bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of HLA-DQA1*05 Genotype in Immunogenicity and Failure to Treatment with Tumour Necrosis Factor-alpha Antagonists in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis
Authors: Rodríguez-Alcolado Leticia , Grueso-Navarro Elena , Arias Ángel , Lucendo Alfredo J , Laserna-Mendieta Emilio J
Published: January 2024

Background

HLA-DQA1*05 carriage has been associated with an increased risk of immunogenicity in patients with immune-mediated inflammatory diseases treated with tumour necrosis factor-alpha [TNF-a] antagonists. Results have shown an inconsistent association with a loss of response [LOR] in patients with inflammatory bowel disease [IBD], which could be modified when using proactive optimisation and association with immunomodulatory drugs.

Aims

To define the association of HLA-DQA1*05 on anti-drug antibody development and loss of response [LOR] to anti-TNF-a in IBD.

Methods

We searched MEDLINE, EMBASE, and SCOPUS, for the period up to August 2023, to identify studies reporting the risk of immunogenicity and/or LOR in IBD patients with HLA-DQA1*05 genotype.

Results

A total of 24 studies comprising 12 papers, 11 abstracts and one research letter, with a total of 5727 IBD patients, were included. In a meta-analysis of 10 studies [2984 patients; 41.9% with HLA-DQA1*05 genotype], HLA-DQA1*05 carriers had higher risk of immunogenicity compared with non-carriers (risk ratio, 1.54; 95% confidence interval [CI], 1.23 − 1.94; I2 = 62%) [low certainty evidence]. Lack of therapeutic drug monitoring [TDM] increased immunogenicity in the presence of risk human leukocyte antigen [HLA] [risk ratio 1.97; 95% CI, 1.35 − 2.88; I2 = 66%], whereas proactive TDM revoked this association [very low certainty of evidence]. A meta-analysis of six studies [765 patients] found that risk for secondary LOR was higher among HLA-DQA1*05 carriers [hazard ratio 2.21; 95% CI, 1.69 − 2.88; I2 = 0%] [very low certainty evidence], although definition and time to assessment varied widely among studies.

Conclusion

HLA-DQA1*05 carriage may be associated with an increased risk of immunogenicity and secondary LOR in IBD patients treated with TNF-a antagonists.
Effects of sodium-glucose co-transporter 2 inhibitors on heart failure events in chronic kidney disease: a systematic review and meta-analysis
Authors: Theodorakopoulou Marieta P , Alexandrou Maria-Eleni , Tsitouridis Alexandros , Kamperidis Vasileios , Pella Eva , Xanthopoulos Andrew , Ziakas Antonios , Triposkiadis Filippos , Vassilikos Vassilios , Papagianni Aikaterini , Sarafidis Pantelis
Published: January 2024

Aims

Sodium-glucose co-transporter 2 (SGLT-2) inhibitors significantly reduce the risk for hospitalizations for heart failure (HF) in patients with diabetes, and HF; findings in patients with chronic kidney disease (CKD) are not uniform. We aimed to perform a meta-analysis exploring the effect of SGLT-2 inhibitors on HF events in patients with CKD and across subgroups defined by baseline kidney function.

Methods and results

A systematic search in major electronic databases was performed. Randomized controlled trials (RCTs) providing data on the effect of SGLT-2 inhibitors on the primary outcome, time to hospitalization or urgent visit for worsening HF in patients with prevalent CKD at baseline or across subgroups stratified by baseline estimated glomerular-filtration-rate (eGFR) were included. Twelve studies (n = 89,191 participants) were included in the meta-analysis. In patients with CKD, treatment with SGLT-2 inhibitors reduced the risk for HF events by 32% compared to placebo [hazard ratio (HR) 0.68; 95% confidence interval (CI) 0.63–0.73]. Reduction in HF events with SGLT-2 inhibitors was more prominent in patients with eGFR <60 ml/min/1.73 m2 (HR 0.68; 95% CI 0.62–0.74) than in those with eGFR ≥60 ml/min/1.73 m2 (HR 0.76; 95% CI 0.69–0.83). Subgroup analysis according to type of SGLT-2 inhibitor showed a consistent treatment effect across all studied agents (p-subgroup-analysis = 0.44). Sensitivity analysis including data from studies including only diabetic patients showed an even more pronounced effect in eGFR subgroup <60 ml/min/1.73 m2 (HR 0.62; 95% CI 0.54–0.70).

Conclusion

Treatment with SGLT-2 inhibitors led to a significant reduction in HF events in patients with CKD. Such findings may change the landscape of prevention of HF events in patients with advanced CKD.

PROSPERO Registration number CRD42022382857.
Morphological risk of acute type A aortic dissection in the mildly to moderately dilated aorta
Authors: Sun Lianjie , Li Haoyou , Feng Xiangzhen , Li Xiao , Wang Guoqing , Sun Jianchao , Zhang Xiaoming , Zhang Wenfeng , Wang Jianxun , Niu Zhaozhuo , Liu Gaoli
Published: January 2024

OBJECTIVES

This study aimed to analyse and determine the role of aortic length and curvature in the pathogenesis of acute type A aortic dissection (ATAAD) with ascending aortic diameters (AADs) <5 cm.

METHODS

We reviewed the clinical and imaging data of patients with ATAAD (n = 201) and ascending aortic dilation (n = 83). Thoracic aortic bending index (TABI) was used to quantify aortic curvature and analyse its role in ATAAD below the diameter risk threshold.

