bluuebunny/crossref_metadata_2025 huggingface dataset:
Cosbin: cosine score-based iterative normalization of biologically diverse samples
Authors: Wu Chiung-Ting , Shen Minjie , Du Dongping , Cheng Zuolin , Parker Sarah J , Lu Yingzhou , Van Eyk Jennifer E , Yu Guoqiang , Clarke Robert , Herrington David M , Wang Yue
Published: October 2022

Motivation

Data normalization is essential to ensure accurate inference and comparability of gene expression measures across samples or conditions. Ideally, gene expression data should be rescaled based on consistently expressed reference genes. However, to normalize biologically diverse samples, the most commonly used reference genes exhibit striking expression variability and size-factor or distribution-based normalization methods can be problematic when the amount of asymmetry in differential expression is significant.

Results

We report an efficient and accurate data-driven method—Cosine score-based iterative normalization (Cosbin)—to normalize biologically diverse samples. Based on the Cosine scores of cross-condition expression patterns, the Cosbin pipeline iteratively eliminates asymmetric differentially expressed genes, identifies consistently expressed genes, and calculates sample-wise normalization factors. We demonstrate the superior performance and enhanced utility of Cosbin compared with six representative peer methods using both simulation and real multi-omics expression datasets. Implemented in open-source R scripts and specifically designed to address normalization bias due to significant asymmetry in differential expression across multiple conditions, the Cosbin tool complements rather than replaces the existing methods and will allow biologists to more accurately detect true molecular signals among diverse phenotypic groups.

Availability and implementation

The R scripts of Cosbin pipeline are freely available at https://github.com/MinjieSh/Cosbin.

Supplementary information

Supplementary data are available at Bioinformatics Advances online.
Outcomes of parastomal hernia repair after national centralization
Authors: Helgstrand Frederik , Henriksen Nadia A
Published: October 2022

Background

In 2010, it was decided to centralize parastomal hernia repairs to five specialized hernia centres in Denmark to improve outcomes. The aim of this nationwide cohort study was to evaluate whether centralization of parastomal hernia repairs has had an impact on outcomes. Specifically, readmission, reoperation for complication, and operation for recurrence were analysed before and after centralization.

Methods

By merging clinical and administrative outcome data from the Danish Hernia Database with those from the Danish National Patient Registry, all patients undergoing parastomal hernia repair in Denmark from 1 January 2007 to 31 December 2018 were included. Centralization was defined as having at least 70 per cent of procedures were performed at one of the five national centres. Readmission, reoperation, and recurrence rates for emergency and elective repairs were evaluated before and after centralization.

Results

In total, 1062 patients were included. Median follow-up was 992 days. Overall, the centralization process took 7 years. For elective repairs, the readmission, reoperation, mortality, and recurrence rates were comparable before and after centralization, but more patients overall and more patients with co-morbidity were offered surgery after centralization. For emergency repairs, there was a significant reduction in rates of reoperation (from 44.9 per cent (48 of 107) to 23 per cent (14 of 62); P = 0.004) and mortality (from 10.3 per cent (11 of 107) to 2 per cent (1 of 62); P = 0.034) after centralization.

Conclusion

Centralization led to more elective operations and better outcomes when emergency repair was needed. Centralization of parastomal hernia repair led to more patients receiving elective repair and significantly improved outcomes after emergency repair.
Lung Lobe Segmentation and Feature Extraction-Based Hierarchical Attention Network for COVID-19 Prediction from Chest X-Ray Images
Authors: Christina Magneta S , Sundar C , Thanabal M S
Published: October 2022

Coronavirus disease 2019 (COVID-19) is a rising respiratory sickness. It causes harsh pneumonia and is considered to cover higher collisions in the healthcare domain. The diagnosis at an early stage is more complex to get accurate treatment for reducing the stress in the clinical sector. Chest X-ray scan is the standard imaging diagnosis test employed for pneumonia disease. Automatic detection of COVID-19 helps to control the community outbreak but tracing this viral infection through X-ray results in a challenging task in the medical community. To automatically detect the viral disease in order to reduce the mortality rate, an effective COVID-19 detection method is modelled in this research by the proposed manta-ray multi-verse optimization-based hierarchical attention network (MRMVO-based HAN) classifier. Accordingly, the MRMVO is the incorporation of manta-ray foraging optimization and multi-verse optimizer. Based on the segmented lung lobes, the features are acquired from segmented regions in such a way that the process of COVID-19 detection mechanism is carried out with the features acquired from interested lobe regions. The proposed method has good performance with the measures, such as accuracy, true positive rate and true negative rate with the values of 93.367, 89.921 and 95.071%.
Alaska pollock gelatin sealant shows long-term efficacy and safety in a pulmonary air leakage rat model
Authors: Yanagihara Takahiro , Maki Naoki , Kawamura Tomoyuki , Kobayashi Naohiro , Kikuchi Shinji , Goto Yukinobu , Ichimura Hideo , Watanabe Shiharu , Taguchi Tetsushi , Sato Yukio
Published: October 2022

OBJECTIVES

Postoperative prolonged air leakage is a frequent complication following lung resection. We have shown the high adhesive quality of a newly developed sealant based on a hydrophobically modified Alaska pollock-derived gelatin (ApGltn) sealant in acute in vivo settings. The purpose of this study was to investigate the long-term efficacy and safety of ApGltn sealant using rats as a preclinical model.

