bluuebunny/crossref_metadata_2025 huggingface dataset:
Tonic ErbB signaling underlies TGFβ-induced activation of ERK and is required for lens cell epithelial to myofibroblast transition
Authors: VanSlyke Judy K. , Boswell Bruce A. , Musil Linda S.
Published: January 2024

Fibrosis is a major, but incompletely understood, component of many diseases. The most common vision-disrupting complication of cataract surgery involves differentiation of residual lens cells into myofibroblasts. In serum-free primary cultures of lens epithelial cells (DCDMLs), inhibitors of either ERK or of ErbB signaling prevent TGFβ from upregulating both early (fibronectin) and late (αSMA) markers of myofibroblast differentiation. TGFβ stimulates ERK in DCDMLs within 1.5 h. Kinase inhibitors of ErbBs, but not of several other growth factor receptors in lens cells, reduce phospho ERK to below basal levels in the absence or presence of TGFβ. This effect is attributable to constitutive ErbB activity playing a major role in regulating the basal levels pERK. Additional studies support a model in which TGFβ-generated reactive oxygen species serve to indirectly amplify ERK signaling downstream of tonically active ErbBs to mediate myofibroblast differentiation. ERK activity is in turn essential for expression of ErbB1 and ErbB2, major inducers of ERK signaling. By mechanistically linking TGFβ, ErbB, and ERK signaling to myofibroblast differentiation, our data elucidate a new role for ErbBs in fibrosis and reveal a novel mode by which TGFβ directs lens cell fate.
SilenceREIN: seeking silencers on anchors of chromatin loops by deep graph neural networks
Authors: Pan Jian-Hua , Du Pu-Feng
Published: January 2024

Silencers are repressive cis-regulatory elements that play crucial roles in transcriptional regulation. Experimental methods for identifying silencers are always costly and time-consuming. Computational methods, which relies on genomic sequence features, have been introduced as alternative approaches. However, silencers do not have significant epigenomic signature. Therefore, we explore a new way to computationally identify silencers, by incorporating chromatin structural information. We propose the SilenceREIN method, which focuses on finding silencers on anchors of chromatin loops. By using graph neural networks, we extracted chromatin structural information from a regulatory element interaction network. SilenceREIN integrated the chromatin structural information with linear genomic signatures to find silencers. The predictive performance of SilenceREIN is comparable or better than other states-of-the-art methods. We performed a genome-wide scanning to systematically find silencers in human genome. Results suggest that silencers are widespread on anchors of chromatin loops. In addition, enrichment analysis of transcription factor binding motif support our prediction results. As far as we can tell, this is the first attempt to incorporate chromatin structural information in finding silencers. All datasets and source codes of SilenceREIN have been deposited in a GitHub repository (https://github.com/JianHPan/SilenceREIN).
Initial steps towards developing a predictive algorithm of disease progression for hidradenitis suppurativa (HS): results from a Cox proportional hazard regression analysis on disease progression among a cohort of 335 Danish patients with HS
Authors: Kjærsgaard Andersen Rune , Pedersen Ole , Eidsmo Liv , Jemec Gregor , Saunte Ditte
Published: January 2024

Background

Hidradenitis suppurativa (HS) is a chronic inflammatory and scarring disease with a wide spectrum of disease severity. The amount of scarring is proportional to the preceding tissue damage and poses a challenge to patients. Severe HS is most often treatment recalcitrant, but hypothetically avoidable through early biologic treatment. Early prediction of individual risk of disease progression is therefore essential for patient management.

Objectives

To investigate risk factors associated with disease progression and to design an algorithm capable of predicting disease ­progression.

Methods

A prospective cohort study of 335 Hurley III-naïve patients with HS, not treated with biologics, was followed for a median of 2 years. Potential risk factors covered basic demographics, HS anamnestic factors and clinical HS factors collected during physical examination. Two separate Cox proportional hazard regression (CPHR) analyses were conducted. A summated ‘progression score’ was calculated and used in the predictive algorithm of severe disease. Subsequent bootstrap sampling was used to validate the predictability of the predictive algorithm.

Results

The CPHR analysis of Transition to severe disease found that active smoking [hazard ratio (HR) 4.01, 95% confidence interval (CI) 1.71–9.40, P = 0.001]; body mass index (BMI) points > 25 at baseline (each point: HR 1.06, 95% CI 1.02–1.09, P < 0.001); active disease in 2 (HR 4.26, 95% CI 1.23–14.84, P = 0.02) and ≥ 3 areas (HR 6.54, 95% CI 1.89–22.72, P = 0.003) all constituted substantial risk factors. Conversely, the CPHR analysis of Disease progression did not yield results of clinical relevance. A ‘progression score’ of 3.04 was used as a threshold in the predictive algorithm of Transition to severe disease and achieved the following test specifics: sensitivity = 0.51, specificity = 0.86, positive predictive value = 0.50, negative predictive value = 0.86.

