bluuebunny/crossref_metadata_2025 huggingface dataset:
Projected climate oligotrophication of the Adriatic marine ecosystems
Authors: Mentaschi Lorenzo , Lovato Tomas , Butenschön Momme , Alessandri Jacopo , Aragão Leonardo , Verri Giorgia , Guerra Roberta , Coppini Giovanni , Pinardi Nadia
Published: February 2024

The Adriatic Sea hosts diverse marine ecosystems, characterized by rich biodiversity and unique ecological dynamics. Its intricate coastal habitats and open waters support a range of species and contribute to the region's ecological and economic significance. Unraveling the consequences of the ongoing climate changes on this delicate environment is essential to ensure the future safeguard of this basin. To tackle this problem, we developed a biogeochemical model for the entire basin, with a horizontal resolution of about 2 km and 120 vertical levels, forced by the projections of atmosphere, hydrology and ocean circulation between 1992 and 2050, under emission scenario RCP8.5. The changes projected between 2031–2050 and 1992–2011 were evaluated on ecoregions characterized by different trophic conditions, identified using a k-medoid classification technique. The results point toward a generalized oligotrophication of the basin, especially intense in the northern estuarine areas, driven by a substantial decrease in river discharge projected for the rivers of the Po Plain. This scenario of unproductive and declining resources, together with the ongoing warming, salinization, and acidification of marine waters, cast doubt on the long-term resilience of the Northern Adriatic food web structure, which has evolved to thrive in high trophic conditions. The outcome of this study provides the stakeholders with a tool to understand how potential long-term decreases in the regimes of the Northern Adriatic Rivers could affect the marine ecosystem and its goods and services in the future.
Predictors of left ventricular ejection fraction in high-risk percutaneous coronary interventions
Authors: Panoulas Vasileios F. , Escaned Javier , Hill Jonathan M. , Barker Erin , Butler Karin , Almedhychy Ali , Tsintzos Stelios I. , O’Neill William W.
Published: February 2024

Revascularization completeness after percutaneous coronary intervention (PCI) is associated with improved long-term outcomes. Mechanical circulatory support [intra-aortic balloon pump (IABP) or Impella] is used during high-risk PCI (HR-PCI) to enhance peri-procedural safety and achieve more complete revascularization. The relationship between revascularization completeness [post-PCI residual SYNTAX Score (rSS)] and left ventricular ejection fraction (LVEF) in HR-PCI has not been established. We investigated LVEF predictors at 90 days post-PCI with Impella or IABP support. Individual patient data (IPD) were analyzed from PROTECT II (NCT00562016) in the base case. IPD from PROTECT II and RESTORE-EF (NCT04648306) were naïvely pooled in the sensitivity analysis. Using complete cases only, linear regression was used to explore the predictors of LVEF at 90 days post-PCI. Models were refined using stepwise selection based on Akaike Information Criterion and included: treatment group (Impella, IABP), baseline characteristics [age, gender, race, New York Heart Association Functional Classification, LVEF, SYNTAX Score (SS)], and rSS. Impella treatment and higher baseline LVEF were significant predictors of LVEF improvement at 90 days post-PCI (p ≤ 0.05), and a lower rSS contributed to the model (p = 0.082). In the sensitivity analysis, Impella treatment, higher baseline LVEF, and lower rSS were significant predictors of LVEF improvement at 90 days (p ≤ 0.05), and SS pre-PCI contributed to the model (p = 0.070). Higher baseline LVEF, higher SS pre-PCI, lower rSS (i.e. completeness of revascularization), and Impella treatment were predictors of post-PCI LVEF improvement. The findings suggest potential mechanisms of Impella include improving the extent and quality of revascularization, and intraprocedural ventricular unloading.
Application of a modified clinical classification for pulmonary arterial hypertension associated with congenital heart disease in children: emphasis on atrial septal defects and transposition of the great arteries. An analysis from the TOPP registry
Authors: Wacker Julie , Humpl Tilman , Berger Rolf M. F. , Ivy Dunbar , Bowers David , Bonnet Damien , Beghetti Maurice
Published: February 2024

Aims

A proportion of patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) do not fit in the current classification. We aimed to analyse the applicability of an adapted clinical classification of PAH-CHD to pediatric patients using the TOPP-1 registry (Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension) and focus on atrial septal defects (ASD) and transposition of the great arteries (TGA).

Methods and results

Hemodynamic and clinical data of all patients with PAH-CHD in the TOPP cohort were reviewed. Patients were classified according to predefined ABCDE categories (A: Eisenmenger syndrome, B: left-to-right shunt, C: coincidental defects, including all ASDs, D: corrected CHD, E: TGA), or as complex CHD (group 5), by 2 independent investigators. In case of disagreement, a third reviewer could either settle a final decision, or the patient was deemed not classifiable. Survival curves were calculated for each group and compared to idiopathic PAH patients of the registry. A total of 223 out of 531 patients in the registry had PAH-CHD, and 193 were categorized to the following groups: A 39(20%), B 27(14%), C 62(32%) including 43 ASDs, D 58(30%), E 7(4%), whereas 6 patients were categorized as group 5, and 10 patients were unable to be classified. No survival difference could be demonstrated between the groups.

