bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gender and personalized medicine
Authors: Legato Marianne J. 
Published: April 2022

Abstract
Almost immediately after the announcement that the human genome had been decoded, those of us working to delineate the impact of biological sex on physiology and the experience of disease were asked repeatedly why the sex of the patient mattered if we were able to characterize an individual’s genome. This was a question based on the traditional and simplistic assumption that gene = function. In fact, as genomic research progressed, it quickly became evident that the phenotype depends not only on the DNA alphabet, but also on how gene activity is regulated by sexually dimorphic epigenetic modifications. Thus, it is clear that personalized medicine does not make biological sex irrelevant, but reflects and reinforces its essential role in shaping individual physiology. In defining the moral and ethical responsibilities of the physician/scientist, this is a crucially important concept. When we identify genomic elements which are demonstrably sex-specific, fashioning gender-specific therapy will inevitably follow. It is equally important for those involved in changing genomic structure/function to be cognizant of the fact that their intervention might have significantly different consequences depending on the sex of the subject. Reports of such interventions rarely if ever comment on this consideration.
Potential challenges to doctor–patient trust posed by personalized medicine
Authors: Cohen Shlomo 
Published: April 2022

Abstract
To maximize the great expected benefits of personalized medicine, we need to be vigilant about its potential drawbacks. One relevant dimension in this respect, which has not received attention in the literature, involves the doctor–patient relationship. Specifically, this chapter examines potential challenges to the relationship of trust between doctor and patient that a thoroughgoing reality of personalized medicine may bring about. Four aspects of clinical trust are examined and analysed: (i) patient trust in the doctor’s wisdom; (ii) trust as a function of a good rapport between doctor and patient; (iii) trust related to confidentiality; and (iv) trust that the patient’s wellbeing is the doctor’s highest priority.
CRISPR—a challenge for national and international regulation
Authors: Nicol Dianne 
Published: April 2022

Abstract
The law and other forms of regulation are important tools in ensuring that the benefits of precision medicines are enjoyed by all society, and that scientific risks and ethical and social concerns associated with these new forms of medicine are appropriately addressed. Though the law appears at times monolithic, it is not permanently set in stone. Nor should it be seen as a single homogeneous mass; rather, there are many diverse components—a ‘regulatory soup’. In the context of innovative health technologies, each new advance is likely to be accompanied by new ethical and social debates, demanding appropriate regulatory responses. This chapter canvasses these issues through the lens of genome editing, which is destined to be the most personalized and precise form of modern medicine. It offers much hope in the treatment of disease, but opens the door to modifications of the human genome that can be passed on to future generations. Currently the law relating to these matters ranges from outright prohibition to less restrictive approaches. There are calls for better and more coordinated regulatory responses, including by leading proponents of the science of genome editing, but finding a global solution is not easy. In the meantime, the regulatory challenges associated with bringing somatic cell genome editing into mainstream clinical practice need more attention. In particular, there needs to be greater focus on the role of law in ensuring distributive justice.
The advent of automated medicine? The values and meanings of precision
Authors: Prainsack Barbara 
Published: April 2022

Abstract
Current visions of precision medicine are contributing to an increasing polarization within healthcare: boutique-style personalized medicine could be available for the select few who can afford to pay for the interpretation of their health data by humans, while the rest of the population will be expected to resort to automated medicine for most of their health concerns. This scenario should be avoided. Expanding the goals of precision medicine to include ‘subjective’ personal outcomes as well as social outcomes that are measured and (also financially) rewarded alongside clinical outcomes would be a step in this process. At the same time, the realization of just access to healthcare, and the improvement of social determinants, is a necessary precondition for precision medicine to benefit societies.
Getting Started on Time-Resolved Molecular Spectroscopy
Authors: Cina Jeffrey A. 
Published: April 2022

