bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential diagnosis of Crohn’s disease and intestinal tuberculosis: development and assessment of a nomogram prediction model
Authors: Zeng Shaoxiong , Lin Ying , Guo Jiaxiang , Chen Xi , Liang Qiong , Zhai Xiaoming , Tao Jin 
Published: November 2022

Abstract
Background
China is a region with a high incidence of tuberculosis, and the incidence of IBD has also been rising rapidly in recent years. Differentiating Crohn’s disease(CD) from intestinal tuberculosis (ITB) has become a very challenging issue. We aimed to develop and assess a diagnostic nomogram to differentiate between CD and ITB to improve the accuracy and practicability of the model.

Methods
A total of 133 patients (CD 90 and ITB 43) were analyzed retrospectively. Univariate and multivariate logistic regression analysis was included to determine the independent predictive factors and establish the regression equation. On this basis, the nomogram prediction model was constructed. The discrimination, calibration and clinical efficiency of the nomogram were assessed using area under the curve(AUC), C-index, calibration curve, decision curve analysis (DCA) and clinical impact curve.

Results
T-SPOT positive, cobblestone appearance, comb sign and granuloma were significant predictors in differentiating CD from ITB. Base on the above independent predictors, a diagnostic nomogram was successfully established. The sensitivity, specificity, accuracy of the prediction model are 94.4%, 93.0%, 94.0% respectively. The AUC and the C-index of the prediction model are both 0.988, which suggest that the model had a good discrimination power. The calibration curve indicated a high calibration degree of the prediction model. The DCA and clinical impact curve indicated a good clinical efficiency of the prediction model which could bring clinical benefits.

Conclusion
A nomogram prediction model for distinguishing CD from ITB was developed and assessed, with high discrimination, calibration and clinical efficiency. It can be used as an accurate and convenient diagnostic tool to distinguish CD from ITB, facilitating clinical decision-making.
Prediction of long-term remission in patients following discontinuation of anti-TNF therapy in ulcerative colitis: a 10 year follow up study
Authors: Johnsen Kay-Martin , Florholmen Jon , Moe Øystein K. , Gundersen Mona , Beilfuss Julia , Kileng Hege , Sørbye Sveinung W. , Goll Rasmus 
Published: November 2022

Abstract
Background
The long-term outcomes of Ulcerative colitis (UC) after discontinuation of biological therapy are largely unknown. There is also a lack of accurate and validated markers that can predict outcome after withdrawal accurately. The aims of this study were to describe the long-term outcomes in UC patients following cessation of anti-TNF therapy and explore potential biomarkers as an approach towards precision medicine.

Methods
Seventy-five patients with moderate to severe UC treated to remission with anti-tumor necrosis factor (TNF) were included in the study. This is a follow-up of previously reported UC outcomes. The patients were categorized as either “Remission” or “Relapse”. The “Relapse” group was divided into subgroups determined by the highest treatment level needed to obtain remission the last 3 years of observation: non-biological therapy, biological therapy or colectomy. Remission were divided in long term remission (LTR), those using immunomodulating drugs (LTR + imids) and those using only 5-amino-salicylate (5-ASA) treatment (LTR) for the past 3 years. Analyses of mucosal gene expression by real-time PCR were performed.

Results
The median (IQR) observation time of all patients included was 121 (111–137) months. Of the 75 patients, 46 (61%) did not receive biological therapy, including 23 (31%) in LTR ± imids. Of these 23 patients, 16 (21%) were defined as LTR with a median observation time of (IQR) 95 (77–113) months. In total 14 patients (19%) underwent colectomy during the 10 years after first remission. Mucosal TNF copies/µg mRNA < 10 000 at anti-TNF discontinuation predicted long-term remission, biological free remission and lower risk of colectomy with a HR 0.36 (0.14–0.92) for long-term remission, HR 0.17 (0.04–0.78) for biological free remission and HR 0.12 (0.01–0.91) for colectomy. IL1RL1 was normalized in LTR phenotype and higher in relapsing UC.

