Miracle-dz/UniFAR-FTUs huggingface dataset:
Paraaortic sentinel lymph node detection in intermediate and high-risk endometrial cancer by transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR)

Objective We aimed to evaluate the accuracy of sentinel lymph node (SLN) mapping with transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR) to detect lymph node (LN) metastases, in patients with intermediate and high-risk endometrial cancer (EC), focusing on its performance to detect paraaortic involvement. Methods Prospective study including women with preoperative intermediate or high-risk EC, according to ESMO-ESGO-ESTRO consensus, who underwent SLN mapping using the TUMIR approach. SLNs were preoperatively localized by planar and single photon emission computed tomography/computed tomography images, and intraoperatively by gamma-probe. Immediately after SLN excision, all women underwent systematic pelvic and paraaortic lymphadenectomy by laparoscopy. Results The study included 102 patients. The intraoperative SLN detection rate was 79.4% (81/102). Pelvic and paraaortic drainage was observed in 92.6% (75/81) and 45.7% (37/81) women, respectively, being exclusively paraaortic in 7.4% (6/81). After systematic lymphadenectomy, LN metastases were identified in 19.6% (20/102) patients, with 45.0% (9/20) showing paraaortic involvement, which was exclusive in 15.0% (3/20). The overall sensitivity and negative predictive value (NPV) of SLNs by the TUMIR approach to detect lymphatic involvement were 87.5% and 97.0%, respectively; and 83.3% and 96.9%, for paraaortic metastases. After applying the MSKCC SLN mapping algorithm, the sensitivity and NPV were 93.8% and 98.5%, respectively. Conclusion The TUMIR method provides valuable information of endometrial drainage in patients at higher risk of paraaortic LN involvement. The TUMIR approach showed a detection rate of paraaortic SLNs greater than 45% and a high sensitivity and NPV for paraaortic metastases in women with intermediate and high-risk EC.
Feeding intolerance during phototherapy in preterm infants

Abstract Objective Many very preterm infants are treated with phototherapy (PT) for hyperbilirubinemia and it has been reported that PT can negatively affect gut perfusion. Thus, our aim was to evaluate the occurrence of feeding intolerance in the course of PT in these patients. Methods We retrospectively studied infants born at 25+0–31+6 weeks from November 2017 to April 2020 who required PT during the first two weeks of life. Patients were used as their own controls recording for each one the occurrence of feeding intolerance after starting PT and the resumption of feeding tolerance after its termination. Results We studied 125 preterm infants of whom 58 (46%) developed a feeding intolerance which disappeared in 47 (81%) of them at the end of PT. Regression analysis showed a trend toward a not significant decrease of risk of feeding intolerance in infants with higher birth weight and age at the start of the first course of PT. Conclusion We found that about half of our patients developed a transient feeding intolerance during PT that ceased in the vast majority of them after termination of the therapy. Further studies are necessary to confirm the correlation between PT and feeding intolerance.
Combined gene deletion of dihydrofolate reductase-thymidylate synthase and pteridine reductase in Leishmania infantum

Our understanding of folate metabolism in Leishmania has greatly benefited from studies of resistance to the inhibitor methotrexate (MTX). Folates are reduced in Leishmania by the bifunctional dihydrofolate reductase thymidylate synthase (DHFR-TS) and by pteridine reductase (PTR1). To further our understanding of folate metabolism in Leishmania, a Cos-seq genome-wide gain of function screen was performed against MTX and against the two thymidylate synthase (TS) inhibitors 5-fluorouracil and pemetrexed. The screen revealed DHFR-TS and PTR1 but also the nucleoside transporter NT1 and one hypothetical gene derived from chromosome 31. For MTX, the concentration of folate in the culture medium affected the enrichment pattern for genes retrieved by Cos-seq. We generated a L. infantum DHFR-TS null mutant that was thymidine auxotroph, a phenotype that could be rescued by the addition of thymidine or by transfection of the flavin dependent bacterial TS gene ThyX. In these DHFR-TS null mutants it was impossible to obtain a chromosomal null mutant of PTR1 except if DHFR-TS or PTR1 were provided episomally. The transfection of ThyX however did not allow the elimination of PTR1 in a DHFR-TS null mutant. Leishmania can survive without copies of either DHFR-TS or PTR1 but not without both. Provided that our results observed with the insect stage parasites are also replicated with intracellular parasites, it would suggest that antifolate therapy in Leishmania would only work if both DHFR-TS and PTR1 would be targeted simultaneously.
Hesperidin protects against the chlorpyrifos‐induced chronic hepato‐renal toxicity in rats associated with oxidative stress, inflammation, apoptosis, autophagy, and up‐regulation of PARP‐1/VEGF

