bluuebunny/crossref_metadata_2025_split huggingface dataset:
Winning hearts and minds: ECG reporting in the first seizure clinic
Authors: Huang Xuya , Malek N. , Simpson J. , Kalladka D. , Dunn F. G. , Leach J. P. 
Published: July 2021

Abstract
Background and aims
An electrocardiogram (ECG) is a mandatory test for anyone presenting with loss of consciousness. Many referrals to the first seizure clinic (FSC) are caused by syncope. We assessed the sensitivity of neurologists’ ECG reporting in detecting rhythm abnormalities including some potentially life-threatening cardiac conditions.

Methods
We audited patients referred to a FSC in Glasgow over 4 years. All ECGs were interpreted by the attending neurologist as standard practice. Subsequently, two cardiologists reviewed the ECGs independently.

Results
Of 160 consecutive patients, 92 patients (58%) were diagnosed as having seizures, 43 (27%) as syncope, and 25 (16%) were unclassified. Twenty eight ECGs thought to be normal by the neurologist were considered abnormal by the cardiologist, including three with long corrected QT interval. The proportion of abnormal ECGs and disparity in reporting between neurologists and cardiologists persisted independent of the underlying diagnosis.

Conclusion
Reporting of ECGs by non-cardiologists may not be adequately sensitive in picking up potentially life threatening cardiac conditions. Cardiologist input into FSCs is recommended to enhance the diagnostic yield.
Association of monocyte-to-high density lipoprotein ratio with arterial stiffness in patients with diabetes
Authors: Mayasari Dyah Samti , Taufiq Nahar , Hariawan Hariadi 
Published: July 2021

Abstract
Background
Previous studies proposed that chronic inflammation in diabetes has a role in abnormal collagen production and elastin degradation, which promotes arterial stiffness. Monocyte-to-High Density Lipoprotein cholesterol ratio (MHR) is a simple measurement associated with inflammation and oxidative stress. However, little is known about the relationship of MHR with arterial stiffness. This study aimed to determine the association of MHR with arterial stiffness in patients with diabetes.

Methods
A total of 81 patients with type 2 diabetes mellitus were enrolled in a cross-sectional study. Arterial stiffness factor in this study was Cardio Ankle Vascular Index (CAVI). We analyzed complete blood count and lipid profile in all participants, then performed statistical analysis to determine the relationship between MHR and CAVI. Receiver operating characteristic (ROC) analysis was used to estimate the cut-off values of MHR to predict CAVI ≥ 9.

Results
Median of MHR in this study was 11.91 with the mean of CAVI was 8.13 ± 0.93. Spearman correlation analysis revealed a significant positive correlation between MHR and CAVI (ρ = 0.239, p = 0.031). Multivariate analysis showed the independent association of MHR to arterial stiffness (β = 0.361, 95% CI 0.023–0.093) and to CAVI ≥ 9 (OR 1.181, 95% CI 1.047–1.332). The cut-off values of MHR for predicting CAVI ≥ 9 were identified as ≥ 13 (OR 3.289, 95% CI 1.036–10.441).

Conclusion
MHR is associated with CAVI in patients with diabetes, irrespective of various potential confounders.
The onset of ulcerative colitis upon Helicobacter pylori eradication in a 72-year-old woman: report of a rare case with a 3-year follow-up
Authors: Homolak J. , Nikolić M. , Potoč D. , Živković M. , Bakula D. , Budimir I. , Pavić I. , Hrabar D. , Ljubičić N. , Vražić D. 
Published: July 2021

Abstract
Background
Epidemiological studies suggest an inverse association between H. pylori infection/exposure and inflammatory bowel disease prevalence/incidence, however, there are no reports of individual patients who developed a "non-transient” ulcerative colitis (UC) following H. pylori eradication.

Case presentation
We report a case of a 72-year-old female with an elderly-onset UC developed upon H. pylori eradication and a 3-year follow-up of the progression to steroid-dependent colitis complicated with enteropathic arthritis and final containment of the disease with golimumab. In our patient, H. pylori eradication was associated with the development of pancolitis that evolved into clinically, endoscopically, and pathohistologically confirmed UC.

