bluuebunny/crossref_metadata_2025 huggingface dataset:
Urbanization and The Dynamics of Change in the Sahel
Authors: Boyer Florence , Lessault David
Published: December 2021

Since independence, Sahelian cities have been experiencing continuous and increasingly strong population growth, linked to migration and to an unfinished demographic transition. In contexts of rapid urbanization, facilities, infrastructure, and services (school, health, sanitation, etc.) are deficient, and a transfer of poverty from rural areas to cities takes place. Sahelian cities are also marked by the youthfulness of their populations, and an important area for research are the questions of what the city does to youth, and what youth does to the city. Knowledge of Sahelian cities remains fragmented. If the dynamics and challenges of capitals such as Dakar, Ouagadougou, or Bamako are fairly well known, those of N’Djamena, Niamey, or Nouakchott are less so. There are few studies of small and medium-sized cities, and these are in need of updating in the contemporary context of decentralization. This chapter surveys the state of knowledge of urbanization in the Sahel, and suggests directions for future research.
Sahelian Migrations Within Africa
Authors: Bredeloup Sylvie
Published: December 2021

This chapter will examine patterns and history of intra-African migration from the Sahel across national borders within Africa, beginning in the colonial period. During colonization, the French often recruited West African workers across borders who served in the army and provided security for French trading posts along the African coasts. At the time of decolonization, shopkeepers in marketplaces, as well as big merchants or gem traders from the Sahel were also entrepreneurs, occupying an intermediate position between native populations and national authorities in international trade networks. Over the decades, tougher controls at borders and intensified deportations despite regional agreements on the free movement of people, the outbreak of civil wars, or of political turmoil have all had a significant impact on population movements from the Sahel, and have also increased insecurity for Sahelian migrants.
Niger
Authors: Mueller Lisa
Published: December 2021

Niger remains one of the least studied countries in Africa, despite its fascinating history and striking need for solutions to political and economic challenges to development. This chapter outlines those challenges, places them in historical context, and assesses the possibilities for relief. Chronic dilemmas include extreme poverty and a fragile democracy that is frequently interrupted by military coups and authoritarian resurgence. Emerging problems include climate change, terrorism, and migration pressures. Nigerien citizens, having long avoided some of the social unrest of other African countries, are increasingly showing signs of discontent as more of them take to the streets in protest to express their frustrations with multifaceted concerns. The overriding theme of Nigerien society is precarious stability: Politics and economics could generally be much worse, but they could also be much better.
Mapping the Sahelian Space
Authors: Walther Olivier J. , Retaillé Denis
Published: December 2021

This chapter examines the geographical meaning of the Sahel and its spatial dynamics. Unlike other approaches that define the Sahel as a bioclimatic zone or as an ungoverned area, it shows that the Sahel is primarily a space of circulation in which uncertainty has historically been overcome by mobility. The first section discusses how precolonial empires relied on a network of markets and cities that facilitated trade and social relationships across the region and beyond. The second section explores changing regional mobility patterns precipitated by colonial powers and the new approach they developed to control networks and flows. The third section discusses the contradiction between the mobile strategies adopted by local herders, farmers, and traders in the Sahel and the territorial development initiatives of modern states and international donors. Particular attention is paid in the last section to how the Sahel was progressively redefined through a security lens.
Ethics
Authors: White Stuart
Published: December 2021

This chapter seeks to clarify some of the core ethical arguments surrounding welfare states. The analysis focuses on three key values. First, we will consider the concept of need. What are basic needs? How do we conceptualize and measure them? Do citizens have rights to what they need? Second, we focus on principles of equality and, third, we look at arguments surrounding the implications of the welfare state for liberty. A final section concludes by noting some normative issues moving increasingly to the forefront of debate. A changing global political context raises new issues about the international salience of these issues, questions which national welfare states have found it difficult to address.
The Regulation of Employment
Authors: Emmenegger Patrick , Marx Paul
Published: December 2021

The regulation of job security is an important, but understudied, aspect of the welfare state. This contribution reviews academic debates that aim to explain the development of job security regulations across time and countries. While earlier debates focused on dismissal protection as an issue contested between capital and labour, the varieties-of-capitalism approach has emphasized the complementarity between job security regulations and the production models in coordinated market economies. Recently, political economists have begun to discuss diverging regulatory trajectories for open-ended and temporary employment contracts. This is argued to produce ‘labour market dualism’ and conflicts within the working class between ‘insiders’ and ‘outsiders’. The labour market crisis that began in 2008 seems to have changed the politics of job security regulations in those countries that were heavily affected.
Religion and Latin Western Europe, 600–1500
Authors: Koziol Geoffrey
Published: December 2021

The medieval Catholic Church evolved. That is, over the course of the Middle Ages everything about the religion changed, yet the changes occurred within well-established patterns and principles that remained constant. Among those patterns were: oscillations between episcopal and papal ideologies of ecclesiastical unity; a papacy whose theoretical claims to authority never matched its actual power; and a commitment to pastoral care. The Church also insisted on doctrinal and institutional conformity, manifested especially in its reliance on creeds that presented non-logical propositions as articles of faith. The result was to generate heresies, but in responding to heresies the Church also educated the laity in matters of faith, while allowing considerable latitude in matters of private and lay devotions. Among such devotions, the ‘bridal mysticism’ of devout women stands as an example of both the limitations and intellectual depth of the religion.
Judaism and Europe
Authors: Freud-Kandel Miri
Published: December 2021

