bluuebunny/crossref_metadata_2025_split huggingface dataset:
ADAR activation by inducing a syn conformation at guanosine adjacent to an editing site
Authors: Doherty Erin E , Karki Agya , Wilcox Xander E , Mendoza Herra G , Manjunath Aashrita , Matos Victorio Jauregui , Fisher Andrew J , Beal Peter A 
Published: October 2022

Abstract
ADARs (adenosine deaminases acting on RNA) can be directed to sites in the transcriptome by complementary guide strands allowing for the correction of disease-causing mutations at the RNA level. However, ADARs show bias against editing adenosines with a guanosine 5′ nearest neighbor (5′-GA sites), limiting the scope of this approach. Earlier studies suggested this effect arises from a clash in the RNA minor groove involving the 2-amino group of the guanosine adjacent to an editing site. Here we show that nucleosides capable of pairing with guanosine in a syn conformation enhance editing for 5′-GA sites. We describe the crystal structure of a fragment of human ADAR2 bound to RNA bearing a G:G pair adjacent to an editing site. The two guanosines form a Gsyn:Ganti pair solving the steric problem by flipping the 2-amino group of the guanosine adjacent to the editing site into the major groove. Also, duplexes with 2′-deoxyadenosine and 3-deaza-2′-deoxyadenosine displayed increased editing efficiency, suggesting the formation of a Gsyn:AH+anti pair. This was supported by X-ray crystallography of an ADAR complex with RNA bearing a G:3-deaza dA pair. This study shows how non-Watson–Crick pairing in duplex RNA can facilitate ADAR editing enabling the design of next generation guide strands for therapeutic RNA editing.
Structural basis of three different transcription activation strategies adopted by a single regulator SoxS
Authors: Shi Jing , Wang Lu , Wen Aijia , Wang Fulin , Zhang Yuqiong , Yu Libing , Li Fangfang , Jin Yuanling , Feng Zhenzhen , Li Jiacong , Yang Yujiao , Gao Fei , Zhang Yu , Feng Yu , Wang Shuang , Zhao Wei , Lin Wei 
Published: October 2022

Abstract
Transcription activation is established through extensive protein–protein and protein–DNA interactions that allow an activator to engage and remodel RNA polymerase. SoxS, a global transcription activator, diversely regulates subsets of stress response genes with different promoters, but the detailed SoxS-dependent transcription initiation mechanisms remain obscure. Here, we report cryo-EM structures of three SoxS-dependent transcription activation complexes (SoxS-TACI, SoxS-TACII and SoxS-TACIII) comprising of Escherichia coli RNA polymerase (RNAP), SoxS protein and three representative classes of SoxS-regulated promoters. The structures reveal that SoxS monomer orchestrates transcription initiation through specific interactions with the promoter DNA and different conserved domains of RNAP. In particular, SoxS is positioned in the opposite orientation in SoxS-TACIII to that in SoxS-TACI and SoxS-TACII, unveiling a novel mode of transcription activation. Strikingly, two universally conserved C-terminal domains of alpha subunit (αCTD) of RNAP associate with each other, bridging SoxS and region 4 of σ70. We show that SoxS interacts with RNAP directly and independently from DNA, remodeling the enzyme to activate transcription from cognate SoxS promoters while repressing transcription from UP-element containing promoters. Our data provide a comprehensive summary of SoxS-dependent promoter architectures and offer new insights into the αCTD contribution to transcription control in bacteria.
Self-reported health change in haemodialysis recipients modulates the effect of frailty upon mortality and hospital admissions: outcomes from a large prospective UK cohort
Authors: Anderson Benjamin M , Qasim Muhammad , Correa Gonzalo , Evison Felicity , Gallier Suzy , Ferro Charles J , Jackson Thomas A , Sharif Adnan 
Published: October 2022

ABSTRACT

Background
Frailty among haemodialysis patients is associated with hospitalization and mortality, but high frailty prevalence suggests further discrimination of risk is required. We hypothesized that incorporation of self-reported health with frailty measurement may aid risk stratification.

Methods
Prospective cohort study of 485 prevalent haemodialysis recipients linked to English national datasets. Frailty Phenotype (FP), Frailty Index (FI), Edmonton Frail Scale (EFS), Clinical Frailty Scale (CFS) and self-reported health change were assessed. Mortality was explored using Fine and Gray regression, and admissions by negative binomial regression.

