bluuebunny/crossref_metadata_2025 huggingface dataset:
Best practices for generating and analyzing 16S rRNA amplicon data to track coral microbiome dynamics
Authors: Silva Denise P. , Epstein Hannah E. , Vega Thurber Rebecca L.
Published: February 2023

Over the past two decades, researchers have searched for methods to better understand the relationship between coral hosts and their microbiomes. Data on how coral-associated bacteria are involved in their host’s responses to stressors that cause bleaching, disease, and other deleterious effects can elucidate how they may mediate, ameliorate, and exacerbate interactions between the coral and the surrounding environment. At the same time tracking coral bacteria dynamics can reveal previously undiscovered mechanisms of coral resilience, acclimatization, and evolutionary adaptation. Although modern techniques have reduced the cost of conducting high-throughput sequencing of coral microbes, to explore the composition, function, and dynamics of coral-associated bacteria, it is necessary that the entire procedure, from collection to sequencing, and subsequent analysis be carried out in an objective and effective way. Corals represent a difficult host with which to work, and unique steps in the process of microbiome assessment are necessary to avoid inaccuracies or unusable data in microbiome libraries, such as off-target amplification of host sequences. Here, we review, compare and contrast, and recommend methods for sample collection, preservation, and processing (e.g., DNA extraction) pipelines to best generate 16S amplicon libraries with the aim of tracking coral microbiome dynamics. We also discuss some basic quality assurance and general bioinformatic methods to analyze the diversity, composition, and taxonomic profiles of the microbiomes. This review aims to be a generalizable guide for researchers interested in starting and modifying the molecular biology aspects of coral microbiome research, highlighting best practices and tricks of the trade.
Emission of cyanobacterial volatile organic compounds and their roles in blooms
Authors: Zuo Zhaojiang
Published: February 2023

Cyanobacteria are photosynthetic prokaryotes and one of dominant species in eutrophicated waters, which easily burst blooms in summer with high irradiance and temperature conditions. In response to high irradiance, high temperature, and nutrient conditions, cyanobacteria release abundant of volatile organic compounds (VOCs) by up-regulating related gene expression and oxidatively degrading β-carotene. These VOCs not only increase offensive odor in waters, but also transfer allelopathic signals to algae and aquatic plants, resulting in cyanobacteria dominating eutrophicated waters. Among these VOCs, β-cyclocitral, α-ionone, β-ionone, limonene, longifolene, and eucalyptol have been identified as the main allelopathic agents, which even directly kill algae by inducing programmed cell death (PCD). The VOCs released from cyanobacteria, especially the ruptured cells, exhibit repelling effects on the herbivores, which is beneficial to survival of the population. Cyanobacterial VOCs might transfer aggregating information among homogeneous species, so the acceptors initiate aggregation to resist the coming stresses. It can be speculated that the adverse conditions can promote VOC emission from cyanobacteria, which play important roles in cyanobacteria dominating eutrophicated waters and even bursting blooms.
Maternal antibiotic treatment during pregnancy attenuates the transport and absorption of maternal antibody IgG through TLR4 and TLR2 receptor
Authors: Ding Yanan , Yao Xiaofeng , Zhang Haihan , He Xi , Song Zehe
Published: February 2023

Maternal antibody IgG, the main antibody in colostrum, plays an important role in neonates protection. Commensal microbiota is closely related to host antibody repertoire. However, there are few reports on how maternal gut microbiota affects maternal antibody IgG transfer. In the present study, we investigated the effects of altering the gut microbiota (treated with antibiotics during pregnancy) on maternal IgG transportation and offspring absorption and explored its underlying mechanisms. Results showed that antibiotic treatment during pregnancy significantly decreased maternal cecal microbial richness (Chao1 and Obesrved species) and diversity (Shannon and Simpson). Plasma metabolome enriched significant changes in the process of bile acid secretion pathway, and the concentration of deoxycholic acid, a secondary metabolite of microorganisms was lowered. Flow cytometry analysis indicated that antibiotic treatment promoted the number of B cells and abated the number of T, DC and M1 cells in intestinal lamina propria of dams. Surprisingly, the serum IgG level in antibiotic treated dams was significantly increased, while IgG contents in colostrum was decreased. Moreover, pregnancy antibiotic treatment in dams was reduced the expression of FcRn, TLR4 and TLR2 in breast of dams and in duodenum and jejunum of neonates. Furthermore, TLR4−/− and TLR2−/− knock-out mice showed a lower FcRn expression in breast of dams and in duodenum and jejunum of neonates. These findings suggest that maternal intestine bacteria may affect the maternal IgG transfer through regulating the breast TLR4 and TLR2 of dams.
Strong restructuration of skin microbiota during captivity challenges ex-situ conservation of amphibians
Authors: Fieschi-Méric Léa , Van Leeuwen Pauline , Hopkins Kevin , Bournonville Marie , Denoël Mathieu , Lesbarrères David
Published: February 2023

