bluuebunny/crossref_metadata_2025 huggingface dataset:
Treed Gaussian Process Regression for Solving Offline Data-Driven Continuous Multiobjective Optimization Problems
Authors: Mazumdar Atanu , López-Ibáñez Manuel , Chugh Tinkle , Hakanen Jussi , Miettinen Kaisa
Published: May 2023

For offline data-driven multiobjective optimization problems (MOPs), no new data is available during the optimization process. Approximation models (or surrogates) are first built using the provided offline data, and an optimizer, for example, a multiobjective evolutionary algorithm, can then be utilized to find Pareto optimal solutions to the problem with surrogates as objective functions. In contrast to online data-driven MOPs, these surrogates cannot be updated with new data and, hence, the approximation accuracy cannot be improved by considering new data during the optimization process. Gaussian process regression (GPR) models are widely used as surrogates because of their ability to provide uncertainty information. However, building GPRs becomes computationally expensive when the size of the dataset is large. Using sparse GPRs reduces the computational cost of building the surrogates. However, sparse GPRs are not tailored to solve offline data-driven MOPs, where good accuracy of the surrogates is needed near Pareto optimal solutions. Treed GPR (TGPR-MO) surrogates for offline data-driven MOPs with continuous decision variables are proposed in this paper. The proposed surrogates first split the decision space into subregions using regression trees and build GPRs sequentially in regions close to Pareto optimal solutions in the decision space to accurately approximate tradeoffs between the objective functions. TGPR-MO surrogates are computationally inexpensive because GPRs are built only in a smaller region of the decision space utilizing a subset of the data. The TGPR-MO surrogates were tested on distance-based visualizable problems with various data sizes, sampling strategies, numbers of objective functions, and decision variables. Experimental results showed that the TGPR-MO surrogates are computationally cheaper and can handle datasets of large size. Furthermore, TGPR-MO surrogates produced solutions closer to Pareto optimal solutions compared to full GPRs and sparse GPRs.
Upgrades of Genetic Programming for Data-Driven Modeling of Time Series
Authors: Murari A. , Peluso E. , Spolladore L. , Rossi R. , Gelfusa M.
Published: May 2023

In many engineering fields and scientific disciplines, the results of experiments are in the form of time series, which can be quite problematic to interpret and model. Genetic programming tools are quite powerful in extracting knowledge from data. In this work, several upgrades and refinements are proposed and tested to improve the explorative capabilities of symbolic regression (SR) via genetic programming (GP) for the investigation of time series, with the objective of extracting mathematical models directly from the available signals. The main task is not simply prediction but consists of identifying interpretable equations, reflecting the nature of the mechanisms generating the signals. The implemented improvements involve almost all aspects of GP, from the knowledge representation and the genetic operators to the fitness function. The unique capabilities of genetic programming, to accommodate prior information and knowledge, are also leveraged effectively. The proposed upgrades cover the most important applications of empirical modeling of time series, ranging from the identification of autoregressive systems and partial differential equations to the search of models in terms of dimensionless quantities and appropriate physical units. Particularly delicate systems to identify, such as those showing hysteretic behavior or governed by delayed differential equations, are also addressed. The potential of the developed tools is substantiated with both a battery of systematic numerical tests with synthetic signals and with applications to experimental data.
Two new species of Marphysa (Annelida, Eunicidae) from southern Australia.
Authors: LAVESQUE NICOLAS , ZANOL JOANA , DAFFE GUILLEMINE , FLAXMAN BETH , HUTCHINGS PAT
Published: May 2023

Two new species of Marphysa Quatrefages, 1866 are described from the southeast coast of Australia. With the presence of only compound spinigers and the branchiae present over many chaetigers, Marphysa baudini n. sp. belongs to the Sanguinea-group. This species has ventral cirri with an inflated base and digitiform tip and thick and wide anodont pectinate chaetae, with 3–5 internal long and thick teeth. With the presence of only compound falcigers, Marphysa davidattenboroughi n. sp., belongs to the “Aenea-group”. This species is characterised by the presence of a bilobed prostomium, a single pair of pygidial cirri and by the presence of thick, and wide anodont pectinate chaetae with 4–6 long internal and thick teeth.
Demonstrating the Potential Impacts of Assimilating FY-4A Visible Radiances on Forecasts of Cloud and Precipitation with a Localized Particle Filter
Authors: Zhou Yongbo , Liu Yubao , Han Wei
Published: May 2023

The Advanced Geostationary Radiation Imager (AGRI) on board the Fengyun-4A (FY-4A) satellite provides visible radiances that contain critical information on clouds and precipitation. In this study, the impact of assimilating FY-4A/AGRI all-sky visible radiances on the simulation of a convective system was evaluated with an observing system simulation experiment (OSSE) using a localized particle filter (PF). The localized PF was implemented into the Data Assimilation Research Testbed (DART) coupled with the Weather Research and Forecasting (WRF) Model. The results of a 2-day data assimilation (DA) experiment generated encouraging outcome at a synoptic scale. Assimilating FY-4A/AGRI visible radiances with the localized PF significantly improved the analysis and forecast of cloud water path (CWP), cloud coverage, rain rate, and rainfall areas. In addition, some positive impacts were produced on the temperature and water vapor mixing ratio in the vicinity of cloudy regions. Sensitivity studies indicated that the best results were achieved by the localized PF configured with a localization distance that is equivalent to the model grid spacing (20 km) and with an adequately short cycling interval (30 min). However, the localized PF could not improve cloud vertical structures and cloud phases due to a lack of related information in the visible radiances. Moreover, the localized PF was compared with the ensemble adjustment Kalman filter (EAKF) and it was indicated that the localized PF outperformed EAKF even when the number of ensemble members was doubled for the latter, indicating a great potential of the localized PF in assimilating visible radiances.
The Manufacturing Holonic Structured Virtual Team Organization: Labour Cost Reduction?
Authors: Torres-Palacio Patricio
Published: May 2023

