bluuebunny/crossref_metadata_2025 huggingface dataset:
APTT and D-dimer as biomarkers for heatstroke in patients with severe heat-related illnesses
Authors: Li Xu , Wang Yuanjie
Published: August 2024

The objective of this study was to analyze the changes of activated partial thromboplastin time (APTT) and D-dimer in severe heatstroke (HS) patients and their value in identifying HS patients and to analyze clinical features and early laboratory test results of heat-related illnesses. Forty-five patients with heat-related illnesses who were admitted to the Department of Emergency and Intensive Care Medicine of Suining Central Hospital from June 2022 to April 2023 were retrospectively analyzed. Patients were divided into 3 groups based on their clinical diagnosis: classic HS group, exertional HS group, and control group. General date and laboratory test results were collected, especially APTT and D-dimer. The receiver operating characteristic curve was used to analyze D-dimer and APTT. : There were differences in gender distribution among the 3 groups. Exertional HS was dominated by male patients, and classic HS was dominated by elderly patients. Binary logistic regression analysis of coagulation index showed a significant correlation between D-dimer and APTT and HS. The receiver operating characteristic curve results showed that APTT and D-dimer had high sensitivity and specificity in the identification of HS with an area under the curve (AUC) of 0.846, sensitivity of 97%, and specificity of 58.3% for APTT and an AUC of 0.861, sensitivity of 72%, and specificity of 91.7% for D-dimer (D-dimer + APTT [AUC, 0.929; sensitivity, 81.8%–91.7%; P < .001]). : The mortality rate of HS is high, and early diagnosis is particularly important. APTT and D-dimer may be used as markers assisting in identifying HS.
Assessment of health literacy and HPV knowledge among university students: An observational study
Authors: Şenocak Taşçi Elif , Baş Dilşat , Kayak Simge , Anik Sema , Erözcan Aleyna , Sönmez Özlem
Published: August 2024

Health literacy (HL) level is related to promotion of health, improved health behaviors, and early diagnosis of diseases, as well as the appropriate use of health services. Human papillomavirus (HPV) vaccination is the primary method of protection against cervical cancer and recommended for women aged 9 to 27. This study aims to assess the university students’ knowledge about HPV and the association between HL and HPV vaccination. In this cross-sectional and descriptive study, an electronic survey was used. Demographic characteristics and anthropometric measurements of the participants were questioned. HPV Knowledge Scale (HPV-KS) and Turkish Health Literacy Scale (THLS-32) were used to evaluate HPV knowledge and HL. Statistical analyzes were performed with SPSS version 26. A total of 361 university students (74% women), aged 21.98 ± 4.72 years, were included in the study. About 52% of the participants were health sciences students. The total THLS-32 score was 34.68 ± 9.37 (95% CI = 33.71–35.65), and the total adequate/excellent HL level was 51%. The mean HPV-KS score of the participants was 10.28 ± 8.15 (95% CI = 9.44–11.12) of a possible 35. Health sciences students had higher rates of HPV awareness (78% vs 65%; P = .007). General HPV knowledge level was significantly better among women (P < .001), >20 years (P = .002), and those with a family history of cancer (P < .001) and significantly lower among students at prep or first year of school (P < .001). There was a weak, positive relation between THLS-32 and HPV-KS score (R = 0.136; P = .01). Participants with higher levels of HPV knowledge (P = .034) and total HPV-KS score (P = .025) were statistically significantly higher in students with adequate/excellent HL. Our results reveal that knowledge about HPV vaccination is closely related to HL levels. Educational interventions on HL may be considered to increase HPV vaccination rates.
The application and effect of presuturing with clips in endoscopic full-thickness resection
Authors: Liu Zhaohui , Li Rui , Sun Dayong , Ding Shihua , Wu Ruinuan
Published: August 2024

There are few studies on presuturing for full-thickness resection. To explore the effect of using clips as a presuturing technique for endoscopic snare resection with an elastic band (ESR-EB). The clinical data of patients who underwent ESR-EB at Shenzhen Second People’s Hospital between May 2023 and May 2024 were collected. The patients were divided into presuture and non-presuture groups according to whether tissues were stitched before resection. The general clinical characteristics, tumor growth position, tumor size, tumor growth pattern, pathological type, operation time, resection time, complication rate, number of clips, and postoperative antibiotic usage rate were compared. A total of 73 patients were enrolled, 55 of whom were included in the presuture group and 18 were included in the non-presuture group. There was no difference in age, sex, tumor position, tumor size, or tumor growth pattern between the 2 groups (P > .05). There was no significant difference between the 2 groups in terms of operation time, resection time, pathological diagnosis, number of clips, or complication rate (P > .05). Complete resection was achieved in all of the patients. The perforation diameter in the presuture group was significantly smaller than that in the non-presuture group ([3.20 ± 1.56] vs [4.67 ± 2.79], [P = .006]). Thirty-three (60%) patients in the presuture group and 16 (88.89%) patients in the non-presuture group received postoperative preventive antibiotics, and the difference between the 2 groups was significant (P = .024). Gastric myometrial lesions <10 mm in diameter can be completely removed via ESR-EB. Clips as a means of presuturing can significantly reduce the perforation diameter and the use of postoperative preventive antibiotics. Moreover, clips as a means of presuturing does not increase the total number of clips used for the procedure and therefore should be considered a feasible, safe and effective technique.
Clinicopathological features and treatment outcome of juvenile idiopathic inflammatory myopathies with anti-melanoma differentiation associated gene 5 antibodies: A case series study
Authors: Liu Long , Hou Ying , Zhao Dandan
Published: August 2024