METHODS

An air leakage rat model with a 5-mm pleural defect was created, to which ApGltn sealant or fibrin sealant was applied. In both groups, the rats were evaluated on days 1, 7, 14 and 28. In the ApGltn sealant group, days 56 and 84 were added to evaluate absorption as sealant was still present on day 28. The number of rats in each subgroup was 4 (for a total of 40). Lung specimens and blood samples were obtained for histological and haematological assessment.

RESULTS

No findings suggesting infection or air leakage were observed. ApGltn sealant was absorbed from day 56 to day 84. Histologically, although neutrophil and lymphocyte infiltrations on the lung side did not differ between groups, those on the sealant side were significantly less in the ApGltn sealant group. Blood sample tests revealed no significant findings suggesting inflammation or organ damage in either group.

CONCLUSIONS

ApGltn sealant showed long-term sealing efficacy and safety with mild inflammation in a pulmonary air leakage rat model. ApGltn sealant is expected to be a safe and effective sealant for clinical applications.
Risk factors for cardiac implantable electronic device infections: a nationwide Danish study
Authors: Olsen Thomas , Jørgensen Ole Dan , Nielsen Jens Cosedis , Thøgersen Anna Margrethe , Philbert Berit Thornvig , Frausing Maria Hee Jung Park , Sandgaard Niels Christian Foldager , Johansen Jens Brock
Published: October 2022

Aims

Cardiac implantable electronic device (CIED) infection is a severe complication to modern management of cardiac arrhythmias. The CIED type and the type of surgery are recognized as risk factors for CIED infections, but knowledge of patient-related risk factors is scarce. This study aimed to identify lifelong patient-related risk factors for CIED infections.

Methods and results

Consecutive Danish patients undergoing a CIED implantation or reoperation between January 1996 and April 2018 were included. The cohort consisted of 84 429 patients undergoing 108 494 CIED surgeries with a combined follow-up of 458 257 CIED-years. A total of 1556 CIED explantations were classified as either pocket (n = 1022) or systemic CIED infection (n = 534). Data were cross-linked with records from the Danish National Patient Registry and the Danish National Prescription Registry. Using multiple-record and multiple-event per subject proportional hazard analysis, specific patient-related risk factors were identified but with several variations amongst the subtypes of CIED infection. CIED reoperations were associated with the highest risk of pocket CIED infection but also CIED type, young age, and prior valvular surgery [hazard ratio (HR): 1.62, 95% confidence interval (CI): 1.29–2.04]. Severe renal insufficiency/dialysis (HR: 2.40, 95% CI: 1.65–3.49), dermatitis (HR: 2.80, 95% CI: 1.92–4.05), and prior valvular surgery (HR: 2.09, 95% CI: 1.59–2.75) were associated with the highest risk of systemic CIED infections. Congestive heart failure, ischaemic heart disease, malignancy, chronic obstructive pulmonary disease, and temporary pacing were not significant at multivariate analysis.

Conclusion

Specific comorbidities and surgical procedures were associated with a higher risk of CIED infections but with variations amongst pocket and systemic CIED infection. Pocket CIED infections were associated with CIED reoperations, young age and more complex type of CIED, whereas systemic CIED infections were associated with risk factors predisposing to bacteraemia.
Fully joint inversion of the 2016 Mw 7.6 Chiloé earthquake
Authors: Bravo F , Peyrat S , Delgado F , Fuentes M , Derode B , Perez A , Campos J
Published: October 2022

A large (Mw 7.6) megathrust earthquake occurred on 2016 December 25 in Southern Chile, south of the Chiloé Island (74.2°W, 43.3°S) in the South America–Nazca subduction zone. This earthquake was the first large event in this seismotectonic segment since the Mw 9.5 1960 Valdivia megathrust earthquake and broke a ~50-km-long segment of the southern part of its rupture zone. Source parameters are inferred from teleseismic broad-bands, strong motions, GPS, cGPS, InSAR and tide gauge data. We show that the joint inversion significantly improves the resolution of the slip distribution, taking advantage of each data set. Our slip models predict a single slip patch of 70 km × 60 km with a maximum slip of 3.2 ± 0.8 m and a moment magnitude of 7.64. The hypothesis from previous studies that the Chiloé earthquake released energy accumulated before the Valdivia earthquake is not supported by the ensemble of geodetic, seismological and tsunami data. Hence, the Chiloé earthquake most likely released all the strain accumulated in the rupture area since the 1960 earthquake.
Longitudinal Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Antibody Responses and Identification of Vaccine Breakthrough Infections Among Healthcare Workers Using Nucleocapsid Immunoglobulin G
Authors: Anderson Mark , Stec Michael , Gosha Amy , Mohammad Taha , Boler Michael , Tojo Suarez Rebeca , Behun Dylan , Landay Alan , Cloherty Gavin , Moy James
Published: October 2022

Background

Long-term studies of vaccine recipients are necessary to understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody durability and assess the impact of booster doses on antibody levels and protection from infection. The identification of vaccine breakthrough infections among fully vaccinated populations will be important in understanding vaccine efficacy and SARS-CoV-2 vaccine escape capacity.

