bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Validation of Novel Nomograms for Predicting Specific Distant Metastatic Sites and Overall Survival of Patients With Soft Tissue Sarcoma
Authors: Tu QiHao , Hu Chuan , Zhang Hao , Kong Meng , Peng Chen , Song MengXiong , Zhao Chong , Wang YuJue , Ma XueXiao 
Published: March 2021

Purpose: The goal of this study is to construct nomograms to effectively predict the distant metastatic sites and overall survival (OS) of soft tissue sarcoma (STS) patients. Methods: STS case data between 2010 and 2015 for retrospective study were gathered from public databases. According to the chi-square and multivariate logistic regression analysis determined independent predictive factors of specific metastatic sites, the nomograms based on these factors were consturced. Subsequently, combined metastatic information a nomogram to predict 1-, 2-, and 3-year OS of STS patients was developed. The performance of models was validated by the area under the curve (AUC), calibration plots, and decision curve analyses (DCA). Results: A total of 7001 STS patients were included in this retrospective study, including 4901 cases in the training group and the remaining 2,100 patients in the validation group. Three nomograms were established to predict lung, liver and bone metastasis, and satisfactory results have been obtained by internal and external validation. The AUCs for predicting lung, liver, and bone metastases in the training cohort were 0.796, 0.799, and 0.766, respectively, and in the validation cohort were 0.807, 0.787, and 0.775, respectively, which means that the nomograms have good discrimination. The calibration curves showed that the models have high precision, and the DCA manifested that the nomograms have great clinical application prospects. Through univariate and multivariate COX regression analyses, 8 independent prognosis factors of age, grade, histological type, tumor size, surgery, chemotherapy, radiatiotherapy and lung metastasis were determined. A nomogram was then constructed to predict the 1-, 2-, and 3-years OS, which has a good performance in both internal and external validations. Conclusion: The nomograms for predicting specific metastatic sites and OS have good discrimination, accuracy and clinical applicability. The models could accurately predict the metastatic risk and survival information, and help clinical decision-making.
Long non-coding RNA PITPNA-AS1 regulates UNC5B expression in papillary thyroid cancer via sponging miR-129-5p
Authors: Mei Shijuan , Zong Huafeng , Zhou Haicheng 
Published: March 2021

Background: Long non-coding RNA (lncRNA) PITPNA antisense RNA 1 (PITPNA-AS1) expression characteristics, function, and mechanism in papillary thyroid cancer are unclear. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was applied for detecting PITPNA-AS1, UNC-5 netrin receptor B (UNC5B) mRNA, and miR-129-5p expressions in papillary thyroid cancer tissues and cell lines. EdU assay, cell counting kit-8 (CCK-8) assay, wound healing assay, and flow cytometry analysis were performed to investigate the biological functions of PITPNA-AS1 in papillary thyroid cancer. Dual-luciferase reporter assay was utilized for determining whether PITPNA-AS1 and miR-129-5p, as well as UNC5B and miR-129-5p could directly bind to each other. Western blot assay was employed for measuring UNC5B protein expression level in papillary thyroid cancer cell lines. Results: PITPNA-AS1 and UNC5B expressions were markedly increased in papillary thyroid cancer tissues and cell lines while miR-129-5p expression was down-regulated. Knockdown of PITPNA-AS1 could significantly inhibit papillary thyroid cancer cell growth and migration and promote cell apoptosis while UNC5B overexpression plasmids or miR-129-5p inhibitors counteracted the knockdown effect of PITPNA-AS1 on papillary thyroid cancer cells. PITPNA-AS1 targeted miR-129-5p to repress its expression and miR-129-5p targeted UNC5B to repress its expression. Silencing PITPNA-AS1 reduced the expression of UNC5B via regulating miR-129-5p expression. Conclusions: PITPNA-AS1 facilitated papillary thyroid cancer cell proliferation and migration, and suppressed apoptosis through miR-129-5p/UNC5B axis.
Revision rates of trapeziometacarpal total joint arthroplasty in relation to occupational hand force requirements
Authors: Kirkeby Lone , Frost Poul , Svendsen Susanne W. , Hansen Torben B. 
Published: March 2021

