bluuebunny/crossref_metadata_2025 huggingface dataset:
Equitable community-based participatory research engagement with communities of color drives All of Us Wisconsin genomic research priorities
Authors: Thareja Suma K , Yang Xin , Upama Paramita Basak , Abdullah Aziz , Torres Shary Pérez , Cocroft Linda Jackson , Bubolz Michael , McGaughey Kari , Lou Xuelin , Kamaraju Sailaja , Ahamed Sheikh Iqbal , Madiraju Praveen , Kwitek Anne E , Whittle Jeffrey , Franco Zeno
Published: October 2024

Objective

The NIH All of Us Research Program aims to advance personalized medicine by not only linking patient records, surveys, and genomic data but also engaging with participants, particularly from groups traditionally underrepresented in biomedical research (UBR). This study details how the dialogue between scientists and community members, including many from communities of color, shaped local research priorities.

Materials and Methods

We recruited area quantitative, basic, and clinical scientists as well as community members from our Community and Participant Advisory Boards with a predetermined interest in All of Us research as members of a Special Interest Group (SIG). An expert community engagement scientist facilitated 6 SIG meetings over the year, explicitly fostering openness and flexibility during conversations. We qualitatively analyzed discussions using a social movement framework tailored for community-based participatory research (CBPR) mobilization.

Results

The SIG evolved through CBPR stages of emergence, coalescence, momentum, and maintenance/integration. Researchers prioritized community needs above personal academic interests while community members kept discussions focused on tangible return of value to communities. One key outcome includes SIG-driven shifts in programmatic and research priorities of the All of Us Research Program in Southeastern Wisconsin. One major challenge was building equitable conversations that balanced scientific rigor and community understanding.

Discussion

Our approach allowed for a rich dialogue to emerge. Points of connection and disconnection between community members and scientists offered important guidance for emerging areas of genomic inquiry.

Conclusion

Our study presents a robust foundation for future efforts to engage diverse communities in CBPR, particularly on healthcare concerns affecting UBR communities.
isoAsp-Quest: workflow development for isoAsp identification using database searches
Authors: Sakaue Hiroaki , Kuno Atsushi
Published: October 2024

A recent study reported that isomerization of aspartyl residues (Asp) occurs in various tissues and proteins in vivo. For a comprehensive analysis of post-translational modifications, the mass spectrometry (MS)-based proteomic approach is a straightforward method; however, the isomerization of Asp does not alter its molecular weight. Therefore, a unique method is required to analyse Asp isomers using MS. Herein, we present a novel strategy, isoAsp-Quest, which is a database search-oriented isoAsp identification method. isoAsp is specifically converted to 18O-labelled Lα-Asp by the enzymatic reaction of protein L-isoaspartyl-O-methyltransferase (PIMT) in 18O water with a mass shift of 2 Da, which, in principle, enables us to distinguish Asp isomers. However, in practise, a labelled Lα-Asp signal overlaps with that of endogenous Lα-Asp, making detection challenging. Therefore, degradation of the endogenous Lα-Asp peptide by AspN and subsequent removal of AspN were performed prior to the PIMT reaction. This strategy was applied to bovine lens α-crystallin. Consequently, several Asp isomerization sites, consistent with human αA-crystallin, were identified in bovine αA-crystallin, indicating that this strategy is also effective for biological proteins. Therefore, isoAsp-Quest enables the analysis of Lβ-Asp in a straightforward and rapid workflow, which may be useful for the quality control of protein products and biomarker discovery.
Burosumab in adults with X-linked hypophosphatemia: real-world experience from a retrospective study in Sydney
Authors: Kumar Shejil , Girgis Christian M , Tran Brian , Alvarez Malu , Clifton-Bligh Roderick J
Published: October 2024

X-linked hypophosphatemia (XLH) is a chronic disabling hereditary musculoskeletal disorder associated with inactivating PHEX mutations and elevated circulating FGF-23 concentrations. In a placebo-controlled trial of adults with XLH, burosumab (anti-FGF-23 antibody) demonstrated durable improvements in phosphate concentrations, and self-reported stiffness and physical limitation. However, real-world data regarding burosumab efficacy and tolerability in adults with XLH is lacking.

A retrospective audit was performed of patients (age ≥ 18-years) who commenced four-weekly subcutaneous burosumab for XLH at Royal North Shore and Westmead Hospitals, Sydney, between January 2021 and June 2024. Patients were managed per standard clinical care and burosumab dose adjusted as necessary according to manufacturer instructions. Electronic medical records were reviewed to collate data regarding patient demographics, XLH-related complications and prior treatment, burosumab dosage and side effects, and pre- and post-burosumab biochemistry and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores.

Of thirteen adults with XLH, all had hypophosphatemia before commencing burosumab (mean 0.64 ± 0.08 mmol/L). Mean WOMAC scores demonstrated baseline impairments in stiffness, pain and physical limitation. Burosumab was administered for median 15 months during follow-up (median dose 70 mg). Hypophosphatemia resolved in all patients within three months of burosumab (mean 1.03 ± 0.38 mmol/L). Two patients developed hyperphosphatemia two weeks after commencing burosumab requiring dose reduction. One patient ceased burosumab in the setting of hypercalcaemia and constipation secondary to pre-existing tertiary hyperparathyroidism. Adverse events were mild, including transient musculoskeletal discomfort (n = 4), restless legs (n = 2), injection site reaction (n = 2) and headache (n = 1). Repeat WOMAC within 12 months of commencing burosumab (n = 9) demonstrated clinically meaningful improvements in stiffness (-33.3 ± 12.5, P<.001) and physical function (-14.3 ± 16.2, P=.029).

