bluuebunny/crossref_metadata_2025 huggingface dataset:
Jacobite Sentiment in Eighteenth-Century Irish Poetry, in Word and in Song
Authors: Nic Éinrí Úna , Ó Cearbhaill Pádraig
Published: September 2022

This chapter examines and illustrates eighteenth-century Irish Jacobite poetry and song against the British and European historical background of the time. Several of the relevant tunes, encompassing both traditional and borrowed material, are examined. Beginning with the defeat of King James II’s army in Ireland, some texts allude to European wars and battles and other historic events in the context of the hoped-for return of the ‘rightful king’ while others are less specific in detail. Certain tunes which were used to create a series of literary songs by poets in response to one another’s compositions have been looked at. In addition to manuscript titles, various sources of tunes for texts—such as internal textual evidence—are elucidated. Special emphasis is placed on eighteenth-century Munster poets and poetry, including compositions of the aisling genre in which an allegorical woman, who is the embodiment of Ireland, conveys a Jacobite message, usually one of hope or defiance. Special consideration is given to songs in which the otherworldly woman is given a vernacular personal name (and often a surname), such as ‘Caitlín Ní Uallacháin’. Finally, the overall value of the material, both textual and musical, is contextualized and affirmed.
Indigenizing the Sociology of Class
Authors: Walter Maggie
Published: September 2022

The concept of social class (class) is intricately entwined into the discipline of sociology. Both the discipline and societal concern with class emerged from disruption of the Industrial, American, and French Revolutions in the 18th and 19th centuries. All noted sociological scholars since those times have addressed class as a core aspect of their work. Yet the literature on the class position of Indigenous Peoples is scant to the point of nonexistence. This chapter examines the place and conceptualizations of class as understood within the Western sociological literature. These conceptualizations are then interrogated on their applicability and their usefulness for Indigenous Peoples living in Anglo-colonized nation-states. The concept of class is then re-envisioned through the theoretical lens of the Indigenous lifeworld. The chapter concludes that the Indigenous class position cannot be understood unless it is placed and analyzed within its present and past social-structural context of colonization.
Strange Encounters?
Authors: Ruffa Chiara , Tulp Chiara
Published: September 2022

Jane Addams is increasingly recognized as a founding figure of the social sciences. This chapter focuses specifically on the legacy of Jane Addams for researchers who engage with fieldwork in its different forms. The modern fieldworker—a researcher who immerses her-/him-/themselves in a research site to observe, deeply understand, and analyze a topic of interest—has to navigate several tensions, ranging from positionality to research ethics and security in the field. Addams was confronted with and had to negotiate similar dilemmas as researcher and social worker in Chicago’s Hull House settlement, as well as throughout her pacifist work during World War I. This chapter identifies and elaborates on six key lessons that Jane Addams’s work and legacy provide to the modern field researcher
Introduction
Authors: Meissner Fran , Sigona Nando , Vertovec Steven
Published: September 2022

Old immigration hubs and new ones worldwide have experienced rapid and increasing movements of people from more varied national, ethnic, linguistic, and religious backgrounds. These movements have emerged along with a diversification of migration channels and migrant legal statuses. Migration-driven trends are profoundly transforming societies’ social, demographic, cultural, economic, and political structures in concurrent but differing ways. Across a range of disciplines and bodies of literature, these complex processes and patterns of social transformation are summarized in the concept of superdiversity. This introduction explores the notion of complex social transformation and its links to researching superdiversity. It also explains the organization of the handbook and briefly introduces the chapters.
Behaviorally Informed Economic and Social Rights
Authors: Gauri Varun
Published: September 2022

Economic and social rights are incorporated into many national constitutions, and courts in many countries are effectively and legitimately enforcing them. However, the large majority of rights rulings addresses the cost of goods and services and focuses exclusively on access. There is now strong evidence that internal, psychological factors limit the enjoyment of economic and social rights, and that behaviorally informed policies can increase welfare and support rights fulfillment. These facts suggest there may exist a duty to use behavioral insights in the provision of social and economic goods and services. The evidence suggests that shifting choice architecture in a manner that moves the burden of proof to powerful actors, simplifying procedures for program eligibility and sign-up, establishing agencies to balance private advertising, promoting medications adherence, changing student beliefs about learning, providing opt-out savings programs, and using behaviorally informed regulation are particularly promising.
Health Promotion and Weight Management for Obesity
Authors: Lillis Jason , Lee-Baggley Dayna
Published: September 2022

Obesity is prevalent and carries substantial individual and societal-level consequences, including increased mortality and high health care costs. Obesity is best viewed as a chronic disease that requires both individual and system-level interventions that take into account a multitude of contributing factors. Acceptance and commitment therapy (ACT) principles and strategies can play a role in the treatment of individuals with obesity primarily by addressing barriers to healthy behavior change by teaching values, acceptance, defusion, and mindfulness skills. Interventions incorporating these ACT methods have shown improved obesity management outcomes relative to current gold standard behavioral treatments, and ACT can be considered evidence for use in this area. However, behavioral treatments in general are limited in terms of reach and effectiveness, and system- and environmental-level interventions will be required to meaningfully address obesity worldwide. Future research on ACT and other contextual therapeutic approaches should focus on addressing these system-level factors in order to support already well-developed individual-level interventions.
The Role of Workers in AI Ethics and Governance
Authors: Nedzhvetskaya Nataliya , Tan J. S.
Published: September 2022