RESULTS

The AAD was <5.0 and <4.0 cm in 78% and 37% of patients with ATAAD, respectively. The median ascending aortic length (AAL) was 104.6 mm (Q1–Q3, 96.5–113.6 mm), and in 62.7% of patients, it was <11 cm. The median TABI was 14.99 mm/cm (Q1–Q3, 14.18–15.86 mm/cm). Patients with ATAAD and those with aortic dilation were matched for AAD, age, sex, height and other clinical factors. After matched, the dissection group had higher AALs (median, 102.9 mm; Q1–Q3, 96.0–112.5 mm vs median, 88.2 mm; Q1–Q3, 83.7–95.9 mm; P < 0.001) and TABI (median, 14.84 mm/cm; Q1–Q3, 14.06–15.83 mm/cm vs median, 13.55 mm/cm; Q1–Q3, 13.03–14.28 mm/cm; P < 0.001). According to the regression analysis, the area under the curve required to distinguish patients with ATAAD from those with aortic dilation was 0.831 in AAL, 0.837 in TABI and 0.907 when AAL was combined with TABI.

CONCLUSIONS

The patients with ATAAD had higher AAL and TABI than those with aortic dilation. The combination of TABI and AAL might be a potential morphological marker for determining ATAAD risk below the current aortic diameter risk threshold.
Modified transmanubrial approach for complicated type 1 cervical rib resection requiring subclavian artery reconstruction
Authors: Petrella Francesco , Rossi Luca , Gatto Arianna , Segramora Vittorio Maria , Del Bene Massimo , Froio Alberto
Published: January 2024

The transmanubrial musculoskeletal sparing approach (TMA) is commonly used for resecting apical lung tumours with vascular involvement. Non-neoplastic conditions which might require surgical exploration of the thoracic outlet include the ‘cervical rib’, a clinical condition consisting of an additional rib forming above the first rib and growing from the base of the neck just above the clavicle. Type 1 cervical rib—when a complete cervical rib articulates with the first rib or manubrium of the sternum—is the most challenging scenario where the subclavian artery can be damaged by continuous compression due to the narrow space between clavicle, first rib and supernumerary cervical rib, requiring prosthetic reconstruction of the involved tract. Here, we describe a modified TMA in which the incision in the neck is conducted posteriorly to the sternocleidomastoid muscle, thus allowing safe dissection of the superior and middle trunk of the brachial plexus.
A semblance-based microseismic event detector for DAS data
Authors: Porras Juan , Pecci Davide , Bocchini Gian Maria , Gaviano Sonja , De Solda Michele , Tuinstra Katinka , Lanza Federica , Tognarelli Andrea , Stucchi Eusebio , Grigoli Francesco
Published: January 2024

Distributed acoustic sensing (DAS) is becoming increasingly popular in microseismic monitoring operations. This data acquisition technology converts fibre-optic cables into dense arrays of seismic sensors that can sample the seismic wavefield produced by active or passive sources with a high spatial density, over distances ranging from a few hundred metres to tens of kilometres. However, standard microseismic data analysis procedures have several limitations when dealing with the high spatial (intersensor spacing up to submetre scale) sampling rates of DAS systems. Here, we propose a semblance-based seismic event detection method that fully exploits the high spatial sampling of the DAS data. The detector identifies seismic events by computing waveform coherence of the seismic wavefield along geometrical hyperbolic trajectories for different curvatures and positions of the vertex, which are completely independent from external information (i.e. velocity models). The method detects a seismic event when the coherence values overcome a given threshold and satisfies our clustering criteria. We first validate our method on synthetic data and then apply it to real data from the FORGE geothermal experiment in Utah, USA. Our method detects about two times the number of events obtained with a standard method when applied to 24 hr of data.
Simulation-based training for endoscopic mitral valve repair: the impact on basic surgical skills for placement of sutures at mitral valve annulus during 2-h training workshop
Authors: Checheili Sobbi Shokoufeh , Jung Yochun , Fillet Marvin , Bakhtiary Farhad , Maessen Jos G , Sardari Nia Peyman
Published: January 2024

OBJECTIVES

The aim of this study was to evaluate the impact of simulation-based training on surgical skills during 2-h learning labs during surgical annual meeting.

METHODS

During the 36th European Association of Cardiothoracic Surgery annual meeting a learning drylab for simulation-based training for endoscopic mitral valve repair was set up. For this purpose, a validated high-fidelity endoscopic mitral valve surgery simulator and a validated suturing map were used. The training lasted 2 h. Technical pre- and post-assessment were carried out based on time and accuracy to place a suture at the posterior mitral valve annulus. The suture had to be placed within 60 s. The suture was considered anatomically correct if it entered and exited the annulus at the designated place (on the posterior annulus) and accurate if placed within the right width (8–12 mm).

RESULTS

In total, 46 participants were included in this study, of whom 18 (38%) were experienced/staff surgeons, 23 (51%) fellows and 5 (11%) residents. Before the training, 48% of the participants failed to place any suture for pre-assessment. After completing the training, 100% of the participants succeeded in placing an anatomically correct suture. There was a significant improvement in the time taken [pre-assessment mean 45 (standard deviation: 25) s vs post-assessment mean 18 (standard deviation: 12) s, P < 0.001] and the accuracy to place a suture in the mitral valve annulus after completing the training (pre-assessment 32.6% vs post-assessment 65.2%, P < 0.001).

