bluuebunny/crossref_metadata_2025 huggingface dataset:
Vasculitis associated with VEXAS syndrome
Authors: Sullivan Megan M , Mead-Harvey Carolyn , Sartori-Valinotti Julio C , Kalantari Kambiz , Kusne Yael N , Patnaik Mrinal M , Mangaonkar Abhishek A , Go Ronald S , Montes Daniel , Reichard Kaaren K , Olteanu Horatiu , Bois Melanie C , Hines Alexander S , Warrington Kenneth J , Koster Matthew J
Published: October 2024

Objectives

To define the prevalence, distribution and characteristics of patients with VEXAS (vacuoles, E1-enzyme, X-linked, autoinflammation, somatic) syndrome who have confirmed vasculitis.

Methods

Patients with VEXAS syndrome, verified by positive UBA1 mutation, were included. Chart review was performed to identify patient characteristics and outcomes. Vasculitis diagnosis was based on either histopathology showing vascular inflammation or non-invasive angiography findings. Summary statistics were calculated.

Results

Eighty-nine patients met inclusion criteria. All were male with a median age of onset of 66.9 years (interquartile range 60.1, 72.7). Median (interquartile range) follow-up was 3.8 (2.2–5.5) years, during which 21 patients (23.6%) had evidence of vasculitis. Vasculitis subtypes included small vessel vasculitis (19.1%), cutaneous medium vessel vasculitis (2.2%) and large vessel vasculitis (2.2%). No patient had more than one vessel size involved. Histopathology in small vessel vasculitis patients was consistent with cutaneous leukocytoclastic vasculitis in the majority, though one patient had leukocytoclastic peritubular capillaritis on renal biopsy. Cranial symptoms (headache, vision changes or jaw pain) were noted in 18.0%. Two additional patients not experiencing cranial symptoms exhibited large vessel involvement with confirmed carotid thickening on non-invasive angiography; one of these had a positive temporal artery biopsy.

Conclusion

VEXAS syndrome manifests as a variable vessel vasculitis in a quarter of patients, with cutaneous small and medium vessel involvement being particularly common. Some patients may have positive ANCA serologies or even renal vasculitis leading to misdiagnosis. Cranial symptoms are common and may mimic GCA, though documented large vessel inflammation is rare.
Inequality and socio-economic divides in parental transfers to young adults in the United States
Authors: Floridi Ginevra
Published: October 2024

Parental transfers of money and co-residence to young-adult children can serve as means of status reproduction. Yet, the relationship between inequality and socio-economic gaps in these forms of parental support has not been studied. Inequality may widen socio-economic differentials in monetary and co-residential transfers, potentially hindering social mobility. I test the association between income inequality and socio-economic divides in parental support to children aged 22–35 in the United States (U.S.), a context where the economic dependence of young adults has increased over decades of high or rising inequality. I link state-level inequality data to longitudinal data on 39,626 parent–child dyads from the Health and Retirement Study (1992–2018). Using state fixed-effects models I investigate how changes in income inequality within states relate to changes in wealth, income, and educational gradients in parental transfers over time. Socio-economic differences in the occurrence and amount of money transfers widen with inequality, as the probability of monetary support decreases among lower-class and lower-educated parents, while the amounts transferred increase among upper-class and higher-educated parents. Moreover, in times of higher inequality, co-residence is more strongly concentrated among lower-class, lower-educated parents. Previous research indicates that receiving money improves labor and housing market outcomes, while co-residence may restrict economic opportunities among young adults from disadvantaged backgrounds. In light of this, my findings suggest that rising U.S. inequality may hinder social mobility by shifting the socio-economic distribution of intergenerational support.
Complex Models of Sequence Evolution Improve Fit, But Not Gene Tree Discordance, for Tetrapod Mitogenomes
Authors: Toups Benjamin S , Thomson Robert C , Brown Jeremy M
Published: October 2024

Variation in gene tree estimates is widely observed in empirical phylogenomic data and is often assumed to be the result of biological processes. However, a recent study using tetrapod mitochondrial genomes to control for biological sources of variation due to their haploid, uniparentally inherited, and non-recombining nature found that levels of discordance among mitochondrial gene trees were comparable to those found in studies that assume only biological sources of variation. Additionally, they found that several of the models of sequence evolution chosen to infer gene trees were doing an inadequate job of fitting the sequence data. These results indicated that significant amounts of gene tree discordance in empirical data may be due to poor fit of sequence evolution models and that more complex and biologically realistic models may be needed. To test how the fit of sequence evolution models relates to gene tree discordance, we analyzed the same mitochondrial data sets as the previous study using 2 additional, more complex models of sequence evolution that each include a different biologically realistic aspect of the evolutionary process: A covarion model to incorporate site-specific rate variation across lineages (heterotachy), and a partitioned model to incorporate variable evolutionary patterns by codon position. Our results show that both additional models fit the data better than the models used in the previous study, with the covarion being consistently and strongly preferred as tree size increases. However, even these more preferred models still inferred highly discordant mitochondrial gene trees, thus deepening the mystery around what we label the “Mito-Phylo Paradox” and leading us to ask whether the observed variation could, in fact, be biological in nature after all.
Duration of a standard phototherapy course in jaundiced newborns with no neurotoxicity risk
Authors: Sarici Serdar Ümit , Arslan Kübra , Babacan Altay , Soylu Demet , Ergür Ayca Törel , Serdar Muhittin Abdulkadir , Sarici Dilek
Published: October 2024