Abstract
This textbook details the basic theory of ultrafast molecular spectroscopy starting from time-dependent quantum mechanical perturbation theory in Hilbert space. The emphasis is on the dynamics of nuclear and electronic motion initiated and monitored by femtosecond laser pulses that underlies nonlinear optical signal formation and interpretation. Topics include short-pulse optical absorption, the molecular adiabatic approximation, transient-absorption spectroscopy, vibrational adiabaticity during conformational change, femtosecond stimulated Raman spectroscopy, multi-dimensional electronic spectroscopy and wave-packet interferometry, and two-dimensional wave-packet interferometry of electronic excitation-transfer systems. Numerous exercises embedded in the text explore and expand upon the physical concepts encountered in this important research field.
Generation of Continental Alkalic Mafic Melts by Tholeiitic Melt–Mush Reactions: a New Perspective from Contrasting Mafic Cumulates and Dikes in Central Tibet
Authors: Wang Jun , Wang Qiang , Zeng Ji-Peng , Ou Quan , Dan Wei , Yang Alexandra Yang , Chen Yi-Wei , Wei Gangjian 
Published: April 2022

Abstract
Alkalic basalts from continental regions have been widely used to fingerprint chemically and lithologically distinct components in the mantle. However, superimposed on mantle source effects are the effects of intra-crustal magma differentiation, which may be underestimated when exclusively considering fractional crystallization (FC) in melt-rich magma chambers. Here we present extensive mineralogical and geochemical data for mafic cumulates and dolerite dikes from central Tibet to demonstrate that tholeiitic magma differentiation occurred in crystal-rich mushes and melt-filled fractures. The mafic cumulates provide a snapshot of the percolation of water-poor (&lt;0.9 wt% H2O), oxide-undersaturated, tholeiitic melts through slightly hotter mushes (50–60% crystals) with a framework of primitive olivine ± plagioclase crystals. The highly corroded olivines indicate that thermo-chemical disequilibrium between the later percolating melts and pre-existing crystal framework triggered melt–mush reactions in an open system. High-temperature (&gt;1060°C) reactions were accompanied by a decreasing melt mass, causing the initial tholeiitic melts to evolve into alkalic mafic melts during slow cooling. This process involved the dissolution and reprecipitation of olivine, plagioclase, and clinopyroxene as well as the late crystallization of high-TiO2 (up to 3.4 wt%) clinopyroxene and kaersutite. In contrast, the same tholeiitic magmas (i.e. dolerite dikes) that intruded the cold country rocks along fractures produced silica-rich residual melts saturated in Fe–Ti oxides and sodic plagioclase by FC during rapid cooling. The residual melt was always in equilibrium with the instantaneous crystal during closed-system FC, so there was no reaction between the interstitial melt and adjacent crystal even after a high degree of crystallization. Alkalic mafic melts that can be formed by melt–mush reactions exhibit strong enrichment of incompatible element contents (e.g. Ti and alkali and rare earth elements) and ratios (e.g. Ce/Y), but little Si enrichment and Mg depletion, compared with the parental tholeiitic magma, which cannot be reproduced by simple FC. We argue that tholeiitic melt–mush reactions at mid- to lower-crustal pressures (≥0.5 GPa) are a new mechanism for the generation of interstitial alkalic mafic melts in continental mush reservoirs. Continental alkalic basalts could be produced by this mechanism if such interstitial melts were concentrated into melt lenses by compaction and then transported rapidly upward to the surface by focused flow.
Race, Crime, and the Public’s Sentencing Preferences
Authors: Doherty David , Dowling Conor M , Miller Michael G , Tuma Michelle D 
Published: April 2022

Abstract
We report findings from a conjoint experiment where respondents indicated what they viewed as an appropriate sentence for a series of hypothetical individuals convicted of federal crimes. The experiment signaled the race of the defendant by using distinctively “Black” and “white” names, allowing us to assess whether Americans are more punitive toward purportedly Black defendants. We also consider whether signals of the defendant’s race condition the effects of the crime and various defendant characteristics. Surprisingly, the direct effect of our signal of defendants’ purported race is null. We present evidence that this null finding is a product of offsetting tendencies: respondents who view persistent racial inequalities as the product of both past and ongoing institutional factors prescribed lengthier sentences for white defendants; those who discount these explanations prescribed lengthier sentences for Black defendants.1 We find only scattered evidence that the signal of defendants’ race moderates the effects of other characteristics of the crime and defendant. Our approach and findings not only offer insights into how racial attitudes shape perceptions regarding what constitutes just punishment for crimes in the contemporary United States, but also demonstrate a novel approach to studying this domain and point to an array of promising avenues for future research.
Surface carboxylation of iron oxide nanoparticles brings reduced macrophage inflammatory response through inhibiting macrophage autophagy
Authors: Deng Di , Fu Shengxiang , Cai Zhongyuan , Fu Xiaomin , Jin Rongrong , Ai Hua 
Published: April 2022

