bluuebunny/crossref_metadata_2025 huggingface dataset:
A 30,000-km journey by Apus apus pekinensis tracks arid lands between northern China and south-western Africa
Authors: Zhao Yanyan , Zhao Xinru , Wu Lan , Mu Tong , Yu Fang , Kearsley Lyndon , Liang Xuan , Fu Jianping , Hou Xiaoru , Peng Peng , Li Xiaoyang , Zhang Tao , Yan Su , Newell Dick , Hewson Chris M. , Townshend Terry , Åkesson Susanne , Liu Yang
Published: June 2022

Background

As a widely distributed and aerial migratory bird, the Common Swift (Apus apus) flies over a wide geographic range in Eurasia and Africa during migration. Although some studies have revealed the migration routes and phenology of European populations, A. a. apus (from hereon the nominate apus), the route used by its East Asian counterpart A. a. pekinensis (from hereon pekinensis) remained a mystery.

Methods

Using light level geolocators, we studied the migration of adult pekinensis breeding in Beijing from 2014 to 2018, and analysed full annual tracks obtained from 25 individuals. In addition, we used the mean monthly precipitation to assess the seasonal variations in humidity for the distribution ranges of the nominate apus and pekinensis. This environmental variable is considered to be critically relevant to their migratory phenology and food resource abundance.

Results

Our results show that the swifts perform a round-trip journey of ca 30,000 km each year, representing a detour of 26% in autumn and 15% in spring compared to the shortest route between the breeding site in Beijing and wintering areas in semi-arid south-western Africa. Compared to the nominate apus, pekinensis experiences drier conditions for longer periods of time. Remarkably, individuals from our study population tracked arid habitat along the entire migration corridor leading from a breeding site in Beijing to at least central Africa. In Africa, they explored more arid habitats during non-breeding than the nominate apus.

Conclusions

The migration route followed by pekinensis breeding in Beijing might suggest an adaptation to semi-arid habitat and dry climatic zones during non-breeding periods, and provides a piece of correlative evidence indicating the historical range expansion of the subspecies. This study highlights that the Common Swift may prove invaluable as a model species for studies of migration route formation and population divergence.
Sulphite addition during steam pretreatment enhanced both enzyme-mediated cellulose hydrolysis and ethanol production
Authors: Zhong Na , Chandra Richard , Yamamoto Minna , Leskinen Timo , Granström Tom , Saddler Jack
Published: June 2022

Sulphite addition during steam pretreatment of softwoods under acidic, neutral and alkaline conditions was assessed to try to minimize lignin condensation. Although pretreatment under neutral/alkaline conditions resulted in effective lignin sulphonation, non-uniform size reduction was observed. In contrast, acidic sulphite steam treatment at 210 °C for 10 min resulted in homogenous particle size reduction and water-insoluble component that was 62% carbohydrate and 33% lignin. This carbohydrate-rich substrate was readily hydrolyzed and fermented which indicated the lack of fermentation inhibitors in the steam-pretreated whole slurry. The use of high solid loading (25% w/v) resulted in a hydrolysis yield of 58% at an enzyme loading of 40 mg protein/g glucan and efficient fermentation (46.6 g/L of ethanol). This indicated that the addition of acidic sulphite at the steam pretreatment of softwoods improved both the enzymatic hydrolysis and fermentation of steam-pretreated whole slurries.

Graphical Abstract
Practices of patient engagement in drug development: a systematic scoping review
Authors: Zvonareva Olga , Craveț Constanța , Richards Dawn P.
Published: June 2022

Background

During the past decade, patient engagement (PE) has attracted significant attention in the field of drug development. Readiness to accept the central importance of patients’ knowledge and contributions has become evident. This study aimed to synthesize evidence on the current state of PE in drug development: what is actually being done and how.

Methods

A systematic scoping review was conducted based on a PRISMA-informed protocol. Search was performed in PubMed, EMBASE and Web of Science, covering the period between 2011 and 2021. For analysis of extracted data, we developed a framework for analyzing PE in Drug Development. The Framework distinguishes a number of different PE types that take place at different stages of drug development and are characterized by the different degrees of power patients have in the process. It allowed us to assess depth and intensity of PE initiatives included in this review.

Results

Most included PE initiatives took place at the stage of designing studies (40 in total). At this stage drug development goals are already set, but the mode of reaching them has not yet been fully determined. PE initiatives on the finetuning details stage followed (16 in total). The finetuning details stage covers the last parts of the drug development trajectory, when only relatively minor issues are still open for patients’ contributions. The least numerous were PE initiatives on the stage of setting up R&D program (13 in total). This stage refers to the early steps in drug development where PE has the potential to make the most impact on shaping the subsequent process. In terms of intensity of engagement, most PE initiatives included in this review align with consultation and involvement types, 26 and 30 initiatives, respectively. Partnership was less frequent in the published accounts of PE (13 initiatives).

Conclusions

This review delineated a contemporary landscape of PE in drug development. Although attention to PE in drug development is relatively recent, a wide range of PE practices has already been initiated. The results indicate the necessity of distinguishing between different types of PE in order to understand consequences of choices regarding depth and intensity of PE.
Malignancy in ankylosing spondylitis: a cross-sectional analysis of a large population database
Authors: Bittar Mohamad , Merjanah Sali , Alkilany Reem , Magrey Marina
Published: June 2022

Background

Increased cancer-risk has been reported with rheumatoid arthritis and systemic lupus erythematosus, but the risk is poorly studied in ankylosing spondylitis (AS). Conflicting data in AS have been reported in Asia and Europe, with lack of US population-based studies. Our objective is to study the prevalence of cancer in patients with AS in the US.