Conclusion
In this 10-year follow-up of UC of patients with moderate to severe disease, 61% of patients experience an altered phenotype to a milder disease course without need of biological therapy. Twenty-one percent of the patients were LTR without any medication except of 5-ASA. Mucosal TNF gene expression and IL1RL1- transcripts may be of clinical utility for long term prognosis in development of precision medicine in UC.
Epidemiology and prognostic analysis of patients with pancreatic signet ring cell carcinoma: a population-based study
Authors: Nie Duorui , Lan Qingxia , Huang Yue , Fang Chongkai , Cao Yang , Chen Yao 
Published: November 2022

Abstract
Background
Pancreatic signet ring cell carcinoma (PSRCC) is a rare tumour subtype with poorly understood epidemiological characteristics and prognosis. We attempted to comprehensively characterise the epidemiology and survival outcomes of PSRCC.

Methods
Patients diagnosed with PSRCC between 2000 and 2018 were identified using Surveillance, Epidemiology and End Results Stat 8.3.9.2 software. Age-adjusted incidence and survival were calculated. Survival curves were plotted using the Kaplan–Meier method, and the differences between survival curves were compared using the log-rank test. Cox proportional hazards models were used to evaluate factors that independently predict overall survival. The primary analysis was a complete case analysis; multiple imputations were employed in a sensitivity analysis.

Results
We identified 585 eligible patients with PSRCC. The overall annual incidence from 2000 to 2018 was 0.349 (95% CI, 0.321–0.379) per million population. The incidence increased significantly in patients over 55 years of age and peaked at about 80 years of age (2.12 per million). Males and Black patients had the highest incidence. The observed survival rates at 1, 2 and 5 years were 20.1, 8.3 and 3.4%, respectively. Survival analysis revealed that primary surgery and chemotherapy are effective treatments for patients with PSRCC (P < 0.05). According to multivariate Cox regression analysis, early stage and receiving surgery and chemotherapy were favourable factors (P < 0.05). Similar conclusions were drawn from the interpolated data.

Conclusions
PSRCC is a highly malignant tumour that predominates in elderly, male and Black patients. The prognosis is poor with a 5-year survival rate of 3.4%; however, multivariate analysis and adjusted models accounting for missing data revealed that early diagnosis, surgery and chemotherapy are effective in improving the prognosis.
A pragmatic randomized controlled trial of rapid on-site influenza and respiratory syncytial virus PCR testing in paediatric and adult populations
Authors: Bibby Helen L. , de Koning Lawrence , Seiden-Long Isolde , Zelyas Nathan , Church Deirdre L. , Berenger Byron M. 
Published: November 2022

Abstract
Background
Rapid/point-of-care respiratory virus nucleic acid tests (NAT) may improve oseltamivir, antibiotic, diagnostic test, and hospital bed utilization. Previous randomized controlled trials (RCT) on this topic have not used standard procedures of an accredited healthcare and laboratory system.

Methods
We conducted a parallel RCT at two hospitals [paediatric = Alberta Children’s Hospital (ACH); primarily adult = Peter Lougheed Centre (PLC)]. Patients with a respiratory viral testing order were randomized to testing at either a central accredited laboratory (standard arm) or with a rapid polymerase chain reaction test at an on-site accredited laboratory followed by standard testing [rapid on-site test (ROST) arm] based on day of specimen receipt at the laboratory. Patients and clinicians were blinded to assignment.
The primary outcome for ACH was inpatient length of stay (LOS) and for PLC was the proportion of inpatients prescribed oseltamivir.

Results
706 patient encounters were included at ACH; 322 assigned to ROST (181 inpatients) and 384 to the standard arm (194 inpatients). 422 patient encounters were included at PLC; 200 assigned to ROST (157 inpatients) and 222 to the standard arm (175 inpatients).
The rate of oseltamivir prescription and number of doses given was reduced in PLC inpatients negative for influenza in the ROST arm compared to standard arm [mean 14.9% (95% CI 9.87–21.9) vs. 27.5% (21.0–35.2), p = 0.0135; mean 2.85 doses (SEM 2.39–3.32) vs. 4.17 doses (3.85–4.49) p = 0.022, respectively]. ROST also significantly reduced oseltamivir use at ACH, reduced chest radiographs (ACH), and laboratory test ordering (PLC), but not antibiotic prescriptions. ROST also reduced the median turnaround time by > 24 h (ACH and PLC).
The LOS at ACH was not significantly different between the ROST and standard arms [median 4.05 days (SEM 1.79–18.2) vs 4.89 days (2.07–22.9), p = 0.062, respectively].
No adverse events were reported.

