Diversity of Expression Patterns of Lr34, Lr67, and Candidate Genes towards Lr46 with Analysis of Associated miRNAs in Common Wheat Hybrids in Response to Puccinia triticina Fungus.

Leaf rust caused by Puccinia triticina (Pt) is one of the most dangerous diseases causing significant losses in common wheat crops. In adult plants resistant to rust, a horizontal adult plant resistance (APR) type is observed, which protects the plant against multiple pathogen races and is distinguished by greater persistence under production conditions. Crucial pleiotropic slow-rust genes such as Lr34, Lr46, Lr67, and Lr68, in combination with other genes of lesser influence, continue to increase durable resistance to rust diseases. Based on our previous results, we selected four candidate genes for Lr46 out of ten candidates and analysed them for expression before and after inoculation by P. triticina. As part of our study, we also investigated the expression patterns of miRNA molecules complementary to Lr34 and the candidate genes. The aim of the study was to analyse the expression profiles of candidate genes for the Lr46 gene and the Lr34 and Lr67 genes responsible for the differential leaf-rust resistance of hybrid forms of the F1 generation resulting from crosses between the Glenlea cultivar and cultivars from Polish breeding companies. In addition, the expression of five miRNAs (tae-miR9653b, tae-miR5384-3p, tae-miR9780, tae-miR9775 and tae-miR164), complementary to Lr34, and selected candidate genes were analysed using stem-loop RT-PCR and ddPCR. Biotic stress was induced in adult plants by inoculation with Pt fungal spores, under controlled conditions. Plant material was collected before and 6, 12, 24, and 48 h after inoculation (hpi). Differences in expression patterns of Lr34, Lr67, and candidate genes (for Lr46) were analysed by qRT-PCR and showed that gene expression changed at the analysed time points. Identification of molecular markers coupled to the Lr genes studied was also carried out to confirm the presence of these genes in wheat hybrids. qRT-PCR was used to examine the expression levels of the resistance genes. The highest expression of Lr46/Yr29 genes (Lr46-Glu2, Lr46-RLK1, Lr46-RLK2, and Lr46-RLK3) occurred at 12 and 24 hpi, and such expression profiles were obtained for only one candidate gene among the four genes analysed (Lr46-Glu2), indicating that it may be involved in resistance mechanisms of response to Pt infection.

TP53 structure-function relationships in metastatic castrate-sensitive prostate cancer and the impact of APR-246 treatment.

PURPOSE: Despite well-informed work in several malignancies, the phenotypic effects of TP53 mutations in metastatic castration-sensitive prostate cancer (mCSPC) progression and metastasis are not clear. We characterized the structure-function and clinical impact of TP53 mutations in mCSPC. PATIENTS AND METHODS: We performed an international retrospective review of men with mCSPC who underwent next-generation sequencing and were stratified according to TP53 mutational status and metastatic burden. Clinical outcomes included radiographic progression-free survival (rPFS) and overall survival (OS) evaluated with Kaplan-Meier and multivariable Cox regression. We also utilized isogenic cancer cell lines to assess the effect of TP53 mutations and APR-246 treatment on migration, invasion, colony formation in vitro, and tumor growth in vivo. Preclinical experimental observations were compared using t-tests and ANOVA. RESULTS: Dominant-negative (DN) TP53 mutations were enriched in patients with synchronous (vs. metachronous) (20.7% vs. 6.3%, p < 0.01) and polymetastatic (vs. oligometastatic) (14.4% vs. 7.9%, p < 0.01) disease. On multivariable analysis, DN mutations were associated with worse rPFS (hazards ratio [HR] = 1.97, 95% confidence interval [CI]: 1.31-2.98) and overall survival [OS] (HR = 2.05, 95% CI: 1.14-3.68) compared to TP53 wild type (WT). In vitro, 22Rv1 TP53 R175H cells possessed stronger migration, invasion, colony formation ability, and cellular movement pathway enrichment in RNA sequencing analysis compared to 22Rv1 TP53 WT cells. Treatment with APR-246 reversed the effects of TP53 mutations in vitro and inhibited 22Rv1 TP53 R175H tumor growth in vivo in a dosage-dependent manner. CONCLUSIONS: DN TP53 mutations correlated with worse prognosis in prostate cancer patients and higher metastatic potential, which could be counteracted by APR-246 treatment suggesting a potential future therapeutic avenue.

Targeting p53 for the treatment of cancer.

