bluuebunny/crossref_metadata_2025 huggingface dataset:
Lower activity of cholesteryl ester transfer protein (CETP) and the risk of dementia: a Mendelian randomization analysis
Authors: Schmidt Amand F. , Davidson Michael H. , Ditmarsch Marc , Kastelein John J. , Finan Chris
Published: October 2024

Background

Elevated concentrations of low-density lipoprotein cholesterol (LDL-C) are linked to dementia risk, and conversely, increased plasma concentrations of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein-A1 (Apo-A1) associate with decreased dementia risk. Inhibition of cholesteryl ester transfer protein (CETP) meaningfully affects the concentrations of these blood lipids and may therefore provide an opportunity to treat dementia.

Methods

Drug target Mendelian randomization (MR) was employed to anticipate the on-target effects of lower CETP concentration (μg/mL) on plasma lipids, cardiovascular disease outcomes, autopsy confirmed Lewy body dementia (LBD), as well as Parkinson’s dementia.

Results

MR analysis of lower CETP concentration recapitulated the blood lipid effects observed in clinical trials of CETP-inhibitors, as well as protective effects on coronary heart disease (odds ratio (OR) 0.92, 95% confidence interval (CI) 0.89; 0.96), heart failure, abdominal aortic aneurysm, any stroke, ischemic stroke, and small vessel stroke (0.90, 95%CI 0.85; 0.96). Consideration of dementia related traits indicated that lower CETP concentrations were associated higher total brain volume (0.04 per standard deviation, 95%CI 0.02; 0.06), lower risk of LBD (OR 0.81, 95%CI 0.74; 0.89) and Parkinson’s dementia risk (OR 0.26, 95%CI 0.14; 0.48). APOE4 stratified analyses suggested the LBD effect was most pronounced in APOE-ε4 + participants (OR 0.61 95%CI 0.51; 0.73), compared to APOE-ε4- (OR 0.89 95%CI 0.79; 1.01); interaction p-value 5.81 × 10− 4.

Conclusions

These results suggest that inhibition of CETP may be a viable strategy to treat dementia, with a more pronounced effect expected in APOE-ε4 carriers.
RadioComics—Santa Claus and the breakthrough reaction
Authors: Lombardo Paolo , Nairz Knud , Boehm Ingrid
Published: October 2024

Graphical Abstract
Dynamic Retrieval Augmented Generation of Ontologies using Artificial Intelligence (DRAGON-AI)
Authors: Toro Sabrina , Anagnostopoulos Anna V. , Bello Susan M. , Blumberg Kai , Cameron Rhiannon , Carmody Leigh , Diehl Alexander D. , Dooley Damion M. , Duncan William D. , Fey Petra , Gaudet Pascale , Harris Nomi L. , Joachimiak Marcin P. , Kiani Leila , Lubiana Tiago , Munoz-Torres Monica C. , O‘Neil Shawn , Osumi-Sutherland David , Puig-Barbe Aleix , Reese Justin T. , Reiser Leonore , Robb Sofia MC. , Ruemping Troy , Seager James , Sid Eric , Stefancsik Ray , Weber Magalie , Wood Valerie , Haendel Melissa A. , Mungall Christopher J.
Published: October 2024

Background

Ontologies are fundamental components of informatics infrastructure in domains such as biomedical, environmental, and food sciences, representing consensus knowledge in an accurate and computable form. However, their construction and maintenance demand substantial resources and necessitate substantial collaboration between domain experts, curators, and ontology experts.

We present Dynamic Retrieval Augmented Generation of Ontologies using AI (DRAGON-AI), an ontology generation method employing Large Language Models (LLMs) and Retrieval Augmented Generation (RAG). DRAGON-AI can generate textual and logical ontology components, drawing from existing knowledge in multiple ontologies and unstructured text sources.

Results

We assessed performance of DRAGON-AI on de novo term construction across ten diverse ontologies, making use of extensive manual evaluation of results. Our method has high precision for relationship generation, but has slightly lower precision than from logic-based reasoning. Our method is also able to generate definitions deemed acceptable by expert evaluators, but these scored worse than human-authored definitions. Notably, evaluators with the highest level of confidence in a domain were better able to discern flaws in AI-generated definitions. We also demonstrated the ability of DRAGON-AI to incorporate natural language instructions in the form of GitHub issues.

Conclusions

These findings suggest DRAGON-AI's potential to substantially aid the manual ontology construction process. However, our results also underscore the importance of having expert curators and ontology editors drive the ontology generation process.
Investigation of parasite genetic variation and systemic immune responses in patients presenting with different clinical presentations of cutaneous leishmaniasis caused by Leishmania aethiopica
Authors: Yizengaw Endalew , Takele Yegnasew , Franssen Susanne , Gashaw Bizuayehu , Yimer Mulat , Adem Emebet , Nibret Endalkachew , Yismaw Gizachew , Cruz Cervera Edward , Ejigu Kefale , Tamiru Dessalegn , Munshea Abaineh , Müller Ingrid , Weller Richard , Cotton James A. , Kropf Pascale
Published: October 2024

Background

Cutaneous leishmaniasis (CL) is a neglected tropical skin disease, caused by the protozoan parasite Leishmania. In Ethiopia, CL is mainly caused by Leishmania aethiopica and can present in different clinical forms. The aim of this study was to assess whether these different forms are associated with differences in parasite genetic and host systemic immune signatures.

