bluuebunny/crossref_metadata_2025_split huggingface dataset:
Explainable Machine Learning for Damage Detection: in Carbon Fiber Composite Plates Under Varying Temperature Conditions
Authors: Schnur Christopher , Moll Jochen , Lugovtsova Yevgeniya , Schütze Andreas , Schneider Tizian 
Published: January 2022

Abstract
Understanding on how a machine learning model interprets data is a crucial step to verify its reliability and avoid overfitting. While the focus of the scientific community is nowadays orientated towards deep learning approaches, which are considered as black box approaches, this work presents a toolbox that is based on complementary methods of feature extraction and selection, where the classification decisions of the model are transparent and can be physically interpreted. On the example of guided wave benchmark data from the open guided waves platform, where delamination defects were simulated at multiple positions on a carbon fiber reinforced plastic plate under varying temperature conditions, the authors could identify suitable frequencies for further investigations and experiments. Furthermore, the authors presented a realistic validation scenario which ensures that the machine learning model learns global damage characteristics rather than position specific characteristics.
Pleiotropy, Natural Selection, and the Evolution of Senescence
Authors: Williams G. C. 
Published: January 2022

A new individual entering a population may be said to have a reproductive probability distribution. The reproductive probability is zero from zygote to reproductive maturity. Later, perhaps shortly after maturity, it reaches a peak value. Then it declines because of the cumulative probability of death. There is a cumulative probability of death with or without senescence.
The selective value of a gene depends on how it affects the total reproductive probability. Selection of a gene that confers an advantage at one age and a disadvantage at another will depend not only on the magnitudes of the effects themselves but also on the times of the effects. An advantage during the period of maximum reproductive probability would increase the total reproductive probability more than a proportionately similar disadvantage later on would decrease it. So natural selection will frequently maximize vigor in youth at the expense of vigor later on and thereby produce a declining vigor (senescence) during adult life. Selection, of course, will act to minimize the rate of this decline whenever possible. The rate of senescence shown by any species will reflect the balance between this direct adverse selection of senescence as an unfavorable character and the indirect favorable selection through the age-related bias in the selection of pleiotropic genes.
Variations in the amount of fecundity increase after maturity, in the adult mortality rate, and in other life history features would affect the shape of the reproductive probability distribution and thereby influence the evolution of senescence. Any factor that decreases the rate of decline in reproductive probability intensifies selection against senescence. Any factor that increases the rate of this decline causes a relaxed selection against senescence and a greater advantage in increasing youthful vigor at the price of vigor later on. These considerations explain much of what is known of phylogenetic variation in rates of senescence. Other deductions from the theory are also supported by limited available evidence. These include the expectation that rapid morphogenesis should be associated with rapid senescence, that senescence should always be a generalized deterioration of many organs and systems, and that postreproductive periods be short and infrequent in any wild population.
Reproduced by permission.

G. C. Williams, Pleiotropy, Natural Selection, and the Evolution of Senescence.
Evolution
11
, 398-411 (1957).
The Maintenance of the Accuracy of Protein Synthesis and Its Relevance to Aging
Authors: Orgel L. E. 
Published: January 2022

The ways in which the accumulation of mutations might contribute to the process of aging in higher organisms or in individual clones of cells has been discussed at length. No corresponding treatment of the consequences of transcription errors in the translation of the DNA message into RNA and protein sequences seems to be available. Here I show that a consideration of the rate of accumulation of such errors leads to a paradox, the resolution of which may be relevant to the problem of aging, and that there are a number of simple experiments that should decide whether this is the case.
Reproduced by permission.