Conclusions

We found a disparity between factors increasing the risk of simple Disease progression and those increasing the risk of Transition to severe disease. For the latter, active smoking, BMI points > 25, active disease in 2 or ≥ 3 areas were all shown to be the clinically relevant factors that could be used to construct an algorithm that correctly predicted progression to severe HS in more than half of all instances.
Artificial intelligence: revolutionizing cardiology with large language models
Authors: Boonstra Machteld J , Weissenbacher Davy , Moore Jason H , Gonzalez-Hernandez Graciela , Asselbergs Folkert W
Published: January 2024

Natural language processing techniques are having an increasing impact on clinical care from patient, clinician, administrator, and research perspective. Among others are automated generation of clinical notes and discharge letters, medical term coding for billing, medical chatbots both for patients and clinicians, data enrichment in the identification of disease symptoms or diagnosis, cohort selection for clinical trial, and auditing purposes. In the review, an overview of the history in natural language processing techniques developed with brief technical background is presented. Subsequently, the review will discuss implementation strategies of natural language processing tools, thereby specifically focusing on large language models, and conclude with future opportunities in the application of such techniques in the field of cardiology.
Post-sternotomy movement strategies in adults: a scoping review
Authors: Wiens Karen , Hayden K Alix , Park Lauren , Colwell Susan , Coltman Christopher , King-Shier Kathryn M
Published: January 2024

Aims

Post-sternotomy movement strategies for adults should be an evidence-informed approach and support a safe, independent return to daily activity. Recent new movement strategies have emerged. The aim of this scoping review was to identify and summarize the available evidence for post-sternotomy movement strategies in adults.

Methods and results

The electronic databases searched included MEDLINE, Embase, Sport Discus, CINAHL, Academic Search Complete, the Cochrane Library, Scopus, and PEDro. The search did not have a date limit. After 2405 duplicates were removed, 2978 records were screened, and 12 were included; an additional 2 studies were identified through reference searching for a total of 14 included studies. A data extraction table was used, and the findings are summarized in a tabular and narrative form. Three post-sternotomy movement strategies were identified in the literature: sternal precautions (SP), modified SP, and Keep Your Move in the Tube (KYMITT™). The authors suggested that the practice of SP was based on expert opinion and not founded in evidence. However, the evidence from the identified articles suggested that new movement strategies are safe and allow patients to choose an increased level of activity that promotes improved functional status and confidence.

Conclusion

More prospective cohort studies and multi-centred randomized control trials are needed; however, the current evidence suggests that modified SP and KYMITT™ are as safe as SP and can promote a patient-centred approach.

Registration

University of Calgary’s Digital Repository PRISM http://hdl.handle.net/1880/115439.
Psychometric testing of the Care Dependency Scale in patients with heart failure and their caregivers
Authors: Durante Angela , Vellone Ercole , Younas Ahtisham , Juarez-Vela Raul , Boyne Josiane , Piredda Michela , De Maria Maddalena
Published: January 2024

Aims

This study aims to (i) test the validity and reliability of the Care Dependency Scale (CDS) for patients with heart failure (HF) and (ii) test the validity and reliability of the proxy version of the CDS assessing informal caregivers’ perception of the dependency level of individuals with HF.

Methods and results

Secondary data analysis was conducted of transnational multicentre cross-sectional design study. A convenience sample comprised of HF patients–informal caregivers’ dyads in three European countries. The CDS was administered to patients and the proxy version to informal caregivers. Factorial validity was tested for each scale using confirmatory factor analysis. Reliability was evaluated with the composite coefficient and Cronbach’s alpha. Construct validity was tested via known group differences. Measurement error was tested to assess responsiveness to changes. A total of 229 patients and 208 caregivers were recruited. Confirmatory factor analysis supported the two-factor structure (Physical Care Dependency and Psychosocial Care Dependency) of the CDS in both HF patients and their caregiver. Reliability estimates were adequate for all reliability coefficients. Construct validity was supported. The measurement error was adequate.

Conclusion

The scale shows acceptable validity and reliability and can be useful for care dependency assessment of patients with HF and their informal caregivers. Further research is needed for assessing the validity and reliability in other cross-cultural settings. The use of the CDS has the potential to effectively enable the development of pertinent care plans, taking dependency into consideration including the perspective of both members of the dyad as a whole.
Allelic combinations of Hd1, Hd16, and Ghd7 exhibit pleiotropic effects on agronomic traits in rice
Authors: Lee Seung Young , Jeung Ji-Ung , Mo Youngjun
Published: January 2024

Heading date is a critical agronomic trait that significantly affects grain yield and quality in rice. As early heading is typically associated with reduced yield due to shorter growth duration, it is essential to harness optimum heading date genes and their allelic combinations to promote heading while minimizing yield penalties. In this study, we identified quantitative trait loci (QTLs) for heading date and other major agronomic traits in a recombinant inbred line (RIL) population derived from a cross between Koshihikari and Baegilmi. Analyses on 3 major QTLs for heading date and their underlying genes (Hd1, Hd16, and Ghd7) revealed their pleiotropic effects on culm length, panicle length, and head rice percentage. Additionally, Ghd7 exhibited pleiotropic effects on panicle number and grain size. Among 8 different types of allelic combinations of the 3 heading date genes, RILs carrying a single nonfunctional hd16 or ghd7 under the functional background of the other 2 genes (Hd1hd16Ghd7 and Hd1Hd16ghd7) showed potential for maintaining yield and quality-related traits while accelerating heading. These results provide valuable insights for fine-tuning heading dates in rice breeding programs.
Effects of Cumulative Cognitive Function Within 1 Year of Discharge on Subsequent Mortality Among Patients Hospitalized for Acute Heart Failure: A Nationwide Prospective Cohort Study
Authors: Wang Wei , Peng Yue , He Guangda , Li Yan , Liu Yanchen , Lei Lubi , Li Jingkuo , Pu Boxuan , Yu Yanwu , Zhang Lihua , Guo Yuanlin
Published: January 2024

Background

To examine the association between cumulative cognitive function and subsequent mortality among patients hospitalized for acute heart failure (AHF).