Methods

SARS-CoV-2 spike (S) receptor-binding domain and nucleocapsid (N) immunoglobulin (Ig) G levels were measured in a longitudinal study of 1000 Chicago healthcare workers who were infection naive or previously infected and then vaccinated. Changes in S and N IgG were followed up through 14 months, and vaccine breakthrough infections were identified by increasing levels of N IgG.

Results

SARS-CoV-2 S IgG antibody levels among previously infected and previously noninfected individuals decreased steadily for 11 months after vaccination. Administration of a booster 8–11 months after vaccination increased S IgG levels >2-fold beyond those observed after 2 doses, resulting in S IgG levels that were indistinguishable between previously infected and uninfected individuals. Increases in N IgG identified vaccine breakthrough infections and showed >15% breakthrough infection rates during the Omicron wave starting in December 2021.

Conclusions

These results demonstrate SARS-CoV-2 antibody changes after vaccination and breakthrough infections and identify high levels of vaccine breakthrough infections during the Omicron wave, based on N IgG increases.
The Person of the Author: Constructing Gendered Scholars in Religious Studies Book Reviews
Authors: Ali Kecia , Serrano Lolo
Published: October 2022

This article uses quantitative and qualitative methods to explore persistent gender biases in fifteen years of book reviews in the Journal of the American Academy of Religion (2006–2020). The JAAR has historically reviewed books by men and relied on male reviewers out of proportion to their share of the academy’s membership. Although these rates have shifted toward balance over time, sexist biases in reviewers’ language and citation practices persist. In keeping with other research on gendered agency in language, we find that reviewers of all genders emphasize male scholars’ expertise and esteem and disproportionately refer to male thinkers and their ideas in reviews, with male reviewers also citing work by men at a much higher rate. We argue that these practices, which both reflect and compound existing inequalities in the field of religious studies as well as in academia and society broadly, should be changed and suggest some strategies for reviewers, editors, and journals to adopt.
Distinct components of alert fatigue in physicians’ responses to a noninterruptive clinical decision support alert
Authors: Murad Douglas A , Tsugawa Yusuke , Elashoff David A , Baldwin Kevin M , Bell Douglas S
Published: October 2022

Objective

Clinical decision support (CDS) alerts may improve health care quality but “alert fatigue” can reduce provider responsiveness. We analyzed how the introduction of competing alerts affected provider adherence to a single depression screening alert.

Materials and Methods

We analyzed the audit data from all occurrences of a CDS alert at a large academic health system. For patients who screen positive for depression during ambulatory visits, a noninterruptive alert was presented, offering a number of relevant documentation actions. Alert adherence was defined as the selection of any option offered within the alert. We assessed the effect of competing clinical guidance alerts presented during the same encounter and the total of all CDS alerts that the same provider had seen in the prior 90 days, on the probability of depression screen alert adherence, adjusting for physician and patient characteristics.

Results

The depression alert fired during 55 649 office visits involving 418 physicians and 40 474 patients over 41 months. After adjustment, physicians who had seen the most alerts in the prior 90 days were much less likely to respond (adjusted OR highest–lowest quartile, 0.38; 95% CI 0.35–0.42; P < .001). Competing alerts in the same visit further reduced the likelihood of adherence only among physicians in the middle two quartiles of alert exposure in the prior 90 days.

Conclusions

Adherence to a noninterruptive depression alert was strongly associated with the provider’s cumulative alert exposure over the past quarter. Health systems should monitor providers’ recent alert exposure as a measure of alert fatigue.
The urban wage premium and spatial sorting on observed and unobserved ability
Authors: Eliasson Kent , Westerlund Olle
Published: October 2022

We estimate static and dynamic agglomeration effects on earnings among university graduates using Swedish longitudinal population register data. The prime interest lies with whether and how the dynamic effects of big city work experience vary by observed ability of workers and whether the effects are portable after relocation. Urban wage premium and spatial sorting of university graduates are analysed by using information on school grades, parental education and university rank. We find that the value of accumulated big city work experience increases with observed ability. The dynamic premium of working in bigger cities is not lost when moving to smaller cities, suggesting that it reflects learning effects and human capital accumulation. Our findings indicate systematic spatial sorting on observed indicators of ability as well as on unobserved productive traits. Sorting on unobserved abilities is driven primarily by graduates in the upper part of the observed ability distribution and is apparent also when taking dynamic learning effects into consideration.
Spermine inhibits PAMP-induced ROS and Ca2+ burst and reshapes the transcriptional landscape of PAMP-triggered immunity in Arabidopsis
Authors: Zhang Chi , Atanasov Kostadin E , Alcázar Rubén
Published: October 2022