Conclusions

This modified classification seems to be more applicable to pediatric PAH-CHD patients than the previous classification, but some patients with PAH-CHD who never had a shunt remain unclassifiable. The role of ASD in pediatric PH should be reconsidered.
Proposed treatment strategy for reactive hypoglycaemia
Authors: Younes Younes R. , Cron Nicholas , Field Benjamin C.T. , Nayyar Vidhu , Clark James , Zachariah Sunil , Lakshmipathy Kavitha , Isuga Jimboy O. , Maghsoodi Negar , Emmanuel Julian
Published: February 2024

Background/aim

Managing reactive hypoglycaemia (RH) poses challenges due to limited and often ineffective treatment options. We report a case series and draw on this to propose a stepwise treatment approach consisting of lifestyle modifications, metformin, GLP-1 analogues, and the use of flash glucose monitoring technology.

Method

A retrospective review was conducted to analyse the management of 11 cases presenting with recurrent RH symptoms.

Result

Two patients experienced successful resolution of symptoms through lifestyle modifications. Metformin alone was effective in treating seven out of nine patients who received pharmacological treatment. Two patients with previous upper gastrointestinal surgery showed a partial response to metformin and benefited further from additional long-acting GLP-1 analogue. Pharmacological intervention led to significant reductions in insulin and C-peptide levels in repeat mixed meal tolerance tests (P-values 0.043 for insulin and 0.006 for C-peptide). Finally, flash glucose monitoring technology was useful in early detection and preventing episodes of hypoglycaemia in one of these patients with persistent symptoms.

Conclusion

These findings highlight the potential efficacy of escalated treatment strategies for RH, including the use of metformin, GLP-1 analogues, and flash glucose monitoring technology.
VGLUT2 and APP family: unraveling the neurobiochemical mechanisms of neurostimulation therapy to STZ-induced diabetes and neuropathy
Authors: Zhang Yitong , Wu Chenxuan , Jiang Wenqi , Cao Yan , Chen Dongtai
Published: February 2024

Diabetic Peripheral Neuropathy (DPN) poses an escalating threat to public health, profoundly impacting well-being and quality of life. Despite its rising prevalence, the pathogenesis of DPN remains enigmatic, and existing clinical interventions fall short of achieving meaningful reversals of the condition. Notably, neurostimulation techniques have shown promising efficacy in alleviating DPN symptoms, underscoring the imperative to elucidate the neurobiochemical mechanisms underlying DPN. This study employs an integrated multi-omics approach to explore DPN and its response to neurostimulation therapy. Our investigation unveiled a distinctive pattern of vesicular glutamate transporter 2 (VGLUT2) expression in DPN, rigorously confirmed through qPCR and Western blot analyses in DPN C57 mouse model induced by intraperitoneal Streptozotocin (STZ) injection. Additionally, combining microarray and qPCR methodologies, we revealed and substantiated variations in the expression of the Amyloid Precursor Protein (APP) family in STZ-induced DPN mice. Analyzing the transcriptomic dataset generated from neurostimulation therapy for DPN, we intricately explored the differential expression patterns of VGLUT2 and APPs. Through correlation analysis, protein-protein interaction predictions, and functional enrichment analyses, we predicted the key biological processes involving VGLUT2 and the APP family in the pathogenesis of DPN and during neurostimulation therapy. This comprehensive study not only advances our understanding of the pathogenesis of DPN but also provides a theoretical foundation for innovative strategies in neurostimulation therapy for DPN. The integration of multi-omics data facilitates a holistic view of the molecular intricacies of DPN, paving the way for more targeted and effective therapeutic interventions.
Enhanced phytoremediation of metal contaminated soils aimed at decreasing the risk of antibiotic resistance dissemination
Authors: Garbisu Carlos , Alkorta Itziar
Published: February 2024

The enhanced phytoremediation of metal contaminated soils holds great promise for the recovery of soil health and functionality, while providing a range of co-benefits, from an environmental and human health perspective, derived from the revegetation of the degraded sites and the concomitant delivery of ecosystem services. Due to diverse evolutionary co-selection mechanisms between metal resistance and antibiotic resistance in bacteria, metal contaminated soils are considered potential reservoirs of antibiotic resistant bacteria (ARB) which can contribute to the existing antibiotic resistance crisis. During the enhanced phytoremediation of metal contaminated soils, the application of organic wastes (e.g., manure, slurry, sewage sludge) as soil amendments can aggravate the risk of antibiotic resistance spread, because they often contain ARB which harbor antibiotic resistance genes (ARGs) that can then be propagated among soil bacterial populations through horizontal gene transfer (HGT). Due to the magnitude and criticality of the antibiotic resistance crisis, as well as the higher risk of spread and dispersal of ARB and ARGs (they make copies of themselves) compared to metals, it is proposed here to aim enhanced phytoremediation strategies towards decreasing the soil resistome (and, hence, the risk of its potential link with the human resistome), while reducing total and/or bioavailable metal concentrations and restoring soil health and the delivery of ecosystem services. To this purpose, a decalogue of practices is tentatively suggested. Finally, a proper management of plant and soil microbial compositions is a most crucial aspect, together with the selection of the right organic wastes and phytoremediation practices.
Chimeric antigen receptor T cells targeting the GM3(Neu5Gc) ganglioside
Authors: Heinzelbecker Julia , Fauskanger Marte , Jonson Ida , Krengel Ute , Løset Geir Åge , Munthe Ludvig , Tveita Anders
Published: February 2024