It is an undeniable fact that business endeavours in modern times are centred on offshore operations. This scenario demands the employment of virtual teams to be seen as an essential requirement. The experiences from COVID-19 pandemic corroborate this reality. Corporations ought to revise their strategies to successfully incorporate technology as a part of their habitual actions. Holonic manufacturing emerges as a powerful communication and collaboration tool for virtual teams to optimize resources and human power. This study is based on an experiment consisting in a simulated automobile assembly industry. Holonic organizations are compared to non-holonic structures in terms of labour costs based on effective work times. The study employed a Holonic Manufacturing Structure to analyse its possible impact on labour cost reduction among several other advantages.
Dynamic cerebral autoregulation in Alzheimer’s disease and mild cognitive impairment: A systematic review
Authors: Heutz Rachel , Claassen Jurgen , Feiner Sanne , Davies Aaron , Gurung Dewakar , Panerai Ronney B , Heus Rianne de , Beishon Lucy C
Published: May 2023

Dynamic cerebral autoregulation (dCA) is a key mechanism that regulates cerebral blood flow (CBF) in response to transient changes in blood pressure (BP). Impairment of dCA could increase vulnerability to hypertensive vascular damage, but also to BP lowering effects of antihypertensive treatment. The literature remains conflicted on whether dCA is altered in Alzheimer’s disease (AD) and mild cognitive impairment (MCI). We summarized available data on dCA in AD and MCI, by searching PubMed, Embase, PsycINFO and Web of Science databases (inception-January 2022). Eight studies (total n = 443) were included in the qualitative synthesis of which seven were eligible for meta-analysis. All studies used Transcranial Doppler (TCD) ultrasonography and transfer function analysis or the autoregulatory index to assess dCA during spontaneous or induced BP fluctuations. Meta-analysis indicated no significant difference between AD, MCI and healthy controls in dCA parameters for spontaneous fluctuations. For induced fluctuations, the available data were limited, but indicative of at least preserved and possibly better autoregulatory functioning in AD and MCI compared to controls. In summary, current evidence does not suggest poorer dCA efficiency in AD or MCI. Further work is needed to investigate dCA in dementia with induced fluctuations controlling for changes in end-tidal carbon dioxide.
Writing on the Wall: Chronicles Written for Public Display at St Paul’s Cathedral, London
Authors: Mason David
Published: May 2023

Not all chronicles were written in books. This article examines a widespread alternative, the tablet (table, tabula), which was a display board typically made of wood and parchment. They were once ubiquitous in churches, but today there are few extant examples. This article offers a ‘textual archaeology’, using manuscripts and antiquarian literature to reconstruct lost texts. It presents a case study at St Paul’s Cathedral, London. It examines the functions and audiences of the London historical tablets, and places them in their spatial, textual and manuscript contexts. Tablets displayed a variety of historiographical genres: chronicles, institutional histories, miracle and saint narratives, and lives and deeds of benefactors. Their spatial location indicates particular concentrations around the main pilgrimage sites of the church. Surviving witnesses hint at a broad audience for these texts in London, including local laymen, clergy and pilgrims. Tablets were used to assert the institutional claims and identity of the church, to inform tourists and pilgrims, and to assist in the creation of public memory through ceremonies and rituals. Tablet chronicles point towards medieval uses of the past that were public-facing, accessible, and engaged with the institutional and cultural life of London.
Book review: Lorenz Böninger, Niccolò di Lorenzo della Magna and the Social World of Florentine Printing, ca. 1470–1493
Authors: Dover Paul M.
Published: May 2023

Lorenz Böninger, Niccolò di Lorenzo della Magna and the Social World of Florentine Printing, ca. 1470–1493. Cambridge, MA: Harvard University Press, 2021, pp. 209. ISBN: 9780674251137.
A New Focus on Cityscapes in Late Medieval German Literature: Rudolf von Ems and Heinrich Kaufringer
Authors: Classen Albrecht
Published: May 2023

Historians have studied the medieval city from many different perspectives already, and even literary historians have endeavoured to identify the evidence in fictional texts pertaining to urban spaces and figures. In many cases, however, the cities as they emerge before our eyes are rather imaginary or dream-like, and lack in historical specificity. This situation changed, as this article demonstrates, with the case of Rudolf von Ems’s Der guote Gêrhart (ca. 1220) and the verse narratives by Heinrich Kaufringer (ca. 1400). This study examines the data we can cull from both sides and presents it as the crucial indicator for the emergence of a new literary discourse dedicated to the world of late medieval cities. We begin to discover, though not yet in any consistent way, the formation of urban protagonists and of narrative contexts that are predicated on urban settings.
Reason vs. Religion in Medieval India: Mainly from Evidence in Persian
Authors: Habib Irfan
Published: May 2023

The pursuit of reason may be defined as the drawing of logical deductions from a study of actual phenomena, and thus be essentially confined to the results gained from access to the various branches of science. It was in Greece where, from the fifth century BCE onward, rational thought was deemed to have developed most. Greek texts exercised undeniable influence on early thought in the Islamic world, Alberūnī’s Kitabu’l Hind being a remarkable product of that influence.

