bluuebunny/crossref_metadata_2025 huggingface dataset:
Early corticosteroid dose tapering in patients with acute exacerbation of idiopathic pulmonary fibrosis
Authors: Anan Keisuke , Kataoka Yuki , Ichikado Kazuya , Kawamura Kodai , Johkoh Takeshi , Fujimoto Kiminori , Tobino Kazunori , Tachikawa Ryo , Ito Hiroyuki , Nakamura Takahito , Kishaba Tomoo , Inomata Minoru , Kamitani Tsukasa , Yamazaki Hajime , Ogawa Yusuke , Yamamoto Yosuke
Published: October 2022

Background

Although corticosteroid therapy with dose tapering is the most commonly used treatment for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), there is no consensus on the tapering regimen. This study aimed to investigate the association between early corticosteroid dose tapering and in-hospital mortality in patients with AE-IPF.

Methods

In this retrospective cohort study, we analyzed the data of a cohort from eight Japanese tertiary care hospitals and routinely collected administrative data from a cohort from 185 Japanese hospitals. Patients with AE-IPF were classified into the early and non-early tapering groups depending on whether the maintenance dose of corticosteroids was reduced within two weeks of admission. Propensity score analysis with inverse probability weighting (IPW) was performed to estimate the effect of early corticosteroid dose tapering.

Results

The multi-center cohort included 153 eligible patients, of whom 47 (31%) died, whereas the administrative cohort included 229 patients, of whom 51 (22%) died. Patients with early tapering tended to have a better prognosis than those without it (unadjusted hazard ratio [95% confidence interval] 0.41 [0.22–0.76] and 0.65 [0.36–1.18] in the multi-center and administrative cohorts, respectively). After IPW, the early tapering group had a better prognosis than the non-early tapering group (IPW-adjusted hazard ratio [95% confidence interval] 0.37 [0.14–0.99] and 0.27 [0.094–0.83] in the multi-center and administrative cohorts, respectively).

Conclusion

Early corticosteroid dose tapering was associated with a favorable prognosis in patients with AE-IPF. Further studies are warranted to confirm the effects of early corticosteroid dose tapering in patients with AE-IPF.
Patient variability in the blood-stage dynamics of Plasmodium falciparum captured by clustering historical data
Authors: Masserey Thiery , Penny Melissa A. , Lee Tamsin E.
Published: October 2022

Background

Mathematical models provide an understanding of the dynamics of a Plasmodium falciparum blood-stage infection (within-host models), and can predict the impact of control strategies that affect the blood-stage of malaria. However, the dynamics of P. falciparum blood-stage infections are highly variable between individuals. Within-host models use different techniques to capture this inter-individual variation. This struggle may be unnecessary because patients can be clustered according to similar key within-host dynamics. This study aimed to identify clusters of patients with similar parasitaemia profiles so that future mathematical models can include an improved understanding of within-host variation.

Methods

Patients’ parasitaemia data were analyzed to identify (i) clusters of patients (from 35 patients) that have a similar overall parasitaemia profile and (ii) clusters of patients (from 100 patients) that have a similar first wave of parasitaemia. For each cluster analysis, patients were clustered based on key features which previous models used to summarize parasitaemia dynamics. The clustering analyses were performed using a finite mixture model. The centroid values of the clusters were used to parameterize two established within-host models to generate parasitaemia profiles. These profiles (that used the novel centroid parameterization) were compared with profiles that used individual-specific parameterization (as in the original models), as well as profiles that ignored individual variation (using overall means for parameterization).

Results

To capture the variation of within-host dynamics, when studying the overall parasitaemia profile, two clusters efficiently grouped patients based on their infection length and the height of the first parasitaemia peak. When studying the first wave of parasitaemia, five clusters efficiently grouped patients based on the height of the peak and the speed of the clearance following the peak of parasitaemia. The clusters were based on features that summarize the strength of patient innate and adaptive immune responses. Parameterizing previous within host-models based on cluster centroid values accurately predict individual patient parasitaemia profiles.

Conclusion

This study confirms that patients have personalized immune responses, which explains the variation of parasitaemia dynamics. Clustering can guide the optimal inclusion of within-host variation in future studies, and inform the design and parameterization of population-based models.
Response to Toshihide Tsuda, Yumiko Miyano and Eiji Yamamoto [1]
Authors: Soskolne Colin L. , Bero Lisa A. , Kramer Shira , Gochfeld Michael , Ramos-Bonilla Juan Pablo , Sass Jennifer , Cranor Carl F. , Advani Shailesh , Mandrioli Daniele
Published: October 2022

Background

In August 2021, we published in Environmental Health a Toolkit for detecting misused epidemiological methods with the goal of providing an organizational framework for transparently evaluating epidemiological studies, a body of evidence, and resultant conclusions. Tsuda et al., the first group to utilize the Toolkit in a systematic fashion, have offered suggestions for its modification.

Main body

Among the suggested modifications made by Tsuda et al., we agree that rearrangement of Part A of the Toolkit to reflect the sequence of the epidemiological study process would facilitate its usefulness. Expansion or adaptation of the Toolkit to other disciplines would be valuable but would require the input of discipline-specific expertise. We caution against using the sections of the Toolkit to produce a tally or cumulative score, because none of the items are weighted as to importance or impact. Rather, we suggest a visual representation of how a study meets the Toolkit items, such as the heat maps used to present risk of bias criteria for studies included in Cochrane reviews. We suggest that the Toolkit be incorporated in the sub-specialty known as “forensic epidemiology,” as well as in graduate training curricula, continuing education programs, and conferences, with the recognition that it is an extension of widely accepted ethics guidelines for epidemiological research.

