on rats in all three groups.The HIPEC procedure was applied to sildenafil group and control group. During the postoperative period, sildenafil was given orally to the sildenafil group. On the 7th day, the anastomotic loop was excised, and bursting pressure, and adhesion were evaluated. Anastomotic loop was evaluated histopathologically. The results were compared statistically.
Results: When the results were evaluated considering bursting pressure, and adhesion between the sildenafil group and control group, there was no difference. Considering adhesion, the sham group was superior to the other two groups. Histopathological examination reveals that the sham group was significantly superior to the other two groups in terms of anastomototic re-epitelization and muscle separation. There was a significant difference between the sildenafil group and the control group in terms of fibrosis and granulation.
Conclusion: On colon anastomosis performed together with HIPEC application, histopathologically positive effects of sildenafil were observed. The burst pressure of colon anastomosis was not significantly different.
Determination of Bioclimatic Factors Associated with Acanthamoeba Distribution Using Ecological Niche Modeling in Two Foci of Turkey
Authors: Evyapan Gülşah , Kavur Hakan , Artun Ozan , Koltaş İsmail Soner
Published: April 2024

Purpose The protozoan parasite Acanthamoeba, which is known to be opportunistic in nature, has a global distribution in the environment and is responsible for causing severe infections in humans.The aims of this study were to determine the presence of Acanthamoeba in water and soil samples using culture methods, to determine the underlying factors affecting its distribution and, to produce the current and future probability model of Acanthamoeba spp in the study areas.
MethodsA total of 20 water samples from hot springs and swimming pools and 20 soil samples were taken from various parks and agricultural areas in Afyon and Kütahya. We have opted to utilize the Maximum Entropy (MaxEnt) modeling algorithm, included 19 bioclimatic (bioclim) variables.
Results We identified positive water samples rate in Afyon and Kütahya were 60% and 100% respectively. Also, we detected 70% and 50% positive rates of soil samples collected in Afyon and Kütahya respectively. Furthermore, it was determined that BIO3, BIO4, BIO13 and BIO15 exhibit the highest degree of influence on both present and anticipated future outcomes. The model's validity was assessed by computing the AUC values for both present and future periods, resulting in values of 0.991 and 0.977, respectively.
ConclusionAccording to the parameters determined to affect the presence of the parasite, it is predicted that the presence of Acanthamoebawill increase in the coming years, especially towards the southwest of Afyon and the southern regions of Kütahya.
Astrocytes mGluR3 deficiency and inhibition restores depressive-like behaviors in CSDS mice
Authors: Chen Mingming , Liu Yatao , Shi Lingling , Hou Tingting , Zhang Wen , Tong Jie , Wan Zhanhai , Ji Chengying , Su Xiaodong , Gao Chaohui , Fu Qian , Liu Ying , Liu Qijing , Gao Boxiong , Jin Wenjie
Published: April 2024

The involvement of metabotropic glutamate receptors (mGluR) in mood regulation has been widely acknowledged. However, the specific changes in the distribution and function of these receptors in astrocytes within mood-related brain regions during depression remain unclear. In this study, we conducted an analysis of astrocytes isolated from mood-related brain regions (mPFC, hippocampus, amygdala, NAc, BNST, and VTA) in CSDS mice to investigate the expression of mGluR3 and mGluR5. Surprisingly, we observed an upregulation of mGluR3 specifically in astrocytes from the mPFC, BNST, and VTA, but not in isolated neurons or microglia. Additionally, we observed an increase in astrocyte reactivation and the release of gliotransmitters (such as glutamate, D-serine, and GABA), while neuronal activities (represented by the frequency and amplitude of sEPSC) were inhibited. Furthermore, we found that by knocking out Grm3 and inhibiting mGluR3 through NAM treatment prior to CSDS, depressive-like behaviors were improved in mice. These findings contribute to a better understanding of the underlying mechanisms of depression and offer new perspectives for the development of antidepressant treatments.
Neurological Complexities in Co-infection: A Case Report of Brucella Meningoencephalitis with Concurrent Epstein-Barr Virus Infection and Bilateral Optic Neuritis
Authors: Dong Jie , Chen Shuru , Liu Baomo , Liu Jing
Published: April 2024

Background
Brucellosis, while primarily known for its systemic manifestations, can occasionally involve the central nervous system, resulting in meningoencephalitis. This report presents an atypical case of Brucella meningoencephalitis, marked by co-infection with Epstein-Barr virus and the development of bilateral optic neuritis, which was further complicated by drug-induced hepatitis against a background of resolved pulmonary tuberculosis.
Case Presentation
We report a unique case of Brucella meningoencephalitis in a 34-year-old male with concurrent Epstein-Barr virus infection and bilateral optic neuritis that was further complicated by drug-induced hepatitis and a history of pulmonary tuberculosis. The diagnosis was confirmed through cerebrospinal fluid metagenomic next-generation sequencing and MRI findings. Treatment was challenging, requiring a multidisciplinary approach due to concurrent hepatic and infectious disease considerations, and ultimately included a tailored combination of antibiotic and supportive therapies.
Conclusions
This case highlights the diagnostic and therapeutic challenges of managing Brucella meningoencephalitis with concurrent conditions. Advanced diagnostic techniques were pivotal in the identification of each condition, and a personalized, multidisciplinary treatment approach was necessary due to the patient’s complex clinical state. This report adds to the body of knowledge on the neurologic complications of brucellosis and underscores the need for close monitoring of patients with relapsing symptoms and concurrent infections.
A novel stage and classification system of ONFH based on the radiologic-histopathological correlation
Authors: Ma Jinhui , shen Mengran , Wang Bailiang , Yue Debo , wang Weiguo , Cheng Liming
Published: April 2024

