bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on the Optical Properties of High Refractive Index TeO2‐PbO‐ZnO‐BaF2 Glass System
Authors: Yin Shiyu , Wang Hao , Li Aifeng , Huang Haoyu , Zhang Jing , Liu Lin , Zhu Yuanzhi
Published: September 2021

The tellurite 60TeO2‐20PbO‐(20‐x)ZnO‐xBaF2 (x = 1, 3, 5, 6, 7, 9, and 11) series glass samples were prepared. The samples’ SEM, XRD, DSC, density, refractive index, and absorption spectra were tested. A self‐made optical platform was used to measure and calibrate the refractive index. The relationship between glass composition and crystallinity was discussed. The effects of density, molar refractive index, and metal standard value on the refractive index of glass samples were studied. The results showed that TPZBF glass has a high refractive index, and the refractive index increases with the increase in BaF2 content.
Ding Chuan Tang Attenuates Airway Inflammation and Eosinophil Infiltration in Ovalbumin‐Sensitized Asthmatic Mice
Authors: Ma Jason , Liu Ming-Xun , Chen Li-Chen , Shen Jiann-Jong , Kuo Ming-Ling
Published: September 2021

Asthma is a T helper 2 (Th2) cell‐associated chronic inflammatory diseases characterized with airway obstruction, increased mucus production, and eosinophil infiltration. Conventional medications for asthma treatment cannot fully control the symptoms, and potential side effects are also the concerns. Thus, complement or alternative medicine (CAM) became a new option for asthma management. Ding Chuan Tang (DCT) is a traditional Chinese herbal decoction applied mainly for patients with coughing, wheezing, chest tightness, and asthma. Previously, DCT has been proved to improve children airway hyperresponsiveness (AHR) in a randomized and double‐blind clinical trial. However, the mechanisms of how DCT alleviates AHR remain unclear. Since asthmatic features such as eosinophil infiltration, IgE production, and mucus accumulation are relative with Th2 responses, we hypothesized that DCT may attenuate asthma symptoms through regulating Th2 cells. Ovalbumin (OVA) was used as a stimulant to sensitize BALB/c mice to establish an asthmatic model. AHR was detected one day before sacrifice. BALF and serum were collected for immune cell counting and antibody analysis. Splenocytes were cultured with OVA in order to determine Th2 cytokine production. Lung tissues were collected for histological and gene expression analyses. Our data reveal that DCT can attenuate AHR and eosinophil accumulation in the 30‐day sensitization asthmatic model. Histological results demonstrated that DCT can reduce cell infiltration and mucus production in peribronchial and perivascular site. In OVA‐stimulated splenocyte cultures, a significant reduction of IL‐5 and IL‐13 in DCT‐treated mice suggests that DCT may alleviate Th2 responses. In conclusion, the current study demonstrates that DCT has the potential to suppress allergic responses through the reduction of mucus production, eosinophil infiltration, and Th2 activity in asthma.
[Retracted] Research on the Development Path of a Cross‐European e‐Commerce Logistics Mode under the Background of “Internet Plus”
Authors: Zhu Wangli , Shi Meixia
Published: September 2021

Cross‐border e‐commerce and the logistics industry are interrelated in specific economic and circulation fields. Based on the development of cross‐border e‐commerce in China and Europe, this paper analyzes the economic development of China’s cross‐border e‐business logistics providers in the context of Internet plus and analyzes the development trend of cross‐border e‐commerce in China and gives suggestions for optimization, with a view to providing cross‐border e‐commerce for the future. In‐depth cooperation provides reference.
An Extra Tree Regression Model for Discharge Coefficient Prediction: Novel, Practical Applications in the Hydraulic Sector and Future Research Directions
Authors: Hameed Mohammed Majeed , AlOmar Mohamed Khalid , Khaleel Faidhalrahman , Al-Ansari Nadhir
Published: September 2021

Despite modern advances used to estimate the discharge coefficient (

C

d

), it is still a major challenge for hydraulic engineers to accurately determine

C

d

for side weirs. In this study, extra tree regression (ETR) was used to predict the

C

d

of rectangular sharp-crested side weirs depending on hydraulic and geometrical parameters. The prediction capacity of the ETR model was validated with two predictive models, namely, extreme learning machine (ELM) and random forest (RF). The quantitative assessment revealed that the ETR model achieved the highest accuracy in the predictions compared to other applied models, and also, it exhibited excellent agreement between measured and predicted

C

d

(correlation coefficient is 0.9603). Moreover, the ETR achieved 6.73% and 22.96% higher prediction accuracy in terms of root mean square error in comparison to ELM and RF, respectively. Furthermore, the performed sensitivity analysis shows that the geometrical parameter such as b/B has the most influence on

C

d

. Overall, the proposed model (ETR) is found to be a suitable, practical, and qualified computer-aid technology for

C

d

modeling that may contribute to enhance the basic knowledge of hydraulic considerations.
Assessing the Performance of DWT-PCA/SVD Face Recognition Algorithm under Multiple Constraints
Authors: Mensah Joseph Agyapong , Asiedu Louis , Mettle Felix O. , Iddi Samuel
Published: September 2021