Methods

Based on a prospective cohort of patients hospitalized for AHF, cognitive function was measured using Mini-Cog test at admission, 1- and 12-month following discharge. Cumulative cognitive function was interpreted by cumulative Mini-Cog score and cumulative times of cognitive impairment. Outcomes included subsequent all-cause and cardiovascular mortality.

Results

1 454 patients hospitalized for AHF with median follow-up of 4.76 (interquartile range [IQR]: 4.18–5.07) years were included. Tertile 1 of cumulative Mini-Cog score had the highest risk of all-cause (hazard ratio [HR]: 1.52, 95% confidence interval [CI]: 1.14–2.03) and cardiovascular mortality (HR: 1.40, 95% CI: 1.02–1.93) compared with Tertile 3; patients with ≥2 times of cognitive impairment had the highest risk of all-cause (HR: 1.34, 95% CI: 1.03–1.73) and cardiovascular mortality (HR: 1.25, 95% CI: 0.93–1.67) compared with patients without any cognitive impairment. Cumulative Mini-Cog score provided the highest incremental prognostic ability in predicting all-cause (C-statistics: 0.64, 95% CI: 0.61–0.66) and cardiovascular mortality (C-statistics: 0.63, 95% CI: 0.60–0.67) risk on the basis of Get With The Guidelines-Heart Failure score.

Conclusions

Poor cumulative cognitive function was associated with increased risk of subsequent mortality and provided incremental prognostic ability for the outcomes among patients with AHF. Longitudinal assessment and monitoring of cognitive function among patients with AHF would be of great importance in identifying patients at greater risk of self-care absence for optimizing personal disease management in clinical practice.
Programmatic quality measures: a new model to promote surgical quality
Authors: Peters Xane , Sage Jill , Collins Courtney , Opelka Frank , Ko Clifford
Published: January 2024

Health care performance metrics are offered predominantly in terms of outcomes, processes, or structural components of health care delivery. However, measurement is limited by variability in data sources, definitions, and workarounds. The American College of Surgeons has recently developed a new type of performance metric known as a “programmatic measure”. These metrics align structures, processes, and outcomes to better coordinate quality measurement with support of frontline care teams. In this multifaceted way, these measures differ from current “single” measures such as targeting surgical site infection. The thematic focus of these measures and alignment of structure-resource components to support processes and outcomes also sets these measures apart from contemporary composite measures. Importantly, structural elements of these measures reflect minimum resources required for patient care, addressing staffing and resource barriers felt by local institutions in addressing numerous existing quality metrics. These metrics will streamline quality reporting to improve care navigation for patients. Clinicians will find more appropriately aligned goals and responsibilities, resulting in increased teamwork and communication. These measures are designed to address the current burdens of overabundant metrics, priority misalignment, and low resources in a patient-centric fashion to better align health care quality and measurement.
miR156b-targeted VvSBP8/13 functions downstream of the abscisic acid signal to regulate anthocyanins biosynthesis in grapevine fruit under drought
Authors: Guo Shuihuan , Zhang Meng , Feng Mingxin , Liu Guipeng , Torregrosa Laurent , Tao Xiaoqing , Ren Ruihua , Fang Yulin , Zhang Zhenwen , Meng Jiangfei , Xu Tengfei
Published: January 2024

Anthocyanins are the primary color components of grapevine berries and wines. In cultivation practices, a moderate water deficit can promote anthocyanin accumulation in red grape skins. Our previous study showed that abscisic acid (ABA) plays a key role in this process. Herein, we identified a microRNA, vv-miR156b, that is generated in grapevine berries in response to drought stress, along with increasing anthocyanin content and biosynthetic structural gene transcripts. In contrast, vv-miR156b short tandem target mimic (STTM) function-loss callus exhibits the opposite phenotype. Results from in vivo and in vitro experiments revealed that the ABA-signaling-regulated transcription factor VvAREB2 binds directly to the ABA-responsive element (ABRE) of the MIR156b promoter and activates miR156b expression. Furthermore, two miR156b downstream targets, VvSBP8 and VvSBP13, exhibited reduced grape anthocyanin content in their overexpressors but there was a contrary result in their CRISPR-edited lines, the decrease in anthocyanin content was rescued in miR156b and SBP8/13 double overexpressors. We further demonstrated that both VvSBP8 and VvSBP13, encoding transcriptional repressors, displayed sufficient ability to interact with VvMYC1 and VvMYBA1, thereby interfering with MYB-bHLH-WD (MBW) repeat transcriptional complex formation, resulting in the repression of anthocyanin biosynthesis. Our findings demonstrate a direct functional relationship between ABA signaling and the miR156-SBP-MBW complex regulatory module in driving drought-induced anthocyanin accumulation in grape berries.
A natural mutation in the promoter of the aconitase gene ZjACO3 influences fruit citric acid content in jujube
Authors: Liu Hanxiao , Zhao Xiangning , Bi Jingxin , Dong Xiaochang , Zhang Chunmei
Published: January 2024

