bluuebunny/crossref_metadata_2025 huggingface dataset:
Co-occurring pathogenic variants in 6q27 associated with dementia spectrum disorders in a Peruvian family
Authors: Alvarez Karla Lucia F. , Aguilar-Pineda Jorge Alberto , Ortiz-Manrique Michelle M. , Paredes-Calderon Marluve F. , Cardenas-Quispe Bryan C. , Vera-Lopez Karin Jannet , Goyzueta-Mamani Luis D. , Chavez-Fumagalli Miguel Angel , Davila-Del-Carpio Gonzalo , Peralta-Mestas Antero , Musolino Patricia L. , Lino Cardenas Christian Lacks
Published: February 2023

Evidence suggests that there may be racial differences in risk factors associated with the development of Alzheimer’s disease and related dementia (ADRD). We used whole-genome sequencing analysis and identified a novel combination of three pathogenic variants in the heterozygous state (UNC93A: rs7739897 and WDR27: rs61740334; rs3800544) in a Peruvian family with a strong clinical history of ADRD. Notably, the combination of these variants was present in two generations of affected individuals but absent in healthy members of the family. In silico and in vitro studies have provided insights into the pathogenicity of these variants. These studies predict that the loss of function of the mutant UNC93A and WDR27 proteins induced dramatic changes in the global transcriptomic signature of brain cells, including neurons, astrocytes, and especially pericytes and vascular smooth muscle cells, indicating that the combination of these three variants may affect the neurovascular unit. In addition, known key molecular pathways associated with dementia spectrum disorders were enriched in brain cells with low levels of UNC93A and WDR27. Our findings have thus identified a genetic risk factor for familial dementia in a Peruvian family with an Amerindian ancestral background.
Regional citrate anticoagulation for replacement therapy in patients with liver failure: A systematic review and meta-analysis
Authors: Peng Bo , Lu Jiaqi , Guo Hebing , Liu Jingyuan , Li Ang
Published: February 2023

Background

Citrate refers to an anticoagulant agent commonly used in extracorporeal organ support. Its application is limited in patients with liver failure (LF) due to the increased risk of citrate accumulation induced by liver metabolic dysfunction. This systematic review aims to assess the efficacy and safety of regional citrate anticoagulation in extracorporeal circulation for patients with liver failure.

Methods

PubMed, Web of Science, Embase, and Cochrane Library were searched. Studies regarding extracorporeal organ support therapy for LF were included to assess the efficacy and safety of regional citrate anticoagulation. Methodological quality of included studies were assessed using the Methodological Index for Non-randomized Studies (MINORS). Meta-analysis was performed using R software (version 4.2.0).

Results

There were 19 eligible studies included, involving 1026 participants. Random-effect model showed an in-hospital mortality of 42.2% [95%CI (27.2, 57.9)] in LF patients receiving extracorporeal organ support. The during-treatment incidence of filter coagulation, citrate accumulation, and bleeding were 4.4% [95%CI (1.6-8.3)], 6.7% [95%CI (1.5-14.4)], and 5.0% [95%CI (1.9-9.3)], respectively. The total bilirubin(TBIL), alanine transaminase (ALT), aspartate transaminase(AST), serum creatinine(SCr), blood urea nitrogen(BUN), and lactate(LA) decreased, compared with those before the treatment, and the total calcium/ionized calcium ratio, platelet(PLT), activated partial thromboplastin time(APTT), serum potential of hydrogen(pH), buffer base(BB), and base excess(BE) increased.

Conclusion

Regional citrate anticoagulation might be effective and safe in LF extracorporeal organ support. Closely monitoring and timely adjusting during the process could reduce the risk for complications. More prospective clinical trials of considerable quality are needed to further support our findings.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022337767.
The prognostic nutritional index represents a novel inflammation-nutrition-based prognostic factor for nasopharyngeal carcinoma
Authors: Jiang Yan-Ming , Huang Shi-Ting , Pan Xin-Bin , Ma Jia-Lin , Zhu Xiao-Dong
Published: February 2023

Purpose

This study explored the relationship between the prognostic nutritional index (PNI) and overall survival rate (OS) in patients with nasopharyngeal carcinoma (NPC), and established and validated an effective nomogram to predict clinical outcomes.

Methods

This study included 618 patients newly diagnosed with locoregionally advanced NPC. They were divided into training and validation cohorts at a ratio of 2:1 based on random numbers. The primary endpoint of this study was OS, progression-free survival (PFS) was the second endpoint. A nomogram was drawn from the results of multivariate analyses. Harrell’s concordance index (C-index), area under the receiver operator characteristic curve (AUC), and decision curve analysis (DCA) were used to evaluate the clinical usefulness and predictive ability of the nomogram and were compared to the current 8th edition of the International Union Against Cancer/American Joint Committee (UICC/AJCC) staging system.

