bluuebunny/crossref_metadata_2025 huggingface dataset:
Compound heterozygous variants of ANKFY1 in a child with infantile-onset proteinuria and movement disorder
Authors: Zhang Luyan , Cheng Xueqin , Wang Chunli , Zhou Wei , Zheng Bixia , Zhang Aihua
Published: June 2024

The ANKFY1 gene encodes a protein that belongs to double zinc finger proteins involved in endocytosis. Only one family with steroid-resistant nephrotic syndrome has been reported carrying a homozygous variant in ANKFY1 so far. Here we describe the second case where a 13-year-old boy presented with infantile-onset proteinuria and movement disorder. Whole-exome sequencing showed compound heterozygous variants (NM_001330063.2: c.2753C>G; p.Ser918Ter, and c.3287–11_3287–10del) in ANKFY1. In vitro functional study revealed the two variants led to reduced protein expression level of ANKFY1. This is the first case of co-existence of renal and nervous system phenotypes in a child with variants in ANKFY1, suggesting that bi-allelic variants in ANKFY1 might be associated with a new neuro-renal syndrome.
Acute kidney injury after non-cardiac major surgery: has it reduced?
Authors: Cho Jeong Min , Kwon Soie , Yang Sunah , Park Jina , Jeong Subin , Park Sehoon , Ryu Jiwon , Kim Sejoong , Lee Jeonghwan , Lee Jung Pyo , Yoon Hyung-Jin , Kim Dong Ki , Joo Kwon Wook , Kim Yon Su , Kim Kwangsoo , Park Minsu , Lee Hajeong
Published: June 2024

Background

It remains unclear whether the incidence of post-operative acute kidney injury (PO-AKI) has been reduced despite the recent emphasis on its early recognition and prevention in clinical practice. We aimed to investigate the trend in the incidence of PO-AKI and to identify the associated factors affecting its changes.

Methods

We gathered clinical data from patients who underwent non-cardiac major surgeries at three referral hospitals from 2005 to 2020. PO-AKI was defined as KDIGO AKI criteria within 7 days after surgery. Severe PO-AKI (S-PO-AKI) was defined as stage 2 or 3 AKI. The temporal change of PO-AKI was evaluated by joinpoint regression analysis and multivariable logistic regression based on a 3-year interval.

Results

Among 138 235 patients, 8156 (5.9%) PO-AKI and 1127 (0.8%) S-PO-AKI occurred, respectively. The patients enrolled in recent years were older and more were women. They had more comorbidities and a higher PO-AKI risk compared with those included in past years. As time passed, the PO-AKI incidence decreased from 8.6% in 2005–07 to 5.1% in 2017–20, whereas S-PO-AKI incidence did not change (0.8% to 0.9%). In joinpoint analysis, PO-AKI incidence tended to decrease with annual percentage change (APC) of –4.2% per year [95% confidence interval (CI) –5.5% to –2.8%, P-value <.001), although S-PO-AKI did not (APC 0.9%, 95% CI –1.1 to 2.9%, P-value = .347). Similarly, the overall PO-AKI incidence decreased but S-PO-AKI did not, even after adjusting covariables.

Conclusion

The incidence of PO-AKI has decreased recently despite the increase in known risk factors; however, the incidence of S-PO-AKI has not decreased in recent years.

Trial registration information

ClinicalTrials.gov Identifier: NCT05986474. Name of registry: Development of Synthetic Medical Data Generation Technology to Predict Postoperative Complications. URL: https://classic.clinicaltrials.gov/ct2/show/NCT05986474. Date of registration: 14 August 2023. Date of enrollment of the first participant to the trial: 27 September 2022, retrospectively registered.
Atrial septal defect becoming clinically evident after cardiac surgery for annuloaortic ectasia: a case report
Authors: Meguro Kentaro , Koitabashi Toshimi , Fujita Teppei , Ako Junya
Published: June 2024

Background

Right ventricular volume overload is the key finding in a patient with previously undiagnosed atrial septal defect (ASD).

Case summary

A 68-year-old female was referred to our hospital due to progressive pulmonary artery dilatation observed on her chest X-ray. Echocardiography revealed a secundum ASD with right ventricular dilatation. She had undergone aortic root replacement and aortic valve replacement for annuloaortic ectasia and aortic insufficiency 12 years prior to the diagnosis. She was also diagnosed with Marfan syndrome, which was supported by family histories. Computed tomography did not show a secundum ASD before the surgery. We finally closed the secundum ASD with catheter closure device.