Abstract
Macrophage autophagy is a common biological response triggered by nanomaterials, which is closely related to the regulation of inflammation. Superparamagnetic iron oxide (SPIO) nanoparticles have been used for study of autophagy response due to their broad biomedical applications. However, few reports have focused on how to regulate the macrophage autophagy response induced by SPIO nanoparticles. In this study, SPIO nanoparticles grafted with carboxyl groups were synthesized and for the comparison of macrophage autophagy with unmodified nanoparticles. The study on the correlation between autophagy and inflammation induced by the two kinds of SPIO nanoparticles was also included, and the one that grafted with carboxyl groups shows a reduction of autophagy and thereby caused a milder inflammatory response. We proposed that the increased amount of albumin adsorption on the surface of carboxylated SPIO nanoparticles, a protein previously proven to attenuate autophagy, can be considered an important reason for reducing autophagy and inflammation. In general, the carboxyl modification of SPIO nanoparticles has been demonstrated to reduce inflammation by inhibiting macrophage autophagy, which may provide some insights for the design of nanomaterials in the future.
Constructing a highly bioactive tendon-regenerative scaffold by surface modification of tissue-specific stem cell-derived extracellular matrix
Authors: Ning Liang-Ju , Cui Jing , He Shu-Kun , Hu Ruo-Nan , Yao Xuan , Zhang Yi , Ding Wei , Zhang Yan-Jing , Luo Jing-Cong , Qin Ting-Wu 
Published: April 2022

Abstract
Developing highly bioactive scaffold materials to promote stem cell migration, proliferation and tissue-specific differentiation is a crucial requirement in current tissue engineering and regenerative medicine. Our previous work has demonstrated that the decellularized tendon slices (DTSs) are able to promote stem cell proliferation and tenogenic differentiation in vitro and show certain pro-regenerative capacity for rotator cuff tendon regeneration in vivo. In this study, we present a strategy to further improve the bioactivity of the DTSs for constructing a novel highly bioactive tendon-regenerative scaffold by surface modification of tendon-specific stem cell-derived extracellular matrix (tECM), which is expected to greatly enhance the capacity of scaffold material in regulating stem cell behavior, including migration, proliferation and tenogenic differentiation. We prove that the modification of tECM could change the highly aligned surface topographical cues of the DTSs, retain the surface stiffness of the DTSs and significantly increase the content of multiple ECM components in the tECM-DTSs. As a result, the tECM-DTSs dramatically enhance the migration, proliferation as well as tenogenic differentiation of rat bone marrow-derived stem cells compared with the DTSs. Collectively, this strategy would provide a new way for constructing ECM-based biomaterials with enhanced bioactivity for in situ tendon regeneration applications.
The cortical and subcortical correlates of face pareidolia in the macaque brain
Authors: Taubert Jessica , Wardle Susan G , Tardiff Clarissa T , Koele Elissa A , Kumar Susheel , Messinger Adam , Ungerleider Leslie G 
Published: April 2022

Abstract
Face detection is a foundational social skill for primates. This vital function is thought to be supported by specialized neural mechanisms; however, although several face-selective regions have been identified in both humans and nonhuman primates, there is no consensus about which region(s) are involved in face detection. Here, we used naturally occurring errors of face detection (i.e. objects with illusory facial features referred to as examples of ‘face pareidolia’) to identify regions of the macaque brain implicated in face detection. Using whole-brain functional magnetic resonance imaging to test awake rhesus macaques, we discovered that a subset of face-selective patches in the inferior temporal cortex, on the lower lateral edge of the superior temporal sulcus, and the amygdala respond more to objects with illusory facial features than matched non-face objects. Multivariate analyses of the data revealed differences in the representation of illusory faces across the functionally defined regions of interest. These differences suggest that the cortical and subcortical face-selective regions contribute uniquely to the detection of facial features. We conclude that face detection is supported by a multiplexed system in the primate brain.
Chancellors as civil lawyers—and the equitable notion of “fraud”
Authors: Lupoi Maurizio 
Published: April 2022

