bluuebunny/crossref_metadata_2025_split huggingface dataset:
FH-like protein 1-Y402H mutation promoted microglial synapse phagocytosis and cognitive impairment in Alzheimer's disease model
Authors: Cheng Yulian , Chen Sihan , Tao Ran , Huang Zhihong , Ye Qinyong , Huang En 
Published: November 2023

Abstract
Background
Studies demonstrated that the complement system was involved in the pathogenesis of Alzheimer’s disease (AD). A genetic screening study in a Chinese cohort identified that two single nucleotide polymorphisms (SNPs) of the complement regulator Factor H (CFH) rs1061170 (Y402H) and rs800292 (V62I) were robustly associated with AD. FH-like protein 1 (FHL-1) is a short alternative splicing derived from CFH gene. Due to its smaller size and more diffuseness, FHL-1 may provide greater protection via blocking complement 3 (C3). This study aims to investigate the role of FHL-1 and its two mutants V62I and Y402H via lentiviral overexpression of FHL-1 wild type (FHL-1WT), FHL-1V62I, and FHL-1Y402H in 5×FAD mice.
Methods
We produced lentivirus of control, FHL-1 wild type (FHL-1WT), FHL-1V62I, and FHL-1Y402H and injected into the hippocampus 5×FAD mice. We employed immunostaining and behavior test to investigate the role of these vectors in AD model.
Results
The result showed that overexpression of FHL-1WT and FHL-1V62I but not FHL-1Y402H ameliorated cognitive impairment in 5×FAD mice. In the other hand, overexpression of FHL-1WT, FHL-1V62I, and FHL-1Y402H did not differently affected the plaque load and astrocytic status. The V62I mutation lightly increased the diffuseness index of amyloid plaque and reduced the number of plaque-associated microglia. Notably, overexpression of FHL-1Y402H prominently promoted synapse phagocytosis by microglia in 5×FAD mice compared to FHL-1WT and FHL-1V62I.
Conclusions
this indicated that microglia-mediated synapse phagocytosis via complement system may be a key contributor to the cognitive impairment in 5×FAD mice independent on amyloid plaque. Our study provides a clue that blocking microglia-mediated synapse phagocytosis would be an effective therapeutic approach and strategy for AD.
Early Tocilizumab Administration was Associated with Decreased Mortality in COVID-19 Hospitalized Patients
Authors: DUAN Shengchen , ZHANG Meng , WANG Yan , ZENG Zhechun , ZUO Huijuan , WAN Jun 
Published: November 2023

Abstract
Background
Coronavirus disease 2019 (COVID-19) is still prevalent at present. Tocilizumab as an effective treatment in COVID-19 is a humanized monoclonal antibody that binds to interleukin 6 (IL-6) receptor. But there is few articles that focused on the efficacious timing of tocilizumab administration. So we aimed to evaluate the efficacy of tocilizumab combined methylprednisolone in hospitalized COVID-19 patients.
Methods
This was a retrospective, observational cohort study. Intervention group selected patients received tocilizumab in addition to methylprednisolone treatment. Patients in the control group received standard of care treatment including methylprednisolone. The primary outcome was the patients’ clinical status, including recover rate at discharge and death rate in hospitalization. And the secondary outcome was the time from admission and methylprednisolone to tocilizumab use.
Results
In total, 112 patients included in this group (56 patients in the intervention group and 56 patients in the control group). The proportions of death during hospitalization was higher in the intervention group than those in the control group (p = 0.043). Both time from methylprednisolone to tocilizumab and time from admission to tocilizumab was much shorter in the recover group than that in the death group of intervention group (p = 0.004 and p = 0.008).
Conclusions
We found that tocilizumab was more used in COVID-19 hospitalized patients who have elevated systemic inflammation and lower Lymphocyte count. And early tocilizumab administration was associated with decreased mortality.
Exploring Mitochondrial Heteroplasmy in Neonates: Implications for Growth Patterns in the First Years of Life
Authors: Cosemans Charlotte , Alfano Rossella , Sleurs Hanne , Martens Dries , Nawrot Tim , Plusquin Michelle 
Published: November 2023

