bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Three Satellite-Derived Surface Downward Longwave Radiation Products in Polar Regions
Authors: Xin Xiaozhou , Yu Shanshan , Sun Daozhong , Zhang Hailong , Li Li , Zhong Bo
Published: October 2022

The radiation budget in polar regions plays an important role in global climate change study. This study investigates the performance of downward longwave radiation (DLR) of three satellite radiation products in polar regions, including GEWEX-SRB, ISCCP-FD, and CERES-SYN. The RMSEs are 35.8, 40.5, and 26.9 W/m2 at all polar sites for GEWEX-SRB, ISCCP-FD, and CERES-SYN. The results in the Arctic are much better than those in the Antarctic, RMSEs of the three products are 34.7 W/m2, 36.0 W/m2, and 26.2 W/m2 in the Arctic and are 38.8 W/m2 and 54.8 W/m2, and 28.6 W/m2 in the Antarctic. Both GEWEX-SRB and CERES-SYN underestimate DLRs at most sites, while ISCCP-FD overestimates DLRs at most sites. CERES-SYN and GEWEX-SRB DLR products can capture most of the DLR seasonal variation in both the Antarctic and Arctic. Though CERES-SYN has the best results that RMSE within 30 W/m2 in most polar sites, the accuracy of satellite products in polar regions still cannot meet the requirement of climate research. The improvement of satellite DLR products in polar regions mainly depends on the quality of improving input atmospheric parameters, the accuracy of improving cloud detection over the snow and ice surface and cloud parameters, and better consideration of spatial resolution and heterogeneity.
A Review on Lignin-Based Carbon Fibres for Carbon Footprint Reduction
Authors: Obasa Victoria Dumebi , Olanrewaju Oludolapo Akanni , Gbenebor Oluwashina Phillips , Ochulor Ezenwanyi Fidelia , Odili Cletus Chiosa , Abiodun Yetunde Oyebolaji , Adeosun Samson Oluropo
Published: October 2022

Carbon fibers (CFs) are made mostly from a non-environmentally friendly polyacrylonitrile (PAN) and little from rayon. PAN-based CFs, require huge amount of energy for its production aside its contributions to the global CO2 emission. Therefore, there is recourse to a more environmentally friendly sources of CFs biomass. Recently lignin has been recognized as a potential renewable raw material for carbon fibers to replace PAN-based. The magnitude and quality of CO2 emission of lignin-based CFs are dependent on the processing route. On this premise; this review examines the various lignin-based CFs processing route adopted by researcher in the recent past to establish the most viable route with minimum carbon footprint emission. Outcome of the review shows that the major advantages of aromatic polymer (AP) generated precursor over PAN is the presence of higher quantity of guaiacyl units and oxygen content which makes the stabilization phase efficient and faster requiring less energy. Though there are several methods and options for the various stages of conversion of lignocellulosic biomass into CFs as highlighted in the study, establishing an optimum processing route will be a trade-off amongst various issues of concern; carcinogenic risk, carbon footprint emission, CFs Yield and mechanical strength of the CFs. Inferences from the study shows that the L-CF significantly produced reduced climatic impact in terms of CO2 emission.
Operational Probabilistic Fog Prediction Based on Ensemble Forecast System: A Decision Support System for Fog
Authors: Parde Avinash N. , Ghude Sachin D. , Dhangar Narendra Gokul , Lonkar Prasanna , Wagh Sandeep , Govardhan Gaurav , Biswas Mrinal , Jenamani R. K.
Published: October 2022

One of the well-known challenges of fog forecasting is the high spatio-temporal variability of fog. An ensemble forecast aims to capture this variability by representing the uncertainty in the initial/lateral boundary conditions (ICs/BCs) and model physics. The present study highlights a new operational Ensemble Forecast System (EFS) developed by the Indian Institute of Tropical Meteorology (IITM), Pune, to predict the fog over the Indo-Gangetic Plain (IGP) region using the visibility (Vis) diagnostic algorithm. The EFS framework comprises the WRF model with a 4 km horizontal resolution, initialized by 21 ICs/BCs. The advantages of probabilistic fog forecasting have been demonstrated by comparing control (CNTL) and ensemble-based fog forecasts. The forecast is verified using fog observations from the Indira Gandhi International (IGI) airport during the winter months of 2020–2021 and 2021–2022. The results show that with a probability threshold of 50%, the ensemble forecasts perform better than the CNTL forecasts. The skill scores of EFS are relatively promising, with a Hit Rate of 0.95 and a Critical Success Index of 0.55; additionally, the False Alarm Rate and Missing Rate are low, with values of 0.43 and 0.04, respectively. The EFS could correctly predict more fog events (37 out of 39) compared with the CNTL forecast (31 out of 39) and shows the potential skill. Furthermore, EFS has a substantially reduced error in predicting fog onset and dissipation (mean onset and dissipation error of 1 h each) compared to the CNTL forecasts.
Rainfall in the Urban Area and Its Impact on Climatology and Population Growth
Authors: da Silva Monteiro Lua , de Oliveira-Júnior José Francisco , Ghaffar Bushra , Tariq Aqil , Qin Shujing , Mumtaz Faisal , Correia Filho Washington Luiz Félix , Shah Munawar , da Rosa Ferraz Jardim Alexandre Maniçoba , da Silva Marcos Vinícius , de Barros Santiago Dimas , Barros Heliofábio Gomes , Mendes David , Abreu Marcel Carvalho , de Souza Amaury , Pimentel Luiz Cláudio Gomes , da Silva Jhon Lennon Bezerra , Aslam Muhammad , Kuriqi Alban
Published: October 2022

