bluuebunny/crossref_metadata_2025 huggingface dataset:
Tourism Destination Potential and Environmental Sustainability of Manila Bay Dolomite Beach
Authors:   Asian Institute of Maritime Studies, Capeña Kyle Cedrick , Clavo Laurance Cris ,   Asian Institute of Maritime Studies, Fiestada John Paul ,   Asian Institute of Maritime Studies, Principe Mark Brian ,   Asian Institute of Maritime Studies
Published: May 2024

Since the country’s tourism have a great impact on the economy, the Philippine government continues to develop and rehabilitate, if necessary, the tourist attractions in the country. One of the country’s rehabilitation projects is at the Manila Bay (Adel, 2022) where the Dolomite Beach, a reclaimed shoreline, is part of the DENR’s Rehabilitation program. Since its opening, it earned the potential to be a tourist destination in the Manila area. However, a number of individuals have raised concerns with regards to sustaining its clean environment given its location as a public destination spot. This prompted the researchers to study the tourism destination potential and environmental sustainability (perception of respondents)) of the Manila Bay Dolomite Beach. Utilizing convenience sampling, 121 respondents (comprising of government officials, residents, and business operators at the beach) were surveyed. Results indicated that Manila Bay Dolomite Beach has a potential to be a tourist attraction, with respondents expressing strong agreement towards its appeal, particularly its shoreline, white sandy beach, and sunsets. Furthermore, respondents demonstrated commitment to environmental protection, as evidenced by their agreement to adhere to rules, dispose of waste responsibly, and act as responsible tourists. Statistical analysis revealed a significant positive correlation (Pearson r = 0.298, p < 0.001) between the potential of the beach as a tourist destination and its environmental sustainability. Thus, the findings emphasized the importance of stakeholders' commitment to environmental conservation for the long-term success of tourism in the area.
Alopecia and Emotional Aspects Related to Hair
Authors: Da Silva Lucielma Maria
Published: May 2024

Introduction: Alopecia is a dermatological condition where hair loss occurs suddenly or gradually in one or more areas of the body, most commonly on the scalp. Studies focusing on the psychosocial and emotional aspects highlight the influence of traumatic situations and stress-related events on the progression of diseases, considered as triggering factors for alopecia. In this context, this study is justified by its aim to describe the disorder, outline the research, and address some issues of concern to researchers and professionals. It highlights that so-called psychosomatic diseases, disorders with an emotional origin, can be factors leading to physical problems that may affect hair, skin, and nails.  
Methodology: This paper aims to describe the approach for making a diagnosis, outline the emotional aspects in response to the disease, and detail the treatments tried and described in the consulted literature. It is a qualitative literature review conducted during November and December 2021, using databases such as Lilac’s, Medline, Pubmed, and Scielo. 
Results and Conclusion: Many studies suggest examining the role of coping and social support, the latter being seriously affected by changes in the appearance of individuals with alopecia.
Development and characterization of poly(lactic-co-glycolic acid) (PLGA) nanoparticles with finasteride and in vivo evaluation of their efficacy in hair growth
Authors: Junqueira Lara Soares , Monteiro Mariana Sato de Souza de Bustamante , Cabral Lucio Mendes
Published: May 2024

Introduction: Alopecia is a condition that affects the hair follicle. Currently, a wide variety of treatments are available, including topical, oral and injectable formulations. Oral therapies are the most adhered to; however, they generally present more adverse effects. As a well-established oral drug therapy, finasteride is presented, which inhibits the enzyme 5-α-reductase, and blocks the conversion of testosterone into dihydrotestosterone. This drug is capable of promoting hair growth, however can lead to adverse effects. Therefore, in this study, poly(lactic-co-glycolic acid) nanoparticles with finasteride were developed, aiming to improve the efficiency of this drug and reduce its systemic side effects.
Methodology: Nanoparticles without the drug and with the drug at 10, 20 and 30mg were developed. The system was characterized by Dynamic Light Scattering, Zeta Potential, Differential Scanning Calorimetry and Fourier Transform Infrared Spectroscopy.

Results and Conclusion: The drug-free nanoparticles had a reaction yield of 91.8%, nanoparticles with 10mg of finasteride showed a yield of 82.6%, with 20mg a yield of 92.9%, and with 30mg a yield of 89.3%. The average diameter ranged from 162.2nm for drug-free nanoparticles, 176.1nm for nanoparticles with 10mg of finasteride, 179.6nm for nanoparticles with 20mg, and 187.7nm for nanoparticles with 30mg. Nanoparticles with 10mg of finasteride showed an encapsulation efficiency of 48.2%, nanoparticles with 20mg an efficiency of 90.7%, and nanoparticles with 30mg an efficiency of 83.2%. The development of nanoparticles and the encapsulation of finasteride were successful. Next, an in vivo study will be conducted to evaluate its efficacy in promoting hair growth orally.
Regulation and organization of the lawyer profession in Romania in accordance with the provisions of Law no. 51/1995
Authors:   University of Medicine, Pharmacy, Science, and Technology “G.E. Palade” Târgu-Mureș, Faculty of Economics and Law, Lawyer, Mureș Bar, ROMANIA, Moldovan Ximena
Published: May 2024