Conclusion

We welcome feedback from the research community about ways to strengthen the Toolkit as it is applied to a broader assemblage of research studies and disciplines, contributing to its value as a living tool/instrument. The application of the Toolkit by Tsuda et al. exemplifies the usefulness of this framework for transparently evaluating, in a systematic way, epidemiological research, conclusions relating to causation, and policy decisions.

Postscript

We note that our Toolkit has, most recently, inspired authors with discipline-specific expertise in the field of Conservation Biology to adapt it for use in the Biological Sciences.
Perfluorinated compounds in adults and their association with fasting glucose and incident diabetes: a prospective cohort study
Authors: Chung Seung Min , Heo Dong-Gyu , Kim Ju-Hyun , Yoon Ji Sung , Lee Hyoung Woo , Kim Jong-Yeon , Moon Jun Sung , Won Kyu Chang
Published: October 2022

Background

The endocrine disruption of perfluorinated compounds is an emerging issue. We aimed to examine the association of serum perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) levels with incident diabetes and fasting serum glucose concentration.

Methods

This prospective cohort study was based on an urban-based cohort subpopulation from the Korean Genome and Epidemiology Study. Serum samples (600 µL) were received from 100 participants in the normoglycemic baseline survey (2004–2013), and concentrations of PFOA and PFOS were measured using mass spectrometry. The incidence of diabetes was tracked in the follow-up survey (2012–2016).

Results

The mean age was 56.4 years (men, 59%). The median serum PFOA and PFOS concentrations were 4.29 ng/mL and 9.44 ng/mL, respectively. PFOA and PFOS concentrations differed according to age, sex, and residential area. After 60 months, 23 patients had diabetes. Log-transformed PFOA (lnPFOA) and log-transformed PFOS (lnPFOS) were significantly higher in those who transitioned to diabetes than in those who did not (both p < 0.05). After multivariate adjustment, lnPFOA (coefficient = 6.98, 95% CI -0.04–14, p = 0.054) and lnPFOS (coefficient = 7.06, 95% CI -0.96–15.08, p = 0.088) predicted increased fasting glucose without statistical significance. In addition, lnPFOA, but not lnPFOS, significantly predicted incident diabetes (HR = 3.98, 95% CI 1.42–11.1, p < 0.01).

Conclusion

Exposure to PFOA and PFOS may have a potential dysglycemic effect. In particular, exposure to PFOA increased the risk of diabetes. Further research with larger sample size is warranted.
Marijuana use and DNA methylation-based biological age in young adults
Authors: Nannini Drew R. , Zheng Yinan , Joyce Brian T. , Gao Tao , Liu Lei , Jacobs David R. , Schreiner Pamela , Liu Chunyu , Horvath Steve , Lu Ake T. , Yaffe Kristine , Sidney Stephen , Greenland Philip , Lloyd-Jones Donald M. , Hou Lifang
Published: October 2022

Background

Marijuana is the third most commonly used drug in the USA and efforts to legalize it for medical and recreational use are growing. Despite the increase in use, marijuana’s effect on aging remains understudied and understanding the effects of marijuana on molecular aging may provide novel insights into the role of marijuana in the aging process. We therefore sought to investigate the association between cumulative and recent use of marijuana with epigenetic age acceleration (EAA) as estimated from blood DNA methylation.

Results

A random subset of participants from The Coronary Artery Risk Development in Young Adults (CARDIA) Study with available whole blood at examination years (Y) 15 and Y20 underwent epigenomic profiling. Four EAA estimates (intrinsic epigenetic age acceleration, extrinsic epigenetic age acceleration, PhenoAge acceleration, and GrimAge acceleration) were calculated from DNA methylation levels measured at Y15 and Y20. Ever use and cumulative marijuana-years were calculated from the baseline visit to Y15 and Y20, and recent marijuana use (both any and number of days of use in the last 30 days) were calculated at Y15 and Y20. Ever use of marijuana and each additional marijuana-year were associated with a 6-month (P < 0.001) and a 2.5-month (P < 0.001) higher average in GrimAge acceleration (GAA) using generalized estimating equations, respectively. Recent use and each additional day of recent use were associated with a 20-month (P < 0.001) and a 1-month (P < 0.001) higher GAA, respectively. A statistical interaction between marijuana-years and alcohol consumption on GAA was observed (P = 0.011), with nondrinkers exhibiting a higher GAA (β = 0.21 [95% CI 0.05, 0.36], P = 0.008) compared to heavy drinkers (β = 0.05 [95% CI − 0.09, 0.18], P = 0.500) per each additional marijuana-year. No associations were observed for the remaining EAA estimates.