Chimeric antigen receptor (CAR) T cell technology has ushered in a new era of immunotherapy, enabling the targeting of a broad range of surface antigens, surpassing the limitations of traditional T cell epitopes. Despite the wide range of non-protein tumor-associated antigens, the advancement in crafting CAR T cells for these targets has been limited. Owing to an evolutionary defect in the CMP-Neu5Ac hydroxylase (CMAH) that abolishes the synthesis of CMP-Neu5Gc from CMP-Neu5Ac, Neu5Gc is generally absent in human tissues. Despite this, Neu5Gc-containing antigens, including the ganglioside GM3(Neu5Gc) have consistently been observed on tumor cells across a variety of human malignancies. This restricted expression makes GM3(Neu5Gc) an appealing and highly specific target for immunotherapy. In this study, we designed and evaluated 14F7-28z CAR T cells, with a targeting unit derived from the GM3(Neu5Gc)-specific murine antibody 14F7. These cells exhibited exceptional specificity, proficiently targeting GM3(Neu5Gc)-expressing murine tumor cells in syngeneic mouse models, ranging from B cell malignancies to epithelial tumors, without compromising safety. Notably, human tumor cells enhanced with murine Cmah were effectively targeted and eliminated by the 14F7 CAR T cells. Nonetheless, despite the detectable presence of GM3(Neu5Gc) in unmodified human tumor xenografts, the levels were insufficient to trigger a tumoricidal T-cell response with the current CAR T cell configuration. Overall, our findings highlight the potential of targeting the GM3(Neu5Gc) ganglioside using CAR T cells across a variety of cancers and set the stage for the optimization of 14F7-based therapies for future human clinical application.
MIHIC: a multiplex IHC histopathological image classification dataset for lung cancer immune microenvironment quantification
Authors: Wang Ranran , Qiu Yusong , Wang Tong , Wang Mingkang , Jin Shan , Cong Fengyu , Zhang Yong , Xu Hongming
Published: February 2024

Background

Immunohistochemistry (IHC) is a widely used laboratory technique for cancer diagnosis, which selectively binds specific antibodies to target proteins in tissue samples and then makes the bound proteins visible through chemical staining. Deep learning approaches have the potential to be employed in quantifying tumor immune micro-environment (TIME) in digitized IHC histological slides. However, it lacks of publicly available IHC datasets explicitly collected for the in-depth TIME analysis.

Method

In this paper, a notable Multiplex IHC Histopathological Image Classification (MIHIC) dataset is created based on manual annotations by pathologists, which is publicly available for exploring deep learning models to quantify variables associated with the TIME in lung cancer. The MIHIC dataset comprises of totally 309,698 multiplex IHC stained histological image patches, encompassing seven distinct tissue types: Alveoli, Immune cells, Necrosis, Stroma, Tumor, Other and Background. By using the MIHIC dataset, we conduct a series of experiments that utilize both convolutional neural networks (CNNs) and transformer models to benchmark IHC stained histological image classifications. We finally quantify lung cancer immune microenvironment variables by using the top-performing model on tissue microarray (TMA) cores, which are subsequently used to predict patients’ survival outcomes.

Result

Experiments show that transformer models tend to provide slightly better performances than CNN models in histological image classifications, although both types of models provide the highest accuracy of 0.811 on the testing dataset in MIHIC. The automatically quantified TIME variables, which reflect proportions of immune cells over stroma and tumor over tissue core, show prognostic value for overall survival of lung cancer patients.

Conclusion

To the best of our knowledge, MIHIC is the first publicly available lung cancer IHC histopathological dataset that includes images with 12 different IHC stains, meticulously annotated by multiple pathologists across 7 distinct categories. This dataset holds significant potential for researchers to explore novel techniques for quantifying the TIME and advancing our understanding of the interactions between the immune system and tumors.
Case report: From palliative to potentially curative – the advent of immunotherapy providing hope to advanced gallbladder adenocarcinoma
Authors: Leong Eugene Kwong Fei , Tan Nigel Chun Hian , Pang Ning Qi , Kow Alfred Wei Chieh
Published: February 2024

Introduction

Biliary tract cancers (BTC) are often diagnosed at an advanced stage where prognosis is poor and curative-intent surgery is infeasible. First-line cisplatin-gemcitabine chemotherapy for advanced gallbladder cancer has remained unchanged over more than a decade, but recent developments in immunotherapy such as durvalumab have highlighted promise as a combination treatment regime with current standard chemotherapy.

Methods

In this case description, we present a case of locally-advanced gallbladder adenocarcinoma involving the biliary confluence that was initially planned for an extended right hepatectomy after portal vein embolization. Interval imaging revealed peritoneal metastasis, which was confirmed on diagnostic laparoscopy and biopsy. The patient underwent 8 cycles of cisplatin 25 mg/m2 and gemcitabine 1,000 mg/m2 chemotherapy on days 1 and 8 of each 21-day cycle, with durvalumab (Imfinzi®) 1,500 mg immunotherapy on day 1 of every cycle, in accordance with the treatment protocol of the TOPAZ-1 trial. Repeat imaging demonstrated a stable primary lesion with no further evidence of peritoneal disease. The patient subsequently underwent curative-intent conversion surgery with an extended right hepatectomy and Roux-en-Y hepaticojejunostomy, which were completed through a fully minimally-invasive laparoscopic approach.

Results

Final pathological TNM classification was ypT1aN0, with near-complete pathological response to pre-surgical therapy, uninvolved margins (R0 resection) and tumour shrinkage from 2.5 centimetres on pre-operative cross-sectional imaging to 0.5 centimetres on final histology. The patient had an uneventful post-operative course, and was fit for discharge by the fourth post-operative day. He remained well after three months of routine post-operative follow-up, with no significant post-operative complications and biochemical or radiological evidence of disease recurrence.

