bluuebunny/crossref_metadata_2025 huggingface dataset:
Post-War Welfare State Development
Authors: Nullmeier Frank , Kaufmann Franz-Xaver
Published: December 2021

The key characteristic of the ‘Golden Age’ (1945–1970s) is the breakthrough of universal social rights as the normative background for social policy and the responsibility of nation-states to ensure social justice, social protection, and poverty reduction. The expansion phase of the welfare state can be described in five dimensions: (1) self-conception: social policy as a special field of policy was transformed into a new type of statehood: the welfare state; (2) finance: social policy expenditure increased massively and social benefits grew faster than GDP; (3) performance: new programmes, higher benefit levels, and the inclusion of more and more groups, as well as the transition to active employment policies, strengthened the welfare state; (4) governance: the nation-state, the labour movement, and the employers are dominant actors in this period, but new social movements were playing an increasingly important role. Moreover, welfare production in this period was not only based on state institutions; (5) outcomes: the history of social policy until the 1970s is a process of tremendous progress, but accompanied by several ambivalent developments that were also the sources of crises in social policy in the next period. Nevertheless, key features of social protection programmes during the Golden Age have survived the wave of privatization and deregulation.
Religion and Classical Europe, Twelfth Century bce–600 ce
Authors: Auffarth Christoph
Published: December 2021

In a history of religion and Europe classical Antiquity is both an example of difference, that is, the polytheistic systems of Greek and Roman religions, and the beginnings of the monotheistic religions, which became the mainstream in medieval and modern Europe. Drawing on the rituals, symbols, and patterns of polytheism as the legacy of the palace cultures in the Ancient Near East and Greece (until 1200 bc), the city-states (poleis) adapted these to non-autocratic societies (polis-religion). In the empires of Hellenism and the Roman Empire itself, religions were not part of a power structure (e.g. a ruler-cult). Rather their urban character allowed a plural neighbourhood, in which the monotheistic religions were well integrated. In late Antiquity a long transformation formed the Middle Ages, when with the rise of Islam the Mediterranean became divided into three parts: the Islamic south, Greek Orthodoxy in the east, and Latin-speaking ‘Europe’ in the north-west.
Christian Democracy and Europe
Authors: van Kersbergen Kees
Published: December 2021

Christian democracy is the heir to the Catholic confessional parties that emerged in the late nineteenth century. It is a Western European phenomenon promoting a particular social policy, aimed at the moderation of social conflicts especially between social classes. With a distinctive ideology and by appealing to religion and religious values, Christian democracy became broadly attractive to all sections of the electorate. Christian democracy was also a key driver of international cooperation and integration, and particularly influential in the formation of the European Union. Yet the overall picture of Christian democratic parties in recent decades has been one of decline. Secularization plays an obvious role here. That said, there is still some room for political movements to respond actively and strategically to changes in their environment. The chapter concludes by discussing some future options for these parties.
Religion-State Relations in Europe
Authors: Madeley John T. S.
Published: December 2021

Europe is often taken to represent a global exception in matters of religion and secularity and some argue that much of the reason for this lies in the way religion-state relations are arranged. This chapter assesses these and related claims while summarily tracing the character, development, and impact of different relationship patterns in Europe as both ‘religion’ and ‘state’ have undergone massive change over the last 500 years. None of the fifty-odd current states of Europe meet any strict standard of religion–state separation; it can be argued nonetheless that the emergent and identifiable common European model is largely consistent with liberal egalitarian values. Key concepts are introduced: secular state, confessional state, religious state, religious establishment, and separationism.
The Conference of European Churches
Authors: Pavlovic Peter
Published: December 2021

This chapter outlines the history and work of the Conference of European Churches (CEC). CEC was founded in the middle of the Cold War in a divided Europe as an instrument promoting dialogue, bridge-building, cooperation, and ecumenical fellowship between churches of Anglican, Orthodox, and Protestant traditions. From its inception, CEC has promoted values of peace, reconciliation, justice, solidarity, and human dignity, and has been engaged in the building of trust and a sense of community in Europe. Through fostering the active engagement of churches in society, CEC has contributed to the discussion on European values and the future of the European project. The final section of the chapter elaborates on the theological foundations framing the churches’ action for justice and the common good. Such pursuits are central to the theological principles underpinning a healthy society.
Islam and Europe
Authors: Cesari Jocelyne
Published: December 2021

This chapter starts by critically analysing the most significant literature on the religiosity of Muslims in Europe. It then discusses two overlapping contexts which are key to explaining these forms of religiosity. On one hand, the global competition for Islamic orthodoxy, and on the other, the transformation of Islamic repertoires and institutions by European governments through the cumulative influence of securitization and secularism. The chapter argues that Islam is a topos activated at different moments in European history, from colonization to post-Second World War immigration. Post-9/11, growing pluralization and an emphasis on security have exacerbated an ‘us versus them’ mentality in which Muslims are definitely ‘them’.
Eastern Religions and Europe
Authors: Baumann Martin
Published: December 2021

