bluuebunny/crossref_metadata_2025 huggingface dataset:
Michael Haneke
Authors: Coulthard Lisa , Stringer Michael
Published: January 2023

With a career spanning almost five decades, Michael Haneke (b. 1942– ) has received international recognition and praise only since the early 2000s. This increasing recognition is evidenced by his film Amour (2012), which won the Cannes Film Festival Palme d’Or, the Best Foreign Language Oscar from the Academy of Motion Picture Arts and Sciences, the Best Film and Best Director awards at the 25th European Film Awards, as well as many other accolades. That this critical reception is slow in coming reflects the challenges that Haneke presents as a director. Provoking audiences, straddling national boundaries, and maintaining an austere directorial style, Haneke represents a complex cinematic auteur who cannot be placed within any clear confines of national traditions or film histories. An exemplar of transnational cinema culture, Haneke is a German-born, Austrian raised filmmaker who defied national boundaries by shifting his cinematic productions to France and the French language in the late 1990s. As a result, critics have often simplified his career trajectory by demarcating the German- and French-language films as representing different styles and themes. But this splitting does not hold after the release of The White Ribbon (2009), a German-language film that thwarted attempts to assign national clarity to Haneke’s cinematic culture and production. These complications are not surprising for those familiar with Haneke’s oeuvre or the scholarly debates around his work—Haneke simply does not fit neatly within any single preordained framework: a modernist working in a postmodern age; an Austrian who makes French, German, and American productions and co-productions; a didactic and stern cynic who wins over interviewers with his affable, forthcoming ways; a pedant who refuses to interpret his own films. As Thomas Elsaesser summarizes in his insightful article “Performative Self-Contradictions: Michael Haneke’s Mindgames” (2010)—Haneke is quite simply a paradox. This paradoxical nature, however, is in opposition to what can be seen as a relatively coherent scholarly discourse about his films—as Peter Brunette notes in his book Michael Haneke (2010), the list of themes associated with Haneke are surprisingly uniform, even canonical: alienation, surveillance, media violence, the fortress of domestic life, non-communication and isolation, guilt, shame, and responsibility. Every scholar who writes on Haneke comments on some configuration or combination of these essential themes. This canonization does not, however, suggest that Haneke’s films lack complexity or are repetitive, one-dimensional, or single minded. Rather, in Haneke we recognize a complexity of thinking that refuses simple answers and rejects easy solutions.
Jerusalem
Authors: Kattan Victor , Quigley John
Published: January 2023

Jerusalem has been the focus of much study by international lawyers and political scientists. That body of literature dates only from the late 1940s, when a proposal to recommend the partition of Palestine came under consideration at the United Nations. During the period of British control (1917–1948), Jerusalem was made the administrative capital of Palestine where the mandatory authorities were based. Prior to the First World War, the sanjak of Jerusalem, which included Bethlehem, Hebron, Jaffa, Gaza, and Beersheba, formed part of an administrative area within the Turkish Empire. It had representatives in the Turkish parliament, who participated in legislative work for the Empire. As a result of this history, the literature on Jerusalem’s status dates only from the mid-twentieth century. That said, the literature has been voluminous. Contention has raged over Jerusalem’s status. Scholars have presented sharply different analyses. Some focus on the religious interest in Jerusalem as a basis for resolving its legal status. Others focus on more traditional factors of international law. The issue is one that is to some extent unique in the literature on sovereignty and status of territory, because rarely is focus placed on a single city. The name “Jerusalem” is used in this bibliography, since that name is commonly found in English-language sources. It is derived from the Hebrew name for the city. The Arabic name is al-Quds.
Categorical Data Analysis in Psychology
Authors: Rindskopf David
Published: January 2023

Categorical data are data for which at least one dependent (outcome) variable is nominal or ordinal. Nominal variables, such as gender, ethnicity, religion, and graduation (or successful completion of any course of study), have a limited number of possible values. Categorical variables are generally divided into two major classes: dichotomous (binary) variables, which have two values (e.g., success vs. failure), and polytomous, which have more than two categories. Polytomous variables are further divided into ordered (ordinal) or unordered. Ordinal variables may have a limited number of categories (such as Likert scales) or a potentially unlimited number of categories, usually a count (e.g., number of times a student interrupts a class). Historical treatment of such data normally involved what was termed nonparametric statistics (e.g., chi-square tests of independence), and involved simple data structures (often just two variables). These methods have evolved to include a wide variety of extensions, including latent variables, graphical causal models, and tree-based methods.
Latina/o/x Archives
Authors: Mills Regina
Published: January 2023