To characterize the clinicopathological features and treatment outcomes of juvenile idiopathic inflammatory myopathies (JIIM) with anti-melanoma differentiation associated gene 5 (MDA5) antibodies in a Chinese cohort. Anti-MDA5 antibody was detected by immunodot assay and indirect immunofluorescence assay on HEK293 cells in a series of Chinese JIIM cohort between 2005 and 2022. The clinical features, histological findings, and treatment outcomes of these anti-MDA5-antibody-positive patients were summarized. Of 59 JIIM patients, 3 (5.08%) were found to be anti-MDA5-antibody-positive. The frequency of anti-MDA5 antibody did not show significant difference between adult idiopathic inflammatory myopathies and JIIM cohorts (P = .720). The disease duration in patients with anti-MDA5 antibody was 2.83 ± 1.04 months. All 3 patients had typical skin lesions including Gottron sign and heliotrope rash, while interstitial lung disease and arthritis was only found in 1 patient. All 3 patients showed normal creatine kinase levels. On muscle biopsy, diffuse major histocompatibility complex class-I expression was seen in 3 patients and myxovirus-resistance protein A expression was found in 2 patients. All patients received long-term follow-up (6.42 ± 4.01 years). They were all drug-free and showed favorable treatment outcome with prednisone and additional immunosuppressant. Our study indicates that anti-MDA5 antibodies may not be common in Chinese JIIM. Anti-MDA5-positive JIIMs are characterized by typical skin lesions of dermatomyositis, normal CK levels, and increased major histocompatibility complex class-I expression. JIIMs with anti-MDA5 generally have good response to immunotherapies.
Association of high serum β2-microglobulin levels with poor functional outcomes in patients with acute ischemic stroke: A cohort study
Authors: Yu Shan , Yin Peng , Li Xiujuan , Xiao Jian , Zhang Hao , Zhou Liangqi , Tian Ying
Published: August 2024

We evaluated the association between serum β2-microglobulin (β2M) levels and prognosis in patients with acute ischemic stroke (AIS) and determined whether the association was affected by any clinical variables. This prospective study included 533 patients with AIS who were admitted to the Hospital of Nanhua Affiliated with the University of South China for treatment from June 1, 2021, to July 31, 2022. Using multiple regression modeling, the association between serum β2M levels and poor functional outcomes—which were classified as being modified Rankin Scale scores of 3 to 6 (composite score of death and major disability), 3 to 5 (major disability), and 6 (death)—were assessed 3 months after stroke onset. At the 3-month follow-up assessment, 209 (47.39%) participants had poor functional outcomes: major disabilities in 150 (34.01%) cases and deaths in 59 (13.38%). After adjusting for important covariates, the group with serum β2M levels in the highest quartile had the highest proportion of individuals with modified Rankin Scale scores of 3 to 6 (odds ratio [OR], 3.54; 95% confidence interval [CI], 1.35–9.33), 3 to 5 (OR, 2.95; 95% CI, 1.21–7.16), or 6 (OR, 1.02; 95% CI, 0.29–3.64) compared with the group having serum β2M levels in the lowest quartiles. The risk prediction for the combined outcome of death and major disability improved after incorporating β2M levels into models that included conventional risk factors. Subgroup analysis revealed a significant impact on the association between serum β2M levels and poor functional outcomes only in patients with AIS whose time from onset to hospitalization was <12 hours (P for interaction < .05). Elevated serum β2M levels were associated with poor functional outcomes in patients with AIS, possibly affected by the time from onset to hospitalization.
Current status and trends of urinary incontinence research in recent 10 years based on VOSviewer visualized analysis: An observational study
Authors: Wang Lei , Luo Zhicheng , Zhao Pengpeng , Yu Yi , Chen Yang , Lin Fuxiang , Xu Zhanping
Published: August 2024

Urinary incontinence (UI) is prevalent and imposes significant social and economic burdens. This study reviews the literature on UI, assesses the current research status, and projects future trends. To visualize and analyze UI-related research, summarize and generalize the knowledge framework of the global UI field, and explore the current state of research and emerging trends, we conducted a comprehensive search of UI-related studies from 2014 to 2024 using the Web of Science Core Collection. Utilizing VOSviewer software, we mapped the scientific landscape and performed visual analytics on collaborative and co-citation networks, keyword co-occurrences, emergent clusters, and timeline mapping to elucidate the research dynamics. A total of 4326 publications were retrieved for further analysis. The United States ranked first in terms of the total number of publications, number of citations, and publication H-index. In terms of institutions, the University of California System had the most total citations and the highest H-index. Neurology and Urodynamics had the most articles published, the highest citation frequency, and the highest H-index. The author with the most citations and the highest average number of citations per article is Abrams P. The author with the highest H-index is Peyronnet B. Based on the keyword analysis, the articles were categorized into several main directions: epidemiological studies, diagnostic studies, treatment studies, female UI studies, and male UI studies. Epidemiology, treatment, and male UI are expected to continue as hot topics. This study demonstrates that UI research is more advanced in Europe and North America and that Neurourology and Urodynamics is the most influential journal in the field. In addition, epidemiology, treatment, and male UI will continue to be prominent topics. Our study contributes to a more comprehensive understanding of the current state of UI research and provides insights into future research directions in the field.
Common variants of vitamin D receptor gene polymorphisms and risk of gastric cancer: A meta-analysis
Authors: Guan Min , Wang Yong
Published: August 2024

Background:

While earlier studies have suggested that variations in the vitamin D receptor (VDR) gene could influence the susceptibility to gastric cancer (GC), the results have shown inconsistency. This meta-analysis aimed to examine the association of 5 common polymorphisms in VDR, including Taq1 rs731236 (T > C), FokI rs2228570 (C > T), Cdx2 rs11568820 (G > A), BsmI rs1544410 (G > A), and ApaI rs7975232 (G > T) with the risk of GC.

