bluuebunny/crossref_metadata_2025_split huggingface dataset:
Forages and pastures symposium: forage biodegradation: advances in ruminal microbial ecology
Authors: Osorio-Doblado A M , Feldmann K P , Lourenco J M , Stewart R L , Smith W B , Tedeschi L O , Fluharty F L , Callaway T R 
Published: May 2023

Abstract
The rumen microbial ecosystem provides ruminants a selective advantage, the ability to utilize forages, allowing them to flourish worldwide in various environments. For many years, our understanding of the ruminal microbial ecosystem was limited to understanding the microbes (usually only laboratory-amenable bacteria) grown in pure culture, meaning that much of our understanding of ruminal function remained a “black box.” However, the ruminal degradation of plant cell walls is performed by a consortium of bacteria, archaea, protozoa, and fungi that produces a wide variety of carbohydrate-active enzymes (CAZymes) that are responsible for the catabolism of cellulose, hemicellulose, and pectin. The past 15 years have seen the development and implementation of numerous next-generation sequencing (NGS) approaches (e.g., pyrosequencing, Illumina, and shotgun sequencing), which have contributed significantly to a greater level of insight regarding the microbial ecology of ruminants fed a variety of forages. There has also been an increase in the utilization of liquid chromatography and mass spectrometry that revolutionized transcriptomic approaches, and further improvements in the measurement of fermentation intermediates and end products have advanced with metabolomics. These advanced NGS techniques along with other analytic approaches, such as metaproteomics, have been utilized to elucidate the specific role of microbial CAZymes in forage degradation. Other methods have provided new insights into dynamic changes in the ruminal microbial population fed different diets and how these changes impact the assortment of products presented to the host animal. As more omics-based data has accumulated on forage-fed ruminants, the sequence of events that occur during fiber colonization by the microbial consortium has become more apparent, with fungal populations and fibrolytic bacterial populations working in conjunction, as well as expanding understanding of the individual microbial contributions to degradation of plant cell walls and polysaccharide components. In the future, the ability to predict microbial population and enzymatic activity and end products will be able to support the development of dynamic predictive models of rumen forage degradation and fermentation. Consequently, it is imperative to understand the rumen’s microbial population better to improve fiber degradation in ruminants and, thus, stimulate more sustainable production systems.
Diagnosis of Multisystem Inflammatory Syndrome in Children by a Whole-Blood Transcriptional Signature
Authors: Jackson Heather R , Miglietta Luca , Habgood-Coote Dominic , D’Souza Giselle , Shah Priyen , Nichols Samuel , Vito Ortensia , Powell Oliver , Davidson Maisey Salina , Shimizu Chisato , Agyeman Philipp K A , Beudeker Coco R , Brengel-Pesce Karen , Carrol Enitan D , Carter Michael J , De Tisham , Eleftheriou Irini , Emonts Marieke , Epalza Cristina , Georgiou Pantelis , De Groot Ronald , Fidler Katy , Fink Colin , van Keulen Daniëlle , Kuijpers Taco , Moll Henriette , Papatheodorou Irene , Paulus Stephane , Pokorn Marko , Pollard Andrew J , Rivero-Calle Irene , Rojo Pablo , Secka Fatou , Schlapbach Luregn J , Tremoulet Adriana H , Tsolia Maria , Usuf Effua , Van Der Flier Michiel , Von Both Ulrich , Vermont Clementien , Yeung Shunmay , Zavadska Dace , Zenz Werner , Coin Lachlan J M , Cunnington Aubrey , Burns Jane C , Wright Victoria , Martinon-Torres Federico , Herberg Jethro A , Rodriguez-Manzano Jesus , Kaforou Myrsini , Levin Michael 
Published: May 2023

Abstract

Background
To identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki disease (KD), bacterial infections, and viral infections.