Methods

Using the Explorys database, we performed a cross-sectional study. Data from AS patients and controls were stratified by 2 rheumatology visits, age groups, clinical characteristics, and frequency of cancers. The data were analyzed using a series of chi-square tests of independence as well as logistic regression to test for association between AS and cancer.

Results

1410 AS patients (12.88%) had cancer. Female AS patients had a lower prevalence of cancer compared to controls (OR 0.840, 95% CI [0.769, 0.916]), while male AS patients had no statistically significant difference (OR 1.011, 95% CI [0.929, 1.099]). Among patients with AS, Skin cancers (squamous cell, malignant melanoma, and basal cell) and head and neck cancers were significantly increased.

Conclusion

Our study demonstrated that the prevalence of “any-type-cancer” was not increased in AS patients compared to controls with no rheumatic disease. Skin, head, and neck cancers were more frequently seen in AS patients.
Efficacy of single and combined applications of entomopathogenic fungi and nematodes against the pupae of colorado potato beetle (Leptinotarsa decemlineata [Say]), (Coleoptera: Chrysomelidae)
Authors: Uzun Yiğit Asiye , Göze Özdemir Fatma Gül , Demirözer Ozan , Nayır Tufan
Published: June 2022

Background

The lethal effects of different entomopathogenic fungi (EPF) and nematodes (EPN) on the pupae of the Colorado Potato Beetle, Leptinotarsa decemlineata (Say) (Coleoptera: Chrysomelidae) were investigated in a two-step study when used separately or together. In the first step, Nostalgist (Beauveria bassiana strain Bb-1, Agrobest Co.), Steinernema feltiae (Filipjev) (Rhabditida: Steinernematidae), Heterorhabditis bacteriophora Poinar, 1976 (Rhabditida: Heterorhabditidae) (Bioglobal Co.), 2 Turkish isolates of Beauveria bassiana BIM-001 and BY2 were applied separately to the pupal stage of pest in the soil. In the experiments, 3 different concentrations (150, 200, and 250 million infective juveniles (IJs)/100 l water) of EPN and a single concentration (1x108 spores/ml for and maximum recommended field dose 1 × 108 CFU/ml) of EPF were used. In the second step, BIM-001 and BY2 isolates of B. bassiana were combined with both EPN species; S. feltiae + B. bassiana BIM-001, S. feltiae + B. bassiana BY2, H. bacteriophora + B. bassiana BIM-001, H. bacteriophora +B. bassiana BY2 were applied to pupae. At this stage, 150 million IJs/100 l water which was the maximum recommended field concentration for EPN and 1 × 108 spores/ml for local EPF isolates were used.

Results

According to the study results, pupae deaths were significantly higher in Nostalgist (74%) than those of B. bassiana BIM-001, B. bassiana BY2, S. feltiae, and H. bacteriophora (P<0.05). While both EPN caused higher mortality than B. bassiana BY2, B. bassiana BIM-001 had the highest mortality rates. The combination of S. feltiae + B. bassiana BIM-001 at the highest mortality rate (80%) was found statistically different and significant from other EPF + EPN treatments on pupae. Moreover, there were non-statistical differences between the other EPF and EPN combinations.

Conclusion

It was found that the combined use of EPF and EPN was more effective on the pupae of L. decemlineata than a single application. According to the results of the study, it may be promising to use EPN and EPF together for the control of the Colorado Potato Beetle pupae.
Optimization of phenol adsorption from synthetic wastewater by synthesized BiFeO3 perovskite material, using split-plot central composite design
Authors: Garba Zaharaddeen Nasiru , Ekwumemgbo Patricia Adamma , Stephen Godwill
Published: June 2022

Background

Optimization of adsorption processes using statistical methods of experiment for the removal of pollutants from wastewater, in an effort to curb the global problem of water pollution, is increasingly being adopted because it is cost-effective and time-saving. In most cases, standard central composite designs (CCDs) are often employed for the optimization processes, where the experimental variables are often randomized completely. However, most experiments especially within the industries often involve factors with some hard-to-change (HTC) levels and some with easy-to-change (ETC) levels, in which case the HTC factor cannot be completely randomized, and this challenge can only be overcome by the use of a split-plot CCD. However, there is scarcity of literature on the use of split-plot CCD for the optimization of adsorption processes, and hence in this study, the prime conditions for the removal of phenol onto BiFeO3 from synthetic wastewater were studied. The effect of three adsorption variables (pH, adsorbent dosage, and shaking time) was investigated using split-plot CCD. pH was considered as the HTC factor due to the amount of time, acid and/or base required to change it, while the adsorbent dosage and contact time were the ETC factors. Quadratic model was developed for the phenol percentage removal.

Results

The optimum adsorption conditions obtained from the study were adsorbent dosage of 0.60 g, pH of 7 as well as contact time of 167 min with desirability of 1. The predicted and experimental values obtained were 89.73 and 89.21%, showing good agreement between the experimental value and those predicted by the quadratic model. Langmuir isotherm model was found to be the best fit for the equilibrium adsorption data giving rise to monolayer adsorption capacity of 106.50 mg/g. The pseudo-second-order kinetic model’s correlation coefficient (R2) was higher than that of the pseudo-second-order kinetic suggesting the applicability of the model to the adsorption of phenol.