Methods:

A comprehensive search was carried out in PubMed, Web of Science, and Scopus to identify relevant studies published until January 2024. Odds ratios (ORs) with 95% confidence intervals (CIs) were utilized to assess the magnitude of associations.

Results:

Nine studies, with 2837 participants (1215 GC cases and 1622 healthy controls), were eligible. The FokI rs2228570 polymorphism showed a significant correlation with heightened susceptibility to GC under the recessive model (OR = 1.52; 95% CI: 1.06–2.19) and homozygote comparison (TT vs CC; OR = 1.59; 95% CI: 1.09–2.31). Taq1 rs731236 was also linked to an elevated risk of GC under the same models (recessive OR = 1.65; 95% CI: 1.14–2.39; homozygote OR = 1.68; 95% CI: 1.11–2.54). In the sensitivity analysis, when studies not adhering to Hardy–Weinberg equilibrium were excluded, the relationship between FokI rs2228570 polymorphism and GC disappeared, while the association for Taq1 rs731236 remained consistent. No significant association was identified for BsmI rs1544410, ApaI rs7975232, and Cdx2 rs11568820.

Conclusion:

This study revealed that FokI rs2228570 and Taq1 rs731236 polymorphisms of VDR might be linked to the odds of GC.
Exploring Determinants of Nurse Retention
Authors: Rothbart Kristin , Leddy Jessica , M. Brady Colleen , Kruse Donna K. , Lancaster Rachelle J.
Published: August 2024

Nurse retention remains a pivotal issue, necessitating urgent strategies aimed at the recruitment and retention of highly qualified nurses. However, there is limited knowledge regarding the influence of nurses’ personal and professional values, along with work environment, on predicting intent to leave an organization. Utilizing a secondary analysis approach, this study employed logistic regression to predict intent to leave among registered nurses (n = 671) using results from the Short Schwartz’s Value Survey, the Nurses Professional Values Scale-3, and the Practice Environment Scale of the Nursing Work Index. Regression analysis indicates that the work environment including “Participation in Hospital Affairs” (B = −.665, odds ratio = .514), “Nurse Manager Ability, Leadership, and Support” (B = −.448, odds ratio = .639), and “Staffing and Resource Adequacy” (B = −.589, odds ratio = .555) are significant predictors of nurses’ intentions to leave. Establishing and maintaining supportive work environments is essential for retention, highlighting the importance of effective leadership.
Assessment of Minimally Invasive Surgical Techniques for Sagittal Craniosynostosis: A Multi-Center Time Series Study
Authors: Prezelski Kayla , Blondin Fernandez Mario S. , Matsumoto Karen , David Lisa R. , Runyan Christopher M. , Patel Kamlesh B. , Kane Alex A. , Hallac Rami R.
Published: August 2024

Background:

Minimally invasive strip craniectomy is a well-established treatment for sagittal craniosynostosis, however the temporality of change in head shape has not been assessed. In this study, we perform head shape analysis to compare time-series-based clinical outcomes between three different surgical techniques across three academic centers for the treatment of sagittal craniosynostosis.

Methods:

Retrospective, longitudinal 3D images were collected from patients who underwent surgery for the correction of sagittal craniosynostosis for up to 5 years post-operation. The surgical methods studied include spring-assisted craniectomy, narrow-strip craniectomy plus orthotic helmet therapy, and wide-strip craniectomy with biparietal and bitemporal barrel stave wedge osteotomies plus orthotic helmet therapy. Postoperative 3D images were binned into six age groups. Cranial index measurements were calculated on 3D images. 3D whole-head composite images were generated for each procedure to visually represent longitudinal outcomes.

Results:

The median with interquartile range (IQR) CI measurements at 3-5 years postoperative follow up were 75.9 [73.1-78.6] for spring-assisted, 75.9 [75.4-78.5] for narrow-strip, and 79.4 [76.4-81.9] for wide-strip. The wide-strip CI was significanly different from the spring-assissted and narrow strip groups (p < 0.001). Concerning 3D analysis, spring-assisted patients showed normalization of frontal bossing and skull height compared to age-matched controls, while wide-strip patients showed greater correction of occipital bulleting. Narrow-strip patients had intermediate results between these outcomes.