Muslim theologians mounted a tirade against rationality (‘aql), in which the ṣūfīs joined; but since ṣūfic moral thought often tended to override Muslim theology, there could arise figures (even if partly imaginary) like Rābi‘a of Basra, who stood up against theology and its fictions. The conflict between ma‘qūlāt (reason) and manqūlāt (theology) was duly imported into India, along with the arrival of the Arabic–Persian sciences in the 13th and 14th centuries. Here poetry in Persian also became a major vehicle undermining theology. The tendency is partly present in Amīr Khusrau of Delhi (extolling love above theology!), but especially in the Iranian poet Ḥāfiz Shīrāzī, where the sāqī and ale-house constituted the major alternative to the pulpit and the mosque. In Indo-Persian poetry the same role is often ascribed to the but (idol) and the butkhāna (temple).

It was under Akbar (r. 1556–1605) that a detailed inquiry (1574 onward) into Islamic beliefs and the doctrines of other religions led to disquiet about their validity. Abū’l Faẓl (d. 1602) became the leading light of a revival of rationality. Akbar’s own critique of Islam was similarly extended to aspects of Hinduism. ‘Urfī represents best the shift to reason, by the boldness of his poetry, rejecting religion for its inadequacy and looking forward to a just world.

The seventeenth century did not fulfil the promise of the 16th. There was continuing interest in religion, shown by Jahāngīr’s formula: Tasawwuf = Vedānta; Dārā Shukoh’s translation of the Upanishads; and Mobad’s unique work Dabistān. But there was no corresponding assertion of rationality, whose votaries were reduced to a small band, last described, c. 1655.
The MBA Marketing Mix Revisited:The Need for the 10Ps Framework in the Indian Context
Authors: Thomas John Kishore , Gopalakrishnan Rejikumar , Kamala Raghavan Ajith Kumar
Published: May 2023

The use of the marketing mix is ubiquitous, six decades after it was first proposed. Over time, numerous variations, augmentations and alternatives have been proposed across spheres of the marketing domain in various specializations and sub-categories. At its core, its essence is its useful function as a toolkit for the marketer in attracting the target-consumer. The 7Ps MBA marketing mix proposed by Jonathan Ivy in this regard assumes significance within India’s B-school market, arguably one of the largest in the world. This study examines whether the 7Ps alone are sufficient in the Indian context. Data exploration finds that aspects of graduate performance are grossly deficient both in terms of outturn and placement, with indications suggesting a lack of trust among the consumers. This study, therefore, conceptualizes an enhanced marketing mix of 10Ps, with the inclusion of pass-rate, placements and probity as three new Ps. Crucially, it includes the performance criterion which was missing in the original 7Ps MBA marketing mix while adding a new component that is pertinent to developing/emerging markets. The study would be useful as it potentially opens up further exploration into services marketing aspects of the multi-billion-dollar MBA industry in India, as well as throwing light on key drivers for positioning and building brand equity among B-schools.
He Looks Like My Father
Authors: White Jones Ashley
Published: May 2023

Social media has kept us connected in many ways but for Black adults, it can be a harrowing reminder of the treatment of Black bodies. This poem was crafted from focus group data on a study of the effects of vicarious racism on the mental health of Black adults in the wake of George Floyd’s death in 2020. This poem uses elements of found poetry and incorporates texts from the narrative (re)telling of Black adults’ emotional impact of seeing racially and police-involved killings of Black men. Participants expressed feelings of anger, powerlessness, and sadness and how watching these videos has led to avoidance behavior for the sake of coping. In this poem titled “He Looks like My Father,” the participant shares a memory of the last video that they watched on social media in 2014 and why they continue to avoid this type of content. It’s traumatizing. It is important to fully reflect on these stories as Black Americans struggle with staying informed and preserving their mental health while being inundated by a continuous feedback loop of Black death. The elements of this poem incorporate repetition and the bolded words are verbatim text from the participant transcript. I acknowledge that my positionality being a Black American woman, with a Black father, and having shared the embodied experience of witnessing Black death via social media influenced the meaning of this poem. As we continue to see a focus on naming racism as a public health threat, this form of vicarious racism is salient and should be explored as health professionals dig deeper into understanding the many ways racism permeates the lives of Black, is a daily stressor, and is a social determinant of mental health equity. These are the narratives from muted lips to unveil your eyes. To view the original version of this poem, see the supplemental material section of this article online.
The association between Patient Assessment of Chronic Illness Care Scores and quality of life in type 2 diabetes patients
Authors: Akan Gülçin , Kartal Asiye
Published: May 2023

Background:

Chronic illness care is an important factor for health promotion in diabetes since it affects health outcomes such as quality of life.