Jujube (Ziziphus jujuba Mill.) is the most economically important fruit tree of the Rhamnaceae and was domesticated from wild or sour jujube (Z. jujuba Mill. var. spinosa Hu). During the process of domestication, there was a substantial reduction in the content of organic acids, particularly malate and citrate, which greatly influence the taste and nutritional value of the fruit. We previously demonstrated that ZjALMT4 is crucial for malate accumulation. However, the mechanism of citrate degradation in jujube remains poorly understood. In the present study, aconitase ZjACO3 was shown to participate in citric acid degradation in the cytoplasm through the GABA pathway. Interestingly, we discovered an E-box mutation in the ZjACO3 promoter (−484A > G; CAAGTG in sour jujube mutated to CAGGTG in cultivated jujube) that was strongly correlated with fruit citrate content; ‘A’ represented a high-citrate genotype and ‘G’ represented a low-citrate genotype. We developed and validated an ACO-based Kompetitive allele-specific PCR (KASP) marker for determining citric acid content. Yeast one-hybrid screening, transient dual-luciferase assays, and overexpression analyses showed that the transcription factor ZjbHLH113 protein directly binds to CAGGTG in the promoter of ZjACO3 in cultivated jujube plants, transcriptionally activating ZjACO3 expression, and enhancing citric acid degradation. Conversely, binding ability of the ZjbHLH113 protein to CAAGTG was weakened in sour jujube, thereby promoting citrate accumulation in the fruit. These findings will assist in elucidating the mechanism by which ZjACO3 modulates citrate accumulation in sour jujube and its cultivars.
Clinical effectiveness of robotic-assisted compared to open or video-assisted lobectomy in Germany: a real-world data analysis
Authors: Eichhorn Martin , Bernauer Eva , Rotärmel Andre , Heurich Manuel , Winter Hauke
Published: January 2024

OBJECTIVES

Despite robotic-assisted thoracic surgery (RATS) lobectomy being on the rise in Europe, the majority of lobectomies in Germany are still performed with an open or thoracoscopic [video-assisted thoracic surgery (VATS)] approach. Empirical evidence in favour of RATS lobectomy is inconsistent. This retrospective cohort study investigates the impact of RATS lobectomy compared with open thoracic surgery (OPEN) and VATS lobectomy on short-term outcomes in Germany using multicentre real-world data.

METHODS

Anonymized routine data from Germany from 2018 to 2020 were retrospectively analysed. These data were provided by 61 German hospitals. Propensity score matching with subsequent generalized linear models was performed for statistical analysis. Additionally, in order to test the robustness of the results, multivariable regression analyses with cluster-robust standard errors were used.

RESULTS

A total of 2498 patients with lobectomy were identified: in 1345 patients OPEN, in 983 VATS and 170 a RATS lobectomy was performed. RATS—compared to OPEN and VATS—reduced length of stay (LOS) by 28% or 4.2 days [confidence interval: 2.9; 5.4] and by 13% or 1.6 days [confidence interval: 0.2; 3.0], respectively. The risk of pneumonia was reduced by 5.3 percentage points in the RATS group compared to both OPEN and VATS (P = 0.07/0.01). RATS—compared to an open approach—reduces the risk of blood transfusions by 8.8 percentage points (P < 0.001) and LOS on the intensive care unit (P < 0.001).

CONCLUSIONS

This study provides strong support that RATS lobectomy outperforms OPEN or VATS lobectomy in terms of hospital LOS, and short-term in-hospital postoperative complications in the real-world scenario in Germany.
Enhancing residue degradation and methane production from active sludge: the role of conductive nanoparticles in anaerobic digestion systems
Authors: Alrawashdeh Khalideh Al bkoor , Al-Tabbal Jalal A , AL-Samrraie La’aly A , Al Bsoul Abeer , Al Zboon Kamel K
Published: January 2024

The effects of stepwise addition of conductive nanoparticles (n-C, n-Cu2O, n-ZnO and n-Al2O3) on anaerobic digestion (AD) performance, biogas and CH4 generation, and the removal efficiency of organic matter were thoroughly assessed. The addition of n-C and n-Al2O3 improved the removal efficiencies of total solid by 19.12% and 8.87%, volatile solid by 22.54% and 11.15%, total chemical oxygen demand by 13.6% and 6.27%, degradation efficacy by 4.87% and 2.3%, biogas yields by 20.62% and 8.27% and CH4 content by 11.49% and 8.63%, respectively. Contrarily, the addition of n-ZnO and n-Cu2O had a negative impact on AD performance and led to significant drops in the production of biogas of 34.3% and 57.3%, respectively.
Multiplicities and Dimensions in Enveloping Tensor Categories
Authors: Knop Friedrich
Published: January 2024

In a previous paper, semisimple tensor categories were constructed from certain regular Mal’cev categories. In this paper, we calculate the tensor product multiplicities and the categorical dimensions of the simple objects. This yields also the Grothendieck ring. The main tool is the subquotient decomposition of the generating objects.
Clinical Cytogenetics: Current Practices and Beyond
Authors: Mathew Mariam T , Babcock Melanie , Hou Ying-Chen Claire , Hunter Jesse M , Leung Marco L , Mei Hui , Schieffer Kathleen , Akkari Yassmine
Published: January 2024

Background

Throughout history, the field of cytogenetics has witnessed significant changes due to the constant evolution of technologies used to assess chromosome number and structure. Similar to the evolution of single nucleotide variant detection from Sanger sequencing to next-generation sequencing, the identification of chromosome alterations has progressed from banding to fluorescence in situ hybridization (FISH) to chromosomal microarrays. More recently, emerging technologies such as optical genome mapping and genome sequencing have made noteworthy contributions to clinical laboratory testing in the field of cytogenetics.