It is not possible to make sense of Judaism today without understanding how it evolved in Europe. It was in Europe that the multiple options took shape for thinking about what Jewishness could mean once it became just one component among others in an individual’s sense of self. At the same time, European Jewry has endured a long and painful journey as it tried to create confident accounts of how Jewish identity could be understood. This journey reflects a struggle faced right across Europe between accommodating difference and acknowledging the inherent limitations of tolerance. With this in mind, this chapter examines the different pathways that have been forged by Jews across Europe as they sought to construct proud interpretations of both Judaism and Jewishness. In so doing, key themes are explored: cultural Judaism, religious reform, assimilation, anti-Semitism, secularization, and Zionism.
France
Authors: Chelini-Pont Blandine
Published: December 2021

For fourteen centuries, French territory was an assemblage of Catholic and monarchical interests; the result is a deep-seated Catholic imprint which endures to this day though more so in some parts of France than in others. After the Revolution, France experimented with various forms of government which promoted a progressive separation between state and religion (meaning the Catholic Church). This was a long, difficult, and at times painful process resulting eventually in a Republic, in which the notion of laïcité became ever more important. Since the 1970s, the French population has become both increasingly indifferent to religion and increasingly diverse. Currently 40 per cent of the population has no religion, and Islam constitutes an important presence in the country. The growth of Islam has provoked a variety of reactions: accommodation, restriction, suspicion, and resentment.
Germany
Authors: Minkenberg Michael
Published: December 2021

This chapter examines the relationship between religion and the state in modern Germany, in particular the church–state regime from German unification onwards, and church involvement in politics at a variety of levels. It contrasts the ‘stubbornness’ of the ‘partnership model’ between church and state with a variety of policy changes, themselves the result of an increasingly fluid context of religious pluralization which puts pressure on the church–state relationship. The chapter aims to capture this tension, both from a historical perspective and in light of current challenges. The first section delineates the historical origins of the German model and its relevance for the relationship between the majority churches (Protestant and Catholic) and democratization. The second section addresses aspects of religion and state at particular levels of interaction: the polity (the constitution), and policies (the influence of churches in public education, and the governance of religious diversity—particularly Muslim rights).
Nordic Europe
Authors: Furseth Inger
Published: December 2021

This chapter examines religious change in the five Nordic countries: Sweden, Denmark, Norway, Finland, and Iceland. Immigration came later to these countries than in many other parts of Europe, but it has transformed Sweden, Norway, and Denmark into relatively diverse societies; Finland and Iceland remain more homogeneous. In spite of these differences, the religious outlook is changing right across the Nordic countries with a decline in membership in the majority churches, falling indices of religious belief and practice in most of them, growing numbers of people who place themselves outside the faith communities, and multiplying forms of spirituality that lie beyond religious institutions altogether. The chapter addresses the implications that these changes have for religion and state relations, and the role of religion in politics, the media, and civil society.
Peripheries
Authors: Davie Grace , Jödicke Ansgar , Makrides Vasilios N.
Published: December 2021

This short chapter contains three case studies: on Malta, Cyprus, and the South Caucasus. Given their respective locations on the southern and south-eastern extremities of Europe, all three have been subject to diverse and at times competing religious currents over many centuries. The impact of these currents needs careful interpretation. In the twenty-first century, Malta remains an actively Catholic society. Cyprus is still divided on ethno-religious lines: Turkish Cypriots are concentrated in the north and Greek Cypriots live in the south. The situation in the South Caucasus is more complex. It is shaped by a mixture of Western European, Russian, and Turkish references, but overall the region remains more a periphery of Europe than of Iran or Asia.
Religion and Revolution in Europe
Authors: Banks Bryan A. , Johnson Edwards Erica
Published: December 2021

The French Revolution and Napoleonic Empire altered the religious landscape of France, Europe, and the wider world. Revolutionaries reduced religion to a matter of opinion in the 10th Article of the Declaration of the Rights of Man and Citizen (1789), legitimizing their seizure of Catholic lands and disavowal of the religious and political hierarchy of Old Regime France and its empire in the process. This in turn ignited a dechristianization campaign, local conflicts between Catholics, Protestants, and Jewish communities, and counter-revolutionary war in France. The violence reverberated well beyond France’s borders, both throughout Europe and in imperial and non-imperial spaces. From Prussia to Portugal to Port-au-Prince, revolutionaries inspired violence against and in defence of religion, drove les religieux across borders and into the borderlands, and sparked debates over secularization (laïcization, in France) and the rights of individuals and collective, religious bodies for generations.
Religion and Nationality in Europe
Authors: Grosby Steven
Published: December 2021