Due to the scarcity of studies linking the variability of rainfall and population growth in the capital cities of Northeastern Brazil (NEB), the purpose of this study is to evaluate the variability and multiscale interaction (annual and seasonal), and in addition, to detect their trends and the impact of urban growth. For this, monthly rainfall data between 1960 and 2020 were used. In addition, the detection of rainfall trends on annual and seasonal scales was performed using the Mann–Kendall (MK) test and compared with the phases of El Niño-Southern Oscillation (ENSO) and Pacific Decadal Oscillation (PDO). The relationship between population growth data and rainfall data for different decades was established. Results indicate that the variability of multiscale urban rainfall is directly associated with the ENSO and PDO phases, followed by the performance of rain-producing meteorological systems in the NEB. In addition, the anthropic influence is shown in the relational pattern between population growth and the variability of decennial rainfall in the capitals of the NEB. However, no capital showed a significant trend of increasing annual rainfall (as in the case of Aracaju, Maceió, and Salvador). The observed population increase in the last decades in the capitals of the NEB and the notable decreasing trend of rainfall could compromise the region’s water security. Moreover, if there is no strategic planning about water bodies, these changes in the rainfall pattern could be compromising.
A Novel Approach to Estimating the Dose of Ambient Air Pollution during Cycling Commutes from Home to School and Route Optimizations
Authors: Gao Yue (Jason) , Ma Xuying , Xiao Shun
Published: October 2022

Students’ exposure to air pollution during active commuting between home and school has been linked with numerous adverse health outcomes. An accurate assessment of cycling students’ dose of air pollution during commutes could help mitigate the adverse health effect of exposure. However, up to date, it is still challenging to fill this research gap. In this study, we proposed a modeling framework to estimate cycling students’ terrain-based dosage of ambient nitrogen dioxide (NO2) during home-school commutes for the very first time. The approach was further applied to compare the benefit and costs of different route choices and examine exposure justice issues during students’ cycling from home to school in Auckland, New Zealand. Results show that most of the cycling students could find an alternative lowest-dose route, and for around 25% of them, a 1% increase in route length was associated with a more than 1% decrease in NO2 dosage. Evidence demonstrates that exposure inequalities existed to some extent during students’ cycling commutes. This study could deepen our understanding of cyclists’ exposure, and some recommendations were also provided to optimize students’ daily active commute routes.
Characteristics of Volatile Organic Compounds and Their Contribution to Secondary Organic Aerosols during the High O3 Period in a Central Industry City in China
Authors: Yao Dan , Li Chenhong , Niu Qiuying , Gao Wenkang , Yu Hao , Yan Guangxuan , Liu Jingda , Cao Zhiguo , Wang Shuai , Wang Yuesi
Published: October 2022

High loads of fine particulate matter (PM2.5) and ozone (O3) pollution occurred frequently since early spring and led to an increasing contribution of secondary organic aerosols (SOA) in organic aerosols. However, the characteristics of precursor volatile organic compounds (VOCs) have rarely been studied. In this study, the continuous observation of VOCs was performed by an offline VOC monitoring system and gas chromatography-mass/flame ionization detector from 1 April 2020 to 31 July 2020; the characterization of VOCs and their contribution to SOA was explored. The results showed that during the observation period, the average mixing ratio of TVOCs was 42.6 ± 11.2 ppbv, and the major VOCs species were OVOCs, followed by alkanes, halocarbons, aromatics, alkenes and acetylene. When the west circulation pattern functioned, the value of aromatics increased, and the relation between PM2.5, O3 and VOCs increased when the high-pressure system controlled by anticyclone functioned. In combination with the results of positive matrix factorization, the main emission sources of ambient VOCs were complex, and the fuel combustion, industry-related emission, vehicle emission, biogenic emission and solvent volatilization accounted for 27.1%, 24.4%, 24.3%, 12.1% and 12.0%, respectively. Moreover, the industry-related emission contributed the greatest to the generation of SOA. This result indicated that the restrictions on aromatics during the industrial process are vital to reducing SOA formation.
Cloud Nowcasting with Structure-Preserving Convolutional Gated Recurrent Units
Authors: Kellerhals Samuel A. , De Leeuw Fons , Rodriguez Rivero Cristian
Published: October 2022

Nowcasting of clouds is a challenging spatiotemporal task due to the dynamic nature of the atmosphere. In this study, the use of convolutional gated recurrent unit networks (ConvGRUs) to produce short-term cloudiness forecasts for the next 3 h over Europe is proposed, along with an optimisation criterion able to preserve image structure across the predicted sequences. This approach is compared against state-of-the-art optical flow algorithms using over two and a half years of observations from the Spinning Enhanced Visible and Infrared Imager (SEVIRI) instrument onboard the Meteosat Second Generation satellite. We show that the ConvGRU trained using our structure-preserving loss function significantly outperforms the optical flow algorithms with an average change in R2, mean absolute error and structural similarity of 12.43%, −8.75% and 9.68%, respectively, across all time steps. We also confirm that merging multiple optical flow algorithms into an ensemble yields significant short-term performance increases (<1 h), and that nowcast skill can vary significantly across different European regions. Furthermore, our results show that blurry images resulting from using globally oriented loss functions can be avoided by optimising for structural similarity when producing nowcasts. We thus showcase that deep-learning-based models using locally oriented loss functions present a powerful new way to produce accurate cloud nowcasts, with important applications to be found in solar power forecasting.
Development of Smart Home Applications Based on Arduino and Android Platforms: An Experimental Work
Authors: Sharkawy Abdel-Nasser , Hasanin Mahmoud , Sharf Mohamed , Mohamed Mahmoud , Elsheikh Ahmed
Published: October 2022