CONCLUSIONS

This study shows a significant improvement in endoscopic skills for mitral valve surgery after completing a 2-h training with a high-fidelity endoscopic mitral valve surgery simulator. This suggests that simulation trainings during scientific annual meetings are effective on surgical skills.
The cost of delay as risk measure in target-based multi-period portfolio selection models
Authors: Liu Jia , Chen Zhiping , Consigli Giorgio
Published: January 2024

Accepted by: Aris Syntetos

Increasingly, in recent years, the fund management industry has evolved towards so-called goal-based investing paradigms, under which investors are assumed to base their portfolio strategies on pre-specified targets to be attained in the future. A similar decision model is common in the wealth management and the life insurance industries where targets may be associated with long-term investment horizons and retirement planning problems. Based on this evidence, we propose in this article a novel risk measure explicitly focusing on the financial cost that may be associated with a delay in reaching those targets. We show that the definition of this risk measure is both rather natural and effective to capture investors’ risk preferences. A dynamic portfolio selection model is developed to assess the effectiveness of the risk measure from financial and risk control perspectives. The introduced risk measure has good properties and it is related to the Value-at-Risk with a given confidence level. Under sufficiently general statistical assumptions, we derive a closed form solution to a mean-risk formulation of the portfolio problem in which the cost of delay is taken as risk measure. Finally, a set of numerical tests validate the proposed portfolio selection model and show a set of comparative results with respect to a classical dynamic mean-variance model.
Escherichia coli CRISPR arrays from early life fecal samples preferentially target prophages
Authors: Dion Moïra B , Shah Shiraz A , Deng Ling , Thorsen Jonathan , Stokholm Jakob , Krogfelt Karen A , Schjørring Susanne , Horvath Philippe , Allard Antoine , Nielsen Dennis S , Petit Marie-Agnès , Moineau Sylvain
Published: January 2024

CRISPR–Cas systems are defense mechanisms against phages and other nucleic acids that invade bacteria and archaea. In Escherichia coli, it is generally accepted that CRISPR–Cas systems are inactive in laboratory conditions due to a transcriptional repressor. In natural isolates, it has been shown that CRISPR arrays remain stable over the years and that most spacer targets (protospacers) remain unknown. Here, we re-examine CRISPR arrays in natural E. coli isolates and investigate viral and bacterial genomes for spacer targets using a bioinformatics approach coupled to a unique biological dataset. We first sequenced the CRISPR1 array of 1769 E. coli isolates from the fecal samples of 639 children obtained during their first year of life. We built a network with edges between isolates that reflect the number of shared spacers. The isolates grouped into 34 modules. A search for matching spacers in bacterial genomes showed that E. coli spacers almost exclusively target prophages. While we found instances of self-targeting spacers, those involving a prophage and a spacer within the same bacterial genome were rare. The extensive search for matching spacers also expanded the library of known E. coli protospacers to 60%. Altogether, these results favor the concept that E. coli’s CRISPR–Cas is an antiprophage system and highlight the importance of reconsidering the criteria use to deem CRISPR–Cas systems active.
Overview of the 8th Social Media Mining for Health Applications (#SMM4H) shared tasks at the AMIA 2023 Annual Symposium
Authors: Klein Ari Z , Banda Juan M , Guo Yuting , Schmidt Ana Lucia , Xu Dongfang , Flores Amaro Ivan , Rodriguez-Esteban Raul , Sarker Abeed , Gonzalez-Hernandez Graciela
Published: January 2024

Objective

The aim of the Social Media Mining for Health Applications (#SMM4H) shared tasks is to take a community-driven approach to address the natural language processing and machine learning challenges inherent to utilizing social media data for health informatics. In this paper, we present the annotated corpora, a technical summary of participants’ systems, and the performance results.

Methods

The eighth iteration of the #SMM4H shared tasks was hosted at the AMIA 2023 Annual Symposium and consisted of 5 tasks that represented various social media platforms (Twitter and Reddit), languages (English and Spanish), methods (binary classification, multi-class classification, extraction, and normalization), and topics (COVID-19, therapies, social anxiety disorder, and adverse drug events).

Results

In total, 29 teams registered, representing 17 countries. In general, the top-performing systems used deep neural network architectures based on pre-trained transformer models. In particular, the top-performing systems for the classification tasks were based on single models that were pre-trained on social media corpora.

Conclusion

To facilitate future work, the datasets—a total of 61 353 posts—will remain available by request, and the CodaLab sites will remain active for a post-evaluation phase.
Topic modeling on clinical social work notes for exploring social determinants of health factors
Authors: Sun Shenghuan , Zack Travis , Williams Christopher Y K , Sushil Madhumita , Butte Atul J
Published: January 2024

Objective

Existing research on social determinants of health (SDoH) predominantly focuses on physician notes and structured data within electronic medical records. This study posits that social work notes are an untapped, potentially rich source for SDoH information. We hypothesize that clinical notes recorded by social workers, whose role is to ameliorate social and economic factors, might provide a complementary information source of data on SDoH compared to physician notes, which primarily concentrate on medical diagnoses and treatments. We aimed to use word frequency analysis and topic modeling to identify prevalent terms and robust topics of discussion within a large cohort of social work notes including both outpatient and in-patient consultations.

Materials and methods

We retrieved a diverse, deidentified corpus of 0.95 million clinical social work notes from 181 644 patients at the University of California, San Francisco. We conducted word frequency analysis related to ICD-10 chapters to identify prevalent terms within the notes. We then applied Latent Dirichlet Allocation (LDA) topic modeling analysis to characterize this corpus and identify potential topics of discussion, which was further stratified by note types and disease groups.