Recovery, expansion, and the visibilization of power have been at the heart of Latina/o/x archives. Latinx people, when identified as a pan-ethnic category, are frequently viewed in hegemonic media and literature as uniformly oppressed, with shared politics, and similar (lack of) access to power. The study of Latinx archives provides three major conclusions that should be essential to Latinx studies as a whole: (1) physical archival spaces privilege light-skinned, colonial-empowered Latinx voices; (2) popular culture and other non-state-sponsored sources provide the opportunity to see the heterogeneity of Latinx experience and history; and (3) definitions of Latinidad are frequently determined by which archives one privileges. The term archives is itself fraught. According to the Society of American Archivists, definitions of the term are fiercely debated, usually in ways that narrow what counts, such as focusing on organizational models and chain of custody or whether an archive has gone through a selection process. However, those who study and create Latinx archives are more interested in expanding the term archive. Latinx archival studies generally agrees that the primary documents of history are skewed toward colonial, imperialist, and hegemonic power structures. The kind of Latinx history that comes from official and state-sponsored archives erases Black, Asian, and Indigenous Latinidades. These archives justify anti-immigrant and racialized violence and privilege white Latinxs who embraced white supremacy or found ways to play its game. However, the selections in this entry also argue for the radical potential of archive-building by Latinx communities as well as the ability for memoir, testimony, oral history, and ethnography to challenge shallow understandings of the Chicano Movement or Puerto Rico’s colonial legacy, for example. The scholarship and curation projects sampled here fill lacunae, provide models for future scholarship and anthologies, and read against the archival grain to recast and recenter marginalized and understudied peoples and histories. This bibliographic entry focuses on providing a general overview of the texts that have influenced Latinx archives and archival studies. In addition, key scholarship that uses Latinx archives as well as texts and projects that create and curate new archives are provided. This entry ends with a section on important Latinx archives, both traditional (physical) and digital.
The Shijing詩經 (Classic of Poetry; Book of Odes)
Authors: Kern Martin
Published: January 2023

The Shijing, or Book of Odes (aka Classic of Poetry, Book of Songs, etc.) is the fountainhead of the Chinese literary tradition. An anthology of 305 undated and anonymous poems that probably arose from the regional courts of the Eastern Zhou period (770–256 bce) and according to tradition was arranged by Confucius (551–479 bce), it contains, in this order, 160 “Airs of the States” (guofeng國風), 74 “Minor Court Hymns” (xiaoya小雅), 31 “Major Court Hymns” (daya大雅), and 40 “Eulogies” (song頌). The poems are customarily believed to have been composed between 1000 and 600 bce; ancient accounts mention their recitation as texts and performance as musical pieces. Recent finds of ancient bamboo manuscripts show that written versions of the anthology, especially of the “Airs of the States,” existed since at least the fourth century bce, though no complete anthology including all four sections of the text is documented yet from before the Western Han (202 bce–9 ce). Numerous short quotations from the poems appear in Warring States period (453–221 bce), philosophical texts to invoke the weight and authority of tradition. These testimonials mark the Shijing as the single most quotable and most widely known text in Chinese antiquity and as the cultural hallmark of the educated elite. While the “Hymns” and “Eulogies” were performed in the religious and political rituals of the Zhou royal house to recall the glory of the founding and heyday of the Western Zhou (1046–771 bce), the original context of the “Airs of the States” remains uncertain. Their simple, repetitive structures are often taken as evidence of their origins in folk song, even though the poems have survived only in the writings of the ancient elite. Unlike especially the “Major Court Hymns,” none of the “Airs” offers a sustained narrative, and few contain any historical reference at all; already in antiquity, their semantic ambiguity gave rise to widely different interpretations. At the Western Han imperial court, the Shijing was officially canonized as one of the Five Classics, the core of Confucian learning. Since then, it has attracted thousands of commentaries, subcommentaries, and studies on all of its literary, historical, and linguistic aspects. In recent decades, new discoveries of ancient manuscripts dating from the last four centuries bce have led to yet another flood of books and articles on the Shijing, in particular from Mainland China.
Destruction in Art Symposium (DIAS)
Authors: Stiles Kristine
Published: January 2023

The phrase “destruction in art” did not exist as a category in the arts before the publication of Gustav Metzger’s manifestos on the topic, beginning with “Auto-Destructive Art,” dated 4 November 1959, and published eight days later in the London Daily Express, on 12 November. Thereafter “destruction in art” entered the general lexicon of the fine arts and became an art-historical idiom following the international Destruction in Art Symposium (DIAS) that Metzger organized in London in 1966 with the assistance of the Irish poet and writer John Sharkey. Together they issued invitations to artists, poets, composers, psychologists, scientists, and intellectuals worldwide, and selected an international group of artists and intellectuals to serve on the “DIAS Honorary Committee.” That committee helped to identify and contact participants and forge guidelines for the symposium. DIAS events, exhibitions, and performances were staged in outdoor sites and theater venues in London throughout September, with the three-day symposium staged in the middle of that month. Symposium participants included artists, poets, composers, a dancer, an architect, a scientist, and two psychoanalysts, all of whom made presentations. Two Austrian participants, Otto Muehl and Günter Brus, presented actions in defiance of the directive not to perform during the symposium. Some fifty individuals from fifteen countries either came to London or sent photographs, sound recordings, poems, manifestos, texts, and ephemera to be displayed and discussed. Among those who sent work was the Argentine artist Kenneth Kemble, who, with a group of seven artists in Buenos Aires, had launched the exhibition Arte Destructivo five years earlier in 1961. Such discoveries were met with an enthusiastic, international response. DIAS became the pivotal event verifying destruction in art as a transnational, transformative phenomenon that confirmed the quality and conceptual complexity of the artistic research and production undertaken by very diverse individual participants. No comprehensive publication exists on DIAS, and while several exhibitions have sought to present both DIAS and destruction in art, none have captured its fundamental interdisciplinary composition, breadth, or depth. This annotated bibliography represents the intellectual bones of destruction in art with DIAS as its cornerstone. I would like to acknowledge Dr. Mitali Routh for assistance in researching this essay.
Art Restitution
Authors: Reed Victoria
Published: January 2023