Results

The PNI cutoff value was 48.1. Univariate analysis revealed that age (p < 0.001), T stage (p < 0.001), N stage (p = 0.036), tumor stage (p < 0.001), PNI (p = 0.001), lymphocyte-neutrophil ratio (NLR, p = 0.002), and lactate dehydrogenase (LDH, p = 0.009) were significantly associated with OS, age (p = 0.001), T-stage (p < 0.001), tumor stage (p < 0.001), N-stage (p = 0.011), PNI (p = 0.003), NLR (p = 0.051), and LDH (p = 0.03) were significantly associated with PFS. Multivariate analysis showed that age (p < 0.001), T-stage (p < 0.001), N-stage(p = 0.02), LDH (p = 0.032), and PNI (p = 0.006) were significantly associated with OS, age (p = 0.004), T-stage (<0.001), N-stage (<0.001), PNI (p = 0.022) were significantly associated with PFS. The C-index of the nomogram was 0.702 (95% confidence interval [CI]: 0.653–0.751). The Akaike information criterion (AIC) value of the nomogram for OS was 1142.538. The C-index of the TNM staging system was 0.647 (95% CI, 0.594–0.70) and the AIC was 1163.698. The C-index, DCA, and AUC of the nomogram demonstrated its clinical value and higher overall net benefit compared to the 8th edition of the TNM staging system.

Conclusion

The PNI represents a new inflammation-nutrition-based prognostic factor for patients with NPC. In the proposed nomogram, PNI and LDH were present, which led to a more accurate prognostic prediction than the current staging system for patients with NPC.
Differential metabolites in cirrhotic patients with hepatitis B and muscle mass loss
Authors: Liu Xuechun , Han Lei , Bi Shenghua , Ding Xueli , Sheng Qi , Jiang Yueping , Guan Ge , Niu Qinghui , Jing Xue
Published: February 2023

Background

Sarcopenia leads to complications (infections, hepatic encephalopathy and ascites) and poor overall survival in patients with cirrhosis, in which the phenotypic presentation is loss of muscle mass. This study aimed to reveal the metabolic profile and identify potential biomarkers in cirrhotic patients with hepatitis B virus and muscle mass loss.

Method

Twenty decompensated cirrhotic patients with HBV and muscle mass loss were designated Group S; 20 decompensated cirrhotic patients with HBV and normal muscle mass were designated Group NS; and 20 healthy people were designated Group H. Muscle mass loss was defined as the skeletal muscle mass index less than 46.96 cm2/m2 for males and less than 32.46 cm2/m2 for females. Gas chromatography–mass spectrometry was used to explore the distinct metabolites and pathways in the three groups.

Results

Thirty-seven metabolic products and 25 associated metabolic pathways were significantly different in the Group S patients from Group NS patients. Strong predictive value of 11 metabolites (inosine-5′-monophosphate, phosphoglycolic acid, D-fructose-6-phosphate, N-acetylglutamate, pyrophosphate, trehalose-6-phosphate, fumaric acid, citrulline, creatinine, (r)-3-hydroxybutyric acid, and 2-ketobutyric acid) were selected as potential biomarkers in Group S patients compared with Group NS patients. Two pathways may be associated with loss of muscle mass in patients with liver cirrhosis: amino acid metabolism and central carbon metabolism in cancer.

Conclusion

Seventy differential metabolites were identified in patients who have liver cirrhosis and loss of muscle mass compared with patients who have cirrhosis and normal muscle mass. Certain biomarkers might distinguish between muscle mass loss and normal muscle mass in HBV-related cirrhosis patients.
Effect of sodium bicarbonate on the physicochemical properties of fermented rice flour and quality characteristics of fermented semi-dried rice noodles
Authors: Xiao Wen , Ding Yuqin , Cheng Ying , Xu Sili , Lin Lizhong
Published: February 2023

Considering the effect that fermentation can improve the quality of rice noodles, and given that fermented rice noodles usually have a significantly acidic taste that is not generally acceptable to consumers, this study aimed to neutralize or eliminate the acidic taste of fermented rice noodles by adding sodium bicarbonate, and improve the quality of fermented rice noodles. The physicochemical properties of fermented rice flour and quality characteristics of fermented semi-dried rice noodles were investigated in this study in relation to the addition of sodium bicarbonate (0∼0.5%, w/w). With the increase of sodium bicarbonate addition, the pH value was increased, and lipid and protein content were decreased in rice flour. Meanwhile, thermal properties and farinograph properties showed that the pasting temperature, dough water absorption, dough development time and dough stability time of rice flour increased with the addition of sodium bicarbonate. Pasting properties and rheological properties results showed that a small amount of sodium bicarbonate (0∼0.1%) could increase the pasting viscosity, storage modulus (G’), and loss modulus (G″) of rice flour. Additionally, the hardness and chewiness of semi-dried rice noodles increased with the addition of sodium bicarbonate from 0 to 0.1%. With the addition of a small amount of sodium bicarbonate (0∼0.1%), x-ray diffraction showed that it could increase the crystallinity of semi-dried rice noodles. Low-field nuclear magnetic resonance showed that A21 increased, and A22 and A23 decreased in semi-dried rice noodles. Scanning electron microscope showed that it could enhance the starch-protein interaction and starch-protein formed an ordered and stable network structure. Finally, the principal component analysis showed that the chewiness, texture and eating quality of semi-dried rice noodles were the best with the addition of sodium bicarbonate at 0.1%. This study provides practical value for the application of alkali treatment in rice products and provides a reference for the improvement of related rice noodles products.
The immunotherapy advancement targeting malignant blastomas in early childhood
Authors: Zang Bolun , Ding Luyue , Liu Linlin , Arun Kumar Senthil , Liu Wei , Zhou Chongchen , Duan Yongtao
Published: February 2023

