Toripalimab: the First Domestic Anti-Tumor PD-1 Antibody in China

Toripalimab (Tuoyi™) is a selective, recombinant, humanized monoclonal antibody against programmed death protein 1 (PD-1) developed by Shanghai Junshi Bioscience Co., Ltd. Toripalimab is able to bind to PD-1 and block the interaction with its ligands. The binding of toripalimab to PD-1 is mainly attributed to the heavy chain of the former and the FG loop of the latter. Toripalimab received a conditional approval in China for the treatment of melanoma (second-line) in December, 2018. It has also received approvals to treat nasopharyngeal carcinoma (first-line and third-line) and urothelial carcinoma (second-line) in 2021. Additionally, several orphan drug designations were granted to toripalimab by the US Food and Drug Administration. Toripalimab has exhibited primary anti-tumor effects in tumors such as melanoma, lung cancer, digestive tract tumors, hepatobiliary and pancreatic tumors, neuroendocrine neoplasms, nasopharyngeal carcinoma and urothelial carcinoma. It showed a satisfactory anti-tumor effect and long-term survival benefits in Chinese melanoma patients, while the combination of axitinib with toripalimab exhibited an impressive result in metastatic mucosal melanoma. As a checkpoint inhibitor, toripalimab was generally well-tolerated in the enrolled patients. Due to different study populations, comparisons could not be made directly between toripalimab and other drugs in most cases. Nevertheless, the introduction of toripalimab may offer a valuable choice for decision-making in the treatment of tumors in the future.

Exact calculations of the thermal properties of two-electron GaAs quantum dots with inverse-square interactions

In this study, we theoretically scrutinize the effect of the inverse-square interaction on the thermal properties of two electrons trapped in a parabolic GaAs quantum dot. The analytical energy spectrum was used to calculate the thermal properties of the system using the canonical ensemble formalism. It was found that the thermal energy increased with the increase in temperature, while it remained almost constant for sufficiently low temperatures; it was also demonstrated that the inverse-square interaction increased the thermal mean energy. Moreover, the heat capacity increased sharply within a low-temperature window and saturated to the value of 2kB in the high-temperature limit. As expected, entropy increased linearly with increasing temperature. It was also shown that both entropy and heat capacity decreased rapidly when the confinement strength increased (or the dot size decreased) in the low-temperature limit, regardless of the influence of the interaction between the electrons. We also show that the number of allowed states of the system decreased as the interaction strength increased (Z(λ = 0) > Z(λ ≠ 0)). Finally, the stability of the system was investigated through F–T curves. The three-dimensional surface for the temperature-dependent mean energy and heat capacity was also plotted. It should be noted that, for the thermal mean energy, partition function, and Helmholtz free energy, the normal physical behavior of the two-oscillator system with Fermi statistics is recovered for λ → 0. However, heat capacity and entropy show exact two-fermion oscillator system behavior. The most impressive result found in this work is that the inverse-square interaction does not affect the heat capacity and entropy at all despite its noticeable effects on the thermal mean energy. This, in turn, facilitates theoretical studies related to finding the distinctive parameters of quantum dots without going into the heavy calculations resulting from the effects of interactions.

POINT CLOUD REGISTRATION AND ACCURACY FOR 3D MODELLING - A REVIEW

Geoinformation is a surveying and mapping field where topography and details on the ground are spatially mapped. The point cloud is one of the data types that is used for measurement and visualisation of Earth features mapping. Point cloud could come from a different source such as terrestrial laser scanned or photogrammetry. The concepts of terrestrial laser scanning and photogrammetry surveying are elaborated in this paper. This paper also presents the method used for point cloud registration; Iterative Closest Point (ICP) and Feature Extraction and Matching (FEM) and the accuracy of laser scanned, and photogrammetric point cloud based on the previous experiments. Experimental analysis conducted in the previous study shows an impressive result on laser scanned point cloud with very mínimum errors compared to photogrammetric point cloud.

