bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival and risk factors associated with mortality in people living with HIV from 2005 to 2018 in Nanjing, China
Authors: Zhu Zhengping , Xu Yuanyuan , Wu Sushu , Li Xin , Shi Hongjie , Dong Xiaoxiao , Xu Wenjiong
Published: October 2022

Background

Although the introduction of antiretroviral therapy (ART) decreased the mortality of people living with Human Immunodeficiency Virus (PLHIV), substantially, hundreds of thousands of people are dying of AIDS each year. The accurate survival patterns and factors related to death among PLHIV were rarely reported. In this study, we evaluated survival status and identified factors associated with death among PLHIV in Nanjing.

Methods

We conducted a retrospective analysis of PLHIV followed-up in Nanjing and registered to the national HIV/AIDS comprehensive management information system from 2005 to 2018. We used the life table to calculate the cumulative survival rates. We applied the Kaplan-Meier to calculate median survival times and employed cox hazard proportional regression to analyze the associated factors related to death.

Results

The median survival time of PLHIV was 11.8 (95%CI:11.6–11.9) years from 2005 to 2018. Among 4,235 PLHIV included in this study, 7.5% had died of AIDS-related disease and the AIDS-related mortality rate was 2.0/100 PYs. The cumulative proportion surviving at the end of the interval was 95.2% over the 1st year, 94.0% over the 2nd year, 91.8% over the 5th year, and 85.4% over the 10th year, respectively. PLHIV who unaccepted ART showed a greater risk of death compared to those who accepted ART (AHR = 16.2, 95%CI:11.9~22.2). For baseline CD4 count, compared to CD4 < 200 cell/μL, higher CD4 count was demonstrated as a protective factor, with AHR = 0.2 (95%CI: 0.1~0.3) for ≥500 cell/μL, AHR = 0.3 (95%CI:0.2~0.4) for 350~499 cell/μL, AHR = 0.4 (95%CI:0.3~0.6 for 200~349 cell/μL). In addition, we observed a higher death risk in PLHIV who were screened through outpatient (AHR = 1.6, 95%CI: 1.1~2.2) and inpatient (AHR = 1.6, 95%CI: 1.1~2.5) compared to through VCT; the age of diagnosis was ≥50 years old (AHR = 9.5, 95%CI: 3.7~24.1) and 25~49 years old (AHR = 5.0, 95%CI: 2.0~12.3) compared to ≤ 24 years old; educated from junior and below (AHR = 3.4, 95%CI: 2.3~5.1) and Senior high school (AHR = 1.7, 95%CI: 1.1~2.7) compared to college and above.

Conclusion

The AIDS-related mortality among PLHIV in Nanjing was relatively low. A higher risk for AIDS-related deaths were observed among PLHIV who unaccepted ART, whose baseline CD4 cell count was<200 cell/μL, older age, and lower educated.
The role of perireceptor events in flavor perception
Authors: Boichot Valentin , Muradova Mariam , Nivet Clément , Proskura Alena , Heydel Jean-Marie , Canivenc-Lavier Marie-Chantal , Canon Francis , Neiers Fabrice , Schwartz Mathieu
Published: October 2022

The sensory perception of food is a complex phenomenon involving the integration of different stimuli (aroma, taste, trigeminal sensations, texture and visual). Flavor compounds activate odorant, taste and trigeminal chemoreceptors, generating a depolarization of the sensory neurons and then the consciousness of food flavor perception. Recent studies are increasingly highlighting the importance of perireceptor events, which include all the molecular events surrounding the receptors, in the modulation of flavor perception. These events affect the quantity and quality of flavor compounds in the environment of chemoreceptors. They include the metabolization of flavor compounds by enzymes present in biological fluids (saliva and mucus) and the oronasal epithelia and noncovalent interactions with binding proteins. Perireceptor mechanisms have been extensively studied in insects and mammals, demonstrating the importance of the entailed processes in the termination of the chemical signal. In humans, research is in full swing. Here, we reviewed the perireceptor mechanisms recently reported in vitro, in biological fluids and in cells and in vivo in humans. These studies indicate that perireceptor mechanisms likely have an important contribution to flavor perception. This mini-review focuses on recent pioneering studies that are paving the way for this new research area. It also suggests that new approaches taking into account the real conditions of food consumption will be required in the future to accurately address this question.
Ex vivo culture of malignant primary B cells
Authors: Canonne Morgane , George Fabienne , Graux Carlos
Published: October 2022

Mature B cell malignancies constitute a wide range of biologically and clinically heterogeneous hematological diseases. Despite an increasingly thorough understanding of the pathophysiology of these pathologies and significant improvements in therapies, a dismal outcome still affects a large number of patients. Therefore, further investigations into new treatment perspectives are highly needed and they depend entirely on theex vivoculture of patient cells. Primary cells usually demand superior culture models, as they are notoriously difficult to cultivate. The literature is not devoid of approaches ranging from two- to three-dimensional systems for culturing mature malignant primary B cells. However, they display substantial protocol inter-variation. This imposes a high risk of failures, repeats, and inconsistent results, which are neither compatible with the rare value of primary cells nor the efficiency of the drug discovery process. In this review, we provide a thorough overview of the different approaches that have been implemented in the literature for the culture of mature malignant primary B cells, and we discuss associated considerations and limitations to assist researchers in determining a fit-for-purpose culture system, thereby attempting to reduce the number of trials and errors as well as associated biomaterial expenditure.
E-cycling and health benefits: A systematic literature review with meta-analyses
Authors: Riiser Amund , Bere Elling , Andersen Lars Bo , Nordengen Solveig
Published: October 2022

