bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of tamarind seed gum on the viscosity behavior, thermal properties, and extrusion characteristics of native corn starch
Authors: Wagner Caleb E. , Richter Jana K. , Dey Debomitra , Finnie Sean , Ganjyal Girish M.
Published: March 2023

Tamarind seed gum (TSG) is a cold‐swelling hydrocolloid with remarkable processing stability and starch synergy. Its use in direct expanded extruded foods has not been documented. The thermal and pasting viscosity properties of six TSG (0%, 0.5%, 1.0%, 2.5%, 5.0%, and 7.5% TSG) and native corn starch blends were characterized by differential scanning calorimetry and ViscoQuick, respectively. These same blends were extruded using a corotating twin‐screw extruder at four screw speeds (SSs) (150, 300, 450, and 600 rpm). System back pressure, motor torque, and specific mechanical energy (SME) were measured. Extrudate quality metrics, such as expansion ratio (ER), water absorption index (WAI), and water solubility index (WSI), were also measured. The pasting viscosities indicated that TSG inclusion increases viscosity but also makes the starch‐gum paste more susceptible to permanent shear degradation. The thermal analysis indicated that TSG inclusion narrowed the melting endotherms and lowered the energy required for melting (p < 0.05) at higher inclusion levels. Extruder back pressure, motor torque, and SME decreased with increasing TSG levels (p < 0.05) as the TSG effectively lowered the melt viscosity at high usage rates. The ER reached a maximum of 3.73 with a 2.5% TSG level extruded at 150 rpm (p < 0.05). The WAI of extrudates increased with TSG inclusion rate at equivalent SSs, whereas WSI behaved oppositely (p < 0.05). Small inclusions of TSG can improve the expansion properties of starch, whereas larger inclusions result in a lubrication effect that mitigates the shear‐induced depolymerization of starch.

Practical Application

The impact of cold‐water soluble hydrocolloids, including tamarind seed gum, on the extrusion process, is poorly understood. From this work, tamarind seed gum effectively modifies the viscoelastic and thermal characteristics of corn starch in a way that enhances the direct expansion characteristics of the starch during extrusion processing. The effect is more beneficial at lower gum inclusion levels as higher levels result in reduced capabilities to translate shear from the extruder into useful transformations of the starch polymers during processing. Small amounts of tamarind seed gum could be used to improve the quality of extruded starch puff snacks.
Geochronology and Geochemistry of the Early Paleozoic Ore‐host Volcanic Sequence in the Kalatag Area, East Tianshan, NW China: Implications for the Tectonic Evolution
Authors: ZHANG Zhenlong , YANG Fuquan , ZHOU Taofa , GENG Xinxia , ZHANG Zhixin , YANG Chengdong , QIU Zhanlin
Published: March 2023

The East Tianshan contains many late Paleozoic magmatic and polymetallic deposits. Recent studies demonstrate that the early Paleozoic volcanic rocks discovered in the northern region of East Tianshan can be subdivided into the Daliugou, Hongliuxia and Kalatag formations. Here, we report zircon U‐Pb ages of volcanic rocks and quartz diorite porphyry, together with whole‐rock geochemical and Sr‐Nd isotope data of early Paleozoic volcanic rocks, in order to investigate their petrogenesis and geodynamic setting. Zircon U‐Pb analyses of the rocks suggest that the Kalatag Formation formed at ca. 438–413 Ma. Geochemical characteristics of the early Paleozoic volcanic rocks exhibit typical subduction‐related features. They have high Mg#(44–75), positiveεNd(t) values (0.25–7.88), low87Sr/86Sr ratios (0.70457 to 0.70588) and young two‐stage Hf isotope model ages (551–446 Ma), consistent with a depleted mantle origin with limited crustal contamination. The basaltic andesite and andesite have relatively high MgO contents (6.1–9.4 wt%), suggesting that they belong to high‐magnesian andesites. They were most likely derived from the partial melting of mantle peridotite caused by the addition of fluids released by subducted oceanic slab. Based on regional geology, geochemical characteristics and previous studies, we infer that the southward subduction of the Junggar Ocean slab resulted in the generation of early Paleozoic volcanic rocks and arc setting‐related metallogenic systems in the Kalatag area.
Heterozygous ATP2A2 missense variant identified in a Shih Tzu with Darier disease
Authors: Kiener Sarah , Yang Ching , Rich Naomi , Jagannathan Vidhya , Mauldin Elizabeth A. , Leeb Tosso
Published: March 2023

Darier disease is caused by heterozygous loss of function variants in the ATP2A2 gene encoding the endoplasmic/sarcoplasmic reticulum Ca2+ pump ATP2A2. Defective intracellular calcium signaling in the epidermis results in a loss of desmosomal adhesion and the development of characteristic skin lesions. In this study, we investigated a Shih Tzu that developed erythematous papules on the ventrum and, over time, the dorsal neck and a nodule in the right ear canal with secondary ear infection. Histopathologic examination demonstrated discrete foci of acantholysis affecting suprabasal layers of the epidermis. Whole genome sequencing of the affected dog identified a heterozygous missense variant, p.N809H, affecting an evolutionarily conserved amino acid residue of the ATP2A2 protein. The highly characteristic clinical and histopathologic findings together with a plausible variant in the only known functional candidate gene establish the diagnosis of canine Darier disease in the studied dog and highlight the potential of genetic analyses as complementary diagnostic approach in veterinary medicine.
Familial hypercholesterolaemia in pregnancy: Australian case series and review
Authors: Nangrahary Mary , Graham Dorothy F. , Pang Jing , Barnett Wendy , Watts Gerald F.
Published: March 2023

Background

Familial hypercholesterolaemia (FH) is associated with a significant increase in the risk of premature coronary artery disease. Pregnancy is likely a vulnerable time for atherosclerosis progression, with a physiological rise in low‐density lipoprotein cholesterol (LDL‐C) further exaggerated by the discontinuation of cholesterol‐lowering therapy.

