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Limiting carbon dioxide emissions is one of the main concerns of green shipping. As an important carbon intensity indicator, the Energy Efficiency Operational Index (EEOI) represents the energy efficiency level of each ship and can be used to guide the operations of ship fleets for liner companies. Few studies have investigated an integrated optimization problem of fleet deployment, voyage planning and speed optimization with consideration of the influences of sailing speed, displacement and voyage option on fuel consumption. To fill this research gap, this study formulates a nonlinear mixed-integer programming model capturing all these elements and subsequently proposes a tailored exact algorithm for this problem. Extensive numerical experiments are conducted to show the efficiency of the proposed algorithm. The largest numerical experiment, with 7 ship routes and 32 legs, can be solved to optimality in four minutes. Moreover, managerial insights are obtained according to sensitivity analyses with crucial parameters, including the weighting factor, unit price of fuel, Suez Canal toll fee per ship, weekly fixed operating cost and cargo load in each leg.

The development of the Internet of things (IoT) and online platforms enables companies and governments to collect data from a much broader spatial and temporal area in the logistics industry. The huge amount of data provides new opportunities to handle uncertainty in optimization problems within the logistics system. Accordingly, various prescriptive analytics frameworks have been developed to predict different parts of uncertain optimization problems, including the uncertain parameter, the combined coefficient consisting of the uncertain parameter, the objective function, and the optimal solution. This tutorial serves as the pioneer to introduce existing literature on state-of-the-art prescriptive analytics methods, such as the predict-then-optimize framework, the smart predict-then-optimize framework, the weighted sample average approximation framework, the empirical risk minimization framework, and the kernel optimization framework. Based on these frameworks, this tutorial further proposes possible improvements and practical tips to be considered when we use these methods. We hope that this tutorial will serve as a reference for future prescriptive analytics research on the logistics system in the era of big data.

To systematically investigate the effects of different protein/energy (P/E) ratio diets on the microstructure and metabolic response of black sea bream liver, fish (initial weight 11.20 ± 0.20 g) were fed three isoenergetic (20.9 kJ/g) diets with varying protein/lipid levels (LR, 28.8% protein/26.3% lipid; MR, 37.5% protein/20.9% lipid; and HR, 42.8% protein/17.3% lipid, P/E ratio increased gradually) for 8 weeks. The lipid and glycogen contents in the liver decreased with increasing dietary P/E ratios ( P < 0.05 ). Histological observation found that the liver of the LR group presented many adipose cells, along with polarized nucleus, massive lipid droplets, and unclear organelle structure. The liver cellular structures of MR and HR groups were normal with some small unmatured lipid droplets. RNA-Seq was applied to investigate the hepatic transcriptome response to different P/E ratio diets of black sea bream. Different levels of gene expressions were identified in the signaling pathways related to energy metabolism, amino acid metabolism, lipid metabolism, carbohydrate metabolism, immune system, etc. The LR diet inhibited the genes related to lipid oxidation, glycolysis, and protein metabolism, whereas the HR diet inhibited those of glycolysis and protein catabolism. The present study provides a comprehensive understanding of the molecular mechanisms behind the effects of different P/E ratio diets on the liver metabolism of black sea bream.

This study aimed to clarify the effect of early glucocorticoid (GC) application on achieving minimal manifestation (MM) status or better in the treatment of myasthenia gravis (MG) in the early clinical phase. A retrospective analysis was performed on 366 patients with MG who had received immunotherapy in the Henan Institute of Medical and Pharmaceutical Sciences Myasthenia Gravis Biobank from January 2015 to September 2022. Patients were divided into two groups: the early mono-GC group (treated with GC within 6 months of MG onset) and delayed mono-GC group. Kaplan-Meier analysis showed that the early mono-GC group achieved MM status earlier and more frequently (Log-rank test, P = 0.0052; hazard ratio [HR], 1.59; P = 0.007). The early mono-GC group had a lower maintenance oral GC dose than delayed mono-GC group. In multivariate Cox regression analysis, early mono-GC (HR, 0.68; P = 0.026), early-onset MG (EOMG) (HR, 0.53; P = 0.004), ocular MG (OMG) (HR, 0.58; P = 0.002), and Myasthenia Gravis Foundation of America (MGFA) IV-V typing (HR, 2.51; P = 0.035) were associated with MM. In conclusion, EOMG, OMG, and low MGFA typing were positive predictors of treatment goals. Early intervention with GC leads to better long-term outcomes and reduces the necessary maintenance dose of oral GC for patients with MG.