Conclusions

The synthesized BiFeO3 could be considered as a viable alternative to the expensive commercial activated carbon for the removal of phenols in wastewater, and the use of split-plot CCD model makes the experiment much easier to run and save time and/or cost due to fewer number of runs and restriction in the randomization of HTC factors.
A combined 2-D and 3-D QSAR modeling, molecular docking study, design, and pharmacokinetic profiling of some arylimidamide-azole hybrids as superior L. donovani inhibitors
Authors: Ugbe Fabian Audu , Shallangwa Gideon Adamu , Uzairu Adamu , Abdulkadir Ibrahim
Published: June 2022

Background

Leishmaniasis is one of the neglected tropical diseases which is prevalent in the tropical regions of the world most especially in Africa. It is caused by the Leishmania species and transmitted to humans majorly through the bite of the female sandfly. This study was carried out in support of the continuous search for new drug molecules effective enough for the treatment of leishmaniasis, and which have very limited side effects. This study was focused on a combined 2-D and 3-D QSAR modeling of thirty-six arylimidamide-azole hybrids, molecular docking study, design, and pharmacokinetic analysis of some selected and newly designed arylimidamide-azole analogs. The density functional theory (DFT) with B3LYP and 6-31G** basis set was employed for the geometry optimization of the various compounds. Genetic function approximation (GFA) and multi-linear regression (MLR) approaches were used for the 2-D QSAR model building, while the fractional factorial design (FFD) and uninformative variable elimination-partial least square (UVEPLS) were employed for building the 3-D QSAR model. Pyridoxal kinase (PdxK) receptor (PDB: 6K91) was the target protein of interest in this study.

Results

The built 2-D and 3-D QSAR models were found to satisfy the requirement of both internal and external validation tests as follows: 2-D QSAR; R2 = 0.9614, R2adj = 0.9513, Q2cv = 0.9350, R2test = 0.6766 and cRp2 = 0.8779, and for 3-D QSAR (UVEPLS at PC = 5); R2 = 0.9839, Q2LOO = 0.7539 and Q2LTO = 0.7367. The CoMFA steric and electrostatic field contributions were 68.96% and 31.04%, respectively. All the designed analogs showed higher predicted activities than that of the template (36). Also, the new compounds showed higher binding affinities (MolDock scores) than that of the reference drug pentamidine (− 141.793 kcal/mol), with 36e showing the highest negative MolDock score of − 208.595 kcal/mol. Additionally, these newly designed compounds were said to be orally bioavailable (excluding 36f and 36g that violated 2 of the Lipinski’s provisions), with perfect intestinal absorption, less difficult to synthesize, AMES toxicity free, and showed strong interactions with the target.

Conclusions

The newly designed compounds especially 36e have shown a marked pharmacological improvement over the template molecule and are therefore recommended for further practical evaluation as superior pyridoxal kinase inhibitors.
The prevalence of ultra-low total IgE level among Egyptian population: impact of age, sex, and socioeconomic class
Authors: Mohamed Manar F. , Gwad Asmaa M. Abd El , Sallam Dina E. , Afifi Amira H. , Abdalgeleel Shaimaa A. , Moustafa Nouran M. , Abougabal Maged T. , Taha Sara I. , El-Moussely Lamiaa M.
Published: June 2022

Background

Immunoglobulin E (IgE) is the least prevalent antibody type; it plays a key role in host immunity against parasitic infections and allergic diseases. Association between IgE deficiency and higher malignancy rates has been suggested in many studies.

Objectives

The goal of our study was to determine the prevalence of ultra-low total IgE levels and their variations according to sex and age among the Egyptian population.

Methodology

This multicenter retrospective cross-sectional study included serum total IgE and CBC records of 1099 children and 993 adults recruited from private and public hospitals in Egypt between 2015 and 2021. Total IgE levels were classified into ultra-low, normal, high, and very high.

Results

Of all included subjects, 0.8% had ultra-low IgE levels and 74.4% had normal IgE levels. High and very high serum total IgE levels were 24.1% and 0.7%, respectively. IgE levels were significantly higher among adults than children 45 (16.5–113.25) IU/ml vs. 20 (10–75) IU/ml; p < 0.001and among private hospital’s patients than the public one (40 (15–98.4) IU/ml vs. 25 (10–98.4) IU/ml; p = 0.002. No significant difference between total IgE serum levels regarding gender (p = 0.825). Total IgE levels were higher among young adults, with a gradual decline among older patients and a peak among the 50 s and 60 s patients. Pearson correlation between IgE and absolute eosinophilic count showed positive correlation but did not reach significant level r = 0.04, p = 0.367.

Conclusion

Age and socioeconomic class have impacts on total IgE levels with a relatively low prevalence of ultra-low IgE among the Egyptian population.
Improving vehicle’s seismic safety by equipping railway bridges with FPB and misalignment control device
Authors: Jin Zhibin , Chen Ke , He Jinzhe
Published: June 2022

Running safety of the railway vehicles on the bridge during earthquakes is a major concern for railway engineering. To reduce the derailment risk of railway vehicles on bridges, friction pendulum bearings (FPB) are proposed to be equipped on simply supported bridges in this study. The full nonlinear behavior of the FPB is introduced into the vehicle-bridge interaction model. The effect of FPB’s manufacturing variations, including the shear pin’s strength and friction coefficient, on the misalignment was investigated. The manufacturing variations of the FPB were found to produce large lateral misalignment, which further contributes to large wheel-rail forces when the vehicle passes over the girder ends. It diminishes the improvement in the vehicle’s seismic safety provided by FPBs. Thus, a misalignment control device is proposed to limit the misalignment of the railway bridges equipped with FPBs. The vehicle-bridge interaction analysis results show that no wheel uplift occurred on the bridge equipped with FPBs and misalignment control devices during an earthquake. It indicates that the FPB significantly reduces the vehicle’s derailment risk on bridges compared with the non-isolated bearings.
Comparative study of tube to tubesheet welding qualification on heat exchanger
Authors: Saffiudeen Mohamed Fayas , Mohammed Fasil T. , Syed Abdullah
Published: June 2022