The objective of the present study is to review and meta-analyze the effect of E-cycling on health outcomes. We included longitudinal experimental and cohort studies investigating the effect of E-cycling on health outcomes. The studies were identified from the seven electronic databases: Web of Science, Scopus, Medline, Embase, PsycINFO, Cinahl and SportDiscus and risk of bias was assessed with the revised Cochrane Collaboration Risk of Bias Tool (RoB2). We performed meta-analysis with random effects models on outcomes presented in more than one study. Our study includes one randomized controlled trial, five quasi experimental trials and two longitudinal cohort studies. The trials included 214 subjects of whom 77 were included in control groups, and the cohort studies included 10,222 respondents at baseline. Maximal oxygen consumption and maximal power output were assessed in four and tree trials including 78 and 57 subjects, respectively. E-cycling increased maximal oxygen consumption and maximal power output with 0.48 SMD (95%CI 0.16–0.80) and 0.62 SMD (95%CI 0.24–0.99). One trial reported a decrease in 2-h post plasma glucoses from 5.53 ± 1.18 to 5.03 ± 0.91 mmol L−1 and one cohort study reported that obese respondents performed 0.21 times more trips on E-bike than respondents with normal weight. All the included studies had a high risk of bias due to flaws in randomization. However, the outcomes investigated in most studies showed that E-cycling can improve health.
Dynamics of microbiota and physicochemical characterization of food waste in a new type of composter
Authors: Gaspar Suelen S. , Assis Lucas L. R. , Carvalho Carla A. , Buttrós Victor Hugo , Ferreira Gustavo Magno dos Reis , Schwan Rosane F. , Pasqual Moacir , Rodrigues Filipe Almendagna , Rigobelo Everlon Cid , Castro Rafael Peron , Dória Joyce
Published: October 2022

Organic wastes are considered the most significant components of urban solid waste, negatively affecting the environment. It is essential to use renewable resources to minimize environmental risks. Composting is one of the most sustainable methods for managing organic waste and involves transforming organic matter into a stable and nutrient-enriched biofertilizer, through the succession of microbial populations into a stabilized product. This work aimed to evaluate the efficiency of the new type of composter and the microbial and physiochemical dynamics during composting aiming to accelerate the degradation of organic waste and produce high-quality compost. Two inoculants were evaluated: (1) efficient microorganisms (EM); (2) commercial inoculum (CI), which were compared to a control treatment, without inoculation. Composting was performed by mixing organic waste from gardening with residues from the University's Restaurant (C/N ratio 30:1). The composting process was carried out in a 1 m3 composter with controlled temperature and aeration. The thermophilic phase for all treatments was reached on the second day. Mature compost was obtained after an average of 120 days, and composting in all treatments showed an increase in the availability of P and micronutrients. The new composter helped to accelerate the decomposition of residues, through the maintenance of adequate oxygen content and temperature control inside the cells, providing high metabolic activity of microorganisms, contributing to an increase in physicochemical characteristics, also reducing the composting time in both treatments. During composting, the bacteria and actinobacteria populations were higher than yeasts and filamentous fungi. The inoculated treatments presented advantages showing more significant mineralization of P-available and micronutrients such as Mn and Zn in terms of the quality of the final product in comparison to the control treatment. Finally, the new composter and the addition of inoculants contributed significantly to the efficiency of the process of composting organic waste.
Ultrasonographic changes in fetal gastrointestinal motility during the last ten days before parturition in dogs
Authors: Siena Giulia , Romagnoli Stefano , Drigo Michele , Contiero Barbara , di Nardo Francesca , Milani Chiara
Published: October 2022

Fetal gastrointestinal motility (FGM) was suggested as useful to assess fetal maturity. Our study aimed to quantify FGM in relation to days before parturition (DBP), maternal size, and sex ratio of pups. During the last ten days of pregnancy, 23 clinically healthy pregnant bitches of 16 different breeds ranging in age from 2 to 9 years and body weight from 3.5 to 56.8 kg were monitored twice. The fetal intestine was observed in longitudinal and transversal scan on 3 of the most caudal fetuses in both uterine horns. Gestational age was counted backward from parturition day. The number of fetuses showing FGM was recorded in time in I (−11/−5 DBP) and II (−4/0 DBP). A Mann–Whitney test was performed to analyze variations of FGM% in relation to time and parity. A Kruskal–Wallis test was performed to identify variations of FGM% in relation to maternal size and sex ratio. Statistical significance was set at α = 0.05. A total of 147 FGM observations on 50 ultrasonographic monitoring points were performed. The FGM% was higher during time II compared to time I (median: 33%, range 0–100% vs. 100%, range 33–100%;P< 0.0001). FGM% was higher in small compared to large size bitches (median: 100%, range 67–100% vs. 67%, range 0–100%;P= 0.01). FGM% was not affected by parity and sex ratio. As previously reported, a significant increase in FGM% was observed in the last five DBP. FGM observation may be influenced by the maternal size, with easier evaluation in small size bitches, as well as ultrasound equipment and positioning.
“Non-healing” claw horn lesions in dairy cows: Clinical, histopathological and molecular biological characterization of four cases
Authors: Alsaaod Maher , Weber Jim , Jensen Tim , Brandt Sabine , Gurtner Corinne , Devaux David , Studer Eveline , Steiner Adrian
Published: October 2022