In this study, we aimed to determine an ordinary/empiric/standard phototherapy treatment protocol for duration without controlling total serum bilirubin (TSB) levels after initiating phototherapy in early-term and full-term jaundiced newborns who had no hyperbilirubinemia neurotoxicity risk factors. We compared two groups, each receiving either 24 h (Group I) or 18 h (Group II) of continuous phototherapy in terms of demographic characteristics and efficacy (rate of decrease in TSB levels with phototherapy). No control TSB measurements were performed in the study groups until the end of phototherapy for the predetermined durations. Declines in TSB after phototherapy were significantly greater in Group I than in Group II, both in terms of mg/dl (11.81 ± 2.93 mg/dl vs. 10.75 ± 2.48 mg/dl, P = .0008) and percentage (56.71 ± 9.06% vs. 52.86 ± 8.37%, P = .0002). However, the rate of TSB reduction after phototherapy in mg/dl/h (0.59 ± 0.13 mg/dl/h vs. 0.49 ± 0.12 mg/dl/h, P = <.0001) and percentage per hour (2.93 ± 0.37% vs. 2.36 ± 0.46%, P = <.0001) were significantly higher in Group II than in Group I. This indicates an inverse time-response relationship between the duration of phototherapy and the response rate in the study groups. Although the 24-h phototherapy course showed greater efficacy concerning the primary bilirubin outcome measures (decline in TSB in mg/dl and %), the 18-h course of phototherapy treatment provided better hourly outcomes and reached its saturation point around the 18th hour. Therefore, an 18-h phototherapy without TSB monitoring until the end of the phototherapy should be considered for jaundiced newborns lacking neurotoxicity risk factors.
Correction of L5 Tilt in 2-Row Vertebral Body Tethering Versus Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis
Authors: De Varona-Cocero Abel , Ani Fares , Kim Nathan , Robertson Djani , Myers Camryn , Ashayeri Kimberly , Maglaras Constance , Protopsaltis Themistocles , Rodriguez-Olaverri Juan C.
Published: October 2024

Study Design:

Single-center retrospective cohort study.

Objective:

To compare the correction of fractional curve and L5 tilt in 2RVBT versus PSF with LIV in the lumbar spine.

Summary of Background Data:

Vertebral body tethering, an AIS fusion-alternative, avoids rigid constructs, allowing for lower instrumented vertebra (LIV) selection. Single-tether constructs break, but mini-open thoracoscopic assistant double-row vertebral body tethering (2RVBT) reduces this. Limited comparative studies exist with posterior spinal fusion (PSF).

Methods:

Retrospective analysis of AIS correction surgeries with lumbar LIV using preoperative and minimum 2-year postoperative imaging. Patients were divided into 2RVBT or PSF groups. Data included age, Riser, UIV, LIV, instrumented levels, and revision rates. Radiographic analyses included preoperative and postoperative main curve Cobb (MCC), secondary curve Cobb (SCC), fractional curve Cobb (FCC), and L5 tilt.

Results:

Ninety-nine patients participated (49 in 2RVBT, 50 in PSF). Preoperatively, secondary CC differed significantly (2RVBT: 44.6±10.4 degrees vs. PSF: 39.5±11.8 degrees, P=0.026), but not L5 tilt, MCC, or FCC. Postoperatively, MCC (2RVBT: 25.7±12.3 degrees vs. PSF: 19.5±7.4 degrees, P=0.003) and SCC (2RVBT: 18.0±8.4 degrees vs. PSF: 14.5±6.6 degrees, P=0.012) varied. Preoperative to postoperative changes in MCC (2RVBT: −32.0±11.3 degrees vs. PSF: −37.2±13.3 degrees, P=0.044) and L5 tilt (−13.8±9.0 degrees vs. PSF: −8.1±6.8 degrees, P=0.001) differed. Revision rates were similar (2RVBT: 2.0%, PSF: 4.0%, P=0.57). In 2RVBT, 3 tethers broke, 1 revision occurred for a broken tether, and 1 pleural effusion needed thoracocentesis. In PSF, 1 superficial infection needed surgery, and 1 revision was for add-on phenomenon. After PSM for Lenke classification, 54 patients remained (27 in each group). At 2 years, 2RVBT showed less MCC correction (−30.8±11.8 degrees vs. −38.9±11.9 degrees, P=0.017), but greater L5 tilt correction (−14.6±10.0 degrees vs. −7.5±6.0 degrees, P=0.003).

Conclusions:

This study with a minimum 2-year radiographic follow-up demonstrates that 2RVBT results in greater L5 tilt correction when compared with posterior spinal fusion after PSM for Lenke classification and similar rates of revision surgery.

