bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic profiles and their associations with TMB, PD-L1 expression, and immune cell infiltration landscapes in synchronous multiple primary lung cancers
Authors: Hu Chunhong , Zhao Lishu , Liu Wenliang , Fan Songqing , Liu Junqi , Liu Yuxuan , Liu Xiaohan , Shu Long , Liu Xianling , Liu Ping , Deng Chao , Qiu Zhenhua , Chen Chen , Jiang Yi , Liang Qingchun , Yang Lingling , Shao Yang , He Qiongzhi , Yu Danlei , Zeng Yue , Li Yizheng , Pan Yue , Zhang Sujuan , Shi Shenghao , Peng Yurong , Wu Fang 
Published: December 2021

BackgroundDiagnosing and treating patients with multiple primary lung cancers (MPLCs) bring challenges to the clinic, and the preliminary evidence has revealed unsatisfying outcomes after targeted therapy and immunotherapy. Therefore, we surveyed genomic profiles of MPLCs and their possible associations with tumor mutation burden (TMB), programmed death-ligand 1 (PD-L1), and the immune cell infiltration landscape.Materials and methodsA total of 112 patients with MPLCs with surgically resected 294 tumors were eligible, and 255 tumors were sequenced using a 1021-gene panel. Immunohistochemistry staining was performed to evaluate the levels of PD-L1 and the density of CD3+/CD8+ tumor-infiltrating lymphocytes (TILs), and CD68+/CD163+ tumor-associated macrophages (TAMs) at the central tumor and invasive margin, and immunotypes were generated based on those variables.ResultsMPLCs often occur simultaneously in non-smoker women younger than 60 years and manifest as ground-glass opacities, adenocarcinoma, and stage I lung lesions. The most frequently mutated genes in the 255 tumors were EGFR (56%), ERBB2 (12%), TP53 (12%), BRAF (11%), RBM10 (11%), and KRAS (9%). We found 87 (77.7%) patients with diverse genomic profiles, and 61 (54.5%) who shared at least one putative driver gene between different tumors presented more aggressive tumors. The median TMB was 1.92 mutations/Mb, and high-TMB (≥3) lesions often harbored EGFRL858R/KRASG12C/RBM10/TP53/LRP1B mutations or wild-type ERBB2. Only 8.1% of patients and 3.9% of lesions were positive for PD-L1 on tumor cells, and this positivity was more frequent in LRP1B/TP53-mutant tumors. EGFRL858R/RBM10/TP53 mutations were positively associated with specific immune cells and an inflamed immunotype, but ERBB2 mutations were negatively correlated. TMB, CD3+TILs, and CD68+/CD163+ TAMs presented with significant heterogeneity among paired tumors (all kappa <0.2), but PD-L1 and CD8 +TILs were more uniformly present in tumor pairs.ConclusionMPLCs are driven by different molecular events and often exhibit low TMB, low PD-L1, and a heterogeneous immune infiltration landscape. Specific genomic profiles are associated with TMB and the tumor immune microenvironmental landscape in MPLCs. Our findings can help to guide MPLCs diagnoses and to identify patient populations that may benefit from immunotherapy and targeted therapy.
Prevalence of curable STIs and bacterial vaginosis during pregnancy in sub-Saharan Africa: a systematic review and meta-analysis
Authors: Nyemba Dorothy Chiwoniso , Haddison Eposi C , Wang Colin , Johnson Leigh Francis , Myer Landon , Davey Dvora Joseph 
Published: December 2021