The desmoplastic stroma in solid tumors presents a formidable challenge to immunotherapies that rely on endogenous or adoptively transferred T cells, however, the mechanisms are poorly understood. To define mechanisms involved, we treated established desmoplastic pancreatic tumors with CAR T cells directed to fibroblast activation protein (FAP), an enzyme highly overexpressed on a subset of cancer-associated fibroblasts (CAFs). Depletion of FAP+CAFs resulted in loss of the structural integrity of desmoplastic matrix. This rendered these highly treatment-resistant cancers susceptible to subsequent treatment with a tumor antigen (mesothelin)-targeted CAR and to anti-PD1 antibody therapy. Mechanisms included overcoming stroma-dependent restriction of T cell extravasation and/or perivascular invasion, reversing immune exclusion, relieving T cell suppression, and altering the immune landscape by reducing myeloid cell accumulation and increasing endogenous CD8+T cell and NK cell infiltration. These data provide strong rationale for combining tumor stroma- and malignant cell-targeted therapies to be tested in clinical trials.

This paper introduces a container transportation scheduling problem in a large logistic company (Yunfeng) in Shanghai City, PR China. This problem considers two types of container transportation orders (i.e., door-to-door orders and warehouse orders) between port yards and the hinterland. Unlike the pickup and delivery problem with time windows, this problem needs to consider not only container pickups and deliveries, but also the loading or unloading of cargo inside containers. Moreover, this problem takes account of some constraints on container transportation regulations in China. We formulate this problem as a mixed-integer programming model and design an improved backtracking search optimization algorithm. Based on the proposed model and algorithm, a vehicle scheduling decision support system is also developed to integrate data collection, preprocessing, Amap (a digital map, navigation, and location service provider in China) interfacing, and optimization. The improvement of the operational efficiency is validated by the usage of the proposed system in practice.

Broad bean paste-meju was fermented by a mixture of broad bean koji and saline; koji fermentation is an essential process for the production of broad bean paste-meju. Aspergillus oryzae was the most widely used in sauce fermentation. The purpose of this study was to research the factory adaptability of the highly efficient A. oryzae PNM003 and further evaluate the effect of fermentation conditions and fermentation strains on koji. A. oryzae PNM003 was compared with the widely used strain HN 3.042 not only in the laboratory but also in factory conditions (large scale). Results showed that the koji made with the same starter in the factory had a greater amount of fungi than that in the laboratory. Bacteria and yeast levels in HN_L koji were higher than in PN_L koji. As for fungi constitution, almost only Aspergillus survived in the end through the microorganism self-purification process during koji fermentation. As for the bacterial constitution, koji was grouped by fermentation conditions instead of fermentation starter. PN koji had higher protease activity and a higher content of total acids, amino acid nitrogen, amino acids, and organic acids in the laboratory conditions. Nevertheless, in factory conditions, PN koji and HN koji had similar indexes. As for volatile flavor compounds, koji made with the two starters in the same condition was grouped together. As for the same starter, there were more flavor compounds metabolized in the factory condition than in the laboratory condition, especially esters and alcohols. The results showed PN was a highly efficient strain to ferment koji, but the advantages were expressed more remarkably in laboratory conditions. In brief, the fermented condition had a greater influence than the fermentation starter for broad bean koji.

IntroductionThis study compared differences in physicochemical characteristics of the vinegar made by a mixed culture (MC) of Saccharomyces cerevisiae and Lactiplantibacillus plantarum and a pure culture (PC) of Saccharomyces cerevisiae.MethodsThe fermentation process was monitored, and metabolomics analysis by Liquid Chromagraphy-Mass Spectrometry (LC-MS) was applied to the compositional differences between PC and MC vinegars, combined with quantification of organic acids, amino acids and B vitamins.ResultsA total of 71 differential metabolites including amino acids, organic acids and carbohydrates, and six possible key metabolic pathways were identified. MC enhanced the malic acid utilization and pyruvate acid metabolism during fermentation, increasing substrate-level phosphorylation, and supplying more energy for cellular metabolism. Higher acidity at the beginning of acetic acid fermentation, resulting from lactic acid production by Lactiplantibacillus plantarum in MC, suppressed the cellular metabolism and growth of Acetobacter pasteurianus, but enhanced its alcohol metabolism and acetic acid production in MC. MC vinegar contained more vitamin B, total flavonoids, total organic acids, amino acids and had a higher antioxidant capacity. MC enhanced the volatile substances, particularly ethyl lactate, ethyl caprate and ethyl caproate, which contributed to a stronger fruity aroma.DiscussionThese results indicated the mixed culture in alcoholic fermentation can effectively enhance the flavor and quality of apple cider vinegar.