Dysfunction of the TP53 (p53) gene occurs in most if not all human malignancies. Two principal mechanisms are responsible for this dysfunction; mutation and downregulation of wild-type p53 mediated by MDM2/MDM4. Because of its almost universal inactivation in malignancy, p53 is a highly attractive target for the development of new anticancer drugs. Although multiple strategies have been investigated for targeting dysfunctional p53 for cancer treatment, only 2 of these have so far yielded compounds for testing in clinical trials. These strategies include the identification of compounds for reactivating the mutant form of p53 back to its wild-type form and compounds for inhibiting the interaction between wild-type p53 and MDM2/MDM4. Currently, multiple p53-MDM2/MDM4 antagonists are undergoing clinical trials, the most advanced being idasanutlin which is currently undergoing testing in a phase III clinical trial in patients with relapsed or refractory acute myeloid leukemia. Two mutant p53-reactivating compounds have progressed to clinical trials, i.e., APR-246 and COTI-2. Although promising data has emerged from the testing of both MDM2/MDM4 inhibitors and mutant p53 reactivating compounds in preclinical models, it is still unclear if these agents have clinical efficacy. However, should any of the compounds currently being evaluated in clinical trials be shown to have efficacy, it is likely to usher in a new era in cancer treatment, especially as p53 dysfunction is so prevalent in human cancers.

Challenges in Forecasting Antimicrobial Resistance.

Antimicrobial resistance is a major threat to human health. Since the 2000s, computational tools for predicting infectious diseases have been greatly advanced; however, efforts to develop real-time forecasting models for antimicrobial-resistant organisms (AMROs) have been absent. In this perspective, we discuss the utility of AMRO forecasting at different scales, highlight the challenges in this field, and suggest future research priorities. We also discuss challenges in scientific understanding, access to high-quality data, model calibration, and implementation and evaluation of forecasting models. We further highlight the need to initiate research on AMRO forecasting using currently available data and resources to galvanize the research community and address initial practical questions.

Human Metapneumovirus Infections during COVID-19 Pandemic, Spain.

We describe an unusual outbreak of respiratory infections caused by human metapneumovirus in children during the sixth wave of COVID-19 in Spain, associated with the Omicron variant. Patients in this outbreak were older than usual and showed more hypoxia and pneumonia, longer length of stay, and greater need for intensive care.

Nocardia pseudobrasiliensis Co-infection in SARS-CoV-2 Patients.

During the SARS-CoV-2 pandemic, few cases of Nocar-dia spp. co-infection have been reported during or after a COVID-19 infection. Nocardia spp. are gram-positive aerobic actinomycetes that stain partially acid-fast, can infect immunocompromised patients, and may cause dis-seminated disease. We report the case of a 52-year-old immunocompromised man who had Nocardia pseudobrasiliensis pneumonia develop after a SARS-CoV-2 in-fection. We also summarize the literature for no-cardiosis and SARS-CoV-2 co-infections. Nocardia spp. infection should remain a part of the differential diagnosis for pneumonia in immunocompromised hosts, regardless of other co-infections. Sulfonamide/carbapenem combina-tions are used as empiric therapy for nocardiosis; species identification and susceptibility testing are required to se-lect the optimal treatment for each patient.

Role of APR3 in cancer: apoptosis, autophagy, oxidative stress, and cancer therapy.

APR3 (Apoptosis-related protein 3) is a gene that has recently been identified to be associated with apoptosis. The gene is located on human chromosome 2p22.3 and contains both transmembrane and EGF (epidermal growth factor)-like domains. Additionally, it has structural sites, including AP1, SP1, and MEF2D, that indicate NFAT (nuclear factor of activated T cells) and NF-κB (nuclear factor kappa-B) may be transcription factors for this gene. Functionally, APR3 participates in apoptosis due to the induction of mitochondrial damage to release mitochondrial cytochrome C. Concurrently, APR3 affects the cell cycle by altering the expression of Cyclin D1, which, in turn, affects the incidence and growth of malignancies and promotes cell differentiation. Previous reports indicate that APR3 is located in lysosomal membranes, where it contributes to lysosomal activity and participates in autophagy. While further research is required to determine the precise role and molecular mechanisms of APR3, earlier studies have laid the groundwork for APR3 research. There is growing evidence supporting the significance of APR3 in oncology. Therefore, this review aims to examine the current state of knowledge on the role of the newly discovered APR3 in tumorigenesis and to generate fresh insights and suggestions for future research.