Polyamines are small polycationic amines whose levels increase during defense. Previous studies support the contribution of the polyamine spermine to defense responses. However, the potential contribution of spermine to pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) has not been completely established. Here, we compared the contribution of spermine and putrescine to early and late PTI responses in Arabidopsis. We found that putrescine and spermine have opposite effects on PAMP-elicited reactive oxygen species (ROS) production, with putrescine increasing and spermine lowering the flg22-stimulated ROS burst. Through genetic and pharmacological approaches, we found that the inhibitory effect of spermine on flg22-elicited ROS production is independent of polyamine oxidation, nitric oxide, and salicylic acid signaling but resembles chemical inhibition of RBOHD (RESPIRATORY BURST OXIDASE HOMOLOG D). Spermine can also suppress ROS elicited by FLS2-independent but RBOHD-dependent pathways, thus pointing to compromised RBOHD activity. Consistent with this, we found that spermine but not putrescine dampens flg22-stimulated cytosolic Ca2+ influx. Finally, we found that both polyamines differentially reshape transcriptional responses during PTI and disease resistance to Pseudomonas syringae. Overall, we provide evidence for the differential contributions of putrescine and spermine to PTI, with an impact on plant defense.
Inferring subhalo effective density slopes from strong lensing observations with neural likelihood-ratio estimation
Authors: Zhang Gemma , Mishra-Sharma Siddharth , Dvorkin Cora
Published: October 2022

Strong gravitational lensing has emerged as a promising approach for probing dark matter (DM) models on sub-galactic scales. Recent work has proposed the subhalo effective density slope as a more reliable observable than the commonly used subhalo mass function. The subhalo effective density slope is a measurement independent of assumptions about the underlying density profile and can be inferred for individual subhaloes through traditional sampling methods. To go beyond individual subhalo measurements, we leverage recent advances in machine learning and introduce a neural likelihood-ratio estimator to infer an effective density slope for populations of subhaloes. We demonstrate that our method is capable of harnessing the statistical power of multiple subhaloes (within and across multiple images) to distinguish between characteristics of different subhalo populations. The computational efficiency warranted by the neural likelihood-ratio estimator over traditional sampling enables statistical studies of DM perturbers and is particularly useful as we expect an influx of strong lensing systems from upcoming surveys.
Mitochondrial aggregation caused by cytochalasin B compromises the efficiency and safety of three-parent embryo
Authors: Li Ying , Shi Sanbao , Yuan Jin , Xiao Xi , Ji Dongmei , Pan Jianxin , Min Zhunyuan , Wang Hao , Sha Hongying , Ji Yazhong
Published: October 2022

It is widely accepted that cytochalasin B (CB) is required in enucleation of the oocyte in order to stabilize the cytoplasm. However, CB treatment results in the uneven distribution of mitochondria, with aggregation towards the nucleus, which might compromise the efficiency and safety of a three-parent embryo. Here, we demonstrated that CB treatment affected mitochondrial dynamics, spindle morphology and mitochondrial DNA carryover in a concentration-dependent manner. Our results showed that mouse oocytes treated with over 1 μg/ml CB exhibited a more aggregated pattern of mitochondria and diminished filamentous actin expression. Abnormal fission of mitochondria together with changes in spindle morphology increased as CB concentration escalated. Based on the results of mouse experiments, we further revealed the practical value of these findings in human oocytes. Chip-based digital PCR and pyrosequencing revealed that the mitochondrial carryover in reconstituted human embryos was significantly reduced by modifying the concentration of CB from the standard 5 μg/ml to 1 μg/ml before spindle transfer and pronuclear transfer. In conclusion, our findings provide an optimal manipulation for improving the efficiency and safety of mitochondrial replacement therapy.
Acute heart failure due to left common iliac arteriovenous fistula: A case of VEXAS syndrome
Authors: Yamaguchi Hiroki , Kobayashi Daisuke , Nakamura Gen , Aida Ryo , Horii Yosuke , Okamoto Takeshi , Murakami Shuichi , Kondo Daisuke , Tsuchida Naomi , Uchiyama Yuri , Maeda Ayaka , Kirino Yohei , Matsumoto Naomichi , Kurosawa Yoichi , Hasegawa Eriko , Wakamatsu Ayako , Narita Ichiei
Published: October 2022