Content

In this review, we journey through some of the most pivotal discoveries that have shaped the development of clinical cytogenetics testing. We also explore the current test offerings, their uses and limitations, and future directions in technology advancements.

Cytogenetics methods, including banding and targeted assessments like FISH, continue to hold crucial roles in cytogenetic testing. These methods offer a rapid turnaround time, especially for conditions with a known etiology involving recognized cytogenetic aberrations. Additionally, laboratories have the flexibility to now employ higher-throughput methodologies to enhance resolution for cases with greater complexity.
Clinical Utility and Benefits of Comprehensive Genomic Profiling in Cancer
Authors: Tjota Melissa Yuwono , Segal Jeremy P , Wang Peng
Published: January 2024

Background

Comprehensive genomic profiling (CGP) with next-generation sequencing detects genetic alterations of hundreds of genes simultaneously and multiple molecular biomarkers with one test. In the personalized medicine era, CGP is increasingly used for cancer diagnosis, treatment selection, and prognosis prediction.

Content

In this review, we summarize the benefits of CGP, clinical utility of CGP, and challenges of setting up CGP in the clinical laboratories. Besides the genetic alterations identified in the cancer-related genes, other biomarkers such as tumor mutational burden, microsatellite instability, and homologous recombination deficiency are critical for initiating targeted therapy. Compared with conventional tests, CGP uses less specimen and shortens the turnaround time if multiple biomarkers need to be tested. RNA fusion assay and liquid biopsy are helpful additions to DNA-based CGP by detecting fusions/splicing variants and complementing tissue-based CGP findings, respectively.

Many previous hurdles for implementing CGP in the clinical laboratories have been gradually alleviated such as the decrease in sequencing cost, availability of both open-source and commercial bioinformatics tools, and improved reimbursement. These changes have helped to make CGP available to a greater population of cancer patients for improving characterization of their tumors and expanding their eligibility for clinical trials. Additionally, sequencing results of the hundreds of genes on CGP panels could be further analyzed to better understand the biology of various cancers and identify new biomarkers.
Cost Effectiveness of Genomic Population Health Screening in Adults: A Review of Modeling Studies and Future Directions
Authors: Wildin Robert S
Published: January 2024

Background

Detecting actionable health risks for genetic diseases prior to symptomatic presentation at population scale using genomic test technologies is a preventive health innovation being piloted in multiple locations. Standard practice is to screen for risks only in those with personal or family history of specific disease. Genomic population heath screening has proven feasible and potentially scalable. The value of this intervention in terms of economic benefit has been scientifically modeled by several groups.

Content

Eight recent cost-effectiveness modeling studies for high penetrance monogenic dominant diseases that used input parameters from 3 different countries are reviewed. Results and their uses in refining implementations are analyzed and the roles for laboratory medicine in facilitating success are discussed.

The reviewed studies generally found evidence for cost-effectiveness of genomic population health screening in at least a subset of their base case screening scenario. Sensitivity analyses identified opportunities for improving the likelihood of cost-effectiveness. On the whole, the modeling results suggest genomic population health screening is likely to be cost-effective for high penetrance disorders in younger adults, especially with achievable reductions in test cost effected partially through combining tests for individual disorders into one screening procedure. Policies founded on the models studied should consider limitations of the modeling methods and the potential for impacts on equity and access in the design and implementation of genomic screening programs.
Effect of the pelleting process on diet formulations with varying levels of crystalline amino acids and reducing sugars on digestibility in growing pigs
Authors: Dunmire Kara M , Lopez Diego A , Zhang Yiqin , Jones Cassandra K , Li Yonghui , Woodworth Jason C , Goodband Robert D , Tokach Michael D , Stark Charles R , Stein Hans H , Paulk Chad B
Published: January 2024

The objective of this experiment was to determine the effects of pelleting on the standardized ileal digestibility (SID) of amino acids (AA) and crude protein (CP) in diets with or without increased concentrations of free AA and reducing sugars (RS). Eight individually housed, ileal cannulated barrows (initially 31.4 kg) were allotted to an 8 × 8 Latin square with eight diets and eight 7-d periods with ileal digesta collected on days 6 and 7. Treatments were arranged in a 2 × 2 × 2 factorial with the main effects of diet form (mash or pellet), crystalline AA (low or high), or RS (low or high), provided by distillers dried grains with solubles and bakery meal. Diets were pelleted to achieve a hot pellet temperature of 85 to 88 °C. Data were analyzed as a Latin square design using the GLIMMIX procedure of SAS 9.4. A feed form × RS interaction (P < 0.026) for SID of tryptophan was observed. Feeding pelleted low RS diets increased SID of tryptophan compared with mash high and low RS diets, and pelleted high RS diets. For the main effects of feed form, the SID of total AA, CP, and indispensable AA was greater (P < 0.042) in pelleted diets compared with mash diets. For the main effects of crystalline AA, pigs fed high crystalline AA had increased (P = 0.007) SID of tryptophan and decreased (P = 0.050) SID of histidine compared with those fed low crystalline AA diets. For the main effects of RS, high RS diets had decreased (P < 0.05) SID of total AA, CP, and indispensable AA compared with low RS diets. In conclusion, pelleting diets increased AA digestibility, and pelleting diets with increased crystalline AA or RS did not affect the improvement in AA digestibility from pelleting. Diets formulated with high crystalline AA had increased SID of tryptophan. Formulating diets with high RS resulted in decreased AA digestibility compared with corn–soybean meal-based diets.
Continuity of Radiologists Between Diagnostic Breast Imaging and Image-Guided Breast Biopsy: Impact on Patient-Reported Biopsy Morbidity Experiences
Authors: McLaughlin Carol , Moorman Sarah E H , Yin Chen , Shankar Prasad R , Davenport Matthew S , Neal Colleen H , Pinsky Renee W , Pujara Akshat C
Published: January 2024

Objective

To determine whether continuity of care between diagnostic breast imaging and subsequent image-guided breast biopsy could reduce patient-reported biopsy-related morbidity.