While the role of states, corporations, and international organizations in AI governance has been extensively theorized, the role of workers has received comparatively little attention. This chapter looks at the role that workers play in identifying and mitigating harms from AI technologies. Harms are the causally assessed “impacts” of technologies. They arise despite technical reliability and are not a result of technical negligence but rather of normative uncertainty around questions of safety and fairness in complex social systems. There is high consensus in the AI ethics community on the benefits of reducing harms but less consensus on mechanisms for determining or addressing harms. This lack of consensus has led to numerous collective actions by workers protesting how harms are identified and addressed in their workplace. This chapter theorizes the role of workers within AI governance and constructs a model of harm reporting processes in AI workplaces. The harm reporting process involves three steps: identification, the governance decision, and the response. Workers draw upon three types of claims to argue for jurisdiction over questions of AI governance: subjection, control over the product of one’s labor, and proximate knowledge of systems. Examining the past decade of AI-related worker activism allows us to understand how different types of workers are positioned within a workplace that produces AI systems, how their position informs their claims, and the place of collective action in staking their claims. This chapter argues that workers occupy a unique role in identifying and mitigating harms caused by AI systems.
Governing Privacy
Authors: Veliz Carissa
Published: September 2022

This chapter explores the nature of privacy and the right to privacy, their value, and ways to protect them. According to the hybrid account of privacy offered, privacy amounts to being personally unaccessed, and enjoying the right to privacy amounts to not losing (negative) control involuntarily over one’s personal information or sensorial space. The hybrid account captures the advantages of both access and control-based accounts of privacy. The chapter goes on to investigate the value of privacy. I argue that privacy is important because it shields citizens from harms that arise from exposure to others; it especially protects people from abuses of power. Privacy, I argue, is not only important for individuals, but also for society, and for liberal democracy in particular. Privacy is as collective as it is personal. Finally, I propose three effective measures to minimize losses of privacy and violations of the right to privacy in the digital age: data minimization, storage limitation, and banning the trade in personal data. The chapter ends by exploring the limits of consent in the context of AI and big data.
The Quality of Working Life
Authors: Guest David
Published: September 2022

The chapter addresses the nature, evolution and impact of the concept of quality of working life and the role of work design as a key component. It covers the period from the initial work of pioneers at the Tavistock Institute of Human Relations to recent attempts to reinvigorate quality of working life research. The ebb and flow of pressures to advance the quality of working life are considered, along with the roles of the various stakeholders, ranging from governments to employees and their representatives. The specific challenges of applying work redesign as a major means of improving the quality of working life are assessed, with some consideration of significant successes and failures. It is argued that while there have been improvements in the overall quality of working life in advanced economies, often aided by legislation, progress in improving the design of work has been more fragmented and unequally spread across the workforce.
Job Quality
Authors: Warhurst Chris , Wright Sally , Mathieu Chris
Published: September 2022

This chapter outlines the parameters and range of concepts that can be attributed to current understanding of job quality. At its heart is a deceptively simple question: what is job quality? This chapter focuses on the parameters and concepts for understanding the variety of approaches to the study of the quality of jobs by outlining a ‘family of concepts’ related to the quality of jobs. The chapter starts by outlining four parameters for analysing the purpose and content of the family of concepts: analytic versus programmatic; subjective versus objective; intrinsic versus extrinsic; and advantageous for whom? It then outlines the seven more commonly used concepts in the family, including decent work, fair work, quality of working life and meaningful work highlighting their scope, content and origin, before turning to job quality itself. The section on job quality highlights core dimensions of job quality based on existing research and which might provide the basis of a future research consensus to the study of the quality of jobs.
Working with enactments in CAT
Authors: Bennett Dawn , Parry Glenys , Fawkes Liz
Published: September 2022

Enactments of problematic reciprocal roles between the therapist and client are expected and commonly experienced during therapy. The concept of enactments is explained and linked to threats to, or ruptures in, the therapeutic alliance. In cognitive analytic therapy (CAT) these enactments are predicted by the reformulation and seen as therapeutic opportunities. Research on how therapists successfully resolve such enactments is described, leading to a model of enactment resolution that has been used both by trainees and more experienced therapists in improving their practice.
Attending to later life
Authors: Catlin Paul , Khan Ellen , Hamill Michelle
Published: September 2022

Later life can be a time when coping strategies are challenged by losses and transitions that can resonate with earlier experiences of trauma, distress, and vulnerability. Using case vignettes this chapter illustrates the reparative possibilities of cognitive analytic therapy (CAT), both within the therapy room and beyond, when attending to the legacy of complex trauma in later life and the re-emergence of early trauma when caring for a relative with dementia. By offering a lifespan model of socially and culturally mediated development, CAT views a person as a ‘work in progress’, a culmination of experiences and relationships that have resulted in the person in the here and now, with the hopeful possibility that, regardless of age, change is possible.
Group CAT
Authors: Brummer Laura , Delisser Cheryl
Published: September 2022

