bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating T Cell Activation and Exhaustion Markers Are Associated With Radiation Pneumonitis and Poor Survival in Non-Small-Cell Lung Cancer
Authors: Berg Janna , Halvorsen Ann Rita , Bengtson May-Bente , Lindberg Morten , Halvorsen Bente , Aukrust Pål , Helland Åslaug , Ueland Thor 
Published: July 2022

IntroductionPersistent inflammation and immune activation in the lungs are associated with adverse outcomes such as radiation pneumonitis (RP) and poor survival in non-small-cell lung cancer (NSCLC) patients. However, it is unknown how this is reflected by leukocyte activation markers in serum.ObjectiveThe aim was to evaluate the serum levels of activation of different leukocyte subsets and to examine those in relation to the pathogenesis of RP and survival in NSCLC.MethodsWe analyzed the serum levels of MPO, sCD25, sTIM-3, sPD-L1, sCD14, sCD163, CCL19 and CCL21 in 66 inoperable NSCLC patients with stage IA-IIIA disease. The patients were treated with stereotactic body radiation therapy (SBRT) or concurrent chemoradiation therapy (CCRT), followed by regular blood sampling for 12 months after treatment and for 5 years for survival.ResultsNineteen (29%) patients developed RP, which occurred more frequently and earlier in patients receiving CCRT than in those receiving SBRT. Increases in sCD25, sTIM-3 and CCL21 levels were observed at the last 6 months of follow-up in patients who had RP after SBRT. Patients who had RP after CCRT had higher sTIM-3 levels during the first 3 months of follow-up. Baseline sCD25 was independently associated with both 2- and 5-year mortality outcomes, while baseline sTIM-3 was independently associated with 2-year mortality.ConclusionWe showed that T cell activation and exhaustion markers such as sCD25 and sTIM-3 are enhanced in patients developing RP and are associated with poor survival in NSCLC.
Necroptosis Identifies Novel Molecular Phenotypes and Influences Tumor Immune Microenvironment of Lung Adenocarcinoma
Authors: Zhao Chen , Xiong Kewei , Adam Abdalla , Ji Zhiqiang , Li Xiangpan 
Published: July 2022

This study aims to investigate the immune and epigenetic mutational landscape of necroptosis in lung adenocarcinoma (LUAD), identify novel molecular phenotypes, and develop a prognostic scoring system based on necroptosis regulatory molecules for a better understanding of the tumor immune microenvironment (TIME) in LUAD. Based on the Cancer Genome Atlas and Gene Expression Omnibus database, a total of 29 overlapped necroptosis-related genes were enrolled to classify patients into different necroptosis phenotypes using unsupervised consensus clustering. We systematically correlated the phenotypes with clinical features, immunocyte infiltrating levels, and epigenetic mutation characteristics. A novel scoring system was then constructed, termed NecroScore, to quantify necroptosis of LUAD by principal component analysis. Three distinct necroptosis phenotypes were confirmed. Two clusters with high expression of necroptosis-related regulators were “hot tumors”, while another phenotype with low expression was a “cold tumor”. Molecular characteristics, including mutational frequency and types, copy number variation, and regulon activity differed significantly among the subtypes. The NecroScore, as an independent prognostic factor (HR=1.086, 95%CI=1.040-1.133, p&lt;0.001), was able to predict the survival outcomes and show that patients with higher scores experienced a poorer prognosis. It could also evaluate the responses to immunotherapy and chemotherapeutic efficiency.In conclusion, necroptosis-related molecules are correlated with genome diversity in pan-cancer, playing a significant role in forming the TIME of LUAD. Necroptosis phenotypes can distinguish different TIME and molecular features, and the NecroScore is a promising biomarker for predicting prognosis, as well as immuno- and chemotherapeutic benefits in LUAD.
Remnant Cholesterol and Dyslipidemia Are Risk Factors for Guillain–Barré Syndrome and Severe Guillain–Barré Syndrome by Promoting Monocyte Activation
Authors: Ding Yaowei , Wang Lijuan , Sun Jialu , Shi Yijun , Li Guoge , Luan Xin , Zheng Guanghui , Zhang Guojun 
Published: July 2022