Materials and Methods

A retrospective review was undertaken of 13 women with familial hypercholesterolemia who were managed during pregnancy between 2007 and 2021 by a multidisciplinary team following individualised risk assessment.

Results

Overall, pregnancy outcomes were good, with no maternal or fetal complications, including congenital abnormalities, maternal cardiac events or hypertensive complications. Loss of statin treatment time ranged between 12 months and 3.5 years resulting from the accumulation of the preconception, pregnancy and lactation periods and was magnified in women having more than one pregnancy. Of seven women treated with cholestyramine, one developed abnormal liver function with an elevated international normalisation ratio which was corrected with vitamin K.

Conclusion

Pregnancy is associated with prolonged cessation of cholesterol‐lowering therapy, a concern with respect to the risk of coronary artery disease in FH. Continuation of statin therapy up to conception and even during pregnancy in patients at higher risk of cardiovascular disease may be justified, especially with increasing evidence supporting the safety of statin therapy during pregnancy. However, more long‐term maternal and fetal data are required for the routine use of statins during pregnancy. Guideline‐informed models of care covering family planning and pregnancy should be implemented for all women with FH.
Acute and chronic impacts of heat stress on planetary health
Authors: Sampath Vanitha , Shalakhti Omar , Veidis Erika , Efobi Jo Ann Ifeoma , Shamji Mohamed H. , Agache Ioana , Skevaki Chrysanthi , Renz Harald , Nadeau Kari C.
Published: March 2023

Heat waves are increasing in intensity, frequency, and duration causing significant heat stress in all living organisms. Heat stress has multiple negative effects on plants affecting photosynthesis, respiration, growth, development, and reproduction. It also impacts animals leading to physiological and behavioral alterations, such as reduced caloric intake, increased water intake, and decreased reproduction and growth. In humans, epidemiological studies have shown that heat waves are associated with increased morbidity and mortality. There are many biological effects of heat stress (structural changes, enzyme function disruption, damage through reactive oxygen or nitrogen species). While plants and animals can mitigate some of these effects through adaptive mechanisms such as the generation of heat shock proteins, antioxidants, stress granules, and others, these mechanisms may likely be inadequate with further global warming. This review summarizes the effects of heat stress on plants and animals and the adaptative mechanisms that have evolved to counteract this stress.
Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma: Results from a German real‐world cohort
Authors: Jost‐Brinkmann Fabian , Demir Münevver , Wree Alexander , Luedde Tom , Loosen Sven H. , Müller Tobias , Tacke Frank , Roderburg Christoph , Mohr Raphael
Published: March 2023

Background and Aims

Phase III trials have established atezolizumab plus bevacizumab as the novel standard of care for patients with unresectable hepatocellular carcinoma (HCC). However, these trials raised concerns regarding treatment efficacy in non‐viral HCC, and it remains unclear whether combination immunotherapy is safe and effective in patients with advanced cirrhosis.

Methods

One hundred patients with unresectable HCC initiated therapy with atezolizumab plus bevacizumab at our centre between January 2020 and March 2022. The control cohort consisted of 80 patients with advanced HCC who received either sorafenib (n = 43) or lenvatinib (n = 37) as systemic treatment.

Results

Overall survival (OS) and progression‐free survival (PFS) were significantly longer within the atezolizumab/bevacizumab group and comparable to phase III data. The benefits in terms of increased objective response rate (ORR), OS and PFS were consistent across subgroups, including non‐viral HCC (58%). The ROC‐optimised neutrophil‐to‐lymphocyte ratio (NLR) cut‐off of 3.20 was the strongest independent predictor of ORR and PFS. In patients with advanced cirrhosis Child–Pugh B, liver function was significantly better preserved with immunotherapy. Patients with Child–Pugh B cirrhosis showed similar ORR but shorter OS and PFS compared to patients with preserved liver function.

Conclusions

Atezolizumab plus bevacizumab showed good efficacy and safety in patients with unresectable HCC and partially advanced liver cirrhosis in a real‐world setting. Moreover, the NLR was able to predict response to atezolizumab/bevacizumab treatment and may guide patient selection.
COVID‐19 infection‐associated platelet and neutrophil activation is blunted by previous anti‐SARS‐CoV‐2 vaccination
Authors: Petito Eleonora , Franco Laura , Falcinelli Emanuela , Guglielmini Giuseppe , Conti Chiara , Vaudo Gaetano , Paliani Ugo , Becattini Cecilia , Mencacci Antonella , Tondi Francesca , Gresele Paolo ,   COVIR‐Study Investigators
Published: March 2023

The effectiveness of vaccination against SARS‐CoV‐2 in preventing COVID‐19 or in reducing severe illness in subjects hospitalized for COVID‐19 despite vaccination has been unequivocally shown. However, no studies so far have assessed if subjects who get COVID‐19 despite vaccination are protected from SARS‐CoV‐2‐induced platelet, neutrophil and endothelial activation, biomarkers associated with thrombosis and worse outcome. In this pilot study, we show that previous vaccination blunts COVID‐19‐associated platelet activation, assessed by circulating platelet‐derived microvesicles and soluble P‐selectin, and neutrophil activation, assessed by circulating neutrophil extracellular trap (NET) biomarkers and matrix metalloproteinase‐9, and reduces COVID‐19‐associated thrombotic events, hospitalization in intensive‐care units and death.
Bone marrow microenvironment disruption and sustained inflammation with prolonged haematologic toxicity after CAR T‐cell therapy
Authors: Kitamura Wataru , Asada Noboru , Naoi Yusuke , Abe Masaya , Fujiwara Hideaki , Ennishi Daisuke , Nishimori Hisakazu , Fujii Keiko , Fujii Nobuharu , Matsuoka Ken‐ichi , Yoshino Tadashi , Maeda Yoshinobu
Published: March 2023