Conclusion

Our case description highlights the immense potential of combination durvalumab immunotherapy with cisplatin-gemcitabine chemotherapy in the treatment of advanced gallbladder adenocarcinoma. The patient’s locally advanced disease was initially planned for complex open surgery, prior to discovery of peritoneal metastasis rendering it inoperable. This was successfully down-staged with combination therapy to eventual R0 resection via minimally-invasive surgery. In addition, this case description demonstrates the feasibility of a fully laparoscopic approach with postulated benefits of diagnostic re-evaluation of peritoneal disease, reduced wound pain and shorter length of hospital stay.
Exploring the origin and fate of surface and sub-surface marine microplastics in the Canary Islands region
Authors: Vega-Moreno Daura , Sicilia-González Sergio , Domínguez-Hernández Cristopher , Moreira-García Enedina , Aguiar-González Borja , Hernández-Borges Javier , Fraile-Nuez Eugenio , Machín Francisco
Published: February 2024

The presence of different types of microplastics (MPs) in the Atlantic Ocean has been well-documented, with data collected from the Canary Islands indicating high concentrations of MPs at four different beaches (hot spots). However, critical gaps persist regarding the abundance of MPs in diverse open ocean regions, at varying depths, and their transport behavior and origin. This study aims to evaluate, for the first time, the large-scale (>100 km) and mesoscale (10-100 km) ocean dynamic processes and the resulting transport of MPs in the region. On the one hand, this study investigates the surface velocity of currents between 27-32°N latitude range, establishing correlation with the accumulation of MPs on diverse beaches across several islands of the archipelago. This analysis goes beyond studying the predominant current by integrating data at a smaller geographical scale over a two-year period. Concurrently, previous and ongoing research suggests the presence of small MPs (SMPs,<1 mm) at high concentration at a depth of 1100 meters in this region. By integrating these vertical profiles of MPs with a deep understanding of the physical processes of the Canary region accumulated over decades of research, our study introduces an innovative model that outlines how SMPs are sink and transported in open oceans by water mases. This comprehensive approach not only enhances our understanding of the complex dynamics influencing the distribution of MPs but also provides crucial insights to address the widespread problem of MP pollution in the Atlantic.
MLFLHMDA: predicting human microbe-disease association based on multi-view latent feature learning
Authors: Chen Ziwei , Zhang Liangzhe , Li Jingyi , Fu Mingyang
Published: February 2024

Introduction

A growing body of research indicates that microorganisms play a crucial role in human health. Imbalances in microbial communities are closely linked to human diseases, and identifying potential relationships between microbes and diseases can help elucidate the pathogenesis of diseases. However, traditional methods based on biological or clinical experiments are costly, so the use of computational models to predict potential microbe-disease associations is of great importance.

Methods

In this paper, we present a novel computational model called MLFLHMDA, which is based on a Multi-View Latent Feature Learning approach to predict Human potential Microbe-Disease Associations. Specifically, we compute Gaussian interaction profile kernel similarity between diseases and microbes based on the known microbe-disease associations from the Human Microbe-Disease Association Database and perform a preprocessing step on the resulting microbe-disease association matrix, namely, weighting K nearest known neighbors (WKNKN) to reduce the sparsity of the microbe-disease association matrix. To obtain unobserved associations in the microbe and disease views, we extract different latent features based on the geometrical structure of microbes and diseases, and project multi-modal latent features into a common subspace. Next, we introduce graph regularization to preserve the local manifold structure of Gaussian interaction profile kernel similarity and add Lp,q-norms to the projection matrix to ensure the interpretability and sparsity of the model.

Results

The AUC values for global leave-one-out cross-validation and 5-fold cross validation implemented by MLFLHMDA are 0.9165 and 0.8942+/−0.0041, respectively, which perform better than other existing methods. In addition, case studies of different diseases have demonstrated the superiority of the predictive power of MLFLHMDA. The source code of our model and the data are available on https://github.com/LiangzheZhang/MLFLHMDA_master.
The effects of transcranial magnetic stimulation for freezing of gait in Parkinson’s disease: a systematic review and meta-analysis of randomized controlled trials
Authors: Liu Zicai , Wen Xin , Xie Xiuying , Liu Yangyou , Tan Cheng , Kuang Shuanghong , Liu Huiyu
Published: February 2024

Background

Freezing of gait (FOG) is one of the most disabling gait disturbances in Parkinson’s disease (PD), affecting mobility and balance severely, thereby leading to an increased risk of falls.

Objectives

The purpose of this systematic review and meta-analysis was to investigate the effects of transcranial magnetic stimulation on FOG in PD.

Methods

Based on PRISMA guidelines, we searched the databases of MEDLINE (PubMed), Cochrane Library, PEDro, Embase, and Web of Science. Studies of the English language published up to July 2023 were searched. We retrieved for studies of randomized controlled trials (RCTs) of transcranial magnetic stimulation to treat FOG after PD and screened by inclusion and exclusion criteria. Risk of bias was assessed using the Cochrane Collaboration’s tool (Revman5.30). Characteristics of RCTs were extracted. The heterogeneity of the trials was measured by I2 statistic. The effect size was expressed by a standardized mean difference (SMD) with a 95% confidence interval (CI).