Results
Over a median 678 (interquartile range 531–812) days, there were 111 deaths, and 1241 hospitalizations. Increasing frailty was associated with mortality on adjusted analyses for FP [subdistribution hazard ratio (SHR) 1.26, 95% confidence interval (CI) 1.05–1.53, P = .01], FI (SHR 1.21, 95% CI 1.09–1.35, P = .001) and CFS (SHR 1.32, 95% CI 1.11–1.58, P = .002), but not EFS (HR 1.08, 95% CI 0.99–1.18, P = .1). Health change interacted with frailty tools to modify association with mortality; only those who rated their health as the same or worse experienced increased mortality hazard associated with frailty by FP (Pinteraction = .001 and 0.035, respectively), FI (Pinteraction = .002 and .007, respectively) and CFS (Pinteraction = .009 and 0.02, respectively). CFS was the only frailty tool associated with hospitalization (incidence rate ratio 1.12, 95% CI 1.02–1.23, P = .02).

Conclusions
We confirm the high burden of hospitalization and mortality associated with haemodialysis patients regardless of frailty tool utilized and introduce the discriminatory ability of self-reported health to identify the most at-risk frail individuals.
Association of chronic kidney disease with total and site-specific cancer incidence in participants of the Japan Public Health Center-based Prospective Study
Authors: Miyamoto Yoshihisa , Katagiri Ryoko , Yamaji Taiki , Inoue Manami , Goto Atsushi , Iwasaki Motoki , Noda Mitsuhiko , Tsugane Shoichiro , Sawada Norie 
Published: October 2022

ABSTRACT

Background
Although studies have found an association between chronic kidney disease (CKD) and cancer incidence, the results are inconsistent.

Methods
This study included participants in the Japan Public Health Center-based Prospective Study who had data on serum creatinine measurements. We assessed the association between estimated glomerular filtration rate (eGFR) and the risk of total and site-specific cancer incidence using a systematic survey in Japan. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for participant demographics and lifestyle factors.

Results
A total of 21 978 participants who met the inclusion criteria were followed up for a mean period of 12.9 years, during which a total of 2997 incident cancer cases were reported. In the multivariable adjusted models, an eGFR of &lt;45 mL/min/1.73 m2 was not significantly associated with total cancer incidence (adjusted HR 1.22, 95% CI 0.94–1.60), compared with an eGFR of 60–89 mL/min/1.73 m2 (reference). The HR among those with eGFRs of ≥90 mL/min/1.73 m2 was 1.10 (95% CI 1.00–1.22).

Conclusions
In this large prospective study, a low eGFR was not significantly associated with an increased risk of total cancer incidence in patients with CKD, which may be partly due to an underpowered sample size. This finding may be due to the many shared risk factors between CKD and cancer.
Probiotic-based nanoparticles for targeted microbiota modulation and immune restoration in bacterial pneumonia
Authors: Fu Jieni , Liu Xiangmei , Cui Zhenduo , Zheng Yufeng , Jiang Hui , Zhang Yu , Li Zhaoyang , Liang Yanqin , Zhu Shengli , Chu Paul K , Yeung Kelvin Wai Kwok , Wu Shuilin 
Published: October 2022

ABSTRACT
While conventional bacterial pneumonia mainly centralizes avoidance of bacterial colonization, it remains unclear how to restore the host immunity for hyperactive immunocompetent primary and immunocompromised secondary bacterial pneumonia. Here, probiotic-based nanoparticles of OASCLR were formed by coating chitosan, hyaluronic acid and ononin on living Lactobacillus rhamnosus. OASCLR nanoparticles could effectively kill various clinic common pathogens and antibacterial efficiency was &gt;99.97%. Importantly, OASCLR could modulate lung microbiota, increasing the overall richness and diversity of microbiota by decreasing pathogens and increasing probiotic and commensal bacteria. Additionally, OASCLR could target inflammatory macrophages by the interaction of OASCLR with the macrophage binding site of CD44 and alleviate overactive immune responses for hyperactive immunocompetent pneumonia. Surprisingly, OASCLR could break the state of the macrophage's poor phagocytic ability by upregulating the expression of the extracellular matrix assembly, immune activation and fibroblast activation in immunocompromised pneumonia. The macrophage's phagocytic ability was increased from 2.61% to 12.3%. Our work provides a potential strategy for hyperactive immunocompetent primary and immunocompromised secondary bacterial pneumonia.
Time-restricted feeding is an intervention against excessive dark-phase sleepiness induced by obesogenic diet
Authors: Wang Xu , Xing Keke , He Mengge , He Ting , Xiang Xinkuan , Chen Tao , Zhang Luoying , Li Haohong 
Published: October 2022