This study reports real-world outcomes of adults with XLH treated with burosumab. Clinical experience from two centres in Sydney support trial findings that burosumab is well-tolerated and associated with improved serum phosphate concentrations and self-reported stiffness and physical function.
Granulomatosis with polyangiitis with lacrimal gland enlargement and pancreatic swelling: A case report and a literature review
Authors: Kawajiri Tetsuya , Iwata Shigeru , Tanaka Katsunori , Sonoda Takeru , Nishikawa Mizuki , Iwamoto Ryuta , Takahashi Yuichi , Kojima Fumiyoshi , Fujii Takao
Published: October 2024

A 62-year-old man had bilateral eyelid swelling for 4 months. Two months before admission, he developed fatigue and lost 5 kg of body weight. Further examination revealed elevated serum C-reactive protein, normal angiotensin-converting enzyme, elevated proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA), and normal immunoglobulin (Ig)G4 concentration. Chest X-ray and computed tomography showed no enlarged hilar lymph nodes, but positron emission tomography-computed tomography showed fluorodeoxyglucose accumulation in both lacrimal glands, in lung nodules, and in the pancreas. Tissue biopsies of the lacrimal glands and pulmonary nodules showed granuloma with giant cells, but no IgG4-positive cells or fibrosis. Pancreatic tissue showed no findings of autoimmune pancreatitis. In the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for granulomatosis with polyangiitis, the total score was 10 points. Final comprehensive diagnosis was granulomatosis with polyangiitis, based on the negative results of differential diseases, such as IgG4-related diseases and sarcoidosis. Prednisolone 60 mg/day was started on Day 8, and rituximab 500 mg/body/week on Day 12. After beginning treatment, general malaise and lacrimal gland enlargement were resolved, PR3-ANCA and C-reactive protein became negative, and the nodular shadow in the lungs disappeared. This is the first report of granulomatosis with polyangiitis presenting both lacrimal gland and pancreatic lesions.
GTSF1 is required for transposon silencing in the unicellular eukaryote Paramecium tetraurelia
Authors: Wang Chundi , Lyv Liping , Solberg Therese , Zhang Haoyue , Wen Zhiwei , Gao Feng
Published: October 2024

The PIWI-interacting RNA (piRNA) pathway is crucial for transposon repression and the maintenance of genomic integrity. Gametocyte-specific factor 1 (GTSF1), a PIWI-associated protein indispensable for transposon repression, has been recently shown to potentiate the catalytic activity of PIWI in many metazoans. Whether the requirement of GTSF1 extends to PIWI proteins beyond metazoans is unknown. In this study, we identified a homolog of GTSF1 in the unicellular eukaryote Paramecium tetraurelia (PtGtsf1) and found that its role as a PIWI-cofactor is conserved. PtGtsf1 interacts with PIWI (Ptiwi09) and Polycomb Repressive Complex 2 and is essential for PIWI-dependent DNA elimination of transposons during sexual development. PtGtsf1 is crucial for the degradation of PIWI-bound small RNAs that recognize the organism's own genomic sequences. Without PtGtsf1, self-matching small RNAs are not degraded and results in an accumulation of H3K9me3 and H3K27me3, which may disturb transposon recognition. Our results demonstrate that the PIWI–GTSF1 interaction also exists in unicellular eukaryotes with a role in transposon silencing.
PlasmidScope: a comprehensive plasmid database with rich annotations and online analytical tools
Authors: Li Yinhu , Feng Xikang , Chen Xuhua , Yang Shuo , Zhao Zicheng , Chen Yu , Li Shuai Cheng
Published: October 2024

Plasmids are extrachromosomal genetic molecules that replicate independent of chromosomes in bacteria, archaea, and eukaryotic organisms. They contain diverse functional elements and are capable of horizontal gene transfer among hosts. While existing plasmid databases have archived plasmid sequences isolated from individual microorganisms or natural environments, there is a need for a comprehensive, standardized, and annotated plasmid database to address the vast accumulation of plasmid sequences. Here, we propose PlasmidScope (https://plasmid.deepomics.org/), a plasmid database offering comprehensive annotations, automated online analysis, and interactive visualization. PlasmidScope harbors a substantial collection of 852 600 plasmids curated from 10 repositories. Along with consolidated background information, PlasmidScope utilizes 12 state-of-the-art tools and provides comprehensive annotations for the curated plasmids, covering genome completeness, topological structure, mobility, host source, tRNA, tmRNA, signal peptides, transmembrane proteins and CRISPR/Cas systems. PlasmidScope offers diverse functional annotations for its 25 231 059 predicted genes from 9 databases as well as corresponding protein structures predicted by ESMFold. In addition, PlasmidScope integrates online analytical modules and interactive visualization, empowering researchers to delve into the complexities of plasmids.
CovalentInDB 2.0: an updated comprehensive database for structure-based and ligand-based covalent inhibitor design and screening
Authors: Du Hongyan , Zhang Xujun , Wu Zhenxing , Zhang Odin , Gu Shukai , Wang Mingyang , Zhu Feng , Li Dan , Hou Tingjun , Pan Peichen
Published: October 2024