The increasing prevalence of bovine digital dermatitis (BDD) contributes to a higher occurrence of secondary infections of exposed corium with Treponema spp. in bovine claws. “Non-healing” claw horn lesions (NHL) clinically resemble BDD lesions. They are severe, cause chronic lameness, and may persist for several months. They poorly respond to standard treatments of BDD and represent a serious welfare issue. In this study, four cases of NHL were classified clinically either as BDD-associated axial horn fissures (BDD-HFA; n = 3) or BDD-associated sole ulcer (BDD-SU; n = 1). In all four cases, pronounced multifocal keratinolysis of the stratum corneum, ulceration, and severe chronic lymphoplasmacytic perivascular to interstitial dermatitis were observed. All lesional samples tested positive for Treponema spp., Fusobacterium (F.) necrophorum, and Porphyromonas (P.) levii by PCRs. BDD-HFA lesions contained Treponema pedis as revealed by genetic identities of 93, 99, and 100%. Treponemes in the BDD-SU lesion were 94% homologous to Treponema phylotype PT3. Fluorescent in situ hybridization (FISH) revealed extensive epidermal infiltration by treponemes that made up > 90% of the total bacterial population in all four lesions. FISH also tested positive for P. levii and negative for F. necrophorum in all four cases, whilst only one BDD-HFA contained Dichelobacter nodosus. Our data point to BDD-associated treponemes and P. levii constituting potential etiological agents in the development of “non-healing” claw horn lesions in cattle.
Case report: Three-dimensionally printed patient-specific acetabular cage for revision surgery of aseptic loosening in a dog with micro total hip replacement
Authors: Kang AhRan , Lee Haebeom , Roh Yoonho , Kim Daehyun , Jeong Seong Mok , Jeong Jaemin
Published: October 2022

A 2-year-old castrated male Pomeranian dog was presented for regular follow-up after micro total hip replacement (mTHR) 16 months prior to presentation. Clinically, the dog did not show any noticeable lameness of the left hindlimb, except for external rotation during walking. However, radiographic findings, namely rotation and medialization of the acetabular cup with a periprosthetic lucent line and bone formation medial to the acetabulum, were interpreted as aseptic loosening of the acetabular component. Because the dog was incompatible with the conventional THR revision method owing to severe bone defects in the acetabulum, a patient-specific titanium acetabular cage prosthesis with biflanges and four cranial and one caudal screw hole was designed for revision surgery. A custom-made acetabular cage was prepared, and it had a 12-mm polyethylene cup fixed with polymethylmethacrylate bone cement and positioned in the acetabulum. After the custom-made acetabular cage was anchored to the pelvic bone with the five cortical screws, reduction of the prostheses was achieved smoothly. The dog showed almost normal limb function without external rotation of the left hindlimb 2 weeks postoperatively. Bone remodeling and stable implant position were noted on radiographic images 3 years after revision surgery, with no evidence of loosening. Based on the clinical outcomes, the use of a custom-made acetabular prosthesis can be an effective treatment option for revision arthroplasty in acetabula with severe bone loss and structural changes in small-breed dogs.
Weibull-Open-World (WOW) Multi-Type Novelty Detection in CartPole3D
Authors: Boult Terrance E. , Windesheim Nicolas M. , Zhou Steven , Pereyda Christopher , Holder Lawrence B.
Published: October 2022

Algorithms for automated novelty detection and management are of growing interest but must address the inherent uncertainty from variations in non-novel environments while detecting the changes from the novelty. This paper expands on a recent unified framework to develop an operational theory for novelty that includes multiple (sub)types of novelty. As an example, this paper explores the problem of multi-type novelty detection in a 3D version of CartPole, wherein the cart Weibull-Open-World control-agent (WOW-agent) is confronted by different sub-types/levels of novelty from multiple independent agents moving in the environment. The WOW-agent must balance the pole and detect and characterize the novelties while adapting to maintain that balance. The approach develops static, dynamic, and prediction-error measures of dissimilarity to address different signals/sources of novelty. The WOW-agent uses the Extreme Value Theory, applied per dimension of the dissimilarity measures, to detect outliers and combines different dimensions to characterize the novelty. In blind/sequestered testing, the system detects nearly 100% of the non-nuisance novelties, detects many nuisance novelties, and shows it is better than novelty detection using a Gaussian-based approach. We also show the WOW-agent’s lookahead collision avoiding control is significantly better than a baseline Deep-Q-learning Networktrained controller.
Optimal Design of a New Rotating Magnetic Beacon Structure Based on Halbach Array
Authors: Li Bo , Yang Binfeng , Xiang Fenghua , Guo Jiaojiao
Published: October 2022

At present, the magnetic signals generated by the common artificial magnetic beacons change periodically with sinusoidal law, and there is a multi-value problem in measuring the target orientation by using the phase information of the magnetic signals. According to the characteristics of Halbach array, a kind of artificial magnetic beacon based on Halbach array is studied. This beacon has the characteristics of magnetic signal aggregation, which can avoid the multi-value problem and facilitate the extraction of phase information. Firstly, the array model is established with MATLAB, the magnetization direction of each permanent magnet is adjusted, and particle swarm optimization is used to find the structural parameters with the strongest magnetic field characteristics. Finally, COMSOL physical simulation software is used to verify the usability of the proposed structure.
Comparison of Fitting Current–Voltage Characteristics Curves of FinFET Transistors with Various Fixed Parameters
Authors: Yang Hsin-Chia , Chi Sung-Ching , Liao Wen-Shiang
Published: October 2022