Methods

Here we analysed the whole genome sequence data for 48 clinical parasite isolates and the systemic immune signature from a cohort of CL patients, who were recruited in Nefas Mewcha, Northern Ethiopia, from January 2019 to January 2022.

Results

Our results show that parasites from CL cases with different presentations in a single Ethiopian setting are from the same genetic population based on a permutation test of genome-wide similarity. Furthermore, a logistic regression test for genome wide association did not identify any individual genetic variants significantly associated with disease presentation. We also measured plasma chemokine and cytokine levels of 129 CL patients presenting with different forms of CL. None of the chemokine [eotaxin, eotaxin-3, interleukin (IL)-8, interferon (IFN)-γ-induced protein-10 (IP-10), monocyte chemoattractant protein (MCP)-1, MCP-4, macrophage-derived chemokines (MDC), macrophage inflammatory protein (MIP)-1α, MIP-1β and thymus- and activation-regulated chemokine (TARC)] or cytokine (IFN-γ, IL-1β, interleukin-2, IL-4, IL-6, IL-10, IL-12p70, IL-13, tumor necrosis factor-α) levels measured were significantly different between the different clinical presentations of CL, as measured by Kruskal–Wallis test. We also compared those with healthy nonendemic controls: our results show a chemokine (IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β and TARC) but not a cytokine immune signature in patients with CL as compared to healthy nonendemic controls, as measured by Mann-Whitney test.

Conclusions

The results of our study did not identify a systemic immune signature or parasite genetic factors associated with different clinical presentation of CL.

Graphical abstract
Brain-to-brain synchrony increased during interpersonal touch in romantic lovers: an EEG-based hyperscanning study
Authors: Zhou Chenghao , Jiang Xiaowei , Chen Yanan , Ge Chunlei , Ao Na , Du Feng
Published: October 2024

Background

Interpersonal touch is an essential element of human social life. It’s unclear whether the neural patterns of interpersonal touch are specific to intimate relationships or generally apply to other social relationships. Romantic lovers are typically intimate and have a high level of interpersonal touch. Currently, researchers focused on the neurobiological basis and neural processes of romantic love.

Methods

110 participants finished two resting-state blocks, no-handholding and handholding conditions, with Electroencephalogram (EEG). We aimed to explore the differences in the brain-brain synchrony pattern of interpersonal touch between romantic lovers and strangers by calculating dynamic interpersonal functional connectivity (dIFC) via EEG-based hyperscanning.

Results

Our results supported that the neural processing of interpersonal touch is a dynamic process. At first half, both groups tended to adapt, and then interpersonal touch increased the dIFC between romantic lovers and decreased the dIFC between strangers. Finally, we employed Support Vector Machine (SVM) to classify EEG signals into two different relationships. SVM recognized two relationships with an accuracy of 71% and 0.77 AUC of ROC at the first half, a 73% accuracy and 0.8 AUC of ROC at the second half.

Conclusions

Our study indicates that interpersonal touch may have different meanings between romantic lovers and strangers. Specifically, interpersonal touch enhances the dIFC between romantic lovers while reducing the dIFC between strangers. The research has important implications for planning touch-based interventions in social and medical care.
Experimental simulation of the ancient production of gold granules
Authors: Tan Panpan , Yang Junchang , Ji Juan
Published: October 2024

Granulation is an ancient and sophisticated decorative technique. The production of granules is a crucial part of this process but has rarely been studied. The present study employed three techniques—pouring method, heating method, and crucible method—to produce gold granules. The success ratio of granule formation, granule surface morphology, microstructure, and formation were analyzed to identify the techniques used in archaeological objects. The cooling medium significantly influenced small granule formation, microstructure, and grain size. Both heating and crucible methods could control the granule formation, but these methods produced distinct microstructures. Based on these experimental granules, the probable production methods of ancient gold balls were identified. The present study provided microscopic information for determining ancient gold granule production techniques.
An analytical study of the tabia mortar from Lin Yimu’s tomb, Zhejiang, China
Authors: Wu Xuan , Jin Cui , Jia Mengjun , Cui Biao , Grifa Celestino , Wang Jixin , Ma Xiao
Published: October 2024

The Lin Yimu’s tomb in Zhejiang Province, China, is a significant Qing Dynasty tabia structure that, despite relatively good preservation, has suffered damage from weathering, necessitating urgent restoration. In this study, we conducted a comprehensive scientific analysis of archaeological samples from the tabia of Lin Yimu’s tomb, employing a range of analytical techniques including X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM/EDX), Fourier transform infrared spectroscopy (FTIR), chemical methods, and measurements of hardness and strength. Analytical results revealed that the main phases of the sample are calcite, quartz, illite/mica, feldspar, with a minor presence of Tung oil. The proportion of calcium carbonate is approximately 27%, and the ratio of earth to sand is 1:2, suggesting a raw material formula mass ratio of lime-earth-sand of 3:4:8. The surface hardness of the sample is measured at 293 ± 15 HL, with a compressive strength of 5.5 ± 0.2 MPa. The sand used in the raw material has a medium particle size of 250 μm, while earth particles are predominantly around 17 μm. The sample exhibits a porosity of 27.5%, with pore sizes concentrated at 95 nm. These findings contribute significantly to our understanding of Qing dynasty tomb construction technologies and provide a solid scientific basis for the restoration of such historical sites.
A self-regulated expiratory flow device for mechanical ventilation: a bench study
Authors: Yang Lianye , Wiersema Ubbo F. , Bihari Shailesh , Broughton Roy , Roberts Andy , Kelley Nigel , McEwen Mark
Published: October 2024

Introduction

Unregulated expiratory flow may contribute to ventilator-induced lung injury. The amount of energy dissipated into the lungs with tidal mechanical ventilation may be used to quantify potentially injurious ventilation. Previously reported devices for variable expiratory flow regulation (FLEX) require, either computer-controlled feedback, or an initial expiratory flow trigger. In this bench study we present a novel passive expiratory flow regulation device.