The rational design of targeted covalent inhibitors (TCIs) has emerged as a powerful strategy in drug discovery, known for its ability to achieve strong binding affinity and prolonged target engagement. However, the development of covalent drugs is often challenged by the need to optimize both covalent warhead and non-covalent interactions, alongside the limitations of existing compound libraries. To address these challenges, we present CovalentInDB 2.0, an updated online database designed to support covalent drug discovery. This updated version includes 8303 inhibitors and 368 targets, supplemented by 3445 newly added cocrystal structures, providing detailed analyses of non-covalent interactions. Furthermore, we have employed an AI-based model to profile the ligandability of 144 864 cysteines across the human proteome. CovalentInDB 2.0 also features the largest covalent virtual screening library with 2 030 192 commercially available compounds and a natural product library with 105 901 molecules, crucial for covalent drug screening and discovery. To enhance the utility of these compounds, we performed structural similarity analysis and drug-likeness predictions. Additionally, a new user data upload feature enables efficient data contribution and continuous updates. CovalentInDB 2.0 is freely accessible at http://cadd.zju.edu.cn/cidb/.
A new framework for SubtiWiki, the database for the model organism Bacillus subtilis
Authors: Elfmann Christoph , Dumann Vincenz , van den Berg Tim , Stülke Jörg
Published: October 2024

Bacillus subtilis is a Gram-positive model bacterium and one of the most-studied and best understood organisms. The complex information resulting from its investigation is compiled in the database SubtiWiki (https://subtiwiki.uni-goettingen.de/v5) in an integrated and intuitive manner. To enhance the utility of SubtiWiki, we have added novel features such as a viewer to interrogate conserved genomic organization, a widget that shows mutant fitness data for all non-essential genes, and a widget showing protein structures, structure predictions and complex structures. Moreover, we have integrated metabolites as new entities. The new framework also includes a documented API, enabling programmatic access to data for computational tasks. Here we present the recent developments of SubtiWiki and the current state of the data for this organism.
Mediterranean Diet and Risk of Hip Fracture: A Systematic Review and Dose-Response Meta-Analysis
Authors: Fa-Binefa Manel , Clara Albert , Lamas Claudia , Elosua Roberto
Published: October 2024

Context

Hip fractures are a major public health concern. Understanding their epidemiologic and biological links with diet and cardiovascular risk may have important implications for prevention.

Objective

To assess the dose-response association of Mediterranean diet (MD) adherence with the risk of hip fracture.

Data Sources

A systematic search was conducted in the PubMed, Scopus, and Web of Science databases for prospective studies. Search terms were “Mediterranean Diet” and “Fracture.”

Data extraction

Data were extracted from 8 studies, encompassing 15 cohorts that included 503 174 individuals. Methodological quality was assessed using the Risk of Bias in Nonrandomized Studies of Interventions.

Data Analysis

The “meta” and “dosresmeta” packages were used in R Studio Software. The results demonstrated that high and moderate MD adherence were associated with a reduced risk of hip fracture (relative risk [RR] = 0.71 [95% CI, 0.55-0.91]; and RR = 0.78[(95% CI, 0.65-0.93], respectively). The effect of the association was similar in men and women. The dose-response pattern of the association was linear: each point increase in MD adherence was associated with a 5.25% reduction in hip fracture risk.

Conclusions

Adherence to MD is associated with a reduction in hip fracture risk, following a linear dose-response pattern. This supports the promotion of this dietary pattern for improving bone health.

Systematic Review Registration

PROSPERO registration no. CRD42023402284.
10 Optimizing implementation and continuous monitoring of a newborn screening program for severe combined immunodeficiency
Authors: Ngan Abigail Netanya , Hildebrand Kyla , Turvey Stuart , James Elliot , Cook Victoria , Cameron Scott , Setiadi Audi , Vallance Hilary , Rakic Bojana , Sinclair Graham , Biggs Catherine M
Published: October 2024

Background

Severe Combined Immunodeficiency (SCID) is an inborn error of immunity characterized by severely low T cell levels and function. Early diagnosis is essential to prevent serious infections and improve outcomes. Newborn screening (NBS) for SCID provides a way to detect SCID and other conditions associated with T cell lymphopenia in the neonatal period.

Objectives

1) Optimize the implementation of a NBS program for SCID in British Columbia (BC), Canada; and 2) create a systematic method for monitoring the diagnoses and outcomes of infants with a positive screen to facilitate continuous improvement of the NBS program.

Design/Methods

An interdisciplinary working group comprised of immunologists, biochemical geneticists, and hematopathologists met at regular intervals prior to and after implementing NBS for SCID in BC. We developed an algorithm for the evaluation and initial management of infants with an abnormal NBS for SCID based on literature review and local expert consensus. Using a REDCap database, we tracked the prevalence, evaluation, diagnoses and outcomes of infants with a positive NBS. The database also monitored diagnoses and outcomes of children referred to Immunology outside of the NBS program. Plan-do-study-act cycles included creation of clinical and educational guidelines on SCID, optimization of abnormal NBS cut-off values, and reflex chromosomal microarray (CMA) testing of infants with confirmed T cell lymphopenia.