Aims:

The aim of this study was to investigate the relationship between the Patient Assessment of Chronic Illness Care and the quality of life in type 2 diabetes patients.

Methods:

The study used a cross-sectional and correlational design. The sample included 317 patients with type 2 diabetes. A socio-demographic and disease-related questionnaire form, the Patient Assessment of Chronic Illness Care (PACIC) scale and the WHOQOL-BREF Quality of Life Scale were used to collect data.

Results:

According to the regression analysis, the stronger predictor affecting all domains of quality of life was the overall PACIC. This study demonstrated the importance of satisfaction level of chronic illness care in the improvement of quality of life. Therefore, the factors affecting the satisfaction level with chronic care services should be determined to improve the quality of life of patients. In addition, healthcare based on the chronic-care model should be provided in the care of the patients.

Conclusions:

PACIC had an important effect on quality of life of the patients. This study demonstrated the importance of satisfaction level on chronic illness care in the improvement of quality of life.
Gluteal muscle and subcutaneous tissue thicknesses in adults: a systematic review and meta-analysis
Authors: Gulnar Emel , Ordu Yadigar , Biyik Bayram Sule , Çalışkan Nurcan
Published: May 2023

Background:

Nurses often administer intramuscular injections at the gluteal site. This study aimed to determine gluteal muscle and subcutaneous tissue thicknesses in adults.

Methods:

Systematic review and meta-analysis. The databases Turkish Medline, Ulakbim, National Thesis Center, Cochrane, Web of Science, Science Direct, PubMed, CINAHL Plus with Full text (EBSCO host), OVID and SCOPUS were screened using the keywords ‘intramuscular injection’, ‘subcutaneous tissue thickness’, ‘muscle tissue thickness’ and ‘needle length’ between April and May 2021. The studies were evaluated with ultrasound. This study was reported according to the PRISMA recommendations.

Results:

Six studies met the eligibility criteria. The total sample size was 734 (women: 432, men: 302). The V method revealed that the ventrogluteal site had a muscle and subcutaneous tissue thickness of 38.071 ± 2.119 and 19.927 ± 2.493 mm, respectively. The geometric method revealed that the ventrogluteal site had a muscle and subcutaneous tissue thickness of 35.989 ± 4.190 and 19.661 ± 3.992 mm, respectively. The geometric method also revealed that the dorsogluteal site had a thickness of 42.560 ± 8.840 mm. According to the V method, females had thicker subcutaneous tissue at the ventrogluteal site than males ( Q = 5.37, df = 1, p = 0.0204). Body mass index did not affect the subcutaneous tissue thicknesses at the ventrogluteal site.

Conclusion:

The results show that gluteal muscle, subcutaneous and total tissue thicknesses vary across injection sites.
Impact of Hindenburg Research Report on the Stock Prices of Adani Group Companies: An Event Study
Authors: Mallesha L.  , Archana H. N.
Published: May 2023

The present study investigates the impact of the Hindenburg Research report on the Adani Group’s stock prices. An event study analysis was conducted over a 21-daywindow period, including 10 days prior to, 10 days after and the day of the event. The results showed that the majority of average abnormal returns and cumulative average abnormal returns were statistically significant during the observation period, particularly in the post-event period. This indicates that the Hindenburg Research report had a significant impact on the stock prices of Adani Group companies. The findings suggest that the Indian stock market may not be efficient in its semi-strong form. Nonetheless, it was also noticed that the stock prices did not immediately respond to the information in the report. This study has significance for investors, firms, policymakers, and regulators as they can utilize it to evaluate such announcement effect on stock prices in the Indian stock market.
Effects of Opioid-Limiting Legislation and Increased Provider Awareness on Postoperative Opioid Use and Complications After Hip Arthroscopy
Authors: Strony John T. , Raji Yazdan , Ina Jason G. , Yu Jiao , Megerian Mark F. , McCollum Samuel W. , Mather Richard C. , Nho Shane J. , Salata Michael J.
Published: May 2023

Background:

On August 31, 2017, Ohio passed legislation that regulates how opioids can be prescribed postoperatively. Studies have shown that such legislation is successful in reducing the morphine milligram equivalents (MMEs) prescribed after certain orthopaedic procedures.

Purpose:

(1) To determine if the opioid prescription–limiting legislation in Ohio reduced the cumulative MMEs prescribed after hip arthroscopy without significantly affecting the rates of emergency department (ED) visits, hospital readmissions, and reoperations within 90 days postoperatively, and (2) to assess risk factors associated with increased postoperative opioid dosing.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

This study included patients who underwent primary and revision hip arthroscopy at a single institution over a 4-year period. The prelegislation (PRE) and postlegislation (POST) groups were defined as patients who underwent surgery before August 31, 2017, and on/after this date, respectively. The Ohio Automated Rx Reporting System was queried for controlled-substance prescriptions from 30 days preoperatively to 90 days postoperatively, and patient medical records were reviewed to collect demographic, medical, surgical, and readmission data. Inverse probability weighting–adjusted mean treatment effect regression models were used to measure the difference in mean outcomes between the PRE and POST cohorts.