A therapy group is an ideal setting to help someone explore, understand, notice, and attempt to challenge what was learnt within their original social group (their family). Groups offer multifaceted opportunities to challenge unhelpful ways of relating in the here and now with the cognitive analytic therapy (CAT) tools and ways of working, enhancing the possibility of accelerating the change process. Within this chapter we draw on the published and unpublished knowledge from the CAT community to bring together an understanding of the therapeutic nature of CAT groups, before turning to guidance on setting up and running CAT groups.
Benefits and Hurdles of Pancreatic β-Cell Replacement
Authors: Bolla Andrea Mario , Montefusco Laura , Pastore Ida , Lunati Maria Elena , Ben Nasr Moufida , Fiorina Paolo
Published: September 2022

Insulin represents a life-saving treatment in patients with type 1 diabetes, and technological advancements have improved glucose control in an increasing number of patients. Despite this, adequate control is often still difficult to achieve and insulin remains a therapy and not a cure for the disease. β-cell replacement strategies can potentially restore pancreas endocrine function and aim to maintain normoglycemia; both pancreas and islet transplantation have greatly progressed over the last decades and, in subjects with extreme glycemic variability and diabetes complications, represent a concrete and effective treatment option. Some issues still limit the adoption of this approach on a larger scale. One is represented by the strict selection criteria for the recipient who can benefit from a transplant and maintain the lifelong immunosuppression necessary to avoid organ rejection. Second, with regard to islet transplantation, up to 40% of islets can be lost during hepatic engraftment. Recent studies showed very preliminarily but promising results to overcome these hurdles: the ability to induce β-cell maturation from stem cells may represent a solution to the organ shortage, and the creation of semi-permeable membranes that envelope or package cells in either micro- or macro- encapsulation strategies, together with engineering cells to be hypo-immunogenic, pave the way for developing strategies without immunosuppression. The aim of this review is to describe the state of the art in β-cell replacement with a focus on its efficacy and clinical benefits, on the actual limitations and still unmet needs, and on the latest findings and future directions.
Identification and Re-consent of Existing Cord Blood Donors for Creation of Induced Pluripotent Stem Cell Lines for Potential Clinical Applications
Authors: Abberton Keren M , McDonald Tricia L , Diviney Mary , Holdsworth Rhonda , Leslie Stephen , Delatycki Martin B , Liu Lin , Klamer Guy , Johnson Phillip , Elwood Ngaire J
Published: September 2022

We aim to create a bank of clinical grade cord blood-derived induced pluripotent stem cell lines in order to facilitate clinical research leading to the development of new cellular therapies. Here we present a clear pathway toward the creation of such a resource, within a strong quality framework, and with the appropriate regulatory, government and ethics approvals, along with a dynamic follow-up and re-consent process of cord blood donors from the public BMDI Cord Blood Bank. Interrogation of the cord blood bank inventory and next generation sequencing was used to identify and confirm 18 donors with suitable HLA homozygous haplotypes. Regulatory challenges that may affect global acceptance of the cell lines, along with the quality standards required to operate as part of a global network, are being met by working in collaboration with bodies such as the International Stem Cell Banking Initiative (ISCBI) and the Global Alliance for iPSC Therapies (GAiT). Ethics approval was granted by an Institutional Human Research Ethics Committee, and government approval has been obtained to use banked cord blood for this purpose. New issues of whole-genome sequencing and the relevant donor safeguards and protections were considered with input from clinical genetics services, including the rights and information flow to donors, and commercialization aspects. The success of these processes has confirmed feasibility and utility of using banked cord blood to produce clinical-grade iPSC lines for potential cellular therapies.
MitoQ alleviates carbon tetrachloride-induced liver fibrosis in mice through regulating JNK/YAP pathway
Authors: Shan Shulin , Liu Zhaoxiong , Liu Zhidan , Zhang Cuiqin , Song Fuyong
Published: September 2022

Background

Liver fibrosis is a pathological wound-healing response caused by chronic liver damage. Mitochondria regulate hepatic energy metabolism and oxidative stress. Accumulating evidence has revealed that increased mitochondrial oxidative stress contributes to the activation of fibrogenesis. However, the roles and underlying mechanisms of mitochondrial oxidative stress in liver fibrosis remain unknown.

Methods and results

In this study, C57BL/6 mice were used to establish a model of liver fibrosis via oral gavage with CCl4 treatment for 8 weeks. Furthermore, intervention experiments were achieved by CCl4 combined with the intraperitoneal injection of mitoquinone mesylate (mitoQ). We demonstrated that the chronic CCl4 exposure resulted in severe hepatic fibrogenesis and significantly promoted the production of reactive oxygen species (ROS) and mitochondrial abnormalities. Besides, JNK/YAP pathway was also activated. By contrast, the administration of mitoQ markedly inhibited the expression of pro-fibrogenic transforming growth factor-β as well as type I collagen. The antifibrotic effects of mitoQ were also confirmed by hematoxylin and eosin staining and Sirius red staining. Moreover, mitoQ substantially reduced CCl4-induced mitochondrial damage and the release of ROS. Further studies suggested that this protection against liver fibrosis was mechanistically related to the inhibition of phosphorylation of JNK and the nuclear translocation of YAP.