Conclusions

These findings suggest cumulative and recent marijuana use are associated with age-related epigenetic changes that are related to lifespan. These observed associations may be modified by alcohol consumption. Given the increase in use and legalization, these findings provide novel insight on the effect of marijuana use on the aging process as captured through blood DNA methylation.
Global dynamics for an SVEIR epidemic model with diffusion and nonlinear incidence rate
Authors: Xu Jinhu
Published: October 2022

In this paper, we investigate an SVEIR epidemic model with reaction–diffusion and nonlinear incidence. We establish the well-posedness of the solutions and the basic reproduction number$\mathfrak{R}_{0}$R0. Moreover, we show that the disease-free steady state is globally asymptotically stable when$\mathfrak{R}_{0}<1$R0<1, whereas the disease will be persistent when$\mathfrak{R}_{0}>1$R0>1. Furthermore, using the method of Lyapunov functional, we prove the global stability of the positive steady state for the spatial homogeneous model.
Myelin repair in Alzheimer’s disease: a review of biological pathways and potential therapeutics
Authors: Hirschfeld Lauren Rose , Risacher Shannon L. , Nho Kwangsik , Saykin Andrew J.
Published: October 2022

This literature review investigates the significant overlap between myelin-repair signaling pathways and pathways known to contribute to hallmark pathologies of Alzheimer’s disease (AD). We discuss previously investigated therapeutic targets of amyloid, tau, and ApoE, as well as other potential therapeutic targets that have been empirically shown to contribute to both remyelination and progression of AD. Current evidence shows that there are multiple AD-relevant pathways which overlap significantly with remyelination and myelin repair through the encouragement of oligodendrocyte proliferation, maturation, and myelin production. There is a present need for a single, cohesive model of myelin homeostasis in AD. While determining a causative pathway is beyond the scope of this review, it may be possible to investigate the pathological overlap of myelin repair and AD through therapeutic approaches.
Recall of reactive cutaneous capillary endothelial proliferation (RCCEP) induced by stereotactic body radiation therapy (SBRT) in a patient with lung squamous cell carcinoma
Authors: Ma Rong , Wang Jia-Lin , Wang Yan-Yang
Published: October 2022

Camrelizumab (SHR-1210) is a humanized IgG4 monoclonal anti-programmed cell death protein 1 (PD-1) antibody that has been shown to inhibit the binding of PD-1 to PD-L1, thereby blocking the immune escape of various types of cancer, including lung squamous cell carcinoma (LSCC). Reactive cutaneous capillary endothelial proliferation (RCCEP) is the most common adverse event in camrelizumab-treated patients. Here, we introduce a case of LSCC with recall RCCEP induced by stereotactic body radiation therapy (SBRT). A 76-year-old LSCC patient developed RCCEP when he received camrelizumab and chemotherapy. After discontinuing camrelizumab treatment, the RCCEP lesions spontaneously regressed and fell off. However, when the patient received subsequent SBRT, the RCCEP occurred again at the same sites. This case may provide clues for additional study of the immune reactivation effect of SBRT or the underlying mechanism of RCCEP.
Tailoring the sampling time of single-sample GFR measurement according to expected renal function: a multisite audit
Authors: McMeekin Helena , Townrow Sam , Barnfield Mark , Bradley Andy , Fongenie Ben , McGowan Daniel R. , Memmott Matthew , Porter Charlotte A. , Wickham Fred , Vennart Nick , Burniston Maria
Published: October 2022

Background

The 2018 BNMS Glomerular Filtration Rate (GFR) guidelines recommend a single-sample technique with the sampling time dictated by the expected renal function, but this is not known with any accuracy before the test. We aimed to assess whether the sampling regime suggested in the guidelines is optimal and determine the error in GFR result if the sample time is chosen incorrectly. We can then infer the degree of flexibility in the sampling regime.

Methods

Data from 6328 patients referred for GFR assessment at 6 different hospitals for a variety of indications were reviewed. The difference between the single-sample (Fleming) GFR result at each sample time and the slope–intercept GFR result at each hospital was calculated. A second dataset of 777 studies from one hospital with nine samples collected from 5 min to 8 h post-injection was analysed to provide a reference GFR to which the single-sample results were compared.

Results

Recommended single-sample times have been revised: for an expected GFR above 90 ml/min/1.73m2 a 2-h sample is recommended; between 50 and 90 ml/min/1.73m2 a 3-h sample is recommended; and between 30 and 50 ml/min/1.73m2 a 4-h sample is recommended. Root mean square error in single-sample GFR result compared with slope–intercept can be kept less than or equal to 3.30 ml/min/1.73m2 by following these recommendations.

Conclusion

The results of this multisite study demonstrate a reassuringly wide range of sample times for an acceptably accurate single-sample GFR result. Modified recommended single-sample times have been proposed in line with the results, and a lookup table has been produced of rms errors across the full range of GFR results for the three sample times which can be used for error reporting of a mistimed sample.
The unseen epidemic: trauma and loneliness in urban midlife women
Authors: Liberatore-Maguire E , Devlin A , Fisher S , Ramsey F , Grunwald H , Brownstein K , Morrison MF
Published: October 2022

Background

Connectedness and attachment are vital parts of humanity. Loneliness, a state of distress in reaction to perceived detachment and isolation, is reported by over one-third of U.S. adults and is associated with numerous physical and mental health consequences. What contributes to loneliness, especially in women and minority populations, is poorly understood, but this population is also at greater risk for abuse and trauma. Our study aimed to further understand loneliness in urban midlife women and to explore the relationship that may exist with trauma(s).

Methods

To identify primacies for mental health care, female midlife participants (N=50) of a long-standing urban community-based cohort focused on health improvement completed a one-time audiotaped interview with both quantitative assessments and a qualitative interview. Loneliness was assessed by the UCLA 3-item Loneliness Scale. Using semi-structured interviews, open-ended questions facilitated a discussion regarding mental health needs and experiences. Interview transcripts were coded and analyzed following a grounded theory methodology. Themes around loneliness and trauma emerged. The transcripts were coded using the same methodology and coders as the individual interviews. Twenty women participated in two optional focus groups.