The p53 reactivator PRIMA-1MET synergises with 5-fluorouracil to induce apoptosis in pancreatic cancer cells.

Pancreatic cancer (PC) is one of the deadliest malignancies; p53 is mutated in approximately 75% of PC patients. Hence, the protein derived from mutant/wild-type TP53 may represent a therapeutic target. Interestingly, a p53 reactivator (PRIMA-1MET) showed promise in clinical trials of haematological malignancies; therefore, it warrants an in vitro evaluation in PC cell lines. To evaluate the antiproliferative effects of PRIMA-1MET, either alone or combined with the common chemotherapy 5-fluorouracil (5-FU), against mutated and wild-type p53 PC cell lines. This study involved p53-mutant (AsPC-1) and p53-wild type (Capan-2) PC cell lines. The cytotoxicity of PRIMA-1MET alone or in combination with 5-FU was evaluated by MTT assay. Synergism was assessed by calculating the combination index (CI) via CalcuSyn software. Fluorescence microscopy was used to analyse apoptosis following acridine orange/ethidium bromide (AO/EB) staining. Morphological changes were investigated with an inverted microscope. Quantitative reverse transcription PCR (RT‒qPCR) was used to measure gene expression. Both PC cell lines were sensitive to PRIMA-1MET monotherapy. Furthermore, PRIMA-1MET and 5-FU had a synergistic effect (CI < 1), reflected by significant enhancement of apoptosis and morphological changes in the combination vs. monotherapy treatments. Moreover, the RT‒qPCR results indicated increased expression of the NOXA and TP73 genes in combination-treated cells. Our data suggested that PRIMA-1MET, whether alone or combined with 5-FU, has an antiproliferative effect on PC cell lines regardless of p53 mutational status. The synergism of the combination was associated with significant apoptosis induction through p53-dependent and p53-independent pathways. Preclinical confirmation of these data in in vivo models is highly recommended.

New insights into the regulation of plant metabolism by O-acetylserine: sulfate and beyond.

Under conditions of sulfur deprivation, O-acetylserine (OAS) accumulates, which leads to the induction of a common set of six genes, called OAS cluster genes. These genes are induced not only under sulfur deprivation, but also under other conditions where OAS accumulates, such as shift to darkness and stress conditions leading to reactive oxygen species (ROS) or methyl-jasmonate accumulation. Using the OAS cluster genes as a query in ATTED-II, a co-expression network is derived stably spanning several hundred conditions. This allowed us not only to describe the downstream function of the OAS cluster genes but also to score for functions of the members of the co-regulated co-expression network and hence the effects of the OAS signal on the sulfate assimilation pathway and co-regulated pathways. Further, we summarized existing knowledge on the regulation of the OAS cluster and the co-expressed genes. We revealed that the known sulfate deprivation-related transcription factor EIL3/SLIM1 exhibits a prominent role, as most genes are subject to regulation by this transcription factor. The role of other transcription factors in response to OAS awaits further investigation.

Short- and mid-term outcomes of abdominoperineal resection with perineal mesh insertion: a single-centre experience.

PURPOSE: Abdominoperineal resection (APR) remains a key procedure for the treatment of low rectal/anorectal cancers. However, perineal wound closure remains challenging, particularly in extralevator abdominoperineal resection (ELAPR) due to gapped tissue planes. Different approaches have been attempted to improve perineal wound repair. The aim of this study is to report our 6-year experience in perineal wound closure utilising biological mesh. METHODS: We conducted a retrospective study using data from our prospectively maintained database, including patients who underwent APR with perineal mesh closure between 2016 and 2021. RESULTS: 49  patients underwent APR with perineal mesh reconstruction for low rectal cancer during the 6-year period. Of these, 63% were males, with a mean age of 68 (± 11), and a mean BMI of 27.9 (± 13.7). 49% (24) of patients received neoadjuvant therapy. 88% (43) of patients underwent standard "S-APR" and only 12% (6) underwent ELAPR. Majority of procedures were laparoscopic (87.8%) with conversion rate of 6.9%. Mean length of stay was 11.7 (± 11.6). The perineal wound infection rate was 30% and only two patient required mesh removal due to entero-cutaneous perineal fistula and pelvic abscess. Perineal hernia was found in only two patients (4.1%). CRM was negative in 81.6% of the patients. Mean follow-up period was 29.2 (± 16.5) months, and disease recurrence occurred in 9 (18.3%) patients with average number of months for recurrence of 21 (± 7). Overall survival during the follow-up period was 91%. CONCLUSION: Our series shows a favourable short- and medium-term outcome with routine insertion of mesh for perineal wound closure.