Level of Evidence:

Level III.
A Rare Case of Carpal Tunnel Syndrome with Bifid Median Nerve and Palmaris Profundus Muscle
Authors: Yamazaki Takahiro , Matsuura Yusuke , Takahashi Hiroki , Ohtori Seiji
Published: October 2024

Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy. We report an extremely rare case of CTS associated with a bifid median nerve and palmaris profundus muscle. A 68-year-old man presented with numbness and pain in the right hand. Intraoperatively, a bifid median nerve was identified, with the ulnar branch severely compressed by the palmaris profundus muscle. The muscle was resected, leading to symptom resolution. Anatomical variations of the median nerve and anomalous muscles should be considered in CTS. Preoperative imaging and open carpal tunnel release are recommended to identify and address such variations.
Association Between Migraine and Open Angle Glaucoma: A 12-Year Nationwide Retrospective Korean Cohort Study
Authors: Kim Hyung Jun , Ro Jun-Soo , Lee Seung Hoon , Moon Jong Youn , Lee Si Hyung
Published: October 2024

Précis:

Patients with migraine showed a significantly increased risk of developing open angle glaucoma (OAG) in the Korean population, without significant differences according to the presence of aura. Our results suggest the presence of migraine as a possible risk factor for OAG.

Purpose:

Previous studies have reported that migraine headaches may be one of the possible risk factors for open angle glaucoma (OAG); however, a consensus has not been reached regarding the association between OAG and migraine. In this study, we examined the risk of developing OAG in migraine patients using a 12-year nationwide cohort.

Materials and Methods:

In this study, data from the Korean National Health Insurance Service-National Sample Cohort database from 2002 to 2015 was used to perform a retrospective cohort study. The study included 1,103,302 subjects, out of which 41,148 were diagnosed with migraine during 2003–2008 and were categorized as the migraine group, while 205,741 patients were selected as controls through propensity score matching at a 1:5 ratio. Subjects with migraine or OAG was ascertained based on the KCD code. Multivariate Cox regression analysis was used to evaluate the hazard rate of OAG onset in the migraine group, and subgroup analysis was performed to identify any differences based on sex and age.

Results:

Multivariate Cox regression analysis showed that the incidence of OAG was significantly greater among patients with migraine than among patients in the comparison group [hazard ratio (HR): 1.238; 95% CI: 1.160–1.132, P <0.001]. Moreover, the risk of developing OAG compared with subjects without migraine did not differ according to the presence of an aura (migraine with aura: HR: 1.235; 95% CI: 1.137–1.342, P < 0.001; migraine without aura: HR: 1.248; 95% CI: 1.143–1.363, P < 0.001). In subgroup analyses, the patients with migraine under 40-year-old were found to have a greater hazard rate (HR: 1.576, 95% CI: 1.268–1.957) of developing OAG in contrast with patients with migraine and over 40-year-old (HR: 1.167, 95% CI: 1.089–1.250) when compared with the corresponding nonmigraine patients.

Conclusion:

This study showed that migraine is a significant risk factor for OAG onset in the Korean population, and the presence of aura did not affect the HR of OAG development.
Lack of progress in cancer-related outcomes after liver transplantation: Mitigating risk and identifying future needs to move this needle
Authors: Liu Alex , Rao Wei , Watt Kymberly D.
Published: October 2024

Malignancy has a crucial impact on long-term survival after liver transplantation. There have been enhanced early detection rates with refined cancer screening and improved prognosis for many cancer diagnoses in the general population with the advent of targeted anticancer therapies. Similar advancements have not occurred in the transplant population over this same timeframe. Individualized strategies to reduce the risk of cancer are needed in this high-risk population. Strict adherence to screening and surveillance specific to the transplant population is required. Lifestyle modifications and medication management (both immunosuppressive and non-immunosuppressive) that may impact cancer risk and outcome are highlighted here. As more effective anticancer therapies evolve, transplant recipients’ access to these agents is paramount to truly impact cancer-related outcomes in this population. With adequate immunosuppression, rejection rates with immunotherapy are lower than previously purported. Prospective studies of immunosuppression modifications needed to minimize rejection and maximize cancer response are ongoing and will reduce the fear from oncology and transplant providers alike, allowing utilization of the most optimal therapy available to the individual. This review aims to assess current data to aid in clinical management and identify the need to facilitate further progress in this field.
Cross-Sectoral Comparisons of Process Quality Indicators of Health Care Across Residential Regions Using Restricted Mean Survival Time
Authors: Šinkovec Hana , Gall Walter , Heinze Georg
Published: October 2024

Background:

Practice guidelines recommend patient management based on scientific evidence. Quality indicators gauge adherence to such recommendations and assess health care quality. They are usually defined as adverse event rates, which may not fully capture guideline adherence over time.

Methods:

For assessing process indicators where compliance to the recommended treatment can be assessed by evaluating a patient's trace in linked routine databases, we propose using restricted mean survival time or restricted mean time lost, which are applicable even in competing risk situations. We demonstrate their application by assessing the compliance of patients with acute myocardial infarction (AMI) to high-power statins over 12 months in Austria’s political districts, using pseudo-observations and employing causal inference methods to achieve regional comparability.

Results:

We analyzed the compliance of 31,678 AMI patients from Austria’s 116 political districts with index AMI between 2011 and 2015. The results revealed considerable compliance variations across districts but also plausible spatial similarities.