Discussion

Ascending aneurysm might mask the presence of secundum ASD. Monitoring the change in pulmonary artery dilatation overtime is useful for the diagnosing secundum ASD.
Ventricular septal defect complicating acute myocardial infarction: diagnosis and management. A Clinical Consensus Statement of the Association for Acute CardioVascular Care (ACVC) of the ESC, the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC and the ESC Working Group on Cardiovascular Surgery
Authors: Schlotter Florian , Huber Kurt , Hassager Christian , Halvorsen Sigrun , Vranckx Pascal , Pöss Janine , Krychtiuk Konstantin , Lorusso Roberto , Bonaros Nikolaos , Calvert Patrick A , Montorfano Matteo , Thiele Holger
Published: June 2024

Ventricular septal defects are a rare complication after acute myocardial infarction with a mortality close to 100% if left untreated. However, even surgical or interventional closure is associated with a very high mortality and currently no randomized controlled trials are available addressing the optimal treatment strategy of this disease. This state-of-the-art review and clinical consensus statement will outline the diagnosis, hemodynamic consequences and treatment strategies of ventricular septal defects complicating acute myocardial infarction with a focus on current available evidence and a focus on major research questions to fill the gap in evidence.
Digest: Are female miniature geckos larger than males?
Authors: Tarimo Eliza
Published: June 2024

What shapes the differences in body size between males and females in miniature species? One potential key factor is reproduction, which could constrain body size evolution because females of miniature species need to remain large enough to lay viable eggs. Glynne and Adams (2024) tested this hypothesis in two gecko families, the Sphaerodactylidae and Phyllodactylidae. Their findings support this hypothesis, indicating that female-biased size differences in miniature species are shaped by selection for reproductive success.
Clinical audit of quality of care among patients with viral hepatitis in primary care in a low endemic region
Authors: Koc Özgür M , Vaes Bert , Robaeys Geert , Catalan Cristian F , Aertgeerts Bert , Nevens Frederik
Published: June 2024

Background

The current hepatitis B (HBV) and hepatitis C virus (HCV) screening practices may fail to detect many infected patients who could benefit from new therapeutic agents to limit progression to cirrhosis and hepatocellular carcinoma.

Objectives

This study assessed the test positivity rate and cascade of care of viral hepatitis patients in primary care in a low endemic region as well as the testing policy of abnormal alanine aminotransferase (ALT) level.

Methods

This is a retrospective clinical audit among primary health care practices in Flanders, Belgium, assessing patients with an active medical file between 2019 and 2021.

Results

A total of 84/89 (94.4%) primary health care practices participated representing 621,573 patients of which 1069 patients (0.17%) were registered as having viral hepatitis, not further specified. Detailed information was available from 38 practices representing 243,723/621,573 (39.2%) patients of which 169 (0.07%) were HBsAg positive and 99 (0.04%) anti-HCV positive. A total of 96/134(71.6%) chronic HBV-infected and 31/77(40.3%) chronic HCV-infected patients were referred to a hepatologist. A total of 30,573/621,573(4.9%) patients had an abnormal ALT level, and by at random selection, more detailed information was obtained on 211 patients. Information on high-risk groups was missing in up to 60%. In patients with abnormal ALT level, HBsAg and anti-HCV testing were conducted in 37/211(17.5%) and 25/211(11.8%), respectively.

Conclusion

In a low endemic region, the testing rate and cascade of care of HBV and HCV-infected patients can be improved in primary care, especially in high-risk groups and patients with abnormal ALT levels.
Response of aerobic anoxygenic phototrophic bacteria to limitation and availability of organic carbon
Authors: Piwosz Kasia , Villena-Alemany Cristian , Całkiewicz Joanna , Mujakić Izabela , Náhlík Vít , Dean Jason , Koblížek Michal
Published: June 2024

Aerobic anoxygenic phototrophic (AAP) bacteria are an important component of freshwater bacterioplankton. They can support their heterotrophic metabolism with energy from light, enhancing their growth efficiency. Based on results from cultures, it was hypothesized that photoheterotrophy provides an advantage under carbon limitation and facilitates access to recalcitrant or low-energy carbon sources. However, verification of these hypotheses for natural AAP communities has been lacking. Here, we conducted whole community manipulation experiments and compared the growth of AAP bacteria under carbon limited and with recalcitrant or low-energy carbon sources under dark and light (near-infrared light, λ > 800 nm) conditions to elucidate how they profit from photoheterotrophy. We found that AAP bacteria induce photoheterotrophic metabolism under carbon limitation, but they overcompete heterotrophic bacteria when carbon is available. This effect seems to be driven by physiological responses rather than changes at the community level. Interestingly, recalcitrant (lignin) or low-energy (acetate) carbon sources inhibited the growth of AAP bacteria, especially in light. This unexpected observation may have ecosystem-level consequences as lake browning continues. In general, our findings contribute to the understanding of the dynamics of AAP bacteria in pelagic environments.
The Nitroplast and Its Relatives Support a Universal Model of Features Predicting Gene Retention in Endosymbiont and Organelle Genomes
Authors: Johnston Iain G
Published: June 2024

Endosymbiotic relationships have shaped eukaryotic life. As endosymbionts coevolve with their host, toward full integration as organelles, their genomes tend to shrink, with genes being completely lost or transferred to the host nucleus. Modern endosymbionts and organelles show diverse patterns of gene retention, and why some genes and not others are retained in these genomes is not fully understood. Recent bioinformatic study has explored hypothesized influences on these evolutionary processes, finding that hydrophobicity and amino acid chemistry predict patterns of gene retention, both in organelles across eukaryotes and in less mature endosymbiotic relationships. The exciting ongoing elucidation of endosymbiotic relationships affords an independent set of instances to test this theory. Here, we compare the properties of retained genes in the nitroplast, recently reported to be an integrated organelle, two related cyanobacterial endosymbionts that form “spheroid bodies” in their host cells, and a range of other endosymbionts, with free-living relatives of each. We find that in each case, the symbiont's genome encodes proteins with higher hydrophobicity and lower amino pKa than their free-living relative, supporting the data-derived model predicting the retention propensity of genes across endosymbiont and organelle genomes.
Understanding Longevity: SIN-3 and DAF-16 Revealed as Independent Players in Lifespan Regulation
Authors: Konwar Chandrika , Maini Jayant , Saluja Daman
Published: June 2024

