bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of quality certification of multidisciplinary head and neck tumor centers
Authors: Modabber Ali , Schick Daniel , Goloborodko Evgeny , Peters Florian , Heitzer Marius , Bock Anna , Kniha Kristian , Hölzle Frank , Schreiber Elke M. , Möhlhenrich Stephan Christian 
Published: April 2021

Abstract
Background
Certification of multidisciplinary tumor centers is nowadays seen as the gold standard in modern oncological therapy for optimization and realization of guideline-based therapy and better outcomes. Single cases are reimbursed based on diagnosis-related groups (DRG). We aimed to review efficiency, cost analysis, and profitability following a certification.

Methods
Tumor board certification at the university hospital Aachen was implemented in 2013. We compared 1251 cases of oropharyngeal cancer treated from 2008 to 2017 before and after certification. For this purpose, several patient characteristics, surgery, and stay-related constants, as well as expenses and reimbursement heights were analyzed statistically.

Results
Following certification, the total case and patient number, surgery duration, hours of mechanical ventilation, case mix index points, DRG reimbursements as well as the costs increased significantly, whereas days of intensive care unit, amount of blood transfusions, patient clinical complexity level (PCCL) and the overall stay were significantly lowered. No changes were observed for the patient’s age and gender distribution. Also, the predetermined stay duration stayed constant.

Conclusions
Certification of head-neck tumor centers causes a concentration of more complex cases requiring higher surgical efforts, which can be processed more efficiently due to a higher level of professionalism. Despite their benefits in cancer care, without compensation, centers may be struggling to cover their expenses in a system, which continuously underestimates them.
Longitudinal trajectories of diet quality and subsequent mortality among Chinese adults: results from the China health and nutrition survey 1997–2015
Authors: Liu Ming-wei , McNaughton Sarah A. , He Qi-qiang , Leech Rebecca 
Published: April 2021

Abstract
Background
China has witnessed a significant nutritional transition. However, there is a gap in the literature investigating the association between change of diet and mortality among Chinese. Thus, we aimed to explore the longitudinal trajectories of diet quality over 10 years (from 1997 to 2006) and the subsequent risk of death till 2015 among Chinese adults.

Methods
Data from the China Health and Nutrition Survey were analyzed in 6398 adults. Dietary intake was assessed using three consecutive 24-h recalls. Diet quality was assessed by the Chinese Healthy Eating Index (CHEI), which includes 17 components and is based on the Dietary Guidelines for Chinese. Latent Class Growth Analysis was conducted to derive trajectories of diet quality over 10 years. Cox proportional hazard regression was used to calculate hazard ratios for total mortality.

Results
Four distinct CHEI trajectories were identified: 1) worsening; 2) low-moderate-low; 3) improving; 4) high-moderate-high. Group 3 had the lowest mortality rate (5.6%) in the subsequent 9 years, while the groups with worsening or low diet quality had a higher mortality rate (Group 1: 7.5%; Group 2: 10.8%). In the fully adjusted model, compared to group 2, mortality rates were lower for group 3 (RR = 0.73; 95% CI: 0.55, 0.97) and group 4 (RR = 0.76; 95% CI: 0.59, 0.98). No associations with mortality were found for the group 1, when compared to group 2.

Conclusions
Long-term improved diet quality and adherence to the Dietary Guidelines for Chinese may decrease the risk of death in Chinese adults.
Relationship between gait quality measures and modular neuromuscular control parameters in chronic post-stroke individuals
Authors: Shin Sung Yul , Kim Yusung , Jayaraman Arun , Park Hyung-Soon 
Published: April 2021

Abstract
Background
Recent evidence suggests that disinhibition and/or hyperexcitation of the brainstem descending pathways and intraspinal motor network diffuse spastic synergistic activation patterns after stroke. This results in simplified or merged muscle sets (i.e., muscle modules or synergies) compared to non-impaired individuals and this leads to poor walking performance. However, the relations of how these neuromuscular deficits influence gait quality (e.g., symmetry or natural walking patterns) are still unclear. The objective of this exploratory study was to investigate the relations of modular neuromuscular framework and gait quality measures in chronic stroke individuals.

