bluuebunny/crossref_metadata_2025 huggingface dataset:
Decadence and Orientalism in England and Germany, 1880-1920
Authors: Herold-Zanker Katharina
Published: March 2024

Decadence and Orientalism in England and Germany, 1880–1920 examines the Orientalist portrayal of Middle Eastern cultures in decadent Literatures in England and Germany at the turn of the century. This book argues that the role of Orientalism in literary decadence uniquely exposes its paradoxical engagement with other cultures. In bringing together two fin-de-siècle European literatures, this comparative study makes a case for the transnational, if not imperial, nature of decadence. The East emerges as an ‘indispensable’ mediator between various versions of European decadences. The book examines the role of the East with specific reference to selected English and German authors: starting from Oscar Wilde’s Victorian vision of Egypt and Arthur Symons’s and Violet Fane’s acquaintance with Constantinople, it moves to Paul Scheerbart’s and Else Lasker-Schüler’s decadent Babylon and Assyria, and concludes by turning to Stefan George’s exclusion of the East from his poetic practice. The geographical reach of the East focuses on regions of the Eastern Mediterranean and Northern Africa. The cultural translation of specifically the Middle East into different European national contexts gains new—sometimes oppositional—meanings, avoiding a one-sided representation of both the East and the two national literatures that absorbed it. In arguing for a decadent cosmopolitanism as a model of heterogeneous inclusivity that reaches beyond the binaries established by Edward Said’s Orientalism, the present book brings twenty-first-century theories of cosmopolitanism into dialogue with art history and literature to uncover striking synergies and interdependences between the different manifestations of decadence in England and Germany.
‘Feeling Oriental’
Authors: Herold-Zanker Katharina
Published: March 2024

This chapter shift the focus onto German decadence. This portion of the book on Paul Scheerbart’s and German-Jewish author Else Lasker-Schüler’s Decadent Oriental fiction of the 1890s and the 1910s reads their shared Nietzschean ‘Anti-Europäertum’ [Anti-Europeanness] as a form of self-Orientalization. Scheerbart’s art historic journalism and interest in Ancient Babylon and Assyria shaped his dramas and short fiction, presenting the East as stage or mirror to Western modernity’s shortcoming. Scheerbart’s architectural writing dedicated to Glasarchitektur, however, also projects a hopeful, utopian vision which, inspired by Eastern craftsmanship, would facilitate the pacifist, transparent coming-together of a global community. More so than Symons, who sought the affiliation with Romani in England and Fane’s association with the Armenians, both authors of the Berlin Bohème longed to embody the East through their fiction, and in Lasker-Schüler’s case, also in real life. The chapter traces Lasker-Schüler creating her own auto-fictional stylization in her male Arabic alter ego, prince ‘Jussuf’, in her Orientalizing prose, and in her correspondence with British Germanist Jethro Bithell. The chapter places emphasis on the role of decadent satire and queered gender performance as tools which these authors adopted to prompt critical self-reflection on Germany’s social progress and the self-inflicted degeneration of Europe at the cusp of the First World War.
The Buried Body
Authors: Portier-Young Anathea E
Published: March 2024

This chapter makes three main moves. First, it argues for the interdependence of prophetic word and body. To make this point, it analyzes the story of the unnamed man of God from Judah and the old prophet of Bethel in 1 Kgs 13 as a parable about prophecy that places both word and body at prophecy’s center and inseparably links the two. It then surveys recent turns to the body and religious experience in biblical studies that lay the groundwork for analysis of biblical prophecy as an embodied phenomenon. Nonetheless, a logocentric model views the prophet primarily as mouthpiece of the deity and prophecy as word or message. After considering factors within the biblical prophetic corpus that have contributed to this logocentric model, it traces the further influence of a dualistic hierarchy of mind/word and body in the West in both ancient and modern periods.
God’s Surrogate (Exodus 3–4)
Authors: Portier-Young Anathea E
Published: March 2024

This chapter examines the third-person call or commissioning narrative of Moses in Exod 3–4. Earlier studies have asserted the function of prophetic call narratives to legitimate or authorize prophetic mission, forge bonds of continuity between prophets and their predecessors, and introduce salient themes found elsewhere in the prophetic book. It is argued here that the embodied encounter between prophet and deity enables and shapes the prophet’s embodied mediation between deity and people. The perceptible signs given to Moses, including the sign of his own transformed body, are guarantee, precursor, and means for performing future acts of power that transform material and social realities. Coordination of body and word in the prophet’s encounter with God lays the groundwork for a correspondingly synergistic prophetic mission.
Ecstasy
Authors: Portier-Young Anathea E
Published: March 2024

Chapter 7 considers prophetic ecstasy as a transformative religious experience. Debates about the existence and nature of prophetic ecstasy in the Hebrew Bible and Old Testament owe partly to prior assumptions about the characteristics of biblical prophecy and Israelite religion and partly to the phenomenological complexity and diverse forms of religious ecstasy. Modern debates are matched by polemics, conflicting assessments, and questions within the biblical texts. But ecstasy is not a marginal feature of biblical prophecy. It enabled a prophet to bridge human and divine realities through the temporary alteration of mind and body. Biblical evidence for induction techniques such as fasting, meditation, music, or rhythmic movement is slender. Prophetic ecstasy was frequently interpreted as a form of spirit possession that could produce visions or supernatural transport. Prophetic ecstasy had the power to make the deity present, reveal hidden realities, and reshape structures of power.
The Longitudinal Reciprocal Relationships of Tooth Brushing Behaviors Between Underserved Children and Their Caregivers
Authors: Endrighi Romano , Henshaw Michelle , Adams William G , Montion Erin , Park Hannah , Borrelli Belinda
Published: March 2024

Background

Tooth brushing is effective in preventing early childhood caries. However, it is unclear how children’s and caregiver’s tooth brushing are reciprocally related.