In this study, we investigated the effects of hesperidin (HSP) on oxidants/antioxidants status, inflammation, apoptotic, and autophagic activity in hepato‐renal toxicity induced by chronic chlorpyrifos (CPF) exposure in rats. We used a total of 35 male albino rats in five groups of seven: control, HSP 100, CPF, CPF + HSP50, and CPF + HSP100. After rats were sacrificed, blood, liver, and kidney samples were collected. Serum levels of aspartate aminotransferases (ALT and AST), alkaline phosphatase (ALP), creatinine, and urea were tested. Then, contents of the superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), glutathione peroxidase (GPx), and glutathione (GSH) were measured to detect the level of oxidative stress in rat liver and renal tissues. We measured inflammatory and autophagy markers of chlorpyrifos induced oxidative stress in the liver and kidney tissues including TNF‐α, iNOS, IL‐1 β, COX‐2, NF‐κB, MAPK14, and Beclin‐1 using ELISA. Histopathological findings were also examined followed by immunohistochemical determination of 8‐OHdG expression. Real‐time PCR (RT‐PCR) was used to examine Cas‐3, Bax, Bcl‐2, PARP‐1, and VEGF, which are associated with apoptosis, autophagy, DNA, and endothelial damage, respectively. In addition, PARP‐1 activity was supported by western blot and immunofluorescence, VEGF activity was supported by western blot methods. Treatment with HSP reduced the effect of CPF on ALT, AST, ALP, and total proteins, and increased its effect on tissue antioxidants. PARP/VEGF, apoptotic, pro‐apoptotic, anti‐apoptotic, and autophagic gene expressions were regulated, and Caspase‐3 and Bax expressions were decreased; Bcl‐2 expression increased in both the liver and kidney samples, and positivity of 8‐OHdG and PARP‐1 were reduced in the CPF plus HSP‐treated group. Overall, the study demonstrates that HSP may reduce the effects of hepato‐renal toxicity caused by CPF by regulating oxidative stress, inflammation, apoptosis, autophagy, and PARP/VEGF genes at biochemical, cellular, and molecular levels.
The Contribution of Macrophages in Old Mice to Periodontal Disease

The prevalence of periodontal disease increases with age. Systemic inflammatory dysregulation also increases with age and has been reported to contribute to the myriad of diseases and conditions that become more prevalent with advanced age. As periodontal disease involves a dysregulated host inflammatory response, the age-related inflammatory dysregulation may contribute to the pathogenesis of periodontal disease in aging populations. However, our understanding of what drives the age-related inflammatory dysregulation is limited. Here, we investigate the macrophage and its contribution to periodontal disease in old and young mice using a ligature-induced periodontal disease model. We demonstrate that control old mice present with an aged periodontal phenotype, characterized by increased alveolar bone loss and increased local inflammatory cytokine expression compared to young mice. Macrophages were demonstrated to be present in the periodontium of old and young mice in equal numbers in controls, during disease induction, and during disease recovery. However, it appears age may have a detrimental effect on macrophage activity during disease recovery. Depletion of macrophages during disease recovery in old mice resulted in decreased inflammatory cytokines within the gingiva and decreased bone loss as measured by micro–computed tomography. In young mice, macrophage depletion during disease recovery had no beneficial or detrimental effect. Macrophage depletion during disease induction resulted in decreased disease severity similarly in young and old mice. Findings from this work support the diverse roles of macrophages in disease induction as well as the active roles of disease recovery, including the resolution of inflammation. Here, we conclude that age-related changes to the macrophage appear to be detrimental to the recovery from disease and may explain, in part, the age-related increase in prevalence of periodontal disease. Future studies examining the specific intrinsic age-related changes to the macrophage will help identify therapeutic targets.
Impact of photobiomodulation and low-intensity pulsed ultrasound adjunctive interventions on orthodontic treatment duration during clear aligner therapy: A retrospective study.

