Case report: Heterogenous SMARCA4-deficient thoracic non-small cell lung carcinoma with various responses to nivolumab

SMARCA4-deficient non-small cell carcinoma is an aggressive neoplasm with poor outcome. Several studies have highlighted its immunochemistry, pathophysiology, and underlying mechanisms, but studies of its definite treatment are few. Here, we report on a 69-year-old male with heterogenous pathological presentations of SMARCA4-deficient non-small cell carcinoma. He initially presented with neck lymphadenopathies. Immunohistochemistry staining and genomic profiling confirmed the diagnosis of SMARCA4-deficient non-small cell carcinoma. The patient responded well to immune checkpoint inhibitors with nivolumab. However, new lesions with various pathological presentations and various responses to nivolumab appeared during the treatment course. The patient survived more than 3 years from the initial diagnosis. This case shows the efficacy of nivolumab to treat SMARCA4-deficient non-small cell lung carcinoma

Anserine Reverses Exercise-Induced Oxidative Stress and Preserves Cellular Homeostasis in Healthy Men

The study tested whether anserine (beta-alanyl-3-methyl-l-histidine), the active ingredient of chicken essence affects exercise-induced oxidative stress, cell integrity, and haematology biomarkers. In a randomized placebo-controlled repeated-measures design, ten healthy men ingested anserine in either a low dose (ANS-LD) 15 mg·kg−1·bw−1, high dose (ANS-HD) 30 mg·kg−1·bw−1, or placebo (PLA), following an exercise challenge (time to exhaustion), on three separate occasions. Anserine supplementation increased superoxide dismutase (SOD) by 50% (p < 0.001, effect size d = 0.8 for both ANS-LD and ANS-HD), and preserved catalase (CAT) activity suggesting an improved antioxidant activity. However, both ANS-LD and ANS-HD elevated glutathione disulfide (GSSG), (both p < 0.001, main treatment effect), and consequently lowered the glutathione to glutathione disulfide (GSH/GSSG) ratio compared with PLA (p < 0.01, main treatment effect), without significant effects on thiobarbituric acid active reactive substances (TBARS). Exercise-induced cell damage biomarkers of glutamic-oxaloacetic transaminase (GOT) and myoglobin were unaffected by anserine. There were slight but significant elevations in glutamate pyruvate transaminase (GPT) and creatine kinase isoenzyme (CKMB), especially in ANS-HD (p < 0.05) compared with ANS-LD or PLA. Haematological biomarkers were largely unaffected by anserine, its dose, and without interaction with post exercise time-course. However, compared with ANS-LD and PLA, ANS-HD increased the mean cell volume (MCV), and decreased the mean corpuscular haemoglobin concentration (MCHC) (p < 0.001). Anserine preserves cellular homoeostasis through enhanced antioxidant activity and protects cell integrity in healthy men, which is important for chronic disease prevention. However, anserine temporal elevated exercise-induced cell-damage, together with enhanced antioxidant activity and haematological responses suggest an augmented exercise-induced adaptative response and recovery

Quantum state tomography via non-convex Riemannian gradient descent

The recovery of an unknown density matrix of large size requires huge computational resources. The recent Factored Gradient Descent (FGD) algorithm and its variants achieved state-of-the-art performance since they could mitigate the dimensionality barrier by utilizing some of the underlying structures of the density matrix. Despite their theoretical guarantee of a linear convergence rate, the convergence in practical scenarios is still slow because the contracting factor of the FGD algorithms depends on the condition number $\kappa$ of the ground truth state. Consequently, the total number of iterations can be as large as $O(\sqrt{\kappa}\ln(\frac{1}{\varepsilon}))$ to achieve the estimation error $\varepsilon$. In this work, we derive a quantum state tomography scheme that improves the dependence on $\kappa$ to the logarithmic scale; namely, our algorithm could achieve the approximation error $\varepsilon$ in $O(\ln(\frac{1}{\kappa\varepsilon}))$ steps. The improvement comes from the application of the non-convex Riemannian gradient descent (RGD). The contracting factor in our approach is thus a universal constant that is independent of the given state. Our theoretical results of extremely fast convergence and nearly optimal error bounds are corroborated by numerical results.Comment: Comments are welcome