Malignant blastomas develop relentlessly in all functional body organs inflicting severe health ailments in younger children. Malignant blastomas exhibit diverse clinical characteristics in compliance with their emergence in functional body organs. Surprisingly, neither of these preferred treatment types (surgery, radiotherapy, and chemotherapy) showed promise or were effective in treating malignant blastomas among child patients. N ew, innovative immunotherapeutic procedures including monoclonal antibodies and chimeric-antigen based receptor (CAR) cell therapy, coupled with the clinical study of reliable therapeutic targets and immune regulatory pathways targeting malignant blastomas, have attracted the attention of clinicians recently.
Serum cytokine levels and other associated factors as possible immunotherapeutic targets and prognostic indicators for lung cancer
Authors: Zhao Yinghao , Jia Shengnan , Zhang Kun , Zhang Lian
Published: February 2023

Lung cancer is one of the most prevalent cancer types and the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all cancer incidences. Lung cancer therapy and prognosis largely depend on the disease’s degree at the diagnosis time. Cytokines are soluble polypeptides that contribute to cell-to-cell communication, acting paracrine or autocrine on neighboring or distant cells. Cytokines are essential for developing neoplastic growth, but they are also known to operate as biological inducers following cancer therapy. Early indications are that inflammatory cytokines such as IL-6 and IL-8 play a predictive role in lung cancer. Nevertheless, the biological significance of cytokine levels in lung cancer has not yet been investigated. This review aimed to assess the existing literature on serum cytokine levels and additional factors as potential immunotherapeutic targets and lung cancer prognostic indicators. Changes in serum cytokine levels have been identified as immunological biomarkers for lung cancer and predict the effectiveness of targeted immunotherapy.
Perioperative oncolytic virotherapy to counteract surgery-induced immunosuppression and improve outcomes in pancreatic ductal adenocarcinoma
Authors: Mansouri Sarah , Daniel Lauren , Amhis Nawal , Leveille Maxime , Boudreau Jeanette E. , Alkayyal Almohanad A. , Collin Yves , Tai Lee-Hwa
Published: February 2023

Pancreatic ductal adenocarcinoma (PDAC) is a high fatality cancer with one of the worst prognoses in solid tumors. Most patients present with late stage, metastatic disease and are not eligible for potentially curative surgery. Despite complete resection, the majority of surgical patients will recur within the first two years following surgery. Postoperative immunosuppression has been described in different digestive cancers. While the underlying mechanism is not fully understood, there is compelling evidence to link surgery with disease progression and cancer metastasis in the postoperative period. However, the idea of surgery-induced immunosuppression as a facilitator of recurrence and metastatic spread has not been explored in the context of pancreatic cancer. By surveying the existing literature on surgical stress in mostly digestive cancers, we propose a novel practice-changing paradigm: alleviate surgery-induced immunosuppression and improve oncological outcome in PDAC surgical patients by administering oncolytic virotherapy in the perioperative period.
Recurrence risk stratification for locally advanced cervical cancer using multi-modality transformer network
Authors: Wang Jian , Mao Yixiao , Gao Xinna , Zhang Yu
Published: February 2023

Objectives

Recurrence risk evaluation is clinically significant for patients with locally advanced cervical cancer (LACC). We investigated the ability of transformer network in recurrence risk stratification of LACC based on computed tomography (CT) and magnetic resonance (MR) images.

Methods

A total of 104 patients with pathologically diagnosed LACC between July 2017 and December 2021 were enrolled in this study. All patients underwent CT and MR scanning, and their recurrence status was identified by the biopsy. We randomly divided patients into training cohort (48 cases, non-recurrence: recurrence = 37: 11), validation cohort (21 cases, non-recurrence: recurrence = 16: 5), and testing cohort (35 cases, non-recurrence: recurrence = 27: 8), upon which we extracted 1989, 882 and 315 patches for model's development, validation and evaluation, respectively. The transformer network consisted of three modality fusion modules to extract multi-modality and multi-scale information, and a fully-connected module to perform recurrence risk prediction. The model's prediction performance was assessed by six metrics, including the area under the receiver operating characteristic curve (AUC), accuracy, f1-score, sensitivity, specificity and precision. Univariate analysis with F-test and T-test were conducted for statistical analysis.

Results

The proposed transformer network is superior to conventional radiomics methods and other deep learning networks in both training, validation and testing cohorts. Particularly, in testing cohort, the transformer network achieved the highest AUC of 0.819 ± 0.038, while four conventional radiomics methods and two deep learning networks got the AUCs of 0.680 ± 0.050, 0.720 ± 0.068, 0.777 ± 0.048, 0.691 ± 0.103, 0.743 ± 0.022 and 0.733 ± 0.027, respectively.

Conclusions

The multi-modality transformer network showed promising performance in recurrence risk stratification of LACC and may be used as an effective tool to help clinicians make clinical decisions.
Nonfunctional ectopic adrenocortical carcinoma in the lung: A case report and literature review
Authors: Nie Limin , Wang Shuyun , Feng Zongfeng , Sun Yuping , Wang Zhen , Dang Qi , Gao Aiqin , Lv Yajuan
Published: February 2023

Background

Ectopic adrenocortical tissues and neoplasms are rare and usually found in the genitourinary system and abdominal cavity. The thorax is an extremely rare ectopic site. Here, we report the first case of nonfunctional ectopic adrenocortical carcinoma (ACC) in the lung.