The legal system in Romania is based on the principle of the rule of law, which ensures equality before the law and the protection of individual rights. Within this system, the lawyer plays an essential role in providing legal services and guaranteeing a fair and just trial for all citizens, representing and defending the rights of his clients before the courts and in other legal proceedings. Through their legal expertise and commitment to justice, lawyers are fundamental pillars of the legal system and help maintain its balance and integrity.
Foreword to the Special Centennial Publication of The Compass
Authors: Walters James
Published: May 2024

On the occasion of the 100th anniversary of the Society of Sigma Gamma Epsilon, it was deemed appropriate to republish from The COMPASS, the Earth Science Journal of SGE, the major papers that have been written in regard to SGE’s history.
PARENTS AND CHILDREN TOGETHER (PACT) FOR A HEALTHY MIND
Authors: Shah Syed Mahboob
Published: May 2024

Non-communicable diseases (NCDs) and poor mental health are the leading cause of premature mortality and morbidity globally. According to global estimates 70% risk factors for NCDs develop during childhood and adolescence. Suicide is leading cause of death among adolescents. Both parents and children need to work together for a healthy future.
HEALTH OF HEALTHCARE WORKERS IS THE WELL-BEING OF THE NATION
Authors: Channa Ghulam Asghar
Published: May 2024

Physical and mental health of the people plays an important role in sustainable development.   Healthy mind and safe circumstances are more important in situations where decisions and actions involving the life and death of people are taken, as in the field of medicine. Recent studies have revealed that the rate of major depression and suicidal behaviour is on the rise among healthcare workers due to stressful working conditions.
Ảnh hưởng của vốn đầu tư gián tiếp nước ngoài đến tăng trưởng kinh tế tại các nước đang phát triển: Vai trò của ổn định tài chính
Authors: Vũ Thị Hải Minh  , Phạm Thị Tuyết Trinh
Published: May 2024

Nghiên cứu tập trung vào vai trò của ổn định tài chính đối với tác động của dòng vốn đầu tư gián tiếp nước ngoài (FPI) đến tăng trưởng kinh tế tại các nền kinh tế đang phát triển. Dữ liệu của 55 nền kinh tế trong giai đoạn 2010–2021 được sử dụng để phân tích bằng mô hình tự hồi qui ngưỡng (TAR). Nghiên cứu chỉ ra rằng, tồn tại giá trị ngưỡng của ổn định tài chính làm tác động của FPI đến tăng trưởng kinh tế thay đổi. Mức ngưỡng tìm được có sự khác biệt khi ổn định tài chính được đo lường bằng FINSTAB1 và FINSTAB2, trong trường hợp có và không có biến tương tác. FPI chỉ có ảnh hưởng tích cực đến tăng trưởng kinh tế khi ổn định tài chính đo bằng FINSTAB1 chạm và vượt qua mức ngưỡng, kết hợp với tác động của FINSTAB1. Khi ổn định tài chính được đo lường thông qua FINSTAB2 bằng và vượt mức ngưỡng, FPI có ảnh hưởng tích cực đến tăng trưởng kinh tế. Kết quả này khẳng định vai trò của ổn định tài chính như một nhân tố hấp thụ các tác động tích cực của FPI.
Comparative Analysis of Shortest Route Problem Algorithms for Emergency Response Services
Authors:   College of Computer Studies, University of Antique, Sibalom, Antique, Philippines, Zamora Jeacar , Angeles Ace Marco Floro ,   College of Computer Studies, University of Antique, Sibalom, Antique, Philippines, Manalo Marnei ,   College of Computer Studies, University of Antique, Sibalom, Antique, Philippines
Published: May 2024

Emergency response services require a fast and shortest possible route when responding to emergency situations that include road accidents, crimes, the occurrence of fires, etc. In this regard, an efficient and robust shortest route locator is essentially important. This study primarily aims to analyze the performance of the various shortest route problem algorithms, including the regular Dijkstra’s algorithm, the Bidirectional search algorithm, and the Multidirectional Dijkstra’s algorithm (MDA). The implementations of these algorithms are evaluated and compared in order to determine which algorithm can be an excellent choice to be adopted by such emergency response services. The results showed that the MDA has efficient performance in both light and heavy traffic situations in terms of speed and response times.
The Gap Between Best Practices and Actual Practices: A BAM Field Study
Authors: Bosch David A.
Published: May 2024

There has been a call for business scholars to do a better job equipping people for BAM. However, there have been very few, if any, published field studies among actual BAM practitioners specifically looking to determine the gap between actual practices and best practices. This qualitative field study in a restricted access nation finds most BAM practitioners do not have business plans, integrated mission plans, an understanding of the triple bottom line concept, or mentors and boards of directors among other things. An understanding of this gap will allow academic institutions to better shape BAM curriculum and courses.
An Tobar Nua A Strategic Mix of Mission and Business
Authors: Locke Larry G.
Published: May 2024