Methods

The device was tested using a commercially available mechanical ventilator with a range of settings (tidal volume 420 ml and 630 ml, max. inspiratory flow rate 30 L/min and 50 L/min, respiratory rate 10 min−1, positive end-expiratory pressure 5 cmH2O), and a test lung with six different combinations of compliance and resistance settings. The effectiveness of the device was evaluated for reduction in peak expiratory flow, expiratory time, mean airway pressure, and the reduction of tidal dissipated energy (measured as the area within the airway pressure–volume loop).

Results

Maximal and minimal reduction in peak expiratory flow was from 97.18 ± 0.41 L/min to 25.82 ± 0.07 L/min (p < 0.001), and from 44.11 ± 0.42 L/min to 26.30 ± 0.06 L/min, respectively. Maximal prolongation in expiratory time was recorded from 1.53 ± 0.06 s to 3.64 ± 0.21 s (p < 0.001). As a result of the extended expiration, the maximal decrease in I:E ratio was from 1:1.15 ± 0.03 to 1:2.45 ± 0.01 (p < 0.001). The greatest increase in mean airway pressure was from 10.04 ± 0.03 cmH2O to 17.33 ± 0.03 cmH2O. Dissipated energy was significantly reduced with the device under all test conditions (p < 0.001). The greatest reduction in dissipated energy was from 1.74 ± 0.00 J to 0.84 ± 0.00 J per breath. The least reduction in dissipated energy was from 0.30 ± 0.00 J to 0.16 ± 0.00 J per breath. The greatest and least percentage reduction in dissipated energy was 68% and 33%, respectively.

Conclusions

The device bench tested in this study demonstrated a significant reduction in peak expiratory flow rate and dissipated energy, compared to ventilation with unregulated expiratory flow. Application of the device warrants further experimental and clinical evaluation.
Laparoscopic repair of gastric conduit obstruction after robot-assisted minimally invasive esophagectomy: a case report
Authors: Moriuchi Toshiyuki , Katsura Yuki , Shirakawa Yasuhiro , Uehara Ayane , Matsubara Kazuki , Ishida Michihiro , Choda Yasuhiro , Mashima Hiroaki , Sawada Hiroyuki , Yoshimitsu Masanori , Matsukawa Hiroyoshi , Shiozaki Shigehiro
Published: October 2024

Background

Gastric conduit obstruction (GCO) is a known complication after esophagectomy. Laparoscopic revision surgery for GCO is relatively rare, with limited reports in the literature. Here, we report a case of GCO after robot-assisted subtotal esophagectomy and posterior mediastinal gastric conduit reconstruction, which was successfully repaired laparoscopically.

Case presentation

A 66-year-old man presented with a passage disorder that became noticeable 14 months after surgery. Fluid passage was difficult, and the patient opted for revision surgery. The conduit had entered and deflected into the mediastinum; it also twisted due to band formation. The revision surgery was performed laparoscopically through five ports. The bands were dissected, esophageal hiatus was sutured, and conduit re-fixed. The intraoperative endoscopy was used to confirm that the obstruction had been released. The lack of adhesion of the posterior half of the gastric conduit wall, combined with postoperative weight loss leading to a decrease in omental volume, as well as inadequate fixation during the initial surgery, are believed to have contributed to the ease of the conduit deviation into the intrathoracic cavity. In addition, the twisting of the conduit due to band formation exacerbated the obstruction.

Conclusions

Laparoscopic revision surgery may become an effective treatment option as the number of minimally invasive esophagectomies is expected to increase in the future. Furthermore, the fixation method during initial surgery should be carefully considered and optimized to prevent gastric conduit obstruction. Additionally, the use of intraoperative endoscopy to evaluate the lumen of the conduit during surgery proved beneficial in this case, highlighting its potential value in identifying and addressing obstruction.
Cold-water coral mortality under ocean warming is associated with pathogenic bacteria
Authors: Chemel Mathilde , Peru Erwan , Binsarhan Mohammad , Logares Ramiro , Lartaud Franck , Galand Pierre E.
Published: October 2024

