bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequently assessed and used prognostic factors for outcome after macular hole surgery: which is better?
Authors: Roth M. , Schön N. , Jürgens L. , Engineer D. , Kirchhoff K. , Guthoff R. , Schmidt J. 
Published: November 2021

Abstract
Background
The aim of this retrospective study was to evaluate commonly used clinical and OCT-morphological parameters, including perifoveal pseudocysts, as prognostic factors for postoperative outcome after macular hole surgery in a retinal referral clinic in North Rhine-Westphalia, Germany.

Methods and material
This was a retrospective analysis of all patients who underwent surgery because of idiopathic MH between 2011 and 2017 in Augenklinik Tausendfensterhaus, Duisburg, Germany. Statistical evaluation of clinical and OCT-based parameters, including the areas of intraretinal pseudocysts, was conducted. The main statistical outcomes were surgical success and visual acuity. Only parameters with a highly significant correlation to the outcome parameters (postoperative visual acuity (VA); surgical success) in univariate analysis were entered in linear and logistic regression analyses.

Results
A total of 189 eyes of 178 patients (71.4% female; mean age 67.5 ± 8.2 a) who underwent surgery because of MH were included. The overall closure rate was 86.8%. The mean best corrected VA increased from 0.7 ± 0.3 logMAR before surgery to 0.5 ± 0.3 logMAR (p < 0.0001). While several clinical and OCT-based parameters as well as calculated indices showed a significant correlation with the outcome measures, the regression analysis showed that the minimum linear diameter was the only parameter that both predicted surgical success (p = 0.015) and was correlated with postoperative VA (p < 0.001).

Conclusion
The minimum linear diameter serves as an easily assessed prognostic factor with the best predictive properties. This result is of great importance for clinical practice, as it simplifies the postsurgical prognosis.
Prostaglandin E2 sensitizes the cough reflex centrally via EP3 receptor-dependent activation of NaV 1.8 channels
Authors: Al-Kandery Al-Shaimaa A. , Rao Muddanna S. , El-Hashim Ahmed Z. 
Published: November 2021

Abstract
Background
Cough hypersensitivity is a major characteristic feature associated with several types of cough, including chronic cough, but its underlying mechanisms remain to be fully understood. Inflammatory mediators, such as prostaglandin E2 (PGE2), have been implicated in both peripheral induction and sensitization of the cough reflex. In this study, using a conscious guinea pig model of cough, we investigated whether PGE2 can sensitize the cough reflex via central actions and, if so, via which mechanisms.

Methods
All drugs were administered by intracerebroventricular (i.c.v.) route and whole-body plethysmograph set-up was used for both induction, using aerosolized citric acid (0.2 M), and recording of cough. Immunohistochemistry was performed to confirm the expression of NaV 1.8 channels in the nucleus tractus solitarius (nTS).

Results
We show that both PGE2 and the non-selective EP1/EP3 agonist, sulprostone, dose-dependently enhanced the citric acid-induced cough (P ≤ 0.001, P ≤ 0.01, respectively). Pretreatment with the EP1 antagonist, ONO-8130, did not affect the sulprostone-induced cough sensitization, whilst the EP3 antagonist, L-798,106, dose-dependently inhibited this effect (P ≤ 0.05). Furthermore, treatment with either the EP2 agonist, butaprost or the EP4 agonist, L-902,688, had no effect on cough sensitization. Additionally, pretreatment with either the TRPV1 antagonist, JNJ-17203212 or the TRPA1 antagonist, HC-030031, alone or in combination, nor with the NaV 1.1, 1.2, 1.3, 1.4, 1.6 and 1.7 channel blocker, tetrodotoxin, had any effect on the cough. In contrast, pretreatment with the NaV 1.8 antagonist, A-803467, dose-dependently inhibited this effect (P ≤ 0.05). Furthermore, NaV 1.8 channels were shown to be expressed in the nTS.

Conclusion
Collectively, our findings show that PGE2 sensitizes the cough reflex centrally via EP3 receptor-dependent activation of NaV 1.8 but independently of TRPV1,TRPA1 and TTX-sensitive sodium channel activation. These results indicate that PGE2 plays an important role in central sensitization of the cough reflex and suggest that central EP3 receptors and/or NaVv 1.8 channels may represent novel antitussive molecular targets.

