bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRISPR-Cas12a exhibits metal-dependent specificity switching
Authors: Nguyen Giang T , Schelling Michael A , Raju Akshara , Buscher Kathryn A , Sritharan Aneisha , Sashital Dipali G 
Published: July 2024

Abstract
Cas12a is the immune effector of type V-A CRISPR-Cas systems and has been co-opted for genome editing and other biotechnology tools. The specificity of Cas12a has been the subject of extensive investigation both in vitro and in genome editing experiments. However, in vitro studies have often been performed at high magnesium ion concentrations that are inconsistent with the free Mg2+ concentrations that would be present in cells. By profiling the specificity of Cas12a orthologs at a range of Mg2+ concentrations, we find that Cas12a switches its specificity depending on metal ion concentration. Lowering Mg2+ concentration decreases cleavage defects caused by seed mismatches, while increasing the defects caused by PAM-distal mismatches. We show that Cas12a can bind seed mutant targets more rapidly at low Mg2+ concentrations, resulting in faster cleavage. In contrast, PAM-distal mismatches cause substantial defects in cleavage following formation of the Cas12a-target complex at low Mg2+ concentrations. We observe differences in Cas12a specificity switching between three orthologs that results in variations in the routes of phage escape from Cas12a-mediated immunity. Overall, our results reveal the importance of physiological metal ion conditions on the specificity of Cas effectors that are used in different cellular environments.
When impact trials are not feasible: alternatives to study the impact of prediction models on clinical practice
Authors: Janse Roemer J , Stel Vianda S , Jager Kitty J , Tripepi Giovanni , Zoccali Carmine , Dekker Friedo W , van Diepen Merel 
Published: July 2024

ABSTRACT
Patients with kidney disease have an uncertain future, with prognosis varying greatly per patient. To get a better idea of what the future holds and tailor interventions to the individual patient, prediction models can be of great value. Before a prediction model can be applied in practice, its performance should be measured in target populations of interest (i.e. external validation) and whether or not it helps improve clinical practice (i.e. whether it impacts clinical practice) should be determined. The impact would ideally be determined using an impact trial, but such a trial is often not feasible, and the impact of prediction models is therefore rarely assessed. As a result, prediction models that may not be so impactful may end up in clinical practice and impactful models may not be implemented due to a lack of impact studies. Ultimately, many prediction models end up never being implemented, resulting in much research waste. To allow researchers to get an indication of a prediction model's impact on clinical practice, alternative methods to assess a prediction model's impact are important. In this paper, we discuss several alternatives, including interviews, case-based surveys, decision comparisons, outcome modelling, before–after analyses and decision curve analyses. We discuss the general idea behind these approaches, including what information can be gathered from such studies and important pitfalls. Lastly, we provide examples of the different alternatives.
Impact of Heating Conventional Cigarettes With a Novel Device on Health-Related Biomarkers and Cigarette Use Patterns Among Chinese Adult Smokers Unwilling to Quit: A Pilot Randomized Controlled Trial
Authors: Chu Shuilian , Li Xiaobo , Zhang Di , Jing Hang , Feng Lin , Zuo Yingting , Li Jiachen , Ma Haomiao , Tong Zhaohui , Liang Lirong 
Published: July 2024

Abstract

Introduction
We evaluated the impact of heating conventional cigarettes with a novel heated tobacco product (HTP) device on biomarkers and cigarette use patterns in Chinese adult smokers unwilling to quit smoking.

Aims and Methods
In this pilot randomized controlled trial, 50 eligible participants were allocated to either control group (smoking conventional cigarettes) or HTP device group (switching to using heated conventional cigarettes by the HTP device). Participants in the HTP device group went through a 2-day run-in period and then used heated conventional cigarettes exclusively for 5 days, followed by flexible use for 14 days. Five biomarkers of exposure (BoEs) were measured at baseline and on day 7. Thirteen biomarkers of biological effect (BoBEs) were measured at baseline and on day 21. Safety, daily cigarette consumption, craving, withdrawal symptoms, and device acceptability, were assessed.

