bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxia with 18F-fluoroerythronitroimidazole integrated positron emission tomography and computed tomography (18F-FETNIM PET/CT) in locoregionally advanced head and neck cancer
Authors: Hu Man , Xie Peng , Lee Nancy Y. , Li Min , Ho Felix , Lian Ming , Zhao Shuqiang , Yang Guoren , Fu Zheng , Zheng Jinsong , Ma Li , Yu Jinming 
Published: October 2019

Abstract
Hypoxia is a well-recognized biological characteristic to therapy resistance and negative prognostic factor in patients with head and neck squamous cell carcinoma (HNSCC). This study aims to investigate the changes of hypoxia measured by 18F-fluoroerythronitroimidazole (FETNIM) uptake on integrated positron emission tomography and computed tomography (PET/CT) during chemoradiotherapy and its prognostic value of clinical outcome in locoregionally advanced HNSCC.
Thirty-two patients with locoregionally advanced HNSCC who received definitive treatment with concurrent chemoradiotherapy underwent FETNIM PET/CT scans before and after 5 weeks of treatment. The intensity of hypoxia using the maximum standardized uptake value (SUVmax) was evaluated both on primary lesion and metastatic lymph node (MLN). The pre-SUVmax and mid-SUVmax were defined as SUVmax on pre- and mid-FETNIM PET/CT. The local control (LC), regional control (RC), distant metastatic-free survival (DMFS), and overall survival (OS) were collected in patient follow-ups.
Mid-SUVmax decreased significantly both in the primary tumor (t = 8.083, P < .001) and MLN (t = 6.808, P < .001) compared to pre-SUVmax. With a median follow-up of 54 months, the 5-year LC, RC, DMFS, and OS rates were 55%, 66.7%, 64.7%, and 55%, respectively, for all of the patients. On univariate analysis, patients with high pre-SUVmax in primary tumor had significantly worse LC (56.3% vs 87.5%, P = .046) and OS (43.8% vs 87.5%, P = .023) than other patients. Patients with high mid-SUVmax had significantly worse DMFS (50% vs 84.6%, P = .049) and OS (33.3% vs 73.1%, P = .028) than other patients. The tumor grade and mid-SUVmax were the significant predictors of OS on multivariate analysis.
In this study, hypoxia in tumor significantly decreased during chemoradiotherapy. The persistent hypoxia predicted poor OS. The data provided evidence that FETNIM PET/CT could be used dynamically for selecting appropriate patients and optimal timing of hypoxia-adapted therapeutic regimens.
Novel IVS7+1G>T mutation of life-threatening congenital factor VII deficiency in neonates
Authors: He Juan , Zhou Wei , Lv Hui , Tao Li , Chen XiaoWen , Wang Ling 
Published: October 2019

Abstract
In neonates, congenital factor VII deficiency (FVIID) is characterized by central nervous system bleeding and gastrointestinal hemorrhage, often resulting in poor prognosis and high mortality.
To improve understanding of FVIID in neonates in Asia, we retrospectively analyzed the clinical manifestations, diagnosis, treatment, clinical course, and genetic diagnosis of 2 cases of neonatal FVIID in the Department of Neonatology, Guangzhou Women and Children's Medical Center, Guangzhou, China, from January 2007 to December 2017 and performed a review of the relevant literature.
Both neonates were female and presented with severe gastrointestinal tract and intracranial hemorrhage. The laboratory findings were characterized by repeated and non–vitamin K1-dependent prolonged of the prothrombin time (PT), Factor VII (FVII) activity was 1.5% and 3%, respectively. Both neonates died of severe intracranial hemorrhage, at 31 days and 6 months after birth, respectively. Gene sequencing results revealed a homozygous mutation in the FVII gene splice site (IVS7+1G>T) in both cases. Upon review of relevant literature published since 1996, we identified 19 cases of neonatal FVIID. The patients were full-term neonates with onset of symptoms mostly within 7 days after birth (73.7%), which included gastrointestinal bleeding (blood stool, vomiting blood; 31.6%), nervous system signs (drowsiness, convulsions, poor response; 26.3%), severe intracranial hemorrhage (84.2%), significantly prolonged PT with significantly decreased FVII activity (89.5%), high mortality, and disability (68.4%). Gene sequencing was performed in 9 of the 19 children evaluated and revealed a mutation in the FVII gene in all cases.
FVIID can be clinically diagnosed based on the presence of prolonged PT that is difficult to correct and significantly decreased FVII activity (≤5%). As mutations in some sites are associated with severe bleeding, genetic diagnosis represents a useful tool for prenatal diagnosis of FVIID. In brief, we should pay great attention to the FVIID onset of the neonatal period, although it is rare but result in life-threatening bleeding with poor prognosis.
Clinical evaluation of monolithic zirconia crowns for posterior teeth restorations
Authors: Tang Zhenyu , Zhao Xinyi , Wang Hui , Liu Bin 
Published: October 2019

Abstract
Although all-ceramic crowns have excellent biocompatibility and esthetic appearance, chipping may occur. The mechanical properties of monolithic zirconia restorative material are superior to those of all-ceramic restorative materials, and chipping caused by chewing hard foods could be avoided. This study aimed to evaluate the clinical efficacy of monolithic zirconia crowns for posterior teeth restorations.
A total of 46 patients requiring posterior teeth restorations involving 49 teeth were treated with monolithic zirconia crown procedure. The treatment results were evaluated according to the modified California Dental Association criteria immediately after the procedure, and at 2, 24, 48, and 96 weeks after the procedure. The plaque index, gingival index, probing depth, crown marginal integrity, and attrition of the abutment teeth, antagonist teeth, corresponding contralateral teeth, and antagonist of the corresponding contralateral teeth were assessed. The patients were followed for up to 96 weeks.
The marginal adaptation results of all 46 patients were evaluated as excellent, resulting in an excellent rate of 100%. Regarding the crown color match, only 3 cases (6.1%) were evaluated as acceptable. Marginal adaptation, anatomic form, crown margin integrity, color match, and gross fracture did not show significant differences compared with the different time points (P = .999). Surface texture at different time did not change significantly (P = .807). During the 96-week follow-up, 1 crack in the antagonist teeth was found in 1 patient. There were no significant differences in wear of the antagonist teeth at different time points (P = .972). The rate of “excellent” evaluation for crown restorations was 93.9% to 100%.
The monolithic zirconia crown had no detectable adverse effects on the periodontal tissues, and the antagonist teeth attrition was small. Therefore, it has good potential in the clinical application of posterior teeth restorations in the short term.
Polymicrobial bacteremia after treatment of transcatheter arterial chemoembolization
Authors: Fang Xue-Yao , Hu Long-Hua , Hang Ya-Ping , Chen Yan-Hui , Xu Xiu-Hua , Hu Xiao-Yan , Liu Yan-Hua , Zhang Nan , Zhong Qiao-Shi 
Published: October 2019

Abstract

Rationale:
Bacteremia caused by polymicrobial infections are rare but dangerous. We report a case of hepatic abscess combined with polymicrobial bacteremia in a 49-year-old male patient after surgery and transcatheter arterial chemoembolization (TACE).

Patient concerns:
The patient was admitted to hospital with metastatic liver cancer for periodic chemotherapy and developed a high fever and tenderness to the liver following surgery and TACE.

Diagnosis:
Hepatic abscess combined with polymicrobial bacteremia.

Interventions:
The clinician formulated a therapy in accordance with the drug susceptibility test and the empirical drug use for anaerobic bacteria. A comprehensive treatment plan was adopted, on the basis of the combination of nitrazole and imipenem as anti-infection drugs as well as continuous abscess drainage.

Outcomes:
After comprehensive therapy, the patient was ultimately discharged without any residual symptoms.

Lessons:
Bloodstream infection caused by multiple bacteria increases the difficulty of anti-infection treatments, leading to poor treatment outcome and high mortality. Therefore, a fast and accurate diagnosis of polymicrobial bacteremia is key for initiation of an effective antimicrobial treatment. Additionally, pre-operative prophylactic antibiotics are advisable when patients have a history of abdominal surgery and are immune-compromised.
Isolated Rosai–Dorfman disease with craniocervical junction involvement in the foramen magnum
Authors: Wang Chao , Zou Yi , Zeng Qingze , Hong Hui , Zheng Congkuan 
Published: October 2019

Abstract

Rationale:
Rosai–Dorfman disease (RDD) is a rare benign histiocytic proliferative disease. RDD with cranio-spinal involvement in the foramen magnum is extremely rare. To the best of our knowledge, only 4 cases of RDD with craniocervical junction involvement have been reported so far. Herein, we present the fifth case of RDD with craniocervical junction.

Patient concerns:
A 26-year-old female presented with a sudden headache, accompanied by nausea and vomiting several times during the past half-month.

Diagnoses:
Magnetic resonance imaging (MRI) showed a well-defined, lobulated, homogenous mass in the left foramen magnum. The lesion was isointense on T1-weighted images (T1WI) and hypointense on T2-weighted images (T2WI), and showed homogeneously obvious enhancement following the intravenous administration of gadolinium. It was dural based and extending inferiorly along the spinal dura up to the cervical spinal canal. The brainstem was compressed and deflected to the right side. Initial diagnosis of meningioma with craniocervical junction involvement in the foramen magnum was made according to MRI findings. Final diagnosis of RDD was confirmed by histopathological and immunohistochemical examinations after subtotally surgical resection.

Interventions:
The bulk of lesion in the foramen magnum was removed surgically with suboccipital craniectomy because of brainstem compression.

Outcomes:
The patient recovered well and was discharged 17 days after the surgery.

Lessons:
RDD should be considered in patients with dural-based, extra-axial, well-circumscribed, hypo- to isointense on T1WI, hypo- to isointense on T2WI, enhancing intracranial or spinal lesions or both.
The association of speckle-type POZ protein with lymph node metastasis and prognosis in cancer patients
Authors: Cheng Fei , Zeng Chunyan , Zeng Ling , Wu Chayan , Chen Youxiang 
Published: October 2019

Abstract

Background:
Speckle-type POZ protein (SPOP) has recently been reported as a prognostic tumor biomarker. However, the predictive value of SPOP remains controversial in human cancers. The current meta-analysis was performed to obtain a comprehensive evaluation of the relationship between SPOP expression and prognosis of cancer patients.

Methods:
Embase, Pubmed, Web of Science, and Chinese Biomedical Literature database were systematically searched up to January 2, 2019. The pooled hazard ratios (HRs) and/or pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to quantitatively assess the relationship of SPOP expression with prognosis and lymph node metastasis (LNM).

Results:
A total of 9 studies with 928 patients were included in this meta-analysis. The results showed that low SPOP expression was significantly related to poor overall survival (high/low: HR = 0.55; 95% CI: 0.38–0.79, P = .001), especially for digestive system cancers (high/low: HR = 0.46; 95% CI: 0.27–0.78, P = .003). However, SPOP expression did not affect progression-free survival in cancer patients (high/low: HR = 2.07; 95% CI: 0.16–26.70, P = .578). Additionally, the association between SPOP overexpression and LNM was positive in patients with clear cell renal cell carcinoma (ccRCC) (OR = 5.26; 95% CI: 1.66–16.68, P = .005) but negative in cancer patients without ccRCC (OR = 0.36; 95% CI: 0.21–0.62, P < .001).

Conclusion:
Decreased SPOP expression could predict poor prognosis of cancer patients, suggesting that SPOP protein may be a useful prognostic biomarker in cancer patients.
Mechanisms of failure of chimeric antigen receptor T-cell therapy
Authors: Li Xiaoqing , Chen Weihong 
Published: October 2019

Purpose of review
Although chimeric antigen receptor T (CART)-cell therapy is best recognized for its antitumor effect in relapsed/refractory B-cell hematological cancers, it is still associated with a high relapse rate.

Recent findings
We firstly analyzed internal immunological and genetic reasons of CD19+ relapse after treatment for R/R B-cell hematological cancers with CART19 cells. The reasons: murine-derived scFv may limit expansion of CART cells. Repeated antigen exposure leads to T-cell exhaustion. Activation of T cells can cause T-cell senescence and high expression of inhibitive receptors, PD-1, CTLA4, TIGIT, LAG-3, CD244, CD160, TIM3, which might be solved by some external pharmacological intervention methods [for instance, the use of FC (Fludarabine, Cyclophosphamide) lymphodepletion regimen, lenalidomide, PD-1 inhibitor, ibrutinib and humanized CD19-CART cells. Secondly, mechanism of CD19 relapse can be attributed to the preexisting of CD19- subclone, the loss or alternative RNA splicing on exon 2 of chromosome 16 on which CD19 gene is located, B-cell transcript factors – paired-box 5 (PAX5) and early B-cell factor 1 (EBF1) are down-regulated to cause lineage-switch from lymphoid to myeloid.

Summary
Although different preparation techniques generates various entities of CART 19 cells, these problems could be conquered by novel agents and novel CAR system.

Video abstract
Although Chimeric Antigen Receptor T (CART) cell therapy is best recognized for its antitumor effect in Relapsed/Refractory B-cell hematological cancers, it still shows a high relapse rate. We review mechanisms of failure of CART therapy. http://links.lww.com/COH/A18.
Proprotein convertase subtilisin/kexin type 9 inhibitors and lipoprotein(a)-mediated risk of atherosclerotic cardiovascular disease: more than meets the eye?
Authors: Boffa Michael B. , Koschinsky Marlys L. 
Published: October 2019

Purpose of review
Evidence continues to mount for elevated lipoprotein(a) [Lp(a)] as a prevalent, independent, and causal risk factor for atherosclerotic cardiovascular disease. However, the effects of existing lipid-lowering therapies on Lp(a) are comparatively modest and are not specific to Lp(a). Consequently, evidence that Lp(a)-lowering confers a cardiovascular benefit is lacking. Large-scale cardiovascular outcome trials (CVOTs) of inhibitory mAbs targeting proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) may address this issue.

Recent findings
Although the ability of PCSK9i to lower Lp(a) by 15–30% is now clear, the mechanisms involved continue to be debated, with in-vitro and in-vivo studies showing effects on Lp(a) clearance (through the LDL receptor or other receptors) and Lp(a)/apolipoprotein(a) biosynthesis in hepatocytes. The FOURIER CVOT showed that patients with higher baseline levels of Lp(a) derived greater benefit from evolocumab and those with the lowest combined achieved Lp(a) and LDL-cholesterol (LDL-C) had the lowest event rate. Meta-analysis of ten phase 3 trials of alirocumab came to qualitatively similar conclusions concerning achieved Lp(a) levels, although an effect independent of LDL-C lowering could not be demonstrated.

Summary
Although it is not possible to conclude that PCSK9i specifically lower Lp(a)-attributable risk, patients with elevated Lp(a) could derive incremental benefit from PCSK9i therapy.
Impact of the microbiota on solid organ transplant rejection
Authors: Sepulveda Martin , Pirozzolo Isabella , Alegre Maria-Luisa 
Published: October 2019

Purpose of review
The microbiota in mammalian hosts can affect maturation and function of the immune system and has been associated with health and disease. We will review new findings on how this dynamic environmental factor impacts alloimmunity and therapy in transplant hosts.

Recent findings
The microbiota changes after transplantation and immunosuppressive therapy. New data indicate that different microbial community structures have distinct impact on graft outcome, from promoting, to inhibiting or being neutral to transplant survival. In addition, we will address reciprocal interactions between the microbiota and immunosuppressive drugs, as well as the suitability of the microbiota as a predictive biomarker and its utility as adjunct therapy in transplantation.

Summary
Advances in microbiome sequencing and wider availability of gnotobiotic facilities are enabling mechanistic investigations into the commensal communities and pathways that modulate allograft outcome, responsiveness to immunosuppression and side effects of drugs. A better understanding of the functions of the microbiota may help mitigate drug toxicity, predict drug dosage and dampen alloimmunity in transplant patients.
Harnessing the Electronic Health Record to Distribute Transition Services to Adolescents With Inflammatory Bowel Disease
Authors: Huang Jeannie S. , Yueh Ryan , Wood Kalie , Ma Stacy , Cruz Rusvelda , Boyd Nancy , Kruth Robin , Parker Jacob 
Published: October 2019

ABSTRACTObjectives:The aim of the study was to evaluate feasibility and utility of an electronic health record (EHR) activity to assess transitional readiness, deliver services to meet individual needs, and to track patient progress.Methods:We developed a Transition EHR activity (TEA) to track patients through a standardized process where transition readiness is annually assessed and services distributed based on need. The process assesses transition skills starting at age 12 years and sets goals through shared decision‐making, delivers resources according to need, reviews patients’ personal medical histories, and documents healthcare transfer to adult gastroenterology. We piloted TEA among patients with inflammatory bowel disease (IBD) ages ≥12 years. Distribution to patients was measured and tolerability assessed via patient self‐report evaluations.Results:Since launch, TEA has been distributed to all eligible patients (N = 53) with a median age of 16 (14,18) years (median [IQR]), 62% male, 58% white, 26% Hispanic at our weekly dedicated IBD clinic. All have performed the transition skills’ self‐assessment and practicum, and set transition goals with their healthcare provider. Of these individuals, 41 (77%) participated in survey feedback. On a utility rating scale of 0 (not helpful at all) to 10 (very helpful), patients reported median (IQR) utility scores of 8 (7,10) for the transition readiness assessment, 9 (7,10) for transition resources provided, and 9 (7,10) for the medical history summary. Most (91%) would recommend TEA to other patients.Conclusions:TEA standardized delivery of resources among pediatric IBD patients and was well received and friendly to clinical workflow.
Transglutaminases, neuronal cell death and neural repair: implications for traumatic brain injury and therapeutics
Authors: Basso Manuela , Milelli Andrea 
Published: October 2019

Purpose of review
Traumatic brain injury (TBI) is one of the leading causes of death in the developed world. Despite advances at the bedside, pharmacological interventions have yet to be successful likely because of the need for a better understanding of disease mechanisms as potential targets for intervention. Recent evidence implicates a family of enzymes, namely transglutaminases, in the pathological mechanisms of TBI.

Recent findings
Transglutaminases are multifunctional, calcium-dependent enzymes that are significantly upregulated in TBI. They are known for their transamidase activity that consists of the covalent crosslinking of glutamines and lysines. Recent data support their ability to aminylate proteins with primary amines such as polyamines or monoamines like serotonin and histamine and to regulate gene transcription.

Summary
In this review, we will discuss data that support a role for transglutaminases, in particular transglutaminase 2, in mitochondrial damage, excitotoxicity and inflammation and their relationship to the pathobiology of TBI. We will review past evidence and outline the need for new experiments that could clarify the role of these enzymes in cell injury and death associated with traumatic brain injury.
Aberrant expression of the COX2/PGE2 axis is induced by activation of the RAF/MEK/ERK pathway in BRAFV595E canine urothelial carcinoma
Authors: Yoshitake R. , Saeki K. , Eto S. , Shinada M. , Nakano R. , Sugiya H. , Endo Y. , Fujita N. , Nishimura R. , Nakagawa T. 
Published: October 2019

AbstractCancer-promoting inflammation is an important event in cancer development. The cyclooxygenase 2 (COX2)/prostaglandin E2 (PGE2) axis is a prominent inducer of inflammation. Canine urothelial carcinoma (cUC) uniquely overexpresses PGE2 and is often managed well with COX inhibitor monotherapy. In most cases, cUC tissue harbours homologous human BRAFV600E mutation, which causes aberrant activation of the RAF/MEK/ERK pathway in human cancer. However, mechanisms underlying aberrant PGE2 production and the importance of the BRAF mutation remain unclear. We show that activation of the RAF/MEK/ERK pathway in BRAF mutant cUC cells leads to COX2 overexpression and PGE2 production. Drug screening revealed that treatment with inhibitors of the arachidonic acid cascade (FDR<0.086), RAF/MEK/ERK pathway (FDR<0.067), and p38/JNK pathway (FDR<0.067) significantly reduced PGE2 production in cUC cells. We also validated the association between RAF/MEK/ERK pathway activation and COX2/PGE2 overexpression in BRAF mutant cUC cells using protein detection techniques. In histochemical analysis, BRAF mutant cUC tissue showed higher COX2 expression. Therefore, the driver mutation in the BRAF gene probably promotes tumour-promoting inflammation. These findings would benefit dogs suffering from cUC and can be extrapolated to human cancer. Finally, cUC can serve as a valuable model to elucidate the association between driver mutations and tumour-promoting inflammation.
Role of Proinsulin Self-Association in MutantINSgene-induced Diabetes of Youth
Authors: Sun Jinhong , Xiong Yi , Li Xin , Haataja Leena , Chen Wei , Mir Saiful A. , Madley Rachel , Larkin Dennis , Anjum Arfah , Dhayalan Balamurugan , Rege Nischay , Wickramasinghe Nalinda D. , Weiss Michael A. , Itkin-Ansari Pamela , Kaufman Randal J. , Ostrov David A. , Arvan Peter , Liu Ming 
Published: October 2019

AbstractAbnormal interactions between misfolded mutant and wild-type (WT) proinsulin in the endoplasmic reticulum (ER) drive the molecular pathogenesis of Mutant-INS-gene induced Diabetes of Youth (MIDY). How these abnormal interactions are initiated remains unknown. Normally, proinsulin-WT dimerizes in the ER. Here, we suggest that the normal proinsulin-proinsulin contact surface, involving the B-chain, contributes to dominant-negative effects of misfolded MIDY mutants. Specifically, we find that proinsulin Tyr-B16, which is a key residue in normal proinsulin dimerization, helps confer dominant-negative behavior of MIDY mutant proinsulin-C(A7)Y. Substitutions of Tyr-B16 with ether Ala, Asp, or Pro in proinsulin-C(A7)Y each decrease the abnormal interactions between the MIDY mutant and proinsulin-WT, rescuing proinsulin-WT export, limiting ER stress, and increasing insulin production in β-cells and human islets. This study reveals the first evidence indicating that noncovalent proinsulin-proinsulin contact initiates dominant-negative behavior of misfolded proinsulin, pointing to a novel therapeutic target to enhance bystander proinsulin export for increased insulin production.