Myeloid sarcoma (MS) is a rare hematological malignancy characterized by the formation of a solid mass of myeloblasts outside the bone marrow, such as in the lymph nodes, skin, or bone. MS may arise
...or concurrently with acute myeloid leukemia (AML), myeloproliferative neoplasm (MPN), or myelodysplastic syndrome (MDS). MS accounts for less than 1% of extramedullary acute myeloid leukemia cases. Phyllodes tumors (PTs) are a rare fibroepithelial breast tumor that can be benign, malignant, or borderline, and account for less than 1% of all breast cancers.
We present a unique case of a 50-year-old woman with both breast MS and borderline PT with malignant features, which presented a diagnostic challenge. The patient initially presented with a mass in her right breast, and the initial fine-needle biopsy revealed the presence of immature myeloperoxidase (MPO)
myeloid cells consistent with MS. Subsequent pathological analysis of tumor tissues after neoadjuvant radiotherapy and chemotherapy showed a borderline PT with malignant features. Following excision of the tumor, the patient experienced a local recurrence, which was also surgically removed. At 8 months post-surgery, the patient remains free of recurrence under close follow-up.
This case highlights the importance of considering the possibility of concurrent malignancies in the differential diagnosis of complex breast masses and underscores the challenges involved in diagnosing and managing such cases. Additionally, we also emphasize the value of neoadjuvant radiotherapy and chemotherapy in MS.
Deep Learning (DL) has recently achieved tremendous success. A variety of DL frameworks and platforms play a key role to catalyze such progress. However, the differences in architecture designs and ...implementations of existing frameworks and platforms bring new challenges for DL software development and deployment. Till now, there is no study on how various mainstream frameworks and platforms influence both DL software development and deployment in practice.
To fill this gap, we take the first step towards understanding how the most widely-used DL frameworks and platforms support the DL software development and deployment. We conduct a systematic study on these frameworks and platforms by using two types of DNN architectures and three popular datasets. (1) For development process, we investigate the prediction accuracy under the same runtime training configuration or same model weights/biases. We also study the adversarial robustness of trained models by leveraging the existing adversarial attack techniques. The experimental results show that the computing differences across frameworks could result in an obvious prediction accuracy decline, which should draw the attention of DL developers. (2) For deployment process, we investigate the prediction accuracy and performance (refers to time cost and memory consumption) when the trained models are migrated/quantized from PC to real mobile devices and web browsers. The DL platform study unveils that the migration and quantization still suffer from compatibility and reliability issues. Meanwhile, we find several DL software bugs by using the results as a benchmark. We further validate the results through bug confirmation from stakeholders and industrial positive feedback to highlight the implications of our study. Through our study, we summarize practical guidelines, identify challenges and pinpoint new research directions, such as understanding the characteristics of DL frameworks and platforms, avoiding compatibility and reliability issues, detecting DL software bugs, and reducing time cost and memory consumption towards developing and deploying high quality DL systems effectively.
Objectives
This meta-analysis aimed to evaluate the effectiveness of HCQ in improving the maternal and fetal outcomes in pregnancies with SLE.
Methods
A literature search was conducted using PubMed, ...MEDLINE, EMBASE, and the Cochrane database for relevant English language articles, and Wanfang, CNKI and VIP for Chinese articles, from the databases’ inception to April 30, 2020. These studies compared the maternal and/or fetal outcomes between pregnant patients with SLE who were administered HCQ during pregnancy (HCQ+ group) and those who were not administered HCQ (HCQ− group). Two investigators extracted the data and assessed the quality using the Newcastle-Ottawa Scale (NOS) and GRADE criteria independently. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated. All statistical analyses were conducted using the Stata 12.0 software.
Results
Nine studies involving 1132 pregnancies were included in the study (3 case controls, 2 prospective cohorts, 4 retrospective cohorts). Preeclampsia, gestational hypertension, and prematurity were significantly lower in the HCQ+ group than in the HCQ− group (OR 0.35, 95% CI 0.21–0.59), (OR 0.41, 95% CI 0.19–0.89) and (OR 0.55, 95% CI 0.36–0.86), respectively. There were no significant differences in the rates of HELLP Syndrome (OR 0.88, 95% CI 0.19–3.96), gestational diabetes (OR 2.3, 95% CI 0.44–12.12), thrombotic events (OR 0.26, 95% CI 0.05–1.51), spontaneous abortion (OR 1.77, 95% CI 0.96–3.26), premature rupture of membranes (OR 0.58, 95% CI 0.24–1.39), oligohydramnios (OR 0.90, 95% CI 0.38–2.14), live birth (OR 1.22, 95% CI 0.60–2.47), stillbirth (OR 1.00, 95% CI 0.50–2.00), congenital malformation (OR 0.53, 95% CI 0.14–2.04), low birth weight (OR 0.77, 95% CI 0.43–1.39), intrauterine distress (OR 1.07, 95% CI 0.41–2.76,), intrauterine growth restriction (OR 0.57, 95% CI 0.06–5.43), or five-minute APGAR score <7 (OR 0.72, 95% CI 0.20–2.58) between the two groups.