The ideal smart home could be automatically controlled using a variety of electronic tools and devices to perform everyday tasks. Smart home automation is crucially beneficial for human life, particularly when considering those with disabilities, inpatients, and elderly populations. In this paper, applications and systems for smart homes are investigated. During experimentation they were controlled via an Android mobile phone and the Arduino platform. Bluetooth Module HC-06 was used to connect the Arduino Uno R3 with the mobile phone. Five smart home applications were developed to control the lighting and electrical sockets, fan speed, temperature- and humidity-meter display/controls, as well as the fire-alarm and toxic-gas alarm systems. Herein, the definition, the graphical user interface, the required main components, and the control circuit connections are prepared and presented for each application. The graphical user interface was created using the RemoteXY website, which is a reliable website for this purpose. The developed applications were tested, and they were found to work efficiently and correctly. Additionally, this innovative system is both cost-effective and affordable (total cost at the time of development was 110 USD).
Dysbiosis and Gastrointestinal Surgery: Current Insights and Future Research
Authors: Gibiino Giulia , Binda Cecilia , Cristofaro Ludovica , Sbrancia Monica , Coluccio Chiara , Petraroli Chiara , Jung Carlo Felix Maria , Cucchetti Alessandro , Cavaliere Davide , Ercolani Giorgio , Sambri Vittorio , Fabbri Carlo
Published: October 2022

Surgery of the gastrointestinal tract can result in deep changes among the gut commensals in terms of abundance, function and health consequences. Elective colorectal surgery can occur for neoplastic or inflammatory bowel disease; in these settings, microbiota imbalance is described as a preoperative condition, and it is linked to post-operative complications, as well. The study of bariatric patients led to several insights into the role of gut microbiota in obesity and after major surgical injuries. Preoperative dysbiosis and post-surgical microbiota reassessment are still poorly understood, and they could become a key part of preventing post-surgical complications. In the current review, we outline the most recent literature regarding agents and molecular pathways involved in pre- and post-operative dysbiosis in patients undergoing gastrointestinal surgery. Defining the standard method for microbiota assessment in these patients could set up the future approach and clinical practice.
Subarachnoid Hemorrhage in Patients with SARS-CoV-2 Infection: Protocol for A Scoping Review
Authors: Cornea Amalia , Simu Mihaela , Rosca Elena Cecilia
Published: October 2022

Subarachnoid hemorrhage (SAH) is a life-threatening condition associated with high mortality and substantial long-term morbidity. The SARS-CoV-2 virus is a new pathogen that causes a disease with variable clinical manifestations. Although the Coronavirus disease 2019 (COVID-19) is associated with hypercoagulopathy, patients may also present with cerebral hemorrhage, including SAH. The present paper reports a protocol for a scoping review that is aimed to provide a comprehensive report on existing literature by examining data on SAH associated with SARS-CoV-2 infection. Our objective is to evaluate the epidemiology, clinical, laboratory, and neuroimaging features of SAH in patients with COVID-19 and to explore the etiology and possible interventions in this pathology. Using appropriate search terms, we will search LitCOVID, the WHO database on COVID-19, and MedRxiv. The inclusion criteria are pre-defined. We will extract the data of eligible studies in standardized forms and will report the results in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). We will provide information for clinicians, healthcare providers, and public health specialists.
Profiles of Caregiver-Reported Executive Function in Children with Down Syndrome
Authors: Van Deusen Kaylyn , Prince Mark A. , Esbensen Anna J. , Edgin Jamie O. , Schworer Emily K. , Thurman Angela John , Patel Lina R. , Daunhauer Lisa A. , Fidler Deborah J.
Published: October 2022

Children with Down syndrome (DS) are at risk for challenges with aspects of executive function (EF). The current study explores whether heterogeneity in EF profiles can be detected within a sample of children with DS. Participants were 69 children with DS, ages 3–10 years (M = 6.23, SD = 1.91). T-scores from a caregiver-report measure of executive function were modeled using latent profile analysis, and auxiliary analyses examined the association between demographic and biomedical factors and probability of profile membership. The two-profile solution was the best fit for the sample, with a profile that involved elevated scores in working memory only (“Working Memory Only” profile; 43% of sample) and a “Multi-Domain” profile that involved elevated scores in planning, inhibition, and working memory (57%). The presence of congenital heart defects was associated with a higher probability of assignment to the Multi-Domain profile. Findings from this study contribute to the characterization of heterogeneous outcomes associated with DS.
The Link between ADHD Symptoms and Antisocial Behavior: The Moderating Role of the Protective Factor Sense of Coherence
Authors: Dayan Haym , Khoury-Kassabri Mona , Pollak Yehuda
Published: October 2022