Many architectures of face recognition modules have been developed to tackle the challenges posed by varying environmental constraints such as illumination, occlusions, pose, and expressions. These recognition systems have mainly focused on a single constraint at a time and have achieved remarkable successes. However, the presence of multiple constraints may deteriorate the performance of these face recognition systems. In this study, we assessed the performance of Principal Component Analysis and Singular Value Decomposition using Discrete Wavelet Transform (DWT-PCA/SVD) for preprocessing face recognition algorithm on multiple constraints (partially occluded face images acquired with varying expressions). Numerical evaluation of the study algorithm gave reasonably average recognition rates of 77.31% and 76.85% for left and right reconstructed face images with varying expressions, respectively. A statistically significant difference was established between the average recognition distance of the left and right reconstructed face images acquired with varying expressions using pairwise comparison test. The post hoc analysis using the Bonferroni simultaneous confidence interval revealed that the significant difference established through the pairwise comparison test was mainly due to the sad expressions. Although the performance of the DWT-PCA/SVD algorithm declined as compared to its performance on single constraints, the algorithm attained appreciable performance level under multiple constraints. The DWT-PCA/SVD recognition algorithm performs reasonably well for recognition when partial occlusion with varying expressions is the underlying constraint.
Evaluation of the Antimalarial Activity of Crude Extract of Eucalyptus globulus Labill. Leaf against Plasmodium berghei in Mice
Authors: Ayalew Mihret , Bekele Azmeraw
Published: September 2021

Introduction. Traditional medicinal plants are used as a common source of developing new and effective antimalarial drugs. E. globulus leaf has been used in the traditional management of malaria in different countries, including Ethiopia. However, there is no in vivo study done on the antimalarial activity of the plant. Thus, this study aimed to evaluate the antimalarial activity of crude extract of E. globulus Labill. leaf in P. berghei-infected mice. Method. The fresh leaves of E. globulus were collected, washed, air-dried, and made as coarse powder. Either sex of mice aged 6 to 8 weeks was used in the experiment. The antimalarial activity of the crude extract was tested in four-day suppressive, curative (Rane’s), and prophylactic (repository) tests. The parameters like level of parasitemia, packed cell volume, body weight, rectal temperature, and mean survival time were recorded. The analysis of the data was done with SPSS version 20 with a 95% confidence interval in one-way ANOVA followed by Tukey’s post hoc test. Results. In all three antimalarial test models, the extract of leaf of E. globulus at all three doses suppressed the level of parasitemia significantly (

p
<
0.001

), increased survival time (

p
<
0.05

to

p
<
0.001

), and prevented a decrease in body weight as compared to the negative control. The middle and large doses of the extract also decreased loss of body temperature (

p
<
0.05

to

p
<
0.001

) compared to the negative control. Reduction of packed cell volume was prevented within the three test doses of the extract in both curative and prophylactic tests and middle and large doses in the 4-day suppressive test compared to the negative control. Conclusion. The crude extract of the plant showed promising antimalarial activity. This supports the traditional use and the in vitro test result of the plant.
Acute Severe Hyponatremia following Hysteroscopic Procedure in a Young Patient: A Case Report and Review of the Literature
Authors: Atieh Anwar S. , Abu Shamma Omar K. , Abdelhafez Mohammad O. , Baniowda Muath A. , Abed Samia , Babaa Basheer H. , Hamadah Abdurrahman , Gharaibeh Kamel A.
Published: September 2021

Background. Hysteroscopic surgery is a minimally invasive procedure used to diagnose and treat intrauterine pathologies. It requires distension of the uterine cavity for the adequate visualization of the operative field. Glycine (1.5%) is one of the most commonly used solutions because it is nonconductive and also has good optical properties. However, acute hyponatremia is a critical complication that can develop after the absorption of a sufficient amount of the irrigation medium. Case Presentation. We report a case of a 43-year-old female patient who developed acute symptomatic hyponatremia (104 mEq/L) and pulmonary edema secondary to hysteroscopic resection of leiomyoma and hastily approached with rapid sodium correction measures. Conclusion. Multiple strategies can be taken to reduce the risk of fluid absorption and subsequent hyponatremia. Moreover, attention should be paid to the treatment approach for patients with acute hyponatremia following hysteroscopic procedures; rapid correction of acute hyponatremia for such patients might be safe, although there is no consensus in the literature, and further trials are needed.
The Closed-Loop System Improved the Control of a Pregnant Patient with Type 1 Diabetes Mellitus
Authors: Guzmán Gómez Guillermo E. , Viggiano Julian A. , Silva-De Las Salas A. , Martínez Veline , Urbano Bonilla María A.
Published: September 2021

Objective. Closed-loop insulin systems represent a technological advance in diabetes management but have rarely been studied in pregnancy. We report a case of a patient with type 1 diabetes mellitus who was previously a user of the Paradigm VEO pump and then migrated to Medtronic 670G. Research Design and Methods. We reviewed the case of a G1P0 patient with type 1 diabetes, treated with the Medtronic 670G system during pregnancy; a comparison with current literature was done. Results. The patient achieved improved glycemic control as measured by time spent in different ranges as follows: <70 mg/dL, 8–4% and 70–180 mg/dL, 83–94%. Secondary outcomes included reduction of stress, anxiety, fear of hypoglycemia, and the psychological burden related to the disease. There were no obstetric or neonatal complications. Conclusion. The Medtronic 670G closed-loop system was used safely in a pregnant woman; nevertheless, further research is needed to validate this system in this patient population.
A Robust Image Encrypted Watermarking Technique for Neurodegenerative Disorder Diagnosis and Its Applications
Authors: Sharma Chirag , Bagga Amandeep , Sobti Rajeev , Shabaz Mohammad , Amin Rashid
Published: September 2021