Background: To explore the influence of the new staging and classification system based on the correlation between MRI and pathological features on the collapse, symptoms and function of femoral head necrosis.
Methods: This retrospective study included 100 patients (200 hips) who were diagnosed with bilateral ONFH. According to the degree of fibrosis in the necrotic area in a mid-coronal section on hip MRI, the MRI stage of ONFH can be divided into three types. Based on the level of inflammatory response, the MRI classification of ONFH can be divided into two types (S1 and S2), and S2 can be divided into three subtypes (S2a, S2b, S2c). The radiological evaluations were based on plain X-rays and MRI. The data were analysed using SPSS 26.0 statistical software.
Results: There was a significant difference in the collapse rate between Type Ⅰ (7.1% ),Type Ⅱ (66.3% ) and Type Ⅲ (92.1%) (P＜0.001). The collapse rate in S1 (11.1%), S2a (66.7%), S2b (85.3%), S2c (77.8%) was significantly different (P＜0.001). There was also a significant difference in pain level and hip function between MRI staging and classification (P＜0.001). The later the stage, the higher the pain level, and similar results in hip functions. With the aggravation of bone marrow edema, the patient’s pain level increases and hip function decreases.
Conclusion: Pathological fibrosis and inflammatory response are important factors that influence ONFH collapse and prognosis. The new MRI stage and classification based on pathology is a supplement to the existing stage and classification.
Effect of rotation curvature correction and inviscid spatial discretization scheme on the aerodynamics of vertical axis wind turbine
Authors: Ma Kaifang , Wang Jiasong , Xue Leiping
Published: April 2024

The effect of rotation-curvature correction and inviscid spatial discretization scheme on the aerodynamic performance and flow characteristics of Darrieus H-type vertical axis wind turbine (VAWT) is investigated based on an in-house solver. This solver is developed on a platform HRAPIF based on the finite volume method (FVM) with the elemental velocity vector transformation (EVVT) approach. The present solver adopts the density-based method with a low Mach preconditioning technique. The turbulence models are the Spalart-Allmaras (SA) model and the \(k - \omega\) shear stress transport (SST) model. The inviscid spatial discretization schemes are the 3rd-order monotone upstream-centered schemes for conservation Laws (MUSCL) scheme and the 5th-order modified weighted essentially non-oscillatory (WENO-Z) scheme. The power coefficient, instantaneous torque of blades, blade wake, and turbine wake are compared and analyzed at different tip speed ratios. The extensive analysis reveals the density-based method can be applied in VAWT numerical simulation; the SST models perform better than the SA models in power coefficient prediction; the rotation-curvature correction is not necessary and the 3rd-order MUSCL is enough for power coefficients prediction; the high-order WENO-Z scheme can capture more flow field details; the rotation-curvature correction and high-order WENO-Z scheme reduce the length of the velocity deficit region in the turbine wake.
Assessment of water quality in the piped water supply system in Bhubaneswar city
Authors: Samal Kshyana Prava , Tarai Ashok Kumar
Published: April 2024

Drinking water of right quantity and approved quality is the basic need for the development of any civilization. As per SDG 6 it is essential to provide equitable water in terms of quality and quantity to every citizen. Due to the huge growth of population along with the increase of infrastructure, educational institutions, industrial growth in the city of Bhubaneswar there is threat to the quality of the supply water. In this context the water sample has been collected from 67 wards of Bhubaneswar from the focused areas near to industry, market complex, educational institutions and near to the construction site in a particular ward. Nearly 15 water quality parameters have been tested and analysed using weighted arithmetic water quality index method. The study found that around 10.46% deviation in pH, 22.69% in hardness, 10.36% in conductivity, 19.16% in DO from the standard limit as per the guidelines of WHO. Also, it was concluded that no more threat to the heavy metal contamination like Lead copper and zinc in any of the samples. After discussion with Public Health Engineering Department, it was found that the deviation of the parameters is due to the ageing of the pipeline system which is under the consideration of their work. It shows that system needs to be monitored frequently for water quality related issues.
Distribution characteristics of Lipoprotein (a) and non-genetic factors in Chinese Han population
Authors: Ma Cong , Gao Linggen , Que Yifan , Zhao Libo , Li Tianzhi , Xu Guogang
Published: April 2024