BackgroundGuillain–Barré syndrome (GBS) is the most common severe acute paralytic neuropathy, with a mortality rate of 5% and permanent sequelae rate of 10%. Currently, the cause of GBS remains unclear. Therefore, we sought to determine potential predictors for GBS and its severity.MethodsA case–control study was performed at Tiantan Hospital in Beijing from January 2017 to December 2021. Laboratory and clinical characteristics were assessed in recruited GBS patients and healthy control individuals (matched by sex and age). The potential risk factors for GBS and severe GBS were assessed using a logistic regression analysis. The mRNA levels of toll-like receptor 4 (TLR4), toll-like receptor 2 (TLR2) and nuclear factor κB (NF-κB) in GBS patients and control PBMCs were detected by fluorescence quantitative PCR. THP-1 cells were costimulated with LPS and free cholesterol to demonstrate the effect of free cholesterol on monocyte activation.ResultsA total of 147 GBS patients and 153 healthy individuals were included in the study. Logistic regression analyses showed that preceding infection, alcohol consumption, remnant cholesterol, homocysteine and the dyslipidemia index were correlated with a higher risk of GBS. In contrast, increased HDL cholesterol was correlated with a lower risk of GBS. Moreover, remnant cholesterol and the dyslipidemia index were significantly correlated with severe GBS. The mRNA levels of TLR4, TLR2 and NF-κB in the PBMCs of GBS patients were significantly higher than those of healthy individuals. LPS activated THP-1 cells, and free cholesterol treatment increased the expression of TLR4, TLR2, NF-κB and IL-1β mRNA in LPS-activated THP-1 cells.ConclusionDyslipidemia was correlated with the risk of GBS and severe GBS. Remnant cholesterol may promote the activation of monocytes in GBS patients. It may be valuable to control lipid levels in the prevention of GBS and severe GBS.
The Syndemic of Substance Use, High-Risk Sexual Behavior, and Violence: A Qualitative Exploration of the Intersections and Implications for HIV/STI Prevention Among Key Populations in Lagos, Nigeria
Authors: Dirisu Osasuyi , Adediran Mayokun , Omole Adekemi , Akinola Akinwumi , Ebenso Bassey , Shoyemi Elizabeth , Eluwa George , Tun Waimar , Adebajo Sylvia 
Published: July 2022

BackgroundKey populations (KP) are defined groups with an increased risk of HIV due to specific higher risk behaviours. KP who use substances engage in risky behaviors that may play a co-active role in HIV transmission and acquisition in Nigeria. This qualitative study explored the 'syndemics' of substance use, sexual risk behavior, violence and HIV infection among KP who use substances.MethodsNineteen sexually active men who have sex with men [MSM] and 18 female sex workers [FSW] aged 16 years and older who use substances were purposively selected to participate in sixteen in-depth interviews and two focus groups. We utilized a syndemic framework to explore the interaction of socio-economic factors, substance use and high-risk sexual practices. The interviews were audio-recorded, transcribed, organized in NVIVO 11 and analyzed using thematic analysis.ResultsMajority (95%) were non-injection substance users (primarily alcohol and marijuana); a few KP also used cocaine and heroin. Sixty percent of participants were between 16-24 years. Substance use utilities and trajectories were heavily influenced by KP social networks. They used substances as a coping strategy for both physical and emotional issues as well as to enhance sex work and sexual activities. Key HIV/STI risk drivers in the settings of substance use during sexual intercourse that emerged from this study include multiple sexual partnerships, condom-less sex, transactional sex, intergenerational sex, double penetration, rimming, and sexual violence. Poverty and adverse socio-economic conditions were identified as drivers of high-risk sexual practices as higher sexual risks attracted higher financial rewards.Conclusions and RecommendationsFindings indicate that KP were more inclined to engage in high-risk sexual practices after the use of substances, potentially increasing HIV risk. The syndemic of substance use, high-risk sexual behavior, adverse socio-economic situations, and violence intersect to limit HIV prevention efforts among KP. The behavioural disinhibition effects of substances as well as social and structural drivers should be considered in the design of targeted KP HIV prevention programs. HIV intervention programs in Nigeria may yield better outcomes if they address the nexus of sexual risk behavior and substance use as well as knowledge and appropriate use of HIV prophylaxis.
Prevalence of Long COVID-19 Symptoms After Hospital Discharge in Frail and Robust Patients
Authors: Damanti Sarah , Cilla Marta , Cilona Maria , Fici Aldo , Merolla Aurora , Pacioni Giacomo , De Lorenzo Rebecca , Martinenghi Sabina , Vitali Giordano , Magnaghi Cristiano , Fumagalli Anna , Gennaro Mazza Mario , Benedetti Francesco , Tresoldi Moreno , Rovere Querini Patrizia 
Published: July 2022