The use of Internet technology has led to the availability of different multimedia data in various formats. The unapproved customers misuse multimedia information by conveying them on various web objections to acquire cash deceptively without the first copyright holder’s intervention. Due to the rise in cases of COVID-19, lots of patient information are leaked without their knowledge, so an intelligent technique is required to protect the integrity of patient data by placing an invisible signal known as a watermark on the medical images. In this paper, a new method of watermarking is proposed on both standard and medical images. The paper addresses the use of digital rights management in medical field applications such as embedding the watermark in medical images related to neurodegenerative disorders, lung disorders, and heart issues. The various quality parameters are used to figure out the evaluation of the developed method. In addition, the testing of the watermarking scheme is done by applying various signal processing attacks.
Influence of Bushen Tiaochong Cycle Therapy on Th1/Th2 Deviation, Sex Hormone Level, and Pregnancy Outcome of Alloimmune Recurrent Spontaneous Abortion
Authors: Wang Peng , Jiang Guilin , Ju Wenjuan , Cai Yaping , Wang Jinrong , Wu Feihua
Published: September 2021

Objective. To analyze the influence of Bushen Tiaochong cycle therapy on Th1/Th2 deviation, sex hormone level, and pregnancy outcome of alloimmune recurrent spontaneous abortion (RSA). Methods. From August 2018 to April 2020, 130 patients with alloimmune RSA who met the inclusion criteria were randomly divided into the control group (n = 65) and the study group (n = 65). The former received lymphocyte immunotherapy (LIT), and the latter received Bushen Tiaochong cycle therapy on the basis of LIT. The treatment ended at 12 w of pregnancy. The total score of traditional Chinese medicine (TCM) syndromes, Th1 cytokine (IL-2), Th2 cytokine (IL-10), and related hormones (chorionic gonadotropin (hCG) and progesterone (P)) were compared between the two groups before and after treatment. The positive rate of blocking antibody (BA), pregnancy success rate, and preterm birth rate were counted. Result. After treatment, the total score of TCM syndromes, IL-2 level, and Th1/Th2 ratio in the two groups decreased significantly, while the levels of IL-10, hCG, and P increased significantly, and the study group improved significantly compared with the control group (

P
<
0.05

). The positive rate of BA and pregnancy success rate in the study group were higher than those in the control group (

P
<
0.05

). There was no significant difference in the preterm birth rate between the two groups (

P
>
0.05

). Conclusion. On the basis of routine western medicine treatment, a combined application of Bushen Tiaochong cycle therapy can significantly improve the Th1/Th2 deviation, serum sex hormone level, and pregnancy outcome in patients with alloimmune RSA.
Changes of Multisectoral Collaboration and Service Delivery in Hypertension Prevention and Control before and after the 2009 New Healthcare Reform in China: An Interrupted Time-Series Study
Authors: Zhang Zhifan , Hu Zhi , Wang Hua , Zhou Qingyu , Li Chengyue , Hao Mo
Published: September 2021

Objectives. There is a need to assess the 2009 new healthcare reform in China on hypertension prevention. It helps to control from the perspectives of multisectoral participation, government responsibility assignment, performance assessment, and service delivery. Design. Interrupted time-series study. Setting. 31 provinces in mainland China. Primary and Secondary Outcome Measures. Based on the content analysis of publicly available policy documents from 31 provinces regarding hypertension prevention and control, we analyzed the changes brought by the 2009 new healthcare reform through four quantitative indicators, including multisector participation (MP), main department responsibility coverage (MDRC), primary department assessment indicator coverage (MDAIC), and service type coverage (STC). We compared the changing trends of four indicators before and after 2009. Results. Nationally, MP, MDRC, and STC grew rapidly and increased to 88.9%, 96.4%, and 77.8%, respectively, in 2017, higher than MDAIC (36.9%). This growth was accelerated by the new healthcare reform, with the highest acceleration in MP (β3 = 6.345,

p
<
0.001

), followed by MDRC (β3 = 3.829,

p
<
0.01

), STC (β3 = 3.799,

p
<
0.001

), and MDAIC (β3 = 3.585,

p
<
0.001

). The MP and MDRC trend changes were higher in the central and western regions than in the east after the reform. Conclusions. Our research showed that the new healthcare reform had a positive effect in promoting multisectoral participation in preventing and controlling hypertension in China, improving the responsibility mechanism, and expanding the types of services provided. The government should lead the coordination and implementation of multidepartmental responsibilities and mobilize nonhealth departments to continuously participate in the prevention and control of chronic diseases by improving incentive and evaluation mechanisms.
Soil-Structure Interaction of Flexible Temporary Trench Box: Parametric Studies Using 3D FE Modelling
Authors: Alam Miah , Chaallal Omar , Galy Bertrand
Published: September 2021

This paper presents the results of two parametric finite-element studies that were carried out using the PLAXIS-3D finite element (FE) computer code. The following objectives and corresponding parameters were considered: (i) to evaluate the soil pressure on the steel trench box shield; the parameters studied were related to soil type and material, and the study considered till, dry sand, wet sand, and sensitive clay soil; (ii) to assess the effect of trench box material and geometry on earth pressure; the parameters studied were related to trench box material (steel versus aluminum) as well as geometry (plate thickness and strut diameter). These studies included simulation of two steel (or aluminum) trench box shields stacked upon each other to cover the total 6 m (20 ft) deep trench. A Mohr-Coulomb (MC) constitutive material model was chosen for FE analysis (FEA). The FEA results were compared to empirical apparent earth pressure diagrams for a sensitive clay. Comparisons showed that the parameters related to the soil and the trench box have a significant influence on earth pressures.
Main Rotor Wake Interference Effects on Tail Rotor Thrust in Crosswind
Authors: Wang Chang , Huang Min Qi , Ma Shuai , Wang Hao Wen , Tang Min
Published: September 2021