Objective: To explore the distribution characteristics and influencing factors of Lipoprotein (a) [Lp(a)] in Chinese Han population.
Methods: In total, 2135 Chinese Han individuals who received physical examinations and lab tests from June 2019 to January 2020 in Health Management Institute, Chinese PLA General Hospital were enrolled in the current study. Basic clinical characteristics including disease history, family history, diet habit, blood lipid were collected.
Results: A total of 1459 males and 676 females were finally enrolled to this research, with an average age of 48.09±7.98 years old and an overall level of LP (a) of 12.46±17.58 mg/dl. LP(a) increased gradually in 20-60 years. Women presented with a higher LP(a) than that of men in all age groups. The multivariate logistic regression revealed that the influencing factors of LP(a) varied with different cut-off points. Hypertension acted as the risk factor (P < 0.05), while fish consumption acted as the protective factor for the increase of LP (a) (P = 0.001) when the cut-off point was 30mg/dl. However, women and hypertension acted as the risk factors for the increase of LP (a) (P< 0.05) when the cut-off point was 50mg/dl.
Conclusion: This research analyzed the clinical characteristics of Chinese Han population and investigated the potential influencing factors. Fish consumption is conducive to the decrease of LP(a). However, women and patients with hypertension should put more emphasis on the monitor of LP(a) and be wary of cardiovascular disease. This study may provide some evidence on the lifestyle management of Chinese Han population.
Nomogram for predicting liver function recovery in hepatitis B virus-related hepatocellular carcinoma patients after ablation therapy
Authors: Liang Xi-tian , Chen Yu-xin , Yang Wei , Han Xue , Cheng Wen
Published: April 2024

Background
This study investigated the ability of the novel visual transient elastography (ViTE) technique combined with the albumin–bilirubin (ALBI) score to predict liver function recovery (LFR) in hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC) patients, considering the potential effect of HBV on HCC progression and poor outcomes.
Methods
Clinical data from 234 HBV patients between January 2022 and August 2023 were retrospectively analysed. Among these patients, 129 had HCC and underwent ablation therapy. All patients underwent preoperative ViTE examination, which recorded their liver stiffness value (LSV), as well as collection of liver function indices before and after ablation. Multivariate logistic regression analysis of risk factors for liver functional deterioration was used to construct a nomogram, which was validated internally.
Results
During the study period, RFA was performed on 100 patients, while MWA therapy was administered to 29 patients with HCC. The LSV exhibited a significant positive correlation with the preoperative ALBI score in patients with HBV, both those with and without HCC (all p < 0.001). Age, ALBI score and LSV, together with ablative data, were found to be independent predictors of liver functional deterioration after therapy (all p < 0.05). The nomogram built on these variables was validated internally and showed good performance (accuracy = 0.810, kappa = 0.607). According to the clinical decision curve analysis, the threshold of the model was 0.07-1, indicating that the model has high clinical value.
Conclusion
Based on the ViTE and ALBI, this nomogram serves to enable the personalized prediction of perioperative LFR for patients with HBV-related HCC following ablation therapy.
Evidence and Rationale for Centromedian Nucleus versus Internal Medullary Lamina Stimulation for Generalized Epilepsy Through Intra-Operative Multi-Modal Electrophysiology Studies
Authors: Gonzalez-Martinez Jorge , Ho Jonathan , Aung Thandar , Damiani Arianna , Tang Lilly , Mallela Arka , Crammond Donald
Published: April 2024

Epilepsy's global impact affects 65 million individuals, of which 30% endure drug-resistant epilepsy (DRE). Surgical excision of the epileptogenic zone remains the primary intervention but is often hampered if patients have generalized epilepsy. Neuromodulation, such thalamic centromedian nucleus (CM) neurostimulation, offers a promising alternative. However, the mechanism is unclear by which neurostimulation of the CM modulates cortical neurophysiology to reduce seizures, hampering progress for more effective targeting of the CM. In this study, we introduce a novel multimodal approach that combines intraoperative thalamic and cortical recordings with diffusion tractography to precisely elucidate CM stimulation targets. Our analysis reveals that stimulation of lower cellular activity CM targets produce greater cortical delta activity that is observed during epileptogenic network disruption. We found that this stimulation target lies within the internal medullary lamina, which differs from standard thalamic targets. Our findings show that a personalized implantation method guided by electrophysiological mapping can enhance neurostimulation targets in treating DRE.
Selective regulation of corticostriatal synapses by astrocytic phagocytosis
Authors: Park Hyungju , Kim Ji-young , Lee Hyoeun , Chung Won-Suk
Published: April 2024

In the adult brain, neural circuit homeostasis depends on the constant turnover of synapses via astrocytic phagocytosis mechanisms. However, it remains unclear whether this process occurs in a circuit-specific manner. Here, we reveal that astrocytes target and reorganize excitatory synapses in the striatum. Using model mice lacking astrocytic phagocytosis receptors in the dorsal striatum, we found that astrocytes constantly remove corticostriatal synapses rather than thalamostriatal synapses. This preferential elimination suggests that astrocytes play a selective role in modulating corticostriatal plasticity and functions via phagocytosis mechanisms. Supporting this notion, corticostriatal long-term potentiation (LTP) and the early phase of motor sequence learning are dependent on astrocytic phagocytic receptors. Together, our findings demonstrate that astrocytes contribute to the connectivity and plasticity of the striatal circuit by preferentially engulfing a specific subset of excitatory synapses within brain regions innervated by multiple excitatory sources.
A mixed-methods study on enhancing the service system of human assisted reproductive technologies: A case study in Hangzhou, China
Authors: Rong Chao , Wu Qun-Hong , Chang Ming , Yan Chun-Hong , Xie Rong-Rong
Published: April 2024