BackgroundA motley postacute symptomatology may develop after COVID-19, irrespective of the acute disease severity, age, and comorbidities. Frail individuals have reduced physiological reserves and manifested a worse COVID-19 course, during the acute setting. However, it is still unknown, whether frailty may subtend some long COVID-19 manifestations. We explored the prevalence of long COVID-19 disturbs in COVID-19 survivals.MethodsThis was an observational study. Patients aged 65 years or older were followed-up 1, 3, and 6 months after hospitalization for COVID-19 pneumonia.ResultsA total of 382 patients were enrolled. Frail patients were more malnourished (median Mini Nutritional Assessment Short Form score 8 vs. 9, p = 0.001), at higher risk of sarcopenia [median Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falls (SARC-F) score 3 vs. 1.5, p = 0.003], and manifested a worse physical performance [median Short Physical Performance Battery (SPPB) score 10 vs. 11, p = 0.0007] than robust individuals, after hospital discharge following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. Frailty was significantly associated with: (i) confusion, as a presenting symptom of COVID-19 [odds ratio (OR) 77.84, 95% CI 4.23–1432.49, p = 0.003]; (ii) malnutrition (MNA-SF: adjusted B –5.63, 95% CI –8.39 to –2.87, p &lt; 0.001), risk of sarcopenia (SARC-F: adjusted B 9.11, 95% CI 3.10–15.13, p = 0.003), impaired muscle performance (SPPB: B –3.47, 95% CI –6.33 to –0.61, p = 0.02), complaints in mobility (adjusted OR 1674200.27, 95% CI 4.52–619924741831.25, p = 0.03), in self-care (adjusted OR 553305.56, 95% CI 376.37–813413358.35, p &lt; 0.001), and in performing usual activities of daily living (OR 71.57, 95% CI 2.87–1782.53, p = 0.009) at 1-month follow-up; (iii) dyspnea [modified Medical Research Council (mMRC): B 4.83, 95% CI 1.32–8.33, p = 0.007] and risk of sarcopenia (SARC-F: B 7.12, 95% CI 2.17–12.07, p = 0.005) at 3-month follow-up; and (iv) difficulties in self-care (OR 2746.89, 95% CI 6.44–1172310.83, p = 0.01) at the 6-month follow-up. In a subgroup of patients (78 individuals), the prevalence of frailty increased at the 1-month follow-up compared to baseline (p = 0.009).ConclusionThe precocious identification of frail COVID-19 survivors, who manifest more motor and respiratory complaints during the follow-up, could improve the long-term management of these COVID-19 sequelae.
Copy Number Variation Analysis of 5p Deletion Provides Accurate Prenatal Diagnosis and Reveals Candidate Pathogenic Genes
Authors: Chu Guoming , Li Pingping , Wen Juan , Zheng Gaoyan , Zhao Yanyan , He Rong 
Published: July 2022