Results

Between October 3, 2022 and June 16, 2023, 28,816 initial samples were tested, and 30 infants had a positive screen for SCID. Of the 30 infants, 10 were ultimately diagnosed with conditions associated with T cell lymphopenia. Diagnosis led to avoidance of live viral vaccines and implementation of infection precaution measures. No infants experienced complications related to live viral vaccine administration, compared to 1 case in the preceding 12 months prior to NBS implementation. In February 2023, the threshold for an abnormal NBS was adjusted to achieve the goal positive screen frequency of 0.1%. Performing reflex CMA testing on infants with confirmed T cell lymphopenia led to rapid diagnosis of chromosomal microdeletion syndromes, avoiding unnecessary second tier testing. Since implementing NBS for SCID in BC, there have been no cases of SCID diagnosed outside of the NBS program.

Conclusion

Establishing an interdisciplinary working group and clinical database facilitated the smooth integration and continuous improvement of NBS for SCID in BC. This model can be applied to other healthcare systems to support teams and ensure the best possible outcomes for affected patients.
46 Micronutrient deficiencies in children and youth with autism spectrum disorder: Findings from a national surveillance study
Authors: Kinlin Laura M , Weinstein Michael , Conway Melanie , Critch Jeff , Erdle Stephanie C , Holland Joanna , Jetty Radha , Shouldice Michelle , Zwaigenbaum Lonnie , Birken Catherine S
Published: October 2024

Background

Children and youth with autism spectrum disorder (ASD) may be at risk of micronutrient deficiencies secondary to feeding problems such as limited dietary repertoire and high-frequency single food intake. The epidemiology of micronutrient deficiencies in the paediatric ASD population has not been studied.

Objectives

To determine minimum incidence, clinical characteristics, and health care utilization for four micronutrient deficiencies in children and youth with ASD in Canada: (1) vitamin A deficiency/xerophthalmia, (2) scurvy, (3) severe, symptomatic vitamin D deficiency, and (4) severe iron-deficiency anemia.

Design/Methods

We conducted a study via the Canadian Paediatric Surveillance Program, an active, population-based surveillance platform, between January 2020 and December 2022. More than 2,500 paediatricians and paediatric subspecialists were asked, monthly, to report cases of children and youth <18 years of age with ASD and one or more of the micronutrient deficiencies under surveillance. Case information was obtained via a detailed clinical questionnaire. Descriptive statistics were used to summarize the data. For average yearly minimum incidence estimates, we used case counts over the 3 year surveillance period, 2021 census data and recent ASD prevalence estimates (2% of children/youth aged 1 to 17 years living in private dwellings in Canada).

Results

Twenty-seven children and youth met the case definition (most male; median age 7.7 years, range 1.8–14.9 years). Multiple deficiencies were diagnosed concurrently in 9/27 (33%). Minimum incidence, per 100,000 children and youth with ASD per year, was 5.1 for scurvy (17 diagnoses); 3.0 for severe iron deficiency anemia (10 diagnoses); 2.1 for severe, symptomatic vitamin D deficiency (7 diagnoses); and <1 for vitamin A deficiency/xerophthalmia (<5 diagnoses). Restricted diet/limited food repertoire, attributed to the patient, was universal (27/27). Number of different foods in the patient’s diet was <10 in nearly all (20/23, 87%). Most patients were non-verbal (19/27, 70%) and of normal weight (18/26, 69%). Two-thirds (18/27, 67%) were admitted to hospital (median duration 8 days, range 3–32 days). One-third (9/27, 33%) underwent an invasive procedure as part of their diagnostic workup.

Conclusion

This surveillance study represents the first population-level examination of the epidemiology of micronutrient deficiencies in children and youth with ASD. Results suggest that micronutrient deficiencies in ASD are rare but clinically important, leading not infrequently to hospital admission and invasive investigations. Clinical characteristics of cases should inform anticipatory guidance and prevention efforts tailored to the paediatric ASD population.
73 Predictors of neurodevelopmental impairment in extreme preterm infants with unremarkable cranial ultrasound: A Canadian population-based cohort
Authors: Afifi Jehier , Richter Lindsay , Lee Seungwoo , Shah Prakesh , Raghuram Kamini , Thomas Karen , Mukerji Amit , Kanungo Jadeep , Lapointe Anie , Morin Alyssa , El-Naggar Walid
Published: October 2024

Background

Extreme preterm infants are at high-risk of brain injury and neurodevelopmental impairment (NDI). Previous studies reported significant NDI (sNDI) in preterm infants with no abnormalities on routine cranial ultrasound screening (CUS), traditionally perceived to have favorable outcomes. Recent data from population-based outlining clinical predictors of sNDI in those infants are lacking.

Objectives

(1) to describe the incidence, perinatal and neonatal characteristics of NDI and sNDI in a large population-based cohort of extreme preterm infants with unremarkable CUS; (2) to develop a prediction model of sNDI (any of: CP ≥ GMFCS stage 3, Bayley III < 70 in any domain, deafness requiring aids, or bilateral blindness) in those infants.

