Quality Quantification and Control via Novel Self-Growing Process-Quality Model of Parts Fabricated by LPBF Process

Laser Powder Bed Fusion (LPBF) presents a more extensive allowable design complexity and manufacturability compared with the traditional manufacturing processes by depositing materials in a layer-wised manner. However, the process variability in the LPBF process induces quality uncertainty and inconsistency. Specifically, the mechanical properties, e.g., tensile strength, are hard to be predicted and controlled in the LPBF process. Much research has recently been reported exploring the qualitative influence of single/two process parameters on tensile strength. In fact, mechanical properties are comprehensively affected by multiple correlated process parameters with unclear and complex interactions. Thus, the study on the quantitative process-quality model of the metal LPBF process is urgently needed to provide an enough-strength component via the metal LPBF process. Recent progress in artificial intelligence (AI) and machine learning (ML) provides new insight into quality prediction in terms of computational accuracy and speed. However, the predictive model quality through the traditional AL/ML is heavily determined by the training data size, and the experimental analysis can be expansive on LPBF. This paper explores the comprehensive effect of the tensile strength of 316L stainless-steel parts on LPBF and proposes a valid quantitative predictive model through a novel self-growing machine-learning framework. The self-growing framework can autonomously expand and classify the growing dataset to provide a high-accuracy prediction with fewer input data. To verify this predictive model of tensile strength, specimens manufactured by the LPBF process with different group process parameters (laser power, scanning speed, and hatch spacing) are collected. The experimental results validate the predicted tensile strengths within a less than 3% deviation.     

Experimental Design,Equilibrium Modeling and Kinetic Studies on the Adsorption of Methylene Blue by Adsorbent: Activated Carbon from Durian Shell Waste

For the first time, activated carbon from a durian shell (ACDS) activated by H₂SO₄ was successfully synthesized in the present study. The fabricated ACDS has a porous surface with a specific surface area of 348.0017 m²·g⁻¹, average capillary volume of 0.153518 cm³·g⁻¹, the average pore diameter of 4.3800 nm; ash level of 55.63%; humidity of 4.74%; density of 0.83 g·cm⁻³; an iodine index of 634 mg·g⁻¹; and an isoelectric point of 6.03. Several factors affecting Methylene Blue (MB) adsorption capacity of ACDS activated carbon was investigated by the static adsorption method, revealing that the adsorption equilibrium was achieved after 90 min. The best adsorbent pH for MB is 7 and the mass/volume ratio is equal to 2.5 g·L⁻¹. The MB adsorption process of ACDS activated carbon follows the Langmuir, Freundlich, Tempkin, and Elovich isotherm adsorption model, which has determined the maximum adsorption capacity for MB of ACDS as q_max = 57.47 mg·g⁻¹. The MB adsorption process of ACDS follows the of pseudo-second-order adsorption kinetic equation. The Weber and Morris Internal Diffusion Model, the Hameed and Daud External Diffusion Model of liquids have been studied to see if the surface phase plays any role in the adsorption process. The results of thermodynamic calculation of the adsorption process show that the adsorption process is dominated by chemical adsorption and endothermic. The obtained results provide an insight for potential applications of ACDS in the treatment of water contaminated by dyes.     

Receptor-Binding Domain (RBD) Antibodies Contribute More to SARS-CoV-2 Neutralization When Target Cells Express High Levels of ACE2

Neutralization assays are experimental surrogates for the effectiveness of infection- or vaccine-elicited polyclonal antibodies and therapeutic monoclonal antibodies targeting SARS-CoV-2. However, the measured neutralization can depend on the details of the experimental assay. Here, we systematically assess how ACE2 expression in target cells affects neutralization by antibodies to different spike epitopes in lentivirus pseudovirus neutralization assays. For high ACE2-expressing target cells, receptor-binding domain (RBD) antibodies account for nearly all neutralizing activity in polyclonal human sera. However, for lower ACE2-expressing target cells, antibodies targeting regions outside the RBD make a larger (although still modest) contribution to serum neutralization. These serum-level results are mirrored for monoclonal antibodies: N-terminal domain (NTD) antibodies and RBD antibodies that do not compete for ACE2 binding incompletely neutralize on high ACE2-expressing target cells, but completely neutralize on cells with lower ACE2 expression. Our results show that the ACE2 expression level in the target cells is an important experimental variable, and that high ACE2 expression emphasizes the role of a subset of RBD-directed antibodies.     