ObjectiveSTIs remain a global public health problem with a high burden among pregnant women. STIs in pregnant women may lead to various adverse pregnancy outcomes. In most sub-Saharan African countries, syndromic management is used for screening and treatment of STIs. We aimed to update and summarise pooled prevalence of curable STIs and bacterial vaginosis (BV) among pregnant women in sub-Saharan Africa.MethodsElectronic databases and reference lists of relevant published and unpublished studies were searched from March 2015 to October 2020. Studies were included if theyestimated prevalence of Chlamydia trachomatis(CT),Trichomonas vaginalis(TV),Neisseria gonorrhoeae(NG),Treponema pallidum(syphilis),Mycoplasma genitalium(MG) and BV among pregnant women in sub-Saharan Africa. Meta-analyses were performed with observed prevalences corrected for diagnostic errors to estimate the pooled prevalence of diagnosed infections by region.ResultsA total of 48 studies met the inclusion criteria, providing 85-point prevalence estimates for curable STIs and BV. Pooled prevalence estimates (with 95% CI and number of women tested) were as follows: MG: 13.5% (4.0–27.2, n=1076); CT: 10.8% (6.9–15.5, n=6700); TV: 13.8% (10.0–18.0, n=9264); NG: 3.3% (2.1–4.7, n=6019); syphilis: 2.9% (2.0–4.0, n=95 308) and BV: 36.6% (27.1–46.6, n=5042). By region, BV was the most prevalent and ranged from 28.5% (24.5–32.8, n=1030) in Eastern Africa to 52.4% (33.5–70.9, n=2305) in Southern Africa; NG had the lowest prevalence, ranging from 1.4% (95% CI 0.1 to 3.1, n=367) in Central Africa to 4.4% (95% CI 2.6 to 6.4, n=4042) in Southern Africa.ConclusionThe prevalence of curable STIs and BV in sub-Saharan Africa is substantial in pregnant women but most prevalent in Southern Africa where HIV prevalence is highest. It is crucial to integrate screening of curable STIs into antenatal care programmes that have previously focused on diagnosis and treatment of syphilis and HIV.
Leaf structural traits of two Restinga plant species with different resistance patterns to iron toxicity
Authors: Santana Brenda Vila Nova , Siqueira-Silva Advanio Inácio , Araújo Talita Oliveira de , Silva Luzimar Campos da 
Published: December 2021

Iron mining activities are a source of particulate iron, which contaminates soil and plants of Restinga biome (Brazil). To investigate the possible effects of iron toxicity on Ipomoea pes-caprae (L.) R. Br. and Canavalia rosea (Sw.) DC. leaves, plants were submitted to different exposure times (12, 36, 108, and 228 hours) and iron concentrations (0.5 or 150 mg·L−1 Fe2+ as FeSO4·7H2O). After 108 hours of iron excess treatment, C. rosea leaves were chlorotic, whereas I. pes-caprae leaves presented venal chlorosis and bronzing after 228 hours of iron excess treatment. The anatomical alterations in I. pes-caprae were more intense and appeared after 36 hours, which was earlier than in C. rosea. The leaf epidermal cells of I. pes-caprae presented alterations in organization, size, and shape, and for both species the epicuticular wax was altered and wax rupture occurred close to the stomata. The positive staining for the presence of iron in leaf tissues matches with damaged areas in I. pes-caprae leaves, indicating direct iron toxicity. Ipomoea pes-caprae presented the most severe symptoms, whereas C. rosea presented the most resistance. The results suggest that, over time, the emission of particulate matter may negatively impact the ecological succession and biodiversity of Restinga.
The opening and closure of oceanic seaways during the Cenozoic: pacemaker of global climate change?
Authors: Bahr André , Kaboth-Bahr Stefanie , Karas Cyrus 
Published: December 2021

Abstract
The opening and constriction of oceanic gateways played an essential role in shaping the global climate throughout Earth's history. In this review, we provide an overview of the best-documented feedbacks between gateway dynamics and climate change throughout the Cenozoic. The discussed tectonically induced events comprise: (i) the opening of the Tasmanian Gateway and the glaciation of Antarctica during the Eocene–Oligocene; (ii) the water-mass exchange between the Atlantic and the Mediterranean via the Strait of Gibraltar that has occurred since the Miocene; and (iii) the closure of the American Seaway and (iv) the constriction of the Indonesian Throughflow, both argued to have been instrumental in the intensification of Northern Hemisphere Glaciation during the late Pliocene and early Pleistocene. Lastly, we look at (v) the climatic impact of the flooding and submergence of the Bering Strait during the Plio-Pleistocene and its influence on the Atlantic Meridional Overturning Circulation. While different in their underlying mechanisms, geographical scale and temporal evolution, these case studies demonstrate that even seemingly small-scale changes in the configuration of ocean seaways fundamentally altered the global climate system via their impact on oceanic currents, global heat transfer and carbon storage.
On Symmetry of Complete Graphs over Quadratic and Cubic Residues
Authors: Mateen M. Haris , Mahmood M. Khalid , Ali Shahbaz , Alam M. D. Ashraful 
Published: December 2021

In this study, we investigate two graphs, one of which has units of a ring

Z

n

as vertices (or nodes) and an edge will be built between two vertices

u

and

v

if and only if

u

3

≡

v

3

mod

n

. This graph will be termed as cubic residue graph. While the other is called Gaussian quadratic residue graph whose vertices are the elements of a Gaussian ring