Purpose

The current study investigated whether the longitudinal relationships between children and caregiver tooth brushing are moderated by a caregiver-targeted child oral health intervention and caregiver depression.

Methods

Secondary analysis of a randomized clinical trial that tested whether caregiver-targeted oral health text messages (OHT) outperformed child wellness text messages (CWT) on pediatric dental caries and oral health behaviors (n = 754, mean child age = 2.9 years, 56.2% Black, 68.3% <poverty level). Tooth brushing behaviors were self-reported by caregivers using a timeline follow-back method at baseline and 4, 12, and 24 months later. Caregiver depressive symptoms were self-reported at baseline. A multigroup random intercept cross-lagged panel model examined relationships between caregiver and child tooth brushing for four post hoc groupings of condition: OHT versus CWT, and caregiver depressive symptoms: high versus low.

Results

Within-participants analyses revealed that caregiver tooth brushing at Months 4 and 12 positively predicted their child’s tooth brushing at Months 12 and 24 for caregivers in the OHT condition with low depressive symptoms (i.e., moderation by depressive symptoms and condition). Similarly, children’s tooth brushing at Month 4 positively predicted caregiver tooth brushing at Month 12 for caregivers in the OHT condition with low depressive symptoms. There were no significant associations among participants in the CWT condition, regardless of depressive symptoms.

Conclusions

Child and caregiver tooth brushing have reciprocal influences, but only for those in the OHT condition with low depressive symptoms.
Single-residue linear and conformational B cell epitopes prediction using random and ESM-2 based projections
Authors: Israeli Sapir , Louzoun Yoram
Published: March 2024

B cell epitope prediction methods are separated into linear sequence-based predictors and conformational epitope predictions that typically use the measured or predicted protein structure. Most linear predictions rely on the translation of the sequence to biologically based representations and the applications of machine learning on these representations. We here present CALIBER ‘Conformational And LInear B cell Epitopes pRediction’, and show that a bidirectional long short-term memory with random projection produces a more accurate prediction (test set AUC=0.789) than all current linear methods. The same predictor when combined with an Evolutionary Scale Modeling-2 projection also improves on the state of the art in conformational epitopes (AUC = 0.776). The inclusion of the graph of the 3D distances between residues did not increase the prediction accuracy. However, the long-range sequence information was essential for high accuracy. While the same model structure was applicable for linear and conformational epitopes, separate training was required for each. Combining the two slightly increased the linear accuracy (AUC 0.775 versus 0.768) and reduced the conformational accuracy (AUC = 0.769).
PANCDR: precise medicine prediction using an adversarial network for cancer drug response
Authors: Kim Juyeon , Park Sung-Hye , Lee Hyunju
Published: March 2024

Pharmacogenomics aims to provide personalized therapy to patients based on their genetic variability. However, accurate prediction of cancer drug response (CDR) is challenging due to genetic heterogeneity. Since clinical data are limited, most studies predicting drug response use preclinical data to train models. However, such models might not be generalizable to external clinical data due to differences between the preclinical and clinical datasets. In this study, a Precision Medicine Prediction using an Adversarial Network for Cancer Drug Response (PANCDR) model is proposed. PANCDR consists of two sub-models, an adversarial model and a CDR prediction model. The adversarial model reduces the gap between the preclinical and clinical datasets, while the CDR prediction model extracts features and predicts responses. PANCDR was trained using both preclinical data and unlabeled clinical data. Subsequently, it was tested on external clinical data, including The Cancer Genome Atlas and brain tumor patients. PANCDR outperformed other machine learning models in predicting external test data. Our results demonstrate the robustness of PANCDR and its potential in precision medicine by recommending patient-specific drug candidates. The PANCDR codes and data are available at https://github.com/DMCB-GIST/PANCDR.
High-throughput prediction of enzyme promiscuity based on substrate–product pairs
Authors: Xing Huadong , Cai Pengli , Liu Dongliang , Han Mengying , Liu Juan , Le Yingying , Zhang Dachuan , Hu Qian-Nan
Published: March 2024

