Miracle-dz/UniFAR-FTUs huggingface dataset:
The Viscoelastic Behavior of Soft Tissues Must be Accounted for in Stapler Design and Surgeon Technique.

BACKGROUND Since its adoption as a surgical technique over a half-century ago, stapling has continually undergone improvements, both in the devices used and in our understanding of tissue mechanics. To best design and use stapling devices, it is beneficial to have an intimate knowledge of the response of tissue to compression and stapling dynamics. This paper provides the relevant background in the field of biomechanics, and in particular addresses the viscoelastic behavior of soft tissues under compression. Biomechanics of Stapling: The change in shape of a solid, or strain, is related to the load applied, or stress. Biological tissues are known to have non-linear relationships between stress and strain, and generally the relationships are anisotropic (dependent upon direction). Further complicating matters, there is typically a time-dependency to the relationship for compression and recovery, resulting in viscoelastic behavior. Hence both the amount and rate of compressive force applied can be expected to impact the outcome of stapling. DISCUSSION The growth of the laparoscopic use of staples has increased the difficulty of device design, as precise control of compression is problematic in extended length staplers. Progressive firing along the cartridge and multi-stage compression have both been found to be beneficial in providing the uniform force needed to produce well-formed staples. Such technical advances can reduce stresses within the stapler, preventing deformation of the stapler arm and undesirable strain in the tissue. Current research includes understanding the effects of changing the rate of compression on staple formation with the hope that further improvements can be achieved in this ever-fruitful method of tissue apposition.
CRISPR/Cas9-Engineered HLA-Deleted Glomerular Endothelial Cells as a Tool to Predict Pathogenic Non-HLA Antibodies in Kidney Transplant Recipients

Significance Statement Evidence for the deleterious role of non-HLA antibodies after kidney transplantation is growing. Still, given the high heterogeneity and the number of potential targets, a candidate-based strategy to detect these antibodies can be misleading. We introduce a cell-based assay using human glomerular endothelial cells deleted for all HLA antigens as targets and recapitulate a large array of potential non-HLA antibodies in a single test. This approach confirms that the global burden of non-HLA antibodies targeting the endothelium is associated with microvascular inflammation and worse graft outcome, independent of HLA donor-specific antibodies. Our results demonstrate the clinical utility of the test for improving the pretransplant evaluation of immunologic risk and for designing mechanism-driven therapeutic approaches targeting non-HLA antibodies. Background After kidney transplantation, donor-specific antibodies against human leukocyte antigen donor-specific antibodies (HLA-DSAs) drive antibody-mediated rejection (ABMR) and are associated with poor transplant outcomes. However, ABMR histology (ABMRh) is increasingly reported in kidney transplant recipients (KTRs) without HLA-DSAs, highlighting the emerging role of non-HLA antibodies (Abs). Methods W e designed a non-HLA Ab detection immunoassay (NHADIA) using HLA class I and II–deficient glomerular endothelial cells (CiGEnCΔHLA) that had been previously generated through CRISPR/Cas9-induced B2M and CIITA gene disruption. Flow cytometry assessed the reactivity to non-HLA antigens of pretransplantation serum samples from 389 consecutive KTRs. The intensity of the signal observed with the NHADIA was associated with post-transplant graft histology assessed in 951 adequate biopsy specimens. Results W e sequentially applied CRISPR/Cas9 to delete the B2M and CIITA genes to obtain a CiGEnCΔHLA clone. CiGEnCΔHLA cells remained indistinguishable from the parental cell line, CiGEnC, in terms of morphology and phenotype. Previous transplantation was the main determinant of the pretransplantation NHADIA result (P<0.001). Stratification of 3-month allograft biopsy specimens (n=298) according to pretransplantation NHADIA tertiles demonstrated that higher levels of non-HLA Abs positively correlated with increased glomerulitis (P=0.002), microvascular inflammation (P=0.003), and ABMRh (P=0.03). A pretransplantation NHADIA threshold of 1.87 strongly discriminated the KTRs with the highest risk of ABMRh (P=0.005, log-rank test). A multivariate Cox model confirmed that NHADIA status and HLA-DSAs were independent, yet synergistic, predictors of ABMRh. Conclusion The NHADIA identifies non-HLA Abs and strongly predicts graft endothelial injury independent of HLA-DSAs.
A novel fluorescent reporter sensitive to serine mis-incorporation