Design/Methods

A retrospective review of a national cohort of preterm infants born at <29 weeks’ gestation between April 2009 and December 2018. We included surviving infants with unremarkable routine CUS (no hemorrhage, periventricular leukomalacia or ventricular dilatation) who had neurodevelopmental assessment at 18-24 month corrected age at one of participating centres in the Canadian Neonatal Follow Up Network. We compared the baseline characteristics between infants with no NDI and those with any NDI and sNDI. The population sample was then randomly split into training and testing datasets in 70:30 ratio for prediction model’s development and validation, respectively. Multivariate logistic regression with GEE accounting for clustering within site was used, adjusted for variables with p-value<0.1 using backward selection procedure. The AUC and the diagnostic properties of the model developed using training dataset was then validated in the testing dataset.

Results

Out of 7463 eligible infants, 4327 (58%) were included. Of those, 2501 (59%) had no NDI and 1736 (41%) had NDI. sNDI accounted for 14% of the cohort and one third of those with NDI. Perinatal and neonatal characteristics of the three groups are shown in Table 1. On internal validation, maternal hypertension, maternal level of education, gestational age, male sex, ROP≥ stage 3 and systemic steroids were predictive of sNDI (Table 2). The prediction model had Sensitivity 0.91, NPV 0.90, and AUC 0.69 (95% CI 0.64-0.73).

Conclusion

In this national cohort, 2 out of 5 extreme preterm infants with unremarkable CUS had NDI and 1 in 7 had sNDI. The developed prediction model had high sensitivity and NPV, but poor discrimination. The findings of this study can help clinicians to identify at-risk infants who may benefit from early targeted interventions.
76 White matter microstructure and motor function at 8 years of age in children born preterm
Authors: Oloomi Sarvenaz , Ufkes Steven , Chau Cecil , Guo Ting , Chau Vann , Synnes Anne , Grunau Ruth E , Miller Steven P
Published: October 2024

Background

White matter injury (WMI) in preterm neonates is characterized by focal areas of white matter necrosis (punctate WMI) and more diffuse impairments in white matter (dysmaturation). White matter dysmaturation is reflected as lower fractional anisotropy (FA) measured by diffusion tensor imaging (DTI). Reduced white matter FA in neonatal DTI has been associated with adverse motor function at early ages in children born preterm. Yet, how white matter FA at school-age relates to motor function at this later age is largely unknown.

Objectives

To assess the relationship between white matter FA and motor function at 8 years of age in children born very preterm.

Design/Methods

110 children born very preterm (mean birth gestational age [GA] 28.19 weeks, range 24-32 weeks) completed MRI scans in the neonatal period and again at 8 years of age (mean age 8.35 years, SD = 0.38). Neonatal WMI was quantified on the neonatal T1-weighted images with significant WMI defined as WMI volume > 40 mm3. FA at 8 years was assessed using tract-based spatial statistics (TBSS). Movement Assessment Battery for Children, 2nd Ed (M-ABC-2) was used to assess fine and gross motor function at 8 years of age. Motor outcomes from the M-ABC total score were grouped as: Significant Movement Difficulty < 56 (below 5th percentile, n = 31), At-risk of Movement Difficulty 57-67 (5th-15th percentile, n = 23), and Unlikely to Have Movement Difficulty > 68 (above 15th percentile, n = 56). FA in the white matter skeleton was compared between motor outcome groups using threshold-free cluster enhancement (TFCE), adjusting for birth GA and significant WMI, and correcting for multiple comparisons across skeleton voxels using permutation testing with 5000 permutations.

Results

Table 1 outlines descriptive differences in the three motor outcome groups. Children born preterm who are Unlikely to Have Movement Difficulty at 8 years had significantly higher FA (p < .05) compared to those At-risk of or with Significant Movement Difficulty, especially in the corpus collosum (Figure 1), controlling for birth GA and significant neonatal WMI. Those with Significant Movement Difficulty had the lowest FA.

Conclusion

In children born preterm at age 8 years, white matter FA is associated with motor performance, independent of significant neonatal WMI. Our findings indicate that white matter dysmaturation persists and has functional significance through school-age.
Predictable shifts from nutrient to energy limitation determine the responses of planktonic autotrophs, bacteria and mixoplankton to browning
Authors: Cagle Sierra , Diehl Sebastian
Published: October 2024

Within aquatic ecosystems, heterotrophic, mixotrophic and autotrophic plankton are entangled in a complex network of competitive, predatory and mutualistic interactions. “Browning,” the increase of colored dissolved organic matter (CDOM) from terrestrial catchments, can affect this network of interactions by simultaneously decreasing light availability and increasing organic carbon and nutrients supplies. Here, we introduce a conceptual, process-based numerical model to investigate the effects of browning on a microbial food web consisting of heterotrophic bacterioplankton, bacterivorous phago-mixoplankton, autotrophic phytoplankton and the resources light, inorganic phosphorus and DOM. Additionally, we explore how the investment in autotrophic vs. phagotrophic resource acquisition influences mixoplankton performance. Several model predictions are in broad agreement with empirical observations under increasing CDOM supply, including increased bacterial biomass and inorganic phosphorous, decreased light penetration, the potential for a unimodal phytoplankton biomass response and a local minimum in mixoplankton biomass. Our results also suggest that mixoplankton with a high investment in phototrophy perform best in many conditions but that phosphorous acquisition via prey is crucial under high light-low nutrient conditions. Overall, our model analyses suggest that responses to altered CDOM supply are largely determined by systematic changes in the relative importance of nutrient vs. energy limitation of each plankton group.
The Curious Case of Black “Conservatives”: Assessing the Validity of the Liberal-Conservative Scale among Black Americans
Authors: Jefferson Hakeem
Published: October 2024