Cold-water corals form vast reefs that are highly valuable habitats for diverse deep-sea communities. However, as the deep ocean is warming, it is essential to assess the resilience of cold-water corals to future conditions. The effects of elevated temperatures on the cold-water coral Lophelia pertusa (now named Desmophyllum pertusum) from the north-east Atlantic Ocean were experimentally investigated at the holobiont level, the coral host, and its microbiome. We show that at temperature increases of + 3 and + 5 °C, L. pertusa exhibits significant mortality concomitant with changes in its microbiome composition. In addition, a metagenomic approach revealed the presence of gene markers for bacterial virulence factors suggesting that coral death was due to infection by pathogenic bacteria. Interestingly, different coral colonies had different survival rates and, colony-specific microbiome signatures, indicating strong colony-specific variability in their response to warming waters. These results suggest that L. pertusa can only survive a long-term temperature increase of < 3 °C. Therefore, regional variations in deep-sea temperature increase should be considered in future estimates of the global distribution of cold-water corals.
The composition of the arbuscular mycorrhizal fungal bacteriome is species dependent
Authors: Lahrach Zakaria , Legeay Jean , Ahmed Bulbul , Hijri Mohamed
Published: October 2024

Background

In addition to their role as endosymbionts for plant roots, arbuscular mycorrhizal fungi (AMF) engage in complex interactions with various soil microorganisms, the rhizosphere, and the root endosphere of host plants. They also host diverse prokaryotic groups within their mycelia, contributing to what is termed multipartite symbiosis. In this study, we examined the impact of three AMF species—Rhizophagus irregularis, R. clarus, and R. cerebriforme—combined with microbial bioaugmentation on the diversity and composition of bacterial communities in the mycelia and hyphosphere. Using a microcosm design to separate the influence of host plant roots from AMF mycelia and Illumina MiSeq amplicon sequencing to analyze the bacterial communities.

Results

Our results revealed that, while AMF identity and microbial bioaugmentation did not affect the structure of bacterial communities in the hyphosphere soil, they significantly altered the communities associated with their mycelia. Although all three AMF species belong to the same genus, with R. irregularis and R. clarus being closely related compared to R. cerebriforme, we observed variations in the bacterial communities associated with their mycelia. Interestingly, the mycelial bacterial community of R. cerebriforme contained 60 bacteriome core taxa exclusive to it, while R. clarus and R. irregularis had 25 and 9 exclusive taxa, respectively.

Conclusion

This study suggests that organismal phylogeny influences the bacterial communities associated with AMF mycelia. These findings provide new insights into AMF and bacterial interactions, which are crucial for the successful deployment of AMF inoculants. The taxonomic diversity of AMF inoculants is important for engineering the plant microbiome and enhancing ecosystem services.
Hybrid surgical approach for a large schwannoma from the cervical esophagus to the upper thoracic esophagus: a case report
Authors: Nakagawa Masashi , Mori Naoki , Saisyo Kohei , Yoshida Takehumi , Isobe Taro , Sakai Hisamune , Hisaka Toru , Ishibashi Nobuya , Fujita Fumihiko
Published: October 2024

Background

Esophageal schwannoma is an extremely rare esophageal submucosal tumor. We report a case of a hybrid surgery for a large esophageal schwannoma that had extended from the cervical to the upper thoracic esophagus by using thoracoscopic and cervical approaches.

Case presentation

A 58-year-old male was referred to our hospital for further examination and treatment of dysphagia and weight loss over the past 6 months. Upper gastrointestinal endoscopy revealed a 5.7-cm submucosal tumor from the cervical esophagus to the upper thoracic esophagus. The submucosal tumor was diagnosed as esophageal schwannoma by endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA). Contrast-enhanced CT showed that the tumor had not invaded surrounding organs. Since the tumor extended from the cervical esophagus to the upper thoracic esophagus, we decided that it should be resected by not only the cervical but also the thoracoscopic approach. In operation, the patient was first placed in the prone position, and a thoracoscopic dissection of the upper thoracic esophagus containing the tumor was performed from the surrounding area. After changing the patient’s position from prone to supine, a cervical skin incision was performed, and we underwent the tumor enucleation. After enucleation, the esophageal wall was thinned, so the right sternocleidomastoid muscle was used to reinforce the esophageal wall. The tumor size of the specimen was 60 × 52 × 42 mm. The postoperative course was uneventful, and the patient was discharged on the 22nd day after surgery.

Conclusions

Enucleation of a large esophageal schwannoma from the cervical to the upper thoracic esophagus could be safely performed using both thoracoscopic and cervical approaches. The sternocleidomastoid muscle flap is useful in the occasion considering stenosis by muscular layer suture.
Distinguishing Genetic Alterations Versus (Epi)Mutations in Silver–Russell Syndrome and Focus on the IGF1R Gene
Authors: Vimercati Alessandro , Tannorella Pierpaola , Guzzetti Sara , Calzari Luciano , Gentilini Davide , Manfredini Emanuela , Gori Giulia , Gaudino Rossella , Antona Vincenzo , Piccione Maria , Daolio Cecilia , Auricchio Renata , Sirchia Fabio , Minelli Antonella , Rossi Elena , Bellini Melissa , Biasucci Giacomo , Raucci Annalisa Russo , Pozzobon Gabriella , Patti Giuseppa , Napoli Flavia , Larizza Lidia , Maghnie Mohamad , Russo Silvia
Published: October 2024

Context

Silver–Russell Syndrome (SRS) is a growth retardation disorder characterized by pre- and postnatal growth failure, relative macrocephaly at birth, prominent forehead, body asymmetry, and feeding difficulties. The main molecular mechanisms are imprinting alterations at multiple loci, though a small number of pathogenic variants have been reported in the SRS genes IGF2-PLAG1-HMGA2 and CDKN1C. However, around 40% of clinically suspected SRS cases do not achieve a molecular diagnosis, highlighting the necessity to uncover the underlying mechanism in unsolved cases.

