bluuebunny/crossref_metadata_2025 huggingface dataset:
Power Circuits: Asymmetries of Global Christianity
Authors: Lukasik Candace , Bruner Jason
Published: April 2024

This article examines the idea of global Christianity in scholarship and the postcolonial and present imperial conditions that underlie it. Through an analysis of the fields of World Christianity and the anthropology of Christianity, it considers how Western Christian histories and power dynamics have impacted Christian traditions of the Global South and seriously considers the pervasive logics of geopolitical power that transform local contexts–not only altering how such communities and traditions are written about, but also impacting the traditions, practices, and people themselves. Thinking with Coptic Orthodox Christians between Egypt and the United States and Born-Again Christians in Uganda, this article examines how global power inequalities in the circuits of ideas, forms of life, and theopolitics are integral to thinking about the idea of global Christianity and its variations in scholarship.
Assessing the impact of meropenem exposure on ceftolozane/tazobactam-resistance development in Pseudomonas aeruginosa using in vitro serial passage
Authors: Fouad Aliaa , Nicolau Samantha E , Tamma Pranita D , Simner Patricia J , Nicolau David P , Gill Christian M
Published: April 2024

Background

Patients infected with difficult-to-treat Pseudomonas aeruginosa are likely to receive meropenem (MEM) empirically before escalation to ceftolozane/tazobactam (C/T). We assessed whether pre-exposure to MEM affected C/T resistance development on C/T exposure.

Materials and methods

Nine clinical P. aeruginosa isolates were exposed to MEM 16 mg/L for 72 h. Then, isolates were serially passaged in the presence of C/T (concentration of 10 mg/L) for 72 h as two groups: an MEM-exposed group inoculated with MEM pre-exposed isolates and a non-MEM control group. At 24 h intervals, samples were plated on drug-free and drug-containing agar (C/T concentration 16/8 mg/L) and incubated to quantify bacterial densities (log10 cfu/mL). Growth on C/T agar indicated resistance development, and resistant population was calculated by dividing the cfu/mL on C/T plates by the cfu/mL on drug-free agar.

Results

At 72 h, resistant populations were detected in 6/9 isolates. In five isolates, MEM exposure significantly increased the prevalence of ceftolozane/tazobactam-resistance development; the percentages of resistance population were 100%, 100%, 53.5%, 31% and 3% for the MEM-exposed versus 0%, 0%, 2%, 0.35% and ≤0.0003% in the unexposed groups. One isolate had a similar resistant population at 72 h between the two groups. The remaining isolates showed no development of resistance, regardless of previous MEM exposure.

Conclusions

MEM exposure may pre-dispose to C/T resistance development and thus limit the therapeutic utility of this β-lactam/β-lactamase inhibitor. Resistance may be a result of stress exposure or molecular-level mutations conferring cross-resistance. Further in vivo studies are needed to assess clinical implications of these findings.
Potential for a minor pine bark beetle pest, Dendroctonus terebrans (Coleoptera: Curculionidae: Scolytinae), to mediate host location by a major pine killer, Dendroctonus frontalis
Authors: Sullivan Brian T , Munro Holly L , Barnes Brittany F , McNichol Bailey H , Shepherd William P , Gandhi Kamal J K
Published: March 2024

The southern pine beetle, Dendroctonus frontalis Zimmermann is an important mortality agent of Pinus in the eastern United States of America where it commonly shares hosts with the black turpentine beetle, Dendroctonus terebrans (Olivier), which infrequently kills trees. Unlike D. frontalis, which must kill its hosts to become established in the bark and reproduce, D. terebrans can occupy living hosts as a parasite. Olfactory mechanisms whereby D. frontalis initially locates hosts have not been demonstrated, whereas D. terebrans responds strongly to host odors. Because D. terebrans produces frontalin, the primary aggregation pheromone component for D. frontalis, and commonly arrives on hosts prior to D. frontalis, it has been hypothesized that D. terebrans pheromone components can mediate D. frontalis location of suitable, living trees. We assessed this possibility with studies of the semiochemical interactions between D. frontalis and D. terebrans. Coupled gas chromatography-electroantennographic detection analyses indicated that D. terebrans produces nine different olfactory stimulants for D. frontalis, nearly all of them known semiochemicals for D. frontalis. A trapping experiment designed to address the potentially confounding influence of lure contamination confirmed that the D. terebrans pheromone component exo-brevicomin enhances attraction of D. frontalis and thus could be an attractive kairomone. In ambulatory bioassays, male D. frontalis were strongly attracted to odors of frass of solitary female and paired D. terebrans, indicating their attraction to the naturally occurring semiochemicals of D. terebrans. Cues from D. terebrans may influence host and mate-finding success of D. frontalis and, thereby, the latter’s virulence.
Heterogeneous effects of a foreign buyer tax on house prices in New South Wales
Authors: Howell Anthony , Mughan Siân , Singla Akheil
Published: April 2024