Aging is the process of gradual physio-biochemical deterioration. Although aging is inevitable, healthy aging is the key to individual and communal well-being. Therefore, it is essential to understand the regulation of aging. SIN-3/Sin-3 is a unique regulatory protein that regulates aging without DNA-binding activity. It functions by establishing multiple protein interactions. To understand the functional mechanism of this transcriptional regulator, the Caenorhabditis elegans protein interactome was assessed for SIN-3 interactions. DAF-16/FOXO emerged as one of the leading contenders for SIN-3-mediated regulation of aging. This study looks at the concerted role of SIN-3 and DAF-16 proteins in lifespan regulation. Phenotypic profiling for the mutants of these genes shows the functional accord between these 2 proteins with similar functions in stress response and vital biological processes. However, there were no significant physical interactions when checked for protein–protein interaction between SIN-3 and DAF-16 proteins. C. elegans genomics and transcriptomics data also indicated the possibilities of concerted gene regulation. This genetic regulation is more likely related to SIN-3 dominance on DAF-16 function. Overall, SIN-3 and DAF-16 proteins have strong functional interactions that ensure healthy aging. The influence of SIN-3 on DAF-16-mediated stress response is one of their convergence points in longevity regulation.
Characterizing Features of Creative Writing in Older Adults
Authors: Orwig William , Schacter Daniel L
Published: June 2024

Objectives

How does creative expression change across the life span? Although creativity is generally preserved well into adulthood, certain cognitive functions, such as episodic detail and ideational fluency, have been shown to decline with age. The present study employs computational linguistic analyses to investigate the salient features of creative writing in older adults.

Methods

We collected short stories from a sample of 50 older adults (age 65≤) which were subsequently rated for creativity by an independent set of participants. Mixed-effects linear regression models were used to describe semantic diversity and perceptual details as predictors of creativity. Semantic diversity reflects the extent to which a narrative connects divergent ideas and is closely associated with creativity. Perceptual details, characterized by sensorial descriptions, have been previously associated with creative writing and may serve to transport readers to alternative times and places. Additionally, we compare these measures to a previously collected sample of stories from younger adults.

Results

Results indicate that the presence of perceptual details and semantic diversity were significant positive predictors of creativity (p < .05). Moreover, we find that stories written by older adults contain fewer perceptual details compared with stories written by younger adults.

Discussion

These results advance our understanding of age-related changes in creativity and highlight the potential role of episodic simulation in writing creative short stories.
Reduced levels of MRE11 cause disease phenotypes distinct from ataxia telangiectasia-like disorder
Authors: Hartlerode Andrea J , Mostafa Ahmed M , Orban Steven K , Benedeck Rachel , Campbell Koral , Hoenerhoff Mark J , Ferguson David O , Sekiguchi JoAnn M
Published: June 2024

The MRE11/RAD50/NBS1 (MRN) complex plays critical roles in cellular responses to DNA double-strand breaks. MRN is involved in end binding and processing, and it also induces cell cycle checkpoints by activating the ataxia-telangiectasia mutated (ATM) protein kinase. Hypomorphic pathogenic variants in the MRE11, RAD50, or NBS1 genes cause autosomal recessive genome instability syndromes featuring variable degrees of dwarfism, neurological defects, anemia, and cancer predisposition. Disease-associated MRN alleles include missense and nonsense variants, and many cause reduced protein levels of the entire MRN complex. However, the dramatic variability in the disease manifestation of MRN pathogenic variants is not understood. We sought to determine if low protein levels are a significant contributor to disease sequelae and therefore generated a transgenic murine model expressing MRE11 at low levels. These mice display dramatic phenotypes including small body size, severe anemia, and impaired DNA repair. We demonstrate that, distinct from ataxia telangiectasia-like disorder caused by MRE11 pathogenic missense or nonsense variants, mice and cultured cells expressing low MRE11 levels do not display the anticipated defects in ATM activation. Our findings indicate that ATM signaling can be supported by very low levels of the MRN complex and imply that defective ATM activation results from perturbation of MRN function caused by specific hypomorphic disease mutations. These distinct phenotypic outcomes underline the importance of understanding the impact of specific pathogenic MRE11 variants, which may help direct appropriate early surveillance for patients with these complicated disorders in a clinical setting.
Overview of crosstalk between stromal and epithelial cells in the pathogenesis of adenomyosis and shared features with deep endometriotic nodules
Authors: Zipponi Margherita , Cacciottola Luciana , Dolmans Marie-Madeleine
Published: June 2024