Results
BoE levels decreased by 26.4 % to 71.4% from baseline in the HTP device group, while BoBE levels did not significantly change in either group. In the HTP group, 56% exclusively used heated conventional cigarettes during the flexible use period, experiencing reduced cravings and withdrawal symptoms, while dual users consumed more cigarettes. Mild to moderate device-related reactions were reported in 36% of users. Satisfaction, taste, and harm reduction belief scores averaged 7.4, 6.6, and 8.7 (out of 10), respectively.

Conclusions
Switching to heated conventional cigarettes with the HTP device may reduce short-term exposure to smoke toxicants. However, it can lead to increased tobacco use among dual users. Further investigation is needed to confirm these preliminary findings.

Trial registration
Chinese Clinical Trial Registry (http://www.chictr.org.cn/), ChiCTR2200065055, October 26, 2022.

Implications
This study is the first to evaluate the impact of heating conventional cigarettes with a novel HTP device on health-related biomarkers and cigarette use patterns among Chinese adult smokers. This novel HTP device can directly heat conventional cigarettes without the necessity for specifically designed tobacco products, avoiding the potential additive risks of traditional HTPs. If the results of this study could be further verified by randomized controlled clinical trials with larger sample sizes, this novel HTP device could serve as a short-term harm reduction alternative for smokers unwilling to quit.
A Systematic Review of Predictors of Vaping Cessation Among Young People
Authors: Kundu Anasua , Seth Siddharth , Felsky Daniel , Moraes Theo J , Selby Peter , Chaiton Michael 
Published: July 2024

Abstract

Background and Aims
Understanding the factors influencing vaping cessation among young people is crucial for targeted interventions. This review aimed to summarize the individual and environmental factors that predict vaping cessation-related behaviors in the young population.

Methods
We systematically searched five databases for studies investigating predictors of vaping cessation behaviors among young people aged 10–35 years. Studies that examined predictors of cessation of cigarettes, other tobacco products, cannabis vaping, and studies evaluating efficacy of cessation interventions were excluded. Quality in Prognosis Studies tool was used to assess risk of bias.

Results
We found 24 studies analyzing predictors of intention to quit vaping (n = 15), quit attempts (n = 11), and vaping abstinence (n = 7). Most studies had low risk of bias, except for study attrition. We identified 107 predictors and grouped them into “probable,” “possible,” “insufficient evidence,” “probably unrelated,” and “inconsistent direction” categories. For “probable” predictors, we found 11 for intention to quit, eight for quit attempts and five for vaping abstinence. Overall, harm perception of vaping, current other tobacco products use, frequency of use, and level of nicotine dependence were common “probable” predictors across three outcomes, with low harm perception of vaping, dual use, and poly tobacco use associated with decreased intention to quit and quit attempts in younger population (~10–19 years).

Conclusions
Predictive modeling studies investigating vaping cessation-related behaviors among young people are still limited. Future research should specifically study the natural history of vaping in youth in different jurisdictions, populations, and age groups to expand our knowledge in this area.

Implications
We identified and categorized predictors of intention to quit vaping, quit attempts, and vaping abstinence among young people. While the “probable” predictors can inform public health and policymakers to plan targeted vaping cessation programs for high-risk populations, raising public harm perception of vaping and encouraging to quit other tobacco products might increase intention to quit and quit attempts among younger population. However, the “possible,” “insufficient evidence” and “inconsistent direction” predictors need further testing by future prospective longitudinal research. Additionally, we emphasized the significance of appropriate study designs, conducting research across various jurisdictions, and different population groups to obtain comprehensive insights.
Molecular Epidemiology of Isoniazid-resistant M tuberculosis in Port-au-Prince, Haiti
Authors: Walsh Kathleen F , Lee Myung Hee , Chaguza Chrispin , Pamphile Widman , Royal Gertrude , Escuyer Vincent , Pape Jean W , Fitzgerald Daniel , Cohen Ted , Ocheretina Oksana 
Published: July 2024

Abstract

Background
Isoniazid-resistant, rifampin-susceptible tuberculosis (Hr-TB) is associated with poor treatment outcomes and higher rates of acquisition of further drug resistance during treatment. Due to a lack of widespread diagnostics, Hr-TB is frequently undetected and its epidemiology is incompletely understood.