This article combines unconditional quantile regressions with difference-in-differences to study the distributive effects of a foreign buyer tax (FBT) on home prices in New South Wales (NSW). The main results reveal that the FBT reduces house prices in NSW but only among the more expensive houses located in desirable neighborhoods of Sydney and with a relatively high share of foreign-born population. We find evidence that the FBT reduces transaction volumes in the same expensive Sydney neighborhoods and immigrant enclaves where house prices are observed to decline, in support of a direct mechanism that the FBT curbs foreign demand. Additional results suggest that more expensive homes are not substituted with less expensive housing, and that some foreign buyers respond to the FBT by divesting away from NSW locations. The main policy implication is that the FBT may help deter foreign buyers from accumulating higher-priced and luxury assets, but may fail to address broader housing affordability concerns facing the local population.
Validation and comparison of prognostic scoring systems in patients with head and neck squamous cell carcinoma treated with nivolumab
Authors: Takenaka Yukinori , Takemoto Norihiko , Otsuka Tomoyuki , Nishio Minako , Tanida Masashi , Fujii Takashi , Hayashi Kazuki , Suzuki Motoyuki , Mori Masashi , Yamamoto Yoshifumi , Uno Atsuhiko , Inohara Hidenori
Published: March 2024

Objective

Several scoring systems have been developed to predict prognosis in patients with refractory cancer. We aimed to validate eight scoring systems and determine the best method for predicting the prognosis of head and neck squamous cell carcinoma treated with nivolumab.

Methods

This multicentre retrospective study involved 154 patients with recurrent and/or metastatic head and neck squamous cell carcinoma treated with nivolumab between 2017 and 2020. Oncological outcomes were assessed according to the scoring systems, including MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio and Hammersmith scores. Objective response, overall survival and progression-free survival were evaluated using logistic regression and Cox proportional hazards analyses. Receiver operating curve analysis was used to calculate the area under the curve and estimate the efficacy of each score.

Results

No significant associations were found between the responses and any score. Seven of the eight scoring systems were associated with disease control (odds ratio, 0.26–0.70). Amongst the eight scoring systems, MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio showed the highest area under the curve for predicting response and disease control. Seven scoring systems were prognostic factors for progression-free survival (hazard ratio, 1.22–1.95). All eight scoring systems were prognostic factors for overall survival (hazard ratio, 1.62–3.83). According to the time-dependent receiver operating characteristics analysis for overall survival, the Hammersmith scoring system had the best predictive ability at 3 months, and the MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio scoring system had the highest area under the curve between 6 and 24 months.

Conclusions

MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio and Hammersmith scoring systems were better predictors of prognosis in patients with head and neck squamous cell carcinoma treated with nivolumab.
Robot-assisted repair of delayed traumatic diaphragmatic hernia: a case report
Authors: Holder Paxton , Bakeer Mohamed-Aly
Published: April 2024

Traumatic diaphragmatic hernia is a sign of severe thoracoabdominal trauma that is often difficult to detect because of nonspecific presenting symptoms, delayed presentation, and distracting injuries. Diagnosis depends on imaging and a high degree of suspicion in patients who present with respiratory or gastrointestinal symptoms after trauma, and prompt surgical repair is required. This case reviews a patient who presented to the emergency department with burning epigastric pain radiating to the left chest and hematemesis ~1 month after sustaining a blunt abdominal injury. Imaging studies revealed a substantial portion of the gastric body in the left hemithorax. Robot-assisted reduction of the stomach was performed followed by repair with tension-free primary closure without mesh reinforcement and gastropexy. The patient was monitored for return of bowel function and discharged upon recovery. This case report highlights the diagnostic challenges of traumatic diaphragmatic hernia and the benefit of robot-assisted repair.
Fuzzy bi-Gödel modal logic and its paraconsistent relatives
Authors: Bílková Marta , Frittella Sabine , Kozhemiachenko Daniil
Published: March 2024

We present an axiomatization of the fuzzy bi-Gödel modal logic ${\textbf{K}\textsf{biG}}^{\textsf{f}}$ formulated in the language containing $\triangle $ (Baaz Delta operator) and treating $-\!-\!< $ (co-implication) as the defined connective. We also consider two paraconsistent relatives of ${\textbf{K}\textsf{biG}}^{\textsf{f}}$ — $\textbf{K}\textsf{G}^{2\pm \textsf{f}}$ and $\textsf{G}^{2\pm \textsf{f}}_{\blacksquare ,\blacklozenge }$. These logics are defined on fuzzy frames with two valuations $e_{1}$ and $e_{2}$ standing for the support of truth and falsity, respectively, and equipped with two fuzzy relations$R^{+}$ and $R^{-}$ used to determine supports of truth and falsity of modal formulas. We construct embeddings of $\textbf{K}\textsf{G}^{2\pm \textsf{f}}$ and $\textsf{G}^{2\pm \textsf{f}}_{\blacksquare ,\blacklozenge }$ into ${\textbf{K}\textsf{biG}}^{\textsf{f}}$ and use them to obtain the characterization of $\textbf{K}\textsf{G}^{2}$- and $\textsf{G}^{2}_{\blacksquare ,\blacklozenge }$-definable frames. Moreover, we study the transfer of ${\textbf{K}\textsf{biG}}^{\textsf{f}}$ formulas into $\textbf{K}\textsf{G}^{2\pm \textsf{f}}$, i.e., formulas that are ${\textbf{K}\textsf{biG}}^{\textsf{f}}$-valid on mono-relational frames $\mathfrak{F}$ and $\mathfrak{F}^{\prime}$ iff they are $\textbf{K}\textsf{G}^{2\pm \textsf{f}}$-valid on their bi-relational counterparts. Finally, we establish $\textsf{PSpace}$-completeness of all considered logics.
CRRfast: an emulator for the cosmological recombination radiation with effects from inhomogeneous recombination
Authors: Lucca Matteo , Chluba Jens , Rotti Aditya
Published: March 2024