Methods
Children presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020 and April 2021 were prospectively recruited. Whole-blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C (n = 38) to those from children with KD (n = 136), definite bacterial (DB; n = 188) and viral infections (DV; n = 138). Genes significantly differentially expressed (SDE) between MIS-C and comparator groups were identified. Feature selection was used to identify genes that optimally distinguish MIS-C from other diseases, which were subsequently translated into RT-qPCR assays and evaluated in an independent validation set comprising MIS-C (n = 37), KD (n = 19), DB (n = 56), DV (n = 43), and COVID-19 (n = 39).

Results
In the discovery set, 5696 genes were SDE between MIS-C and combined comparator disease groups. Five genes were identified as potential MIS-C diagnostic biomarkers (HSPBAP1, VPS37C, TGFB1, MX2, and TRBV11-2), achieving an AUC of 96.8% (95% CI: 94.6%–98.9%) in the discovery set, and were translated into RT-qPCR assays. The RT-qPCR 5-gene signature achieved an AUC of 93.2% (95% CI: 88.3%–97.7%) in the independent validation set when distinguishing MIS-C from KD, DB, and DV.

Conclusions
MIS-C can be distinguished from KD, DB, and DV groups using a 5-gene blood RNA expression signature. The small number of genes in the signature and good performance in both discovery and validation sets should enable the development of a diagnostic test for MIS-C.
A genomic score to predict local control among patients with brain metastases managed with radiation
Authors: Lamba Nayan , Cagney Daniel N , Catalano Paul J , Kim Dewey , Elhalawani Hesham , Haas-Kogan Daphne A , Wen Patrick Y , Wagle Nikhil , Aizer Ayal A 
Published: May 2023

AbstractBackgroundClinical predictors of local recurrence following radiation among patients with brain metastases (BrM) provide limited explanatory power. We developed a DNA-based signature of radiotherapeutic efficacy among patients with BrM to better characterize recurrence risk.MethodsWe identified 570 patients with 1487 BrM managed with whole-brain (WBRT) or stereotactic radiation therapy at Brigham and Women’s Hospital/Dana-Farber Cancer Institute (2013–2020) for whom next-generation sequencing panel data (OncoPanel) were available. Fine/Gray’s competing risks regression was utilized to compare local recurrence on a per-metastasis level among patients with versus without somatic alterations of likely biological significance across 84 genes. Genes with a q-value ≤ 0.10 were utilized to develop a “Brain-Radiation Prediction Score” (“Brain-RPS”).ResultsGenomic alterations in 11 (ATM, MYCL, PALB2, FAS, PRDM1, PAX5, CDKN1B, EZH2, NBN, DIS3, and MDM4) and 2 genes (FBXW7 and AURKA) were associated with decreased or increased risk of local recurrence, respectively (q-value ≤ 0.10). Weighted scores corresponding to the strength of association with local failure for each gene were summed to calculate a patient-level RPS. On multivariable Fine/Gray’s competing risks regression, RPS [1.66 (1.44–1.91, P &lt; .001)], metastasis-associated edema [1.60 (1.16–2.21), P = .004], baseline size [1.02 (1.01–1.03), P &lt; .001] and receipt of WBRT without local therapy [4.04 (2.49–6.58), P &lt; .001] were independent predictors of local failure.ConclusionsWe developed a genomic score to quantify local recurrence risk following brain-directed radiation. To the best of our knowledge, this represents the first study to systematically correlate DNA-based alterations with radiotherapeutic outcomes in BrM. If validated, Brain-RPS has potential to facilitate clinical trials aimed at genome-based personalization of radiation in BrM.
A Phase II Study of Neoadjuvant PLD/Cyclophosphamide and Sequentialnab-Paclitaxel Plus Dual HER2 Blockade in HER2-Positive Breast Cancer
Authors: Yang Ji-Xin , Yang Yu-Qing , Hu Wen-Yu , Yang Lu , Wu Jiang , Wen Xin-Xin , Yu Jing , Huang Mei-Ling , Xu Dong-Dong , Tie Dan-Chen , Wang Lei , Li Fan-Fan , Li Nan-Lin 
Published: May 2023

