bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Anti-Apoptotic Protein C17ORF58 Is Critical for the Maintenance of Human Peripheral T-Cell Lymphomas By Suppressing BBC3-Induced Apoptosis
Authors: Tobon Julian , Opavska Jana , Libby Kaitlynn , Abdelghany Reem , Veizaj David , Sabripour Bayan , Shaw Jaclyn , Thompson Candalyn , Opavsky Rene 
Published: December 2024

Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of T- and NK-cell malignancies characterized by diverse cells of origin, varied cytogenetic, molecular, and morphological phenotypes, and antigen variability. They account for approximately 15% of non-Hodgkin lymphomas. Despite treatments with conventional chemotherapy like CHOP and R-CHOP, as well as targeted therapies such as belinostat, romidepsin, pralatrexate, and brentuximab vedotin, the overall 5-year survival rate remains low at 20-30%. Thus, improving PTCL therapies necessitates the identification of novel targets crucial for lymphoma cell survival.
C17ORF58 is an uncharacterized human gene that encodes several isoforms with molecular weights of 37 kDa, 11 kDa, and 9 kDa. The longest isoform encodes a protein with a predicted consensus disordered region and signal peptide in the N-terminal region, as well as a Netrin-like domain in the C-terminal region. Such structural features are found in complement proteins and various proteases, but its function remains unclear. C17ORF58 is overexpressed in the vast majority of human PTCL subtypes, including Anaplastic Large Cell Lymphoma, Angioimmunoblastic Lymphoma, and PTCL-Not Otherwise Specified (PTCL-NOS). The mouse homolog of C17ORF58, 1810010H24Rik, is highly expressed in various normal tissues, including the lungs, heart, kidneys, and skeletal muscle, but at low levels in the brain. In hematopoietic organs, 1810010H24Rik protein expression varies, with low levels in the bone marrow and medium levels in the thymus and spleen, potentially indicating a role in blood cell maturation. Interestingly, the protein is up-regulated in mouse T-cell lymphoma induced by the loss of DNA methyltransferase 3a, suggesting that, as in humans, increased expression is closely linked to PTCL development.
The downregulation of C17ORF58 does not affect the proliferation of normal primary human T-cells or the human embryonic kidney cell line HEK293T. In contrast, the loss of C17ORF58 function in T-cell lymphoma and leukemia lines T8ML-1 and Jurkat inhibits proliferation by inducing G2-M arrest and apoptosis. Loss of C17ORF58 leads to the upregulation of numerous signaling pathways, including p53 and MAPK signaling, apoptosis, angiogenesis, and hypoxia. Consistently, C17ORF58 knockdown in T-cell lines results in the upregulation of numerous pro-apoptotic genes, including BBC3 (PUMA), EPAS1, ATF5, DUSP8, S100A6, and CHAC1. Importantly, shRNA-mediated knockdown of BBC3 suppresses apoptosis induced by C17ORF58 loss of function, suggesting that BBC3 is a key downstream target negatively regulated by C17ORF58.
Altogether, our data suggest that C17ORF58 is an anti-apoptotic protein exerting its activity by suppressing BBC3-induced apoptosis, presenting a potential novel target for improving PTCL therapies.
Elts Score Is an Effective Tool to Predict Leukemia-Related Mortality in Peruvian Patients with Chronic Myeloid Leukemia
Authors: López Córdova Naty , Mallma Soto Victor Ivan , Samanez-Figari Cesar , Pizarro-Perea Marlies , Arteta Cecilia , Calderon Hafid , Calle Cindy , Carbone Ethan , Castillo Claudia , Diaz Bardales Carol , Huaman Veronica , Jimenez Tornero Gledy , Molina Maribel , Sanchez Jorge , Seminario Victor E , Vargas Olga , Vera Maria Alejandra , Untama José L. 
Published: December 2024