This chapter begins with the Orientalist constructions of Eastern religions from the mid-sixteenth to the late nineteenth century. Subsequently, in Colonial Times, Asian reformers campaigned for Hinduism and Buddhism in the West leading to the establishing of the first institutions in Europe around 1900. From the 1960s onward, Europe saw the arrival of Hindu gurus and Buddhist teachers, later followed by the immigration of Asian workers and refugees. The conclusion highlights key constructions and images of Eastern religions and points to the ongoing processes of secularizationand commercialization which have repackaged practices and artefacts of Eastern religions for European preferences. The chapter argues that since the earliest encounters, Eastern religions represent both hope and promise for European philosophers, scholars, and practitioners. An awareness of the varied European imaginings enables a better understanding of the continuing fascination of Eastern religions on the part of sympathizers, practitioners, and the population in general.
Ireland and the United Kingdom
Authors: Ganiel Gladys , Steven Martin
Published: December 2021

This chapter examines the role of religion in Ireland and the United Kingdom in four stages, focusing on how divisions between Protestantism and Catholicism have contributed to political tensions and, at times, violence: (a) from the colonization of Ireland by Britain until the end of the Irish Civil War in 1923, when religion was used both to justify colonialism and to oppose it; (b) state-building in the early twentieth century, when religion impacted politics and society in ways that diverged from the wider European Christian democratic movement; (c) a period of secularization in the late twentieth century; and (d) a period of religious change, but at the same time persistence, in the late twentieth and early twenty-first centuries. It concludes by examining the impact of religion on the 2016 Brexit referendum vote, arguing that Brexit has destabilized political and religious relationships between the islands, with particular reference to Northern Ireland and Scotland.
Southeast Europe
Authors: Makrides Vasilios N.
Published: December 2021

This chapter charts the religious landscape of Southeast Europe and considers its religious specificities in their historical and geographical context. To this purpose, it discusses the significance of the Orthodox Christian heritage of Byzantium; the cleavage between Eastern and Western Christianity (both Roman Catholicism and Protestantism) and inter-confessional dynamics; the presence of Islam and the long period of Ottoman rule; the existence of other religions in the region; the role of Russia in Southeast European affairs; ethno-religious identities and the rise of nationalism; the communist and the post-communist periods; and finally, the negative discourse about the Balkans in the context of Southeast European distinctiveness, the modernization process, and the potential for religion in this.
Religion and Dictatorship in Europe
Authors: Steigmann-Gall Richard
Published: December 2021

This chapter explores the intersection of religion and dictatorship after the First World War. It examines the question of institutional relations between church and state, and seeks to explore how these relations shed light on the ideological relationship between religious traditions and fascism in particular. It does this by considering comparative perspectives across Europe, especially with regard to church–state relations but also in terms of politics, ideology, and culture. It goes on to explore the cases of Italian fascism and German Nazism, demonstrating how these regimes have typically been understood, as well as how they perpetuated a distinctive religious politics.
Neural processing associated with cognitive empathy in pedophilia and child sexual offending
Authors: Schuler Miriam , Mohnke Sebastian , Amelung Till , Beier Klaus M , Walter Martin , Ponseti Jorge , Schiffer Boris , Kruger Tillmann H C , Walter Henrik
Published: December 2021

Behavioral studies found evidence for superior cognitive empathy (CE) in pedophilic men without a history of child sexual offending (P − CSO) compared to pedophilic men with a history of child sexual offending (P + CSO). Functional magnetic resonance imaging (fMRI) studies also point to differences between P − CSO and P + CSO. Neural processing associated with CE has not yet been investigated. Therefore, the present study aimed to explore the neural correlates of CE in subjects with pedophilia with (P + CSO) and without (P − CSO) child sexual offending. 15 P + CSO, 15 P − CSO and 24 teleiophilic male controls (TC) performed a CE task during fMRI. We observed reduced activation in the left precuneus (Pcu) and increased activation in the left anterior cingulate cortex (ACC) in P − CSO compared to P + CSO. P − CSO also showed stronger connectivity between these regions, which might reflect a top-down modulation of the Pcu by the ACC toward an increased self-focused emotional reaction in social situations. There was also evidence for increased right superior temporal gyrus activation in P − CSO that might constitute a potentially compensatory recruitment due to the dampened Pcu activation. These findings provide first evidence for altered neural processing of CE in P − CSO and underline the importance of addressing CE in pedophilia and CSO in order to uncover processes relevant to effective prevention of child sexual abuse.
Prioritization of Surgery in Cancer Patients During the COVID-19 Pandemic
Authors: Donckier Vincent , Estache Antonio , Liberale Gabriel , Goldman Michel
Published: December 2021

