julilili42/papers huggingface dataset:
Efficacy of Prehabilitation Before Cardiac Surgery
2022-09-23

Objective Patients awaiting cardiac surgery seem to benefit from exercise-based prehabilitation, but the impact on different perioperative outcomes compared with standard care is still unclear. Design Eligible nonrandomized/randomized controlled studies investigating the impact of exercise-based prehabilitation in adults scheduled for elective cardiac surgery were searched on December 16, 2020, from electronic databases, including MEDLINE, CENTRAL, and CINAHL. The data were pooled and a meta-analysis was conducted. Results Of 1490 abstracts, six studies ( n = 665) were included into the review and meta-analysis. At postintervention interval and at postsurgery interval, 6-min-walking distance improved significantly in exercise-based prehabilitation group compared with controls (mean difference, 75.4 m; 95% confidence interval, 13.7 to 137.1 m, P = 0.02, and 30.5 m, 95% confidence interval, 8.5 to 52.6 m, P = 0.007, respectively). Length of hospital stay was significantly shorter in exercise-based prehabilitation group (mean difference, −1.00 day; 95% confidence interval, −1.78 to −0.23 day, P = 0.01). Participation in exercise-based prehabilitation revealed a significant decrease in the risk of postoperative atrial fibrillation in patients 65 yrs or younger (risk ratio, 0.34; 95% confidence interval, 0.14 to 0.83, P = 0.02). Conclusions The participation in exercise-based prehabilitation significantly improves postintervention and postsurgery 6-min walking distance, length of hospital stay, and decreases the risk of postoperative atrial fibrillation in patients 65 yrs or younger compared with controls.
Discovery and Development of First-in-Class ACKR3/CXCR7 Superagonists for Platelet Degranulation Modulation
2022-09-23

The atypical chemokine receptor 3 (ACKR3), formerly known as CXC-chemokine receptor 7 (CXCR7), has been postulated to regulate platelet function and thrombus formation. Herein, we report the discovery and development of first-in-class ACKR3 agonists, which demonstrated superagonistic properties with <i>E</i><sub>max</sub> values of up to 160% compared to the endogenous reference ligand CXCL12 in a β-arrestin recruitment assay. Initial in silico screening using an ACKR3 homology model identified two hits, <b>C10</b> (EC<sub>50</sub> 19.1 μM) and <b>C11</b> (EC<sub>50</sub> = 11.4 μM). Based on these hits, extensive structure-activity relationship studies were conducted by synthesis and testing of derivatives. It resulted in the identification of the novel thiadiazolopyrimidinone-based compounds <b>26</b> (LN5972, EC<sub>50</sub> = 3.4 μM) and <b>27</b> (LN6023, EC<sub>50</sub> = 3.5 μM). These compounds are selective for ACKR3 versus CXCR4 and show metabolic stability. In a platelet degranulation assay, these agonists effectively reduced P-selectin expression by up to 97%, suggesting potential candidates for the treatment of platelet-mediated thrombosis.
Lower affective empathy in oral contraceptive users: a cross-sectional fMRI study
2022-09-23

Abstract Evidence accumulates that oral contraceptive (OC) use modulates various socio-affective behaviors, including empathic abilities. Endogenous and synthetic sex hormones, such as estrogens and progestogens, bind to receptor sites in brain regions (i.e. frontal, limbic, and cerebellar) involved in socio-affective processing. Therefore, the aim of this study was to investigate the role of OC use in empathy. In a cross-sectional functional magnetic resonance imaging study, women in different hormonal states, including OC use (n = 46) or being naturally cycling in the early follicular (fNC: n = 37) or peri-ovulatory phase (oNC: n = 28), performed a visual, sentence-based empathy task. Behaviorally, OC users had lower empathy ratings than oNC women. Congruently, whole-brain analysis revealed significantly larger task-related activation of several brain regions, including the left dorsomedial prefrontal gyrus (dmPFG), left precentral gyrus, and left temporoparietal junction in oNC compared to OC women. In OC users, the activity of the left dmPFG and precentral gyrus was negatively associated with behavioral and self-reported affective empathy. Furthermore, empathy-related region-of-interest analysis indicated negative associations of brain activation with synthetic hormone levels in OC women. Overall, this multimodal, cross-sectional investigation of empathy suggests a role of OC intake in especially affective empathy and highlights the importance of including synthetic hormone levels in OC-related analyses.
Genome Sequencing and Transcriptome Profiling in Twins Discordant for Mayer-Rokitansky-Küster-Hauser Syndrome
2022-09-23