Introduction:
The ELTS (EUTOS-long-term survival) score was developed to predict the probability of leukemia-related mortality in patients with chronic myeloid leukemia (CML) diagnosed in the chronic phase (CP). In Perú, there is a lack of registries that reflect the mortality associated with leukemia in CML patients.
Objectives:
This study aims to evaluate the impact of the ELTS score and the SOKAL score to estimate leukemia-related mortality in a cohort of patients from 6 hospitals in Lima-Perú.
Methodology:
A real-life observational retrospective study collected epidemiological and clinical data of de novo CML patients diagnosed between 2007 and 2024, from 6 hemato-oncology centers in Lima. Patients were treated according to each center's guidelines and resources, and the data was obtained from their respective databases.
Results:
In 507 CP-CML patients (ratio male/female 1.77) with a median age of 45.48 years old (7 - 90 yo), the Sokal score was low in 19.9% (n= 101), intermediate in 25.6% (n=130), and high in 54.4% (n=276). ELTS score was low in 37.1% (n=188), intermediate in 33.5% (n=170), and high in 29.4% (n=149) of patients.
There was a total of 85 deaths in all the cohort, of which 53 were leukemia-related, 29 were non-leukemia-related and 3 were from unknown causes. According to the ELTS score, there were 22 (14.8%), 16 (9.4%), and 15 (8%) leukemia-related deaths in the group of high, intermediate, and low risk, respectively. With the Sokal score, the leukemia-related deaths were 32 (11.6%), 7 (5.4%), and 14 (13.9%) in the group of high, intermediate, and low risk, respectively.
The cumulative incidence of leukemia-related mortality according to the ELTS score at 5 and 10 years was: 17.5% and 32.3% (high risk), 9.1% and 23.6% (intermediate risk), 5.39% and 14.1% (low risk) respectively (p=0.013). According to the Sokal score, we did not find a statistically significant difference in leukemia-related mortality in the different groups.
Conclusions:
In this Peruvian cohort, we found that the ELTS score was an effective tool for estimating the risk of leukemia-related mortality, in contrast to the Sokal score. To our knowledge, this is one of the first studies in Latin America about the impact of ELTS score in CML patients.
Non-Canonical Genetics of Hereditary Spherocytosis: A Clinical Case Report
Authors: Banks Alexander S , Flier Sarah N , Heeney Matthew M. 
Published: December 2024

A 7-year old male with Duane Retraction Syndrome and ADHD exhibited progressive lethargy, jaundice, and splenomegaly following multiple bouts upper respiratory infection symptoms. Lethargy persisted despite the resolution of URI, lethargy persisted. He had long-standing anemia (Hb 9-10g/dL), reticulocytosis (ARC 0.4-0.5 M cells/uL), elevated MCHC (34-36 g/dL) and spherocytes on blood smear lead to a clinical diagnosis of hereditary spherocytosis (HS). There is no family history of HS or other hemolytic anemias. Osmotic fragility was slightly increased and erythrocyte Band 3 expression by flow cytometry was reduced.
Although the clinical severity of HS is highly variable, patients typically present with hemolytic anemia and progressive splenomegaly at a frequency of 1:1000-2000 in the population. Loss-of-function mutations within 5 genes (ANK1, EPB42, SLC4A1, SPTB, and SPTA1) cause defects in cytoskeletal structure. The result is increased cell fragility and decreased cellular half-life due to weakened linkage of the erythrocyte plasma membrane to the cytoskeleton. Genetic testing of a limited panel of anemia-associated genes revealed only a heterozygous variant of unknown significance, EPB42 (chr15-43220725-C-T/ rs150530456/c.100+1G&gt;A) affecting splicing of the minor transcript EPB42-206. In contrast, patients with complete loss of function of EPB42 exhibit autosomal recessive HS Type 5. We performed whole genome sequencing to identify other genetic changes that could contribute to the onset HS. Our patient has low polygenic risk scores for variants affect surrogate markers of HS-associated traits including changes in reticulocyte count and mean corpuscular hemoglobin concentration (MCHC). Finally, we nominate rare variants as potentially pathogenic based on the following criteria: low observed frequency in the population, the predicted effect of the variant on protein function, high levels of protein expression in mature erythrocytes, and the observed consequence of these variations on hematological parameters in the UK Biobank population. In the absence of a single, large-effect mutation, we propose an oligogenic composite of factors producing a mild clinical case of hereditary spherocytosis.
Cytogenetic Risk Stratification in a Centre Colombian Multiple Myeloma Patients
Authors: Sandoval-Sus Jose , Sossa Claudia , Salazar Luis Antonio , Peña-Castellanos Angela , Rosales Acevedo Manuel Leonidas , Orozco Oviedo Carlos Alberto , Perez Carlos Andres , Morales Chacon Katherinee , Luna-Gonzalez Maria , Prada-Sepúlveda Ana María , Alvarez Juliana , Tarazona-Bohórquez Melanie , Ochoa Miguel 
Published: December 2024