Conclusion

In conclusion, these findings revealed that mitoQ attenuated liver fibrosis by inhibiting ROS production and the JNK/YAP signaling pathway. Selective targeting JNK/YAP may serve as a therapeutic strategy for retarding progression of chronic liver disease.
Crossover in Adjuvant Trastuzumab Trials
Authors: Tuia Jordan E. , Olivier Timothée , Prasad Vinay K.
Published: September 2022

Objectives:

Design and reporting of randomized control trials for drug therapies in the adjuvant setting require a nuanced consideration of patient crossover. Adjuvant trials can be susceptible to the misuse of crossover and may distort the interpretation of findings. We sought to investigate and describe crossover and/or postprogression access to trastuzumab within adjuvant trastuzumab randomized control trials for human epidermal growth factor receptor 2–positive breast cancer patients.

Methods:

Seven clinical trials for adjuvant trastuzumab in human epidermal growth factor receptor 2–positive breast cancer were identified through a meta-analysis published in the Lancet. Primary study publications were located through MEDLINE, Google Scholar, and trials were identified, when possible, using Clincialtrials.gov.

Results:

Sixteen publications, describing 7 studies, were reviewed. Four (57%) trials reported offering patients within the control arm the opportunity to crossover and receive trastuzumab in the adjuvant setting. Two (29%) trials did not report nor discuss crossover within the publication. Five (71%) trials reported the total number of patients who crossed over among the control arms. No trials specified the proportion of control patients who received trastuzumab at recurrence.

Conclusions:

Trials for adjuvant trastuzumab did not disambiguate between crossover (1) in the adjuvant setting or (2) at recurrence. Due to the low reported rate of crossover, it is questionable if participants received the standard of care.
Initial Experience With Two Active Transcutaneous Bone-Anchored Hearing Implants
Authors: Schwam Zachary G. , Perez Enrique R. , Oh Samuel , Wong Kevin , Fan Caleb , Cosetti Maura K. , Wanna George B.
Published: September 2022

Objective

To analyze our institutional experience with two active transcutaneous bone-anchored hearing aids.

Study Design

Retrospective cohort study.

Setting

Tertiary academic otology-neurotology practice.

Patients

Patients with conductive or mixed hearing losses meeting criteria to receive active transcutaneous bone-anchored hearing aids.

Interventions

Implantation with one of two active transcutaneous bone-anchored hearing aids.

Outcome Measures

Operative time, dural exposure and decompression, use of lifts, implant position, ease of use, qualitative patient satisfaction, complication rates.

Results

Ten patients received Implant 1 and 11 patients received Implant 2. The most common underlying etiologies of hearing loss were chronic suppurative otitis media in 33.3%, atresia/microtia in 23.8%, and cholesteatoma in 23.8%. Average operative times were 99.3 minutes for Implant 1 and 80.9 minutes for Implant 2 (p = 0.263). Implant 1 required lifts in 60%, dural exposure in 50%, and dural compression in 30%. Overall, placement was difficult in 47.6% of cases. There were no intraoperative complications. There were higher rates of issues with sound quality (27.3% versus 0.0%, p = 0.123) and poor cosmesis (36.4% versus 10.0%, p = 0.360) with Implant 2. Functional gain was not recorded, but all patients derived qualitative benefit from their implant. Three patients had local wound complications that self-resolved or were treated with antibiotics. One patient implanted at an outside institution required explant because of multiple infections.

Conclusions

There were no statistically significant differences in outcomes comparing Implants 1 and 2; however, Implant 2 had much higher rates of issues with audio quality and poor cosmesis. Placing Implant 1 often required special techniques.
Dilemma in approach to stroke in sickle cell disease patient: A case report
Authors: Okar Lina , Ali Alzoubi Hadeel , Shukur Mahmud Safa , Elyas Ahmed , Yassin Mohamed A.
Published: September 2022

Introduction:

Cerebrovascular accidents in sickle cell disease (SCD) patients carry a high socioeconomic impact and represent the most important cause of morbidity, neurological deficits, and impaired quality of life in SCD young population.

Patent foramen ovale (PFO) is prevalent in 25% of the general population and it is associated with ischemic stroke in the young population via paradoxical embolism, yet there are no specific guidelines to address how to manage SCD patients with PFO who suffer a stroke.

Patient concerns and diagnosis:

Here we present a young SCD patient, aged 24 years, who suffered a stroke in childhood and later was discovered to have a PFO on subsequent echocardiography. The patient has been receiving blood transfusion therapy since 3 years of age.

Interventions and outcomes:

No treatment was administered to the patient.

The intervention that was done was echocardiography with a bubble study to detect PFO.