Reverse pedal operational property in front crosswind flight condition is a potential hazard for accidents involving loss of tail rotor effectiveness (LTE), which is closely related to the main rotor (MR) wake interference on the tail rotor (TR). As understanding of this interaction is vital for the early warning strategy development, the MR wake influence effect on TR thrust and the effect of helicopter yaw stability are examined in this study. For this purpose, the comparison of TR thrust and flow field with wind azimuth and speed in front crosswind environment was performed by experiment and CFD simulation, respectively. Test campaign was performed at a5.5 m×4 mwind tunnel in the China Aerodynamics Research and Development Center using a high-position bottom-blade forward-rotating TR and a counterclockwise rotating MR to address the TR thrust under wind speeds of 8–22 m/s with 50°, 60°, and 70° wind azimuths. The influence of MR disc loading was also contrasted. CFD analysis was used to gain insight into the flow physics responsible for the interference effect. It was conducted with unsteady Reynolds-averaged Navier–Stokes simulations, where the MR using the actuator disk approach and the TR blade rotation was modeled via a sliding mesh method. Results indicated that the MR disc vortex has a remarkable interference effect on the TR aerodynamic performance characteristic and that the effect is sensitive to the wind speed, wind direction, and MR disc loading. The observed yaw instability is considered to be related to the lesser inflow introduced by the MR disc vortex due to the change in the relative position of the disc vortex filament and TR with the wind azimuth. The increase in TR thrust at moderate wind speeds is due to the increase in leading edge dynamic pressure caused by the opposite swirl direction of the disc vortex contrasted to the TR. The MR disc loading affects the TR thrust due to the change of disc vortex strength and position.
A BRCA1 Coiled-Coil Domain Variant Disrupting PALB2 Interaction Promotes the Development of Mammary Tumors and Confers a Targetable Defect in Homologous Recombination Repair
Authors: Pulver Emilia M. , Mukherjee Chirantani , van de Kamp Gerarda , Roobol Stefan J. , Rother Magdalena B. , van der Gulden Hanneke , de Bruijn Roebi , Lattanzio Maria Valeria , van der Burg Eline , Drenth Anne Paulien , Verkaik Nicole S. , Hahn Kerstin , Klarenbeek Sjoerd , de Korte-Grimmerink Renske , van de Ven Marieke , Pritchard Colin E.J. , Huijbers Ivo J. , Xia Bing , van Gent Dik C. , Essers Jeroen , van Attikum Haico , Ray Chaudhuri Arnab , Bouwman Peter , Jonkers Jos
Published: September 2021

The BRCA1 tumor suppressor gene encodes a multidomain protein for which several functions have been described. These include a key role in homologous recombination repair (HRR) of DNA double-strand breaks, which is shared with two other high-risk hereditary breast cancer suppressors, BRCA2 and PALB2. Although both BRCA1 and BRCA2 interact with PALB2, BRCA1 missense variants affecting its PALB2-interacting coiled-coil domain are considered variants of uncertain clinical significance (VUS). Using genetically engineered mice, we show here that a BRCA1 coiled-coil domain VUS, Brca1 p.L1363P, disrupts the interaction with PALB2 and leads to embryonic lethality. Brca1 p.L1363P led to a similar acceleration in the development of Trp53-deficient mammary tumors as Brca1 loss, but the tumors showed distinct histopathologic features, with more stable DNA copy number profiles in Brca1 p.L1363P tumors. Nevertheless, Brca1 p.L1363P mammary tumors were HRR incompetent and responsive to cisplatin and PARP inhibition. Overall, these results provide the first direct evidence that a BRCA1 missense variant outside of the RING and BRCT domains increases the risk of breast cancer.

Significance:

These findings reveal the importance of a patient-derived BRCA1 coiled-coil domain sequence variant in embryonic development, mammary tumor suppression, and therapy response.

See related commentary by Mishra et al., p. 6080
Targeting the IRE1α/XBP1 Endoplasmic Reticulum Stress Response Pathway in ARID1A-Mutant Ovarian Cancers
Authors: Zundell Joseph A. , Fukumoto Takeshi , Lin Jianhuang , Fatkhudinov Nail , Nacarelli Timothy , Kossenkov Andrew V. , Liu Qin , Cassel Joel , Hu Chih-Chi Andrew , Wu Shuai , Zhang Rugang
Published: September 2021

The SWI/SNF chromatin-remodeling complex is frequently altered in human cancers. For example, the SWI/SNF component ARID1A is mutated in more than 50% of ovarian clear cell carcinomas (OCCC), for which effective treatments are lacking. Here, we report that ARID1A transcriptionally represses the IRE1α–XBP1 axis of the endoplasmic reticulum (ER) stress response, which confers sensitivity to inhibition of the IRE1α–XBP1 pathway in ARID1A-mutant OCCC. ARID1A mutational status correlated with response to inhibition of the IRE1α–XBP1 pathway. In a conditional Arid1aflox/flox/Pik3caH1047R genetic mouse model, Xbp1 knockout significantly improved survival of mice bearing OCCCs. Furthermore, the IRE1α inhibitor B-I09 suppressed the growth of ARID1A-inactivated OCCCs in vivo in orthotopic xenograft, patient-derived xenograft, and the genetic mouse models. Finally, B-I09 synergized with inhibition of HDAC6, a known regulator of the ER stress response, in suppressing the growth of ARID1A-inactivated OCCCs. These studies define the IRE1α−XBP1 axis of the ER stress response as a targetable vulnerability for ARID1A-mutant OCCCs, revealing a promising therapeutic approach for treating ARID1A-mutant ovarian cancers.