Methods
We studied the molecular epidemiology of Hr-TB among all patients diagnosed with culture-positive pulmonary tuberculosis between January 1 and June 30, 2017, at an urban referral tuberculosis clinic in Port-au-Prince, Haiti. Demographic and clinical data were extracted from the electronic medical record. Archived diagnostic Mycobacterium tuberculosis isolates were tested for genotypic and phenotypic isoniazid resistance using the Genotype MTBDRplus assay (Hain, Nehren, Germany) and culture-based testing, respectively. All isoniazid-resistant isolates and a randomly selected subset of isoniazid-susceptible isolates underwent whole-genome sequencing to confirm the presence of mutations associated with isoniazid resistance, to validate use of Genotype MTBDRplus in this population, and to identify potential transmission links between isoniazid-resistant isolates.

Results and Conclusions
Among 845 patients with culture-positive pulmonary tuberculosis in Haiti, 65 (7.7%) had Hr-TB based on the Genotype MTBDRplus molecular assay. Age &lt; 20 years was significantly associated with Hr-TB (odds ratio, 2.39; 95% confidence interval, 1.14, 4.70; P = .015). Thirteen (20%) isoniazid-resistant isolates were found in 5 putative transmission clusters based on a single nucleotide polymorphism distance of ≤ 5. No patients in these transmission clusters were members of the same household. Adolescents are at higher risk for Hr-TB. Strains of isoniazid-resistant M tuberculosis are actively circulating in Haiti and transmission is likely occurring in community settings.
Ecology, Jurisprudence, and Private International Law
Authors: Vilaça Guilherme Vasconcelos 
Published: July 2024

Abstract
In her new book, The Law’s Ultimate Frontier: Towards an Ecological Jurisprudence—A Global Horizon in Private International Law, Horatia Muir Watt proclaims a new vision of legality: an ecological jurisprudence. Its originality lies in the role played by private international law as a tool for legal and political imagination in the Anthropocene. I first present carefully the whole argument as Muir Watt offers it. Then I turn to a critical examination of the work and show how the book fits a much broader intellectual landscape that aims to do justice to the natural and cultural ‘Other’ and how, despite all its sophistication and erudition, the Levinasian grounds, conflict of law’s genealogy, planetary ontology and amateur bricolage she builds upon to establish a novel jurisprudence raise as many complications as achievements. Ultimately, and as a general lesson for holistic and multidisciplinary theorising about law, this article identifies some crucial choices any future model of legality combining both a theory of justice and a vision of law as a linking device needs to overcome in order to ensure we can deal simultaneously with the divergent local and planetary dimensions summoned by the threat of extinction without hastily replacing morality for law and politics.
America First
Authors: Ostovar Afshon 
Published: July 2024

Abstract
This chapter examines how the foreign policy inclinations of Donald Trump reshaped U.S. involvement in the Middle East. Turkey, Saudi Arabia, and the UAE grew more ambitious and assertive as they faced less pushback from Washington, further stoking competition in the region’s conflicts. Turkey’s anger regarding U.S. support to Kurds in Syria, and Iran’s backing of Shia militias against ISIS in Iraq, drove Ankara to be more assertive in both countries. With the liberation of Mosul and Raqqa, ISIS had been territorially defeated. But Turkey’s fears of Kurdish empowerment provoked a showdown with Washington. Trump’s disinterest in the Syrian war caused him to submit to Erdoğan’s demands for the withdrawal of U.S. forces. Despite attempts from his administration to preserve the U.S. force presence, Trump ordered a withdrawal. Turkey’s corresponding military occupation of northern Syria followed, which triggered a crisis in U.S.-Turkish relations.
Evolutionary Medicine
Authors: Stearns Stephen C. , Medzhitov Ruslan 
Published: July 2024