The cosmological recombination radiation (CRR) is one of the guaranteed ΛCDM spectral distortion (SD) signals. Even if very small in amplitude, it provides a direct probe of the three recombination eras, opening the path for testing one of the key pillars in our cosmological interpretation of the measured CMB anisotropies. Here, we develop a new emulator, CRRfast, to quickly and accurately represent the CRR for a wide range of cosmologies, using the state-of-the-art CosmoSpec code as a reference. CRRfast has been made publicly available both as stand-alone code and as part of class, thereby completing the set of average ΛCDM sources of SDs that can be modelled with class. With this newly developed pipeline we investigate the full constraining power of SDs within ΛCDM and highlight possible future applications to experimental design optimization. Furthermore, we show that the inhomogeneous evolution of the recombination process imprints second-order contributions to the CRR spectrum, leading to a broadening and shifting of the CRR features. These second-order terms are naturally captured by the emulator and allow us to evaluate the contribution of the ΛCDM primordial perturbations to the average CRR as well as to illustrate the effect of perturbed recombination due to Primordial Magnetic Fields (PMFs). As it turns out, while the second-order ΛCDM signal can be neglected, it could be significantly enhanced in the beyond-ΛCDM models. In particular in the case of PMFs, we demonstrate that through these non-linear terms the parameter space relevant to the Hubble tension could be tested with future CMB spectrometers.
Unveiling the Cosmic Cradle: clustering and massive star formation in the enigmatic Galactic bubble N59
Authors: Paulson Sonu Tabitha , Mallick K K , Ojha D K
Published: March 2024

In this paper, we have conducted an investigation focused on a segment of the Spitzer mid-infrared bubble N59, specifically referred to as R1 within our study. Situated in the inner Galactic plane, this region stands out for its hosting of five 6.7 GHz methanol masers, as well as numerous compact $\mathrm{H}\, \rm {{\small II}}$ regions, massive clumps, filaments, and prominent bright rims. As 6.7 GHz masers are closely linked to the initial phases of high-mass star formation, exploring regions that exhibit a high abundance of these maser detections provides an opportunity to investigate relatively young massive star-forming sites. To characterize the R1 region comprehensively, we utilize multiwavelength (archival) data from optical to radio wavelengths, together with 13CO and C18O data. Utilizing the Gaia DR3 data, we estimate the distance towards the bubble to be 4.66 ± 0.70 kpc. By combining near-infrared (NIR) and mid-infrared (MIR) data, we identify 12 Class I and 8 Class II sources within R1. Furthermore, spectral energy distribution (SED) analysis of selected sources reveals the presence of four embedded high-mass sources with masses ranging from 8.70 to 14.20 M⊙. We also identified several O and B-type stars from radio continuum analysis. Our molecular study uncovers two distinct molecular clouds in the region, which, although spatially close, occupy different regions in velocity space. We also find indications of a potential hub-filament system fostering star formation within the confines of R1. Finally, we propose that the feedback from the $\mathrm{H}\, \rm {{\small II}}$ regions has led to the formation of prominent Bright Rimmed Clouds (BRCs) within our region of interest.
Towards high-field applications: high-performance, low-cost iron-based superconductors
Authors: Dong Chiheng , Xu Qingjin , Ma Yanwei
Published: March 2024

High magnetic fields play a crucial role in advancing basic sciences, fusion energy, and magnetic resonance imaging systems. However, the widespread use of high-field magnets requires affordable high-temperature superconducting wires that can carry large supercurrents. Iron-based superconductors offer an economically attractive solution to push forward important yet costly scientific programs, such as nuclear fusion reactors and next-generation particle accelerators. In this review, we start with the fabrication of iron-based superconducting wires and tapes and continue to discuss several key factors governing the current transport properties. State-of-the-art wires and tapes are introduced with emphasis on grain boundary characteristics, flux pinning, and anisotropy. The architecture of flexible conductors enables low cost, high mechanical strength, and high thermal stability. Recent progress in practical applications, including superconducting joints and insert coils, is also reviewed. Finally, we propose several key questions faced by iron-based superconductors in future practical applications.
Occupational dose measurement in interventional cardiology practice
Authors: Wickramasinghe Sachini Udara , Ramanathan Vijitha , Sarasanandarajah Sivananthan , De Zoyza Manjuka , Paranamana Roshan
Published: March 2024

Ensuring the safety of healthcare workers in interventional cardiology necessitates effective monitoring of occupational radiation exposure. This study aims to assess the accuracy of the over-apron single dosimetric approach compared with double dosimetric methods and explore the relationship between under-apron and over-apron doses. This investigation showed that the prescribed annual dose constraint of 20 mSv year−1 was not exceeded by the maximum annual occupational doses determined by dosimetric algorithms, which were 0.13 ± 0.02, 0.15 ± 0.02 and 0.27 ± 0.04 mSv, respectively. The study demonstrated excellent statistically significant correlations among single and double dosimetric algorithms and between direct under-apron and over-apron doses. Consequently, single dosimetric algorithms could effectively estimate doses for double dosimetric algorithms, highlighting the limited added value of under-apron measurements. These findings significantly impact the practice of interventional cardiology in Sri Lanka, playing a crucial role in enhancing radiation protection measures.
Adductor Canal Block versus Femoral Nerve Block in Total Knee Arthroplasty
Authors: Berikashvili Levan B. , Yadgarov Mikhail Ya. , Kuzovlev Artem N. , Smirnova Anastasia V. , Kadantseva Kristina K. , Kuznetsov Ivan V. , Polyakov Petr A. , Likhvantsev Valery V.
Published: April 2024