Conclusions:

Restricted mean survival time and restricted mean time lost provide interpretable estimates of patients’ expected time in compliance (lost), well-suited for risk-adjusted entity comparisons in the presence of (measurable) confounding, censoring, and competing risks.
18F-THK5351 PET Is Superior to Conventional MRI in Identifying Inflammatory Lesions by Imaging Astrogliosis in 2 Cases of Neurosyphilis
Authors: Kotani Risa , Hatano Keiko , Ishibashi Kenji , Iwata Atsushi
Published: October 2024

18F-labeled THK5351 PET can visualize ongoing astrogliosis by estimating monoamine oxidase B levels and can be used as a neuroinflammation marker for identifying inflammatory lesions by imaging astrogliosis. Assessment of its performance is of interest, especially when compared with conventional MRI. Here, we present 2 cases of neurosyphilis, in which 18F-THK5351 PET identified inflammatory lesions by imaging astrogliosis, whereas MRI had difficulty detecting the lesions. Hence, this study suggests that 18F-THK5351 PET is superior to conventional MRI in identifying inflammatory lesions and that this feature of 18F-THK5351 can provide insights into the pathophysiology of neurosyphilis in living patients.
Repair of Cleft Palate in Adult Patients; Impact of Speech Therapy Following Surgical Intervention in Africa
Authors: Olusanya Adeola , Ibrahim Amina Musa , Ezeanochie Nwamaka Njideka , Adamson Olawale Olatunbosun , Horne Sara , Eshete Abebe Mekonen
Published: October 2024

Cleft lip and palate anomalies constitute both aesthetic and functional impairments for affected individuals. While an individual with an unrepaired cleft palate may adjust somewhat to the associated feeding challenges as he or she gets older, the consequent speech impairment is amenable primarily to surgery. It is pertinent to assess how well speech function is restored in individuals with cleft after surgical repairs. Findings of such assessments may inform on the factors affecting the impact of surgical intervention, and what additional interventions may be required and may form the baseline for further investigations into the speech characteristics of adults who have had delayed palatal repairs. No African report was found assessing speech outcomes in patients who had palatal repairs after the age of 18 years. This study is to assess the impact of speech therapy on adults who had their palates repaired at or after the age of 18 years. A retrospective review of “Smile Train” speech data was done. The speech data were videos of syllable and sentence screeners. The samples were individually assessed by 3 cleft speech therapy interventionists based on a predetermined set of parameters. These parameters were scored such that the higher the core, the poorer the outcome. The scores did not show statistically significant differences between the pre and post-speech therapy scores.
Application of 3D-Slicer Software in the Treatment of Gliomas
Authors: Liu Jinkai , Wang Bing
Published: October 2024

Purpose:

To explore the application of 3D-Slicer multimodal image fusion technology in the surgical treatment of gliomas.

Method:

A retrospective analysis of clinical data from 48 cases of intracranial gliomas treated with 3D-Slicer multimodal image fusion technology from September 2021 to February 2023. Preoperative cranial CT, MRI, TOF-MRA, DTI, and MRV sequence examinations were completed. DICOM format medical imaging data were processed using the 3D-Slicer software. Multimodal fusion and 3-dimensional reconstruction of the tumor and surrounding structures were conducted to clarify the relationship between the tumor and surrounding structures. The surgery path was simulated through 3D virtual visualization images, enabling precise preoperative planning and assisting in surgical treatment.

Results:

Out of 48 patients, complete tumor resection was achieved in 45 cases. One case encountered severe postoperative cerebral edema, no infections were reported, 1 patient had slightly reduced muscle strength after surgery compared with before, and no cases of severe neurological function damage or surgical death were recorded.

Conclusion:

3D-Slicer multimodal image fusion technology can assist in detailed preoperative planning for the surgical treatment of intracranial glioma, reducing surgical complications, improving the rate of total tumor resection, and reducing postoperative complications.
Financial Toxicity in Complex Gastrointestinal Surgery and Correlation with Patient Reported Outcomes
Authors: Young Lindsey , Vergara Rosemary , Henriquez John , Fong Alvis , Al-Assil Talal , Shebrain Saad , Munene Gitonga
Published: October 2024

Objectives:

To describe financial toxicity (FT) in patients who have undergone gastrointestinal (GI) surgery and its correlation with patients’ emotional (EWB) and social well-being (SWB).

Background:

FT describes the financial burden associated with treatment and its impact on patient outcomes. Few prior studies have examined FT in gastrointestinal surgery and its impact on patient quality of life.

Methods:

Patients who underwent gastrointestinal surgery at our institution were assessed for FT with a validated instrument between Jan 2022 and Jan 2023. EWB and SWB were assessed with a validated instrument. Risk factors for FT were determined using a multivariable model. The correlation between FT and patient EWB and SWB was assessed using Pearson correlation.

Results:

188 patients were surveyed, the majority had pancreatic resections (n = 90, 47.9%), 59 (31.4%) patients experienced FT. On multivariable analysis, categories associated with increased likelihood of exhibiting financial toxicity included single marital status and not receiving chemotherapy and/or radiation therapy, with odds ratio (95% C.I) of [3.02 (1.07, 8.51), P=.037] and [3.86 (1.3, 11.44), P=.015) respectively. Higher EWB and SWB scores directly correlated with higher FT scores.