The prioritization of surgical oncology over other elective interventions during COVID-19 has failed to preserve the quality of care in oncology and will likely lead to an increase of cancer-related mortality in the coming years. We propose five components for systems to improve the organization of surgical oncology during future crises, namely (1) a multidisciplinary governance structure employing predictive models and risk/benefit evaluations, (2) predefined quality objectives based on measurable markers (regularly reviewed and adapted), (3) temporary flexibility in therapeutic algorithms and authorization procedures (with associated safeguards), (4) systems to ensure access to transparent, apolitical information, and (5) explicit, dedicated logistical surgical capacities to optimize coordination and resource allocation.
Quality and readability of online health information on menopausal hormone therapy in Canada: what are our patients reading?
Authors: Murtaza Fahmeeda , Shirreff Lindsay , Huang Lina N. , Jacobson Michelle , Jarcevic Radomir , Christakis Marie K.
Published: December 2021

Objective:

To assess the quality and readability of 24 of the most accessed menopause hormone therapy (MHT) websites by Canadian women.

Methods:

The top 24 websites from Google, Bing, and Yahoo were identified using the search term “hormone replacement therapy.” Five menopause specialists assessed website content quality using the DISCERN Instrument, Journal of the American Medical Association (JAMA) benchmarks, and Abbott's Scale. Two reviewers assessed website credibility using the Health on the Net Foundation Code of Conduct certification, and website readability using the Simple Measure of Gobbledygook, Flesch-Kincaid Grade Level, and Flesch-Kincaid Read Ease formulae.

Results:

Scores for quality of information varied. The mean JAMA score was low at 2.3 ± 1.1 (out of 4). Only one website met all benchmarks. Fourteen websites (58%) had a good/excellent DISCERN score, while four (17%) had a poor/very poor score. For Abbott's Scale, both the mean authorship score at 2.2 ± 1.0 (out of 4) and mean content score at 45.9 ± 9.8 (out of 100) were low. Inter-rater reliability was high for all tools. Fifteen websites (63%) were Health on the Net Foundation Code of Conduct certified. The mean Flesch-Kincaid Read Ease was 42.7 ± 10.3, mean Flesch-Kincaid Grade Level was 12.3 ± 1.9, and mean Simple Measure of Gobbledygook grade level was 11.3 ± 1.5. Only one website presented content at a reading level recommended for the public. Websites meeting more JAMA benchmarks were significantly less readable (P < 0.05).

Conclusion:

Although good quality MHT information exists online, several resources are inaccurate or incomplete. Overall, these resources are not considered comprehensible by the public. There is a need to disseminate accurate, comprehensive, and understandable MHT information online.
The effects of estrogen deficiency and aging on myocardial deformation and motion in normotensive female rats
Authors: Maluleke Tshiamo T. , Millen Aletta M.E. , Michel Frédéric S.
Published: December 2021

Objective:

Estrogen deficiency is associated with left ventricular (LV) dysfunction in postmenopausal women and ovariectomized rats. Whether the relationship between estrogen deficiency and LV dysfunction is independent of cardiovascular disease (CVD) risk factors remains uncertain. This study assessed the effects of short-term and long-term estrogen deficiency on cardiac structure and function using conventional and speckle tracking echocardiography, independent of traditional CVD risk factors.

Methods:

Female Sprague-Dawley rats were divided into short-term (6 wks) ovariectomized (n = 9), short-term sham-operated (n = 10), long-term (6 mo) ovariectomized (n = 8), and long-term sham-operated (n = 9) groups. Cardiac geometry, systolic and diastolic function, and myocardial deformation and motion were measured using echocardiography.

Results:

Ovariectomy had no effect on conventional echocardiography measures of cardiac structure or function. Compared with short-term, long-term groups had reduced LV internal diameter (false discovery rate [FDR] adjusted P = 0.05) and impaired relaxation (e’; FDR adjusted P = 0.0005) independent of body mass and blood pressure (BP). Global longitudinal strain was impaired in ovariectomized compared with sham-operated rats (FDR adjusted P = 0.05), but not after adjusting for body mass and BP (FDR adjusted P = 0.16). Global longitudinal strain (FDR adjusted P = 0.05), strain rate (FDR adjusted P = 0.002), and velocity (FDR adjusted P = 0.04) were impaired in long-term compared with short-term groups. Global longitudinal strain rate remained impaired after adjustments for body mass and BP (FDR adjusted P = 0.02).

Conclusions:

Estrogen deficiency does not independently cause cardiac remodeling, LV dysfunction, or impaired myocardial deformation. Traditional CVD risk factors accompanying estrogen deficiency may account for cardiac remodeling and dysfunction observed in postmenopausal women.
Prevalence and factors associated with overactive bladder and stress urinary incontinence in the Japan Nurses’ Health Study
Authors: Nagai Kazue , Homma Yukio , Ideno Yuki , Hayashi Kunihiko
Published: December 2021

Objective:

In this study, we aimed to investigate the prevalence and factors associated with urinary symptoms using cross-sectional data from the Japan Nurses’ Health Study, a prospective cohort study among female nurses.

Methods:

A total of 12,198 women were included. We calculated the prevalence of urinary symptoms. Odds ratios with 95% confidence intervals were estimated to determine the odds for overactive bladder (OAB), stress urinary incontinence, and mixed urinary incontinence.