Abstract

Background: Mitochondrial heteroplasmy reflects genetic diversity within individuals due to the presence of varying mitochondrial DNA (mtDNA) sequences, possibly affecting mitochondrial function and energy production in cells. Rapid growth during early childhood is a critical development with long-term implications for health and well-being. In this study, we investigated if cord blood mtDNA heteroplasmy is associated with rapid growth at six and 12 months and overweight in childhood at four to six years.
Methods: This study included 200 mother-child pairs of the ENVIRONAGE birth cohort. Whole mitochondrial genome sequencing was performed to determine mtDNA heteroplasmy levels (in variant allele frequency; VAF) in cord blood. Rapid growth was defined for each child as the difference between WHO-SD scores of predicted weight at either six or 12 months and birth weight. Logistic regression models were used to determine the association of mitochondrial heteroplasmy with rapid growth and childhood overweight. Determinants of relevant cord blood mitochondrial heteroplasmies were identified using multiple linear regression models.
Results: One % increase in VAF of cord blood MT-D-Loop16362T>C heteroplasmy was associated with rapid growth at six (OR=1.03; 95% CI: 1.01 to 1.05; p=0.001) and 12 months (OR=1.02; 95% CI: 1.00 to 1.03; p=0.02). Furthermore, this variant was associated with childhood overweight at four to six years (OR=1.01; 95% CI 1.00 to 1.02; p=0.05). Additionally, rapid growth at six (OR=3.00; 95% CI: 1.49 to 6.14; p=0.002) and 12 months (OR=4.05; 95% CI: 2.06 to 8.49; p<0.001) was also associated with childhood overweight at four to six years. Furthermore, we identified maternal age, pre-pregnancy BMI, maternal education, parity, and gestational age as determinants of cord blood MT-D-Loop16362T>C heteroplasmy.
Conclusions: Our findings, based on mitochondrial DNA genotyping, offer insights into the molecular machinery leading to rapid growth in early life, potentially explaining a working mechanism of the development towards childhood overweight.
High-resolution co-seismic fault offsets of the 2023 Türkiye earthquake ruptures using satellite imagery
Authors: Provost Floriane , Karabacak Volkan , Malet Jean-Philippe , Woerd Jerôme Van Der , Meghraoui Mustapha , Masson Frédéric , Ferry Matthieu , Michéa David , Pointal Elisabeth 
Published: November 2023

Abstract
On February 6, 2023, southern Türkiye was hit by two major earthquakes at 01:17 UTC (Mw=7.8, Pazarcık, Kahramanmaraş) and at 10:30 UTC (Mw=7.6, Elbistan, Kahramanmaraş) leading to severe damages at the complex junction of the Dead Sea Fault (DSF), the Cyprus arc and the East Anatolian fault zone (EAFZ). The ruptures propagated along several known strands of the southwestern termination of the EAFZ, the main Pazarcık and Karasu valley faults and the Çardac-Sürgü fault. Here, we present the high-resolution mapping of the entire coseismic surface rupture and an estimation of the rupture width, the total and on-fault offset, and of the diffuse deformation obtained a few days after the two mainshocks. The mapping is derived from image correlation of optical Sentinel-2 satellite imagery and is validated with offset measurements collected on the ground. We found that the ruptures extend over lengths of 310 km and 140 km for the Mw 7.8 and Mw 7.6 mainshocks, respectively. The maximum offsets reach 7.5 ± 0.8 m and 8.7 ± 0.8 m, near the epicenters of the Mw 7.8 and Mw 7.6, respectively. We propose a segmentation of the two ruptures based on these observations, and further discuss the location of potential supershear rupture. The use of optical image correlation complemented by field investigations along earthquake faults provides new insights into the seismic hazard assessment.
Abnormal heart rate responses to exercise in non-severe COPD: Relationship with pulmonary vascular volume and ventilatory efficiency
Authors: Shi Minghui , Qumu Shiwei , Wang Siyuan , Peng Yaodie , Yang Lulu , Huang Ke , He Ruoxi , Dong Feng , Niu Hongtao , Yang Ting , Wang Chen 
Published: November 2023