Conclusion:

Patients undergoing complex gastrointestinal surgery often experience financial toxicity that affects patient reported outcomes. Financial toxicity is associated with identifiable pre-operative factors that can be utilized to screen patients for interventions that may mitigate some of the harmful effects of FT.
What Are the Most Popular Articles in Urogynecology and Who Is Disseminating Them
Authors: Williams Stephanie Nicole , Fitzgerald Jocelyn
Published: October 2024

Importance

This research describes which articles published in Urogynecology are garnering the most attention online. Understanding which articles are having the largest impact in the online community has become increasingly important due to the exponential increase in the use of social media on the internet.

Objective

The Altmetric Attention Score (AAS) is a quantitative and qualitative measure of the articles’ online attention in social media and news outlets, blogs, and reference managers. The aim of this study was to provide an analysis of those accessing and sharing the 100 most popular articles published in Urogynecology.

Study Design

This was a retrospective descriptive analysis. Using Dimensions, a “linked research knowledge system,” data about each article’s demographics on Twitter and other media sources was extracted from each of the articles within Urogynecology with the highest AAS. No articles were excluded. The articles were categorized by topic and metrics of online sharing were compared among categories.

Results

Fifteen categories were created. Sexual health and education articles had the highest average Altmetric scores per article and reached the highest impressions per article and had the highest average follower count per Twitter user. On average, social justice in medicine had the highest number of tweets per article. Tweets were most often composed by members of the public (58%) compared with health care practitioners (14%), researchers (13%), and science communicators (12%).

Conclusions

Sexual health and education articles had the highest average AAS and impressions on Twitter. We observed a difference in which articles are being shared most among the general public and health care professionals. The general public comprised a majority of those sharing articles online regardless of category. Additionally, there may be a disparity in research, its funding, and online scientific communications within the field of urogynecology.
Variation in Overactive Bladder Treatment Type by Social Determinants of Health
Authors: Muñoz Jaclyn M. , Kim Edward K. , Andy Uduak U. , Mumford Sunni L. , Harvie Heidi S.
Published: October 2024

Importance

There is limited understanding of the relationship between social determinants of health (SDOH) and types of overactive bladder/urgency urinary incontinence (OAB/UUI) treatments.

Objectives

Our objective was to determine if OAB/UUI treatment type differs by SDOH, including insurance and estimated median household income (EMHI).

Study Design

This was a cross-sectional study of adult patients assigned female at birth with OAB/UUI, identified from 2017 to 2022 within a tertiary academic health system. The primary outcome was any OAB/UUI treatment provision. Secondary outcomes included specific treatments and specialty care. We examined associations between SDOH and OAB/UUI treatments using univariable analysis and multivariable logistic regression.

Results

Among 33,002 patients with OAB/UUI, 15.4% received treatment. Treatment provision was associated with American Indian/Alaska Native or Black/African American race, Latina ethnicity, Medicaid, low-income Medicare, or Medicare Advantage (vs private insurance) and EMHI ranging from $26,500 to $100,000 (compared with EMHI >$100,000). Patients with Black/African American race, Medicaid or no insurance, and EMHI ≤$80,000 had higher odds of anticholinergic prescription and lower odds of β3-agonist prescription. Advanced therapy was associated with traditional Medicare, Medicare Advantage, and EMHI $26,500–$100,000 and negatively associated with Asian race. Specialty care was associated with Black/African American race, Medicaid, Medicare Advantage, no insurance, and EMHI ≤$80,000.

Conclusions

Overactive bladder/urgency urinary incontinence treatment provision was associated with American Indian/Alaska Native and Black/African American race, Latina ethnicity, Medicaid, low-income Medicare, or Medicare Advantage insurance. Patients with Black/African American race and with lower EMHI had higher odds of receiving anticholinergic therapy and lower odds of receiving β3-agonist medication, despite higher likelihood of specialty care.
Measurement Matters: A Metrological Approach to Renal Preimplantation Biopsy Evaluation to Address Uncertainty in Organ Selection
Authors: Ayorinde John O.O. , Loizeau Xavier , Bardsley Victoria , Thomas Spencer Angus , Romanchikova Marina , Samoshkin Alex , Pettigrew Gavin J.
Published: October 2024

Background.

Preimplantation biopsy combines measurements of injury into a composite index to inform organ acceptance. The uncertainty in these measurements remains poorly characterized, raising concerns variability may contribute to inappropriate clinical decisions.

Methods.

We adopted a metrological approach to evaluate biopsy score reliability. Variability was assessed by performing repeat biopsies (n = 293) on discarded allografts (n = 16) using 3 methods (core, punch, and wedge). Uncertainty was quantified using a bootstrapping analysis. Observer effects were controlled by semi-blinded scoring, and the findings were validated by comparison with standard glass evaluation.

Results.

The surgical method strongly determined the size (core biopsy area 9.04 mm2, wedge 37.9 mm2) and, therefore, yield (glomerular yield r = 0.94, arterial r = 0.62) of each biopsy. Core biopsies yielded inadequate slides most frequently. Repeat biopsy of the same kidney led to marked variation in biopsy scores. In 10 of 16 cases, scores were contradictory, crossing at least 1 decision boundary (ie, to transplant or to discard). Bootstrapping demonstrated significant uncertainty associated with single-slide assessment; however, scores were similar for paired kidneys from the same donor.

