bluuebunny/crossref_metadata_2025_split huggingface dataset:
The usefulness of pretreatment controlling nutritional status score for predicting recurrence in patients with esophageal squamous cell carcinoma undergoing neoadjuvant immunochemotherapy: A real-world study
Authors: Feng Jifeng , Wang Liang , Yang Xun , Chen Qixun , Cheng Xiangdong 
Published: November 2022

BackgroundThe controlling nutritional status (CONUT) score, as an immune-nutritional index, has been reported to be related to prognosis in several cancers. Neoadjuvant immunochemotherapy (nICT) is an emerging pattern for cancer treatment in recent years. However, the usefulness of CONUT in esophageal squamous cell carcinoma (ESCC) with nICT has not been reported so far. This study attempted to clarify the usefulness of CONUT in predicting disease-free survival (DFS) in ESCC with nICT.MethodsTwo hundred sixteen ESCC patients receiving nICT between 2019 and 2021 were retrospectively enrolled. Based on CONUT, the patients were divided into two groups: low groups (score ≤ 2) and high (score ≥ 3) groups. The relationships between CONUT and clinical characteristics were estimated. Cox regression analyses with hazard ratios (HRs) and 95% confidence intervals (CIs) were also performed to evaluate the prognostic factors of DFS.ResultsFifty-nine (27.3%) patients achieved pathologic complete response (pCR), and 30 (13.9%) cases had a recurrence. There were 150 cases (69.4%) in low CONUT group and 66 cases (30.6%) in high CONUT group, respectively. The results revealed that vessel invasion (P = 0.037), postoperative pneumonia (P = 0.001), advanced ypT stage (P = 0.011), cTNM stage (P = 0.007), and ypTNM stage (P &lt; 0.001) were significantly related to patients with a high CONUT score. A high pCR rate was found in patients with a low CONUT score (33.3% vs. 13.6%, P = 0.003), and a high recurrence rate was found in patients with a high CONUT score (24.2% vs. 9.3%, P = 0.004), respectively. Patients with a low CONUT score had a better 1-year DFS than those with a high CONUT score (90.7% vs. 75.8%, P = 0.004). Multivariate analyses indicated that the pretreatment CONUT score was an independent predictor regarding DFS (HR = 2.221, 95% CI: 1.067–4.625, P = 0.033).ConclusionA better response and a lower recurrence were found in ESCC patients with a lower pretreatment CONUT. As a useful index for immune-nutritional status, the CONUT might be a reliable prognostic indicator in ESCC patients with nICT.
Dissecting the impact of molecular T-cell HLA mismatches in kidney transplant failure: A retrospective cohort study
Authors: Lemieux William , Fleischer David , Yang Archer Yi , Niemann Matthias , Oualkacha Karim , Klement William , Richard Lucie , Polychronakos Constantin , Liwski Robert , Claas Frans , Gebel Howard M. , Keown Paul A. , Lewin Antoine , Sapir-Pichhadze Ruth 
Published: November 2022

IntroductionKidney transplantation is the optimal treatment in end-stage kidney disease, but de-novo donor specific antibody development continues to negatively impact patients undergoing kidney transplantation. One of the recent advances in solid organ transplantation has been the definition of molecular mismatching between donors and recipients’ Human Leukocyte Antigens (HLA). While not fully integrated in standard clinical care, cumulative molecular mismatch at the level of eplets (EMM) as well as the PIRCHE-II score have shown promise in predicting transplant outcomes. In this manuscript, we sought to study whether certain T-cell molecular mismatches (TcEMM) were highly predictive of death-censored graft failure (DCGF).MethodsWe studied a retrospective cohort of kidney donor:recipient pairs from the Scientific Registry of Transplant Recipients (2000-2015). Allele level HLA-A, B, C, DRB1 and DQB1 types were imputed from serologic types using the NMDP algorithm. TcEMMs were then estimated using the PIRCHE-II algorithm. Multivariable Accelerated Failure Time (AFT) models assessed the association between each TcEMM and DCGF. To discriminate between TcEMMs most predictive of DCGF, we fit multivariable Lasso penalized regression models. We identified co-expressed TcEMMs using weighted correlation network analysis (WGCNA). Finally, we conducted sensitivity analyses to address PIRCHE and IMGT/HLA version updates.ResultsA total of 118,309 donor:recipient pairs meeting the eligibility criteria were studied. When applying the PIRCHE-II algorithm, we identified 1,935 distinct TcEMMs at the population level. A total of 218 of the observed TcEMM were independently associated with DCGF by AFT models. The Lasso penalized regression model with post selection inference identified a smaller subset of 86 TcEMMs (56 and 30 TcEMM derived from HLA Class I and II, respectively) to be highly predictive of DCGF. Of the observed TcEMM, 38.14% appeared as profiles of highly co-expressed TcEMMs. In addition, sensitivity analyses identified that the selected TcEMM were congruent across IMGT/HLA versions.ConclusionIn this study, we identified subsets of TcEMMs highly predictive of DCGF and profiles of co-expressed mismatches. Experimental verification of these TcEMMs determining immune responses and how they may interact with EMM as predictors of transplant outcomes would justify their consideration in organ allocation schemes and for modifying immunosuppression regimens.
Management of stent-related tracheoesophageal fistula in complex post-tuberculosis tracheobronchial stenosis: A case report
Authors: Bai Yang , Yin Yuting , Chi Jing , Li Shuang , Li Yishi , Guo Shuliang 
Published: November 2022