L. E. Orgel, The Maintenance of the Accuracy of Protein Synthesis and Its Relevance to Aging.
Proc. Natl. Acad. Sci. U.S.A.
49
, 517-521 (1963).
No Difference between Spinal Anesthesia with Hyperbaric Ropivacaine and Intravenous Dexmedetomidine Sedation with and without Intrathecal Fentanyl: A Randomized Noninferiority Trial
Authors: Lee Seung Cheol , Kim Tae Hyung , Choi So Ron , Park Sang Yoong 
Published: January 2022

To enhance the duration of single-shot spinal anesthesia, intrathecal fentanyl and intravenous dexmedetomidine are widely used as adjuvants to local anesthetics. This noninferiority trial evaluated whether hyperbaric ropivacaine alone can produce a noninferior duration of sensory block in comparison to hyperbaric ropivacaine with intrathecal fentanyl in patients under dexmedetomidine sedation. Methods. Fifty patients scheduled for elective lower limb surgery under spinal anesthesia were randomly assigned in a double-blind fashion to receive either hyperbaric ropivacaine 15 mg (Group R) or hyperbaric ropivacaine 15 mg with intrathecal fentanyl 20 μg (Group RF). Intravenous dexmedetomidine (1 μg/kg for 10 min, followed by 0.5 μg/kg/h) was administered in both groups. The primary outcome of this study was the time to two-dermatomal regression of sensory block. The noninferiority margin for the mean difference was −10 min. Characteristics of the block, intraoperative and postoperative side effects, postoperative pain score, and analgesic consumption were assessed as secondary outcomes. Results. There was no difference in the two-dermatomal regressions of sensory block between the two groups (Group R 70.4 ± 10.2 min, Group RF 71.2 ± 12.4 min,

p

= 0.804) with a mean difference of 0.8 min (−7.2 to 5.6, 95% confidence interval). Thus, the noninferiority of hyperbaric ropivacaine alone was established. There were no significant differences in the secondary outcomes between the two groups. Conclusions. Under intravenous dexmedetomidine sedation, the duration of spinal anesthesia with hyperbaric ropivacaine alone was noninferior to that of hyperbaric ropivacaine with intrathecal fentanyl. This suggests that addition of intrathecal fentanyl to hyperbaric ropivacaine may not be necessary in patients receiving intravenous dexmedetomidine.
Quantification of T- and B-cell Immune Receptor Distribution Diversity Characterizes Immune Cell Infiltration and Lymphocyte Heterogeneity in Clear Cell Renal Cell Carcinoma
Authors: Ferrall-Fairbanks Meghan C. , Chakiryan Nicholas H. , Chobrutskiy Boris I. , Kim Youngchul , Teer Jamie K. , Berglund Anders , Mulé James J. , Fournier Michelle , Siegel Erin M. , Dhillon Jasreman , Falasiri Seyed Shayan A. , Arturo Juan F. , Katende Esther N. , Blanck George , Manley Brandon J. , Altrock Philipp M. 
Published: January 2022

Abstract

Immune-modulating systemic therapies are often used to treat advanced cancer such as metastatic clear cell renal cell carcinoma (ccRCC). Used alone, sequence-based biomarkers neither accurately capture patient dynamics nor the tumor immune microenvironment. To better understand the tumor ecology of this immune microenvironment, we quantified tumor infiltration across three distinct ccRCC patient tumor cohorts using complementarity determining region-3 (CDR3) sequence recovery counts in tumor-infiltrating lymphocytes and a generalized diversity index (GDI) for CDR3 sequence distributions. GDI can be understood as a curve over a continuum of diversity scales that allows sensitive characterization of distributions to capture sample richness, evenness, and subsampling uncertainty, along with other important metrics that characterize tumor heterogeneity. For example, richness quantified the total unique sequence count, while evenness quantified similarities across sequence frequencies. Significant differences in receptor sequence diversity across gender and race revealed that patients with larger and more clinically aggressive tumors had increased richness of recovered tumoral CDR3 sequences, specifically in those from T-cell receptor alpha and B-cell immunoglobulin lambda light chain. The GDI inflection point (IP) allowed for a novel and robust measure of distribution evenness. High IP values were associated with improved overall survival, suggesting that normal-like sequence distributions lead to better outcomes. These results propose a new quantitative tool that can be used to better characterize patient-specific differences related to immune cell infiltration, and to identify unique characteristics of tumor-infiltrating lymphocyte heterogeneity in ccRCC and other malignancies.