Throughout European history, the relationship between religion and nationality has been varied and complex. Numerous times religion has been a bearer of national traditions and a nation has been a bearer of religious traditions, as can be seen in the Church’s conciliarism and the use of the Biblical image of Israel in Christian Hebraism. However, there have also existed sharp tensions between religion and nationality, as can be seen in how the New Testament has been understood and in Canon law. These variations must be accounted for. Why and how has religion both contributed to the consolidation and continued existence of a nation, and been disruptive of that consolidation and continued existence? When pursuing answers posed by these questions, a more accurate understanding of culture, religion, and nationality will be necessary by taking into account the distinction between unity and uniformity.
Deproblematizing the Federal–Unitary Dichotomy: Insights from a Public Opinion Survey about Approaches to Designing a Political System in Afghanistan
Authors: Mobasher Mohammad Bashir , Qadam Shah Mohammad
Published: December 2021

This study draws on results of an opinion survey about public views in Afghanistan regarding concepts related to federalism. We argue that concepts such as unitarism, federalism, centralization, and decentralization are highly politicized and often misunderstood when they enter the public discourse. As the survey results indicate, the association of ethnic groups with different systems of governance, although popular in Afghanistan, is misleading. A concurrent majority of ethnic groups takes a more nuanced approach of favoring central authorities on some issues, local authorities on others, and shared or divided authorities on the rest. The findings are helpful in contributing to a better understanding of how Afghans view federalism, and also by providing guidance to constitution-makers in designing institutional arrangements and distributions of power that address society’s needs.
Lockdown on Peace? COVID-19’s Impact on Women Peacebuilders
Authors: Santos Agnieszka Fal-Dutra , Salamat Nikou , Bölükoğlu Sena , Baron B Kathryn , Choi Christine , Gasperetti Heidi M
Published: December 2021

COVID-19 threatens to slow progress on the implementation of peace agreements, and reverse hard-won gains of women peacebuilders’ work towards holistic, gender-equal peace, rooted in human security. Through an analysis of in-depth interviews from a purposive sample of women peacebuilders in Colombia, South Sudan, the Philippines, and Ukraine, this article contributes to a greater understanding of the pandemic’s impact on women’s peace activism, as these peacebuilders adapted to emerging realities and became first responders. We argue that the pandemic has deepened the marginalization of women peacebuilders from formal peace processes, possibly to detriment of both immediate recovery and long-term peacebuilding.
The Homodigital Propeller Flap: A New Tool for Fingertip Reconstruction. Surgical Technique, Anatomical Study, and Clinical Relevance
Authors: Roulet Steven , Delgove Anaïs , Chirez Pierre , Chaput Benoit , Casoli Vincent , Pelissier Philippe , Pinsolle Vincent , Lepivert Jean-Christophe
Published: December 2021

Background:

An ideal flap for fingertip injuries should cover a significant loss of substance and avoid joint flexion to prevent later contracture and joint stiffness. In this study, the authors describe a modified homodigital island flap—the homodigital propeller flap—to better meet these requirements.

Methods:

An anatomical model of fingertip loss is used to analyze the advancement achieved without flexion of the finger. Twenty-four fresh-frozen fingers were dissected. Wires were inserted to maintain joints in extension. The skin paddle was similar in location to a homodigital island flap. The neurovascular bundle was dissected without exceeding the proximal interphalangeal joint and was released from the proximal half of the paddle. Then, the homodigital propeller flap was rotated 180 degrees to cover the defect. A mixture of India ink and barium sulfate was injected into the pedicle artery after the release of the proximal half of the flap from the neurovascular pedicle to assess residual flap vascularization. India ink highlights the residual subcutaneous vascularization network of the cutaneous paddle. A radiographic study of the flap was then performed to visualize the subcutaneous vascular network of the cutaneous paddle.

Results:

The homodigital propeller flap achieved an average cutaneous advancement of 18 mm (range, 15 to 22 mm) and allowed full coverage of cutaneous defects for all fingers while maintaining the proximal interphalangeal joint in strict extension.

Conclusions:

The homodigital propeller flap is a refinement of the classic homodigital island flap. It allows efficient coverage of fingertip defects because of a large advancement without flexion of the finger, reducing the risk of stiffness.
Utility of Dermal Wound Matrices Compared with Local-Tissue Rearrangement and Free Flap Reconstruction for Oncologic Scalp Wounds: A Multidisciplinary Dual Matched-Pair Analysis
Authors: Othman Sammy , Shakir Sameer , Azoury Saïd C. , Lukowiak Tess , Shin Thuzar M. , Sobanko Joseph F. , Miller Christopher J. , Etzkorn Jeremy R. , Fischer John P. , Kovach Stephen J.
Published: December 2021

Background:

Local tissue rearrangement, free flap reconstruction, and Bilayer Wound Matrix represent reconstructive modalities for coverage of scalp defects; however, preferred indications are less clear. The authors aimed to evaluate the efficacy of these interventions.

Methods:

A retrospective review (2008 to 2019) was performed of subjects requiring soft-tissue reconstruction of oncologic scalp wounds. Subjects were dual matched into two comparative cohorts: (1) local tissue rearrangement versus Bilayer Wound Matrix, and (2) free flap reconstruction versus Bilayer Wound Matrix. Ninety-day wound coverage, hospital length of stay, operative time, and wound complications were compared.