In the deep submicron regime, FinFET successfully suppresses the leakage current using a 3D fin-like channel substrate, which gets depleted and blocks possible leakage as the gate is applied with a bias wholly wrapping the channel. Fortunately, a scanning photo-lithography using extensive ultraviolet (EUV) and multi-mask task carefully resolves critical dimension issues. The ensuing anisotropic plasma dry etching is somehow a subsequent challenging process, which consumes the edge of original ‘I’-shape epitaxial silicon and causes dimension loss, and thus produces fin-like bodies as prepared channels. In order to protect the transistors from malfunction due to dimension over-etching, fin width is taken to be 120 nanometers, while the channel lengths vary. The prepared transistors are measured and characteristic curves are fitted for analysis. Measured current versus voltage characteristic curves are fitted with three parameters (transistor geometry constant, threshold voltage, and Early voltage) in the conventional current-voltage formula, which are allowed to vary as the short channel effects or process-related issues are taken into account. In this paper, one of the three is deliberately set to be fixed for a transistor, and the others are freely chosen and determined to reach minimum variation. Various conclusions through comparisons and analysis may give important feasible applications in the future.
Projecting Changes in Rainfall Extremes for the Huai River Basin in the Context of 1.5 °C and 2 °C Global Warming
Authors: Wang Yueyang , Wang Yanjun , Wang Yan , Ju Qin , Jin Junliang , Bao Zhenxin
Published: October 2022

It is indisputable that global warming has triggered more frequent extreme weather and in turn led to severe flood disasters. To understand the trend of extreme rainfall under 1.5 °C and 2 °C warming, we investigated the historical variation and future trends in extreme rainfall for the Huai River basin, which has frequently been hit by floods, using recorded meteorological data and a projection of five General Circulation Models in the Coupled Model Intercomparison Project 6. We used the years 1995–2014 as the baseline period to study the temporal and spatial changes in extreme rainfall under 1.5 °C and 2.0 °C warming scenarios. The results indicated that (1) temperatures in the Huai River basin have risen significantly from 1995 to 2014, but there are insignificant variation trends in annual precipitation (AP), intensive precipitation (R95P), maximum daily precipitation (Rx1d) and heavy rain days (Rr50) during the same time span. (2) From 2015 to 2100, both temperature and extreme rainfall indices show increase trends, with a higher rate of increase under a higher emission scenario. (3) Under the warming scenario of 1.5 °C, AP, R95P, Rx1d and Rr50 in the basin will likely increase by 4.6%, 5.7%, 6.2% and 13.4%, respectively, compared with that in the baseline period. Under the warming scenario of 2.0 °C, AP, R95P, Rx1d and Rr50 will probably increase by 7.3%, 7.4%, 10.9% and 19.0%, respectively. (4) Spatially, the changes in extreme rainfall indices under the warming scenarios of 1.5 °C and 2.0 °C generally tend to increase from north to south. Higher intensity extreme rainfall will likely extend to the whole of the Huai River basin. It is therefore essential to study adaptive measures to cope with flooding in the Huai River basin induced by the increase in future rainfall extremes.
Pollution Characteristics of Water-Soluble Inorganic Ions in PM2.5 from a Mountainous City in Southwest China
Authors: Huang Yimin , Zhang Liuyi , Peng Chao , Chen Yang , Li Tingzhen , Yang Fumo
Published: October 2022

In order to explore the characteristics of water-soluble inorganic ions (WSIIs) in the atmosphere of Wanzhou, a small mountainous city in Chongqing, four representative seasonal PM2.5 samples and gaseous precursors (SO2 and NO2) were collected from April 2016 to January 2017. The WSIIs (including Cl−, NO3−, SO42−, Na+, NH4 +, K+, Mg2+, and Ca2+) were analyzed by ion chromatography. During the sampling period, daily PM2.5 concentration varied from 3.47 to 156.30 μg·m−3, with an average value of 33.38 μg·m−3, which was lower than the second-level annual limit of NAAQS-China. WSIIs accounted for 55.6% of PM2.5, and 83.1% of them were secondary inorganic ions (SNA, including SO42−, NO3−, and NH4+). The seasonal variations of PM2.5 and WSIIs were similar, with the minimum in summer and the maximum in winter. PM2.5 samples were the most alkaline in summer, weakly alkaline in spring and winter, and close to neutral in fall. The annual average ratio of NO3−/SO42− was 0.54, indicating predominant stationary sources for SNA in Wanzhou. NO3−, SO42−, and NH4+ mainly existed in the form of (NH4)2SO4 and NH4NO3. The results of the principal component analysis (PCA) showed that the major sources of WSIIs in Wanzhou were the mixture of secondary inorganic aerosols, coal combustion, automobile exhaust (49.53%), dust (23.16%), and agriculture activities (9.68%). The results of the backward trajectory analysis showed that aerosol pollution in Wanzhou was mainly caused by local emissions. The enhanced formation of SNA through homogeneous and heterogeneous reactions contributed to the winter PM2.5 pollution event in Wanzhou.
Analysis of the Sporadic-E Layer Behavior in Different American Stations during the Days around the September 2017 Geomagnetic Storm
Authors: Resende Laysa C. A. , Zhu Yajun , Arras Christina , Denardini Clezio M. , Chen Sony S. , Moro Juliano , Barros Diego , Chagas Ronan A. J. , Da Silva Lígia A. , Andrioli Vânia F. , Marchezi José P. , Carrasco Alexander J. , Wang Chi , Li Hui , Liu Zhengkuan
Published: October 2022