Objectives:

The quality of postoperative analgesia in total knee arthroplasty is crucial for patient recovery, rehabilitation and hospital stay duration. In line with the above, а single-shot adductor canal block has been considered as surpassing method over continuous femoral nerve block. However, continuous adductor canal block and single-shot femoral nerve block ‘kept overboard’ the discussion. This study aims to compare the effectiveness of various types of adductor and femoral nerve blocks on clinically relevant outcomes in patients following total knee arthroplasty.

Methods:

A systematic review and network meta-analysis were conducted following ‘PRISMA-NMA’ and Cochrane Handbook guidelines. Eligibility criteria included randomized trials and, where these were lacking for a comparison, non-randomized studies involving adults undergoing primary total knee arthroplasty, comparing single-shot adductor canal block, continuous adductor canal block, single-shot femoral nerve block, and continuous femoral nerve block.

Results:

A total of 36 studies involving 3308 patients were included. Single-shot adductor canal block showed higher pain scores and opioid consumption but better functional recovery at 24-h compared to continuous femoral nerve block. However, this trend vanishes by the 48-h assessment post-surgery. Continuous adductor canal block had higher opioid consumption but better functional recovery and shorter hospital stay compared to continuous femoral nerve block. Single-shot adductor canal block showed higher pain scores but comparable opioid consumption and functional recovery to continuous adductor canal block.

Discussion:

The shift from continuous femoral nerve block to single-shot adductor canal block as the preferred method for pain relief after total knee arthroplasty may be premature. While the latter improves mobility, it falls short in pain control and doesn’t shorten hospital stays. Continuous adductor canal block shows promise but is currently underappreciated, and single-shot femoral nerve block is often overshadowed by other techniques in regional anesthesia. Further high-quality, multicenter randomized controlled trials are needed to validate these findings.
Reduced macular thickness and vascular density in abnormal glucose metabolism patients: A meta-analysis of optical coherence tomography (OCT) and OCT angiography studies
Authors: Fu Xiangyu , Ren Xiang , Chen Wenyue , Chen Danian
Published: April 2024

Background:

Alterations in macular thickness and vascular density before clinically visible diabetic retinopathy (DR) remain inconclusive. This study aimed to determine whether retinal manifestations in abnormal glucose metabolism (AGM) patients differ from those in the healthy individuals.

Methods:

PubMed, Embase, and Web of Science were searched between 2000 and 2021. The eligibility criteria were AGM patients without DR. Primary and secondary outcomes measured by optical coherence tomography (OCT) and OCT angiography (OCTA) were analyzed and expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs). A random-effects model was used in the data synthesis. The potential publication bias for the variables was evaluated using Egger’s test.

Results:

A total of 86 observational studies involving 13,773 participants and 15,416 eyes were included. OCT revealed that compared to healthy controls, the total macular thickness of AGM patients was thinner, including the thickness of fovea (–0.24, 95% CI [–0.39, –0.08];P = 0.002,I2 = 87.7%), all regions of parafovea (–0.32, 95% CI [–0.54, –0.11];P = 0.003;I2 = 71.7%) and the four quadrants of perifovea; the thickness of peripapillary retinal nerve fiber layer (pRNFL), macular retinal nerve fiber layer (mRNFL), and ganglion cell layer (GCL) also decreased. OCTA indicated that the superficial and deep vascular density decreased, the foveal avascular zone (FAZ) area enlarged, and the acircularity index (AI) reduced in AGM individuals.

Conclusions:

Retinal thinning and microvascular lesions have occurred before the advent of clinically detectable DR; OCT and OCTA may have the potential to detect these preclinical changes.

Registration:

PROSPERO; http://www.crd.york.ac.uk/prospero/; No. CRD42021269885.
Role of Primary Care Clinician Concern During Screening for Early Identification of Autism
Authors: Wieckowski Andrea Trubanova , Ramsey Riane K. , Coulter Kirsty , Eldeeb Sherief Y. , Algur Yasemin , Ryan Victoria , Stahmer Aubyn C. , Robins Diana L.
Published: April 2024

Objective:

The aim of this study was to evaluate the added value of primary care clinician (PCC)-indicated concern during primary care universal standardized screening in early identification of autism.

Methods:

Toddlers were screened for autism during primary care checkups (n = 7,039, aged 14.24–22.43 months) in 2 studies. Parents completed the Modified Checklist for Autism in Toddlers, Revised, with Follow-Up. For each participant, PCCs indicated whether they had autism concerns (optional in 1 study—before or after viewing screening results, required before viewing screen results in the other). Children at high likelihood for autism from screen result and/or PCC concern (n = 615) were invited for a diagnostic evaluation; 283 children attended the evaluation.