ABSTRACT High-fidelity translation was considered a requirement for living cells. The frozen accident theory suggested that any deviation from the standard genetic code should result in the production of so much mis-made and non-functional proteins that cells cannot remain viable. Studies in bacterial, yeast, and mammalian cells show that significant levels of mistranslation (1–10% per codon) can be tolerated or even beneficial under conditions of oxidative stress. Single tRNA mutants, which occur naturally in the human population, can lead to amino acid mis-incorporation at a codon or set of codons. The rate or level of mistranslation can be difficult or impossible to measure in live cells. We developed a novel red fluorescent protein reporter that is sensitive to serine (Ser) mis-incorporation at proline (Pro) codons. The mCherry Ser151Pro mutant is efficiently produced in Escherichia coli but non-fluorescent. We demonstrated in cells and with purified mCherry protein that the fluorescence of mCherry Ser151Pro is rescued by two different tRNASer gene variants that were mutated to contain the Pro (UGG) anticodon. Ser mis-incorporation was confirmed by mass spectrometry. Remarkably, E. coli tolerated mistranslation rates of ~10% per codon with negligible reduction in growth rate. Conformational sampling simulations revealed that the Ser151Pro mutant leads to significant changes in the conformational freedom of the chromophore precursor, which is indicative of a defect in chromophore maturation. Together our data suggest that the mCherry Ser151 mutants may be used to report Ser mis-incorporation at multiple other codons, further expanding the ability to measure mistranslation in living cells.
Müller Glial Expression of REDD1 Is Required for Retinal Neurodegeneration and Visual Dysfunction in Diabetic Mice

Clinical studies support a role for the protein regulated in development and DNA damage response 1 (REDD1) in ischemic retinal complications. To better understand how REDD1 contributes to retinal pathology, we examined human single-cell sequencing data sets and found specificity of REDD1 expression that was consistent with markers of retinal Müller glia. Thus, we investigated the hypothesis that REDD1 expression specifically in Müller glia contributes to diabetes-induced retinal pathology. The retina of Müller glia-specific REDD1 knockout (REDD1-mgKO) mice exhibited dramatic attenuation of REDD1 transcript and protein expression. In the retina of streptozotocin-induced diabetic control mice, REDD1 protein expression was enhanced coincident with an increase in oxidative stress. In the retina of diabetic REDD1-mgKO mice, there was no increase in REDD1 protein expression, and oxidative stress was reduced compared with diabetic control mice. In both Müller glia within the retina of diabetic mice and human Müller cell cultures exposed to hyperglycemic conditions, REDD1 was necessary for increased expression of the gliosis marker glial fibrillary acidic protein. The effect of REDD1 deletion in preventing gliosis was associated with suppression of oxidative stress and required the antioxidant transcription factor nuclear factor erythroid-2-related factor 2 (Nrf2). In contrast to diabetic control mice, diabetic REDD1-mgKO mice did not exhibit retinal thinning, increased markers of neurodegeneration within the retinal ganglion cell layer, or deficits in visual function. Overall, the findings support a key role for Müller glial REDD1 in the failed adaptive response of the retina to diabetes that includes gliosis, neurodegeneration, and impaired vision.
Volatile organic compounds from exhaled breath in schizophrenia