Mechanisms of prolonged cytopenia (PC) after chimeric antigen receptor (CAR) T‐cell therapy, an emerging therapy for relapsed or refractory diffuse large B‐cell lymphoma, remain elusive. Haematopoiesis is tightly regulated by the bone marrow (BM) microenvironment, called the ‘niche’. To investigate whether alterations in the BM niche cells are associated with PC, we analysed CD271+ stromal cells in BM biopsy specimens and the cytokine profiles of the BM and serum obtained before and on day 28 after CAR T‐cell infusion. Imaging analyses of the BM biopsy specimens revealed that CD271+ niche cells were severely impaired after CAR T‐cell infusion in patients with PC. Cytokine analyses after CAR T‐cell infusion showed that CXC chemokine ligand 12 and stem cell factor, niche factors essential for haematopoietic recovery, were significantly decreased in the BM of patients with PC, suggesting reduced niche cell function. The levels of inflammation‐related cytokines on day 28 after CAR T‐cell infusion were consistently high in the BM of patients with PC. Thus, we demonstrate for the first time that BM niche disruption and sustained elevation of inflammation‐related cytokines in the BM following CAR T‐cell infusion are associated with subsequent PC.
Cutaneous reactions following COVID‐19 vaccination assessed by dermatologists: a single‐institutional study in Germany
Authors: Wang Rosi , Mathes Sonja , Claussen Carla , Biedermann Tilo , Brockow Knut
Published: March 2023

Background and objectives

Cutaneous reactions following COVID‐19 vaccination have been frequently described, whereas larger case series by dermatologists are lacking. This study assesses SARS‐CoV‐2 vaccination‐associated skin reactions, severity, treatment, course, eliciting vaccines, allergy test results and tolerance to revaccination.

Patients and methods

Single‐institutional, non‐interventional study of dermatologists assessing cutaneous manifestations in 83 patients in Germany.

Results

93 reactions were presented. Manifestations clustered into immediate (n = 51, 54.8%) and delayed hypersensitivity reactions (n = 10, 10.8%), chronic inflammatory skin diseases (n = 13, 14.0%), reactivation of latent herpes virus infection (pityriasis rosea/herpes zoster; n = 9; 9.7%) and others (n = 10, 10.8%). Vaccination was associated with new (76.3%) – mostly hypersensitivity reactions – or exacerbation of known skin diseases (23.7%), in this case predominantly chronic inflammatory skin diseases. Reactions occurred primarily within the first week (72.8%) and after first vaccination (62.0%). Treatment was required in 83.9% and hospitalization in 19.4%. In 48.8% revaccination led to recurrence of the same reactions. Disease was ongoing at last consultation in 22.6%, primarily in chronic inflammatory skin diseases. Allergy tests were performed in 15 patients (18.1%) and resulted negative.

Conclusions

It can be assumed that vaccination may trigger immune activation‐related reactions especially in those patients predisposed to develop respective skin diseases.
Clinical measures for children with cerebral palsy: Challenges and approaches
Authors: Rosenbaum Peter
Published: March 2023

This commentary is on the original article by Verheyen et al. on pages 1343–1356 of this issue.
Association between serum calcium level and type 2 diabetes: An NHANES analysis and Mendelian randomization study
Authors: Zhai Zhiyu , Deng Yun , He Yunbiao , Chen Li , Chen Xia , Zuo Lei , Liu Mingliang , Mao Minzhi , Li Sha , Hu Haiping , Chen Haiyan , Wei Yuan , Zhou Qin , Hao Guang , Peng Shuang
Published: March 2023

Aims

This study investigated the association between serum calcium levels and the prevalence of T2D using a cross‐sectional study and Mendelian randomization analysis.

Methods

Cross‐sectional data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Serum calcium levels were divided into three groups (low, medium and high groups) according to the tertiles. Logistic regression was used to estimate the association between serum calcium levels and T2D prevalence. Instrumental variables for serum calcium levels were obtained from the UK Biobank and a two‐sample MR analysis was performed to examine the causal relationship between genetically predicted serum calcium levels and the risk of T2D.

Results

A total of 39,645 participants were available for cross‐sectional analysis. After adjusting for covariates, participants in the high serum calcium group had significantly higher odds of T2D (OR = 1.18, 95% CI = 1.07, 1.30, p = 0.001) than those in the moderate group. Restricted cubic spline plots showed a J‐shaped curve relationship between serum calcium level and prevalence of T2D. Consistently, Mendelian randomization analysis showed that higher genetically predicted serum calcium levels were causally associated with a higher risk of T2D (OR = 1.16, 95% CI: 1.01, 1.33, p = 0.031).