Results:

Rates of PCC-indicated autism concerns were similar whether PCCs were required or encouraged to indicate concerns. High likelihood of autism indication on both screen and PCC concern resulted in the highest positive predictive value for autism and positive predictive value for any developmental disorder, as well as the highest evaluation attendance, with no significant difference between the positive screen-only and PCC concern-only groups. Although the frequency of PCC-indicated autism concern did not differ significantly based on the child's cognitive level, PCCs were more likely to identify children with more obvious autism characteristics compared with more subtle autism characteristics as having autism.

Conclusion:

The findings support the recommendation of the American Academy of Pediatrics that both screening and surveillance for autism be incorporated into well-child visits. High likelihood of autism on either screen or PCC concern should trigger a referral for an evaluation.
Long-term outcomes of patients with autoimmune hepatitis induced cirrhosis after immunosuppressive treatment
Authors: Hatoum Sara , Rockey Don C.
Published: March 2024

Introduction

Autoimmune hepatitis is an immune-mediated liver disease that results in hepatic inflammation and subsequent fibrosis. We aimed to assess the natural history of autoimmune hepatitis in patients who had cirrhosis at the time of diagnosis.

Methods

We examined consecutive patients with autoimmune hepatitis (based on the revised International Autoimmune Hepatitis Group criteria) and cirrhosis who had long-term follow-up between 2012 and 2018. Complete clinical data, including longitudinal data, was obtained for each patient to determine clinical and biochemical outcomes. Decompensating events were defined as complications of portal hypertension.

Results

Thirty-four patients presenting with autoimmune hepatitis induced cirrhosis (age 50, 17–81; 71% women) were followed for an average of 8 years post-diagnosis. Fourteen (41%) patients had a decompensating event at diagnosis. All patients were begun on treatment; index decompensating events resolved in all patients. Twenty-six (76%) patients had normalization of transaminases; in this group, 4 (15%) patients developed one or more new decompensating events and 1 patient (4%) died. Of the 8 (24%) patients who did not have transaminase normalization, 6 (75%) developed one or more new decompensating events and 5 (62%) died or underwent liver transplant. There was a significant association between achieving normalization of transaminases and protection from developing a decompensating event (P = 0.003) and liver transplant or death (P = 0.001).

Conclusion

Most patients with autoimmune hepatitis with cirrhosis at presentation achieved normalization of transaminases with treatment and rarely developed further decompensating events. We speculate that some of these patients had stabilization or reversal of portal hypertension.
NewVibrio choleraesequences from Eastern and Southern Africa alter our understanding of regional cholera transmission
Authors: Xiao Shaoming , Abade Ahmed , Boru Waqo , Kasambara Watipaso , Mwaba John , Ongole Francis , Mmanywa Mariam , Trovão Nídia Sequeira , Chilengi Roma , Kwenda Geoffrey , Orach Christopher Garimoi , Chibwe Innocent , Bwire Godfrey , Stine O. Colin , Milstone Aaron M. , Lessler Justin , Azman Andrew S. , Luo Wensheng , Murt Kelsey , Sack David A. , Debes Amanda K. , Wohl Shirlee
Published: March 2024

Despite ongoing containment and vaccination efforts, cholera remains prevalent in many countries in sub-Saharan Africa. Part of the difficulty in containing cholera comes from our lack of understanding of how it circulates throughout the region. To better characterize regional transmission, we generated and analyzed 118Vibrio choleraegenomes collected between 2007-2019 from five different countries in Southern and Eastern Africa. We showed thatV. choleraesequencing can be successful from a variety of sample types and filled in spatial and temporal gaps in our understanding of circulating lineages, including providing some of the first sequences from the 2018-2019 outbreaks in Uganda, Kenya, Tanzania, Zambia, and Malawi. Our results present a complex picture of cholera transmission in the region, with multiple lineages found to be co-circulating within several countries. We also find evidence that previously identified sporadic cases may be from larger, undersampled outbreaks, highlighting the need for careful examination of sampling biases and underscoring the need for continued and expanded cholera surveillance across the African continent.
WITHDRAWN: Association between neutrophil to-lymphocyte ratio (NLR) and outcome of septic patients with atrial fibrillation (AF): A retrospective observational study based on Medical Information Mart for Intensive Care IV
Authors: Tang Weiyi , Shi Weizhen , Li Liangyao , tang kui
Published: March 2024

Withdrawal Statement

The authors have withdrawn this manuscript because due to the discovery that the original data requires reanalysis to ensure the accuracy and completeness of the results, we have decided to withdraw the submission. A revision will be submitted once these concerns have been adequately addressed. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Improving prediction models of amyotrophic lateral sclerosis (ALS) using polygenic, pre-existing conditions, and survey-based risk scores in the UK Biobank
Authors: Jin Weijia , Boss Jonathan , Bakulski Kelly M. , Goutman Stephen A. , Feldman Eva L. , Fritsche Lars G. , Mukherjee Bhramar
Published: March 2024

Background and Objectives

Amyotrophic lateral sclerosis (ALS) causes profound impairments in neurological function and a cure for this devastating disease remains elusive. Early detection and risk stratification are crucial for timely intervention and improving patient outcomes. This study aimed to identify predisposing genetic, phenotypic, and exposure-related factors for Amyotrophic lateral sclerosis using multi-modal data and assess their joint predictive potential.