The purpose was to determine revision rates after trapeziometacarpal total joint arthroplasty in working age patients, hypothesizing that higher occupational hand force requirements lead to higher revision rates. We conducted a follow-up study of patients operated 2003–2015. Self-reported job titles at the time of primary surgery were linked with a job exposure matrix to estimate occupational hand force requirements. Time until revision was analysed using Cox regression. The study comprised 222 patients aged 39–65 years (mean 55, SD 6), including 133 patients in the labour market. The median follow-up period was 5 years (interquartile range 4–7) and the overall revision rate was 5/100 person-years. For high versus low occupational hand force requirements, the hazard ratio was 1.5 (95% confidence interval 0.5–4.4). For patients outside the labour market, the hazard ratio was 2.3 (0.9–5.6). Our results did not indicate large effects of high occupational hand force requirements on revision rates. Level of evidence: IV
Novel risk factors and outcomes in inflammatory bowel disease patients with Clostridioides difficile infection
Authors: Voth Elida , Solanky Dipesh , Loftus Edward V. , Pardi Darrell S. , Khanna Sahil 
Published: March 2021

Background: Patients with inflammatory bowel disease (IBD) are at significantly increased risk for Clostridioides difficile infection (CDI) with an increased risk of adverse outcomes including increased in-hospital mortality, IBD treatment failure, re-hospitalization, and high CDI recurrence rates. The existing literature on predictors of these adverse outcomes is limited. We evaluated four potentially modifiable novel risk factors [body mass index (BMI), statin use, opioid use, and antidepressant use] on CDI risk and adverse outcomes in these patients. Methods: Using a retrospective design, variables were abstracted from records for patients with IBD and CDI from 2008 to 2013. Statistical analysis comprised descriptive statistics and univariate and multivariate logistic regression analyses. Results: There were 137 patients with IBD and CDI included in this study. On multivariate analysis controlling for age, 43% of patients in the overweight BMI category had severe or severe, complicated CDI, compared with 22% of patients in the underweight/normal BMI [odds ratio (OR) 2.85, p = 0.02] and 19% in the obese category (OR 3.95, p = 0.04). Statin use was associated with severe or severe, complicated CDI when controlling for age and BMI (OR 5.66, p = 0.01). There was no association between statin use and IBD exacerbations following CDI. Opioid and antidepressant use were not associated with disease severity or frequency of IBD exacerbations following CDI. Conclusions: An overweight BMI and statin use were associated with severe or severe, complicated CDI in IBD patients. Further studies are needed to better understand how these factors impact management of patients with IBD to improve clinical outcomes and potentially reduce the risk of complications from CDI.
Complications and surgical results of stone-directed antegrade pyelography compared to the retrograde pyelographic access method in percutaneous nephrolithotomy using ‘bull’s eye’ technique: A randomized clinical trial
Authors: Irani Dariush , Haghpanah Abdolreza , Hosseini Mohammad Mehdi , Malekmakan Leila , Ashraf Mohammad Ali , Raeisi Shahraki Hadi 
Published: March 2021

Objectives: This study aimed to evaluate the differences in outcomes and complications in stone-directed antegrade pyelography using the ‘bull’s eye’ technique in patients with renal stones versus the conventional method of percutaneous nephrolithotomy (PCNL). Although conventional PCNL access using retrograde pyelography is useful, it is time-consuming and may cause postoperative discomfort. Herein, we report our experience in the application of this new technique. Methods: Between January 2017 and June 2018, 100 patients participated in this randomized clinical trial. Stone-directed antegrade pyelography using the ‘bull’s eye’ technique under fluoroscopic guidance was used for percutaneous access in the intervention group. The second group, consisting of those who had undergone conventional PCNL using retrograde pyelography and ‘bull’s eye’ technique in the same period, were considered as the controls. Pre- and postoperative laboratory examinations, surgical results and complications were recorded and compared between the two groups. Results: A single calyceal puncture in partial staghorn and staghorn stone patients was sufficient in 72.2% of the antegrade group and in 78.9% of the retrograde group ( p=0.69). The double-puncture technique was necessary for 71.9% of renal pelvis stones in the antegrade group and for 9.4% in the retrograde group ( p<0.001). The antegrade approach reduced the mean operative time and analgesic requirement significantly ( p<0.001). No statistically significant difference, however, was found between the two groups regarding stone migration to the ureter, radiation time and postoperative complications. Conclusions: The stone-directed antegrade approach using the ‘bull’s eye’ technique is a safe and accurate method in PCNL access in patients with radiopaque and semi-opaque renal stones.
Low-dose CT for diagnosing intestinal obstruction and pneumoperitoneum; need for retakes and diagnostic accuracy
Authors: Larsen Nis E , Mikkelsen Eva , Knudsen Anders R , Larsen Lars P 
Published: March 2021