Since the first description of adenomyosis more than 150 years ago, multiple hypotheses have attempted to explain its pathogenesis. Indeed, research over recent years has greatly enhanced our knowledge of the underlying causes. This has opened up avenues for the development of strategies for both disease prevention and treatment of its main symptoms, such as pelvic pain, heavy menstrual bleeding, and infertility. However, the current means are still largely ineffective, so it is vital that we shed light on the pathways involved. Dysregulated mechanisms and aberrant protein expression have been identified as contributing factors in interactions between endometrial epithelial and stromal cells, ultimately leading to the growth of adenomyotic lesions. These include collective cell migration, epithelial-to-mesenchymal transition, hormonal influence, and signaling from non-coding RNAs and extracellular vesicles. We provide a concise summary of the latest insights into the crosstalk between glands and stroma in ectopic adenomyotic lesion formation. While there is an abundance of literature on similarities between adenomyosis and deep endometriosis, there are insufficient data on the cytochemical, molecular, and pathogenetic mechanisms of these two disorders. However, various shared features, including alterations of cell adhesion molecules, abnormal hormone regulation, and the presence of cancer-driving mutations and epigenetic modifications, have been identified. Nevertheless, the pathogenic mechanisms that contribute to the cause and development of these enigmatic diseases have not been fully elucidated yet.
Resistance and adaptation to globalization: Case studies of the Japanese textile industry
Authors: Tomita Terumasa
Published: June 2024

In the age of economic globalization, industries and corporations are increasingly faced with new market realities owing to the intensification of international competition. This study posits that corporations either use resistance through political voice or decide to restructure to adapt to these realities. Three Japanese textile industries with poor competitiveness were selected as case studies and were observed from the perspective of corporate survival strategies. The towel industry in Imabari City, Ehime Prefecture, implemented resistance through a voice strategy; the glove industry in Higashikagawa City, Kagawa Prefecture, chose to move manufacturing overseas as an adjustment strategy; and the uniform industry in Kurashiki City, Okayama Prefecture, chose to utilize foreign workers as another adjustment strategy. These findings address the gap between prior research on ‘adaptation’ and research on political ‘resistance’ and demonstrate that variations exist in the strategies employed by less competitive industries.
Transcriptomic insights into the shift of trophic strategies in mixotrophic dinoflagellate Lepidodinium in the warming ocean
Authors: Chen Jiawei , Deng Lixia , Pang Mengwen , Li Yingdong , Xu Zhimeng , Zhang Xiaodong , Liu Hongbin
Published: June 2024

The shift between photoautotrophic and phagotrophic strategies in mixoplankton significantly impacts the planktonic food webs and biogeochemical cycling. Considering the projected global warming, studying how temperature impacts this shift is crucial. Here, we combined the transcriptome of in-lab cultures (mixotrophic dinoflagellate Lepidodinium sp.) and the metatranscriptome dataset of the global ocean to investigate the mechanisms underlying the shift of trophic strategies and its relationship with increasing temperatures. Our results showed that phagocytosis-related pathways, including focal adhesion, regulation of actin cytoskeleton, and oxidative phosphorylation, were significantly stimulated in Lepidodinium sp. when cryptophyte prey were added. We further compared the expression profiles of photosynthesis and phagocytosis genes in Lepidodinium sp. in the global sunlit ocean. Our results indicated that Lepidodinium sp. became more phagotrophic with increasing temperatures when the ambient chlorophyll concentration was >0.3 mg.m−3 (~20.58% of the ocean surface) but became more photoautotrophic with increasing temperatures when the chlorophyll concentration was between 0.2 and 0.3 mg.m−3 (~11.47% of the ocean surface). Overall, we emphasized the crucial role of phagocytosis in phago-mixotrophy and suggested that the expression profile of phagocytosis genes can be a molecular marker to target the phagotrophic activity of mixoplankton in situ.
Asgard archaeal selenoproteome reveals a roadmap for the archaea-to-eukaryote transition of selenocysteine incorporation machinery
Authors: Huang Biyan , Xiao Yao , Zhang Yan
Published: June 2024

Selenocysteine (Sec) is encoded by the UGA codon that normally functions as a stop signal and is specifically incorporated into selenoproteins via a unique recoding mechanism. The translational recoding of UGA as Sec is directed by an unusual RNA structure, the SECIS element. Although archaea and eukaryotes adopt similar Sec encoding machinery, the SECIS elements have no similarities to each other with regard to sequence and structure. We analyzed >400 Asgard archaeal genomes to examine the occurrence of both Sec encoding system and selenoproteins in this archaeal superphylum, the closest prokaryotic relatives of eukaryotes. A comprehensive map of Sec utilization trait has been generated, providing the most detailed understanding of the use of this nonstandard amino acid in Asgard archaea so far. By characterizing the selenoproteomes of all organisms, several selenoprotein-rich phyla and species were identified. Most Asgard archaeal selenoprotein genes possess eukaryotic SECIS-like structures with varying degrees of diversity. Moreover, euryarchaeal SECIS elements might originate from Asgard archaeal SECIS elements via lateral gene transfer, indicating a complex and dynamic scenario of the evolution of SECIS element within archaea. Finally, a roadmap for the transition of eukaryotic SECIS elements from archaea was proposed, and selenophosphate synthetase may serve as a potential intermediate for the generation of ancestral eukaryotic SECIS element. Our results offer new insights into a deeper understanding of the evolution of Sec insertion machinery.
Creating a next-generation phenotype library: the health data research UK Phenotype Library
Authors: Thayer Daniel S , Mumtaz Shahzad , Elmessary Muhammad A , Scanlon Ieuan , Zinnurov Artur , Coldea Alex-Ioan , Scanlon Jack , Chapman Martin , Curcin Vasa , John Ann , DelPozo-Banos Marcos , Davies Hannah , Karwath Andreas , Gkoutos Georgios V , Fitzpatrick Natalie K , Quint Jennifer K , Varma Susheel , Milner Chris , Oliveira Carla , Parkinson Helen , Denaxas Spiros , Hemingway Harry , Jefferson Emily
Published: June 2024