Numerous studies have established the link between ADHD and antisocial behavior, one of the most serious functional impairments caused by the disorder. However, research on protective factors that mitigate this link is still lacking. The Salutogenic Model of Health offers the “Sense of Coherence” (SOC), establishing that individuals who see their lives as logical, meaningful, and manageable are more resistant to various risk factors and diseases. The present study examines for the first time whether SOC is also a protective factor against different ADHD-related types of antisocial behaviors (severe/mild violent behavior, verbal violence, property crimes, public disorder, and drug abuse). A total of 3180 participants aged 15–50 completed online questionnaires assessing the level of ADHD symptoms, antisocial behaviors, and SOC. Structural equation modeling was applied to examine the research hypothesis. An interaction between ADHD symptoms and SOC was found in predicting each type of antisocial behavior (beta = −0.06–−0.17, p < 0.01). The link between ADHD symptoms and antisocial behavior was significantly weaker for high than low SOC participants, regardless of age group. The current study found that people with high SOC are protected against the effect of ADHD symptoms on one of the most serious functional impairments, antisocial behavior. These findings suggest that SOC is a protective factor from the adverse effects of ADHD symptoms, justifying further prospective and intervention studies.
Sexual Differences in Addictions and Dual Disorders: Importance of Gender Perspective
Authors: Benito Ana , Rodríguez de Fonseca Fernando , Haro Gonzalo
Published: October 2022

Sex (the biological attributes of females and males) and gender (socially constructed roles, behaviours, and identities) both affect molecular and cellular processes, protective and vulnerability factors, social and relational life [...]
Clinical Characteristics and Prognostic Risk Factors of Parasellar Chondrosarcoma
Authors: Zhang Linpeng , Wang Chen , Qi Xueling , Zhang Xufei , Yan Changxiang , Liu Ning , Yang Yakun , Ren Ming , Liu Yabo , Fu Xiaojun , Han Song , Zeng Xianwei
Published: October 2022

Background: Parasellar chondrosarcomas are extremely rare. This study describes the characteristics of parasellar chondrosarcoma and analyzes the risk factors and prognosis based on the resection degree. Methods: Fifteen patients with pathologically diagnosed parasellar chondrosarcoma were retrospectively analyzed for the clinical data, surgical methods, and prognosis to identify relationships between the surgical resection degree, tumor recurrence, and imaging characteristics. Results: Twelve patients had eye dysfunction and ptosis. Differentiation from other parasellar tumors by imaging is difficult. The preoperative Karnofsky Performance Scale (KPS) score positively correlated with the tumor resection degree (p = 0.026) and negatively correlated with the maximum tumor diameter (p = 0.001). Tumor recurrence negatively correlated with the resection degree (p = 0.009). The postoperative KPS score positively correlated with the preoperative KPS score (p < 0.001) and tumor resection degree (p = 0.026), and negatively correlated with the maximum tumor diameter (p = 0.016) and age (p = 0.047). An improved KPS score positively correlated with the tumor resection degree (p = 0.039). Patients who underwent total resection of the chondrosarcoma had longer progression-free survival than those who underwent partial resection (p = 0.0322). Conclusion: Parasellar chondrosarcomas are difficult to resect completely. Preoperative KPS score is an important factor for the degree of resection. KPS score, age, maximum tumor diameter, and resection degree may be important prognostic factors.
Noninvasive Characterization of Functional Pathways in Layer-Specific Microcircuits of the Human Brain Using 7T fMRI
Authors: Deshpande Gopikrishna , Wang Yun
Published: October 2022

Layer-specific cortical microcircuits have been explored through invasive animal studies, yet it is not possible to reliably characterize them functionally and noninvasively in the human brain. However, recent advances in ultra-high-field functional magnetic resonance imaging (fMRI) have made it feasible to reasonably resolve layer-specific fMRI signals with sub-millimeter resolution. Here, we propose an experimental and analytical framework that enables the noninvasive functional characterization of layer-specific cortical microcircuits. Specifically, we illustrate this framework by characterizing layer-specific functional pathways in the corticogeniculate network of the human visual system by obtaining sub-millimeter fMRI at 7T using a task which engages the magnocellular pathway between the lateral geniculate nucleus (LGN) and the primary visual cortex. Our results demonstrate that: (i) center-surround inhibition in magnocellular neurons within LGN is detectable using localized fMRI responses; (ii) feedforward (LGN → layers VI/IV, layer IV → layer VI) and feedback (layer VI → LGN) functional pathways, known to exist from invasive animal studies, can be inferred using dynamic directional connectivity models of fMRI and could potentially explain the mechanism underlying center-surround inhibition as well as gain control by layer VI in the human visual system. Our framework is domain-neutral and could potentially be employed to investigate the layer-specific cortical microcircuits in other systems related to cognition, memory and language.
Risk of Cardiovascular Disease Death in Older Malignant Melanoma Patients: A Population-Based Study
Authors: Miao Jiapeng , Wang Yujie , Gu Xiaoyu , Lin Wenrui , Ouyang Zhen , Wang Mi , Chen Mingliang , Zhao Shuang , Wang Xianggui , Su Juan
Published: October 2022

Noncancer deaths account for a large proportion of deaths in patients with malignant melanoma (MM), but the risk of cardiovascular disease (CVD) death in older MM patients remains unclear. This study aimed to estimate the risk of CVD death in older MM patients. Data on older MM patients were obtained in the Surveillance, Epidemiology, and End Results database. Risk of CVD death was calculated by standardized mortality rates (SMRs), cumulative mortality and proportion of different causes of death. MM patients had a higher risk of CVD death than general populations (SMR = 1.98; 95% CI 1.93–2.03, p < 0.001). CVD death was more common in MM patients who were diagnosed at age 85 or older, had a localized stage, were white, had surgical treatment, had a primary head/neck/upper limb site and had a low-grade and superficial spreading/lentigo malignant pathologic type. Cumulative CVD mortality was more common than primary cancer in all older age groups, male or female, and patients with localized-stage disease. Other than primary cancer, CVD was the main cause of death in older patients diagnosed with MM. Our findings highlight CVD death is an important competing event of deaths in older MM patients, and more attention should be paid to reducing CVD death to improve survival.
High Hemin Concentration Induces Escape from Senescence of Normoxic and Hypoxic Colon Cancer Cells
Authors: Borkowska Agata , Olszewska Aleksandra , Skarzynska Weronika , Marciniak Marta , Skrzeszewski Maciej , Kieda Claudine , Was Halina
Published: October 2022