OBJECTIVE To assess the efficiency of low-intensity pulsed ultrasound (LIPUS) and photobiomodulation (PBM) interventions in accelerating orthodontic tooth movement during clear aligner therapy (CAT). MATERIALS AND METHODS This retrospective study was carried out on the records of 84 subjects who were treated using CAT. Twenty-eight patients were treated using CAT with a daily use of LIPUS for 20 minutes, 28 patients were treated using CAT with a daily use of PBM for 10 minutes, and 28 patients were treated using CAT alone. The total duration of treatment was recorded for all patients. One-way analysis of variance and post hoc Tukey test were used to assess whether there was any significant difference in total treatment duration among the three groups (P < .05). RESULTS The mean treatment durations in days were 719 ± 220, 533 ± 242, and 528 ± 323 for the control, LIPUS, and PBM groups, respectively. The LIPUS group showed a 26% reduction, on average, in treatment duration when compared with the control group, whereas the PBM group showed an average 26.6% reduction in the treatment duration when compared with the control group. The results showed that there were statistically significant differences among the groups (P = .011). Treatment durations were significantly reduced in the LIPUS and PBM groups as compared with the control (P = .027 and P = .023, respectively), with no statistically significant differences between the LIPUS and PBM groups (P = .998). CONCLUSIONS Daily use of LIPUS or PBM as adjunctive interventions during CAT could reduce the duration of orthodontic treatment.
Hydraulic consequences of enzymatic breakdown of grapevine pit membranes.

Xylella fastidiosa (Xf) is the xylem-dwelling bacterial agent associated with Pierce's Disease (PD), which leads to significant declines in productivity in agriculturally important species like grapevine (Vitis vinifera). Xf spreads through the xylem network by digesting the pit membranes between adjacent vessels, thereby potentially changing the hydraulic properties of the stem. However, the effects of Xf on water transport varies depending on the plant host and the infection stage, presenting diverse outcomes. Here, we investigated the effects of polygalacturonase, an enzyme known to be secreted by Xf when it produces biofilm on the pit membrane surface, on stem hydraulic conductivity and pit membrane integrity. Experiments were performed on six grapevine genotypes with varying levels of PD resistance, with the expectation that pit membrane resistance to degradation by polygalacturonase may play a role in PD-resistance. Our objective was to study a single component of this pathosystem in isolation to better understand the mechanisms behind reported changes in hydraulics, thereby excluding the biological response of the plant to the presence of Xf in the vascular system. Pit membrane damage only occurred in stems perfused with polygalacturonase. Although the damaged pit membrane area was small (2-9% of the total pit aperture area), membrane digestion led to significant changes in the median air-seeding thresholds, and most importantly, shifted frequency distribution. Finally, enzyme perfusion also resulted in a universal reduction in stem hydraulic conductivity, suggesting the development of tyloses may not be the only contributing factor to reduced hydraulic conductivity in infected grapevine.
Global and Parallel Cortical Processing Based on Auditory Gamma Oscillatory Responses in Humans

Abstract Gamma oscillations are physiological phenomena that reflect perception and cognition, and involve parvalbumin-positive γ-aminobutyric acid-ergic interneuron function. The auditory steady-state response (ASSR) is the most robust index for gamma oscillations, and it is impaired in patients with neuropsychiatric disorders such as schizophrenia and autism. Although ASSR reduction is known to vary in terms of frequency and time, the neural mechanisms are poorly understood. We obtained high-density electrocorticography recordings from a wide area of the cortex in 8 patients with refractory epilepsy. In an ASSR paradigm, click sounds were presented at frequencies of 20, 30, 40, 60, 80, 120, and 160 Hz. We performed time-frequency analyses and analyzed intertrial coherence, event-related spectral perturbation, and high-gamma oscillations. We demonstrate that the ASSR is globally distributed among the temporal, parietal, and frontal cortices. The ASSR was composed of time-dependent neural subcircuits differing in frequency tuning. Importantly, the frequency tuning characteristics of the late-latency ASSR varied between the temporal/frontal and parietal cortex, suggestive of differentiation along parallel auditory pathways. This large-scale survey of the cortical ASSR could serve as a foundation for future studies of the ASSR in patients with neuropsychiatric disorders.
Low-Risk Human Leukocyte Antigen Genes and Mild Villous Atrophy Typify Celiac Disease With Immunoglobulin A Deficiency