Conclusions.

Our investigation highlights the risks of relying on single-slide assessment to quantify organ injury. Biopsy evaluation is subject to uncertainty, meaning each slide is better conceptualized as providing an estimate of the kidney’s condition rather than a definitive result. Pooling multiple assessments could improve the reliability of biopsy analysis, enhancing confidence. Where histological quantification is necessary, clinicians should seek to develop new protocols using more tissue and consider automated methods to assist pathologists in delivering analysis within clinical time frames.
Development of acute Pseudomonas aeruginosa and Acinetobacter baumannii lung mono-challenge models in mice using oropharyngeal instillation.
Authors: Jurado-Martín Irene , Ma Chaoying , Rezk Nouran , Sainz-Mejías Maite , Hou Yueran , Baugh John A. , McClean Siobhán
Published: October 2024

Antimicrobial resistant pathogens such as Pseudomonas aeruginosa and Acinetobacter baumannii can cause potentially fatal infections in susceptible individuals, with respiratory tract infections among the most common clinical presentation. The development of novel treatments or prophylactic interventions to combat these infections is urgently needed, and requires robust, reliable animal models for their preclinical evaluation. In particular, the bacterial burden needs to be accurately determined before and after administration of the potential therapy under evaluation to quantitate the effectiveness of the treatment. We provide two reliable, non-invasive murine acute lung challenge models with either P. aeruginosa or A. baumannii using an oropharyngeal aspiration technique, which has been widely overlooked in studies testing vaccines or treatments for these pathogens. Here, we show that this non-surgical technique to deliver suspensions into mouse lungs does not significantly impact animal welfare (based on welfare monitoring and weight) and allows uniform bilateral distribution of the bacterial dose resulting in even bioburden in both lungs. The optimal timepoint for humane killing and organ harvest was 24 h after challenge for both pathogens, and at least 4x106 and 107 CFU/mouse were needed to obtain a reproducible P. aeruginosa or A. baumannii bioburden, respectively. These mouse challenge models offer a valuable tool to assess therapeutic interventions against P. aeruginosa or A. baumannii infections.
ORCO: Ollivier-Ricci Curvature-Omics — an unsupervised method for analyzing robustness in biological systems
Authors: Simhal Anish K. , Weistuch Corey , Murgas Kevin , Grange Daniel , Zhu Jiening , Oh Jung Hun , Elkin Rena , Deasy Joseph O.
Published: October 2024

Although recent advanced sequencing technologies have improved the resolution of genomic and proteomic data to better characterize molecular phenotypes, efficient computational tools to analyze and interpret the large-scale omic data are still needed. To address this, we have developed a network-based bioinformatic tool called Ollivier-Ricci curvature-omics (ORCO). ORCO incorporates gene interaction information with omic data into a biological network, and computes Ollivier-Ricci curvature (ORC) values for individual interactions. ORC, an edge-based measure, indicates network robustness and captures global gene signaling changes in functional cooperation using a consistent information passing measure, thereby helping identify therapeutic targets and regulatory modules in biological systems. This tool can be applicable to any data that can be represented as a network. ORCO is an open-source Python package and publicly available on GitHub athttps://github.com/aksimhal/ORC-Omics.
InteracTor: A new integrative feature extraction toolkit for improved characterization of protein structural properties
Authors: Silva Jose Cleydson F. , Schuster Layla , Sexson Nick , Kirst Matias , Resende Marcio F. R. , Dias Raquel
Published: October 2024

Understanding the structural and functional diversity of protein families is crucial for elucidating their biological roles. Traditional analyses often focus on primary and secondary structures, which include amino acid sequences and local folding patterns like alpha helices and beta sheets. However, primary and secondary structures alone may not fully represent the complex interactions within proteins. To address this limitation, we developed a new algorithm (InteracTor) to analyze proteins by extracting features from their three-dimensional (3D) structures. The toolkit extracts interatomic interaction features such as hydrogen bonds, van der Waals interactions, and hydrophobic contacts, which are crucial for understanding protein dynamics, structure, and function. Incorporating 3D structural data and interatomic interaction features provides a more comprehensive understanding of protein structure and function, potentially enhancing downstream predictive modeling capabilities. By using the extracted features in Mutual Information scoring (MI), Principal Component Analysis (PCA), t-distributed Stochastic Neighbor Embedding (t-SNE), Uniform Manifold Approximation and Projection (UMAP), and hierarchical clustering analysis as use cases, we identified clear separations among protein structural families, highlighting distinct functional aspects. Our analysis revealed that interatomic interaction features were more informative than protein secondary structure features, providing insights into potential structural and functional properties. These findings underscore the significance of considering tertiary structure in protein analysis, offering a robust framework for future studies aiming at enhancing the capabilities of models for protein function prediction and drug discovery.
T-scope V4: miniaturized microscope for optogenetic tagging in freely behaving animals
Authors: Wang Yuteng , Vergara Pablo , Hasegawa Satoshi , Tomita Naoki , Cherasse Yoan , Naoi Toshie , Sakurai Takeshi , Sugaya Yuki , Kano Masanobu , Sakaguchi Masanori
Published: October 2024