Objective

Evaluate the frequency of genetic variants in undiagnosed SRS patients [Netchine–Harbison Clinical Scoring System (NH-CSS) ≥ 4], and investigate whether (epi)genetic patients may be distinguished from genetic patients.

Methods

One hundred thirty-two clinically SRS patients without (epi)genetic deregulations were investigated by whole-exome (n = 15) and targeted (n = 117) Sequencing. Clinical data from our cohort and from an extensive revision of the literature were compared.

Results

Pathogenic variants were identified in 9.1% of this cohort: 3% in IGF2, PLAG1, and HMGA2 genes and 3% in the IGF1R gene, associated with IGF-1 resistance (IGF1RES), an SRS differential diagnosis. Overall, IGF2-PLAG1-HMGA2 and IGF1R account for 3.6% of SRS with NH-CSS score ≥ 4. A clinical cross-comparison of (epi)genetic vs genetic SRS underlined (epi)genotype-phenotype correlation highlighted the prevalence of body asymmetry and relative macrocephaly in mosaic (epi)genetic SRS and recurrence of genetic familial cases. Furthermore, overlapping features were evidenced in (epi)genetic SRS and IGF1RES patients.

Conclusion

Our study explores the frequency of genetic SRS, underscores body asymmetry as a distinctive phenotype in (epi)genetic SRS and suggests IGF1R sequencing in a SRS diagnostic flowchart.
Tumor Volume Doubling Time of Less Than 1 Year Is Associated With a Higher Risk of Death From Medullary Thyroid Cancer
Authors: Behairy Noha , Leonardi Anthony J , Gubbi Sriram , Kumari Sonam , Pascoal Mateus , Bharadwaj Ashwin , Dorgham Amr , Wright Elizabeth C , Abijo Tomilowo , Uttarkar Vikram Chandra Nayan , Veeraraghavan Padmasree , Cochran Craig , Akshintala Srivandana , Glod John , Klubo-Gwiezdzinska Joanna
Published: October 2024

Context

Tumor volume doubling time (TVDT) is emerging as a useful tool in predicting oncologic outcomes. There are limited data on the prognostic role of TVDT in metastatic medullary thyroid cancer (MTC).

Objective

The goal of this study was to assess the value of TVDT in predicting disease-specific survival (DSS) in patients with hereditary and sporadic MTC.

Methods

This was an Institutional Review Board–approved cohort study including patients with metastatic MTC having at least 3 consecutive imaging studies. TVDT of up to the 5 largest lesions per organ was calculated using a standardized formula. The association between TVDT and DSS was analyzed using Kaplan-Meier survival curves. Cox proportional regression model was used to account for confounding factors.

Results

The study sample consisted of 51 patients presenting with 286 metastatic lesions measured with 457 scans during the follow-up of 51 (IQR, 25-102) months. Median age was 19 years (IQR, 15-41), 53% female patients. Cumulative volumes of all metastatic lesions and proportion of patients with TVDT of < 1 year were higher in patients with sporadic as compared with hereditary MTC (P < .01). Factors independently associated with shorter DSS were TVDT of < 1 year based on 3 initial and 3 last scans as well as lung, brain, and prostate as the organs with the fastest growing tumor. TVDT based on 2-dimensional and 3-dimensional measurements showed strong correlation (r = 0.94, P < .05).

Conclusion

Measurements from 3 baseline and 3 most recent scans preceding follow-up visit enable calculation of TVDT and can be used as predictors of mortality from MTC.
Giant Intracranial Meningiomas Requiring Surgery in 2 Transgender Women Treated With Cyproterone Acetate
Authors: Balcerek Matthew I , Hovelroud Rachel , Ruhl Matthew , Nolan Brendan J
Published: October 2024

Progestin-associated meningioma is a rare complication of cyproterone acetate (CPA), an anti-androgen commonly prescribed in feminizing hormone therapy regimens for transgender and gender-diverse individuals. A dose-response association has been observed, particularly with longer-term exposure to doses ≥ 50 mg daily; however, the dose below which CPA use is safe remains unclear. We herein report the cases of 2 transgender women using CPA who developed meningioma. Novel aspects of our cases include: (i) the presence of symptomatic giant meningiomas (> 5 cm), including multiple meningiomas in one patient, requiring urgent surgical intervention; (ii) meningioma development with both high-dose, long duration and low-dose, shorter duration CPA; and (iii) the presence of a PIK3CA missense variant in one patient, which may play a role in the pathogenesis of progestin-associated meningioma. Our cases highlight the real-world risk of this likely underreported adverse effect and underscore the importance of clinician vigilance for neurological sequelae. We suggest using the lowest dose of CPA that maintains adequate androgen suppression, with consideration of alternative anti-androgens where appropriate.
A Case of Refractory Thyroid Storm Despite Correction of Peripheral Thyroid Hormone Levels
Authors: Evans Madeline , Prince Grace , Majety Priyanka
Published: October 2024