Results

Participants had a mean age of 50, with the majority identifying as Black/African American (N=37) and unemployed (N=33). Three themes emerged regarding perceived causes of loneliness: trauma, the burden of responsibilities for others, and secondary to unhealthy relationships. Loneliness associated with trauma will be explored here; other themes are beyond the scope of this paper and will be discussed in subsequent analyses. Quantitative results suggest that physical abuse (loneliness scores 5.4 vs. 4.0, p=0.003), as well as emotional abuse and neglect (loneliness scores 5.6 vs. 4.4, p=0.01), were associated with greater loneliness.

Conclusion

In urban midlife low-income women, lifetime physical abuse and emotional abuse/neglect are associated with increased feelings of loneliness. Qualitative data provide insight into how participants viewed their traumatic histories, ways in which the trauma has ongoing influence, and how they experience loneliness. Though further investigation is needed, trauma-informed approaches should be considered in both primary care and mental health settings with a focus on mitigating loneliness and providing appropriate support and trauma treatment.
Bilateral vocal cords paralysis requiring urgent tracheostomy on COVID-19 patient: a case report
Authors: Omura Kazuya , Kurahashi Kiyoyasu
Published: October 2022

Background

SARS-CoV-2 infection has many manifestations, including otolaryngological symptoms.

Case presentation

A 60-year-old man with severe dyspnea underwent endotracheal intubation followed by 68 h of mechanical ventilation. After extubation, he left the ICU without any significant complications. Four days after the extubation, he developed dyspnea, which deteriorated the next 2 days, and stridor became evident. A fiberoptic laryngoscope revealed bilateral vocal cord edema and paralysis, which required an emergency airway. We decided to perform an awake tracheostomy under local anesthesia while considering protection for airborne infection to healthcare providers. The tracheostomy was closed when the edema and paralysis of the vocal cords were ameliorated.

Conclusions

A COVID-19 patient who underwent injurious ventilation developed vocal cord paralysis and edema 6 days after extubation, leading to an emergency tracheostomy. Close attention to the upper airway of COVID-19 patients is essential since the pathophysiology of the present incident may be specific to the viral infection.
Sketch of 2018 dengue outbreak in a megacity, Bangladesh
Authors: Amin Mohammad Robed , Islam Mohammad Rafiqul , Bhuiyan Muktadir , Islam Md. Shahnoor , Islam Fathema , Tuli Habiba Jannatun , Nawar Afra , Tabassum Tamanna , Fardous Jannatul , Hasan Mohammad Jahid
Published: October 2022

Background

Dengue has become a major public health threat in Bangladesh since 2000, when the first outbreak was reported. Each outbreak has distinct characteristics, and thus, the report of the outbreak helps to understand the disease process and subsequent clinical management of these patients. On that ground, the study was designed to sketch the clinico-epidemiological characteristics of the 2018 dengue outbreak in Bangladesh.

Methods

This hospital-based cross-sectional study was conducted in one of the largest public medical college hospitals and a single private hospital located in the southern and northern parts of the megacity of the country. A total of 297 confirmed dengue cases were assessed with a preformed pretested questionnaire. Clinico-epidemiological and laboratory parameters were reported along with sociodemographic details. Statistical analysis was performed with SPSS 20.

Results

Male patients were predominantly affected by dengue infection. The mean age of the patients was 31.24 ± 13.99 (SD) years, with a range from 2 to 85 years. Eighty-two percent of patients reported from the Dhaka metropolitan city. The highest percentage of cases (37.1%) was isolated from Bansree, Dhaka city, followed by Rampura (21.4%) and Khilgaon (6.2%). In addition to common symptoms, e.g., fever (90.6%), headache (90.6%), chills (81.8%), anorexia and vomiting (76.4%), backache, and redness of the eyes were two prominent symptoms that affected more than two-thirds of the study population. On the other hand, less common symptoms, such as cough, abdominal pain, and respiratory distress, were present in 39.7%, 33.7%, and 15.5% of patients, respectively. Overall, 17.6% of patients were hypotensive during admission, with a mean systolic blood pressure of 107.65 ± 18.17 (SD) mmHg. Other prominent signs were dehydration (80.5%) and rash (33%).

Conclusion

This outbreak was especially characterized by gastrointestinal symptoms, which were predominant along with other typical features.
Fulminant myocarditis-associated expanded dengue syndrome in pregnant woman: a case report
Authors: Wijaya Wilson Saputra , Krisnawati Ika
Published: October 2022

Background

Dengue fever is a mosquito-borne viral disease whose incidence has increased globally, with Indonesia as hyperendemic. In Indonesia, around 17.4% of febrile cases were due to dengue. Expanded dengue syndrome is a term for dengue fever with atypical manifestations in other organs such as renal, respiratory, and cardiac. Dengue myocarditis remains underdiagnosed and usually has a low risk of heart failure. However, pregnancy increases the risk of expanded dengue syndrome, with the incidence six times higher in pregnant women. Due to limited studies about myocarditis treatment during pregnancy, it is critical to understand the effects of heart drugs and the importance of treatment choices with limited selection during fulminant myocarditis.