AbstractBackgroundNeoadjuvant trastuzumab/pertuzumab (HP) plus chemotherapy for HER2-positive breast cancer (BC) achieved promising efficacy. The additional cardiotoxicity still existed. Brecan study evaluated the efficacy and safety of neoadjuvant pegylated liposomal doxorubicin (PLD)/cyclophosphamide and sequential nab-paclitaxel based on HP (PLD/C/HP-nabP/HP).Patients and MethodsBrecan was a single-arm phase II study. Eligible patients with stages IIA-IIIC HER2-positive BC received 4 cycles of PLD, cyclophosphamide, and HP, followed by 4 cycles of nab-paclitaxel and HP. Definitive surgery was scheduled after 21 days for patients completing treatment or experiencing intolerable toxicity. The primary endpoint was the pathological complete response (pCR).ResultsBetween January 2020 and December 2021, 96 patients were enrolled. Ninety-five (99.0%) patients received 8 cycles of neoadjuvant therapy and all underwent surgery with 45 (46.9%) breast-conserving surgery and 51 (53.1%) mastectomy. The pCR was 80.2% (95%CI, 71.2%-87.0%). Four (4.2%) experienced left ventricular insufficiency with an absolute decline in LVEF (43%-49%). No congestive heart failure and ≥grade 3 cardiac toxicity occurred. The objective response rate was 85.4% (95%CI, 77.0%-91.1%), including 57 (59.4%) complete responses and 25 (26.0%) partial responses. The disease control rate was 99.0% (95%CI, 94.3%-99.8%). For overall safety, ≥grade 3 AEs occurred in 30 (31.3%) and mainly included neutropenia (30.2%) and asthenia (8.3%). No treatment-related deaths occurred. Notably, age of &gt;30 (P = .01; OR = 5.086; 95%CI, 1.44-17.965) and HER2 IHC 3+ (P = .02; OR = 4.398; 95%CI, 1.286-15.002) were independent predictors for superior pCR (ClinicalTrials.gov Identifier NCT05346107).ConclusionBrecan study demonstrated the encouraging safety and efficacy of neoadjuvant PLD/C/HP-nabP/HP, suggesting a potential therapeutic option in HER2-positive BC.
Immune-mediated diseases and risk of incident cardiovascular diseases: a prospective cohort study
Authors: Yu Yuetian , Sun Ying , Wang Yuying , Yu Yuefeng , Wang Bin , Chen Chi , Tan Xiao , Lu Yingli , Wang Ningjian 
Published: May 2023

Abstract

Objectives
Disorders of immune system may impact cardiovascular health; however, comprehensive study is lacking. We aimed to analyse the association of total and 20 individual immune-mediated diseases (IMDs) with risk of incident cardiovascular disease (CVD).

Methods
In this prospective cohort study, 414 495 participants (55.6% women; mean age 55.9 years) from UK Biobank with baseline assessment at 2006–10 were included. Among them, 21 784 participants had prevalent IMDs. Information on IMDs at baseline and incidence of CVDs during follow-up were recorded. Cox proportional hazard models were used to estimate the association between IMDs and CVDs risk.

Results
During the median follow-up of 12.1 years, there were 6506 cases of CVDs in participants with IMDs (29.9%) and 77 699 cases in those without IMDs (19.8%). After multivariable adjustment, participants with IMDs were significantly associated with an increased risk of total CVD [hazard ratio (HR) 1.57; 95% CI 1.52–1.61]. Among the 20 IMDs, 16 showed significant associations with CVD (all P &lt; 0.0025 after Bonferroni correction), with HR ranging from 1.34 (1.16–1.54) for celiac disease to 2.75 (2.10–3.61) for SLE. Participants with any IMD exposure had a higher risk of all individual CVD events, with HR ranging from 1.34 (1.14–1.58) for cerebral hemorrhage to 1.80 (1.54–2.11) for pericardium diseases. IMD duration &lt;5, 5–10 and &gt;10 years was associated with 55%, 59% and 56% increased risk of total CVD, respectively.