Results:

A total of 546 patients (228 PRE, 318 POST) were identified. There was a 25% reduction in the cumulative MMEs prescribed to the POST group as compared with the PRE group during the first 90 days postoperatively (840 vs 1125 MME, respectively; P < .01). The legislation was associated with a significant decrease in the cumulative MMEs prescribed in the first 90 postoperative days (mean treatment effect = –280.6; P < .01), and there were no significant between-group differences in the frequency of ED encounters (8.8% PRE, 11.6% POST; P = .32), hospital readmissions (1.3% PRE, 0.9% POST; P = .70), or reoperations (0.9% PRE, 0.6% POST; P ≥ .99) during this period. Preoperative opioid use was a significant independent risk factor for increased cumulative MMEs in the first 90 days postoperatively (β = 275; P < .01).

Conclusion:

Opioid prescription–limiting legislation in Ohio was associated with significant reductions in opioid MMEs dosing in the 90-day period following hip arthroscopy. This legislation had no significant effect on ED utilization, hospital readmissions, or reoperations within the same period. Preoperative opioid use was a significant risk factor for increased MME dosing after hip arthroscopy.
Book review: Asit Biswas and Shubh Brat Sarkar (Eds.), Dalit Poems, Songs and Dialogues from Bengal in English Translation
Authors: Pal Bidisha
Published: May 2023

Asit Biswas and Shubh Brat Sarkar (Eds.), Dalit Poems, Songs and Dialogues from Bengal in English Translation (Kolkata: Ababil Books, 2019), 266 pp., ₹495, ISBN: 978-8-1939-3923-9 (Paperback).
Revisiting Multiculturalism in Ambedkar’s Thought: A Theoretical Perspective
Authors: Gochhayat Artatrana
Published: May 2023

Dr Bhimrao Ramji Ambedkar (1891–1956) was not only the messiah of the downtrodden people in India but was also the champion of minority rights, women’s rights, farmer’s and labourer’s rights. He was an individualist as well as a communitarian. He was a modernist, rationalist and moralist. His philosophy covers a wide range of ideas including justice, liberty, equality, democracy, minority rights, women’s rights, group representation, social exclusion and inclusion, majority–minority conflicts, cultural and linguistic diversity and identity and recognition which offer a non-western experience of the early part of twentieth century to the present-day literature on multiculturalism. But his ideas have paid little scholarly attention both in western and Indian scholarships. The existing scholarships on B. R. Ambedkar largely highlight on his socio-economic, cultural, religious, political and constitutional ideas. But his multicultural ideas are hardly explored in academic discourses. This article thus attempts first to highlight on some leading theorists of multiculturalism and their views and then discusses Ambedkar’s multicultural ideas. The article, however, restricts itself to some selected theorists of multiculturalism for deliberation only with an aim to compare them with Ambedkar’s writings.
Book review: Juned Shaikh, Outcaste Bombay: City Making and the Politics of the Poor
Authors: Jogdand P. G.
Published: May 2023

Juned Shaikh, Outcaste Bombay: City Making and the Politics of the Poor. Orient BlackSwan Private Ltd, 2021, 227 pp., ₹995.
Circulating tumor DNA adds specificity to PET after axicabtagene ciloleucel in large B-cell lymphoma
Authors: Dean Erin A. , Kimmel Gregory J. , Frank Matthew J. , Bukhari Ali , Hossain Nasheed M. , Jain Michael D. , Dahiya Saurabh , Miklos David B. , Altrock Philipp M. , Locke Frederick L.
Published: May 2023

We examined the meaning of metabolically active lesions on 1-month restaging nuclear imaging of patients with relapsed/refractory large B-cell lymphoma receiving axicabtagene ciloleucel (axi-cel) by assessing the relationship between total metabolic tumor volume (MTV) on positron emission tomography (PET) scans and circulating tumor DNA (ctDNA) in the plasma. In this prospective multicenter sample collection study, MTV was retrospectively calculated via commercial software at baseline, 1, and 3 months after chimeric antigen receptor (CAR) T-cell therapy; ctDNA was available before and after axi-cel administration. Spearman correlation coefficient (rs) was used to study the relationship between the variables, and a mathematical model was constructed to describe tumor dynamics 1 month after CAR T-cell therapy. The median time between baseline scan and axi-cel infusion was 33 days (range, 1-137 days) for all 57 patients. For 41 of the patients with imaging within 33 days of axi-cel or imaging before that time but no bridging therapy, the correlation at baseline became stronger (rs, 0.61; P < .0001) compared with all patients (rs, 0.38; P = .004). Excluding patients in complete remission with no measurable residual disease, ctDNA and MTV at 1 month did not correlate (rs, 0.28; P = .11) but correlated at 3 months (rs, 0.79; P = .0007). Modeling of tumor dynamics, which incorporated ctDNA and inflammation as part of MTV, recapitulated the outcomes of patients with positive radiologic 1-month scans. Our results suggested that nonprogressing hypermetabolic lesions on 1-month PET represent ongoing treatment responses, and their composition may be elucidated by concurrently examining the ctDNA.
A comparison of feature selection methodologies and learning algorithms in the development of a DNA methylation-based telomere length estimator
Authors: Doherty Trevor , Dempster Emma , Hannon Eilis , Mill Jonathan , Poulton Richie , Corcoran David , Sugden Karen , Williams Ben , Caspi Avshalom , Moffitt Terrie E. , Delany Sarah Jane , Murphy Therese M.
Published: May 2023