Results

A total of 488 articles were screened, after screening sixteen RCTs involved in 408 patients were included in the qualitative analysis, and 15 RCTs were included in meta-analysis. The outcome measures included FOG-Q, walking time, TUG, and UPDRS. Six studies used FOG-Q as outcome measure, six studies used walking time, four studies used TUG, and six studies used UPDRS. Compared with placebo treatment, transcranial magnetic stimulation has positive significant effects in improving gait status with increased walking speed (SMD = −0.41, 95% CI = −0.75 to −0.06, I2 = 7% p = 0.02), FOG-Q scores (SMD = −0.55, 95% CI = −0.89 to −0.21, I2 = 29%, p = 0.002), UPDRS scores (SMD = −1.08, 95% CI = −1.39 to −0.78, I2 = 49%, P < 0.001) and the time of TUG (SMD = −0.56, 95% CI = −0.88 to −0.23, I2 = 25%, p = 0.02) decreased.

Conclusion

Transcranial magnetic stimulation could significantly improving gait conditions in PD patients with FOG.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/#recordDetails, CRD42023434286.
Synthesis and evaluation of gold nanoparticles conjugated with five antigenic peptides derived from the spike protein of SARS-CoV-2 for vaccine development
Authors: Farfán-Castro Susan , García-Soto Mariano J. , Betancourt-Mendiola Lourdes , Cervantes Jacquelynne , Segura René , González-Ortega Omar , Rosales-Mendoza Sergio
Published: February 2024

Introduction: The development of innovative anti-COVID-19 vaccines is a need to ensure the population’s immunity worldwide, with broad protection against variants of concern and low cost as the main goals. Gold nanocarriers are potential entities that could aid in the development of innovative vaccines having thermal stability, high immunogenicity, and safety as the main attributes. Moreover, this approach could lead to adjuvant-free formulations, which will reduce the costs of vaccines.

Methods: In this study, five peptides (P1, P2, P3, P4, and P5) corresponding to linear epitopes of the SARS-CoV-2 spike (S) protein were chemisorbed on gold nanoparticles (AuNP) of 20 nm, prefunctionalized with heterobifunctional polyethylene glycol, by using glutaraldehyde as crosslinker to generate nanovaccine prototypes.

Results and discussion: The surface modification was confirmed by DLS with an increase of 31.7 ± 1.8 nm in the hydrodynamic diameter and an average ζ potential of −8.3 ± 2.2 mV in PBS (as excipient). The coupling concentration achieved was 23.7 ± 7.1 μg of peptide per mg AuNP. These AuNP-based conjugates showed no inherent toxicity in assays performed with HEK293T cells, in which a 100–1,000 μg/mL concentration range only led to a temporary decrease of up to 30% in cell viability after 48 h of treatment with restoration by 72 h. The immunogenicity of the conjugates produced was assessed in test mice subjected to three subcutaneous doses at 2-week intervals. Significant levels of IgM against each target peptide were observed at an early stage of the immunization scheme in all groups, reaching maximum levels after the second dose, whereas the IgG response increased after the third dose. The AuNP-P2, AuNP-P3, and AuNP-P5 conjugates induced the highest levels of IgG antibodies, lasting for at least 2 months after the last boost, with a predominance of the IgG1 subclass. Although the magnitude of the response induced by the gold conjugates was comparable to that with alum as adjuvant, these nanoconjugates induced a longer response. Our data support the use of AuNP as carriers in innovative vaccines against SARS-CoV-2.
Endovascular treatment strategy and clinical outcome of tentorial dural arteriovenous fistula
Authors: Zhang Guangjian , Zhang Weiwei , Chang Hanxiao , Shen Yuqi , Ma Chencheng , Mao Lei , Li Zheng , Lu Hua
Published: February 2024

Introduction

To evaluate treatment strategies and clinical outcomes following endovascular embolization of tentorial dural arteriovenous fistulas.

Methods

We retrospectively analyzed 19 patients with tentorial dural arteriovenous fistulas admitted to the Department of Neurosurgery at Jiangsu Provincial People’s Hospital between October 2015 and May 2022, all treated with endovascular therapy. To collect and analyze patients’ clinical presentation, imaging data, postoperative complications, and prognosis and to analyze the safety and clinical outcomes of endovascular treatment of tentorial dural arteriovenous fistulas.

Results

Imaging cure was achieved in 18 patients, with the arterial route chosen for embolization in 17 patients and the venous route in one patient; one patient received partial embolization. Staged embolization was performed in four patients. At postoperative follow-up of 9–83 months (37.8 ± 21.2), all 19 patients had recovered well (mRS score ≤ 2). Three patients experienced perioperative complications: intraoperative Onyx reflux into the middle cerebral artery in one patient; postoperative permanent limited left visual field loss and deafness in the left ear in one patient; and transient diplopia, vertigo, and decreased pain and temperature sensation of the left limb in one patient, with no abnormalities on post-procedure magnetic resonance examinations. A total of 17 patients completed a postoperative digital subtraction angiography review during follow-up, and one patient had a recurrence of an arteriovenous fistula.

Conclusion

Endovascular treatment of tentorial dural arteriovenous fistulas is safe and effective. Reduction of the Borden or Cognard classification via eliminating cortical venous reflux through multi-staged embolization or combined open surgery is a reasonable goal of treatment where complete obliteration of the fistula is not achievable.
Mindfulness meditation styles differently modulate source-level MEG microstate dynamics and complexity
Authors: D’Andrea Antea , Croce Pierpaolo , O’Byrne Jordan , Jerbi Karim , Pascarella Annalisa , Raffone Antonino , Pizzella Vittorio , Marzetti Laura
Published: February 2024

Background

The investigation of mindfulness meditation practice, classically divided into focused attention meditation (FAM), and open monitoring meditation (OMM) styles, has seen a long tradition of theoretical, affective, neurophysiological and clinical studies. In particular, the high temporal resolution of magnetoencephalography (MEG) or electroencephalography (EEG) has been exploited to fill the gap between the personal experience of meditation practice and its neural correlates. Mounting evidence, in fact, shows that human brain activity is highly dynamic, transiting between different brain states (microstates). In this study, we aimed at exploring MEG microstates at source-level during FAM, OMM and in the resting state, as well as the complexity and criticality of dynamic transitions between microstates.