Case presentation

A 71-year-old Chinese man presented with vague left-sided chest pain and irritable cough for 1 month. Thoracic computed tomography revealed a heterogeneously enhancing 5.3 × 5.8 × 6.0-cm solitary mass in the left lung. Radiological findings suggested a benign tumor. The tumor was surgically excised upon detection. Histopathological examination using hematoxylin and eosin staining showed that the cytoplasm of the tumor cells was rich and eosinophilic. Immunohistochemical profiles (inhibin-a+, melan-A+, Syn+) indicated that the tumor had an adrenocortical origin. The patient showed no symptoms of hormonal hypersecretion. The final pathological diagnosis was non-functional ectopic ACC. The patient was disease-free for 22 months and is still under follow-up.

Conclusions

Nonfunctional ectopic ACC in the lung is an extremely rare neoplasm that can be easily misdiagnosed as primary lung cancer or lung metastasis, both preoperatively and on postoperative pathological examination. This report may provide clues to clinicians and pathologists regarding the diagnosis and treatment of nonfunctional ectopic ACC.
Organoid drug screening report for a non-small cell lung cancer patient with EGFR gene mutation negativity: A case report and review of the literature
Authors: Pan Yuetian , Cui Hongshang , Song Yongbin
Published: February 2023

Patients with non-small cell lung cancer (NSCLC) who carry epidermal growth factor receptor (EGFR) mutations can benefit significantly from EGFR tyrosine kinase inhibitors (EGFR TKIs). However, it is unclear whether patients without EGFR mutations cannot benefit from these drugs. Patient-derived tumor organoids (PDOs) are reliable in vitro tumor models that can be used in drug screening. In this paper, we report an Asian female NSCLC patient without EGFR mutation. Her tumor biopsy specimen was used to establish PDOs. The treatment effect was significantly improved by anti-tumor therapy guided by organoid drug screening.
Molecular features and predictive models identify the most lethal subtype and a therapeutic target for osteosarcoma
Authors: Zheng Kun , Hou Yushan , Zhang Yiming , Wang Fei , Sun Aihua , Yang Dong
Published: February 2023

Background

Osteosarcoma is the most common primary malignant bone tumor. The existing treatment regimens remained essentially unchanged over the past 30 years; hence the prognosis has plateaued at a poor level. Precise and personalized therapy is yet to be exploited.

Methods

One discovery cohort (n=98) and two validation cohorts (n=53 & n=48) were collected from public data sources. We performed a non-negative matrix factorization (NMF) method on the discovery cohort to stratify osteosarcoma. Survival analysis and transcriptomic profiling characterized each subtype. Then, a drug target was screened based on subtypes’ features and hazard ratios. We also used specific siRNAs and added a cholesterol pathway inhibitor to osteosarcoma cell lines (U2OS and Saos-2) to verify the target. Moreover, PermFIT and ProMS, two support vector machine (SVM) tools, and the least absolute shrinkage and selection operator (LASSO) method, were employed to establish predictive models.

Results

We herein divided osteosarcoma patients into four subtypes (S-I ~ S-IV). Patients of S- I were found probable to live longer. S-II was characterized by the highest immune infiltration. Cancer cells proliferated most in S-III. Notably, S-IV held the most unfavorable outcome and active cholesterol metabolism. SQLE, a rate-limiting enzyme for cholesterol biosynthesis, was identified as a potential drug target for S-IV patients. This finding was further validated in two external independent osteosarcoma cohorts. The function of SQLE to promote proliferation and migration was confirmed by cell phenotypic assays after the specific gene knockdown or addition of terbinafine, an inhibitor of SQLE. We further employed two machine learning tools based on SVM algorithms to develop a subtype diagnostic model and used the LASSO method to establish a 4-gene model for predicting prognosis. These two models were also verified in a validation cohort.

Conclusion

The molecular classification enhanced our understanding of osteosarcoma; the novel predicting models served as robust prognostic biomarkers; the therapeutic target SQLE opened a new way for treatment. Our results served as valuable hints for future biological studies and clinical trials of osteosarcoma.
Deep learning for automatic head and neck lymph node level delineation provides expert-level accuracy
Authors: Weissmann Thomas , Huang Yixing , Fischer Stefan , Roesch Johannes , Mansoorian Sina , Ayala Gaona Horacio , Gostian Antoniu-Oreste , Hecht Markus , Lettmaier Sebastian , Deloch Lisa , Frey Benjamin , Gaipl Udo S. , Distel Luitpold Valentin , Maier Andreas , Iro Heinrich , Semrau Sabine , Bert Christoph , Fietkau Rainer , Putz Florian
Published: February 2023

Background

Deep learning-based head and neck lymph node level (HN_LNL) autodelineation is of high relevance to radiotherapy research and clinical treatment planning but still underinvestigated in academic literature. In particular, there is no publicly available open-source solution for large-scale autosegmentation of HN_LNL in the research setting.

Methods

An expert-delineated cohort of 35 planning CTs was used for training of an nnU-net 3D-fullres/2D-ensemble model for autosegmentation of 20 different HN_LNL. A second cohort acquired at the same institution later in time served as the test set (n = 20). In a completely blinded evaluation, 3 clinical experts rated the quality of deep learning autosegmentations in a head-to-head comparison with expert-created contours. For a subgroup of 10 cases, intraobserver variability was compared to the average deep learning autosegmentation accuracy on the original and recontoured set of expert segmentations. A postprocessing step to adjust craniocaudal boundaries of level autosegmentations to the CT slice plane was introduced and the effect of autocontour consistency with CT slice plane orientation on geometric accuracy and expert rating was investigated.