ABSTRACTHigh-fat diet (HFD)-induced obesity is a growing epidemic and major health concern. While excessive daytime sleepiness (EDS) is a common symptom of HFD-induced obesity, preliminary findings suggest that reduced wakefulness could be improved with time-restricted feeding (TRF). At present, however, the underlying neural mechanisms remain largely unknown. The paraventricular thalamic nucleus (PVT) plays a role in maintaining wakefulness. We found that chronic HFD impaired the activity of PVT neurons. Notably, inactivation of the PVT was sufficient to reduce and fragment wakefulness during the active phase in lean mice, similar to the sleep–wake alterations observed in obese mice with HFD-induced obesity. On the other hand, enhancing PVT neuronal activity consolidated wakefulness in mice with HFD-induced obesity. We observed that the fragmented wakefulness could be eliminated and reversed by TRF. Furthermore, TRF prevented the HFD-induced disruptions on synaptic transmission in the PVT, in a feeding duration-dependent manner. Collectively, our findings demonstrate that ad libitum access to a HFD results in inactivation of the PVT, which is critical to impaired nocturnal wakefulness and increased sleep, while TRF can prevent and reverse diet-induced PVT dysfunction and excessive sleepiness. We establish a link between TRF and neural activity, through which TRF can potentially serve as a lifestyle intervention against diet/obesity-related EDS.
Multi-scale nest survival analysis suggests new cavities improve nest success for the Green-barred Woodpecker, but not the Campo Flicker, in a threatened woodland of Argentina
Authors: Jauregui Adrián , Gonzalez Exequiel , Segura Luciano N 
Published: October 2022

Abstract
Understanding factors affecting nest survival of woodpeckers in threatened landscapes is a key tool for land managers, particularly when conservation depends on public policies. However, information of Neotropical woodpeckers breeding in southern temperate forests is noticeably sparse despite the worrying conservation status of these ecosystems and woodpeckers’ key role as cavity providers. Our objective was to assess the relationship between tree cavity features, vegetation structure, and landscape configuration on the nest survival of the Green-barred Woodpecker (Colaptes melanochloros) and the Campo Flicker (C. campestris). We monitored nests of these woodpeckers during 3 breeding seasons from 2015 to 2018 in a woodland of east-central Argentina threatened by selective tree logging and soil material extraction. We recorded features that presumably influence nest survival at a micro-scale (cavity, cavity-tree features, and foliage cover around the cavity) and a macro-scale (forest cover and shape index within a 500-m circle around the nest). We did not find support for a relationship between daily nest survival rates (DSR) and cavity features, vegetation structure, or landscape configuration. However, new cavities were more successful than reused ones for the Green-barred Woodpecker. We also found a surprisingly high rate (~33% of nest failures) of nest abandonment for both species. Abandonment may be a factor regulating this population and causes of abandonment warrants further investigation. Given the importance of new cavities to the success of Green-barred Woodpeckers, our results indicate the preservation of medium-size trees (20 cm &lt; diameter at breast height [DBH] &lt; 50 cm) with wood softened by degradation processes (preferred by the species to excavate cavities) would facilitate persistence both of this woodpecker and the cavity nesting community. Effective audit of soil material extraction and controlled selective timber logging practices (including preservation of mature trees) in compliance with existing regulations could contribute to this type of habitat maintenance.
The Rise and Fall of Collective Leadership
Authors: Shirk Susan L. 
Published: October 2022