Objective5p deletion syndrome, that characterized by cat-like cry and peculiar timbre of voice, is believed to be one of the most common pathogenic copy number variations (CNVs). Variable critical regions on 5p involving a variety of genes contribute to the phenotypic heterogeneity without specific correlation. The objective of this study was to examine the genotype–phenotype correlation of 5p deletion syndrome, and to redefine 5p deletion syndrome relevant regions. In addition, we demonstrate the potential use of whole genome sequencing (WGS) to identify chromosomal breakpoints in prenatal diagnosis.MethodsThree families with women undergoing prenatal diagnosis and two children were recruited. Karyotyping, CNV-seq, fluorescence in situ hybridization, WGS, and Sanger sequencing were performed to identify the chromosomal disorder.ResultsWe reported three families and two children with CNVs of 5p deletion or combined 6p duplication. Five different sizes of 5p deletion were detected and their pathogenicity was determined, including 5p15.33-p15.31 [1–7,700,000, family1-variant of uncertain significance (VUS)], 5p15.33 (1–3,220,000, family 2-VUS), 5p15.33-p15.31 (1–7,040,000, family 3-VUS), 5p15.33-p15.31 (1–8,740,000, child 1-pathogenic) and 5p15.31-p15.1 (8,520,001–18,080,000, child 2-pathogenic). One duplication at 6p25.3-p24.3 (1–10,420,000) was detected and determined as likely pathogenic. The chromosomal breakpoints in family 3 were successfully identified by WGS.ConclusionSome critical genes that were supposed to be causative of the symptoms were identified. Relevant region in 5p deletion syndrome was redefined, and the chr5:7,700,000–8,740,000 region was supposed to be responsible for the cat-like cry. The great potential of WGS in detecting chromosomal translocations was demonstrated. Our findings may pave the way for further research on the prevention, diagnosis, and treatment of related diseases.
Analysis of Optic Nerve in Adults With Amblyopia Using OCTA
Authors: Lu Hui , Zhang Tonggang , Yue Tao , Li Xiaoqin , Ma Bingfen , Liu Hongxia 
Published: July 2022

ObjectiveThe aim was to quantify and compare papillary and peripapillary vessel density in amblyopic eyes of adults and age-matched controls.MethodsThis cross-sectional study involved 20 eyes from 10 subjects with anisometropic amblyopia and 12 eyes of 6 age- and gender-matched healthy controls. Optical coherence tomography angiography (OCTA) was performed on all participants. SPSS 20 was used for data analysis.ResultsThe mean subject age was 35.7 ± 10.04 years (range 18–47) in the amblyopia group and 34.67 ± 6.92 years (range 23–42) in the control group. The diopter of amblyopia ranges from +3 to +5 ds. The mean inside optic disk capillary vessel density (CVD) was 41.88 ± 6.55% in amblyopic eyes, 49.23 ± 6.55% in fellow eyes, and 50.23 ± 4% in control eyes (p &lt; 0.05). The mean inside optic disk all vessel density (AVD) was 52.97 ± 6.71% in amblyopic eyes, 59.87 ± 4.59% in fellow eyes, and 60.45 ± 2.8% in control eyes (p &lt; 0.05). The amblyopic eye of participants showed a decrease in vessel density in the inside optic disk than in the fellow eyes and healthy subjects.ConclusionOur present study revealed lower vessel density inside the optic disc of adult patients with anisometropic amblyopia. However, further studies are really needed to determine the clinical relevance of this finding.
Impact of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) GFR Estimating Equations on CKD Prevalence and Classification Among Asians
Authors: Betzler Bjorn Kaijun , Sultana Rehena , He Feng , Tham Yih Chung , Lim Cynthia Ciwei , Wang Ya Xing , Nangia Vinay , Tai E. Shyong , Rim Tyler Hyungtaek , Bikbov Mukharram M. , Jonas Jost B. , Kang Se Woong , Park Kyu Hyung , Cheng Ching-Yu , Sabanayagam Charumathi 
Published: July 2022