Results

Blinded expert ratings for deep learning segmentations and expert-created contours were not significantly different. Deep learning segmentations with slice plane adjustment were rated numerically higher (mean, 81.0 vs. 79.6, p = 0.185) and deep learning segmentations without slice plane adjustment were rated numerically lower (77.2 vs. 79.6, p = 0.167) than manually drawn contours. In a head-to-head comparison, deep learning segmentations with CT slice plane adjustment were rated significantly better than deep learning contours without slice plane adjustment (81.0 vs. 77.2, p = 0.004). Geometric accuracy of deep learning segmentations was not different from intraobserver variability (mean Dice per level, 0.76 vs. 0.77, p = 0.307). Clinical significance of contour consistency with CT slice plane orientation was not represented by geometric accuracy metrics (volumetric Dice, 0.78 vs. 0.78, p = 0.703).

Conclusions

We show that a nnU-net 3D-fullres/2D-ensemble model can be used for highly accurate autodelineation of HN_LNL using only a limited training dataset that is ideally suited for large-scale standardized autodelineation of HN_LNL in the research setting. Geometric accuracy metrics are only an imperfect surrogate for blinded expert rating.
Unmanipulated haploidentical hematopoietic stem cell transplantation for pediatric de novo acute megakaryoblastic leukemia without Down syndrome in China: A single-center study
Authors: Huang Junbin , Hu Guanhua , Suo Pan , Bai Lu , Cheng Yifei , Wang Yu , Zhang XiaoHui , Liu KaiYan , Sun YuQian , Xu LanPing , Kong Jun , Yan ChenHua , Huang Xiaojun
Published: February 2023

Background

AMKL without DS is a rare but aggressive hematological malignant disease in children, and it is associated with inferior outcomes. Several researchers have regarded pediatric AMKL without DS as high-risk or at least intermediate-risk AML and proposed that upfront allogenic hematopoietic stem cell transplantation (HSCT) in first complete remission might improve long-term survival.

Patients and method

We conducted a retrospective study with twenty-five pediatric (< 14 years old) AMKL patients without DS who underwent haploidentical HSCT in the Peking University Institute of Hematology, Peking University People’s Hospital from July 2016 to July 2021. The diagnostic criteria of AMKL without DS were adapted from the FAB and WHO: ≥ 20% blasts in the bone marrow, and those blasts expressed at least one or more of the platelet glycoproteins: CD41, CD61, or CD42. AMKL with DS and therapy related AML was excluded. Children without a suitable closely HLA-matched related or unrelated donor (donors with more than nine out of 10 matching HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ loci), were eligible to receive haploidentical HSCT. Definition was adapted from international cooperation group. All statistical tests were conducted with SPSS v.24 and R v.3.6.3.

Results

The 2-year OS was 54.5 ± 10.3%, and the EFS was 50.9 ± 10.2% in pediatric AMKL without DS undergoing haplo-HSCT. Statistically significantly better EFS was observed in patients with trisomy 19 than in patients without trisomy 19 (80 ± 12.6% and 33.3 ± 12.2%, respectively, P = 0.045), and OS was better in patients with trisomy 19 but with no statistical significance (P = 0.114). MRD negative pre-HSCT patients showed a better OS and EFS than those who were positive (P < 0.001 and P = 0.003, respectively). Eleven patients relapsed post HSCT. The median time to relapse post HSCT was 2.1 months (range: 1.0–14.4 months). The 2-year cumulative incidence of relapse (CIR) was 46.1 ± 11.6%. One patient developed bronchiolitis obliterans and respiratory failure and died at d + 98 post HSCT.

Conclusion

AMKL without DS is a rare but aggressive hematological malignant disease in children, and it is associated with inferior outcomes. Trisomy 19 and MRD negative pre-HSCT might contribute to a better EFS and OS. Our TRM was low, haplo-HSCT might be an option for high-risk AMKL without DS.
Prognostic value of prognostic nutritional index score and controlling nutritional status score in patients with glioblastoma: A comprehensive meta-analysis
Authors: Peng Jie , Li Xiaoyu , Huang Mingsheng , Ma Mincai , Huang Qin , Huang Ning , Cheng Yuan
Published: February 2023

Introduction

Several nutritional indicators, including the prognostic nutritional index (PNI) score and the controlling nutritional status (CONUT) score, have been shown to predict the prognosis of patients with glioblastoma. The present meta-analysis was performed to further evaluate the prognostic value of PNI and CONUT scores in patients with glioblastoma.

Method

The PubMed, EMBASE and Web of Science databases were comprehensively searched for studies that evaluated the ability of PNI and CONUT scores to predict the prognosis of patients with glioblastoma. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated by univariate and multivariate analyses.