Conclusions

The results of this study suggest that higher serum calcium levels are causally associated with a higher risk of T2D. Further studies are needed to clarify whether intervening in high serum calcium could reduce the risk of T2D.
Rate of change of J‐integral in creep‐fatigue condition
Authors: Tiwari Abhishek
Published: March 2023

The operational conditions in next generation power plants and other high temperature applications such as turbine blades in jet engines demand the component to perform under extreme conditions where metallic materials show time dependent deformation under cyclic loading conditions. Under creep‐fatigue loading condition, the crack tip is exposed to both time dependent and independent plastic deformation. Conventional crack characterizing parameters such as (C
)
has shown good correlation with dominant damage‐based crack velocity, (d
/d
)
. However, the true definition or prediction of crack driving forces under such scenario are vague due to limited theoretical validity of the conventional crack tip characterizing parameters, such as
or C
. In this work, the concept of configurational forces are applied for the first time to understand the creep‐fatigue crack growth behavior. The crack growth is simulated using node‐release technique and the configurational forces are calculated using post processing the finite element results for calculation of d
/d
.
The predictive value of the dynamic risk outcome scales (DROS) for recidivism in (forensic) clients with mild intellectual disabilities or borderline intellectual functioning
Authors: Delforterie M. J. , Hesper B. L. , Nijman H. L. I. , Korzilius H. P. L. M. , Turhan A. , Didden R.
Published: March 2023

Background

The dynamic risk outcome scales (DROS) was developed to assess treatment progress of clients with mild intellectual disability or borderline intellectual functioning using dynamic risk factors. We studied the predictive value of the DROS on various classifications and severity levels of recidivism.

Method

Data of 250 forensic clients with intellectual disabilities were linked to recidivism data from the Judicial Information Service in the Netherlands. Receiver operating characteristics (ROC) analyses were used to determine the predictive values.

Results

The DROS total score could not significantly predict recidivism. A DROS recidivism subscale predicted general, violent and other recidivism. These predictive values were comparable to those of a Dutch tool validated for risk assessment in the general forensic population.

Conclusions

The DROS recidivism subscale predicted various classifications of recidivism better than chance. At present, the DROS appears to have no added value beyond the HKT‐30 for the purpose of risk assessment.
Genome‐wide association studies for additive and dominance effects for body composition traits in commercial crossbred Piétrain pigs
Authors: Heidaritabar Marzieh , Bink Marco C. A. M. , Dervishi Elda , Charagu Patrick , Huisman Abe , Plastow Graham S.
Published: March 2023

Fat depth (FD) and muscle depth (MD) are economically important traits and used to estimate carcass lean content (LMP), which is one of the main breeding objectives in pig breeding programmes. We assessed the genetic architectures of body composition traits for additive and dominance effects in commercial crossbred Piétrain pigs using both 50 K array and sequence genotypes. We first performed a genome‐wide association study (GWAS) using single‐marker association analysis with a false discovery rate of 0.1. Then, we estimated the additive and dominance effects of the most significant variant in the quantitative trait loci (QTL) regions. It was investigated whether the use of whole‐genome sequence (WGS) will improve the QTL detection (both additive and dominance) with a higher power compared with lower density SNP arrays. Our results showed that more QTL regions were detected by WGS compared with 50 K array (n = 54 vs. n = 17). Of the novel associated regions associated with FD and LMP and detected by WGS, the most pronounced peak was on SSC13, situated at ~116–118, 121–127 and 129–134 Mbp. Additionally, we found that only additive effects contributed to the genetic architecture of the analysed traits and no significant dominance effects were found for the tested SNPs at QTL regions, regardless of panel density. The associated SNPs are located in or near several relevant candidate genes. Of these genes, GABRR2, GALR1, RNGTT, CDH20 and MC4R have been previously reported as being associated with fat deposition traits. However, the genes on SSC1 (ZNF292, ORC3, CNR1, SRSF12, MDN1, TSHZ1, RELCH and RNF152) and SSC18 (TTC26 and KIAA1549) have not been reported previously to our best knowledge. Our current findings provide insights into the genomic regions influencing composition traits in Piétrain pigs.
Development and validation of the fall‐related injury risk in nursing homes (INJURE‐NH) prediction tool
Authors: Duprey Matthew S. , Zullo Andrew R. , Gouskova Natalia A. , Lee Yoojin , Capuano Alyssa , Kiel Douglas P. , Daiello Lori A. , Kim Dae Hyun , Berry Sarah D.
Published: March 2023

Background

Existing models to predict fall‐related injuries (FRI) in nursing homes (NH) focus on hip fractures, yet hip fractures comprise less than half of all FRIs. We developed and validated a series of models to predict the absolute risk of FRIs in NH residents.

Methods

Retrospective cohort study of long‐stay US NH residents (≥100 days in the same facility) between January 1, 2016 and December 31, 2017 (n = 733,427) using Medicare claims and Minimum Data Set v3.0 clinical assessments. Predictors of FRIs were selected through LASSO logistic regression in a 2/3 random derivation sample and tested in a 1/3 validation sample. Sub‐distribution hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated for 6‐month and 2‐year follow‐up. Discrimination was evaluated via C‐statistic, and calibration compared the predicted rate of FRI to the observed rate. To develop a parsimonious clinical tool, we calculated a score using the five strongest predictors in the Fine‐Gray model. Model performance was repeated in the validation sample.

Results

Mean (Q1, Q3) age was 85.0 (77.5, 90.6) years and 69.6% were women. Within 2 years of follow‐up, 43,976 (6.0%) residents experienced ≥1 FRI. Seventy predictors were included in the model. The discrimination of the 2‐year prediction model was good (C‐index = 0.70), and the calibration was excellent. Calibration and discrimination of the 6‐month model were similar (C‐index = 0.71). In the clinical tool to predict 2‐year risk, the five characteristics included independence in activities of daily living (ADLs) (HR 2.27; 95% CI 2.14–2.41) and a history of non‐hip fracture (HR 2.02; 95% CI 1.94–2.12). Performance results were similar in the validation sample.