Many Black Americans identify as conservative on surveys, despite their allegiance to the Democratic Party. Prominent theoretical accounts claim this mismatch results from identity-based considerations. I revisit this long-standing puzzle and offer an alternative explanation with broad implications for studying political attitudes and behavior across the social sciences. Leveraging data from the American National Election Studies, I demonstrate that the terms “liberal” and “conservative” are unfamiliar to many Black Americans, compromising the usefulness and validity of the liberal-conservative scale for Black respondents. Respondents unfamiliar with these terms misapply them and choose ideological labels that fail to align with their partisan preferences. Consequently, scholars and political actors make incorrect and imprecise inferences about the contours of Black politics. Findings also raise new concerns about the generalizability of claims that rely on ideological self-identification measures, including popular claims about mass polarization and partisan-ideological sorting among the American public. Critically, this work suggests a need for caution when using concepts that vary in their meaningfulness across social groups.
Stress granules and organelles: coordinating cellular responses in health and disease
Authors: Liu Ying , Li Yin , Zhang Peipei
Published: October 2024

Membrane-bound organelles and membraneless organelles (MLOs) coordinate various biological processes within eukaryotic cells. Among these, stress granules (SGs) are significant cytoplasmic MLOs that form in response to cellular stress, exhibiting liquid-like properties alongside stable substructures. SGs interact with diverse organelles, thereby influencing cellular pathways that are critical in both health and disease contexts. This review discusses the interplay between SGs and organelles and explores the methodologies employed to analyze interactions between SGs and other MLOs. Furthermore, it highlights the pivotal roles SGs play in regulating cellular responses and the pathogenesis of amyotrophic lateral sclerosis. Gaining insights into these interactions is essential for deciphering the mechanisms underlying both physiological processes and pathological conditions.
The Hedging Channel of Exchange Rate Determination
Authors: Liao Gordon Y , Zhang Tony
Published: October 2024

We propose the currency hedging channel that connects countries’ external imbalances to their exchange rate behavior. We present a model in which investors increase their currency hedging during periods of financial distress in proportion to their net foreign asset exposure. This behavior coupled with constrained financial intermediation explains observed relationships between gradually adjusting external imbalances and volatile spot and forward exchange rates. We find empirical support for the hedging channel in both the conditional and unconditional moments of exchange rates, option prices, and countries’ uses of Federal Reserve swap lines.
Prevalence and clinical value of autoantibodies directed against lysobisphosphatidic acid in antiphospholipid syndrome
Authors: Lambert Mathilde , Robin Maxime , Munier Lucie , Beziane Abdou , Mège Jean-Louis , Bertin Daniel , Bardin Nathalie
Published: October 2024

Objectives

To assess the prevalence and clinical significance of autoantibodies against lysobisphophatidic acid (aLBPA) in patients with APS.

Methods

We conducted a retrospective analysis involving 91 patients with persistent conventional aPLs: 60 patients with at least one clinical event of APS (symptomatic group) and 31 without (asymptomatic group), as well as 33 aPL-negative controls. Detection of aLBPA in serum samples was performed using an enzyme-linked immunosorbent assay (ELISA) specifically designed for this study.

Results

The prevalence of aLBPA is significantly higher in patients with persistent aPL than that of the control group (P < 0.0001). Among patients with persistent aPL, our findings reveal a significantly higher prevalence of aLBPA in asymptomatic patients compared with their symptomatic counterparts (P = 0.027). Notably, patients positive for IgG aPL alone demonstrated a greater likelihood of presenting clinical events suggestive of APS.

Conclusion

The combined assay of aLBPA and conventional aPL could be used to stratify patients with persistent aPL. This combined approach could serve as a valuable tool in the management of this complex autoimmune disease, particularly in guiding decisions regarding the initiation of primary thromboprophylaxis in asymptomatic patients with persistent aPL.
Co-created improvement goals and strategies for implementing SBIRT and MAUD in primary care settings in a facilitator-supported, tailored implementation study
Authors: Kenzie Erin S , Weekley Tiff , Barnes Chrystal , Seater Mellodie , Sánchez Victoria , Hatch Brigit A , Coury Jennifer , Davis Melinda M
Published: October 2024

Evidence-based approaches to screening and treatment for unhealthy alcohol use have the potential to reduce morbidity and mortality but are currently underutilized in primary care settings. To support implementation of screening, brief intervention, and referral to treatment (SBIRT) and medication-assisted treatment for alcohol use disorder (MAUD) by identifying goals co-developed by clinics and practice facilitators in a flexible implementation study. In a pragmatic implementation study, we used practice facilitation to support the implementation of SBIRT and MAUD in 48 clinical practices across Oregon, Washington, and Idaho. Our study used a tailored approach, in which facilitators and clinics co-identified implementation goals based on clinic needs. We used clinic contact logs, individual interviews, group periodic reflections with practice facilitators, and exit interviews with clinic staff to inform qualitative analysis. With support from practice facilitators, clinics identified goals spanning SBIRT, MAUD, reporting, targeted patient outreach, and quality improvement capacity. Goals addressed both the technical (e.g. data tracking) and social (e.g. staff training) aspects of SBIRT and MAUD. A decision tree summarizes emergent findings into a tool to support future implementation of SBIRT in primary care settings. A facilitator-supported, tailored approach to SBIRT implementation enabled clinics to identify a variety of goals to improve SBIRT and MAUD implementation. These identified priorities, along with a decision tree describing the hierarchical structure of these goals, could support future implementation efforts.
The impact of mild episodic ketosis on microglia and hippocampal long‐term depression in 5xFAD mice
Authors: Di Lucente Jacopo , Ramsey Jon J. , Jin Lee‐Way , Maezawa Izumi
Published: October 2024