Results:

In total, 361 subjects were included. Following matching, 126 subjects constituted the local tissue rearrangement versus Bilayer Wound Matrix cohort, and 56 constituted the free flap reconstruction versus Bilayer Wound Matrix cohort. Local tissue rearrangement/Bilayer Wound Matrix median defect size was 35 ± 42.5 cm2. Local tissue rearrangement provided significantly better wound coverage at 90 days (95.2 percent) compared to Bilayer Wound Matrix (84.1 percent) (p< 0.040). Median defect size in the free flap reconstruction/Bilayer Wound Matrix cohort was 100 ± 101.1 cm2. Ninety-day success (free flap reconstruction, 92.9 percent; Bilayer Wound Matrix, 96.4 percent;p< 1.00) and reoperation rates (14.3 percent versus 3.6 percent;p< 0.352) were similar. However, free flap reconstruction had significantly greater operative times (418 minutes versus 100 minutes;p< 0.001).

Conclusions:

Local tissue rearrangement may be more reliable for smaller wounds (<100 cm2) compared to Bilayer Wound Matrix. Bilayer Wound Matrix may have comparable efficacy to free flap reconstruction for larger defects (150 to 250 cm2), and may be more cost-effective, given greater operative time and length of stay associated with free flap reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Risk Factors Associated With an Impaired Antibody Response in Kidney Transplant Recipients Following 2 Doses of the SARS-CoV-2 mRNA Vaccine
Authors: Yi Stephanie G. , Moore Linda W. , Eagar Todd , Graviss Edward A. , Nguyen Duc T. , Ibrahim Hassan , Huang Howard J. , Hobeika Mark , McMillan Robert , Saharia Ashish , Mobley Constance , Podder Hemangshu , Drews Ashley , Ghobrial R. Mark , Gaber A. Osama , Knight Richard J.
Published: December 2021

Background.

Data about vaccine efficacy in solid organ transplant patients are limited. We previously reported our initial observation of a 6.2% immunogenicity rate in kidney transplant recipients (KTRs) after administration of 1 dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine. We sought to report our observations of anti-SARS-CoV-2 antibody in KTRs after 2 doses of the SARS-CoV-2 mRNA vaccine.

Methods.

We identified 105 KTRs who received 2 doses of the Pfizer-BioNTech or Moderna mRNA-1273 vaccine per availability and had anti-SARS-CoV-2 labs obtained at least 2 wk following administration of the second dose. Antibody testing was performed using 3 clinically validated qualitative and semiquantitative assays.

Results.

KTRs had a 36.2% antibody response rate, whereas an age ≥68 years and a longer time from transplant were factors associated with antibody response.

Conclusions.

The low antibody response in KTRs may be associated with the immunosuppressive state. More data are needed to evaluate if KTRs may require higher vaccine doses or an additional booster dose to increase their ability to mount an immune response to the SARS-CoV-2 vaccine.
Rhodobacter amnigenus sp. nov. and Rhodobacter ruber sp. nov., isolated from freshwater habitats
Authors: Chen Wen-Ming , Chang Ting-Hsuan , Yang Che-Chia , Sheu Der-Shyan , Jheng Li-Cheng , Sheu Shih-Yi
Published: December 2021

Two bacterial strains, designated HSP-20Tand CCP-1T, isolated from freshwater habitats in Taiwan, were characterized by polyphasic taxonomy. Both strains were Gram-stain-negative, aerobic, non-motile and rod-shaped. Cells of strains HSP-20Tand CCP-1Tformed pink and dark red coloured colonies, respectively. Both strains contained bacteriochlorophylla, and showed optimum growth under anaerobic conditions by photoheterotrophy, but no growth by photoautotrophy. Phylogenetic analyses based on 16S rRNA gene and whole-genome sequences indicated that both strains belonged to the genusRhodobacter. Analysis of 16S rRNA gene sequences showed that strains HSP-20Tand CCP-1Tshared 98.3 % sequence similarity and were closely related toRhodobacter tardusCYK-10T(96.0 %) andRhodobacter flagellatusSYSU G03088T(96.0 %), respectively. Both strains shared common chemotaxonomic characteristics including Q-10 as the major isoprenoid quinone, C18 : 1 ω7cas the predominant fatty acid, and phosphatidylethanolamine, phosphatidylglycerol and phosphatidylcholine as the main polar lipids. The DNA G+C content of both strains was 66.2 mol%. The average nucleotide identity, average amino acid identity and digital DNA–DNA hybridization values between these two novel isolates and their closest relatives were below the cut-off values of 95–96, 90 and 70 %, respectively, used for species demarcation. On the basis of phenotypic and genotypic properties and phylogenetic inference, both strains should be classified as novel species within the genusRhodobacter, for which the namesRhodobacter amnigenussp. nov. (=BCRC 81193T=LMG 31334T) andRhodobacter rubersp. nov. (=BCRC 81189T=LMG 31335T) are proposed.
Leucobacter soli sp. nov., from soil amended with humic acid
Authors: Kämpfer Peter , McInroy John A. , Clermont Dominique , Neumann-Schaal Meina , Criscuolo Alexis , Busse Hans-Jürgen , Glaeser Stefanie P.
Published: December 2021