Hemoglobin from either red meat or bowel bleeding may promote oxidative stress and increase the risk of colorectal cancer (CRC). Additionally, solid cancers or their metastases may be present with localized bruising. Escape from therapy-induced senescence (TIS) might be one of the mechanisms of tumor re-growth. Therefore, we sought to study whether hemin can cause escape from TIS in CRC. To induce senescence, human colon cancer cells were exposed to a chemotherapeutic agent irinotecan (IRINO). Cells treated with IRINO exhibited common hallmarks of TIS. To mimic bleeding, colon cancer cells were additionally treated with hemin. High hemin concentration activated heme oxygenase-1 (HO-1), induced escape from TIS and epithelial-to-mesenchymal transition, and augmented progeny production. The effect was even stronger in hypoxic conditions. Similar results were obtained when TIS cells were treated with another prooxidant agent, H2O2. Silencing of antioxidative enzymes such as catalase (CAT) or glutathione peroxidase-1 (GPx-1) maintained colon cancer cells in a senescent state. Our study demonstrates that a high hemin concentration combined with an increased activity of antioxidative enzymes, especially HO-1, leads to escape from the senescence of colon cancer cells. Therefore, our observations could be used in targeted anti-cancer therapy.
Avoiding Pitfalls in Thermal Dose Effect Relationship Studies: A Review and Guide Forward
Authors: Carrapiço-Seabra Carolina , Curto Sergio , Franckena Martine , Rhoon Gerard C. Van
Published: October 2022

The challenge to explain the diffuse and unconclusive message reported by hyperthermia studies investigating the thermal dose parameter is still to be unravelled. In the present review, we investigated a wide range of technical and clinical parameters characterising hyperthermia treatment to better understand and improve the probability of detecting a thermal dose effect relationship in clinical studies. We performed a systematic literature review to obtain hyperthermia clinical studies investigating the associations of temperature and thermal dose parameters with treatment outcome or acute toxicity. Different hyperthermia characteristics were retrieved, and their influence on temperature and thermal dose parameters was assessed. In the literature, we found forty-eight articles investigating thermal dose effect relationships. These comprised a total of 4107 patients with different tumour pathologies. The association between thermal dose and treatment outcome was the investigated endpoint in 90% of the articles, while the correlation between thermal dose and toxicity was investigated in 50% of the articles. Significant associations between temperature-related parameters and treatment outcome were reported in 63% of the studies, while those between temperature-related parameters and toxicity were reported in 15% of the studies. One clear difficulty for advancement is that studies often omitted fundamental information regarding the clinical treatment, and among the different characteristics investigated, thermometry details were seldom and divergently reported. To overcome this, we propose a clear definition of the terms and characteristics that should be reported in clinical hyperthermia treatments. A consistent report of data will allow their use to further continue the quest for thermal dose effect relationships.
The Lung Microbiota and Lung Cancer: A Growing Relationship
Authors: Bou Zerdan Maroun , Kassab Joseph , Meouchy Paul , Haroun Elio , Nehme Rami , Bou Zerdan Morgan , Fahed Gracia , Petrosino Michael , Dutta Dibyendu , Graziano Stephen
Published: October 2022

The lung is home to a dynamic microbial population crucial to modulating immune balance. Interest in the role of the lung microbiota in disease pathogenesis and treatment has exponentially increased. In lung cancer, early studies suggested an important role of dysbiosis in tumor initiation and progression. These results have helped accelerate research into the lung microbiota as a potential diagnostic marker and therapeutic target. Microbiota signatures could represent diagnostic biomarkers of early-stage disease. Lung microbiota research is in its infancy with a limited number of studies and only single-center studies with a significant methodological variation. Large, multicenter longitudinal studies are needed to establish the clinical potential of this exciting field.
Identification of Novel MET Exon 14 Skipping Variants in Non-Small Cell Lung Cancer Patients: A Prototype Workflow Involving in Silico Prediction and RT-PCR
Authors: Das Riku , Jakubowski Maureen A. , Spildener Jessica , Cheng Yu-Wei
Published: October 2022