Abstract
Professor Lupoi traces equity’s origins back to Rome’s ius commune. He explains that Chancellors were doctors in civil law. Until Henry VIII’s breach with Rome, Chancellors were also Bishops. Their cultural and spiritual anchors were very distinct from those dispensing justice in common law courts. In the course of the fourteenth century common law courts surrendered their discretionary powers and disavowed any reliance on conscience and opted for rigor juris. Equitable doctrines, enacted by Chancellors and Masters who knew only Roman and canon law, prevented unconscientious exercise of a plaintiff’s rights at law. Professor Lupoi explains the similarity between “fraus” in Roman law and “fraud” in English equity and that whilst France, Germany and other countries of continental Europe squandered the Roman law inheritance, English equity holds the torch for Roman principles.
Transcriptome and metabolome changes in Chinese cedar during cold acclimation reveal the roles of flavonoids in needle discoloration and cold resistance
Authors: Zhang Yingting , Yang Liwei , Hu Hailiang , Yang Junjie , Cui Jiebing , Wei Guangqian , Xu Jin 
Published: April 2022

Abstract
Cryptomeria fortunei growth and development are usually affected by low temperatures. Despite the evergreen nature of this species, most needles turn yellowish-brown in cold winters. The underlying discoloration mechanisms that cause this phenomenon in response to cold acclimation remain poorly understood. Here, we measured the pigment content and ultrastructure of normal wild-type (Wt) and evergreen mutant (GM) C. fortunei needles and performed integrated transcriptomic and metabolomic analyses to explore potential discoloration mechanisms. The results showed that the needle chlorophyll content of these two genotypes decreased in winter. Wt needles showed greater decrease in the chlorophyll content and local destruction of chloroplast ultrastructure and contained larger amounts of flavonoids than GM needles, as shown by metabolomics analysis. We subsequently identified key differentially expressed genes in the flavonoid biosynthesis pathway and observed significantly upregulated flavonol synthase expression in Wt needles compared with GM needles that significantly increased the anthoxanthin (flavones and flavonols) content, which is likely a key factor underlying the difference in needle color between these two genotypes. Therefore, flavonoid metabolism may play important roles in the cold resistance and needle discoloration of C. fortunei, and our results provide an excellent foundation for the molecular mechanism of C. fortunei in response to cold stress.
Predictors of Adjustment to Living with an Ostomy: Results of a Cross-sectional Study
Authors: Dellafiore Federica , Manara Duilio F. , Arrigoni Cristina , Baroni Irene , Di Pasquale Cristina , Nania Tiziana , Caruso Rosario , Villa Giulia 
Published: April 2022

ABSTRACT

Objective
To describe predictors of adjustment to living with an ostomy among Italian adults with an enterostomy or a colostomy.

Methods
A multicenter, cross-sectional design was performed, sampling 403 patients with an ostomy in three different outpatient clinics of northern Italy between April 2018 and December 2020. Data were collected by stoma therapists in ambulatory settings using the Italian version of the Ostomy Adjustment Inventory-23 and patient medical records.

Results
Acceptance was lower among women, patients who underwent emergency surgery, those with a urostomy, and those with a body mass index of less than or equal to 25 kg/m2. Negative feelings were associated with higher body mass index, colostomies, shorter length of time of living with an ostomy, and emergency ostomy creation.