Methods

Utilizing data from the UK Biobank, we analyzed an unrelated set of 292 ALS cases and 408,831 controls of European descent. Two polygenic risk scores (PRS) are constructed: “GWAS Hits PRS” and “PRS-CS,” reflecting oligogenic and polygenic ALS risk profiles, respectively. Time-restricted phenome-wide association studies (PheWAS) were performed to identify pre-existing conditions increasing ALS risk, integrated into phenotypic risk scores (PheRS). A poly-exposure score (“PXS”) captures the influence of environmental exposures measured through survey questionnaires. We evaluate the performance of these scores for predicting ALS incidence and stratifying risk, adjusting for baseline demographic covariates.

Results

Both PRSs modestly predicted ALS diagnosis, but with increased predictive power when combined (covariate-adjusted receiver operating characteristic [AAUC] = 0.584 [0.525, 0.639]). PheRS incorporated diagnoses 1 year before ALS onset (PheRS1) modestly discriminated cases from controls (AAUC = 0.515 [0.472, 0.564]). The “PXS” did not significantly predict ALS. However, a model incorporating PRSs and PheRS1 improved prediction of ALS (AAUC = 0.604 [0.547, 0.667]), outperforming a model combining all risk scores. This combined risk score identified the top 10% of risk score distribution with a 4-fold higher ALS risk (95% CI: [2.04, 7.73]) versus those in the 40%-60% range.

Discussions

By leveraging UK Biobank data, our study uncovers predisposing ALS factors, highlighting the improved effectiveness of multi-factorial prediction models to identify individuals at highest risk for ALS.
Real-World Genetic Characteristics of Candidates for Implantable Cardioverter-Defibrillators with Dilated Cardiomyopathy
Authors: Kim In-Soo , Kim Yoonjung , Seo Jiwon , Chung Hyemoon , Son Jung-Woo , Ha Sang Jin , Shim Jaemin , Kim Jong-Youn , Rim Se-Joong , Lee Kyung-A , Choi Eui-Young
Published: March 2024

Background

The real-world prevalence of sudden cardiac death (SCD)–related gene mutations and their relationship with implantable cardioverter-defibrillator (ICD) implantation in dilated cardiomyopathy (DCM) has not been clearly investigated.

Methods

This study included patients with sporadic DCM with persistent left ventricular ejection fraction (LVEF) ≤ 35% even after 3 months of guideline-directed medical treatment or those with an ICD for secondary prevention and LVEF < 50%. Genetic tests targeting 444 pan-cardiomyopathy genes (including 36 core DCM genes) were performed, along with the collection of clinical and electrophysiological information.

Results

A total of 105 patients were enrolled (median age, 65.0 [57.5–75.0] years), and 33 (31%) were women. The average LVEF was 27.4 ± 5.9%, and 46 patients (44%) had ICD or cardiac resynchronization therapy with ICD (34 for primary prevention and 12 for secondary prevention purpose) at the time of enrollment. Fourteen patients (13%) had pathogenic (P) or likely pathogenic (LP) variants (comprising 6TTN, 4DSP, 2TNNT2, 1RBM20,1DSGand 1MYBPC3, one patients had bothDSPandRBM20), and 59 patients (56%) had P/LP/variant of uncertain significance (VUS) in the 36 core DCM genes. Twenty-eight patients (27%) harbored SCD-related gene variants (14DSP, 11FLNC, 9RBM20and 2TMEM43). The prevalence of SCD gene variants tended to be higher in the secondary prevention and non-ICD groups (33.3% for secondary purposes, 11.8% for primary purposes, and 33.8% for non-ICD; p = 0.058).

Conclusions

In patients with advanced heart failure and DCM, P/LP-validated DCM variants were not common in sporadic cases. However, when extended to VUS, approximately half of the patients had core DCM-related variants. The prevalence of SCD variants was not lower in the non-ICD group, thus suggesting a potential risk of fatal arrhythmia.

(Trial registration: CRIS KCT0004913)
Interoperability of phenome-wide multimorbidity patterns: a comparative study of two large-scale EHR systems
Authors: Strayer Nick , Vessels Tess , Choi Karmel , Zhang Siwei , Li Yajing , Han Lide , Sharber Brian , Hsi Ryan S , Bejan Cosmin A , Bick Alexander G. , Balko Justin M , Johnson Douglas B , Wheless Lee E , Wells Quinn S , Philips Elizabeth J , Pulley Jill M , Self Wesley H , Chen Qingxia , Hartert Tina , Wilkins Consuelo H , Savona Michael R , Shyr Yu , Roden Dan M , Smoller Jordan W , Ruderfer Douglas M , Xu Yaomin
Published: March 2024

Background

Electronic health records (EHR) are increasingly used for studying multimorbidities. However, concerns about accuracy, completeness, and EHRs being primarily designed for billing and administrative purposes raise questions about the consistency and reproducibility of EHR-based multimorbidity research.

Methods

Utilizing phecodes to represent the disease phenome, we analyzed pairwise comorbidity strengths using a dual logistic regression approach and constructed multimorbidity as an undirected weighted graph. We assessed the consistency of the multimorbidity networks within and between two major EHR systems at local (nodes and edges), meso (neighboring patterns), and global (network statistics) scales. We present case studies to identify disease clusters and uncover clinically interpretable disease relationships. We provide an interactive web tool and a knowledge base combining data from multiple sources for online multimorbidity analysis.