Significance:

These findings indicate that pharmacological inhibition of the IRE1α–XBP1 pathway alone or in combination with HDAC6 inhibition represents an urgently needed therapeutic strategy for ARID1A-mutant ovarian cancers.
Mode of Delivery, Birth Characteristics, and Early-Onset Non-Hodgkin Lymphoma in a Population-Based Case–Control Study
Authors: Dwyer Kayla E. , Wang Rong , Cozen Wendy , Cartmel Brenda , Wiemels Joseph L. , Morimoto Libby M. , Metayer Catherine , Ma Xiaomei
Published: September 2021

Background:

The etiology of non-Hodgkin lymphoma (NHL) in children and in adolescents and young adults (AYA) is not well understood.

Methods:

We evaluated potential associations between mode of delivery, birth characteristics, and NHL risk in a population-based case–control study, which included 3,064 cases of NHL [490 with Burkitt lymphoma, 981 with diffuse large B-cell lymphoma (DLBCL), and 978 with T-cell NHL) diagnosed at the age of 0 to 37 years in California during 1988 to 2015 and 153,200 controls frequency matched on year of birth. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from an unconditional multivariable logistic regression model that included year of birth and birth characteristics.

Results:

Individuals born via cesarean section had a decreased risk of pediatric Burkitt lymphoma (age 0–14 years; OR = 0.71, 95% CI: 0.51–0.99) and pediatric T-cell NHL (OR = 0.73, 95% CI: 0.55–0.97) compared with those born vaginally. Having a birth order of second (OR = 0.73, 95% CI: 0.57–0.93) or third or higher (OR = 0.76, 95% CI: 0.58–0.99) was associated with a lower risk of pediatric T-cell NHL compared with first-borns. AYA (age 15–37 years) with a heavier birthweight had an elevated risk of DLBCL (OR for each kg = 1.16, 95% CI: 1.00–1.35). Associations between other birth characteristics, including plurality, maternal age, maternal education, and NHL risk, also exhibited variations across subgroups based on age of diagnosis and histologic subtype.

Conclusions:

These findings support a role of mode of delivery and birth characteristics in the etiology of early-onset NHL.

Impact:

This study underscores the etiologic heterogeneity of early-onset NHL.
Generalizability and Transportability of the National Lung Screening Trial Data: Extending Trial Results to Different Populations
Authors: Inoue Kosuke , Hsu William , Arah Onyebuchi A. , Prosper Ashley E. , Aberle Denise R. , Bui Alex A.T.
Published: September 2021

Background:

Randomized controlled trials (RCT) play a central role in evidence-based healthcare. However, the clinical and policy implications of implementing RCTs in clinical practice are difficult to predict as the studied population is often different from the target population where results are being applied. This study illustrates the concepts of generalizability and transportability, demonstrating their utility in interpreting results from the National Lung Screening Trial (NLST).

Methods:

Using inverse-odds weighting, we demonstrate how generalizability and transportability techniques can be used to extrapolate treatment effect from (i) a subset of NLST to the entire NLST population and from (ii) the entire NLST to different target populations.

Results:

Our generalizability analysis revealed that lung cancer mortality reduction by LDCT screening across the entire NLST [16% (95% confidence interval [CI]: 4–24)] could have been estimated using a smaller subset of NLST participants. Using transportability analysis, we showed that populations with a higher prevalence of females and current smokers had a greater reduction in lung cancer mortality with LDCT screening [e.g., 27% (95% CI, 11–37) for the population with 80% females and 80% current smokers] than those with lower prevalence of females and current smokers.

Conclusions:

This article illustrates how generalizability and transportability methods extend estimation of RCTs' utility beyond trial participants, to external populations of interest, including those that more closely mirror real-world populations.

Impact:

Generalizability and transportability approaches can be used to quantify treatment effects for populations of interest, which may be used to design future trials or adjust lung cancer screening eligibility criteria.
Efficacy and Safety of Patritumab Deruxtecan (HER3-DXd) in EGFR Inhibitor–Resistant, EGFR-Mutated Non–Small Cell Lung Cancer
Authors: Jänne Pasi A. , Baik Christina , Su Wu-Chou , Johnson Melissa L. , Hayashi Hidetoshi , Nishio Makoto , Kim Dong-Wan , Koczywas Marianna , Gold Kathryn A. , Steuer Conor E. , Murakami Haruyasu , Yang James Chih-Hsin , Kim Sang-We , Vigliotti Michele , Shi Rong , Qi Zhenhao , Qiu Yang , Zhao Lihui , Sternberg David , Yu Channing , Yu Helena A.
Published: September 2021

Receptor tyrosine-protein kinase ERBB3 (HER3) is expressed in most EGFR-mutated lung cancers but is not a known mechanism of resistance to EGFR inhibitors. HER3-DXd is an antibody–drug conjugate consisting of a HER3 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. This phase I, dose escalation/expansion study included patients with locally advanced or metastatic EGFR-mutated non–small cell lung cancer (NSCLC) with prior EGFR tyrosine kinase inhibitor (TKI) therapy. Among 57 patients receiving HER3-DXd 5.6 mg/kg intravenously once every 3 weeks, the confirmed objective response rate by blinded independent central review (Response Evaluation Criteria in Solid Tumors v1.1) was 39% [95% confidence interval (CI), 26.0–52.4], and median progression-free survival was 8.2 (95% CI, 4.4–8.3) months. Responses were observed in patients with known and unknown EGFR TKI resistance mechanisms. Clinical activity was observed across a broad range of HER3 membrane expression. The most common grade ≥3 treatment-emergent adverse events were hematologic toxicities. HER3-DXd has clinical activity in EGFR TKI–resistant cancers independent of resistance mechanisms, providing an approach to treat a broad range of drug-resistant cancers.