We describe the case of a 78-year-old man presenting with multiple oedematous erythemas, fever, and arthralgia who subsequently developed neutrophil infiltration into the cartilage of the bilateral auricularis, consistent with relapsing polychondritis. A skin biopsy of the erythema on his right arm showed dense neutrophilic infiltration into the dermis, while a bone marrow aspirate revealed myelodysplastic syndromes with characteristic vacuoles in myeloid precursor cells. Although the patient achieved remission with high-dose oral prednisolone, the inflammatory symptoms relapsed, and he was resistant to colchicine and cyclosporine. The patient spontaneously developed left leg oedema and high-output cardiac failure caused by an arteriovenous fistula with a common iliac artery aneurysm. We successfully performed a two-stage surgery using internal iliac artery coil embolisation and endovascular aortic repair of the iliac aneurysm. We assumed the patient was suffering from large-vessel vasculitis such as giant cell arteritis or Takayasu’s arteritis. We treated him with tocilizumab in addition to prednisolone, and the febrile events and elevated C-reactive protein levels improved. One year later, sequencing of ubiquitylation-initiating E1 enzyme using peripheral blood leucocytes revealed somatic variants (c.121A>C p.Met41Leu), confirming the diagnosis of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. This case suggests that arteriovenous fistula could be a complication of VEXAS syndrome with large-vessel vasculitis, and adequate surgical intervention and prompt diagnosis are essential for rescue. Although arteriovenous fistula is a rare complication of VEXAS syndrome, physicians should be aware of this complication to ensure prompt diagnosis and timely surgical intervention.
CARD 2023: expanded curation, support for machine learning, and resistome prediction at the Comprehensive Antibiotic Resistance Database
Authors: Alcock Brian P , Huynh William , Chalil Romeo , Smith Keaton W , Raphenya Amogelang R , Wlodarski Mateusz A , Edalatmand Arman , Petkau Aaron , Syed Sohaib A , Tsang Kara K , Baker Sheridan J C , Dave Mugdha , McCarthy Madeline C , Mukiri Karyn M , Nasir Jalees A , Golbon Bahar , Imtiaz Hamna , Jiang Xingjian , Kaur Komal , Kwong Megan , Liang Zi Cheng , Niu Keyu C , Shan Prabakar , Yang Jasmine Y J , Gray Kristen L , Hoad Gemma R , Jia Baofeng , Bhando Timsy , Carfrae Lindsey A , Farha Maya A , French Shawn , Gordzevich Rodion , Rachwalski Kenneth , Tu Megan M , Bordeleau Emily , Dooley Damion , Griffiths Emma , Zubyk Haley L , Brown Eric D , Maguire Finlay , Beiko Robert G , Hsiao William W L , Brinkman Fiona S L , Van Domselaar Gary , McArthur Andrew G
Published: October 2022

The Comprehensive Antibiotic Resistance Database (CARD; card.mcmaster.ca) combines the Antibiotic Resistance Ontology (ARO) with curated AMR gene (ARG) sequences and resistance-conferring mutations to provide an informatics framework for annotation and interpretation of resistomes. As of version 3.2.4, CARD encompasses 6627 ontology terms, 5010 reference sequences, 1933 mutations, 3004 publications, and 5057 AMR detection models that can be used by the accompanying Resistance Gene Identifier (RGI) software to annotate genomic or metagenomic sequences. Focused curation enhancements since 2020 include expanded β-lactamase curation, incorporation of likelihood-based AMR mutations for Mycobacterium tuberculosis, addition of disinfectants and antiseptics plus their associated ARGs, and systematic curation of resistance-modifying agents. This expanded curation includes 180 new AMR gene families, 15 new drug classes, 1 new resistance mechanism, and two new ontological relationships: evolutionary_variant_of and is_small_molecule_inhibitor. In silico prediction of resistomes and prevalence statistics of ARGs has been expanded to 377 pathogens, 21,079 chromosomes, 2,662 genomic islands, 41,828 plasmids and 155,606 whole-genome shotgun assemblies, resulting in collation of 322,710 unique ARG allele sequences. New features include the CARD:Live collection of community submitted isolate resistome data and the introduction of standardized 15 character CARD Short Names for ARGs to support machine learning efforts.
Steroidal or non-steroidal MRAs: should we still enable RAASi use through K binders?
Authors: Gregg L Parker , Navaneethan Sankar D
Published: October 2022

Renin–angiotensin–aldosterone system inhibitors (RAASi) and mineralocorticoid receptor antagonists (MRAs) are important interventions to improve outcomes in patients with chronic kidney disease and heart failure, but their use is limited in some patients by the development of hyperkalemia. The risk of hyperkalemia may differ between agents, with one trial showing lower risk of hyperkalemia with the novel non-steroidal MRA finerenone compared with steroidal MRA spironolactone. Novel potassium binders, including patiromer and sodium zirconium cyclosilicate, are available interventions to manage hyperkalemia and enable continuation of RAASi and MRAs in patients who could benefit from these treatments. These agents bind free potassium ions in the lumen of the gastrointestinal tract to prevent the absorption of dietary potassium and increase potassium secretion. Several studies showed that potassium binders are effective compared with placebo for preventing hyperkalemia or steroidal MRA discontinuation, but none has evaluated whether this strategy impacts clinically important endpoints such as cardiovascular events. Due to this and other limitations related to cost, clinical availability, pill burden and patient selection, alternative potential strategies to mitigate hyperkalemia may be more practical. Conservative strategies include increased monitoring and use of loop or thiazide diuretics to increase urinary potassium excretion. Non-steroidal MRAs may have a lower risk of hyperkalemia than steroidal MRAs and have stronger anti-inflammatory and anti-fibrotic effects with resultant reduced risk of kidney disease progression. Sodium-glucose cotransporter-2 inhibitors also decrease hyperkalemia risk in patients on MRAs and decrease cardiovascular events and kidney disease progression. These may be better first-line interventions to obviate the need for potassium binders and offer additional benefits.
Adolescent fluoxetine exposure increases ERK-related signaling within the prefrontal cortex of adult male Sprague-Dawley rats
Authors: Themann Anapaula , Rodriguez Minerva , Garcia-Carachure Israel , Lira Omar , Iñiguez Sergio D
Published: October 2022