Case presentation

We reported a case of an adult pregnant woman in her second trimester with fulminant myocarditis-associated expanded dengue syndrome based on criteria. The patient suddenly worsened with progressive cardiomegaly and lung edema accompanied by cardiogenic shock. Multidisciplinary treatment management has been given to improve cardiac function and other organs due to dengue by considering the risk and family consent. The patient recovered from myocarditis, and the cardiac size has reduced.

Conclusions

Fulminant myocarditis is a serious complication of expanded dengue syndrome, and aggressive therapy is required to prevent it. Further investigations and a multidisciplinary system are required to reduce or minimize fetal abnormalities.
Unpaired training: Optimize the seismic data denoising model without paired training data
Authors: Ma Haitao , Ba He , Li Yue , Zhao Yuxing , Wu Ning
Published: October 2022

With the development of seismic exploration technology, distributed acoustic sensing (DAS) has recently received attention in geophysics. However, owing to the complexity of the layout techniques in the DAS systems, and the unknown or harsh exploration environment, seismic data acquired by this technique usually contain the noise of diverse components, which increases the difficulty in subsequent data analysis and interpretation. This study has (1) trained a deep learning model that effectively suppressed noise with augmented noise data sets to obtain a high signal-to-noise ratio in the DAS vertical seismic profile (VSP) records, (2) introduced an attention module to enhance the extraction and recognition of signal features to recover effective signals under substantial noise interference, and (3) introduced adversarial loss and cycle-consistent loss to replace the commonly used L1 norm or L2 norm to train the network. The obtained hybrid training set containing unpaired synthetic and unpaired field data sets for model pretraining and fine tuning effectively improves the denoising performance of the seismic field data. In summary, this study develops an unpaired training-based DAS seismic data denoising method that transformed noisy DAS VSP data into noise-free data. By analyzing the noise suppression results of other methods, including qualitative and quantitative analyses, we demonstrate that our method successfully suppressed multiple types of noise in the DAS VSP data. The study has indicated clear and continuous signals in the denoising results and improved the denoising performance on the seismic field data.
Separating seismic diffractions by an improved Cook-distance singular value decomposition method
Authors: Chen Zongnan , Zhao Jingtao , Peng Suping , Sheng Tongjie
Published: October 2022

When seismic waves encounter abrupt points of stratum or lithology in the process of propagation, such as fault edges, pinch-out points, or the protrusion of unconformity surfaces, the Snell law will break down and many diffractions will be generated. However, the diffraction information is typically masked by strong reflections; thus, separating diffractions is one key issue for diffraction imaging. The traditional singular value decomposition (SVD) method with the ability for wavefield decomposition and reconstruction is useful in removing strong reflections of large singular values. However, the continuously changing characteristics of the singular value of steep-slope reflections make it difficult to choose a suitable parameter for separating diffractions. To solve the problem of singular value selection in diffractions reconstruction by the SVD method, we have developed a Cook-distance SVD method by mathematically least-squares measuring the contribution of every singular value. The Cook-distance SVD can amplify the difference between continuously changing singular values and easily find the singular values representing diffractions. Synthetic examples and field data applications demonstrate that our Cook-distance SVD method can avoid parameter testing and has good performance in diffraction separation and can highlight reservoir-involved small-scale geologic edges and scatterers.
Dual-Acting Peptides Target EZH2 and AR: A New Paradigm for Effective Treatment of Castration-Resistant Prostate Cancer
Authors: Han Zhengyang , Rimal Ujjwal , Khatiwada Prabesh , Brandman Jacob , Zhou Jun , Hussain Muhammad , Viola Ronald E , Shemshedini Lirim
Published: October 2022

Prostate cancer starts as a treatable hormone-dependent disease, but often ends in a drug-resistant form called castration-resistant prostate cancer (CRPC). Despite the development of the antiandrogens enzalutamide and abiraterone for CRPC, which target the androgen receptor (AR), drug resistance usually develops within 6 months and metastatic CRPC (mCRPC) leads to lethality. EZH2, found with SUZ12, EED, and RbAP48 in Polycomb repressive complex 2 (PRC2), has emerged as an alternative target for the treatment of deadly mCRPC. Unfortunately, drugs targeting EZH2 have shown limited efficacy in mCRPC. To address these failures, we have developed novel, dual-acting peptide inhibitors of PRC2 that uniquely target the SUZ12 protein component, resulting in the inhibition of both PRC2 canonical and noncanonical functions in prostate cancer. These peptides were found to inhibit not only the EZH2 methylation activity, but also block its positive effect on AR gene expression in prostate cancer cells. Since the peptide effect on AR levels is transcriptional, the inhibitory peptides can block the expression of both full-length AR and its splicing variants including AR-V7, which plays a significant role in the development of drug resistance. This dual-mode action provides the peptides with the capability to kill enzalutamide-resistant CRPC cells. These peptides are also more cytotoxic to prostate cancer cells than the combination of enzalutamide and an EZH2 inhibitory drug, which was recently suggested to be an effective treatment of mCRPC disease. Our data show that such a dual-acting therapeutic approach can be more effective than the existing front-line drug therapies for treating deadly mCRPC.
ZBTB20 Regulates Prolactin Expression and Lactotrope Function in Adult Mice
Authors: Han Qing , Yan Xuede , Ye Yufei , Han Linhui , Ma Xianhua , Wang Ting , Cao Dongmei , Zhang Weiping J
Published: October 2022