Conclusions:

There was no statistically significant regression in longitudinal CI measurements across the three techniques aimed at treating sagittal craniosynostosis. Longitudinal comparison of 3D head shape outcome demonstrated satisfactory correction of scaphocephalic deformity across all three surgical groups.
Comprehensive Mapping and Dynamic Monitoring of the Temporal Branch of the Facial Nerve in Complex Cranial Reconstruction Surgery and Revision Cranioplasty
Authors: Silverstein Justin W. , Avshalomov Elizabeth , Ablyazova Faina , Stark Katherine G. , Ben-Shalom Netanel
Published: August 2024

Facial nerve (FN) injury is a significant risk during complex cranial reconstruction surgeries, especially in revision cases where normal anatomy is distorted. The authors introduce a technique to mitigate FN injury, including preoperative FN mapping, intraoperative FN mapping, and continuous FN monitoring. Preoperative mapping uses a handheld ball-tip stimulator to elicit compound muscle action potentials (CMAP) in the frontalis muscle. Needle electrodes are placed above the orbital margin to record responses, starting at the stylomastoid foramen and extending until the entire temporal branch is mapped. Intraoperatively, continuous mapping is achieved using an electrified insulated suction device, allowing dynamic mapping during soft tissue dissection. Continuous monitoring involves placing stimulation electrodes near the stylomastoid foramen and recording CMAP responses from the frontalis and orbicularis oculi/orbicularis oris muscles. The authors tested this technique in 5 patients. The authors successfully mapped the temporal branch of the FN with isolated frontalis CMAP recordings in all patients. Intraoperative FN mapping and continuous monitoring were successfully performed in all cases. Two patients experienced complete cessation of FN CMAPs, which resumed upon loosening the tension on the myocutaneous flap held by fishhooks. One patient showed a 39% decrement in frontalis CMAP that did not recover. Despite these issues, all patients had intact FN function postoperatively and at follow-up. Our technique shows promise in mitigating FN injury during complex cranial reconstruction and cranioplasty revision surgery. Further research with a larger cohort is needed to confirm efficacy and statistical significance.
The Morphometric Analysis of the Ethmoid Roof for Endoscopic Sinus Surgery With Multidetector Computed Tomography
Authors: Acar Musa , Şeker Büşra , Uğur Sultan
Published: August 2024

Most potential major complications in endoscopic sinus surgery are related to the ethmoid bone. To prevent complications, it is necessary to define the concept of a “dangerous ethmoid.” The coronal multidetector computed tomography (MDCT) scans of a total of 271 patients, including 101 patients under 18 years old and 170 patients over 18 years old, were examined. For each patient, the depth of the olfactory fossa (DOF), the width of the olfactory fossa (WOF), the angle between the lateral lamella and the cribriform plate (LLCPA), the length of the lateral lamella (LLL), the distance between the nasal floor and the ethmoid roof (NFERL), and the width of the olfactory cleft (WOC) were recorded. The Keros and Gera types were determined. NFERL was found to be significantly higher in males across all age groups. WOC was significantly higher in males only under 18 years old. Only LLCPA was found to be significantly higher on the right side in both sexes. It was determined that NFERL increased with age, while WOC increased with age until 18. Keros type III and Gera type C, which are called dangerous types, were detected in 28 and 24 cases in total, respectively. The data obtained from significant anatomical landmarks in pediatric and adult cases provide useful information about the region in preoperative planning. The analysis results of the prevalence of Keros and Gera classifications allow the identification of high-risk anatomical conditions within the ethmoid.
Concept design overview: a question of choices and compromise
Authors: Waldon Chris , Muldrew Stuart I. , Keep Jonathan , Verhoeven Roel , Thompson Terry , Kisbey-Ascott Mark
Published: August 2024

The Spherical Tokamak for Energy Production (STEP) programme hypothesizes that a compact machine offers a route to reduced capital cost that directly tackles the barrier to entry of this potentially transformative technology. History has shown that with an unsolved, complex and highly interdependent design challenge, there is a need to balance exploration of the problem with progress. Almost all complex systems arise from the evolutionary improvement of simpler systems which is an approach the programme has adopted by working through a virtual natural selection of design families towards a single concept consistent with the initiating hypothesis. Issues are uncovered and solved more rapidly this way because the effort is focused on an end. In this current phase, STEP has had to be an agile fast-moving programme to work with what emerges as well as what was planned, to sit with uncertainty and to embrace self-organizing principles. The complex decision-making and compromises in emerging trades have led to a concept respectful of the tight aspect ratio hypothesis which carefully balances cost, performance and deliverability. It remains a high-risk and high-reward programme, but the character of the challenge is better understood building confidence and enhancing capability to advance the evolving design further.

This article is part of the theme issue ‘Delivering Fusion Energy – The Spherical Tokamak for Energy Production (STEP)’.
Resolving the diagnostic odyssey in inherited retinal dystrophies through long-read genome sequencing
Authors: Fabian-Morales Gerardo , Ordoñez-Labastida Vianey , Rowell William J. , Lambert Christine , Fanslow Cairbre , Robertson Alexander , Zenteno Juan C.
Published: August 2024

Background

Inherited Retinal Dystrophies (IRDs) are visually disabling monogenic diseases with remarkable genetic and phenotypic heterogeneity. Mutations in more than 300 different genes have been identified as disease causing. Genetic diagnosis of IRDs has been greatly improved thanks to the incorporation of Next Generation Sequencing (NGS) approaches. However, the current IRD molecular diagnosis yield using NGS is approximately 60% and negative cases can be explained by variants that are not usually identified by the widely used short reads-NGS such as structural variants (SVs) or by variants located in uncovered, low complexity, repetitive, highly homologous, or GC-rich regions. Long-read genome sequencing (LR-GS) is an emerging technology that produces 10-20 kb reads and is expected to overcome short-read sequencing limitations in the clinical context, thus improving the diagnostic yield in heterogeneous diseases as IRDs.

Objective

To describe LR-GS utility in 3 unrelated, previously unsolved IRD cases.