Significance:
Assessment of tumor-infiltrating T-cell and B-cell diversity in renal cell carcinoma advances the understanding of tumor-immune system interactions, linking tumor immune ecology with tumor burden, aggressiveness, and patient survival.
See related commentary by Krishna and Hakimi, p. 764
Novel Group C Oncolytic Adenoviruses Carrying a miRNA Inhibitor Demonstrate Enhanced Oncolytic Activity In Vitro and In Vivo
Authors: Doerner Johannes , Sallard Erwan , Zhang Wenli , Solanki Manish , Liu Jing , Ehrke-Schulz Eric , Zirngibl Hubert , Lieber André , Ehrhardt Anja 
Published: January 2022

Abstract
Oncolytic adenoviruses (OAd) represent an attractive treatment option for cancer. Clinical efficacy of commonly utilized human adenovirus type 5 (Ad5)-based oncolytic viruses is limited by variable expression levels of the coxsackie- and adenovirus receptor (CAR) in tumor cells and high prevalence of neutralizing antibodies against human Ad5. However, previous studies have highlighted alternative human Ad types as promising candidates for oncolytic therapy. In this study, we generated novel OAds based on Ad1, -2, -5, and -6 derived from species C Ads. These OAds contain a 24-bp deletion in the early gene E1A for tumor selective replication and express the RNAi inhibitor P19. We examined these OAds for in vitro anticancer activity on various cancer cell lines derived from lung, colon, gynecologic, bone, and pancreatic carcinoma. In most surveyed cell lines, OAds based on Ad1, -2, and -6 demonstrated higher cell lysis capability compared with Ad5, suggesting enhanced oncolytic potential. Moreover, enhanced oncolytic activity was associated with P19 expression in a cell type–dependent manner. We further explored a A549 tumor xenograft mouse model to compare the novel OAds directly with Ad5 and H101, an oncolytic adenovirus used in clinical trials. These P19-containing OAds based on Ad1, -2, and -6 showed significantly decelerated tumor progression compared with H101, indicating better antitumor potency in vivo. Our studies provide a novel path for OAd development based on alternative Ad types with improved effectiveness by RNA interference suppression.
Mineralocorticoid Receptor Antagonist Use and Hard Renal Outcomes in Real-World Patients With Chronic Kidney Disease
Authors: Oka Tatsufumi , Sakaguchi Yusuke , Hattori Koki , Asahina Yuta , Kajimoto Sachio , Doi Yohei , Kaimori Jun-Ya , Isaka Yoshitaka 
Published: January 2022

Background:
Real-world evidence about mineralocorticoid receptor antagonist (MRA) use has been limited in chronic kidney disease, particularly regarding its association with hard renal outcomes.

Methods:

In this retrospective cohort study, adult chronic kidney disease outpatients referred to the department of nephrology at an academic hospital between January 2005 and December 2018 were analyzed. The main inclusion criteria were estimated glomerular filtration rate ≥10 and <60 mL/min per 1.73 m
2
and follow-up ≥90 days. The exposure of interest was MRA use, defined as the administration of spironolactone, eplerenone, or potassium canrenoate. The primary outcome was renal replacement therapy initiation, defined as the initiation of chronic hemodialysis, peritoneal dialysis, or kidney transplantation. A marginal structural model using inverse probability of weighting was applied to account for potential time-varying confounders.

Results:

Among a total of 3195 patients, the median age and estimated glomerular filtration rate at baseline were 66 years and 38.4 mL/min per 1.73 m
2
, respectively. During follow-up (median, 5.9 years), 770 patients received MRAs, 211 died, and 478 started renal replacement therapy. In an inverse probability of weighting-weighted pooled logistic regression model, MRA use was significantly associated with a 28%-lower rate of renal replacement therapy initiation (hazard ratio, 0.72 [95% CI, 0.53–0.98]). The association between MRA use and renal replacement therapy initiation was dose-dependent (
P
for trend <0.01) and consistent across patient subgroups. The incidence of hyperkalemia (>5.5 mEq/L) was somewhat higher in MRA users but not significant (hazard ratio, 1.14 [95% CI, 0.88–1.48]).