Kelly and Susan Curry had a tough decision to make. In the summer of 2015 their Galway, Ireland based businesses were all well-staffed and running smoothly. Profits had never materialized for the Curries but, nonetheless, both were both excited about the new opportunity they faced. They had been presented with the idea of expanding part of their missional work, particularly their work in secondary religious education retreats, throughout the Republic of Ireland. Should they move forward with the expansion immediately or first seek to strengthen the financial performance of the businesses? If they were to focus on generating profits in the businesses, what strategic changes should they make to achieve that goal?
Utilizing Vocational Discernment in a Leadership Development Course
Authors: Schaffer Regan Harwell
Published: May 2024

The purpose of this paper is to describe the development of a newly created course designed for undergraduate business students to help them explore their vocational calling as they develop as leaders. The foundation of this course, titled “Leadership through the Eyes of Faith,” is a biblical theology of work and vocation which is explored through a variety of discernment exercises designed to increase self-awareness and assist students in determining personal, professional, and spiritual goals. An overview of the course format and assignments along with student reflection on the process are included.
The Hope and Peril of Introducing a Course on Christian Business Leadership into a College of Business Curriculum
Authors: McMahone Marty
Published: May 2024

This paper examines the advantages and pitfalls of establishing a class in the business school to reflect on the impact of the Christian faith on business decisions. In class, students learn to apply broad Christian principles to specific business situations. Having a specific class allows an instructor to specialize in both theological and business concerns and supports a clear, intentional integration of faith into the business world. It does not eliminate the need to integrate faith in other parts of the curriculum; instead, it makes that integration even more important so that the message of the college is consistent.
Student-Managed Investment Funds in Religiously Affiliated and Independent Colleges and Universities
Authors: Saunders Kent T.
Published: May 2024

Many colleges and universities now offer student-managed investment fund (SMIF) courses where students simultaneously manage a portfolio of real dollar investments and earn academic credit. This paper compares and contrasts the investment policies and objectives between religiously affiliated and independent private colleges and universities. Universities that offer SMIF courses as a part of their undergraduate finance curriculum were categorized as either a religiously affiliated or an independent private university. An instructor survey was administered to collect data on the specific investment policies with special consideration to socially responsible investment concerns. Additional data was gathered from U.S. News & World Report and the Integrated Postsecondary Education Data System (IPEDS) in order to control for institution size, academic reputation, and other institutional variables. Comparison variables of interest include the size of the fund under student control, whether or not socially responsible investment policies are implemented, and whether or not margin trading and derivative trading are permissible investment strategies. The results of this study outline differences in the practice of socially responsible investing between the institution types and provide a glimpse into some of the unique concerns that religiously affiliated schools consider when operating student-managed investment funds.
Book Review: Income Distribution
Authors: Stamm K. Brad
Published: May 2024

Book Review: Income Distribution
The Disciplined Writer: Two Steps to Creating Academically Legitimate Integration Papers
Authors: Black Janice A. , Smith Yvonne S.
Published: May 2024

The academic vocation has two parts: teaching and scholarship. As a matter of practical spirituality, there are increasing calls for Christian business professors to do research, particularly faith-integration research. This paper outlines the process by which faith-integration scholarship can be mapped on the academic writing process. Specifically, the key issues of legitimacy - quality and rigor - are discussed. Finally, we offer two practical principles for the writer of academically legitimate integration papers: The Rule of Three, and The Rule of Ten Thousand and give examples of how to apply each.
Venture Out: An Entrepreneurial Introduction to Business
Authors: Lynn Monty L.
Published: May 2024

Venture Out is a semester-long project which introduces elementary business skills and concepts from an entrepreneurial perspective. Student teams research and select a product to sell to students, create a mini-business plan, and present their plan to a board of judges from the business community. If their request is approved (up to $500), teams purchase and sell their product. After repaying the loan, teams donate their profits to a beneficiary and they reflect on their performance and lessons learned. Venture Out benefits students, the academic business program, and the community in tangible ways. Venture Out and other classroom-as-organization (CAO) programs are described.
An Interactive Interest Rate Activity for Financial Management
Authors: Halberg Richard
Published: May 2024

Students often have little understanding of appropriate interest rates, since textbook problems routinely provide a rate. In this activity, small groups establish interest rates and identify concerns for several realistic loan requests. This prepares the class for a brief lecture on interest rate components, including the risk-free rate and various risk premiums. Follow-up discussion of the loan requests and possible changes enables the instructor to assess the lecture’s effectiveness and misunderstandings. Biblical references to debt, interest, and usury can be used as a lead-in to the topic or as a follow-up to integrate Christian faith with this topic.
Using Demonstration Experiments to Illustrate the Pitfalls of Unintentional Moral Relativism
Authors: Kellaris James J.
Published: May 2024

Unintentional moral relativism (UMR) is a judgmental phenomenon involving inadvertent misapplication of an ethical standard believed to be objective or absolute. It occurs when a decision maker intends to apply an ethical standard, but circumstances change the application of the standard without the decision-maker’s awareness, such that the standard is inadvertently misapplied. Research evidence and classroom experience show that even individuals who ascribe strongly to moral absolutes are prone to the pitfalls of UMR. This article offers three examples of experiments that can be done as classroom demonstrations to illustrate proneness to circumstantial biases that can influence students’ ethical judgment.
Case Study: Herr Foods Inc.
Authors: Redmer Timothy A. O.
Published: May 2024