Conclusions
HCQ treatment during pregnancy could reduce the risk of preeclampsia, pregnancy hypertension and prematurity in SLE patients. The certainty of evidence is high but majority of the studies included are retrospective studies and not randomized controlled trials. Therefore, the multidisciplinary management of pregnant patients with SLE should promote HCQ use, irrespective of disease activity or severity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
A unique approach toward the preparation of cyclohexenynone equivalents was successfully developed via oxidative dearomatization of aryne precursors, featuring multiple functionalities on the target ...rings. Upon activation, these in situ formed cyclohexenynone intermediates exhibit good to excellent reactivity with various trapping agents. Moreover, an unprecedented cascade was discovered with aryl allyl sulfoxides, revealing a deeper utilization of the alkyne bond by concomitantly introducing one nucleophile and two electrophiles.
The most prevalent and devastating form of organ damage in systemic lupus erythematosus (SLE) is lupus nephritis (LN). LN is characterized by glomerular injury, inflammation, cell proliferation, and ...necrosis, leading to podocyte injury and tubular epithelial cell damage. Assays for urine biomarkers have demonstrated significant promise in the early detection of LN, evaluation of disease activity, and tracking of reaction to therapy. This is because they are non-invasive, allow for frequent monitoring and easy self-collection, transport and storage. Podocyte injury is believed to be a essential factor in LN. The extent and type of podocyte injury could be connected to the severity of proteinuria, making podocyte-derived cellular debris and injury-related urinary proteins potential markers for the diagnosis and monitoring of LN. This article focuses on studies examining urinary biomarkers associated with podocyte injury in LN, offering fresh perspectives on the application of biomarkers in the early detection and management of LN.
The enrichment of innate immune cells and the enhanced inflammation represent the hallmark of non-alcoholic steatohepatitis (NASH), the advanced subtype with a significantly increased risk of ...progression to end-stage liver diseases within the spectrum of non-alcoholic fatty liver disease. Neutrophils are traditionally recognized as key components in the innate immune system to defend against pathogens. Recently, a growing body of evidence supports neutrophils as emerging key player in mediating the transition from steatosis to NASH, which is largely inspired by the histological findings in human liver biopsy indicating the enhanced infiltration of neutrophils as one of the key histological features of NASH. In this review, we discuss data regarding histological perspectives of hepatic infiltration of neutrophils in NASH. We also highlight the pathophysiological role of neutrophils in promoting metabolic inflammation in the liver through the release of a vast array of granule proteins, the interaction with other pro-inflammatory immune cells, and the formation of neutrophil extracellular traps. Neutrophil granule proteins possess pleiotropic effects on regulating neutrophil biology and functions. A variety of granule proteins (including lipocalin-2, myeloperoxidase, proteinase 3, neutrophil elastase, etc.) produced by neutrophils enhance liver metabolic inflammation, thereby promoting NASH progression by mediating neutrophil-macrophage interaction. Therapeutically, pharmacological inhibitors targeting neutrophil granule proteins hold promise to combat NASH. In addition, this article also summarizes potentials of neutrophils and its derived various granule proteins for the accurate, even non-invasive diagnosis of NASH.
Graphic abstract
People with dermatomyositis (DM) or polymyositis (PM) often die from cancer, pulmonary, cardiac complications, or infections. In such cases, DM or PM might not be designated as the underlying cause ...of death (UCD) for mortality tabulation. In this study, we investigated DM/PM mortality trends in the USA from 1981 to 2020 with respect to UCD and multiple causes of death (MCD) data.
We used the MCD data to identify all deaths with DM or PM mentioned anywhere on the death certificate and as the UCD in the USA from 1981-1982 to 2019-2020. We calculated age-adjusted mortality rates (AAMRs) and annual percentage changes (APCs) based on joinpoint regression analysis.