A Gram-positive, non-spore-forming actinobacterium (IMT-300T) was isolated from soil amended with humic acid in Malvern, AL, USA. This soil has been used for 50+years for the cultivation of earthworms for use as fish bait. Based on 16S rRNA gene sequence similarity studies, strain IMT-300T was shown to belong to the genus

Leucobacter

and was closely related to the type strain of ‘Leucobacter margaritiformis’ L1T (97.8%). Similarity to all other type strains of

Leucobacter

species was lower than 97.2 %. The average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between the IMT-300T genome assembly and those of the closest relative

Leucobacter

type strain were 81.4 and 23.3 % (

Leucobacter chironomi

), respectively. The peptidoglycan of strain IMT-300T contained l-2,4-diaminobutyric acid as the diagnostic diamino acid. In addition, glycine, d- and l-alanine and d-glutamic acid were found. The peptidoglycan type represents a variant of B2δ (B11). The major quinones were menaquinones MK-10 and MK-11. The polar lipid profile consisted of the major lipids diphosphatidylglycerol, phosphatidylglycerol and moderate to minor amounts of two unidentified phospholipids, two unidentified glycolipids and an unidentified aminophospholipid. The polyamine pattern contained major amounts of spermidine and spermine. Strain IMT-300T contained the major fatty acids C15 : 0 anteiso, C16 : 0 iso and C17 : 0 anteiso, like other members of the genus

Leucobacter

. The results of ANI and dDDH analyses and physiological and biochemical tests allowed a genotypic and phenotypic differentiation of strain IMT-300T from the most closely related

Leucobacter

species. Strain IMT-300T represents a novel

Leucobacter

species, for which we propose the name Leucobacter soli sp. nov., with the type strain IMT-300T (CIP 111803T=DSM 110505T=CCM 9020T=LMG 31600T).
Alternating anti-prion regimens reduce combination drug resistance but do not further extend survival in scrapie-infected mice
Authors: Beauchemin Kathryn S. , Rees Judy R. , Supattapone Surachai
Published: December 2021

Prion diseases are fatal and infectious neurodegenerative diseases in humans and other mammals caused by templated misfolding of the endogenous prion protein (PrP). Although there is currently no vaccine or therapy against prion disease, several classes of small-molecule compounds have been shown to increase disease-free incubation time in prion-infected mice. An apparent obstacle to effective anti-prion therapy is the emergence of drug-resistant strains during static therapy with either single compounds or multi-drug combination regimens. Here, we treated scrapie-infected mice with dynamic regimens that alternate between different classes of anti-prion drugs. The results show that alternating regimens containing various combinations of Anle138b, IND24 and IND116135 reduce the incidence of combination drug resistance, but do not significantly increase long-term disease-free survival compared to monotherapy. Furthermore, the alternating regimens induced regional vacuolation profiles resembling those generated by a single component of the alternating regimen, suggesting the emergence of strain dominance.
A large, curated, open-source stroke neuroimaging dataset to improve lesion segmentation algorithms
Authors: Liew Sook-Lei , Lo Bethany , Donnelly Miranda R. , Zavaliangos-Petropulu Artemis , Jeong Jessica N. , Barisano Giuseppe , Hutton Alexandre , Simon Julia P. , Juliano Julia M. , Suri Anisha , Ard Tyler , Banaj Nerisa , Borich Michael R. , Boyd Lara A. , Brodtmann Amy , Buetefisch Cathrin M. , Cao Lei , Cassidy Jessica M. , Ciullo Valentina , Conforto Adriana B. , Cramer Steven C. , Dacosta-Aguayo Rosalia , Rosa Ezequiel de la , Domin Martin , Dula Adrienne N. , Feng Wuwei , Franco Alexandre R. , Geranmayeh Fatemeh , Gramfort Alexandre , Gregory Chris M. , Hanlon Colleen A. , Hordacre Brenton G. , Kautz Steven A. , Khlif Mohamed Salah , Kim Hosung , Kirschke Jan S. , Liu Jingchun , Lotze Martin , MacIntosh Bradley J. , Mataró Maria , Mohamed Feroze B. , Nordvik Jan E. , Park Gilsoon , Pienta Amy , Piras Fabrizio , Redman Shane M. , Revill Kate P. , Reyes Mauricio , Robertson Andrew D. , Seo Na Jin , Soekadar Surjo R. , Spalletta Gianfranco , Sweet Alison , Telenczuk Maria , Thielman Gregory , Westlye Lars T. , Winstein Carolee J. , Wittenberg George F. , Wong Kristin A. , Yu Chunshui
Published: December 2021