Significance:

In metastatic EGFR-mutated NSCLC, after disease progression on EGFR TKI therapy, treatment approaches include genotype-directed therapy targeting a known resistance mechanism or chemotherapy. HER3-DXd demonstrated clinical activity spanning known and unknown EGFR TKI resistance mechanisms. HER3-DXd could present a future treatment option agnostic to the EGFR TKI resistance mechanism.

See related commentary by Lim et al., p. 16.

This article is highlighted in the In This Issue feature, p. 1
ALG1-CDG: A Patient with a Mild Phenotype and Literature Review
Authors: Öncül Ümmühan , Kose Engin , Eminoğlu Fatma Tuba
Published: September 2021

ALG1-congenital disorder of glycosylation (ALG1-CDG) is an autosomal recessive multisystem disease. We here present a patient with a mild phenotype of ALG1-CDG. A 15-month-old female was referred with hypotonia, failure to thrive, and developmental delay. At 8 months of age, failure to thrive, feeding difficulties and developmental delay became apparent, and an epileptic seizure was observed at 11 months of age. Progressive deterioration and swallowing difficulty were observed. A brain MRI revealed a widening of the cerebrospinal fluid spaces and ventricular system, and decreased protein C, protein S and antithrombin III levels were identified. The isoelectric focusing showed a type 1 pattern. A homozygous c.1076C>T (p.Ser359Leu) variant was found in the ALG1 gene. CDG should be taken into consideration in patients presenting with unexplained multisystem involvement.
Taxane-Induced Upper Gastrointestinal Bleeding
Authors: Liu Yao , Hiramoto Brent , Kwok Janet , Ibrahim Ahmad , Tatishchev Sergei , Kang Irene , Modi Rushabh
Published: September 2021

Docetaxel is a taxane, which is a class of chemotherapy agent used in the treatment of multiple malignancies. It is known to have gastrointestinal side effects which can range from mild symptoms such as nausea and diarrhea to more severe complications such as neutropenic enterocolitis. In the current literature, taxanes have not been described to cause upper gastrointestinal bleeding and melena. Here, we present a case of a 54-year-old woman with breast cancer who developed dizziness, fatigue, and melena after receiving chemotherapy. Esophagogastroduodenoscopy revealed diffuse gastric erosions as well as ulceration and linear superficial lesions in the duodenum; biopsies from these sites showed taxane-induced toxicity. Her bleeding resolved with medical therapy and subsequent removal of docetaxel from her chemotherapy regimen. This case identifies upper gastrointestinal bleeding as a previously undescribed side effect of docetaxel therapy. Recent docetaxel use should be included in the differential diagnosis for upper gastrointestinal bleed, and diagnosis should lead to consideration of cessation of docetaxel or substitution with another chemotherapeutic agent.
Late Presentation of Aortopulmonary Window with Tetralogy of Fallot: Report of a Very Rare Case
Authors: Al-Manzo Muhammad Ishtiaque Sayeed , Biswas Prodip Kumar , Azad M.A.K. , Patwary Eliyas , Hossain Jesmin , Shamsuddin Abul Kalam
Published: September 2021

Aortopulmonary window (APW) itself is a rare congenital cardiac malformation and its association with Tetralogy of Fallot (TOF) makes it more uncommon. We report a case of APW with TOF who presented at 4-year 10 months of age. As the boy was still in operable state, after thorough preoperative evaluation successful surgical repair was done.
Nails Involvement in Winiwarter-Buerger Disease
Authors: Starace Michela V.R. , Alessandrini Aurora , Tosti Antonella , Piraccini Bianca Maria
Published: September 2021

Introduction: Buerger disease, or thromboangiitis obliterans, is an inflammatory and occlusive process involving small and medium size arteries and veins, which generally affects the lower limbs of young adult male with the habit of smoking. Case Presentation: This paper reports 2 patients who developed nail lesions as the first sign of Buerger disease. Conclusion: Signs and symptoms of Buerger’s disease are secondary to the inflammatory process and arterial occlusion which results in severe ischemia. Involvement of nails is not common, but we found 2 different clinical features which have not been previously reported in the literature: chronic paronychia, and proximal leukonychia or onycholysis and nail bed erosion.
Etanercept-Induced Anti-Glomerular Basement Membrane Disease
Authors: Al-Chalabi Saif , Wu Henry H.L. , Chinnadurai Rajkumar , Ponnusamy Arvind
Published: September 2021