Abstract
This chapter describes the collective leadership led by Hu Jintao and how it degenerated. During Hu’s first term of office, his administration adopted a series of moderate measures to attempt to modernize CCP rule. He expanded the size of CCP’s top decision-making body to balance power and broaden representation within the Party-state, adopted a lighter and more transparent approach in dealing with the media, and supported more redistributive policies to improve people’s livelihood. However, Hu’s collective leadership model began to show its inherent flaws during his second term in office. Being hamstrung by his predecessor Jiang Zeming, Hu lacked the centralized authority to contain the bureaucratic overreach of the stovepiped interest groups in his control coalition and industrial bureaucracies that log-rolled by supporting one another’s programs. The collective leadership at the top, which is supposed to be the embodiment of intraparty democracy, morphed into an unchecked oligarchic rule that brewed corruption, inequality, and even open leadership splits. The urgency to clean up the mess of the oligarchic rule later leads to the Party acceptance of a strong leader, enabling the rise of Xi.
Conclusion
Authors: Shirk Susan L. 
Published: October 2022

Abstract
This concluding chapter restates the central argument of this book that China’s aggressive posture in international affairs and tight control over domestic society actually began under Hu Jintao’s collective leadership and have intensified under Xi Jinping’s personalistic rule. Understanding how collective leadership and personalistic rule actually operate is important for devising effective policies to testing whether or not China is still influenceable. The chapter also offers policy suggestions to each side for stabilizing relations and avoiding war. No one expects Xi to change his leadership style or choose someone to be his successor at the upcoming Party congress. The chapter then discusses Xi’s attempt to make China a respectable global power instead of being ostracized as a rogue state. It also acknowledges the festering resentment triggered by the US’ hostile rhetoric and actions, which could be a liability in stabilizing relations between the two countries. The chapter suggests that America’s best response to China’s overreach is to temper its reactions, avoid becoming more like China, and become a better version of an open-market democracy.
Public Officials
Authors: Howard Christopher 
Published: October 2022

Abstract
Democratic officials tend to pay more attention to poverty-related issues than their Republican counterparts. Neither party, however, has talked much about these issues in their recent party platforms or State of the Union speeches. Democrats may “own” the poverty issue, based on their rhetoric, but the price of ownership has been remarkably low. Like labor unions, Democratic officials focus on workers and working families without mentioning the working poor. Government should take care of the poor by raising the minimum wage and expanding the Earned Income Tax Credit. Democrats seldom mention a role for charities. Like business groups, Republican officials believe that less government will lead to economic growth and widespread prosperity. Republicans talked more about the role of churches and charities when George W. Bush was president than when Donald Trump was in office.
Postscript: The Social Safety Net and the Pandemic
Authors: Howard Christopher 
Published: October 2022

Abstract
Who Cares depicts the social safety net before the Covid-19 pandemic began. This postscript offers an initial assessment of how the social safety net performed under historic stress. While the rhetoric of caring changed a little, the practice changed a lot. The public safety net expanded substantially. Through stimulus checks and expansions to Unemployment Insurance, the national government offered more income support to many more Americans. The number of Medicaid and SNAP recipients also grew. Eviction moratoriums helped many low-income residents stay in their apartments. Because the national government took unprecedented steps, most types of material hardship did not increase—a remarkable achievement. Yet many of these steps were temporary. The Build Back Better initiative would strengthen the social safety net while also helping the middle class, but it was stalled in Congress.
Unemployment Insurance After the Great Recession
Authors: Klerman Jacob Alex 
Published: October 2022

Abstract
This chapter discusses the goals of unemployment insurance (UI) programs and American and European experiences with unemployment and UI programs, particularly during the Great Recession and the COVID recession. It reviews the American and European literature on the impact of the details of UI programs, including benefit level, benefit duration, and monitoring of job search, on the length of benefit receipt and subsequent earnings. Based on experience during the Great Recession and the COVID recession and a review of the impact literature, the chapter considers the role of UI programs during both recessions and several possible reforms to such programs, particularly low-intensity activation programs (e.g., mandatory meetings to verify job search). The chapter concludes that the available evidence suggests that UI (and higher benefits) increases unemployment duration and that low-intensity activation programs—when rigorously enforced—have the potential to moderate lower unemployment.
Activation in Eight European Social Assistance Programs
Authors: Lødemel Ivar , Moreira Amílcar 
Published: October 2022