Genetic Analysis and Physical Mapping of Oat Adult Plant Resistance Loci Against Puccinia coronata f. sp. avenae.

Six quantitative trait loci (QTLs) for adult plant resistance against oat crown rust (Puccinia coronata f. sp. avenae) were identified from mapping three recombinant inbred populations. Using genotyping-by-sequencing with markers called against the OT3098 v1 reference genome, the QTLs were mapped on six different chromosomes: Chr1D, Chr4D, Chr5A, Chr5D, Chr7A, and Chr7C. Composite interval mapping with marker cofactor selection showed that the phenotypic variance explained by all identified QTLs for coefficient of infection range from 12.2 to 46.9%, whereas heritability estimates ranged from 0.11 to 0.38. The significant regions were narrowed down to intervals of 3.9 to 25 cM, equivalent to physical distances of 11 to 133 Mb. At least two flanking single-nucleotide polymorphism markers were identified within 10 cM of each QTL that could be used in marker-assisted introgression, pyramiding, and selection. The additive effects of the QTLs in each population were determined using single-nucleotide polymorphism haplotype data, which showed a significantly lower coefficient of infection in lines homozygous for the resistant alleles. Analysis of pairwise linkage disequilibrium also revealed high correlation of markers and presence of linkage blocks in the significant regions. To further facilitate marker-assisted breeding, polymerase chain reaction allelic competitive extension (PACE) markers for the adult plant resistance loci were developed. Putative candidate genes were also identified in each of the significant regions, which include resistance gene analogs that encode for kinases, ligases, and predicted receptors of avirulence proteins from pathogens.

Postoperative perineal hernia repair: what is the evidence?

The present study determined the characteristics of perineal hernia treatment in the literature, and the incidence of postoperative recurrence was stratified according to repair techniques. A systematic search of the available literature on the treatment of postoperative perineal hernias was performed using a major database. The types of repair techniques and outcome were entered into an electronic database and a pooled analysis was performed. A total of 213 cases of postoperative perineal hernia repair were collected from 20 relevant articles in the literature after excluding case reports (n < 3). Synthetic mesh was the material used most frequently for perineal hernia repair (55.9%). The most frequently used approach in perineal hernia repair was the perineal approach (56.5%). The recurrence rate was highest with the use of biological mesh (40.4%) and the perineal approach (35.6%). The recurrence rate was lowest in the combined abdominal & perineal approach (0%), followed by the abdominal approach (8.8%) and the laparoscopic approach (11.8%). A number of different repair techniques have been described in the literature. The use of synthetic mesh via a combined abdominal-perineal approach or intraabdominal/laparoscopic approach was shown to be associated with a reduced postoperative recurrence rate.

Resistance to Powdery Mildew Is Conferred by Different Genetic Loci at the Adult-Plant and Seedling Stages in Winter Wheat Line Tianmin 668.

Winter wheat line Tianmin 668 was crossed with susceptible cultivar Jingshuang 16 to develop 216 recombinant inbred lines (RILs) for dissecting its adult-plant resistance (APR) and all-stage resistance (ASR) against powdery mildew. The RIL population was genotyped on a 16K genotyping by target sequencing single-nucleotide polymorphism array and phenotyped in six field trials and in the greenhouse. Three loci-QPmtj.caas-2BL, QPmtj.caas-2AS, and QPmtj.caas-5AL-conferring APR to powdery mildew were detected on chromosomes 2BL, 2AS, and 5AL, respectively, of Tianmin 668. The effect of resistance to powdery mildew for QPmtj.caas-2BL was greater than that of the other two loci. A Kompetitive allele-specific PCR marker specific for QPmtj.caas-2BL was developed and verified on 402 wheat cultivars or breeding lines. Results of virulence and avirulence patterns to 17 Blumeria graminis f. sp. tritici isolates, bulked segregant analysis-RNA-sequencing, and a genetic linkage mapping identified a resistance allele at locus Pm4 in Tianmin 668 based on the seedling phenotypes of the RIL population. The PCR-based DNA sequence alignment and cosegregation of the functional marker with the phenotypes of the RIL population demonstrated that Pm4d was responsible for the ASR to isolate Bgt1 in Tianmin 668. The dissection of genetic loci for APR and ASR may facilitate the application of Tianmin 668 in developing powdery mildew-resistant wheat cultivars.