Methods

Ten right-handed Theravada Buddhist monks with a meditative expertise of minimum 2,265 h participated in the experiment. MEG data were acquired during a randomized block design task (6 min FAM, 6 min OMM, with each meditative block preceded and followed by 3 min resting state). Source reconstruction was performed using eLORETA on individual cortical space, and then parcellated according to the Human Connect Project atlas. Microstate analysis was then applied to parcel level signals in order to derive microstate topographies and indices. In addition, from microstate sequences, the Hurst exponent and the Lempel-Ziv complexity (LZC) were computed.

Results

Our results show that the coverage and occurrence of specific microstates are modulated either by being in a meditative state or by performing a specific meditation style. Hurst exponent values in both meditation conditions are reduced with respect to the value observed during rest, LZC shows significant differences between OMM, FAM, and REST, with a progressive increase from REST to FAM to OMM.

Discussion

Importantly, we report changes in brain criticality indices during meditation and between meditation styles, in line with a state-like effect of meditation on cognitive performance. In line with previous reports, we suggest that the change in cognitive state experienced in meditation is paralleled by a shift with respect to critical points in brain dynamics.
Transcriptome profile analysis in spinal cord injury rats with transplantation of menstrual blood-derived stem cells
Authors: Qi Longju , Jiang Wenwei , He Wenhua , Li Xiangzhe , Wu Jiahuan , Chen Shiyuan , Liao Zehua , Yu Shumin , Liu Jinyi , Sun Yuyu , Wu Qinfeng , Dong Chuanming , Wang Qinghua
Published: February 2024

Introduction

Menstrual blood-derived stem cells (MenSCs) are vital in treating many degenerative and traumatic disorders. However, the underlying molecular mechanisms remain obscure in MenSCs-treating spinal cord injury (SCI) rats.

Methods

MenSCs were adopted into the injured sites of rat spinal cords at day 7 post surgery and the tissues were harvested for total RNA sequencing analysis at day 21 after surgery to investigate the expression patterns of RNAs. The differentially expressed genes (DEGs) were analyzed with volcano and heatmap plot. DEGs were sequentially analyzed by weighted gene co-expression network, functional enrichment, and competitive endogenous RNAs (ceRNA) network analysis. Next, expression of selected miRNAs, lncRNAs, circRNAs and mRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics packages and extra databases were enrolled to scoop the genes functions and their interaction relationships.

Results

A total of 89 lncRNAs, 65 circRNAs, 120 miRNAs and 422 mRNAs were significantly upregulated and 65 lncRNAs, 72 circRNAs, 74 miRNAs, and 190 mRNAs were significantly downregulated in the MenSCs treated rats compared to SCI ones. Current investigation revealed that MenSCs treatment improve the recovery of the injured rats and the most significantly involved pathways in SCI regeneration were cell adhesion molecules, nature killer cell mediated cytotoxicity, primary immunodeficiency, chemokine signaling pathway, T cell receptor signaling pathway and B cell receptor signaling pathway. Moreover, the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA ceRNA network of SCI was constructed. Finally, the protein-protein interaction (PPI) network was constructed using the top 100 DE mRNAs. The constructed PPI network included 47 nodes and 70 edges.

Discussion

In summary, the above results revealed the expression profile and potential functions of differentially expressed (DE) RNAs in the injured spinal cords of rats in the MenSCs-treated and SCI groups, and this study may provide new clues to understand the mechanisms of MenSCs in treating SCI.
Fenugreek derived diosgenin as an emerging source for diabetic therapy
Authors: Tak Yamini , Kaur Manpreet , Chitranashi Abhishek , Samota Mahesh Kumar , Verma Preeti , Bali Manoj , Kumawat Chiranjeev
Published: February 2024

Diabetes is a chronic metabolic disease that endangers the entire body’s tissues and organs. Diabetes impairs glucose and insulin regulation in the human body by causing pancreatic cell damage. Diabetes modifies pathways such as serine/threonine protein kinase (Akt) and Protein kinase C (PKC)/- glucose transporter 4 (GLUT4), peroxisome proliferator-activated receptor (PPAR) glucose absorption, and inhibits α-amylase and α-glucosidase, Sodium/glucose cotransporter 1 (SGLT-1), and Na+-K+-ATPase activity. Diabetes may also be caused by a decrease in the expression of sterol regulatory element binding protein 1 (SREBP-1) and its target genes, fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), and acetyl-CoA carboxylase α (ACC), as well as a decrease in the levels of C/EBP homologous protein (CHOP), Caspase12, and Caspase3 proteins. Diabetes has long been linked to diseases of the cardiovascular, nervous, skeletal, reproductive, hepatic, ocular, and renal systems. Diosgenin, a steroidal compound derived from fenugreek, aids in the prevention of diabetes by altering cellular pathways in favor of healthy bodily functions. Diosgenin is a new nutraceutical on the market that claims to cure diabetes in particular. This article focuses on diosgenin extraction and purification, fenugreek bioactive compounds, pharmacological properties of diosgenin, mode of action of diosgenin to cure diabetes, and dosages.
Outcome of patients with stage I immature teratoma after surveillance or adjuvant chemotherapy
Authors: Marino Giuseppe , Grassi Tommaso , De Ponti Elena , Negri Serena , Testa Filippo , Giuliani Daniela , Delle Marchette Martina , Dell’Oro Cristina , Fumagalli Diletta , Donatiello Gianluca , Besana Giulia , Marchetta Liliana , Bonazzi Cristina Maria , Lissoni Andrea Alberto , Landoni Fabio , Fruscio Robert
Published: February 2024