In response to the current worldwide amphibian extinction crisis, conservation instances have encouraged the establishment of ex-situ collections for endangered species. The resulting assurance populations are managed under strict biosecure protocols, often involving artificial cycles of temperature and humidity to induce active and overwintering phases, which likely affect the bacterial symbionts living on the amphibian skin. However, the skin microbiota is an important first line of defense against pathogens that can cause amphibian declines, such as the chytrid Batrachochytrium dendrobatidis (Bd). Determining whether current husbandry practices for assurance populations might deplete amphibians from their symbionts is therefore essential to conservation success. Here, we characterize the effect of the transitions from the wild to captivity, and between aquatic and overwintering phases, on the skin microbiota of two newt species. While our results confirm differential selectivity of skin microbiota between species, they underscore that captivity and phase-shifts similarly affect their community structure. More specifically, the translocation ex-situ is associated with rapid impoverishment, decrease in alpha diversity and strong species turnover of bacterial communities. Shifts between active and overwintering phases also cause changes in the diversity and composition of the microbiota, and on the prevalence of Bd-inhibitory phylotypes. Altogether, our results suggest that current husbandry practices strongly restructure the amphibian skin microbiota. Although it remains to be determined whether these changes are reversible or have deleterious effects on their hosts, we discuss methods to limit microbial diversity loss ex-situ and emphasize the importance of integrating bacterial communities to applied amphibian conservation.
Antibiofilm activity and NMR-based metabolomic characterization of cell-free supernatant of Limosilactobacillus reuteri DSM 17938
Authors: Vitale Irene , Spano Mattia , Puca Valentina , Carradori Simone , Cesa Stefania , Marinacci Beatrice , Sisto Francesca , Roos Stefan , Grompone Gianfranco , Grande Rossella
Published: February 2023

The microbial biofilm has been defined as a “key virulence factor” for a multitude of microorganisms associated with chronic infections. Its multifactorial nature and variability, as well as an increase in antimicrobial resistance, suggest the need to identify new compounds as alternatives to the commonly used antimicrobials. The aim of this study was to assess the antibiofilm activity of cell-free supernatant (CFS) and its sub-fractions (SurE 10 K with a molecular weight <10 kDa and SurE with a molecular weight <30 kDa), produced by Limosilactobacillus reuteri DSM 17938, vs. biofilm-producing bacterial species. The minimum inhibitory biofilm concentration (MBIC) and the minimum biofilm eradication concentration (MBEC) were determined via three different methods and an NMR metabolomic analysis of CFS and SurE 10K was performed to identify and quantify several compounds. Finally, the storage stability of these postbiotics was evaluated by a colorimetric assay by analyzing changes in the CIEL*a*b parameters. The CFS showed a promising antibiofilm activity against the biofilm developed by clinically relevant microorganisms. The NMR of CFS and SurE 10K identifies and quantifies several compounds, mainly organic acids and amino acids, with lactate being the most abundant metabolite in all the analyzed samples. The CFS and SurE 10 K were characterized by a similar qualitative profile, with the exception of formate and glycine detected only in the CFS. Finally, the CIEL*a*b parameters assess the better conditions to analyze and use these matrices for the correct preservation of bioactive compounds.
Inhibitory effect of carvacrol against Alternaria alternata causing goji fruit rot by disrupting the integrity and composition of cell wall
Authors: Zhao Lunaike , Wang Junjie , Zhang Huaiyu , Wang Peng , Wang Cong , Zhou Yueli , Li Huanhuan , Yu Shukun , Wu Rina
Published: February 2023

Goji (Lycium barbarum L.) is a widely planted crop in China that is easily infected by the pathogenic fungus Alternaria alternata, which causes rot after harvest. Previous studies showed that carvacrol (CVR) significantly inhibited the mycelial growth of A. alternata in vitro and reduced Alternaria rot in goji fruits in vivo. The present study aimed to explore the antifungal mechanism of CVR against A. alternata. Optical microscopy and calcofluor white (CFW) fluorescence observations showed that CVR affected the cell wall of A. alternata. CVR treatment affected the integrity of the cell wall and the content of substances in the cell wall as measured by alkaline phosphatase (AKP) activity, Fourier transform-infrared spectroscopy (FT-IR), and X-ray photoelectron spectroscopy (XPS). Chitin and β-1,3-glucan contents in cells decreased after CVR treatment, and the activities of β-glucan synthase and chitin synthase decreased. Transcriptome analysis revealed that CVR treatment affected cell wall-related genes in A. alternata, thereby affecting cell wall growth. Cell wall resistance also decreased with CVR treatment. Collectively, these results suggest that CVR may exert antifungal activity by interfering with cell wall construction, leading to impairment of cell wall permeability and integrity.
Comparative investigation on heterotrophic denitrification driven by different biodegradable polymers for nitrate removal in mariculture wastewater: Organic carbon release, denitrification performance, and microbial community
Authors: Feng Yuna , Wang Lu , Yin Zhendong , Cui Zhengguo , Qu Keming , Wang Dawei , Wang Zhanying , Zhu Shengmin , Cui Hongwu
Published: February 2023

Heterotrophic denitrification is widely studied to purify freshwater wastewater, but its application to seawater wastewater is rarely reported. In this study, two types of agricultural wastes and two types of synthetic polymers were selected as solid carbon sources in denitrification process to explore their effects on the purification capacity of low-C/N marine recirculating aquaculture wastewater (NO3−-N 30 mg/L, salinity 32‰). The surface properties of reed straw (RS), corn cob (CC), polycaprolactone (PCL) and poly3-hydroxybutyrate-hydroxypropionate (PHBV) were evaluated by Brunauer–Emmett–Teller, Scanning electron microscope and Fourier-transform infrared spectroscopy. Short-chain fatty acids, dissolved organic carbon (DOC), and chemical oxygen demand (COD) equivalents were used to analyze the carbon release capacity. Results showed that agricultural waste had higher carbon release capacity than PCL and PHBV. The cumulative DOC and COD of agricultural waste were 0.56–12.65 and 1.15–18.75 mg/g, respectively, while those for synthetic polymers were 0.07–1.473 and 0.045–1.425 mg/g, respectively. The removal efficiency of nitrate nitrogen (NO3−-N) was CC 70.80%, PCL 53.64%, RS 42.51%, and PHBV 41.35%. Microbial community analysis showed that Proteobacteria and Firmicutes were the most abundant phyla in agricultural wastes and biodegradable natural or synthetic polymers. Quantitative real-time PCR indicated the conversion from nitrate to nitrogen was achieved in all four carbon source systems, and all six genes had the highest copy number in CC. The contents of medium nitrate reductase, nitrite reductase and nitrous oxide reductase genes in agricultural wastes were higher than those in synthetic polymers. In summary, CC is an ideal carbon source for denitrification technology to purify low C/N recirculating mariculture wastewater.
UPLC-MS based integrated plasma proteomic and metabolomic profiling of TSC-RAML and its relationship with everolimus treatment
Authors: Wang Zhan , Liu Xiaoyan , Wang Wenda , Xu Jiyu , Sun Haidan , Wei Jing , Yu Yuncui , Zhao Yang , Wang Xu , Liao Zhangcheng , Sun Wei , Jia Lulu , Zhang Yushi
Published: February 2023