Spread of SARS-CoV-2 Variants on Réunion Island, France, 2021.

In January 2021, after detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, genomic surveillance was established on Réunion Island to track the introduction and spread of SARS-CoV-2 lineages and variants of concern. This system identified 22 SARS-CoV-2 lineages, 71% of which were attributed to the Beta variant.

Genome-wide association study for resistance in bread wheat (Triticum aestivum L.) to stripe rust (Puccinia striiformis f. sp. tritici) races in Argentina.

BACKGROUND: Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most devastating diseases of the wheat crop. It causes significant reductions in both grain yield and grain quality. In recent years, new and more virulent races have overcome many of the known resistance genes in Argentinian germplasm. In order to identify loci conferring resistance to the local races of Pst for effective utilization in future breeding programs, a genome-wide association study (GWAS) was performed using a collection of 245 bread wheat lines genotyped with 90 K SNPs. RESULTS: To search for adult plant resistance (APR) the panel was evaluated for disease severity (DS) and area under disease progress curve (AUDPC) in field trials during two years under natural infection conditions. To look for seedling or all-stage resistance (ASR) the panel was evaluated to determine infection type (IT) under greenhouse conditions against two prevalent races in Argentina. The phenotypic data showed that the panel possessed enough genetic variability for searching for sources of resistance to Pst. Significant correlations between years were observed for Pst response in the field and high heritability values were found for DS (H2 = 0.89) and AUDPC (H2 = 0.93). Based on GWAS, eight markers associated with Pst resistance (FDR < 0.01) were identified, of these, five were associated with ASR (on chromosomes 1B, 2A, 3A and 5B) and three with APR (on chromosomes 3B and 7A). These markers explained between 2% and 32.62% of the phenotypic variation. Five of the markers corresponded with previously reported Yr genes/QTL, while the other three (QYr.Bce.1B.sd.1, QYr.Bce.3A.sd and QYr.Bce.3B.APR.2) might be novel resistance loci. CONCLUSION: Our results revealed high genetic variation for resistance to Argentinian stripe rust races in the germplasm used here. It constitutes a very promising step towards the improvement of Pst resistance of bread wheat in Argentina. Also, the identification of new resistance loci would represent a substantial advance for diversifying the current set of resistance genes and to advance in the improvement of the durable resistance to the disease.

A reference-anchored oat linkage map reveals quantitative trait loci conferring adult plant resistance to crown rust (Puccinia coronata f. sp. avenae).

KEY MESSAGE: We mapped three adult plant resistance (APR) loci on oat chromosomes 4D and 6C and developed flanking KASP/PACE markers for marker-assisted selection and gene pyramiding. Using sequence orthology search and the available oat genomic and transcriptomic data, we surveyed these genomic regions for genes that may control disease resistance. Sources of durable disease resistance are needed to minimize yield losses in cultivated oat caused by crown rust (Puccinia coronata f. sp. avenae). In this study, we developed five oat recombinant inbred line mapping populations to identify sources of adult plant resistance from crosses between five APR donors and Otana, a susceptible variety. The preliminary bulk segregant mapping based on allele frequencies showed two regions in linkage group Mrg21 (Chr4D) that are associated with the APR phenotype in all five populations. Six markers from these regions in Chr4D were converted to high-throughput allele specific PCR assays and were used to genotype all individuals in each population. Simple interval mapping showed two peaks in Chr4D, named QPc.APR-4D.1 and QPc.APR-4D.2, which were detected in the OtanaA/CI4706-2 and OtanaA/CI9416-2 and in the Otana/PI189733, OtanaD/PI260616, and OtanaA/CI8000-4 populations, respectively. These results were validated by mapping two entire populations, Otana/PI189733 and OtanaA/CI9416, genotyped using Illumina HiSeq, in which polymorphisms were called against the OT3098 oat reference genome. Composite interval mapping results confirmed the presence of the two quantitative trait loci (QTL) located on oat chromosome 4D and an additional QTL with a smaller effect located on chromosome 6C. This mapping approach also narrowed down the physical intervals to between 5 and 19 Mb, and indicated that QPc.APR-4D.1, QPc.APR-4D.2, and QPc.APR-6C explained 43.4%, 38.5%, and 21.5% of the phenotypic variation, respectively. In a survey of the gene content of each QTL, several clusters of disease resistance genes that may contribute to APR were found. The allele specific PCR markers developed for these QTL regions would be beneficial for marker-assisted breeding, gene pyramiding, and future cloning of resistance genes from oat.