Abstract
Evolutionary medicine covers all areas of medical research and practice in which evolutionary insights provide added value. Core concepts include mismatch, trade-offs, and the systems perspective. Important insights include the nature of sick persons and of diseases. Major themes are the evolution of aging; pathogen emergence and evolution, including resistance and virulence; the roles of the microbiota in health and disease; cancer, both the evolutionary history that makes us vulnerable to it and the independent evolution of every cancer; the evolution of reproduction, including placental invasion and the risk of metastasis; quality control of gametes and zygotes, childbirth, menstruation, and menopause; evolutionary hypotheses for mental disorders; and applications in the clinic and in public health, including phage therapy, adaptive therapy for solid tumours, and evolutionary aspects of vaccine development and use.
Defenses
Authors: Stearns Stephen C. , Medzhitov Ruslan 
Published: July 2024

Abstract
This chapter is focused on defence mechanisms and their contributions to health and disease. Defences evolve in response to common negative environmental factors that can impact on organismal fitness and survival. Common negative environmental factors include infections, predation, toxins, cold, starvation, and dehydration. Specialized defenses evolved to protect from each of these factors. In some cases, defenses are elaborated into functional systems, notably, the immune system. Most defenses evolved as elaborations of different homeostatic mechanisms that are threatened by the environmental stressors. The degree of elaboration varies between species, depending on the extent and severity of an environmental stressor in species ecology. All defenses operate at a cost to other physiological functions, as they have higher biological priority of ensuring survival in the face of environmental insult. Consequently, many disease symptoms are due to expression of defenses. Either insufficient or excessive defenses can result in diseases driven, respectively, by the cost of defense, or by inadequate protection from the environmental insult.
Applying evolutionary thinking to public health
Authors: Stearns Stephen C. , Medzhitov Ruslan 
Published: July 2024

Abstract
This chapter applies evolutionary thinking to issues in public health. It first discusses the conflicts between individual and societal interests, the socio-economic determinants of health, and the global burden of disease. Phenotypic responses to mismatch help to explain metabolic diseases. Important population consequences of individual decisions include the herd immunity produced by vaccination and its breakdown when too few people get vaccinated and the evolution of antibiotic resistance through the accumulation of many decisions to treat individuals. Emerging diseases are public health problems increasingly affected by population growth and global change. Vaccination is a key option for controlling them. We discuss vaccine development and application for influenza, Ebola, Covid-19, and HIV/AIDS.
Relationships
Authors: Ganz Marshall 
Published: July 2024

Abstract
In this chapter the author focuses on the foundational importance of relationships, highlighting why civic relationships are the threads with which robust democracy is woven. According to Tocqueville, civic relationships or associations are important because they facilitate learning, solidarity, and self-governance. Civic relationships are based on a commitment to shared purpose or values as the moral foundation of a political community. The author then discusses how leaders practice relationship-building in any given campaign depending on overall campaign strategy. The author then shows how organizers can create collective capacity through the purposeful formation of civic relationships that can enable democracy to work.
Conclusion
Authors: Ganz Marshall 
Published: July 2024

Abstract
This conclusive chapter reflects on the interplay of leadership, organizing, and action in practicing democracy. The five core practices of building relationships, storytelling, strategizing, acting, and structuring are based on the belief that all people can learn, grow, and shape their destiny in concert with others. The chapter then features how the global financial crisis of 2008 and the COVID-19 crisis negatively affected people, which further highlighted the divide between those in power and privilege and those who are not. In the United States, real challenges to the status quo have often come in the form of social movements. The chapter then elaborates on the work and purpose of movements.
Dreaming the New Woman
Authors: Bond Jennifer 
Published: July 2024