Objective

To enable reproducible research at scale by creating a platform that enables health data users to find, access, curate, and re-use electronic health record phenotyping algorithms.

Materials and Methods

We undertook a structured approach to identifying requirements for a phenotype algorithm platform by engaging with key stakeholders. User experience analysis was used to inform the design, which we implemented as a web application featuring a novel metadata standard for defining phenotyping algorithms, access via Application Programming Interface (API), support for computable data flows, and version control. The application has creation and editing functionality, enabling researchers to submit phenotypes directly.

Results

We created and launched the Phenotype Library in October 2021. The platform currently hosts 1049 phenotype definitions defined against 40 health data sources and >200K terms across 16 medical ontologies. We present several case studies demonstrating its utility for supporting and enabling research: the library hosts curated phenotype collections for the BREATHE respiratory health research hub and the Adolescent Mental Health Data Platform, and it is supporting the development of an informatics tool to generate clinical evidence for clinical guideline development groups.

Discussion

This platform makes an impact by being open to all health data users and accepting all appropriate content, as well as implementing key features that have not been widely available, including managing structured metadata, access via an API, and support for computable phenotypes.

Conclusions

We have created the first openly available, programmatically accessible resource enabling the global health research community to store and manage phenotyping algorithms. Removing barriers to describing, sharing, and computing phenotypes will help unleash the potential benefit of health data for patients and the public.
Contemporary International Criminal Law After Critique
Authors: Burgis-Kasthala Michelle , Sander Barrie
Published: June 2024

Contemporary international criminal law (ICL) is a well-established field of scholarship and practice that wields significant influence in framing how certain events come to be understood and acted upon. Yet, as the field has increasingly captured the public’s attention and imagination, a body of critical scholarship has risen in prominence that seeks to test and challenge ICL’s underlying assumptions. In such a climate, this article suggests that ICL not only has moved beyond its inception and consolidation phases, but is beginning to emerge from its critical period towards a ‘post-critical’ phase where critique is becoming increasingly normalized within the field, with both reformist and structurally oriented reappraisals more readily acknowledged within ICL’s imaginary. Situated in this ‘post-critical’ moment, this article examines the extent to which the vocabulary and institutions of ICL may be productively (re-)engaged in the pursuit of emancipatory ends. After providing an overview of the strands of critique that have become increasingly prominent, we reflect on three avenues for engaging with the field of ICL ‘after critique’: first, critical engagement, centred on a commitment to revealing and detailing silenced and marginalized experiences and methods within the field itself; second, tactical and strategic engagement, which points to the ways in which actors choose to engage with imperfect legal frameworks for particular struggles; and finally, decolonial and abolitionist (dis-)engagement which takes as its point of departure the rejection of both colonial and carceral logics per se, especially in light of their historical and persisting patterns of patriarchal and racialized domination. Ultimately, in linking ICL with historical and contemporary anti-colonial and anti-carceral struggles, we seek not only to disrupt ICL progress narratives, but also to show how earlier, often-sidelined ways of imagining forms of harm and their repair may provide potentially more productive ways of engaging with ICL ‘after critique’.
Termite IPM in historic sites
Authors: Su Nan-Yao
Published: June 2024

Given the traditional use of wood, historical structures are susceptible to termite damage which can irreversibly affect their historical significance. Methods like drilling into the foundation for termiticide injection are impractical and potentially harmful to the structural integrity of these structures. Moreover, the location of these structures in ecologically sensitive areas prohibits the use of soil termiticides due to potential contamination of groundwater, rivers, or oceans. Termite Integrated Pest Management (IPM) strategies include baiting programs that use minimal quantities of benign insecticides to reduce environmental impact. This approach is consistent with the risk management component of termite IPM. Bait systems are proven to be effective in eliminating termite colonies, contributing to the benefit component of IPM by preserving the value of historical sites. This article discusses successful baiting interventions at notable locations such as the Statue of Liberty National Monument, New York, USA, the Christiansted National Historic Site in St. Croix, US Virgin Islands, and the Historic Tzu-Su Temple in Taiwan.
Advancing clinical trial equity through integration of telehealth and decentralized treatment
Authors: Brown Eleanor , Fisher George Albert , Shelton Andrew , Chang Daniel T , Pollom Erqi
Published: June 2024

Innovative strategies to increase clinical trial accessibility and equity are needed. We conducted a retrospective review of a phase II investigator-initiated trial to determine whether the modification of clinical trial design to decentralize study treatment can improve trial accessibility among underrepresented groups. Sociodemographic characteristics, including area deprivation indices, as well as study site travel distance, time, and costs were compared between enrolled participants who received chemotherapy locally and participants who did not. Participants who received chemotherapy locally lived substantially farther from the study site (median = 95.90 vs 25.20 miles, P = .004), faced a greater time burden traveling to the study site (median = 115.00 vs 34.00 minutes, P = .002), and had higher travel-related costs for a single trip to the study site (median = $62.81 vs $16.51, P = .004). This study highlights opportunities for alleviating financial and time burdens associated with clinical trial participation, promoting equity in clinical research.