Plant turnarounds are one of the most critical events in the Saudi Arabian oil and gas industries. Shutdowns have the potential to affect the plant’s cash flow and objectives either in a constructive nor a bad way. A heat exchanger is an essential equipment for some procedures in the oil and gas refineries plant and it will decide the plant’s shutdown span. In a heat exchanger, welded tube to tubesheet joint is a basic factor which requires a different qualification. In this paper, tube to tubesheet welding for various material combination (carbon steel-stainless steel, stainless steel-stainless steel, and alloy steel-alloy steel) is qualified. According to American Society of Mechanical Engineers (ASME) Section IX QW-193 mock up qualification is done and QW-193.1 to QW-193.1.3 (visual test, liquid penetrant test and macro etching test) likewise is followed and lab tested for acceptance criteria. Ten model welds are needed to determine the eligibility of each procedure according to the required standard and totally 60 models (every 20) tried to rate this 3 procedure qualification record and welder qualification test record (PQR / WQTR). Qualification of the sheet from tube to tube follows all needed variables referred to in QW-288. This study proposes the improved minimum and maximum value for current (I), voltage (V), and travel speed (mm/min) required for above said materials qualifications. Further discourse is made over the heat input (KJ/mm), after effects of minimum leak path all things considered (Macro etching test), and classifies the range qualified against utilized base material for better understanding according to QW-288 essential variables.
Experimental investigation of flow pattern at 180° bend with rigid bed in effect of twin convergent bridge piers
Authors: Sedighi Farid , Vaghefi Mohammad , Zarei Elham
Published: June 2022

The generation of vortices in sharp bends of rivers is a well-known phenomenon. However, their influence on the bridge pier has not been investigated deeply. This study studies the flow pattern around the twin convergent bridge pier in a sharp bend by an experimental approach. The test facility includes a channel located at Advanced Hydraulic Laboratory, Persian Gulf University, with a 1 m width and 2 m central radius. The flow 3D velocity is measured along the bend by an ADV velocimeter. It is realized that the most important vortex from a sediment transport point of view is located adjacent to a pier in a plane just parallel to the flow direction. Furthermore, it could be concluded that the pier influencing range has an approximate dimension of 10 times pier diameter in a plane parallel to flow and 3 timer pier diameters in the vertical plane. Results and discussions are presented throughout the paper.
Enhancing class F fly ash geopolymer concrete performance using lime and steam curing
Authors: Diab Muhammad Ahmad
Published: June 2022

Background

Producing fly ash geopolymer concrete (FGPC) which can be cured by air, water, or steam instead of thermal curing without decreasing its mechanical properties will facilitate using FGPC in cast-in situ applications and precast concrete industry. Furthermore, it will decrease the consumed energy in FGPC production. This research attempts to achieve this goal by investigating the efficacy of supplementing class F FGPC with lime while using different curing processes to generate lime-fly ash geopolymer concrete (L-FGPC) that could be a feasible alternative to ordinary FGPC.

Methods

The studied variables included lime content, molarity of sodium hydroxide (NaOH), additional water content, curing type, and moisture of aggregates. The comparative criteria were setting times of fresh concrete, mechanical properties of hardened concrete, and voids ratio. SEM and X-ray diffraction tests were used to validate test results.

Conclusions

Steam curing generated the best mechanical properties of L-FGPC. Using 2% lime content with steam-cured L-FGPC yielded proper setting times and the best mechanical properties. Microstructure tests revealed compact microstructure and decreased voids ratio upon using 2% lime content in L-FGPC. Increasing molarity of NaOH, decreasing additional water content, and decreasing moisture of aggregates enhanced L-FGPC’s mechanical properties.
A simple laboratory method to simulate calcite-bonded loose-structured soil samples for collapsibility study
Authors: Opukumo Alfred Wilson , Davie Colin T. , Glendinning Stephanie
Published: June 2022

Calcite is one of the commonest bond elements in natural collapsible soils. Where calcite occurs in significant amounts, the soils are considered calcareous. Collapsible soils are characterised by high porosity, high-void ratio, and low-dry density, with the soil particles held together in a honeycomb structure by a bonding agent like clay, suction or calcite. Collapse usually occurs when the bonding agent is lost through wetting, dissolution and/or stressing. Thus, understanding the behaviour of a bonding agent in the collapse phenomenon is critical to design safe and economic foundations built on collapsible soils. For a better interpretation, laboratory-simulated soils have the advantage to ensure controlled soil properties and somewhat homogeneity as against natural soils. Unfortunately, there is no standardized procedure for simulating calcite-bonded collapsible soils. A novel reaction setup developed in-house has been adopted to precipitate calcite bonding through lime gassing. Samples of silt-clay-lime mixes of differing proportions were prepared into varying dry densities to achieve collapsible soil features, and then, CO2was passed through the mixes placed in the reaction setup. Gassing was done for 24 h. Samples were labelled A1, A2, A3, B1, B2, B3, C1, C2 and C3, where A, B and C represented silt/clay initial proportioning of 50/50, 35/65 and 20/80, respectively, while 1, 2 and 3 represented lime contents of approximately 9, 20 and 33%, respectively. After gassing, three different methods (acid–base colour indicator,calculated mass gain (CMG), andexperimental determination of CaCO3content) were used to confirm the presence or content of CaCO3precipitate. Results revealed high levels of successes in terms of lime conversion to calcite and relative homogeneity of samples with collapsible features.
Criminal sanctions for suicidality in the 21st Century UK
Authors: Thomson Alex B. , Eales Sarah , McAllister Emma , Molodynski Andrew
Published: June 2022

