Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel Insights to Assess Climate Resilience in Goats Using a Holistic Approach of Skin-Based Advanced NGS Technologies

A novel study was conducted to elucidate heat-stress responses on a number of hair- and skin-based traits in two indigenous goat breeds using a holistic approach that considered a number of phenotypic and genomic variables. The two goat breeds, Kanni Aadu and Kodi Aadu, were subjected to a simulated heat-stress study using the climate chambers. Four groups consisting of six goats each (KAC, Kaani Aadu control; KAH, Kanni Aadu heat stress; KOC, Kodi Aadu control; and KOH, Kodi Aadu heat stress) were considered for the study. The impact of heat stress on caprine skin tissue along with a comparative assessment of the thermal resilience of the two goat breeds was assessed. The variables considered were hair characteristics, hair cortisol, hair follicle quantitative PCR (qPCR), sweating (sweating rate and active sweat gland measurement), skin histometry, skin-surface infrared thermography (IRT), skin 16S rRNA V3-V4 metagenomics, skin transcriptomics, and skin bisulfite sequencing. Heat stress significantly influenced the hair fiber characteristics (fiber length) and hair follicle qPCR profile (Heat-shock protein 70 (HSP70), HSP90, and HSP110). Significantly higher sweating rate, activated sweat gland number, skin epithelium, and sweat gland number (histometry) were observed in heat stressed goats. The skin microbiota was also observed to be significantly altered due to heat stress, with a relatively higher alteration being noticed in Kanni Aadu goats than in Kodi Aadi goats. Furthermore, the transcriptomics and epigenetics analysis also pointed towards the significant impact of heat stress at the cellular and molecular levels in caprine skin tissue. The higher proportion of differentially expressed genes (DEGs) along with higher differentially methylated regions (DMRs) in Kanni Aadu goats due to heat stress when compared to Kodi Aadu goats pointed towards the better resilience of the latter breed. A number of established skin, adaptation, and immune-response genes were also observed to be significantly expressed/methylated. Additionally, the influence of heat stress at the genomic level was also predicted to result in significant functional alterations. This novel study thereby highlights the impact of heat stress on the caprine skin tissue and also the difference in thermal resilience exhibited by the two indigenous goat breeds, with Kodi Aadu goats being more resilient.
Drug-Induced Liver Injury Caused by Capecitabine: A Case Report and a Literature Review

Chemotherapy is widely used in cancer treatment, and the drug Capecitabine is often used in treatment of breast cancer and usually well-tolerated. Toxicity from Capecitabine typically involves hand-foot syndrome, fatigue, nausea, reduced appetite, and diarrhea, while severe liver toxicity is rarely seen. We present a case of a 63-year-old female with metastatic breast cancer, without liver metastasis, who developed a severe drug-induced liver injury (DILI) with critically elevated liver enzyme levels as reaction to Capecitabine treatment with seemingly no evident explanation as to why. The patient had a RUCAM score of 7 and a Naranjo score of 6 implying that this association between Capecitabine and the liver injury falls into the “probable” category. The patient recovered completely and was then successfully treated with other cytotoxic drugs without any sign of liver engagement. An in-depth literature search based on Pubmed database was performed to obtain information about Capecitabine, liver injury, and chemotherapy-associated acute hepatic toxicity. The following keywords were used: Capecitabine, chemotherapy, liver toxicity, and hepatic toxicity. Five studies were found showing some similarities to this case documenting hepatic injury after Capecitabine treatment including hepatic steatosis and moderately elevated liver enzymes. However, no studies were found reporting a severe DILI with highly elevated enzyme levels as immediate response to Capecitabine treatment. No reason could be identified as for why the patient developed an acute toxic liver reaction to Capecitabine. This case calls for more attention to the potential severe liver toxicity of an otherwise well-tolerated drug.
Antinociceptive, Sedative and Excitatory Effects of Intravenous Butorphanol Administered Alone or in Combination with Detomidine in Calves: A Prospective, Randomized, Blinded Cross-Over Study