Background One of the main concerns using low-dose (LD) CT for evaluation of patients with suspected intestinal obstruction or pneumoperitoneum is the potential need to make an additional standard-dose (SD) CT scan (retake) due to insufficient diagnostic accuracy of the LD CT. Purpose To determine the frequency of retakes and evaluate the diagnostic accuracy of LD CT for the assessment of intestinal obstruction and pneumoperitoneum. Material and Methods This retrospective study registered all LD CT scans over a one-year period at Aarhus University Hospital, Denmark in patients with suspected intestinal obstruction or perforation, comprising a total of 643 LD CT scans. A retake was defined as a SD CT scan of the abdomen and pelvis performed with or without intravenous contrast within 72 h after the initial LD CT due to either continued suspicion of intestinal obstruction or perforation or due to unclarified secondary findings. The sensitivity and specificity of LD CT for diagnosing intestinal obstruction and pneumoperitoneum compared to the discharge diagnoses of the scanned patients were determined. Results The frequency of retakes was 3%. The overall LD CT sensitivity and specificity for assessment of patients with suspected intestinal obstruction and pneumoperitoneum was 83% and 99%, respectively, but higher in certain subgroups. Conclusions LD CT led to few retakes and had a high diagnostic accuracy for diagnosing intestinal obstruction and pneumoperitoneum. Thus, LD CT can be recommended as the examination of choice in patients with suspected intestinal obstruction or perforation in order to reduce radiation dose.
The Abbreviated Mental Test Score; Is There a Need for a Contemporaneous Update?
Authors: Peters Kizzie A. , Howe Thomas J. , Rossiter Daniel , Hutchinson Kirsty J. , Rosell Philip A. 
Published: March 2021

Introduction: Designed in 1972 the Abbreviated Mental Test Score (AMTS) is widely used to assess a cognition on hospital admission. The Nottingham Hip Fracture Score uses this in predicting morbidity/mortality in neck of femur fracture. The consequences of misappropriating cognitive impairment could have lasting implications. Questions about the monarchy or World War One and Two may be inappropriate for today’s diverse society. Materials and Methods: 100 patients were questioned during routine fracture clinic appointments. Patients were asked: In what year did WWII start? Who is the current monarch? Please state a memorable event in your lifetime that you would not expect another person of the same age to forget. Two-tailed Z-tests were performed between the observed proportions and those from the original AMTS validation study. Results: Only 47% (n = 47) were able to correctly answer the year in which WW2 started. A statistically significant difference when compared to the upper and lower limits from the original study (z = -4.191, p < .001.). Significance was not seen in the second question, with 97% (n-97) identifying the monarch correctly. 51% (n = 51) of participants suggested the terrorist attack on the World Trade Centre in New York as an alternative memorable event. Discussion: Some hospitals now use the 4 “A”s Test (4-AT) as a screening tool for delirium. Without amendments to the Nottingham Hip Fracture Score, AMTS use is likely to continue in orthogeriatric patients. Over time there will be a need for the AMTS to be reviewed so that it remains a true assessment of cognition. Its limitations regarding language and culture is widely acknowledged and several validated variants have been published in the literaure. Conclusions: We highlight a potential future issue with the AMTS and raise considerations for the development of an alternative question to better meet the needs of the orthogeriatric population.
Autophagy is dispensable for the maintenance of hematopoietic stem cells in neonates
Authors: Hashimoto Michihiro , Umemoto Terumasa , Nakamura-Ishizu Ayako , Matsumura Takayoshi , Yokomizo Tomomasa , Sezaki Maiko , Takizawa Hitoshi , Suda Toshio 
Published: March 2021