Aim: To profile the plasma proteomics and metabolomics of patients with renal cysts, sporadic angiomyolipoma (S-AML) and tuberous sclerosis complex related angiomyolipoma (TSC-RAML) before and after everolimus treatment, and to find potential diagnostic and prognostic biomarkers as well as reveal the underlying mechanism of TSC tumorigenesis.

Materials and Methods: We retrospectively measured the plasma proteins and metabolites from November 2016 to November 2017 in a cohort of pre-treatment and post-treatment TSC-RAML patients and compared them with renal cyst and S-AML patients by ultra-performance liquid chromatography-mass spectrometer (UPLC-MS). The tumor reduction rates of TSC-RAML were assessed and correlated with the plasma protein and metabolite levels. In addition, functional analysis based on differentially expressed molecules was performed to reveal the underlying mechanisms.

Results: Eighty-five patients with one hundred and ten plasma samples were enrolled in our study. Multiple proteins and metabolites, such as pre-melanosome protein (PMEL) and S-adenosylmethionine (SAM), demonstrated both diagnostic and prognostic effects. Functional analysis revealed many dysregulated pathways, including angiogenesis synthesis, smooth muscle proliferation and migration, amino acid metabolism and glycerophospholipid metabolism.

Conclusion: The plasma proteomics and metabolomics pattern of TSC-RAML was clearly different from that of other renal tumors, and the differentially expressed plasma molecules could be used as prognostic and diagnostic biomarkers. The dysregulated pathways, such as angiogenesis and amino acid metabolism, may shed new light on the treatment of TSC-RAML.
Intermuscular coherence of plantar and dorsiflexor muscles in older adults with Parkinson’s disease and age-matched controls during bipedal and unipedal stance
Authors: Smart Rowan R. , Toumi Anis , Harris Owen D. , Cremoux Sylvain , Dalton Brian H. , Wile Daryl J. , Jakobi Jennifer M.
Published: February 2023

Introduction

Postural instability increases with age and is exacerbated in neurological disorders such as Parkinson’s disease (PD). Reducing the base of support from bipedal to unipedal stance increases center of pressure (CoP) parameters and intermuscular coherence in lower-leg muscles of healthy older adults. To further develop an understanding of postural control in an altered state of neurological impairment, we explored intermuscular coherence in lower-leg muscles and CoP displacement in older adults with PD.

Methods

This study measured surface EMG from the medial (MG) and lateral (LG) gastrocnemii, soleus (SOL), and tibialis anterior (TA), and examined EMG amplitude and intermuscular coherence during bipedal and unipedal stance on a force plate with firm (no foam) and compliant (standing on foam) surface conditions in nine older adults with PD (70±5 years, 6 females) and 8 age-matched non-Parkinsonian older adults (5 females). Intermuscular coherence was analyzed between agonist-agonist and agonist-antagonist muscle pairs in the alpha (8-13 Hz) and beta (15-35 Hz) frequency bands.

Results

CoP parameters increased from bipedal to unipedal stance in both groups (p < 0.01), but did not increase from the firm to compliant surface condition (p > 0.05). During unipedal stance, CoP path length was shorter in older adults with PD (2027.9 ± 1074.1 mm) compared to controls (3128.5 ± 1198.7 mm) (p < 0.01). Alpha and beta agonist-agonist and agonist-antagonist coherence increased by 28% from bipedal to unipedal stance (p > 0.05), but did not differ between older adults with PD (0.09 ± 0.07) and controls (0.08 ± 0.05) (p > 0.05). The older adults with PD also had greater normalized EMG amplitude of the LG (63.5 ± 31.7%) and TA (60.6 ± 38.4%) during the balance tasks (p > 0.05) than the non-Parkinsonian counterparts.

Discussion

Older adults with PD had shorter path lengths during unipedal stance and required greater muscle activation than older adults without PD to perform the tasks, but intermuscular coherence did not differ between the groups. This may be attributable to their early disease stage and high motor function.
mGluR5 in amygdala modulates fear memory generalization
Authors: Xuan Shou-Min , Su Ya-Wen , Liang Yi-Meng , Gao Zhen-Jie , Liu Chun-Yan , Fan Bu-Fang , Shi Yan-Wei , Wang Xiao-Guang , Zhao Hu
Published: February 2023

Introduction

Fear memory generalization is regarded as the core characteristic of posttraumatic stress disorder (PTSD) development. However, the mechanism that contributes to the generalization of conditioned fear memory is still unclear. The generalization is generally considered to be a mismatch that occurs during memory consolidation.