BackgroundThe covered self-expandable metallic stents (SEMS) have been used to manage benign tracheobronchial stenosis, especially the complex post-tuberculosis (TB) tracheobronchial stenosis (PTTS) with cartilage destruction or malacia. This procedure could lead to stent-related tracheoesophageal fistula (TEF).Case presentationA 21-year-old woman, who had one covered Y-shaped SEMS inserted to manage complex PTTS 2 years ago, presented with dyspnea and frequent coughing on drinking water. The bronchoscopy confirmed extensive granulation tissue hyperplasia and a TEF on the upper edge of the covered SEMS. The covered SEMS was removed in three steps, and another fully covered Y-shape SEMS (Microtech Co., Ltd., Nanjing, China) was inserted to restore patency in the tracheobronchial tree and occlude the TEF orifice. Recombinant bovine basic fibroblast growth factor (rbFGF) (6,000 IU/time) was sprayed into and around the fistula through the V-System single-use cannula via the flexible bronchoscope every other week. The patient showed sustained clinical and radiographic improvement, and the TEF healed.ConclusionWe presented a three-step bronchoscopic approach to managing a stent-related TEF in a patient with complex PTTS. Subsequently, regular bronchoscopic debridement of granulation tissue developing on the upper edge of SEMS is necessary to maintain the stent patency and reduce the risk of recurrent stent-related TEF. A fully covered SEMS associated with the local administration of rbFGF seems to offer an alternative simplified one-stage procedure for the temporary management of TEF combined with complex PTTS in non-surgical candidates.
Organomineral fertilizer application enhances Perilla frutescens nutritional quality and rhizosphere microbial community stability in karst mountain soils
Authors: Li Ying , Shen Qi , An Xiaochi , Xie Yuanhuan , Liu Xiuming , Lian Bin 
Published: November 2022

IntroductionApplications of organomineral fertilizer (OMF) are important measures for developing organic agriculture in karst mountain areas. However, the influence of OMF on the structure and function of soil microbial diversity and their relationship with crop yield and quality are still unclear.MethodsBased on soil science, crop science, and high-throughput sequencing methods, we investigated the changes of rhizosphere soil microbial communities of Perilla frutescens under different fertilization measures. Then, the relationship between P. frutescens yield and quality with soil quality was analyzed.ResultsThe results showed that the addition of OMF increased the amount of total carbon and total potassium in soil. OF, especially OMF, improved P. frutescens yield and quality (e.g., panicle number per plant, main panicle length, and unsaturated fatty acid contents). Both OF and OMF treatments significantly increased the enrichment of beneficial microorganism (e.g., Bacillus, Actinomadura, Candidatus_Solibacter, Iamia, Pseudallescheria, and Cladorrhinum). The symbiotic network analysis demonstrated that OMF strengthened the connection among the soil microbial communities, and the community composition became more stable. Redundancy analysis and structural equation modeling showed that the soil pH, available phosphorus, and available potassium were significantly correlated with soil microbial community diversity and P. frutescens yield and quality.DiscussionOur study confirmed that OMF could replace CF or common OF to improve soil fertility, crop yield and quality in karst mountain soils.
Structural characterization and conformational dynamics of alpha-1 antitrypsin pathogenic variants causing alpha-1-antitrypsin deficiency
Authors: Shaik Noor Ahmad , Saud Al-Saud Najla Bint , Abdulhamid Aljuhani Thamer , Jamil Kaiser , Alnuman Huda , Aljeaid Deema , Sultana Nasreen , El-Harouni Ashraf AbdulRahman , Awan Zuhier Ahmed , Elango Ramu , Banaganapalli Babajan 
Published: November 2022