In vitro and in vivo study of GSK2830371 and RG7388 combination in liver adenocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) is an adenocarcinoma arising from the intrahepatic bile duct and accounts for the second highest incidence of primary liver cancers after hepatocellular carcinoma. The lack of effective treatment leads to a poor prognosis for advanced iCCA, so new targeted therapy is needed. The impairment of wild-type (WT) p53 tumor suppressor function by its negative regulators frequently occurs in iCCA. Therefore, restoration of WT p53 function by inhibiting its negative regulators is a therapeutic strategy being explored for cancer treatment. Combining an MDM2 inhibitor (MDM2i, RG7388) to stabilize p53 and a WIP1 inhibitor (WIP1i, GSK2830371) to increase p53 phosphorylation enhances p53 function. The combination of MDM2 and WIP1 inhibitors has been reported in several cancer types but in vivo studies are lacking. In the current study, liver adenocarcinoma cell lines, RBE and SK-Hep-1, were treated with RG7388 alone and in combination with GSK2830371. Cell proliferation, clonogenicity, protein and mRNA expressions, and cell cycle distribution were performed to investigate the effect and mechanism of growth suppression. To evaluate the antitumor efficacy of RG7388 and GSK2830371 in vivo, SK-Hep-1 xenografts in NOD-SCID mice were treated with combination therapy for two weeks. The combination of MDM2i and WIP1i significantly increased the growth inhibition, cytotoxicty, p53 protein expression, and phosphorylation (Ser15), leading to transactivation of downstream targets (p21^WAF1 and MDM2). The in vivo results demonstrated that the combination treatment can significantly inhibit tumor growth. In this study, the liver adenocarcinoma cell lines responded to combination treatment via reactivation of p53 function evidenced by increased p53 expression, phosphorylation and expression of its downstream targets. This efficacy was also demonstrated in vivo. The current research provides a novel strategy for targeting the p53 pathway in liver adenocarcinoma that warrants further investigation.     

Moderate Colitis Not Requiring Intravenous Steroids Is Associated with Improved Survival in Stage IV Melanoma after Anti-CTLA4 Monotherapy,But Not Combination Therapy

BackgroundFor patients with melanoma, gastrointestinal immune-related adverse events are common after receipt of anti-CTLA4 therapy. These present difficult decision points regarding whether to discontinue therapy. Detailing the situations in which colitis might predict for improved survival and how this is affected by discontinuation or resumption of therapy can help guide clinical decision-making.Materials and MethodsPatients with stage IV melanoma receiving anti-CTLA4 therapy from 2008 to 2019 were analyzed. Immune-related colitis treated with ≥50 mg prednisone or equivalent daily or secondary immunosuppression was included. Moderate colitis was defined as receipt of oral glucocorticoids only; severe colitis was defined as requiring intravenous glucocorticoids or secondary immunosuppression. The primary outcome was overall survival (OS).ResultsIn total, 171 patients received monotherapy, and 91 received dual checkpoint therapy. In the monotherapy group, 25 patients developed colitis and a nonsignificant trend toward improved OS was observed in this group. Notably, when colitis was categorized as none, moderate or severe, OS was significantly improved for moderate colitis only. This survival difference was not present after dual checkpoint therapy. There were no differences in known prognostic variables between groups, and on multivariable analysis neither completion of all ipilimumab cycles nor resumption of immunotherapy correlated with OS, while the development of moderate colitis did significantly affect OS.ConclusionThis single-institution retrospective series suggests moderate colitis correlates with improved OS for patients with stage IV melanoma treated with single-agent anti-CTLA4, but not dual agent, and that this is true regardless of whether the immune-checkpoint blockade is permanently discontinued.     

Urinary Antibiotics and Dietary Determinants in Adults in Xinjiang,West China

The Xinjiang autonomous region, located in west China, has a unique ethnic structure and a well-developed livestock industry. People in this region have a high risk of exposure to antibiotics, but the exposure level to antibiotics in relation to dietary determinants is unknown. In this study, 18 antibiotics, including four human antibiotics (HAs), four veterinary antibiotics (VAs), and 10 preferred veterinary antibiotics (PVAs) were detected in the urine of approximately half of the 873 adults in Xinjiang, including Han Chinese (24.6%), Hui (25.1%), Uighur (24.6%), and Kazakh (25.7%). Logistic regression was used to analyze the association between antibiotic exposure levels and adult diet and water intake. The detection percentage of antibiotics in the urine of adults in Xinjiang ranged from 0.1% to 30.1%, with a total detection percentage of all antibiotics of 49.8%. HAs, VAs and PVAs were detected in 12.3%, 10.3%, and 40.5%, respectively. Fluoroquinolones were the antibiotics with the highest detection percentage (30.1%) and tetracyclines were the antibiotics with the highest detected concentration (17 ng/mL). Adults who regularly ate pork, consumed fruit daily, and did not prefer a plant-based diet were associated with thiamphenicol, norfloxacin, and fluoroquinolones, respectively. These results indicated that adults in the Xinjiang autonomous region were extensively exposed to multiple antibiotics, and some types of food were potential sources of exposure. Special attention should be paid to the health effects of antibiotic exposure in humans in the future.     