Methods

Foot shocks and tones were given as unconditioned stress and conditioned stress, respectively for fear conditioning training. Immunofluorescence staining, western blotting and qPCR were performed to determine the expression of different genes in amygdala of mice after fear conditioning training. Cycloheximide was used as a protein synthesis inhibitor and 2-methyl-6-phenylethynyl-pyridine was injected for mGluR5 inhibition.

Results

Fear conditioning using caused incremental generalization, which was clearly observed during training. The density of c-Fos+ cells or the synaptic p-NMDAR expression did not differ with stress intensities. Strong-shock fear conditioning could induce significant mGluR5 de novo synthesis in the amygdala, which was not observed in the weak-shock group. Inhibition of mGluR5 impaired fear memory generalization induced by strong-shock fear conditioning, but the generalization level induced by weak-shock training was enhanced.

Discussion

These results indicated that mGluR5 in the amygdala is critical to the function of inappropriate fear memory generalization and suggested that this may be a potential target for the treatment of PTSD.
Improved space breakdown method – A robust clustering technique for spike sorting
Authors: Ardelean Eugen-Richard , Ichim Ana-Maria , Dînşoreanu Mihaela , Mureşan Raul Cristian
Published: February 2023

Space Breakdown Method (SBM) is a clustering algorithm that was developed specifically for low-dimensional neuronal spike sorting. Cluster overlap and imbalance are common characteristics of neuronal data that produce difficulties for clustering methods. SBM is able to identify overlapping clusters through its design of cluster centre identification and the expansion of these centres. SBM’s approach is to divide the distribution of values of each feature into chunks of equal size. In each of these chunks, the number of points is counted and based on this number the centres of clusters are found and expanded. SBM has been shown to be a contender for other well-known clustering algorithms especially for the particular case of two dimensions while being too computationally expensive for high-dimensional data. Here, we present two main improvements to the original algorithm in order to increase its ability to deal with high-dimensional data while preserving its performance: the initial array structure was substituted with a graph structure and the number of partitions has been made feature-dependent, denominating this improved version as the Improved Space Breakdown Method (ISBM). In addition, we propose a clustering validation metric that does not punish overclustering and such obtains more suitable evaluations of clustering for spike sorting. Extracellular data recorded from the brain is unlabelled, therefore we have chosen simulated neural data, to which we have the ground truth, to evaluate more accurately the performance. Evaluations conducted on synthetic data indicate that the proposed improvements reduce the space and time complexity of the original algorithm, while simultaneously leading to an increased performance on neural data when compared with other state-of-the-art algorithms.

Code available at

https://github.com/ArdeleanRichard/Space-Breakdown-Method.
Potential association among posterior fossa bony volume and crowdedness, tonsillar hernia, syringomyelia, and CSF dynamics at the craniocervical junction in Chiari malformation type I
Authors: Wang Shengxi , Zhang Dongao , Wu Kun , Fan Wayne , Fan Tao
Published: February 2023

Objective

The characteristic morphological parameters (bony posterior fossa volume (bony-PFV), posterior fossa crowdness, cerebellar tonsillar hernia, and syringomyelia) and CSF dynamics parameters at the craniocervical junction (CVJ) in Chiari malformation type I (CMI) were measured. The potential association between these characteristic morphologies and CSF dynamics at CVJ was analyzed.

Methods

A total of 46 cases of control subjects and 48 patients with CMI underwent computed tomography and phase-contrast magnetic resonance imaging. Seven morphovolumetric measures and four CSF dynamics at CVJ measures were performed. The CMI cohort was further divided into “syringomyelia” and “non-syringomyelia” subgroups. All the measured parameters were analyzed by the Pearson correlation.

Results

Compared with the control, the posterior cranial fossa (PCF) area, bony-PFV, and CSF net flow were significantly smaller (P < 0.001) in the CMI group. Otherwise, the PCF crowdedness index (PCF CI, P < 0.001) and the peak velocity of CSF (P < 0.05) were significantly larger in the CMI cohort. The mean velocity (MV) was faster in patients with CMI with syringomyelia (P < 0.05). In the correlation analysis, the degree of cerebellar tonsillar hernia was correlated with PCF CI (R = 0.319, P < 0.05), MV (R = −0.303, P < 0.05), and the net flow of CSF (R = −0.300, P < 0.05). The Vaquero index was well correlated with the bony-PFV (R= −0.384, P < 0.05), MV (R = 0.326, P < 0.05), and the net flow of CSF (R = 0.505, P < 0.05).

Conclusion

The bony-PFV in patients with CMI was smaller, and the MV was faster in CMI with syringomyelia. Cerebellar subtonsillar hernia and syringomyelia are independent indicators for evaluating CMI. Subcerebellar tonsillar hernia was associated with PCF crowdedness, MV, and the net flow of CSF at CVJ, while syringomyelia was associated with bony-PFV, MV, and the net flow of CSF at the CVJ. Thus, the bony-PFV, PCF crowdedness, and the degree of CSF patency should also be one of the indicators of CMI evaluation.
Risk factors of hemorrhagic transformation in acute ischaemic stroke: A systematic review and meta-analysis
Authors: Sun Jiacheng , Lam Christina , Christie Lauren , Blair Christopher , Li Xingjuan , Werdiger Freda , Yang Qing , Bivard Andrew , Lin Longting , Parsons Mark
Published: February 2023

Background

Hemorrhagic transformation (HT) following reperfusion therapies for acute ischaemic stroke often predicts a poor prognosis. This systematic review and meta-analysis aims to identify risk factors for HT, and how these vary with hyperacute treatment [intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT)].