Results

Word frequency analysis primarily identified medical-related terms associated with specific ICD10 chapters, though it also detected some subtle SDoH terms. In contrast, the LDA topic modeling analysis extracted 11 topics explicitly related to social determinants of health risk factors, such as financial status, abuse history, social support, risk of death, and mental health. The topic modeling approach effectively demonstrated variations between different types of social work notes and across patients with different types of diseases or conditions.

Discussion

Our findings highlight LDA topic modeling’s effectiveness in extracting SDoH-related themes and capturing variations in social work notes, demonstrating its potential for informing targeted interventions for at-risk populations.

Conclusion

Social work notes offer a wealth of unique and valuable information on an individual’s SDoH. These notes present consistent and meaningful topics of discussion that can be effectively analyzed and utilized to improve patient care and inform targeted interventions for at-risk populations.
Determination of Seven Human Milk Oligosaccharides (HMOs) in Infant Formula and Adult Nutritionals: First Action 2022.07
Authors: Bénet Thierry , Frei Nathalie , Spichtig Véronique , Cuany Denis , Austin Sean
Published: January 2024

Background

Human milk oligosaccharides (HMOs) are important components of breast milk and may be responsible for some of the benefits of breastfeeding, including resistance to infections and the development of a healthy gut microbiota. Selected HMOs are now available for addition to infant formula, and suitable methods to control the dosing rate are needed.

Objective

To develop and validate a suitable method for the analysis of HMOs in infant formula.

Method

A method was developed for the determination of seven human milk oligosaccharides (2′-fucosyllactose, 3-fucosyllactose, 3′-sialyllactose, 6′-sialyllactose (6′SL), 2′,3-difucosyllactose, lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT)) in infant formula and adult nutritionals. The oligosaccharides are labeled at their reducing end with 2-aminobenzamide, separated by liquid chromatography and detected using a fluorescence detector. Maltodextrins are enzymatically hydrolyzed before analysis to prevent potential interference; likewise, an optional β-galactosidase treatment can be used to remove β-galactooligosaccharides. Fructooligosaccharides or polydextrose do not generally interfere with the analysis.

Results

The method has been validated in a single laboratory on infant formula and adult nutritionals. The seven HMOs were spiked into eight matrixes at three or four spike levels, giving a total of 176 data points. Recoveries were in the range of 90.9–109% in all cases except at the lowest spike level in one matrix (elemental formula), where the LNT recovery was 113%, the LNnT recovery was 111%, and the 6′SL recovery was 121%. Relative repeatabilities (RSD(r)) were in the range of 0.1–4.2%. The performance is generally within the requirements outlined in the Standard Method Performance Requirements (SMPR®) published by AOAC INTERNATIONAL.

Conclusions

The method developed is suitable for the determination of seven HMOs in infant formula and demonstrated good performance during single-laboratory validation.

Highlights

A method has been developed that is suitable for the determination of seven HMOs in infant formula.
Relevance of Secondary Enrichment in the Detection of Salmonella spp. in Food Samples by qPCR According to DIN 10135
Authors: Codony Francesc , Agustí Gemma , Barreto Lina , Asensio Daniel
Published: January 2024

Background

When detecting Salmonella spp. in food samples, unlike with culture-based procedures where there are solid standards, PCR techniques are generally dominated by commercial solutions, often backed by the conformity of reference organizations, and based on rigorous validation studies. The few independent standards that exist are not subject to revision and improvement to the same extent as the manufacturer’s methods. Moreover, since commercial networks do not promote them, they are implemented less in everyday practice. The German standard DIN 10135 is an example of this. In this method, before PCR detection, a primary enrichment (16–20 h) followed by a secondary selective enrichment of at least 6 h is needed. Nevertheless, it allows the possibility of only applying the first step if evidence of their correct operation is provided.

Objective

To evaluate how necessary is the secondary enrichment for DIN 10135 standard.

Methods

Short and complete enrichment steps were compared in the context of the evaluation of the limit of detection for 11 types of food. Additionally, a blind assay was performed with 75 food samples.

Results

The data show that a simple primary enrichment may be sufficient and that the second selective enrichment with the tested matrixes would not be strictly essential. The blind study obtained a 98.6% of trueness and precision of 100%.

Conclusions

At least for the end consumer products, a secondary enrichment of 6 h is not necessary for all the products tested.

Highlights

In the context of the DIN 10135 standard, the primary enrichment (16–20 h, 37 ± 1°C) can be enough for detecting Salmonella spp.
Comparison of Six Aptamer-Aptamer Pairs on Rapid Detection of SARS-CoV-2 by Lateral Flow Assay
Authors: Çam Derin Dilek , Gültekin Enes , Gündüz Elif , Otlu Barış
Published: January 2024

Background

SARS-CoV-2 is a threat to humanity. Both the spike (S) protein and its receptor binding domain (sRBD) are extensively used for rapid detection. Although real-time reverse transcription polymerase chain reaction (rRT-PCR) is mostly used method for the molecular detection of SARS-CoV-2, rapid assays for antigenic detection are always needed. Lateral flow assays (LFAs) are the most commonly used tests for this purpose, and aptamers having stability and long shelf life are used as capture reagents.

Objective

This study aimed to develop the LFAs based on the aptamer pairs for the antigenic detection of SARS-CoV-2 with the naked eye.