Criminal sanctions including court orders, prosecution and imprisonment persist as responses to suicidality in the UK even where there is no public danger. Their prevalence, the level of clinical involvement and outcomes are unclear. There is an urgent need to examine the national picture of harms, benefits and the responsibilities of mental health professionals.
Immune-related gene expression signature in patients with recurrent/metastatic head and neck cancer treated with immunotherapy.
Authors: Licitra Lisa F. , Serafini Mara Serena , Pistore Federico , Lenoci Deborah , Airoldi Mario , Cossu Rocca Maria , Strojan Primoz , Grasic Kuhar Cvetka , Merlano Marco C. , Denaro Nerina , Perri Francesco , Argiris Athanassios , Gurizzan Cristina , Perrone Federica , Ghi Maria Grazia , Cassano Alessandra , Allegrini Giacomo , De Cecco Loris , Bossi Paolo
Published: June 2022

6051

Background: In platinum-resistant recurrent-metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients (pts), survival improvements have been achieved with immune checkpoint inhibitors (ICI), however this benefit is limited to a relatively small subgroup of pts. Predictive biomarkers are still under investigation and their contribution to the clinic has been limited. An immune-related cluster (Cl6) has been defined by means of a metanalysis in locally advanced HNSCC. Methods: Gene expression profiling was performed on two cohorts of platinum resistant R/M HNSCC pts treated with ICI alone: i) 20 patients as training set, divided in long-term (OS >18 months; n=12) and short-term (OS < 6 months; n=8) survivors matched according to site of recurrence (distant metastases only, or locoregional recurrence with/out metastases); ii) 80 patients enrolled in a phase II trial (EudraCT number: 2017-000562-30; NIVACTOR study) as testing set. The molecular subtyping stratification (De Cecco, Oncotarget 2015) was applied. Subsequently, a score was determined between each sample and the centroids for the 6 clusters previously identified. The threshold point was imputed in the training set as the closest value to the observed prevalence. A Cox multivariable analysis including TMB, CPS and TPS PD-L1 status, age, tumoral subsite and performance status (PS) was performed. Results: Among all the clusters, Cl6 turned out to be significant and applied to training set it provided evidence to discriminate pts’ survivals (AUC=0.86, 95%CI=0.7-1.0; p=2E-05). The stratification based on Cl-6 along with the cut-off point defined in the training set were challenged in the testing set: samples were divided in 28 (35%) having high Cl-6 scores and 52 (65%) with low scores, reaching HR=0.46 (95% CI= 0.27-0.76; p=0.0024). Multivariate analysis showed that only Cl6 (high vs low, HR=0.44; p=0.00443) and PS (1,2 vs 0, HR 1.85; p=0.02686) resulted to be significant on pts’ OS. Conclusions: By analysing two series of pts receiving immunotherapy alone, we identified an immune-related gene expression signature, able to discriminate the prognosis of platinum-resistant R/M HNSCC pts. The multivariate analysis confirmed the immune-related Cl6 as factor linked to outcome in pts treated with immunotherapy, as well as it confirmed the importance of PS. An analysis of the signature on pts receiving first line treatment with immunotherapy is currently ongoing. [Table: see text]
The mutational landscape of medullary thyroid carcinoma using whole-exome sequencing in China.
Authors: Huang Chen , Di Jinxi , Jiang Ruiying , Wang Xiaowei , Wang Ye , Feng Qianqian , Liu Siyao , Niu Yun , Shi Yanfen , Lin Jie , Wang Bei , Luo Jie , Zhong Dingrong , Tong Jie
Published: June 2022

6054

Background: Medullary thyroid carcinoma (MTC) is a rare malignancy, and its molecular pathogenesis is far from being understood. Therefore, a relatively comprehensive and accurate genomic profiling is needed for the future molecular diagnosis, treatment and early prevention of MTC patients. Methods: In this study, we investigated both the somatic and germline mutational spectrum of MTC, whole-exome sequencing (WES) was performed on tumor samples and matched noncancerous tissues from 30 MTC patients. Genetic alterations were defined and analyzed using MutSigCV and novel germline mutations were identified using MutationTaster and cross-referenced in PubMed. Results: In somatic mutational spectrum we found the top three significantly mutated genes (SMGs) in our MTC samples were RET, FAM186A and PRG4 genes (33%, 33% and 27%, respectively). For the germline mutations, FAT4 was detected as the most common mutated genes, following by RET and FAT1. Besides, we identified 30 novel germline mutations such as IGF1R, PDK1, NOTCH1, RPTOR, MPL, SETD2 and ARID2. Those mutated genes have been previously associated with neurofibromatosis, Lynch syndrome and other diseases respectively and now predicted potential functional pathogenicity in the patients with MTC. Conclusions: The study elucidated a relatively more comprehensive genomic landscape of MTC. In addition to the RET gene, which has been studied extensively, other SMGs may also be of interest including novel germline mutations. These findings may indicate the potential basis of molecular diagnosis, early prevention and targeted therapeutic options for patients with MTC in the future.
Impact on xerostomia for patients with nasopharyngeal carcinoma treated with superficial parotid lobe-sparing intensity-modulated radiation therapy (SPLS-IMRT): A prospective phase II randomized controlled study.
Authors: Huang Huageng , Miao Jingjing , Zhao Chong , Wang Lin
Published: June 2022