Material & Methods

LR-GS was performed on 3 probands with IRDs and previous inconclusive genetic testing with NGS (either exome or gene panel sequencing). Whole genome libraries were prepared using SMRTbell® prep kit. Sequencing was performed on the PacBio Revio system.

Results

A definite diagnosis was established in the 3 cases. A homozygous deep intronic variant c.4885+740A>T inUSH2Awas identified in a proband with Usher syndrome; A homozygous intragenic deletion involvingEYSexon 24 was found in a proband with Retinitis pigmentosa. Finally, a proband with Usher syndrome was found to be a compound heterozygous for aUSH2Adeep intronic variant and a multiexonic duplication involvingUSH2Aexons 22-32.

Conclusion

Our case series show the efficiency in a clinical setting of LR-GS to detect disease-causing variants that were missed by current NGS techniques, improving thus the molecular diagnosis rate in genetically heterogeneous diseases as IRDs
Validation of dementia care-related scales among informal caregivers of Latinos with dementia or mild cognitive impairment
Authors: Perales-Puchalt Jaime , Checa Irene , Espejo Begoña , Martín Carbonell Marta de la C. , Fracachán-Cabrera Mónica , Baker Christina , Ramírez-Mantilla Mariana , Mendez-Asaro Prisca , Zimmer Malissia , Williams Kristine , Allen Greiner K. , Zaudke Jana , Arreaza Hector , Velez-Uribe Idaly , Moore Henry , Sepulveda-Rivera Vanessa , Meyer Kylie , Benton Donna , Kittle Krystal , Gillen Lindsey , Burns Jeffrey M
Published: August 2024

Objectives

To test the psychometric properties of several dementia care-related scales among Latinos in the US.

Design

We leveraged secondary baseline data from a one-arm mHealth trial on dementia caregiver support. We included 100 responses for caregiver-focused scales and 88 responses for care recipient-focused scales. Scales included the Neuropsychiatric Inventory Questionnaire Severity and Distress scales, six-item Zarit Burden Inventory, Ten-item Center for Epidemiologic Studies Depression Scale, Geriatric Depression Inventory, Quality of Life in Alzheimer’s Disease, and Single-item Satisfaction With Life Scale. We calculated concurrent validity using Pearson and Spearman correlations and expected correlations amongst all variables in line with the Stress Process Framework. We calculated internal consistency reliability using Cronbach’s alpha.

Results

All concurrent validity correlations followed the expected directionality, with 19/21 inter-scale correlations in the total sample reaching statistical significance (p<0.05), and 17/21 reaching at least a low correlation (0.3). Cronbach’s alpha ranged from 0.832 to 0.879 in all scales in the total sample.

Conclusion

The English and Spanish caregiver-administered scales tested in this manuscript have good psychometric properties.

Clinical Implications

The dementia care-related scales are now appropriately available for use among US Latinos in research and clinical contexts.
Priority Setting for Multicenter Research Among Adults with Cerebral Palsy: A Qualitative Study
Authors: Sarmiento Cristina A. , Gannotti Mary , Cohen Jocelyn , Hurvitz Edward
Published: August 2024

Purpose

Identify priorities for adult cerebral palsy (CP) research by engaging individuals with lived experience, clinical investigators, and community leaders.

Materials and Methods

Qualitative descriptive study using iterative focus groups, followed by inductive thematic analysis. Participants included adults with CP and caregivers, clinical investigators, and community leaders in the CP and disability spaces. We explored research priorities among three research areas identified a priori– bone health, kidney health, and preventive care.

Results

We conducted four focus groups (20 participants with lived experience; 10 clinical investigators; 9 community leaders). Most participants felt all topic areas were very important, though preventive care emerged as the top priority. We identified three overarching themes that cut across the various research areas discussed: patient and provider knowledge gaps; a precision medicine approach for adult CP care; and the need to address ableism.

Conclusions

Adults with CP face unique healthcare needs and risks as they age, and the evidence base to guide their care lags significantly behind. Our study identified preventive care as the top research priority for the adult CP research agenda. Next steps in this line of research should focus on interventions to facilitate primary and preventive care interactions for adults with CP.
CYP76BK1 orthologs catalyze furan and lactone ring formation in clerodane diterpenoids across the mint family
Authors: Schlecht Nicholas J. , Lanier Emily R. , Andersen Trine B. , Brose Julia , Holmes Daniel , Hamberger Björn R.
Published: August 2024

The Lamiaceae (mint family) is the largest known source of furanoclerodanes, a subset of clerodane diterpenoids with broad bioactivities including insect antifeedant properties. TheAjugoideaesubfamily, in particular, accumulates significant numbers of structurally related furanoclerodanes. The biosynthetic capacity for formation of these diterpenoids is retained across most Lamiaceae subfamilies, including the early-divergingCallicarpoideaewhich forms a sister clade to the rest of Lamiaceae.VacCYP76BK1, a cytochrome P450 monooxygenase fromVitex agnus-castus, was previously found to catalyze the formation of the proposed precursor to furan and lactone-containing labdane diterpenoids. Through transcriptome-guided pathway exploration, we identified orthologs ofVacCYP76BK1inAjuga reptansandCallicarpa americana.Functional characterization demonstrated that both could catalyze the oxidative cyclization of clerodane backbones to yield a furan ring. Subsequent investigation revealed a total of tenCYP76BK1orthologs across six Lamiaceae subfamilies. Through analysis of available chromosome-scale genomes, we identified fourCYP76BK1members as syntelogs within a conserved syntenic block across divergent subfamilies. This suggests an evolutionary lineage that predates the speciation of the Lamiaceae. Functional characterization of theCYP76BK1orthologs affirmed conservation of function, as all catalyzed furan ring formation. Additionally, some orthologs yielded two novel lactone ring moieties. The presence of theCYP76BK1orthologs across Lamiaceae subfamilies closely overlaps with the distribution of reported furanoclerodanes. Together, the activities and distribution of theCYP76BK1orthologs identified here support their central role in furanoclerodane biosynthesis within the Lamiaceae family. Our findings lay the groundwork for biotechnological applications to harness the economic potential of this promising class of compounds.