Simple Summary Surgical procedures are routinely performed in calves, both under sedation and general anesthesia. The availability of analgesic drugs is limited in food-producing animals, making their perioperative management challenging. Few are the studies assessing the extent of pharmacological antinociception obtained when administering sedative and analgesics in cattle and the tools used are mainly qualitative. With the present study, we aimed at assessing the antinociceptive effect of butorphanol with or without detomidine in calves, using the modulation of the trigeminocervical reflex threshold as the main outcome. The trigeminocervical reflex threshold is a quantifiable nociceptive reflex that can be used to assess the modulation of pain processing. As secondary aims, physiological and behavioral effects of the administered treatments were evaluated, and the temporal profile of drug activity was described. This study provides quantitative evidence of the efficacy of butorphanol administered alone or combined with detomidine in calves. The presented findings can now contribute to optimizing the application of these drugs in clinical practice. Abstract (1) Background: The diagnostic and therapeutic procedures performed under sedation or general anesthesia in bovines are numerous. The analgesic drugs that can be legally used are few, making perioperative analgesia challenging. (2) Methods: Calves were administered butorphanol 0.1 mg kg−1 alone (SB) or combined with 0.02 mg kg−1 of a detomidine (DB) IV. The antinociceptive effect (trigeminocervical reflex threshold (TCRt)), as well as the behavioral (sedation and excitation) and physiological (heart and respiratory rate) changes were investigated. Five time windows were defined: BL (30 min pre-injection), T1 (0–30 min post-injection (PI)), T2 (31–60 min PI), T3 (61–90 min PI) and T4 (91–120 min PI). (3) Results: Both groups had a significative increase in TCRt at T1-T4 compared to the BL. The TCRt was significatively higher in DB than in SB at T1, T2 and T4. Heart rate decreased significatively in DB compared to that in BL. Calves were significantly more sedated in the DB group, and significantly more excited in the SB group compared to the BL. (4) Conclusions: Butorphanol alone has a statistically significant antinociceptive effect, but it elicits marked excitation, limiting its clinical applicability under this dosing regimen. The co-administration of detomidine eliminated the excitatory effect and induced consistent sedation and a significantly more pronounced antinociceptive effect.
The role of carbonaceous aerosols on short‐term variations of precipitation over North Africa

Subtropical North Africa has been subject to extensive droughts in the late 20th century, linked to changes in the sea surface temperature (SST). However, climate models forced by observed SSTs cannot reproduce the magnitude of the observed rainfall reduction. Here, we propose aerosol indirect effects (AIE) as an important positive feedback mechanism. Model results are presented using two sets of sensitivity experiments designed to distinguish the role of aerosol direct/semi‐direct and indirect effects on regional precipitation. Changes in cloud properties due to the presence of carbonaceous aerosols are proposed as a key mechanism to explain the reduced rainfall over subtropical North Africa.
Metabolomics in Acute Kidney Injury: The Clinical Perspective

Background: Acute kidney injury (AKI) affects increasing numbers of hospitalized patients worldwide. The diagnosis of AKI is made too late in most individuals since it is still based on dynamic changes in serum creatinine. In recent years, new AKI biomarkers have been identified; however, none of these can reliably replace serum creatinine yet. Metabolomic profiling (metabolomics) allows the concomitant detection and quantification of large numbers of metabolites from biological specimens. The current article aims to summarize clinical studies on metabolomics in AKI diagnosis and risk prediction. Methods: The following databases were searched for references: PubMed, Web of Science, Cochrane Library, and Scopus, and the period lasted from 1940 until 2022. The following terms were utilized: ‘AKI’ OR ‘Acute Kidney Injury’ OR ‘Acute Renal Failure’ AND ‘metabolomics’ OR ‘metabolic profiling’ OR ‘omics’ AND ‘risk’ OR ‘death’ OR ‘survival’ OR ‘dialysis’ OR ‘KRT’ OR ‘kidney replacement therapy’ OR ‘RRT’ OR ‘renal replacement therapy’ OR ‘recovery of kidney function’ OR ‘renal recovery’ OR ‘kidney recovery’ OR ‘outcome’. Studies on AKI risk prediction were only selected if metabolomic profiling allowed differentiation between subjects that fulfilled a risk category (death or KRT or recovery of kidney function) and those who did not. Experimental (animal-based) studies were not included. Results: In total, eight studies were identified. Six studies were related to the diagnosis of AKI; two studies were performed on metabolic analysis in AKI risk (death) prediction. Metabolomics studies in AKI already helped to identify new biomarkers for AKI diagnosis. The data on metabolomics for AKI risk prediction (death, KRT, recovery of kidney function), however, are very limited. Conclusions: Both the heterogenous etiology and the high degree of pathogenetic complexity of AKI most likely require integrated approaches such as metabolomics and/or additional types of ‘-omics’ studies to improve clinical outcomes in AKI.
Targeting RNA Structure to Inhibit Editing in Trypanosomes