Currently, there are few reports of patients with locally advanced lung cancer achieving a clinical complete response by medical treatment. Preoperative neoadjuvant immunotherapy combined with chemotherapy is an option for patients with unresectable, locally advanced nonsmall cell lung cancer (NSCLC) which is of great potential, and may change traditional treatment paradigms. There are relatively few large-scale, high-quality randomized-controlled trials yet, and limitations such as short postoperative follow-up period and immature disease-free survival and overall survival data still persist. Thus, evidence-based medical evidence is urgently needed. It is worthy to explore the further treatment of patients who achieved complete response after initial treatment, though lacking of evidence by now.We report a stage IIIA lung squamous cell carcinoma case who achieved a major pathologic remission after neoadjuvant treatment with tislelizumab and chemotherapy.Our case study contributes to the existing evidence on the feasibility, efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC.

We model the boundary-layer flashback (BLF) of CH$_4$/H$_2$/air swirling flames via large-eddy simulations with the flame-surface-density method (LES-FSD), in particular, at high pressures. A local displacement speed model tabulating the stretched flame speed is employed to account for the thermo-diffusive effects, flame surface curvature, and heat loss in LES-FSD. The LES-FSD well captures the propagation characteristics during the BLF of swirling flames. In the LES-FSD for lean CH$_4$/H$_2$/air flames at 2.5 bar, the critical equivalence ratio for flashback decreases with the increasing hydrogen volume fraction, consistent with the experiments. This is due to the improved modeling of effects of the flame stretch and heat loss on the local displacement speed. We also develop a simple model to predict the BLF limits of swirling flames. The model estimates the critical bulk velocity for given reactants and swirl number, via the balance between the flame-induced pressure rise and adverse pressure for boundary-layer separation. We validate the model against 14 datasets of CH$_4$/H$_2$/air swirling flame experiments, with the hydrogen volume fractions in fuel from 50% to 100%. The present model well estimates the flashback limits in various operating conditions., Comment: 29 pages, 16 figures

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E-commerce, new retail, and other changes have highlighted the requirement of high efficiency and accuracy in the logistics service. As an important section in logistics and supply chain management, warehouses need to respond positively to the increasing requirement. The “smart warehouse” system, which is equipped with emerging warehousing technologies, is increasingly attracting the attention of industry and technology giants as an efficient solution for the future of warehouse development. This study provides a holistic view of operations management problems within the context of smart warehouses. We provide a framework to review smart warehouse operations management based on the characteristics of smart warehouses, including the perspectives of information interconnection, equipment automation, process integration, and environmental sustainability. A comprehensive review of relevant literature is then carried out based on the framework with four perspectives. This study could provide future research directions on smart warehouses for academia and industry practitioners.

A colorimetric NIR fluorescent probe for detecting ClO− has been synthesized. And it had outstanding advantages: one-step synthesis, high sensitivity , selectivity and successful application in actual water samples, living cells and zebrafish.

Background Several immune checkpoint inhibitors have been implemented for cancer treatment which have shown some degree of antitumor effcacy, while immune-related adverse events (irAEs) that affect multiple organ functions ensue which obviously should not be neglected. Though less common than other kinds of irAEs, Immune checkpoint inhibitors (ICIs) related Isolated ACTH deficiency (IAD) may cause long-term damage to pituitary-adrenal axis. Several case reports are available about IAD during anti-PD-1 therapy. We report the first case of immune checkpoint inhibitor-induced IAD following 3 month of sintilimab therapy. Case presentation A 66-year-old Chinese man was diagnosed with stage IIIB lung adenocarcinoma with involving ipsilateral intrapulmonary and hilar lymph node metastasis. After 3 months of combination therapy of nedaplatin, pemetrexed and sintilimab, the patient presented with general fatigue, nausea and vomiting. Laboratory investigation at admission revealed hyponatremia and hypokalemia. Further investigation revealed adrenocorticotropic hormone and cortisol levels were far below than normal limits. His other pituitary hormone levels were normal, except for mild elevation of follicle stimulating hormone and estradiol. Cranic magnetic resonance imaging showed a normal pituitary gland. Isolated adrenocorticotropic hormone deficiency was diagnosed, and corticosteroid replacement therapy was administered, leading to a significant improvement of his symptoms while ACTH level maintaining low level. Conclusions Our patient developed isolated ACTH deficiency during combination cancer treatment with chemotherapy and sintilimab. Although isolated ACTH deficiency due to anti-PD-1 including sintilimab therapy is rare occurrence, it can often cause severe clinical symptoms. Its diagnosis basically relies on clinical symptoms and endocrinological examination. Unlike traditional hypophysitis diagnosed by cranial MRI, pituitary MRI of IAD due to anti-PD-1 often indicates normal pituitary gland implying that over-reliance on imaging findings is not recommended. Even if clinical symptoms have relieved after corticosteroid replacement therapy was commenced, low levels of ACTH or cortisol could maintain for a long period which highlights the need for long term corticosteroid therapy. The purpose of the current report was to provide increased awareness of early detection and therapy of IAD.