Trial Registration: ClinicalTrials.gov identifier: NCT04380337.
(032) A REVIEW OF VESTIBULECTOMY PATHOLOGY FINDINGS AND A CALL TO ACTION TO STANDARDIZE PATHOLOGY REPORTING
Authors: Dumas K , Mikkilineni A , Odenwald E , Bahng J , Krapf J , Goldstein A , Cigna S
Published: June 2024

Introduction

There is no standardization for pathology reporting of vestibulectomy specimens. Our current understanding of neuroproliferative vestibulodynia is limited, but it is understood to be mediated by the accumulation c-afferent nociceptors and mast cells. Histopathology is fundamental to our understanding of disease mechanism and treatment. Given how much remains unknown about the histology, physiology, and neuroplasticity of the vestibule, it is imperative that we take every opportunity to fully examine this tissue and its complex role in pain.

Objective

Describe current pathology reporting practices for vestibulectomy specimens

Methods

Data was collected using Epic and Cerner report tools to identify any patients between 1/2017 to 10/2023 with a surgical history of vestibulectomy. Forty-five patients were identified & confirmed to have a history of vestibulectomy. Charts were reviewed to locate surgical pathology reports (available through hospital EMR, CRISP, or Care Everywhere).

Results

Pathology reports were available for 37 patients. Thirty-one of these reports (84%) were from our own institution; six reports were from outside hospitals. Marked variability in pathology reporting was noted between pathologists and institutions. All but one pathology report notes inflammation. The one report that does not include language about inflammation only notes “negative for dysplasia or malignancy”. Twenty-nine reports comment on the absence of dysplasia, including two reports from other institutions. All pathology reports from our institution (100%), note lymphoid infiltrate; however, this is not noted on any of the 6 pathology reports from other hospitals. Nineteen of the 31 specimens (61%) examined at our institution included specific stains to test for mast cells and nerve fibers. Nineteen specimens were evaluated with Giemsa staining and 8 specimens were evaluated with CD117 staining to assess for mast cell density (measured in mast cells/hpf). The range of mast cell density was 1/hpf to 25/hpf, and the average mast cell density was 8.1/hpf. All 19 specimens stained with S100 noted a relative increase in nerve fibers in the superficial dermis.

Conclusions

Histopathology is a window of opportunity to better understand the pathophysiology of neuroproliferative vestibulodynia. There is no standard when it comes to examining and reporting on vestibulectomy specimens. This results in reporting inconsistencies, which limits our ability to compile data and draw clinical conclusions. As surgeons we can collaborate to advance our understanding of the pathophysiology of vestibulodynia. This starts with communicating with our pathology colleagues, requesting appropriate stains, and setting a standard for reporting.

Disclosure

Any of the authors act as a consultant, employee or shareholder of an industry for: Patty Brisben Foundation.
(033) ABSENCE OF GENDER-AFFIRMING HYSTERECTOMIES FROM HYSTERECTOMY SEXUAL FUNCTION OUTCOMES LITERATURE
Authors: De Moya A , Watson K , Rowen T
Published: June 2024

Introduction

Gender affirming healthcare is a multidisciplinary field that includes (but is not limited to) the following interventions: hormonal therapy and gender affirming surgery (chest surgery, hysterectomy, oophorectomy, metoidioplasty, phalloplasty, etc.). Gender-affirming hormone therapy has been shown to positively impact orgasm duration and satisfaction level among both transgender men and women. Research on sexual wellbeing after gender affirming surgery (GAS) indicates positive effects on sexual health outcomes; however, the literature lacks sufficient studies to make evidence-based recommendations.

Objective

To synthesize and review the current state of literature on sexual outcomes following gender affirming hysterectomies as background to inform a planned study on this topic.

Methods

This project is a literature review of peer-reviewed journal articles on sexual function and pleasure outcomes following hysterectomies, with a particular focus on gender affirming hysterectomies. We considered various cohort studies, systematic reviews, position statements, and meta-analyses in our review.

Results

No research currently exists on sexual function or orgasm experience after gender affirming hysterectomy. Current literature exploring sexual function post-hysterectomy only includes cisgender populations (indications typically include cancer risk reduction, pelvic pain, and/or abnormal uterine bleeding). Studies have found mixed results regarding sexual function in cisgender women post-hysterectomy and/or oophorectomy, including changes to anxiety and depression, sexual health and wellness, both in a positive and negative direction. Other analyses found no significant change in sexual function post-hysterectomy in cisgender women. Based on these findings, hysterectomies have mixed effects on sexual satisfaction & function in cisgender populations but there is no data to guide transgender populations.