Lactotropes are prolactin (PRL)-secreting endocrine cells in the anterior pituitary. We have established the zinc finger protein ZBTB20 as an essential transcription factor for lactotrope specification, the disruption of which results in complete loss of lactotropes in mice. However, the potential role of ZBTB20 in mature lactotropes remains unclear. Here we demonstrate that ZBTB20 acts as a critical cell-autonomous regulator for PRL expression in mature lactotropes in adult mice. Via a CRISPR/Cas9 approach, we first generated a tamoxifen-inducible Prl-CreER knockin mouse line that could efficiently mediate gene recombination specifically in lactotropes. Conditional deletion of the Zbtb20 gene specifically in mature lactotropes at adulthood led to a substantial decrease in PRL levels both in the pituitary and in plasma, without significant alterations of lactotrope relative density in the pituitary from male or female mice. Furthermore, conditional disruption of Zbtb20 in adult female mice did not significantly change pregnancy-elicited lactotrope expansion, but caused an impaired mammary gland expansion and lactation due to the PRL defect. Thus, our data point to an important role of ZBTB20 in regulating PRL expression and lactotrope function at adulthood.
Maternal Age, Early Childhood Temperament, and Youth Outcomes
Authors: Yu Wei-hsin , Yan Hope Xu
Published: October 2022

Demographers and family researchers have long debated whether early childbearing has negative consequences on the offspring, but few have considered that the benefits of delayed childbearing (or the lack thereof) may not be universal. Using sibling data from the National Longitudinal Survey of Youth 1979 Children and Young Adults, we investigate how the relevance of mothers' age at childbirth to youth outcomes (academic performance, years of education completed, and psychological distress) may differ for youth whose early-childhood behavioral disposition (i.e., temperament) indicated varying degrees of insecure attachment. Results from family fixed-effects models, which take into account much of the unobserved heterogeneity among families, show that having an older mother is associated with improved educational and psychological outcomes for youth with a rather insecure early temperament. In contrast, mothers' age at childbirth hardly matters for children with a secure disposition. Further analysis indicates that the moderating effect of maternal age cannot be explained by the mother's first-birth timing, education, work status, income, or family stability. Older mothers' higher likelihood of prior child-rearing experience explains part of the older-mother advantage for temperamentally insecure children. However, the aging process, which equips older mothers with enhanced maturity, more calmness, and therefore greater capacity to overcome adversities, seems to account for the smaller detrimental effects of an insecure disposition on their children.
Job Search and Hiring with Limited Information about Workseekers’ Skills
Authors: Carranza Eliana , Garlick Robert , Orkin Kate , Rankin Neil
Published: October 2022

We assess South African workseekers’ skills and disseminate the assessment results to explore how limited information affects firm and workseeker behavior. Giving workseekers assessment results that they can credibly share with firms increases workseekers’ employment and earnings and better aligns their skills, beliefs and search strategies. Giving workseekers assessment results that they cannot easily share with firms has similar effects on beliefs and search, but smaller effects on employment and earnings. Giving assessment results only to firms shifts interview decisions. These findings show that getting credible skill information to the right agents can improve outcomes in the labor market. (JEL J22, J23, J24, J31, J41, J64, O15)
Βελτιστοποίηση της κατανομής των καλλιεργειών κάτω από περιβαλλοντικούς περιορισμούς στη λεκάνη απορροής του Σπερχειού ποταμού
Authors: Φυτιλής Κωνσταντίνος
Published: October 2022