Simultaneous Penile Gangrene and Testicular Infarction Secondary to Calciphylaxis in a Uremic Patient

We report here a 46-year-old man with end stage renal disease (ESRD) secondary to type 2 diabetes, who had been on hemodialysis for 5 years. He had a painful glans lesion for 1 week. Five days later, he also complained of right testicular pain. Computed tomography of the pelvis demonstrated calcification of both penile arteries. Scrotal sonography revealed right testicular infarction. He received partial penectomy and right orchiectomy because of progressive lesions and intractable pain. Pathologic examination revealed testicular and penile tissue with necrotizing inflammation accompanied by multifocal calcification in the tunica media, compatible with calciphylaxis. This is the first report to document simultaneous penile gangrene and testicular infarction secondary to calciphylaxis

Knockdown of PsbO leads to induction of HydA and production of photobiological H2 in the green alga Chlorella sp. DT

Green algae are able to convert solar energy to H2 via the photosynthetic electron transport pathway under certain conditions. Algal hydrogenase (HydA, encoded by HYDA) is in charge of catalyzing the reaction: 2H+ + 2e− ↔ H2 but usually inhibited by O2, a byproduct of photosynthesis. The aim of this study was to knockdown PsbO (encoded by psbO), a subunit concerned with O2 evolution, so that it would lead to HydA induction. The alga, Chlorella sp. DT, was then transformed with short interference RNA antisense-psbO (siRNA-psbO) fragments. The algal mutants were selected by checking for the existence of siRNA-psbO fragments in their genomes and the low amount of PsbO proteins. The HYDA transcription and the HydA expression were observed in the PsbO-knockdown mutants. Under semi-aerobic condition, PsbO-knockdown mutants could photobiologically produce H2 which increased by as much as 10-fold in comparison to the wild type

T Oligo-Primed Polymerase Chain Reaction (TOP-PCR): A Robust Method for the Amplification of Minute DNA Fragments in Body Fluids.

Body fluid DNA sequencing is a powerful noninvasive approach for the diagnosis of genetic defects, infectious agents and diseases. The success relies on the quantity and quality of the DNA samples. However, numerous clinical samples are either at low quantity or of poor quality due to various reasons. To overcome these problems, we have developed T oligo-primed polymerase chain reaction (TOP-PCR) for full-length nonselective amplification of minute quantity of DNA fragments. TOP-PCR adopts homogeneous "half adaptor" (HA), generated by annealing P oligo (carrying a phosphate group at the 5' end) and T oligo (carrying a T-tail at the 3' end), for efficient ligation to target DNA and subsequent PCR amplification primed by the T oligo alone. Using DNA samples from body fluids, we demonstrate that TOP-PCR recovers minute DNA fragments and maintains the DNA size profile, while enhancing the major molecular populations. Our results also showed that TOP-PCR is a superior method for detecting apoptosis and outperforms the method adopted by Illumina for DNA amplification