Conclusion
Total and individual IMDs were associated with an increased risk of overall CVDs. It is important to consider primary prevention of CVD in patients with IMD and dysregulation of immune system in the cardiovascular health.
Belgian court of appeal rules on inheritance tax treatment of a distribution by a Liechtenstein foundation
Authors: Appermont Niels 
Published: May 2023

Abstract
In a judgment of 5 April 2022, the Court of Appeal of Ghent ruled on a case regarding the qualification of a distribution by Liechtenstein Stiftung under Belgian inheritance taxation. While the constitution of and the transfer of assets to a private foundation, or even a distribution by a private foundation after the death of the founder normally does not trigger Belgian inheritance taxation, the Court ultimately ruled that the distributions should be subject to inheritance taxation, based on the (perceived) existence of an ‘agreement’ between the wife of the founder, who was designated as the ‘first beneficiary’ and the second beneficiaries. This judgment raises a number of questions regarding the correct interpretation of the relevant Belgian tax provisions and the correct application of the applicable Liechtenstein legislation. This article provides an in-depth assessment of this judgment and serves as a cautionary tale for any private foundation which has a founder and/or beneficiaries resident in Belgium.
Casein and pea enriched high-protein diet attenuates arsenic provoked apoptosis in testicles of adult rats
Authors: Biswas Sagnik , Pal Priyankar , Mondal Rubia , Mukhopadhyay Prabir Kumar 
Published: May 2023

Abstract
Arsenic toxicity is a major health issue that also threats male reproductive system leading to impairment of fertility. The antioxidant capacity of casein and pea enriched formulated high-protein diet (FHPD) is found to be effective in different toxicity management. The present study was endeavored to investigate the mitigatory aspect of FHPD on arsenic stimulated testicular apoptosis. Adult male rats were maintained on either normal diet as control (Gr I, n = 8) and arsenic (As2O3) treated at a dose of 3 mg/kg/rat/day (Gr II, n = 8) or on isocaloric FHPD as supplemented (Gr III, n = 8) with same dose of arsenic for 30 consecutive days. Testicular histomorphometry, spermatokinetics, testicular functional marker enzymes, serum gonadotrophins, oxidative stress markers, testicular deoxyribonucleic acid (DNA) damage, and apoptosis markers were evaluated to assess the reprotoxicity of arsenic and subsequent protection by FHPD. FHPD protected the histopathological alterations and also restored normal spermatogenesis. Altered enzymatic activities of testicular functional markers like lactate dehydrogenase, γ-glutamyl transferase, acid phosphatase, and alkaline phosphatase were also regularized. FHPD also reinstated the normal level of follicle stimulating hormone (FSH), luteinising hormone (LH), and also normalized the enzymatic activities of testicular glutathione peroxidase and glutathione reductase. Testicular DNA damage was also prevented by FHPD supplementation. Testicular apoptosis marked by the altered messenger ribonucleic acid and protein expression of apoptotic markers like Bax, Bcl-2, caspase 9, and caspase 3 were also attenuated upon FHPD supplementation along with diminution of arsenic accumulation in testicular tissues. FHPD not only mitigated the adverse effects of arsenic induced gonadotoxicity but also helped in sustaining the normal reproductive functions.
Comparison of Clinical Prediction Rules in Pre-school Aged Children With Septic Hip Arthritis Due to Different Pathogens
Authors: Hagedoorn Nienke N. , Olijve Laudi , Kang Laurant , Walls Tony , Davis Joshua 
Published: May 2023

Background:
Although differentiating between transient synovitis and septic hip arthritis is challenging, clinical prediction rules such as the Kocher criteria (KC) have been shown to help with the diagnosis of septic hip arthritis in children. Their performance in septic arthritis due to less virulent pathogens such as Kingella Kingae, however is unknown. We aimed to describe the performance of these clinical prediction rules in pre-school children with septic hip arthritis due to different pathogens. We hypothesised that the number of KC or modified KC met would be lower in children with septic hip arthritis caused by K. kingae, compared to those caused by Staphylococcus aureus.