Background: Infertility is a widespread medical condition Assisted Reproductive Technology (ART) stands as an effective treatment for infertility; however, the existing reproductive healthcare system lacks comprehensive development.. Methods: Employing both stratified and random sampling methods, one hospital from each provincial and municipal level in Hangzhou was selected, yielding a sample comprising 139 patients and 8 medical personnel. The analysis utilized a mixed-methods research approach.
Results: 43.88% of the respondents considered a price range of 20,000 to 40,000 RMB as acceptable. Regarding the desired time to conceive, 73.38% of respondents aimed to conceive within six months. Patients under 30 and those between 30 to 35 years showed greater preference for assisted reproductive hospitals with higher success rates. Patients intending for a single pregnancy were likelier than those considering multiple pregnancies to view comprehensive or fixed-sum insurance coverage as more influential in increasing their willingness to conceive.
Conclusion: Standardization of a well-coordinated and organized assisted reproductive medical consortium should be promoted. Enhancement of the diagnosis and treatment level in assisted reproductive services is essential. Humanistic care should be reinforced. A scientifically guided approach to determining assisted reproductive service pricing should progressively inform the reasonable expansion of medical insurance coverage. Enhanced supervision over abortion institutions is crucial. A societal atmosphere conducive to marriage and childbearing at an appropriate age should be fostered.
Surgical Delay-Associated Mortality Risk Varies by Subtype in Loco-Regional Breast Cancer Patients in SEER-Medicare
Authors: Leslie Macall , Pathak Rashmi , Dooley William C. , Squires Ronald A. , Rui Hallgeir , Chervoneva Inna , Tanaka Takemi
Published: April 2024

Substantial evidence supports that delay of surgery after breast cancer diagnosis is associated with increased mortality risk, leading to the introduction of a new Commission on Cancer quality measure for receipt of surgery within 60 days of diagnosis for non-neoadjuvant patients. Breast cancer subtype is a critical prognostic factor and determines treatment options; however, it remains unknown whether surgical delay-associated breast cancer-specific mortality (BCSM) risk differs by subtype. This retrospective cohort study aimed to assess whether the impact of delayed surgery on survival varies by subtype (hormone [HR]+/HER2-, HR-/HER2-, and HER2+) in patients with loco-regional breast cancer who received surgery as their first treatment between 2010–2017 using the SEER-Medicare. Continuous time to surgery from diagnostic biopsy (TTS; days) in reference to TTS = 30 days. BCSM were evaluated as flexibly dependent on continuous time (days) to surgery from diagnosis (TTS) using Cox proportional hazards and Fine and Gray competing-risk regression models, respectively, by HR status. Inverse propensity score-weighting was used to adjust for demographic, clinical, and treatment variables impacting TTS. Adjusted BCSM risk grew with increasing TTS across all subtypes, however, the pattern and extent of the association varied. HR+/HER2- patients exhibited the most pronounced increase in BCSM risk associated with TTS, with approximately exponential growth after 42 days, with adjusted subdistribution hazard ratios (sHR) of 1.21 (95% CI: 1.06–1.37) at TTS = 60 days, 1.79 (95% CI: 1.40–2.29) at TTS = 90 days, and 2.83 (95% CI: 1.76–4.55) at TTS = 120 days. In contrast, both HER2 + and HR-/HER2- patients showed slower, approximately linear growth in sHR, although non-significant in HR-HER2-.
Integrated single-cell and bulk RNA-seq for constructing a prognostic risk model of immune-related genes in colorectal cancer
Authors: Xiong Yan , Xiong Weiqiang , Wang Yanhua , He Chuan , Zhan Yimei , Pan Lili , Luo Liangping , Song Rongfeng
Published: April 2024

Colorectal cancer (COAD) ranks as the second leading cause of global cancer-related deaths. However, effective therapeutic strategies for advanced colorectal cancer remain limited. Despite the success of immunotherapy in cancer treatment, its applicability is significantly constrained by the heterogeneity of the tumor microenvironment. Therefore, the aim of this study is to develop an immune-related feature model at the single-cell level, categorize colorectal cancer patients based on gene transcription levels, and predict patients' prognosis, immune status, and treatment response. By analyzing single-cell transcriptomic data (scRNA-seq) of COAD, we identified eight cell types and selected immune cell marker genes (IRGs) for subsequent analysis. Utilizing these IRGs, we established an immune-related model to classify patients into high and low-risk groups for predicting overall survival (OS). The low-risk group exhibited high tumor mutation burden (TMB), increased immune activation, high microsatellite instability (MSI-H), longer overall survival (OS), and better response to immunotherapy. Conversely, the high-risk group displayed microsatellite stability (MSS), low TMB, immune suppression, and other characteristics. Additionally, we validated the model's performance in predicting immune treatment responses using external data from the IMvigor210 cohort. In summary, combining single-cell and bulk tissue transcriptome sequencing, we constructed a survival risk prognosis model that categorizes patients into high and low-risk groups. This model enables the prediction of patients' immune cell status, immune-related functions, and immunotherapy effectiveness. These findings provide valuable insights into the immune status, prognosis assessment, and the development of effective immunotherapeutic approaches for colorectal cancer.
FTO ameliorates learning and memory impairment by activating PI3K/AKT/mTOR signaling pathway in a neurodevelopmental model of schizophrenia
Authors: li mengdie , Zhong Yongjie , Zhang Ling , Song Zhen , Wei Chuke , Zhang Kai , Liu Huanzhong , Yang Yating
Published: April 2024