Methods

Electronic databases PubMed and EMBASE were used to search relevant studies. Pooled odds ratio (OR) with 95% confidence interval (CI) were estimated.

Results

A total of 120 studies were included. Atrial fibrillation and NIHSS score were common predictors for any intracerebral hemorrhage (ICH) after reperfusion therapies (both IVT and EVT), while a hyperdense artery sign (OR = 2.605, 95% CI 1.212–5.599, I2 = 0.0%) and number of thrombectomy passes (OR = 1.151, 95% CI 1.041–1.272, I2 = 54.3%) were predictors of any ICH after IVT and EVT, respectively. Common predictors for symptomatic ICH (sICH) after reperfusion therapies were age and serum glucose level. Atrial fibrillation (OR = 3.867, 95% CI 1.970–7.591, I2 = 29.1%), NIHSS score (OR = 1.082, 95% CI 1.060–1.105, I2 = 54.5%) and onset-to-treatment time (OR = 1.003, 95% CI 1.001–1.005, I2 = 0.0%) were predictors of sICH after IVT. Alberta Stroke Program Early CT score (ASPECTS) (OR = 0.686, 95% CI 0.565–0.833, I2 =77.6%) and number of thrombectomy passes (OR = 1.374, 95% CI 1.012–1.866, I2 = 86.4%) were predictors of sICH after EVT.

Conclusion

Several predictors of ICH were identified, which varied by treatment type. Studies based on larger and multi-center data sets should be prioritized to confirm the results.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=268927, identifier: CRD42021268927.
Sex differences in chronic pain-induced mental disorders: Mechanisms of cerebral circuitry
Authors: Shen Zuqi , Li Wei , Chang Weiqi , Yue Na , Yu Jin
Published: February 2023

Mental disorders such as anxiety and depression induced by chronic pain are common in clinical practice, and there are significant sex differences in their epidemiology. However, the circuit mechanism of this difference has not been fully studied, as preclinical studies have traditionally excluded female rodents. Recently, this oversight has begun to be resolved and studies including male and female rodents are revealing sex differences in the neurobiological processes behind mental disorder features. This paper reviews the structural functions involved in the injury perception circuit and advanced emotional cortex circuit. In addition, we also summarize the latest breakthroughs and insights into sex differences in neuromodulation through endogenous dopamine, 5-hydroxytryptamine, GABAergic inhibition, norepinephrine, and peptide pathways like oxytocin, as well as their receptors. By comparing sex differences, we hope to identify new therapeutic targets to offer safer and more effective treatments.
Association between sarcopenia and survival in patients with gynecologic cancer: A systematic review and meta-analysis
Authors: Lin Wen-Li , Nguyen Thi-Hoang-Yen , Lin Cheng-Yao , Wu Li-Min , Huang Wen-Tsung , Guo How-Ran
Published: February 2023

Background

Despite prior attempts to evaluate the effects of sarcopenia on survival among patients with gynecologic cancer, the results of these studies have not been consistent. The present study evaluated the association between sarcopenia and survival among patients with gynecologic cancer by aggregating multiple studies.

Methods

We performed a literature search using computerized databases and identified additional studies included in the bibliographies of retrieved articles. The quality of each study was evaluated using the Newcastle–Ottawa Scale, and meta-analyses were performed to evaluate overall survival (OS) and progression-free survival (PFS). We constructed a forest plot for each outcome and assessed publication bias using Begg’s test. Heterogeneity was assessed using I2 statistics.

Results

From the 5,933 initially identified articles, 16 studies describing 2,031 participants with a mean age of 60.34 years were included in the meta-analysis. We found that compared with patients with gynecologic cancer but without sarcopenia, patients with sarcopenia had worse OS, with a pooled hazard ratio (HR) of 2.61 (95% confidence interval [CI]:1.52–4.46), and worse PFS (HR: 1.37, 95% CI: 1.09–1.73). The quality of studies was generally good, and no publication bias was detected among studies for either OS or PFS. Although 4 of 12 studies were of fair quality, we conducted a sensitivity analysis excluding studies or fair quality and obtained similar results.

Conclusions

These meta-analysis results suggest that sarcopenia is associated with worse OS and PFS among patients with gynecologic cancer. The use of different case definitions appeared to be a major source of heterogeneity among the studies. Further studies remain necessary to confirm our findings, especially those examining OS and PFS, because publication bias was identified.
Proteomic quantification of receptor tyrosine kinases involved in the development and progression of colorectal cancer liver metastasis
Authors: Vasilogianni Areti-Maria , Al-Majdoub Zubida M. , Achour Brahim , Peters Sheila Annie , Rostami-Hodjegan Amin , Barber Jill
Published: February 2023

Introduction

Alterations in expression and activity of human receptor tyrosine kinases (RTKs) are associated with cancer progression and in response to therapeutic intervention.

Methods

Thus, protein abundance of 21 RTKs was assessed in 15 healthy and 18 cancerous liver samples [2 primary and 16 colorectal cancer liver metastasis (CRLM)] matched with non-tumorous (histologically normal) tissue, by a validated QconCAT-based targeted proteomic approach.