To identify potential genetic causes for Mayer-Rokitansky-Küster-Hauser syndrome (MRKH), we analyzed blood and rudimentary uterine tissue of 5 MRKH discordant monozygotic twin pairs. Assuming that a variant solely identified in the affected twin or affected tissue could cause the phenotype, we identified a mosaic variant in ACTR3B with high allele frequency in the affected tissue, low allele frequency in the blood of the affected twin, and almost absent in blood of the unaffected twin. Focusing on MRKH candidate genes, we detected a pathogenic variant in GREB1L in one twin pair and their unaffected mother showing a reduced phenotypic penetrance. Furthermore, two variants of unknown clinical significance in PAX8 and WNT9B were identified. In addition, we conducted transcriptome analysis of affected tissue and observed perturbations largely similar to those in sporadic cases. These shared transcriptional changes were enriched for terms associated with estrogen and its receptors pointing at a role of estrogen in MRKH pathology. Our genome sequencing approach of blood and uterine tissue of discordant twins is the most extensive study performed on twins discordant for MRKH so far. As no clear pathogenic differences were detected, research to evaluate other regulatory layers are required to better understand the complex etiology of MRKH.
Thermography Supported Color Duplex Ultrasound Accelerates ALT Perforator Imaging
2022-09-23

Abstract Background The anterolateral thigh flap is a versatile and dependable perforator flap and is a popular choice in the reconstruction of various body sites. The variable perforator anatomy suggests preoperative perforator imaging to improve safety and speed of dissection. An innovative perforator imaging technique is thermography, which lately gained attention in plastic surgery. Methods Thirty-two healthy participants were included in this randomized study. One thigh was examined with dynamic infrared thermography and consecutively with ultrasound, while the contralateral thigh was examined with ultrasound as standalone technology. Results The application of dynamic infrared thermography prior to ultrasound perforator identification significantly accelerated the ultrasound examination duration by 90 to 130 seconds. The mean duplex ultrasound examination duration correlated positively with the hotspot and perforator quantity per thigh. Conclusion The addition of thermographic perforator mapping can accelerate color duplex ultrasound anterolateral thigh perforator imaging. Furthermore, thermography supplements color duplex ultrasound with crucial information on angiosome location.
Identification of a Novel Renal Metastasis Associated CpG-Based DNA Methylation Signature (RMAMS)
2022-09-23

Approximately 21% of patients with renal cell cancer (RCC) present with synchronous metastatic disease at the time of diagnosis, and metachronous metastatic disease occurs in 20–50% of cases within 5 years. Recent advances in adjuvant treatment of aggressive RCC following surgery suggest that biomarker-based prediction of risk for distant metastasis could improve patient selection. Biometrical analysis of TCGA-KIRC data identified candidate loci in the NK6 homeobox 2 gene (NKX6-2) that are hypermethylated in primary metastatic RCC. Analyses of NKX6-2 DNA methylation in three gene regions including a total of 16 CpG sites in 154 tumor-adjacent normal tissue, 189 RCC, and 194 metastatic tissue samples from 95 metastasized RCC patients revealed highly significant tumor-specific, primary metastatic-specific, and metastatic tissue-specific hypermethylation of NKX6-2. Combined CpG site methylation data for NKX6-2 and metastasis-associated genes (INA, NHLH2, and THBS4) demonstrated similarity between metastatic tissues and metastatic primary RCC tissues. The random forest method and evaluation of an unknown test cohort of tissues using receiver operator characteristic curve analysis revealed that metastatic tissues can be differentiated by a median area under the curve of 0.86 (p = 1.7 × 10−8–7.5 × 10−3) in 1000 random runs. Analysis of variable importance demonstrated an above median contribution for decision-making of at least one CpG site in each of the genes, suggesting superior informativity for sites annotated to NHLH2 and NKX6-2. Thus, DNA methylation of NKX6-2 is associated with the metastatic state of RCC tissues and contributes to a four-gene-based statistical predictor of tumoral and metastatic renal tissues.
Amyloid‐Related Imaging Abnormalities in the DIAN‐TU‐001 Trial of Gantenerumab and Solanezumab: Lessons from a Trial in Dominantly Inherited Alzheimer Disease
2022-09-24