Accurate lesion segmentation is critical in stroke rehabilitation research for the quantification of lesion burden and accurate image processing. Current automated lesion segmentation methods for T1-weighted (T1w) MRIs, commonly used in rehabilitation research, lack accuracy and reliability. Manual segmentation remains the gold standard, but it is time-consuming, subjective, and requires significant neuroanatomical expertise. We previously released a large, open-source dataset of stroke T1w MRIs and manually segmented lesion masks (ATLAS v1.2, N=304) to encourage the development of better algorithms. However, many methods developed with ATLAS v1.2 report low accuracy, are not publicly accessible or are improperly validated, limiting their utility to the field. Here we present ATLAS v2.0 (N=955), a larger dataset of T1w stroke MRIs and manually segmented lesion masks that includes both training (public) and test (hidden) data. Algorithm development using this larger sample should lead to more robust solutions, and the hidden test data allows for unbiased performance evaluation via segmentation challenges. We anticipate that ATLAS v2.0 will lead to improved algorithms, facilitating large-scale stroke rehabilitation research.
Analysis of single-cell RNA-sequencing data to identify quiescent and proliferating neural cell populations in Glioblastoma
Authors: Vikram Rajeev , Chou Wen□Cheng , Wu Pei-Ei , Chen Wei-Ting , Shen Chen-Yang
Published: December 2021

Background

Diffuse Glioblastoma (GBM) has high mortality and remains one of the most challenging type of cancer to treat. Identifying and characterizing the cells populations driving tumor growth and therapy resistance has been particularly difficult owing to marked inter and intra tumoral heterogeneity observed in these tumors. These tumorigenic populations contain long lived cells associated with latency, immune evasion and metastasis.

Methods

Here, we analyzed the single-cell RNA-sequencing data of high grade glioblastomas from four different studies using integrated analysis of gene expression patterns, cell cycle stages and copy number variation to identify gene expression signatures associated with quiescent and cycling neuronal tumorigenic cells.

Results

The results show that while cycling and quiescent cells are present in GBM of all age groups, they exist in a much larger proportion in pediatric glioblastomas. These cells show similarities in their expression patterns of a number of pluripotency and proliferation related genes. Upon unbiased clustering, these cells explicitly clustered on their cell cycle stage. Quiescent cells in both the groups specifically overexpressed a number of genes for ribosomal protein, while the cycling cells were enriched in the expression of high-mobility group and heterogeneous nuclear ribonucleoprotein group genes. A number of well-known markers of quiescence and proliferation in neurogenesis showed preferential expression in the quiescent and cycling populations identified in our analysis. Through our analysis, we identify ribosomal proteins as key constituents of quiescence in glioblastoma stem cells.

Conclusions

This study identifies gene signatures common to adult and pediatric glioblastoma quiescent and cycling stem cell niches. Further research elucidating their role in controlling quiescence and proliferation in tumorigenic cells in high grade glioblastoma will open avenues in more effective treatment strategies for glioblastoma patients.
Sub-communities of the vaginal microbiota in pregnant and non-pregnant women
Authors: Symul Laura , Jeganathan Pratheepa , Costello Elizabeth K. , France Michael , Bloom Seth M. , Kwon Douglas S. , Ravel Jacques , Relman David A. , Holmes Susan
Published: December 2021

Diverse and non-Lactobacillus-dominated vaginal microbial communities are associated with adverse health outcomes such as preterm birth and the acquisition of sexually transmitted infections. Despite the importance of recognizing and understanding the key risk-associated features of these communities, their heterogeneous structure and properties remain ill-defined. Clustering approaches are commonly used to characterize vaginal communities, but they lack sensitivity and robustness in resolving substructures and revealing transitions between potential sub-communities. Here, we address this need with an approach based on mixed membership topic models, using longitudinal data from cohorts of pregnant and non-pregnant study participants. We identify several non-Lactobacillus-dominated sub-communities common to both cohorts and independent of reproductive status. In non-pregnant individuals, we find that the menstrual cycle modulates transitions between and within sub-communities. In addition, a specific non-Lactobacillus-dominated sub-community, which was associated with preterm delivery in pregnant participants, was also more common during menses, a time of elevated vaginal inflammation in non-pregnant participants. Overall, our analyses based on mixed membership models reveal substructures of vaginal ecosystems which may have important clinical and biological associations.
Language Models for the Prediction of SARS-CoV-2 Inhibitors
Authors: Blanchard Andrew E , Gounley John , Bhowmik Debsindhu , Shekar Mayanka Chandra , Lyngaas Isaac , Gao Shang , Yin Junqi , Tsaris Aristeidis , Wang Feiyi , Glaser Jens
Published: December 2021

The COVID-19 pandemic highlights the need for computational tools to automate and accelerate drug design for novel protein targets. We leverage deep learning language models to generate and score drug candidates based on predicted protein binding affinity. We pre-trained a deep learning language model (BERT) on ∼9.6 billion molecules and achieved peak performance of 603 petaflops in mixed precision. Our work reduces pre-training time from days to hours, compared to previous efforts with this architecture, while also increasing the dataset size by nearly an order of magnitude. For scoring, we fine-tuned the language model using an assembled set of thousands of protein targets with binding affinity data and searched for inhibitors of specific protein targets, SARS-CoV-2 Mpro and PLpro. We utilized a genetic algorithm approach for finding optimal candidates using the generation and scoring capabilities of the language model. Our generalizable models accelerate the identification of inhibitors for emerging therapeutic targets.
Syntaxin 5 determines Weibel-Palade body size and Von Willebrand factor secretion by controlling Golgi architecture
Authors: Kat Marije , Karampini Ellie , Hoogendijk Arie Johan , Bürgisser Petra , Mulder Aat A. , van Alphen Floris , Olins Jenny , Geerts Dirk , van den Biggelaar Maartje , Margadant Coert , Voorberg Jan , Bierings Ruben
Published: December 2021