Results:

The mean age and body mass index (standard deviation, range) were 46.5 (±8.1, 27-82) years and 22.1 (±3.1, 12.9-44.6) kg/m2, respectively. The prevalence of OAB was 9.5% (OAB with urinary incontinence [-wet]: 5.4%, OAB without urinary incontinence: 4.1%), that of stress urinary incontinence (without OAB-wet) was 13.9%, and that of mixed urinary incontinence was 2.1%. Multivariable-adjusted logistic regression analysis showed a significant association between OAB and age 45 to 54 years, and postmenopausal status was moderately associated with OAB in that analysis. In the multivariable-adjusted model, age groups 45 to 49 and 50 to 54 years, body mass index 23-27.4 and ≥ 27.5 kg/m2, and parous status were significantly associated with stress urinary incontinence (without OAB-wet).

Conclusions:

This study showed a significant association of OAB with ages 45 to 54 years and postmenopausal status. Further studies should consider the association between time since menopause and OAB symptoms in the perimenopausal period. A high body mass index and parous status are strongly associated with stress urinary incontinence, and stress urinary incontinence symptoms may become less frequent after menopause.

Video Summary:

http://links.lww.com/MENO/A853.
Decision aids and shared decision making in urogynecology
Authors: Marques Felisha , Josloff Kevan , Hung Kristin , Wakamatsu May , Sepucha Karen R.
Published: December 2021

Objectives:

To examine the efficacy and acceptability of decision aids (DAs) in counseling urogynecology patients with prolapse, stress urinary incontinence, or refractory overactive bladder.

Methods:

This pilot study enrolled 33 patients into a control group that underwent usual care without a DA, followed by 33 patients into an intervention group where providers utilized a DA for counseling. Postvisit patient surveys assessed differences in treatment preference, knowledge, and in patient-physician collaboration using SURE, CollaboRATE, and Shared Decision Making (SDM) Process scales. Postvisit provider surveys assessed their perception of the usefulness and the difficulty of using a DA and visit length. Independent t tests were used for continuous variables (Knowledge and SDM Process scores) and Chi-Square for categorical variables (treatment preference, SURE, and CollaboRATE).

Results:

The majority of eligible patients 66/71 (93%) completed the survey. The intervention group trended toward higher knowledge scores (72% vs 60%, P 
= 0.06), clearer treatment preferences (85% vs 67%, P 
= 0.08), higher rates of top SURE scale scores (91% vs 73%, P 
= 0.11), and top CollaboRATE scores (75% vs 52%, P 
= 0.07). SDM process scores were similar across groups (3.2 vs 3.2, P 
= 0.96). Providers used the DA in 73% of intervention group visits and rated the visit length as “normal” in both groups (70% vs 76%, P 
= 0.78).

Conclusions:

There were no statistically significant differences between the control group and the intervention group. The use of DAs was acceptable to providers and indicated a trend toward increased patient knowledge, treatment preference, and satisfaction. A larger study is warranted to examine the impact of DAs on decision making and patient experience.

Video Summary:

http://links.lww.com/MENO/A856.
Salvage of Extensively Scarred Hands: Wide Awake Tenolysis and Interpositional Free Tissue Transfer
Authors: Ghoraba Samir M. , Alsharkawy Kareem G. , Hammad Mostafa , Samak Haitham A.
Published: December 2021

Background:

This study introduced a dedicated technical approach to extensive hand adhesions, combined with failed primary nerve reconstruction. Wide awakelocal anesthesia no tourniquet (WALANT) tenolysis and interpositional free tissue transfer forge the main facets of the proposed reconstructive strategy.

Methods:

A prospective study was conducted, including 22 patients diagnosed with extensive tendon adhesions in addition to failed primary nerve repair. After wide awake tenolysis, 20 adipofascial radial forearm flaps and two ALT flaps were used to wrap the tendons, whereas the nerves were grafted after complete separation from the tendons. Nerve recovery; final total range of motion of the fingers; and the disabilities of the arm, shoulder, and hand score were recorded in detail.

Results:

All flaps healed uneventfully. Final assessment of the median nerve revealed M3 or more motor power and S3 sensory recovery in all patients except one patient who attained no muscle power at all and S1 as regards the sensory assessment. The ulnar nerve evaluation revealed that two of five patients did not recover motor power at all (M0), and the remaining three patients recovered M3 motor power with variable sensory outcomes. Final assessment of total range of motion of the fingers and the DASH score showed a statistically significant improvement except for one patient.