Objective To determine the characteristics of participants with amyloid‐related imaging abnormalities (ARIA) in a trial of gantenerumab or solanezumab in dominantly inherited Alzheimer disease (DIAD). Methods 142 DIAD mutation carriers received either gantenerumab SC (n = 52), solanezumab IV (n = 50), or placebo (n = 40). Participants underwent assessments with the Clinical Dementia Rating® (CDR®), neuropsychological testing, CSF biomarkers, β‐amyloid positron emission tomography (PET), and magnetic resonance imaging (MRI) to monitor ARIA. Cross‐sectional and longitudinal analyses evaluated potential ARIA‐related risk factors. Results Eleven participants developed ARIA‐E, including 3 with mild symptoms. No ARIA‐E was reported under solanezumab while gantenerumab was associated with ARIA‐E compared to placebo (odds ratio [OR] = 9.1, confidence interval [CI][1.2, 412.3]; p = 0.021). Under gantenerumab, APOE‐ɛ4 carriers were more likely to develop ARIA‐E (OR = 5.0, CI[1.0, 30.4]; p = 0.055), as were individuals with microhemorrhage at baseline (OR = 13.7, CI[1.2, 163.2]; p = 0.039). No ARIA‐E was observed at the initial 225 mg/month gantenerumab dose, and most cases were observed at doses &gt;675 mg. At first ARIA‐E occurrence, all ARIA‐E participants were amyloid‐PET+, 60% were CDR &gt;0, 60% were past their estimated year to symptom onset, and 60% had also incident ARIA‐H. Most ARIA‐E radiologically resolved after dose adjustment and developing ARIA‐E did not significantly increase odds of trial discontinuation. ARIA‐E was more frequently observed in the occipital lobe (90%). ARIA‐E severity was associated with age at time of ARIA‐E. Interpretation In DIAD, solanezumab was not associated with ARIA. Gantenerumab dose over 225 mg increased ARIA‐E risk, with additional risk for individuals APOE‐ɛ4(+) or with microhemorrhage. ARIA‐E was reversible on MRI in most cases, generally asymptomatic, without additional risk for trial discontinuation. ANN NEUROL 2022;92:729–744
Glucogallin Attenuates the LPS-Induced Signaling in Macrophages and Protects Mice against Sepsis
2022-09-24

The anti-oxidant and anti-inflammatory effect of beta-glucogallin (BGG), a plant-derived natural product, was evaluated in both in vitro and in vivo studies. For the in vitro study, the ability of BGG pre-treatment to quench LPS-induced effects compared to LPS alone in macrophages was investigated. It was found that BGG pre-treatment showed a significant decrease in ROS, NO, superoxide, and pro-inflammatory cytokines (TNF-alpha, IL-4, IL-17, IL-1β, and IL-6) and increased reduced glutathione coupled with the restoration of mitochondrial membrane potential. Gene profiling and further validation by qPCR showed that BGG pre-treatment downregulated the LPS-induced expression of c-Fos, Fas, MMP-9, iNOS, COX-2, MyD88, TRIF, TRAF6, TRAM, c-JUN, and NF-κB. We observed that BGG pre-treatment reduced nuclear translocation of LPS-activated NF-κB and thus reduced the subsequent expressions of NLRP3 and IL-1β, indicating the ability of BGG to inhibit inflammasome formation. Molecular docking studies showed that BGG could bind at the active site of TLR4. Finally, in the LPS-driven sepsis mouse model, we showed that pre-treatment with BGG sustained toxic shock, as evident from their 100% survival. Our study clearly showed the therapeutic potential of BGG in toxic shock syndrome.
Risk analysis of systemic side effects of tumescent local anaesthesia in the surgical treatment of geriatric and multimorbid patients with skin cancer
2022-09-24