Background and aims: The MET exon 14 skipping (METex14) is an oncogenic driver mutation that provides a therapeutic opportunity in non-small cell lung cancer (NSCLCs) patients. This event often results from sequence changes at the MET canonical splicing sites. We characterize two novel non-canonical splicing site variants of MET that produce METex14. Materials and Methods: Two variants were identified in three advanced-stage NSCLC patients in a next-generation sequencing panel. The potential impact on splicing was predicted using in silico tools. METex14 mutation was confirmed using reverse transcription (RT)-PCR and a Sanger sequencing analysis on RNA extracted from stained cytology smears. Results: The interrogated MET (RefSeq ID NM_000245.3) variants include a single nucleotide substitution, c.3028+3A>T, in intron 14 and a deletion mutation, c.3012_3028del, in exon 14. The in silico prediction analysis exhibited reduced splicing strength in both variants compared with the MET normal transcript. The RT-PCR and subsequent Sanger sequencing analyses confirmed METex14 skipping in all three patients carrying these variants. Conclusion: This study reveals two non-canonical MET splice variants that cause exon 14 skipping, concurrently also proposes a clinical workflow for the classification of such non-canonical splicing site variants detected by routine DNA-based NGS test. It shows the usefulness of in silico prediction to identify potential METex14 driver mutation and exemplifies the opportunity of routine cytology slides for RNA-based testing.
Cell-Free DNA–Based Multi-Cancer Early Detection Test in an Asymptomatic Screening Population (NHS-Galleri): Design of a Pragmatic, Prospective Randomised Controlled Trial
Authors: Neal Richard D. , Johnson Peter , Clarke Christina A. , Hamilton Stephanie A. , Zhang Nan , Kumar Harpal , Swanton Charles , Sasieni Peter
Published: October 2022

We report the design of the NHS-Galleri trial (ISRCTN91431511), aiming to establish whether a multi-cancer early detection (MCED) test that screens asymptomatic individuals for cancer can reduce late-stage cancer incidence. This randomised controlled trial has invited approximately 1.5 million persons and enrolled over 140,000 from the general population of England (50–77 years; ≥3 years without cancer diagnosis or treatment; not undergoing investigation for suspected cancer). Blood is being collected at up to three annual visits. Following baseline blood collection, participants are randomised 1:1 to the intervention (blood tested by MCED test) or control (blood stored) arm. Only participants in the intervention arm with a cancer signal detected have results returned and are referred for urgent investigations and potential treatment. Remaining participants in both arms stay blinded and return for their next visit. Participants are encouraged to continue other NHS cancer screening programmes and seek help for new or unusual symptoms. The primary objective is to demonstrate a statistically significant reduction in the incidence rate of stage III and IV cancers diagnosed in the intervention versus control arm 3–4 years after randomisation. NHS-Galleri will help determine the clinical utility of population screening with an MCED test.
Effectiveness of Organized Mammography Screening for Different Breast Cancer Molecular Subtypes
Authors: Ding Lilu , Greuter Marcel J. W. , Truyen Inge , Goossens Mathijs , Van der Vegt Bert , De Schutter Harlinde , Van Hal Guido , de Bock Geertruida H.
Published: October 2022

Background: Screening program effectiveness is generally evaluated for breast cancer (BC) as one disease and without considering the regularity of participation, while this might have an impact on detection rate. Objectives: To evaluate the short-term effectiveness of a mammography screening program for the major molecular subtypes of invasive BC. Methods: All women who participated in the screening program and were diagnosed with screen-detected or interval BC in Flanders were included in the study (2008–2018). Molecular subtypes considered were luminal and luminal-HER2-positive, human epidermal growth factor receptor 2-positive, and triple-negative BC (TNBC). The relationship between the BC stage at diagnosis (early (I–II) versus advanced (III–IV)) and the method of detection (screen-detected or interval) and the relationship between the method of detection and participation regularity (regular versus irregular) were evaluated by multi-variable logistic regression models. All models were performed for each molecular subtype and adjusted for age. Results: Among the 12,318 included women, BC of luminal and luminal-HER2-positive subtypes accounted for 70.9% and 11.3%, respectively. Screen-detected BC was more likely to be diagnosed at early stages than interval BC with varied effect sizes for luminal, luminal-HER2-positive, and TNBC with OR:2.82 (95% CI: 2.45–3.25), OR:2.39 (95% CI: 1.77–3.24), and OR:2.29 (95% CI: 1.34–4.05), respectively. Regular participation was related to a higher likelihood of screening detection than irregular participation for luminal, luminal-HER2-positive, and TNBC with OR:1.21 (95% CI: 1.09–1.34), OR: 1.79 (95% CI: 1.38–2.33), and OR: 1.62 (95% CI: 1.10–2.41), respectively. Conclusions: Regular screening as compared to irregular screening is effective for all breast cancers except for the HER2 subtype.
Effect of Autotransfusion in HCC Surgery on Survival and Recurrence: A Systematic Review and Meta-Analysis
Authors: Murtha-Lemekhova Anastasia , Fuchs Juri , Ritscher Emil , Hoffmann Katrin
Published: October 2022