Conclusion:

WALANT tenolysis and interposition of well-vascularized fascial flaps along with simultaneous nerve grafts in extensively scarred hands provided goodfunctional outcomes.
Attachment Issues: A Case Report of a Promising Sternal Implantation with 3D-printed Polyethylene
Authors: Bidois Lauren M. , Porter Chris , Singh Harsh P.
Published: December 2021

Sternal reconstruction is beneficial for chest wall stability, respiratory function, and cosmetics, with no superior prosthesis or method thus far identified. We present a case of sternal reconstruction in a patient 6 years post sternal removal using a 3D-printed, patient-specific, polyethylene prosthesis with reasonable short-term outcomes. We believe a polyethylene prosthesis shows advantages over other materials and is worth further investigation, providing a technique for attaching said prosthesis to the native tissues is established.
Experimental evolution to identify undescribed mechanisms of resistance to a novel cationic peptide antibiotic
Authors: Santos-Lopez A , Fritz MJ , Lombardo JB , Burr AHP , Heinrich VA , Marshall CW , Cooper VS
Published: December 2021

A key strategy for resolving the antibiotic resistance crisis is the development of new drugs with antimicrobial properties. The engineered cationic antimicrobial peptide WLBU2 (also known as PLG0206) is a promising broad-spectrum antimicrobial compound that has completed Phase I clinical studies. It has activity against Gram-negative and Gram-positive bacteria including infections associated with biofilm. No definitive mechanisms of resistance to WLBU2 have been identified. Here, we used experimental evolution under different levels of mutation supply and whole genome sequencing (WGS) to detect the genetic pathways and probable mechanisms of resistance to this peptide. We propagated populations of wild-type and mutatorPseudomonas aeruginosain the presence of WLBU2 and performed WGS of evolved populations and clones. Populations that survived WLBU2 treatment acquired a minimum of two mutations, making the acquisition of resistance more difficult than for most antibiotics, which can be tolerated by mutation of a single target. Major targets of resistance to WLBU2 included theorfNandpmrBgenes, previously described to confer resistance to other cationic peptides. More surprisingly, mutations that increase aggregation such as thewsppathway were also selected despite the ability of WLBU2 to kill cells growing in a biofilm. The results show how the experimental evolution and WGS can identify genetic targets and actions of new antimicrobial compounds and predict pathways to resistance of new antibiotics in clinical practice.
SARS-CoV-2 B.1.1.529 variant (Omicron) evades neutralization by sera from vaccinated and convalescent individuals
Authors: Rössler Annika , Riepler Lydia , Bante David , Laer Dorothee von , Kimpel Janine
Published: December 2021

Recently, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.1.529 (Omicron) has been described.

Here, we analyze titers of neutralizing antibodies of sera from convalescent or vaccinated individuals against the new B.1.1.529 variant and compared them with titers against other Variants of Concern (B.1.1.7, B.1.351, B.1617.2) using replication competent SARS-CoV-2 variants.

We found that sera from vaccinated individuals neutralized the B.1.1.529 variant to a much lesser extent than any other variant analyzed. Neutralization capacity against B.1.1.529 was maintained best against sera from super immune individuals (infected and vaccinated or vaccinated and infected).
Systematic multi-level analysis of an organelle proteome reveals new peroxisomal functions
Authors: Yifrach Eden , Holbrook-Smith Duncan , Bürgi Jérôme , Othman Alaa , Eisenstein Miriam , Van Roermund Carlo W.T , Visser Wouter , Tirosh Asa , Bibi Chen , Galor Shahar , Weil Uri , Fadel Amir , Peleg Yoav , Waterham Hans R , Wanders Ronald J A , Wilmanns Matthias , Zamboni Nicola , Schuldiner Maya , Zalckvar Einat
Published: December 2021

Seventy years following the discovery of peroxisomes, their proteome remains undefined. Uncovering the complete peroxisomal proteome, the peroxi-ome, is crucial for understanding peroxisomal activities and cellular metabolism. We used high-content microscopy to uncover the peroxi-ome of the model eukaryote – Saccharomyces cerevisiae. This strategy enabled us to expand the known organellar proteome by ∼40% and paved the way for performing systematic, whole-organellar proteome assays. Coupled with targeted experiments this allowed us to discover new peroxisomal functions. By characterizing the sub-organellar localization and protein targeting dependencies into the organelle, we unveiled non-canonical targeting routes. Metabolomic analysis of the peroxi-ome revealed the role of several newly-identified resident enzymes. Importantly, we found a regulatory role of peroxisomes during gluconeogenesis, which is fundamental for understanding cellular metabolism. With the current recognition that peroxisomes play a crucial part in organismal physiology, our approach lays the foundation for deep characterization of peroxisome function in health and disease.
Awake mouse brain photoacoustic and optical imaging through a transparent ultrasound cranial window
Authors: Mirg Shubham , Chen Haoyang , Turner Kevin L. , Liu Jinyun , Gluckman Bruce J. , Drew Patrick J. , Kothapalli Sri-Rajasekhar
Published: December 2021