Methods
Sixteen chronic post-stroke individuals participated in this study. Full lower body three-dimensional kinematics and electromyography (EMG) were concurrently measured during overground walking at a comfortable speed. We first examined changes in gait quality measures across the number of muscle modules using linear regression model. Then, a stepwise multiple regression was used to investigate the optimal combination of the neuromuscular parameters that associates with gait quality measures.

Results
We observed that subjects who had a lower number of muscle modules revealed reduced function (i.e., speed) and greater asymmetry in the kinematic parameters including limb length, footpath area, knee flexion/extension, and hip abduction/adduction (all p < 0.05). We also found that the combination of input variables from the modular neuromuscular control framework significantly associated with gait quality measures (average $${R}^{2}=42.5\mathrm{\%}$$

R

2

=
42.5
%

). Those variables included variability accounted for ($$VAF$$

VAF

) information from the muscle modules and area under the EMG envelope curves of the quadriceps (i.e., rectus femoris and vastus lateralis) and tibialis anterior muscles.

Conclusions
The results suggest that there exists a significant correlation between the neuromuscular control framework and the gait quality measures. This study helps to understand the underlying mechanism of disturbances in gait quality and provides insight for a more comprehensive outcome measure to assess gait impairment after stroke.
Discriminating the eight genotypes of the porcine circovirus type 2 with TaqMan-based real-time PCR
Authors: Link Ellen Kathrin , Eddicks Matthias , Nan Liangliang , Ritzmann Mathias , Sutter Gerd , Fux Robert 
Published: April 2021

Abstract
Background
The porcine circovirus type 2 (PCV2) is divided into eight genotypes including the previously described genotypes PCV2a to PCV2f and the two new genotypes PCV2g and PCV2h. PCV2 genotyping has become an important task in molecular epidemiology and to advance research on the prophylaxis and pathogenesis of PCV2 associated diseases. Standard genotyping of PCV2 is based on the sequencing of the viral genome or at least of the open reading frame 2. Although, the circovirus genome is small, classical sequencing is time consuming, expensive, less sensitive and less compatible with mass testing compared with modern real-time PCR assays. Here we report about a new PCV2 genotyping method using qPCR.

Methods
Based on the analysis of several hundred PCV2 full genome sequences, we identified PCV2 genotype specific sequences or single-nucleotide polymorphisms. We designed six TaqMan PCR assays that are specific for single genotypes PCV2a to PCV2f and two qPCRs targeting two genotypes simultaneously (PCV2g/PCV2d and PCV2h/PCV2c). To improve specific binding of oligonucleotide primers and TaqMan probes, we used locked nucleic acid technology. We evaluated amplification efficiency, diagnostic sensitivity and tested assay specificity for the respective genotypes.

Results
All eight PCV2 genotype specific qPCRs demonstrated appropriate amplification efficiencies between 91 and 97%. Testing samples from an epidemiological field study demonstrated a diagnostic sensitivity of the respective genotype specific qPCR that was comparable to a highly sensitive pan-PCV2 qPCR system. Genotype specificity of most qPCRs was excellent. Limited unspecific signals were obtained when a high viral load of PCV2b was tested with qPCRs targeting PCV2d or PCV2g. The same was true for the PCV2a specific qPCR when high copy numbers of PCV2d were tested. The qPCR targeting PCV2h/PCV2c showed some minor cross-reaction with PCV2d, PCV2f and PCV2g.

Conclusion
Genotyping of PCV2 is important for routine diagnosis as well as for epidemiological studies. The introduced genotyping qPCR system is ideal for mass testing and should be a valuable complement to PCV2 sequencing, especially in the case of simultaneous infections with multiple PCV2 genotypes, subclinically infected animals or research studies that require large sample numbers.
Obesity and intestinal stem cell susceptibility to carcinogenesis
Authors: Pourvali Katayoun , Monji Hadi 
Published: April 2021

Abstract
Background
Obesity is a top public health problem associated with an increase in colorectal cancer incidence. Stem cells are the chief cells in tissue homeostasis that self-renew and differentiate into other cells to regenerate the organ. It is speculated that an increase in stem cell pool makes cells susceptible to carcinogenesis. In this review, we looked at the recent investigations linking obesity/high-fat diet-induced obesity to intestinal carcinogenesis with regard to intestinal stem cells and their niche.