Z

n

i

of the form

α
=
a
+
i
b
,
β
=
c
+
i

d

, where

a
,
b
,
c
,
d

are the units of

Z

n

. Two vertices

α

and

β

are adjacent to each other if and only if

α

2

≡

β

2

mod

n

. In this piece of work, we characterize cubic and Gaussian quadratic residue graphs for each positive integer

n

in terms of complete graphs.
Trilaciclib Prior to Chemotherapy in Patients with Metastatic Triple-Negative Breast Cancer: Final Efficacy and Subgroup Analysis from a Randomized Phase II Study
Authors: Tan Antoinette R. , Wright Gail S. , Thummala Anu R. , Danso Michael A. , Popovic Lazar , Pluard Timothy J. , Han Hyo S. , Vojnović Željko , Vasev Nikola , Ma Ling , Richards Donald A. , Wilks Sharon T. , Milenković Dušan , Xiao Jie , Sorrentino Jessica , Horton Janet , O'Shaughnessy Joyce 
Published: December 2021

Abstract

Purpose:
We report final antitumor efficacy results from a phase II study of trilaciclib, an intravenous cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, administered prior to gemcitabine plus carboplatin (GCb) in patients with metastatic triple-negative breast cancer (NCT02978716).

Patients and Methods:
Patients were randomized (1:1:1) to group 1 [GCb (days 1, 8); n = 34], group 2 [trilaciclib prior to GCb (days 1, 8); n = 33], or group 3 [trilaciclib (days 1, 8) and trilaciclib prior to GCb (days 2, 9); n = 35]. Subgroup analyses were performed according to CDK4/6 dependence, level of programmed death-ligand 1 (PD-L1) expression, and RNA-based immune signatures using proportional hazards regression. T-cell receptor (TCR) β CDR3 regions were amplified and sequenced to identify, quantify, and compare the abundance of each unique TCRβ CDR3 at baseline and on treatment.

Results:
Median overall survival (OS) was 12.6 months in group 1, not reached in group 2 (HR = 0.31; P = 0.0016), 17.8 months in group 3 (HR = 0.40; P = 0.0004), and 19.8 months in groups 2 and 3 combined (HR = 0.37; P &lt; 0.0001). Efficacy outcomes were comparable regardless of cancer CDK4/6 dependence status and immune signatures. Administering trilaciclib prior to GCb prolonged OS irrespective of PD-L1 status but had greater benefit in the PD-L1–positive population. T-cell activation was enhanced in patients receiving trilaciclib.

Conclusions:
Administering trilaciclib prior to GCb enhanced antitumor efficacy, with significant improvements in OS. Efficacy outcomes in immunologic subgroups and enhancements in T-cell activation suggest these improvements may be mediated via immunologic mechanisms.
Buddhist Homiletics on Grief
Authors: Szántó Péter-Dániel 
Published: December 2021

Abstract
The study first introduces a hitherto completely unstudied anonymous work, for which I reconstruct the title *Saddharmaparikathā. This substantial text is a Buddhist homiletician’s guidebook with sample sermons in Sanskrit on a rich variety of topics. I argue that it dates from the 5th century and that it was possibly authored in a Saṃmatīya environment. I first discuss the unique manuscript transmitting the text, the structure and contents of the work, what information it can provide for the tradition of preaching and its importance for Buddhist studies. In the second half, I provide a sample chapter ‘On Grief’ with an annotated translation.
Intentional self-harm in culturally and linguistically diverse communities: A study of hospital admissions in Victoria, Australia
Authors: Pham Thi Thu Le , O’Brien Kerry S , Berecki-Gisolf Janneke , Liu Sara , Gibson Katharine , Clapperton Angela 
Published: December 2021

Purpose: To examine the rates and profiles of intentional self-harm hospital admissions among people from culturally and linguistically diverse and non-culturally and linguistically diverse backgrounds. Methods: A retrospective analysis of 29,213 hospital admissions for self-harm among people aged 15 years or older in Victoria, Australia, was conducted using data from the Victorian Admitted Episodes Dataset between 2014/2015 and 2018/2019. The Victorian Admitted Episodes Dataset records all hospital admissions in public and private hospitals in Victoria (population 6.5 million). Population-based incidence of self-harm, logistic regression and percentages (95% confidence intervals) were calculated to compare between culturally and linguistically diverse groups by birthplaces and the non-culturally and linguistically diverse groups of self-harm admissions. Results: When grouped together culturally and linguistically diverse individuals had lower rates of (hospital-treated) self-harm compared with the non-culturally and linguistically diverse individuals. However, some culturally and linguistically diverse groups such as those originating from Sudan and Iran had higher rates than non-culturally and linguistically diverse groups. Among self-harm hospitalised patients, those in the culturally and linguistically diverse group (vs non-culturally and linguistically diverse group) were more likely to be older, Metropolitan Victorian residents, from the lowest socioeconomic status, and being ever or currently married. Self-harm admissions by persons born in Southern and Eastern Europe were the oldest of all groups; in all other groups number of admissions tended to decrease as age increased whereas in this group the number of admissions increased as age increased. Conclusion: There was considerable heterogeneity in rates of hospital-treated self-harm in culturally and linguistically diverse communities, with some countries of origin (e.g. Sudan, Iran) having significantly higher rates. Some of this variation may be due to factors relating to the mode of entry into Australia (refugee vs planned migration), and future research needs to examine this possibility and others, to better plan for support needs in the culturally and linguistically diverse communities most affected by self-harm. Combining all culturally and linguistically diverse people into one group may obscure important differences in self-harm. Different self-harm prevention strategies are likely to be needed for different culturally and linguistically diverse populations.
Effectiveness of additional resistance and balance training and telephone support program in exercise-based cardiac rehabilitation on quality of life and physical activity: Randomized control trial
Authors: Tamulevičiūtė-Prascienė Egle , Beigienė Aurelija , Lukauskaitė Urtė , Gerulytė Kamilė , Kubilius Raimondas , Bjarnason-Wehrens Birna 
Published: December 2021