Art restitution is the return of stolen or improperly traded cultural property to its rightful owner. Critical to determining whether a work of art should be restituted is if it was subject to a transfer that was unlawful or invalid, such as a theft, expropriation, illicit trafficking, or a sale made under duress. The process of restitution therefore hinges on the provenance (history of possession and physical movement) of the object in question, along with a consideration of applicable laws that may govern ownership, import and export, and other ethical and policy frameworks. While there have been disputes over the ownership of works of art for years, the topic grew increasingly important during the 20th century, when many nations passed legislation seeking to prevent the removal of culturally significant artifacts from their borders. Artwork was restituted on a large scale following the widespread displacement of cultural property under the National Socialist regime and during World War II. The rightful ownership of archaeological material became the focus of particular scrutiny after the signing of the 1970 UNESCO Convention on the Means of Prohibiting and Preventing the Illicit Import, Export and Transfer of Ownership of Cultural Property. In 1990, the United States passed the Native American Graves Protection and Repatriation Act to facilitate claims for Native American human remains, burial goods, sacred objects, and items of cultural patrimony. It was not, however, until the turn of the 21st century that these issues came fully to the fore in the art world. In the 1990s and early 2000s, high-profile restitution claims for art stolen during the Holocaust and World War II and for antiquities looted and smuggled from their countries of origin prompted participants in the art trade to become more aware of the importance of provenance and rightful ownership. Since then, there have been increasing calls to restitute works of art removed from previously colonized areas, especially in the Global South, to their current countries of origin. Ownership claims have been facilitated by the expansion of the internet, which has made the holdings of museums, commercial galleries, and auction houses publicly accessible. The increasing transparency of the art world and the development of online databases have expedited the resolution of claims. Thanks to such tools, it has become possible more easily to register and locate lost or stolen works of art. As the field of art restitution is relatively new, the body of literature on the topic is principally from the late 20th and early 21st centuries and continues to grow rapidly.
Sequential Speciation and Cascading Divergence
Authors: Hood Glen Ray
Published: January 2023

A central, long-standing, and largely untested premise in evolutionary ecology is that “biodiversity begets biodiversity” in a process referred to as “sequential” or “cascading” divergence or speciation. The hypothesis of sequential speciation postulates that as populations diverge and new species form (i.e., the process of speciation), they create new niches for interacting organisms to utilize and adapt to in kind, potentially catalyzing a chain reaction of speciation events upwards across trophic levels. As a result, the process of sequential speciation has been inferred to help explain a number of observational and correlative patterns in ecology and evolutionary biology, such as adaptive radiations following mass extinctions, increased species richness in tropical climates, and the incredible diversity of one of the most speciose group of animals on the planet, specialist insects. However, the most direct evidence for the process of sequential speciation comes from tritrophic systems of interacting organisms involving plants, insects that feed on these plants, and insect natural enemies that feed on these plant-feeding insects. This article first provides a broad overview of the sequential speciation literature and a guide to important reviews that detail the current state of the field. To best understand and study sequential speciation, it is important to understand how it differs from and is similar to related concepts in evolutionary ecology. In this regard, this article provides literature that defines the process and contrasts sequential speciation and strict cocladogenesis, a coevolutionary phenomenon that can result in similar patterns of biodiversity. Next, references are provided that highlight the general implications for sequential speciation and detail indirect evidence from multiple subfields of biology that implicate the process in generating biodiversity. The article then details several resources that define the conditions conducive for sequential speciation, summarizes the primary literature providing direct evidence in support of the process, and references specific studies that test for but find no evidence of sequential speciation. Lastly, the bibliography concludes by detailing future directions and considerations for studying sequential speciation and its role for understanding patterns of species diversity.
STAT6 suppression prevents bleomycin‐induced dermal fibrosis
Authors: Huang Jingjing , Puente Hydia , Wareing Nancy E. , Wu Minghua , Mayes Maureen D. , Karmouty‐Quintana Harry , Assassi Shervin , Mills Tingting W.
Published: January 2023