The screening of enzymes for catalyzing specific substrate–product pairs is often constrained in the realms of metabolic engineering and synthetic biology. Existing tools based on substrate and reaction similarity predominantly rely on prior knowledge, demonstrating limited extrapolative capabilities and an inability to incorporate custom candidate-enzyme libraries. Addressing these limitations, we have developed the Substrate–product Pair-based Enzyme Promiscuity Prediction (SPEPP) model. This innovative approach utilizes transfer learning and transformer architecture to predict enzyme promiscuity, thereby elucidating the intricate interplay between enzymes and substrate–product pairs. SPEPP exhibited robust predictive ability, eliminating the need for prior knowledge of reactions and allowing users to define their own candidate-enzyme libraries. It can be seamlessly integrated into various applications, including metabolic engineering, de novo pathway design, and hazardous material degradation. To better assist metabolic engineers in designing and refining biochemical pathways, particularly those without programming skills, we also designed EnzyPick, an easy-to-use web server for enzyme screening based on SPEPP. EnzyPick is accessible at http://www.biosynther.com/enzypick/.
Bias correction models for electronic health records data in the presence of non-random sampling
Authors: Kim Jiyu , Anthopolos Rebecca , Zhong Judy
Published: March 2024

Electronic health records (EHRs) contain rich clinical information for millions of patients and are increasingly used for public health research. However, non-random inclusion of subjects in EHRs can result in selection bias, with factors such as demographics, socioeconomic status, healthcare referral patterns, and underlying health status playing a role. While this issue has been well documented, little work has been done to develop or apply bias-correction methods, often due to the fact that most of these factors are unavailable in EHRs. To address this gap, we propose a series of Heckman type bias correction methods by incorporating social determinants of health selection covariates to model the EHR non-random sampling probability. Through simulations under various settings, we demonstrate the effectiveness of our proposed method in correcting biases in both the association coefficient and the outcome mean. Our method augments the utility of EHRs for public health inferences, as we show by estimating the prevalence of cardiovascular disease and its correlation with risk factors in the New York City network of EHRs.
Loss-of-function variants in GLMN are associated with generalized skin hyperpigmentation with or without glomuvenous malformation
Authors: Jiang Xingyuan , Yang Chao , Wang Zhaoyang , Liang Lina , Gong Zhuoqing , Huang Shimiao , Xu Zigang , Zhang Bin , Pei Xiaoping , Cai Liangqi , Wang Huijun , Lin Zhimiao
Published: March 2024

Background

Inherited hyperpigmented skin disorders comprise a group of entities with considerable clinical and genetic heterogenicity. The genetic basis of a majority of these disorders remains to be elucidated.

Objectives

This study aimed to identify the underlying gene for an unclarified disorder of autosomal-dominant generalized skin hyperpigmentation with or without glomuvenous malformation.

Methods

Whole-exome sequencing was performed in five unrelated families with autosomal-dominant generalized skin hyperpigmentation. Variants were confirmed using Sanger sequencing and a minigene assay was employed to evaluate the splicing alteration. Immunofluorescence and transmission electron microscopy (TEM) were used to determine the quantity of melanocytes and melanosomes in hyperpigmented skin lesions. GLMN knockdown by small interfering RNA assays was performed in human MNT-1 cells to examine melanin concentration and the underlying molecular mechanism.

Results

We identified five variants in GLMN in five unrelated families, including c.995_996insAACA(p.Ser333Thrfs*11), c.632 + 4delA, c.1470_1473dup(p.Thr492fs*12), c.1319G > A(p.Trp440*) and c.1613_1614insTA(Thr540*). The minigene assay confirmed that the c.632 + 4delA mutant resulted in abolishment of the canonical donor splice site. Although the number of melanocytes remained unchanged in skin lesions, as demonstrated by immunofluorescent staining of tyrosinase and premelanosome protein, TEM revealed an increased number of melanosomes in the skin lesion of a patient. The GLMN knockdown MNT-1 cells demonstrated a higher melanin concentration, a higher proportion of stage III and IV melanosomes, upregulation of microphthalmia-associated transcription factor and tyrosinase, and downregulation of phosphorylated p70S6 K vs. mock-transfected cells.

Conclusions

We found that loss-of-function variants in GLMN are associated with generalized skin hyperpigmentation with or without glomuvenous malformation. Our study implicates a potential role of glomulin in human skin melanogenesis, in addition to vascular morphogenesis.
Real-world practice and outcomes in pilonidal surgery: Pilonidal Sinus Treatment Studying The Options (PITSTOP) cohort
Authors: Brown Steven R , Hind Daniel , Strong Emily , Bradburn Mike , Din Farhat , Lee Ellen , Lund Jon , Moffatt Christine , Morton Jonathan , Senapati Asha , Jones Helen , Lee Matthew J ,   PITSTOP Management Group, Ali K , Brady R , Branagan G , Chaudri S , Di Fabio F , Dennison G , Donnelly D , Evans M , Gerald F , Gonzalez S , Grainger J , Hardy A , Husain N , Kapur S , Keogh K , Lim M , Mackey P , Maeda Y , Mangam S , Mazarelo F , Muhammad K , Pawa N , Pearce L , Pitt J , Rajaganeshan R , Shackley P , Simmonds R , Stevenson R , Torkington J , Vaughan-Shaw P , Dale Vimalachandran , Wilson J
Published: March 2024

Background

Numerous surgical approaches exist for the treatment of pilonidal disease. Current literature on treatment is of poor quality, limiting the ability to define optimal intervention. The aim of this study was to provide real-world data on current surgical practice and report patient and risk-adjusted outcomes, informing future trial design.