Graphical Abstract
Treatment outcomes of re-irradiation using stereotactic ablative radiotherapy to lung: a propensity score matching analysis
Authors: Lee Tae Hoon , Kim Dong-Yun , Wu Hong-Gyun , Lee Joo Ho , Kim Hak Jae 
Published: November 2021

AbstractBackgroundThe purpose of this study was to compare the treatment efficacy and safety of re-irradiation (re-RT) using stereotactic ablative radiotherapy (SABR) and initial SABR for primary, recurrent lung cancer or metastatic lung tumor.MethodsA retrospective review of the medical records of 336 patients who underwent lung SABR was performed. Re-RT was defined as the overlap of the 70% isodose line of second-course SABR with that of the initial radiotherapy, and 20 patients were classified as the re-RT group. The median dose of re-RT using SABR was 54 Gy (range 48–60 Gy), and the median fraction number was 4 (range 4–6). One-to-three case-matched analysis with propensity score matching was used, and 60 patients were included in the initial SABR group of the matched cohort.ResultsThe 1- and 2-year local control rates for the re-RT group were 73.9% and 63.3% and those for the initial SABR group in the matched cohort were 92.9% and 87.7%, respectively (P = 0.013). There was no difference in distant metastasis-free, progression-free, and overall survival rates. The crude grade ≥ 2 toxicity rates were 40.0% for the re-RT group and 25.0% for the initial SABR group (P = 0.318). Re-RT group had higher acute grade ≥ 2 toxicity rates (25.0% vs 5.0%,P = 0.031). One incident of grade 3 toxicity (pulmonary) was reported in the re-RT group; there was no grade 4‒5 toxicity.ConclusionsThe local control rate of the in-field re-RT SABR was lower than that of the initial SABR without compromising the survival rates. The toxicity of re-RT using SABR was acceptable.
Correlation between neutrophil-to-lymphocyte ratio and postoperative mortality in elderly patients with hip fracture: a meta-analysis
Authors: Chen Yu-Hang , Chou Ching-Hsin , Su Hsin-Hsien , Tsai Yu-Ting , Chiang Ming-Hsiu , Kuo Yi-Jie , Chen Yu-Pin 
Published: November 2021

Abstract
Introduction
The neutrophil-to-lymphocyte ratio (NLR) is a crucial prognosis predictor following several major operations. However, the association between NLR and the outcome after hip fracture surgery is unclear. In this meta-analysis, we investigated the correlation between NLR and postoperative mortality in geriatric patients following hip surgery.

Method
PubMed, Embase, Cochrane library, and Google Scholar were searched for studies up to June 2021 reporting the correlation between NLR and postoperative mortality in elderly patients undergoing surgery for hip fracture. Data from studies reporting the mean of NLR and its 95% confidence interval (CI) were pooled. Both long-term (≥ 1 year) and short-term (≤ 30 days) mortality rates were included for analysis.

Result
Eight retrospective studies comprising a total of 1563 patients were included. Both preoperative and postoperative NLRs (mean difference [MD]: 2.75, 95% CI: 0.23–5.27; P = 0.03 and MD: 2.36, 95% CI: 0.51–4.21; P = 0.01, respectively) were significantly higher in the long-term mortality group than in the long-term survival group. However, no significant differences in NLR were noted between the short-term mortality and survival groups (MD: − 1.02, 95% CI: − 3.98 to 1.93; P = 0.5).

Conclusion
Higher preoperative and postoperative NLRs were correlated with a higher risk of long-term mortality following surgery for hip fracture in the geriatric population, suggesting the prognostic value of NLR for long-term survival. Further studies with well-controlled confounders are warranted to clarify the predictive value of NLR in clinical practice in geriatric patients with hip fracture.
Use of a suspended and straightened knee joint position when fixing steel plates can prevent the increase in postoperative posterior tibial slope after open‑wedge high tibial osteotomy
Authors: Ma Wenru , Han Zengshuai , Sun Shengnan , Chen Jinli , Zhang Yi , Yu Tengbo 
Published: November 2021