Methods

This was a prospective, pragmatically randomized, 2-arm health utilities analysis of 200 women undergoing diagnostic breast imaging followed by US- or stereotactic-guided breast biopsy at a single quaternary care center from September 3, 2019, to April 10, 2023. Breast biopsy–naive women with a BI-RADS 4 or 5 finding at diagnostic imaging were randomly scheduled for the typically first available biopsy appointment. One day after biopsy, enrolled patients were administered the Testing Morbidities Index (TMI). The primary outcome was the difference in TMI summary utility scores in patients who did vs did not have the same radiologist perform diagnostic imaging and biopsy.

Results

Response rates were 63% (100/159) for the different radiologist cohort and 71% (100/140) for the same radiologist cohort; all respondents answered all questions in both arms. Mean time to biopsy was 7 ± 6 days and 10 ± 9 days, and the number of participating radiologists was 11 and 18, respectively. There was no difference in individual measured domains (pain, fear, or anxiety before procedure; pain, embarrassment, fear, or anxiety during procedure; mental or physical impact after procedure; all P >.00625) or in overall patient morbidity (0.83 [95% CI, 0.81–0.85] vs 0.82 [95% CI: 0.80–0.84], P = .66).

Conclusion

Continuity of care between diagnostic breast imaging and image-guided breast biopsy did not affect morbidity associated with breast biopsy, suggesting that patients should be scheduled for the soonest available biopsy appointment rather than waiting for the same radiologist.
Synovium and infrapatellar fat pad share common mesenchymal progenitors and undergo coordinated changes in osteoarthritis
Authors: Li Jun , Gui Tao , Yao Lutian , Guo Hanli , Lin Yu-Lieh , Lu Jiawei , Duffy Michael , Zgonis Miltiadis , Mauck Robert , Dyment Nathaniel , Zhang Yejia , Scanzello Carla , Seale Patrick , Qin Ling
Published: January 2024

Osteoarthritis (OA) affects multiple tissues in the knee joint, including the synovium and intra-articular adipose tissue (IAAT) that are attached to each other. However, whether these two tissues share the same progenitor cells and hence function as a single unit in joint homeostasis and diseases is largely unknown. Single-cell transcriptomic profiling of synovium and infrapatellar fat pad (IFP), the largest IAAT, from control and OA mice revealed five mesenchymal clusters and predicted mesenchymal progenitor cells (MPCs) as the common progenitors for other cells: synovial lining fibroblasts (SLFs), myofibroblasts (MFs), and preadipocytes 1 and 2. Histologic examination of joints in reporter mice having Dpp4-CreER and Prg4-CreER that label MPCs and SLFs, respectively, demonstrated that Dpp4+ MPCs reside in the synovial sublining layer and give rise to Prg4+ SLFs and Perilipin+ adipocytes during growth and OA progression. After OA injury, both MPCs and SLFs gave rise to MFs, which remained in the thickened synovium at later stages of OA. In culture, Dpp4+ MPCs possessed mesenchymal progenitor properties, such as proliferation and multilineage differentiation. In contrast, Prg4+ SLFs did not contribute to adipocytes in IFP and Prg4+ cells barely grew in vitro. Taken together, we demonstrate that the synovium and joint fat pad are one integrated functional tissue sharing common mesenchymal progenitors and undergoing coordinated changes during OA progression.
Genetic susceptibility and late bone outcomes in childhood acute lymphoblastic leukemia survivors
Authors: Nadeau Geneviève , Yazdanpanah Mojgan , Yazdanpanah Nahid , Forgetta Vincenzo , Girard Simon , Sinnett Daniel , Krajinovic Maja , Alos Nathalie , Manousaki Despoina
Published: January 2024

Childhood acute lymphoblastic leukemia (cALL) survivors are at increased risk for bone comorbidities, but accurate screening tools for such comorbidities are limited. Polygenic scores (PGS) could stratify cALL survivors for risk of long–term adverse bone outcomes. We evaluated 214 (51% female) cALL survivors from the Prévenir les Effets TArdifs de la LEucémie study (median age 21 yr). Bone mineral density (BMD) measurements were obtained using dual X–ray absorptiometry at the lumbar spine (LS-BMD), femoral neck (FN-BMD), and total body (TB-BMD), and vertebral fractures (VF) were documented using the vertebral deformity criterion. We computed a PGS for adult heel quantitative ultrasound speed of sound (gSOS), known to be associated with the risk of osteoporotic fracture, using imputed genotype data of the participants, and tested it for association with BMD Z-scores and VF risk, adjusting for clinical risk factors, and in sex and prognostic risk-stratified analyses. We found that a gSOS below the mean was associated with lower BMD in all three sites in univariate and multivariate models. In univariate analyses, 1 SD increase in gSOS conferred a 0.16 SD increase in LS-BMD (95% CI 0.005-0.31), whereas a gSOS above the mean was associated with a 0.31 SD higher LS-BMD (95% CI 0.008-0.61), a 0.36 SD higher TB-BMD (95% CI 0.06-0.67), and a 0.43 SD higher FN-BMD (95% CI 0.13-0.72). Models combining gSOS with clinical risk factors explained up to 16% of the variance of BMD phenotypes and obtained an area under the receiver operating characteristic curve for VF of 0.77 in subgroup analyses. Cranial radiation, high cumulative glucocorticoid doses, high risk group, and male sex were significant risk factors for lower BMD Z-scores. In conclusion, a PGS, in combination with clinical risk factors, could be used as a tool to risk stratify cALL survivors for treatment–related bone morbidity.
Bone loss after discontinuation of denosumab: the devil is in the details
Authors: Minisola Salvatore , Cipriani Cristiana , Colangelo Luciano , Pepe Jessica
Published: January 2024