Abstract
Hematopoietic stem cells (HSCs) undergo self-renewal or differentiation to sustain lifelong hematopoiesis. HSCs are preserved in quiescence with low mitochondrial activity. Recent studies indicate that autophagy contributes to HSC quiescence through suppressing mitochondrial metabolism. However, it remains unclear whether autophagy is involved in the regulation of neonatal HSCs, which proliferate actively. In this study, we clarified the role of autophagy in neonatal HSCs using 2 types of autophagy-related gene 7 (Atg7)-conditional knockout mice: Mx1-Cre inducible system and Vav-Cre system. Atg7-deficient HSCs exhibited excess cell divisions with enhanced mitochondrial metabolism, leading to bone marrow failure at adult stage. However, Atg7 deficiency minimally affected hematopoiesis and metabolic state in HSCs at neonatal stage. In addition, Atg7-deficient neonatal HSCs exhibited long-term reconstructing activity, equivalent to wild-type neonatal HSCs. Taken together, autophagy is dispensable for stem cell function and hematopoietic homeostasis in neonates and provide a novel aspect into the role of autophagy in the HSC regulation.
Unmarried or less-educated patients with mantle cell lymphoma are less likely to undergo a transplant, leading to lower survival
Authors: Glimelius Ingrid , Smedby Karin E. , Albertsson-Lindblad Alexandra , Crowther Michael J. , Eloranta Sandra , Jerkeman Mats , Weibull Caroline E. 
Published: March 2021

Abstract
It is unknown how many mantle cell lymphoma (MCL) patients undergo consolidation with autologous hematopoietic cell transplantation (AHCT), and the reasons governing the decision, are also unknown. The prognostic impact of omitting AHCT is also understudied. We identified all MCL patients diagnosed from 2000 to 2014, aged 18 to 65 years, in the Swedish Lymphoma Register. Odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression models were used to compare the likelihood of AHCT within 18 months of diagnosis. All-cause mortality was compared between patients treated with/without AHCT using hazard ratios (HRs) and 95% CIs estimated from Cox regression models. Probabilities of being in each of the following states: alive without AHCT, alive with AHCT, dead before AHCT, and dead after AHCT, were estimated over time from an illness-death model. Among 369 patients, 148 (40%) were not treated with AHCT within 18 months. Compared with married patients, never married and divorced patients had lower likelihood of undergoing AHCT, as had patients with lower educational level, and comorbid patients. Receiving AHCT was associated with reduced all-cause mortality (HR = 0.58, 95% CI: 0.40-0.85). Transplantation-related mortality was low (2%). MCL patients not receiving an AHCT had an increased mortality rate, and furthermore, an undue concern about performing an AHCT in certain societal groups was seen. Improvements in supportive functions potentially increasing the likelihood of tolerating an AHCT and introduction of more tolerable treatments for these groups are needed.
Using mitochondrial activity to select for potent human hematopoietic stem cells
Authors: Qiu Jiajing , Gjini Jana , Arif Tasleem , Moore Kateri , Lin Miao , Ghaffari Saghi 
Published: March 2021