Background
The pathogenesis of cognitive dysfunction in schizophrenia (SCZ) is still unclear, and m6A methylation may be involved in the neuropsychiatric diseases. The aim of this study was to investigate the effect of m6A methylation on learning and memory impairment induced by a neurodevelopmental model of SCZ.
Methods
Perinatal NMDA receptor antagonist combined with post-weaning social isolation (MK-SI) was used to construct a neural development model of SCZ. FTO adeno-associated virus (AAV) was injected into the hippocampus by stereotaxic technique. Then, it is evaluated by a series of behavioral tests. Brain tissue was analyzed by m6A dot blot, LC-MS/MS, qRT-PCR, western blot, tissue staining, MeRIP-seq, and colorimetry.
Results
Our results showed that FTO mediates m6A modification in the hippocampus of MK-SI mice, leading to learning and memory impairment. AAV9 FTO knockdown (FTO-KD) aggravated learning and memory impairment induced by MK-SI model. In contrast, AAV9 FTO overexpression (FTO-OE) reversed these effects. In addition, FB23-2 inhibited the reversal effect of FTO-OE in MK-SI mice, further confirming the important role of FTO in MK-SI-induced learning and memory impairment. Next, using high-throughput sequencing analysis, we found that the PI3K/AKT/mTOR signaling pathway may play a key role. In addition, the expression of the apoptotic protein Bax and the pro-apoptotic protein Bcl-2 were regulated by FTO.
Conclusions
In summary, the demethylase FTO mediated m6A modification to induce learning and memory impairment, highlighting the important role played by FTO in cognitive dysfunction in the MK-SI model.
Comparison of Targeted Next Generation Sequencing Assays in Non-small cell lung cancer Patients
Authors: Drejeriene Ieva , Gruode Jurate , Cicenas Saulius , Loizides Charalambos , Eliades Alexia , Achilleos Achilleas , Kypri Elena , Tsangaras Kyriakos , Ioannides Marios , Koumbaris George , Stanciute Diana , Krasauskas Arnoldas
Published: April 2024

Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer the mutational spectrum of which has been extensively characterized. Treatment of patients with NSCLC based on their molecular profile is now part of the standard clinical care. The aim of this study was firstly to investigate two different NGS-based tumor profile genetic tests and secondly to assess the clinical actionability of the mutations and their association with survival and clinicopathological characteristics. Overall, 52 mutations were identified in 31 patients by either one or both assays. The most frequently mutated genes were TP53 (40.4%), KRAS (13.46%) and EGFR (9.62%). TP53 and KRAS mutations were associated with worst overall survival while KRAS was positively correlated with adenocarcinoma. The two methods showed a high concordance for the commonly covered genomic regions (97.14%). Ten mutations were identified in a genomic region exclusively covered by the NIPD Genetics custom tumor profile assay. Likewise, one MET mutation was identified by the Ion Amliseq assay in a genomic region exclusively covered by Ion Amliseq. In conclusion both assays showed highly similar results in the commonly covered genomic areas, however, the NIPD Genetics assay identified additional clinically actionable mutations that can be applied in clinical practice for personalized treatment decision making for patients with NSCLC.
Optimising (Re-)Irradiation for Locally Recurrent Head and Neck Cancer: Impact of Dose-Escalation, Salvage Surgery, PEG Tube Dependence and Biomarkers on Oncological Outcomes
Authors: Schleifenbaum Julia Katharina , Morgenthaler Janis , Sharma Shachi Jenny , Klußmann Jens Peter , Linde Philipp , Wegen Simone , Rosenbrock Johannes , Baues Christian , Fokas Emmanouil , Khor Richard , Ng Sweet Ping , Marnitz Simone , Trommer Maike
Published: April 2024