Thyroid storm is a life-threatening complication of hyperthyroidism that necessitates early diagnosis for aggressive, effective treatment. We present a patient with a newly diagnosed multinodular goiter who presented to the emergency department with leg swelling, dyspnea, tremors, and atrial fibrillation with elevation in thyroid hormone levels consistent with thyrotoxicosis. Despite improvement in peripheral hormone levels on maximized medical treatment with beta-blockers, methimazole, glucocorticoids, cholestyramine, and potassium iodide, she continued to clinically decline with new encephalopathy, heart failure, and liver and kidney dysfunction while receiving treatment. Work-up for alternative causes of her clinical decompensation was unrevealing. Plasmapheresis was initiated, with further reduction in thyroid hormone levels without clinical improvement. Cases in the literature do report incidences of severe thyrotoxicosis refractory to traditional treatment measures; however, generally, these cases involve a failure to reduce thyroid hormone levels with medical treatment and subsequent consideration of plasmapheresis. Our case suggests that clinical improvement in thyroid storm does lag behind biochemical improvement in select patients, and delayed clinical improvement or even severity of symptoms may warrant earlier consideration of plasmapheresis in such patients.
Successful Transition to Sulfonylurea for Relapsed Monogenic Diabetes Due to Rare 6q23.3 Duplication
Authors: Hassan Doha , Allen David B , Chen Melinda
Published: October 2024

Transient neonatal diabetes mellitus (TNDM) due to 6q duplication usually presents in the first 4 months of life, resolves before 18 months of life, and recurs in adolescence or adulthood. Insulin is the first-line treatment for chromosome 6–related neonatal diabetes in infancy. While there is no ideal treatment for patients with relapsed TNDM, residual β-cell function after remission of neonatal diabetes indicates a potential role for insulin secretagogues. Patients with 6q24 duplication have been successfully transitioned from insulin to sulfonylureas (SUs) in adolescence. We present the first report to our knowledge of TNDM secondary to a rare 6q23.3 duplication for which reemergence of diabetes was successfully transitioned from insulin to SU treatment. The successful transition to SU improved glycemic control, cost-effectiveness, and overall quality of life, while decreasing occurrence of hypoglycemia.
Infrastructural Attachments
Authors: Park Emma
Published: October 2024

Set against critiques of neoliberal capitalism in the present, Infrastructural Attachments argues that the technopolitics of austerity have been the organizing logic of statecraft in Kenya since the late nineteenth century, calling into question the novelty of austerity as a mode of governance and a lived experience. Using infrastructures as a lens to explore state formation over the long twentieth century—roads in the early colonial period, radio broadcasting from the interwar through the postwar periods, and mobile phones and digital financial services in the present—historian Emma Park reveals that as the state drew on private capital to make up for limited budgets, it inaugurated a peculiar political-economic form: the corporate-state. For more than a century—in pursuit of minimizing costs and maximizing profits—the corporate-state crucially relied on the exploitation and expropriation of its subject-citizens. By foregrounding these workers, Park interrogates how Kenyans’ knowledge and expertise has been rescaled and subsumed, quietly underwriting the development of infrastructural expertise, the circuits of finance upon which (post)colonial infrastructural expansion has been premised, and the forms of profit-making it has enabled.
Introduction
Authors: Amar Paul
Published: October 2024

The introduction traces how this collective intervention emerged from Rio de Janeiro, where scholar-activists have generated globally relevant tools for organizing and concepts for alternative governance shaped by five centuries of transnational exchanges and comobilizations, not just with the North and across the Americas but with the African continent, including the regions of today’s Angola and Congo. Rio has served as a transfer hub and site of innovation for collective resistance. Rio’s progressive concepts and resistance models fought their way onto the stage of history as they confronted and exposed the social origins, ideologies, and weak-points of emergent hard-right political regimes. Rio’s social movements, media influencers, community organizers, cultural figures, student organizations, Afro-Brazilian religious groupings, and a broad front of new feminist, ecology, Black, queer, and labor mobilizations did not just provide resistance; they engineered a series of triumphs and articulated new methods of being and of being political.
Rot Politics and the Cunning of Anticorruption / Política de Podridão e a Ardileza da Anti-corrupção
Authors: Mitchell Sean T. , Brêtas Thayane
Published: October 2024

Corruption is an extremely flexible political category in contemporary Brazilian political discourse. It can be stretched to mean everything from simple robbery by politicians to undue influence of private interests in politics, perceived erosion of sexual moralities, and the undermining of race, class, gender, and sexual hierarchies; and, crucially, it is the term through which deficiencies in health care, education, security, and other public services and goods are often explained and understood. Drawing on ethnographic research, this chapter examines the polysemy of corruption among Cariocas from many class backgrounds to examine how the flexibility of the concept helped created conditions for a cross-class, right-wing political coalition that is novel in Brazilian history and, in important ways, centered on Rio de Janeiro. In doing so, the chapter focuses on how the rise of a popular far right in Rio sheds light on many contemporary uses of the term corruption worldwide.
Elactivism / Vereativismo
Authors: Cunha Monica , Cortana Leonard
Published: October 2024

The authors of this chapter—one of the first woman activists from the social movement of mothers of youth killed by state violence to be elected to office in Rio, and a scholar-filmmaker—focus on the switch from Black women grassroots organizers to elected municipal representatives. Black women whose children were victims of police violence have a place in formal politics, their role going beyond fighting for justice for their sons. They reinscribe new values into favela communities and fight against the created categories of being Black or favelado. The concept of elactivism/vereativista encapsulates a political praxis when a leader of these groups redeploys their grassroots experience into a campaign for elected office while keeping strong ties with their communities. Far from being translations of identity politics frameworks, elactivism/verativismo highlights the necessity of embracing a politics of presence, reaffirming the institution’s role as a public forum open to everyone.
Black Brotherhood Urbanism / Urbanismo Confrarial Negro
Authors: Coutinho Marcos
Published: October 2024