Background

The field of epigenomics holds great promise in understanding and treating disease with advances in machine learning (ML) and artificial intelligence being vitally important in this pursuit. Increasingly, research now utilises DNA methylation measures at cytosine–guanine dinucleotides (CpG) to detect disease and estimate biological traits such as aging. Given the challenge of high dimensionality of DNA methylation data, feature-selection techniques are commonly employed to reduce dimensionality and identify the most important subset of features. In this study, our aim was to test and compare a range of feature-selection methods and ML algorithms in the development of a novel DNA methylation-based telomere length (TL) estimator. We utilised both nested cross-validation and two independent test sets for the comparisons.

Results

We found that principal component analysis in advance of elastic net regression led to the overall best performing estimator when evaluated using a nested cross-validation analysis and two independent test cohorts. This approach achieved a correlation between estimated and actual TL of 0.295 (83.4% CI [0.201, 0.384]) on the EXTEND test data set. Contrastingly, the baseline model of elastic net regression with no prior feature reduction stage performed less well in general—suggesting a prior feature-selection stage may have important utility. A previously developed TL estimator, DNAmTL, achieved a correlation of 0.216 (83.4% CI [0.118, 0.310]) on the EXTEND data. Additionally, we observed that different DNA methylation-based TL estimators, which have few common CpGs, are associated with many of the same biological entities.

Conclusions

The variance in performance across tested approaches shows that estimators are sensitive to data set heterogeneity and the development of an optimal DNA methylation-based estimator should benefit from the robust methodological approach used in this study. Moreover, our methodology which utilises a range of feature-selection approaches and ML algorithms could be applied to other biological markers and disease phenotypes, to examine their relationship with DNA methylation and predictive value.
Faster and more accurate pathogenic combination predictions with VarCoPP2.0
Authors: Versbraegen Nassim , Gravel Barbara , Nachtegael Charlotte , Renaux Alexandre , Verkinderen Emma , Nowé Ann , Lenaerts Tom , Papadimitriou Sofia
Published: May 2023

Background

The prediction of potentially pathogenic variant combinations in patients remains a key task in the field of medical genetics for the understanding and detection of oligogenic/multilocus diseases. Models tailored towards such cases can help shorten the gap of missing diagnoses and can aid researchers in dealing with the high complexity of the derived data. The predictor VarCoPP (Variant Combinations Pathogenicity Predictor) that was published in 2019 and identified potentially pathogenic variant combinations in gene pairs (bilocus variant combinations), was the first important step in this direction. Despite its usefulness and applicability, several issues still remained that hindered a better performance, such as its False Positive (FP) rate, the quality of its training set and its complex architecture.

Results

We present VarCoPP2.0: the successor of VarCoPP that is a simplified, faster and more accurate predictive model identifying potentially pathogenic bilocus variant combinations. Results from cross-validation and on independent data sets reveal that VarCoPP2.0 has improved in terms of both sensitivity (95% in cross-validation and 98% during testing) and specificity (5% FP rate). At the same time, its running time shows a significant 150-fold decrease due to the selection of a simpler Balanced Random Forest model. Its positive training set now consists of variant combinations that are more confidently linked with evidence of pathogenicity, based on the confidence scores present in OLIDA, the Oligogenic Diseases Database (https://olida.ibsquare.be). The improvement of its performance is also attributed to a more careful selection of up-to-date features identified via an original wrapper method. We show that the combination of different variant and gene pair features together is important for predictions, highlighting the usefulness of integrating biological information at different levels.

Conclusions

Through its improved performance and faster execution time, VarCoPP2.0 enables a more accurate analysis of larger data sets linked to oligogenic diseases. Users can access the ORVAL platform (https://orval.ibsquare.be) to apply VarCoPP2.0 on their data.
Genomic benchmarks: a collection of datasets for genomic sequence classification
Authors: Grešová Katarína , Martinek Vlastimil , Čechák David , Šimeček Petr , Alexiou Panagiotis
Published: May 2023

Background

Recently, deep neural networks have been successfully applied in many biological fields. In 2020, a deep learning model AlphaFold won the protein folding competition with predicted structures within the error tolerance of experimental methods. However, this solution to the most prominent bioinformatic challenge of the past 50 years has been possible only thanks to a carefully curated benchmark of experimentally predicted protein structures. In Genomics, we have similar challenges (annotation of genomes and identification of functional elements) but currently, we lack benchmarks similar to protein folding competition.

Results

Here we present a collection of curated and easily accessible sequence classification datasets in the field of genomics. The proposed collection is based on a combination of novel datasets constructed from the mining of publicly available databases and existing datasets obtained from published articles. The collection currently contains nine datasets that focus on regulatory elements (promoters, enhancers, open chromatin region) from three model organisms: human, mouse, and roundworm. A simple convolution neural network is also included in a repository and can be used as a baseline model. Benchmarks and the baseline model are distributed as the Python package ‘genomic-benchmarks’, and the code is available at https://github.com/ML-Bioinfo-CEITEC/genomic_benchmarks.