A miniaturized microscope (i.e., miniscope) enables the imaging of neuronal activity using calcium sensors while simultaneously manipulating that activity using opsins in freely moving animals. However, many miniscopes use light-emitting diodes with broadband emission, leading to unintentional opsin stimulation by light intended solely for calcium sensor activation (a phenomenon referred to as “biological crosstalk”). To address this issue, we previously developed a miniscope including a port for chosen light sources, such as lasers, by restructuring the open-source UCLA Miniscope v3. However, targeting the same neuronal soma for both excitable opsin stimulation and calcium sensor imaging remained a challenge. Here, we integrated features from the UCLA Miniscope v4 into our new T-scope V4 miniscope. In optogenetic tagging experiments, we demonstrated that a 445-nm blue laser can be used to image neuronal activity with the calcium sensor GCaMP6s without inadvertently stimulating the ChrimsonR opsin, allowing for simultaneous neuronal activity imaging and manipulation in freely moving mice. Thus, the T-scope V4 can serve as a powerful tool for probing causal relationships between neuronal activity and its function in living animals.

Highlights

We developed the T-scope V4 that integrates features of the UCLA Miniscope v4

This miniscope prevents “biological crosstalk” between sensors and opsins

This tool can help probe causal brain-behavior relationships in living animals
R3DFEM: an R package for running the 3D-CMCC-FEM model
Authors: Vangi Elia , Dalmonech Daniela , Collalti Alessio
Published: October 2024

Forest ecosystems account for about one-third of the Earth’s land area, and monitoring their structure and dynamics is essential for understanding the land’s carbon cycle and their role in the greenhouse gas balance. In this framework, process-based forest models (PBFMs) allow studying, monitoring and predicting forest growth and dynamics, capturing spatial and temporal patterns of carbon fluxes and stocks. The ‘Three Dimensional-Coupled Model Carbon Cycle - Forest Ecosystem Module’ (3D-CMCC-FEM) is a well-known eco-physiological, biogeochemical, biophysical process-based model, able to simulate energy, carbon, water and nitrogen fluxes and their allocation in homogeneous and heterogenous forest ecosystem. The model is specifically designed to represent forest stands, from simple ones to those with complex structures, involving several cohorts competing for light and other resources in a prognostic way. Currently, the model is implemented in C-language, which can be challenging for the broad public to use, and thus limiting its applications. In this paper, we present the open-source R package ‘R3DFEM’ which introduces efficient methods for: i) generating and handling input data needed for the model initialization; ii) running model simulations with different set up and exploring input; and iii) plotting output data. The functions in the R-package are designed to be user-friendly and intended for all R users with little to advanced coding skills, who aim to perform simulations using the 3D-CMCC-FEM. Here we present the package and its functionalities using some real case study and model applications.
Chromosome-level haplotype-resolved genome assembly provides insights into the highly heterozygous genome of Italian ryegrass (Lolium multiflorum Lam.)
Authors: Chen Yutang , Kiesbauer Jenny , Copetti Dario , Frei Daniel , Frey Juerg E , Grieder Christoph , Koelliker Roland , Studer Bruno
Published: October 2024

Italian ryegrass (Lolium multiflorum Lam.) is an important forage grass, providing a major source of feed for ruminants in temperate regions. Due to its highly heterozygous and repeat-rich genome, high-quality chromosome-level genome assemblies are scarce for Italian ryegrass. Here, we sequenced the genome of a genotype from the Italian ryegrass cultivar 'Rabiosa' (hereafter referred to as Rabiosa), and we obtained Oxford Nanopore Technologies long reads (~60-fold coverage), Illumina short reads (~85-fold coverage) and high-throughput chromosome conformation capture data (~60-fold coverage). With Rabiosa as the parent, we constructed an F1 population consisting of 305 individuals, which were genotyped by reduced representation sequencing for linkage map construction and quantitative trait loci (QTL) analysis. Using whole-genome sequencing data of Rabiosa and the genetic linkage map, we first generated a chromosome-level unphased haploid assembly (scaffold N50 of 338.75 Mb, total BUSCO score of 94.60%). Then, based on the unphased assembly and a reference-based phasing approach, we generated a chromosome-level haplotype-resolved assembly containing both haplotypes (scaffold N50 of ~250 Mb and total BUSCO score of ~90% for each haplotype). Between the two haplotypes of Rabiosa, we observed a highly collinear gene order at chromosome level and a high sequence variation at local level. With a graph-based reference built from the unphased and the haplotype-resolved assemblies of Rabiosa, we conducted a QTL analysis, and two QTL significantly associated with stem rust resistance were detected. The genome assemblies of Rabiosa will serve as invaluable genomic resources to facilitate genomic applications in forage grass research and breeding.
Improving the reliability of molecular string representations for generative chemistry
Authors: Reboul Etienne , Wefers Zoe , Waldispühl Jérôme , Taly Antoine
Published: October 2024

Generative chemistry has seen rapid development recently. However, models based on string representations of molecules still rely largely on SMILES1and SELFIES2that have not been developed for this context. The goal of this study is to first analyze the difficulty encountered by a small generative model when using SMILES and SELF- IES. Our study found that SELFIES and canonical SMILES3are not fully reliable representations, i.e. do not ensure both the viability and fidelity of samples. Viable samples represent novel, unique molecules with correct valence, while fidelity ensures the accurate reproduction of chemical properties from the training set. In fact, 20% of the samples generated using Canonical SMILES as input representation do not corre-spond to valid molecules. At variance, samples generated using SELFIES less faithfully reproduce the chemical properties of the training dataset.