Background: Alpha-1 antitrypsin deficiency (A1ATD) is a progressive lung disease caused by inherited pathogenic variants in the SERPINA1 gene. However, their actual role in maintenance of structural and functional characteristics of the corresponding α-1 anti-trypsin (A1AT) protein is not well characterized.Methods: The A1ATD causative SERPINA1 missense variants were initially collected from variant databases, and they were filtered based on their pathogenicity potential. Then, the tertiary protein models were constructed and the impact of individual variants on secondary structure, stability, protein-protein interactions, and molecular dynamic (MD) features of the A1AT protein was studied using diverse computational methods.Results: We identified that A1ATD linked SERPINA1 missense variants like F76S, S77F, L278P, E288V, G216C, and H358R are highly deleterious as per the consensual prediction scores of SIFT, PolyPhen, FATHMM, M-CAP and REVEL computational methods. All these variants were predicted to alter free energy dynamics and destabilize the A1AT protein. These variants were seen to cause minor structural drifts at residue level (RMSD = &lt;2Å) of the protein. Interestingly, S77F and L278P variants subtly alter the size of secondary structural elements like beta pleated sheets and loops. The residue level fluctuations at 100 ns simulation confirm the highly damaging structural consequences of all the six missense variants on the conformation dynamics of the A1AT protein. Moreover, these variants were also predicted to cause functional deformities by negatively impacting the binding energy of A1AT protein with NE ligand molecule.Conclusion: This study adds a new computational biology dimension to interpret the genotype-protein phenotype relationship between SERPINA1 pathogenic variants with its structural plasticity and functional behavior with NE ligand molecule contributing to the Alpha-1-antitrypsin deficiency. Our results support that A1ATD complications correlates with the conformational flexibility and its propensity of A1AT protein polymerization when misfolded.
Normal left atrial diameter is associated with better performance on a cognitive screener among a cohort of ischemic stroke patients
Authors: Gootee Emma , Stein Colin , Walker Alex , Daneshvari Nicholas O. , Blaha Michael J. , Lima Joao A. C. , Gottesman Rebecca F. , Johansen Michelle C. 
Published: November 2022

BackgroundCardiac structure is an important determinant of ischemic stroke (IS) etiology; however, whether an association between cardiac structural markers and cognition post-IS exists is not yet established. The aim of this study is to examine the association between LAD and LVEF with cognitive performance among IS patients.MethodsIS patients admitted to the Johns Hopkins Hospital (2017–2019) underwent transthoracic echocardiography. IS was classified (TOAST) by a masked reviewer. Left atrial diameter (LAD) was evaluated as a non-linear continuous variable with one spline knot at 4 cm; left ventricle ejection fraction (LVEF) was dichotomized, then further evaluated as a non-linear continuous variable with spline knots at 50% and 70%. Patients were contacted by telephone on average 422 days post-stroke and administered the Six-Item Screener (SIS) to assess for dementia. SIS scores were dichotomized into low and high, imputing low scores for non-answerers. Multivariable logistic regression determined the association of SIS category with LAD or LVEF. A sensitivity analysis re-evaluated the association between SIS category and LAD, excluding participants with atrial fibrillation (AF).ResultsParticipants (N = 108) were on average 61 years old (range = 18–89 years), 55% male, and 63% Black. Among patients considered to have a normal LAD (≤ 4 cm), a 1 mm larger LAD was associated with 1.20 greater odds (95%CI = 1.05–1.38) of scoring in the high SIS category in the final adjustment model. This association remained significant when excluding participants with prevalent AF. There was no association between a 1 mm larger LAD and SIS category among patients with a LAD &gt;4 cm in both the primary analysis and the sensitivity analysis. There was no association between LVEF and SIS category.ConclusionsIn this prospective study, among ischemic stroke patients with a LAD within the normal range, a 1 mm increase in LAD was associated with higher scores on a telephone cognitive battery, without an association found among those with a LAD &gt;4 cm.
The accumulation of muscle RING finger-1 in regenerating myofibers: Implications for muscle repair in immune-mediated necrotizing myopathy
Authors: Yang Meng-Ge , Zhang Qing , Wang Hong , Ma Xue , Ji Suqiong , Li Yue , Xu Li , Bi Zhuajin , Bu Bitao 
Published: November 2022