Result

Ten articles were included in this meta-analysis, involving 1406 patients with glioblastoma. Univariate analyses showed that a high PNI score was predictive of greater overall survival (OS; HR 0.50; 95% CI, 0.43, 0.58; I2 = 0%) and progression free survival (PFS; HR 0.63; 95% CI, 0.50, 0.79; I2 = 0%), whereas a low CONUT score predictive of longer OS (HR 2.39; 95% CI, 1.77, 3.23; I2 = 25%). Multivariate analyses showed that high PNI score (HR 0.64; 95% CI, 0.49, 0.84; I2 = 24%) and low CONUT score (HR 2.79; 95% CI, 2.01, 3.89; I2 = 39%) were independently associated with longer OS, whereas PNI score was not significantly associated with PFS (HR 1.02; 95% CI, 0.65, 1.59; I2 = 0%).

Conclusion

PNI scores and CONUT scores have prognostic value in patients with glioblastoma. Additional large-scale studies, however, are required to confirm these results.
Case report: A rare case of thyrotropin-secreting pituitary macroadenoma with diffuse calcification presenting with hyperthyroidism and literature review
Authors: Yan Huiying , Yan Chaolong , Mao Jiannan , Jin Wei
Published: February 2023

Background

Thyroid-stimulating hormone (TSH)-secreting pituitary adenomas (TSHomas) are rare and usually present with hyperthyroidism. Calcification in pituitary tumors is an infrequent finding. Herein, we report an extremely rare case of TSHoma with diffuse calcification.

Case description

A 43-year-old man was admitted to our department with a complaint of palpitations. An endocrinological examination revealed elevated serum levels of TSH, free triiodothyronine (FT3), and free thyroxin, whereas the physical examination revealed no obvious abnormality. Computerized tomography (CT) showed a sellar mass with diffuse calcification. Contrast-enhanced T1-weighted images revealed a less-enhancing tumor without obvious suprasellar or parasellar expansion. The tumor was completely removed via endoscopic transnasal-sphenoidal surgery. Microscopically, nests of cells were inconspicuous among the diffuse psammoma bodies. Expression of TSH was patchy, and only several TSH-positive cells were observed. Postoperatively, the serum levels of TSH, FT3, and FT4 decreased to their normal range. Follow-up MR images showed no evidence of residual tumor or regrowth after the resection.

Conclusions

Herein, we report a rare case of TSHoma with diffuse calcification that presented with hyperthyroidism. A correct and early diagnosis was made according to the European Thyroid Association guidelines. This tumor was completely removed via endoscopic transnasal-transsphenoidal surgery (eTSS), and thyroid function was normalized after the operation.
Breast cancer subtype and clinical characteristics in women from Peru
Authors: Zavala Valentina A. , Casavilca-Zambrano Sandro , Navarro-Vásquez Jeannie , Tamayo Lizeth I. , Castañeda Carlos A. , Valencia Guillermo , Morante Zaida , Calderón Mónica , Abugattas Julio E. , Gómez Henry L. , Fuentes Hugo A. , Liendo-Picoaga Ruddy , Cotrina Jose M. , Neciosup Silvia P. , Roque Katia , Vásquez Jule , Mas Luis , Gálvez-Nino Marco , Fejerman Laura , Vidaurre Tatiana
Published: February 2023

Introduction

Breast cancer is a heterogeneous disease, and the distribution of the different subtypes varies by race/ethnic category in the United States and by country. Established breast cancer-associated factors impact subtype-specific risk; however, these included limited or no representation of Latin American diversity. To address this gap in knowledge, we report a description of demographic, reproductive, and lifestyle breast cancer-associated factors by age at diagnosis and disease subtype for The Peruvian Genetics and Genomics of Breast Cancer (PEGEN-BC) study.

Methods

The PEGEN-BC study is a hospital-based breast cancer cohort that includes 1943 patients diagnosed at the Instituto Nacional de Enfermedades Neoplásicas in Lima, Peru. Demographic and reproductive information, as well as lifestyle exposures, were collected with a questionnaire. Clinical data, including tumor Hormone Receptor (HR) status and Human Epidermal Growth Factor Receptor 2 (HER2) status, were abstracted from electronic medical records. Differences in proportions and mean values were tested using Chi-squared and one-way ANOVA tests, respectively. Multinomial logistic regression models were used for multivariate association analyses.

Results

The distribution of subtypes was 52% HR+HER2-, 19% HR+HER2+, 16% HR-HER2-, and 13% HR-HER2+. Indigenous American (IA) genetic ancestry was higher, and height was lower among individuals with the HR-HER2+ subtype (80% IA vs. 76% overall, p=0.007; 152 cm vs. 153 cm overall, p=0.032, respectively). In multivariate models, IA ancestry was associated with HR-HER2+ subtype (OR=1.38,95%CI=1.06-1.79, p=0.017) and parous women showed increased risk for HR-HER2+ (OR=2.7,95%CI=1.5-4.8, p<0.001) and HR-HER2- tumors (OR=2.4,95%CI=1.5-4.0, p<0.001) compared to nulliparous women. Multiple patient and tumor characteristics differed by age at diagnosis (<50 vs. >=50), including ancestry, region of residence, family history, height, BMI, breastfeeding, parity, and stage at diagnosis (p<0.02 for all variables).