Optical resolution photoacoustic microscopy (OR-PAM) can map the cerebral vasculature at capillary level resolution. However, the OR-PAM setup’s bulky imaging head makes awake mouse brain imaging challenging and inhibits its integration with other optical neuroimaging modalities. Moreover, the glass cranial windows used for optical microscopy are unsuitable for OR-PAM due to the acoustic impedance mismatch between the glass plate and the tissue. To overcome these challenges, we propose a lithium niobate based transparent ultrasound trans-ducer (TUT) as a cranial window on a thinned mouse skull. The TUT cranial window simplifies the imaging head considerably due to its dual functionality as an optical window and ultrasound transducer. The window remains stable for six weeks, with no noticeable inflammation and minimal bone regrowth. The TUT window’s potential is demonstrated by imaging the awake mouse cerebral vasculature using OR-PAM, intrinsic optical signal imaging and two-photon microscopy. The TUT cranial window can potentially also be used for ultrasound stimulation and simultaneous multimodal imaging of the awake mouse brain.
Towards Biophysical Markers of Depression Vulnerability
Authors: Pinotsis D.A. , Fitzgerald S. , See C. , Sementsova A. , Widge A. S.
Published: December 2021

A major difficulty with treating psychiatric disorders is their heterogeneity: different neural causes can lead to the same phenotype. To address this, we propose describing the underlying pathophysiology in terms of interpretable, biophysical parameters of a neural model derived from the electroencephalogram. We analyzed data from a small patient cohort of patients with depression and controls. We constructed biophysical models that describe neural dynamics in a cortical network activated during a task that is used to assess depression state. We show that biophysical model parameters are biomarkers, that is, variables that allow subtyping of depression at a biological level. They yield a low dimensional, interpretable feature space that allowed description of differences between individual patients with depressive symptoms. They capture internal heterogeneity/variance of depression state and achieve significantly better classification than commonly used EEG features. Our work is a proof of concept that a combination of biophysical models and machine learning may outperform earlier approaches based on classical statistics and raw brain data.
Dopamine D2Rs Coordinate Cue-Evoked Changes in Striatal Acetylcholine Levels
Authors: Martyniuk Kelly M. , Torres-Herraez Arturo , Rubinstein Marcelo , Labouesse Marie A. , Kellendonk Christoph
Published: December 2021

In the striatum, acetylcholine (ACh) neuron activity is modulated co-incident with dopamine (DA) release in response to unpredicted rewards and reward predicting cues and both neuromodulators are thought to regulate each other. While this co-regulation has been studied using stimulation studies, the existence of this mutual regulation in vivo during natural behavior is still largely unexplored. One long-standing controversy has been whether striatal DA is responsible for the induction of the cholinergic pause or whether D2R modulate a pause that is induced by other mechanisms. Here, we used genetically encoded sensors in combination with pharmacological and genetic inactivation of D2Rs from cholinergic interneurons (CINs) to simultaneously measure ACh and DA levels after CIN D2R inactivation. We found that CIN D2Rs are not necessary for the induction of cue induced dips in ACh levels but regulate dip lengths and rebound ACh levels. Importantly, D2R inactivation strongly decreased the temporal correlation between DA and Ach signals not only at cue presentation but also during the intertrial interval. This points to a general mechanism by which D2Rs coordinate both signals. At the behavioral level D2R antagonism increased the latency to lever press, which was not observed in CIN-selective D2R knock out mice. This latency correlated with the cue evoked dip length supporting a role of the ACh dip and it’s regulation by D2Rs in motivated behavior. Overall, our data indicate that striatal DA coordinate phasic ACh and DA signals via CIN D2Rs which is important for the regulation of motivated behavior.
Timing of exposure is critical in a highly sensitive model of SARS-CoV-2 transmission
Authors: Ganti Ketaki , Ferreri Lucas M. , Lee Chung-Young , Bair Camden R. , Delima Gabrielle K. , Holmes Kate E. , Suthar Mehul S. , Lowen Anice C.
Published: December 2021

Transmission efficiency is a critical factor determining the size of an outbreak of infectious disease. Indeed, the propensity of SARS-CoV-2 to transmit among humans precipitated and continues to sustain the COVID-19 pandemic. Nevertheless, the number of new cases among contacts is highly variable and underlying reasons for wide-ranging transmission outcomes remain unclear. Here, we evaluated viral spread in golden Syrian hamsters to define the impact of temporal and environmental conditions on the efficiency of SARS-CoV-2 transmission through the air. Our data show that exposure periods as brief as one hour are sufficient to support robust transmission. However, the timing after infection is critical for transmission success, with the highest frequency of transmission to contacts occurring at times of peak viral load in the donor animals. Relative humidity and temperature had no detectable impact on transmission when exposures were carried out with optimal timing. However, contrary to expectation, trends observed with sub-optimal exposure timing suggest improved transmission at high relative humidity or high temperature. In sum, among the conditions tested, our data reveal the timing of exposure to be the strongest determinant of SARS-CoV-2 transmission success and implicate viral load as an important driver of transmission.
Protein interaction network analysis reveals growth conditions-specific crosstalk between chromosomal DNA replication and other cellular processes in E. coli
Authors: Morcinek-Orłowska Joanna , Walter Beata Maria , Forquet Raphaël , Cysewski Dominik , Carlier Maxime , Meyer Sam , Glinkowska Monika
Published: December 2021

