bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Validation of Diffuse Large B Cell Lymphoma International Prognostic Index for High Grade B Cell Lymphoma with and without MYC and BCL2 or BCL6 Rearrangements: An Institutional Review
Authors: Kanagalingam Gowthami , Vyas Vrinda , Basnet Alina , Brooks Garry , Smith Alexandria 
Published: November 2019

Background:
Diffuse large B cell lymphoma (DLBCL) NOS is the most common histologic subtype of non-Hodgkin lymphoma (NHL). Double hit lymphoma is re-classified as high-grade B cell lymphoma, with and without MYC and BCL2 or BCL6 rearrangements (HGBCL) in 2016. The International Prognostic Index (IPI) is the main prognostic tool for DLBCL NOS. We aimed to identify if IPI index scores can accurately predict the prognosis in patients with HGBCL.
Methods:
We observed the outcome of a cohort of patients (pts) with DLBCL NOS and HGBCL diagnosed and treated from 2008-2019 at SUNY Upstate Medical University. Fisher's exact test was used for the 2X2 comparison analysis.
Results:
24 pts (82.8%) had DLBCL NOS and 5 (17.2%) pts had HGBCL. The median age was 58 yrs (13-81 yrs). 65.5% were males and 79.3% were caucasians. 8 pts had bone marrow involvement, 1 pt had brain metastasis and 12 pts had bulky disease. 15 DLBCL NOS pts (68.2%) and 4 HGBCL pts (80%) had low-intermediate IPI (</=3). 7 DLBCL NOS pts (31.8%) and 1 HGBCL pt (20%) had high IPI (>/=4). 2 DLBCL NOS pts (13.33%) vs 1 HGBCL pt (25%) died in the low-intermediate IPI group. None of the DLBCL NOS pts (0%) vs 1 HGBCL pt (100%) died in the high risk group.
Conclusion:
Our study sample size is very small to identify prognostic relation of IPI score to predict the outcome for HGBCL. Our observation raises the hypothesis that patient with HGBCL might have a worse prognosis despite low IPI score which needs to be validated in a larger study population.

Disclosures
No relevant conflicts of interest to declare.
Platelet Dysfunction Detected Using Rotational Thromboelastometry (ROTEM) in Severely Thrombocytopenic Patients with a Bleeding Phenotype
Authors: Choi Philip Young-Ill , Hicks Sarah , Gardiner Elizabeth E. , Crispin Philip , Slade James , D'Rozario James , Parish Christopher , Coupland Lucy 
Published: November 2019

Background: Thrombocytopenia occurs reasonably frequently with the underlying causes being numerous and requiring time to delineate. Patients may present with active bleeding or low platelet counts may be detected incidentally. Treatments are varied, refractory cases are not uncommon, and in those who do respond, relapses occur. The clinician's principal concern is to limit the risk of a life-threatening hemorrhage, however, the platelet count is an unreliable predictor of bleeding risk. Adult patients presenting with platelet counts < 20 x 109/L present the greatest safety dilemma for clinicians. Previous studies using ROTEM in adult ITP patients with platelet counts < 60 x 109/L and paediatric cases with platelet counts < 30 x 109/L demonstrated that clot firmness parameters correlated with bleeding score1. Our aim, therefore, was to perform ROTEM analysis on patients with a platelet count <20 x 109/L and correlate with bleeding status.
Methods: Patients referred to the Haematology Department of The Canberra Hospital with thrombocytopenia were consented to the study. Blood was collected into Na-citrate tubes and analysed within 4 hr of collection. Each patient had an EXTEM and FibTEM assay performed on a ROTEM Delta machine. The measurement of fibrinogen levels was commenced part-way through the study. Data was analysed using PRISM software.
Results: Twenty-five blood samples were analysed from 21 patients (17 primary ITP, 2 secondary ITP, 1 AML, 1 sepsis), 7 samples were treatment naive. Platelet count ranged from 0-17 x 109/L (mean 7.1 +/- 5.7) Even in this severely thrombocytopenic cohort, platelet count was a poor predictor of bleeding risk, as was the fibrin clot amplitude measured with FibTEM. In comparison, the calculated value for platelet contribution to clot formation (EXTEM A10 minus FibTEM A10) plotted against the platelet count demonstrated that subjects with a bleeding phenotype had a reduced platelet contribution to clot formation in comparison to their non-bleeding counterparts (Figure).
Conclusions: ROTEM has the capacity to detect platelet dysfunction associated with bleeding in severely thrombocytopenic patients. Further studies are underway to elucidate determinants of platelet dysfunction such as specific anti-glycoprotein antibodies that may inhibit platelet function.
Reference #1: Lindsey A. Greene et al., British Journal of Haematology 166: 592-600 (2014)
Figure