ABSTRACT Objectives: We aimed to establish if in celiac disease (CD) with immunoglobulin A deficiency (IgAD) duodenal histopathology is influenced by human leukocyte antigen (HLA)-DQB1∗02 alleles dosage. Clinical differences between patients with CD and patients with CD and IgAD (CD-IgAD) were also evaluated. Methods: Five hundred and sixteen CD and 16 patients with CD-IgAD, enrolled over the time of 8 years, took part in this study. The severity of duodenal histopathology and frequency of CD at-risk HLA class II genes were compared in patients with CD versus patients with CD-IgAD. HLA class II genotypes were subdivided into two categories of genetic risk: high: HLA-DR3/DR7, -DR3/DR3, -DR4/DR4 -DR3/DR4 and low: HLA-DR5/DR7, -DR3/X, -DR4/X and X/X, where X means neither -DR3 nor -DR4. Then, they were compared with two types of duodenal histopathology: 0, 1, 2 and 3a of mild villous atrophy (MVA) and 3b and 3c of severe villous atrophy (SVA) according to the Marsh-Oberhuber classification. Clinical data concerning gender, number of esophagogastroduodenoscopies (EGDs) and association with other autoimmune diseases were obtained from medical records. Results: In comparison with CD, CD-IgAD showed an increased frequency of MVA (P < 0.0001). Furthermore, CD-IgAD with MVA showed an increase of HLA low-risk genotypes (P = 0.036) and half HLA-DQ2 heterodimers (P = 0.0443). Interestingly, CD-IgAD demanded an increased number of EGDs to reach the diagnosis of CD (P = 0.0104) and autoimmune liver diseases were more frequent compared to CD (P = 0.0049). Conclusions: CD-IgAD is associated with MVA, low-risk HLA class II genes, an increased number of EGDs and autoimmune liver diseases.
Disorders of Secondary Neurulation : Mainly Focused on Pathoembryogenesis

Recent advancements in basic research on the process of secondary neurulation and increased clinical experience with caudal spinal anomalies with associated abnormalities in the surrounding and distal structures shed light on further understanding of the pathoembryogenesis of the lesions and led to the new classification of these dysraphic entities. We summarized the changing concepts of lesions developed from the disordered secondary neurulation shown during the last decade. In addition, we suggested our new pathoembryogenetic explanations for a few entities based on the literature and the data from our previous animal research. Disordered secondary neurulation at each phase of development may cause corresponding lesions, such as failed junction with the primary neural tube (junctional neural tube defect and segmental spinal dysgenesis), dysgenesis or duplication of the caudal cell mass associated with disturbed activity of caudal mesenchymal tissue (caudal agenesis and caudal duplication syndrome), failed ingression of the primitive streak to the caudal cell mass (myelomeningocele), focal limited dorsal neuro-cutaneous nondisjunction (limited dorsal myeloschisis and congenital dermal sinus), neuro-mesenchymal adhesion (lumbosacral lipomatous malformation), and regression failure spectrum of the medullary cord (thickened filum and filar cyst, low-lying conus, retained medullary cord, terminal myelocele and terminal myelocystocele). It seems that almost every anomalous entity of the primary neural tube may occur in the area of secondary neurulation. Furthermore, the close association with the activity of caudal mesenchymal tissue in secondary neurulation involves a wider range of surrounding structures than in primary neurulation. Although the majority of the data are from animals, not from humans and many theories are still conjectural, these changing concepts of normal and disordered secondary neurulation will provoke further advancements in our management strategies as well as in the pathoembryogenetic understanding of anomalous lesions in this area.
Comprehensive genomic analysis contrasting primary colorectal cancer and matched liver metastases: a retrospective study