Percutaneous Transhepatic Treatment of Benign Bile Duct Strictures Using Retrievable Covered Stents: Long-Term Outcomes in 148 Patients

ObjectiveTo investigate the long-term outcomes of percutaneous treatment of benign biliary strictures using temporary placement of a retrievable expanded polytetrafluoroethylene (PTFE) covered stent.Materials and MethodsWe retrospectively analyzed the outcomes of 148 patients (84 male and 64 female; age range, 11–92 years) who underwent percutaneous transhepatic placement and removal of a retrievable PTFE-covered stent for the treatment of benign biliary strictures between March 2007 and August 2019 through long-term follow-up. Ninety-two patients had treatment-naïve strictures and 56 had recurrent/refractory strictures.ResultsStent placement was technically successful in all 148 patients. The mean indwelling period of the stent was 2.4 months (median period, 2.3 months; range, 0.2–7.7 months). Stent migration, either early or late, occurred in 28 (18.9%) patients. Clinical success, defined as resolution of stricture after completing stent placement and removal, was achieved in 94.2% (131 of 139 patients). The overall complication rate was 15.5% (23 of 148 patients). During the mean follow-up of 60.2 months (median period, 52.7 months; range, 1.6–146.1 months), 37 patients had a recurrence of clinically significant strictures at 0.5–124.5 months after removal of biliary stent and catheter (median, 16.1 months). The primary patency rates at 1, 3, 5, 7, and 10 years after removal of biliary stent and catheter were 88.2%, 70.0%, 66.2%, 60.5%, and 54.5%, respectively. In the multivariable Cox proportional hazard regression analysis, sex, age, underlying disease, relation to surgery, stricture type, biliary stones, history of previous treatment, and stricture site were not significantly associated with the primary patency.ConclusionLong-term outcomes suggest that percutaneous treatment of benign biliary strictures using temporary placement of retrievable PTFE-covered stents may be a clinically effective method.     

Kinase fusion-related thyroid carcinomas: distinct pathologic entities with evolving diagnostic implications

Activating genomic alterations in protein kinases represent a major driving force in thyroid carcinogenesis. Recently, oncogenic kinase fusions have been a central subject of pharmaceutical development, with a rapidly growing number of inhibitors validated for treating molecularly matched malignancies. Thyroid carcinomas harbor actionable kinase fusions in 10–15% of cases, occupying an increasingly recognized subpopulation of thyroid carcinomas with enhanced attention to molecular profiling. With advances in kinase-based cancer therapy, several challenges have emerged for pathologists. To interrogate an expanding list of targetable genes, the diagnostic paradigm has shifted from conventional single-gene methods toward high-throughput nucleic acid sequencing. Considering the relatively low incidence of most kinase fusions, a selective approach for molecular testing that utilizes histologic and immunohistochemical findings in triaging cases becomes essential for laboratory resource management. Moreover, kinase inhibitor resistance inevitably evolves, requiring a multimodal approach to optimal therapy, despite targeted therapies showing an enhanced, durable response. In this review, we assess the current clinicopathologic understanding and ongoing investigational topics in kinase fusion-related thyroid carcinomas.     

Chronic granulomatous disease: a case report.

Chronic granulomatous disease is one form of the phagocyte function disorder. Unlike most patients with chronic granulomatous disease who develop signs and symptoms of chronic and recurrent pyogenic infections during the first 2 years of life, patients with mild forms of the disease may not present until the teenage years or even adulthood. Thus, the diagnosis in these mild-form patients is often delayed. This paper describes a patient with the mild form of chronic granulomatous disease. A 7-year-old boy was admitted to our ward with intermittent high fever and a left neck mass present for about 1 week. He had a history of persistent infection in the bilateral lower face lasting for about 1 year during his fourth year of life. Family history was unremarkable except that the patient's elder sister had a history of persistent oral mucosal wound infection for about 1 year during the fifth year of life. On physical examination, there were scars over the patient's bilateral lower face. Bacterial culture of pus drained from the neck mass revealed Burkholderia cepacia, a rare species in patients without immunodeficiency. A series of antibiotics, including oxacillin, clindamycin, and piperacillin, was given, and two incision operations for drainage and debridement were performed. The neck mass resolved completely about 1.5 months later. This history indicated that the patient might have chronic granulomatous disease. A definite absence of superoxide activity in the patient's granulocytes detected by chemiluminescence and nitroblue tetrazolium dye test confirmed this diagnosis.