Fibrosis of the skin and internal organs is a hallmark of systemic sclerosis (SSc). Although the pathogenesis of SSc is poorly understood, increasing evidence suggests that interleukins (IL)‐4 and − 13 contribute to the pathogenesis of skin fibrosis by promoting collagen production and myofibroblast differentiation. Signal transducers and activators of transcription 6 (STAT6) is one of the most important downstream transcription factors activated by both IL‐4 and IL‐13. However, it is not completely understood whether STAT6 plays a role during the pathogenesis of skin fibrosis in SSc. In this study, we observed increased STAT6 phosphorylation in fibrotic skin samples collected from SSc patients as well as bleomycin‐injected murine mice. Knockout of Stat6 in mice significantly (1) suppressed the expression of fibrotic cytokines including Il13, Il17, Il22, Ccl2, and the alternatively activated macrophage marker Cd206; (2) reduced the production of collagen and fibronectin, and (3) attenuated late‐stage skin fibrosis and inflammation induced by bleomycin. Consistently, mice treated with STAT6 inhibitor AS1517499 also attenuated skin fibrosis on day 28. In addition, a co‐culture experiment demonstrated that skin epithelial cells with STAT6 knockdown had reduced cytokine expression in response to IL‐4/IL‐13, and subsequently attenuated fibrotic protein expression in skin fibroblasts. On the other side, STAT6 depletion in skin fibroblasts attenuated IL‐4/IL‐13‐induced cytokine and fibrotic marker expression, and reduced CXCL2 expression in co‐cultured keratinocytes. In summary, our study highlighted an important yet not fully understood role of STAT6 in skin fibrosis by driving innate inflammation and differentiation of alternatively activated macrophages in response to injury.
Combined Effect of Omega-3 Fatty Acid and Vitamin D3 on Oxidized LDL-C and Non–HDL-C Levels in People With Vitamin D Deficiency: A Randomized Controlled Trial
Authors: Mehdawi Amani , Mohammad Beisan A. , Mosleh Ibrahim , Khader Heba A. , Habash Maha , Nassar Razan I. , Awwad Shady , Hasoun Luai , Abu-Samak Mahmoud S.
Published: January 2023

The present randomized clinical trial (RCT) was conducted on Jordanian participants with vitamin D deficiency (VDD) with no other medical conditions, to evaluate the combined effect of 1,25-dihydroxy vitamin D3 (Vit.D3) and omega-3 fatty acid (n-3FA) supplements (D+) on oxidized low-density lipoprotein (Ox-LDL) and non–high-density lipoprotein cholesterol (non–HDL-C) levels as common predictors of cardiovascular diseases (CVDs). Participants were randomized into 4 groups as follows: a control group (C) that received no supplementations, a Vit.D3 group that received 50,000 IU of Vit.D3 every week, an n-3FA group that received 300 mg of omega-3 fatty acid every day, and a D+ group that received a combination of both supplements, with the same dosage administered by the previous groups but with a 4–6-hour time interval between Vit.D3 and n-3FA administration to avoid any possible interaction. All supplementations were administered orally for 8 weeks. Forty-seven participants were allocated to each group. Twenty-six in the control group, 37 participants in the Vit.D3 group, 37 participants in the n-3FA group, and 46 participants in the D+ group completed the study to the end. The D+ supplementations significantly increased non–HDL-C (118.99 ± 60.98 to 155.26 ± 43.36 mg/dL, P << 0.05) but decreased Ox–LDL-C levels (69.29 ± 37.69 to 52.81 ± 17.30 pg/mL, P = 0.03). The stepwise regression showed that the serum LDL-C level was the main independent variable involved in the elevation of non-HDL levels (R2 = 0.837) observed at the end of the trial in the D+ group. The groups that were supplemented with either Vit.D3 alone or n-3FA alone had an insignificant decrease in the level of Ox–LDL-C. In conclusion, despite the observed hyperlipidemic effect, the combination treatment is recommended by the research team because the decrease in Ox-LDL may offset the hyperlipidemic effect.
Symptom experience during the late reproductive stage versus the menopausal transition in the Spanish-language Women Living Better survey
Authors: Cortés Yamnia I. , Coslov Nina , Richardson Marcie K. , Woods Nancy Fugate
Published: January 2023

Objectives

The aim of this study was to characterize and compare the symptoms women self-report during the late reproductive stage and the menopausal transition.

Methods

This cross-sectional analysis used data from the Spanish-language Women Living Better survey. Women aged 35 to 55 years completed an 82-item online survey to assess menstrual cycle patterns, changes, and 61 symptoms sometimes associated with menopause. Women's menstrual patterns were classified as late reproductive stage or menopausal transition using the Stages of Reproductive Aging Workshop. Demographic and health-related data were collected, including age, country of residence, race/ethnicity, education, parity, smoking, and alcohol use. Descriptive statistics characterized reported symptoms, and logistic regression models examined associations between reproductive stage and symptoms.

Results

Of 853 respondents, 358 women were included in the sample analyzed. Participants were on average 40 ± 4.1 years old, 46% reported difficulty paying for basics, 34% lived in Spain, and 20% lived in Mexico. A similar proportion of women in the late reproductive stage and menopausal transition reported 8 of 18 symptom groups. Women in the late reproductive stage had a lower age-adjusted odds of musculoskeletal pain (odds ratio, 0.35; 95% CI, 0.19-0.66) and lower odds of decreased interest in sex (odds ratio, 0.49; 95% CI, 0.25-0.92). Both groups of women reported a similar interference with personal relationships.