There has been a disproportionate increase in fluoxetine (FLX) prescription rates within the juvenile population. Thus, we evaluated how adolescent FLX exposure alters expression/phosphorylation of proteins from the extracellular signal-regulated kinase (ERK)-1/2 cascade within the adult prefrontal cortex (PFC). Male Sprague-Dawley rats were exposed to FLX (20 mg/kg) for 15 consecutive days [postnatal day (PD) 35–49]. At PD70 (adulthood), we examined protein markers for ERK1/2, ribosomal S6 kinase (RSK) and mammalian target of rapamycin (mTOR). FLX-pretreatment decreased body weight, while increasing PFC phosphorylation of ERK1/2 and RSK, as well as total mTOR protein expression in adulthood. We provide first-line evidence that juvenile FLX pretreatment induces long-term decreases in body weight gain, along with neurobiological changes in the adult PFC—highlighting that early life antidepressant exposure increases ERK-related signaling markers in later life.
Prologue
Authors: Shirk Susan L.
Published: October 2022

This chapter recaps the increasingly hostile standoff between China and the world in various domains, such as economic and technological decoupling, territorial disputes, and pandemic cooperation. Unlike the conventional wisdom that primarily attributes the deteriorating relationships to the shifting balance of power or the rise of populist politicians or the “China-containment” strategy in the West, the author introduces her argument that emphasizes the spillover effect of Chinese domestic politics. The swing toward confrontation in Chinese policy began under collective leadership in Hu Jintao’s second term of office and increased under Xi Jinping’s overcentralization of coercive power. The international backlash is growing and leading to a new cold war that is very different from the US-Soviet cold war because of economic interdependence.
Going to Extremes
Authors: Shirk Susan L.
Published: October 2022

This chapter explores how Xi Jinping’s consolidation of domestic political power shapes his foreign policy. After Xi recentralized the fragmented bureaucracy, streamlined the policymaking process, and effectively established himself as the commander-in-chief through various campaigns, he chose a more aggressive foreign policy approach rather than pacifying its Asian neighbors and the United States. With the backing of a unified force combing the PLA, the Coast Guard, and the public security apparatus, Xi has been stepping up the control over China’s border regions, such as Tibet, Xinjiang, and Hong Kong, punishing China’s Asian neighbors, such as South Korea, for cozying up to the United States, and actively expanding its global influence through projects like One Belt One Road. Xi has propelled China’s overreach on the global stage initiated since Hu’s second term to the next level.
Downward Spiral
Authors: Shirk Susan L.
Published: October 2022

This chapter discusses how Xi Jinping’s rule and American responses have interacted to cause US-China relations to deteriorate under the Trump and Biden administrations. During the Trump administration, China’s increasingly belligerent foreign policy brought hawkish elements to the fore especially during Trump’s campaign for re-election. After Biden entered the White House, Xi Jinping doubled down on his global overreach rather than signaling a desire for reconciliation. With the recent cases of China’s border clash with India, trade sanctions to punish Australia, the more frequent maritime incursions in Asia, and the support for Russia’s invasion of Ukraine, this chapter concludes that the overreaching is likely to be more acute in Xi’s third term. It also recognizes that China’s peaceful rise would require gradual political reform that is missing today under Xi Jinping.
The Stages of Dementia
Authors: Noble James M.
Published: October 2022

This chapter discusses the stages of dementia. People with dementia may pass through the stages of mild, moderate, and severe dementia slowly or quickly. The exact duration of each stage can be difficult to predict, but a recognizable progression within each stage is nearly always seen, and when someone has moved from one stage to the next is apparent. The prognosis of dementia can be viewed in the short term (over the next few months) and the long term (what lies ahead further in the future). With the exception of dementia immediately following a single large stroke and dementia resulting from untreated subcortical vascular disease, all other forms of dementia progress over time. Overall, more than two-thirds of functional abilities are lost in the final stage of dementia, which is known as the terminal decline. The chapter then considers life expectancy in dementia.
Lifestyle Management and Nonpharmacologic Therapies for People with Dementia and Their Caregivers
Authors: Noble James M.
Published: October 2022

This chapter highlights the role of lifestyle management and nonpharmacologic therapies in the treatment and prevention of dementia. Once dementia is diagnosed, it is important to consider non-medication approaches that may help with memory loss. Diet and exercise have the potential to address some of the early brain changes in dementia, but their role in controlling or delaying dementia symptoms remains uncertain. In addition to diet and physical exercise, activities involving socialization and cognitive stimulation may help aspects of dementia and have overlapping benefits, such as the physical activity involved in leaving the home to attend a social activity. Some aspects of lifestyle management may have no proven bearing on dementias, but these practices are still important in managing the long-term health needs associated with aging, including fighting frailty; maintaining muscle strength, mobility, and balance; and reducing cardiovascular risks. The chapter then considers the importance of developing a prescriptive, proactive plan of care. It also looks at methods to support the health and well-being of caregivers.
Gaining Access and Losing Information
Authors: Dunaway Johanna , Searles Kathleen
Published: October 2022