Mutual aid societies of Black freedmen and enslaved individuals, particularly Bantu-speaking groups from what is now Angola and Mozambique, came together to build municipal welfare and self-governance organizations known as brotherhoods or confraternal organizations. These groups emerged in the cities of coastal Brazil to build and maintain churches, with a spectrum of political, economic, and social functions. Black brotherhood, here, challenges the idea that urban modernity and contemporary city geography were colonial by-products—images of social hygiene imposed from above by Iberian or French planners. This chapter features Black brotherhoods’ role in urban expansion and resists dominant white narratives of the contemporary city’s formation. It offers Black individual spaces not solely defined by subalternity or reification. Churches built and operated by Black mutual aid societies made essential contributions to the expansion of Rio during the first half of the eighteenth century and continue to shape the fabric of Rio today.
Anti–White Patriarchal Ultramodernity / Ultramodernidade Anti-blancopatriarcal
Authors: Pinho Osmundo
Published: October 2024

The focus in this chapter is on working-class neighborhoods, anti-Black moral panic, and identifying contractions of modernity through ultramodernity. This chapter traces the process by which subjectivities and cultural practices incorporate the contradictions of modernity—what is here referred to as ultramodernity—and its promises of universal emancipation vis-à-vis the raw materiality of race and gender. Through case studies—in the popular (working-class) neighborhood of Jardim Catarina—the chapter traces processes of universalization and individualism, as seen from a context of urban poverty. To trace the implications of these overlapping processes, the chapter discusses the process of subjectivation mediated through relative material deprivation.
Quilombo Portness / Quilombismo Portuário
Authors: Sodré João Gabriel Rabello , Lisio Amanda de
Published: October 2024

Despite popular perception, racial capitalism and indentured labor fail to create a neatly closed or coherent system. Rio’s portside areas have been at the center of privately led renovation projects since 2011. Paralleling these efforts, Afro-Brazilian memorialization processes involving the ruins of the Valongo, the hemisphere’s most significant slave trade wharf, have contrasted with and challenged this urban intervention. Established as a slave trade shore in the eighteenth century, this section of Rio de Janeiro’s bayside area consolidated as an important Afro-Brazilian zone in the nineteenth century. This chapter, drawing from sources of Rio’s historically global port area, juxtaposes the concepts of porosity and quilombismo in order to propose the concept of portness. As a place of movement, culture, death, life, and resistance, Rio’s port area constitutes an analytical unit that allows for a better understanding of grassroots developments taking place at the global stage.
Involved With as Police Method / Envolvido-Com e Proximidade Punitiva
Authors: Muniz Jacqueline de Oliveira , Cecchetto Fatima , Monteiro Rodrigo
Published: October 2024

Involved with crime (envolvido-com) is used in favelas and among the police in Rio de Janeiro. The term articulates a police epistemology anchored in a form of social common sense that has come to dominate discourses about violence in Rio and which informs a methodology of policing. It is thus ultimately rooted in beliefs that the police spring from the same moral, cultural, and geographic origins as populations they surveil, categorize, and punish. Police see themselves as having made a conscious choice to become a human living correctly—becoming a cop and not a bandit, having clawed their way out of the same physical and social milieu that produces bandits. This, they feel, earns them both human rights and a duty to employ their classificatory eye, formed by life at the margins, to take in who is and is not involved with crime, and who is deserving of death.
Pentecostal Repertoires and Narco-warfare Grammars / Repertórios Pentecostais e Gramáticas do Narco-conflito
Authors: Teixeira Cesar Pinheiro
Published: October 2024

Based on ethnographic research involving former bandits, policemen, Pentecostal evangelicals, and actors linked to NGO social projects, this chapter examines situations that make up urban violence. The concept of criminal subjection is used to analyze three great native logics of action that make up a kind of field of solutions to violence: war and death, religious conversion, and social inclusion. Adopting criminal subjection as part of a larger conceptual framework helps focus and capture an essentialist representation of criminalized populations, central to the continued deployment of urban-based violence. Criminal subjection is part of a broader network of repression in Rio embedded in a local subjectivity. Other cultural contexts may be composed of their own repertoires or repertoires similar to those indicated here, which may also make evident the moral grammar of subjectivity that regulates the boundaries between the legitimacy of life and death in urban conflicts.
Genderphobic Binarism / Binarismo Gênerofóbico
Authors: Moreira Vitória
Published: October 2024

The popularization of feminist and LGBTQ+ struggles have been accompanied by a growing resistance to the incorporation of the concept of gender. In conservative settings, gender ideology refers to the idea that gender is an ideological farce that denies natural or divine divisions between the sexes. Often associated with right-wing and authoritarian populist rhetoric, combating gender ideology—with its strategic plasticity—mobilizes diverse and sometimes unlikely alliances against what they consider to be a civilizational threat. In Brazil, the fight against gender is concentrated in the area of education, arguing to protect children against ostensible mass manipulation and the destruction of the family. If, on the one hand, genderphobic binarism has the characteristics of a counteroffensive, or backlash, to the expansion of minority rights, then it appears, on the other hand, as a complex mobilization platform built from the feeling of fear of a malleable enemy.
What causes cardiac mitochondrial failure at high environmental temperatures?
Authors: Hickey Anthony J. R. , Harford Alice R. , Blier Pierre U. , Devaux Jules B.
Published: October 2024