Conclusions

Late–reproductive-stage women experience multiple symptoms often associated with menopause. A better understanding of symptoms experienced among Spanish-speaking women may lead to more personalized health care and facilitate anticipatory guidance about menopause. Future cross-cultural studies focusing on symptoms during the late reproductive stage are necessary.
Treatment Utilization for Posttraumatic Stress Disorder in a National Sample of Veterans and Nonveterans
Authors: Ranney Rachel M. , Maguen Shira , Bernhard Paul A. , Holder Nicholas , Vogt Dawne , Blosnich John R. , Schneiderman Aaron I.
Published: January 2023

Objective:

The current study sought to compare rates of posttraumatic stress disorder (PTSD) treatment utilization (medication and psychotherapy) among veterans and nonveterans—and to investigate which factors are associated with treatment utilization among veterans versus nonveterans.

Methods:

Participants were 2775 individuals (veteran, n=2508; nonveteran, n=267) meeting criteria for probable PTSD (determined by the PTSD Checklist) drawn from a nationwide, population-based survey. Participants reported demographic information, trauma history, mental health symptoms, insurance coverage, and treatment history.

Results:

Analyses revealed that the majority of veterans and nonveterans with probable PTSD had not received any PTSD treatment (56% of veterans and 86% of nonveterans). Population-weighted logistic regression models demonstrated that veterans with probable PTSD were substantially more likely to receive medication and psychotherapy for PTSD than nonveterans with probable PTSD. Logistic regression models demonstrated that, among veterans, having Veterans Affairs health care coverage was most strongly associated with receiving PTSD medication and psychotherapy. Black (vs. White) veterans were less likely to have received PTSD medication and psychotherapy. In contrast, among nonveterans, being married or divorced (vs. never married) was most strongly associated with receiving PTSD medication, and reporting a history of sexual trauma was most strongly associated with receiving PTSD psychotherapy.

Conclusion:

Given that most individuals do not receive PTSD treatment, additional understanding of treatment barriers and facilitators for both veterans and nonveterans is needed to improve intervention reach.
A retrospective study of clinical features and prognosis of patients with Graves’ disease and ophthalmopathy
Authors: Rui Zhong Ying , Yin Xue , Wang Xuan , Shen Jie , Zheng Wei
Published: January 2023

Objective

To retrospectively investigate the clinical characteristics of patients with Graves’ disease (GD) accompanied by ophthalmopathy (GO) and the prognosis of single 131I therapy.

Methods

In total, 665 patientswith Graves’ disease were enrolled in this study, including 115 patients with GO and 550 patients without GO. On the one hand, the clinical characteristics of the two groups were recorded. On the other hand, the prognosis after more than 6 months of 131I therapy was divided into three groups: recovered, hypothyroidism and unhealed.

Results

Compared with GD-alone patients, GD patients with GO were younger, had a higher thyrotrophin receptor antibody (TRAb), heavier thyroid mass and higher dose of single 131I therapy (all P < 0.05). Furthermore, patients were younger in the clinical active score ≥3 group and had higher FT4 level in the mild GO group (all P < 0.05). Among these, age and TRAb were independent risk factors for GO in GD patients (P < 0.05). When age was <52.5 years and TRAb was >24.01 IU/L, GD patients were more likely to develop GO (P < 0.001). After at least 6 months of single 131I therapy, compared with GD-alone patients, the prognosis was poor in GD patients with GO (P < 0.05).

Conclusion

Young GD patients with heavy thyroid mass and high TRAb are more likely to have GO. Younger GO patients are more likely to be active stage and the level of thyroid function was inversely correlated with the severity of GO. When the age and TRAb have exceeded the cutoff value, we should pay more attention to the occurrence of GO and shorten the follow-up interval appropriately. Patients with GD combined with GO have a poor prognosis.
Vaginal Candida albicans: High Frequency of in Vitro Fluconazole Resistance in a Select Population—A Brief Note
Authors: Agrawal Pranjal , Yazdy Golsa , Ghanem Khalil G. , Handa Victoria L. , Schumacher Christina M. , Sobel Jack D. , Zhang Sean X. , Tuddenham Susan
Published: January 2023

In this select population, we found a high frequency of in vitro fluconazole resistance in vaginal Candida albicans. Resistance did not reliably predict future susceptibility.

Among clinician-ordered vaginal cultures positive for Candida albicans, 30% exhibited fluconazole resistance. Resistance did not reliably predict future susceptibility. Prospective studies to verify associations with demographic and clinical factors as well as to correlate in vitro resistance with treatment response and longitudinal resistance patterns are needed.
HIV Pre-exposure Prophylaxis Persistence and Adherence Among Men Who Have Sex With Men in Four US Cities
Authors: Chapin-Bardales Johanna , Haaland Richard , Martin Amy , Holder Angela , Butts Virginia A. , Sionean Catlainn , Sey Ekow Kwa , Brady Kathleen A. , Raymond Henry F. , Opoku Jenevieve , Kuo Irene , Paz-Bailey Gabriela , Wejnert Cyprian ,   for the NHBS Study Group
Published: January 2023

Background:

HIV pre-exposure prophylaxis (PrEP) persistence and adherence are critical to ending the HIV epidemic in the United States.