Significance Statement

The discovery and functional characterization ofCYP76BK1orthologs across diverse Lamiaceae subfamilies revealed novel chemistry and their central role in furanoclerodane biosynthesis, providing insights into the metabolic landscape and dynamic evolution of this plant family over approximately 50 million years. These findings pave the way for targeted biosynthetic engineering efforts and the sustainable production of furanoclerodane compounds, offering promising prospects for agricultural and pharmaceutical applications.
The archaeal family 3 polyphosphate kinase reveals a function of polyphosphate as energy buffer under low energy charge
Authors: Höfmann Svenja , Schmerling Christian , Stracke Christina , Niemeyer Felix , Schaller Torsten , Snoep Jacky L. , Bräsen Christopher , Siebers Bettina
Published: August 2024

Inorganic polyphosphate, a linear polymer of orthophosphate residues linked by phosphoanhydride bonds, occurs in all three domains of life and plays a diverse and prominent role in metabolism and cellular regulation. While the polyphosphate metabolism and its physiological significance have been well studied in bacteria and eukaryotes including human, there are only few studies in archaea available so far. In Crenarchaeota including members ofSulfolobaceae, the presence of polyphosphate and degradation via exopolyphosphatase has been reported and there is some evidence for a functional role in metal ion chelation, biofilm formation, adhesion and motility, however, the nature of the crenarchaeal polyphosphate kinase is still unknown. Here we used the crenarchaeal model organismSulfolobus acidocaldariusto study the enzymes involved in polyphosphate synthesis. The two genes annotated as thymidylate kinase (saci_2019andsaci_2020), localized downstream of the exopolyphosphatase, were identified as the missing polyphosphate kinase inS. acidocaldarius(SaPPK3). Thymidylate kinase activity was confirmed for Saci_0893. Notably Saci_2020 showed no polyphosphate kinase activity on its own but served as regulatory subunit (rPPK3) and was able to enhance polyphosphate kinase activity of the catalytically active subunit Saci_2019 (cPPK3). Heteromeric polyphosphate kinase activity is reversible and shows a clear preference for polyP-dependent nucleotide kinase activity, i.e. polyP-dependent formation of ATP from ADP (12.4 U/mg) and to a lower extent of GDP to GTP whereas AMP does not serve as substrate. PPK activity in the direction of ATP-dependent polyP synthesis is rather low (0.25 U/mg); GTP was not used as phosphoryl donor. A combined experimental modelling approach using quantitative31P NMR allowed to follow the reversible enzyme reaction for both ATP and polyP synthesis. PolyP synthesis was only observed when the ATP/ADP ratio was kept high, using an ATP recycling system. In absence of such a recycling system, all incubations with polyP and PPK would reach an equilibrium state with an ATP/ADP ratio between 3 and 4, independent of the initial conditions. Structural and sequence comparisons as well as phylogenetic analysis reveal that theS. acidocaldariusPPK is a member of a new PPK family, named PPK3, within the thymidylate kinase family of the P-loop kinase superfamily, clearly separated from PPK2. Our studies show that polyP, in addition to its function as phosphate storage, has a special importance for the energy homeostasis ofS. acidocaldariusand due to its reversibility serves as energy buffer under low energy charge enabling a quick response to changes in cellular demand.
Number of ancestors and length of identity-by-descent tracks over time
Authors: Eriksen Mikkel Spallou , Renaud Gabriel
Published: August 2024

The divergence between genetic ancestors (those who have contributed to an individual’s DNA) and genealogical ancestors (individuals recognized as ancestors in a societal context) evolves significantly over time. This study focuses on small, insular populations, where the number of genetic ancestors can swiftly encompass the entirety of genealogical ancestors. Additionally, in these populations, runs of homozygosity (ROHs) frequently occur due to random chance. This study used a forward-in-time simulation based on the Wright-Fisher model to analyze genealogical and genetic relatedness, haplotype block lengths, and runs of homozygosity (ROH) across generations. In small, insular populations, the number of genetic ancestors rapidly encompassed the total number of potential ancestors, and ROHs occurred frequently due to genetic drift. Our results showed that while genealogical ancestors followed an initial exponential growth phase before stabilizing, genetic ancestors grew more slowly. This was especially the case when the initial population size was large. These findings highlight the high frequency of ROHs in smaller populations, providing insights into the genetic structure of historically isolated groups.
Altered Copper Transport in Oxidative Stress-Dependent Brain Endothelial Barrier Dysfunction Associated with Alzheimer’s Disease
Authors: Hossain Md. Selim , Das Archita , Rafiq Ashiq M. , Deák Ferenc , Bagi Zsolt , Outlaw Rashelle , Sudhahar Varadarajan , Yamamoto Mai , Kaplan Jack H. , Ushio-Fukai Masuko , Fukai Tohru
Published: August 2024