Von Willebrand factor (VWF) is a multimeric hemostatic protein primarily synthesized in endothelial cells (ECs). VWF is stored in endothelial storage organelles, the Weibel-Palade bodies (WPBs), whose biogenesis strongly depends on VWF anterograde trafficking and Golgi architecture. Elongated WPB morphology is correlated to longer VWF strings with better adhesive properties. We previously identified the SNARE SEC22B, which is involved in anterograde ER-to-Golgi transport, as a novel regulator of WPB elongation. To elucidate novel determinants of WPB morphology we explored endothelial SEC22B interaction partners in a mass spectrometrybased approach, identifying the Golgi SNARE Syntaxin 5 (STX5). We established STX5 knockdown in ECs using shRNA-dependent silencing and analyzed WPB and Golgi morphology, using confocal and electron microscopy. STX5-depleted ECs exhibited extensive Golgi fragmentation and decreased WPB length, which was associated with reduced intracellular VWF levels, and impaired stimulated VWF secretion. However, the secretion-incompetent organelles in shSTX5 cells maintained WPB markers such as Angiopoietin 2, P-selectin, Rab27A, and CD63. Taken together, our study has identified SNARE protein STX5 as a novel regulator of WPB biogenesis.
Mutations on RBD of SARS-CoV-2 Omicron variant result in stronger binding to human ACE2 receptor
Authors: Lupala Cecylia S. , Ye Yongjin , Chen Hong , Su Xiao-Dong , Liu Haiguang
Published: December 2021

The COVID-19 pandemic caused by the SARS-CoV-2 virus has led to more than 270 million infections and 5.3 million of deaths worldwide. Several major variants of SARS-CoV-2 have emerged and posed challenges in controlling the pandemic. The recently occurred Omicron variant raised serious concerns about reducing the efficacy of vaccines and neutralization antibodies due to its vast mutations. We have modelled the complex structure of the human ACE2 protein and the receptor binding domain (RBD) of Omicron Spike protein (S-protein), and conducted atomistic molecular dynamics simulations to study the binding interactions. The analysis shows that the Omicron RBD binds more strongly to the human ACE2 protein than the original strain. The mutations at the ACE2-RBD interface enhance the tight binding by increasing hydrogen bonding interaction and enlarging buried solvent accessible surface area.
De novo apical domain formation inside the Drosophila adult midgut epithelium
Authors: Chen Jia , St Johnston Daniel
Published: December 2021

In the adult Drosophila midgut, basal intestinal stem cells give rise to enteroblasts that integrate into the epithelium as they differentiate into enterocytes. Integrating enteroblasts must generate a new apical domain and break through the septate junctions between neighbouring enterocytes, while maintaining barrier function. We observe that enteroblasts form an apical membrane initiation site when they reach the septate junction between the overlying enterocytes. A space appears above the enteroblast as Cadherin clears from its apical surface. New septate junctions then form laterally with neighbouring enterocytes and the AMIS develops into pre-apical compartment with a fully-formed brush border. Finally, the overlying septate junction dissolves and the pre-enterocyte reaches the gut lumen. Enteroblasts therefore form an apical domain before they have a free apical surface. The process of enteroblast integration resembles lumen formation in mammalian epithelial cysts, highlighting the similarities between the fly midgut and mammalian epithelia.
Transcriptomic heterogeneity of Sox2-expressing pituitary cells
Authors: Fletcher Patrick A. , Prévide Rafael M. , Smiljanic Kosara , Sherman Arthur , Coon Steven L. , Stojilkovic Stanko S.
Published: December 2021

The mammalian pituitary gland is a complex organ consisting of hormone-producing cells (HPC), nonhormonal folliculostellate cells (FSC) and pituicytes, vascular pericytes and endothelial cells, and putative Sox2-expressing stem cells. Here, we used scRNAseq analysis of adult female rat pituitary cells to study the heterogeneity of pituitary cells with a focus on evaluating the transcriptomic profile of the Sox2-expressing population. Samples containing whole pituitary and separated anterior and posterior lobe cells allowed the identification of all expected pituitary resident cell types and lobe-specific subpopulations of vascular cells. Sox2 was expressed uniformly in all FSC, pituicytes, and a fraction of HPC. FSC comprised two subclusters; FSC1 contained more cells but expressed less genetic diversity compared to FSC2. The latter contained proliferative cells, expressed genes consistent with stem cell niche formation, including tight junctions, and shared genes with HPC. The FSC2 transcriptome profile was also consistent with the activity of pathways regulating cell proliferation and stem cell pluripotency, including the Hippo and Wnt pathways. The expression of other stem cell marker genes was common for FSC and pituicytes (Sox9, Cd9, Hes1, Vim, S100b) or cell type-specific (FSC: Prop1, Prrx1, Pitx1, Pitx2, Lhx3; pituicytes: Fgf10, Tbx3, Lhx2, Nkx2-1, Rax). FSC and pituicytes also expressed other astroglial marker genes, some common and other distinct, consistent with their identities as astroglial cells of the pituitary. These data suggest functional heterogeneity of FSC, with a larger fraction representing classical FSC, and a smaller fraction containing active stem-like cells and HPC-committed progenitors.
Isolation and comparative analysis of antibodies that broadly neutralize sarbecoviruses
Authors: Liu Lihong , Iketani Sho , Guo Yicheng , Casner Ryan G. , Reddem Eswar R. , Nair Manoj S. , Yu Jian , Chan Jasper F-W. , Wang Maple , Cerutti Gabriele , Li Zhiteng , Castagna Candace D. , Corredor Laura , Chu Hin , Yuan Shuofeng , Poon Vincent Kwok-Man , Chan Chris Chun-Sing , Chen Zhiwei , Luo Yang , Cunningham Marcus , Chavez Alejandro , Yin Michael T. , Perlin David S. , Tsuji Moriya , Yuen Kwok-Yung , Kwong Peter D. , Sheng Zizhang , Huang Yaoxing , Shapiro Lawrence , Ho David D.
Published: December 2021