Introduction:
Locoregional recurrence (LR) is common in locally-advanced head and neck cancer (HNSCC), posing challenges for treatment. We analysed outcome parameters and toxicities for patients being treated with radiotherapy (RT) for LR-HNSCC and investigated patient and disease related prognostic factors in this prognostically unfavourable group.
Methods
This analysis includes 101 LR-HNSCC patients treated with RT, radio-chemotherapy (RCT) or radio-immunotherapy (RIT) between 2010–2018. Patient characteristics, tumour and treatment details were retrospectively collected. Overall survival (OS), progression-free survival (PFS) and toxicities were assessed.
Results
62% of patients were radiotherapy-naïve (initial RT) while 38% were re-irradiated at site of LR (re-RT). Median OS for initial RT was 17 months, for re-RT 9 months (p = 0.005). In the RCT subgroup, patients with initial RT had significantly longer OS with 27 months compared to re-RT 12 months (p = 0.006). Patients requiring a percutaneous feeding tube had significantly shorter OS (12 vs. 27 months) in multivariate analysis. Significant factors for longer OS in univariate analysis included salvage surgery, haemoglobin levels ≥ 12g/dl, low inflammatory status (Glasgow Prognostic Score 0), radiation doses ≥ 50 Gy. We detected 37 (15%) ≥ Grade III events for initial RT and 19 (15%) for re-RT patients.
Conclusion
We identified key prognostic factors including feeding tube dependence, anaemia, and inflammation status that could guide treatment decision. Our findings suggest salvage surgery as preferred treatment option with postoperative RT in high risk situations. A radiation dose of ≥ 50 Gy should be administered to achieve better outcomes. Adverse events due to re-RT are acceptable using an OAR-driven approach.
The dimethyloxalylglycine-functionalized nanofibers for in situ regeneration of infected developing dental roots
Authors: Woo Kyung Mi , Yoo Yeon-Jee , Eun-Hye Lee , Bae Jieun , Kim Woo Jin , Park Chan Ho , Chung Shin Hye , Shon Won Jun , Lee WooCheol
Published: April 2024

In situ regeneration in restorative dentistry focuses on repairing tissues directly at the injury site by using engineered biomaterials to guide endogenous cell activity. This approach aims to simplify treatment processes and improve outcomes for conditions like developing teeth with necrotic pulp infections. This study explores the potential of poly(ε-caprolactone) fibers (PCLF) functionalized with dimethyloxalylglycine (DMOG) for in situ regeneration in the context of dental root repair in immature teeth with necrotic pulp and apical periodontitis. In vivo application to a model in beagle dogs demonstrated the effectiveness of PCLF/DMOG in promoting root development, apical closure, and clearing infectious lesions, contrasting with calcium hydroxide paste, contemporary regenerative endodontic treatment controls that showed thin root growth and resilient persistent infection. Mechanistically, the sustained release of DMOG from PCLF/DMOG significantly enhanced the expression of hypoxia-inducible factor 1-alpha and upregulated genes associated with angiogenesis and neurogenesis, including vascular endothelial growth factor-A and nerve growth factor. The PCLF/DMOG upregulated antimicrobial peptides, facilitated efferocytic activities, and promoted macrophage polarization to the M2 phenotype. These findings highlight the potential of PCLF/DMOG scaffolds for dental root regeneration, offering a promising approach for treating immature teeth with necrotic pulp and apical periodontitis through in situ regeneration.
Mid-term outcomes of endoscopic vein harvesting in coronary artery bypass graft: A retrospective cohort study
Authors: Wang Wuwei , Liu Yiming , Qi Haoyu , Liu Yafeng , Jiang Yunfei , Fan Rui , Shao Junjie , Chen Wen , Su Cunhua , Chen Xin
Published: April 2024

OBJECTIVES
Endoscopic vein harvesting (EVH) is an alternative technique to obtain the saphenous vein for coronary artery bypass graft (CABG) surgery. We aimed to evaluate the early and mid-term outcomes of patients with EVH in CABG.
METHODS
This cohort study included consecutive isolated CABG patients in Nanjing First Hospital from July 2020 to December 2022 using propensity score matching methods. Patients were classified to EVH group and open vein harvesting (OVH) group according to the vein harvesting methods. The primary outcome was the all-cause death, and the secondary outcomes were major adverse cardiovascular events (MACEs) including cardiovascular death, heart failure, myocardial infarction and revascularization and asymptomatic survival in the follow-up.
RESULTS
Totally 1247 patients were included in the study with 849 in OVH group and 398 in EVH group. Patients with EVH were more female, diabetes, higher body mass index, more multi-vessel and left main diseases. 308 pairs were formed after the matching. There was no significant difference in the rates of in-hospital death (EVH vs. OVH, 2.3% vs. 1.3%, P = 0.543). During the 3 years follow-up, EVH grafts were considered not inferior to OVH grafts, no differences were found in all-cause death [8.5% vs. 5.0%, hazard ratio (HR) 1.565, 95% confidence interval (CI): 0.77–3.17, P = 0.21], MACEs (8.1% vs. 7.1%, HR 1.165, 95CI: 0.51–2.69, P = 0.71) and asymptomatic survival (66.7% vs. 72.5%, HR 1.117, 95%CI: 0.65–1.92, P = 0.68).
CONCLUSIONS
EVH grafts were considered comparable to OVH grafts in patients following CABG in the 3 years follow-up.
Assessing Patient Experiences with a Virtual Triage and Assessment Centre (VTAC): A Mixed-Method Study Using an Online Survey and Semi-Structured Interviews in Renfrew County, Ontario.
Authors: St-Amant Antoine , Peixoto Cayden , Bair-Patel Dez , Heideman Martha , Menkhorst Kayla , Fitzsimon Jonathan
Published: April 2024