In semiconductor manufacturing, an extremely stringent quality control is enforced for wafer fabrication processes. Consequently, cleaning operations that clear residual chemical gases and heat in ...

As an essential carrier of cross-border trade, the maritime supply chain has always been plagued by long service cycles, complex structures, and heterogeneous information from multiple sources. In ...

It is of great necessity to exploit a real-time, highly selective and sensitive method for hypochlorite (ClO

During natural disasters or accidents, an emergency logistics network aims to ensure the distribution of relief supplies to victims in time and efficiently. When the coronavirus disease 2019 (COVID-19) emerged, the government closed the outbreak areas to control the risk of transmission. The closed areas were divided into high-risk and middle-/low-risk areas, and travel restrictions were enforced in the different risk areas. The distribution of daily essential supplies to residents in the closed areas became a major challenge for the government. This study introduces a new variant of the vehicle routing problem with travel restrictions in closed areas called the two-echelon emergency vehicle routing problem with time window assignment (2E-EVRPTWA). 2E-EVRPTWA involves transporting goods from distribution centers (DCs) to satellites in high-risk areas in the first echelon and delivering goods from DCs or satellites to customers in the second echelon. Vehicle sharing and time window assignment (TWA) strategies are applied to optimize the transportation resource configuration and improve the operational efficiency of the emergency logistics network. A tri-objective mathematical model for 2E-EVRPTWA is also constructed to minimize the total operating cost, total delivery time, and number of vehicles. A multi-objective adaptive large neighborhood search with split algorithm (MOALNS-SA) is proposed to obtain the Pareto optimal solution for 2E-EVRPTWA. The split algorithm (SA) calculates the objective values associated with each solution and assigns multiple trips to shared vehicles. A non-dominated sorting strategy is used to retain the optimal labels obtained with the SA algorithm and evaluate the quality of the multi-objective solution. The TWA strategy embedded in MOALNS-SA assigns appropriate candidate time windows to customers. The proposed MOALNS-SA produces results that are comparable with the CPLEX solver and those of the self-learning non-dominated sorting genetic algorithm-II, multi-objective ant colony algorithm, and multi-objective particle swarm optimization algorithm for 2E-EVRPTWA. A real-world COVID-19 case study from Chongqing City, China, is performed to test the performance of the proposed model and algorithm. This study helps the government and logistics enterprises design an efficient, collaborative, emergency logistics network, and promote the healthy and sustainable development of cities.

Air emissions from ships have become an important issue in sustainable shipping because of the low quality of the marine fuel consumed by ships. To reduce sulfur emissions from shipping, the International Maritime Organization has established emission control areas (ECAs) where ships must use low-sulfur fuel with at most 0.1% sulfur or take equivalent emission-reduction measures. The use of low-sulfur fuel increases the costs for liner shipping companies and affects their operations management. This study addresses a holistic liner shipping service planning problem that integrates fleet deployment, schedule design, and sailing path and speed optimization, considering the effect of ECAs. We propose a nesting algorithmic framework to address this new and challenging problem. Semianalytical solutions are derived for the sailing path and speed optimization problem, which are used in the schedule design. A tailored algorithm is applied to solve schedule design problems, and the solutions are used in fleet deployment. The fleet deployment problem is then addressed by a dynamic programming-based pseudo-polynomial time algorithm. Numerical experiments demonstrate that considering the effect of ECAs in liner shipping operations management can reduce over 2% of the costs, which is significant considering that the annual operating cost of a shipping company’s network can be as high as several billion dollars.

In the era of sharing economy and the mobility-as-service, the last mile delivery system is undergoing revolutionary changes with emerging a lot of new operation modes and policies. The crowdsourced delivery mode has become a novel and popular practice in the last mile delivery industry. This mode brings a novel way for facilitating the efficiency of last mile delivery on the basis of the shared mobility. This paper studies an open vehicle routing problem (OVRP) for the shared mobility based last mile delivery mode, in which parcel delivery orders are disseminated within a circle to attract occasional vehicles (or couriers) to fulfill these orders. Different from the traditional OVRP, this study further considers the decision of the above mentioned circle’s radius, which should be balanced between attracting enough vehicles and reducing additional cost (reward) for covering vehicles’ empty trips to the pickup location. This paper proposes a nonlinear mixed-integer programming model for the problem. A column generation based solution method is implemented to solve the model. Some numerical experiments are also conducted to validate the efficiency of the solution method and draw out some managerial implications for the practitioners. The proposed methodology in this paper may be potentially benefit not only for reducing the last mile delivery cost but also for promoting the modern transportation paradigm revolution to ridesharing and mobility-as-service.