Objectives To evaluate 20 days and 3 months follow-up effectiveness of cardiac rehabilitation (CR) enhanced by resistance/balance training and telephone-support program compared to usual CR care in improving quality of life, clinical course and physical activity behavior. Design Single-centre randomized controlled trial. Setting Inpatient CR clinic Subjects 116 (76.1 ± 6.7 years, 50% male) patients 14.5 ± 5.9 days after valve surgery/intervention were randomized to intervention group (IG, n = 60) or control group (CG, n = 56). Intervention Additional resistance/balance training (3 days/week) during phase-II CR and telephone-support program during 3-month follow-up. CG patients were provided with usual CR care. Main measures Short Form 36 Health Survey scales, European Quality of Life 5 Dimensions 3 Level Version QoL index, visual analog scale, clinical course, and physical activity behavior assessed with standardized questionnaires. Results IG reported statistically significant higher mental component score (48.5 ± 6.91 vs. 40.3 ± 11.21 at the baseline, 50.8 ± 9.76 vs. 42.6 ± 9.82 after 20 days, 49.4 ± 8.45 vs. 40.5 ± 8.9 after 12 weeks follow up), general health (48.6 ± 3.17 vs. 45.0 ± 2.95 at the baseline, 53.6 ± 3.02 vs. 43.8 ± 2.55 after 20 days, 53.2 ± 3.11 vs. 44.2 ± 3.07 after 12 weeks) and role limitations due to emotional problems (48.5 ± 15.2 vs. 27.7 ± 11.5 at the baseline, 72.7 ± 12.6 vs. 30.5 ± 11.2 after 20 days, 66.6 ± 14.2 vs. 36.1 ± 11.2 after 12 weeks) in all three assessments ( p < 0.05). CG patients had more documented hospital admissions (4 (8%) vs 10 (25%), p = 0.027), atrial fibrillation paroxysms (3 (6.0%) vs. 10 (35.0%), p = 0.011) and blood pressure swings (13 (26%) vs. 20 (50%), p = 0.019). IG patients chose more different physical activities (1.7 ± 0.7 vs. 1.25 ± 0.63, p = 0.002), spent more time being physical active every day (195.6 ± 78.6 vs. 157.29 ± 78.8, p = 0.002) Conclusions The addition of resistance/balance exercises and telephone-support program 12 weeks after to the CR could linked to higher physical activity levels and fewer clinical complications but did not lead to a significant improvement in quality of life.
How is Online Disinhibition Related to Adolescents’ Cyberbullying Perpetration? Empathy and Gender as Moderators
Authors: Wang Xingchao , Qiao Yuran , Li Wenqing , Dong Wanghao 
Published: December 2021

The present study examined the relationship between online disinhibition and adolescents’ cyberbullying perpetration and investigated whether empathy and gender would moderate this relationship. A total of 2407 Chinese adolescents aged 11–16 years completed the questionnaires to measure their online disinhibition, empathy, and cyberbullying perpetration. Results indicated that high levels of online disinhibition were associated with high levels of cyberbullying perpetration, even after controlling for key covariates related to cyberbullying perpetration. Empathy significantly moderated the relationship between online disinhibition and cyberbullying perpetration. Specifically, this relationship was not significant at high levels of empathy. Moreover, the impact of empathy was moderated by gender. For male adolescents, online disinhibition was significantly associated with cyberbullying perpetration only when their empathy was low. For female adolescents, the relationship between online disinhibition and cyberbullying perpetration became nonsignificant, regardless of whether they had a low or high level of empathy.
CFRP composite drilling through electrical discharge machining using aluminum as fixture plate
Authors: Pattanayak Suvranshu , Sahoo Ananda Kumar , Sahoo Susanta Kumar 
Published: December 2021