Conclusions
In a RCT representing implementation of ROST in an accredited laboratory system, we found that a ROST improved oseltamivir utilization and is the first RCT to show reduced ancillary testing in both paediatric and adult populations. A larger study is required to assess reduction in paediatric LOS as ACH was underpowered. These findings help justify the implementation of rapid on-site respiratory virus testing for inpatients.
Trial registration ISRCTN, number 10110119, Retrospectively Registered, 01/12/2021.
Granulomatous interstitial nephritis with CTLA-4 haploinsufficiency: a case report
Authors: Kohatsu Kaori , Suzuki Tomo , Takimoto Madoka , Matsui Katsuomi , Hashiguchi Akinori , Koike Junki , Shirai Sayuri 
Published: November 2022

Abstract
Background
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an essential inhibitory regulator of immune activation. CTLA-4 haploinsufficiency is known to be associated with dysregulation of FOXP3+ regulatory T cells, hyperactivation of effector T cells, and lymphocytic infiltration of multiple organs. However, there have only been a few reports of renal involvement with CTLA-4. Herein, we present a case of acute granulomatous tubulointerstitial nephritis (TIN) in a patient with CTLA-4 haploinsufficiency.

Case presentation
A 44-year-old man presented with a 3-week history of fever and malaise, and subsequently developed acute kidney injury (AKI) a few days after treatment with levofloxacin (LVFX). A kidney biopsy and immunohistochemical staining revealed granulomatous TIN with dominantly infiltrating CD4+ T cells. General symptoms and renal impairment showed improvement after discontinuation of LVFX and initiation of oral steroids. However, they worsened following steroid tapering. Further, a colon biopsy analysis showed similar findings to the renal tissue analysis. We suspected that granulomatous TIN was possibly associated with CTLA-4 haploinsufficiency. Therefore, the patient was transferred to another hospital for further treatment of CTLA-4 haploinsufficiency using immunosuppressive agents.

Conclusions
There have been few reports regarding renal involvement of CTLA-4 haploinsufficiency. In the present case, granulomatous TIN could have arisen due to instability of immune regulatory functions, such as CTLA-4 haploinsufficiency, and treatment with LVFX could have triggered immunologic activation and severe inflammation as well as renal dysfunction.
Analysis of cellular and cell free mitochondrial DNA content and reactive oxygen species levels in maternal blood during normal pregnancy: a pilot study
Authors: Srivastava Anubhav , Srivastava Pransu , Mathur Shashank , Mishra Suman , Abbas Sabiya , Gupta Amrit , Mishra Prabhaker , Tiwari Meenakshi , Sharma Lokendra Kumar 
Published: November 2022

Abstract
Background
Alterations in mitochondrial signatures such as mitochondrial DNA (mtDNA) content in maternal blood have been linked to pregnancy-related complications. However, changes in maternal mtDNA content, their distribution and associated signaling during normal pregnancies are not clear; which could suggest their physiological role in maternal adaptation to pregnancy related changes and a reference threshold. The aim of this study: to assess the distribution of mtDNA in peripheral blood and their association with circulatory ROS levels across different trimesters of healthy pregnancy.

Methods
In this pilot cross sectional study, blood samples of normal pregnant women from each trimester (total = 60) and age-matched non-pregnant (NP) women as control group (n = 20) were analyzed for a) the relative distribution of mtDNA content in cellular and cell free (plasma) fractions using relative quantitative polymerase chain reaction (qPCR) and b) the levels of circulating reactive oxygen species (ROS) by measurement of plasma H2O2. The results were compared between pregnant and NP groups and within trimesters for significant differences, and were also analyzed for their correlation between groups using statistical methods.

Results
While, we observed a significant decline in cellular mtDNA; plasma mtDNA was significant increased across all trimesters compared to NP. However, from comparisons within trimesters; only cellular mtDNA content in 3rd trimester was significantly reduced compared to 1st trimester, and plasma mtDNA did not differ significantly among different trimesters. A significantly higher level of plasma H2O2 was also observed during 3rd trimester compared to NP and to 1st trimester. Correlation analysis showed that, while cellular mtDNA content was negatively correlated to plasma mtDNA and to plasma H2O2 levels; plasma mtDNA was positively correlated with plasma H2O2 content.