Abstract
Hematopoietic cell transplantation is a critical curative approach for many blood disorders. However, obtaining grafts with sufficient numbers of hematopoietic stem cells (HSCs) that maintain long-term engraftment remains challenging; this is due partly to metabolic modulations that restrict the potency of HSCs outside of their native environment. To address this, we focused on mitochondria. We found that human HSCs are heterogeneous in their mitochondrial activity as measured by mitochondrial membrane potential (MMP) even within the highly purified CD34+CD38−CD45RA−CD90+CD49f+ HSC population. We further found that the most potent HSCs exhibit the lowest mitochondrial activity in the population. We showed that the frequency of long-term culture initiating cells in MMP-low is significantly greater than in MMP-high CD34+CD38−CD45RA−CD90+ (CD90+) HSCs. Notably, these 2 populations were distinct in their long-term repopulating capacity when transplanted into immunodeficient mice. The level of chimerism 7 months posttransplantation was &gt;50-fold higher in the blood of MMP-low relative to MMP-high CD90+ HSC recipients. Although more than 90% of both HSC subsets were in G0, MMP-low CD90+ HSCs exhibited delayed cell-cycle priming profile relative to MMP-high HSCs. These functional differences were associated with distinct mitochondrial morphology; MMP-low in contrast to MMP-high HSCs contained fragmented mitochondria. Our findings suggest that the lowest MMP level selects for the most potent, likely dormant, stem cells within the highly purified HSC population. These results identify a new approach for isolating highly potent human HSCs for further clinical applications. They also implicate mitochondria in the intrinsic regulation of human HSC quiescence and potency.
Dissecting pathways to thrombocytopenia in a mouse model of visceral leishmaniasis
Authors: Rani Gulab Fatima , Preham Olivier , Ashwin Helen , Brown Najmeeyah , Hitchcock Ian S. , Kaye Paul M. 
Published: March 2021

Abstract
Visceral leishmaniasis is an important yet neglected parasitic disease caused by infection with Leishmania donovani or L infantum. Disease manifestations include fever, weight loss, hepatosplenomegaly, immune dysregulation, and extensive hematological complications. Thrombocytopenia is a dominant hematological feature seen in both humans and experimental models, but the mechanisms behind this infection-driven thrombocytopenia remain poorly understood. Using a murine model of experimental visceral leishmaniasis (EVL), we demonstrated a progressive decrease in platelets from day 14 after infection, culminating in severe thrombocytopenia by day 28. Plasma thrombopoietin (TPO) levels were reduced in infected mice, at least in part because of the alterations in the liver microenvironment associated with granulomatous inflammation. Bone marrow (BM) megakaryocyte cytoplasmic maturation was significantly reduced. In addition to a production deficit, we identified significant increases in platelet clearance. L donovani–infected splenectomized mice were protected from thrombocytopenia compared with sham operated infected mice and had a greater response to exogenous TPO. Furthermore, infection led to higher levels of platelet opsonization and desialylation, both associated with platelet clearance in spleen and liver, respectively. Critically, these changes could be reversed rapidly by drug treatment to reduce parasite load or by administration of TPO agonists. In summary, our findings demonstrate that the mechanisms underpinning thrombocytopenia in EVL are multifactorial and reversible, with no obvious residual damage to the BM microenvironment.
Familial hemiplegic migraine type 2 due to a novel missense mutation in ATP1A2
Authors: Antonaci Fabio , Ravaglia Sabrina , Grieco Gaetano S. , Gagliardi Stella , Cereda Cristina , Costa Alfredo 
Published: March 2021

Abstract
Background
The mechanisms of genotype-phenotype interaction in Familiar Hemiplegic migraine type 2 (FHM2) are still far from clear. Different ATP1A2 mutations have been described, with a spectrum of phenotypes ranging from mild to severe. No genotype-phenotype correlations have been attempted.

Case presentation
We describe an Italian family with FHM and a missense ATP1A2 variant (L425H) not previously described. The clinical picture was mild in all the affected members.

Conclusions
Co-segregation of the variant with the aura phenotype was complete in this family, suggesting a 100% penetrance. In silico protein prediction softwares indicate that this variant may change the 3D structure of ATPA1A2 at the cytoplasmic loop between the two central transmembrane helices. Milder FHM phenotypes are rarely reported in literature, likely because case reports are biased towards the most severe phenotypes, with milder forms possibly misdiagnosed as sporadic migraine with aura forms (MAs), even with complex auras. Further studies taking into account intra-familiar variability and functional consequences on the channel protein may help clarify genotype-phenotype correlations.