Conclusions

We developed and validated a series of risk prediction models that can identify NH residents at greatest risk for FRI. In NH, these models should help target preventive strategies.
Intracellular glucose starvation inhibits osteogenic differentiation in human periodontal ligament cells
Authors: Deng Xin , Kato Hirohito , Taguchi Yoichiro , Nakata Takaya , Umeda Makoto
Published: March 2023

Background

Periodontal ligament cells (PDLCs), as mesenchymal cells in the oral cavity, are closely linked to periodontal tissue regeneration. However, the effect of local glucose deficiency on periodontal tissue regeneration, such as immediately post‐surgery, remains unknown.

Objective

In the present study, we investigated the effect of a low‐glucose environment on the proliferation and osteogenic differentiation of PDLCs.

Materials and Methods

We used media with five glucose concentrations (100, 75, 50, 25, and 0 mg/dL) and focused on the effects of a low‐glucose environment on the proliferation, osteogenic differentiation, and autophagy of PDLCs. Additionally, we focused on changes in lactate production in a low‐glucose environment and investigated the involvement of lactate with AZD3965, a monocarboxylate transporter‐1 (MCT‐1) inhibitor.

Results

The low‐glucose environment inhibited PDLCs proliferation, migration, and osteogenic differentiation, and induced the expression of the autophagy‐related factors LC3 and p62. Lactate and ATP production were decreased under low‐glucose conditions. The addition of AZD3965 (MCT‐1 inhibitor) in normal glucose conditions caused a similar trend as in low‐glucose conditions on PDLCs.

Conclusion

Our results suggest lactate production through glucose metabolism in the osteogenic differentiation of PDLCs. A low‐glucose environment decreased lactate production, inhibiting cell proliferation, migration, and osteogenic differentiation and inducing autophagy in PDLCs.
Concentrations, pharmacokinetics and selected pharmacodynamics of morphine and its active metabolites following oral administration to horses
Authors: Poth Meghan K. M. , McKemie Daniel S. , Traynham Megan , Kass Philip H. , Knych Heather K.
Published: March 2023

The metabolism and pharmacokinetics of intravenous (i.v.) morphine in the horse have been described; however, administration of therapeutic doses has also been associated with neuroexcitation and adverse gastrointestinal effects. In this study, we hypothesized that oral administration would lead to comparable concentrations of morphine and its presumed active metabolite, morphine 6‐glucuronide (M6G) without the adverse effects associated with i.v. administration. Eight horses were administered a single i.v. dose of 0.2 mg/kg morphine and oral doses of 0.2, 0.6, and 0.8 mg/kg of morphine in a four‐way balanced crossover design, with a 2‐week washout period between doses. Concentrations of morphine and metabolites were determined, and pharmacokinetic parameters determined. Physiologic and behavioral outcomes including the number of steps taken, changes in heart rate, and gastrointestinal borborygmi were assessed. Oral administration of morphine resulted in higher concentrations of morphine metabolites, including M6G (Cmax: 11.6–37.8 ng/mL (0.6 mg/kg); 15.8–42.6 ng/mL (0.8 mg/kg)), compared with i.v. Bioavailability was 36.5%, 27.6% and 28.0% for 0.2, 0.6 and 0.8 mg/kg, respectively. Behavioral and physiologic changes were noted in all groups but were less prominent with oral compared with i.v. administration. Results of the current study are encouraging for further study, specifically anti‐nociceptive effects of morphine following oral administration.
Technologies, strategies, and cautions when deconvoluting genome‐wide association signals: FTO in focus
Authors: Pahl Matthew C. , Grant Struan F. A. , Leibel Rudolph L. , Stratigopoulos George
Published: March 2023

Genome‐wide association studies have revealed a plethora of genetic variants that correlate with polygenic conditions. However, causal molecular mechanisms have proven challenging to fully define. Without such information, the associations are not physiologically useful or clinically actionable. By reviewing studies of the FTO locus in the genetic etiology of obesity, we wish to highlight advances in the field fueled by the evolution of technical and analytic strategies in assessing the molecular bases for genetic associations. Particular attention is drawn to extrapolating experimental findings from animal models and cell types to humans, as well as technical aspects used to identify long‐range DNA interactions and their biological relevance with regard to the associated trait. A unifying model is proposed by which independent obesogenic pathways regulated by multiple FTO variants and genes are integrated at the primary cilium, a cellular antenna where signaling molecules that control energy balance convene.
Modulation of circulating cytokine production in alcoholic patients infected with Strongyloides stercoralis
Authors: Souza Alex Bruno da Silva , De Souza Joelma Nascimento , Oliveira Cíntia de Lima , Barreto Nilo Manoel Pereira Vieira , Costa Wéslei Almeida , Oliveira Ricardo Riccio , Teixeira Márcia Cristina Aquino , Soares Neci Matos
Published: March 2023

Strongyloidiasis control is associated with a Th2 immune response. However, alcohol ingestion plays an important role in modulating the immune system. The aim of this study is to evaluate the occurrence of Strongyloides stercoralis infection in alcoholic patients, the levels of circulating cytokines (IFN‐γ, IL‐2, IL‐4, IL‐5, IL‐10, IL‐15 and IL‐17), and its correlation with modulation of parasitic load in alcoholic individuals infected with S. stercoralis. A total of 336 alcoholic patients, treated at the Alcoholic Care and Treatment Center were included in this study. The cytokine levels were measured by a commercial ELISA in 80 sera divided into four groups with 20 individuals each: alcoholics infected (ASs+) and not infected (ASs‐) with S. stercoralis and non‐alcoholics infected (NASs+) and not infected (NASs‐) with the helminth. S. stercoralis frequency in alcoholic patients was 16.1% (54/336). The parasitic load varied from 1 to 546 larvae/g of faeces, median and interquartile range (IQR) of 9 and 1.0–62.5 larvae/g of faeces, while in non‐alcoholic individuals the parasitic load was less than 10 larvae/g of faeces. Levels of circulating IL‐4 were significantly higher in ASs+ when compared with NASs‐ group (p < .05). An inverse correlation between serum levels of IFN‐γ and parasitic load in alcoholic patients infected with S. stercoralis was observed (r = −601; p < 0.01). These results suggest that modulation of IFN‐γ production occurs in alcoholic individuals with high parasitic burden.
Association of faecal volatiles and steroids with behavioural expression during oestrous cycle of sheep (Ovis aries)
Authors: Yaseen Anjaleena , Hussain Tarique , Hameed Amjad
Published: March 2023