BackgroundMuscle RING finger-1 (MuRF-1) plays a key role in the degradation of skeletal muscle proteins. We hypothesize the involvement of MuRF-1 in immune-mediated necrotizing myopathy (IMNM).MethodsMuscle biopsies from patients with IMNM (n = 37) were analyzed and compared to biopsies from patients with dermatomyositis (DM, n = 13), dysferlinopathy (n = 9) and controls (n = 7) using immunostaining.ResultsMuRF-1 staining could be observed in IMNM, DM and dysferlinopathy biopsies, whereas the percentage of MuRF-1 positive myofibers was significantly higher in IMNM than in dysferlinopathy (p = 0.0448), and positively correlated with muscle weakness and disease activity in IMNM and DM. Surprisingly, MuRF-1 staining predominantly presented in regenerating fibers but not in atrophic fibers. Moreover, MuRF-1-positive fibers tended to be distributed around necrotic myofibers and myofibers with sarcolemma membrane attack complex deposition. Abundant MuRF-1 expression in IMNM and DM was associated with rapid activation of myogenesis after muscle injury, whereas relatively low expression of MuRF-1 in dysferlinopathy may be attributed to damaged muscle regeneration.ConclusionsMuRF-1 accumulated in regenerating myofibers, which may contribute to muscle injury repair in IMNM and DM. MuRF-1 staining may help clinicians differentiate IMNM and dysferlinopathy.
A novel nomogram model for clinical outcomes of severe subarachnoid hemorrhage patients
Authors: Huang Han-Yu , Yuan Bin , Chen Shu-Juan , Han Yan-ling , Zhang Xin , Yu Qing , Wu Qi 
Published: November 2022

BackgroundSystemic responses, especially inflammatory responses, after aneurysmal subarachnoid hemorrhage (SAH) are closely related to clinical outcomes. Our study aimed to explore the correlation between the systemic responses in the acute stage and the mid-term outcomes of severe SAH patients (Hunt-Hess grade III-V).Materials and methodsSevere SAH patients admitted to Jinling Hospital from January 2015 to December 2019 were retrospectively analyzed in the study. The univariate and multivariate logistic regression analyses were used to explore the risk factors of 6-month clinical outcomes in severe SAH patients. A predictive model was established based on those risk factors and was visualized by a nomogram. Then, the predictive nomogram model was validated in another severe SAH patient cohort from January 2020 to January 2022.ResultsA total of 194 patients were enrolled in this study. 123 (63.4%, 123 of 194) patients achieved good clinical outcomes at the 6-month follow-up. Univariate and multivariate logistic regression analysis revealed that age, Hunt-Hess grade, neutrophil-to-lymphocyte ratio (NLR), and complications not related to operations were independent risk factors for unfavorable outcomes at 6-month follow-up. The areas under the curve (AUC) analysis showed that the predictive model based on the above four variables was significantly better than the Hunt-Hess grade (0.812 vs. 0.685, P = 0.013). In the validation cohort with 44 severe SAH patients from three different clinical centers, the AUC of the prognostic nomogram model was 0.893.ConclusionThe predictive nomogram model could be a reliable predictive tool for the outcome of severe SAH patients. Systemic inflammatory responses after SAH and complications not related to operations, especially hydrocephalus, delayed cerebral ischemia, and pneumonia, might be the important risk factors that lead to poor outcomes in severe SAH patients.
Clinical features and therapeutic outcomes of alveolar soft part sarcoma in children: A single-center, retrospective study
Authors: Tan Zhichao , Liu Jiayong , Xue Ruifeng , Fan Zhengfu , Bai Chujie , Li Shu , Gao Tian , Zhang Lu , Wang Xinyu 
Published: November 2022