Findings
High-fat diet-induced obesity may rise intestinal carcinogenesis by increased Intestinal stem cells (ISC)/progenitor’s population, stemness, and niche independence through activation of PPAR-δ with fatty acids, hormonal alterations related to obesity, and low-grade inflammation. However, these effects may possibly relate to the interaction between fats and carbohydrates, and not a fatty acid per se. Nonetheless, literature studies are inconsistency in their results, probably due to the differences in the diet components and limitations of genetic models used.

Conclusion
High-fat diet-induced obesity affects carcinogenesis by changing ISC proliferation and function. However, a well-matched diet and the reliable colorectal cancer models that mimic human carcinogenesis is necessary to clearly elucidate the influence of high-fat diet-induced obesity on ISC behavior.
Massive parallel sequencing in a family with rectal cancer
Authors: Wallander Karin , Thutkawkorapin Jessada , Sahlin Ellika , Lindblom Annika , Lagerstedt-Robinson Kristina 
Published: April 2021

Abstract
Background
We have previously reported a family with a suspected autosomal dominant rectal and gastric cancer syndrome without any obvious causative genetic variant. Here, we focused the study on a potentially isolated rectal cancer syndrome in this family.

Methods
We included seven family members (six obligate carriers). Whole-exome sequencing and whole-genome sequencing data were analyzed and filtered for shared coding and splicing sequence and structural variants among the affected individuals.

Results
When considering family members with rectal cancer or advanced adenomas as affected, we found six new potentially cancer-associated variants in the genes CENPB, ZBTB20, CLINK, LRRC26, TRPM1, and NPEPL1. All variants were missense variants and none of the genes have previously been linked to inherited rectal cancer. No structural variant was found.

Conclusion
By massive parallel sequencing in a family suspected of carrying a highly penetrant rectal cancer predisposing genetic variant, we found six genetic missense variants with a potential connection to the rectal cancer in this family. One of them could be a high-risk genetic variant, or one or more of them could be low risk variants. The p.(Glu438Lys) variant in the CENPB gene was found to be of particular interest. The CENPB protein binds DNA and helps form centromeres during mitosis. It is involved in the WNT signaling pathway, which is critical for colorectal cancer development and its role in inherited rectal cancer needs to be further examined.
FDG-PET/CT in intensive care patients with bloodstream infection
Authors: Pijl Jordy P. , Londema Mark , Kwee Thomas C. , Nijsten Maarten W. N. , Slart Riemer H. J. A. , Dierckx Rudi A. J. O. , van der Voort Peter H. J. , Glaudemans Andor W. J. M. , Pillay Janesh 
Published: April 2021

Abstract
Background
2-Deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) is an advanced imaging technique that can be used to examine the whole body for an infection focus in a single examination in patients with bloodstream infection (BSI) of unknown origin. However, literature on the use of this technique in intensive care patients is scarce. The purpose of this study was to evaluate the diagnostic yield of FDG-PET/CT in intensive care patients with BSI.

Methods
In this retrospective cohort study, all intensive care patients from our Dutch university medical center who had culture-proven BSI between 2010 and 2020 and underwent FDG-PET/CT to find the focus of infection were included. Diagnostic performance was calculated and logistic regression analysis was performed to evaluate the association between FDG-PET/CT outcome and C-reactive protein level (CRP), leukocyte count, duration of antibiotic treatment, duration of ICU stay, quality of FDG-PET/CT, and dependency on mechanical ventilation. In addition, the impact of FDG-PET/CT on clinical treatment was evaluated.

Results
30 intensive care patients with BSI were included. In 21 patients, an infection focus was found on FDG-PET/CT which led to changes in clinical management in 14 patients. FDG-PET/CT achieved a sensitivity of 90.9% and specificity of 87.5% for identifying the focus of infection. Poor quality of the FDG-PET images significantly decreased the likelihood of finding an infection focus as compared to reasonable or good image quality (OR 0.16, P = 0.034). No other variables were significantly associated with FDG-PET/CT outcome. No adverse events during the FDG-PET/CT procedure were reported.