6059

Background: In the intensity-modulated radiation therapy (IMRT) era, xerostomia remains one of the most common radiation-induced toxicities in nasopharyngeal carcinoma (NPC) patients. We first proposed the superficial parotid lobe–sparing IMRT (SPLS-IMRT) technique in NPC, which has been proved to significantly reduce the mean doses of bilateral entire parotid glands and superficial parotid lobes. To further validate its clinical benefits, we conducted a prospective phase II randomized controlled study to compare the incidence of xerostomia in NPC patients treated with SPLS-IMRT and conventional IMRT (C-IMRT). Methods: Patients with histologically confirmed NPC who met the eligibility criteria were randomly assigned in a 1:1 ratio to receive either SPLS-IMRT or C-IMRT. The V36 (the percentage volume receiving a dose of 36 Gy) of the entire parotid gland was constrained to be less than 40% in both groups. Additionally, V26 (the percentage volume receiving a dose of 26 Gy) of the superficial parotid lobe was constrained to be less than 30% in the SPLS-IMRT group. The primary endpoint was the incidence of xerostomia at 12 months post-IMRT. The secondary endpoints included the xerostomia questionnaire (XQ) score, unstimulated salivary flow rate (USFR), stimulated salivary flow rate (SSFR), and survival outcomes. Results: From January 2018 to September 2018, 90 patients were enrolled (45 per group). Eighty-two patients were included for xerostomia analysis (42 in the SPLS-IMRT group and 40 in the C-IMRT group). At 12 months post-IMRT, the incidence of xerostomia in the SPLS-IMRT group was significantly lower than that in the C-IMRT group (83.4% vs. 95.0%; P = 0.007), especially the grade 3 xerostomia (0% vs. 12.5%; P < 0.001). However, the median change in XQ score (XQchange) was similar between the two groups (11.9 points vs. 14.1 points; P = 0.194). Moreover, there was a significantly higher median fractional USFR (0.67 vs. 0.35; P = 0.024) and SSFR (0.66 vs. 0.32; P = 0.021) in the SPLS-IMRT group than the C-IMRT group. All 90 patients were included for survival analysis. With a median follow-up time of 37.8 months (IQR, 33.9–38.5 months), the 3-year locoregional relapse-free survival, distant metastasis-free survival, and overall survival in the SPLS-IMRT and C-IMRT groups were 92.5% vs. 90.9% (hazard ratio [HR], 1.84; P = 0.477), 83.8% vs. 81.7% (HR, 1.13; P = 0.816), and 88.9% vs. 88.2% (HR, 0.96; P = 0.949), respectively. Conclusions: SPLS-IMRT significantly reduced the incidence of xerostomia at 12 months post-IMRT in NPC by recovering parotid gland function earlier than C-IMRT, without compromising survivals. Phase III clinical trials are needed to confirm this result. Clinical trial information: NCT05020067.
Quality of life and two-year results of a randomized phase III study of dysphagia-optimized intensity modulated radiotherapy (DO-IMRT) versus standard IMRT (S-IMRT) in head and neck cancer.
Authors: Nutting Christopher , Rooney Keith , Foran Bernadette , Pettit Laura , Beasley Matthew , Finneran Laura , Roe Justin , Tyler Justine , Roques Tom , Cook Audrey , Petkar Imran , Bhide Shree , Srinivasan Devraj , Boon Cheng , De Winton Emma , Frogley Robert , Sydenham Mark Adrian , Emson Marie , Hall Emma ,   On behalf of the DARS Investigators
Published: June 2022

6065

Background: Most newly diagnosed oro- & hypopharngeal cancers (OPC, HPC) are treated with (chemo)RT with curative intent but at the consequence of adverse effects on quality of life. We investigated if using DO-IMRT to reduce RT dose to the dysphagia/aspiration related structures (DARS) improved swallowing function compared to S-IMRT. Methods: Patients with T1-4, N0-3, M0 OPC/HPC were randomised 1:1 to S-IMRT (65 Gray (Gy)/30 fractions (f) to primary & nodal tumour; 54Gy/30f to remaining pharyngeal subsite & nodal areas at risk of microscopic disease) or DO-IMRT. The volume of the superior & middle pharyngeal constrictor muscle (PCM) (OPC) or inferior PCM (HPC) lying outside the high-dose target volume was set a mandatory mean dose constraint in DO-IMRT. Treatment allocation was by minimisation balanced by centre, use of induction/concomitant chemotherapy, tumour site & AJCC stage. Primary endpoint was mean MD Anderson Dysphagia Inventory (MDADI) composite score 12 months after RT. Secondary endpoints included University of Washington (UW)-Qol, Performance Status Scale Head & Neck (PSS-HN) domain scores (range: 0-100), swallow volume, swallow capacity and local control. Results: 112 patients (56 S-IMRT, 56 DO-IMRT) were randomised from 22 UK & Ireland centres from 06/2016 - 04/2018. 111/112 had RT doses as prescribed (1 patient died before RT). Outcome measures at 12 and 24 months are summarised below. DO-IMRT had higher MDADI scores at 12 (p = 0.04) and 24 (p = 0.07) months. Clinically important improvements in swallowing function were seen in patients receiving DO-IMRT using PSS-HN domains and the UW-QoL tool. Conclusions: DO-IMRT improved patient reported swallowing function compared with S-IMRT. Improvements were seen in overall MDADI as well as functional scores in both PSS-HN and UW-QoL. Clinical trial information: 25458988. [Table: see text]
Neoadjuvant chemotherapy plus tislelizumab followed by concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: A single-arm, phase II trial.
Authors: Chen Qiu-Yan , Mai Hai-Qiang , Tang Lin-Quan , Luo Meijuan , Zhao Chong , Mo Hao-Yuan , Sun Rui , Luo Dong-Hua , Wang Lin , Guo Shan-Shan , Xie Siyi , Li Su-Chen , Liu Sai-Lan , Li Xiao Yun , Peng Jing-Yun , Qiu Hui-Zhi , Sun Xue-Song , Liu LiTing
Published: June 2022