AbstractBackgroundPosterior tibial slope (PTS) increases after medial open-wedge high tibial osteotomy (OWHTO) is challenging for patients. This study aims to determine whether use of a suspended and straightened knee joint position during the fixing of steel plates can prevent an increase in the PTS after OWHTO.MethodsThis study retrospectively analyzed 112 subjects (122 knees) [34 males, 78 females; mean age 59.1 ± 6.6 (range 48–76) years; mean body mass index 28.06 ± 3.61 kg/m2] who underwent OWHTO. A total of 78 knees that were suspended and extended by placing a sterile cloth ball under the ipsilateral ankle during the fixing of steel plates comprised the suspended and straightened knee joint position (SSP) group, and 44 knees that were kept naturally straightened without placing a sterile cloth ball under the ipsilateral ankle during the fixing of steel plates comprised the naturally straightened knee joint position (NSP) group. Patients were clinically assessed according to the visual analog pain scale (VAS), the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index, the Knee Society Scores (KSS) knee and function scores, the Hospital for Special Surgery (HSS) knee scores and the Lysholm knee scores. Radiological assessment was performed according to the changes in the PTS between preoperation, 1-day postoperation, and the final follow-up periods. Ultimately, the difference in postoperative PTS changes between the two groups was statistically analyzed. The median follow-up period was 2.2 years (range 1.6–3.7 years).ResultsIn the final follow-up period, significant improvements were observed in the clinical VAS scores, WOMAC scores, KSS knee and function scores, HSS scores and the Lysholm knee scores in both groups (P < 0.001), and no difference was found between the two groups. Radiological assessment showed that there was no statistical difference in the preoperative PTS between the two groups. The 1-day postoperative PTS and the most recent follow-up PTS were significantly greater than the preoperative PTS in the NSP group (t = − 3.213, − 6.406, allP < 0.001), but no significant increase was seen in the SSP group (P > 0.05). The increase in PTS in the NSP group was significantly greater than that in the SSP group at the 1-day postoperative (t = 2.243,P = 0.030) and final follow-up periods (t = 6.501,P < 0.001).ConclusionsFor OWHTO, the use of a suspended and straightened knee joint position rather than a naturally straightened knee joint position during the fixing of steel plates could effectively prevent the increase in postoperative PTS.Level of Evidence: Retrospective Study Level III.
Predictors of heart failure symptoms in hereditary hemorrhagic telangiectasia patients with hepatic arteriovenous malformations
Authors: Cusumano Lucas R. , Tesoriero Joseph A. , Wilsen Craig B. , Sayre James , Quirk Matthew , McWilliams Justin P. 
Published: November 2021

Abstract
Background
Hepatic arteriovenous malformations (AVMs) in hereditary hemorrhagic telangiectasia (HHT) patients are most commonly hepatic artery to hepatic venous shunts which can result in high-output heart failure. This condition can be debilitating and is a leading cause of liver transplantation in HHT patients. However, it is not known what characteristics can discriminate between asymptomatic patients and those who will develop heart failure symptoms.

Results
176 patients with HHT were evaluated with computed tomography angiography (CTA) between April 2004 and February 2019 at our HHT Center of Excellence. 63/176 (35.8%) patients were found to have hepatic AVMs on CTA. 18 of these patients were excluded because of the presence of another condition which could confound evaluation of heart failure symptoms. In the remaining 45 patients included in our cohort, 25/45 (55.6%) patients were classified as asymptomatic and 20/45 (44.4%) were classified as symptomatic, and these groups were compared.
In symptomatic patients, mean common hepatic artery (CHA) diameter was significantly higher (11.1 versus 8.4 mm) and mean hemoglobin levels were significantly lower (10.7 vs 12.6 g/dL). A stepwise multiple logistic regression analysis demonstrated that both CHA diameter and hemoglobin level were independent predictors of heart failure symptoms with ORs of 2.554 (95% CI 1.372–4.754) and 0.489 (95% CI 0.299–0.799), respectively. The receiver operator characteristic (ROC) curve of our analysis demonstrated an AUC of 0.906 (95% CI 0.816–0.996), sensitivity 80.0% (95% CI 55.7–93.4%), and specificity 75.0% (95% CI 52.9–89.4%).

Conclusions
CTA is an effective and easily reproducible method to evaluate hepatic involvement of HHT. Utilizing CTA, clinical, and laboratory data we determined CHA diameter and hemoglobin level were independent predictors of heart failure symptoms.
The genetic analysis of Chinese patients with clonal cytopenias using targeted next-generation sequencing
Authors: Zhang Lijuan , Shi YuYe , Chen Yue , Tao Shandong , Shi Wenting , He Zhengmei , Chen Kankan , Wang Chunling , Yu Liang 
Published: November 2021

Abstract
Background
Clonal hematopoiesis (CH) can be found in various myeloid neoplasms (MN), such as myelodysplastic syndromes (MDS), myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN), also in pre-MDS conditions.

Methods
Cytogenetics is an independent prognostic factor in MDS, and fluorescence in-situ hybridization (FISH) can be used as an adjunct to karyotype analysis. In the past 5 years, only 35 of 100 newly diagnosed MDS and MDS/MPN patients were identified abnormalities, who underwent the FISH panel. In addition, we examined a cohort of 51 cytopenic patients suspected MDS or MDS/MPN with a 20-gene next generation sequencing (NGS), including 35 newly diagnosed MN patients and 16 clonal cytopenias of undetermined significance (CCUS) patients.