Methods

This UK-wide multicentre prospective cohort study, including patients (aged over 16 years) who had definitive treatment for symptomatic pilonidal disease, was conducted between May 2019 and March 2022. Patient and disease characteristics, and intervention details were analysed. Data on patient-reported outcomes, including pain, complications, treatment failure, wound issues, and quality of life, were gathered at various time points up to 6 months after surgery. Strategies were implemented to adjust for risk influencing different treatment choices and outcomes.

Results

Of the 667 participants consenting, 574 (86.1%) were followed up to the study end. Twelve interventions were observed. Broadly, 59.5% underwent major excisional surgery and 40.5% minimally invasive surgery. Complications occurred in 45.1% of the cohort. Those who had minimally invasive procedures had better quality of life and, after risk adjustment, less pain (score on day 1: mean difference 1.58, 95% c.i. 1.14 to 2.01), fewer complications (difference 17.5 (95% c.i. 9.1 to 25.9)%), more rapid return to normal activities (mean difference 25.9 (18.4 to 33.4) days) but a rate of higher treatment failure (difference 9.6 (95% c.i. 17.3 to 1.9)%). At study end, 25% reported an unhealed wound and 10% had not returned to normal activities.

Conclusion

The burden after surgery for pilonidal disease is high and treatment failure is common. Minimally invasive techniques may improve outcomes at the expense of a 10% higher risk of treatment failure.
Histopathological, Clinical, And Molecular (HICAM) score for patients with colorectal liver metastases
Authors: Martín-Cullell Berta , Virgili Anna C , Riera Pau , Fumagalli Caterina , Mirallas Oriol , Pelegrín Francisco J , Sánchez-Cabús Santiago , Molina Víctor , Szafranska Justyna , Páez David
Published: March 2024

Background

Histopathological and molecular features have been proposed to hold prognostic information, but few have been validated. The aim of this retrospective study was to validate the Genetic And Morphological Evaluation (‘GAME’) score and assess the impact of histological characteristics on the prognosis in patients with colorectal liver metastases.

Methods

Data were collected from 176 patients with metastatic colorectal cancer undergoing liver resection at Hospital de la Santa Creu i Sant Pau. Patients were classified into Genetic And Morphological Evaluation score groups and relapse-free survival and overall survival were calculated. Histopathological changes in colorectal liver metastases were documented and prognostic variables were selected to create a post-surgery score, called the Histopathological, Clinical, And Molecular (‘HICAM’) score.

Results

Regarding the Genetic And Morphological Evaluation score, the high-risk group had a median relapse-free survival of 8.8 months, compared with 20.5 months for the low-risk group (P = 0.005), and the high-risk group had a median overall survival of 37.8 months, compared with 67.0 months for the low-risk group (P = 0.005). Histological examination of 144 liver samples showed that the desertic immune phenotype was associated with worse overall survival in the multivariable analysis (P = 0.020). The Histopathological, Clinical, And Molecular score variables were age at diagnosis, tumour burden score, carcinoembryonic antigen levels greater than or equal to 20 ng/ml, primary tumour resection, TNM stage at diagnosis, molecular status, histopathological growth patterns, and immune phenotypes of the liver. The high-risk group had a median relapse-free survival of 8.4 months, compared with 20.4 months for the low-risk group (P < 0.001), and a median overall survival of 30.4 months, compared with 105.0 months for the low-risk group (P < 0.001).

Conclusion

The Genetic And Morphological Evaluation score was validated as a preoperative prognostic tool to predict candidacy for liver resection. The Histopathological, Clinical, And Molecular score could be useful to assess adjuvant treatment after hepatic resection.
Discrepant changes in structure–function coupling in dancers and musicians
Authors: Gao Kexin , He Hui , Lu Bao , Xie Qiushui , Lu Jing , Yao Dezhong , Luo Cheng , Li Gujing
Published: March 2024

Dance and music are well known to improve sensorimotor skills and cognitive functions. To reveal the underlying mechanism, previous studies focus on the brain plastic structural and functional effects of dance and music training. However, the discrepancy training effects on brain structure–function relationship are still blurred. Thus, proficient dancers, musicians, and controls were recruited in this study. The graph signal processing framework was employed to quantify the region-level and network-level relationship between brain function and structure. The results showed the increased coupling strength of the right ventromedial putamen in the dance and music groups. Distinctly, enhanced coupling strength of the ventral attention network, increased coupling strength of the right inferior frontal gyrus opercular area, and increased function connectivity of coupling function signal between the right and left middle frontal gyrus were only found in the dance group. Besides, the dance group indicated enhanced coupling function connectivity between the left inferior parietal lobule caudal area and the left superior parietal lobule intraparietal area compared with the music groups. The results might illustrate dance and music training’s discrepant effect on the structure–function relationship of the subcortical and cortical attention networks. Furthermore, dance training seemed to have a greater impact on these networks.
A case report of a young woman with pulmonary emboli and a right coronary artery-to-coronary sinus fistula
Authors: Karthik V , Anosike Chinedum , Zivlas Christos
Published: March 2024

Background

Coronary artery fistulae are rare cardiovascular anomalies that can present with atypical symptomatology and therefore pose diagnostic challenges, especially in young patients.

