Notes

Sarcomatoid hepatocellular carcinoma in a young Africa woman.
Diseases in marine eukaryotic organisms caused by opportunistic pathogens represent a serious threat to our oceans with potential downstream consequences for ecosystem functioning. Disease outbreaks affecting macroalgae are of particular concern due to their critical role as habitat-forming organisms. However, there is limited understanding of the molecular strategies used by macroalgae to respond to opportunistic pathogens. In this study, we used mRNA-sequencing analysis to investigate the early antipathogen response of the model macroalga Delisea pulchra (Rhodophyta) under the environmental conditions that are known to promote the onset of disease. Using de novo assembly methods, 27,586 unique transcripts belonging to D. pulchra were identified that were mostly affiliated with stress response and signal transduction processes. Differential gene expression analysis between a treatment with the known opportunistic pathogen, Aquimarina sp. AD1 (Bacteroidota), and a closely related benign strain (Aquimarina sp. AD10) revealed a downregulation of genes coding for predicted protein metabolism, stress response, energy generation and photosynthesis functions. The rapid repression of genes coding for core cellular processes is likely to interfere with the macroalgal antipathogen response, later leading to infection, tissue damage and bleaching symptoms. Overall, this study provides valuable insight into the genetic features of D. pulchra, highlighting potential antipathogen response mechanisms of macroalgae and contributing to an improved understanding of host-pathogen interactions in a changing environment.Microbial nitrogen (N) immobilization, which typically results in soil N retention but based on the balance of gross N immobilization over gross N production, affects the fate of the anthropogenic reactive N. However, global patterns and drivers of soil gross immobilization of ammonium (INH4 ) and nitrate (INO3 ) are still only tentatively known. DMAMCL in vitro Here, we provide a comprehensive analysis considering gross N production rates, soil properties, and climate and their interactions for a deeper understanding of the patterns and drivers of INH4 and INO3 . By compiling and analyzing 1966 observations from 274 15 N-labelled studies, we found a global average of INH4 and INO3 of 7.41 ± 0.72 and 2.03 ± 0.30 mg N kg-1 day-1 with a ratio of INO3 to INH4 (INO3 INH4 ) of 0.79 ± 0.11. Soil INH4 and INO3 increased with increasing soil gross N mineralization (GNM) and nitrification (GN), microbial biomass, organic carbon, and total N and decreasing soil bulk density. Our analysis revealed that GNM and GN were the main stimulators for INH4 and INO3 , respectively. The structural equation modeling showed that higher soil microbial biomass, total N, pH, and precipitation stimulate INH4 and INO3 through enhancing GNM and GN. However, higher temperature and soil bulk density suppress INH4 and INO3 by reducing microbial biomass and total N. Soil INH4 varied with terrestrial ecosystems, being greater in grasslands and forests, which have higher rates of GNM, than in croplands. The highest INO3 INH4 was observed in croplands, which had higher rates of GN. The global average of GN to INH4 was 2.86 ± 0.31, manifesting a high potential risk of N loss. We highlight that anthropogenic activities that influence soil properties and gross N production rates likely interact with future climate changes and land uses to affect soil N immobilization and, eventually, the fate of the anthropogenic reactive N.
Chronic migraine is a highly disabling primary headache disorder that is the most common diagnosis of patients seen at tertiary headache centres. Typical oral preventive therapies are associated with many limitations that impact their therapeutic utility. Erenumab was the first available calcitonin gene-related peptide monoclonal antibody in the UK. It had proven efficacy in migraine prevention in clinical trials and limited real-world data in tertiary settings.

We audited our first 92 patients (n=73 females) with severely disabling chronic migraine who were given monthly erenumab 70mg sc for 6months between December 2018 and December 2019.

At 3months, monthly migraine days were significantly reduced by a median of 4days, and all other variables also showed significant improvement. The improvement was not affected by baseline analgesic use status. More than half of our patients experienced a clinically meaningful improvement in migraine days. No serious adverse events were reported.

Our real-world data with erenumab demonstrate it is effective and well tolerated in managing patients with chronic migraine in a tertiary care setting.
Our real-world data with erenumab demonstrate it is effective and well tolerated in managing patients with chronic migraine in a tertiary care setting.Ectopic thymomas (ETs) are rare thymic neoplasms that arise from atypical anatomical sites and present a diagnostic challenge for clinicians as they can be mistaken for other pathological entities on fine needle aspiration (FNA) cytology.
Hidradenitis suppurativa (HS) is a chronic, inflammatory, debilitating skin disease characterized by painful deep lesions and associated with substantial disease burden.

The objective of this study was to describe physician- and patient-reported clinical unmet needs from a real-world perspective.

This study used data from the Adelphi HS Disease Specific Programme, a point-in-time survey of dermatologists and their patients with HS in Europe and the United States. Dermatologists completed patient record forms (PRFs) for 5-7 consecutively consulting patients with HS; patients or carers of patients also optionally completed a patient/carer self-completion questionnaire (PSC/CSC). Data collection included demographics, symptomatology and impact on quality of life (QoL).