Pomalidomide-Dexamethasone in the Management of Heavily Pretreated Multiple Myeloma

Pomalidomide is a new generation IMID, with a very good compliance, thanks to oral administration, which can be used also in heavily pretreated patients, in a domestic setting. In this retrospective observational trial, It has been evaluated efficacy and tolerance of pomalidomide plus dexamethasone (PD) as salvage regimen in heavily pretreated patients with relapsed and refractory MM (rrMM), whose prognosis is particularly severe. 57 patients (31 M/26 F), with rrMM, median age at diagnosis 69 years (r. 52-86), and median age at start of treatment 76 years (r.56-90) treated with several lines of treatments (median 7, r. 2-11), every refractory to all the drugs previously received (also Bortezomib, Thalidomide and Lenalidomide), received Pomalidomide-Dexamethasone (Pomalidomide 4 mg for 21 days, Dexamethasone 40 mg days 1,8,15,22, pegfilgrastim day +8) every 28 days, until progression. ISS was equally distributed, and cytogenetic at relapse was evaluable in 14 patients. All the patients had previously been treated with schedule containing bortezomib and IMIDs. 63% (36/57) had undergone at least to a single ASCT. All patients were relapsed and refractory to last therapies received before PD. Pomalidomide was well tolerated, with grade 3-4 transfusion-dependent anemia in 58% (33/57) of patients, 44% (23/57) grade 3-4 neutropenia (pegfilgrastim in primary prophylaxis was given, no hospitalization was required, no septic shocks were observed), 40% (23/57) grade 3-4 thrombocytopenia without hemorrhagic events and transfusion-dependence. No severe extra-hematologic toxicity was observed. According to IMWG, ORR1 (≥PR) was 47.3% (27/57: 5 CR, 11 VGPR, 7 PR, 4 MR), but, considering that we are evaluating a cohort of heavily pretreated patients, with poor prognosis, another parameter should be considered, ORR2 (≥SD), considering stable disease as a successful result in progressive MM. ORR2 was 77.1% (17 SD). These can be considered as impressive result in this subset of patients. Oral treatment gives a really good compliance, in frail and unfit patients, and response, when present, is always really fast (median time to response: 2 months (r.1-6)), median OS from diagnosis was 94 months (range 21-234), median OS from start of pomalidomide was 9 months (range 1-25). Nine patients have surprisingly achieved a notable response (3 VGPR, 4 PR, 2 MR) after failure of novel agents (i.e. Carfilzomib, Daratumumab and Pomalidomide). Pomalidomide-dexamethasone has shown significant efficacy and a very good compliance, thanks to oral administration, in a particularly severe setting of heavily pretreated patients, relapsed and refractory to all available therapeutic resources, also after failure of novel agents. Disclosures Martinelli: Stemline Therapeutics: Consultancy; Incyte: Consultancy; Pfizer: Consultancy, Speakers Bureau; Roche: Consultancy; Celgene /BMS: Consultancy, Speakers Bureau; Daichii Sankyo: Consultancy; Jazz Pharmaceuticals: Consultancy; Abbvie: Consultancy; Astellas: Consultancy, Speakers Bureau.

Carfilzomib-Lenalidomide-Dexamethasone in the Management of Lenalidomide-Refractory Multiple Myeloma

Carfilzomib is an epoxyketone proteasome inhibitor of second generation, proved to be effective and safe in relapsed and refractory Multiple Myeloma (rrMM), in combination with dexamethasone or lenalidomide and dexamethasone. In this retrospective observational trial, it has been evaluated efficacy and safety of carfilzomib, in combination with lenalidomide-dexamethasone (KRD) as salvage regimen in patients with rrMM, refractory to lenalidomide, where lenalidomide-based regimens have no proven efficacy. 41 patients (23 M/18 F), with rrMM, median age at diagnosis 63.7 years (r. 43-82), median age at start of treatment 67 years (r. 48-84) previously treated with several lines of treatments (median 3, r. 2-11), underwent to KRD regimen (ASPIRE trial schedule) for a median treatment cycles of 8 (r 2-18). ISS was equally distributed, and all patients had previously been treated with bortezomib and IMIDs, and were refractory to this agents. 61% (19/31) of them had undergone at least to a single ASCT. According to IMWG criteria, after a median follow-up of 9 months (r. 2-18), ORR was 68,2% (28/41: 9 CR, 12 VGPR, 7 PR) with 5 progressive diseases (PD) and 8 patients in stable disease (SD): this can be considered as an impressive result in this subset of rrMM patients, refractory to lenalidomide. In particular, for 11 patients, KRD was, after having achieved at least a PR, a bridge to second/third autologous SCT. Median time to response was 1.3 months (r.1-4), median OS from diagnosis was 62 months (r. 9-170), median OS from start of Carfilzomib was 11 months (r. 2-18). Carfilzomib was well tolerated, with grade 2 anemia in 39%(16/41) of patients, successfully managed by ESAs, without necessity of blood transfusions; 29% (12/41) grade 3-4 neutropenia (pegfilgrastim in primary prophylaxis was given, no ospedalization was required, no septic shocks were observed); 34% (14/41) grade 2, 21% (9/41) grade 3 and 12% (5/41) grade 4 thrombocytopenia, without hemorrhagic events and transfusion-dependency. Moreover, it was observed pneumonia in 39% (16/41) of patients, treated by common antibiotic drugs and always solved. A cardiac monitoring was performed for all patients: hypertension (grade 2-3) in 34% (14/41) of patients; fatigue in 39% (16/31) of patients. Carfilzomib-Lenalidomide-Dexamethasone has shown significant efficacy in a particularly severe setting of patients, relapsed and refractory to all available therapeutic resources, also lenalidomide, and it could be considered as a bridge to a second autologous or allogenic SCT. Disclosures Martinelli: Jazz Pharmaceuticals: Consultancy; Stemline Therapeutics: Consultancy; Astellas: Consultancy, Speakers Bureau; Celgene /BMS: Consultancy, Speakers Bureau; Abbvie: Consultancy; Daichii Sankyo: Consultancy; Roche: Consultancy; Pfizer: Consultancy, Speakers Bureau; Incyte: Consultancy.