Conclusions
The case of our patient provides a unique clinical context for a growing body of literature suggesting molecular mechanisms involved in the interaction of genes, environment, and microbiota to be of critical importance in the etiopathogenesis of UC, and thus, provides a valuable set of complementary translational information for preclinical and epidemiological research on the topic.
Increasing incidence of non-HBV- and non-HCV-related hepatocellular carcinoma: single-institution 20-year study
Authors: Nagaoki Yuko , Hyogo Hideyuki , Ando Yuwa , Kosaka Yumi , Uchikawa Shinsuke , Nishida Yuno , Teraoka Yuji , Morio Kei , Fujino Hatsue , Ono Atsushi , Nakahara Takashi , Murakami Eisuke , Yamauchi Masami , Okamoto Wataru , Kawaoka Tomokazu , Tsuge Masataka , Hiramatsu Akira , Miki Daiki , Imamura Michio , Takahashi Shoichi , Chayama Kazuaki , Aikata Hiroshi 
Published: July 2021

Abstract
Background
We previously reported on the trends in the etiologies of hepatocellular carcinoma (HCC) diagnosed in patients between 1995 and 2009. The aims of our updated study were to evaluate the incidence, nonhepatitis B and nonhepatitis C viral (NBNC) etiologies, and clinical characteristics of HCCs occurring in patients between 1992 and 2018.

Methods
The study enrolled 2171 consecutive patients with HCC between 1992 and 2018. Their medical records were reviewed. The patients were divided into two groups, patients with early diagnoses from 1992 to 2009 and those with late diagnoses from 2010 to 2018.

Results
NBNC-HCC occurred in 514 patients (23.6%). The percentage of patients with HCC who had NBNC-HCC increased from 26.5% in 2009 to 46.3% in 2018. Patients with NBNC-HCC were older (median ages from 67 to 73 years). Type 2 diabetes mellitus (48.5–60.3%: P = 0.008), hypertension (48.5–57.4%: P = 0.047), and hyperlipidemia (39.2–53.8%: P = 0.001) increased significantly in recent years. The median FIB-4 index decreased (4.37–3.61: P = 0.026) and the median platelet count increased (15.1–17.9 × 104/μL: P = 0.013). Among the 514 patients with NBNC-HCC, 194 underwent hepatic resection for nonalcoholic steatohepatitis (NASH) (15%), alcoholic liver disease (ALD) (29%), and cryptogenic hepatitis (56%). Cirrhosis was detected in 72%, 39%, and 16% of patients with NASH, ALD, and cryptogenic hepatitis, respectively. The prevalence of cirrhosis in patients with NASH was significantly higher than the prevalence of cirrhosis in the other groups (P < 0.001). Overall, 70% of the non-malignant liver tissue of patients with NBNC-HCC was not involved with cirrhosis. On the other hand, the median FIB-4 index in patients with cryptogenic HCC was 2.56, which was a significantly lower value than those values in the other groups of patients. The FIB-4 index considered as one of useful screening of HCC.

Conclusions
The prevalence of NBNC-HCC has increased rapidly even in a regional university hospital. Metabolic syndrome may be an important risk factor for HCC. HCC was also found in patients with non-cirrhotic livers. The FIB-4 index may be a useful screening method for HCC in patients with NBNC.
Impacts of tai chi exercise on functional fitness in community-dwelling older adults with mild degenerative knee osteoarthritis: a randomized controlled clinical trial
Authors: Chen Po-Yin , Song Chen-Yi , Yen Hsin-Yen , Lin Pi-Chu , Chen Su-Ru , Lu Liang-Hsuan , Tien Chen-Li , Wang Xin-Miao , Lin Chueh-Ho 
Published: July 2021

Abstract
Background
Degenerative osteoarthritis (OA) often leads to pain and stiffness of the affected joints, which may affect the physical performance and decrease the quality of life of people with degenerative knee OA. Compared to traditional exercise, tai chi is a safe exercise with slow movements which can facilitate physical functioning and psychological well being, and might be suitable for improving the physical activities of older adults with knee OA. Therefore, this study investigated the impacts of tai chi exercise on the functional fitness of community-dwelling older adults with degenerative knee OA.

Methods
Sixty-eight community-dwelling older adults with knee OA were recruited from the local community to participate in this randomized controlled clinical trial. All subjects were randomly assigned to either an TCE group that practiced tai chi exercise (TCE) (n = 36) or a control group (CON) (n = 32) that received regular health education programs twice per week for 12 weeks. Outcome measurements were determined using functional fitness tests before and after the intervention, including a 30-s chair stand (number of repeats), 30-s arm-curl (number of repeats), 2-min step (number of steps), chair sit-and-reach (reaching distance, cm), back-scratch flexibility (distance between hands, cm), single-leg stand (time, s), functional reach (reaching distance, cm), 8-foot up-and-go (time, s), and 10-m walk tests (time, s). Pre-post comparisons of functional fitness were analyzed using the ANCOVA test with SPSS software version 18.0.