Mitochondrial RNA editing in trypanosomes represents an attractive target for developing safer and more efficient drugs for treating infections with trypanosomes because this RNA editing pathway is not found in humans. Other workers have targeted several enzymes in this editing system, but not the RNA. Here, we target a universal domain of the RNA editing substrate, which is the U-helix formed between the oligo-U tail of the guide RNA and the target mRNA. We selected a part of the U-helix that is rich in G-U wobble base pairs as the target site for the virtual screening of 262,000 compounds. After chemoinformatic filtering of the top 5000 leads, we subjected 50 representative complexes to 50 nanoseconds of molecular dynamics simulations. We identified 15 compounds that retained stable interactions in the deep groove of the U-helix. The microscale thermophoresis binding experiments on these five compounds show low-micromolar to nanomolar binding affinities. The UV melting studies show an increase in the melting temperatures of the U-helix upon binding by each compound. These five compounds can serve as leads for drug development and as research tools to probe the role of the RNA structure in trypanosomal RNA editing.
Genome-Wide DNA Methylation and Transcriptome Integration Associates DNA Methylation Changes with Bovine Subclinical Mastitis Caused by Staphylococcus chromogenes

Staphylococcus chromogenes (SC) is a common coagulase-negative staphylococcus described as an emerging mastitis pathogen and commonly found in dairy farms. This study investigated the potential involvement of DNA methylation in subclinical mastitis caused by SC. The whole-genome DNA methylation patterns and transcriptome profiles of milk somatic cells from four cows with naturally occurring SC subclinical mastitis (SCM) and four healthy cows were characterized by next-generation sequencing, bioinformatics, and integration analyses. Comparisons revealed abundant DNA methylation changes related to SCM, including differentially methylated cytosine sites (DMCs, n = 2,163,976), regions (DMRs, n = 58,965), and methylation haplotype blocks (dMHBs, n = 53,098). Integration of methylome and transcriptome data indicated a negative global association between DNA methylation at regulatory regions (promoters, first exons, and first introns) and gene expression. A total of 1486 genes with significant changes in the methylation levels of their regulatory regions and corresponding gene expression showed significant enrichment in biological processes and pathways related to immune functions. Sixteen dMHBs were identified as candidate discriminant signatures, and validation of two signatures in more samples further revealed the association of dMHBs with mammary gland health and production. This study demonstrated abundant DNA methylation changes with possible involvement in regulating host responses and potential as biomarkers for SCM.
Lung Ultrasound to Determine the Effect of Lower vs. Higher PEEP on Lung Aeration in Patients without ARDS—A Substudy of a Randomized Clinical Trial

Background: Ventilation with lower positive end–expiratory pressure (PEEP) may cause loss of lung aeration in critically ill invasively ventilated patients. This study investigated whether a systematic lung ultrasound (LUS) scoring system can detect such changes in lung aeration in a study comparing lower versus higher PEEP in invasively ventilated patients without acute respiratory distress syndrome (ARDS). Methods: Single center substudy of a national, multicenter, randomized clinical trial comparing lower versus higher PEEP ventilation strategy. Fifty–seven patients underwent a systematic 12–region LUS examination within 12 h and between 24 to 48 h after start of invasive ventilation, according to randomization. The primary endpoint was a change in the global LUS aeration score, where a higher value indicates a greater impairment in lung aeration. Results: Thirty–three and twenty–four patients received ventilation with lower PEEP (median PEEP 1 (0–5) cm H2O) or higher PEEP (median PEEP 8 (8–8) cm H2O), respectively. Median global LUS aeration scores within 12 h and between 24 and 48 h were 8 (4 to 14) and 9 (4 to 12) (difference 1 (–2 to 3)) in the lower PEEP group, and 7 (2–11) and 6 (1–12) (difference 0 (–2 to 3)) in the higher PEEP group. Neither differences in changes over time nor differences in absolute scores reached statistical significance. Conclusions: In this substudy of a randomized clinical trial comparing lower PEEP versus higher PEEP in patients without ARDS, LUS was unable to detect changes in lung aeration.
Classifying Genetic Lines in Pork Production by Ileal Crude Protein and Amino Acid Digestibility in Growing Pigs