Bendamustine-Bortezomib-Dexamethasone in Heavily Pretreated Multiple Myeloma: Old PLUS New Drugs in NOVEL Agents' Era

Bendamustine is an old bi-functional alkylating agent which has proved to be effective in relapsed, refractory and in new diagnosed Multiple Myeloma (MM). Thus, aiming to provide further insights in this field, also in novel agents'era, we present here a retrospective, real-life analysis of patients with relapsed/refractory MM (rrMM), who had received salvage therapy with bendamustine in combination with bortezomib and dexamethasone (BVD) 81 patients (44 M/37 F), with rrMM, median age at diagnosis 59.4 years (r. 36-82), median age at start of treatment 63.6 years (r.37-86) treated with several lines of treatments (median 6, r. 2-11), every refractory to all the drugs previously received (also Bortezomib), received BVD (B 90 mg/sqm days 1,2; V 1.3 mg/sqm days 1,4,8,11, D 20 mg days 1,2,4,5,8,9,11,12, Pegfilgrastim day +4) every 28 days, until progression. All patients had previously received bortezomib-based and IMIDs-based treatments, and 32% (26/81) had also received radiotherapy. 69% (56/81) had undergone single or double autologous and three (2%) allogeneic stem cell transplant. All patients were relapsed and refractory to last therapies received before BVD. Bendamustine was well tolerated, with grade 3-4 transfusion-dependent anemia in 56% (46/81) of patients, and 43% (35/81) grade 3-4 neutropenia (no ospedalization was required, no septic shocks were observed). No severe extrahematologic toxicity was observed, only grade 1 gastrointestinal side effect (nausea), treated by common antiemetic drugs. According to IMWG, ORR was 63% (51/81: 7 CR, 18 VGPR, 15 PR, 11 MR) with 11 PD and 19 patients in SD, which can be considered as an impressive result in this subset of rrMM patients. In particular, for 11 patients, BVD was, after having achieved at least a PR, a bridge to second auSCT, and for two patients a bridge to alloSCT. Eight patients have surprisingly achieved a notable PR after failure of novel agents (i.e. Carfilzomib, Daratumumab and Pomalidomide). Median time to response was 1.3 months (r.1-3), median OS from diagnosis was 67.3 months (r.6-151), median OS from start of Bendamustine was 9.6 months (r.2-36). The triplet Bendamustine-Bortezomib-Dexamethasone has shown significant efficacy in a particularly severe setting of patients, relapsed and refractory to all available therapeutic resources, and, in particular cases, it could be considered as a bridge to a second autologous or allogenic SCT, also after failure of novel agents. Disclosures Martinelli: Abbvie: Consultancy; Jazz Pharmaceuticals: Consultancy; Daichii Sankyo: Consultancy; Celgene /BMS: Consultancy, Speakers Bureau; Roche: Consultancy; Pfizer: Consultancy, Speakers Bureau; Incyte: Consultancy; Stemline Therapeutics: Consultancy; Astellas: Consultancy, Speakers Bureau.