Abstract Objectives This study aims to find out whether volatile organic compounds (VOCs) from exhaled breath differ significantly between patients with schizophrenia and healthy controls and whether it might be possible to create an algorithm that can predict the likelihood of suffering from schizophrenia. Methods To test this theory, a group of patients with clinically diagnosed acute schizophrenia as well as a healthy comparison group has been investigated, which have given breath samples during awakening response right after awakening, after 30 min and after 60 min. The VOCs were measured using Proton-Transfer-Reaction Mass Spectrometry. Results By applying bootstrap with mixed model analysis (n = 1000), we detected 10 signatures (m/z 39, 40, 59, 60, 69, 70, 74, 85, 88 and 90) showing reduced concentration in patients with schizophrenia compared to healthy controls. These could safely discriminate patients and controls and were not influenced by smoking. Logistic regression forward method achieved an area under the receiver operating characteristic curve (AUC) of 0.91 and an accuracy of 82% and a machine learning approach with bartMachine an AUC of 0.96 and an accuracy of 91%. Conclusion Breath gas analysis is easy to apply, well tolerated and seems to be a promising candidate for further studies on diagnostic and predictive clinical utility.
Effects of α-glycerol monolaurate on intestinal morphology, nutrient digestibility, serum profiles, and gut microbiota in weaned piglets.

This experiment was conducted to investigate the effects of dietary supplementation of α-glycerol monolaurate (α-GML) on the growth performance, nutrient digestibility, serum profiles, intestinal morphology, and gut microbiota of weaned piglets. A total of 96 healthy 28-day-old (Duroc × Landrace × Yorkshire) weaned piglets with body weight of 8.34 ± 0.05 kg were randomly divided into 2 treatment groups with 6 replicate pens and 8 piglets per pen. The control group was fed a basal diet, and the experimental group was fed the basal diet supplemented with 1,000 mg/kg α-GML. The experiment lasted for 28 days. Dietary supplementation with α-GML had no effect on average daily gain (ADG), average daily feed intake (ADFI), or gain to feed ratio (G:F) in piglets (P > 0.05); however, it reduced (P < 0.05) diarrhea rate of piglets on days 15 to 28. The apparent total tract digestibility (ATTP) of dry matter (DM), crude protein (CP), ether extract (EE), and gross energy (GE) on day 14, and DM, organic matter (OM), CP, EE, and GE on day 28 increased (P < 0.05) with α-GML supplementation. Moreover, higher (P < 0.05) glutathione peroxidase (GSH-Px) activity and interleukin-10 (IL-10) concentration, and lower (P < 0.05) malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) concentrations were observed in piglets supplemented with α-GML compared with the control group on day 14. Compared with the control group, the villus height/crypt depth in the duodenum and villus height in the jejunum and ileum were significantly greater (P < 0.05) in the α-GML group. Dietary α-GML supplementation significantly increased (P < 0.05) the relative abundance of Firmicutes, while decreasing (P < 0.05) Bacteroidota and Campilobacterota in the cecal contents; significantly increased (P < 0.05) the relative proportion of Lactobacillus and Blautia species, reduced (P < 0.05) Eubacterium_rectale_ATCC_33656, Campylobacter, and uncultured_bacterium_Alloprevotella species. Thus, dietary α-GML supplementation at 1,000 mg/kg reduces diarrhea rate, improves intestinal morphology, nutrient digestibility, antioxidant capacity, and immune status, and ameliorates gut microbiota in weaned piglets.
Diagnosis of malignant biliary obstruction: pondering over the ERCP, MRCP and histology

Objective To compare the diagnostic accuracy of endoscopic retrograde cholangiopancreatography (ERCP), magnetic resonance pancreatography (MRCP) and histological examination for malignant biliary obstruction. Methods This retrospective study included patients admitted for biliary obstruction caused by biliary tree malignancy that underwent ERCP, MRCP and histological examination. Data were collected from the medical records. The primary endpoints were the area under the receiver operating characteristic (AUROC) curve value, sensitivity, specificity and overall diagnostic accuracy of the three procedures in terms of a final diagnosis of obstructive biliary malignancy; and the agreement between ERCP, MRCP and histological examination with the final diagnosis. Results A total of 160 patients were included in the study (85 males, 53.1%; mean ± SD age, 69.31 ± 10.96 years). Considering the final diagnosis, the performance of MRCP, ERCP and histology in assessing biliary tumours produced AUROC values of 0.88 (95% confidence interval [CI] 0.75, 0.90), 0.94 (95% CI 0.85, 0.99) and 0.80 (95% CI 0.70, 0.82), respectively. ERCP presented higher sensitivity, overall diagnostic accuracy and agreement with the final diagnosis than MRCP and histological examination. Conclusion These current data suggest that invasive methods such as ERCP with biopsy remain more reliable than non-invasive methods.
Endothelin 2, a key player in ovulation and fertility.