Results

It was demonstrated, for the first time, that the abundance of EGFR, INSR, VGFR3 and AXL, is lower in tumours relative to livers from healthy individuals whilst the opposite is true for IGF1R. EPHA2 was upregulated in tumour compared with histologically normal tissue surrounding it. PGFRB levels were higher in tumours relative to both histologically normal tissue surrounding tumour and tissues taken from healthy individuals. The abundances of VGFR1/2, PGFRA, KIT, CSF1R, FLT3, FGFR1/3, ERBB2, NTRK2, TIE2, RET, and MET were, however, comparable in all samples. Statistically significant, but moderate correlations were observed (Rs > 0.50, p < 0.05) for EGFR with INSR and KIT. FGFR2 correlated with PGFRA and VGFR1 with NTRK2 in healthy livers. In non-tumorous (histologically normal) tissues from cancer patients, there were correlations between TIE2 and FGFR1, EPHA2 and VGFR3, FGFR3 and PGFRA (p < 0.05). EGFR correlated with INSR, ERBB2, KIT and EGFR, and KIT with AXL and FGFR2. In tumours, CSF1R correlated with AXL, EPHA2 with PGFRA, and NTRK2 with PGFRB and AXL. Sex, liver lobe and body mass index of donors had no impact on the abundance of RTKs, although donor age showed some correlations. RET was the most abundant of these kinases in non-tumorous tissues (~35%), while PGFRB was the most abundant RTK in tumours (~47%). Several correlations were also observed between the abundance of RTKs and proteins relevant to drug pharmacokinetics (enzymes and transporters).

Discussion

DiscussionThis study quantified perturbation to the abundance of several RTKs in cancer and the value generated in this study can be used as input to systems biology models defining liver cancer metastases and biomarkers of its progression.
Promotion of colorectal cancer by transcription factor BHLHE40 involves upregulation of ADAM19 and KLF7
Authors: Sui Yuan , Jiang Hanlin , Kellogg Collyn M. , Oh Sangphil , Janknecht Ralf
Published: February 2023

BHLHE40 is a transcription factor, whose role in colorectal cancer has remained elusive. We demonstrate that the BHLHE40 gene is upregulated in colorectal tumors. Transcription of BHLHE40 was jointly stimulated by the DNA-binding ETV1 protein and two associated histone demethylases, JMJD1A/KDM3A and JMJD2A/KDM4A, which were shown to also form complexes on their own and whose enzymatic activity was required for BHLHE40 upregulation. Chromatin immunoprecipitation assays revealed that ETV1, JMJD1A and JMJD2A interacted with several regions within the BHLHE40 gene promoter, suggesting that these three factors directly control BHLHE40 transcription. BHLHE40 downregulation suppressed both growth and clonogenic activity of human HCT116 colorectal cancer cells, strongly hinting at a pro-tumorigenic role of BHLHE40. Through RNA sequencing, the transcription factor KLF7 and the metalloproteinase ADAM19 were identified as putative BHLHE40 downstream effectors. Bioinformatic analyses showed that both KLF7 and ADAM19 are upregulated in colorectal tumors as well as associated with worse survival and their downregulation impaired HCT116 clonogenic activity. In addition, ADAM19, but not KLF7, downregulation reduced HCT116 cell growth. Overall, these data have revealed a ETV1/JMJD1A/JMJD2A→BHLHE40 axis that may stimulate colorectal tumorigenesis through upregulation of genes such as KLF7 and ADAM19, suggesting that targeting this axis represents a potential novel therapeutic avenue.
Endoscopic surveillance of Lynch syndrome at a highly specialized center in Sweden: An observational study of interval colorectal cancer and individual risk factors
Authors: Jamizadeh Nigin , Walton Bernstedt Sophie , Haxhijaj Adrianna , Andreasson Anna , Björk Jan , Forsberg Anna , Backman Ann-Sofie
Published: February 2023

Introduction

Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC). In order to detect CRCs amongst LS patients, regular colonoscopies are recommended. However, an international agreement on an optimal surveillance interval has not yet been reached. In addition, few studies have investigated factors that could potentially increase the CRC risk amongst LS patients.

Aims

The primary aim was to describe the frequency of CRCs detected during endoscopic surveillance and to estimate the interval from a clean colonoscopy to CRC detection amongst LS patients. The secondary aim was to investigate individual risk factors, including sex, LS genotype, smoking, aspirin use and body mass index (BMI), on CRC risk amongst patients that develop CRC before and during surveillance.

Material and methods

Clinical data and colonoscopy findings from 366 LS patients’ 1437 surveillance colonoscopies were collected from medical records and patient protocols. Logistic regression and Fisher’s exact test were used to investigate associations between individual risk factors and CRC development. Mann-Whitney U test was used to compare the distribution of TNM stages of CRC detected before surveillance and after index.

Results

CRC was detected in 80 patients before surveillance and in 28 patients during surveillance (10 at index and 18 after index). During the surveillance programme, CRC was detected within 24 months in 65% of the patients, and after 24 months within 35% of the patients. CRC was more common amongst men, previous and current smokers, and the odds of developing CRC also increased with an increasing BMI. CRCs were more often detected amongst MLH1 and MSH2 carriers during surveillance, compared to the other genotypes.

Conclusions

We found that 35% of the CRC cases detected during surveillance were found after 24 months. MLH1 and MSH2 carriers were at higher risk of developing CRC during surveillance. Additionally, men, current or previous smokers, and patients with a higher BMI were at higher risk of developing CRC. Currently, LS patients are recommended a “one-size-fits-all” surveillance program. The results support the development of a risk-score whereby individual risk factors should be taken into consideration when deciding on an optimal surveillance interval.
Corona enhancement combined with microvascular invasion for prognosis prediction of macrotrabecular-massive hepatocellular carcinoma subtype
Authors: Yang Lili , Wang Meng , Zhu Yanyan , Zhang Jiahui , Pan Junhan , Zhao Yanci , Sun Ke , Chen Feng
Published: February 2023

Objectives

The macrotrabecular-massive (MTM) subtype of hepatocellular carcinoma (HCC) is aggressive and associated with an unfavorable prognosis. This study aimed to characterize MTM-HCC features based on contrast−enhanced MRI and to evaluate the prognosis of imaging characteristics combined with pathology for predicting early recurrence and overall survival after surgery.