Case summary

A 34-year-old woman presented with left-sided pleuritic chest pain, haemoptysis, and flu-like symptoms. Initial evaluation revealed multiple left-sided pulmonary emboli, and her transthoracic echocardiography showed turbulent flow in a dilated coronary sinus. A right coronary artery (RCA) to coronary sinus fistula was confirmed by computed tomography coronary angiogram. The patient was treated with lifelong anticoagulation, and a subsequent stress cardiac magnetic resonance imaging did not show inducible myocardial ischaemia. As such, the patient was managed conservatively.

Discussion

Utilization of multi-modality imaging is of utmost importance for diagnostic and therapeutic purposes in coronary artery fistulae. In this case report, our patient presented with unprovoked pulmonary emboli, which could be caused by the turbulent flow and stasis, due to the RCA-to-coronary sinus fistula.
Preventing childhood obesity in general practice: a qualitative study of GPs, practice nurses, and practice managers
Authors: Gooey Michelle , Hailu Haimanot , Sturgiss Elizabeth , Advocat Jenny , Bergmeier Heidi , Skouteris Helen
Published: March 2024

Background

General practitioners (GPs) in Australia have an important role to play in preventing childhood obesity. Activities such as growth monitoring and promotion of healthy behaviours can contribute to obesity prevention efforts; however, the practicalities of how this is done are poorly documented.

Objectives

Objectives were to understand current attitudes and practices regarding promoting healthy childhood growth and development and preventing childhood obesity in general practice, and identify practical barriers and enablers to routinely incorporating this into general practice based on the observations and personal experiences of general practice staff.

Methods

A descriptive qualitative study was undertaken with Australian general practice staff. Barriers and enablers underwent thematic analysis and mapped to the ecological model.

Results

Interviews were conducted with 9 GPs, 4 nurses, and 2 practice managers. Participants agreed that growth monitoring and healthy behaviour promotion should be done for children with a healthy weight. However, the thematic analysis indicated that obesity prevention in clinics is not supported well by the broader general practice system, there are complexities associated with obesity prevention discussions, and the COVID-19 pandemic has intensified challenges in general practice. Two themes for obesity prevention enablers were identified; these related to bridging the implementation gap and the need for changes outside the clinic to support behaviour within the clinic. Ecological model mapping implicated multiple ecological levels for each theme.

Conclusion

Childhood obesity prevention through growth monitoring and healthy behaviour promotion is relevant to general practice; however, more support is needed to enable implementation and embed these practices day-to-day.
The Left-Right Side-Specific Neuroendocrine Signaling from Injured Brain: An Organizational Principle
Authors: Watanabe Hiroyuki , Kobikov Yaromir , Nosova Olga , Sarkisyan Daniil , Galatenko Vladimir , Carvalho Liliana , Maia Gisela H , Lukoyanov Nikolay , Lavrov Igor , Ossipov Michael H , Hallberg Mathias , Schouenborg Jens , Zhang Mengliang , Bakalkin Georgy
Published: March 2024

A neurological dogma is that the contralateral effects of brain injury are set through crossed descending neural tracts. We have recently identified a novel topographic neuroendocrine system (T-NES) that operates via a humoral pathway and mediates the left-right side-specific effects of unilateral brain lesions. In rats with completely transected thoracic spinal cords, unilateral injury to the sensorimotor cortex produced contralateral hindlimb flexion, a proxy for neurological deficit. Here, we investigated in acute experiments whether T-NES consists of left and right counterparts and whether they differ in neural and molecular mechanisms. We demonstrated that left- and right-sided hormonal signaling is differentially blocked by the δ-, κ- and µ-opioid antagonists. Left and right neurohormonal signaling differed in targeting the afferent spinal mechanisms. Bilateral deafferentation of the lumbar spinal cord abolished the hormone-mediated effects of the left-brain injury but not the right-sided lesion. The sympathetic nervous system was ruled out as a brain-to-spinal cord-signaling pathway since hindlimb responses were induced in rats with cervical spinal cord transections that were rostral to the preganglionic sympathetic neurons. Analysis of gene–gene co-expression patterns identified the left- and right-side-specific gene co-expression networks that were coordinated via the humoral pathway across the hypothalamus and lumbar spinal cord. The coordination was ipsilateral and disrupted by brain injury. These findings suggest that T-NES is bipartite and that its left and right counterparts contribute to contralateral neurological deficits through distinct neural mechanisms, and may enable ipsilateral regulation of molecular and neural processes across distant neural areas along the neuraxis.
Reduced synaptic depression in human neurons carrying homozygous disease-causing STXBP1 variant L446F
Authors: Öttl Miriam , Toonen Ruud F , Verhage Matthijs
Published: March 2024