Ovulation is the fundamental biological process during which an oocyte is expelled from the ovary, and it is an essential step toward establishing pregnancy. Understanding regulatory mechanisms governing the ovulation process is essential for diagnosing and treating causes of infertility, identifying contraceptive targets, and developing novel contraception methods. EDN2 is a 21-amino acid long peptide that is transiently synthesized by granulosa cells of the ovulatory follicle prior to ovulation and plays an essential role in ovulation via promoting contraction in the myofibroblast cells of the theca layer of the follicle. This review describes the organization of the endothelin system, summarizes recent findings on the expression and synthesis of the endothelin system in the ovary, illustrates the roles that EDN2 plays in regulating ovulation, and discusses EDN2 as a potential target of contraception.
Supporting in situ conservation of the genetic diversity of crop wild relatives using genomic technologies

The last decade has witnessed huge technological advances in genomics, particularly in DNA sequencing. Here, we review the actual and potential application of genomics in supporting in situ conservation of crop wild relatives (CWRs). In addition to helping in prioritization of protection of CWR taxa and in situ conservation sites, genome analysis is allowing the identification of novel alleles that need to be prioritized for conservation. Genomics is enabling the identification of potential sources of important adaptive traits that can guide the establishment or enrichment of in situ genetic reserves. Genomic tools also have the potential for developing a robust framework for monitoring and reporting genome‐based indicators of genetic diversity changes associated with factors such as land use or climate change. These tools have been demonstrated to have an important role in managing the conservation of populations, supporting sustainable access and utilization of CWR diversity, enhancing accelerated domestication of new crops and forensic genomics thus preventing misappropriation of genetic resources. Despite this great potential, many policy makers and conservation managers have failed to recognize and appreciate the need to accelerate the application of genomics to support the conservation and management of biodiversity in CWRs to underpin global food security. Funding and inadequate genomic expertise among conservation practitioners also remain major hindrances to the widespread application of genomics in conservation.
The prognostic value of the lymph node ratio in patients with distal cholangiocarcinoma after curative intended surgery: A single-center retrospective study

Backgrounds/Aims The goal of the present study was to evaluate the prognostic value of lymph node ratio (LNR) in distal cholangiocarcinoma (DCC) after curative intended surgery. Methods Clinicopathological data of 162 DCC patients who underwent radical intended surgery between 2012 and 2020 were analyzed retrospectively. Prognostic factors related to overall survival (OS) and disease-free survival (DFS) were evaluated. Results Median OS time and DFS time were 41 and 29 months, and 5-year OS rate and DFS rate were 44.7% and 38.1%, respectively. In the univariate analysis, significant prognostic factors for OS were histologic differentiation, American Joint Committee on Cancer (AJCC) stage, positive lymph node count, LNR, R1 resection, and perineural invasion. Preoperative carcinoembryonic antigen, carbohydrate antigen 19-9, infiltrative type, histologic differentiation, AJCC stage, positive lymph node count, LNR, R1 resection, perineural invasion, and lymph-vascular invasion were significant prognostic factors for DFS in the univariate analysis. In the multivariate analysis, histologic differentiation, R1 resection, and LNR were the independent prognostic factors for both OS and DFS. The LNR ≥ 0.2 group had a significantly poor prognosis in terms of OS (hazard ratio, 3.915; p = 0.002) and DFS (hazard ratio, 5.840; p < 0.001). Conclusions LNR has significant value as a prognostic factor of DCC related to OS and DFS. LNR has the potential to be used as a modified staging system with furthermore studies.
Spatiotemporal target selection for intracranial neural decoding of abstract and concrete semantics