Method

Gold nanoparticles (AuNPs) were used as labels, and six sandwich models by three different aptamers were prepared using 4 μM and 8 μM probes and two kinds of membranes for developing the LFAs.

Results

The 8 μM probe concentration and M2 membrane showed the best recognition of both the synthetic sRBD and SARS-CoV-2 coming from the naso/oropharingeal swabs by designed LFAs as 100% sensitivity and 93.3% specificity compared to the antibody-detecting LFAs.

Conclusions

Our developed strip assays based on aptamer pairs recognized the target directly in 5–6 min with the naked eye. It was also concluded that aptamer pairs, membrane types, assay buffers, and probe concentrations have a significant role in the detection of SARS-CoV-2 by LFAs.

Highlights

The detection of SARS-CoV-2 in clinical samples was demonstrated with the best aptamer pairs, sensitively and selectively among the designed six aptamer pairs for LFAs. Developed LFAs can be an alternative method to the conventional antibody-based LFAs for SARS-CoV-2 detection.
Stability Study Through Water Activity Measurements for Dispensed Powdered Raw Materials
Authors: Prada-Ramírez Harold A , Montes-Tamara Juan Pablo , Rico-Jimenez Eduardo A , Fonseca Juan Camilo
Published: January 2024

Background

Holding times for raw materials are relevant since they enable us to understand the allowable time that a raw material can be kept under ideal storage conditions before the start of the manufacturing process without its quality attributes being affected. The quantification of water activity can be used as an indicator of the microbiological, physicochemical, and organoleptic stability of a specimen, since low water activity retards autohydrolysis and microbiological growth.

Objective

The main purpose of this investigation was to test the stability of powdered raw materials for a maximum holding time of 8 days through water activity measurements. Thus microbiological, physicochemical, and organoleptic measurements were carried out in parallel and simultaneously to experimentally establish a relationship between the status of the water activity of processed raw materials and the microbiological, physicochemical, and organoleptic results.

Methods

The raw materials were stored for a maximum holding time of 8 days, in accordance with United States Pharmacopeia monographs. For all the raw materials tested, water activity measurements were performed using the dew point chilled-mirror method on days 0, 3, and 8. On days 0 and 8, microbiological, physicochemical, and organoleptic assessments were performed.

Results

It was established that under these storage conditions, the processed raw materials exhibited water activity below 0.60 during the entire holding time. However, there were statistically significant differences in water activity levels between days 0, 3, and 8 (ANOVA P < 0.05). Despite observing statistically significant differences between days, the microbiological, physicochemical, and organoleptic features were within specification at those water activity levels below 0.60.

Conclusions

Water activity below 0.60 does not allow the growth of microorganisms, and the organoleptic and physicochemical features remain unperturbed. The results indicate that water activity can be used as an indicator of the microbiological load and chemical stability of the raw materials tested.

Highlights

This research provides evidence that corroborates that water activity status may be used as a reliable indicator for the microbiological burden and physicochemical features of pharmaceutical material during stability studies.
Effects of a second iron-dextran injection administered to piglets during lactation on differential gene expression in liver and duodenum at weaning
Authors: Pierce James L , Lyons J Wesley , Chevalier Tyler B , Lindemann Merlin D
Published: January 2024

Six female littermate piglets were used in an experiment to evaluate the mRNA expression in tissues from piglets given one or two 1 mL injections of iron dextran (200 mg Fe/mL). All piglets in the litter were administered the first 1 mL injection < 24 h after birth. On day 7, piglets were paired by weight (mean body weight = 1.72 ± 0.13 kg) and one piglet from each pair was randomly selected as control (CON) and the other received a second injection (+Fe). At weaning on day 22, each piglet was anesthetized, and samples of liver and duodenum were taken from the anesthetized piglets and preserved until mRNA extraction. differential gene expression data were analyzed with a fold change cutoff (FC) of |1.2| P < 0.05. Pathway analysis was conducted with Z-score cutoff of P < 0.05. In the duodenum 435 genes were significantly changed with a FC ≥ |1.2| P < 0.05. In the duodenum, Claudin 1 and Claudin 2 were inversely affected by + Fe. Claudin 1 (CLDN1) plays a key role in cell-to-cell adhesion in the epithelial cell sheets and was upregulated (FC = 4.48, P = 0.0423). Claudin 2 (CLDN2) is expressed in cation leaky epithelia, especially during disease or inflammation and was downregulated (FC = −1.41, P = 0.0097). In the liver, 362 genes were expressed with a FC ≥ |1.2| P < 0.05. The gene most affected by a second dose of 200 mg Fe was hepcidin antimicrobial peptide (HAMP) with a FC of 40.8. HAMP is a liver-produced hormone that is the main circulating regulator of Fe absorption and distribution across tissues. It also controls the major flows of Fe into plasma by promoting endocytosis and degradation of ferroportin (SLC4A1). This leads to the retention of Fe in Fe-exporting cells and decreased flow of Fe into plasma. Gene expression related to metabolic pathway changes in the duodenum and liver provides evidence for the improved feed conversion and growth rates in piglets given two iron injections preweaning with contemporary pigs in a companion study. In the duodenum, there is a downregulation of gene clusters associated with gluconeogenesis (P < 0.05). Concurrently, there was a decrease in the mRNA expression of genes for enzymes required for urea production in the liver (P < 0.05). These observations suggest that there may be less need for gluconeogenesis, and possibly less urea production from deaminated amino acids. The genomic and pathway analyses provided empirical evidence linking gene expression with phenotypic observations of piglet health and growth improvements.
Rehydration post-transport: duration of oral fluid therapy on behavior, biochemical measures of hydration, and health of neonatal dairy calves
Authors: Pempek Jessica A , England Zachary , Habing Gregory G , Niehaus Andrew
Published: January 2024