Although a mechanism accounting for hyperthermic death at critical temperatures remains elusive, the mitochondria of crucial active excitable tissues (i.e. heart and brain) may well be key to this process. Mitochondria produce ∼90% of the ATP required by cells to maintain cellular integrity and function. They also integrate into biosynthetic pathways that support metabolism as a whole, allow communication within the cell, and regulate cellular health and death pathways. We have previously shown that cardiac and brain mitochondria demonstrate decreases in the efficiency of, and absolute capacity for ATP synthesis as temperatures rise, until ultimately there is too little ATP to support cellular demands, and organ failure follows. Importantly, substantial decreases in ATP synthesis occur at temperatures immediately below the temperature of heart failure, and this suggests a causal role of mitochondria in hyperthermic death. However, what causes mitochondria to fail? Here, we consider the answers to this question. Mitochondrial dysfunction at high temperature has classically been attributed to elevated leak respiration suspected to result from increased movement of protons (H+) through the inner mitochondrial membrane (IMM), thereby bypassing the ATP synthases. In this Commentary, we introduce some alternative explanations for elevated leak respiration. We first consider respiratory complex I and then propose that a loss of IMM structure occurs as temperatures rise. The loss of the cristae folds of the IMM may affect the efficiency of H+ transport, increasing H+ conductance either through the IMM or into the bulk water phases of mitochondria. In either case, O2 consumption increases while ATP synthesis decreases.
Bioinformatics-driven refinement of the commonly used TPI nonsense-mediated decay reporter system
Authors: Peter Laura , Walotka Lara , Ptok Johannes , Meyer Caroline , Schüller Dominik , Schaal Heiner , Müller Lisa
Published: October 2024

The cellular nonsense-mediated decay (NMD) pathway recognizes and degrades mRNAs with unusual structural features, such as long 3′ UTRs or overlapping reading frames, and therefore serves as a transcript quality control mechanism. A broad spectrum of today's knowledge about the nonsense-mediated mRNA decay pathway has been discovered using NMD reporter systems, mostly consisting of multiple exons, with a wild-type and a premature termination codon-containing variant. In a preliminary NMD study, we used the seven-exon triose phosphate isomerase (TPI) reporter and observed that in this well-known NMD reporter, surprisingly, not all splice sites are used constitutively, but additional cryptic splice sites are used. As this is more frequently observed in the construction of minigenes, especially when unknown splicing regulatory elements (SREs) are removed, for example, by shortening introns, this may affect the reliability of such reporters. To demonstrate how such minigenes can be improved in general with respect to constitutive splice site recognition, we restored an intron length in the TPI reporter or made bioinformatic adjustments to SREs or intrinsic strength of the splice sites themselves. As a result, this NMD reporter could be made more robust and specific for the evaluation of NMD sensitivity within a single transcript. The modifications of the TPI reporter shown here as examples can generally be used for the transfer of cellular multiexon transcripts to minigenes.
Branch site recognition by the spliceosome
Authors: Tholen Jonas
Published: October 2024

The spliceosome is a eukaryotic multimegadalton RNA–protein complex that removes introns from transcripts. The spliceosome ensures the selection of each exon-intron boundary through multiple recognition events. Initially, the 5′ splice site (5′ SS) and branch site (BS) are bound by the U1 small nuclear ribonucleoprotein (snRNP) and the U2 snRNP, respectively, while the 3′ SS is mostly determined by proximity to the branch site. A large number of splicing factors recognize the splice sites and recruit the snRNPs before the stable binding of the snRNPs occurs by base-pairing the snRNA to the transcript. Fidelity of this process is crucial, as mutations in splicing factors and U2 snRNP components are associated with many diseases. In recent years, major advances have been made in understanding how splice sites are selected inSaccharomyces cerevisiaeand humans. Here, I review and discuss the current understanding of the recognition of splice sites by the spliceosome with a focus on recognition and binding of the branch site by the U2 snRNP in humans.
Casting and Forging techniques Found in Bronze vessels Excavated from Mangduksa Temple Site in Gyeongju
Authors: Kim So Jin , Kim Young Do
Published: October 2024

Metallographic analysis of microstructure, chemical composition and hardness was carried out on 7 bronze vessels from Mangduksa temple site in Gyeongju. Result show that the technology of bronze vessels divided into casting and forging followed by quenching. Tin contents of casting bronzes were around 11∼14 wt%, forging bronzes were about 21∼23 wt% tin. Kundika and dish of casting bronzes were Cu-Sn-Pb alloys and 5 bowl samples were produced using Cu-Sn binary alloy materials. These show that the manufacturing technology was applied different depends on the Sn contents. Also 4 bowls of approximately 20 wt% tin were manufactured by forging and quenching at above 520℃ avoid formation of the brittle δ phase. The non-metallic inclusions in the 7 bronze samples are divided into Cu-S and Cu-Fe-S-Se systems, indicating that the copper ore used the production is different. It was confirmed that casting bronze vessels had lower micro-hardness values than forging samples, and that hardness values changed depending on Sn content and processing.