Disclosures
D'Rozario: Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees.
Viability of Stem Cells without Cryopreservation: How Good and How Long?
Authors: Khine Mie Mie , Thandar Hnin Mya , Gyi Aye Aye 
Published: November 2019

Although cryopreservation of stem cells is a standard practice for autologous haematopoietic progenitor cells transplantation to treat haematologic malignancies, it has many limitations including toxicities of cryo-protectant, requirement for cryopreservation facilities as well as trained personnel which causes barriers for transplant programs in resource limited countries. To overcome these limitations, a newly established first transplant centre at the North Okkalapa General and Teaching Hospital of Myanmar has been using ordinary refrigerator at 4 degree Celsius to store autologous peripheral blood stem cells collected by apheresis during the interval between collection and transplantation for patients with multiple myeloma who underwent high dose melphalan therapy and autologous stem cell rescue. During early days of the centre, in addition to microbiological testing, to ensure the quality of stem cells, serial measurement for stem cell count and viability were made on daily basis till the day of transplant and continued testing if adequate samples of aliquots were available for analysis. Viable CD34+ cells were analyzed by BD FACS Canto II flow cytometer using BD stem cell enumeration kits that incorporate 7-Amino Actinomycin D viability dyes. The results of the viable CD34+counts of 13 myeloma patients, 5 males and 8 females, median age- 57 years, who underwent autologous peripheral blood stem cell transplantation during early periods of the transplant center from May 2014 to January, 2019, were retrospectively reviewed for the quality of stem cells from the non-cryopreserved methods. Mean CD34 + cells enumerated at the time of reinfusion were 3.45 x 106 cells/kg (range 1.45 - 4.87 x 106 cells/kg). The mean viability of stem cells on day of collection (day 0) were 96.13% (range 83.33% -100%) which was almost unchanged one day after collection (day 1) at 95.93% (85.70% -99.24%). On second and third day after collection, mean viability of the collected cells although fallen below 90% were reasonably preserved at 88.7% (81.74-95.61) on day 2 and 88.08% (87.07-89.09) on day 3, and 85.37% on day 4. Median neutrophil engraftment time was 11 days (range 9-12) and that for platelet engraftment was 16 days (range 9-44). There were no graft failure or mortality during first 100 days. It was encouraging to observe that even at the refrigerator temperature at 4degree Celsius, without any additives or manipulation, stem cell viability could be maintained above 85% minimum of four days with good transplant outcome. Further studies are needed to investigate maximum storage period which could allow reasonable viability and function of the stem cells.

Disclosures
No relevant conflicts of interest to declare.
Mouse APOBEC1 cytidine deaminase can induce somatic mutations in chromosomal DNA
Authors: Caval Vincent , Jiao Wenjuan , Berry Noémie , Khalfi Pierre , Pitré Emmanuelle , Thiers Valérie , Vartanian Jean-Pierre , Wain-Hobson Simon , Suspène Rodolphe 
Published: November 2019