This study was investigated to determine the faecal volatiles, steroid hormones and their correlation with behavioural signs during oestrous cycle in sheep (Ovis aries). This experiment was monitored from pro‐oestrous to met‐oestrous phases for correlation of endocrine dependence biochemical constituents in faeces and blood to detection of oestrous biomarkers. Medroxyprogesterone acetate sponges were used for 8 days to bring uniformity of oestrus in sheep. Faeces were collected during different phases of cycle and subjected to determination of fatty acids, minerals, oestrogens and progesterone analysis. Likewise, blood samples were also obtained for enzymatic and no‐enzymatic antioxidants. The results revealed that faecal progesterone and oestrogen levels significantly increased during pro‐oestrous and oestrous phase, respectively (p < .05). The blood plasma enzymatic levels showed significant demarcation during the oestrous phase than other periods (p < .05). There were also reported marked variations in volatile fatty acids across different phases of the oestrous cycle. Interestingly, methyl octanoate, methyl cis‐10 pentadecenoate and methyl heptadecanoate volatiles were found to be specific to oestrus period. In addition, methyl hexanoate, methyl palmitoleate and methyl cis‐9 oleate were identified in met‐oestrus, indicating their possible role to be an oestrous biomarker. It is concluded that the pattern of volatile compounds and faecal steroids, in association with behavioural patterns, could be measured as a non‐invasive method of heat detection in sheep.
Successful treatment of 5‐fluorouracil toxicosis with hemodialysis
Authors: Henry Jessica S. , Buoncompagni Simona , Ross Sheri , Istvan Stephanie A. , Rizzo Kaila , Cowgill Larry D. , Press Saya A.
Published: March 2023

Objective

To describe the successful treatment of lethal dose 5‐fluorouracil (5‐FU) toxicosis using hemodialysis.

Case Summary

A 4‐month‐old intact female Golden Retriever was presented to the emergency department after ingesting 20 g of 5% 5‐FU cream. The puppy developed refractory seizures and became comatose with uncontrolled tonic–clonic convulsions. Because of the low molecular weight and minimal protein binding of 5‐FU, a single hemodialysis treatment was employed for detoxification. The puppy improved clinically posttreatment and was successfully discharged 3 days after admission. Postingestion leukopenia and neutropenia occurred but were responsive to treatment with filgrastim. The puppy is neurologically normal and has no lasting effects 1 year postingestion.

New or Unique Information Provided

To the authors’ knowledge, this is the first reported case in veterinary medicine of a potentially fatal 5‐FU ingestion that has been treated with intermittent hemodialysis.
Accuracy of data in abstracts of veterinary ophthalmology research articles published in peer‐reviewed journals
Authors: Handel Karin W. , Ofri Ron , Sebbag Lionel
Published: March 2023

Objective

Assess the accuracy of abstracts in published veterinary ophthalmology articles.

Procedures

Abstracts and contents of 204 original research articles in veterinary ophthalmology published in seven peer‐reviewed journals between 2016–2020 were reviewed. Abstracts were considered inconsistent if they contained data that were either missing from or inconsistent with corresponding data in the article's body. Each abstract was graded between 0 (inaccurate) to 3 (accurate), and each inconsistency was subjectively classified as minor or major. The influence of selected variables was assessed: journal, impact factor, year of publication, number of words in abstract, study type (prospective/retrospective), and characteristics of the corresponding author [institution (academia/private practice), country of domicile (native/non‐native English), number of publications].

Results

Most abstracts were accurate, with 1%, 4%, 9% and 86% receiving a score of 0, 1, 2 and 3, respectively. When detected, most inconsistencies were considered minor (77%). Although not statistically significant (p ≥ .130), the proportion of articles with a perfect score (=3) was higher in prospective (88%) vs. retrospective (81%) studies, academia (88%) vs. private practice (78%), and studies from corresponding authors domiciled in English (89%) vs. non‐English (83%) speaking countries. A significant but very weak (r = −0.15 to −0.19; p ≤ .034) negative correlation was found between accuracy score and number of words, as well as 1‐year and 5‐year impact factors.