Conclusions

Deep learning techniques revolutionized many biological fields but mainly thanks to the carefully curated benchmarks. For the field of Genomics, we propose a collection of benchmark datasets for the classification of genomic sequences with an interface for the most commonly used deep learning libraries, implementation of the simple neural network and a training framework that can be used as a starting point for future research. The main aim of this effort is to create a repository for shared datasets that will make machine learning for genomics more comparable and reproducible while reducing the overhead of researchers who want to enter the field, leading to healthy competition and new discoveries.
High-resolution structural variants catalogue in a large-scale whole genome sequenced bovine family cohort data
Authors: Lee Young-Lim , Bosse Mirte , Takeda Haruko , Moreira Gabriel Costa Monteiro , Karim Latifa , Druet Tom , Oget-Ebrad Claire , Coppieters Wouter , Veerkamp Roel F. , Groenen Martien A. M. , Georges Michel , Bouwman Aniek C. , Charlier Carole
Published: May 2023

Background

Structural variants (SVs) are chromosomal segments that differ between genomes, such as deletions, duplications, insertions, inversions and translocations. The genomics revolution enabled the discovery of sub-microscopic SVs via array and whole-genome sequencing (WGS) data, paving the way to unravel the functional impact of SVs. Recent human expression QTL mapping studies demonstrated that SVs play a disproportionally large role in altering gene expression, underlining the importance of including SVs in genetic analyses. Therefore, this study aimed to generate and explore a high-quality bovine SV catalogue exploiting a unique cattle family cohort data (total 266 samples, forming 127 trios).

Results

We curated 13,731 SVs segregating in the population, consisting of 12,201 deletions, 1,509 duplications, and 21 multi-allelic CNVs (> 50-bp). Of these, we validated a subset of copy number variants (CNVs) utilising a direct genotyping approach in an independent cohort, indicating that at least 62% of the CNVs are true variants, segregating in the population. Among gene-disrupting SVs, we prioritised two likely high impact duplications, encompassing ORM1 and POPDC3 genes, respectively. Liver expression QTL mapping results revealed that these duplications are likely causing altered gene expression, confirming the functional importance of SVs. Although most of the accurately genotyped CNVs are tagged by single nucleotide polymorphisms (SNPs) ascertained in WGS data, most CNVs were not captured by individual SNPs obtained from a 50K genotyping array.

Conclusion

We generated a high-quality SV catalogue exploiting unique whole genome sequenced bovine family cohort data. Two high impact duplications upregulating the ORM1 and POPDC3 are putative candidates for postpartum feed intake and hoof health traits, thus warranting further investigation. Generally, CNVs were in low LD with SNPs on the 50K array. Hence, it remains crucial to incorporate CNVs via means other than tagging SNPs, such as investigation of tagging haplotypes, direct imputation of CNVs, or direct genotyping as done in the current study. The SV catalogue and the custom genotyping array generated in the current study will serve as valuable resources accelerating utilisation of full spectrum of genetic variants in bovine genomes.
Phylogeny of the plant receptor-like kinase (RLK) gene family and expression analysis of wheat RLK genes in response to biotic and abiotic stresses
Authors: Yan Jun , Su Peisen , Meng Xianyong , Liu Pingzeng
Published: May 2023

Background

The receptor-like kinase (RLK) gene families in plants contains a large number of members. They are membrane proteins with an extracellular receptor domain and participate in biotic and abiotic stress responses.

Results

In this study, we identified RLKs in 15 representative plant genomes, including wheat, and classified them into 64 subfamilies by using four types of phylogenetic trees and HMM models. Conserved exon‒intron structures with conserved exon phases in the kinase domain were found in many RLK subfamilies from Physcomitrella patens to Triticum aestivum. Domain distributions of RLKs were also diagrammed. Collinearity events and tandem gene clusters suggested that polyploidization and tandem duplication events contributed to the member expansions of T. aestivum RLKs. Global expression pattern analysis was performed by using public transcriptome data. These analyses were involved in T. aestivum, Aegilops tauschii and Brachypodium distachyon RLKs under biotic and abiotic stresses. We also selected 9 RLKs to validate the transcriptome prediction by using qRT‒PCR under drought treatment and with Fusarium graminearum infection. The expression trends of these 9 wheat RLKs from public transcriptome data were consistent with the results of qRT‒PCR, indicating that they might be stress response genes under drought or F. graminearum treatments.