BackgroundAlveolar soft part sarcoma (ASPS) is a rare sarcoma that has been shown to be highly effective to antiangiogenic agents and immune checkpoint inhibitors, but most reported studies about ASPS were concentrated on adult population. In this study, we aimed to describe the clinical features and therapeutic outcomes of ASPS in children.MethodsWe retrospectively reviewed the records of patients with ASPS in our institution since Jan 2015. All patients included in this study were pathologically confirmed ASPS and aged under 12 years at the time of initial diagnosis. Demographic characteristics, tumor sizes, primary tumor sites, metastasis, treatments used, therapeutic responses and survivals were evaluated.ResultsWe identified a total of 56 patients to be initially diagnosed as ASPS since Jan 2015. A predisposition of high occurrence in head and neck (32.1%) was observed (versus 41.1% in limbs and 21.4% in trunk). 26 (46.4%) patients developed metastasis at the time of diagnosis or during follow-up. Tumors in tongue, pharynx and larynx had the least likelihood to metastasize (7.7%, P&lt;0.05). Observation was recommended for 15 stage IV patients with only pulmonary metastasis. 7 (46.7%) patients remained stable until last follow up. The 1-year PFS rate was 83.3% and median progression-free survival time (PFS) was 29.4 months. 15 patients with progressive disease received mono or combined therapy. 11 patients received PD-1 monotherapy. 2 patients achieved partial response and 5 stable disease. The overall response rate was 18.2%. The median PFS of this group was 22.0 months, and the 1-year PFS rate was 70.0%. 4 patients received a combination therapy of PD-1 inhibitors plus tyrosine kinase inhibitors. All of them remained stable. No disease-related death occurred during follow-up.ConclusionsASPS exhibits a higher occurrence in head and neck in children. ASPS originating from glossopharyngeal region tends to have a lower metastasis rate. ASPS displays a more indolent growth pattern in children, which makes observation a preferable choice for children with sole pulmonary metastasis. Pediatric ASPS appears to be less effective to targeted therapy and immunotherapy than adults. The treatment of progressive ASPS in children remains challenging.
Are contrast enhanced mammography and digital breast tomosynthesis equally effective in diagnosing patients recalled from breast cancer screening?
Authors: Siminiak Natalia , Pasiuk-Czepczyńska Anna , Godlewska Antonina , Wojtyś Piotr , Olejnik Magdalena , Michalak Joanna , Nowaczyk Piotr , Gajdzis Paweł , Godlewski Dariusz , Ruchała Marek , Czepczyński Rafał 
Published: November 2022

PurposeFull-field digital mammography (FFDM) is widely used in breast cancer screening. However, to improve cancer detection rates, new diagnostic tools have been introduced. Contrast enhanced mammography (CEM) and digital breast tomosynthesis (DBT) are used in the diagnostic setting, however their accuracies need to be compared.The aim of the study was to evaluate the diagnostic performance of CEM and DBT in women recalled from breast cancer screening program.MethodsThe study included 402 consecutive patients recalled from breast cancer screening program, who were randomized into two groups, to undergo either CEM (202 patients) or DBT (200 patients). All visible lesions were evaluated and each suspicious lesion was histopathologically verified.ResultsCEM detected 230 lesions; 119 were classified as benign and 111 as suspicious or malignant, whereas DBT identified 209 lesions; 105 were classified as benign and 104 as suspicious or malignant. In comparison to histopathology, CEM correctly detected cancer in 43 out of 44 cases, and DBT in all 33 cases, while FFDM identified 15 and 18 neoplastic lesions in two groups, respectively. CEM presented with 97% sensitivity, 63% specificity, 70% accuracy, 38% PPV and 99% NPV, while DBT showed 100% sensitivity, 60% specificity, 32%, PPV, 100% NPV and 66% accuracy. The CEM’s AUC was 0.97 and DBT’s 0.99. The ROC curve analysis proved a significant (p&lt;0.000001) advantage of both CEM and DBT over FFDM, however, there was no significant difference between CEM and DBT diagnostic accuracies (p=0.23).ConclusionsIn this randomized, prospective study CEM and DBT show similar diagnostic accuracy.