AbstractBackgroundAPOBEC1 (A1) enzymes are cytidine deaminases involved in RNA editing. In addition to this activity, a few A1 enzymes have been shown to be active on single stranded DNA. As two human ssDNA cytidine deaminases APOBEC3A (A3A), APOBEC3B (A3B) and related enzymes across the spectrum of placental mammals have been shown to introduce somatic mutations into nuclear DNA of cancer genomes, we explored the mutagenic threat of A1 cytidine deaminases to chromosomal DNA.ResultsMolecular cloning and expression of various A1 enzymes reveal that the cow, pig, dog, rabbit and mouse A1 have an intracellular ssDNA substrate specificity. However, among all the enzymes studied, mouse A1 appears to be singular, being able to introduce somatic mutations into nuclear DNA with a clear 5’TpC editing context, and to deaminate 5-methylcytidine substituted DNA which are characteristic features of the cancer related mammalian A3A and A3B enzymes. However, mouse A1 activity fails to elicit formation of double stranded DNA breaks, suggesting that mouse A1 possess an attenuated nuclear DNA mutator phenotype reminiscent of human A3B.ConclusionsAt an experimental level mouse APOBEC1 is remarkable among 12 mammalian A1 enzymes in that it represents a source of somatic mutations in mouse genome, potentially fueling oncogenesis. While the orderRodentiais bereft of A3A and A3B like enzymes it seems that APOBEC1 may well substitute for it, albeit remaining much less active. This modifies the paradigm that APOBEC3 and AID enzymes are the sole endogenous mutator enzymes giving rise to off-target editing of mammalian genomes.
Community resource referral needs among African American dementia caregivers in an urban community: a qualitative study
Authors: Abramsohn Emily M. , Jerome Jessica , Paradise Kelsey , Kostas Tia , Spacht Wesley Alexandra , Lindau Stacy Tessler 
Published: November 2019

Abstract
Background
African American caregivers of community-residing persons with dementia are mostly unpaid and have high rates of unmet basic and health needs. The National Alzheimer’s Project Act (NAPA) mandates improved coordination of care for persons with dementia and calls for special attention to racial populations at higher risk for Alzheimer’s Disease or related dementias (ADRD) to decrease health disparities. The purpose of this study is to describe the perceptions of African American caregivers of people with dementia about community resources needed to support caregiving as well as their own self-care.

Methods
Using a qualitative study design, in-depth, semi-structured qualitative interviews were conducted with caregivers (N = 13) at an urban geriatric clinic to elicit community resource needs, barriers to and facilitators of resource use and how to optimize clinical referrals to community resources. Caregivers were shown a community resource referral list (“HealtheRx”) developed for people with dementia and were queried to elicit relevance, gaps and insights to inform delivery of this information in the healthcare setting. Data were iteratively coded and analyzed using directed content analysis. Results represent key themes.

Results
Most caregivers were women (n = 10, 77%) and offspring (n = 8, 62%) of the person with dementia. Community resource needs of these caregivers included social, entertainment, personal self-care and hospice services. Main barriers to resource use were the inability to leave the person with dementia unsupervised and the care recipient’s disinterest in participating in their own self-care. Facilitators of resource use included shared caregiving responsibility and learning about resources from trusted sources. To optimize clinical referrals to resources, caregivers wanted specific eligibility criteria and an indicator of dementia care capability.

Conclusions
African American caregivers in this study identified ways in which community resource referrals by clinicians can be improved to meet their caregiving and self-care needs.
Clinical and whole-exome sequencing findings in two siblings from Hani ethnic minority with congenital glycosylation disorders
Authors: Zhang Zhen , Huang Ti-Long , Ma Jing , He Wen-Ji , Gu Huaiyu 
Published: November 2019

Abstract
Background
PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans. The mutations of PMM2-CDG might lead to the loss of PMM2, which is responsible for the conversion of mannose 6- phosphate into mannose 1-phosphate. Most patients with PMM2-CDG have central nervous system involvement, abnormal coagulation, and hepatopathy. The neurological symptoms of PMM2-CDG are intellectual disability (ID), cerebellar ataxia, and peripheral neuropathy. Now, over 100 new CDG cases have been reported. However, each type of CDG is very rare, and CDGs are problematic to diagnose. In addition, few CDGs have been reported in the Chinese population.

Case presentation
Here we present a Hani ethnic minority family including two siblings with congenital glycosylation disorders. Whole-exome sequencing revealed compound heterozygous for one novel mutation (c.241–242 del variant) and previously reported mutation (c.395 T > C) in gene of PMM2. Two mutations were found in proband and her sibling by whole-exome sequencing. The mutations were identified in this family by Sanger sequencing and no mutations were detected in the normal control.