Conclusions
This study suggested that normal pregnancy is associated with an opposing trend of reduced cellular mtDNA with increased circulatory mtDNA and H2O2 levels, which may contribute to maternal adaptation, required during different stages of pregnancy. Estimation of mtDNA distribution and ROS level in maternal blood could show mitochondrial functionality during normal pregnancy, and could be exploited to identify their prognostic/ diagnostic potential in pregnancy complications.
The prognostic significance of the circumferential resection margin in esophageal squamous cell carcinoma patients without neoadjuvant treatment
Authors: Yang Zhaoyang , Lin Hua , Wang Zhen , Rong Lulu , Zhang Xuchen , Wang Lin , Qin Jianjun , Xue Xuemin , Li Yin , Xue Liyan 
Published: November 2022

Abstract
Background
Circumferential resection margin (CRM) is very important in esophageal cancer, but its diagnostic criteria has not been unified. The College of American Pathologists (CAP) and the Royal College of Pathologists (RCP) provide two different criteria. The aim of this study is to evaluate the long-term prognostic significance of CRM status with different CRM criteria in esophageal squamous cell carcinoma (ESCC).

Methods
Influence of CRM status according to the CAP and RCP criteria on long-term survival of 838 patients with resected pT3 tumors and without neoadjuvant therapy was analyzed. Patients stratified into three groups on the basis of tumor distance from the CRM (CRM > 1 mm, 0-1 mm, and 0 mm) were also analysed.

Results
Positive CRM was found in 59 (7%) patients according to the CAP criteria and 317 (37.8%) patients according to the RCP criteria. Univariate and multivariate survival analysis showed that CRM status, according to three different criteria, was independent prognostic factor. However, subgroup analysis showed that the prognostic value of CRM status was limited to certain metastatic lymph node load. In pN0 subgroup, patients with CRM > 1 mm had better prognosis than patients with CRM 0-1 mm. Patients with CRM 0 mm had worse outcome than patients with CRM > 0 mm in pN1-2 subgroup. But CRM status had no prognosis value in pN3 subgroup.

Conclusions
The CRM status is an important prognostic factor in ESCC patients, but this effect was limited to patients without or with less lymph node metastasis (pN0-2). In clinical practice, we recommend the 1 mm-three-tier criteria as it provides more prognostic value than the traditional two-tier criteria.
Impact of GTF2H1 and RAD54L2 polymorphisms on the risk of lung cancer in the Chinese Han population
Authors: Geng Tingting , Li Miao , Chen Rong , Yang Shuangyu , Jin Guoquan , Jin Tinabo , Chen Fulin 
Published: November 2022

Abstract
Background
Repair pathway genes play an important role in the development of lung cancer. The study aimed to assess the correlation between single nucleotide polymorphisms (SNPs) in DNA repair gene (GTF2H1 and RAD54L2) and the risk of lung cancer.

Methods
Five SNPs in GTF2H1 and four SNPs in RAD54L2 in 506 patients with lung cancer and 510 age-and gender-matched healthy controls were genotyped via the Agena MassARRAY platform. The influence of GTF2H1 and RAD54L2 polymorphisms on lung cancer susceptibility was assessed using logistic regression analysis by calculating odds ratios (ORs) and their corresponding 95% confidence intervals (CIs).

Results
RAD54L2 rs9864693 GC genotype increased the risk of lung cancer (OR = 1.33, 95%CI: 1.01–1.77, p = 0.045). Stratified analysis found that associations of RAD54L2 rs11720298, RAD54L2 rs4687592, RAD54L2 rs9864693 and GTF2H1 rs4150667 with lung cancer risk were found in subjects aged ≤ 59 years. Precisely, a protective effect of RAD54L2 rs11720298 on the occurrence of lung cancer was observed in non-smokers and drinkers. GTF2H1 rs4150667 was associated with a decreased risk of lung cancer in subjects with BMI ≤ 24 kg/m2. RAD54L2 rs4687592 was associated with an increased risk of lung cancer in drinkers. In addition, GTF2H1 rs3802967 was associated with a reduced risk of lung squamous cell carcinoma.

Conclusion
Our study first revealed that RAD54L2 rs9864693 was associated with an increased risk of lung cancer in the Chinese Han population. This study may increase the understanding of the effect of RAD54L2 and GTF2H1 polymorphisms on lung cancer occurrence.
Drivers of socioeconomic inequalities of child hunger during COVID-19 in South Africa: evidence from NIDS-CRAM Waves 1–5
Authors: Alaba Olufunke A. , Hongoro Charles , Thulare Aquina , Lukwa Akim Tafadzwa 
Published: November 2022