Conclusion
FDG-PET/CT has a high diagnostic yield for detecting the infection focus in patients with BSI admitted to intensive care. Poor PET image quality was significantly associated with a decreased likelihood of finding the infection focus in patients with BSI. This could be improved by adequate dietary preparation and cessation of intravenous glucose and glucose-regulating drugs. Recent advances in PET/CT technology enable higher image quality with shorter imaging time and may contribute to routinely performing FDG-PET/CT in intensive care patients with BSI of unknown origin.
The role of intra-articular neuronal CCR2 receptors in knee joint pain associated with experimental osteoarthritis in mice
Authors: Ishihara Shingo , Obeidat Alia M. , Wokosin David L. , Ren Dongjun , Miller Richard J. , Malfait Anne-Marie , Miller Rachel E. 
Published: April 2021

Abstract
Background
C–C chemokine receptor 2 (CCR2) signaling plays a key role in pain associated with experimental murine osteoarthritis (OA) after destabilization of the medial meniscus (DMM). Here, we aimed to assess if CCR2 expressed by intra-articular sensory neurons contributes to knee hyperalgesia in the early stages of the model.

Methods
DMM surgery was performed in the right knee of 10-week-old male wild-type (WT), Ccr2 null, or Ccr2RFP C57BL/6 mice. Knee hyperalgesia was measured using a Pressure Application Measurement device. CCR2 receptor antagonist (CCR2RA) was injected systemically (i.p.) or intra-articularly (i.a.) at different times after DMM to test its ability to reverse knee hyperalgesia. In vivo Ca2+ imaging of the dorsal root ganglion (DRG) was performed to assess sensory neuron responses to CCL2 injected into the knee joint cavity. CCL2 protein in the knee was measured by ELISA. Ccr2RFP mice and immunohistochemical staining for the pan-neuronal marker, protein gene product 9.5 (PGP9.5), or the sensory neuron marker, calcitonin gene-related peptide (CGRP), were used to visualize the location of CCR2 on intra-articular afferents.

Results
WT, but not Ccr2 null, mice displayed knee hyperalgesia 2–16 weeks after DMM. CCR2RA administered i.p. alleviated established hyperalgesia in WT mice 4 and 8 weeks after surgery. Intra-articular injection of CCL2 excited sensory neurons in the L4-DRG, as determined by in vivo calcium imaging; responses to CCL2 increased in mice 20 weeks after DMM. CCL2, but not vehicle, injected i.a. rapidly caused transient knee hyperalgesia in naïve WT, but not Ccr2 null, mice. Intra-articular CCR2RA injection also alleviated established hyperalgesia in WT mice 4 and 7 weeks after surgery. CCL2 protein was elevated in the knees of both WT and Ccr2 null mice 4 weeks after surgery. Co-expression of CCR2 and PGP9.5 as well as CCR2 and CGRP was observed in the lateral synovium of naïve mice; co-expression was also observed in the medial compartment of knees 8 weeks after DMM.

Conclusions
The findings suggest that CCL2-CCR2 signaling locally in the joint contributes to knee hyperalgesia in experimental OA, and it is in part mediated through direct stimulation of CCR2 expressed by intra-articular sensory afferents.
Analysis of the clinical characteristics of insulin autoimmune syndrome induced by exogenous insulin in diabetic patients
Authors: Li Zuojun , Yi Dan , Zheng Lijuan , Li Shiran , Fang Weijin , Wang Chunjiang 
Published: April 2021

Abstract
Background
The exact incidence, clinical features and uniform diagnostic criteria of exogenous insulin autoimmune syndrome (EIAS) are still unclear. The purpose of this study is to explore the clinical characteristics of EIAS and to provide a structural approach for clinical diagnosis, treatment and prevention.

Methods
The literature on EIAS in Chinese and English from 1970 to 2020 was collected for retrospective analysis.

Results
A total of 122 patients (33 males and 73 females) were included in the study with a median age of 67 years (range 14–86) and a median HbA1c of 7.7%. EIAS mainly occurred in type 2 diabetes mellitus patients using premixed insulin. Symptoms manifested were hypoglycemia in 86.54%, recurrent episodes of symptomatic hypoglycemia in 35.58%, nocturnal hypoglycemia along with daytime hyperglycemia in 21.15% and recurrent hypoglycemia after discontinued insulin in 64.43%. The onset of symptoms occurred at night, in the early morning or during fasting, ranging from a few days to 78 months after the administration of insulin. The mean blood glucose level during the hypoglycemic phase was 2.21 mmol/L (range 1–3.4), and the serum insulin levels were mainly ≥ 100 U/mL and were associated with low C-peptide levels (≤ 10 ng/ml). Insulin autoantibodies (IAAs) were positive in all EIAS patients. The 75-g extended oral glucose tolerance test (OGTT) mainly showed a diabetic curve. Pancreatic imaging was unremarkable. Withdrawal of insulin alone or combination of oral hypoglycemic agents or replacement of insulin formulations or with corticosteroid treatment eliminated hypoglycemia in a few days to 3 months. IAA turned negative in 6 months (median, range 1–12). No hypoglycemia episodes were observed at a median follow-up of 6 months (range 0.5–60).