Vignette

A 47-year-old postmenopausal woman with osteoporosis was treated with denosumab, which was discontinued due to side effects. She was therefore transitioned to a yearly intravenous infusion of zoledronic acid. An increase in bone turnover markers together with bone loss at the lumbar spine was observed before the second infusion, suggesting an overshooting of bone resorption due to denosumab discontinuation. On physical examination, the patient was restless and reported having lost about 10 kg since the last visit. A solitary left inferior thyroid nodule was noted on neck palpation. Circulating thyroid hormone levels were elevated, with suppressed thyroid-stimulating hormone. A thyroid scan showed increased uptake in the left inferior nodule with suppression of the remainder of the thyroid gland. A diagnosis of hyperthyroidism due to toxic adenoma was made. The patient was treated with radioactive iodine ablation, with consequent complete normalization of thyroid function. She continued yearly treatment with zoledronic acid. She remained clinically well with no further fractures. Bone turnover markers were appropriately suppressed and bone mineral density increased in the spine and hip. This case illustrates how the overshooting phenomenon following denosumab discontinuation may be compounded by the development of secondary conditions, which can result in suboptimal response to antiresorptive osteoporosis medications.
Burosumab vs conventional therapy in children with X-linked hypophosphatemia: results of the open-label, phase 3 extension period
Authors: Ward Leanne M , Högler Wolfgang , Glorieux Francis H , Portale Anthony A , Whyte Michael P , Munns Craig F , Nilsson Ola , Simmons Jill H , Padidela Raja , Namba Noriyuki , Cheong Hae Il , Sochett Etienne , Muroya Koji , Tanaka Hiroyuki , Pitukcheewanont Pisit , Gottesman Gary S , Biggin Andrew , Perwad Farzana , Chen Angel , Lawrence Merritt II John , Imel Erik A
Published: January 2024

In a randomized, open-label phase 3 study of 61 children aged 1–12 years old with X-linked hypophosphatemia (XLH) previously treated with conventional therapy, changing to burosumab every 2 weeks (Q2W) for 64 weeks improved the phosphate metabolism, radiographic rickets, and growth compared with conventional therapy. In this open-label extension period (weeks 64–88), 21 children continued burosumab Q2W at the previous dose or crossed over from conventional therapy to burosumab starting at 0.8 mg/kg Q2W with continued clinical radiographic assessments through week 88. Efficacy endpoints and safety observations were summarized descriptively for both groups (burosumab continuation, n = 6; crossover, n = 15). At week 88 compared with baseline, improvements in the following outcomes were observed in the burosumab continuation and crossover groups, respectively: mean (SD) RGI-C rickets total score (primary outcome), +2.11 (0.27) and +1.89 (0.35); mean (SD) RGI-C lower limb deformity score, +1.61 (0.91) and +0.73 (0.82); and mean (SD) height Z-score + 0.41 (0.50) and +0.08 (0.34). Phosphate metabolism normalized rapidly in the crossover group and persisted in the continuation group. Mean (SD) serum alkaline phosphatase decreased from 169% (43%) of the upper limit of normal (ULN) at baseline to 126% (51%) at week 88 in the continuation group and from 157% (33%) of the ULN at baseline to 111% (23%) at week 88 in the crossover group. During the extension period, treatment-emergent adverse events (AEs) were reported in all 6 children in the burosumab continuation group and 14/15 children in the crossover group. The AE profiles in the randomized and extension periods were similar, with no new safety signals identified. Improvements from baseline in radiographic rickets continued in the extension period among children with XLH who remained on burosumab. Children who crossed over from conventional therapy to burosumab demonstrated a rapid improvement in phosphate metabolism and improved rickets healing over the ensuing 22 weeks.
Comparison of physiological and behavioral nutrition-related factors in people with and without adolescent idiopathic scoliosis, from cohort data at 8 to 20 years
Authors: Ng Phoebe T T , Tucker Kylie , Zahir Syeda Farah , Izatt Maree T , Straker Leon , Claus Andrew
Published: January 2024