Discussion

The characteristics of the PEGEN-BC study participants do not suggest heterogeneity by tumor subtype except for IA genetic ancestry proportion, which has been previously reported. Differences by age at diagnosis were apparent and concordant with what is known about pre- and post-menopausal-specific disease risk factors. Additional studies in Peru should be developed to further understand the main contributors to the specific age of onset and molecular disease subtypes in this population and develop population-appropriate predictive models for prevention.
Sociodemographic characteristics of pediatric patients with vascular malformations: Results of a single site study
Authors: Mohnasky Michael , Brondon Jennifer , Lee Sang Yub , Kim Kyung Rae
Published: February 2023

Vascular malformations, the abnormal development of blood vessels, are a rare set of congenital anomalies. The sociodemographic factors associated with vascular malformations in pediatric patients are poorly understood. This study examined sociodemographic factors of 352 patients presenting to a single vascular anomaly center from July 2019 to September 2022. Characteristics such as race, ethnicity, sex, age at presentation, degree of urbanization, and insurance status were recorded. This data was analyzed by comparing the different types of vascular malformations, including arteriovenous malformation, capillary malformation, venous malformation (VM), lymphatic malformation (LM), lymphedema, and overgrowth syndrome. Patients were primarily white, not Hispanic or Latino, female, had private health insurance, and were from the most urban setting. No differences in sociodemographic factors were found among the different vascular malformations except patients with VM presented at a later age than patients with LM or overgrowth syndrome. This study provides novel insight into the sociodemographic factors of pediatric patients presenting with vascular malformations and indicates a need for their improved recognition for the timely initiation of treatment.
Steroid-resistant nephrotic syndrome associated with certain SGPL1 variants in a family: Case report and literature review
Authors: Yang Siying , He Yonghua , Zhou Jianhua , Yuan Huiqing , Qiu Liru
Published: February 2023

Objectives

Steroid-resistant nephrotic syndrome (SRNS) is a clinical syndrome characterized by the lack of response to standard steroid therapy, usually progressing to end-stage renal disease. We reported two cases of female identical twins with SRNS caused by SGPL1 variants in one family, reviewed the relevant literature, and summarized their clinical phenotypes, pathological types, and genotypic characteristics.

Methods

Two cases of nephrotic syndrome caused by SGPL1 variants were admitted to Tongji Hospital, affiliated with Tongji Medical College of Huazhong University of Science and Technology. Their clinical data were retrospectively collected, and the peripheral blood genomic DNA was captured and sequenced by whole exome sequencing. Related literature published in PubMed, CNKI, and Wan fang databases was reviewed.

Results

We described two Chinese identical twin girls with isolated SRNS due to compound heterozygous variants in the SGPL1 (intron4 c.261 + 1G > A and intron12 c.1298 + 6T > C). The patients were followed up for 60.0 months and 53.0 months, respectively, having no extra-renal manifestations. They all died due to renal failure. A total of 31 children with SGPL1 variants causing nephrotic syndrome (including the reported two cases) were identified through a literature review.

Conclusions

These two female identical twins were the first reported cases of isolated SRNS caused by SGPL1 variants. Almost all homozygous and compound heterozygous variants of SGPL1 had extra-renal manifestations, but compound heterozygous variants in the intron of SGPL1 may have no obvious extra-renal manifestations. Additionally, a negative genetic testing result does not completely rule out genetic SRNS because the Human Gene Mutation Database or ClinVar is constantly being updated.
The role of breastfeeding as a protective factor against the development of the immune-mediated diseases: A systematic review
Authors: Alotiby Amna A.
Published: February 2023

Introduction

Breast milk is rich in nutrients and immunological factors capable of protecting infants against various immunological diseases and disorders. The current systematic review has been framed with the objective of studying the role of breastfeeding as a protective factor against the development of immune-mediated diseases.

Methods

The database and website searches were performed using PubMed, PubMed Central, Nature, Springer, Nature, Web of Science, and Elsevier. The studies were scrutinized based on the nature of participants and the nature of disease considered. The search was restricted to infants with immune-mediated diseases such as diabetes mellitus, allergic conditions, diarrhoea, and rheumatoid arthritis.

Results

We have included 28 studies, out of which seven deal with diabetes mellitus, two rheumatoid arthritis, five studies about Celiac Disease, twelve studies about allergic/ asthma/wheezing conditions and one study on each of the following diseases: neonatal lupus erythematosus and colitis.

Discussion

Based on our analysis, breastfeeding in association with the considered diseases was found to be positive. Breastfeeding is involved as protective factor against various diseases. The role of breastfeeding in the prevention of diabetes mellitus has been found to be significantly higher than for other diseases.
Biglycan regulates bone development and regeneration
Authors: Shainer Reut , Kram Vardit , Kilts Tina M. , Li Li , Doyle Andrew D. , Shainer Inbal , Martin Daniel , Simon Carl G. , Zeng-Brouwers Jinyang , Schaefer Liliana , Young Marian F. ,   Genomics and Computational Biology Core
Published: February 2023

Endochondral bone development and regeneration relies on activation and proliferation of periosteum derived-cells (PDCs). Biglycan (Bgn), a small proteoglycan found in extracellular matrix, is known to be expressed in bone and cartilage, however little is known about its influence during bone development. Here we link biglycan with osteoblast maturation starting during embryonic development that later affects bone integrity and strength. Biglycan gene deletion reduced the inflammatory response after fracture, leading to impaired periosteal expansion and callus formation. Using a novel 3D scaffold with PDCs, we found that biglycan could be important for the cartilage phase preceding bone formation. The absence of biglycan led to accelerated bone development with high levels of osteopontin, which appeared to be detrimental to the structural integrity of the bone. Collectively, our study identifies biglycan as an influencing factor in PDCs activation during bone development and bone regeneration after fracture.
Transcriptome, proteome and functional characterization reveals salt stress tolerance mechanisms in upland cotton (Gossypium hirsutum L.)
Authors: Sun Kangtai , Mehari Teame Gereziher , Fang Hui , Han Jinlei , Huo Xuehan , Zhang Jingxia , Chen Yu , Wang Dongmei , Zhuang Zhimin , Ditta Allah , Khan Muhammad K.R. , Zhang Jun , Wang Kai , Wang Baohua
Published: February 2023