Optimizing Effect of Wavy Leading Edge (WLE) in Rectangular Wing and Taper Wing

Experimental and numerical research have been performed to investigate the Wavy Leading Edge (WLE) effect on the rectangular wing. The WLE is inspired by humpback whale flipper morphology which is blunt and rounded in certain form pattern. This flipper shape plays an important role for its behaviour specially capturing their prey. This advantage could be applied to other systems such as fin stabilizers or wind turbines. Steady cases in various aspect ratios were conducted to find out the optimum effect of WLE with baseline NACA 0018 profile at Reynolds number 1.4 x 105. The chord length of the wing (c) was 125 mm. The WLE shape defined as wavelength (W) 8% of c and amplitude (d) is 5% of c. The aspect ratio (AR) variations were 1.6; 3.9; 5.1; 7.9 and 9.6. A simple rectangular form of the wing was selected to analysis the WLE effect on the various ARs. The taper wing shape is applied to find out the WLE effect at the AR 7.9. three types of taper ratio (TR) are 0.1; 0.3 and 0.5. The results show that the WLE on the taper wing has better advantage to control the stall in steady case. Another impressive result was the WLE wing with AR 7.9 and TR 0.3 has the best lift coefficient and pressure distribution.Keywords: stall, wavy leading edge, steady case, rectangle wing, taper wing, aspect ratio.

Evaluating the Performance of Autoregressive Model for Solar Radiation Forecasting

The solar radiation data taken from 14 meteorological stations in Nigeria has been analyzed. The periodic component of the data which covered a period of 13 (mostly 1977-1989) years was removed via Fourier analysis while the residual series was subjected to autoregressive analysis. It was evident from the t-test and autocorrelation plots of the modified (i.e. without the periodic component) series that there exist significant persistence at nine stations including Sokoto, Nguru, Kano, Maiduguri, Bauchi, Yola, Minna, Ibadan, and Benin. The autocorrelation at Jos, Bida, Ikeja, Enugu and Port Harcourt were however found to be insignificant. As the sample partial autocorrelation function cuts off after lag 1, a non-seasonal autoregressive model of order 1, AR (1), was identified for stations with autocorrelation. The Q-statistic of error series suggested that the models were adequate as identified. Moreover, the exploratory plots of the model residual series showed agreement with the quantitative statistics and thus enforces the inference that the models were adequate for monthly mean daily global solar radiation forecasts at some of the study stations. It is interesting to note that all the stations within the sub-sahelian region showed significant persistence whereas all the stations in the coastal region except Benin were found with insignificant autocorrelation. Expectedly, the performance evaluation of the model gave impressive result for the stations within the sub-sahelian region but a relatively weak result for the coastal region. The result for the midland region was mixed whereas it was difficult to conclude on the Guinea savannah region with result from only one station.

An Optimized Adaptive Protection Scheme for Numerical and Directional Overcurrent Relay Coordination Using Harris Hawk Optimization

The relay coordination problem is of dire importance as it is critical to isolate the faulty portion in a timely way and thus ensure electrical network security and reliability. Meanwhile a relay protection optimization problem is highly constraint and complicated problem to be addressed. To fulfill this purpose, Harris Hawk Optimization (HHO) is adapted to solve the optimization problem for Directional Over-current Relays (DOCRs) and numerical relays. As it is inspired by the intelligent and collegial chasing and preying behavior of hawks for capturing the prey, it shows quite an impressive result for finding the global optimum values. Two decision variables; Time Dial Settings (TDS) and Plug Settings (PS) are chosen as the decision variables for minimization of overall operating time of relays. The proposed algorithm is implemented on three IEEE test systems. In comparison to other state-of-the-art nature inspired and traditional algorithms, the results demonstrate the superiority of HHO.

Self-Harm Detection for Mental Health Chatbots

Chatbots potentially address deficits in availability of the traditional health workforce and could help to stem concerning rates of youth mental health issues including high suicide rates. While chatbots have shown some positive results in helping people cope with mental health issues, there are yet deep concerns regarding such chatbots in terms of their ability to identify emergency situations and act accordingly. Risk of suicide/self-harm is one such concern which we have addressed in this project. A chatbot decides its response based on the text input from the user and must correctly recognize the significance of a given input. We have designed a self-harm classifier which could use the user’s response to the chatbot and predict whether the response indicates intent for self-harm. With the difficulty to access confidential counselling data, we looked for alternate data sources and found Twitter and Reddit to provide data similar to what we would expect to get from a chatbot user. We trained a sentiment analysis classifier on Twitter data and a self-harm classifier on the Reddit data. We combined the results of the two models to improve the model performance. We got the best results from a LSTM-RNN classifier using BERT encoding. The best model accuracy achieved was 92.13%. We tested the model on new data from Reddit and got an impressive result with an accuracy of 97%. Such a model is promising for future embedding in mental health chatbots to improve their safety through accurate detection of self-harm talk by users.