Dermatologists (N = 312) completed PRFs for 1787 patients with HS; patient- and carer-reported questionnaires (PSC/CSC) were completed for 33.1% (591/1787) of patients. The mean age was 34.4 ± 12.2 years and 57.6% of patients were female (a high disease burden despite being actively treated by a dermatologist. This study demonstrates that the burden of HS disease is generally poorly managed with a considerable impact observed on patients' QoL.
Patients with HS experienced a high disease burden despite being actively treated by a dermatologist. This study demonstrates that the burden of HS disease is generally poorly managed with a considerable impact observed on patients' QoL.
PPKs represent a heterogeneous group of disorders with hyperkeratosis of palmar and/or plantar skin. PPK, hair shaft abnormalities, cardiomyopathy and arrhythmias can be caused by mutations in desmosomal genes, e.g. desmoplakin (DSP). PPK should trigger genetic testing to reveal mutations with possible related cardiac disease.

To report a large multigenerational family with a novel DSP mutation associated with early-onset PPK and adult-onset cardiomyopathy and arrhythmias.

A custom-designed in-house panel of 35 PPK related genes was used to screen mutations in the index patient with focal PPK. The identified DSP mutation was verified by Sanger sequencing. DNA samples from 20 members of the large multigenerational family were sequenced for the DSP mutation. Medical records were reviewed. Clinical dermatological evaluation was performed, including light microscopy of hair samples. Cardiac evaluation included clinical examination, echocardiography, cardiac magnetic resonance imaging (CMR), electrocardiograagement of cardiomyopathies and arrhythmias.Facing phosphate deficiency, phytoplankton use alkaline phosphatase (AP) to scavenge dissolved organophosphate (DOP). AP is a multitype (e.g., PhoA, PhoD) family of hydrolases and is known as a promiscuous enzyme with broad DOP substrate compatibility. Yet, whether the multiple types differentiate on substrates and collaborate to provide physiological flexibility remain elusive. Here we identify PhoA and PhoDs and document the functional differentiation between PhoA and a PhoD (PhoD_45757) in Phaeodactylum tricornutum. CRISPR/Cas9-based mutations and physiological analyses reveal that (1) PhoA is a secreted enzyme and contributes the majority of total AP activity whereas PhoD_45757 is intracellular and contributes a minor fraction of the total AP activity, (2) AP gene expression compensates for each other after one is disrupted, (3) the DOP→PhoA→phosphate_uptake and the DOP_uptake→PhoD→phosphate pathways function interchangeably for some DOP substrates. These findings shed light on the underpinning of AP's multiformity and have important implications in phytoplankton phosphorus-nutrient niche differentiation, physiological plasticity, and competitive strategy.
Interventions for individuals involved in sexual offending behaviours are likely to be more effective if adapted to focus on their specific characteristics, suggesting that men who engage in sexual offences against children over the Internet should be treated differently from those who have actual physical contact against children.

The goal of this study is to explore possible associations between the criminogenic cognitions and behaviours of men using online child sexual exploitation material (CSEM) and variables relevant to intervention. We hypothesised that antisocial tendencies, sexual, emotional and relational problems and self-regulation problems, as well as cognitive distortions would be associated with CSEM use.

Ninety-eight men who had been convicted of at least one online CSEM-related offence, but no child contact sexual offences, at any time between 2001 and 2020 were recruited in the province of Quebec (Canada). Cases were reviewed to identify cognitive and behavioural criminogenic factors audy.
Because online CSEM-related offenders present heterogeneous risks and needs, a 'one-size-fits-all' intervention is unlikely to be optimal for most of them. Our findings suggest a way of classifying risks and needs to facilitate more focused interventions. Future research should evaluate the relative effectiveness of general interventions compared to those tailored towards the dimensions of risks and needs identified in this study.
Cervical cancer is one of the most common malignant tumors in women, and it is essential to explore potential biomarkers such as glycopeptides closely related to cancer in physiological samples of cervical cancer patients. Sample pretreatment is required before direct detection using mass spectrometry because there are certain limitations. Meanwhile, it is still highly desired to promote the functionalization and application of metal-organic framework (MOF)-derived materials.

Using a post-synthesis modification method, a novel type of boric acid-functionalized MOF probe (designated as UiO-66@PEI@Au@B(OH)
) is prepared for recognition of glycopeptides. The results are obtained using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and nano-liquid chromarography-tandem mass spectrometry.

The UiO-66@PEI@Au@B(OH)
probe exhibits a low detection limit (0.6fmol μL
), an excellent recovery rate, comparatively good reusability and selectivity (HRP digestsBSA digests =1500). When UiO-66@PEI@Au@B(OH)
is used to selectively capture glycopeptides from the serum of a healthy person and a cervical cancer patient, 101 glycopeptides corresponding to 54 glycoproteins and 108 glycopeptides corresponding to 57 glycoproteins are detected, respectively.
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