Abstract
Background
Despite being a prognostic predictor, cardiac autonomic dysfunction (AD) has not been well investigated in chronic obstructive pulmonary disease (COPD). We aimed to characterise computed tomography (CT), spirometry, and cardiopulmonary exercise test (CPET) features of COPD patients with cardiac AD and the association of AD with CT-derived vascular and CPET-derived ventilatory efficiency metrics.
Methods
This observational cohort study included stable, non-severe COPD patients. They underwent clinical evaluation, spirometry, CPET, and CT. Cardiac AD was determined based on abnormal heart rate responses to exercise, including chronotropic incompetence (CI) or delayed heart rate recovery (HRR) during CPET.
Results
Out of 49 patients, 24 (49%) had CI, and 15 (31%) had delayed HRR. According to multivariate analyses, CI was independently related to reduced vascular volume (VV; VV ≤ median; OR [5–95% CI], 7.26 [1.56–33.91]) and low ventilatory efficiency (nadir VE/VCO2 ≥ median; OR [5–95% CI], 10.67 [2.23–51.05]). Similar results were observed for delayed HRR (VV ≤ median; OR [5–95% CI], 11.46 [2.03–64.89], nadir VE/VCO2 ≥ median; OR [5–95% CI], 6.36 [1.18–34.42]).
Conclusions
Cardiac AD is associated with impaired pulmonary vascular volume and ventilatory efficiency. This suggests that lung blood perfusion abnormalities may occur in these patients. Further confirmation is required in a large population-based cohort.
The etiology-specific effects of impaired functional status on liver transplant outcomes
Authors: Lee David Uihwan Uihwan , Bhowmick Kuntal , Althwanay Aldanah , Sandlow Sarah , Wiseman Michal , Lee Ki Jung , Fan Gregory Hongyuan , Chou Hannah , Chou Harrison , Schuster Kimberly , Lee KeeSeok , Lominadze Zurabi 
Published: November 2023

Abstract

Background & Aims: Pre-liver transplant (LT) functional status is an important determinant of prognosis post LT. There is insufficient data on how functional status affects outcomes of transplant recipients based on the specific etiology of liver disease. We stratified LT recipients by etiology of liver disease to evaluate the effects of functional status on post-LT prognosis in each subgroup.
Methods: 2005-2019 United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research (STAR) was used to select patients with liver transplant. A total of 14,290 patients were included in the analysis. These patients were stratified by functional status according to Karnofsky Performance Scale (KPS) score: no assistance, some assistance, or total assistance. They were then further divided into six diagnosis categories: metabolic dysfunction-associated steatohepatitis (MASH), hereditary disorders, hepatitis C, hepatitis B, autoimmune disease (AID), and alcoholic liver disease (ALD). Primary endpoints included all-cause mortality and graft failure, while secondary endpoints included organ-specific causes of death. Those under the age of 18 and those with non-whole liver or prior liver transplantation were excluded.
Results: Patients with MASH requiring some assistance (aHR: 1.57, 95% CI 1.03–2.39, p=0.04) and those requiring total assistance (aHR: 2.32, 95% CI 1.48–3.64, p<0.001) had higher incidences of graft failure compared to those requiring no assistance. Those with MASH requiring total assistance had a higher all-cause mortality rate than those needing no assistance (aHR: 1.62, 95% CI 1.38–1.89, p<0.001). Patients with hereditary causes of liver disease showed a lower incidence of all-cause mortality in recipients needing some assistance compared with those needing no assistance (aHR: 0.52, 95% CI 0.34–0.80, p=0.003). LT recipients with hepatitis C, AID, and ALD all showed higher incidences of all-cause mortality in the total assistance cohort when compared to the no assistance cohort. For the secondary endpoints of specific cause of death, transplant recipients with MASH needing total assistance had higher rates of death due to general cardiac causes, graft rejection, general infectious causes, sepsis, general renal causes, and general respiratory causes.
Conclusion: Patients with MASH cirrhosis demonstrated the worst overall outcomes, suggesting that this population may be particularly vulnerable. Poor functional status in patients with end-stage liver disease from hepatitis B or hereditary disease was not associated with a significantly increased rate of adverse outcomes, suggesting that the KPS score may not be broadly applicable to all patients awaiting LT.
Creation of prestige ileostomy and when Release down: our observation
Authors: Saad Hassan A. , Baz Azza , Riad Mohamed , Eraky Mohamed E , Farid Mohamed I , Sharaf Khaled , El-Taher Ahmed k , Arafa Ahmed Salah 
Published: November 2023