Abstract
Dreaming the New Woman uncovers the voices of Chinese women who attended Protestant missionary schools for girls in the early twentieth century. It is an oral history based on seventy-five interviews with alumnae from five girls’ middle schools across East China, including McTyeire and St. Mary’s in Shanghai, Riverside Academy in Ningbo, Hangzhou Union Girls’ School in Hangzhou, and the Laura Haygood School in Suzhou. In the past, missionary schoolgirls have been labeled “foreign puppets” or have been seen as “passive recipients” of a Western-style education. This book puts at the center of the analysis pupils’ own understanding of what it meant to be female, Chinese, and possibly Christian during the wars and revolutions of the first half of China’s turbulent twentieth century. By focusing on the experiences of women who attended these schools, the book provides fresh perspectives on the role of Christianity in the emergence of the Chinese New Woman. It explores how students experimented with new roles as they tried on overlapping school, Christian, patriotic, gendered, and Communist identities. In the process they envisioned a new form of gendered Christian modernity which became a part of an elite identity for Chinese women in the Republican era.
Engaging in YPAR With Early Elementary School Students
Authors: Morizio Laura J. 
Published: July 2024

Abstract
Through participation in youth participatory action research (YPAR), young children can exercise their right to make positive changes within their communities. The physical spaces that are shared throughout the YPAR process can provide children with a safe environment within which they can explore and process feelings around complex social issues affecting them. One promising avenue through which to engage early elementary students in YPAR is through the use of expressive methods that can take the shape of various forms of creative expression, including but not limited to art, music, drama, dance, writing, storytelling, and shared reading. The use of expressive methods within a YPAR framework can help center young students’ voices as they communicate personal beliefs and explore ideas for collective community growth and development. This chapter provides an example case applying expressive methods using arts and shared reading in YPAR, illustrating the use of multiple techniques to create an accessible environment for participants.
Brewers and brewing spaces
Authors: Paulette Tate 
Published: July 2024

AbstractThe chapter “Brewers and Brewing Spaces” introduces the brewers of ancient Mesopotamia and the spaces where they brewed their beer. It begins with a visit to two breweries excavated in the ancient cities of Girsu and Lagash. The chapter then explores three brewing locales: brewery, tavern, and home. The discussion of breweries begins with the written evidence for brewers and breweries, before turning to the archaeological remains of several possible breweries uncovered. The discussion of taverns begins with the archaeological evidence for taverns and then returns to the Epic of Gilgamesh and Shiduri, tavern keeper at the edge of the world. A look at naditu priestesses and the tavern business then leads into a broader consideration of the written evidence for tavern keepers. The discussion of homebrewing begins with a series of letters that reference brewing in the home and then turns to the archaeological evidence for homebrewing.
Lobbying for the Priesthood, 1970–1973
Authors: Harris Matthew L. 
Published: July 2024

Abstract
This chapter looks at two athletic protests—by Colorado State University and the University of Washington—which forced the church to wage an aggressive public relations campaign to defend Mormon racial teachings. This chapter also addresses how Black Latter-day Saints pressed church leaders to grant Black men the priesthood and Black families access to Mormon temples. In response, the First Presidency appointed three apostles—Gordon B. Hinckley, Thomas S. Monson, and Boyd K. Packer—to meet with Black Latter-day Saints Ruffin Bridgeforth, Darius Gray, and Eugene Orr, who demanded the priesthood. The church didn’t give in to their demands, but the leadership allowed Black Latter-day Saints to form a support group called Genesis so they could hold their own monthly worship services under the guidance of White priesthood holders.
The Maṟavaṉīśvaragṛhattu Mahādeva of Ciṟupaḻuvūr
Authors: Gillet Valérie 
Published: July 2024

Abstract
The construction by the Paḻuvēṭṭaraiyars of a small shrine next to the Tiruvālantuṟai Mahādeva, the Maṟavaṉīśvara, constitutes the subject of the fifth and last chapter. Constructed by at least the early 10th century, the Maṟavaṉīśvara was almost abandoned until recently. The inscriptions from the first half of the 10th century engraved on its walls record donations made to the nearby Tiruvālantuṟai Mahādeva, indicating the intrinsic relation between these two temples at that time. It is only by the second half of the 10th century, when the Tiruvālantuṟai Mahādeva was reconstructed in stone and donations were engraved on its walls, that gifts were made to the Maṟavaṉīśvara only. This did not last long, though. By the end of the 10th century, donations were no longer inscribed on the walls of the short-lived Maṟavaṉīśvara temple.