Methods:
In this retrospective multicentre study conducted in Australia and New Zealand between 2012-2016, we included children with confirmed septic hip arthritis due to S. aureus (n=29), K. kingae (n=20), other pathogens (n=32), and no pathogen identified (n=48). We applied the KC (temperature, weight-bearing, erythrocyte sedimentation rate, white blood cell count) and the modified KC (C-reactive protein added) and assessed their sensitivity for septic hip arthritis, using cut offs of KC ≥ 3 and modified KC ≥ 4.

Results:
The score of the KC and the modified KC was not lower in K. kingae compared to S. aureus (P=0.27, P=0.21). In addition, both the sensitivity for the KC (S. aureus 18/29 (62.1%); K. kingae 12/20 (60.0%)), and for the modified KC (S. aureus 18/29 (62.1%); K. kingae 12/20 (60.0%)) did not differ between K. kingae and S. aureus. Of all children with septic hip arthritis, the sensitivity of both the KC and modified KC were 56.6% (95%CI 47.6-65.3).

Conclusions:
The clinical prediction rules had comparable performance in K. kingae infections to those caused by S. aureus. Concerningly, less than 60% of the children with confirmed septic hip arthritis met the cut-off values. These prediction rules lack sensitivity to rule-out septic hip arthritis in the early assessment of pre-school aged children with acute hip pain.

Level of Evidence:
Level III Diagnostic.
Hemiepiphysiodesis for Lower Extremity Coronal Plane Angular Correction in the Distal Femur and Proximal Tibia in Children With Achondroplasia
Authors: Makarewich Christopher A. , Zhang Emily , Stevens Peter M. 
Published: May 2023

Background:
Achondroplasia is the most prevalent form of skeletal dysplasia, affecting more than 250,000 individuals. Lower extremity angular deformities, particularly genu varum, are common in children with achondroplasia, often resulting in pain and limitation of function. The authors aim to determine the utility of lower extremity growth modulation with hemiepiphysiodesis in children with achondroplasia for correction of coronal plane deformities about the knee.

Methods:
The authors performed a retrospective chart review of a single center from 1/1/2000 to 12/31/2020 to identify pediatric patients with achondroplasia treated with hemiepiphysiodesis as their initial procedure at the distal femur and/or proximal tibia. Patients with adequate records and who had completed their treatment were included. Data collected included duration of treatment, complications, need for osteotomy, and radiographic measurements including initial and final mechanical axis deviation, knee mechanical axis zone, mechanical lateral distal femoral angle and medial proximal tibia angle.

Results:
Ten patients with 17 limbs met our criteria. Nine patients (15 limbs) were treated for genu varum and 1 patient (2 limbs) was treated for genu valgum. Prior to treatment, the mechanical axis fell in zone 3 in 59% of limbs and zone 2 in 41%. Average correction in mechanical axis deviation was 26.1 mm. Average change in mechanical lateral distal femoral angle was 10.3 degrees per limb, and average change in medial proximal tibia angle was 7.1 degrees per limb. Average treatment duration was 909 days. At final follow up, 81% (14/17) of limbs had the mechanical axis in zone 1, with the remaining 18% (3/17) in zone 2. No patient/limb underwent subsequent distal femur or proximal tibia osteotomy for coronal plane alignment.

Conclusions:
Children with achondroplasia can successfully be treated with hemiepiphysiodesis to correct coronal plane deformities at the distal femur and proximal tibia. Using this technique, no patient in our series required an osteotomy for genu varum/valgum.