Recent developments in manufacturing require holes on composite materials, especially on the carbon fiber reinforced polymer (CFRP) with smooth hole periphery, low delamination, burr formation, taper, better circularity, and a high processing speed. Its non-conductive surface (epoxy layering) limits its machining through electrical discharge machining (EDM). To overcome this limitation, an aluminum fixture has been designed to guide the copper electrode of EDM for producing holes on a CFRP sheet of 1 mm thickness at low machining complexity, cost, time, delamination, burr in hole periphery and without affecting the material’s surface quality and performance. Even components with high geometrical complexity can also be drilled through this approach. Here, a multi-quality analysis called grey relational analysis is developed for examining the hole quality attributes, considering peak current, pulse on and off time, and flushing pressure as input parameters. This approach points out the optimum factor level setting and critical parameters (pulse-on time and peak current) that regulate the hole attributes (entrance and exit diameter, circularity, taper, material removal, and tool wear rate). An artificial neural network model has been designed and trained through experimental data sets. This model can also be adopted during the determination of hole quality attributes when the parameter settings are beyond a defined boundary, as the regression analysis value is very close to 1, and model performance is 4.99e-10. Peak current = 4 A, pulse-on time = 25 µs, pulse-off time=25 µs, and flushing pressure = 0.6 MPa were the optimum drilling parameters. In the initial hole, average burr length is 391.75 μm, and delamination of 539.3 μm is noticed. But burr formation is very negligible with delamination of 350.7 μm being observed with uniform circularity (0.979), low taper angle (−0.81354°), and TWR (0.000069 g/min) under optimum drilling conditions through this drilling approach.
Prospects and Impediments of Railway Infrastructure Development in Ghana: Impact of Standard Gauge Railway (SGR) Technology
Authors: Awal Iddrisu Mohammed , Senadjki Abdelhak , Nee Au Yong Hui 
Published: December 2021

There is limited understanding concerning the practicable challenges that could impede the developmental process of railway infrastructure projects, and the possible negative effect of the Standard Gauge Railway (SGR) technology in Ghana. Given that the majority of the population are unfamiliar with the newly planned railway system. Our research intends to contribute towards the development of human capital and elevating the standard of living through the assertion of productive policies to ensure rapid infrastructure development by highlighting not only the socio-economic impact, but the negative impact of the railway infrastructure in the society. Also, this study discusses the possible challenges that could hinder the railway infrastructure development process. This study employs face-to-face interviews and Focus Group Discussions (FGDs) interview sessions that assimilate 35 respondents. Data collected is transcribed verbatim and analysed thematically. The findings reveal that corruption, unstable political discourse, lack of modern technology, and the impact of the Covid19 pandemic are among the critical challenges to hinder the progress and completion of the railway infrastructure development. By-laws should be designated ensuring that every uncompleted national project must be completed and not abandoned by the successive governments regardless of political differences. JEL Classifications: R4, O1, Q18, Q55, Q51
Quality assessment of baby wet wipes
Authors: Cheriaa Rim , Boubaker Jaouachi 
Published: December 2021

A wet wipe is a commercial product made of a fibrous substrate impregnated with a lotion that often comes folded and individually wrapped for convenience. The present work relates to wet wipes’ composition to clean the baby’s body. Wet wipes were produced from two spunlace nonwoven fabrics consisting of polyester/viscose and a wetting solution. Objective performance evaluation was carried out to determine the efficiency of the wipes for manufacturing and end uses. The lotion formula comprising surfactants, a solubilizer, preservative compounds, perfumes, and mainly purified water is selected to deliver the intended benefits of a baby wet wipe. Besides, physical, mechanical characteristics, and moisture management parameters of the wet wipe fabrics were measured. Optimal lotion (oil–water emulsion) stirring conditions were illustrated using optical microscopy. Lotion foamability appears as an undesirable phenomenon upon the manufacturing of the wet wipe. A mixture design, an extreme vertices design, was used to study the influence of the compounds on the foam volume. The relative contribution of each compound in the lotion to generate bath foam was discussed. Because wet media are more effective than dry media for surface cleaning, the optimum wet pick-up ensuring the best wiping efficiency about of 83.2% was found to be about 3 g of lotion for 1 g of fabric. Assuming that a wipe sample could be performed in less than 3 min, it was also confirmed that the developed wipe remains effective with a moisture content of 242% and can be comparable with other commercial wipes.