BackgroundIn 2021, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) validated a new equation for estimated glomerular filtration rate (eGFR). However, this new equation is not ethnic-specific, and prevalence of CKD in Asians is known to differ from other ethnicities. This study evaluates the impact of the 2009 and 2021 creatinine-based eGFR equations on the prevalence of CKD in multiple Asian cohorts.MethodsEight population-based studies from China, India, Russia (Asian), Singapore and South Korea provided individual-level data (n = 67,233). GFR was estimated using both the 2009 CKD-EPI equation developed using creatinine, age, sex, and race (eGFRcr [2009, ASR]) and the 2021 CKD-EPI equation developed without race (eGFRcr [2021, AS]). CKD was defined as an estimated glomerular filtration rate (eGFR) &lt;60 mL/min/1.73m2 (G3-G5). Prevalence of eGFR categories was compared within each study and within subgroups of age, sex, body mass index (BMI), diabetes, and hypertension status. The extent of reclassification was examined using net reclassification improvement (NRI).FindingsOf 67,233 adults, CKD prevalence was 8.6% (n = 5800/67,233) using eGFRcr (2009, ASR) and 6.4% (n = 4307/67,233) using eGFRcr (2021, AS). With the latter, CKD prevalence was reduced across all eight studies, ranging from −7.0% (95% CI −8.5% to −5.4%) to −0.4% (−1.3% to 0.5%), and across all subgroups except those in the BMI &lt; 18.5% subgroup. Net reclassification index (NRI) was significant at −2.33% (p &lt; 0.001). No individuals were reclassified as a higher (more severe) eGFR category, while 1.7%−4.2% of individuals with CKD were reclassified as one eGFR category lower when eGFRcr (2021, AS) rather than eGFRcr (2009, ASR) was used.InterpretationeGFRcr (2021, AS) consistently provided reduced CKD prevalence and higher estimation of GFR among Asian cohorts than eGFRcr (2009, ASR). Based on current risk-stratified approaches to CKD management, more patients reclassified to lower-risk GFR categories could help reduce inappropriate care and its associated adverse effects among Asian renal patients. Comparison of both equations to predict progression to renal failure or adverse outcomes using prospective studies are warranted.FundingNational Medical Research Council, Singapore.
Altered Brain Function Activity in Patients With Dysphagia After Cerebral Infarction: A Resting-State Functional Magnetic Resonance Imaging Study
Authors: Li Lei , Liu Jiayu , Liang Fenxiong , Chen Haidong , Zhan Rungen , Zhao Shengli , Li Tiao , Peng Yongjun 
Published: July 2022

ObjectiveDysphagia after cerebral infarction (DYS) has been detected in several brain regions through resting-state functional magnetic resonance imaging (rs-fMRI). In this study, we used two rs-fMRI measures to investigate the changes in brain function activity in DYS and their correlations with dysphagia severity.MethodIn this study, a total of 22 patients with DYS were compared with 30 patients without dysphagia (non-DYS) and matched for baseline characteristics. Then, rs-fMRI scans were performed in both groups, and regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuation (fALFF) values were calculated in both groups. The two-sample t-test was used to compare ReHo and fALFF between the groups. Pearson's correlation analysis was used to determine the correlations between the ReHo and fALFF of the abnormal brain regions and the scores of the Functional Oral Intake Scale (FOIS), the Standardized Bedside Swallowing Assessment (SSA), the Videofluoroscopic Swallowing Study (VFSS), and the Penetration-Aspiration Scale (PAS).ResultsCompared with the non-DYS group, the DYS group showed decreased ReHo values in the left thalamus, the left parietal lobe, and the right temporal lobe and significantly decreased fALFF values in the right middle temporal gyrus and the inferior parietal lobule. In the DYS group, the ReHo of the right temporal lobe was positively correlated with the SSA score and the PAS score (r = 0.704, p &lt; 0.001 and r = 0.707, p &lt; 0.001, respectively) but negatively correlated with the VFSS score (r = −0.741, p &lt; 0.001). The ReHo of the left parietal lobe was positively correlated with SSA and PAS (r = 0.621, p = 0.002 and r = 0.682, p &lt; 0.001, respectively) but negatively correlated with VFSS (r = −0.679, p = 0.001).ConclusionThe changes in the brain function activity of these regions are related to dysphagia severity. The DYS group with high ReHo values in the right temporal and left parietal lobes had severe dysphagia.
Tolerance to Dizziness Intensity Increases With Age in People With Chronic Dizziness
Authors: Prell Tino , Mendorf Sarah , Axer Hubertus 
Published: July 2022