Anti-glomerular basement membrane (anti-GBM) disease is a rare form of small-vessel vasculitis that typically causes rapidly progressive glomerulonephritis with or without alveolar haemorrhage. Previously, there has only been one reported case of tumour necrosis factor-α (TNF-α) antagonist-induced anti-GBM disease. Here, we describe the first reported case of etanercept-induced anti-GBM disease. A 55-year-old Caucasian man was referred to our tertiary specialist renal centre with a history of painless macroscopic haematuria. The patient has been receiving weekly etanercept injections over the past 12 months for psoriatic arthropathy. The serum immunology panel results highlighted a significantly raised anti-GBM titre (370.1 U). Etanercept was stopped, and the patient was empirically commenced on pulsed methylprednisolone, cyclophosphamide, and plasma exchange. A renal biopsy showed crescentic glomerulonephritis. Few days after admission, he tested positive for coronavirus disease 2019 (COVID-19), and a decision was made to withhold cyclophosphamide. There was further decline in renal function with hyperkalaemia for which he received 2 sessions of haemodialysis. He was restarted on cyclophosphamide upon discharge. The patient was switched to rituximab treatment afterwards as he developed leucopenia 2 weeks following the commencement of cyclophosphamide. The serum creatinine level continued to improve and remained dialysis-independent. In conclusion, with the increased use of etanercept and other TNF-α antagonists, the prescribing clinician must be aware of the rare but life-threatening drug-induced vasculitis. We recommend careful monitoring of renal indices with the use of this class of medications.
Euploid First-Trimester Cystic Hygroma: A More Benign Entity than Previously Thought?
Authors: Malone Ciara M. , Mullers Sieglinde , Kelliher Nollaig , Dalrymple Jane , O’Beirnes Joan , Flood Karen , Malone Fergal
Published: September 2021

Objective: Studies summarizing the outcome of first-trimester septated cystic hygroma are generally based on small studies or from multiple centers with limited ascertainment. We reviewed the natural history of a large cohort of such cases from a single tertiary referral center, with the aim being to establish contemporary outcome data, particularly in the setting of normal karyotype. Methods: A retrospective cohort study from 2007 to 2017 was conducted at a single tertiary referral prenatal diagnosis center. Data were analyzed from a prospectively collated fetal anomaly database. Search terms were “increased nuchal translucency (NT),” “cystic hygroma,” and “septated cystic hygroma.” All cases were confirmed to have NT >3 mm with septations. Cases of simple increased NT without septations were excluded. Results: During the study period, over 110,000 pregnancies were delivered at our center, resulting in 410 cases of septated cystic hygroma diagnosed prior to 14 weeks’ gestation. Pregnancy outcome was obtained in 99% (405/410) of cases, with detailed pathology outcome available in 92% (378/410). A total of 87% (351/405) underwent invasive prenatal testing, and postnatal chromosome status was established in further 27 cases. A total of 61% (230/378) had abnormal chromosomal status. Of the 39% (148/378) with normal chromosomal status, only 13% (19/148) had a significant structural fetal abnormality, which included 7 cardiac and 12 noncardiac abnormalities. Overall, the perinatal loss was 62% (253/405). The total survival rate in the setting of euploid cystic hygroma without structural abnormality was 84% (108/129). Conclusions: Counseling regarding outcomes in the setting of first-trimester septated cystic hygroma initially focuses on the strong likelihood of an abnormal karyotype, which occurs in 61% of cases. However, once fetal chromosomal abnormality is excluded, our results demonstrate only a 13% incidence of major structural fetal abnormality, which appears significantly less than previously reported. Normal fetuses have a 77% survival rate. These data represent the largest single-center study of first-trimester cystic hygroma with complete outcome data and therefore will be useful for contemporary patient counseling. Such counseling can be more positive than previously expected, once chromosomal abnormality is first excluded.
Fli1 Promotes Vascular Morphogenesis by Regulating Endothelial Potential of Multipotent Myogenic Progenitors
Authors: Ferdous Anwarul , Singh Sarvjeet , Luo Yuxuan , Abedin Md. J. , Jiang Nan , Perry Cameron E. , Evers Bret M. , Gillette Thomas G. , Kyba Michael , Trojanowska Maria , Hill Joseph A.
Published: September 2021

Rationale:

Fetal growth and survival depend critically on proper development and integrity of the vascular system. Fli1 (Friend leukemia integration 1), a member of the Ets family of transcription factors, plays critical roles in vascular morphogenesis and homeostasis at mid-gestation, the developmental stage at which expression of its upstream regulator, Etv2, ceases. However, molecular mechanisms of Fli1 action in vascular morphogenesis remain incompletely understood.

Objective:

To dissect molecular mechanisms of vascular morphogenesis governed by Fli1.

Methods and Results:

Utilizing
Fli1
promoter-driven lineage-specific
LacZ
expression, Fli1 loss-of-function strategies, and a series of molecular techniques, we demonstrate that
Fli1
expression in multipotent myogenic progenitor cells (MPCs) occurs independent of Etv2, and loss of Fli1 expression results in a significant increase in LacZ
+
cells in mesoderm within somites and limb buds, leading to reciprocal regulation of the expression of several key endothelial and myogenic genes and vascular abnormalities. Conversely, embryos harboring conditional Fli1 gain-of-function in MPCs manifested aberrant vasculogenesis with lack of myogenesis. Mechanistically, elevated Fli1 activity in myoblasts and in adult MPCs (also called satellite cells) of X-linked muscular dystrophic
mdx
mice markedly induced endothelial, but attenuated myogenic, gene expression and differentiation. Importantly, ectopic expression of Myf5 or MyoD, two key myogenic regulators, in Fli1-expressing myoblasts restored their differentiation potential, indicating that levels of Fli1 and myogenic regulators in MPCs inversely regulate their endothelial versus myogenic potential.