Oxidative stress and blood-brain barrier (BBB) disruption due to brain endothelial barrier dysfunction contribute to Alzheimer’s Disease (AD), which is characterized by beta-amyloid (Aβ) accumulation in senile plaques. Copper (Cu) is implicated in AD pathology and its levels are tightly controlled by several Cu transport proteins. However, their expression and role in AD, particularly in relation to brain endothelial barrier function remains unclear. In this study, we examined the expression of Cu transport proteins in the brains of AD mouse models as well as their involvement in Aβ42-induced brain endothelial barrier dysfunction. We found that the Cu uptake transporter CTR1 was upregulated, while the Cu exporter ATP7A and/or ATP7B were downregulated in the hippocampus of AD mouse models, and in Aβ42-treated human brain microvascular endothelial cells (hBMECs). In the 5xFAD AD mouse model, Cu levels (assessed by ICP-MS) were elevated in the hippocampus. Moreover, Aβ42-induced reactive oxygen species (ROS) production, ROS-dependent loss in barrier function in hBMEC (measured by transendothelial electrical resistance), and tyrosine phosphorylation of VE-cadherin were all inhibited by either a membrane permeable Cu chelator or by knocking down CTR1 expression. These findings suggest that dysregulated expression of Cu transport proteins may lead to intracellular Cu accumulation in the AD brain, and that Aβ42 promotes ROS-dependent brain endothelial barrier dysfunction and VE-Cadherin phosphorylation in a CTR1-Cu-dependent manner. Our study uncovers the critical role of Cu transport proteins in oxidative stress-related loss of BBB integrity in AD.

Highlights

Upregulation of the Cu importer CTR1 and downregulation of the Cu exporter ATP7A in the hippocampus of AD mouse models

Aβ42 increases CTR1 expression while reduces ATP7A and ATP7B levels in human brain microvascular ECs.

Aβ42 triggers increased reactive oxygen species (ROS) production in human brain microvascular ECs through a CTR1- and Cu-dependent manner.

Aβ42 induces endothelial barrier dysfunction in human brain microvascular ECs through a CTR1-Cu-ROS-pendent manner.
Selective autophagy fine-tunes Stat92E activity by degrading Su(var)2-10/PIAS during glial injury signaling inDrosophila
Authors: Vincze Virág , Esküdt Zsombor , Fehér-Juhász Erzsébet , Chhatre Aishwarya Sanjay , Jipa András , Csordós Martin , Galambos Anna Rita , Feil-Börcsök Dalma , Juhász Gábor , Szabó Áron
Published: August 2024

Glial immunity plays a pivotal role in the maintenance of nervous system homeostasis and in responses to stress conditions, including neural injuries. The transcription factor Stat92E is activated independently of the canonical JAK/STAT pathway inDrosophilaglial cells following central nervous system injury to shape glial reactivity towards degenerating axons. However, the upstream regulatory mechanisms governing Stat92E activation remain elusive. Here we reveal that selective autophagy mediates degradation of the PIAS SUMO ligase family member Stat92E repressor, Su(var)2-10 in glia. Autophagic elimination of Su(var)2-10 mediated by its co-localization and interaction with the core autophagy factor Atg8a is required for efficient Stat92E-dependent transcription after injury. In line with this, we demonstrate that autophagy is essential for the upregulation of an innate immune pathway in glial cells following axon injury, characterized by the induction ofvirus-induced RNA 1(vir-1). We propose that autophagic Su(var)2-10 breakdown controls Stat92E activation to allow glial reactivity. These findings identify a critical role for autophagy in glial immunity as part of neural injury responses.
Hemifusomes and Interacting Proteolipid Nanodroplets: Formation of a Novel Cellular Organelle Complex
Authors: Tavakoli Amirrasoul , Hu Shiqiong , Ebrahim Seham , Kachar Bechara
Published: August 2024

Within cells, vesicle fusion, scission, and the formation of intraluminal vesicles are critical processes that facilitate traffic, degradation, and recycling of cellular components, and maintenance of cellular homeostasis. Despite significant advancements in elucidating the molecular mechanisms that drive these dynamic processes, the direct in situ visualization of membrane remodeling intermediates remains challenging. Here, through the application of cryo-electron tomography in mammalian cells, we have identified a previously undescribed vesicular organelle complex with unique membrane topology: heterotypic hemifused vesicles that share extended hemifusion diaphragms (HDs) with a 42 nm proteolipid nanodroplet (PND) at their rim. We have termed these organelle complexes “hemifusomes”. The HDs of hemifusomes exhibit a range of sizes and curvatures, including the formation of lens-shaped compartments encapsulated within the membrane bilayer. The morphological diversity of the lens-shaped vesicle aligns with a step-wise process of their intraluminal budding, ultimately leading to their scission and the generation of intraluminal vesicles. We propose that hemifusomes function as versatile platforms for protein and lipid sorting and as central hubs for the biogenesis of intraluminal vesicles and the formation of multivesicular bodies.
Scanning probe microscopy elucidates gelation and rejuvenation of biomolecular condensates
Authors: Naghilou Aida , Armbruster Oskar , Mashaghi Alireza
Published: August 2024