Abstract
In Europe, conditional activation took hold in the 1990s. In that period, national programs differed substantially, and most of the nations pursued a strategy focused more on strengthening the human resources of recipients than to imposing conditions. This changed in the following decade, and this chapter shows that, until the onset of the 2008 crisis, the main trend in the governance of activation concerned the strengthening of work obligations for minimum income recipients. This was, however, not accompanied by a strengthening of sanctions but instead by efforts to adjust the delivery of activation services to the individual needs of minimum income recipients. Developments after the Great Recession have not led to a strengthening of the level of protection of those most in need; rather, they signified a reversal of the move toward more individualized and tailored services and a deepening of the focus on work-first strategies.
Whither Activation Policies?
Authors: Martin John P. 
Published: October 2022

Abstract
The author has previously argued that activation strategies performed well during the Great Recession and subsequent recovery in some, but not all, countries of the Organisation for Economic Cooperation and Development. At the same time, it is pertinent to look to the future and consider what challenges the activation paradigm is likely to face over the coming decades when US and European labor markets will have to cope with aging workforces and immigration, to name but two. In this chapter, the author sets out his views on four such challenges: how activation can be applied to the large numbers of working-age recipients of other inactive benefits, how activation can ensure career progression, the growing trend toward private provision of activation services, and the potential and pitfalls of digitization as applied to the delivery of activation.
Dementia, Mild Cognitive Impairment, and Normal Changes of Aging
Authors: Noble James M. 
Published: October 2022

Abstract
This chapter differentiates dementia from mild cognitive impairment and normal changes of aging. Dementia is a collective, or “umbrella,” term given to a group of diseases affecting the brain that cause someone to develop difficulty in thinking, speaking, remembering, or behaving in the way they did throughout their normal adult life. Age is an important factor in dementia, both in why some people may develop it and in how it is named. A late-onset dementia typically refers to dementia that develops at age 60 years or later, whereas early-onset dementia, a far less common form, begins before age 60. Alzheimer’s disease is the most common form of dementia. Before someone develops dementia with obvious changes in instrumental activities of daily living, most people pass through a transitional stage called mild cognitive impairment. Mild cognitive impairment broadly falls into two main categories: amnestic and nonamnestic.
Diagnosing Dementia
Authors: Noble James M. 
Published: October 2022

Abstract
This chapter reviews the steps a physician will take to make a diagnosis of dementia. No matter the medical situation when going to a doctor for a dementia evaluation or anything else, physicians first develop an approach to making a diagnosis by taking a history. Questions asked in clarifying the history aim to determine the duration of symptoms, the pattern of changes, the earliest and most pervasive cognitive changes, evidence of changes in behavior, and the presence or absence of changes in physical function. After the history is obtained, a physical examination provides information complementary to the history and serves to refine the approach to a diagnosis. The actual examination comprises two major components: the general medical examination and the neurologic examination. At the conclusion of the history and examination, most doctors will order diagnostic tests—such as blood work, or phlebotomy, and brain imaging—to screen for reversible causes of dementia. In addition to cognitive evaluations, patients may be referred for formal neuropsychological testing. The chapter also considers biomarker-based tests, nuclear medicine neuroimaging, cerebrospinal fluid analyses, and genetic testing.
Where, Why, and How Dementia Affects the Brain
Authors: Noble James M. 
Published: October 2022

Abstract
This chapter examines brain anatomy from its structure to its microscopic cells, how the parts of the brain relate to one another, how dementia develops, and why certain symptoms occur. The human body has three nervous systems. The central nervous system includes the brain and related structures in the head along with the spinal cord. The peripheral nervous system is made up of all of the nerves that exit the brain and spinal cord; it carries sensory information from the skin and body and sends movement signals from the spinal cord to muscles in the arms, legs, and trunk. The third nervous system combines parts of the central and peripheral nervous systems and is called the autonomic nervous system. To best understand the process of dementia, it is important to understand the lobes of the cerebrum (frontal, parietal, temporal, and occipital) and their functions. The chapter then looks at deeper brain structures, which are broadly called the basal ganglia; the vascular supply of the brain; the main cells of the nervous system; cerebrospinal fluid; the relationship between brain anatomy and brain changes in dementia; and neurotransmission.