Findings

Analyzing data from 500,000 patients across Vanderbilt University Medical Center and Mass General Brigham health systems, we observed a strong correlation in disease frequencies ( Kendall’sτ= 0.643) and comorbidity strengths (Pearsonρ= 0.79). Consistent network statistics across EHRs suggest similar structures of multimorbidity networks at various scales. Comorbidity strengths and similarities of multimorbidity connection patterns align with the disease genetic correlations. Graph-theoretic analyses revealed a consistent core-periphery structure, implying efficient network clustering through threshold graph construction. Using hydronephrosis as a case study, we demonstrated the network’s ability to uncover clinically relevant disease relationships and provide novel insights.

Interpretation

Our findings demonstrate the robustness of large-scale EHR data for studying phenome-wide multimorbidities. The alignment of multimorbidity patterns with genetic data suggests the potential utility for uncovering shared biology of diseases. The consistent core-periphery structure offers analytical insights to discover complex disease interactions. This work also sets the stage for advanced disease modeling, with implications for precision medicine.

Funding

VUMC Biostatistics Development Award, the National Institutes of Health, and the VA CSRD
Design of a Clinical Balance Tool for Fall Risk Assessments: A Development and Usability Study
Authors: Garvin Jennifer Hornung , Yazzie Virginia M. , Katsuyama Natalie A. , Rudloff Truman , Worthen-Chaudhari Lise C. , Chaudhari Ajit M.W.
Published: March 2024

Background

Falls are a significant source of early morbidity and mortality in the aging population, yet clinical changes that lead to increased fall risks often escape early identification and intervention. A device to measure postural control would facilitate evidence-based fall risk assessment.

Objectives

Our objectives were to iteratively develop a prototype quantitative posture instrument (QuPI) to replace the weight scale and to assess barriers and facilitators of its implementation in a clinical setting.

Methods

We undertook a formative evaluation and usability study of two QuPI prototypes in primary care, medical oncology, sports medicine, cardiology, and endocrinology outpatient clinics. Clinicians evaluated an initial QuPI prototype and completed a semi-structured interview to determine critical functionality, inform design, and assess usability. The QuPI was modified according to the results, and a new prototype was tested and evaluated.

Results

Eighteen clinicians participated in both rounds of interviews. Clinicians who participated (referred to as participants) reported willingness to use the QuPI with all patients during the first round of interviews and stated they would replace their current weight scale with the modified QuPI during the second round of interviews. Participants identified design elements that were both facilitators and barriers to use. Usability scores for both prototypes were excellent. Despite several national guidelines for fall risk assessments, lack of consistent use of guidelines by care teams was found to be a barrier to effective fall risk assessments.

Conclusion

The QuPI provides a new method for quantifying fall risks with good user acceptance, usability, and clinical feasibility without disrupting workflow. The QuPI supplemented and facilitated the use of standard algorithms for fall risk assessment. Greater education of the entire care team regarding evidence-based fall risk assessment will promote adherence to guidelines and fall prevention.
Characteristics and antiviral treatment eligibility of newly diagnosed hepatitis B patients at a teaching hospital in Ghana: Implications for prevention and management
Authors: Daniels Joseph , Nartey Yvonne A. , Djankpa Francis , Simpore Jacques , Obiri-Yeboah Dorcas
Published: March 2024

Hepatitis B virus (HBV) infection poses a considerable public health challenge in limited-resource settings especially in the sub-Saharan African region. Even though HBV infection is incurable, timely treatment is effective in preventing disease progression to liver cirrhosis or hepatocellular carcinoma. However, not all infected patients require treatment. The aim of this study was to determine the clinical, immunological, and virological profiles of newly diagnosed adult HBV patients at a tertiary healthcare center in Ghana and to determine the antiviral treatment eligibility rate based on current guidelines of the World Health Organization (WHO). A hospital-based cross-sectional study involving total sampling of 220 treatment naïve HBV surface antigen positive clients was carried out. A structured questionnaire was used to collect data and detailed clinical and laboratory assessment (serological, biochemical and virological) was carried out. Data were entered and analyzed with STATA version 16. The median age at diagnosis was 34 years (IQR 26.0 – 41.5) with a male to female ratio of 1:1.5. A total of 138 participants (62.7%) were diagnosed with HBV infection following voluntary testing. There was a median delay of 8.5 months (IQR 3.0 – 22.5) between initial diagnosis and patients’ presentation for medical care. In all, 24 patients (10.9%) had abnormal clinical examination findings, 172 patients (78.2%) had HBV DNA levels ≤ 2000 IU/ml while 8 (3.6%) were seropositive for HBeAg. A small proportion of patients had concomitant human immunodeficiency virus (2.7%) and hepatitis C virus (1.4%) infections. Treatment eligibility rate was very low among newly diagnosed HBV infected patients seeking medical care (n=14, 6.4%) following the WHO guidelines for treatment eligibility. Thus, increasing screening rate among the general population, early linkage to clinical care of screen positives and vaccination of screen negatives will help reduce HBV related clinical conditions in resource limited countries.
Biomechanical regulation of cell shapes promotes branching morphogenesis of the ureteric bud epithelium
Authors: Kurtzeborn Kristen , Iaroshenko Vladislav , Zárybnický Tomáš , Koivula Julia , Anttonen Heidi , Brigdewater Darren , Krishnan Ramaswamy , Chen Ping , Kuure Satu
Published: March 2024

Background

Branching morphogenesis orchestrates organogenesis in many tissues including kidney, where ureteric bud branching determines kidney size and nephron number. Defects in branching morphogenesis result in congenital renal anomalies which manifest as deviations in size, function, and nephron number thus critically compromising the lifelong renal functional capacity established during development. Advances in the genetic and molecular understanding of ureteric bud branching regulation have proved insufficient to improve prognosis of congenital renal defects. Thus, we addressed mechanisms regulating three-dimensional (3D) ureteric bud epithelial cell morphology and cell shape changes during novel branch initiation to uncover the contributions of cellular mechanics on cellular functions and tissue organization in normal and branching-compromised bud tips.