Background
In March 2020, the Renfrew County Virtual Triage and Assessment Centre (VTAC) was launched as a large-scale, innovative, hybrid healthcare program. VTAC aims to alleviate pressure on emergency departments by providing additional and more equitable access to family physicians and allied health professionals. This study’s objective was to evaluate patients’ experiences with VTAC.
Methods
In this sequential explanatory mixed-method study, we distributed 397 online surveys and conducted 10 semi-structured interviews with Renfrew County residents aged 18 and above who had utilized VTAC at least once since 2023. Survey data were analyzed through descriptive statistics, chi-squared tests, and a multivariate binary logistic regression, while semi-structured interviews were coded and analyzed using reflexive thematic analysis.
Results
Our findings demonstrate widespread satisfaction with VTAC, and a perception of receiving high-quality care. This was irrespective of demographic characteristics, health status, or appointment modality. In our interviews, four main themes emerged: “Healthcare in Renfrew County”, “Accessing VTAC”, “VTAC Clinical Care”, and “Improving VTAC”. These themes underscore major difficulties residents encounter in accessing healthcare in Renfrew County and illustrate that services from VTAC align with a genuine population-level need, offering a valuable contribution to addressing some of these challenges.
Conclusion
Our study highlights that Renfrew County is grappling with a crisis of access to healthcare, and that VTAC fills a crucial gap, primarily by providing timely access to a family doctor. The findings provide evidence of patient acceptability and satisfaction with VTAC, potentially guiding the design of future healthcare programs.
Specifying implementation strategies used in delivering services for HIV, gender-based violence and sexual and reproductive health to adolescent girls and young women in community health systems in Zambia
Authors: Zulu Joseph Mumba , Maritim Patricia , Silumbwe Adam , Wang Bo , Chavula Malizgani Paul , Munakampe Margarate , Halwiindi Hikabasa , Hazemba Alice Ngoma , Matenga Tulani.Francis L. , Mweemba Mable , Menon J. Anitha , Kim Deogwoon , Musukuma Mwiche , Zyambo Cosmas , MacDonell Karen , Mweemba Oliver , Simpungwe Matilda Kakungu , Phiri Henry
Published: April 2024

Background
Adolescent girls and young women (AGYW) in Zambia experience challenges including gender-based violence (GBV) and difficulty obtaining care for sexual and reproductive health (SRH) and treatment for HIV. Implementation strategies for delivering GBV, SRH and HIV services targeted to AGYW in community health systems (CHS) have not been fully specified. We sought to define and specify common implementation strategies being used in Zambia.
Methods
In a qualitative case study in 3 districts, we interviewed 29 key informants from government bodies, NGOs, and community leaders; we also conducted 23 in-depth interviews with AGYW aged between 10 and 24 years. Analysis of the data used thematic analysis based on the four CHS lenses (programmatic, relational, collective action, and critical lenses) and on the Expert Recommendations for Implementing Change (ERIC) compilation of implementation strategies.
Results
Implementation strategies identified under the programmatic lens were 1) changing infrastructure, which included increasing health facilities and delivering adolescent- and young people-friendly services; 2) training and educating stakeholders, which consisted of increasing capacity building, developing and using educational materials, ongoing training and educational outreach visits; and 3) adapting and tailoring services to context, which included delivering integrated services and developing by-laws. Relational lens strategies were 1) developing stakeholder interrelationships such as building a coalition of service providers; and 2) using new funding through cost-sharing among stakeholders. Under the collective action lens, implementers mainly engaged consumers, by increasing demand using community networks, using mass media to share information, and intervening with patients to enhance uptake of services. The critical lens showed that effective implementation of GBV, SRH and HIV services was affected by structural and socio- cultural factors such as social stigma and cultural norms.
Conclusion
This study builds on the ERIC compilation of implementation strategies by identifying and specifying implementation strategies used in the delivery of HIV, GBV and services for AGYW in community health systems. We provide additional evidence on the importance of relational and collective-action approaches in strengthening community-engaged implementation and dissemination.
Analysis of factors influencing the complications of severe acute pancreatitis combined with hemorrhage
Authors: Shao Liang , Wan Jianhua , He Wenhua , Zhu Yong , Zhu Yin , Liu Jing , Liu Fen , Lu Nonghua , Xia Liang
Published: April 2024