E. coli and many other bacterial species can alter their cell cycle according to nutrient availability. Under optimal conditions bacteria grow and divide very fast but they slow down the cell cycle when conditions deteriorate. This adaptability is underlined by mechanisms coordinating cell growth with duplication of genetic material and cell division. Several mechanisms regulating DNA replication process in E. coli have been described with biochemical details so far. Nevertheless we still don’t fully understand the source of remarkable precision that allows bacterial cells to coordinate their growth and chromosome replication. To shed light on regulation of E. coli DNA replication at systemic level, we used affinity purification coupled with mass spectrometry (AP-MS) to characterize protein-protein interactions (PPIs) formed by key E. coli replication proteins, under disparate bacterial growth conditions and phases. We present the resulting dynamic replication protein interaction network (PIN) and highlight links between DNA replication and several cellular processes, like outer membrane synthesis, RNA degradation and modification or starvation response.

Importance

DNA replication is a vital process, ensuring propagation of genetic material to progeny cells. Despite decades of studies we still don’t fully understand how bacteria coordinate chromosomal DNA duplication with cell growth and cell division under optimal and stressful conditions. At molecular level, regulation of processes, including DNA replication, is often executed through direct protein-protein interactions (PPIs). In this work we present PPIs formed by the key E. coli replication proteins under three different bacterial growth conditions. We show novel PPIs with confirmed impact on chromosomal DNA replication. Our results provide also alternative explanations of genetic interactions uncovered before by others for E.coli replication machinery.
Low circulating adropin levels in late-middle aged African Americans with poor cognitive performance
Authors: Aggarwal Geetika , Malmstrom Theodore K. , Morley John E. , Miller Douglas K. , Nguyen Andrew D. , Butler Andrew A.
Published: December 2021

We recently reported accelerated cognitive decline in Europeans aged >70 years with low circulating adropin levels. Adropin is a small, secreted peptide that is highly expressed in the human nervous system. Expression profiling indicate relationships between adropin expression in the human brain and pathways that affect dementia risk. Moreover, increased adropin expression or treatment using synthetic adropin improves cognition in mouse models of aging. Here we report that low circulating adropin concentrations also associate with poor cognition (worst quintile for a composite score derived from the MMSE and semantic fluency test) in late-middle aged community-dwelling African Americans (OR=0.775, P<0.05; age range 45-65y, n=352). The binomial logistic regression controlled for sex, age, education, cardiometabolic disease risk indicators, and obesity. Previous studies using cultured cells from the brains of human donors suggest high expression in astrocytes. In snRNA-seq data from the middle temporal gyrus (MTG) of human donors, adropin expression is higher in astrocytes relative to other cell types. Advanced age suppresses adropin expression in all cell-types, with no effect of dementia status. In cultured human astrocytes, adropin expression also declines with donor age. Additional analysis indicated positive correlations between adropin amd transcriptomic signatures of energy metabolism and protein synthesis that are adversely affected by donor age. Adropin expression is also suppressed by pro-inflammatory factors. Collectively, these data indicate low circulating adropin levels are a potential early risk indicator of cognitive impairment. Suppression of astrocyte adropin expression in the brain is a plausible link between aging, neuroinflammation, and risk of cognitive decline.
Nanoscale architecture and coordination of actin cores within the sealing zone of human osteoclasts
Authors: Portes Marion , Mangeat Thomas , Escallier Natacha , Raynaud-Messina Brigitte , Thibault Christophe , Maridonneau-Parini Isabelle , Vérollet Christel , Poincloux Renaud
Published: December 2021

Osteoclasts are unique in their capacity to degrade bone tissue. To achieve this process, osteoclasts form a specific structure called the sealing zone, which creates a close contact with bone and confines the release of protons and hydrolases for bone degradation. The sealing zone is composed of actin structures called podosomes nested in a dense actin network. The organization of these actin structures inside the sealing zone at the nano scale is still unknown. Here, we combine cutting-edge microscopy methods to reveal the nanoscale architecture and dynamics of the sealing zone formed by human osteoclasts on bone surface. Random illumination microscopy allowed the identification and live imaging of densely packed actin cores within the sealing zone. A cross-correlation analysis of the fluctuations of actin content at these cores indicates that they are locally synchronized. Further examination shows that the sealing zone is composed of groups of synchronized cores linked by α-actinin1 positive filaments, and encircled by adhesion complexes. Thus, we propose that the confinement of bone degradation mediators is achieved through the coordination of islets of actin cores and not by the global coordination of all podosomal subunits forming the sealing zone.
Boron Supply Restores Aluminum-Blocked Auxin Transport by Modulation PIN2 Trafficking in the Arabidopsis Roots
Authors: Tao Lin , Feng Yingming , Li Yalin , Li Xuewen , Meng Xiaodong , Li Meng , Pirayesh Niloufar , Mahmud Sakil , Shabala Sergey , Baluška František , Shi Lei , Yu Min
Published: December 2021