Simple Summary Breeding programs in pigs have been very successful in recent decades, although the different selection directions have resulted in highly variable growth rates between the genotypes. Simultaneously, the absorption of nutrients may also show differences subject to the genotype of the animals. As far as the development of the feeding strategies is concerned, the main objective is to maximize profitability; therefore, future methods in swine nutrition must also support the different growth rates of the animals through the improved absorption of nutrients. One of the most common tools used to reduce feed costs is the optimization of the dietary lysine-to-energy ratio, because lysine is the first limiting amino acid for swine, and energy content is one of the most defining parameters of their diet. Pigs of different genetic potential can be classified with a high accuracy in respect of their crude protein and amino acid digestive capacity. Consequently, the ileal digestibility of crude protein and amino acids in growing pigs of different genotypes should serve as a basis for the development of genotype-specific feeding strategies. Further studies are needed to identify the differences in the crude protein and amino acid digestibility of cross-bred pigs with different genetic potentials. Abstract The first aim of the study was to evaluate the effect of different dietary lysine (LYS) to energy (DE) ratios on the apparent ileal digestibility (AID) of crude protein (CP) and selected amino acids (AA) in growing pigs (40–60 kg) of different genotypes. The second aim was to classify genotypes into groups based on the AID of CP and AAs. The trials were conducted on a total of 90 cross-bred barrows (30 animals/genotype) in two replicates. Before the trial series, the experimental animals (average initial body weight (BW) = 40.9 ± 8.5 kg) were surgically fitted with post valve T-cannula (PVTC). The diets were formulated with six different total LYS/DE ratios. Titanium dioxide (TiO2) was added to the diets (5 g/kg) as an indigestible marker. Based on our results, it can be concluded that the LYS/DE ratio of the diets affected the AID of the CP and AA in different ways by each genotype (p < 0.05). It can also be concluded that pigs of different genetic potential can be classified with a high accuracy (91.7%) in respect of their CP and AA digestive capacity. Our results indicate the development of genetic-profile-based swine nutrition technologies as a future direction.
RNA-Seq Transcriptome Analysis and Evolution of OsEBS, a Gene Involved in Enhanced Spikelet Number per Panicle in Rice

Spikelet number per panicle (SNP) is one of the most important yield components in rice. Rice ENHANCING BIOMASS AND SPIKELET NUMBER (OsEBS), a gene involved in improved SNP and yield, has been cloned from an accession of Dongxiang wild rice. However, the mechanism of OsEBS increasing rice SNP is poorly understood. In this study, the RNA-Seq technology was used to analyze the transcriptome of wildtype Guichao 2 and OsEBS over-expression line B102 at the heading stage, and analysis of the evolution of OsEBS was also conducted. A total of 5369 differentially expressed genes (DEGs) were identified between Guichao2 and B102, most of which were down-regulated in B102. Analysis of the expression of endogenous hormone-related genes revealed that 63 auxin-related genes were significantly down-regulated in B102. Gene Ontogeny (GO) enrichment analysis showed that the 63 DEGs were mainly enriched in eight GO terms, including auxin-activated signaling pathway, auxin polar transport, auxin transport, basipetal auxin transport, and amino acid transmembrane transport, most of which were directly or indirectly related to polar auxin transport. Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis further verified that the down-regulated genes related to polar auxin transport had important effects on increased SNP. Analysis of the evolution of OsEBS found that OsEBS was involved in the differentiation of indica and japonica, and the differentiation of OsEBS supported the multi-origin model of rice domestication. Indica (XI) subspecies harbored higher nucleotide diversity than japonica (GJ) subspecies in the OsEBS region, and XI experienced strong balancing selection during evolution, while selection in GJ was neutral. The degree of genetic differentiation between GJ and Bas subspecies was the smallest, while it was the highest between GJ and Aus. Phylogenetic analysis of the Hsp70 family in O. sativa, Brachypodium distachyon, and Arabidopsis thaliana indicated that changes in the sequences of OsEBS were accelerated during evolution. Accelerated evolution and domain loss in OsEBS resulted in neofunctionalization. The results obtained from this study provide an important theoretical basis for high-yield rice breeding.
Ectopic Expression of a Maize Gene ZmDUF1645 in Rice Increases Grain Length and Yield, but Reduces Drought Stress Tolerance