Conclusions
This is the first report to describe mutations in two siblings of Hani ethnic minority which is one of five ethnic groups found only in Yunnan with a population of more than 1 million.
The value of miR-155 as a biomarker for the diagnosis and prognosis of lung cancer: a systematic review with meta-analysis
Authors: Shao Chuchu , Yang Fengming , Qin Zhiqiang , Jing Xinming , Shu Yongqian , Shen Hua 
Published: November 2019

Abstract
Background
Recently, a growing number of studies have reported the coorelation between miR-155 and the diagnosis and prognosis of lung cancer, but results of these researches were still controversial due to insufficient sample size. Thus, we carried out the systematic review and meta-analysis to figure out whether miR-155 could be a screening tool in the detection and prognosis of lung cancer.

Methods
A meta-analysis of 13 articles with 19 studies was performed by retrieving the PubMed, Embase and Web of Science. We screened all correlated literaters until December 1st, 2018. For the diagnosis analysis of miR-155 in lung cancer, sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the ROC curve (AUC) were pooled to evaluate the accuracy of miRNA-155 in the diagnosis of lung cancer. For the prognosis analysis of miR-155 in lung cancer, the pooled HRs and 95% CIs of miR-155 for overall survival/disease free survival/progression-free survival (OS/DFS/PFS) were calculated. In addition, Subgroup and meta-regression analyses were performed to distinguish the potential sources of heterogeneity between studies.

Results
For the diagnostic analysis of miR-155 in lung cancer, the pooled SEN and SPE were 0.82 (95% CI: 0.72–0.88) and 0.78 (95% CI: 0.71–0.84), respectively. Besides, the pooled PLR was 3.75 (95% CI: 2.76–5.10), NLR was 0.23 (95% CI: 0.15–0.37), DOR was 15.99 (95% CI: 8.11–31.52) and AUC was 0.87 (95% CI: 0.84–0.90), indicating a significant value of miR-155 in the lung cancer detection. For the prognostic analysis of miR-155 in lung cancer, up-regulated miRNA-155 expression was not significantly associated with a poor OS (pooled HR = 1.26, 95% CI: 0.66–2.40) or DFS/PFS (pooled HR = 1.28, 95% CI: 0.82–1.97).

Conclusions
The present meta-analysis demonstrated that miR-155 could be a potential biomarker for the detection of lung cancer but not an effective biomarker for predicting the outcomes of lung cancer. Furthermore, more well-designed researches with larger cohorts were warranted to confirm the value of miR-155 for the diagnosis and prognosis of lung cancer.
MSCs helped reduce scarring in the cornea after fungal infection when combined with anti-fungal treatment
Authors: Zhou Yue , Chen Yuqing , Wang Suiyue , Qin Fangyuan , Wang Liya 
Published: November 2019

Abstract
Background
Fungal Keratitis (FK) is an infective keratopathy with extremely high blindness rate. The damaging effect of this disease is not only the destruction of corneal tissue during fungal infection, but also the cornea scar formed during the healing period after infection control, which can also seriously affect a patient’s vision. The purpose of the study was to observe the effect of umbilical cord mesenchymal stem cells (uMSCs) on corneal scar formation in FK.

Methods
The FK mouse model was made according to a previously reported method. Natamycin eye drops were used for antifungal treatment 24 h after modeling. There are four groups involved in the study, including control group, FK group, vehicleinj FK group and uMSCsinj FK group. Mice in uMSCsinj FK group received repeated subconjunctival injections of uMSCs for 3 times at the 1d, 4d and 7d after FK modeling. At 14d, 21d and 28d after trauma, clinical observation, histological examination, second harmonic generation and molecular assays were performed.

Results
The uMSCs topical administration reduced corneal scar formation area and corneal opacity, accompanying with decreased corneal thickness and inflammatory cell infiltration, following down-regulated fibrotic-related factors α-SMA, TGFβ1, CTGF, and COLI and finally inhibited phosphorylation of TGFβ1/Smad2 signaling pathway during FK corneal fibrosis.