Η κατανομή/διαχείριση των καλλιεργειών ( crops distribution/management) αποτελεί σημαντικό πρόβλημα στον πρωτογενή τομέα, κάτι που οδηγεί στην αύξηση της παραγωγής και συνεπάγεται την αύξηση του κέρδους. Έχουν χρησιμοποιηθεί αρκετοί τρόποι κατανομής, πολλοί από τους οποίους παρουσίασαν σημαντικά αποτελέσματα. Ο γραμμικός προγραμματισμός (linear programming) ή αλλιώς γραμμική βελτιστοποίηση, είναι μέθοδος για την επίτευξη του καλύτερου αποτελέσματος (πχ. μεγιστοποίηση κέρδους) σε ένα μαθηματικό υπόδειγμα, του οποίου οι προϋποθέσεις (περιορισμοί) είναι ένα σύνολο γραμμικών σχέσεων των μεταβλητών του. Στη παρούσα μελέτη γίνεται χρήση του γραμμικού προγραμματισμού για μεγιστοποίηση της απόδοσης των καλλιεργειών σε μία αγροτική περιοχή προς βελτιστοποίηση. Πιο συγκεκριμένα, χρησιμοποιείται το εργαλείο solver του excel που επιλύει γραμμικά προβλήματα, ώστε να πραγματοποιηθεί κατανομή των καλλιεργειών στην περιοχή μελέτης (ΛΑΠ π. Σπερχειού) κάτω από περιβαλλοντικούς περιορισμούς, με σκοπό τη βελτιστοποίηση της παραγωγής.Πριν αναπτυχθεί η μεθοδολογία και προκύψουν τα αποτελέσματα, γίνεται εκτενής μελέτη για το πως μπορεί να συμβάλλει ο γραμμικός προγραμματισμός στην αγροτική ανάπτυξη. Διεξοδικότερα, αναφέρονται χαρακτηριστικά παραδείγματα που μας οδηγούν στο συμπέρασμα, ότι η επιλογή της συγκεκριμένης μεθοδολογίας είναι άκρως επιτυχής. Η βιβλιογραφία που αναφέρεται στο τέλος, περιέχει σημαντικά άρθρα που αξιοποιήθηκαν, ώστε το αντικείμενο μελέτης να γίνει πιο σαφές και κατανοητό.Επιπλέον, γίνεται πλήρης περιγραφή της περιοχής μελέτης με προσδιορισμό των καλλιεργειών που απαντώνται, καθώς και αναφορά στους υπόλοιπους τομείς οικονομίας. Τεκμηριώνονται πλήρως οι περιορισμοί που λαμβάνονται υπόψη και τα δεδομένα αξιολογούνται και διασταυρώνονται από αξιόπιστες πηγές (πχ. ΕΛΓΑ, ΟΠΕΚΕΠΕ, Περιφέρεια Στερεάς Ελλάδας, Corine Land Cover 2018 κτλ.).Τα αποτελέσματα που προκύπτουν από την εφαρμογή του γραμμικού προγραμματισμού στην περιοχή μελέτης – εφαρμόστηκε 23 φορές η μεθοδολογία στη λεκάνη απορροής του π. Σπερχειού, καθώς και σε κάθε μια από τις 22 υπολεκάνες του – δείχνουν ότι οι περιορισμοί είναι αυτοί, που καθορίζουν τα αποτελέσματα της μεθοδολογίας. Είναι προτιμότερο για πιο ορθά αποτελέσματα, το μοντέλο γραμμικού προγραμματισμού (με τη χρήση του εργαλείου solver) να εφαρμόζεται σε μικρές γεωργικές εκτάσεις.Έτσι, καταλήγουμε σε σημαντικά συμπεράσματα έπειτα από τη σύγκριση των αποτελεσμάτων που προκύπτουν για τη σωστή κατανομή των καλλιεργειών στη συγκεκριμένη περιοχή μελέτης. Αυτό καταλήγει στην αύξηση της παραγωγής κάτω από ορισμένους περιβαλλοντικούς περιορισμούς, τους οποίους θα δούμε εκτενέστερα.
Gender, digital financial services and vulnerability in the era of pandemics: A cross-sectional analysis
Authors: Amidu Mohammed , Akakpo Agnes Akpene , Mensah James Kwame , Asiedu Edward
Published: October 2022

Background: The COVID-19 pandemic has rapidly spread across the world, infecting millions and causing economic disruption on an unprecedented scale. While everyone is affected by the COVID-19 pandemic, vulnerable communities are at the greatest risk. The objective of this study is to examine the relationship between digital financial services (DFS), gender, and the vulnerability of informal settlement dwellers to COVID-19.

Methods: We sampled a total of 2,697 households from 101 informal settlements across eleven out of sixteen administrative regions of Ghana. The regions were selected based on the relative severity of the pandemic, and the associated national lockdown regulations.

Results: Adopting the multiple regression analytical technique, the results reveal three main findings: First, we observe that males in informal settlements are more likely to be exposed to infected people or a person who died from COVID-19 than females. However, women are more likely to be vulnerable to the pandemic than men as vulnerable populations have a higher susceptibility to pandemics due to less capacity to implement preparedness and response strategies due to disparities in their societal status. Finally, we find that the vulnerability of informal dwellers is moderated by the use of digital financial services.

Conclusions: Our results provide policy implications for authorities designing policies to address vulnerability to pandemics in poor informal settlements in Africa.
A MULTISCALE APPROACH TO INVESTIGATE THE EFFECT OF TEMPERATURE AND CRYSTALLINITY ON THE DEVELOPMENT OF RESIDUAL STRESSES IN SEMICRYSTALLINE PEEK
Authors: KASHMARI KHATEREH , DESHPANDE PRATHAMESH , PATIL SAGAR , MAIARU MARIANNA , ODEGARD GREGORY M.
Published: October 2022

Thermoplastic Matrix Composites (TMC) are shown to have a considerable commercial interest in cutting-edge industries due to their superior mechanical and chemical properties and the resistance to high temperatures. During the processing, TMCs are subjected to a wide range of elevated temperatures involving different cooling and heating cycles which result in the development of internal residual stresses in the matrix. In semicrystalline polymers such as PEEK, formation of crystalline regions during the processing causes shrinkage in the matrix leading to generation of additional residual stresses. Optimization of materials, manufacturing and design of components reduces development cycle time and cost for future hightechnology applications of TMCs. It has been shown that manufacturing of TMCs has a huge impact on the microstructure of these material, which in turn control the in-service performance. Since the thermo-mechanical properties of composite materials are defined by phenomena at multiple length scales, to have precise estimation of these residual stresses, a computational approach is required to combine simulation tools at multiple length scale. In this study, a multiscale approach has been introduced based on the Integrated Computational Material Engineering (ICME) which integrates Molecular Dynamics (MD) and Finite Element Analysis (FEA) to predict the induced residual stresses during processing. In the first step, thermoelastic properties of semicrystalline PEEK are determined as function of crystallinity content at different processing temperature at nanoscale using MD and micromechanics modeling. In the next step, the evolution of thermo-elastic properties during the crystallization is achieved using computational and experimental data. These results will be used to estimate the induced residual stresses of composites at higher length scales. This two-scale approach will allow us to virtually characterize material properties and predict the residual stress state of composites during manufacturing as a function of processing parameters and investigate the effect of temperature and temperature history on semi-crystalline PEEK thermal-mechanical properties.
A GENERAL DEHOMOGENIZATION METHOD FOR BEAM ANALYSES
Authors: CHIU RONG , YU WENBIN
Published: October 2022