Setting:

In 2017 National HIV Behavioral Surveillance, HIV-negative men who have sex with men (MSM) in 4 US cities completed a survey, HIV testing, and dried blood spots at recruitment.

Methods:

We assessed 3 PrEP outcomes: persistence (self-reported PrEP use at any time in the past 12 months and had tenofovir, emtricitabine, or tenofovir diphosphate detected in dried blood spots), adherence at ≥4 doses/week (self-reported past-month PrEP use and tenofovir diphosphate concentration ≥700 fmol/punch), and adherence at 7 doses/week (self-reported past-month PrEP use and tenofovir diphosphate concentration ≥1250 fmol/punch). Associations with key characteristics were examined using log-linked Poisson regression models with generalized estimating equations.

Results:

Among 391 MSM who took PrEP in the past year, persistence was 80% and was lower among MSM who were younger, had lower education, and had fewer sex partners. Of 302 MSM who took PrEP in the past month, adherence at ≥4 doses/week was 80% and adherence at 7 doses/week was 66%. Adherence was lower among MSM who were younger, were Black, and had fewer sex partners.

Conclusions:

Although persistence and adherence among MSM were high, 1 in 5 past-year PrEP users were not persistent and 1 in 5 past-month PrEP users were not adherent at levels that would effectively protect them from acquiring HIV (ie, ≥4 doses/week). Efforts to support PrEP persistence and adherence should include MSM who are young, are Black, and have less education.
Clinical experiences with intranasal esketamine for major depressive disorder resistant to treatment and with a psychiatric emergency: case presentations
Authors: Pompili Maurizio , Sarli Giuseppe , Erbuto Denise , Manfredi Giovanni , Comparelli Anna
Published: January 2023

Recently, esketamine became availableas an intranasal formulation, proposed for treatment-resistant depression (TRD). Three cases of TRD are presented, two with features of a psychiatric emergency. The first case is a 35-year-old man with MDD onset at the age of 27 years, with five previous failed therapies. The second patient is a middle-aged man with a 21-year MDD onset and six previous antidepressant treatments discontinued for poor therapeutic effects and tolerability. He also presented suicidal ideation with intent and a history of a failed suicide attempt by self-cutting his forearms. The third case is a 28-year-old female with a first MDD episode in 2020, treated first with amitriptyline and then with intravenous clomipramine. She had a history of a previous suicide attempt by self-cutting and, by her admission, showed active suicidal ideation with intent. In all three cases, a rapid reduction of depressive symptoms was observed with a subsequent complete resolution of suicidal ideation and intent in the two patients with such risk. Intranasal esketamine treatment was carried out with concomitant oral antidepressant therapy. The third patient reported the only recorded side effect: dissociation 20 min after every esketamine administration. Our preliminary experience proved esketamine’s effectiveness on TRD symptoms and successful outcomes in psychiatric emergencies such as suicide risk.
Characterization of microglia behaviour in healthy and pathological conditions with image analysis tools
Authors: Martinez Aleix , Hériché Jean-Karim , Calvo Maria , Tischer Christian , Otxoa-de-Amezaga Amaia , Pedragosa Jordi , Bosch Anna , Planas Anna M. , Petegnief Valérie
Published: January 2023

Microglia are very sensitive to changes in the environment and respond through morphological, functional and metabolic adaptations. To depict the modifications microglia undergo under healthy and pathological conditions, we developed free access image analysis scripts to quantify microglia morphologies and phagocytosis. Neuron–glia cultures, in which microglia express the reporter tdTomato, were exposed to excitotoxicity or excitotoxicity + inflammation and analysed 8 h later. Neuronal death was assessed by SYTOX staining of nucleus debris and phagocytosis was measured through the engulfment of SYTOX+particles in microglia. We identified seven morphologies: round, hypertrophic, fried egg, bipolar and three ‘inflamed’ morphologies. We generated a classifier able to separate them and assign one of the seven classes to each microglia in sample images. In control cultures, round and hypertrophic morphologies were predominant. Excitotoxicity had a limited effect on the composition of the populations. By contrast, excitotoxicity + inflammation promoted an enrichment in inflamed morphologies and increased the percentage of phagocytosing microglia. Our data suggest that inflammation is critical to promote phenotypical changes in microglia. We also validated our tools for the segmentation of microglia in brain slices and performed morphometry with the obtained mask. Our method is versatile and useful to correlate microglia sub-populations and behaviour with environmental changes.
A bittersweet fate: detection of serotype switching in Pseudomonas aeruginosa
Authors: Anbo Mikkel , Jelsbak Lars
Published: January 2023

High-risk clone types in

Pseudomonas aeruginosa

are problematic global multidrug-resistant clones. However, apart from their ability to resist antimicrobial treatment, not much is known about what sets these clones apart from the multitude of other clones. In high-risk clone ST111, it has previously been shown that replacement of the native serotype biosynthetic gene cluster (O4) by a different gene cluster (O12) by horizontal gene transfer and recombination may have contributed to the global success of this clone. However, the extent to which isolates undergo this type of serotype switching has not been adequately explored in