Conclusion
The results confirmed that uMSCs can improve corneal opacity during the scar formation stage of FK, and exert anti-inflammatory and anti-fibrotic effects.
Prevalence and risk factors of intestinal parasitic infestations among preschool children in Sekota town, Waghimra zone, Ethiopia
Authors: Kassaw Mesfin Wudu , Abebe Ayele Mamo , Tlaye Kenean Getaneh , Zemariam Alemu Birara , Abate Biruk Beletew 
Published: November 2019

Abstract
Background
Intestinal parasitic infestations triggered considerable gastrointestinal morbidity, malnutrition, and mortality worldwide. In particular, young children in developing countries affected most. Helminthiasis infestation accounts for 10–20% of prevalence on preschool children worldwide. Unfortunately, small children below 5 years are uniquely susceptible to intestinal parasitic infestations in poor communities. This is because of children’s behavior like playing with soil and putting hand -to- mouth habit. Thus, the aim of this study was to assess the prevalence and risk factors of intestinal parasitic infestations among preschool children in Sekota town, Ethiopia.

Methods
A community-based cross-sectional study was carried out on 378 preschool children in Sekota town from February 15 – March 10/2019. Stool specimens were collected and examined for intestinal parasites using wet mount and formal ether concentration technique. The risk factors of intestinal parasites were assessed using a pretested structured questionnaire. The data were entered and analyzed using Epi-data version 4.2.0.0 and SPSS-version 23 statistical software respectively. Both bivariable and multivariable analysis was carried out, and potential co-linearity was tested for closely similar variables. Variables with P value less than 0.05 in multivariable analysis was considered as statistically significant and reported with 95% CI and odds ratio.

Results
The prevalence of intestinal parasitic infestations in Sekota town on wet mount and formal ether concentration techniques was 83(21.9%), (95% CI, 17.7–26.3%) and 113(29.9%), (95% CI, 25.1–34.8%) respectively.
In multivariable analysis, not taking medication as periodical deworming (AOR, 95% CI), (2.5, 1.5–4.3), presence of animals in the living room (AOR, 95% CI) (3.1, 1.8–5.3), and being a government employee as an occupation (AOR, 95% CI), (3.4, 1.1–10.0) were increasing the odds of intestinal parasitic infestations.

Conclusions
The prevalence of intestinal parasitic infestations in Sekota town is high, which is a public health problem. The risk factors that contributed to intestinal parasitic infestations in this study were preventable and modifiable. Therefore, the concerned bodies need to emphasis on periodical deworming and keeping animals in separate room.
Patient characteristics, burden and pharmacotherapy of treatment-resistant schizophrenia: results from a survey of 204 US psychiatrists
Authors: Correll Christoph U. , Brevig Thomas , Brain Cecilia 
Published: November 2019

Abstract
Background
Minimal/non-response to antipsychotic treatment, and persistent positive symptoms despite treatment, are common among patients with schizophrenia. The aim of this study was to characterize a US treatment-resistant schizophrenia (TRS) population in terms of patient demographics, burden of symptoms, treatment history, and factors influencing therapeutic choice.

Methods
In an online survey, 204 psychiatrists self-selected and completed three patient records: two TRS and one schizophrenia (‘non-TRS’).

Results
Respondents reported that 29.5% of their schizophrenia caseload had TRS. Selected TRS (n = 408) vs non-TRS (n = 204) patients were more likely to be unemployed (74.5% vs 45.1%, p < 0.001), hospitalized at least once (93.4% vs 74.0%, p < 0.001), and to have physical/psychiatric comorbidities including obesity (40.2% vs 23.5%, p < 0.001) and depression (38.7% vs 25.0%, p = 0.001). Psychiatric symptoms were more frequent and severe in TRS, and interfered more with social and functioning domains. Of positive symptoms, eliminating delusions and hallucinations was considered most important to improve a patient’s long-term prognosis. In TRS, clozapine monotherapy was the most common treatment (15.9%), though ranked fifth of ten options to treat TRS. Psychiatrists typically increased the antipsychotic dose or added a second antipsychotic before initiating clozapine or switching antipsychotics. Antipsychotic switches were most commonly due to lack of efficacy (TRS = 71.4% vs non-TRS = 54.3%, p < 0.001) and intolerability (34.4% vs 38.4%, p = 0.22) with the prior antipsychotic. Persistent hallucinatory behavior was the top symptom leading to treatment switches in TRS (63.9% vs 37.1%, p < 0.001).

Conclusions
According to psychiatrists, symptoms have a greater clinical burden on patients with TRS than non-TRS. TRS is commonly managed by antipsychotic dose increases/combinations, with clozapine the fifth preference despite being the only approved TRS medication. New treatments are needed for patients who do not respond to available antipsychotics.