Conclusions

More research is needed on sexual health outcomes (i.e., sexual pleasure, arousal, and orgasm) after gender affirming surgery, as very few studies examine the role of sexual function, including desire, arousal, pain and orgasm in patients’ lives post-GAS. No studies investigate sexual satisfaction post-gender affirming hysterectomy despite it being an important GAS for transgender men. Research on this procedure in this specific population will inform evidence-based practices and recommendations, elucidate sex outcomes when the main indication for a hysterectomy is gender affirmation, and advance our understanding of sexual pleasure overall. This author team is initiating a study to address this critical question.

Disclosure

No.
(100) MASTURBATION: AN UNDERUTILIZED TREATMENT?
Authors: Dubinskaya A , Toubi K , Anger J , Eilber K
Published: June 2024

Introduction

Certain types of masturbation have been shown to affect genital and genitourinary health. However, the full range of health benefits associated with masturbation and its various forms remains inadequately studied.

Objective

This study aimed to investigate the literature addressing utilization of masturbation for various health conditions among females.

Methods

We conducted a systematic literature review of PubMed, Embase, and Medline from January 1980 to November 2023, adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search incorporated keywords such as “masturbation,” “sexual pleasure,” “benefits of masturbation,” “sexual self-stimulation,” “solo sex,” “onanism,” and “self-pleasure.” Inclusion criteria for the analysis were clinical trials, cohort studies, and reviews with cisgender women over 18 years old as participants, and masturbation utilized as an intervention. Exclusion criteria were case reports, surveys, studies involving men, or those with a history of gender dysphoria.

Results

A total of 176 studies were initially identified. Only five studies met all inclusion and exclusion criteria. Among these, four were clinical trials, and one was a systematic review. All but one study investigated the role of masturbation in the ability to orgasm with or without a partner. Orgasmic function was noted to be improved among participants in these four studies. One study investigated the endocrine changes associated with orgasm and found a significant elevation in post-orgasmic prolactin, similar to men. Participants in all the studies were cisgender women aged 18 to 55, predominantly heterosexual. The intervention duration ranged from 10 minutes per session to multiple sessions over the course of five weeks, with only one study specifying the mode of masturbation (vibrators). Four of the studies used erotica and pornography as augmentation to masturbation, and a partner was involved in the intervention in two of the studies. Only one study employed formal quantitative methods for outcome assessment.

Conclusions

Masturbation has primarily been investigated as an intervention for orgasmic dysfunction. There is a significant need for studies examining different types of masturbation and their effects on general and genitourinary health.

Disclosure

No.
The microbial-driven nitrogen cycle and its relevance for plant nutrition
Authors: Koch Hanna , Sessitsch Angela
Published: June 2024

Nitrogen (N) is a vital nutrient and an essential component of biological macromolecules such as nucleic acids and proteins. Microorganisms are major drivers of N-cycling processes in all ecosystems, including the soil and plant environment. The availability of N is a major growth-limiting factor for plants and it is significantly affected by the plant microbiome. Plants and microorganisms form complex interaction networks resulting in molecular signaling, nutrient exchange, and other distinct metabolic responses. In these networks, microbial partners influence growth and N use efficiency of plants either positively or negatively. Harnessing the beneficial effects of specific players within crop microbiomes is a promising strategy to counteract the emerging threats to human and planetary health due to the overuse of industrial N fertilizers. However, in addition to N-providing activities (e.g. the well-known symbiosis of legumes and Rhizobium spp.), other plant–microorganism interactions must be considered to obtain a complete picture of how microbial-driven N transformations might affect plant nutrition. For this, we review recent insights into the tight interplay between plants and N-cycling microorganisms, focusing on microbial N-transformation processes representing N sources and sinks that ultimately shape plant N acquisition.
Impact-induced deformation away from the impact point on small asteroids
Authors: Liu P -Y , Campo Bagatin A , Benavidez P G , Richardson D C
Published: June 2024

We investigated the propagation of energy and momentum inside a small gravitational aggregate asteroid following a hypervelocity impact, comparable to NASA’s Double Asteroid Redirection Test (DART) on asteroid Dimorphos. We show that the impact energy damps rapidly inside different kinds of granular structures, unable to reach the antipodal hemisphere of the impact. However, global reshaping of the asteroid after the formation of a sizeable (${\gt}1/3$ of target size) crater causes meter-range displacement of boulders on the antipodal hemisphere due to mass rearrangement to achieve a new equilibrium shape. As a result, a surface depression opposite to the crater is formed, which may produce some surface refreshment. The boulder mass ejection following the synthetic DART-like impact is estimated to be at least $0.1\, {{\ \rm per\ cent}}$ of the mass of the Dimorphos-like target, in agreement with recent detections of boulders ejected from the actual DART impact.
A Relational View of Homosexuality
Authors: Cordeiro-Rodrigues Luís
Published: June 2024