Results
Results revealed that participants’ functional fitness in the TCE group had significantly higher adjusted mean post-tests scores than that in the CON group after the intervention, including the 8-foot up-and-go (s) (mean difference [MD]=-2.92 [-3.93, -1.91], p = 2.39*10− 7), 30-s arm curl (MD = 4.75 (2.76, 6.73), p = 1.11*10− 5), 2-min step (MD = 36.94 [23.53, 50.36], p = 7.08*10− 7), 30-s chair stand (MD = 4.66 [2.97, 6.36], p = 6.96*10− 7), functional-reach (MD = 5.86 [3.52, 8.20], p = 4.72*10− 6), single-leg stand with eyes closed (MD = 3.44 [1.92, 4.97], p = 2.74*10− 5), chair sit-and-reach (MD = 3.93 [1.72, 6.15], p = 0.001), and single-leg stand with eyes opened (MD = 17.07 [6.29, 27.85], p = 0.002), with large effect sizes (η²=0.14 ~ 0.34).

Conclusions
Community-dwelling older adults with knee OA in the TCE group had better functional fitness performances after the 12-week tai chi intervention than those receiving only health education.
Mucosal eosinophilic infiltration may be a characteristic of human intestinal spirochetosis
Authors: Ogata Sho , Shimizu Ken , Tominaga Susumu , Matsukuma Susumu 
Published: July 2021

Abstract
Background
Human intestinal spirochetosis (HIS) is an infectious disease of large intestines caused by Brachyspira species, and most HIS cases are asymptomatic or exhibit mild intestinal symptoms. The host reaction to HIS remains unclear, and we examined HIS-related mucosal inflammatory features histologically.

Methods
From the archival HIS cases in a single medical center, 24 endoscopically taken specimens from 14 HIS cases (male:female = 10:4; 28–73 yrs) were selected as not containing polypoid or neoplastic lesions. Stromal neutrophils, eosinophils, and mast cells, and intraepithelial neutrophils and eosinophils, (sNeu, sEo, sMast, iNeu, and iEo, respectively) were counted, and the presence or absence of lymphoid follicles/aggregates (LFs) was also examined. Association of the above inflammation parameters and spirochetal infection parameters (such as degrees of characteristic fringe distribution, of spirochetal cryptal invasion, and of spirochetal intraepithelial invasion) were also analysed.

Results
iNeu was observed in 29.2%, iEo in 58.3%, and LFs in 50.0% of the specimens. Maximal counts of sNeu, sEo, sMast, iNeu, and iEo averaged 8.4, 21.5, 6.0, 0.5 and 1.5, respectively. Strong correlation between the maximum counts of iNeu and iEo (p < 0.001, r = 0.81), and correlations between those of iEo and sNeu (p = 0.0012, r = 0.62) and between those of iEo and sEo (p = 0.026, r = 0.45) were observed. iNeu was influenced by fringe formation (p < 0.05) and spirochetal crypt involvement (p < 0.05).

Conclusions
HIS was accompanied by inflammatory reactions, and among these, mucosal eosinophilic infiltration may be a central indicator and host reaction of HIS.
Obesity, chronic disease, age, and in-hospital mortality in patients with covid-19: analysis of ISARIC clinical characterisation protocol UK cohort
Authors: Yates Thomas , Zaccardi Francesco , Islam Nazrul , Razieh Cameron , Gillies Clare L. , Lawson Claire A. , Chudasama Yogini , Rowlands Alex , Davies Melanie J. , Docherty Annemarie B. , Openshaw Peter J. M. , Baillie J. Kenneth , Semple Malcolm G. , Khunti Kamlesh 
Published: July 2021

Abstract
Background
Although age, obesity and pre-existing chronic diseases are established risk factors for COVID-19 outcomes, their interactions have not been well researched.

Methods
We used data from the Clinical Characterisation Protocol UK (CCP-UK) for Severe Emerging Infection developed by the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC). Patients admitted to hospital with COVID-19 from 6th February to 12th October 2020 were included where there was a coded outcome following hospital admission. Obesity was determined by an assessment from a clinician and chronic disease by medical records. Chronic diseases included: chronic cardiac disease, hypertension, chronic kidney disease, chronic pulmonary disease, diabetes and cancer. Mutually exclusive categories of obesity, with or without chronic disease, were created. Associations with in-hospital mortality were examined across sex and age categories.