Abstract
background
The benefits of ghost ileostomy (GI) in avoiding formal covering ileostomies in > 80% of cancer patients have been documented in numerous studies. However, none of the articles explained precisely how the GI tract was removed in the end in 80% of patients for whom formal maturation was not necessary.
Goal
To describe and evaluate the GIRD technique, including possible issues, hospital stays, and procedure times, for patients with GI for rectal carcinoma who underwent low anterior resection (LAR/uLAR) or ultra-low anterior resection (LAR/uLAR).
Methods
In this prospective cohort study, patients underwent restorative colorectal resection with GI for rectal cancer. Patients’ ease of GI release and any problems that might arise were then examined. Information was gathered, examined, and deduced.
Results
The final statistical analysis included 26 patients who required GIRD. Between the seventh and sixteenth postoperative days (POD), treatment was performed, all patients recovered well, and no additional surgeries were required. No further analgesics or injections of local anesthesia were required for any of the patients. The surgery took an average of five minutes, and none of the patients experienced any notable difficulties with GI release. No post-procedural issues emerged.
Conclusion
Without the need for anesthesia or additional analgesics, the GIRD approach is a rapid, easy, and safe operation that can be performed at the patient's bedside around the tenth POD.
Cellular and clinical impact of Protein Phosphatase Enzyme epigenetic silencing in multiple cancer tissues.
Authors: Wiltshire Edward , Joshi Ricky S. 
Published: November 2023

Abstract
Background
Protein Phosphatase Enzymes (PPE) and protein kinases simultaneously control phosphorylation mechanisms that tightly regulate intracellular signaling pathways and stimulate cellular responses. In human malignancies, PPE and protein kinases are frequently mutated resulting in uncontrolled kinase activity and PPE suppression, leading to cell proliferation, migration and resistance to anti-cancer therapies. Cancer associated DNA hypermethylation at PPE promoters gives rise to transcriptional silencing (epimutations) and is a hallmark of cancer. Despite recent advances in sequencing technologies, data availability and computational capabilities, only a fraction of PPE have been reported as transcriptionally inactive as a consequence of epimutations. Using the Infinium HumanMethylation450 BeadChip, we compared DNA methylation profiles from 705 cancer patients in 5 major tissues and 3 cancer cell models against a cohort of healthy controls.
Results
Here, we report epimutations in PPE (and their interacting proteins or PPEIP) are a frequent occurrence in the cancer genome and manifest independent of transcriptional activity. We observed that different tumors have varying susceptibility to epimutations and identify specific cellular signalling networks that are primarily affected by epimutations. Additionally, RNA-seq analysis showed the negative impact of epimutations on most (not all) Protein Tyrosine Phosphatase transcription. Finally, we detected novel clinical biomarkers that inform on patient mortality and anti-cancer treatment sensitivity.
Conclusions
We propose that DNA hypermethylation marks at PPEIP frequently contribute to the pathogenesis of malignancies and within the precision medicine space, hold promise as biomarkers to inform on clinical features such as patient survival and therapeutic response.
Automation of MKID Simulations for Array Building With AEM (Automated Electromagnetic MKID simulations)
Authors: McAleer Cáthal , Creaner Oisin , Bracken Colm , Ulbricht Gerhard , De Lucia Mario , Piercy Jack , Ray Tom 
Published: November 2023

Abstract

Microwave Kinetic Inductance Detectors (MKIDs) are photon detectors comprised of superconducting LC resonators with unique resonant frequencies corresponding to their geometrical structure. As each pixel has a unique resonance, simulations of every pixel in a kilo pixel array are impractical and current methods of interpolation across pixels are shown to lead to reduced pixel yield. We introduce a new software called AEM (Automated Electromagnetic MKID simulations) that automates the construction and simulation of every simulated MKID pixel in an array according to specified resonant frequencies and a Qc range. We show automated designs to have an increased pixel yield, accuracy in resonance frequency and Qc value when compared to interpolated structures. We also demonstrate a simulated trial of AEM for 100 MKIDs between 4–8 GHz to produce MKIDs with accuracies of ± 0.188 MHz with a runtime of 10 hours 45 minutes.
An in-depth analysis of young adults with osteonecrosis secondary to developmental dysplasia of the hip who underwent total hip arthroplasty
Authors: Nayar Sandeep Krishan , Marks Avi , Hashemi-Nejad Aresh , Roposch Andreas 
Published: November 2023