Abstract Decoding the inner representation of a word meaning from human cortical activity is a substantial challenge in the development of speech brain–machine interfaces (BMIs). The semantic aspect of speech is a novel target of speech decoding that may enable versatile communication platforms for individuals with impaired speech ability; however, there is a paucity of electrocorticography studies in this field. We decoded the semantic representation of a word from single-trial cortical activity during an imageability-based property identification task that required participants to discriminate between the abstract and concrete words. Using high gamma activity in the language-dominant hemisphere, a support vector machine classifier could discriminate the 2-word categories with significantly high accuracy (73.1 ± 7.5%). Activities in specific time components from two brain regions were identified as significant predictors of abstract and concrete dichotomy. Classification using these feature components revealed that comparable prediction accuracy could be obtained based on a spatiotemporally targeted decoding approach. Our study demonstrated that mental representations of abstract and concrete word processing could be decoded from cortical high gamma activities, and the coverage of implanted electrodes and time window of analysis could be successfully minimized. Our findings lay the foundation for the future development of semantic-based speech BMIs.
Protease‐activated receptor‐2 dependent and independent responses of bone cells to prostate cancer cell secretory products

Metastatic prostate cancer lesions in the skeleton are frequently characterized by excessive formation of bone. Prostate cancer cells secrete factors, including serine proteases, that are capable of influencing the behavior of surrounding cells. Some of these proteases activate protease‐activated receptor‐2 (PAR2), which is expressed by osteoblasts (bone‐forming cells) and precursors of osteoclasts (bone‐resorbing cells). The aim of the current study was to investigate a possible role for PAR2 in regulating the behavior of bone cells exposed to metastatic prostate cancer cells.
Iron deficiency in heart failure patients: the French CARENFER prospective study

Iron deficiency (ID) is reported as one of the main co‐morbidities in patients with chronic heart failure (CHF), which then influences quality of life and prognosis. The CARENFER study aimed to assess the prevalence of ID in a large panel of heart failure (HF) patients at different stages of the disease.
Patient-Centered Treatment of Chronic Migraine With Medication Overuse

Overuse of acute (e.g., abortive) pain medication is commonly noted in patients with chronic headache disorders, particularly migraine. Whether such overuse is a primary contributor to headache chronification and, more particularly, what the optimal treatment strategies for such patients are remain uncertain.1-4 The traditional view reflected in the International Classification of Headache Disorders (ICHD-3)5 is that most people with chronic headaches have medication overuse headache, the majority of whom will improve on discontinuation of the overused medication, including their responsiveness to preventive medication, and that patients should be cautioned not to exceed dose limitations to prevent the development of chronic headache. The diagnosis of 8.2 medication-overuse headache is extremely important clinically. Epidemiologic evidence from many countries indicates that more than half of people with headache on 15 or more days/mo have 8.2 medication-overuse headache. Clinical evidence shows that the majority of patients with this disorder improve after discontinuation of the overused medication, as does their responsiveness to preventative treatment. Simple advice on the causes and consequences of 8.2 medication-overuse headache is an essential part of its management and can be provided with success in primary care. An explanatory brochure is often all that is necessary to prevent or discontinue medication overuse. Prevention is especially important in patients prone to frequent headache.5
Anticollision Safety Design and Control Methodology for Human-Symbiotic Robot Manipulator

This paper describes a design methodology for a human-symbiotic robot manipulator which mainly focuses on guarantee of human's safety and abilities of human-robot collaboration. In this paper, we classify the safety design parameters into four categories, such as shock absorption materials, motion controls, collision statements, and safety indices.First, physical models of shock absorption covers, realization of emergency stop and passive impedance control, experimental conditions of generalized human-robot collision, and severity indices for producing moderate injury are described. Next, human-robot collisions are simulated through a combination of there parameters, and the effects of each parameter on anticollision safety are arranged. Then, the several remarks for deciding design parameters are conducted from the experiment and simulation results.As the summarization of this paper, a safety design and control methodology for human symbiotic robot manipulator is proposed by synthesizing these remarks.