MUNC18-1 is an essential protein of the regulated secretion machinery. De novo, heterozygous mutations in STXBP1, the human gene encoding this protein, lead to a severe neurodevelopmental disorder. Here, we describe the electrophysiological characteristics of a unique case of STXBP1-related disorder caused by a homozygous mutation (L446F). We engineered this mutation in induced pluripotent stem cells from a healthy donor (STXBP1LF/LF) to establish isogenic cell models. We performed morphological and electrophysiological analyses on single neurons grown on glial micro-islands. Human STXBP1LF/LF neurons displayed normal morphology and normal basal synaptic transmission but increased paired-pulse ratios and charge released, and reduced synaptic depression compared to control neurons. Immunostainings revealed normal expression levels but impaired recognition by a mutation-specific MUNC18-1 antibody. The electrophysiological gain-of-function phenotype is in line with earlier overexpression studies in Stxbp1 null mouse neurons, with some potentially human-specific features. Therefore, the present study highlights important differences between mouse and human neurons critical for the translatability of pre-clinical studies.
Black Alaskans Health Needs Assessment during COVID-19 Pandemic: Implications for Social Work
Authors: Mbise Amana , Hodge-Growden Celeste , Bemben Thea , Shimizu Rei
Published: March 2024

At the peak of the COVID-19 pandemic it became clear that Black people were experiencing more severe symptoms and had higher rates of mortality from COVID-19 than White people. However, data on racial differences in death and hospitalization rates in Alaska were less clear. To address this, the Alaska Black Caucus initiated the first Black Alaskans health needs assessment to understand the health status, needs, and resources of the Black community of Alaska. This article reports on the design, implementation, and descriptive results from the survey portion of the first community health needs assessment of Black Alaskans. The findings indicate that a majority of Black Alaskans report being moderately healthy, having access to health insurance, owning their homes, and having a favorable view of their neighborhood. However, too many are unable to work due to poor physical or mental health challenges and are diagnosed with one or more chronic health diseases. In addition, Black Alaskans experience high rates of substance abuse, have untreated mental health conditions, consume tobacco products at a high rate, and are not screening for some cancers. The article will conclude by presenting additional strategies for improving healthcare access and responsiveness for Black Alaskans.
Metagenomic insights into jellyfish-associated microbiome dynamics during strobilation
Authors: Peng Saijun , Ye Lijing , Li Yongxue , Wang Fanghan , Sun Tingting , Wang Lei , Zhao Jianmin , Dong Zhijun
Published: March 2024

Host-associated microbiomes can play key roles in the metamorphosis of animals. Most scyphozoan jellyfish undergo strobilation in their life cycles, similar to metamorphosis in classic bilaterians. The exploration of jellyfish microbiomes may elucidate the ancestral mechanisms and evolutionary trajectories of metazoan–microbe associations and interactions during metamorphosis. However, current knowledge of the functional features of jellyfish microbiomes remains limited. Here, we performed a genome-centric analysis of associated microbiota across four successive life stages (polyp, early strobila, advanced strobila, and ephyra) during strobilation in the common jellyfish Aurelia coerulea. We observed shifts in taxonomic and functional diversity of microbiomes across distinct stages and proposed that the low microbial diversity in ephyra stage may be correlated with the high expression of the host-derived antimicrobial peptide aurelin. Furthermore, we recovered 43 high-quality metagenome-assembled genomes and determined the nutritional potential of the dominant Vibrio members. Interestingly, we observed increased abundances of genes related to the biosynthesis of amino acids, vitamins, and cofactors, as well as carbon fixation during the loss of host feeding ability, indicating the functional potential of Aurelia-associated microbiota to support the synthesis of essential nutrients. We also identified several potential mechanisms by which jellyfish-associated microbes establish stage-specific community structures and maintain stable colonization in dynamic host environments, including eukaryotic-like protein production, bacterial secretion systems, restriction-modification systems, and clustered regularly interspaced short palindromic repeats-Cas systems. Our study characterizes unique taxonomic and functional changes in jellyfish microbiomes during strobilation and provides foundations for uncovering the ancestral mechanism of host–microbe interactions during metamorphosis.
A Feminist Critique of International Practices
Authors: Chessé Alice , Sondarjee Maïka
Published: March 2024

Feminist social theories, especially intersectional and decolonial ones, have been footnotes at best in practice-oriented research in international relations. This disciplinary exclusion of gender studies’ concepts from “international practice theories” (IPTs) or the "practice turn" has marginalized inquiries into power and reflexivity in action. As a result, IPTs have failed to theorize how practitioners’ reflexivity is shaped by local manifestations of systemic lines of difference like race, gender, coloniality, or class. This Theory Note argues that intersectional and decolonial feminist approaches can address this gap. We demonstrate that positionality and privilege condition practical reflexivity by shaping (1) normative interpretations of the world, (2) the content of social critique, and (3) the reception of such critique. Taking feminists as foundational theorists of international practices is critical to addressing some ontological challenges encountered by current IPT scholarship. In this Theory Note, we develop a productive conversation between the two bodies of literature around concepts of background knowledge and competence, which allows for a better understanding of the interplay of structural power and individual reflexivity in everyday interactions.
Perspectives of patients, parents, and health care providers on facilitators of and barriers to the transition from pediatric to adult care in inflammatory bowel disease: a qualitative descriptive study
Authors: Bihari Allison , Wine Eytan , Seow Cynthia H , Goodman Karen J , Kroeker Karen I
Published: March 2024

Background

The typical transition from pediatric to adult care in patients with inflammatory bowel disease occurs with an increase in health care utilization and a decrease in adherence to medications and scheduled appointments. An effective transition could reduce negative impacts but requires identifying opportunities to improve this process. This study aims to describe barriers and facilitators of transition according to patients, parents, and health care providers.