As the human population grows rapidly, food shortages will become an even greater problem; therefore, increasing crop yield has become a focus of rice breeding programs. The maize gene, ZmDUF1645, encoding a putative member of the DUF1645 protein family with an unknown function, was transformed into rice. Phenotypic analysis showed that enhanced ZmDUF1645 expression significantly altered various traits in transgenic rice plants, including increased grain length, width, weight, and number per panicle, resulting in a significant increase in yield, but a decrease in rice tolerance to drought stress. qRT-PCR results showed that the expression of the related genes regulating meristem activity, such as MPKA, CDKA, a novel crop grain filling gene (GIF1), and GS3, was significantly changed in the ZmDUF1645-overexpression lines. Subcellular colocalization showed that ZmDUF1645 was primarily localized on cell membrane systems. Based on these findings, we speculate that ZmDUF1645, like the OsSGL gene in the same protein family, may regulate grain size and affect yield through the cytokinin signaling pathway. This research provides further knowledge and understanding of the unknown functions of the DUF1645 protein family and may serve as a reference for biological breeding engineering to increase maize crop yield.
Computed Tomographic Assessment of Pituitary Gland Dimensions in Domestic Short-Haired Cats

Simple Summary The pituitary gland is crucial in regulating metabolic processes. Tumors in this gland can be subtle, meaning that establishing reference values for the pituitary dimensions is pivotal. Computed tomography is commonly used to identify pituitary alterations, plan surgery or radiation therapy, and monitor treatment responses. This study aimed to determine the normal pituitary size, and the pituitary-to-brain ratio, in a group of domestic short-haired cats by computed tomography. The study also aimed to explore the correlations between body weight, age, sex, and pituitary dimensions, and assess the inter- and intra-agreement between operators in measuring pituitary dimensions. The study showed that the normal range for pituitary dimensions is wider than previously reported. The study also showed a low correlation between body weight, age, and pituitary dimensions. The intra-operator agreement in measuring pituitary dimensions was good/excellent, but the inter-operator agreement was moderate/good, likely due to differences in expertise. The reference values obtained from this study could help in better evaluating the pituitary gland in domestic short-haired cats with suspected pituitary neoplastic lesions. Abstract The detection of subtle changes in the pituitary dimensions has relevant clinical implications. In cats, a few studies have established the cut-off values of the pituitary gland’s dimensions using small and inhomogeneous samples. The aims of this study were: to determine by computed tomography (CT) the pituitary linear dimensions and the pituitary-to-brain (P:B) ratio in a sample of domestic short-haired (DSH) cats; to assess the effects of sex, age, and weight on pituitary dimensions; and to evaluate the inter- and intra-observer agreement for such measurements. All skull CTs of DSH cats performed over four years using a multidetector CT and a standardized protocol were retrospectively reviewed. The exclusion criteria were: clinical, laboratory, or CT alterations of the pituitary gland, brain diseases, fractures of the neurocranium, and diabetes. The pituitary dimensions and brain area were assessed by two different observers using multiplanar reconstructions and automated segmentation tools. Fifty-one cats were included in the final sample. The intraclass correlation coefficients for intra- and inter-observer reliability were good/excellent, and moderate/good, respectively. No differences between sexes were detected, and negligible correlations were found between age and weight. According to this study, a pituitary gland with a height > 4 mm or a P:B ratio > 0.49 mm should be considered enlarged.