BackgroundDizziness is a common complaint in older adults. To know which factors are instrumental in enabling patients with chronic dizziness to tolerate their symptoms to a certain degree in everyday life can help to develop tailored therapies.MethodsData from 358 patients with chronic dizziness and vertigo who had attended a multimodal daycare treatment program were recorded. Data included sociodemographic parameters, dizziness-related characteristics, the Vertigo Symptom Scale (VSS), and the Hospital Anxiety and Depression Scale (HADS). Descriptive statistics, elastic net regression, and mediation analysis were used.ResultsA higher tolerance of dizziness was associated with higher age, higher intensity of dizziness, lower burden of dizziness, higher HADS depression, structural reason for dizziness (type), permanent dizziness, absence of attacks, and longer disease duration. In contrast, younger persons with attack-like dizziness reported to tolerate less dizziness. Age had a significant direct effect on tolerance (72% of the total effect) and a significant indirect effect via intensity on tolerance (28% of the total effect) in the mediation analysis.ConclusionIt can only be speculated that negative stereotypes about age-related complaints may play a role in this. Why older people tolerate more dizziness and to what extent this may contribute to lower healthcare utilization need to be investigated in further studies.
Movement Disorders Associated With Cerebral Artery Stenosis: A Nationwide Study
Authors: Park Kye Won , Choi Nari , Oh Eungseok , Lyoo Chul Hyoung , Baek Min Seok , Kim Han-Joon , Yoo Dalla , Lee Jee-Young , Choi Ji-Hyun , Lee Jae Hyeok , Koh Seong-Beom , Sung Young Hee , Cho Jin Whan , Yang Hui-Jun , Park Jinse , Shin Hae-Won , Ahn Tae-Beom , Ryu Ho-Sung , You Sooyeoun , Choi Seong-Min , Kim Bum Joon , Lee Seung Hyun , Chung Sun Ju 
Published: July 2022

BackgroundStudies of secondary movement disorder (MD) caused by cerebrovascular diseases have primarily focused on post-stroke MD. However, MD can also result from cerebral artery stenosis (CAS) without clinical manifestations of stroke. In this study, we aimed to investigate the clinical characteristics of MD associated with CAS.Materials and MethodsA nationwide multicenter retrospective analysis was performed based on the data from patients with CAS-associated MDs from 16 MD specialized clinics in South Korea, available between January 1999 and September 2019. CAS was defined as the &gt;50% luminal stenosis of the major cerebral arteries. The association between MD and CAS was determined by MD specialists using pre-defined clinical criteria. The collected clinical information included baseline demographics, features of MD, characteristics of CAS, treatment, and MD outcomes. Statistical analyses were performed to identify factors associated with the MD outcomes.ResultsThe data from a total of 81 patients with CAS-associated MD were analyzed. The mean age of MD onset was 60.5 ± 19.7 years. Chorea was the most common MD (57%), followed by tremor/limb-shaking, myoclonus, and dystonia. Atherosclerosis was the most common etiology of CAS (78%), with the remaining cases attributed to moyamoya disease (MMD). Relative to patients with atherosclerosis, those with MMD developed MD at a younger age (p &lt; 0.001) and had a more chronic mode of onset (p = 0.001) and less acute ischemic lesion (p = 0.021). Eight patients who underwent surgical treatment for CAS showed positive outcomes. Patients with acute MD onset had a better outcome than those with subacute-to-chronic MD onset (p = 0.008).ConclusionsThis study highlights the spectrum of CAS-associated with MD across the country. A progressive, age-dependent functional neuronal modulation in the basal ganglia due to CAS may underlie this condition.