The development of sporadic-E (Es) layers over five Digisonde stations in the American sector is analyzed. This work aims to investigate the dynamic of such layers during the days around the geomagnetic storm that occurred on 8 September 2017. Therefore, a numerical model (MIRE) and Radio Occultation (RO) technique are used to analyze the E layer dynamics. The results show a downward movement in low-middle latitudes due to the wind components that had no significant changes before, during, and after the geomagnetic storm. In fact, our data and simulations showed weak Es layers over Boulder, Cachoeira Paulista, and Santa Maria, even though the winds were not low. However, the RO data show the terdiurnal and quarterdiurnal influence in the Es layer formation, which can explain this behavior. In addition, we observed an atypical Es layer type, slant Es layer (Ess), during the main phase of the magnetic storm over Boulder. The possible cause of the Ess layers was gravity waves. Another interesting point is the spreading Es layer occurrence associated with the Kelvin–Helmholtz Instability (KHI). Finally, it is confirmed that the disturbed electric field only influenced the Es layer dynamics in regions near the magnetic equator.
L-Shell Ionization Cross Sections for Silver by Low-Energy Electron Impacts
Authors: Mukoyama Takeshi , Tőkési Károly
Published: October 2022

The L-subshell ionization cross sections and total L–X-ray production cross sections for the Ag atom by the electron impact near the ionization threshold were calculated with a classical-trajectory Monte Carlo method. The results were compared with experimental data, quantum mechanical calculations, and the cross sections by positron impact. It was demonstrated that the classical treatments are useful for electron–atom collisions at energies higher than about six times the binding energies of target electrons but overestimate L-shell ionization and L–X-ray production cross sections at low energies near the threshold. Possible reasons for this discrepancy are discussed.
External Validation of the Colon Life Nomogram for Predicting 12-Week Mortality in Dutch Metastatic Colorectal Cancer Patients Treated with Trifluridine/Tipiracil in Daily Practice
Authors: Hamers Patricia A. H. , Wensink G. Emerens , van Smeden Maarten , Vink Geraldine R. , Smabers Lidwien P. , Lunenberg Renee A. , Laclé Miangela M. , Koopman Miriam , May Anne M. , Roodhart Jeanine M. L.
Published: October 2022

Background: Predicting prognosis in refractory metastatic colorectal cancer (mCRC) patients is needed to guide decision making. The Colon Life nomogram was developed to predict 12-week mortality in refractory mCRC patients. The aim of this study is to validate the Colon Life nomogram in last line/refractory patients receiving trifluridine/tipiracil (FTD/TPI) in daily practice. Methods: The validation cohort consists of 150 QUALITAS study patients, an observational substudy of the Prospective Dutch CRC cohort, who were treated with FTD/TPI between 2016 and 2019. Model performance was assessed on discrimination, calibration, and clinical usefulness. The additional prognostic value of baseline quality of life (QoL) and thymidine kinase (TK1) expression in tissue was explored. Results: Of the 150 patients, 25 (16.7%) died within 12 weeks of starting FTD/TPI treatment. The C-statistic was 0.63 (95% C.I. 0.56–0.70). The observed/expected ratio was 0.52 (0.37–0.73). The calibration intercept and slope were −1.06 (−1.53 to −0.58) and 0.41 (0.01–0.81), respectively, which indicated overestimation of 12-week mortality by the nomogram. Decision curve analysis showed the nomogram did not yield a positive net benefit at clinically meaningful thresholds for predicted 12-week mortality. Addition of QoL to the nomogram improved the C-statistic to 0.85 (0.81–0.89). TK1 expression was associated with progression-free survival but not with overall survival. Conclusion: We demonstrated evident miscalibration of the Colon Life nomogram upon external validation, which hampers its use in clinical practice. We recommend conducting a study with a sufficiently large sample size to update the Colon Life nomogram or to develop a new model including QoL.
Impact of T790M Mutation Status on Later-Line Osimertinib Treatment in Non-Small Cell Lung Cancer Patients
Authors: Tang Yan-Jei , Chang John Wen-Cheng , Chang Ching-Fu , Huang Chen-Yang , Yang Cheng-Ta , Kuo Chih-Hsi Scott , Fang Yueh-Fu , Hsu Ping-Chih , Wu Chiao-En
Published: October 2022

Background: Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) designed to overcome acquired T790M resistance mutations in non-small cell lung cancer (NSCLC). However, the efficacy of osimertinib in patients without acquired T790M mutations has not been well studied. This study aimed to evaluate the efficacy of osimertinib in patients treated with first- and second-generation EGFR-TKIs followed by later-line osimertinib treatment. Patients: The clinical data and survival outcomes of 172 patients with advanced NSCLC treated with osimertinib following frontline EGFR-TKIs at Chang Gung Memorial Hospital from 2014 to 2018 were retrospectively reviewed. T790M mutations were detected using tissue sequencing and/or liquid biopsy. Results: A total of 172 EGFR-mutated NSCLC patients treated with frontline EGFR-TKI therapy followed by later-line osimertinib were enrolled in the current study and divided into three groups based on the T790M status (positive, negative, or unknown T790M). Patients with NSCLC harboring acquired T790M mutation treated with osimertinib had the best objective response rate (ORR) (52.6%, 25.0%, and 32.0%, p = 0.044), disease control rate (DCR) (79.3%, 41.7%, and 68.0%, p = 0.011), and progression-free survival (PFS, median PFS, 12.6, 3.1, 10.4 months, p = 0.001) among the three groups (positive, negative, and unknown T790M, respectively). However, a marked difference was found between positive and negative T790M mutations but not between positive and unknown T790M mutations. Univariate analysis was performed to identify potential prognostic factors for PFS in 172 patients treated with osimertinib. Lung metastasis (p < 0.001), brain metastasis (p < 0.009), number of metastatic sites (p < 0.001), PFS with frontline EGFR-TKIs (p = 0.03), and T790M status (p = 0.006) were identified as prognostic factors for PFS with osimertinib. Multivariate analysis showed that lung metastasis (p < 0.001) and PFS with frontline EGFR-TKIs and T790M status were independent prognostic factors. Conclusion: This study confirmed the greater efficacy of later-line osimertinib for NSCLC with acquired T790M mutation than for NSCLC without acquired T790M mutation. Detection of the T790M mutation after frontline treatment (first- and second-generation EGFR-TKI) is crucial for prolonging the survival of NSCLC patients harboring EGFR mutation. Osimertinib may be considered an option for NSCLC with unknown T790M mutations, as a certain subpopulation may benefit from osimertinib.
Women with Cervical High-Risk Human Papillomavirus: Be Aware of Your Anus! The ANGY Cross-Sectional Clinical Study
Authors: Jacot-Guillarmod Martine , Balaya Vincent , Mathis Jérôme , Hübner Martin , Grass Fabian , Cavassini Matthias , Sempoux Christine , Mathevet Patrice , Pache Basile
Published: October 2022