(Background)Recent studies have revealed that colorectal cancer (CRC) displays intratumor genetic heterogeneity, and the cancer microenvironment play an important role in the proliferation, invasion, and metastasis of CRC. (Methods)We performed genomic analysis on 22 paired patients with primary CRC and synchronous colorectal liver metastasis (CRLM) using whole-exome sequencing, cancer gene panels, and microarray gene expression profiling. In addition, immunohistochemical analysis was used to confirm the protein expression of genes identified as highly expressed in CRLM by DNA microarray analysis. (Results)A total of 22 paired patients were enrolled in this study, including 13 (59.1%) colon and 9 (40.9%) rectal cancer patients. All patients had synchronous liver metastasis and did not have any other extrahepatic metastases. We identified 11 probes (10 genes) that were highly expressed in CRLM compared to CRC, from 36022 probes obtained from primary CRC, CRLM, and normal liver tissues, using gene expression analysis with DNA microarray. Of the 11 probes (10 genes), 5 genes classified as encoding “matricellular proteins” (osteopontin, periostin, thrombospondin-2, MGP, and GPNMB) were selected for immunohistochemical analysis.Osteopontin was strongly expressed in CRLM (6 of 22 cases: 27.3%) but not in CRC (0 of 22: 0%; p=0.02). Periostin also showed strong immunoreactivity in CRLM (17 of 22: 68.2%) compared to 7 of 22 (31.8%) in CRC (p=0.006). Thrombospondin-2 showed strong immunoreactivity both in CRC and CRLM (54.5% in CRC, 45.5% in CRLM; p=0.55). GPNMB and MGP were rarely positive for both CRC and CRLM. A comparison of immunoreactive positive factors for these 5 genes revealed the complexities of gene expression in CRLM. Of the cases, 16 (72.7%) CRC revealed zero or only one positive immunoreactivity. On the other hand, CRLM revealed more frequent multiple immunoreactivity; 16 cases (72.7%) shared 2 or more factors, which was statistically more frequent in CRLM than in CRC (p=0.007). (Conclusions)This study revealed the genomic heterogeneity between paired primary CRC and CRLM in terms of cancer cell microenvironment. This finding will lead to new diagnostic and therapeutic targets in the era of genome-guided personalized cancer treatment. (Trial registration)This study was retrospectively registered.
Clinical and biomechanical factors associated with falls and rheumatoid arthritis: baseline cohort with longitudinal nested case–control study

Abstract Objective To identify the clinical and biomechanical characteristics associated with falls in people with RA. Methods A total of 436 people ≥60 years of age with RA completed a 1 year prospective survey of falls in the UK. At baseline, questionnaires recorded data including personal and medical history, pain and fatigue scores, health-related quality of life (HRQoL), physical activity and medication history. The occurrence of falls wasmonitored prospectively over 12 months by monthly self-reporting. A nested sample of 30 fallers (defined as the report of one or more falls in 12 months) and 30 non-fallers was evaluated to assess joint range of motion (ROM), muscle strength and gait parameters. Multivariate regression analyses were undertaken to determine variables associated with falling. Results Compared with non-fallers (n = 236), fallers (n = 200) were older (P = 0.05), less likely to be married (P = 0.03), had higher pain scores (P < 0.01), experienced more frequent dizziness (P < 0.01), were frequently taking psychotropic medications (P = 0.02) and reported lower HRQoL (P = 0.02). Among those who underwent gait laboratory assessments, compared with non-fallers, fallers showed a greater anteroposterior (AP; P = 0.03) and medial-lateral (ML) sway range (P = 0.02) and reduced isokinetic peak torque and isometric strength at 60° knee flexion (P = 0.03). Fallers also showed shorter stride length (P = 0.04), shorter double support time (P = 0.04) and reduced percentage time in swing phase (P = 0.02) and in knee range of motion through the gait cycle (P < 0.01). Conclusion People with RA have distinct clinical and biomechanical characteristics that place them at increased risk of falling. Assessment for these factors may be important to offer more targeted rehabilitation interventions.
Modelling the Impact of Vector Control on Lymphatic Filariasis Programs: Current Approaches and Limitations

Abstract Vector control is widely considered an important tool for lymphatic filariasis (LF) elimination but is not usually included in program budgets and has often been secondary to other policy questions in modelling studies. Evidence from the field demonstrates that vector control can have a large impact on program outcomes and even halt transmission entirely, but implementation is expensive. Models of LF have the potential to inform where and when resources should be focused, but often simplify vector dynamics and focus on capturing human prevalence trends, making them comparatively ill-designed for direct analysis of vector control measures. We review the recent modelling literature and present additional results using a well-established model, highlighting areas of agreement between model predictions and field evidence, and discussing the possible determinants of existing disagreements. We conclude that there are likely to be long-term benefits of vector control, both on accelerating programs and preventing resurgence.