Abstract Background Due to demographic change and increased UV exposure, the number of dermatosurgical procedures in the elderly is increasing. Data on the occurrence of systemic side effects during and after treatment with tumescent local anaesthesia are limited and do not refer to details such as volume and composition of local anaesthetics or epinephrine additive. Objectives The aim of this study was to investigate the risk of systemic side effects in elderly patients undergoing skin tumour surgery with tumescent local anaesthesia. Methods Investigation of systemic complications in patients (≥75 years) who underwent head and neck skin tumour surgery under tumescent local anaesthesia at the Department of Dermatology, University Medical Centre Tübingen, between October 2018 and March 2020. Results In total 782 patients (479 males, 303 females) with a mean age of 83.3 years (range: 75.1–102.2 years) could be included. A total of 2940 procedures were performed. Patients were assigned to two groups. The old–old group (≥75–84 years) included 491 patients and the oldest–old group (≥85 years) included 291 patients. The total inpatient stay and thus mean follow‐up period was 4.9 days (range 1–28 days). 92.0% (719/782) suffered from pre‐existing comorbidities. Systemic complications occurred in 10.2% (80/782; old–olds: 8.6%, oldest–olds: 13.1%). Hypertensive crisis (&gt;180/120 mmHg) requiring intervention (6.7%) that occurred intraoperatively or during the inpatient stay was the most frequent systemic complication. Cardiac arrhythmias occurred postoperatively in 0.8% of cases. No life‐threatening complications directly related to tumescent local anaesthesia were found. Conclusions Skin tumour surgery in tumescent local anaesthesia for the elderly is safe, and complications caused by general anaesthesia can be avoided. Systemic complications can occur, but are usually mild, are caused by pre‐existing diseases and perioperative excitement, and can be rapidly detected and well treated by monitoring. There is no direct correlation of complications to high‐tumescent concentrations or volume quantities.
Peritoneal regression grading score (PRGS) in peritoneal metastasis: how many biopsies should be examined?
2022-09-24

Abstract Objectives The four-tied peritoneal regression grading score (PRGS) is increasingly used to evaluate the response of peritoneal metastases (PM) to chemotherapy. The minimal number of peritoneal biopsies needed for PRGS determination remains unclear. Methods A prospective cohort of 89 PM patients treated with 210 pressurized intraperitoneal aerosol chemotherapy (PIPAC) cycles was investigated. Four biopsies from every abdominal quadrant were recommended. Histological tumor response was defined as a stable or decreasing mean PRGS between therapy cycles, progression increasing. We compared the diagnostic uncertainty induced by missing biopsies to the histological response. Results A total of 49 patients had at least two PIPAC and were eligible for therapy response assessment. Mean PRGS decreased from 2.04 (CI 5–95% 1.85–2.27) to 1.79 (CI 5–95% 1.59–2.01), p=0.14, as a proof of therapy effectiveness. 35 (71.4%) patients had a stable or decreasing PRGS (therapy response), 14 (28.6%) a PRGS increase (disease progression). Histology showed agreement between four biopsies in 42/210 laparoscopies (20%), between ≥3 biopsies in 103 (49%), and between ≥2 biopsies in 169 laparoscopies (81%). Mean loss of information with one missing biopsy was 0.11 (95% CI=0.13) PRGS points, with two missing biopsies 0.18 (95% CI 0.21). In 9/49 patients (18.3%), the loss of information with one less biopsy exceeded the change in PRGS under therapy. Conclusions A minimum of three biopsies is needed to diagnose PM progression with an accuracy superior to 80%. Missing biopsies often result in a false diagnosis of tumor progression.
A statistical approach to study the spatial heavy metal distribution in soils in the Kushk Mine, Iran
2022-09-25

Abstract The present study was conducted for the spatial distribution and concentration evaluation of heavy metals, including Cu, Cd, Mn, Fe, Zn, and Pb, within 102 soil samples collected from Kushk Mine in Bafgh, Iran. This work employed hierarchical clustering analysis (HCA), principal component analysis (PCA), and spatial distribution patterns, to perform element distribution evaluation within the area. The distributions of heavy metals in the entire area were exhibited in the form of maps. The average concentrations of Cd, Cu, Mn, Fe, Zn, and Pb were found to be 0.39, 0.26, 5.3, 4.1, 51.9, and 40.9 mg.kg −1 , respectively. Based on the PCA and HCA findings, the heavy metals were divided into two groups. The first group included Pb, Cd, Zn, and Cu. In the first group, altered threshold‐surpassing anthropogenic and lithogenic pollution was found to be the main factor accounting for Pb and Zn. The second group involved Fe and Mn, which could be impacted by either anthropogenic and lithogenic factors. Furthermore, the geo‐statistical results demonstrated higher contents of the heavy metals in the south of the mine and in the vicinity of the mine tailings. It may be concluded from the results that the heavy metal contents of the area are impacted by anthropogenic and lithogenic factors.
Translation and psychometric properties of the German version of the “Interprofessional Socialization and Valuing Scale” (ISVS-21-D)
2022-09-25