Ketotherapeutics is a potential metabolic intervention for mitigating dementias; however, its mechanisms and optimal methods of application are not well understood. Our previous in vitro study showed that β‐hydroxybutyrate (BHB), a major ketone body, reverses pathological features of amyloid‐β oligomer (AβO)‐activated microglia. Here we tested the in vivo effects of BHB on microglia and synaptic plasticity in the 5xFAD Alzheimer's disease (AD) mouse model. A short 1‐week regimen of daily intraperitoneal injection of BHB (250 mg/kg), which induced brief and mild daily episodic ketosis, was sufficient to mitigate pro‐inflammatory microglia activation and reduce brain amyloid‐β deposition by enhancing phagocytosis. Remarkably, it mitigated the deficits of hippocampal long‐term depression but not long‐term potentiation, and this effect was linked to suppression of NLRP3 inflammasome‐generated IL‐1β. As ketogenic diets are known for poor compliance, our study opens the possibility for alternative approaches such as short‐term BHB injections or dietary ketone esters that are less restrictive, potentially safer, and easier for compliance.
Impact of Anastomotic Leakage After Colorectal Cancer Surgery on Quality of Life: A Systematic Review
Authors: Gielen Anke H.C. , Heuvelings Danique J.I. , Sylla Patricia , van Loon Yu-Ting , Melenhorst Jarno , Bouvy Nicole D. , Kimman Merel L. , Breukink Stephanie O. ,   On behalf of the CoReAL Collaborative
Published: October 2024

BACKGROUND:

Colorectal anastomotic leakage remains one of the most frequent and dreaded postoperative complications after colorectal resection. However, limited research has been conducted on the impact of this complication on the quality of life of patients who have undergone colorectal cancer surgery.

OBJECTIVE:

The aim of this systematic review was to identify, appraise, and synthesize the available evidence regarding the quality of life in patients with anastomotic leakage after oncological colorectal resections to inform clinical decision-making.

DATA SOURCES AND STUDY SELECTION:

PubMed, Embase, and the Cochrane Library were searched for studies reporting quality of life using validated questionnaires in patients with anastomotic leakage after oncological colorectal resections. The literature search was performed systematically and according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

OUTCOMES:

Outcomes from quality-of-life questionnaires of patients with and without anastomotic leakage were analyzed.

RESULTS:

Thirteen articles reporting on 4618 individual patients were included, among which 527 patients developed anastomotic leakage. Quality of life was evaluated using 10 distinct questionnaires administered at various postoperative time points, ranging from 1 month to 14 years. Quality-of-life outcomes differed across studies and time points, but overall scores were most negatively affected by anastomotic leakage up to 12 months postoperatively.

LIMITATIONS:

There was a high heterogeneity between the included studies based on the questionnaires used and the time of assessment.

CONCLUSIONS:

The published evidence suggests that anastomotic leakage after oncologic colorectal resection is associated with impaired quality of life, especially within the first postoperative year. The impact of anastomotic leakage on quality of life warrants further evaluation and discussion with patients.
Immunohistochemistry-Assisted Mohs Surgery for Invasive Eyelid and Periorbital Cutaneous Melanoma
Authors: Asamoah Eucabeth M. , Demer Addison M. , Trischman Thomas E. , Bangalore Kumar Anagha , Vidal Nahid Y. , Wagner Lilly H.
Published: October 2024

BACKGROUND

Prior studies describe wide local excision and “slow Mohs” outcomes for periocular melanoma. Mohs micrographic surgery (MMS) with immunohistochemistry maximizes tissue preservation and offers same-day comprehensive margin evaluation, which facilitates expedited repair, and coordination of oculoplastic reconstruction when necessary.

OBJECTIVE

To describe oncologic and reconstructive outcomes of invasive periocular cutaneous melanoma treated with immunohistochemistry-assisted MMS.

MATERIALS AND METHODS

Invasive melanoma cases affecting the eyelids or periorbital region treated with MMS between 2008 and 2018 were reviewed. Eyelid tumors and those in adjacent subunits were compared. Main outcome measures were recurrence, melanoma-specific death, and postreconstructive complications.

RESULTS

Of 42 cases, 28 were classified as periorbital and 14 as eyelid involving. Most were T1 (37, 88.1%). There was 1 local recurrence in a patient with persistent positive conjunctival margin (2.4%). No local recurrences were observed in cases where negative Mohs margins were achieved, and no melanoma-related deaths occurred. Eyelid tumors were more likely to result in lid margin involving defects and require oculoplastic reconstruction. Eyelid complications developed in 10 cases (23.8%), and 5 (11.9%) required revision surgery.