Homosexuality is criminalised and socially condemned in many places in Africa. This fact seems to suggest that African moral philosophy would likely render homosexuality immoral. Indeed, some of the African philosophical literature tries to suggest that homosexuality is morally wrong. Contrasting with this view, in this article, I will show that Afro-communitarian ethics implies that homosexuality is morally permissible and, indeed, can be an excellent way to promote social harmony. I defend this theory by drawing out the implications of social harmony, and also respond to potential objections from African intellectuals and new natural law theorists.
Changing the Frame: New Epistemic Frameworks and Social Transformation in African Feminist Theory
Authors: Graness Anke , Kopf Martina
Published: June 2024

This article discusses African feminist approaches to decolonization and social transformation. In recent years, there has been a significant shift in African feminist scholarship towards African concerns and Africa-centered solutions. Today’s turn to Indigenous knowledge, social structures, and gender relations is no longer just about shedding light on the precolonial past, but about fundamentally changing the epistemic framework in the sense of developing alternative epistemologies beyond the dominant ‘Western’ framework. But what is meant by ‘alternative epistemologies’? How do African feminist thinkers conceptualize social change today? And how do they relate epistemic and social change in their thinking? These questions are explored in this article, focusing on work by Sylvia Tamale (Uganda), Wangari Maathai (Kenya), and Anthonia Kalu (Nigeria) and drawing on the discourse of ecofeminism and Ubuntu as two models of alternative epistemologies.
A new anti-CRISPR gene promotes the spread of drug-resistance plasmids in Klebsiella pneumoniae
Authors: Jiang Chunyu , Yu Chengzhi , Sun Shuyi , Lin Jiajia , Cai Mufeng , Wei Zhenquan , Feng Lingling , Li Jianhui , Zhang Yan , Dong Ke , Guo Xiaokui , Qin Jinhong , Zhang Yu
Published: June 2024

The Klebsiella pneumoniae (K. pneumoniae, Kp) populations carrying both resistance-encoding and virulence-encoding mobile genetic elements (MGEs) significantly threaten global health. In this study, we identified a new anti-CRISPR gene (acrIE10) on a conjugative plasmid with self-target sequence in K. pneumoniae with type I-E* CRISPR-Cas system. AcrIE10 interacts with the Cas7* subunit of K. pneumoniae I-E* CRISPR-Cas system. The crystal structure of the AcrIE10-KpCas7* complex suggests that AcrIE10 suppresses the I-E* CRISPR-Cas by binding directly to Cas7 to prevent its hexamerization, thereby preventing the surveillance complex assembly and crRNA loading. Bioinformatic and functional analyses revealed that AcrIE10 is functionally widespread across diverse species. Our study reports a novel anti-CRISPR and highlights its potential role in spreading resistance and virulence among pathogens.
Modelling developments in consciousness within a multidimensional framework
Authors: Hansen Mads Jørgensen
Published: June 2024

A recent advancement in consciousness science has been the introduction of a multidimensional framework of consciousness. This framework has been applied to global states of consciousness, including psychedelic states and disorders of consciousness, and the consciousness of non-human animals. The multidimensional framework enables a finer parsing of both various states of consciousness and forms of animal consciousness, paving the way for new scientific investigations into consciousness. In this paper, the multidimensional model is expanded by constructing temporal profiles. This expansion allows for the modelling of changes in consciousness across the life cycles of organisms and the progression over time of disorders of consciousness. The result of this expansion is 2-fold: (i) it enables new modes of comparison, both across stages of development and across species; (ii) it proposes that more attention be given to the various types of fluctuations that occur in patients who are suffering from disorders of consciousness.
A novel approach to induce early remission in high-risk primary membranous nephropathy
Authors: Kochoyan Zinaida , Dobronravov Vladimir A
Published: June 2024

Background

This prospective single-arm trial with historic controls evaluated the efficacy and safety of treatment based on a combination of rituximab, intravenous cyclophosphamide and corticosteroids (RCP) administered at lower cumulative doses for the induction of early remission in primary membranous nephropathy (PMN).

Methods

We prospectively enrolled 30 high-risk PMN patients with persistent nephrotic syndrome (NS) and elevated antibodies to the phospholipase A2 receptor who underwent RCP therapy. We compared the effectiveness of RCP with that of historic controls who received rituximab-based therapy (RTX, n = 15) or cyclosporine + corticosteroids (CSA, n = 42). The primary outcomes were complete remission (CR) and overall remission (OR) by Month 12 and the time to remission.

Results

In the RCP group, the OR and CR rates by 12 months (97% and 60%) were higher than those in the RTX group (60% and 7%, P ≤ .009) and the CSA group (50% and 24%, P ≤ .003). The median time to OR [2.8 (1.6–3.9) months] was shorter compared with RTX [7.1 (3.4–17.5) months, P = .008] and CSA [7.3 (6.0–13.6) months, P < .001]. In adjusted Cox regression, hazard ratios for OR and CR attainment for RCP versus other treatments were 5.2 (95% CI 2.8–9.6) and 4.8 (95% CI 2.2–10.3), respectively. Propensity score–matched group analyses confirmed these results. One serious adverse event occurred in the RCP group in the follow-up of 56 patient-years.

Conclusions

RCP therapy is considered effective and safe for inducing early remission in high-risk PMN patients.