Results
The analysis included 27,624 women with 6407 (23.2%) in-hospital deaths and 35,065 men with 10,001 (28.5%) in-hospital deaths. The prevalence of chronic disease in women and men was 66.3 and 68.5%, respectively, while that of obesity was 12.9 and 11.1%, respectively. Association of obesity and chronic disease status varied by age (p < 0.001). Under 50 years of age, obesity and chronic disease were associated with in-hospital mortality within 28 days of admission in a dose-response manner, such that patients with both obesity and chronic disease had the highest risk with a hazard ratio (HR) of in-hospital mortality of 2.99 (95% CI: 2.12, 4.21) in men and 2.16 (1.42, 3.26) in women compared to patients without obesity or chronic disease. Between the ages of 50–69 years, obesity and chronic disease remained associated with in-hospital COVID-19 mortality, but survival in those with obesity was similar to those with and without prevalent chronic disease. Beyond the age of 70 years in men and 80 years in women there was no meaningful difference between those with and without obesity and/or chronic disease.

Conclusion
Obesity and chronic disease are important risk factors for in-hospital mortality in younger age groups, with the combination of chronic disease and obesity being particularly important in those under 50 years of age. These findings have implications for targeted public health interventions, vaccination strategies and in-hospital clinical decision making.
Characteristic of HBV nucleic acid amplification testing yields from blood donors in China
Authors: Wu Danxiao , Wang Xiaojuan , Feng Fangjun , Wang Dairong , Hu Yiqin , Yu Yang , Huang Jihong , Wang Min , Dong Jie , Wu Yaling , Zhu Hong , Zhu Faming 
Published: July 2021

Abstract
Background
Nucleic acid amplification testing (NAT) for blood screening has been previously performed in some countries to determine NAT yields. The current study sought to explore the non-discriminating reactive NAT yields using individual-NAT (ID-NAT) and characteristics of HBV NAT yields through a 10-year retrospective analysis in Zhejiang, China.

Methods
Blood donations were analyzed using individual-NAT mode by the transcription-mediated amplification (TMA) method. Supplementary HBV serological tests were performed using chemiluminescent immunoassay, and HBV viral load assay was performed by real-time polymerase chain reaction. Follow-up studies were performed in partial donors with low HBV viral loads.

Results
Non-discriminating reactive NAT yields and HBV NAT yields varied in different years. The yields ranged from 853.73 per million to 2018.68 per million and 624.60 per million to 1669.50 per million, respectively. In the 476 NAT yields, 19 were probable window periods (WP), 33 probable occult hepatitis B virus infections (OBIs), 409 were confirmed OBIs and 15 were chronic HBV infections. ID-NAT results were categorized in four groups, and the findings showed that the levels of HBV DNA viral loads were different in the four different groups (χ2 = 275.02, p < 0.01). HBV viral load distribution was significantly different between anti-HBs positive and anti-HBc positive samples (χ2 = 49.429, p < 0.01). Notably, only 42.03% donors were NAT repeated positive in the 138 repeat donors’ follow up tests.

Conclusion
NAT screening of blood donations can reduce the risk of transfusion-transmitted HBV infections. Positive proportions of anti-HBs and anti-HBc are correlated with the HBV viral load level. However, low level of viral load donors pose risks in HBV NAT assays, and show fluctuating state for HBV viral load and leads to non-repeated NAT results during follow up studies.
Visualization of the human enteric nervous system by probe confocal laser endomicroscopy: a first real-time observation of Hirschsprung’s disease and allied disorders
Authors: Harada Atsushi , Shimojima Naoki , Kobayashi Masakuni , Kamba Shunsuke , Hirobe Seiichi , Sumiyama Kazuki 
Published: July 2021

Abstract
Background
Our group previously proved that the human enteric nervous system can be visualized with confocal laser endomicroscopy after topical application of cresyl violet using surgically resected intestine specimens. The present report documents the first in vivo visualization of the human enteric nervous system with confocal laser endomicroscopy using local cresyl violet staining. The aim of this study was to evaluate the technical feasibility and clinical efficiency of confocal laser endomicroscopy in patients with Hirschsprung’s disease and allied disorders in vivo.

Methods
Confocal laser endomicroscopy was performed in vivo in two patients to confirm the presence of the enteric nervous system during surgery in patients with Hirschsprung’s disease and allied disorders. Cresyl violet was gently injected from the serosal side into the muscular layer of the intestine, and scanning was performed within 30 min. Then, the scanned intestines were resected, and the visualized area of the specimens was pathologically evaluated.

Results
The ganglion cell nuclei and the enteric nervous system network were clearly visualized intraoperatively in both cases. The morphological findings were similar to the pathological findings of the enteric nervous system in both cases although the period of visibility was brief.

Conclusion
This study demonstrated the first, real-time observation of the enteric nervous system in humans using confocal laser endomicroscopy and suggest the potential to identify the enteric nervous system intra-operatively during surgery for Hirschsprung’s disease and allied disorders.
Salvage surgery for patients with residual/persistent diseases after improper or insufficient treatment of oral squamous cell carcinoma: can we rectify these mistakes?
Authors: He Yue , Liu Zhonglong , Sheng Surui , Gao Weijin , Tang Xiao , Li Xiaoguang , Ma Chunyue 
Published: July 2021

Abstract
Background
Patterns of failure after treatment of oral and squamous cell carcinomas (OSCC) are diversified, with recurrences being one of the common causes. A special group of patients are sometimes encountered in the outpatient clinic for improper or insufficient initial treatment with reports of positive margins, implying residual/persistent diseases. The question of whether these patients can be surgically salvaged remain unanswered.

Methods
A retrospective study was performed between January 2013 and December 2017 for patients with residual or rapid recurrent (within 3 months) OSCCs, who received salvage surgeries in our institution. The patients with residual/persistent OSCCs were those with microscopic or macroscopic positive surgical margins, while those with rapid recurrent OSCCs were those with close or negative margins, but unabated painful symptoms right after treatment. Both clinicopathological and prognostic variables were analyzed. The focus was also directed towards lessons for possible initial mistakes, resulting in these residual/persistent diseases.

Results
Of 103 patients, 68 (66%) were men, with mean age of 56.3 years. The overall survival reached 60.2%. Regarding the primary OSCC status, most of our patients (n = 75, 72.8%) were diagnosed with ycT2–3 stages. Besides, most patients were found with macroscopic residual diseases (52.4%) before our salvage surgery. The sizes of the residual/persistent OSCCs were generally under 4 cm (87.3%) with minimally residual in 21 (20.4%). Among all the variables, primary T stage (p = 0.003), and residual lesion size (p < 0.001) were significantly associated with the prognosis in multivariate analysis. Though the causes for the initial surgical failure were multifactorial, most were stemmed from poor planning and unstandardized execution.

Conclusions
Cases with residual/persistent OSCCs were mostly due to mistakes which could have been avoided under well-round treatment plans and careful surgical practice. Salvage surgery for cases with smaller residual/persistent OSCCs is still feasible with acceptable outcomes.
Characterization of newly established Pralatrexate-resistant cell lines and the mechanisms of resistance
Authors: Oiwa Kana , Hosono Naoko , Nishi Rie , Scotto Luigi , O’Connor Owen A. , Yamauchi Takahiro 
Published: July 2021

Abstract
Background
Pralatrexate (PDX) is a novel antifolate approved for the treatment of patients with relapsed/refractory peripheral T-cell lymphoma, but some patients exhibit intrinsic resistance or develop acquired resistance. Here, we evaluated the mechanisms underlying acquired resistance to PDX and explored potential therapeutic strategies to overcome PDX resistance.

Methods
To investigate PDX resistance, we established two PDX-resistant T-lymphoblastic leukemia cell lines (CEM and MOLT4) through continuous exposure to increasing doses of PDX. The resistance mechanisms were evaluated by measuring PDX uptake, apoptosis induction and folate metabolism-related protein expression. We also applied gene expression analysis and methylation profiling to identify the mechanisms of resistance. We then explored rational drug combinations using a spheroid (3D)-culture assay.

Results
Compared with their parental cells, PDX-resistant cells exhibited a 30-fold increase in half-maximal inhibitory concentration values. Induction of apoptosis by PDX was significantly decreased in both PDX-resistant cell lines. Intracellular uptake of [14C]-PDX decreased in PDX-resistant CEM cells but not in PDX-resistant MOLT4 cells. There was no significant change in expression of dihydrofolate reductase (DHFR) or folylpolyglutamate synthetase (FPGS). Gene expression array analysis revealed that DNA-methyltransferase 3β (DNMT3B) expression was significantly elevated in both cell lines. Gene set enrichment analysis revealed that adipogenesis and mTORC1 signaling pathways were commonly upregulated in both resistant cell lines. Moreover, CpG island hypermethylation was observed in both PDX resistant cells lines. In the 3D-culture assay, decitabine (DAC) plus PDX showed synergistic effects in PDX-resistant cell lines compared with parental lines.

Conclusions
The resistance mechanisms of PDX were associated with reduced cellular uptake of PDX and/or overexpression of DNMT3B. Epigenetic alterations were also considered to play a role in the resistance mechanism. The combination of DAC and PDX exhibited synergistic activity, and thus, this approach might improve the clinical efficacy of PDX.