Conclusion:

Recommendations need to be put in place regarding screening for PFO in patients with SCD, in addition to highlighting issues of whether screening needs to be done in patients who have not developed stroke, and if PFO were to be found, what would be the best management approach and how will prognosis be affected.
Clinical features and mortality of COVID-19 patients admitted to ICU according to SOFA score
Authors: Gómez-Romero Francisco Javier , Muñoz-Rodríguez José Ramón , Serrano-Oviedo Leticia , García-Jabalera Inmaculada , López-Juárez Pilar , Pérez-Ortiz José Manuel , Redondo-Calvo Francisco Javier ,   the COVID-19 SESCAM Network
Published: September 2022

The Sequential Organ Failure Assessment (SOFA) could function as an effective risk stratification tool in the admission of critically ill patients with COVID-19 and would allow stratification based on a risk assessment. We aimed to examine whether the SOFA score is useful to define 2 severity profiles in COVID-19 patients admitted to ICU: mild with SOFA < 5, and severe with SOFA ≥ 5.

A retrospective cohort, multicenter study was conducted from February 11 to May 11, 2020. We analyzed patients admitted to all ICUs of the 14 public hospitals of the Castilla-La Mancha Health Service at the beginning of the pandemic and with SARS-CoV-2 infection. Patients were divided in 2 groups according to the level of severity by SOFA at admission to the ICU. Cox regression was used to evaluate factors associated with survival and Kaplan-Meier test to examine survival probability.

In total, 405 patients with a complete SOFA panel were recruited in the 14 participating ICUs. SOFA <5 group showed that age above 60 years and D-dimer above 1000 ng/mL were risk factors associated with lower survival. In SOFA ≥ 5 it was found that high blood pressure was a risk factor associated with shorter survival. Kaplan-Meier showed lower survival in SOFA ≥ 5 in combination with high blood pressure, time since viral symptom onset to admission in ICU < 7 days, D-dimer ≥1000 ng/mL and respiratory pathology. However, SOFA < 5 showed only higher age (≥60 years) associated with lower survival.

Age over 60 years and D-dimer over 1000 ng/mL were risk factors reflecting lower survival in patients with SOFA < 5. Moreover, SOFA ≥ 5 patients within a week after COVID-19 onset and comorbidities such as high blood pressure and previous respiratory pathology showed lower survival.
Plasma presepsin level predicts acute kidney injury in patients with sepsis in the emergency department
Authors: Kim Sin Young , Hong Dae Young , Lee Kyeong Ryong , Paik Jin Hui , Jung Hyun Min
Published: September 2022

Acute kidney injury (AKI) is a common complication in patients with sepsis. We evaluated the potential prognostic value of plasma presepsin to predict AKI in patients with sepsis in the emergency department. A total of 193 patients diagnosed with sepsis based on the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) were included in this observational study. AKI was defined according to the Kidney Disease Improving Global Outcomes clinical practice guideline. Plasma presepsin levels were measured on admission to the emergency department. We compared plasma presepsin levels between patients who did and those who did not develop AKI.

AKI occurred in 100 (51.8%) patients. The median plasma presepsin level was significantly higher in patients with AKI than in those without AKI (1061 pg/mL vs 495 pg/mL, P <.001). Plasma presepsin levels were significantly increased in patients with AKI stage 3 compared with those with AKI stages 1 and 2 (P =.001). The area under the curve of presepsin for predicting AKI was 0.793 (95% confidence interval: 0.729–0.848). The optimal presepsin cutoff value for predicting AKI was >572 pg/mL, with a sensitivity of 77.0% and specificity of 81.7%.

Plasma presepsin level is a valuable biomarker for the prediction of AKI in patients with sepsis in the emergency department.
HIV Linkage to Care and Pre-Exposure Prophylaxis Among Persons in Non–Health Care Sites Who Are Tested for HIV for the First Time, United States, 2019
Authors: Beltrami John , Rao Shubha , Wang Guoshen , Minor Patrick , Dunbar Erica
Published: September 2022

Context:

The Centers for Disease Control and Prevention recommends that all persons aged 13 to 64 years are tested for human immunodeficiency virus (HIV). However, results from US surveys show that 50% of persons and less had ever tested for HIV.

Program:

The Centers for Disease Control and Prevention annually funds 60 health departments to conduct comprehensive HIV prevention and surveillance activities that include HIV testing.

Implementation:

We selected the 31 health departments with quality data (ie, ≤20% missing or invalid values for variables to verify linkage to HIV medical care and new HIV diagnoses) in 2019. Main outcomes were new HIV diagnoses, linkage, and pre-exposure prophylaxis (PrEP) awareness and referrals. We used SAS 9.4 to conduct descriptive, chi-square, and multivariate regression analyses. Our objectives were to determine outcomes and characteristics of persons in non–health care settings who tested for HIV for the first time.

Evaluation:

Compared with persons who previously tested for HIV, persons who tested for the first time were more likely to be aged 13 to 29 years than aged 30 years and older (62.0% [24 295/39 192] vs 42.1% [61 911/147 087], P < .001) and have a higher percentage of new HIV diagnoses (0.6% [242/39 320] vs 0.5% [667/147 475], P < .001). Among persons who tested for the first time, overall percentages of linkage, PrEP awareness, and PrEP referral were 73.4%, 33.3%, and 30.8%, respectively. Compared with referent groups, persons who tested for the first time in the South and had a new HIV diagnosis were less likely to be linked (adjusted prevalence ratio [aPR] = 0.72, 95% confidence interval [CI]: 0.59-0.89); persons who inject drugs were less likely to be aware of PrEP (aPR = 0.84, 95% CI: 0.77-0.91); and persons in the Northeast were less likely to receive PrEP referrals (aPR = 0.28, 95% CI: 0.26-0.31).