This case takes a unique inside look into the issues and decision process facing a company in the snack-food industry at a time of increased scrutiny regarding the health issues of certain foods, diets, and lifestyles. The fast-food industry already appears to be a target of interest, and actions have begun by fast-food companies and markets to counteract public perception. Will the snack-food industry encounter the same challenges? Do companies need to be taking a proactive or wait-and-see approach to the health and lifestyle related issues? Herr Foods top management, with a particular emphasis in the marketing and operations area, have been addressing the health food issue with a continuous review of their product line, operating procedures, new product development, and marketing strategies. A decision needs to be made by top management regarding the introduction of more health sensitive snack foods.
Preparing Business Students to be Salt and Light: Three Models of Faith Formation in Business Tested Head-to-Head
Authors: Edgell Margaret
Published: May 2024

This study responds to the need for empirical work on the complex nature and dynamics of faith formation. A survey of business students tested three models of faith formation by indicating which aspects of these models best reflected perceived experience. Classic secular theory dominates the student development literature, including in the Christian academy. As a result, secular theory influences heavily the thinking of Christian student-life professionals. A first model was derived from classic secular theory. A cutting-edge model from the secular literature offered a second model. A third model was derived by the author from an explicitly Christian philosophy of education. The author expected this empirical study to verify the already highly verified classic secular model. Even so, the author’s model was verified most strongly of the three models. This result offers encouragement to business faculty who teach according to their own explicitly Christian working models of how their students mature in their faith. Relevant literature, research warrant, methodology, and results are discussed below.
John Wesley and the Goal of Maximizing Shareholder Wealth
Authors: Adams Scott A.
Published: May 2024

This paper explores the use of John Wesley sermon number 50, “The Use of Money,” in corporate finance class when discussing shareholder wealth maximization. Wesley provides a framework to help keep the focus on good stewardship and away from greed. The paper will first provide the background as to why Wesley’s teaching is appropriate for wealth maximization. The paper will then demonstrate the use of this sermon in class.
Toward Leading a Team: A New Script
Authors: Steen Todd P. , VanderVeen Steve
Published: May 2024

In the classroom and in life, it is rare to find teams that perform to their potential. While scholarly papers addressing the issue of team building and leadership focus on knowledge and are theoretical in nature, this paper provides a script that professors can use over the course of a semester to instruct students on how to create productive teams. The script, however, is not a "cookbook” for team building; rather, it provides a process, ideas, and references for bonding people together in a common cause. Inherent in this script are values consistent with Christianity, collaboration, and servant leadership. Although this script is reflective of what happens in the classroom, it can be adapted for other venues such as teams and committees in the corporation and in the church.
What Should Professors Teach about the Protestant Work Ethic?
Authors: Smith Virgil O. , Smith Yvonne S.
Published: May 2024

The purpose of this paper is to argue that Christian professors need to teach students to question assumptions underlying business constructs, even familiar constructs. The Protestant work ethic (PWE) is an important and influential work ethic, but after analysis, it will be shown to be neither biblical nor Protestant. By this we mean that some key definitional elements of the PWE are not Biblical and are not philosophically compatible with the theologies of Martin Luther or John Calvin. Our conclusion is that Christian professors should use the PWE as a cautionary tale to help Christian students evaluate worldviews. The authors suggest several classroom exercises to help students develop their skills in testing assumptions.
Total Depravity, Middle Managers, and Conscience: A Response to Klay, Lunn, TenHaken, Porter, and Smith
Authors: VanderVeen Steve
Published: May 2024

There are at least three articles worth reading in this issue of The JBIB: “Middle Management as a Calling” by Robin Klay, John Lunn, and VickiTenHaken; “The Complexities of Vocation and Business: A Rejoinder To ‘Middle Management as a Calling’” by Brian Porter; and “Simplicity for Simplicity and Complexity for Complexity: A Response to ‘Middle Management as a Calling’” by Virgil Smith.
The Perceived Godly Stockbroker: A Rejoinder
Authors: Fields W. Calvin
Published: May 2024

I’m just dying to know what happened to Dr. VanderVeen during his last year in undergraduate school that turned him away from the cloth and toward the stock exchange industry. Please, tell us what happened. Anyway, I am familiar with Hill’s (1997) book, having required it for my business ethics students. I have also done some research in this area, so I would like to make some observations about VanderVeen’s article in the present issue of The JBIB.
Editor's Perspective: When Scripture and Culture Clash
Authors: Smith Yvonne S.
Published: May 2024

When Scripture and culture clash, which wins? The relative authority of the Bible versus cultural norms is a fundamental issue for the Journal of Biblical Integration in Business (JBIB) (e.g. Fields & Bekker, 2011; Johnson, 1996). It is a question that every author and reader of this journal must answer, continuously (II Cor. 10:5).
Just Business: Christian Ethics for the Marketplace by Alexander Hill
Authors: Johnson Sharon G.
Published: May 2024

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Three Bible Studies Focusing on the Workplace
Authors: Johnson Sharon G.
Published: May 2024

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Biblical Integration: Understanding the World Through the Word by Mark Eckel
Authors: Johnson Sharon G.
Published: May 2024