Perineal wound healing after abdominoperineal resection for rectal cancer: a retrospective cohort study.

PURPOSE: Delayed perineal wound healing is a common complication after abdominoperineal resection (APR) in rectal cancer. The primary aim of this study was to evaluate the number of patients with delayed wound healing after APR. Secondary aims were to identify risk factors, and describe treatment. METHODS: Prospectively collected data from the Swedish Colorectal Cancer Registry (SCRCR) was used for retrospective analysis of APR performed at Skåne University Hospital Malmö between 2013 and 2018. Medical charts were retrospectively reviewed. Delayed healing was defined as non-healed perineal wound 30 days postoperatively. Patients undergoing extralevator APR requiring reconstruction were excluded. Statistical analysis was made using SPSS. Risk factors for impaired wound healing were analyzed using a multivariable model. RESULTS: A total of 162 patients were included, of which 114 underwent standard APR (sAPR) and 48 patients intersphincteric APR (isAPR). In the total population, 69% (111/162) were male, with median age 71 (26-87). The overall healing rate was 52% (85/162); 44% (50/114) in sAPR vs 73% (35/48) in isAPR (P < 0.001). Risk factors for impaired healing after multivariable analysis were BMI > 30 (OR 7.0; CI 95% 1.8-26.2, P = 0.004), reoperation (OR 7.9; CI 95% 1.6-39.8, P = 0.013), neoadjuvant radiotherapy (OR 5.2; CI 95% 1.02-25.1, P = 0.047) and sAPR (OR 2.598; CI 95% 1.05-6.41, P = 0.038). Eight percent (13/162) required an intervention (Clavien-Dindo ≥ 3). CONCLUSION: Delayed perineal wound healing is a frequent complication after APR but the majority could be treated conservatively. Several risk factors were identified. Further studies aiming at interventions reducing delayed perineal wound healing after APR are warranted.

Measuring case severity: a novel tool for benchmarking and clinical documentation improvement.

BACKGROUND: Severity of illness (SOI) is an All Patients Refined Diagnosis Related Groups (APR DRG) modifier based on comorbidity capture. Tracking SOI helps hospitals improve performance and resource distribution. Furthermore, benchmarking SOI plays a key role in Quality Improvement (QI) efforts such as Clinical Documentation Improvement (CDI) programs. The current SOI system highly relies on the 3 M APR DRG grouper that is updated annually, making it difficult to track severity longitudinally and benchmark against hospitals with different patient populations. Here, we describe an alternative SOI scoring system that is grouper-independent and that can be tracked longitudinally. METHODS: Admission data for 2019-2020 U.S. News and World Report Honor Roll facilities were downloaded from the Vizient Clinical Database and split into training and testing datasets. Elixhauser comorbidities, body systems developed from the Healthcare Cost and Utilization Project (HCUP), and ICD-10-CM complication and comorbidity (CC/MCC) indicators were selected as the predictors for orthogonal polynomial regression models to predict patients' admission and discharge SOI. Receiver operating characteristic (ROC) and Precision-Recall (PR) analysis, and prediction accuracy were used to evaluate model performance. RESULTS: In the training dataset, the full model including both Elixhauser comorbidities and body system CC/MCC indicators had the highest ROC AUC, PR AUC and predication accuracy for both admission (ROC AUC: 92.9%; PR AUC: 91.0%; prediction accuracy: 85.4%) and discharge SOI (ROC AUC: 93.6%; PR AUC: 92.8%; prediction accuracy: 86.2%). The model including only body system CC/MCC indicators had similar performance for admission (ROC AUC: 92.4%; PR AUC: 90.4%; prediction accuracy: 84.8%) and discharge SOI (ROC AUC: 93.1%; PR AUC: 92.2%; prediction accuracy: 85.6%) as the full model. The model including only Elixhauser comorbidities exhibited the lowest performance. Similarly, in the validation dataset, the prediction accuracy was 86.2% for the full model, 85.6% for the body system model, and 79.3% for the comorbidity model. With fewer variables and less model complexity, the body system model was more efficient and was determined to be the optimal model. The probabilities generated from this model, named J_Score and J_Score_POA, successfully measured SOI and had practical applications in assessment of CDI performance. CONCLUSIONS: The J_Scores generated from the body system model have significant value in evaluating admission and discharge severity of illness. We believe that this new scoring system will provide a useful tool for healthcare institutions to benchmark patients' illness severity and augment Quality Improvement (QI) efforts.