Conclusion

In this study, we identified, classified, evolved, and expressed RLKs in wheat and related plants. Thus, our results will provide insights into the evolutionary history and molecular mechanisms of wheat RLKs.
Effects of HDAC inhibitors on neuroblastoma SH-SY5Y cell differentiation into mature neurons via the Wnt signaling pathway
Authors: Choi Jiyun , Hwang Jinsu , Ramalingam Mahesh , Jeong Han-Seong , Jang Sujeong
Published: May 2023

Histone deacetylase (HDAC) inhibitors affect cell homeostasis, gene expression, and cell cycle progression and promote cell terminal differentiation or apoptosis. However, the effect of HDAC inhibition on SH-SY5Y cells, which are neuroblastoma cells capable of differentiating into neurons under specific conditions, such as in the presence of retinoic acid (RA), is unknown. In this study, we hypothesized that HDAC inhibitors induced the neuronal differentiation of SH-SY5Y cells. To test this hypothesis, we used phase contrast microscopy, immunocytochemistry (ICC), qPCR, and western blotting analysis. MS-275 and valproic acid (VPA), two HDAC inhibitors, were selected to evaluate neuronal differentiation. It was confirmed that cells treated with MS-275 or VPA differentiated into mature neurons, which were distinguished by bipolar or multipolar morphologies with elongated branches. In addition, the mRNA expression of neuronal markers (Tuj1 and NEFH) and the oligodendrocyte marker (CNP) was significantly increased with MS-275 or VPA treatment compared to that with RA treatment. In addition, the protein expression of the other neuronal markers, Tuj1 and NeuN, was highly increased with HDAC inhibitor treatments compared to that with RA treatment. Furthermore, we confirmed that noncanonical Wnt signaling was upregulated by HDAC inhibitors via MAPK signaling and the Wnt/JNK pathway. Therefore, both MS-275 and VPA promoted the differentiation of SH-SY5Y cells into mature neurons via the Wnt signaling pathway.
Role of tillage measures in mitigating waterlogging damage in rapeseed
Authors: Tian Xiaoqin , Li Zhuo , Liu Yonghong , Li Wei
Published: May 2023

Background

Tillage measures have been effectively adopted for mitigating waterlogging damage in field crops, yet little is known about the role of tillage measures in crop responses to waterlogging. A field experiment was performed to investigate the effect of conventional planting (CK), small ridge planting (SR), big ridge planting (BR) and film side planting (FS) on soil available nutrients and enzymatic activity, chlorophyll contents, leaf nutrients, soluble protein, soluble sugar, nitrate reductase, antioxidant enzyme activity, lipid peroxidation, agronomic traits and yield of rapeseed under waterlogging stress conditions.

Results

Tillage measures remarkably improved rapeseed growth and yield parameters under waterlogging stress conditions. Under waterlogging conditions, rapeseed yield was significantly increased by 33.09 and 22.70% in the SR and BR groups, respectively, compared with CK. Correlation analysis showed that NO3−-N, NH4+-N, and urease in soils and malonaldehyde (MDA), superoxide dismutase (SOD), and nitrate reductase in roots were the key factors affecting rapeseed yield. The SR and BR groups had significantly increased NO3−-N by 180.30 and 139.77%, NH4+-N by 115.78 and 66.59%, urease by 41.27 and 26.45%, SOD by 6.64 and 4.66%, nitrate reductase by 71.67 and 26.67%, and significantly decreased MDA content by 14.81 and 13.35% under waterlogging stress, respectively, compared with CK. In addition, chlorophyll and N content in leaves, soluble sugar and POD in roots, and most agronomic traits were also significantly enhanced in response to SR and BR under waterlogging conditions.

Conclusion

Overall, SR and BR mitigated the waterlogging damage in rapeseed mainly by reducing the loss of soil available nitrogen, decreasing the MDA content in roots, and promoting urease in soils and SOD and nitrate reductase in roots. Finally, thorough assessment of rapeseed parameters indicated that SR treatment was most effective followed by BR treatment, to alleviate the adverse effects of waterlogging stress.
Severe cardiogenic shock and cardiac arrest due to fulminant cardiac sarcoidosis: a case report
Authors: Chakrala Teja , Prakash Roshni O. , Jain Anshul , Vautier R. Ashton , Prasada Sahil , Al-Ani Mohammed , Ahmed Mustafa M.
Published: May 2023

Background

Cardiac sarcoidosis is found to occur in approximately 5% of patients with sarcoidosis. Its presentation can typically range from complete heart block to ventricular arrhythmias. This condition can rarely present with severe heart failure and cardiogenic shock requiring aggressive and timely management strategies. Advanced imaging techniques are usually required to assist with its diagnosis.

Case presentation

A 70-year-old woman with a history of pulmonary sarcoidosis presented with non-ST elevation myocardial infarction, congestive hepatopathy, and acute renal failure. Left heart catheterization showed evidence of non-obstructive coronary artery disease, and right heart catheterization revealed severely elevated filling pressures and depressed cardiac index. She underwent aggressive diuresis and placement of an intra-aortic balloon pump in addition to initiation of inotropic and vasopressor support. While in the cardiac intensive care unit, she experienced frequent episodes of ventricular tachycardia and went into cardiac arrest requiring cardiopulmonary resuscitation. High clinical suspicion for cardiac sarcoidosis was confirmed by cardiac magnetic resonance imaging findings. After starting immunosuppressive therapy for cardiac sarcoidosis, she demonstrated clinical improvement.

Conclusion

Patients with cardiac sarcoidosis may remain asymptomatic or present with conduction abnormalities and arrhythmias. They rarely present with severe biventricular heart failure and cardiogenic shock, and in such cases, they require timely initiation of pharmacologic and device therapies, along with implementation of mechanical circulatory support.