Background
The complication of hemorrhage in patients with severe acute pancreatitis (SAP) is an important influencing factor for poor prognosis, and the existing research is still insufficient. Therefore, this study aimed to analyze the influencing factors of hemorrhage in SAP patients.
Methods
Reviewing the clinical data of SAP patients admitted to our hospital from January 2019 to December 2022, this study evaluated the independent influencing factors of bleeding based on the propensity score matching method and multivariate logistic regression analysis, established a Nomogram prediction model for predicting SAP patients with concurrent bleeding, and drew the ROC curve while observing prognosis.
Results
A total of 804 patients were finally included according to the nadir criteria, and 97 (12.1%) were found to have hemorrhage complications. After screening by propensity score matching method, 440 patients were identified including 88 patients with bleeding. In univariate and multivariate logistic regression analysis, computed tomography severity index score (CTSI) score (OR: 1.771, 95% CI: 1.434–2.187, P < 0.001), Infected Pancreatic Necrosis (IPN) (OR: 4.407, 95% CI: 1.854–10.476, P < 0.001), Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥ 15 (OR: 12.323, 95% CI: 5.015–30.282, P < 0.001), Abdominal Compartment Syndrome (ACS) (OR: 3.685, 95% CI: 1.462–9.287, P = 0.006), and Continuous Renal Replacement Therapy (CRRT) (OR: 0.251, 95% CI: 0.094–0.670, P = 0.006) were identified as independent influencing factors for SAP with concurrent bleeding. Accordingly, we constructed a Nomogram prediction model with an area under the curve of the ROC curve of AUC of 0.924. The median time of hospital stay in ICU and total hospital stay was significantly higher in the bleeding group than in the non-bleeding group (30VS7, 48VS18, P < 0.001), and the number of deaths in the bleeding group was significantly higher than that in the non-bleeding group (46.6%VS6.5%, P < 0.001).
Conclusion
Complications of SAP hemorrhage suggest poor prognosis; therefore, for patients with elevated CTSI score and APACHE II score, combined IPN and ACS, the focus should be on strengthening hemorrhage surveillance, CRRT may be performed if necessary to improve the condition and reduce the risk of bleeding.
A scoping review of the impacts of forest dynamics on acari-borne diseases: beyond forest fragmentation
Authors: Blache Nolwenn , Chalvet-Monfray Karine , Déprés Christophe , Morand Serge
Published: April 2024

Background:
Forest cover has undergone significant changes, which have accelerated over recent decades. Acari vectors such as ticks and chigger mites are intricately linked to forest ecosystems because of the suitable hosts and microclimates they provide. However, the implications of forest cover change and dynamics on acari vectors and their pathogens remain poorly understood. This study aims to investigate the impacts of forest dynamics on the risk of acari-borne diseases worldwide through a comprehensive review of the literature.
Methods:
We conducted a scoping review following the PRISMA Method to retrieve citations related to forest dynamics and acari-borne diseases. Eligibility criteria were predefined and relevant data were extracted from selected articles. The analysis employed a descriptive approach and thematic narrative synthesis.
Results:
Our review reveals that the influence of forest dynamics on acari-borne diseases and related vectors was predominantly discussed within a Western context, particularly with regard to Ixodes ticks and Lyme disease. Four types of forest dynamics have been identified in the literature: deforestation, fragmentation, conversion and reforestation. However, there was no consensus on the impacts of those dynamics on the vectors and their associated pathogens. Studies have reported conflicting findings including: protective or risk effects, nonlinear relationships, dependent effects influenced by additional factors altering relationships or nonsignificant effects. Those outcomes had been reported across different forest dynamics and various locations. Although, there is limited empirical evidence on tropical contexts as well as for reforestation and conversion dynamics, making it difficult to draw conclusions regarding pathogen and vector trends. Differences in results trends emerge when comparing the entire article sample (n = 111) to empirical studies (n = 73), with literature reviews often overestimating the dilution effect observed in empirical research. Finally, our review identifies a notable absence of studies on scrub typhus disease in the context of forest dynamics.
Conclusions:
This scoping review offers a novel and comprehensive overview of global literature on the impacts of forest dynamics on acari vectors and the infectious agents they transmit. It highlights research gaps and the need for future research targeting specific forest dynamics, particularly chigger mite vectors in a tropical context.
Differences in characteristics and outcomes of older patients hospitalized for COVID-19 after introduction of vaccination.
Authors: Smits Rosalinde , Raaij Bas F.M. van , Trompet Stella , Linden Caroline M.J. van der , Bol Jessica M. van der , Jansen Steffy W.M. , Polinder-Bos Harmke A. , Willems Hanna C. , de Glind Esther M.M. van , Minnema Julia , Tap Lisanne , Mooijaart Simon P.
Published: April 2024

Purpose: The aim of the present study was to investigate characteristics and outcomes in vaccinated and unvaccinated older patients hospitalized for COVID-19 infection.
Methods: A retrospective multicentre cohort study among patients aged ≥70 years hospitalized for COVID-19 infection.
Results: 263 vaccinated and 82 unvaccinated patients were included. Vaccinated patients were older (median age 79 vs. 76 years; p<0.001), had more comorbidities (median Charlson Comorbidity Index (CCI) 2 vs. 1; p0.016) and were frailer (Clinical Frailty Scale (CFS) ≥4 68% vs. 49%; p0.015). Vaccinated patients were admitted earlier after symptom onset (median 5 days vs. 7 days) but were equally ill at time of hospital admission. After correction for frailty, comorbidity and disease severity, risk of in-hospital mortality was three times lower for vaccinated patients (HR 0.30 95% CI 0.16-0.56; p<0.001) compared to unvaccinated patients.
Conclusion: Compared to older unvaccinated patients hospitalized for COVID-19, vaccinated patients were frailer, had more comorbidities but, independent of these factors, a three times lower risk for in-hospital mortality. These findings may trigger pro-active geriatric advance care planning, aimed toward early rehabilitation.