Level of Evidence:
Therapeutic level IV, Case series.
Diverse Drug Classes Partition into Human Sweat: Implications for Both Sweat Fundamentals and for Therapeutic Drug Monitoring
Authors: Ruwe Theresa , White Evyn , Zebertavage Aidan S. , Runnoe David , Fay Dan , Daumeyer Henry , Tracy Timothy S. , Uchtman Kara Fay , Begtrup Gavi , Yuan Yuchan , Heikenfeld Jason , Buggele William A. 
Published: May 2023

Abstract:
Therapeutic drug monitoring to optimize drug therapy typically relies on the inconvenience of repeated plasma sampling. Sweat is a potential alternative biofluid convenient for sampling. However, limited information exists regarding the range of drugs excreted in sweat and their correlation with plasma concentrations. This study evaluated drugs in sweat and plasma of an ambulatory clinical cohort. Pilocarpine-induced sweat was collected from ambulatory participants at a single instance using an absorbent nylon mesh, followed by concurrent blood sampling for ratio and correlation analyses. In a model drug study, the pharmacokinetics of acetaminophen in sweat and plasma were compared. Of the 14 drugs and 2 metabolites monitored in the clinical study, all compounds were present in sweat and plasma; however, the sweat-to-plasma ratio varied substantially across the drugs. Opioids and methocarbamol demonstrated the highest concentrations in sweat, sometimes exceeding plasma concentrations. Selected antidepressants and muscle relaxants were also detected in sweat at a 2–10-fold dilution to the plasma. Others, such as gabapentin and pregabalin, were highly diluted (>30-fold) in sweat compared with plasma. Together, these data suggest that molecular attributes, specifically hydrophobicity (logP) and charge state at physiologic pH (7.4), enable reasonable prediction of sweat-to-plasma drug correlation. These findings demonstrated that sweat could be used as an alternative biofluid for therapeutic drug monitoring. The findings also suggest that although it has been broadly accepted that small hydrophobic molecules most likely have a strong plasma correlation, there is a small window of hydrophobicity and charge state that permits sweat partitioning.
Respiratory Coinfections in Children With SARS-CoV-2
Authors: Westbrook Adrianna , Wang Tingyu , Bhakta Kushmita , Sullivan Julie , Gonzalez Mark D. , Lam Wilbur , Rostad Christina A. 
Published: May 2023

Background:
As the transmission of endemic respiratory pathogens returns to prepandemic levels, understanding the epidemiology of respiratory coinfections in children with SARS-CoV-2 is of increasing importance.

Methods:
We performed a retrospective analysis of all pediatric patients 0–21 years of age who had a multiplexed BioFire Respiratory Panel 2.1 test performed at Children’s Healthcare of Atlanta, Georgia, from January 1 to December 31, 2021. We determined the proportion of patients with and without SARS-CoV-2 who had respiratory coinfections and performed Poisson regression to determine the likelihood of coinfection and its association with patient age.

Results:
Of 19,199 respiratory panel tests performed, 1466 (7.64%) were positive for SARS-CoV-2, of which 348 (23.74%) also had coinfection with another pathogen. The most common coinfection was rhino/enterovirus (n = 230, 15.69%), followed by adenovirus (n = 62, 4.23%), and RSV (n = 45, 3.507%). Coinfections with SARS-CoV-2 were most commonly observed in the era of Delta (B.1.617.2) predominance (190, 54.60%), which coincided with periods of peak rhino/enterovirus and RSV transmission. Although coinfections were common among all respiratory pathogens, they were significantly less common with SARS-CoV-2 than other pathogens, with exception of influenza A and B. Children <2 years of age had the highest frequency of coinfection and of detection of any pathogen, including SARS-CoV-2. Among children with SARS-CoV-2, for every 1-year increase in age, the rate of coinfections decreased by 8% (95% CI, 6–9).

Conclusions:
Respiratory coinfections were common in children with SARS-CoV-2. Factors associated with the specific pathogen, host, and time period influenced the likelihood of coinfection.