Conclusions

Although relatively uncommon, data in abstracts that are inconsistent or missing from the article's body do occur in veterinary ophthalmology articles, and could adversely influence a reader's interpretation of study findings.
The role of systematics for understanding ecosystem functions: Proceedings of the Zoologica Scripta Symposium, Oslo, Norway, 25 August 2022
Authors: Bachmann Lutz , Beermann Jan , Brey Thomas , de Boer Hugo J. , Dannheim Jennifer , Edvardsen Bente , Ericson Per G. P. , Holston Kevin C. , Johansson Veronika A. , Kloss Paul , Konijnenberg Rebecca , Osborn Karen J. , Pappalardo Paula , Pehlke Hendrik , Piepenburg Dieter , Struck Torsten H. , Sundberg Per , Markussen Stine Svalheim , Teschke Katharina , Vanhove Maarten P. M.
Published: March 2023

On 25 August 2022, the Zoologica Scripta ‐ An International Journal of Systematic Zoology and the Norwegian Academy of Sciences and Letters arranged a symposium entitled ‘The role of systematics for understanding ecosystem functions’ in the Academy's premises in Oslo, Norway. The symposium aimed at offering a forum for exploring and discussing trends and future developments in the field of systematics. Eleven international experts contributed expertise on various issues related to global challenges, such as biodiversity assessments, databases, cutting‐edge analysis tools, and the consequences of the taxonomic impediment. Here, we compiled a multi‐author proceedings paper of the symposium contributions that are arranged in chapters and presents the content and the key conclusions of the majority of the presentations.
Indigenous people from Amazon show genetic signatures of pathogen-driven selection
Authors: Couto-Silva Cainã M. , Nunes Kelly , Venturini Gabriela , Araújo Castro e Silva Marcos , Pereira Lygia V. , Comas David , Pereira Alexandre , Hünemeier Tábita
Published: March 2023

Ecological conditions in the Amazon rainforests are historically favorable for the transmission of numerous tropical diseases, especially vector-borne diseases. The high diversity of pathogens likely contributes to the strong selective pressures for human survival and reproduction in this region. However, the genetic basis of human adaptation to this complex ecosystem remains unclear. This study investigates the possible footprints of genetic adaptation to the Amazon rainforest environment by analyzing the genomic data of 19 native populations. The results based on genomic and functional analysis showed an intense signal of natural selection in a set of genes related to
Trypanosoma cruzi
infection, which is the pathogen responsible for Chagas disease, a neglected tropical parasitic disease native to the Americas that is currently spreading worldwide.
A simple catch: Fluctuations enable hydrodynamic trapping of microrollers by obstacles
Authors: van der Wee Ernest B. , Blackwell Brendan C. , Balboa Usabiaga Florencio , Sokolov Andrey , Katz Isaiah T. , Delmotte Blaise , Driscoll Michelle M.
Published: March 2023

It is known that obstacles can hydrodynamically trap bacteria and synthetic microswimmers in orbits, where the trapping time heavily depends on the swimmer flow field and noise is needed to escape the trap. Here, we use experiments and simulations to investigate the trapping of microrollers by obstacles. Microrollers are rotating particles close to a bottom surface, which have a prescribed propulsion direction imposed by an external rotating magnetic field. The flow field that drives their motion is quite different from previously studied swimmers. We found that the trapping time can be controlled by modifying the obstacle size or the colloid-obstacle repulsive potential. We detail the mechanisms of the trapping and find two remarkable features: The microroller is confined in the wake of the obstacle, and it can only enter the trap with Brownian motion. While noise is usually needed to escape traps in dynamical systems, here, we show that it is the only means to reach the hydrodynamic attractor.
Rational polyelectrolyte nanoparticles endow preosteoclast-targeted siRNA transfection for anabolic therapy of osteoporosis
Authors: Zhang Zheng , Ding Peng , Meng Yichen , Lin Tao , Zhang Zhanrong , Shu Haoming , Ma Jun , Cohen Stuart Martien , Gao Yang , Wang Junyou , Zhou Xuhui
Published: March 2023

Targeted transfection of siRNA to preosteoclasts features the potential of anti-osteoporosis, yet challenge arises from the development of satisfied delivery vehicles. Here, we design a rational core-shell nanoparticle (NP) composed of cationic and responsive core for controlled load and release of small interfering RNA (siRNA) and compatible polyethylene glycol shell modified with alendronate for enhanced circulation and bone-targeted delivery of siRNA. The designed NPs perform well on transfection of an active siRNA (siDcstamp) that interferes Dcstamp mRNA expression, leading to impeded preosteoclast fusion and bone resorption, as well as promoted osteogenesis. In vivo results corroborate the abundant siDcstamp accumulation on bone surfaces and the enhanced trabecular bone mass volume and microstructure in treating osteoporotic OVX mice by rebalancing bone resorption, formation, and vascularization. Our study validates the hypothesis that satisfied transfection of siRNA enables preserved preosteoclasts that regulate bone resorption and formation simultaneously as potential anabolic treatment for osteoporosis.
Tissue-embedded stretchable nanoelectronics reveal endothelial cell–mediated electrical maturation of human 3D cardiac microtissues
Authors: Lin Zuwan , Garbern Jessica C. , Liu Ren , Li Qiang , Mancheño Juncosa Estela , Elwell Hannah L.T. , Sokol Morgan , Aoyama Junya , Deumer Undine-Sophie , Hsiao Emma , Sheng Hao , Lee Richard T. , Liu Jia
Published: March 2023

Clinical translation of stem cell therapies for heart disease requires electrical integration of transplanted cardiomyocytes. Generation of electrically matured human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) is critical for electrical integration. Here, we found that hiPSC-derived endothelial cells (hiPSC-ECs) promoted the expression of selected maturation markers in hiPSC-CMs. Using tissue-embedded stretchable mesh nanoelectronics, we achieved a long-term stable map of human three-dimensional (3D) cardiac microtissue electrical activity. The results revealed that hiPSC-ECs accelerated the electrical maturation of hiPSC-CMs in 3D cardiac microtissues. Machine learning–based pseudotime trajectory inference of cardiomyocyte electrical signals further revealed the electrical phenotypic transition path during development. Guided by the electrical recording data, single-cell RNA sequencing identified that hiPSC-ECs promoted cardiomyocyte subpopulations with a more mature phenotype, and multiple ligand-receptor interactions were up-regulated between hiPSC-ECs and hiPSC-CMs, revealing a coordinated multifactorial mechanism of hiPSC-CM electrical maturation. Collectively, these findings show that hiPSC-ECs drive hiPSC-CM electrical maturation via multiple intercellular pathways.
A self-attention–based neural network for three-dimensional multivariate modeling and its skillful ENSO predictions
Authors: Zhou Lu , Zhang Rong-Hua
Published: March 2023