AbstractBackgroundChild hunger has long-term and short-term consequences, as starving children are at risk of many forms of malnutrition, including wasting, stunting, obesity and micronutrient deficiencies. The purpose of this paper is to show that the child hunger and socio-economic inequality in South Africa increased during her COVID-19 pandemic due to various lockdown regulations that have affected the economic status of the population.MethodsThis paper uses the National Income Dynamics Study-Coronavirus Rapid Mobile Survey (NIDS-CRAM WAVES 1–5) collected in South Africa during the intense COVID-19 pandemic of 2020 to assess the socioeconomic impacts of child hunger rated inequalities. First, child hunger was determined by a composite index calculated by the authors. Descriptive statistics were then shown for the investigated variables in a multiple logistic regression model to identify significant risk factors of child hunger. Additionally, the decomposable Erreygers' concentration index was used to measure socioeconomic inequalities on child hunger in South Africa during the Covid-19 pandemic.ResultsThe overall burden of child hunger rates varied among the five waves (1–5). With proportions of adult respondents indicated that a child had gone hungry in the past 7 days: wave 1 (19.00%), wave 2 (13.76%), wave 3 (18.60%), wave 4 (15, 68%), wave 5 (15.30%). Child hunger burden was highest in the first wave and lowest in the second wave. The hunger burden was highest among children living in urban areas than among children living in rural areas. Access to electricity, access to water, respondent education, respondent gender, household size, and respondent age were significant determinants of adult reported child hunger. All the concentrated indices of the adult reported child hunger across households were negative in waves 1–5, suggesting that children from poor households were hungry. The intensity of the pro-poor inequalities also increased during the study period. To better understand what drove socioeconomic inequalites, in this study we analyzed the decomposed Erreygers Normalized Concentration Indices (ENCI). Across all five waves, results showed that race, socioeconomic status and type of housing were important factors in determining the burden of hunger among children in South Africa.ConclusionThis study described the burden of adult reported child hunger and associated socioeconomic inequalities during the Covid-19 pandemic. The increasing prevalence of adult reported child hunger, especially among urban children, and the observed poverty inequality necessitate multisectoral pandemic shock interventions now and in the future, especially for urban households.
Patient-related healthcare costs for diarrhoea, Guillain Barré syndrome and invasive non-typhoidal salmonellosis in Gondar, Ethiopia, 2020
Authors: van Wagenberg Coen P. A. , Delele T. Guadu , Havelaar Arie H. 
Published: November 2022

Abstract
Background
Globally, foodborne diseases result in a significant disease burden with low- and middle-income countries disproportionately affected. Estimates of healthcare costs related to foodborne disease can aid decision makers to take action to mitigate risks and prevent illness. However, only limited data on the African continent are available, especially related to more severe sequelae. We provide estimates of direct and indirect (non)-medical costs of patients with diarrhoea, Guillain-Barré syndrome (GBS), and invasive non-typhoidal salmonellosis (iNTS) in three healthcare facilities in Gondar, Ethiopia.

Methods
We used healthcare data from patient records, interviews with family caregivers and 2020 healthcare resource unit costs. Descriptive statistical analysis was performed. For diarrhoea, differences in mean and median transformed costs between healthcare facilities and etiologies (Campylobacter spp., enterotoxigenic Escherichia coli, non-typhoidal Salmonella enterica) were analysed with ANOVA and chi squared tests. Contribution of healthcare facility, dehydration severity, sex, age and living area to transformed costs was identified with linear regression. Results are in 2020 USD per patient. To extrapolate to national level, 2017 national incidence estimates were used.

Results
Mean direct medical costs were 8.96 USD for diarrhoea (health centre 6.50 USD, specialised hospital 9.53 USD, private clinic 10.56 USD), 267.70 USD for GBS, and 47.79 USD for iNTS. Differences in costs between diarrhoea patients were mainly associated with healthcare facility. Most costs did not differ between etiologies. Total costs of a diarrhoea patient in the specialised hospital were 67 USD, or 8% of gross national income per capita. For direct medical plus transport costs of a GBS and iNTS patient in the specialised hospital, this was 33% and 8%, respectively. Of the 83.9 million USD estimated national non-typhoidal Salmonella enterica related cost, 12.2% was due to iNTS, and of 187.8 million USD related to Campylobacter spp., 0.2% was due to GBS.

Conclusion
Direct medical costs per patient due to GBS and iNTS were 30 respectively five times those due to diarrhoea. Costs of a patient with diarrhoea, GBS or iNTS can be a substantial part of a household’s income. More severe sequalae can add substantially to cost-of-illness of foodborne hazards causing diarrheal disease.