Discussion:

Non–health care sites should consider increasing HIV testing, PrEP awareness, and prompt referrals to PrEP and HIV treatment services for persons who have never previously tested.
Comprehensive Improvement of Cardiology Inpatient Transfers: A Bed-availability Triggered Approach
Authors: Moore Judson A. , Eilers Lindsay F. , Willis Amanda J. , Chance Michael D. , La Salle Julie A. , Delgado Ellen H. , Bien Katie M. , Goldman Jordana R. , Sheth Shreya S.
Published: September 2022

Introduction:

Patient transfers pose a potential risk during hospitalizations. Structured communication practices are necessary to ensure effective handoffs, but occur amidst competing priorities and constraints. We sought to design and implement a multidisciplinary process to enhance communication between pediatric cardiovascular intensive care unit and cardiology floor teams with a comprehensive approach evaluating efficiency, safety, and culture.

Methods:

We conducted a prospective quality improvement study to enact a bed-availability triggered bedside handoff process. The primary aim was to reduce the time between handoff and unit transfer. Secondary metrics captured the impact on safety (reported safety events, overnight transfers, bounce backs, and I-PASS utilization), efficiency (transfer latency, unnecessary patient handoffs, and cumulative time providers were engaged in handoffs), and culture (team members perceptions of satisfaction, collaboration, and handoff efficiency via survey data).

Results:

Eighty-two preimplementation surveys, 26 stakeholder interviews, and 95 transfers were completed during the preintervention period. During the postintervention period, 145 handoffs were audited. We observed significant reductions in transfer latency, unnecessary handoffs, and cumulative provider handoff time. Overnight transfers decreased, and no negative impact was observed in reported safety events or bouncebacks. Survey results showed a positive impact on collaboration, efficiency, and satisfaction among team members.

Conclusions:

Developing safer handoff practices require a collaborative, structured, and stepwise approach. Advances are attainable in high-volume centers, and comprehensive measurement of change is necessary to ensure a positive impact on the overall patient and provider environment.
Atomistic Simulations and Network-Based Energetic Profiling of Binding and Allostery in the SARS-CoV-2 Spike Omicron BA.1, BA.1.1, BA.2 and BA.3 Subvariant Complexes with the Host Receptor: Revealing Hidden Functional Roles of the Binding Hotspots in Mediating Epistatic Effects and Long-Range Communication with Allosteric Pockets
Authors: Verkhivker Gennady , Agajanian Steve , Kassab Ryan , Krishnan Keerthi
Published: September 2022

In this study, we performed all-atom MD simulations of the RBD-ACE2 complexes for BA.1, BA.1.1, BA.2, an BA.3 Omicron subvariants, conducted a systematic mutational scanning of the RBD-ACE2 binding interfaces and analysis of electrostatic effects. The binding free energy computations of the Omicron RBD-ACE2 complexes and comprehensive examination of the electrostatic interactions quantify the driving forces of binding and provide new insights into energetic mechanisms underlying evolutionary differences between Omicron variants. A systematic mutational scanning of the RBD residues determines the protein stability centers and binding energy hotpots in the Omicron RBD-ACE2 complexes. By employing the ensemble-based global network analysis, we proposed a community-based topological model of the Omicron RBD interactions that characterized functional roles of the Omicron mutational sites in mediating non-additive epistatic effects of mutations. Our findings suggested that non-additive contributions to the binding affinity may be mediated by R493, Y498, and Y501 sites and are greater for the Omicron BA.1.1 and BA.2 complexes that display the strongest ACE2 binding affinity among the Omicron subvariants. A network-centric adaptation model of the reversed allosteric communication is unveiled in this study that established a robust connection between allosteric network hotspots and potential allosteric binding pockets. Using this approach, we demonstrated that mediating centers of long-range interactions could anchor the experimentally validated allosteric binding pockets. Through an array of complementary approaches and proposed models, this comprehensive and multi-faceted computational study revealed and quantified multiple functional roles of the key Omicron mutational site R493, R498 and Y501 acting as binding energy hotspots, drivers of electrostatic interactions as well as mediators of epistatic effects and long-range communications with the allosteric pockets.
DeepVariant calling provides insights into race diversity and its implication for sorghum breeding
Authors: Ruperao Pradeep , Gandham Prasad , Odeny Damaris A , Selvanayagam Sivasubramani , Thirunavukkarasu Nepolean , Das Roma R , Srikanda Manasa , Gandhi Harish , Habyarimana Ephrem , Manyasa Eric , Nebie Baloua , Deshpande Santosh P , Rathore Abhishek
Published: September 2022