As mobile devices proliferate, people turn to their smartphones for their information needs. While increased access to information via mobile devices benefits an informed citizenry, it isn’t clear that access equates to more learning. To reconcile competing accounts of mobile devices as a democratic leveler or divider, this book advances a framework that distinguishes between physical access and cognitive access to explain how technology—and mobile technology specifically—affects information processing following exposure. In this chapter, the interdisciplinary approach and framework put forward in this book are first situated in a history of media effects research, articulating the need for increased attention to the effects of communication technology on the presentation and content of information. This tradition motivates the theoretical and empirical work set forth in this book, with important implications for democracy and the news industry.
Mobile Effects on Access and Exposure
Authors: Dunaway Johanna , Searles Kathleen
Published: October 2022

This chapter reviews global and domestic patterns of internet access and mobile use. It explores wired and mobile internet access and reach by demographics, across countries, and across time. The data show not only the increasing use of mobile devices, but a growing dependence on mobile-only internet access among many. In conclusion, this chapter posits a trade-off between breadth and depth when it comes to exposure to digital news and political information, wherein mobile technology reaches a large audience but with great limitations on the depth of exposure. Broadly, these data offer support for the physical and cognitive access (PCA) framework.
News Exposure and Information Processing in a Post-Broadcast Media Environment
Authors: Dunaway Johanna , Searles Kathleen
Published: October 2022

This concluding chapter describes the empirical, theoretical, and methodological contributions made in this book. This chapter also discusses the normative implications for ongoing debates about lingering and systematic digital information inequities, how information communication technology can help or hinder an informed citizenry, and practical consequences for journalists and news consumers in a mobile world. We situate our findings, framework, and theory in the history of the literature on media effects before we conclude with a discussion about how our framework and theory are applicable to other changing communication technologies and how they might be usefully applied in future political communication research.
Application
Authors: Ní Chaoimh Eadaoin
Published: October 2022

Chapter 4 looks at case law that invoke (with or without success) the Legislative Priority Rule across a range of sectors, including the Common Agricultural Policy, public health and safety, consumer protection, and environmental protection. What emerges is a jurisprudence that oscillates between pre-empting national competence in these fields and authorizing EU compliant regulation, and from imposing the EU standard, to deciding that it does not apply. Far from signalling incoherence or subjectivity, this case law generally reflects the EU legislative acquis, which seeks to both integrate and regulate the internal market for goods. In other words, it is varied exactly because the underlying EU legislation is varied. What is more, the Legislative Priority Rule can provide a framework for the European Court of Justice to interpret and enforce such legislation in a generally coherent and Treaty-compliant way. That said, reliance on the Rule can sometimes engender confusion, inconsistencies, and, in extremis, a risk that certain acts of national (legislation-based) discretion could escape review.
Towards a New Framework for Review
Authors: Ní Chaoimh Eadaoin
Published: October 2022

Previous chapters characterize the Legislative Priority Rule as the European Court of Justice’s ‘constitutional compass’ in distributing power in the presence of EU product legislation. For the Rule to enjoy this status, EU product legislation must be acknowledged as accommodating a more complex vertical distribution of power than what is often assumed. To this end, the book suggests replacing ‘harmonization models’ with a new framework which describes the impact of EU legislation in a better way than previous attempts, and assesses the impact of this legislation. This new framework abandons the traditional binary vision promoted under minimum/total harmonization in favour of a new categorization for national measures, including national acts of Treaty-based discretion, direct implementation, and legislation-based discretion. The new framework also identifies regulatory character as a distinct feature of an EU secondary measure, thus decoupling the existence of national discretion from application or not of the Legislative Priority Rule. In doing so, the book advances a more nuanced understanding of secondary legislation as it interacts with the free movement of goods and national law. This can in turn guide the Court’s approach to dispute resolution and enhance the transparency of its judgments, while ensuring respect for the hierarchy of norms.
Objective Imperatives
Authors: Walker Ralph C. S.
Published: October 2022

Kant has been much misunderstood. Partly this is his own fault; he is not a clear writer, and his attempts to simplify led his readers into considerable confusion. He holds that the moral law is objective, and is not derived from anything or anyone else. In this its status resembles that of pure theoretical reason, which includes logic and mathematics. He argues that the source of value does not lie in any end: the source of value is the moral law, which gives value to the end it requires us to promote. Thus he rejects consequentialism, and also sentimentalism and moral relativism.
Meter, Language, History, and the “Whole Human”
Authors: Eldridge Hannah Vandegrift
Published: October 2022

This chapter outlines the central questions and problems for metrical theory and practice in the years between 1720 and 1800. It takes the vigorous debate over whether and how to write hexameters (the meter of Homeric epic) in German as a central example demonstrating that meter is not defined solely by the phonological characteristics of a given language. In the second half, the chapter shows how metrical debates shaped and were shaped by the Late Enlightenment’s quest to understand how language plays a vital role in a subjectivity determined not only by reason but also by the emotions and the body as part of the quest for an aesthetics and anthropology of the “whole human.”
From Meter to Media and Materiality
Authors: Eldridge Hannah Vandegrift
Published: October 2022