P. aeruginosa

. In the present study, a bioinformatics tool has been developed and utilized to provide a first estimate of serotype switching in groups of multidrug resistant (MDR) clinical isolates. The tool detects serotype switching by analysis of core-genome phylogeny and in silico serotype. Analysis of a national survey of MDR isolates found a prevalence of 3.9 % of serotype-switched isolates in high-risk clone types ST111, ST244 and ST253. A global survey of MDR isolates was additionally analysed, and it was found that 2.3 % of isolates had undergone a serotype switch. To further understand this process, we determined the exact boundaries of the horizontally transferred serotype O12 island. We found that the size of the serotype island correlates with the clone type of the receiving isolate and additionally we found intra-clone type variations in size and boundaries. This suggests multiple serotype switch events. Moreover, we found that the housekeeping gene gyrA is co-transferred with the O12 serotype island, which prompted us to analyse this allele for all serotype O12 isolates. We found that 95 % of ST111 O12 isolates had a resistant gyrA allele and 86 % of all O12 isolates had a resistant gyrA allele. The rates of resistant gyrA alleles in isolates with other prevalent serotypes are all lower. Together, these results show that the transfer and acquisition of serotype O12 in high-risk clone ST111 has happened multiple times and may be facilitated by multiple donors, which clearly suggests a strong selection pressure for this process. However, gyrA-mediated antibiotic resistance may not be the only evolutionary driver.
Innate immune receptor C5aR1 regulates cancer cell fate and can be targeted to improve radiotherapy in tumours with immunosuppressive microenvironments
Authors: Beach Callum , MacLean David , Majorova Dominika , Melemenidis Stavros , Nambiar Dhanya K. , Kim Ryan K. , Valbuena Gabriel N , Guglietta Silvia , Krieg Carsten , Darvish Damavandi Mahnaz , Suwa Tatsuya , Easton Alistair , Domingo Enric , Moon Eui Jung , Jiang Dadi , Jiang Yanyan , Koong Albert C , Woodruff Trent M. , Graves Edward E. , Maughan Tim , Buczacki Simon J. A. , Stucki Manuel , Le Quynh-Thu , Leedham Simon J. , Giaccia Amato J. , Olcina Monica M
Published: January 2023

An immunosuppressive microenvironment causes poor tumour T-cell infiltration and is associated with reduced patient overall survival in colorectal cancer. How to improve treatment responses in these tumours is still a challenge. Using an integrated screening approach to identify cancer-specific vulnerabilities, we identify complement receptor C5aR1 as a druggable target which when inhibited improves radiotherapy even in tumours displaying immunosuppressive features and poor CD8+ T-cell infiltration. While C5aR1 is well-known for its role in the immune compartment, we find that C5aR1 is also robustly expressed on malignant epithelial cells, highlighting potential tumour-cell specific functions. C5aR1 targeting results in increased NF-κB-dependent apoptosis specifically in tumours and not normal tissues; indicating that in malignant cells, C5aR1 primarily regulates cell fate. Collectively, these data reveal that increased complement gene expression is part of the stress response mounted by irradiated tumours and that targeting C5aR1 can improve radiotherapy even in tumours displaying immunosuppressive features.
Chemo- and optogenetic activation of hypothalamic Foxb1-expressing neurons and their terminal endings in the rostral-dorsolateral PAG leads to tachypnea, bradycardia, and immobility
Authors: Cola Reto B. , Roccaro-Waldmeyer Diana M. , Naim Samara , Babalian Alexander , Seebeck Petra , Alvarez-Bolado Gonzalo , Celio Marco R.
Published: January 2023

Foxb1-expressing neurons occur in the dorsal premammillary nucleus (PMd) and further rostrally in the parvafox nucleus, a longitudinal cluster of neurons in the lateral hypothalamus of rodents. The descending projection of these Foxb1+neurons end in the dorsolateral part of the periaqueductal gray (dlPAG). The functional role of the Foxb1+neuronal subpopulation in the PMd and the parvafox nucleus remains elusive. In this study, the activity of the Foxb1+neurons and of their terminal endings in the dlPAG was selectively altered by employing chemo- and optogenetic tools. Our results show that in whole-body barometric plethysmography, hM3Dq-mediated, global Foxb1+neuron excitation activates respiration. Time-resolved optogenetic gain-of- function manipulation of the terminal endings of Foxb1+neurons in the rostral third of the dlPAG leads to abrupt immobility and bradycardia. Chemogenetic activation of Foxb1+cell bodies and ChR2-mediated excitation of their axonal endings in the dlPAG led to a phenotypical presentation congruent with a “freezing-like” situation during innate defensive behavior.
Paresthesia during spinal cord stimulation depends on synchrony of dorsal column axon activation
Authors: Sagalajev Boriss , Zhang Tianhe , Abdollahi Nooshin , Yousefpour Noosha , Medlock Laura , Al-Basha Dhekra , Ribeiro-da-Silva Alfredo , Esteller Rosana , Ratté Stéphanie , Prescott Steven A.
Published: January 2023