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How to Beat Burnout by Frank Minirth, Don Hawkins, Paul Meier, and Richard Flournoy
Authors: Smith Yvonne S.
Published: May 2024

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Integration Reinforced Through Apologetics: Two Case Illustrations
Authors: Chewning Richard C. , Haak Delia
Published: May 2024

Chewning and Haak offer two case illustrations: one in management decision-making and the other in marketing. The illustrations could be used to help students identify what they believe and why they believe it, while teaching them how to biblically defend their world/lifeview.
"Will you tell me the ways you’ve been keeping beautiful to stay alive?"
Authors: Ochoa Orlando , Ozuna León
Published: May 2024

Orlando Ochoa and León Ozuna write to each other and reflect on the details of their friendship, love, loneliness, and sex across distance. This epistolary/poetic exchange is an answer to the question of how Ochoa and Ozuna—Mexican poets and lovers from the Rio Grande Valley of South Texas—keep alive in the world.
Letter to My City
Authors: Aghedo Nyami
Published: May 2024

In this poem-letter the speaker addresses their hometown, a place of familiarity and contradiction. Through exploring the dark past of Southern North Carolina an intimate account of living in community is illustrated.
Preguntas y frases para una nieta americana
Authors: de Hinojosa Alana
Published: May 2024

“Preguntas y frases” is an imagined letter from my grandmother. It is composed of Spanish words and phrases (including missing accents and misspellings) as my grandmother, Esther, wrote them in 1983 in a series of letters she sent to my mother while my mother was living abroad in Ecuador. In those letters, Esther spoken plainly with her daughter—principally, by questioning her decision to leave the United States and asking that my mother back home to Calexico, California.

Many years after my grandmother’s death, my mother found these letters tucked away in the house attic. When my mother shared these letters with me, it was startling for me to see and hear so clearly my grandmother’s voice and way of speaking after so many years since her passing. In response, I wrote “Preguntas y frases para una nieta americana.” The title is inspired by Teresa Palomo Acosta’s poem “Preguntas y frases para una bisabuela española” in which Acosta reflects on her Spanish heritage by writing a letter to her great Spanish grandmother. In contrast, “Preguntas y frases para una nieta americana” reflects on American assimilation and what is lost, protected, and honored across three generations of Mexican American women. The letter is my imagination of what my grandmother would say to me today if she were to write me—and speak plainly—as she had with my mother all those years ago.
A Letter to My Newborn
Authors: McMillan Caitilin
Published: May 2024

This letter takes place as a conversation with my newborn about the struggles and desires I see on the horizon at the moment of writing. The letter’s simple style and straightforward language invite you to immerse yourself in an intimate sharing between myself and my one-year-old and consider the perspective of a young child coming to grips with the world around them. I draw on past conversations with my mother about her illness and her ecological work, as well as elements of our family history working and living on the river Clyde. Falling somewhere between a poem, a story and a letter, I explore themes of change and hope, ecological precarity, health and illness, and a path towards more livable worlds. Two photos included with the letter share intimate moments with the reader related to my writing – the moment Clyde reaches for his grandmother at the water’s edge, an ode to the river on which she grew up and after which he is named; and the moment my mother unfolds her hand letting an edible flower sit delicately along her hand’s life lines as an offering of nourishment and interconnection.
I Wish
Authors: King DeWitt
Published: May 2024

The letter charts my relationship to geography through a letter to Donald Deskin Jr. From Black geographer junior scholar to pioneering Black geographer, this letter uses Black geographies as an analytic to think through Black geographical knowledge, practice and kinship.
Dear Dad
Authors: Anderson Christian
Published: May 2024

This letter remembers the writer's father, considering the disquieted contexts of his life and early death. These contexts connect to histories and conditions far more extensive than any individual life, and suggest difficult questions about inheritance, relationality, aftermath, settler being, and more, with which the writer continues to grapple.
A Letter for Missing and Disappeared Archives
Authors: Iralu Elspeth
Published: May 2024

In this letter, Elspeth Iralu initiates a time-travelling correspondence with her paternal grandfather, Vichazelhu Iralu, about his dreams for the Naga sovereignty movement. The letter grieves the loss of personal and political archives that were stolen, disappeared, and destroyed through processes of colonization. Iralu offers letter-writing, shaped by Naga modes of storytelling, as an anticolonial epistemology that enacts Naga sovereignty in the here and now.
Dear Abolition
Authors: Purifoy Danielle
Published: May 2024

In the wake of her uncle’s 2021 death from COVID-19 in a Michigan prison, Danielle Purifoy reflects on what his life and art taught her about abolition, and what kind of place could have given him a different life…and death.