Traditional multiscale methods homogenize a beam-like structure into a material point in 1D continuum with effective properties computed over a structure gene (SG) in terms of a 2D cross-section or a 3D segment with spanwise periodicity. Such methods lose accuracy when dealing with real beam-like structures usually not uniform or periodic along the spanwise direction. Thus, traditional multiscale methods cannot be rigorously applied to these cases and some refined methods have been proposed to analysis beam structure featuring spanwise heterogeneity. However, those methods usually require specific geometries assumption, assume material to be isotropic and homogeneous, or only predict macroscopic behavior without detailed dehomogenization analysis for local stresses recovery. In our previous work, we proposed Heterogeneous Beam Element (HBE) based on Mechanics of Structure Genome (MSG) to analyze beam-like structures featuring spanwise heterogeneity. Despite more accurate in predicting both macroscopic behavior and local stresses than traditional methods, errors in local stresses predictions on the SG boundary are inevitable due to the invoked assumptions of boundary conditions. In this paper, we propose a general dehomogenization methods for beam modeling (GDMB) based on HBE to better predict local stresses when the macroscopic behavior from other beam models are available. The results show that GDMB improves accuracy of the HBE dehomogenization and provides accurate stresses predictions based on a beam analysis.
THE EFFECT OF PLY WAVINESS ON DAMAGE INITIATION AND GROWTH IN COMPOSITES UNDER FULLY REVERSED CYCLIC LOADING
Authors: DÍAZ-MONTIEL PAULINA , HEISE JAROD , KIM HYONNY , VENKATARAMAN SATCHI
Published: October 2022

This paper presents results of an experimental investigation of composites with embedded ply waviness defects subjected to cyclic loads. The aim is to investigate the influence of ply waviness defects on the initiation, interaction, and evolution of fatigue damage mechanisms. The composite laminates with ply waviness are tested in a four-point bend sandwich beam configuration. Fully reversed fatigue testing until failure and interrupted fatigue testing were conducted, and the sequence of fatigue damage mechanisms was studied via digital image correlation analysis. Results showed that during fully reversed cyclic loads, shear strains localize at the ply waviness region, which amplifies the stresses in surrounding plies. The failure mechanisms near the defect include delamination, matrix cracking, and ply splitting. However, at small ply waviness amplitudes, failure did not initiate at the defect but at other sites in the laminate where the strength was locally reduced. In these laminates, failure mechanisms due to microstructural defects compete and dominate the fatigue failure mechanisms at regions of ply waviness defects.
NUMERICAL MODELING OF ULTRASONIC ASSESSMENT IN ADDITIVELY MANUFACTURED COMPOSITE MATERIALS
Authors: CHUKOVENKOVA MARIYA , DRACH BORYS , ZAGRAI ANDREI
Published: October 2022

Additive manufacturing (AM) is a layer-by-layer process of building the parts that allows to create objects with different shapes and geometries. AM is especially suited for fabrication of composite materials. The mechanical properties of the composite parts depend on fiber density, distribution and orientation. However, variability of printing parameters leads to uncertainties in the composite properties or initiation of damage. In this contribution, we demonstrate potential of ultrasonic techniques for damage detection and assessment of materials properties through experimental testing and numerical modeling. Numerical models were validated with laboratory data and enable further guidelines for experimental testing. A set of nylon composite samples were fabricated via Markforged Mark Two™ composite 3D printer with different layer thicknesses. The samples include solid blocks and blocks with simulated cracks. This enables exploration of the influence of the process parameters on the mechanical properties of the additively manufactured nylon cubes. Elastic properties were calculated for all tested samples in three directions using the ultrasonic technique. Crack detection was conducted for damaged specimens. Numerical model for wave propagation within the nylon specimens was developed and validated using experimental data. Also, numerical simulations for wave propagation within the additively manufactured Onyx™ composite (reinforced with carbon fiber) specimens were conducted.
BOND-BASED PERIDYNAMICS WITH STRETCH AND ROTATION KINEMATICS FOR MODELING COMPOSITE LAMINATES
Authors: MADENCI ERDOGAN , BARUT ATILA , PHAN NAM
Published: October 2022

This study presents the bond-based (BB) peridynamics (PD) with stretch and rotation kinematics for modeling the linear elastic deformation of a composite laminate. The laminate experiences only in-plane and transverse shear deformations and disregards the transverse normal deformation. The PD equilibrium equation for a laminate is derived under the assumption of small deformation and is solved by employing implicit techniques. The in-plane PD forces are expressed by considering the PD bond interactions among the points. The forces arising from the interaction of adjacent layers are expressed by considering a pointwise approach that utilizes PD differential operator (PDDO) in conjunction with the shear-lag theory. The micro-moduli associated with stretch and rotation are directly related to the constitutive relations between stress and strain components in continuum mechanics. It is restricted to only one constraint on the material constants leading to a fixed value of in-plane shear modulus. The capability of this approach is demonstrated by considering progressive failure in a quasi-isotropic laminate with a pre-existing crack. It employs critical stretch, the critical skew (relative rotation) angle and critical delamination angle in the bond breakage criteria.