Background: The chronic blood shortage has forced clinicians to seek alternatives to allogeneic blood transfusions during surgery. Due to anatomic uniqueness resulting in a vast vasculature, liver surgery can lead to significant blood loss, and an estimated 30% of patients require blood transfusions in major hepatectomy. Allogeneic transfusion harbors the risk of an immunologic reaction. However, the hesitation to reinfuse a patient’s own blood during cancer surgery is reinforced by the potentiality of reintroducing and disseminating tumor cells into an individual undergoing curative treatment. Two methods of autotransfusions are common: autotransfusion after preoperative blood donation and intraoperative blood salvage (IBS). We aim to investigate the effect of autotransfusion on recurrence and survival rates of patients undergoing surgery for HCC. Methods: The protocol for this meta-analysis was registered at PROSPERO prior to data extraction. MEDLINE, Web of Science and Cochrane Library were searched for publications on liver surgery and blood salvage (autologous transfusion or intraoperative blood salvage). Comparative studies were included. Outcomes focused on long-term oncologic status and mortality. Hazard ratios (HR) estimated outcomes with a fixed-effects model. Risk of bias was assessed using ROBINS-I, and certainty of evidence was evaluated with GRADE. Separate analyses were performed for liver transplantation and hepatectomies. Results: Fifteen studies were included in the analysis (nine on transplantation and six on hepatectomies), and they comprised 2052 patients. Overall survival was comparable between patients who received intraoperative blood salvage (IBS) or not for liver transplantation (HR 1.13, 95% CI [0.89, 1.42] p = 0.31). Disease-free survival also was comparable (HR 0.97, 95% CI [0.76, 1.24], p = 0.83). Autotransfusion after prior donation was predominantly used in hepatectomy. Patients who received autotransfusion had a significantly better overall survival than the control (HR 0.71, 95% CI [0.58, 0.88], p = 0.002). Disease-free survival was also significantly higher in patients with autotransfusion (HR 0.88, 95% CI [0.80, 0.96], p = 0.005). Although overall, the certainty of evidence is low and included studies exhibited methodological heterogeneity, the heterogeneity of outcomes was low to moderate. Conclusion: Autotransfusion, including intraoperative blood salvage, does not adversely affect the overall or disease-free survival of patients with HCC undergoing resection or transplantation. The results of this meta-analysis justify a randomized-controlled trial regarding the feasibility and potential benefits of autotransfusion in HCC surgery.
Long-Term Breast Cancer Outcomes of Pregnancy-Associated Breast Cancer (PABC) in a Prospective Cohort
Authors: Jo Hyunji , Park Seri , Kim Hye Ryeon , Kim Hongsik , Hong Joohyun , Lee Jeong Eon , Yu Jonghan , Chae Byung Joo , Lee Se Kyung , Ryu Jai Min , Oh Soo-young , Choi Suk Joo , Kim Ji-Yeon , Ahn Jin Seok , Im Young-Hyuck , Nam Eun Mi , Nam Seok Jin , Park Yeon Hee
Published: October 2022

Background: Given that peak age of breast cancer (BC) is younger in Asians than in Western populations, relatively higher prevalence of pregnancy-associated breast cancer (PABC) has been reported. This study aimed to analyze the characteristics and clinical outcomes of PABC in Korea. Methods: We defined PABC as BC diagnosed during pregnancy or in the first postpartum year. We compared the clinicopathological characteristics and BC outcomes between patients with PABC and non-PABC patients in the prospective YBC cohort from Samsung Medical Center. Results: In total, 1492 patients were initially enrolled, and 1364 patients were included, of which 93 had PABC (6.8%). The median age of patients with PABC was 34 years. Hormone receptor expression was lower (64.6% vs 74.6%) and frequency of HER2 overexpression was higher (26.9% vs 17.6%) in patients with PABC than in non-PABC patients. The 5-year overall survival (OS) rates were 83.2% and 93.4% in patients with PABC and non-PABC patients, respectively (p < 0.001). The 5-year disease-free survival (DFS) rates were 72.2% and 83.8% in PABC and non-PABC patients. Conclusion: Compared to non-PABC patients, patients with PABC had poorer OS and DFS in this prospective cohort. Exploratory biomarker analysis for PABC is warranted.
Midostaurin Modulates Tumor Microenvironment and Enhances Efficacy of Anti-PD-1 against Colon Cancer
Authors: Lai Cheng-Ta , Chi Chih-Wen , Wu Shu-Hua , Shieh Hui-Ru , Yen Jiin-Cherng , Chen Yu-Jen
Published: October 2022

Immunotherapy modulating the tumor microenvironment (TME) immune function has a promising effect on various types of cancers, but it remains as a limited efficacy in colon cancer. Midostaurin (PKC412) has been used in the clinical treatment of fms-like tyrosine kinase 3 (FLT3)-mutant acute myeloid leukemia and has demonstrated immunomodulatory activity. We aimed to evaluate the effect of midostaurin on the modulation of TME and the efficacy of anti-programmed cell death protein 1 (PD-1) against colon cancer. Midostaurin inhibited the growth of murine CT26 and human HCT116 and SW480 cells with multinucleation and micronuclei formation in morphology examination. The cell cycle arrested in the G2/M phase and the formation of the polyploid phase was noted. The formation of cytosolic DNA, including double-strand and single-strand DNA, was increased. Midostaurin increased mRNA expressions of cGAS, IRF3, and IFNAR1 in colorectal adenocarcinoma cells and mouse spleen macrophages. The protein expressions of Trex-1, c-KIT, and Flt3, but not PKCα/β/γ and VEGFR1, were down-regulated in midostaurin-treated colorectal adenocarcinoma cells and macrophages. Trex-1 protein expression was abrogated after FLT3L activation. In vivo, the combination of midostaurin and anti-PD-1 exhibited the greatest growth inhibition on a CT26-implanted tumor without major toxicity. TME analysis demonstrated that midostaurin alone decreased Treg cells and increased neutrophils and inflammatory monocytes. NKG2D+ and PD-1 were suppressed and M1 macrophage was increased after combination therapy. When combined with anti-PD-1, STING and INFβ protein expression was elevated in the tumor. The oral administration of midostaurin may have the potential to enhance anti-PD-1 efficacy, accompanied by the modulation of cytosolic DNA-sensing signaling and tumor microenvironment.
Potential Role of Sphingolipidoses-Associated Lysosphingolipids in Cancer
Authors: Dubot Patricia , Astudillo Leonardo , Therville Nicole , Carrié Lorry , Pettazzoni Magali , Cheillan David , Stirnemann Jérôme , Levade Thierry , Andrieu-Abadie Nathalie , Sabourdy Frédérique
Published: October 2022