 
Improved clinical data imputation via classical and quantum determinantal point processes
Authors: Kazdaghli Skander , Kerenidis Iordanis , Kieckbusch Jens , Teare Philip
Published: May 2024

Imputing data is a critical issue for machine learning practitioners, including in the life sciences domain, where missing clinical data is a typical situation and the reliability of the imputation is of great importance. Currently, there is no canonical approach for imputation of clinical data and widely used algorithms introduce variance in the downstream classification. Here we propose novel imputation methods based on determinantal point processes (DPP) that enhance popular techniques such as the multivariate imputation by chained equations and MissForest. Their advantages are twofold: improving the quality of the imputed data demonstrated by increased accuracy of the downstream classification and providing deterministic and reliable imputations that remove the variance from the classification results. We experimentally demonstrate the advantages of our methods by performing extensive imputations on synthetic and real clinical data. We also perform quantum hardware experiments by applying the quantum circuits for DPP sampling since such quantum algorithms provide a computational advantage with respect to classical ones. We demonstrate competitive results with up to 10 qubits for small-scale imputation tasks on a state-of-the-art IBM quantum processor. Our classical and quantum methods improve the effectiveness and robustness of clinical data prediction modeling by providing better and more reliable data imputations. These improvements can add significant value in settings demanding high precision, such as in pharmaceutical drug trials where our approach can provide higher confidence in the predictions made.
Sympathetic Motor Neuron Dysfunction is a Missing Link in Age-Associated Sympathetic Overactivity
Authors: de la Cruz Lizbeth , Bui Derek , Moreno Claudia M. , Vivas Oscar
Published: May 2024

Overactivity of the sympathetic nervous system is a hallmark of aging. The cellular mechanisms behind this overactivity remain poorly understood, with most attention paid to likely central nervous system components. In this work, we hypothesized that aging also affects the function of motor neurons in the peripheral sympathetic ganglia. To test this hypothesis, we compared the electrophysiological responses and ion-channel activity of neurons isolated from the superior cervical ganglia of young (12 weeks), middle-aged (64 weeks), and old (115 weeks) mice. These approaches showed that aging does impact the intrinsic properties of sympathetic motor neurons, increasing spontaneous and evoked firing responses. A reduction of KCNQ channel currents emerged as a major contributor to age-related hyperexcitability. Thus, it is essential to consider the effect of aging on motor components of the sympathetic reflex as a crucial part of the mechanism involved in sympathetic overactivity.
Pervasive relaxed selection on spermatogenesis genes coincident with the evolution of polygyny in gorillas
Authors: Bowman Jacob D. , Silva Neide , Schüftan Erik , Almeida Joana M. , Brattig-Correia Rion , Oliveira Raquel A. , Tüttelmann Frank , Enard David , Navarro-Costa Paulo , Lynch Vincent J.
Published: May 2024

Gorillas have a polygynous social system in which the highest-ranking male has almost exclusive access to females and sires most of the offspring in the troop. Such behavior results in a dramatic reduction of sperm competition, which is ultimately associated with numerous traits that cause low efficacy of gorilla spermatogenesis. However, the molecular basis behind the remarkable erosion of the gorilla male reproductive system remains unknown. Here, we explored the genetic consequences of the polygynous social system in gorillas by testing for altered selection intensity across 13,310 orthologous protein-coding genes from 261 Eutherian mammals. We identified 578 genes with relaxed purifying selection in the gorilla lineage, compared with only 96 that were positively selected. Genes under relaxed purifying selection in gorillas have accumulated numerous deleterious amino acid substitutions, their expression is biased towards male germ cells, and are enriched in functions related to meiosis and sperm biology. We tested the function of gorilla relaxed genes previously not implicated in sperm biology using the
Drosophila
model system and identified 41 novel spermatogenesis genes required for normal fertility. Furthermore, by exploring exome/genome sequencing data of infertile men with severe spermatogenic impairment, we found that the human orthologs of the gorilla relaxed genes are enriched for loss-of-function variants in infertile men. These data provide compelling evidence that reduced sperm competition in gorillas is associated with relaxed purifying selection on genes related to male reproductive function. The accumulation of deleterious mutations in these genes likely provides the mechanistic basis behind the low efficacy of gorilla spermatogenesis and uncovers new candidate genes for human male infertility.
Connecting Chromatin Structures to Gene Regulation Using Dynamic Polymer Simulations
Authors: Fu Yi , Zhao Tianxiao , Clark Finnegan , Nomikou Sofia , Tsirigos Aristotelis , Lionnet Timothée
Published: May 2024

The transfer of regulatory information between distal loci on chromatin is thought to involve physical proximity, but key biophysical features of these contacts remain unclear. For instance, it is unknown how close and for how long two loci need to be in order to productively interact. The main challenge is that it is currently impossible to measure chromatin dynamics with high spatiotemporal resolution at scale. Polymer simulations provide an accessible and rigorous way to test biophysical models of chromatin regulation, yet there is a lack of simple and general methods for extracting the values of model parameters. Here we adapt the Nelder-Mead simplex optimization algorithm to select the best polymer model matching a given Hi-C dataset, using the
MYC
locus as an example. The model’s biophysical parameters predict a compartmental rearrangement of the
MYC
locus in leukemia, which we validate with single-cell measurements. Leveraging trajectories predicted by the model, we find that loci with similar Hi-C contact frequencies can exhibit widely different contact dynamics. Interestingly, the frequency of productive interactions between loci exhibits a non-linear relationship with their Hi-C contact frequency when we enforce a specific capture radius and contact duration. These observations are consistent with recent experimental observations and suggest that the dynamic ensemble of chromatin configurations, rather than average contact matrices, is required to fully predict productive long-range chromatin interactions.
Connecting Chromatin Structures to Gene Regulation Using Dynamic Polymer Simulations
Authors: Fu Yi , Clark Finnegan , Nomikou Sofia , Tsirigos Aristotelis , Lionnet Timothee
Published: May 2024