Anogenital human papillomaviruses (HPV) are highly prevalent in sexually active populations, with HR-HPV being associated with dysplasia and cancers. The consequences of cervical HPV infection are well-known, whereas those of the anus are less clear. The correlation of cervical and anal HPVs with the increasing number of anal cancers in women has not been studied yet. The objective of our prospective study was to determine whether cervical and anal HPV correlated in a cohort of women recruited in a university hospital in Switzerland. Recruitment was conducted in the gynecology clinic, the colposcopy clinic, and the HIV clinic. Cervical and anal HPV genotyping and cytology were performed. Overall, 275 patients were included (360 were initially planned), and among them, 102 (37%) had cervical HR-HPV. Patients with cervical HR-HPV compared to patients without cervical HR-HPV were significantly younger (39 vs. 44 yrs, p < 0.001), had earlier sexual intercourse (17.2 vs. 18.3 yrs, p < 0.01), had more sexual partners (2.9 vs. 2.2, p < 0.0001), more dysplastic cervical cytology findings (42% vs. 19%, p < 0.0001) and higher prevalence of anal HR-HPV (59% vs. 24%, p < 0.0001). Furthermore, the HR-HPV group reported more anal intercourse (44% vs. 29%, p < 0.015). Multivariate analysis retained anal HR-HPV as independent risk factor for cervical HR-HPV (OR3.3, CI 1.2–9.0, p = 0.02). The results of this study emphasize that it is of upmost importance to screen women for anal HR-HPV when diagnosing cervical HR-HPV.
Compound C Inhibits Ovarian Cancer Progression via PI3K-AKT-mTOR-NFκB Pathway
Authors: Ghoneum Alia , Gonzalez Daniela , Afify Hesham , Shu Junjun , Hegarty Abigail , Adisa Jemima , Kelly Michael , Lentz Samuel , Salsbury Freddie , Said Neveen
Published: October 2022

Epithelial Ovarian cancer (OvCa) is the leading cause of death from gynecologic malignancies in the United States, with most patients diagnosed at late stages. High-grade serous cancer (HGSC) is the most common and lethal subtype. Despite aggressive surgical debulking and chemotherapy, recurrence of chemo-resistant disease occurs in ~80% of patients. Thus, developing therapeutics that not only targets OvCa cell survival, but also target their interactions within their unique peritoneal tumor microenvironment (TME) is warranted. Herein, we report therapeutic efficacy of compound C (also known as dorsomorphin) with a novel mechanism of action in OvCa. We found that CC not only inhibited OvCa growth and invasiveness, but also blunted their reciprocal crosstalk with macrophages, and mesothelial cells. Mechanistic studies indicated that compound C exerts its effects on OvCa cells through inhibition of PI3K-AKT-NFκB pathways, whereas in macrophages and mesothelial cells, CC inhibited cancer-cell-induced canonical NFκB activation. We further validated the specificity of the PI3K-AKT-NFκB as targets of compound C by overexpression of constitutively active subunits as well as computational modeling. In addition, real-time monitoring of OvCa cellular bioenergetics revealed that compound C inhibits ATP production, mitochondrial respiration, and non-mitochondrial oxygen consumption. Importantly, compound C significantly decreased tumor burden of OvCa xenografts in nude mice and increased their sensitivity to cisplatin-treatment. Moreover, compound C re-sensitized patient-derived resistant cells to cisplatin. Together, our findings highlight compound C as a potent multi-faceted therapeutic in OvCa.
A Clinically Significant Prostate Cancer Predictive Model Using Digital Rectal Examination Prostate Volume Category to Stratify Initial Prostate Cancer Suspicion and Reduce Magnetic Resonance Imaging Demand
Authors: Morote Juan , Borque-Fernando Ángel , Triquell Marina , Campistol Miriam , Celma Anna , Regis Lucas , Abascal José M. , Servian Pol , Planas Jacques , Mendez Olga , Esteban Luis M. , Trilla Enrique
Published: October 2022