6068

Background: Neoadjuvant treatment with gemcitabine plus cisplatin (GP) prior to concurrent chemoradiotherapy (CCRT) has favorable survival outcomes with acceptable toxicity in patients with locoregionally advanced nasopharyngeal carcinoma (LANPC), 10% of whom achieved complete response (CR) after neoadjuvant treatment. Immune checkpoint blockade therapy plus GP regimen has been shown to improve the survival in recurrent or metastatic NPC. We investigated the efficacy and safety of neoadjuvant treatment with GP plus tislelizumab, an anti-PD-1 monoclonal antibody, in previously untreated LANPC. Methods: In this phase II, single-armed Simon two-stage study, eligible patients are of age 18-70, with adequate haematological, renal, and hepatic function, diagnosed with staged III-IVa（AJCC 8th） non-keratinizing LANPC. Enrolled patients received intravenous gemcitabine (1000 mg/m2) on days 1 and 8, cisplatin (80 mg/m2) on day 1, and tislelizumab (200mg) on day 1 every 3 weeks for 3 cycles followed by standard CCRT. The primary endpoint was CR rate after neoadjuvant treatment, using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator. The secondary endpoints included pathology complete response (pCR) rate, 2-year progress-free survival (PFS), overall survival (OS), locoregional failure-free survival (LRRFS), distant metastasis-free survival (DMFS), and toxicity. This study is registered with ClinicalTrials.gov, NCT04833257, all enrolled patients have finished their treatment and the follow-up is ongoing. Results: From April 14th 2021 to August 5th, 2021, a total of 63 patients (median age 46y, 74.6% male) were enrolled at Sun Yat-sen University Cancer Center. As of January 31st, 2022, the median follow-up is 7.37 months, no patients had disease progression. The CR rate after neoadjuvant treatment was 41.3% (95% CI, 28.8% to 53.8%). The ORR and pCR rate were 88.9% (95% CI, 80.9% to 96.9%) and 75.8% (95% CI, 64.8% to 86.8%), respectively. The incidence of acute treatment-related AEs (trAEs) and immune-related adverse events (irAEs) of grade 3 or 4 was 69.8% and 3.2%, respectively. All of irAEs for grade 3 or 4 were hepatotoxicity and skin rash. Long-term efficacy is awaited. Conclusions: Neoadjuvant treatment with GP plus tislelizumab achieved impressive CR rate and pCR rate with manageable toxicities. Further follow-up is needed to confirm the long-term efficacy. Clinical trial information: NCT04833257.
Factors associated with adherence to remote patient monitoring for early detection of dehydration risk during radiation treatment for head and neck cancer.
Authors: Phillips Sarah , Shinn Eileen H. , Garden Adam S. , Beadle Beth Michelle , Camero Maria , Baum George , Shete Sanjay , Farcas Emilia , Patrick Kevin , Peterson Susan K.
Published: June 2022

6076

Background: Remote patient monitoring (RPM) may improve the early detection and mitigation of cancer treatment-related complications, health-related outcomes and quality of life. RPM’s success may depend, in part, on patients’ adherence to remote monitoring protocols. However, factors that influence adherence to RPM are largely unknown. Daily blood pressure/pulse (BP/P), weight, and electronic patient-reported outcomes (ePROs) were monitored remotely in head and neck cancer (HNC) patients undergoing radiation treatment (RT) to identify dehydration risk. We evaluated potential factors associated with RPM adherence. Methods: During RT (average 6 to 7 weeks), participants were asked to take daily (Monday-Friday) measures of BP/P and weight using Bluetooth-enabled devices and to complete daily ePROs using a mobile tablet application (app). Data were provided to their physicians for daily review. The MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) was completed at baseline and end of RT, and 6-8 weeks post-RT completion. The Patient Activation Measure (PAM) was completed at baseline and 6-8 weeks post-RT completion. A device usability survey measuring perceived usefulness of RPM was completed at the end of RT. Adherence to daily monitoring was recorded objectively. Longitudinal analyses compared the relationship between demographic, clinical, and PRO data and monitoring adherence. Results: Participants (n = 169) were 80% male, 87% White, and 91% married. Overall adherence to monitoring BP/P, weight, and ePROs was 83%, 82% and 74%, respectively. Greater HN-specific symptom severity and interference was associated with decreased adherence to daily monitoring of BP/P, weight, and ePROs (P< 0.021). Higher PAM scores were associated with higher adherence to daily monitoring of BP/P only (p = 0.006). Participants reported modest levels of perceived usefulness of RPM across four categories: symptom management, early problem detection, illness monitoring by healthcare provider, and feeling of security during RT. Only a single item indicating perceived feeling of security was associated with greater adherence to daily monitoring of blood pressure/pulse (p = 0.032) and weight (p = 0.007). Conclusions: A benefit of frequent RPM may be early detection and mitigation of symptoms during RT for HNC, however, increasing symptom burden experienced during treatment may interfere with adherence to daily monitoring. Better adherence may be attributed to patients perceiving a sense of security from daily monitoring and may suggest a potentially important value that patients gain from RPM. Understanding factors that impact patient adherence to RPM may help improve acceptability and clinical utility of RPM in oncology. Clinical trial information: NCT02253238.
A phase II study to evaluate the efficacy and safety of camrelizumab plus famitinib in advanced or metastatic thyroid cancer.
Authors: Ji Dongmei , Shen Weina , Kuang Muyu , Liu Ying , Li Huajun , Wang Yu , Ji Qinghai
Published: June 2022