Nutrition-related variables including lower body mass index (BMI), lower bone mineral density (BMD), altered body composition and hormone levels have been reported in adolescent idiopathic scoliosis (AIS). The aims of this study were to determine if physiological and behavioral nutrition-related factors differ between people with and without AIS, and to quantify their relationship with AIS, in unbiased cohort sample. BMI, presence of an eating disorder, leptin, adiponectin, BMD, vitamin D, lean mass, and fat mass were compared between those with and without AIS at ages 8, 10, 14, 17, and 20 years, and multiple logistic regression was performed between these variables and AIS. Lower total body BMD (median, 1.0 g/cm2 vs 1.1 g/cm2; p = .03) and lean mass (median, 38.8 kg vs 46.0 kg; p = .04) at age 20 years were observed in those with AIS compared to those without scoliosis. At age 20, the odds of AIS were 3.23 times higher for adolescents with an eating disorder compared to those with no eating disorder (95% CI, 1.02–8.63) when adjusted for BMI. Every 1 kg/m2 increase in BMI decreased the odds of AIS by 0.88 times (95% CI, 0.76–0.98), after adjusting for eating disorder diagnosis. In conclusion, lower BMI in mid-adolescence and presence of eating disorder outcomes, lower BMD, and lower lean mass in late adolescence were associated with the presence of AIS. Current data do not explain the mechanisms for these associations but suggest that serum leptin, adiponectin, and vitamin D are unlikely to be contributing factors. Conclusive determination of the prevalence of eating disorders in AIS will require further studies with larger sample sizes.
The impact of COVID-19 on 2020 monthly incidence trends of primary brain and other CNS tumors
Authors: Cioffi Gino , Waite Kristin A , Price Mackenzie , Neff Corey , Kruchko Carol , Ostrom Quinn T , Barnholtz-Sloan Jill S
Published: January 2024

Background

To mitigate disease spread, restrictions implemented in the United States surrounding the COVID-19 pandemic created an environment that led to delays in cancer diagnosis. The data needed to accurately analyze the impact of the pandemic on brain and CNS tumor incidence has not been available until now. Utilizing incidence data from the Central Brain Tumor Registry of the United States (CBTRUS) we analyzed the impact of the COVID-19 pandemic on primary brain and other CNS tumor incidence for the first year of the pandemic.

Methods

Monthly age-adjusted incidence rates and incidence trends for 2019 and 2020 were determined for age at diagnosis, sex, race, ethnicity, diagnostic confirmation, behavior, tumor histopathology, and county-level urbanization. Monthly incidence rate ratios comparing 2020 and 2019 were evaluated for the same factors.

Results

Overall, there was a notable decrease in incidence rates in March–May 2020 when compared to 2019. These decreases were driven by nonmalignant tumors, with a 50% incidence decrease between March 2020 and 2019. Individuals who were Black had a larger incidence decrease in early 2020 than individuals who were White. Radiographically confirmed tumors saw larger incidence decreases than histologically confirmed tumors. There were no changes in monthly incidence of glioblastoma in 2020 compared to 2019.

Conclusions

These data provide evidence that disruptions in medical care, such as governmental and health care mandates, in response to the COVID-19 pandemic resulted in an overall decreased incidence of primary brain tumors in early 2020.
Exploring Alzheimer's disease: a comprehensive brain connectome-based survey
Authors: Zhang Lu , Qu Junqi , Ma Haotian , Chen Tong , Liu Tianming , Zhu Dajiang
Published: January 2024

Dementia is an escalating global health challenge, with Alzheimer's disease (AD) at its forefront. Substantial evidence highlights the accumulation of AD-related pathological proteins in specific brain regions and their subsequent dissemination throughout the broader area along the brain network, leading to disruptions in both individual brain regions and their interconnections. Although a comprehensive understanding of the neurodegeneration-brain network link is lacking, it is undeniable that brain networks play a pivotal role in the development and progression of AD. To thoroughly elucidate the intricate network of elements and connections constituting the human brain, the concept of the brain connectome was introduced. Research based on the connectome holds immense potential for revealing the mechanisms underlying disease development, and it has become a prominent topic that has attracted the attention of numerous researchers. In this review, we aim to systematically summarize studies on brain networks within the context of AD, critically analyze the strengths and weaknesses of existing methodologies, and offer novel perspectives and insights, intending to serve as inspiration for future research.
Mitochondrial Outer Membrane Translocase MoTom20 Modulates Mitochondrial Morphology and Is Important for Infectious Growth of the Rice Blast Fungus Magnaporthe oryzae
Authors: Wu Shuang , Zhang Ying , Xu Lele , Zhang Haibo , Li Yuhe , Yang Leiyun , Zhang Zhengguang , Zhang Haifeng
Published: January 2024

Mitochondria are highly dynamic organelles that constantly change their morphology to adapt to the cellular environment through fission and fusion, which is critical for a cell to maintain normal cellular functions. Despite the significance of this process in the development and pathogenicity of the rice blast fungus Magnaporthe oryzae, the underlying mechanism remains largely elusive. Here, we identified and characterized a mitochondrial outer membrane translocase, MoTom20, in M. oryzae. Targeted gene deletion revealed that MoTom20 plays an important role in vegetative growth, conidiogenesis, penetration, and infectious growth of M. oryzae. The growth rate, conidial production, appressorium turgor, and pathogenicity are decreased in the Δ Motom20 mutant compared with the wild-type and complemented strains. Further analysis revealed that MoTom20 localizes in mitochondrion and plays a key role in regulating mitochondrial fission and fusion balance, which is critical for infectious growth. Finally, we found that MoTom20 is involved in fatty-acid utilization, and its yeast homolog ScTom20 is able to rescue the defects of Δ Motom20 in mitochondrial morphology and pathogenicity. Overall, our data demonstrate that MoTom20 is a key regulator for mitochondrial morphology maintenance, which is important for infectious growth of the rice blast fungus M. oryzae.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .