bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and external validation of a novel nomogram for predicting cancer-specific survival in patients with ascending colon adenocarcinoma after surgery: a population-based study
Authors: Zhang Yi Fan , Ma Cheng , Qian Xiao Ping 
Published: April 2022

Abstract

Background
This study aimed to develop and validate a novel nomogram to predict the cancer-specific survival (CSS) of patients with ascending colon adenocarcinoma after surgery.

Methods
Patients with ascending colon adenocarcinoma were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2015 and randomly divided into a training set (5930) and a validation set (2540). The cut-off values for age, tumour size and lymph node ratio (LNR) were calculated via X-tile software. In the training set, independent prognostic factors were identified using univariate and multivariate Cox analyses, and a nomogram incorporating these factors was subsequently built. Data from the validation set were used to assess the reliability and accuracy of the nomogram and then compared with the 8th edition of the American Joint Committee on Cancer (AJCC) tumour-node-metastasis (TNM) staging system. Furthermore, external validation was performed from a single institution in China.

Results
A total of 8470 patients were enrolled from the SEER database, 5930 patients were allocated to the training set, 2540 were allocated to the internal validation set and a separate set of 473 patients was allocated to the external validation set. The optimal cut-off values of age, tumour size and lymph node ratio were 73 and 85, 33 and 75 and 4.9 and 32.8, respectively. Univariate and multivariate Cox multivariate regression revealed that age, AJCC 8th edition T, N and M stage, carcinoembryonic antigen (CEA), tumour differentiation, chemotherapy, perineural invasion and LNR were independent risk factors for patient CSS. The nomogram showed good predictive ability, as indicated by discriminative ability and calibration, with C statistics of 0.835 (95% CI, 0.823–0.847) and 0.848 (95% CI, 0.830–0.866) in the training and validation sets and 0.732 (95% CI, 0.664–0.799) in the external validation set. The nomogram showed favourable discrimination and calibration abilities and performed better than the AJCC TNM staging system.

Conclusions
A novel validated nomogram could effectively predict patients with ascending colon adenocarcinoma after surgery, and this predictive power may guide clinicians in accurate prognostic judgement.
KIF14 affects cell cycle arrest and cell viability in cervical cancer by regulating the p27Kip1 pathway
Authors: Zhang Jie , Buranjiang Gulimire , Mutalifu Zuohelaguli , Jin Hua , Yao Liyan 
Published: April 2022

Abstract
Background
Cervical cancer is a kind of malignant gynecological tumor. The first choice for treating cervical cancer is still a combination of surgery and chemoradiotherapy, but the 5-year survival rate remains poor. Therefore, researchers are trying to find new ways to diagnose and treat cervical cancer early.

Methods
The expression level of KIF14 in cells and tissues was determined via qRT–PCR. The ability of the cells to proliferate, migrate, and invade was examined using CCK-8 assay kits, colony formation assays, and Transwell chambers. The expression levels of Cyclin D1, Cyclin B1, p21, and p27 were also detected using western blot assays.

Results
The results suggested that p27 is a key regulatory factor in the KIF14-mediated regulation of the cell cycle. In addition, KIF14 knockdown promotes malignancy in cervical cancer cells by inhibiting p27 degradation, resulting in cell cycle arrest.

Conclusions
KIF14 is an oncogene in cervical cancer, and knocking down KIF14 causes cell cycle arrest by inhibiting p27 degradation, thus affecting cell viability, proliferation, and migration. These results provide a potential therapeutic target for cervical cancer.
Does conventional morphological evaluation still play a role in predicting blastocyst formation?
Authors: Jiang Xiaoming , Cai Jiali , Liu Lanlan , Liu Zhenfang , Wang Wenjie , Chen Jinhua , Yang Chao , Geng Jie , Ma Caihui , Ren Jianzhi 
Published: April 2022

Abstract
Background
Advanced models including time-lapse imaging and artificial intelligence technologies have been used to predict blastocyst formation. However, the conventional morphological evaluation of embryos is still widely used. The purpose of the present study was to evaluate the predictive power of conventional morphological evaluation regarding blastocyst formation.

Methods
Retrospective evaluation of data from 15,613 patients receiving blastocyst culture from January 2013 through December 2020 in our institution were reviewed. Generalized estimating equations (GEE) were used to establish the morphology-based model. To estimate whether including more features regarding patient characteristics and cycle parameters improve the predicting power, we also establish models including 27 more features with either LASSO regression or XGbosst. The predicted number of blastocyst were associated with the observed number of the blastocyst and were used to predict the blastocyst transfer cancellation either in fresh or frozen cycles.

Results
Based on early cleavage and routine observed morphological parameters (cell number, fragmentation, and symmetry), the GEE model predicted blastocyst formation with an AUC of 0.779(95%CI: 0.77–0.787) and an accuracy of 74.7%(95%CI: 73.9%-75.5%) in the validation set. LASSO regression model and XGboost model based on the combination of cycle characteristics and embryo morphology yielded similar predicting power with AUCs of 0.78(95%CI: 0.771–0.789) and 0.754(95%CI: 0.745–0.763), respectively. For per-cycle blastocyst yield, the predicted number of blastocysts using morphological parameters alone strongly correlated with observed blastocyst number (r = 0.897, P < 0.0001) and predicted blastocyst transfer cancel with an AUC of 0.926((95%CI: 0.911–0.94).

Conclusion
The data suggested that routine morphology observation remained a feasible tool to support an informed decision regarding the day of transfer. However, models based on the combination of cycle characteristics and embryo morphology do not increase the predicting power significantly.
Immune activation and inflammatory biomarkers as predictors of venous thromboembolism in lymphoma patients
Authors: Otasevic Vladimir , Mihaljevic Biljana , Milic Natasa , Stanisavljevic Dejana , Vukovic Vojin , Tomic Kristina , Fareed Jawed , Antic Darko 
Published: April 2022

Abstract
Background
Lymphomas are characterized by elevated synthesis of inflammatory soluble mediators that could trigger the development of venous thromboembolism (VTE). However, data on the relationship between specific immune dysregulation and VTE occurrence in patients with lymphoma are scarce. Therefore, this study aimed to assess the association between inflammatory markers and the risk of VTE development in patients with lymphoma.

Methods
The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lactate dehydrogenase (LDH), total protein (TP), and albumin were assessed in 706 patients with newly diagnosed or relapsed lymphoma. Data were collected for all VTE events, while the diagnosis of VTE was established objectively based on radiographic studies. ROC (receiver operating characteristic) curve analysis was performed to define the optimal cutoff values for predicting VTE.

Results
The majority of patients was diagnosed with aggressive non-Hodgkin lymphoma (58.8%) and had advanced stage disease (59.9%). Sixty-nine patients (9.8%) developed VTE. The NLR, PLR, ESR, CRP, and LDH were significantly higher in the patients with lymphoma with VTE, whereas the TP and albumin were significantly lower in those patients. Using the univariate regression analysis, the NLR, PLR, TP, albumin, LDH, and CRP were prognostic factors for VTE development. In the multivariate regression model, the NLR and CRP were independent prognostic factors for VTE development. ROC curve analysis demonstrated acceptable specificity and sensitivity of the parameters: NLR, PLR, and CRP for predicting VTE.

Conclusion
Inflammatory dysregulation plays an important role in VTE development in patients with lymphoma. Widely accessible, simple inflammatory parameters can classify patients with lymphoma at risk of VTE development.
Evaluation of multinodular goiter and primary hyperparathyroidism leads to a diagnosis of AL amyloidosis
Authors: Patel Chavez Chandani , Morales Hernandez Maria del Mar , Kresak Jesse , Woodmansee Whitney W. 
Published: April 2022

AbstractBackgroundAmyloid goiter, defined as excess amyloid within the thyroid gland in such quantities that it produces a clinically apparent goiter, is a very rare manifestation of systemic amyloidosis with cases commonly seen in the setting of Amyloid A (AA) amyloidosis. Amyloid goiter as the primary clinical manifestation secondary to Amyloid light chain (AL) amyloidosis is very rare. We present a case of AL amyloidosis with initial manifestation as goiter with amyloid deposition in the thyroid and the parathyroid gland.Case PresentationA 73 year old male presented with goiter and compressive symptoms of dysphagia and hoarseness. Laboratory workup revealed normal thyroid function, nephrotic range proteinuria, elevated serum calcium level with an elevated parathyroid hormone level (PTH) consistent with primary hyperparathyroidism. Thyroid ultrasound showed an asymmetric goiter with three dominant nodules. Cervical computed tomography revealed a goiter with substernal extension and deviation of the trachea. Fine needle aspiration was unsatisfactory. There was also evidence of osteoporosis and hypercalciuria with negative Sestamibi scan for parathyroid adenoma. The patient underwent a total thyroidectomy and one gland parathyroidectomy. Pathology revealed benign thyroid parenchyma with diffuse amyloid deposition in the thyroid and parathyroid gland that stained apple green birefringence under polarized light on Congo Red stain. Immunochemical staining detected AL amyloid deposition of the lambda type. Bone marrow biopsy revealed an excess monoclonal lambda light chain of plasma cells consistent with a diagnosis of AL amyloidosis secondary to multiple myeloma affecting the kidney, thyroid, parathyroid gland, and heart. He was treated with 4 cycles of chemotherapy with a decrease in the M spike and light chains with a plan to pursue a bone marrow transplant.ConclusionAmyloid goiter as the primary clinical manifestation secondary to AL amyloidosis with deposition in the thyroid and parathyroid gland is rare. The top differential for amyloid deposits in the thyroid includes systemic amyloidosis or medullary thyroid carcinoma. The definitive diagnosis lies in the histopathology of the thyroid tissue. To diagnose systemic amyloidosis as the etiology for a goiter, a solid understanding of the causes of systemic amyloidosis coupled with a thorough evaluation of the patient’s history and laboratory data is necessary.
SEMA6A/RhoA/YAP axis mediates tumor-stroma interactions and prevents response to dual BRAF/MEK inhibition in BRAF-mutant melanoma
Authors: Loria Rossella , Laquintana Valentina , Scalera Stefano , Fraioli Rocco , Caprara Valentina , Falcone Italia , Bazzichetto Chiara , Di Martile Marta , Rosanò Laura , Del Bufalo Donatella , Bossi Gianluca , Sperduti Isabella , Terrenato Irene , Visca Paolo , Soddu Silvia , Milella Michele , Ciliberto Gennaro , Falcioni Rita , Ferraresi Virginia , Bon Giulia 
Published: April 2022

Abstract
Background
Despite the promise of dual BRAF/MEK inhibition as a therapy for BRAF-mutant (BRAF-mut) melanoma, heterogeneous responses have been observed in patients, thus predictors of benefit from therapy are needed. We have previously identified semaphorin 6A (SEMA6A) as a BRAF-mut-associated protein involved in actin cytoskeleton remodeling. The purpose of the present study is to dissect the role of SEMA6A in the biology of BRAF-mut melanoma, and to explore its predictive potential towards dual BRAF/MEK inhibition.

Methods
SEMA6A expression was assessed by immunohistochemistry in melanoma cohort RECI1 (N = 112) and its prognostic potential was investigated in BRAF-mut melanoma patients from DFCI and TCGA datasets (N = 258). The molecular mechanisms regulated by SEMA6A to sustain tumor aggressiveness and targeted therapy resistance were investigated in vitro by using BRAF-mut and BRAF-wt melanoma cell lines, an inducible SEMA6A silencing cell model and a microenvironment-mimicking fibroblasts-coculturing model. Finally, SEMA6A prediction of benefit from dual BRAF/MEK inhibition was investigated in melanoma cohort RECI2 (N = 14).

Results
Our results indicate higher protein expression of SEMA6A in BRAF-mut compared with BRAF-wt melanoma patients and show that SEMA6A is a prognostic indicator in BRAF-mut melanoma from TCGA and DFCI patients cohorts. In BRAF-mut melanoma cells, SEMA6A coordinates actin cytoskeleton remodeling by the RhoA-dependent activation of YAP and dual BRAF/MEK inhibition by dabrafenib+trametinib induces SEMA6A/RhoA/YAP axis. In microenvironment-mimicking co-culture condition, fibroblasts confer to melanoma cells a proliferative stimulus and protect them from targeted therapies, whereas SEMA6A depletion rescues the efficacy of dual BRAF/MEK inhibition. Finally, in BRAF-mut melanoma patients treated with dabrafenib+trametinib, high SEMA6A predicts shorter recurrence-free interval.

Conclusions
Overall, our results indicate that SEMA6A contributes to microenvironment-coordinated evasion of melanoma cells from dual BRAF/MEK inhibition and it might be a good candidate predictor of short-term benefit from dual BRAF/MEK inhibition.
Volunteerism during humanitarian crises: a practical guide
Authors: Bailey Heatherlee , Kaplan Lewis J. 
Published: April 2022

AbstractVolunteerism to provide humanitarian aid occurs in response to disasters, crises, and conflict. Each of those volunteerism triggers engenders personal risk borne by the healthcare volunteer while rendering aid and merit specific evaluation. Factors that impact decision-making with regard to volunteering are personal, structural and crisis specific. Practical approaches to travel and on-scene safety benefit volunteers and should inform planning and preparation for volunteerism-driven travel. These approaches include planning for evacuation and potential rescue. These unique skills and approaches are generally not part of medical education outside of military service. The global medical community, including medical professional organizations, should embrace this opportunity to improve medical education and professional development to support humanitarian aid volunteerism. Disaster, crisis, or conflict-driven healthcare volunteerism highlights the core elements of altruism, dedication, and humanity that permeate clinician’s drive to render aid and save lives.
Pioneer transcription factors are associated with the modulation of DNA methylation patterns across cancers
Authors: Lemma Roza Berhanu , Fleischer Thomas , Martinsen Emily , Ledsaak Marit , Kristensen Vessela , Eskeland Ragnhild , Gabrielsen Odd Stokke , Mathelier Anthony 
Published: April 2022

AbstractMethylation of cytosines on DNA is a prominent modification associated with gene expression regulation. Aberrant DNA methylation patterns have recurrently been linked to dysregulation of the regulatory program in cancer cells. To shed light on the underlying molecular mechanism driving this process, we hypothesised that aberrant methylation patterns could be controlled by the binding of specific transcription factors (TFs) across cancer types. By combining DNA methylation arrays and gene expression data with TF binding sites (TFBSs), we explored the interplay between TF binding and DNA methylation in 19 cancer types. We performed emQTL (expression–methylation quantitative trait loci) analyses independently in each cancer type and identified 13 TFs whose expression levels are correlated with local DNA methylation patterns around their binding sites in at least 2 cancer types. The 13 TFs are mainly associated with local demethylation and are enriched for pioneer function, suggesting a specific role for these TFs in modulating chromatin structure and transcription in cancer patients. Furthermore, we confirmed that de novo methylation is precluded across cancers at CpGs lying in genomic regions enriched for TF binding signatures associated with SP1, CTCF, NRF1, GABPA, KLF9, and/or YY1. The modulation of DNA methylation associated with TF binding was observed at cis-regulatory regions controlling immune- and cancer-associated pathways, corroborating that the emQTL signals were derived from both cancer and tumor-infiltrating cells. As a case example, we experimentally confirmed that FOXA1 knock-down is associated with higher methylation in regions bound by FOXA1 in breast cancer MCF-7 cells. Finally, we reported physical interactions between FOXA1 with TET1 and TET2 both in an in vitro setup and in vivo at physiological levels in MCF-7 cells, adding further support for FOXA1 attracting TET1 and TET2 to induce local demethylation in cancer cells.
Epigenome-wide contributions to individual differences in childhood phenotypes: a GREML approach
Authors: Neumann Alexander , Pingault Jean-Baptiste , Felix Janine F. , Jaddoe Vincent W. V. , Tiemeier Henning , Cecil Charlotte , Walton Esther 
Published: April 2022

AbstractBackgroundDNA methylation is an epigenetic mechanism involved in human development. Numerous epigenome-wide association studies (EWAS) have investigated the associations of DNA methylation at single CpG sites with childhood outcomes. However, the overall contribution of DNA methylation across the genome (R2Methylation) towards childhood phenotypes is unknown. An estimate ofR2Methylationwould provide context regarding the importance of DNA methylation explaining variance in health outcomes. We therefore estimated the variance explained by epigenome-wide cord blood methylation (R2Methylation) for five childhood phenotypes: gestational age, birth weight, and body mass index (BMI), IQ and ADHD symptoms at school age. We adapted a genome-based restricted maximum likelihood (GREML) approach with cross-validation (CV) to DNA methylation data and applied it in two population-based birth cohorts: ALSPAC (n = 775) and GenerationR(n = 1382).ResultsUsing information from > 470,000 autosomal probes we estimated that DNA methylation at birth explains 32% (SDCV = 0.06) of gestational age variance and 5% (SDCV = 0.02) of birth weight variance. TheR2Methylationestimates for BMI, IQ and ADHD symptoms at school age estimates were near 0% across almost all cross-validation iterations.ConclusionsThe results suggest that cord blood methylation explains a moderate degree of variance in gestational age and birth weight, in line with the success of previous EWAS in identifying numerous CpG sites associated with these phenotypes. In contrast, we could not obtain a reliable estimate for school-age BMI, IQ and ADHD symptoms. This may reflect a null bias due to insufficient sample size to detect variance explained in more weakly associated phenotypes, although the trueR2Methylationfor these phenotypes is likely below that of gestational age and birth weight when using DNA methylation at birth.
Severe disseminated Veillonella parvula infection including endocarditis, bilateral psoas abscess, discitis, and osteomyelitis but sparing spinal and hip prostheses: a case report
Authors: Richards Tobias , Stephen Juan , Lui Chok Lin 
Published: April 2022

Abstract
Background
Veillonella species are an opportunistically pathogenic commensal anaerobic Gram-negative coccus commonly found in the oral, genitourinary, respiratory, and intestinal tract of humans and some animals. Infection is rare, even in immunocompromised hosts, and has been identified to cause a wide array of different infections, including endocarditis, osteomyelitis, and meningitis.

Case presentation
An 82-year-old Caucasian male retired ex-gymnast presented to the emergency department with a 2-week history of acute on chronic lower back pain without clear precipitant. He displayed no systemic symptoms, and had not sustained any recent injuries. Initial blood and radiological investigation did not reveal an infective or mechanical cause for his pain; however, a few days into admission, he developed a fever and signs of sepsis. A thorough septic screen was performed, including a spinal magnetic resonance imaging scan, which did not reveal any abnormalities. Blood cultures revealed Veillonella parvula bacteremia, with subsequently repeated magnetic resonance imaging displaying rapid disseminated infection including bilateral psoas abscess, discitis, and osteomyelitis. Infective endocarditis was later identified with echocardiogram. He received intravenous ceftriaxone and later oral amoxicillin and clavulanic and recovered on 6-month follow-up.

Conclusions
This case illustrates the potential pathogenicity and unexpected rapid course of Veillonella parvula infection even in an immunocompetent host presenting with back pain. This case highlights the critical importance of a thorough septic screen when investigating patients for early signs of sepsis.
Endogenous health risks, poverty traps, and the roles of health insurance in poverty alleviation
Authors: Liao Pu , Zhang Xun , Zhang Wanlu 
Published: April 2022

Abstract
Background
Family education investment is a key factor in reducing intergenerational transmission of poverty. At the price of higher health risk, the poor may overdraw their bodies to earn more money to invest in education. This study investigates the effect of physical overdraft, health risks and health insurance on poverty and economic growth.

Methods
This paper proposes an economic development model of endogenous health risks and poverty by setting up a physical overdraft decision. Furthermore, we introduce mutual health insurance mechanism to analyze its poverty alleviation effects.

Results
First, this study shows that health risks weaken the economy and are among the leading causes of poverty. Second, mutual health insurance can alleviate, but not completely eliminate, the negative impact of health risks on the economy. Third, appropriate health insurance arrangements can lift some or even all poor households out of poverty.

Conclusion
Health risks have a significant effect on poverty. Furthermore, health insurance mechanisms have the advantages of transferring health risks, reducing poverty and improving health equity.