Large biases and uncertainties remain in real-time predictions of El Niño–Southern Oscillation (ENSO) using process-based dynamical models; recent advances in data-driven deep learning algorithms provide a promising mean to achieve superior skill in the tropical Pacific sea surface temperature (SST) modeling. Here, a specific self-attention–based neural network model is developed for ENSO predictions based on the much sought-after Transformer model, named 3D-Geoformer, which is used to predict three-dimensional (3D) upper-ocean temperature anomalies and wind stress anomalies. This purely data-driven and time-space attention-enhanced model achieves surprisingly high correlation skills for Niño 3.4 SST anomaly predictions made 18 months in advance and initiated beginning in boreal spring. Further, sensitivity experiments demonstrate that the 3D-Geoformer model can depict the evolution of upper-ocean temperature and the coupled ocean-atmosphere dynamics following the Bjerknes feedback mechanism during ENSO cycles. Such successful realizations of the self-attention–based model in ENSO predictions indicate its great potential for multidimensional spatiotemporal modeling in geoscience.
Isolation of an Ecotropic Porcine Endogenous Retrovirus PERV-C from a Yucatan SLA
D/D
Inbred Miniature Swine
Authors: Rodrigues Costa Michael , Fischer Nicole , Gronewold Antonia , Gulich Barbara , Godehardt Antonia W. , Tönjes Ralf R.
Published: March 2023

Yucatan SLA
D/D
haplotype miniature swine are candidates as organ donors for xenotransplantation. A full-length replication-competent PERV-C provirus was characterized. The provirus was chromosomally mapped in the pig genome.
In vitro
, the virus showed increased infectivity compared to other functional PERV-C isolates. Data may be used for targeted knockout to generate PERV-C free founder animals.
Evidence for a Causal Role for Escherichia coli Strains Identified as Adherent-Invasive (AIEC) in Intestinal Inflammation
Authors: Kittana Hatem , Gomes-Neto João C. , Heck Kari , Juritsch Anthony F. , Sughroue Jason , Xian Yibo , Mantz Sara , Segura Muñoz Rafael R. , Cody Liz A. , Schmaltz Robert J. , Anderson Christopher L. , Moxley Rodney A. , Hostetter Jesse M. , Fernando Samodha C. , Clarke Jennifer , Kachman Stephen D. , Cressler Clayton E. , Benson Andrew K. , Walter Jens , Ramer-Tait Amanda E.
Published: March 2023

Inflammatory bowel disease (IBD) is associated with an altered gut microbiota composition, including expansion of
Proteobacteria
. Many species in this phylum are thought to contribute to disease under certain conditions, including adherent-invasive
Escherichia coli
(AIEC) strains, which are enriched in some patients.
Episodic magmatism in the Lianhuashan tectonic belt: Implications for late Mesozoic crustal reworking in SE South China
Authors: Xin Yujia , Li Jianhua , Zhang Yueqiao , Dong Shuwen
Published: March 2023

The Lianhuashan tectonic belt preserves abundant evidence of episodic magmatism and deformation that is crucial for understanding the late Mesozoic crustal reworking in SE South China. Here, we report zircon U-Pb ages, geochemical, and Sr−Nd−Hf isotopic data for representative granitoids and volcanic rocks to clarify the episodic magmatism in the Lianhuashan tectonic belt and its association with regional tectonic evolution. Our results define three episodes of magmatism. The Late Jurassic (160−150 Ma) magmatic rocks show high CaO/Na2O and molar CaO/(MgO + FeOt) (CMF) ratios and enriched Sr−Nd−Hf isotopes that are consistent with high-temperature melting of psammitic sources. The Early Cretaceous (144−131 Ma) magmatic rocks display variable CaO/Na2O ratios and zircon εHf(t) values (−12.0 to −2.5), which implies binary mixing of melts from pelitic and basaltic sources. The Late Cretaceous (ca. 94 Ma) magmatic rocks show high A/CNK and low CaO/Na2O and CMF ratios, which are characteristics of pelite-derived melts. They have zircon Hf isotopes (−4.4 to −1.9) that are slightly higher than those of the Early Cretaceous rocks, which is consistent with partial melting of diverse sources with more involvement of juvenile crust. These magmatic records, coupled with regional structural observations, suggest that the Lianhuashan tectonic belt underwent alternating crustal shortening and extension during the Late Jurassic to Cretaceous time. The Late Jurassic magmatism possibly marks the initiation of crustal extension following Middle Jurassic retro-arc crustal shortening related to the advancing Paleo-Pacific subduction. In the Cretaceous, the two magmatic flare-ups were separated by a magmatic lull associated with crustal shortening. The magmatic flare-ups occurred coevally with two stages of regional extension, as evidenced by widespread generations of basins and extensional domes. The time consistency implies that the magmatism was associated with or facilitated crustal extension that occurred at a regional scale and may have resulted from slab rollback during subduction retreat. We suggest that the magmatism and extension provide essential evidence of the crustal reworking in SE South China governed by the Paleo-Pacific subduction. Changes in the slab dynamics (steepening and shallowing) may control the flare-up, lull, and resumption of magmatism, as well as alternating episodes of crustal extension and shortening.