The transfer of regulatory information between distal loci on chromatin is thought to involve physical proximity, but key biophysical features of these contacts remain unclear. For instance, it is unknown how close and for how long two loci need to be in order to productively interact. The main challenge is that it is currently impossible to measure chromatin dynamics with high spatiotemporal resolution at scale. Polymer simulations provide an accessible and rigorous way to test biophysical models of chromatin regulation, yet there is a lack of simple and general methods for extracting the values of model parameters. Here we adapt the Nelder-Mead simplex optimization algorithm to select the best polymer model matching a given Hi-C dataset, using the
MYC
locus as an example. The model’s biophysical parameters predict a compartmental rearrangement of the
MYC
locus in leukemia, which we validate with single-cell measurements. Leveraging trajectories predicted by the model, we find that loci with similar Hi-C contact frequencies can exhibit widely different contact dynamics. Interestingly, the frequency of productive interactions between loci exhibits a non-linear relationship with their Hi-C contact frequency when we enforce a specific capture radius and contact duration. These observations are consistent with recent experimental observations and suggest that the dynamic ensemble of chromatin configurations, rather than average contact matrices, is required to fully predict long-range chromatin interactions.
Partial rejuvenation of the spermatogonial stem cell niche after gender-affirming hormone therapy in trans women
Authors: Delgouffe Emily , Silva Samuel Madureira , Chalmel Frédéric , Cools Wilfried , Raets Camille , Tilleman Kelly , T’Sjoen Guy , Baert Yoni , Goossens Ellen
Published: May 2024

Although the impact of gender-affirming hormone therapy (GAHT) on spermatogenesis in trans women has already been studied, data on its precise effects on the testicular environment is poor. Therefore, this study aimed to characterize, through histological and transcriptomic analysis, the spermatogonial stem cell niche of 106 trans women who underwent standardized GAHT, comprising estrogens and cyproterone acetate. A partial dedifferentiation of Sertoli cells was observed, marked by the co-expression of androgen receptor and anti-Müllerian hormone which mirrors the situation in peripubertal boys. The Leydig cells also exhibited a distribution analogous to peripubertal tissue, accompanied by a reduced insulin-like factor 3 expression. Although most peritubular myoid cells expressed alpha-smooth muscle actin 2, the expression pattern was disturbed. Besides this, fibrosis was particularly evident in the tubular wall and the lumen was collapsing in most participants. A spermatogenic arrest was also observed in all participants. The transcriptomic profile of transgender tissue confirmed a partial rejuvenation and, in addition, detected inflammation processes occurring in the samples. The present study shows that GAHT changes the spermatogonial stem cell niche by partially rejuvenating the somatic cells and inducing fibrotic processes. These findings are important to further understand how estrogens and testosterone suppression affect the testis environment, and in the case of orchidectomized testes as medical waste material, their potential use in research.
High-density sampling reveals volume growth in human tumours
Authors: Angaji Arman , Owusu Michel , Velling Christoph , Dick Nicola , Weghorn Donate , Berg Johannes
Published: May 2024

In growing cell populations such as tumours, mutations can serve as markers that allow tracking the past evolution from current samples. The genomic analyses of bulk samples and samples from multiple regions have shed light on the evolutionary forces acting on tumours. However, little is known empirically on the spatio-temporal dynamics of tumour evolution. Here, we leverage published data from resected hepatocellular carcinomas, each with several hundred samples taken in two and three dimensions. Using spatial metrics of evolution, we find that tumour cells grow predominantly uniformly within the tumour volume instead of at the surface. We determine how mutations and cells are dispersed throughout the tumour and how cell death contributes to the overall tumour growth. Our methods shed light on the early evolution of tumours in vivo and can be applied to high-resolution data in the emerging field of spatial biology.
Shortcutting from self-motion signals: quantifying trajectories and active sensing in an open maze
Authors: Xu Jiayun , Girardi-Schappo Mauricio , Béïque Jean-Claude , Longtin André , Maler Leonard
Published: May 2024

Animals navigate by learning the spatial layout of their environment. We investigated spatial learning of mice in an open maze where food was hidden in one of a hundred holes. Mice leaving from a stable entrance learned to efficiently navigate to the food without the need for landmarks. We develop a quantitative framework to reveal how the mice estimate the food location based on analyses of trajectories and active hole checks. After learning, the computed “target estimation vector” (TEV) closely approximated the mice’s trajectory and its hole check distribution. We propose that the TEV can be precisely connected to the properties of hippocampal place cells. Finally, we provide the first demonstration that, after learning the location of two food sites, the mice took a shortcut between the sites, demonstrating that they had generated a cognitive map.
Geometry and dynamics of representations in a precisely balanced memory network related to olfactory cortex
Authors: Meissner-Bernard Claire , Zenke Friedemann , Friedrich Rainer W
Published: May 2024