A predictive model including age, PCa family history, biopsy status (initial vs repeat), DRE (normal vs abnormal), serum prostate-specific antigen (PSA), and DRE prostate volume ca-tegory was developed to stratify initial PCa suspicion in 1486 men with PSA > 3 ng/mL and/or abnormal DRE, in whom mpMRI followed; 2- to 4-core TRUS-guided biopsies where Prostate Imaging Report and Data System (PI-RADS) > 3 lesions and/or 12-core TRUS systematic biopsies were performed in one academic institution between 1 January 2016–31 December 2019. The csPCa detection rate, defined as International Society of Uro-Pathology grade group 2 or higher, was 36.9%. An external validation of designed BCN-RC 1 was carried out on 946 men from two other institutions in the same metropolitan area, using the same criteria of PCa suspicion and diagnostic approach, yielded a csPCa detection rate of 40.8%. The areas under the receiver operating characteristic curves of BCN-RC 1 were 0.823 (95% CI: 0.800–0.846) in the development cohort and 0.837 (95% CI: 0.811–0.863) in the validation cohort (p = 0.447). In both cohorts, BCN-RC 1 exhibited net benefit over performing mpMRI in all men from 8 and 12% risk thresholds, respectively. At 0.95 sensitivity of csPCa, the specificities of BCN-RC 1 were 0.24 (95% CI: 0.22–0.26) in the development cohort and 0.34 (95% CI: 0.31–0.37) in the validation cohort (p < 0.001). The percentages of avoided mpMRI scans were 17.2% in the development cohort and 22.3% in the validation cohort, missing between 1.8% and 2% of csPCa among men at risk of PCa. In summary, BCN-RC 1 can stratify initial PCa suspicion, reducing the demand of mpMRI, with an acceptable loss of csPCa.
The Role of ctDNA in Gastric Cancer
Authors: Mencel Justin , Slater Susanna , Cartwright Elizabeth , Starling Naureen
Published: October 2022

Circulating tumour DNA (ctDNA) has potential applications in gastric cancer (GC) with respect to screening, the detection of minimal residual disease (MRD) following curative surgery, and in the advanced disease setting for treatment decision making and therapeutic monitoring. It can provide a less invasive and convenient method to capture the tumoural genomic landscape compared to tissue-based next-generation DNA sequencing (NGS). In addition, ctDNA can potentially overcome the challenges of tumour heterogeneity seen with tissue-based NGS. Although the evidence for ctDNA in GC is evolving, its potential utility is far reaching and may shape the management of this disease in the future. This article will review the current and future applications of ctDNA in GC.
Mannose and Hyaluronic Acid Dual-Modified Iron Oxide Enhances Neoantigen-Based Peptide Vaccine Therapy by Polarizing Tumor-Associated Macrophages
Authors: Nie Ying , Shi Lu , Zhang Yanan , Guo Yunfei , Gu Hongchen
Published: October 2022

Neoantigen-based cancer vaccine therapy is a breakthrough in the field of immunotherapy. However, it is difficult for vaccines against neoantigens to overcome the immunosuppressive microenvironment, where tumor-associated macrophages (TAMs) play a significant role. Herein, we report an iron oxide nanoparticle modified with hyaluronic acid and mannose to reshape the tumor microenvironment by targeting and repolarizing TAMs from protumor M2 to antitumor M1 phenotype. Mannose decoration could confer the nanoparticle-enhanced TAM targeting ability, while hyaluronic acid and iron oxide could repolarize M2-like macrophages both in vitro and in vivo. Combined with antigenic peptides, this nanovaccine could significantly increase the infiltration of CD8+ T cells into tumor tissue and strongly activate dendritic cells in sentinel lymph nodes. Finally, we used the dual-modified nanoparticles to first convert the tumor microenvironment and then the nanovaccine administration in a TC1 tumor model to further enhance efficacy. This strategy inhibited tumor growth and achieved a 40% cure rate in mice (two of five). In summary, this study provides a potent and rationally designed nanoadjuvant to enhance antitumor efficiency and facilitate delivery of neoantigen vaccines by repolarizing TAMs and harmonizing immune cells.
Factors That Affect the Formation of Chromosomal Translocations in Cells
Authors: Canoy Reynand Jay , Shmakova Anna , Karpukhina Anna , Shepelev Mikhail , Germini Diego , Vassetzky Yegor
Published: October 2022

Chromosomal translocations are products of the illegitimate repair of DNA double-strand breaks (DSBs). Their formation can bring about significant structural and molecular changes in the cell that can be physiologically and pathologically relevant. The induced changes may lead to serious and life-threatening diseases such as cancer. As a growing body of evidence suggests, the formation of chromosomal translocation is not only affected by the mere close spatial proximity of gene loci as potential translocation partners. Several factors may affect formation of chromosomal translocations, including chromatin motion to the potential sources of DSBs in the cell. While these can be apparently random events, certain chromosomal translocations appear to be cell-type-specific. In this review, we discuss how chromosomal translocations are formed and explore how different cellular factors contribute to their formation.
Semantic Segmentation of Pancreatic Cancer in Endoscopic Ultrasound Images Using Deep Learning Approach
Authors: Seo Kangwon , Lim Jung-Hyun , Seo Jeongwung , Nguon Leang Sim , Yoon Hongeun , Park Jin-Seok , Park Suhyun
Published: October 2022

Endoscopic ultrasonography (EUS) plays an important role in diagnosing pancreatic cancer. Surgical therapy is critical to pancreatic cancer survival and can be planned properly, with the characteristics of the target cancer determined. The physical characteristics of the pancreatic cancer, such as size, location, and shape, can be determined by semantic segmentation of EUS images. This study proposes a deep learning approach for the segmentation of pancreatic cancer in EUS images. EUS images were acquired from 150 patients diagnosed with pancreatic cancer. A network with deep attention features (DAF-Net) is proposed for pancreatic cancer segmentation using EUS images. The performance of the deep learning models (U-Net, Attention U-Net, and DAF-Net) was evaluated by 5-fold cross-validation. For the evaluation metrics, the Dice similarity coefficient (DSC), intersection over union (IoU), receiver operating characteristic (ROC) curve, and area under the curve (AUC) were chosen. Statistical analysis was performed for different stages and locations of the cancer. DAF-Net demonstrated superior segmentation performance for the DSC, IoU, AUC, sensitivity, specificity, and precision with scores of 82.8%, 72.3%, 92.7%, 89.0%, 98.1%, and 85.1%, respectively. The proposed deep learning approach can provide accurate segmentation of pancreatic cancer in EUS images and can effectively assist in the planning of surgical therapies.
Imaging Hallmarks of Sarcoma Progression Via X-ray Computed Tomography: Beholding the Flower of Evil
Authors: Popova Elena , Tkachev Sergey , Reshetov Igor , Timashev Peter , Ulasov Ilya
Published: October 2022