The objective of this study was to determine the impact of 0, 1, 2, or 3 d of oral electrolyte solutions (OES) following transport on calf behavior, biochemical measures of hydration, and subsequent health. Two cohorts of 60 Holstein bull calves ~3 to 7 d of age were included in this experiment. Calves (n = 30/treatment) were randomized to 1 of 4 treatments on arrival at a calf-raising facility: (1) 1-d OES, (2) 2-d OES, (3) 3-d OES, or (4) no OES (control). Calves were evaluated for signs of arthritis, depression, dehydration, diarrhea, fever, navel inflammation, and respiratory disease on arrival (day 0) and 1, 2, 3, and 7 d after arrival. Blood was obtained following each examination to assess biochemical measures of hydration, including serum electrolytes, glucose, hematocrit, lactate, pH, and serum total protein (STP). Calves were fitted with 3D accelerometers attached to the right hind leg along the metatarsus bone to continuously measure lying time. Linear regression models with Gaussian or Poisson link functions were used to test differences between treatments in blood parameters, as well as disease frequency and behavior, respectively. Calves spent the most time lying immediately post-transport (day 0); however, there was no effect of OES treatment on lying time. On arrival, 90% (95% CI: 84.6% to 95.4%) of calves had mild to moderate dehydration, and there was no significant difference in hydration status across treatments. Mildly dehydrated calves that received 1- and 2-d OES had higher STP concentration compared to the control. Moderately dehydrated calves that received 3- vs. 1-d OES had higher (101.4 vs. 93.7 mmol/L, respectively; P = 0.01) glucose concentration, and 3- vs. 2-d OES (101.4 vs. 96.2, respectively; P = 0.07) calves tended to have higher glucose concentration. The prevalence of failed transfer of passive immunity (STP < 5.1 g/dL) and hypoglycemia (glucose < 4.95 mmol/L) was 26.7% (18.6% to 34.7%) and 76.5% (68.7% to 84.2%), respectively. The frequency of moderate dehydration was lower for calves that received 2-d OES compared to the control (count ratio: 0.4; 0.2% to 0.8%; P = 0.009). These results underline the need for more research on rehydration strategies to help inform calf processing protocols. Future research should investigate preconditioning strategies to minimize the impact of marketing and transport on dairy calves. Continued nutritional-based research is also needed to better support calves’ recovery post-transport.
Effect of supplementing a Bacillus subtilis-based probiotic on performance, intestinal integrity, and serum antioxidant capacity and metabolites concentrations of heat-stressed growing pigs
Authors: González Fernanda , Cervantes Miguel , Morales Adriana , Valle José Alan , Camacho Reyna Lucero , ngélica Morales-Becerra A , Bernal Hugo , aría Mendoza Santa M , Htoo John K
Published: January 2024

Exposing pigs to heat stress (HS) seems to modify the intestinal microbiota which may compromise the integrity of the small intestine epithelia. Probiotics, live microorganisms, can help pigs to maintain a healthy intestinal environment. Eighty pigs (21.6 ± 3.4 kg body weight) exposed to HS or thermal neutral (TN) conditions were used to evaluate the effect of a Bacillus subtilis-based probiotic on performance, body temperature, and intestinal integrity. Treatments were: TN pigs fed a control diet without (TN-C) or with 1 × 106 CFU probiotic/g of feed (TN-P), and HS pigs fed a control without (HS-C) or with probiotic (HS-P). The control diet was formulated with wheat, soybean meal, and free amino acids (AA). Feed and water were freely available during the 21-d study. At completion, samples from duodenum, jejunum, and ileum were collected to analyze epithelial histology and tight junction protein expression; antioxidant activity, and free AA and metabolites in serum. Relative abundance of Lactobacillus, Bifidobacterium, Escherichia coli, and Bacillus in ileal content was analyzed. Ambient temperature in the TN room ranged from 19 to 25 °C, and in HS room from 30 to 38.5 °C. Intestinal temperature in HS-P pigs was lower than in HS-C pigs. Weight gain and feed intake reduced, but feed:gain and respiration rate increased in HS compared to TN pigs, regardless of diet (P < 0.01). Probiotic increased weight gain and improved feed:gain (P < 0.05) in both TN and HS pigs, but feed intake did not differ. Heat stress decreased villi height in jejunum and villi height:crypt depth in duodenum and jejunum (P < 0.05). Probiotic increased villi height in duodenum and ileum, and villi height:crypt depth in all small intestine segments (P < 0.05). Relative abundance of Lactobacillus and Bifidobacterium tended to reduce, and E. coli tended to increase (P < 0.10) in ileal content of HS-C pigs. Ileal relative abundance of Bacillus was higher (P < 0.01) in HS-P pigs than in HS-C and TN-C pigs. Cystathionine, homocysteine, hydroxylysine, α-amino-adipic acid, citrulline, α-amino-n-butyric acid, P-Ser, and taurine were higher in HS than in TN pigs (P < 0.05). These data confirm the negative effect of HS on performance, body temperature, and intestinal integrity of pigs. These data suggest that supplementing 1 × 106 CFU probiotic/g of feed based on Bacillus subtilis DSM 32540 may help to counteract the negative effects of HS on the performance and intestinal integrity of pigs.
The Effect of Using Virtual Reality During Burn Dressing on Pain, Anxiety and Fear Felt in Children: A Randomized Controlled Trial
Authors: Kılıç Ümmühan , Tural Büyük Esra
Published: January 2024