Biological memory networks are thought to store information by experience-dependent changes in the synaptic connectivity between assemblies of neurons. Recent models suggest that these assemblies contain both excitatory and inhibitory neurons (E/I assemblies), resulting in co-tuning and precise balance of excitation and inhibition. To understand computational consequences of E/I assemblies under biologically realistic constraints we built a spiking network model based on experimental data from telencephalic area Dp of adult zebrafish, a precisely balanced recurrent network homologous to piriform cortex. We found that E/I assemblies stabilized firing rate distributions compared to networks with excitatory assemblies and global inhibition. Unlike classical memory models, networks with E/I assemblies did not show discrete attractor dynamics. Rather, responses to learned inputs were locally constrained onto manifolds that ‘focused’ activity into neuronal subspaces. The covariance structure of these manifolds supported pattern classification when information was retrieved from selected neuronal subsets. Networks with E/I assemblies therefore transformed the geometry of neuronal coding space, resulting in continuous representations that reflected both relatedness of inputs and an individual’s experience. Such continuous representations enable fast pattern classification, can support continual learning, and may provide a basis for higher-order learning and cognitive computations.
Transcriptomic profiling of Schlemm’s canal cells reveals a lymphatic-biased identity and three major cell states
Authors: Balasubramanian Revathi , Kizhatil Krishnakumar , Li Taibo , Tolman Nicholas , Bhandari Aakriti , Clark Graham , Bupp-Chickering Violet , Kelly Ruth A. , Zhou Sally , Peregrin John , Simón Marina , Montgomery Christa , Stamer W Daniel , Qian Jiang , John Simon W.M.
Published: May 2024

Schlemm’s canal (SC) is central in intraocular pressure regulation but requires much characterization. It has distinct inner and outer walls, each composed of Schlemm’s canal endothelial cells (SECs) with different morphologies and functions. Recent transcriptomic studies of the anterior segment added important knowledge, but were limited in power by SEC numbers or did not focus on SC. To gain a more comprehensive understanding of SC biology, we performed bulk RNA sequencing on C57BL/6J SC, blood vessel, and lymphatic endothelial cells from limbal tissue (∼4500 SECs). We also analyzed mouse limbal tissues by single-cell and single-nucleus RNA sequencing (C57BL/6J and 129/Sj strains), successfully sequencing 903 individual SECs. Together, these datasets confirm that SC has molecular characteristics of both blood and lymphatic endothelia with a lymphatic phenotype predominating. SECs are enriched in pathways that regulate cell-cell junction formation pointing to the importance of junctions in determining SC fluid permeability. Importantly, and for the first time, our analyses characterize 3 molecular classes of SECs, molecularly distinguishing inner wall from outer wall SECs and discovering two inner wall cell states that likely result from local environmental differences. Further, and based on ligand and receptor expression patterns, we document key interactions between SECs and cells of the adjacent trabecular meshwork (TM) drainage tissue. Also, we present cell type expression for a collection of human glaucoma genes. These data provide a new molecular foundation that will enable the functional dissection of key homeostatic processes mediated by SECs as well as the development of new glaucoma therapeutics.
Direct modulation of TRPM8 ion channels by rapamycin and analog macrolide immunosuppressants
Authors: Tóth Balázs István , Bazeli Bahar , Janssens Annelies , Lisztes Erika , Racskó Márk , Kelemen Balázs , Herczeg Mihály , Nagy Tamás Milán , Kövér Katalin E , Mitra Argha , Borics Attila , Bíró Tamás , Voets Thomas
Published: May 2024

Rapamycin (sirolimus), a macrolide compound isolated from the bacterium
Streptomyces hygroscopicus
, is widely used as oral medication for the prevention of transplant rejection and the treatment of lymphangioleiomyomatosis. It is also incorporated in coronary stent coatings to prevent restenosis and in topical preparations for the treatment of skin disorders. Rapamycin’s
in vivo
activities are generally ascribed to its binding to the protein FKBP12, leading to potent inhibition of the mechanistic target of rapamycin kinase (mTOR) by the FKBP12-rapamycin complex. The specific rapamycin-induced interaction between domains from mTOR and FKBP12 is also frequently employed in cell biological research, for rapid chemically-induced protein dimerization strategies. Here we show that rapamycin activates TRPM8, a cation channel expressed in sensory nerve endings that serves as the primary cold sensor in mammals. Using a combination of electrophysiology, Saturation Transfer Triple-Difference (STTD) NMR spectroscopy and molecular docking-based targeted mutagenesis, we demonstrate that rapamycin directly binds to TRPM8. We identify a rapamycin-binding site in the groove between voltage sensor-like domain and the pore domain, distinct from the interaction sites of cooling agents and known TRPM8 agonists menthol and icilin. Related macrolide immunosuppressants act as partial TRPM8 agonists, competing with rapamycin for the same binding site. These findings identify a novel molecular target for rapamycin and provide new insights into the mechanisms of TRPM8 activation, which may assist in the development of therapies targeting this ion channel. Moreover, our findings also indicate that caution is needed when using molecular approaches based on rapamycin-induced dimerization to study ion channel regulation.