This chapter locates (roughly) contemporary arguments about metrics in a wider history of metrical claims, revealing both affinities and breaks with that history. It analyzes these arguments in three almost entirely separate fields: first, historical overviews primarily designed for university or secondary school students; next, what is known in German Studies as “posthermeneutic” literary theory, which imports most of its concepts from information theory and mathematics; and, third, disciplines that study language and literature using quantitative and empirical methods. It highlights what is innovative and productive in each of them, adding contemporary approaches to the moments of eighteenth- and nineteenth-century metrical debates that help us think about meter and poetic experience. At the same time, it notes the shortcomings of each approach and the problems caused by their isolation from each other and literary studies as a whole.
Core Argument, Objections, Replies, and Outlook
Authors: Vickers Peter
Published: October 2022

This concluding discussion comes in two parts. First, the chapter draws on the lessons from all the previous chapters to lay out (i) the criteria for future-proof science, (ii) the core argument behind these criteria, and (iii) a workable strategy for actually identifying future-proof science. The book can be seen as building on the ‘externalist’ suggestion put forward by Oreskes (2019) that the best strategy is to use certain tools to critically assess the status of the scientific consensus, as a proxy for evaluating the entire wealth of first-order evidence from a large number of different perspectives. The shift from ‘internal’ evidence to ‘external’ evidence supports calls for adjustments to science education in our schools, with greater emphasis on teaching the ‘external’, second-order, or ‘sociological’ evidence for scientific claims. Second, this chapter raises some possible, outstanding objections, and provides preliminary responses.
Introduction
Authors: Hasan Zoya
Published: October 2022

The Introduction provides a historical outline of political trends that underlie the decline of the Indian National Congress. It provides an overview of the central arguments in the text: the role of ideology and organization in the making and unmaking of the Congress. The crisis and decline of the Congress are explained in the context of the rise of the Right and its impact on the politics of the Congress at the national level. A review of the decade of 2009–19 gives us insights into the processes of transformations that have changed India and grounded the Congress party in the midst of the rise of the Right.
Secular Politics on the Back Foot
Authors: Hasan Zoya
Published: October 2022

This chapter looks at the retreat of secular politics in the wider context of the rise of the Hindu Right and its critique of the Congress party’s secular practice. The politicisation of religion is responsible for secular decline, but that party alone is not responsible for it. The Congress party, too, is guilty of using religious issues for narrow political gains. The chapter argues that the Congress attempt to co-opt communitarian issues from time to time, especially issues of the Hindu Right, has not helped the party to regain support as it failed to pick up electoral dividends from this competitive wooing of the Hindu vote. But with all its inconsistencies and compromises, there is recognition on its part that secularism is essential for democracy. This stands out as the most crucial distinction between the Congress and the BJP’s political discourse, and it was this platform of secularism that kept communal polarization at bay for several decades. Whether secularism can remain India’s defining ideology in the future will depend on the strategies the Congress adopts to counter divisive politics engendered by this regime.
One of the Greatest Mysteries of Philosophy
Authors: Magri Tito
Published: October 2022

Besides conceptual change, Hume’s imagination replaces the intellect also in regard of substantive cognitive achievements. It allows explaining the difference between conception and cognition, which Hume thinks the other philosophers had ignored. Hume denies that any element of content can close the gap between conception and cognition. Rather, what marks cognition off is the attitude of assent to truth, a mode of conception that imagination, the vivacity of ideas, conveys to some of its ideas. Cognitive states with contents and attitudes issuing from the imagination constitute a mental kind: belief, the mental state that realizes in our nature probability, the imaginative and inferential kind of cognition. Belief differs from sense and memory or knowledge because of its origin and structure as well as of its cognitive roles. In particular it is uniquely susceptible to formation and revision by doxastic deliberation, our ordinary form of cognitive activity.
The Aeroplane and the Making of Modern India
Authors: Iqbal Aashique Ahmed
Published: October 2022

The aeroplane played a small but significant role in India’s transformation from colony to republic. Through the prism of aviation, both civil and military, this book traces the story of India’s journey from the Second World War to the emergence of India as a sovereign state. Drawing on archives in India and the United Kingdom, untapped personal collections, and newspaper reports it points to the critical impact of aviation on the shaping of modern South Asia. Control of aviation enabled the Indian state to survive the twin crises of partition and the war in Kashmir. The aeroplane also served as a potent symbol of modernity. The strategic and ideological importance of aircraft was not lost on other contenders for power in South Asia. The Indian princes and Pakistan both also invested substantially in aviation with a view to entrenching their sovereignty. The book makes two key arguments. First, a study of the state’s relationship with aviation reveals that independent India conceptualized sovereignty in ways that diverged radically from its colonial predecessor, stressing the importance of ruptures over continuities in explaining decolonization. Second, that aviation was critical to securing and legitimating independent India. Indeed, the indispensability of aircraft would be confirmed by the independent Indian government’s decision in 1953 to nationalize aviation, heralding an era of near-total state control of aviation. This book is the first comprehensive history of aviation in India and makes important interventions in a number of fields including histories of technology, warfare, politics, transport, and law.