Due to evolutionary divergence, sorghum race populations exhibit vast genetic and morphological variations. A k-mer-based sorghum race sequence comparison identified the conserved k-mers of all sorghum race accessions and the race-specific genetic signatures identified the gene variability in 10,321 genes (PAVs). To understand the sorghum race structure, diversity and domestication, deep learning-based variant calling approach was employed in a set of genotypic data derived from a diverse panel of 272 sorghum accessions. The data resulted in 1.7 million high-quality genome-wide SNPs and identified selective signature (both positive and negative) regions through a genome-wide scan with different (iHS and XP-EHH) statistical methods. We discovered 2,370 genes associated with selection signatures including 179 selective sweep regions distributed over 10 chromosomes. Localization of these regions undergoing selective pressure with previously reported QTLs and genes revealed that the signatures of selection could be related to the domestication of important agronomic traits such as biomass and plant height. The developed k-mer signatures will be useful in the future to identify the sorghum race and SNP markers assist in plant breeding programs.
Defining antigen targets to dissect vaccinia virus (VACV) and Monkeypox virus (MPXV)-specific T cell responses in humans
Authors: Grifoni Alba , Zhang Yun , Tarke Alison , Sidney John , Rubiro Paul , Reina-Campos Maria , Filaci Gilberto , Dan Jennifer , Scheuermann Richard H. , Sette Alessandro
Published: September 2022

The current Monkeypox virus (MPXV) outbreak in non-endemic countries is raising concern about the pandemic potential of novel orthopoxviruses. Little is known regarding MPXV immunity in the context of MPXV infection or vaccination with Vaccinia-based vaccines (VACV). As with vaccinia, T cells are likely to provide an important contribution to overall immunity to MPXV. Here we leveraged the epitope information available in Immune Epitope Database (IEDB) on VACV to predict potential MPXV targets recognized by CD4+ and CD8+ T cell responses. We found a high degree of conservation between VACV epitopes and MPXV, and defined T cell immunodominant targets. These analyses enabled the design of peptide pools able to experimentally detect VACV-specific T cell responses and MPXV cross-reactive T cells in a cohort of vaccinated individuals. Our findings will facilitate the monitoring of cellular immunity following MPXV infection and vaccination.
A dual function for the chromatin organizer Special A-T rich Binding Protein 1 in B-lineage cells
Authors: Thomas Morgane , Martin Ophélie Alyssa , Bruzeau Charlotte , Pollet Justine , Bender Sébastien , Carrion Claire , Le Noir Sandrine , Pinaud Eric
Published: September 2022

SATB1 (Special A-T rich Binding protein 1) is a cell type specific factor involved in chromatin remodelling events that participate in the regulation of the genetic network in developing T cells and neurons. In T cells, SATB1 is a key factor required for lineage commitment, VDJ recombination, development and maturation. In B cells, SATB1 is described as binding to the MARs-Eµ regions of the IgH locus. Considering that its expression varies during differentiation, the involvement of this factor needed to be clarified in B cells. Using a KO mouse model deleting SATB1 from the pro-B cell stage, we were able to examine the consequences of SATB1 deletion in naive and activated B cell subsets. Our model indicates firstly that SATB1 is not essential for B cell development and the establishment of a broad IgH repertoire. Second, we show that this factor exhibits an ambivalent function in mature B cells, acting sequentially as a positive and negative regulator of Ig gene transcription in naive and activated cells, respectively. Third, our study indicates that the negative regulatory function of SATB1 in B cells extends to the germinal center response in which this factor limits somatic hypermutation of Ig genes. This finding suggests that SATB1 may limit the introduction of unwanted mutations into B cells.
Phase separation-based visualization of protein-protein interactions and kinase activities in plants
Authors: Safi Alaeddine , Smagghe Wouter , Gonçalves Amanda , Xu Ke , Fernandez Ana Ibis , Cappe Benjamin , Riquet Franck B. , Mylle Evelien , Van Damme Daniël , Geelen Danny , Jaeger Geert De , Beeckman Tom , Leene Jelle Van , Vanneste Steffen
Published: September 2022

Protein activities depend heavily on protein complex formation and dynamic post-translational modifications, such as phosphorylation. Their dynamic nature is notoriously difficult to monitor in planta at cellular resolution, often requiring extensive optimization and high-end microscopy. Here, we generated and exploited the SYnthetic Multivalency in PLants (SYMPL)-vector set to study protein-protein interactions (PPIs) and kinase activities in planta based on phase separation. This technology enabled easy detection of inducible, binary and ternary protein-protein interactions among cytoplasmic, nuclear and plasma membrane proteins in plant cells via a robust image-based readout. Moreover, we applied the SYMPL toolbox to develop an in vivo reporter for SnRK1 kinase activity, allowing us to visualize tissue-specific, dynamic SnRK1 activation upon energy deprivation in stable transgenic Arabidopsis plants. The applications of the SYMPL cloning toolbox lay the foundation for the exploration of PPIs, phosphorylation and other post-translational modifications with unprecedented ease and sensitivity.
A Meta-learning based Graph-Hierarchical Clustering Method for Single Cell RNA-Seq Data
Authors: Pan Zixiang , Lin Yuefan , Zhang Haokun , Zeng Yuansong , Yu Weijiang , Yang Yuedong
Published: September 2022