Results
Compared with the CCUS group, the MN group had higher male ratio (22/13 vs 10/6), cytogenetics abnormalities rate (41.4% vs 21.4%) and frequency of a series of mutations, such as ASXL1 (28.6% vs 25%), U2AF1 (25.7% vs 25%), RUNX1 (20% vs 0.0%); also, higher adverse mutations proportion (75% vs 85.2%), and double or multiple mutations (54.3% vs 43.75%). There were 7 MN patients and 4 CCUS patients who experienced cardio-cerebrovascular embolism events demonstrated a significant difference between the two groups (25% vs 20%). Ten of the 11 patients had somatic mutations, half had DNA methylation, while the other half had RNA splicing. Additionally, six patients had disease transformation, and four patients had mutated U2AF1, including two CCUS cases and two MDS-EB cases. Following up to January 2021, there was no significant difference in over survival between the CCUS and MN groups.

Conclusion
NGS facilitates the diagnosis of unexplained cytopenias. The monitoring and management of CCUS is necessary, also cardio-cerebrovascular embolism events in patients with CH need attention in the clinical practice.
Conditional deletion of ROCK2 induces anxiety-like behaviors and alters dendritic spine density and morphology on CA1 pyramidal neurons
Authors: Weber Audrey J. , Adamson Ashley B. , Greathouse Kelsey M. , Andrade Julia P. , Freeman Cameron D. , Seo Jung Vin , Rae Rosaria J. , Walker Courtney K. , Herskowitz Jeremy H. 
Published: November 2021

AbstractRho-associated kinase isoform 2 (ROCK2) is an attractive drug target for several neurologic disorders. A critical barrier to ROCK2-based research and therapeutics is the lack of a mouse model that enables investigation of ROCK2 with spatial and temporal control of gene expression. To overcome this, we generated ROCK2fl/fl mice. Mice expressing Cre recombinase in forebrain excitatory neurons (CaMKII-Cre) were crossed with ROCK2fl/fl mice (Cre/ROCK2fl/fl), and the contribution of ROCK2 in behavior as well as dendritic spine morphology in the hippocampus, medial prefrontal cortex (mPFC), and basolateral amygdala (BLA) was examined. Cre/ROCK2fl/fl mice spent reduced time in the open arms of the elevated plus maze and increased time in the dark of the light–dark box test compared to littermate controls. These results indicated that Cre/ROCK2fl/fl mice exhibited anxiety-like behaviors. To examine dendritic spine morphology, individual pyramidal neurons in CA1 hippocampus, mPFC, and the BLA were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and neuronal 3D reconstructions for morphometry analysis. In dorsal CA1, Cre/ROCK2fl/fl mice displayed significantly increased thin spine density on basal dendrites and reduced mean spine head volume across all spine types on apical dendrites. In ventral CA1, Cre/ROCK2fl/fl mice exhibited significantly increased spine length on apical dendrites. Spine density and morphology were comparable in the mPFC and BLA between both genotypes. These findings suggest that neuronal ROCK2 mediates spine density and morphology in a compartmentalized manner among CA1 pyramidal cells, and that in the absence of ROCK2 these mechanisms may contribute to anxiety-like behaviors.
Immunoassay standardization for the detection of immunoglobulin A (IgA) against Porphyromonas gingivalis antigens in saliva of individuals with and without leprosy
Authors: Calheira Mariana Costa , Trindade Soraya Castro , Falcão Michelle Miranda Lopes , Barbosa Luciana Sales Conceição , Carvalho Gislene Regina Batista , Machado Paulo Roberto Lima , Gomes-Filho Isaac Suzart , de Jesus Campos Elisangela , de Carvalho-Filho Paulo Cirino , Xavier Márcia Tosta , de Farias Antonio Pedro Fróes , Filho José Tadeu Raynal Rocha , de Santana Passos-Soares Johelle 
Published: November 2021