We identified 12,249 (3985 with DM and 7097 with PM) and 23,608 (8264 with DM and 15,344 with PM) people who died between 1981 and 2020 according to the UCD and MCD data, respectively. For DM, the APC was - 6.7% (from 1981-1982 to 1985-1986), - 0.1% (from 1985-1986 to 2003-2004), and - 1.9% (from 2003-2004 to 2019-2020) according UCD and was - 1.2% (from 1981-1982 to 2003-2004), - 2.5% (from 2003-2004 to 2015-2016), and 2.8% (from 2015-2016 to 2019-2020) according MCD. For PM, the APC was 1.9% (from 1981-1982 to 1989-1990), - 2.3% (from 1989-1990 to 2005-2006), and - 5.2% (from 2005-2006 to 2019-2020) according UCD and was 1.3% (from 1981-1982 to 1991-1992) and - 4.1% (from 1991-1992 to 2019-2020) according MCD.
We identified two times as many DM/PM deaths using the MCD as those identified using the UCD. Similar downward DM/PM mortality trends were noted according to UCD and MCD. However, the year of significant decline in PM mortality was about 10 years earlier according to MCD than those according to UCD.
Objective
To examine the age differences in secular trends in black–white disparities in mortality from systemic lupus erythematosus (SLE) among women in the United States from 1988 to 2017.
Methods
...We used mortality data to calculate age-specific SLE and all-causes (as reference) mortality rates and black/white mortality rates ratios among women from 1988 to 2017. Annual percent change was estimated using joinpoint regression analysis.
Results
We identified 10,793 and 4,165,613 black women and 19,455 and 31,129,528 white women who died between 1988 and 2017 from SLE and all-causes, respectively. The black/white SLE mortality rate ratio according joinpoint regression model was 6.6, 7.2, 4.4, and 1.4 for decedents aged 0–24, 25–44, 45–64, and 65+ years in 1988 and was 7.2, 5.9, 4.1, and 1.9, respectively in 2017. No significant decline trend was noted and the annual percent change was 0.3%, –0.7%, –0.2%, and 1.0%, respectively. On the contrast, the black/white all-causes mortality rate ratio was 2.0, 2.5, 1.8, and 1.0, respectively in 1988 and was 1.7, 1.3, 1.5, and 0.9, respectively in 2017, a significant decline trend was noted in each age group.
Conclusions
Black adults, youths and adolescents had four to seven times higher SLE mortality rates than their white counterparts and the black–white disparities persisted during the past three decades. On the contrast, black women had less than two times higher all-causes mortality rates than their white counterparts and black–white disparities significantly diminish during the past three decades.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Melanoma can be stratified into unique subtypes based on distinct pathologies. The acral/mucosal melanoma subtype is characterized by aberrant and constitutive activation of the proto-oncogene ...receptor tyrosine kinase C-KIT, which drives tumorigenesis. Treatment of these melanoma patients with C-KIT inhibitors has proven challenging, prompting us to investigate the downstream effectors of the C-KIT receptor. We determined that C-KIT stimulates MAP kinase-interacting serine/threonine kinases 1 and 2 (MNK1/2), which phosphorylate eukaryotic translation initiation factor 4E (eIF4E) and render it oncogenic. Depletion of MNK1/2 in melanoma cells with oncogenic C-KIT inhibited cell migration and mRNA translation of the transcriptional repressor SNAI1 and the cell cycle gene CCNE1. This suggested that blocking MNK1/2 activity may inhibit tumor progression, at least in part, by blocking translation initiation of mRNAs encoding cell migration proteins. Moreover, we developed an MNK1/2 inhibitor (SEL201), and found that SEL201-treated KIT-mutant melanoma cells had lower oncogenicity and reduced metastatic ability. Clinically, tumors from melanoma patients harboring KIT mutations displayed a marked increase in MNK1 and phospho-eIF4E. Thus, our studies indicate that blocking MNK1/2 exerts potent antimelanoma effects and support blocking MNK1/2 as a potential strategy to treat patients positive for KIT mutations.
According to their structure, receptors can be divided into killer cell immunoglobulin-like receptors (KIRs), killer cell lectin-like receptors (KLRs), and natural cytotoxic receptors (NCR). ...uNK ...cells transform spiral arteries into highly dilated blood vessels, ensuring low-pressure blood flow to the placenta and developing fetus Figure 1A. Studies have shown that anti-β2GPI antibodies inhibit trophoblastic cell autophagy, induce excessive activation of inflammasomes, and increase secretion of pro-inflammatory factor IL-1β, thereby triggering excessive activation of the maternal and fetal interface inflammatory response. ...low-dose rapamycin increased the number of uNK cells and decreased the expression levels of NKG2D, NKP30, and NKP46 through autophagy in aborted NK cell-depleted mice, thus promoting embryo absorption in aborted mouse models.
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