Sarcomas are a leading cause of cancer death in individuals younger than 20 years of age and represent the largest group of rare solid tumors. To date, more than 100 morphological subtypes of sarcomas have been described, among which epidemiology, clinical features, management, and prognosis differ significantly. Delays and errors in the diagnosis of sarcomas limit the number of effective therapeutic modalities and catastrophically worsen the prognosis. Therefore, the development of an algorithm for the early accurate diagnosis of sarcomas seems to be as important as the development of novel therapeutic advances. This literature review aims to summarize the results of recent investigations regarding the imaging of sarcoma progression based on the use of X-ray computed tomography (CT) in preclinical studies and in current clinical practice through the lens of cancer hallmarks. We attempted to summarize the main CT imaging features of soft-tissue and bone sarcomas. We noted the development of new molecular markers with high specificity to antibodies and chemokines, which are expressed in particular sarcoma subtypes to reach tumor type-specific imaging. We demonstrate the possibility of the use of X-ray computed microtomography (micro-CT) for non-destructive 3D visualization of solid tumors by increasing the visibility of soft tissues with X-ray scattering agents. Based on the results of recent studies, we hypothesize that micro-CT enables the visualization of neovascularization and stroma formation in sarcomas at high-resolution in vivo and ex vivo, including the novel techniques of whole-block and whole-tissue imaging. Finding correlations between CT, PET/CT, and micro-CT imaging features, the results of the histopathological specimen examination and clinical outcomes may significantly increase the accuracy of soft-tissue and bone tumor diagnostics, which leads to the initiation of appropriate histotype-specific management in a timely manner and, consequently, to improved outcomes.
Improving Time-to-Treatment for Advanced Non-Small Cell Lung Cancer Patients through Faster Single Gene EGFR Testing Using the Idylla™ EGFR Testing Platform
Authors: Banyi Norbert , Alex Deepu , Hughesman Curtis , McNeil Kelly , N. Ionescu Diana , Ma Carmen , Yip Stephen , Melosky Barbara
Published: October 2022

Introduction: Patients with advanced-stage non-small cell lung cancer (NSCLC) may benefit from a short time-to-treatment (TTT). Predictive biomarker testing is performed prior to treatment, as recommended by various international expert consensus bodies. Genetic testing is more time-intensive than immunohistochemistry (IHC) and commonly contributes to prolonged TTT. For epidermal growth factor receptor-positive patients (EGFR+), further genetic testing may not be required due to the mutual exclusivity of actionable mutations. Methods: The trial cohort (N = 238) received both BC Cancer NGS panel (Oncopanel) and Idylla EGFR testing. Data were also collected for a control cohort (N = 220) that received Oncopanel testing. For each patient, the time that the lab received the sample, the time taken to report the NGS and Idylla tests, the time of first treatment, and the final treatment regimen were recorded. Results: A concordance frequency of 98.7% (232/235) was observed between the Idylla and NGS panel. The lab turnaround time (TAT) was faster for the Idylla test by an average of 12.4 days (N = 235, p < 0.01). Overall, the average TTT in the trial cohort (N = 114) was 10.1 days faster (p < 0.05) than the control (N = 114), leading to a 25% reduction in TTT. For patients treated based on EGFR positivity, the mean TTT was 16.8 days faster (p < 0.05) in the trial cohort (N = 33) than the control cohort (N = 28), leading to a 48% reduction in TTT. Conclusion: Using the Idylla EGFR test as part of the molecular testing repertoire in advanced-stage NSCLC patients could significantly reduce TTT.
Effect of Different Altitudes on Morpho-Physiological Attributes Associated with Mango Quality
Authors: Zhang Cuixian , Yi Huaifeng , Gao Xianyu , Bai Tianqi , Ni Zhangguang , Chen Yufu , Wang Meicun , Zhang Yong , Pan Jihong , Yu Weilin , Xie Dehong
Published: October 2022

Mango (Mangifera indica L.) is a widely cultivated fruit in tropical and subtropical areas at altitudes ranging from 100 to 1500 m above sea level (masl). However, little is known about the effects of altering altitudes on the morpho-physiological traits determining the commercial value of mango. Therefore, we systematically investigated a commercial mango cultivar at eight altitudes ranging from 680 to 1400 masl to check the environmental impact on morpho-physiological attributes and volatile compounds using analysis of variance, principal component analysis, clustering, and correlation. We observed an increase in fruit weight and size from 680 to 1000 masl elevation and a gradual decrease at higher altitudes above 1000 msl. In contrast, quality parameters, including total soluble solids and total sugar, decreased with the increase in altitude, while the total acid increased with the increase in altitude. Moreover, we characterized the dried fruit, pericarp, and sarcocarp for aromatic compounds and identified 110 volatile compounds. The accumulation pattern of the volatiles suggested a considerable influence of environmental factors associated with altering altitudes. However, there was no clear trend in the volatile accumulation at different altitudes. We further determined the ten most frequently occurring volatiles at different altitudes and tissues. For instance, Alpha-Guaiene was only identified at 1000–1215 masl altitudes in dried fruit, while Beta-Ocimene showed the highest accumulation at 900 masl in dried fruit and pericarp. Together, our study provides clues on the impact of the altitude on mango fruit yield and quality attributes, which will guide future agronomic practices.