Conclusions
Being young and having a high level of education are protective against psychosocial problems and help promote acceptance and social engagement. The findings of this study help identify patients who are likely to be more vulnerable and need greater support through specific educational and motivational interventions.
Social Support, Social Isolation, and Burnout: Cross-Sectional Study of U.S. Residents Exploring Associations With Individual, Interpersonal, Program, and Work-Related Factors
Authors: Leep Hunderfund Andrea N. , West Colin P. , Rackley Sandra J. , Dozois Eric J. , Moeschler Susan M. , Vaa Stelling Brianna E. , Winters Richard C. , Satele Daniel V. , Dyrbye Liselotte N. 
Published: April 2022

Purpose
To examine associations of social support and social isolation with burnout, program satisfaction, and organization satisfaction among a large population of U.S. residents and fellows and to identify correlates of social support and social isolation.

Method
All residents and fellows enrolled in graduate medical education programs at Mayo Clinic sites were surveyed in February 2019. Survey items measured social support (emotional and tangible), social isolation, burnout, program satisfaction, and organization satisfaction. Factors of potential relevance to social support were collected (via the survey, institutional administrative records, and interviews with program coordinators and/or program directors) and categorized as individual, interpersonal, program, or work-related factors (duty hours, call burden, elective time, vacation days used before survey administration, required away rotations, etc.). Multivariable regression analyses were conducted to examine relationships between variables.

Results
Of 1,146 residents surveyed, 762 (66%) from 58 programs responded. In adjusted models, higher emotional and tangible support were associated with lower odds of burnout and higher odds of program and organization satisfaction, while higher social isolation scores were associated with higher odds of burnout and lower odds of program satisfaction and organization satisfaction. Independent predictors of social support and/or social isolation included age, gender, relationship status, parental status, postgraduate year, site, ratings of the program leadership team, ratings of faculty relationships and faculty professional behaviors, satisfaction with autonomy, and vacation days used before survey administration.

Conclusions
This study demonstrates that social support and social isolation are strongly related to burnout and satisfaction among residents and fellows. Personal and professional relationships, satisfaction with autonomy, and vacation days are independently associated with social support and/or social isolation, whereas most program and work-related factors are not. Additional studies are needed to determine if social support interventions targeting these factors can improve well-being and enhance satisfaction with training.
Tendon Healing in a Mouse Model of Loeys-Dietz Syndrome: Controlled Study Using a Patellar Tendon Transection Model
Authors: Cottrill Ethan J. , Bowen Caitlin J. , Pennington Zach A. , Murray Jason A. , Rajkovic Christian J. , Dietz Harry C. , Sponseller Paul D. 
Published: April 2022

Background:
Loeys-Dietz syndrome (LDS) is a rare autosomal-dominant connective tissue disorder caused by genetic mutations in the transforming growth factor-β (TGFβ) signaling pathway. In addition to vascular malformations, patients with LDS commonly present with bone and tendon abnormalities, including joint laxity. While TGFβ signaling dysregulation has been implicated in many of these clinical manifestations, the degree to which it influences the tendinopathy and tendon healing issues in LDS has not been determined.

Methods:
Wound healing after patellar tendon transection was compared between wild-type (WT) and Tgfbr2-mutant (LDS) mice (7 mice per group). In all mice, the right patellar tendon was transected at midsubstance, while the left was untouched to serve as a control. Mice were euthanized 6 weeks after surgery. Tendon specimens were harvested for histopathologic grading according to a previously validated scoring metric, and gene expression levels of Mmp2, Tgfb2, and other TGFβ-signaling genes were assayed. Between-group comparisons were made using 1-way analysis of variance with post hoc Tukey honestly significant difference testing.

Results:
Expression levels of assayed genes were similar between LDS and WT tendons at baseline; however, at 6 weeks after patellar tendon transection, LDS tendons showed sustained elevations in Mmp2 and Tgfb2 compared with baseline values; these elevations were not seen in normal tendons undergoing the same treatments. Histologically, untreated LDS tendons had significantly greater cellularity and cell rounding compared with untreated WT tendons, and both WT and LDS tendons had significantly worse histologic scores after surgery.

Conclusion:
We present the first mechanistic insight into the effect of LDS on tendons and tendon healing. The morphologic differences between LDS and WT tendons at baseline may help explain the increased risk of tendon/ligament dysfunction in patients with LDS, and the differential healing response to injury in LDS may account for the delayed healing and weaker repair tissue.

Level of Evidence:
Level V.