Uncovering the underlying mechanism of salt tolerance is important to breed cotton varieties with improved salt tolerance. In this study, transcriptome and proteome sequencing were performed on upland cotton (Gossypium hirsutum L.) variety under salt stress, and integrated analysis was carried out to exploit salt-tolerance genes in cotton. Enrichment analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed on differentially expressed genes (DEGs) obtained from transcriptome and proteome sequencing. GO enrichment was carried out mainly in the cell membrane, organelle, cellular process, metabolic process, and stress response. The expression of 23,981 genes was changed in physiological and biochemical processes such as cell metabolism. The metabolic pathways obtained by KEGG enrichment included glycerolipid metabolism, sesquiterpene and triterpenoid biosynthesis, flavonoid production, and plant hormone signal transduction. Combined transcriptome and proteome analysis to screen and annotate DEGs yielded 24 candidate genes with significant differential expression. The quantitative real-time polymerase chain reaction (qRT-PCR) validation of the candidate genes showed that two genes (Gh_D11G0978 and Gh_D10G0907) responded significantly to the induction of NaCl, and these two genes were further selected as target genes for gene cloning and functional validation through virus-induced gene silencing (VIGS). The silenced plants exhibited early wilting with a greater degree of salt damage under salt treatment. Moreover, they showed higher levels of reactive oxygen species (ROS) than the control. Therefore, we can infer that these two genes have a pivotal role in the response to salt stress in upland cotton. The findings in this research will facilitate the breeding of salt tolerance cotton varieties that can be grown on saline alkaline lands.
Biological insights from multi-omics analysis strategies: Complex pleotropic effects associated with autophagy
Authors: Ding Geng , Mugume Yosia , Dueñas Maria Emilia , Lee Young Jin , Liu Meiling , Nettleton Daniel S. , Zhao Xuefeng , Li Ling , Bassham Diane C. , Nikolau Basil J.
Published: February 2023

Research strategies that combine molecular data from multiple levels of genome expression (i.e., multi-omics data), often referred to as a systems biology strategy, has been advocated as a route to discovering gene functions. In this study we conducted an evaluation of this strategy by combining lipidomics, metabolite mass-spectral imaging and transcriptomics data from leaves and roots in response to mutations in two AuTophaGy-related (ATG) genes of Arabidopsis. Autophagy is an essential cellular process that degrades and recycles macromolecules and organelles, and this process is blocked in the atg7 and atg9 mutants that were the focus of this study. Specifically, we quantified abundances of ~100 lipids and imaged the cellular locations of ~15 lipid molecular species and the relative abundance of ~26,000 transcripts from leaf and root tissues of WT, atg7 and atg9 mutant plants, grown either in normal (nitrogen-replete) and autophagy-inducing conditions (nitrogen-deficient). The multi-omics data enabled detailed molecular depiction of the effect of each mutation, and a comprehensive physiological model to explain the consequence of these genetic and environmental changes in autophagy is greatly facilitated by the a priori knowledge of the exact biochemical function of the ATG7 and ATG9 proteins.
Phylogenetic data reveal a surprising origin of Euphorbia orphanidis (Euphorbiaceae) and environmental modeling suggests that microtopology limits its distribution to small patches in Mt. Parnassus (Greece)
Authors: Faltner Felix , Wessely Johannes , Frajman Božo
Published: February 2023

The Mediterranean Basin is one of the most biodiverse areas in the world, harboring 25,000 plant species, of which 60% are endemic. Some of them have narrow distributions, such as Euphorbia orphanidis, which is only known from alpine screes on Mt. Parnassos in Greece. Its exact distribution in this mountain was, however, poorly known, and its phylogenetic origin was also unclear. We performed extensive field work in Mt. Parnassos and could register E. orphanidis only in five patches of limestone screes in the eastern part of this mountain range, emphasizing its very narrow distribution, which is likely limited by topography influencing water availability as indicated by environmental modeling. We also registered 31 accompanying species and thus characterized its habitat. Using nuclear ribosomal internal transcribed spacer and plastid ndhF–trnL and trnT–trnF sequences, we show that it belongs to E. sect. Patellares, despite not having connate raylet leaves typical for this section, and not to E. sect. Pithyusa as previously suggested. The relationships among the species of E. sect. Patellares are poorly resolved, suggesting their simultaneous divergence that dated to the late Pliocene, which coincided with the establishment of the Mediterranean climate. The relative genome size of E. orphanidis is in the range of that for the other members of E. sect. Patellares, suggesting that it is diploid. Finally, we performed multivariate morphological analyses to generate a comprehensive description of E. orphanidis. Based on its narrow distribution and the anticipated negative impact of global warming, we consider this species endangered. Our study demonstrates how microrelief can limit the distribution of plants in topographically heterogeneous mountain environments and likely plays an important, yet neglected, role in shaping the distribution patterns of plants in the Mediterranean Basin.