Methods

This retrospective study included 123 patients with HCC that underwent preoperative contrast−enhanced MRI and surgery, between July 2020 and October 2021. Multivariable logistic regression was performed to investigate factors associated with MTM-HCC. Predictors of early recurrence were determined with a Cox proportional hazards model and validated in a separate retrospective cohort.

Results

The primary cohort included 53 patients with MTM-HCC (median age 59 years; 46 male and 7 females; median BMI 23.5 kg/m2) and 70 subjects with non-MTM HCC (median age 61.5 years; 55 male and 15 females; median BMI 22.6 kg/m2) (All P>0.05). The multivariate analysis identified corona enhancement (odds ratio [OR]=2.52, 95% CI: 1.02–6.24; P=0.045) as an independent predictor of the MTM-HCC subtype. The multiple Cox regression analysis identified corona enhancement (hazard ratio [HR]=2.56, 95% CI: 1.08–6.08; P=0.033) and MVI (HR=2.45, 95% CI: 1.40–4.30; P=0.002) as independent predictors of early recurrence (area under the curve=0.790, P<0.001). The prognostic significance of these markers was confirmed by comparing results in the validation cohort to those from the primary cohort. Corona enhancement combined with MVI was significantly associated with poor outcomes after surgery.

Conclusions

A nomogram for predicting early recurrence based on corona enhancement and MVI could be used to characterize patients with MTM-HCC and predict their prognosis for early recurrence and overall survival after surgery.
Sacituzumab govitecan and radiotherapy in metastatic, triple-negative, and BRCA-mutant breast cancer patient with active brain metastases: A case report
Authors: di Mauro Pierluigi , Schivardi Greta , Pedersini Rebecca , Laini Lara , Esposito Andrea , Amoroso Vito , Laganà Marta , Grisanti Salvatore , Cosentini Deborah , Berruti Alfredo
Published: February 2023

Background

Triple-negative breast cancer (TNBC) is an aggressive cancer subtype, owing to its high metastatic potential: Patients who develop brain metastases (BMs) have a poor prognosis due to the lack of effective systemic treatments. Surgery and radiation therapy are valid options, while pharmacotherapy still relies on systemic chemotherapy, which has limited efficacy. Among the new treatment strategies available, the antibody-drug conjugate (ADC) sacituzumab govitecan has shown an encouraging activity in metastatic TNBC, even in the presence of BMs.

Case presentation

A 59-year-old woman was diagnosed with early TNBC and underwent surgery and subsequent adjuvant chemotherapy. A germline pathogenic variant in BReast CAncer gene 2 (BRCA2) was revealed after genetic testing. After 11 months from the completion of adjuvant treatment, she had pulmonary and hilar nodal relapse and began first-line chemotherapy with carboplatin and paclitaxel. However, after only 3 months from starting the treatment, she experienced relevant disease progression, due to the appearance of numerous and symptomatic BMs. Sacituzumab govitecan (10 mg/kg) was started as second-line treatment as part of the Expanded Access Program (EAP). She reported symptomatic relief after the first cycle and received whole-brain radiotherapy (WBRT) concomitantly to sacituzumab govitecan treatment. The subsequent CT scan showed an extracranial partial response and a near-to-complete intracranial response; no grade 3 adverse events were reported, even if sacituzumab govitecan was reduced to 7.5 mg/kg due to persistent G2 asthenia. After 10 months from starting sacituzumab govitecan, a systemic disease progression was documented, while intracranial response was maintained.

Conclusions

This case report supports the potential efficacy and safety of sacituzumab govitecan in the treatment of early recurrent and BRCA-mutant TNBC. Despite the presence of active BMs, our patient had a progression-free survival (PFS) of 10 months in the second-line setting and sacituzumab govitecan was safe when administered together with radiation therapy. Further real-world data are warranted to confirm sacituzumab govitecan efficacy in this patient population.
Labor epidural analgesia and risk of autism Spectrum disorders in offspring: A systematic review and meta-analysis
Authors: Fang Ling-ling , Zhou Yuan-yue , Jiang Hai-yin , Shi Yu-dan
Published: February 2023

Background

The effect of labor epidural anesthesia (LEA) on the risk of autism spectrum disorder (ASD) in offspring has been investigated recently, and available results are inconsistent.

Methods

We searched the PubMed and EMBASE databases for relevant studies and performed a systematic review and meta-analysis of the literature. Subgroup analyses were conducted to assess the sources of heterogeneity. Both fixed and random effects models were used was used to estimate overall relative risk.

Results

Our results showed that LEA was associated with an increased risk of ASD in offspring [HR = 1.3, 95% confidence interval (CI): 1.25–1.35; P < 0.001] after combining crude estimates from the included studies. This association was gradually reduced, but still statistically significant, when potential confounding factors were considered (HR 1.13, 95% CI 1.03–1.25, P = 0.014). However, there was no significant association when we combined data of siblings from other pregnancies (HR = 1.07, 95% CI: 0.99–1.16, P = 0.076), implying that the association was due to confounding factors.

Conclusion

The statistically significant association between LEA and ASD in the offspring can be partially explained by unmeasured confounding.