AbstractBackgroundPatients with osteonecrosis of the femoral head secondary to DDH frequently require total hip arthroplasty (THA), but it is not well understood which factors necessitate this requirement. We determined the incidence of THA in patients who have osteonecrosis secondary to DDH and factors associated with need for THA.MethodsWe included patients who received closed or open reductions between 1995 and 2005 with subsequent development of osteonecrosis. We determined osteonecrosis according to Bucholz and Ogden; osteoarthritis severity (Kellgren-Lawrence), subluxation (Shenton’s line); neck-shaft angle; and acetabular dysplasia (centre-edge and Sharp angles). We also recorded the number of operations of the hip in childhood and reviewed case notes of patients who received THA to describe clinical findings prior to THA. We assessed the association between radiographic variables and the need for THA using univariate logistic regression.ResultsOf 140 patients (169 hips), 22 patients received 24 THA (14%) at a mean age of 21.3 ± 3.7 years. Associated with the need for THA were grade III osteonecrosis (OR 4.25; 95% CI 1.70-10.77; p=0.0019), grade IV osteoarthritis (21.8; 7.55-68.11; p<0.0001) and subluxation (8.22; 2.91-29.53; p=0.0003). All patients who required THA reported at least 2 of: severe pain including at night, stiffness, and reduced mobility. Acetabular dysplasia and number of previous operations were not associated with the need for THA.ConclusionsWe identified a 14% incidence of THA by age 34 years in patients with osteonecrosis secondary to DDH. Grade III osteonecrosis (global involvement femoral head and neck) was strongly associated with THA, emphasising the importance to avoid osteonecrosis when treating DDH.
Transcutaneous bilirubin reliability during and after phototherapy depending on skin color
Authors: Candel-Pau Júlia , Maya-Enero Silvia , Garcia-Garcia Jordi , Duran-Jordà Xavier , López-Vílchez María Ángeles 
Published: November 2023

Abstract
Purpose
Measurement of transcutaneous bilirubin (TcB) is a non-invasive, widely used technique to estimate serum bilirubin (SB). However, its reliability in multiethnic populations during and after phototherapy is still controversial even in covered skin. The aim of this study was to determine the reliability of TcB in covered (cTcB) and exposed (eTcB) skin during and after phototherapy in a multiethnic population of neonates according to Neomar’s neonatal skin color scale.
Methods
Prospective, observational study comparing SB and TcB. We determined SB when clinically indicated and, at the same time, measured cTcB under a photo-opaque patch and eTcB next to it with a jaundice meter (Dräger JM-105TM). All dyads TcB-SB were compared, both globally and according to skin color.
Results
We obtained data from 200 newborns (color1: 44, color2: 111, color3: 41, color4: 4) and compared 296 dyads TcB/SB. Correlation between cTcB and SB is strong during (0.74–0.83) and after (0.79–0.88) phototherapy, both globally and by color group. The SB-cTcB bias depends on gestational age during phototherapy and on skin color following phototherapy. The correlation between eTcB and SB during phototherapy is not strong (0.54), but becomes so 12 hours after discontinuing phototherapy (0.78).
Conclusions
Our study supports the reliability of cTcB to assess SB during and after phototherapy, with differences among skin tones after the treatment. The use of cTcB and Neomar’s scale during and mainly after phototherapy may help reduce the number of blood samples required.
Evaluation of Potential Flood Areas in the Basin of Lake Ladik Through AHP and GIS Integration, (Samsun, Turkey)
Authors: OCAK Fatih , BAHADIR Muhammet 
Published: November 2023

Abstract

Floods are a problem of many countries on a global scale. In Turkey, especially in the summer months, large floods occur in the Black Sea Region coastal belt. The number and the destructive power of experienced floods are increasing day by day. It is not possible to prevent the occurrence of floods. But it is possible to take the necessary measures to prevent it from turning into a disaster. Recently, susceptibility analyses have been carried out for floods and similar natural disasters and the results help decision-makers. Within the scope of this study, flood susceptibility analysis was carried out by using multiple geographical factors together in the Basin of Lake Ladik of Samsun Province in the Black Sea Region. In the study, Analytical Hierarchy Process (AHP), Geographic Information Systems (GIS) and Remote Sensing (RS) techniques were used, which are multi-criteria decision-making methods. In this context, flood susceptibility analysis of the basin was carried out by using nine (9) different geographical factors (slope, aspect, lithology, soil, basin size, land use, landforms, precipitation, and drainage density). As a result of the study, for floods, there were identified four (4) different levels as low, medium, high, and very high; and 36.77% of the basin was found to be low, 30.03% was medium, 11.43% was high and 21,77% was found to be sensitive to possible floods at a very high level. The results of the study are also important for decision-makers to make flood risk planning.