Sphingolipids play a key structural role in cellular membranes and/or act as signaling molecules. Inherited defects of their catabolism lead to lysosomal storage diseases called sphingolipidoses. Although progress has been made toward a better understanding of their pathophysiology, several issues still remain unsolved. In particular, whether lysosphingolipids, the deacylated form of sphingolipids, both of which accumulate in these diseases, are simple biomarkers or play an instrumental role is unclear. In the meanwhile, evidence has been provided for a high risk of developing malignancies in patients affected with Gaucher disease, the most common sphingolipidosis. This article aims at analyzing the potential involvement of lysosphingolipids in cancer. Knowledge about lysosphingolipids in the context of lysosomal storage diseases is summarized. Available data on the nature and prevalence of cancers in patients affected with sphingolipidoses are also reviewed. Then, studies investigating the biological effects of lysosphingolipids toward pro or antitumor pathways are discussed. Finally, original findings exploring the role of glucosylsphingosine in the development of melanoma are presented. While this lysosphingolipid may behave like a protumorigenic agent, further investigations in appropriate models are needed to elucidate the role of these peculiar lipids, not only in sphingolipidoses but also in malignant diseases in general.
Pharmacotherapy for Advanced Non-Small Cell Lung Cancer with Performance Status 2 without Druggable Gene Alterations: Could Immune Checkpoint Inhibitors Be a Game Changer?
Authors: Ikeda Satoshi , Naito Tateaki , Miura Satoru , Ito Kentaro , Furuya Naoki , Misumi Toshihiro , Ogura Takashi , Kato Terufumi
Published: October 2022

Most pivotal clinical trials in advanced non-small cell lung cancer (NSCLC) have excluded patients with poor performance status (PS), and data on the efficacy and safety of pharmacotherapy have not been fully accumulated. For NSCLC patients with PS 2 and without druggable genetic alterations, monotherapy with cytotoxic agents or carboplatin-based combination therapy is usually administered based on the results of several randomized trials. However, the evidence of cytotoxic chemotherapy for patients with PS 2 is insufficient, with limited efficacy and toxicity concerns. Immune checkpoint inhibitors (ICIs) are a promising treatment for patients with PS 2 because of lower incidence of severe toxicity compared to cytotoxic chemotherapy. Meanwhile, several reports suggest that anti-PD-1 antibodies monotherapy is less effective for patients with PS 2, especially for those with PS 2 caused by disease burden. Although the combination therapy of nivolumab and ipilimumab is a promising treatment option, there is a divergence in efficacy data between clinical trials. The standard of care for advanced NSCLC with PS 2 has not been established, and future therapeutic strategies should take into account the heterogeneity of the PS 2 population.
CD8A as a Prognostic and Immunotherapy Predictive Biomarker Can Be Evaluated by MRI Radiomics Features in Bladder Cancer
Authors: Zheng Zongtai , Guo Yadong , Huang Xiongsheng , Liu Ji , Wang Ruiliang , Qiu Xiaofu , Liu Shenghua
Published: October 2022

As an important member of T cytotoxic pathway-related genes, CD8a molecule (CD8A) may be a useful biomarker of immunotherapeutic response and immune cell infiltration. We aimed to investigate the clinical predictive value of CD8A in prognosis and tumor microenvironment (TME) and preoperatively predict the expression of CD8A using radiogenomics in bladder cancer (BCa). Among 12 T cytotoxic pathway-related genes, CD8A was a novel protective gene and had the highest correlations with T cells and Macrophages M1 in BCa. In advanced cancer patients treated with immunotherapy, low CD8A expression was associated with immunotherapeutic failure and poor survival outcomes. CD8A expression was highly related to tumor mutation burden, critical immune checkpoint genes and several types of tumor-infiltrating immune cells, predicting effective response to immunotherapy. The preoperative MRI radiomics features and RNA-sequence data of 111 BCa samples were used to develop a radiomics signature that achieved good performance in the prediction of CD8A expression in both the training (area under curve (AUC): 0.857) and validation sets (AUC: 0.844). CD8A is a novel indicator for predicting the prognosis and immunotherapeutic response in BCa. A radiomics signature has the potential to preoperatively predict the expression of CD8A in BCa patients.
Oncologic Imaging and Radiomics: A Walkthrough Review of Methodological Challenges
Authors: Stanzione Arnaldo , Cuocolo Renato , Ugga Lorenzo , Verde Francesco , Romeo Valeria , Brunetti Arturo , Maurea Simone
Published: October 2022

Imaging plays a crucial role in the management of oncologic patients, from the initial diagnosis to staging and treatment response monitoring. Recently, it has been suggested that its importance could be further increased by accessing a new layer of previously hidden quantitative data at the pixel level. Using a multi-step process, radiomics extracts potential biomarkers from medical images that could power decision support tools. Despite the growing interest and rising number of research articles being published, radiomics is still far from fulfilling its promise of guiding oncologic imaging toward personalized medicine. This is, at least partly, due to the heterogeneous methodological quality in radiomic research, caused by the complexity of the analysis pipelines. In this review, we aim to disentangle this complexity with a stepwise approach. Specifically, we focus on challenges to face during image preprocessing and segmentation, how to handle imbalanced classes and avoid information leaks, as well as strategies for the proper validation of findings.