Comprehensive understanding of dynamics and disease-associated solidification of biomolecular condensates is closely tied to analysis of their mechanical characteristics. Despite recent technical advances in rheological studies of condensates, these still vastly rely on methods restricted to small forces, rendering measurements of droplets with higher elasticities and after transition to solid challenging. Here, we develop assays for in-depth mechanical characterization of biomolecular condensates by scanning probe microscopy. We demonstrate this technique by measuring the rheological behavior of heterotypic poly-L-lysine heparin condensates, showcasing their multi-route liquid to gel transition, as well as their rejuvenation by chemical alterations to the medium. Due to the wide-spread application of scanning probe microscopy in biological fields, its capability for rapid, high throughput, high force range studies, and integration with nanoscale morphological measurements, our probe-based method is a significant breakthrough in investigating condensate behavior, leading to accelerated development of therapies.
Responses of root architectural and anatomical traits to low nitrogen stress in rice
Authors: Tian Tian , Lynch Jonathan P. , Brown Kathleen M.
Published: August 2024

Improving nitrogen use efficiency in rice would provide economic and environmental benefits, but little is known about root morphological and anatomical responses to low nitrogen. In this study, two sets of rice genotypes, one set from the RDP1 panel, and one set of recombinant inbred lines, were used to characterize responses to gradual nitrogen depletion by plant uptake and movement of nitrogen to deeper soil strata as a result of leaching, so that more nitrogen was available at depth in aerobic soil mesocosms in a greenhouse. There was significant genetic variation in shoot biomass reductions in response to low nitrogen. The root to shoot biomass ratio was increased by low nitrogen in both sets of genotypes. Relative investment in nodal root number was accentuated with low nitrogen, and shoot biomass was correlated with numbers and lengths of nodal and large lateral roots. There was genetic variation for nodal root number and length in both sets of genotypes. Anatomical responses to low nitrogen were assessed in nodal roots of the RILs, where root cross-sectional area, stele area, and metaxylem vessel number were reduced by low nitrogen, and root diameter was reduced in the RDP1 genotypes. There were significant interactions of nitrogen with genotype for stele area and percent aerenchyma in the RILs. Genetic variation for low nitrogen responses may be useful for selection of rice lines with greater nitrogen acquisition under nitrogen-leaching conditions.
Live Cell Painting: image-based profiling in live cells using Acridine Orange
Authors: Garcia-Fossa Fernanda , Moraes-Lacerda Thaís , Rodrigues-da-Silva Mariana , Diaz-Rohrer Barbara , Singh Shantanu , Carpenter Anne E. , Cimini Beth A. , de Jesus Marcelo Bispo
Published: August 2024

Image-based profiling has been used to analyze cell health, drug mechanism of action, CRISPR-edited cells, and overall cytotoxicity. Cell Painting is a broadly used image-based assay that uses morphological features to capture how cells respond to treatments. However, this method requires cell fixation for staining, which prevents examining live cells. To address this limitation, here we present Live Cell Painting (LCP), a high-content method based on Acridine orange, a metachromatic dye that labels different organelles and cellular structures. We began by showing that LCP can be applied to follow acidic vesicle redistribution of cells exposed to acidic vesicles inhibitors. Next, we show that LCP can identify subtle changes in cells exposed to silver nanoparticles that are not detected by techniques such as MTT assay. In drug treatments, LCP was helpful in assessing the dose-response relationship and creating profiles that allow clustering of drugs that cause liver injury. Here, we present an affordable and easy-to-use image-based assay capable of assessing overall cell health and showing promise for use in various applications such as assessing drugs and nanoparticles. We envisage the use of Live Cell Painting as an initial screening of overall cell health while providing insights into new biological questions.
Temperature effects on interspecific eavesdropping in the wild
Authors: Rossi Sarina M. , Fowler-Finn Kasey D. , Gray David A.
Published: August 2024

Mating signals are targets of conspecific signal recognition and sexual selection, but are also subject to abiotic temperature effects and to biotic interspecific eavesdroppers. In crickets, the male calling song becomes faster at warmer temperatures, and female crickets’ recognition of male song tracks temperature in a coordinated manner, termed ‘temperature coupling.’ But female crickets are not the only ecologically relevant listeners: some cricket species are parasitized byOrmia ochracea, a parasitoid fly which finds its cricket hosts by eavesdropping on male cricket song. How temperature affects parasitoid fly phonotaxis to song is largely unexplored, with only one previous study conducted under field conditions. Here we explore six possible patterns of thermal effects on fly responses to cricket song, including temperature coupling, using field playbacks of syntheticGryllus lineaticepssongs designed to be species-typical at various temperatures. We find that temperature does affect fly response, but that the temperature deviation of songs from ambient does not impact numbers of flies caught. We extend this finding by comparing the temperatures of the air and ground to show that temperature coupling is unlikely to be effective given microhabitat variation and differential rates of cooling in the evening hours when flies are most active. Our results can be interpreted more broadly to suggest (i) temperature effects on intraspecific communication systems may be more tightly coupled than are effects on interspecific eavesdropping, and (ii) variation in thermal microhabitats in the field make it difficult to translate laboratory physiological responses to natural selection in the wild.

Lay Summary

Mating signals and signal recognition change with temperature, and sometimes mating signals are intercepted by predators or parasites. By using playbacks of cricket song in the wild, we show that temperature changes do affect the response of a parasitoid fly to cricket song. However, parasitoid responses are not tightly coupled to temperature induced changes in cricket song, in part due to unpredictable variation in microhabitat temperatures typical of crickets and flies.