CONCLUSION

Mohs micrographic surgery for periocular melanoma results in low rates of local recurrence and melanoma-specific death. Initial tumor location can aid in reconstructive planning.
Microneedling With Topical Insulin Versus Microneedling With Placebo in the Treatment of Postacne Atrophic Scars: A Randomized Control Trial
Authors: Abdelhay Rania Mounir , Ali Manar Saeed , Gad Leila Zeiad , Mahran Nahla Maher
Published: October 2024

BACKGROUND

Among the treatment modalities for post-acne scars, microneedling is considered a safe and effective method.

OBJECTIVE

To compare the efficacy and safety of combined microneedling with topical insulin versus microneedling with placebo (topical saline) in treating atrophic acne scars.

METHODS and MATERIALS

Twenty-one patients with atrophic post-acne scars were randomized and treated in a split face manner with 4 sessions at 3-week intervals of microneedling using dermapen, followed by application of insulin on one side of the face and saline (placebo) on the other side. Evaluation of response was done before the sessions and after 1 month of the last session using the Global Scarring Grading System of Goodman & Baron and Lipper & Perez scores, Patient reported acne scar improvement using a 4-point scale, patient satisfaction, and the facial acne scar quality of life tools.

RESULTS

Both therapeutic modalities yielded a statistically significant improvement of atrophic acne scars. By comparing both modalities, there was no statistical significance regarding clinical improvement and side effects.

CONCLUSION

Using topical insulin combined with microneedling may have a value in improving atrophic acne scars, suggesting further evaluation using different delivery systems, insulin formulations, and assessment modalities.
Study on the event-related potential in recognition of emotional words between typical “five-state personality”
Authors: Yang Qian , Yang Qiuli , Sun Yalun , Fu Yanyan , Du Jian
Published: October 2024

Objective:

To explore the event-related potential (ERP) differences of people with typical traditional Chinese medicine (TCM) “five-state personality” in the task of judging the emotional attributes (positive, neutral, and negative) of Chinese words.

Methods:

The “five-state personality test” was applied to screen the typical TCM “five-state personality,” and 3 groups were established, including positive personality, negative personality, and atypical personality. The differences in electroencephalogram (EEG) components in the task of judging the emotional attributes of Chinese words were collected using ERPs. The 3 personality groups ×3 words with emotional attributes were analyzed by two-way analysis of variance (ANOVA).

Results:

The N1 and P300 components were induced successfully. The analysis of the mean values of corresponding electrodes in the left frontal lobe, right frontal lobe, frontal lobe, and parietal lobe showed that in the typical negative personality group, the absolute value of N1 amplitude was smaller in the prefrontal and frontal lobes, and the latency was shorter in the left frontal lobe, while in the typical positive personality group, the absolute value of N1 amplitude was larger in the left frontal lobe. In the prefrontal and frontal lobes, the N1 peak absolute value of negative words was higher, the latency was longer, and the N1 latency of neutral words was shorter. The N1 latency of positive words was shorter in the parietal lobe. In the right frontal and frontal lobes, the P300 peak of negative words was higher, and the latency was longer, while the latency of positive words was longer in the parietal lobe. In addition, there was some interaction between personality groups and emotional attributes of words.

Conclusions:

When people with typical “five-state personality” judge the emotional attributes of words, the absolute value of N1 amplitude in the left prefrontal lobe of typical positive personality group is high, while that of typical negative personality group is small, and the latency is short. The P300 latency of negative words is longer in the right frontal and frontal lobes, and that of positive words is longer in the parietal lobes, with a more significant difference in the positive personality group.
Increasing Utilization of Intratympanic Injections among Medicare Fee-for-Service Providers
Authors: Fujiwara Rance J.T. , Tan Donald , Kutz Joe Walter
Published: October 2024

Objective

To characterize national practice patterns and geographic variations in intratympanic injections among Medicare providers.

Study Design

Retrospective cross-sectional analysis of intratympanic injections performed in the Medicare fee-for-service population from 2013 to 2021.

Setting

Center for Medicare & Medicaid Services Physician and Other Practitioners database.

Participants

Providers performing outpatient intratympanic injections, documented by Current Procedural Terminology code 69801.

Intervention(s)

Intratympanic injections.

Main Outcome Measure(s)

The number of intratympanic injections performed by individual providers, states, and geographic regions, as well as reimbursements, was analyzed annually.

Results

A total of 159,236 in-office intratympanic injections were performed. The Center for Medicare & Medicaid Services reimbursed $25,407,086; out-of-pocket patient costs were $6,591,514. The mean Medicare reimbursement rate and out-of-pocket cost per injection were $159.56 and $41.38, respectively. From 2013 to 2021, the number of intratympanic injections increased from 13,117 to 20,711 injections, representing a 57.9% increase. On linear regression, an additional 989.9 injections were performed each year (95% CI 766.4–1,213.4, p < 0.001). The number of providers performing injections also increased from 1,828 to 2,834 from 2013 to 2021 (b = 125.6 [95% CI 111.3–140.0], p < 0.001). The population-controlled annual mean number of injections varied substantially across the United States, ranging from 12.0 injections per 100,000 beneficiaries in Oklahoma to 255.2 injections per 100,000 beneficiaries in Alabama.

Conclusions

The number of intratympanic injections administered in the Medicare population has increased from 2013 to 2021. There is variability in practice patterns and utilization of intratympanic injections among otolaryngologists in the United States.