This study was conducted to determine the effect of using virtual reality (VR) during burn dressing on the level of fear, anxiety, and pain that children would experience. This randomized controlled trial was conducted in a pretest-posttest design. Randomization of the participants (n = 65) was performed with the block randomization method. Then, 33 children were included in the intervention and 32 children in the control group with simple sequential randomization. The study data were collected using the “Family and Child Personal Information Form,” “Physiological Parameters Registration Form,” “Wong–Baker Faces Pain Scale,” “Children’s Fear Scale,” and “Children’s Anxiety Meter-State.” The chi-square test, t-test, Shapiro–Wilk, mean, and percentile distributions were used for the data analysis. After dressing, the physiological parameters of the children who used VR were found to be within normal limits (HR: 108.48 ± 12.43, O2: 98.39 ± 1.14) compared to the children who did not use (HR: 117.38 ± 15.25, O2: 97.81 ± 1.35) (P < .05). After the dressing, children using VR (0.85 ± 1.23) were determined to have less fear than those who did not use them (3.03 ± 1.06), and similarly, children who used VR (2.64 ± 2.73) experienced less anxiety than those who did not use them (5.84 ± 2.26). When the pain levels were evaluated, the VR group (1.79 ± 2.04) was reported to feel less pain compared to the control group (5.50 ± 2.36). The VR used by children aged 5-10 years during burn dressing has been found to affect their physiological parameters and is effective in reducing fear, anxiety, and pain levels.
Inhibition of RANKL improves the skeletal phenotype of adenine-induced chronic kidney disease in mice
Authors: Metzger Corinne E , Kittaka Mizuho , LaPlant Alec N , Ueki Yasuyoshi , Allen Matthew R
Published: January 2024

Skeletal fragility and high fracture rates are common in CKD. A key component of bone loss in CKD with secondary hyperparathyroidism is high bone turnover and cortical bone deterioration through both cortical porosity and cortical thinning. We hypothesized that RANKL drives high bone resorption within cortical bone leading to the development of cortical porosity in CKD (study 1) and that systemic inhibition of RANKL would mitigate the skeletal phenotype of CKD (study 2). In study 1, we assessed the skeletal properties of male and female Dmp1-cre RANKLfl/fl (cKO) and control genotype (Ranklfl/fl; Con) mice after 10 wk of adenine-induced CKD (AD; 0.2% dietary adenine). All AD mice regardless of sex or genotype had elevated blood urea nitrogen and high PTH. Con AD mice in both sexes had cortical porosity and lower cortical thickness as well as high osteoclast-covered trabecular surfaces and higher bone formation rate. cKO mice had preserved cortical bone microarchitecture despite high circulating PTH as well as no CKD-induced increases in osteoclasts. In study 2, male mice with established AD CKD were either given a single injection of an anti-RANKL antibody (5 mg/kg) 8 wk post-induction of CKD or subjected to 3×/wk dosing with risedronate (1.2 μg/kg) for 4 wk. Anti-RANKL treatment significantly reduced bone formation rate as well as osteoclast surfaces at both trabecular and cortical pore surfaces; risedronate treatment had little effect on these bone parameters. In conclusion, these studies demonstrate that bone-specific RANKL is critical for the development of high bone formation/high osteoclasts and cortical bone loss in CKD with high PTH. Additionally, systemic anti-RANKL ligand therapy in established CKD may help prevent the propagation of cortical bone loss via suppression of bone turnover.
When Learning Negative Brand Associations Leads to Positive Evaluations of Effectiveness
Authors: Saint Clair Julian K , Cunha Marcus
Published: January 2024

Research on associative learning suggests that marketers can enhance consumer attitudes by repeatedly pairing their brands with pleasant or “positively-valenced” stimuli (e.g., attractive models, babies, cute animals) rather than unpleasant or “negatively-valenced” stimuli (e.g., garbage cans and disgusting insects)—an evaluative conditioning effect also known as affect transfer. In this research, we combine the associative learning and the goal pursuit literatures to show that the influence of affect transfer on brands depends on the mindset that is active at the time of judgment. Four experiments and one field study uniquely demonstrate that negatively-valenced brand pairings may become desirable when consumers have an instrumentality mindset, which increases attention to the instrumentality, or effectiveness, of a given consumption behavior. This pattern of results occurs due to a bidirectional association between unpleasantness and instrumentality, making a brand with negative associations seem more effective. Results are robust across contexts (health, entertainment, news) and persist regardless of whether the (un)pleasant images are within or adjacent to the advertisement. The effect attenuates when consumers have a weaker association between unpleasantness and instrumentality, and reverses when consumers are cued to focus on favorability (vs. instrumentality). Contributions and implications for associative learning and brand management are discussed.
Emergence of a multilocus mutator genotype in mutator Escherichia coli experimental populations under repeated lethal selection
Authors: Elgrail Mitra Maria , Sprouffske Kathleen , Dartey Jude O , Garcia Arlene M
Published: January 2024