Methods

This study used a qualitative description approach. The lead author conducted semi-structured interviews with 17 patients, 13 parents, and 15 providers recruited from Western Canada. Latent content analysis identified themes in interview transcripts.

Results

The theme of preparedness emerged across all groups as a transition facilitator. Other facilitators that emerged included patient characteristics, supportive parents, home environment, and supportive adult care team. Themes of barriers that emerged included patient factors, “hovering parents” and family factors, navigating a new health care system, and travel distance.

Conclusions

This study describes facilitators and barriers according to each stakeholder involved in the transition process. Future studies should focus on designing and evaluating interventions aimed at promoting facilitators and addressing identified barriers in patients preparing to transition from pediatric to adult care.
The Market Dynamics of Collective Ignorance and Spiraling Risk
Authors: Pellandini-Simányi Léna , Barnhart Michelle
Published: March 2024

In some markets, offerings become riskier over time as producers introduce new versions that are made more affordable by increasing their risk. Existing theories suggest consumers adopt riskier versions either because they become more risk tolerant or they trade higher risk for lower price—both of which presume consumers know the risks. We reveal a third explanation: evolving market dynamics that increasingly encourage consumer inattention to risk and produce “collective ignorance.” We identify factors of collective inattention and propose a three-stage model of development of collective ignorance by analyzing the case of risk buildup in the Hungarian mortgage market. Data include archival materials and interviews with borrowers, lenders, and regulators. Initially, producers offer low-risk products, and social, cultural, and institutional factors encourage attention to risk. Consumers attentive to and capable of assessing risk become early adopters. Over time, increasing adoption and changes in market factors divert consumers’ attention from risk, shifting it to price. Under insufficient regulation, risk escalates: producers repeatedly cut price by offering increasingly risky products, while rising collective ignorance leads even risk-averse consumers to adopt them. We offer theoretical contributions to research on the social construction of risk, the attitude–behavior gap, and neoliberal responsibilization.
TRAF3 regulation of proximal TLR signaling in B cells
Authors: Ybarra Tiffany K , Bishop Gail A
Published: March 2024

Toll-like receptors are pattern recognition receptors that bridge the innate and adaptive immune responses and are critical for host defense. Most studies of Toll-like receptors have focused upon their roles in myeloid cells. B lymphocytes express most Toll-like receptors and are responsive to Toll-like receptor ligands, yet Toll-like receptor–mediated signaling in B cells is relatively understudied. This is an important knowledge gap, as Toll-like receptor functions can be cell type specific. In striking contrast to myeloid cells, TRAF3 inhibits TLR-mediated functions in B cells. TRAF3-deficient B cells display enhanced IRF3 and NFκB activation, cytokine production, immunoglobulin isotype switching, and antibody production in response to Toll-like receptors 3, 4, 7, and 9. Here, we address the question of how TRAF3 impacts initial B-cell Toll-like receptor signals to regulate downstream activation. We found that TRAF3 in B cells associated with proximal Toll-like receptor 4 and 7 signaling proteins, including MyD88, TRAF6, and the tyrosine kinase Syk. In the absence of TRAF3, TRAF6 showed a greater association with several Toll-like receptor signaling proteins, suggesting that TRAF3 may inhibit TRAF6 access to Toll-like receptor signaling complexes and thus early Toll-like receptor signaling. In addition, our results highlight a key role for Syk in Toll-like receptor signaling in B cells. In the absence of TRAF3, Syk activation was enhanced in response to ligands for Toll-like receptors 4 and 7, and Syk inhibition reduced downstream Toll-like receptor–mediated NFκB activation and proinflammatory cytokine production. This study reveals multiple mechanisms by which TRAF3 serves as a key negative regulator of early Toll-like receptor signaling events in B cells.
Cytoreductive nephrectomy in the era of immune checkpoint inhibitors: a US Food and Drug Administration pooled analysis
Authors: Fallah Jaleh , Gittleman Haley , Weinstock Chana , Chang Elaine , Agrawal Sundeep , Tang Shenghui , Pazdur Richard , Kluetz Paul G , Suzman Daniel L , Amiri-Kordestani Laleh
Published: March 2024

Background

This pooled analysis of patient-level data from trials evaluated the clinical outcomes of patients with metastatic renal cell carcinoma with or without cytoreductive nephrectomy before a combination of immune checkpoint inhibitor and antiangiogenic therapy.

Methods

Data from 5 trials of immune checkpoint inhibitors plus antiangiogenic therapy were pooled. Only patients with stage 4 disease at initial diagnosis were included to ensure that nephrectomy was performed for cytoreductive purposes and not to previously treat an earlier stage of disease. The effect of cytoreductive nephrectomy before immune checkpoint inhibitor therapy on outcomes was evaluated using the Kaplan-Meier method and a Cox proportional hazards regression model, adjusted for age, sex, risk group, performance status, and the presence of sarcomatoid differentiation.