Introduction Immuno checkpoint inhibitors (ICIs) including anti-PD-L1 antibody have shown certain therapeutic effects on various cancer types. Here, we reported a case of the patient with resectable non-small cell lung cancer (NSCLC) showing a complete response to nivolumab combined with chemotherapy. Patient information A 66-year-old male was diagnosed with stage IIIA large cell lung cancer, cT2N2M0, who was considered impossible to have a tumor resection due to his right hilar node enlargement. The diameter of the neoplasms was 22mm, and the patient wanted to get the chance of surgery. Light of all, surgery was the only radical treatment option and therefore planned. Interventions After administering 2 cycles of nivolumab combined with paclitaxel and cisplatin, the second chest computed tomography (CT) after the first scanning revealed the tumor apparent shrinking and vascular compression was disappeared than before. We performed a right upper lobectomy and mediastinal lymph node dissection. Pathologically, we confirmed no large cell lung cancer cells in the resected lung specimen. Outcomes The follow-up showing that patient remains alive without recurrence to these days. Conclusion This case report may provide a clue to the future development of induction therapy using nivolumab and surgery. The combined treatment of nivolumab and chemotherapy is likely to be considered as an optional management of resectable NSCLC.

Supplemental material, sj-docx-2-jad-10.1177_10870547221112941 for Comparing Treatment Outcomes in Children and Adolescents With ADHD to Other Disorders Within an Australian and Dutch Outpatient Cohort by Leanne Payne, Sanna L. Roest, Zhen Qi Lu, Nardia Zendarski, Matthew Bisset, Emma Sciberras, Stephen Stathis, Bart M. Siebelink, Robert R. J. M. Vermeiren, Mark A. Bellgrove, David Coghill and Christel M. Middeldorp in Journal of Attention Disorders

Supplemental material, sj-docx-1-jad-10.1177_10870547221112941 for Comparing Treatment Outcomes in Children and Adolescents With ADHD to Other Disorders Within an Australian and Dutch Outpatient Cohort by Leanne Payne, Sanna L. Roest, Zhen Qi Lu, Nardia Zendarski, Matthew Bisset, Emma Sciberras, Stephen Stathis, Bart M. Siebelink, Robert R. J. M. Vermeiren, Mark A. Bellgrove, David Coghill and Christel M. Middeldorp in Journal of Attention Disorders

Additional file 3. Standardized scores of the QLQ-C30 and the QLQ-CR29 questionnaires.

Supplemental material, sj-docx-2-jad-10.1177_10870547221112941 for Comparing Treatment Outcomes in Children and Adolescents With ADHD to Other Disorders Within an Australian and Dutch Outpatient Cohort by Leanne Payne, Sanna L. Roest, Zhen Qi Lu, Nardia Zendarski, Matthew Bisset, Emma Sciberras, Stephen Stathis, Bart M. Siebelink, Robert R. J. M. Vermeiren, Mark A. Bellgrove, David Coghill and Christel M. Middeldorp in Journal of Attention Disorders

Additional file 2. Survival cures for patients who received one course of radiotherapy (n = 11) and two courses of radiotherapy (n = 46). (A) Local progression-free survival; (B) distant metastasis-free survival; (C) progression-free survival; (D) cancer specific survival; (E) overall survival.

Supplemental material, sj-docx-1-jad-10.1177_10870547221112941 for Comparing Treatment Outcomes in Children and Adolescents With ADHD to Other Disorders Within an Australian and Dutch Outpatient Cohort by Leanne Payne, Sanna L. Roest, Zhen Qi Lu, Nardia Zendarski, Matthew Bisset, Emma Sciberras, Stephen Stathis, Bart M. Siebelink, Robert R. J. M. Vermeiren, Mark A. Bellgrove, David Coghill and Christel M. Middeldorp in Journal of Attention Disorders

Additional file 1. Cancer-specific survival for patients who had clinical complete response (n = 42) after treatment and those who hadn’t (n = 15).

This article investigates a low carbon-oriented berth allocation and quay crane assignment problem considering vessels’ uncertain arrival time and loading/unloading workload for vessels. A two-stag...