Conclusions
EIAS is an autoimmune disease caused by insulin-binding antibodies in susceptible subjects. Insulin antibodies change glucose dynamics and could increase the incidence of hypoglycemic episodes. Detection of insulin antibodies is the diagnostic test. Changing therapeutic modalities reduced the incidence of hypoglycemic episodes.
Athletic identity and sport commitment in athletes after anterior cruciate ligament reconstruction who have returned to sports at their pre-injury level of competition
Authors: Ohji Shunsuke , Aizawa Junya , Hirohata Kenji , Mitomo Sho , Ohmi Takehiro , Jinno Tetsuya , Koga Hideyuki , Yagishita Kazuyoshi 
Published: April 2021

Abstract
Background
This study aimed to determine the relationships between athletic identity and sport commitment and return to sports (RTS) status in athletes after anterior cruciate ligament reconstruction (ACLR).

Methods
Thirty-nine participants post-ACLR (8–24 months) were included in this cross-sectional study. Measures included the athletic identity measurement scale and sport commitment scale. In addition, we measured kinesiophobia and psychological readiness using the Tampa Scale for Kinesiophobia and ACL-Return to sport after injury scale. The subjects were categorized into Yes-RTS or No-RTS based on two questions to determine whether they were returning to sport at the same level of competition as before the injury. A Chi-squared test, Fisher’s exact test, unpaired t-test, and Mann-Whitney’s U test were used to analyze the data.

Results
The Yes-RTS group had significantly higher scores on the athletic identity measurement scale (P = 0.023, effect size [ES] = − 0.36), sport commitment scale (P = 0.027, ES = − 0.35), and ACL-Return to sport after injury scale (P = 0.002, ES = − 0.50) and significantly lower Tampa Scale for Kinesiophobia scores (P = 0.014, ES = − 0.39) compared to the No-RTS group.

Conclusion
Athletes who returned to sports at the same level of competition as before the injury had higher athletic identity and sport commitment and lower kinesiophobia compared to those who did not return to sports at the same level of competition. These self-beliefs regarding sport may play an important role in post-ACLR athletes’ RTS.
The dark side of histones: genomic organization and role of oncohistones in cancer
Authors: Amatori Stefano , Tavolaro Simona , Gambardella Stefano , Fanelli Mirco 
Published: April 2021

Abstract
Background
The oncogenic role of histone mutations is one of the most relevant discovery in cancer epigenetics. Recurrent mutations targeting histone genes have been described in pediatric brain tumors, chondroblastoma, giant cell tumor of bone and other tumor types. The demonstration that mutant histones can be oncogenic and drive the tumorigenesis in pediatric tumors, led to the coining of the term “oncohistones.” The first identified histone mutations were localized at or near residues normally targeted by post-translational modifications (PTMs) in the histone N-terminal tails and suggested a possible interference with histone PTMs regulation and reading.

Main body
In this review, we describe the peculiar organization of the multiple genes that encode histone proteins, and the latter advances in both the identification and the biological role of histone mutations in cancer. Recent works show that recurrent somatic mutations target both N-terminal tails and globular histone fold domain in diverse tumor types. Oncohistones are often dominant-negative and occur at higher frequencies in tumors affecting children and adolescents. Notably, in many cases the mutations target selectively only some of the genes coding the same histone protein and are frequently associated with specific tumor types or, as documented for histone variant H3.3 in pediatric glioma, with peculiar tumors arising from specific anatomic locations.

Conclusion
The overview of the most recent advances suggests that the oncogenic potential of histone mutations can be exerted, together with the alteration of histone PTMs, through the destabilization of nucleosome and DNA–nucleosome interactions, as well as through the disruption of higher-order chromatin structure. However, further studies are necessary to fully elucidate the mechanism of action of oncohistones, as well as to evaluate their possible application to cancer classification, prognosis and to the identification of new therapies.