This study tested a hypothesis that boron (B) supply alleviates aluminum (Al) toxicity by modifying auxin distribution in functionally different root zones. Auxin distribution and transport at various Al and B ratios were analyzed using the range of molecular and imaging techniques. Al stress resulted in increased auxin accumulation in root apical meristem (MZ) and transition zones (TZ) while reducing its content in elongation zone (EZ). This phenomenon was explained by reduction in basipetal auxin transport caused by Al blockage of PIN2 endocytosis, regulated at posttranscriptional level. This inhibition of PIN2 endocytosis was dependent on actin filaments and microtubules. B supply facilitated the endocytosis and exocytosis of PIN2 carriers via recycling endosomes conjugated with IAA to modify Al-induced auxin depletion in the EZ. However, disruption of auxin signaling with auxinole did not alleviate Al-induced inhibition of root growth. B supply alleviates Al-induced inhibition of root growth via restoring the endocytic recycling of PIN2 proteins involved in the basipetal (shootward) auxin transport, restoring Al-induced auxin depletion in the elongation zone.

Short summary

Aluminum-intensified PIN2 abundance, nontranscriptional, via repressing PIN2 endocytosis to block polar auxin transport, and this adverse effect could be alleviated by boron supply.
Community access to rectal artesunate for malaria (CARAMAL): a large-scale observational implementation study in the Democratic Republic of the Congo, Nigeria and Uganda
Authors: Lengeler Christian , Burri Christian , Awor Phyllis , Athieno Prosciova , Kimera Joseph , Tumukunde Gloria , Angiro Irene , Tshefu Antoinette , Okitawutshu Jean , Kalenga Jean-Claude , Omoluabi Elizabeth , Akano Babatunde , Ayodeji Kazeem , Okon Charles , Yusuf Ocheche , Brunner Nina C , Delvento Giulia , Lee Tristan , Lambiris Mark , Visser Theodoor , Napier Harriet G , Cohen Justin M , Buj Valentina , Signorell Aita , Hetzel Manuel W ,   the CARAMAL Consortium
Published: December 2021

The key to reducing malaria deaths in highly endemic areas is prompt access to quality case management. Given that many severe cases occur at peripheral level, rectal artesunate (RAS) in the form of suppositories was developed in the 1990s. RAS allows the rapid initiation of life-saving antimalarial treatment, before referral to a health facility with full case management capabilities. One randomized controlled trial published in 2009 showed a protective effect of RAS pre-referral treatment against overall mortality of 26%, but with significant differences according to study sites and length of referral. Two important issues remained unaddressed to-date: (1) whether the mortality impact of RAS observed under controlled trial conditions could be replicated under real-world circumstances; and (2) clear operational guidance for the wide-scale implementation of RAS, including essential health system determinants for optimal impact.

From 2018 to 2020, the Community Access to Rectal Artesunate for Malaria (CARAMAL) project was conducted as a large-scale observational implementation study in Nigeria, Uganda and the Democratic Republic of the Congo (DRC). CARAMAL aimed to provide high-quality field evidence on the two issues above, in three remote settings with high malaria endemicity. In order to achieve this, a number of complementary study components were implemented. The core of the CARAMAL study was the Patient Surveillance System (PSS), which allowed to track cases of severe febrile illness from first contact at the periphery to a referral health facility, and then on to a Day 28 visit at the home of the patient. Community and provider cross-sectional surveys complemented the PSS.

Here we describe in some detail RAS implementation, as well as the key CARAMAL study components and basic implementation experience. This manuscript provides an extensive reference document for the companion papers describing the impact, referral process, post-referral treatment and cost-effectiveness of the RAS intervention.
Adverse event reviews in healthcare: What matters to patients and their family? A qualitative study exploring the perspective of patients and family
Authors: McQueen Jean , Gibson Kyle , Manson Moira , Francis Morag
Published: December 2021

Objectives

Explore what ‘good’ patient and family involvement in healthcare adverse event reviews may involve.

Design

Data was collected using semi-structured telephone interviews. Interview transcripts were analysed using an inductive thematic approach.

Setting

NHS Scotland.

Participants

19 interviews were conducted with patients who had experienced an adverse event during the provision of their healthcare, or their family member.

Results

Four key themes were derived from these interviews: trauma, communication, learning and litigation.

Conclusions

Findings suggest there are many advantages of actively involving patients and their families in adverse event reviews. An open, collaborative, person-centred approach which listens to, and involves, patients and their families is perceived to lead to improved outcomes for all. For the patient and their family, it can help with reconciliation following a traumatic event and help restore their faith in the healthcare system. For the health service, listening and involving people will likely enhance learning with subsequent improvements in healthcare provision with reduction in risk of similar events occurring for other patients. Communicating in a compassionate manner could also decrease litigation claims following an adverse event. Overall, having personalised conversations and a streamlined review process, with open engagement to enhance learning, was important to most participants in this study.