Dedifferentiated liposarcoma can induce a leukemoid reaction

SummaryLiposarcoma is one of the most common malignant soft tissue neoplasms in adults; however, few reports of liposarcoma had been described the expression of leukocytosis and granulocyte-colony stimulating factor (G-CSF). In this report, we present the rare case of a patient who had de-differentiated liposarcoma and elevated G-CSF levels that resulted in a leukemoid reaction. The patient was a 65-year-old man who had been lame for one month due to right thigh swelling. His body temperature was slightly elevated at 38°C and leukocytosis with an elevated white blood cell (WBC) count (41500/μL) was noted. The findings of computed tomography of the lower extremities indicated the presence of a malignancy. Therefore, an incision biopsy was performed. Based on the finding of magnetic resonance imaging (MRI) and the biopsy pathology report, we diagnosed the patient with liposarcoma. Moreover, the preoperative serum G-CSF level was elevated (261.8 pg/mL). An en bloc excision including the entire biopsy pathway was performed 5 days after admission. After en bloc excision of the tumor, WBC count, C-reactive protein (CRP) level, and G-CSF expression decreased. The final pathologic report confirmed the diagnosis of de-differentiated liposarcoma. No local recurrence or distant metastasis was detected in the follow-up image study, and the patient has remained asymptomatic 2 years after surgery. The case described here is a rare type of liposarcoma that produces G-CSF, which in turn, induces leukocytosis. Liposarcoma with elevated G-CSF levels resulting in a leukemoid reaction may indicate a poorly differentiated cell type and may be associated with a poor prognosis; however, en bloc excision of the tumor remains the primary treatment for this type of tumor. Moreover, the WBC count and G-CSF serum level can be as the tools monitoring the tumor recurrence

Clinical characteristics and treatment outcomes of patients with tubo-ovarian abscess at a tertiary care hospital in Northern Taiwan

Background/PurposeControversy exists regarding the need for surgical intervention in patients with tubo-ovarian abscess (TOA). This study was aimed at investigating the clinical characteristics and treatment outcomes in patients with TOA at a tertiary care hospital in Taiwan.MethodsThe medical records of 83 patients who presented at the hospital with TOA between January 1, 2006, and December 31, 2007, were retrospectively reviewed. Outcomes of patients who received medical treatment alone or underwent surgical intervention were analyzed using univariate and logistic regression analyses.ResultsAmong the 83 patients with TOA, 13 patients (15.7%) underwent surgical intervention, and 70 patients (84.3%) received medical treatment alone. Significant variables related to surgical treatment in the univariate analysis were length of stay (short vs. long; t = −2.267, p = 0.026), department of admission (emergency room vs. outpatient department; χ2 = 7.459, p = 0.006), number of live births (nulliparous vs. multiparous; χ2 = 18.202, p = 0.001), and C-reactive protein (CRP) level (high vs. low; t = −2.250, p = 0.028). Logistic regression analysis performed to determine influential factors for surgical treatment showed that the operation odds ratio of three to four live births versus no live births was 33.995 (p = 0.043) and that of two live births versus no live births was 13.598 (p = 0.026).ConclusionPatients with TOA who underwent surgery had a longer duration of hospitalization. Among the patients who underwent surgical intervention, those admitted to the emergency room had higher CRP levels and were more likely to be multiparous

Metabolic Stress-Induced Phosphorylation of KAP1 Ser473 Blocks Mitochondrial Fusion in Breast Cancer Cells

Mitochondrial dynamics during nutrient starvation of cancer cells likely exert profound effects on their capability for metastatic progression. Here, we report that KAP1 (TRIM28), a transcriptional coadaptor protein implicated in metastatic progression in breast cancer, is a pivotal regulator of mitochondrial fusion in glucose-starved cancer cells. Diverse metabolic stresses induced Ser473 phosphorylation of KAP1 (pS473-KAP1) in a ROS- and p38-dependent manner. Results from live-cell imaging and molecular studies revealed that during the first 6 to 8 hours of glucose starvation, mitochondria initially underwent extensive fusion, but then subsequently fragmented in a pS473-KAP1-dependent manner. Mechanistic investigations using phosphorylation-defective mutants revealed that KAP1 Ser473 phosphorylation limited mitochondrial hyperfusion in glucose-starved breast cancer cells, as driven by downregulation of the mitofusin protein MFN2, leading to reduced oxidative phosphorylation and ROS production. In clinical specimens of breast cancer, reduced expression of MFN2 corresponded to poor prognosis in patients. In a mouse xenograft model of human breast cancer, there was an association in the core region of tumors between MFN2 downregulation and the presence of highly fragmented mitochondria. Collectively, our results suggest that KAP1 Ser473 phosphorylation acts through MFN2 reduction to restrict mitochondrial hyperfusion, thereby contributing to cancer cell survival under conditions of sustained metabolic stress