Systematic Review Registration

Identifier CRD42022302892.
Granulomatous inflammation in inborn errors of immunity
Authors: Sacco Keith A. , Gazzin Andrea , Notarangelo Luigi D. , Delmonte Ottavia M.
Published: February 2023

Granulomas have been defined as inflammatory infiltrates formed by recruitment of macrophages and T cells. The three-dimensional spherical structure typically consists of a central core of tissue resident macrophages which may merge into multinucleated giant cells surrounded by T cells at the periphery. Granulomas may be triggered by infectious and non-infectious antigens. Cutaneous and visceral granulomas are common in inborn errors of immunity (IEI), particularly among patients with chronic granulomatous disease (CGD), combined immunodeficiency (CID), and common variable immunodeficiency (CVID). The estimated prevalence of granulomas in IEI ranges from 1%–4%. Infectious agents causing granulomas such Mycobacteria and Coccidioides presenting atypically may be ‘sentinel’ presentations for possible underlying immunodeficiency. Deep sequencing of granulomas in IEI has revealed non-classical antigens such as wild-type and RA27/3 vaccine-strain Rubella virus. Granulomas in IEI are associated with significant morbidity and mortality. The heterogeneity of granuloma presentation in IEI presents challenges for mechanistic approaches to treatment. In this review, we discuss the main infectious triggers for granulomas in IEI and the major forms of IEI presenting with ‘idiopathic’ non-infectious granulomas. We also discuss models to study granulomatous inflammation and the impact of deep-sequencing technology while searching for infectious triggers of granulomatous inflammation. We summarize the overarching goals of management and highlight the therapeutic options reported for specific granuloma presentations in IEI.
PROTACs: Walking through hematological malignancies
Authors: Bou Malhab Lara J. , Alsafar Habiba , Ibrahim Saleh , Rahmani Mohamed
Published: February 2023

Proteolysis targeting chimeras (PROTACs) are heterobifunctional small molecules that uses the proteasome ubiquitin system to target proteins of interest and promote their degradation with remarkable selectivity. Importantly, unlike conventional small molecule inhibitors, PROTACs have proven highly effective in targeting undruggable proteins and those bearing mutations. Because of these considerations, PROTACs have increasingly become an emerging technology for the development of novel targeted anticancer therapeutics. Interestingly, many PROTACs have demonstrated a great potency and specificity in degrading several oncogenic drivers. Many of these, following extensive preclinical evaluation, have reached advanced stages of clinical testing in various cancers including hematologic malignancies. In this review, we provide a comprehensive summary of the recent advances in the development of PROTACs as therapeutic strategies in diverse hematological malignancies. A particular attention has been given to clinically relevant PROTACs and those targeting oncogenic mutants that drive resistance to therapies. We also discus limitations, and various considerations to optimize the design for effective PROTACs.
Unraveling the significance of exosomal circRNAs in cancer therapeutic resistance
Authors: Kang Fanhua , Yan Yuanliang , Liu Yuanhong , Liang Qiuju , Xu Zhijie , Zhu Wei , Thakur Abhimanyu
Published: February 2023

Exosomes are nanoscale extracellular vesicles secreted by a variety of cells, affecting the physiological and pathological homeostasis. They carry various cargoes including proteins, lipids, DNA, and RNA and have emerged as critical mediators of intercellular communication. During cell–cell communication, they can internalize either by autologous or heterologous recipient cells, which activate different signaling pathways, facilitating malignant progression of cancer. Among different types of cargoes in exosomes, the endogenous non-coding RNAs, such as circular RNAs (or circRNAs), have gained tremendous attention for their high stability and concentration, playing promising functional roles in cancer chemotherapeutic response by regulating the targeted gene expression. In this review, we primarily described the emerging evidence demonstrating the important roles of circular RNAs derived from exosomes in the regulation of cancer-associated signaling pathways that were involved in cancer research and therapeutic interventions. Additionally, the relevant profiles of exosomal circRNAs and their biological implications have been discussed, which is under investigation for their potential effect on the control of cancer therapeutic resistance.
A comparison of urinary bladder weight in male and female mice across five models of diabetes and obesity
Authors: Erdogan Betül R. , Michel Martina B. , Matthes Jan , Castañeda Tamara R. , Christen Urs , Arioglu-Inan Ebru , Michel Martin C. , Pautz Andrea
Published: February 2023

Introduction: Diabetes often leads to lower urinary tract dysfunction. The most frequently assessed parameter of urinary bladder dysfunction in animal models of diabetes is an enlargement of the bladder, which is consistently observed in type 1 and less consistently in type 2 diabetes. The vast majority of studies on bladder weight in animal models of diabetes and obesity has been performed in males, and no studies have directly compared this outcome parameter between sexes.

Methods: Therefore, we have compared bladder weight and bladder/body weight ratio in five mouse models of obesity and diabetes (RIP-LCMV, db/db, ob/ob (two studies), insulin receptor substrate 2 (IRS2) knock-out mice and mice on a high-fat diet; pre-specified secondary analysis of a previously reported study).

Results: In a pooled analysis of the control groups of all studies, females exhibited slightly lower glucose levels, lower body weight, and lower bladder weight, but bladder/body weight ratio was similar in both sexes (0.957 vs. 0.986 mg/g, mean difference 0.029 [−0.06; 0.118]). Among the six diabetic/obese groups, bladder/body weight ratio was similar in both sexes in three but smaller in female mice in three other groups. The mRNA expression of a panel of genes implied in the pathophysiology of bladder enlargement and/or fibrosis and inflammation did not differ systematically between sexes.

Conclusions: We conclude that sex differences in diabetes/obesity-associated bladder enlargement may be model dependent.