Conclusions:

Fli1 governs vascular morphogenesis by regulating endothelial potential by inversely regulating endothelial versus myogenic programs in MPCs. Our data uncover an important and previously unrecognized mechanism of vascular morphogenesis governed by Fli1 and highlight the physiological significance of the fine tuning of Fli1 activity in multipotent progenitors for proper vascular and muscle morphogenesis during development and disease.
The Paris Agreement as Analogy in Global Environmental Politics
Authors: Chan Nicholas
Published: September 2021

The Paris Agreement is increasingly being used as an analogy in global environmental politics to discuss issues beyond climate change. This Forum article explores the two main ways in which this analogy has been discursively employed: as a symbol of diplomatic success to be emulated and as a model for institutional treaty design. It illustrates the broader meanings associated with the Paris Agreement, reflecting its preeminent public and political profile among environmental issues just a few years into its history and its potential significance in shaping subsequent global environmental negotiations.
Invasive Species in Post-2020 Global Environmental Politics
Authors: Cruz Jesann Gonzalez , Johnson McKenzie F.
Published: September 2021

As goods and people more rapidly traverse our interconnected world, invasive alien species (IAS) are increasingly frequent, ecologically damaging, economically significant, and culturally concerning. Through examinations of IAS, global environmental politics (GEP) scholars can more deeply engage long-standing and newly emerging research problems within the three areas of global governance, global political economy, and environmental security. First, GEP scholars can use IAS research to further develop insights about the impact of problem structure on global governance. Second, examining IAS dispersal risks and associated costs, as well as intercountry variation in management responses, can generate insights about North–South power dynamics in the global political economy and how distributive conflict is likely to shape future invasion risk. Third, notions of environmental security in GEP scholarship can be challenged and further developed by examining the conceptualization and operationalization of “biosecurity” amid increasingly diverse multispecies assemblages. Greater research attention to IAS in GEP is long overdue, and we intend for this article to open novel pathways for GEP interdisciplinary research on IAS.
Do Infants Really Learn Phonetic Categories?
Authors: Feldman Naomi H. , Goldwater Sharon , Dupoux Emmanuel , Schatz Thomas
Published: September 2021

Early changes in infants’ ability to perceive native and nonnative speech sound contrasts are typically attributed to their developing knowledge of phonetic categories. We critically examine this hypothesis and argue that there is little direct evidence of category knowledge in infancy. We then propose an alternative account in which infants’ perception changes because they are learning a perceptual space that is appropriate to represent speech, without yet carving up that space into phonetic categories. If correct, this new account has substantial implications for understanding early language development.
A new species of Ceratostema (Ericaceae: Vaccinieae) from Ecuador
Authors: JIMÉNEZ MARCO M. , VÉLEZ-ABARCA LEISBERTH , OCUPA HORNA LUIS , JARAMILLO NELSON , BAQUERO LUIS E.
Published: September 2021

Tribe Vaccinieae Reichenbach with more than 800 species contains most of the neotropical taxa of Ericaceae Jussieu (Pedraza-Peñalosa 2015a: 35). Species of genus Vaccinium Linneaus (1753: 349) known as blueberries or mortiños in Spanish, are members of Vaccinieae well-known for their economic importance (Pedraza-Peñalosa 2015b: 100). The genus Ceratostema Jussieu (1789: 163) was created by Antoine Jussieu and Ceratostema peruvianum Gmelin (1791: 676) was designated as the type species (Luteyn 1986: 485). It was first treated by Smith in 1952, who published a brief description and an artificial key, recognizing 16 species at that time (Smith 1952). Luteyn (1986) reviewed the genus and provided an updated artificial key to 23 species, including three new ones. Subsequently, a new species from Peru was added and thirteen more from Ecuador were included in the genus (Luteyn 1992, 1996, 2005).
The moss family Rhachitheciaceae (Dicranales, Bryophyta) in Thailand
Authors: CHANTANAORRAPINT SAHUT , SEVANAKUN NILOBON , SUWANMALA ORAWANYA , SUKKHARAK PHIANGPHAK , PRINTARAKUL NARIN , HE SI
Published: September 2021

A taxonomic study of the family Rhachitheciaceae in Thailand is presented based on newly collected materials from field surveys and herbarium specimens. Two species are recognized, including Hypnodontopsis spathulata and Rhachithecium perpusillum. Hypnodontopsis spathulata, previously known only from the type locality, is reported here as a new genus and species record for Thailand. A key to species, taxonomic descriptions and illustrations are provided. In addition, the lectotype of Zygodon perpusillus (=Rhachithecium perpusillum) is also designated here.
Trojan-Like Peptide Drug Conjugate Design and Construction for Application in Treatment of Triple-Negative Breast Cancer
Authors: Xiao Chuanguang , Han Jieru , Bai Jixiang , Xia Yanjie , Wang Shuhui
Published: September 2021

Clinical treatment of triple negative breast cancer (TNBC) is very poor for lack of effective treatment combination selection. Protein C receptor (PROCR) is a novel cancer stem marker in TNBC patients tumor tissues. Developed based on peptide BP10 with affinity to PROCR as a targeting
element, constructing a peptide drug conjugate of BP10 covalently coupling doxorubicin with disulfide bonds. This study demonstrated that the constructed BP10-DOX can selectively target Triplenegative breast cancer cells expressing PROCR and controlled release of DOX in response to the GSH
environment. Moreover, BP10-DOX improves the therapeutic efficiency on MDA-MB-231 cells in vitro. Further evidence obtained from in vivo xenograft experiments revealed that administration of BP10-DOX enhanced the antitumor efficacy. This study developed a promising chemotherapy
strategy for TNBC.