AbstractLeprosy reactions are immune processes that cause neural damage in individuals with leprosy. As periodontitis is an infectious disease related to its development, specific antibodies to periodontal pathogens must be evaluated to better understand the humoral mechanisms underlying this relationship. Therefore, the objective of this study was to standardize an immunoassay to measure IgA specific to P. gingivalis antigens in the saliva of individuals with leprosy. An ELISA checkerboard titration was performed. A validation test involving 53 individuals with leprosy, 24 with and 19 without periodontitis, was conducted and a ROC curve constructed to calculate sensitivity and specificity. The coefficient of the optical densities was 2.21 and 2.66 for P. gingivalis crude extract and the recombinant protein HmuY, respectively. Sensitivity and specificity for the P. gingivalis crude extract were 66.7% and 73.7%, respectively, and for HmuY, were 62.5% and 52.6%, respectively. Specific recognition of P. gingivalis occurred predominantly in individuals with periodontitis, which validates the use of this test for studying periodontitis in individuals with leprosy.Trial registration CAEE 64476117.3.0000.0049, 21/07/2017, retrospectively registered
Infection with severe fever with thrombocytopenia virus in healthy population: a cohort study in a high endemic region, China
Authors: Ye Xiao-Lei , Dai Ke , Lu Qing-Bin , Huang Yan-Qin , Lv Shou-Ming , Zhang Pan-He , Li Jia-Chen , Zhang Hai-Yang , Yang Zhen-Dong , Cui Ning , Yuan Chun , Liu Kun , Zhang Xiao-Ai , Zhang Jiu-Song , Li Hao , Yang Yang , Fang Li-Qun , Liu Wei 
Published: November 2021

Abstract
Background
Severe fever with thrombocytopenia (SFTS) caused by SFTS virus (SFTSV) was a tick-borne hemorrhagic fever that posed significant threat to human health in Eastern Asia. The study was designed to measure the seroprevalence of SFTSV antibody in healthy population residing in a high endemic region.

Methods
A cohort study was performed on healthy residents in Shangcheng County in Xinyang City from April to December in 2018, where the highest SFTS incidence in China was reported. Anti-SFTSV IgG was measured by indirect enzyme-linked immunosorbent assay and neutralizing antibody (NAb) was detected by using PRNT50. The logistic regression models were performed to analyze the variables that were associated with seropositive rates.

Results
Totally 886 individuals were recruited. The baseline seroprevalence that was tested before the epidemic season was 11.9% (70/587) for IgG and 6.8% (40/587) for NAb, which was increased to 13.4% (47/350) and 7.7% (27/350) during the epidemic season, and further to 15.8% (80/508) and 9.8% (50/508) post epidemic. The IgG antibody-based seropositivity was significantly related to the patients aged ≥ 70 years old [adjusted odds ratio (OR) = 2.440, 95% confidence interval (CI): 1.334–4.461 compared to the group of < 50 years old, P = 0.004], recent contact with cats (adjusted OR = 2.195, 95% CI: 1.261–3.818, P = 0.005), and working in tea garden (adjusted OR = 1.698, 95% CI: 1.002–2.880, P = 0.049) by applying multivariate logistic regression model. The NAb based seropositivity was similarly related to the patients aged ≥ 70 years old (adjusted OR = 2.691, 95% CI: 1.271–5.695 compared to the group of < 50 years old, P = 0.010), and recent contact with cats (OR = 2.648, 95% CI: 1.419–4.941, P = 0.002). For a cohort of individuals continually sampled with 1-year apart, the anti-SFTSV IgG were maintained at a stable level, while the NAb level reduced.

Conclusions
Subclinical infection might not provide adequate immunity to protect reinfection of SFTSV, thus highlighting the ongoing threats of SFTS in endemic regions, which called for an imperative need for vaccine development. Identification of risk factors might help to target high-risk population for public health education and vaccination in the future.

Graphical Abstract
Improved quantitative microbiome profiling for environmental antibiotic resistance surveillance
Authors: Ott Amelie , Quintela-Baluja Marcos , Zealand Andrew M. , O’Donnell Greg , Haniffah Mohd Ridza Mohd , Graham David W. 
Published: November 2021

Abstract
Background
Understanding environmental microbiomes and antibiotic resistance (AR) is hindered by over reliance on relative abundance data from next-generation sequencing. Relative data limits our ability to quantify changes in microbiomes and resistomes over space and time because sequencing depth is not considered and makes data less suitable for Quantitative Microbial Risk Assessments (QMRA), critical in quantifying environmental AR exposure and transmission risks.

Results
Here we combine quantitative microbiome profiling (QMP; parallelization of amplicon sequencing and 16S rRNA qPCR to estimate cell counts) and absolute resistome profiling (based on high-throughput qPCR) to quantify AR along an anthropogenically impacted river. We show QMP overcomes biases caused by relative taxa abundance data and show the benefits of using unified Hill number diversities to describe environmental microbial communities. Our approach overcomes weaknesses in previous methods and shows Hill numbers are better for QMP in diversity characterisation.

Conclusions
Methods here can be adapted for any microbiome and resistome research question, but especially providing more quantitative data for QMRA and other environmental applications.