Conclusions:
MRA users showed a better renal prognosis across various chronic kidney disease subgroups in a real-world chronic kidney disease population.
On Learning Interpreted Languages with Recurrent Models
Authors: Paperno Denis 
Published: January 2022

Abstract
Can recurrent neural nets, inspired by human sequential data processing, learn to understand language? We construct simplified data sets reflecting core properties of natural language as modeled in formal syntax and semantics: recursive syntactic structure and compositionality. We find LSTM and GRU networks to generalize to compositional interpretation well, but only in the most favorable learning settings, with a well-paced curriculum, extensive training data, and left-to-right (but not right-to-left) composition.
Resilience in Agroecosystems: An Index Based on a Socioecological Systems Approach
Authors: Suarez-Pardo Andrea , Villegas-Palacio Clara , Berrouet Lina 
Published: January 2022

Abstract
This article presents an agroecosystem resilience index (ARI) relative to two types of exogenous drivers: biophysical and socioeconomic threats. The ARI is based on a theoretical framework of socioecological systems and draws upon multicriteria analysis. The multicriteria consist of variables related to natural, productive, socioeconomic, and institutional systems that are weighted and grouped through expert judgment. The index was operationalized in the Rio Grande basin (RGB), in the Colombian Andes. The ARI was evaluated at the household level using information from 99 RGB households obtained through workshops, individual semistructured interviews, and surveys. The ARI is a continuous variable that ranges between 0 and 1 and results in five categories of resilience: very low, low, medium, high, and very high. When faced with climate change impacts, 19% of households showed low resilience, 64% showed medium resilience, and 16% showed high resilience according to the ARI. When faced with price fluctuations, 23% of households showed low resilience, 65% showed medium resilience, and 11% showed high resilience. Key variables associated with high resilience include the diversity of vegetation cover, households that have forests on their properties, a high degree of connectivity with other patches of forest, diversification of household economic activities, profitability of economic activities, availability of water sources, and good relationships with local institutions.
The Effect of COVID-19 Pandemic on the Global Supply Chain Operations: A System Dynamics Approach
Authors: Heidary Mojtaba Hajian 
Published: January 2022

Epidemic outbreaks are one of the important sources of the risk in the global supply chains. Before the COVID-19 pandemic, global industries that were unprepared for disruptions experienced a decline due to the pandemic. A global supply chain is a complex system set of dynamics that could be analyzed by the system dynamics approach. In this article, the impact of the recent pandemic on the global supply chain is simulated in different scenarios. A system dynamic model is developed to carry out the simulations. In order to consider the impact of the pandemic on the exogenous and endogenous variables, a force majeure factor is defined in the model. Global features considered in this article are the export and import operations, the exchange rate and the rate of tariff. In this article, a scenario analysis is performed to analyze two important factors of the global supply chain: force majeure factor and delivery delay. Results showed that improving the flexibility of production capacity is one of the important strategies that global supply chain managers should pursue. JEL Codes: F23, P45, C15, C63, E37, F17
The Temporal Relationship Between Self-Acceptance and Generativity over Two Decades
Authors: Joshanloo Mohsen 
Published: January 2022

Generativity is defined as a concern for the well-being of future generations, which involves both caring and a will to extend the self into the future. Extant research indicates that generativity plays an important role in successful aging. The present study sought to examine the temporal relationship between self-acceptance and generativity over about 2 decades. The data were drawn from the three waves of the Midlife in the United States (MIDUS) project, collected with intervals of about 10 years ( N = 4,167). The random-intercept cross-lagged panel model was used for data analysis. It was found that self-acceptance prospectively predicted generativity, whereas generativity did not predict self-acceptance. Thus, coming to terms with various aspects of one’s personality and past life contributes to higher future levels of generativity.
Level of Stress and Coping Strategies Seen Among Parents of Neonates Admitted in NICU
Authors: Pathak Geetanjali , Dixit Rahul , Singh Niranjan K. , Vijaywargiya Taruna , Lal Narottam 
Published: January 2022