Single cell sequencing techniques enable researchers view complex bio-tissues from a more precise perspective to identify cell types. However, more and more recent works have been done to find more detailed subtypes within already known cell types. Here, we present MeHi-SCC, a method which utilized meta-learning protocol and brought in multi scRNA-seq datasets’ information in order to assist graph-based hierarchical sub-clustering process. In result, MeHi-SCC outperformed current-prevailing scRNA clustering methods and successfully identified cell subtypes in two large scale cell atlas. Our codes and datasets are available online athttps://github.com/biomed-AI/MeHi-SCC
Predicting cell population-specific gene expression from genomic sequence
Authors: Michielsen Lieke , Reinders Marcel J.T. , Mahfouz Ahmed
Published: September 2022

Most regulatory elements, especially enhancer sequences, are cell population-specific. One could even argue that a distinct set of regulatory elements is what defines a cell population. However, discovering which non-coding regions of the DNA are essential in which context, and as a result, which genes are expressed, is a difficult task. Some computational models tackle this problem by predicting gene expression directly from the genomic sequence. These models are currently limited to predicting bulk measurements and mainly make tissue-specific predictions. Here, we present a model that leverages single-cell RNA-sequencing data to predict gene expression. We show that cell population-specific models outperform tissue-specific models, especially when the expression profile of a cell population and the corresponding tissue are dissimilar. Further, we show that our model can prioritize GWAS variants and learn motifs of transcription factor binding sites. We envision that our model can be useful for delineating cell population-specific regulatory elements.
Proteomic signatures of the serological response to flu vaccination in a large human cohort study
Authors: Wu Shaohuan , Pushalkar Smruti , Maity Shuvadeep , Pressler Matthew , Rendleman Justin , Vitrinel Burcu , Carlock Michael , Ross Ted , Choi Hyungwon , Vogel Christine
Published: September 2022

The serological response to the influenza virus vaccine is highly heterogeneous for reasons that are not entirely clear. While the impact of demographic factors such as age, body mass index (BMI), sex, prior vaccination and titer levels are known to impact seroconversion, they only explain a fraction of the response. To identify signatures of the vaccine response, we quantified 273 proteins from serum samples of 160 flu vaccine recipients (2019-2020 season). We found that levels of proteins functioning in cholesterol transport were positively associated with seroconversion, likely linking to the known impact of BMI. When adjusting seroconversion for the demographic factors, we identified additional, unexpected signatures: proteins regulating actin cytoskeleton dynamics were significantly elevated in participants with high adjusted seroconversion. Viral strain specific analysis showed that this trend was largely driven by the H3N2 strain. Further, we identified complex associations between adjusted seroconversion and other factors: levels of proteins of the complement system associated positively with adjusted seroconversion in younger participants, while they were associated negatively in the older population. We observed the opposite trends for proteins of high density lipoprotein remodeling, transcription, and hemostasis. In sum, careful integrative modeling can extract new signatures of seroconversion from highly variable data that suggest links between the humoral response as well as immune cell communication and migration.
Functional MRS studies of GABA and Glutamate/Glx – a systematic review and meta-analysis
Authors: Pasanta Duanghathai , He Jason L. , Ford Talitha , Oeltzschner Georg , Lythgoe David J. , Puts Nicolaas A.
Published: September 2022

Functional magnetic resonance spectroscopy (fMRS) can be used to investigate neurometabolic responses to external stimuli in-vivo, but findings are inconsistent. We performed a systematic review and meta-analysis on fMRS studies of the primary neurotransmitters Glutamate (Glu), Glx (Glutamate + Glutamine), and GABA. Data were extracted, grouped by metabolite, stimulus domain, and brain region, and analysed by determining standardized effect sizes. The quality of individual studies was rated. When results were analysed by metabolite type small to moderate effect sizes of 0.29-0.47 (p < 0.05) were observed for changes in Glu and Glx regardless of stimulus domain and brain region, but no significant effects were observed for GABA. Further analysis suggests that Glu, Glx and GABA responses differ by stimulus domain or task and vary depending on the time course of stimulation and data acquisition. Here, we establish effect sizes and directionality of GABA, Glu and Glx response in fMRS. This work highlights the importance of standardised reporting and minimal best practice for fMRS research.
Synaptic status differentially regulates neurofilaments in dendritic spines
Authors: Gürth Clara-Marie , do Rego Barros Fernandes Lima Maria Augusta , Cereceda Delgado Angel Rafael , Palacios Victor Macarrón , Hubrich Jasmine , D’Este Elisa
Published: September 2022

Neurofilaments are one of the main cytoskeletal components in neurons and they can be found in the form of oligomers at pre- and postsynapses. How their presence is regulated at the postsynapse remains widely unclear. Here we systematically quantified by immunolabeling the occurrence of the neurofilament isoform triplet neurofilament light (NFL), medium (NFM), and heavy (NFH) at the postsynapse with STED nanoscopy together with markers of synaptic strength and activity. Our data shows that within dendritic spines neurofilament isoforms rarely colocalize with each other and that they are present to different extents, with NFL being the most abundant isoform. The amount of the three isoforms correlates with markers of postsynaptic strength and presynaptic activity to varying degrees: while NFL shows moderate correlation to both synaptic traits suggesting its involvement in synaptic response, NFM and NFH were only correlated on a low level. By quantifying the presence of neurofilaments at the postsynapse within the context of the synaptic status, this work sheds new light on the regulation of synaptic neurofilaments and their possible contribution to psychiatric disorders.