Methods

We explored epithelial cell behavior at all scales by utilizing a combination of mouse genetics and a custom machine-learning segmentation pipeline in MATLAB. Ureteric bud epithelial cell shapes and sizes were quantified in 3D wholemount kidneys. A combination with live imaging of fluorescently labelled UB cells, traction force microscopy, and primary UB cells were used to determine how basic cellular features and niche biomechanics contribute to complex novel branch point determination in the process that aims at gaining optimal growth and epithelial density in a limited space.

Results

Machine learning-based segmentation of tip epithelia identified geometrical round-to-elliptical transformation as a key cell shape change facilitating shifts in growth direction that enable propitious branching complexity. Cell shape and molecular analyses in branching-compromised epithelia demonstrated a failure to condense cell size and conformation. Analysis of branching-compromised ureteric bud derived epithelial cells demonstrated disrupted E-CADHERIN and PAXILLIN mediated adhesive forces and defective cytoskeletal dynamics as detected by fluorescent labelling of actin in primary ureteric bud epithelial cells. Branching-compromised ureteric bud epithelial cells showed wrinkled nuclear shapes and alterations in MYH9-based microtubule organization, which suggest a stiff cellular niche with disturbed sensing of and response to biomechanical cues.

Conclusions

Our results indicate that the adhesive forces within the epithelium and towards the niche composed of nephron progenitors must dynamically fluctuate to allow complexity in arborization during new branch formation. The data collectively propose a model where epithelial cell crowding in tandem with stretching transforms individual cells into elliptical and elongated shapes. This creates local curvatures that drive new branch formation during the ampulla-to-asymmetric ampulla transition of ureteric bud.
CHANGE-seq-BE enables simultaneously sensitive and unbiasedin vitroprofiling of base editor genome-wide activity
Authors: Lazzarotto Cicera R. , Katta Varun , Li Yichao , Urbina Elizabeth , Lee GaHyun , Tsai Shengdar Q.
Published: March 2024

Base editors (BE) enable programmable conversion of nucleotides in genomic DNA without double-stranded breaks and have substantial promise to become new transformative genome editing medicines. Sensitive and unbiased detection of base editor off-target effects is important for identifying safety risks unique to base editors and translation to human therapeutics, as well as accurate use in life sciences research. However, current methods for understanding the global activities of base editors have limitations in terms of sensitivity or bias. Here we present CHANGE-seq-BE, a novel method to directly assess the off-target profile of base editors that is simultaneously sensitive and unbiased. CHANGE-seq-BE is based on the principle of selective sequencing of adenine base editor modified genomic DNAin vitro, and provides an accessible, rapid, and comprehensive method for identifying genome-wide off-target mutations of base editors.
Life history traits influence the dynamics of genetic diversity in a refugium population undergoing expansion and contraction
Authors: Vishwakarma Ravi , Sgarlata Gabriele Maria , Soriano-Panos David , Rasteiro Rita , Maie Tiago , Paixao Tiago , Tournebize Remi , Chikhi Lounes
Published: March 2024

Species ranges are dynamic, experiencing expansions, contractions or shifts as a response to habitat changes induced by extrinsic factors such as climate change and, more recently, human activities. While the scientific literature has explored the genetic effects of spatial processes, published studies rarely incorporate life-history traits to study the effect of such changes on species living in the same environments. There is thus a gap in our understanding regarding the variation in genetic diversity patterns among species with distinct life-history traits such as growth rates and generation times, experiencing the same habitat change scenarios. In this study, we first used spatial simulations to investigate the temporal dynamics of genetic diversity within refugium populations experiencing a range expansion followed by a stationary and a contraction period. We explored different scenarios, varying both the speed of contraction and the life-history traits of the simulated species. In addition, we used a simpler panmictic model for which we derived analytical results. Altogether, we identified three temporal dynamics of genetic diversity in the refugium population during the contraction phase: scenarios where genetic diversity i) decreased throughout the contractions, ii) increased for periods that could be greater than thousands of years before plateauing and then decreasing or iii) followed a persistent increasing trend, without any visible effect of the expansion or contraction. We show that these different temporal dynamics can be predicted by comparing the observed expected heterozygosity (He) to the values expected if the species were at equilibrium within the refuge (He refuge) and within the whole landscape (He landscape). We also observe that there are scenarios where a rapid contraction maintains more diversity just at the end of the contraction, as widely believed and as reported in a previous simulation study. However, we also observe the opposite pattern for a wide range of parameters. The widespread idea that observing high diversity levels in a refugium population is due to a recent and rapid habitat loss is thus not necessarily true and will depend on various life history traits and how they relate to habitat change dynamics.