As a mitigation strategy of the previously identified problems we have developed data augmentation procedures for both SELFIES and SMILES. Simplifying the com-plex syntax of SELFIES yielded only marginal improvements in stability and overall fidelity to the training set. For SMILES, we developed a stochastic data augmentation procedure called ClearSMILES, which reduces the vocabulary size needed to represent a SMILES dataset, explicitly represents aromaticity via Kekuĺe SMILES,3and reduces the effort required by deep learning models to process SMILES. ClearSMILES reduced the error rate in samples by an order of magnitude, from 20% to 2.2%, and improved the fidelity of samples to the training set.
Data-driven evaluation of suitable immunogens for improved antibody selection
Authors: Waury Katharina , Kvartsberg Hlin , Zetterberg Henrik , Blennow Kaj , Teunissen Charlotte E. , Abeln Sanne
Published: October 2024

Antibodies are indispensable in laboratory and clinical applications due to their high specificity and affinity for protein antigens. However, selecting the right protein fragments as immunogens for antibody production remains challenging. Leveraging the Human Protein Atlas, this study systematically evaluates immunogen properties aiming to identify key factors that influence their suitability. Antibodies were classified as successful or unsuccessful based on standardized validation experiments, and the structural and functional properties of their immunogens were analyzed. Results indicated that longer immunogens often resulted in more successful but less specific antibodies. Shorter immunogens (50 residues or fewer) with disordered or unfolded regions at the N- or C-terminus and long coil stretches, were more likely to generate successful antibodies. Conversely, immunogens with high beta sheet content, multiple secondary structure elements, transmembrane regions, or disulfide bridges were associated with poorer antibody performance. Post-translational modification sites within immunogens appeared to mark beneficial regions for antibody generation. To support antibody selection, a novel R package, immunogenViewer, was developed, enabling researchers to easily apply these insights when immunogen sequences are disclosed. By providing a deeper understanding of immunogen suitability, this study promotes the development of more effective antibodies, ultimately addressing issues of reproducibility and reliability in antibody-based research. The findings are highly relevant to the research community, as end-users often lack control over the immunogen selection process in antibody production.
Unveiling Novel Hyperglycosylated Analog of Human Erythropoietin: A Comprehensive Computational Exploration
Authors: Thahsin Naima , Khan Khairul Islam , Sakib Mohammad Nazmus , Rahman Mohammad Shahedur
Published: October 2024

Introduction

The capability of human erythropoietin (hEPO) to treat anemia by stimulating erythropoiesis, has made it become one of the world’s leading biopharmaceuticals. An effective way to improve the efficiency of recombinant hEPO drugs is increasing glycosylation which can increase its serum half-life and thereby it’sin vivobiological activity. In this context, the objective of the present study was to explore potential glycosylation sites in hEPO to develop new hyperglycosylated analogous drug.

Materials and Methods

A rational computational strategy was executed to select compatible region of hEPO for inserting N-linked glycosylation consensus motif (N-X-S/T), thus designing a number of analogs. The 3D models of the analogs were constructed by homology modeling and validated by variousin silicotools. The probability of glycosylation was checked and hyperglycosylated models of the selected analogs were developed. Molecular docking and molecular dynamics simulation were performed to select the best analog.

Results

Among 40 analogs designed in this study, Analog-71.1 showed most promising results. Four possible sites of this analog showed good probability for glycosylation. According to the molecular docking study, the analog obtained high docking score (2313.711) and formed highest number of (25) hydrogen bonds with erythropoietin receptors, which indicated strong and stable interaction with the receptors. Moreover, the steady trajectory of RMSD, Rgyr, RMSF and other findings obtained from MD simulation confirmed the structural stability of the analog.

Conclusions

Our overall study has selected Analog-71.1 as a potential candidate to develop new analogous drug with enhanced efficiency, which needs further experimental analyses.
Interpretable multi-omics integration with UMAP embeddings and density-based clustering
Authors: Castellano-Escuder Pol , Zachman Derek K. , Han Kevin , Hirschey Matthey D.
Published: October 2024

Integrating high-dimensional cellular multi-omics data is crucial for understanding various layers of biological control. Single ‘omic methods provide important insights, but often fall short in handling the complex relationships between genes, proteins, metabolites and beyond. Here, we present a novel, non-linear, and unsupervised method called GAUDI (Group Aggregation via UMAP Data Integration) that leverages independent UMAP embeddings for the concurrent analysis of multiple data types. GAUDI uncovers non-linear relationships among different omics data better than several state-of-the-art methods. This approach not only clusters samples by their multi-omic profiles but also identifies latent factors across each omics dataset, thereby enabling interpretation of the underlying features contributing to each cluster. Consequently, GAUDI facilitates more intuitive, interpretable visualizations to identify novel insights and potential biomarkers from a wide range of experimental designs.