6085

Background: Many studies have confirmed that the combination with anti-vascular drugs can significantly improve the efficacy of anti-PD-1/PD-L1 inhibitor in a variety of tumors. Camrelizumab is a humanized anti-programmed cell death receptor 1 (PD-1) antibody. Famitinib is a tyrosine kinase inhibitor which exhibits anti-angiogenesis and antiproliferative effects via targeting VEGFR-2, c-Kit and PDGFR-β. Herein, we aimed to evaluate the efficacy and safety of camrelizumab plus famitinib in the treatment of advanced or metastatic thyroid cancer. Methods: A single-arm, open-label phase II study was conducted, patients (pts) with advanced or metastatic thyroid cancer were recruited, including radioiodine-refractory differentiated thyroid cancer (group 1), differentiated thyroid cancer ineligible for 131I treatment (group 2), medullary thyroid cancer (group 3) and anaplastic thyroid cancer (group 4). Pts received camrelizumab 200mg i.v. on day 1 of each 21-day cycle and oral famitinib 20mg po qd in 21-day cycles until progressive disease or drug intolerance. The primary endpoint was objective response rate (ORR). The secondary endpoints were safety, adverse events (AEs), duration of response (DoR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Results: Between Jan 14, 2020 and Feb 9, 2022, 74 pts were enrolled. There were 12/26/5/31 pts in group 1/2/3/4 respectively. Median follow-up time was 11.4 months. In group 1, of 12 evaluable pts, confirmed ORR, ORR and DCR accounted for 33.3%, 41.7% and 100.0%, respectively. In group 2, of 25 evaluable pts, the confirmed ORR and DCR were 44.0% and 96.0%, respectively. In group 3, of 5 evaluable pts, the confirmed ORR and DCR were 40.0% and 100.0%, respectively. In group 4, of 24 evaluable pts, the confirmed ORR, ORR and DCR were 62.5%, 75% and 95.8%, respectively. PFS and OS were not yet mature for group 1-3, and in group 4, of all enrolled pts, estimated median PFS was 8.4 months and estimated median OS was 13.6 months. 73 pts were included in safety set. The most common treatment related AEs were diarrhea (37.0%), palmoplantiplanar swelling syndrome (34.2%), hypertension (31.5%) and fatigue (31.5%). Conclusions: Camrelizumab plus famitinib demonstrated promising anti-tumor efficacy with acceptable toxicity in pts with advcanced or metastatic thyroid cancer. Clinical trial information: NCT04521348.
The effect of anlotinib on unresectable differentiated thyroid cancer (T4): A retrospective study.
Authors: Wu Xin , Luo Han , Peng Xingchen , Li Peiheng , Kong Xiangyu , Tan Qiaoyue , Liu Jun , Huang Rui , Li Zhihui
Published: June 2022

6096

Background: Though the majority of differentiated thyroid cancer (DTC) patients obtained a good prognosis after standardized therapy, approximately 15% of DTC patients will progress to unresectable disease. Part of locally advanced (T4) thyroid cancer patients with progressive invasion into vasculature/windpipe/esophagus lost the surgery opportunity because of difficult in achieving R0/R1 resection. The study aimed to evaluate the efficacy and safety of anlotinib in T4 PTC. Methods: Retrospectively included T4 papillary thyroid cancer (PTC) patients from West China Hospital of Sichuan University between Sep. 2020 and Feb. 2022. The patients were prescribed with Anlotinib (12 mg orally daily, two weeks on/one week off) at least two courses. The tumor response was defined by RECIST v. 1.1. The primary endpoint was objective response rate (ORR). Results: The study included 22 T4 PTC patients, including 8 patients with lung metastasis. The median age of patients was 59.2 years, 8/22 patients were male. The median follow-up was 5.5 months (2-13 months). Totally, the ORR was 68.2% (CR: 9.1%; PR: 59.1%), disease control rate (DCR) was 95.5% (SD: 27.3%), one patient progressed (PD). 8 patients with lung metastasis, the ORR was 75% (6/8). The average tumor shrinkage rate was 42.1%. And two female patients (T4aN1M1 and T4bN1M0 respectively) obtained CR. Additionally, one juvenile patient (14 y) also response to Anlotinib treatment with 55.2% tumor shrinkage, and no obvious AE was observed in this patient. Most adverse events (AEs) were grade 1 or 2. Common AEs of all grades were hypertension (68.2%), hypertriglyceridemia (36.4%), proteinuria (31.8%), and tended to discontinue when treatment ceased. Conclusions: Anlotinib demonstrated antitumor activity in the treatment of unresectable T4 PTC; Juvenile PTC patients also response to Anlotinib treatment; Anlotinib treatment was tolerable in T4 PTC patients.