Spinal cord stimulation (SCS) reduces chronic pain. Conventional (40-60 Hz) SCS engages spinal inhibitory mechanisms by activating low-threshold mechanoreceptive afferents with axons in the dorsal columns (DCs). But activating DC axons typically causes a buzzing sensation (paresthesia) that can be uncomfortable. Kilohertz-frequency (1-10 kHz) SCS produces analgesia without paresthesia and is thought, therefore, not to activate DC axons, leaving its mechanism unclear. Here we show in rats that kilohertz-frequency SCS activates DC axons but causes them to spike less synchronously than conventional SCS. Spikes desynchronize because axons entrain irregularly when stimulated at intervals shorter than their refractory period, a phenomenon we call overdrive desynchronization. Effects of overdrive desynchronization on evoked compound action potentials were verified in simulations, rats, pigs, and a chronic pain patient. Whereas synchronous spiking in DC axons is necessary for paresthesia, asynchronous spiking is sufficient to produce analgesia. Asynchronous activation of DC axons thus produces paresthesia-free analgesia.
Phylogenetic modeling of enhancer shifts in African mole-rats reveals regulatory changes associated with tissue-specific traits
Authors: Parey Elise , Frost Stephanie , Uribarren Ainhoa , Park Thomas J. , Zoettl Markus , Smith Ewan St. John , Berthelot Camille , Villar Diego
Published: January 2023

Changes in gene regulation have long been thought to underlie most phenotypic differences between species. Subterranean rodents, and in particular the naked mole-rat, have attracted substantial attention due to their proposed phenotypic adaptations, which include hypoxia tolerance, metabolic changes and cancer resistance. However, it is largely unknown what regulatory changes may associate with these phenotypic traits, and whether these are unique to the naked mole-rat, the mole-rat clade or also present in other mammals. Here, we investigate regulatory evolution in heart and liver from two African mole-rat species and two rodent outgroups using genome-wide epigenomic profiling.

First, we adapted and applied a phylogenetic modeling approach to quantitatively compare epigenomic signals at orthologous regulatory elements, and identified thousands of promoter and enhancer regions with differential epigenomic activity in mole-rats. These elements associate with known mole-rat adaptation in metabolic and functional pathways, and suggest candidate genetic loci that may underlie mole-rat innovations. Second, we evaluated ancestral and species-specific regulatory changes in the study phylogeny, and report several candidate pathways experiencing stepwise remodeling during the evolution of mole-rats – such as the insulin and hypoxia response pathways. Third, we report non-orthologous regulatory elements overlap with lineage-specific repetitive elements and appear to modify metabolic pathways by rewiring of HNF4 and RAR/RXR transcription factor binding sites in mole-rats.

These comparative analyses reveal how mole-rat regulatory evolution informs previously reported phenotypic adaptations. Moreover, the phylogenetic modeling framework we propose here improves upon the state-of-the-art by addressing known limitations of inter-species comparisons of epigenomic profiles, and has broad implications in the field of comparative functional genomics.
Afrothismiaceae (Dioscoreales), a new fully mycoheterotrophic family endemic to tropical Africa
Authors: Cheek Martin , Gomez Marybel Soto , Graham Sean W. , Rudall Paula J.
Published: January 2023

Afrothismiais a genus of non-photosynthetic mycoheterotrophs from the forests of continental tropical Africa. Multiple phylogenetic inferences using molecular data recover the genus as sister to a clade comprising mycoheterotrophic Thismiaceae and the photosynthetic family Taccaceae, contrary to earlier placements ofAfrothismiaand Thismiaceae within Burmanniaceae. Morphological support for separatingAfrothismiafrom the rest of Thismiaceae has depended on the zygomorphic flowers ofAfrothismia(although some South American species ofThismiaare also zygomorphic) and their clusters of root tubers, each with a terminal rootlet. The number of described species ofAfrothismiahas recently increased substantially, from four to 16, which has provided additional morphological characters that support its distinction from Thismiaceae. Most notably, the ovary inAfrothismiahas a single stalked placenta, and circumscissile fruits from which seeds are exserted by placental elevation (in Thismiaceae, in contrast, there are three placentas, a deliquescing fruit lid, and the seeds are not exserted).Afrothismiastamens are inserted in the lower perianth tube where they are attached to the stigma, and individual flowers are subtended by a single large dorsal bract (in Thismiaceae, stamens are inserted at the mouth of the tube, free of and distant from the stigma, and each flower is subtended by a loose whorl of (2-)3(−4) bracts). Here we formally characterise Afrothismiaceae and review what is known of its development, seed germination, interactions with mycorrhizal Glomeromycota, biogeography, phylogeny and pollination biology. All but one (Afrothismia insignis; Vulnerable) of the 13 species assessed on the IUCN Red List of Threatened Species are either Endangered or Critically Endangered; one species (A. pachyanthaSchltr.) is considered to be extinct.