Objective

Immature teratomas are rare malignant ovarian germ cell tumours, typically diagnosed in young women, where fertility-sparing surgery is the treatment of choice. The role of adjuvant chemotherapy in stage I disease remains controversial. We evaluated the impact of surveillance versus chemotherapy on the recurrence rate in stage I immature teratomas.

Methods

We collected a single centre retrospective series of patients with stage I immature teratomas treated with fertility-sparing surgery at San Gerardo Hospital, Monza, Italy, between 1980 and 2019. Potential risk factors for recurrence were investigated by multivariate logistic regression.

Results

Of the 74 patients included, 12% (9/74) received chemotherapy, while 88% (65/74) underwent surveillance. Median follow-up was 188 months. No difference in recurrence was found in stage IA/IB and IC immature teratomas [10% (6/60) vs. 28.6% (4/14) (P=0.087)], grade 1, grade 2, and grade 3 [7.1% (2/28) vs. 14.3% (4/28) vs. 22.2% (4/18) (p=0.39)], and surveillance versus chemotherapy groups [13.9% (9/65) vs. 11.1% (1/9)) (p = 1.00)]. In univariate analysis, the postoperative approach had no impact on recurrence. The 5-year disease-free survival was 87% and 90% in the surveillance and chemotherapy groups, respectively; the overall survival was 100% in both cohorts.

Conclusions

Our results support the feasibility of surveillance in stage I immature teratomas. Adjuvant chemotherapy may be reserved for relapses. However, the potential benefit of chemotherapy should be discussed, especially for high-risk tumours. Prospective series are warranted to confirm our findings.

What is already known on this topic

To date, no consensus has been reached regarding the role of adjuvant chemotherapy in stage I immature teratomas of the ovary. Some studies suggest that only surveillance is an acceptable choice. However, guidelines are not conclusive on this topic.

What this study adds

No difference in terms of recurrence was observed between the surveillance and the adjuvant chemotherapy group. All patients who relapsed were successfully cured with no disease-related deaths.

How this study might affect research, practice or policy

Adjuvant chemotherapy should be appropriately discussed with patients. However, it may be reserved for relapse according to our data.
PBRM1 loss is associated with increased sensitivity to MCL1 and CDK9 inhibition in clear cell renal cancer
Authors: Fultang Norman , Schwab Ashley M. , McAneny-Droz Sophia , Grego Alexander , Rodgers Stephanie , Torres Brian Vidal , Heiser Diane , Scherle Peggy , Bhagwat Neha
Published: February 2024

MCL1 is a member of the BCL2 family of apoptosis regulators, which play a critical role in promoting cancer survival and drug resistance. We previously described PRT1419, a potent, MCL1 inhibitor with anti-tumor efficacy in various solid and hematologic malignancies. To identify novel biomarkers that predict sensitivity to MCL1 inhibition, we conducted a gene essentiality analysis using gene dependency data generated from CRISPR/Cas9 cell viability screens. We observed that clear cell renal cancer (ccRCC) cell lines with damaging PBRM1 mutations displayed a strong dependency on MCL1. PBRM1 (BAF180), is a chromatin-targeting subunit of mammalian pBAF complexes. PBRM1 is frequently altered in various cancers particularly ccRCC with ~40% of tumors harboring damaging PBRM1 alterations. We observed potent inhibition of tumor growth and induction of apoptosis by PRT1419 in various preclinical models of PBRM1-mutant ccRCC but not PBRM1-WT. Depletion of PBRM1 in PBRM1-WT ccRCC cell lines induced sensitivity to PRT1419. Mechanistically, PBRM1 depletion coincided with increased expression of pro-apoptotic factors, priming cells for caspase-mediated apoptosis following MCL1 inhibition. Increased MCL1 activity has been described as a resistance mechanism to Sunitinib and Everolimus, two approved agents for ccRCC. PRT1419 synergized with both agents to potently inhibit tumor growth in PBRM1-loss ccRCC. PRT2527, a potent CDK9 inhibitor which depletes MCL1, was similarly efficacious in monotherapy and in combination with Sunitinib in PBRM1-loss cells. Taken together, these findings suggest PBRM1 loss is associated with MCL1i sensitivity in ccRCC and provide rationale for the evaluation of PRT1419 and PRT2527 for the treatment for PBRM1-deficient ccRCC.
Extreme temperatures increase the risk of pediatric pneumonia: a systematic review and meta-analysis
Authors: Makrufardi Firdian , Triasih Rina , Nurnaningsih Nurnaningsih , Chung Kian Fan , Lin Sheng-Chieh , Chuang Hsiao-Chi
Published: February 2024

Introduction

The impact of climate change on ambient temperatures threatens to worsen pediatric pneumonia-related outcomes considerably. This study examined the associations of temperature variation and extreme temperature with pediatric pneumonia-related events using a meta-analysis.