Understanding of the processes associated with socialization into collaborative work plays an important role in interprofessional education and collaborative practice. In order to evaluate changes in socialization toward interprofessional collaborative practice a measure is needed that captures professional beliefs, attitudes and behaviors of individuals in learning activities and in workplace practice. This article presents the translation and psychometric properties of the German Version of the Interprofessional Socialization and Valuing Scale (ISVS-21). Following translation from English to German, data of the German version of the questionnaire (ISVS-21-D) was collected in six different interprofessional education and practice settings amongst undergraduate students and health professionals. In total, 494 responses were analyzed. Results showed high reliability with Cronbach's alpha .90. Although not all fit indices are in the desired range, results give preliminary indication of the underlying single factor of the ISVS-21-D and suggest that the German version of the ISVS-21-D is a reliable instrument that can be used to measure interprofessional socialization in German health professionals and health care students as well as within other disciplines.
Immunopeptidome Diversity in Chronic Lymphocytic Leukemia Identifies Patients with Favorable Disease Outcome
2022-09-25

Chronic lymphocytic leukemia (CLL) is characterized by recurrent relapses and resistance to treatment, even with novel therapeutic approaches. Despite being considered as a disease with low mutational burden and thus poor immunogenic, CLL seems to retain the ability of eliciting specific T cell activation. Accordingly, we recently found non-mutated tumor-associated antigens to play a central role in CLL immunosurveillance. Here, we investigated the association of total and CLL-exclusive HLA class I and HLA class II peptide presentation in the mass spectrometry-defined immunopeptidome of leukemic cells with clinical features and disease outcome of 57 CLL patients. Patients whose CLL cells present a more diverse immunopeptidome experienced fewer relapses. During the follow-up phase of up to 10 years, patients with an HLA class I-restricted presentation of high numbers of total and CLL-exclusive peptides on their malignant cells showed a more favorable disease course with a prolonged progression-free survival (PFS). Overall, our results suggest the existence of an efficient T cell-based immunosurveillance mediated by CLL-associated tumor antigens, supporting ongoing efforts in developing T cell-based immunotherapeutic strategies for CLL.
Exploration of cortical ß-Amyloid load in Alzheimer’s disease using quantitative susceptibility mapping at 9.4T
2022-09-25

ABSTRACT Early detection of β-Amyloid (Aβ) deposits in Alzheimer’s disease (AD) patients may enable treatment in the early stages of the disease. To date, there are no validated, specific, and non-invasive routines for early Aβ detection which are suitable for clinical practice. Ultra-high resolution quantitative susceptibility mapping (QSM) at 14.1T has previously shown different contrasts in cortical areas of an AD sample that resembled distinct Aβ spatial patterns in histological sections of the same specimen. These contrasts appeared different in the QSM from a healthy control (HC) sample where, instead, no plaques were detected. In a few cases, this distinction in the cortical magnetic effects (para- and diamagnetic) between AD and HC was also observed in vivo using ultra- high resolution single-echo Acquisition Weighted (AW) gradient echo MRI at 9.4T. Based on this evidence, a method to quantify the paramagnetic and diamagnetic effects of Aβ to possibly distinguish between AD and HC was developed. In this study, we extended those results and explored the ability to use QSM to estimate β-Amyloid plaque load in the cortex of 7 elderly patients with early AD and 7 healthy age-matched HC. Besides ultra-high resolution AW images, we acquired lower resolution multi-echo (MTE) data and compared the previously used RESHARP- based method for background removal (“AW-filter”, with a high Tikhonov term and a small kernel size) with a method widely used in the literature (“mild-filter”, with a low-regularization term and a large kernel size) for the MTE processing. Paramagnetic and diamagnetic QSM changes were assessed in 16 cortical areas. All methods enabled the detection of regions with high QSM values (up to 45 ppb in AD and up to 25 ppb in HC) and known as early Aβ accumulation areas in AD progression. A distinct cortical pattern was observed at both spatial resolutions using the AW-filter. This was not the case with the mild-filter at the lower resolution. AW-QSM outperformed MTE maps with the AW-filter for the detection of areas with prominent cortical paramagnetic effects, including regions where Aβ accumulation happens in the earliest AD stages, such as the precuneus and posterior cingulate cortex. Diamagnetic changes were more prominent than the paramagnetic effects regardless of the spatial resolution used and this difference was further enhanced with the mild-filter. This explorative study points toward the development of more accessible clinical methods to non-invasively detect effects of Aβ accumulation in AD patients by exploring cortical features that can be detected by ultra-high field QSM at different spatial resolutions.