Effect of colostrum on the acute-phase response in neonatal dairy calves.

The core part of the mammal innate immune system is the acute-phase response (APR), during which acute-phase proteins (APP) are synthesized. Colostrum contains immunomodulating factors such as proinflammatory cytokines and APP in large quantities. We looked at proinflammatory cytokines [IL-1ß, IL-6, and tumor necrosis factor-α (TNF-α)] and APP [serum amyloid A (SAA) and haptoglobin (Hp)] in colostrum and in calves' serum. The aim of this study was to evaluate the effects of colostrum on the calves' systemic APR and the associations of the calves' serum APR with short- and long-term weight gain (at the age of 1, 3, and 9 mo). A total of 143 female dairy calves were studied during their first 3 wk of life. The calves were separated from their mothers immediately after birth and bottle-fed 3 L of quality-controlled colostrum once within 2 h after birth. Serum samples were collected once a week during the first 3 wk of life (a total of 1-3 samples per calf). Mean sampling age (±standard deviation) was 4.3 (±2.0) d in the first week, 11.0 (±2.0) d in the second week, and 18.0 (±2.0) d in the third week. Linear regression models were used to study associations of colostrum APP and cytokine concentration with serum APR markers and for studying associations of colostrum and serum APR markers with calves' average daily weight gain (ADWG). Mixed linear regression models were used to compare serum concentrations of APR markers by study weeks. The colostrum IL-6 concentrations were positively associated with serum IL-6 in the first 3 wk of life. Colostrum IL-1ß was positively associated with calves' serum IL-1ß during the first week of life, and colostrum TNF-α was positively associated with calves' serum TNF-α during the first 2 wk of life. Serum IL-1ß concentrations differed over the 3 wk, being the highest during the first week and the lowest during the second week. For IL-6, the concentration during the first week was the highest, and for TNF-α, a steady decline in the concentration was observed. Serum SAA concentrations were elevated during the first 2 wk of life and subsequently declined during the third week. Albumin concentrations were lowest in the first week, whereas Hp concentrations were highest during the second week. Serum concentrations of SAA, Hp, IL-6, and TNF-α during the second week were negatively associated with ADWG at 9 mo of age. The SAA concentrations during the third week of age had a negative association with 9-mo ADWG. Serum Hp concentrations in the third week were negatively associated with 3-mo ADWG. The results of our study suggest that colostrum cytokines influence calf serum cytokine concentrations. Thus, they influence the newborn calves' adaptation to the environment and the development of their immune system. Factors that activate an APR during the second and third week of life have a long-term influence on calves' development.

Transperineal minimally invasive abdominoperineal resection for low rectal cancer: standardized technique and clinical outcomes.

BACKGROUND: Despite the increasing utilization of transanal total mesorectal excision as a promising approach for low rectal cancer, the feasibility and safety of transperineal minimally invasive abdominoperineal resection (tp-APR) remain unclear. METHODS: In total, 25 patients who underwent tp-APR between April 2017 and May 2020 (tp-APR group) and 27 patients who underwent conventional laparoscopic APR between May 2009 and September 2016 (lap-APR group) for low rectal cancer were enrolled in this retrospective study. Clinical outcomes were compared between the groups before and after propensity score matching. The primary outcome was the incidence of the overall postoperative complications with Clavien-Dindo grade II or above. Standardized technique of tp-APR was also demonstrated. RESULTS: On comparison, operative time, intraoperative blood loss, and overall postoperative complications with Clavien-Dindo grade II or above were significantly less in the tp-APR group both before and after propensity score matching. The rates of urinary disturbance and perineal wound infection were significantly less in the tp-APR group after matching. Further, postoperative hospital stay was significantly shorter in the tp-APR group both before and after matching. However, pathological outcomes did not differ between the groups before and after matching. There has been no local recurrence in the tp-APR group with a median follow-up period of 18 months. CONCLUSION: Standardized tp-APR for low rectal cancer is feasible and seems superior to conventional laparoscopic APR in terms of short-term outcomes. Further larger-scale studies with a longer follow-up period are required to evaluate oncological outcomes.