Methods

We systematically searched PubMed, Medline, Embase, and Web of Science databases for relevant literature, and the quality of evidence was assessed. Fixed and random-effects meta-analyses were performed to calculate the pooled relative risks (RRs) of the associations with pneumonia-related events.

Results

We observed that a 1°C temperature variation increased the RR of pneumonia events by 1.06-fold (95% confidence interval (CI): 1.03–1.10). A 1°C temperature variation increased the RR by 1.10-fold of the pediatric pneumonia hospital admissions (95% CI: 1.00–1.21) and 1.06-fold of the pediatric pneumonia emergency department visits (95% CI: 1.01-1.10). Extreme cold increased the RR by 1.25-fold of the pediatric pneumonia events (95% CI: 1.07–1.45). A 1°C temperature variation increased the RR of pneumonia events in children by 1.19-fold (95% CI: 1.08–1.32), girls by 1.03-fold (95% CI: 1.02–1.05), and in temperate climate zones by 1.07-fold (95% CI: 1.03–1.11). Moreover, an increase in extreme cold increased the RR of pneumonia events in children by 2.43-fold (95% CI: 1.72–3.43), girls by 1.96-fold (95% CI: 1.29–2.98) and in temperate climate zones by 2.76-fold (95% CI: 1.71–4.47).

Conclusion

Our study demonstrated that pediatric pneumonia events are more prevalent among children, particularly girls, and individuals residing in temperate climate zones. Climate change represents an emergent public health threat, affecting pediatric pneumonia treatment and prevention..

Systematic Review Registration

PROSPERO (CRD42022378610).
Single-cell RNA-seq reveals a link of ovule abortion and sugar transport in Camellia oleifera
Authors: Zhao Songzi , Rong Jun
Published: February 2024

Camellia oleifera is the most important woody oil crop in China. Seed number per fruit is an important yield trait in C. oleifera. Ovule abortion is generally observed in C. oleifera and significantly decreases the seed number per fruit. However, the mechanisms of ovule abortion remain poorly understood at present. Single-cell RNA sequencing (scRNA-seq) was performed using mature ovaries of two C. oleifera varieties with different ovule abortion rates (OARs). In total, 20,526 high-quality cells were obtained, and 18 putative cell clusters were identified. Six cell types including female gametophyte, protoxylem, protophloem, procambium, epidermis, and parenchyma cells were identified from three main tissue types of ovule, placenta, and pericarp inner layer. A comparative analysis on scRNA-seq data between high- and low-OAR varieties demonstrated that the overall expression of CoSWEET and CoCWINV in procambium cells, and CoSTP in the integument was significantly upregulated in the low-OAR variety. Both the infertile ovule before pollination and the abortion ovule producing after compatible pollination might be attributed to selective abortion caused by low sugar levels in the apoplast around procambium cells and a low capability of hexose uptake in the integument. Here, the first single-cell transcriptional landscape is reported in woody crop ovaries. Our investigation demonstrates that ovule abortion may be related to sugar transport in placenta and ovules and sheds light on further deciphering the mechanism of regulating sugar transport and the improvement of seed yield in C. oleifera.
Flavonoids influence key rhizocompetence traits for early root colonization and PCB degradation potential of Paraburkholderia xenovorans LB400
Authors: Ghitti Elisa , Rolli Eleonora , Vergani Lorenzo , Borin Sara
Published: February 2024

Introduction

Flavonoids are among the main plant root exudation components, and, in addition to their role in symbiosis, they can broadly affect the functionality of plant-associated microbes: in polluted environments, for instance, flavonoids can induce the expression of the enzymatic degradative machinery to clean-up soils from xenobiotics like polychlorinated biphenyls (PCBs). However, their involvement in root community recruitment and assembly involving non-symbiotic beneficial interactions remains understudied and may be crucial to sustain the holobiont fitness under PCB stress.

Methods

By using a set of model pure flavonoid molecules and a natural blend of root exudates (REs) with altered flavonoid composition produced by Arabidopsis mutant lines affected in flavonoid biosynthesis and abundance (null mutant tt4, flavonoid aglycones hyperproducer tt8, and flavonoid conjugates hyperaccumulator ttg), we investigated flavonoid contribution in stimulating rhizocompetence traits and the catabolic potential of the model bacterial strain for PCB degradation Paraburkholderia xenovorans LB400.

Results

Flavonoids influenced the traits involved in bacterial recruitment in the rhizoplane by improving chemotaxis and motility responses, by increasing biofilm formation and by promoting the growth and activation of the PCB-degradative pathway of strain LB400, being thus potentially exploited as carbon sources, stimulating factors and chemoattractant molecules. Indeed, early rhizoplane colonization was favored in plantlets of the tt8 Arabidopsis mutant and reduced in the ttg line. Bacterial growth was promoted by the REs of mutant lines tt4 and tt8 under control conditions and reduced upon PCB-18 stress, showing no significant differences compared with the WT and ttg, indicating that unidentified plant metabolites could be involved. PCB stress presumably altered the Arabidopsis root exudation profile, although a sudden “cry-for-help” response to recruit strain LB400 was excluded and flavonoids appeared not to be the main determinants. In the in vitro plant–microbe interaction assays, plant growth promotion and PCB resistance promoted by strain LB400 seemed to act through flavonoid-independent mechanisms without altering bacterial colonization efficiency and root adhesion pattern.

Discussions

This study further contributes to elucidate the vast array of functions provided by flavonoids in orchestrating the early events of PCB-degrading strain LB400 recruitment in the rhizosphere and to support the holobiont fitness by stimulating the catabolic machinery involved in xenobiotics decomposition and removal.