Mutator alleles, which confer increased mutation rates, are known to spontaneously emerge and “hitchhike” to fixation in evolving asexual populations. Theory predicts that in an evolving asexual mutator population, a second mutator allele may spontaneously arise and hitchhike to fixation. Here, we describe an empirical test of the hypothesis of repeated hitchhiking. The starting population was a clonal strain of mutL−Escherichia coli whose mutation rate was 100-fold higher than wild type. We exposed the mutL− strain to a series of three antibiotics in increasing order of selective strength: fosfomycin, rifampicin, and streptomycin. Two independent replicates of the experiment were performed. As predicted, elevated mutation rates and enrichment for multilocus mutators (which bear more than one mutator allele) were observed in the end point populations of both experiments. DNA sequencing revealed an identical spontaneous 1-bp insertion in the mutator gene mutT in both end point populations. In the multilocus mutators, the causal relationship between the mutT− mutations and the increase in mutation rate was supported with mutT+ plasmid complementation tests. Surprisingly, when the experiment was repeated with the antibiotics deployed in decreasing order of selective strength, enrichment for multilocus mutators was not observed. Our data support the likelihood that the mutT− mutations rose to fixation in both populations, consistent with the hypothesis of repeated mutator hitchhiking. The escalation of mutation rates in asexual populations is relevant to multiple biological scenarios, including antibiotic resistance, host–pathogen interactions, and carcinogenesis.
Infants Receiving a Single Dose of Nirsevimab to Prevent RSV Do Not Have Evidence of Enhanced Disease in Their Second RSV Season
Authors: Dagan Ron , Hammitt Laura L , Seoane Nuñez Beatriz , Baca Cots Manuel , Bosheva Miroslava , Madhi Shabir A , Muller William J , Zar Heather J , Chang Yue , Currie Alexander , Grenham Amy , Shroff Manish , Takas Therese , Mankad Vaishali S , Leach Amanda , Villafana Tonya
Published: January 2024

To characterize nirsevimab in the prevention of RSV, children from the Phase 3 MELODY trial were followed through their second RSV season. No increase in medically attended RSV lower respiratory tract infections or evidence of antibody-dependent enhancement of infection or disease severity was found for nirsevimab vs placebo recipients.

Clinical Trial Registration: Clinicaltrials.gov, NCT03979313, https://clinicaltrials.gov/ct2/show/NCT03979313.
NuSTAR and Swift observations of two supergiant fast X-ray transients: AX J1841.0−0536 and SAX J1818.6−1703
Authors: Bozzo E , Ferrigno C , Romano P
Published: January 2024

Supergiant fast X-ray transients are wind-fed binaries hosting neutron star accretors, which display a peculiar variability in the X-ray domain. Different models have been proposed to explain this variability and the strength of the compact object magnetic field is generally considered a key parameter to discriminate among possible scenarios. We present here the analysis of two simultaneous observational campaigns carried out with Swift and NuSTAR targeting the supergiant fast X-ray transient sources AX J1841.0−0536 and SAX J1818.6−1703. A detailed spectral analysis is presented for both sources, with the main goal of hunting for cyclotron resonant scattering features that can provide a direct measurement of the neutron star magnetic field intensity. AX J1841.0−0536 was caught during the observational campaign at a relatively low flux. The source broad-band spectrum was featureless and could be well-described by using a combination of a hot blackbody and a power-law component with no measurable cut-off energy. In the case of SAX J1818.6−1703, the broad-band spectrum presented a relatively complex curvature which could be described by an absorbed cut-off power law (including both a cut-off and a folding energy) and featured a prominent edge at ∼7 keV, compatible with being associated to the presence of a ‘screen’ of neutral material partly obscuring the X-ray source. The fit to the broad-band spectrum also required the addition of a moderately broad (∼1.6 keV) feature centred at ∼14 keV. If interpreted as a cyclotron resonant scattering feature, our results would indicate for SAX J1818.6−1703 a relatively low-magnetized neutron star (∼1.2 × 1012 G).
New candidate hypervelocity red clump stars in the inner Galactic bulge
Authors: Luna A , Marchetti T , Rejkuba M , Leigh N W C , Alonso-García J , Valenzuela Navarro A , Minniti D , Smith L C
Published: January 2024

We search for high-velocity stars in the inner region of the Galactic bulge using a selected sample of red clump stars. Some of those stars might be considered hypervelocity stars (HVSs). Even though the HVSs ejection relies on an interaction with the supermassive black hole (SMBH) at the centre of the Galaxy, there are no confirmed detections of HVSs in the inner region of our Galaxy. With the detection of HVSs, ejection mechanism models can be constrained by exploring the stellar dynamics in the Galactic centre through a recent stellar interaction with the SMBH. Based on a previously developed methodology by our group, we searched with a sample of preliminary data from version 2 of the Vista Variables in the Via Lactea (VVV) Infrared Astrometric Catalogue (VIRAC2) and Gaia DR3 data, including accurate optical and near-infrared proper motions. This search resulted in a sample of 46 stars with transverse velocities larger than the local escape velocity within the Galactic bulge, of which four are prime candidate HVSs with high-proper motions consistent with being ejections from the Galactic centre. Adding to that, we studied a sample of reddened stars without a Gaia DR3 counterpart and found 481 stars with transverse velocities larger than the local escape velocity, from which 65 stars have proper motions pointing out of the Galactic centre and are candidate HVSs. In total, we found 69 candidate HVSs pointing away from the Galactic centre with transverse velocities larger than the local escape velocity.