Results

A total of 981 patients were included. The estimated median progression-free survival with and without nephrectomy was 15 and 11 months, respectively; the adjusted hazard ratio was 0.71 (95% confidence interval = 0.59 to 0.85). The estimated median overall survival with and without nephrectomy was 46 and 28 months, respectively; the adjusted hazard ratio was 0.63 (95% confidence interval = 0.51 to 0.77). Objective response was 60% of patients with vs 46% of patients without cytoreductive nephrectomy.

Conclusions

Patients with metastatic renal cell carcinoma who undergo cytoreductive nephrectomy before immune checkpoint inhibitor plus antiangiogenic therapy had improved outcomes compared with patients without cytoreductive nephrectomy. Selection factors for cytoreductive nephrectomy may be prognostic and could not be fully controlled for in this retrospective analysis. Prospective determination of and stratification by prior cytoreductive nephrectomy may be considered when designing clinical trials to assess the impact of this factor on prognosis.
A goodness of fit framework for relational event models
Authors: Amati Viviana , Lomi Alessandro , Snijders Tom A B
Published: March 2024

We introduce a novel procedure to assess the goodness of fit in relational event models. Building on existing auxiliary variable approaches developed in network modelling, the procedure involves a comparison between statistics computed on observed relational event sequences and statistics calculated on event sequences simulated from the fitted model. We argue that the internal time structure of the relational mechanisms assumed to generate the observations under the model is an important aspect of the fit of a model to observed relational event sequences. We establish the empirical value of the proposed goodness of fit approach in an analysis of data that we collected on collaborative patient-referral relations among healthcare organizations. The illustrative case study that we develop reveals distinctive features of relational event models that have been ignored or overlooked in received empirical studies.
Nonparametric identification of causal effects in clustered observational studies with differential selection
Authors: Ye Ting , Westling Ted , Page Lindsay , Keele Luke
Published: March 2024

The clustered observational study (COS) design is the observational counterpart to the clustered randomized trial. COSs are common in both education and health services research. In education, treatments may be given to all students within some schools but withheld from all students in other schools. In health studies, treatments may be applied to clusters such as hospitals or groups of patients treated by the same physician. In this paper, we study the identification of causal effects in COS designs. We focus on the prospect of differential selection of units to clusters, which occurs when the units’ cluster selections depend on the clusters’ treatment assignments. Extant work on COSs has made an implicit assumption that rules out the presence of differential selection. We derive the identification results for designs with differential selection and that contexts with differential cluster selection require different adjustment sets than standard designs. We outline estimators for designs with and without differential selection. Using a series of simulations, we outline the magnitude of the bias that can occur with differential selection. We then present 2 empirical applications focusing on the likelihood of differential selection.
On the instrumental variable estimation with many weak and invalid instruments
Authors: Lin Yiqi , Windmeijer Frank , Song Xinyuan , Fan Qingliang
Published: March 2024

We discuss the fundamental issue of identification in linear instrumental variable (IV) models with unknown IV validity. With the assumption of the ‘sparsest rule’, which is equivalent to the plurality rule but becomes operational in computation algorithms, we investigate and prove the advantages of non-convex penalized approaches over other IV estimators based on two-step selections, in terms of selection consistency and accommodation for individually weak IVs. Furthermore, we propose a surrogate sparsest penalty that aligns with the identification condition and provides oracle sparse structure simultaneously. Desirable theoretical properties are derived for the proposed estimator with weaker IV strength conditions compared to the previous literature. Finite sample properties are demonstrated using simulations and the selection and estimation method is applied to an empirical study concerning the effect of body mass index on diastolic blood pressure.
Hoarseness due to subcutaneous emphysema: a rare presentation of diverticular perforation
Authors: Bormann Sydney L , Wood Rebekah , Guido Jenny M
Published: March 2024

Pneumomediastinum and subcutaneous emphysema usually result from alveolar rupture and rarely from colonic perforation. Although steroid use has been shown to increase the risk of complicated diverticulitis, there is limited data on the role Addison’s disease may play in the development of colonic perforation. We present a rare case of a patient with Addison’s disease who presented with hoarseness and was found to have massive subcutaneous emphysema, pneumomediastinum, and pneumoretroperitoneum secondary to complicated diverticulitis.
Three cases of non-infectious necrotizing stromal keratitis after corneal refractive surgery
Authors: Chen Hu , Shen Ting , Tan Ling Tong
Published: March 2024

We reported three cases of aseptic necrotizing stromal keratinitis after corneal refractive surgery (two with small incision lenticule extraction and one with femtosecond laser-laser-assisted insitu keratomileusis). There were three young women who had undergone corneal refractive surgery had white aseptic infiltrating foci along or away from the stroma in both eyes or one eye on regular review, all of whom denied systemic disease or chronic ocular disease. Two patients were diagnosed with aseptic necrotizing corneal stromal inflammation, and one patient was diagnosed with delayed necrotizing corneal stromal inflammation. In our opinion, before corneal refractive surgery, medical history inquiry is very important. More attention should be paid to patients with vaccination history and foreign travel history. In addition, the possibility of delayed corneal stromal inflammation should be considered for patients with poor binocular corrected vision.