The devastation caused by SARS-CoV-2 has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptor-binding domain (RBD)-directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses and thus its promise as an agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well conserved among sarbecoviruses, but also uncovered a new antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine.

One sentence summary

A monoclonal antibody that neutralizes or binds all sarbecoviruses tested and represents a reproducible antibody class.
Correlation between faecal microbial taxa and ulcerative colitis in different phases of disease activity in a north Indian cohort
Authors: Juyal Garima , Sood Ajit , Midha Vandana , Singh Arshdeep , Singh Dharmatma , Mahajan Ramit , Verma Vijay , Bhatnagar Rakesh , Joshi Mohan C
Published: December 2021

Background and Aims

A link between gut microbiota and Ulcerative colitis (UC) has been established in several studies. However, only a few studies have examined specific changes in microbiota associated with different phases of disease activity in UC. In this study, we attempted to identify differentially abundant taxa between (i) UC patients and healthy controls and (ii) different phases of disease activity, in a genetically distinct north Indian (NI) population.

Methods

16S rRNA (V3–V4) sequencing of 105 patients with UC [newly diagnosed (n=14); patients in remission (n=36) and active disease (relapse, n=55)]; and 36 healthy controls was performed and analysed.

Results

Lower gut microbial diversity; enrichment of lactate-producing bacteria namely Streptococcus, Bifidobacterium and Lactobacillus; and depletion of butyrate-producing bacteria (e.g., Lachnospiraceae and Ruminococcaceae), were observed among UC patients. Subgroup analysis revealed differential abundance of Escherichia-Shigella, Streptococcus, Enterococcus and Faecalibacterium in newly diagnosed UC patients. No discrete microbial features were observed between patients in remission and those with active disease. Co-occurrence network analysis revealed a mutualistic association between opportunistic pathogens and Bifidobacterium and Lactobacillus and antagonistic relationship with butyrate-producers.

Conclusion

This first faecal microbiome study among NI UC cohort elucidated dysanaerobiosis; loss of short chain fatty acid producers and enrichment of inflammation associated microbes; population specific differential microbial genera; and a potential microbial signature for early dysbiosis.
Racial and ethnic disparities in COVID-19 vaccinations in the United States during the booster rollout
Authors: Faust Jeremy Samuel , Renton Benjamin , Essien Utibe R. , Gounder Céline R. , Lin Zhenqiu , Krumholz Harlan M.
Published: December 2021

Background

We sought to quantify whether there were statistically significant disparities along race and ethnicity lines during the early rollout of Covid-19 vaccine booster doses in the United States. We also studied whether such disparities replicated or widened disparities that had already been observed during the initial series rollout as of 2 months earlier (Janssen) or 6 months earlier (Pfizer-BioNTech or Moderna), which comprised the booster-eligible population.

Methods

This cross-sectional study of US adults (ages ≥18 years) used public data from US Centers for Disease Control and Prevention. The observed shares of vaccine doses for each race and ethnicity were compared to the expected shares, predicted based upon the compositions of the booster-eligible and initial series-eligible populations.

Results

As of November 16, 2021, 123.5 million US adults were eligible for a booster dose of either the Pfizer-BioNTech, Moderna, or Janssen vaccines. Of these, 21.7 million had received a booster dose, among whom race and ethnicity information was available for 18.8 million booster recipients.

A statistically significant higher share of Non-Hispanic White and Non-Hispanic Multiple/Other race individuals had received a booster vaccination than projected based on the composition of the booster-eligible population. A statistically significant lower share of Hispanic, Non-Hispanic American Indian/Alaskan Native, Non-Hispanic Asian, Non-Hispanic Black, and Non-Hispanic Native Hawaiian/Other Pacific Islander individuals had received a booster vaccination than expected based on the booster-eligible population. A secondary analysis of the booster-eligible population found that some of these disparities had already occurred at the time of the initial series. However, the booster campaign widened all of those disparities and added new disparities for Non-Hispanic American Indian/Alaskan Native and Non-Hispanic Native Hawaiian/Other Pacific Islander individuals.

Conclusion

Disparities in Covid-19 vaccine administration on race and ethnicity lines occurred during the initial series rollout in the US. However, these disparities were not merely replicated but widened by the early booster rollout.