Aim To assess the level of stress and coping strategies in parents of neonates admitted in Neonatal Intensive Care Unit (NICU) at a tertiary care centre in North India. Materials and methods It was a descriptive/observational cross-sectional study of 3 year duration with a sample size of 224. All parents willing to participate and who could understand English or Hindi were included in the study after the informed consent. Stress levels and coping strategies were assessed using a validated questionnaire between 2nd to 7th day of admission. Demographic data was collected and parental stress and coping was quantified using likert scale. The data was analyzed using SPSS Version 20.0. Results Most of the parents were moderately stressed (93.3%). The most impactful stress domain was ‘Emotional’ and the most impactful question out of that domain was ‘constant fear of child’s recovery’. Of all the coping strategies, cognitive strategy was mostly used by parents. There was a negative correlation between stress and coping strategies (r = –0.09) but the result was statistically insignificant (p-value = 0.16). Of all the demographic variables, the birth order of the baby was significantly related to stress (p-value < 0.05), while parent’s education, monthly family income and area of residence were significantly related to coping (p-value < 0.05, <0.05 and <0.001, respectively). Conclusion Most of the parents were moderately stressed, with cognitive strategy being the most used by parents as the coping mechanism.
Triple combination of BET plus PI3K and NF-κB inhibitors exhibit synergistic activity in adult T-cell leukemia/lymphoma
Authors: Daenthanasanmak Anusara , Bamford Richard N. , Yoshioka Makoto , Yang Shyh-Ming , Homan Philip , Karim Baktiar , Bryant Bonita R. , Petrus Michael N. , Thomas Craig J. , Green Patrick L. , Miljkovic Milos D. , Conlon Kevin C. , Waldmann Thomas A. 
Published: January 2022

AbstractAdult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell lymphoproliferative malignancy caused by human T-cell leukemia virus type 1 (HTLV-1). ATL is an orphan disease with no curative drug treatment regimens urgently needing new combination therapy. HTLV-1-infected cells rely on viral proteins, Tax and HBZ (HTLV-1-b-ZIP factor), to activate the transcription of various host genes that are critical for promoting leukemic transformation. Inhibition of bromodomain and extraterminal motif (BET) protein was previously shown to collapse the transcriptional network directed by BATF3 super-enhancer and thereby induced ATL cell apoptosis. In the current work, by using xenograft, ex vivo, and in vitro models, we demonstrated that I-BET762 (BETi) synergized with copanlisib (PI3Ki) and bardoxolone methyl (NF-κBi) to dramatically decrease the growth of ATL cells. Mechanistically, the triple combination exhibited synergistic activity by down-regulating the expression of c-MYC while upregulating the level of the glucocorticoid-induced leucine zipper (GILZ). The triple combination also enhanced apoptosis induction by elevating the expression of active caspase-3 and cleaved PARP. Importantly, the triple combination prolonged the survival of ATL-bearing xenograft mice and inhibited the proliferation of ATL cells from peripheral blood mononuclear cells (PBMCs) of both acute and smoldering/chronic ATL patients. Therefore, our data provide the rationale for a clinical trial exploring the multiagent combination of BET, PI3K/AKT, and NF-κB inhibitors for ATL patients and expands the potential treatments for this recalcitrant malignancy.
Growth and chemotaxis of nematodes reduced upon exposure to Third Fork Creek surface water
Authors: Gerald Carresse , Deshazo Boris , Patterson Hayden , Spence Porché 
Published: January 2022

AbstractBackgroundThird Fork Creek is a historically impaired urban stream that flows through the city of Durham, North Carolina.Caenorhabditis elegans(C. elegans) are non-parasitic, soil and aquatic dwelling nematodes that have been used frequently as a biological and ecotoxicity model. We hypothesize that exposure to Third Fork Creek surface water will inhibit the growth and chemotaxis ofC. elegans. Using our ring assay model, nematodes were enticed to cross the water samples to reach a bacterial food source which allowed observation of chemotaxis. The total number of nematodes found in the bacterial food source and the middle of the plate with the water source was recorded for 3 days.ResultsOur findings suggest a reduction in chemotaxis and growth on day three in nematodes exposed to Third Fork Creek water samples when compared to the control (pvalue < 0.05). These exploratory data provide meaningful insight to the quality of Third Fork Creek located near a Historically Black University.ConclusionsFurther studies are necessary to elucidate the concentrations of the water contaminants and implications for human health. The relevance of this study lies within the modelC.elegansthat has been used in a plethora of human diseases and exposure research but can be utilized as an environmental indicator of water quality impairment.