Introduction:
Multiple myeloma (MM) is a heterogeneous disease with patient outcomes influenced by guest factors, clinical presentation, and genetic abnormalities. This study aimed to classify MM patients into risk groups based on cytogenetic markers and assess their impact on survival.
Methods:
We conducted a prospective cross-sectional study involving 50 MM patients (aged &gt;18 years) treated at Clinica Foscal between October 1, 2021, and July 31, 2023. Patients with smoldering MM were excluded. Genetic studies (FISH, molecular studies, and karyotyping) were performed.
Results:
The cohort consisted of 52% men with a median age of 67 years (range: 46-91). Most patients were urban residents (86%) with health insurance coverage (62%). The most common MM subtype was IgG kappa (38%), followed by IgG lambda (18%) and IgA kappa (12%). Cytogenetic abnormalities included del13q (32.5%), amp1q21 (20%), t(4;14) (15%), and t(11;14) (12%). Abnormal karyotypes were observed in 69% of patients.
Using the Mayo Stratification for Myeloma and Risk-Adapted Therapy (mSMART) scale, 46% of patients were classified as high risk, while 18% were categorized as standard risk. According to the Revised International Staging System (R-ISS), 14% were classified as stage I, 56% as stage II, and 18% as stage III. Among those with abnormal karyotypes, 27.6% were high-risk by mSMART, and 58.6% were stage II by R-ISS.
First-line chemotherapy included Lenalidomide-Bortezomib-Dexamethasone (VRD) in 54.5% of patients, Cyclophosphamide-Bortezomib-Dexamethasone (CyBorD) in 27.3%, Daratumumab plus VRD in 2.3%, and other regimens in 15.9%. No patient achieved complete remission before 4 cycles. Due to the sample size and limited follow-up, the impact of risk stratification on treatment response could not be fully assessed.
Regarding overall survival (OS), at the time of analysis, only the R-ISS showed a statistically significant difference in OS, favoring patients classified as stage I.
Conclusion:
Cytogenetic markers are crucial prognostic factors in MM. In this study, only the R-ISS scale demonstrated utility in refining risk stratification within the follow-up period. Extended follow-up is necessary to establish the prognostic value of other risk stratification scales and to evaluate their potential role in guiding first-line treatment decisions.
Results of Protocol of Treatment-Free Remission in a Small Cohort of Patients with Chronic Myeloid Leukemia in a Essalud Hospital, Lima - Peru
Authors: Pizarro-Perea Marlies , Untama José L. , Navarro-Cabrera Juan Ramon 
Published: December 2024

INTRODUCTION
Chronic Myeloid Leukemia is a disease whose prognosis and survival have significantly improved since the beginning of the use of tirosinkinase inhibitors (TKI). Achieving a sustained deep molecular response has lead to start succesful treatment suspension programs in other settings and stablished guidelines and recommendatios to carry out this suspension of TKI. The object of this work is to present a Real World data in a hospital in a developing country with limited resources. This kind of programs allow us to improved quality of life of patients, however, is mandatory a close follow up specially at the beginning to asses if a restart treatment is needed.

METHODS
An observational, descriptive and retrospective study was performed collecting data from patients with Chronic Myeloid Leukemia (CML) registered at the data base of our institution.

RESULTS
At our hospital, from a cohort of 398 patients with diagnosis of CML between 1996 and 2024 registered in the data base, we performed a count of whom treatment was suspended. A total of 17 patients between 2016 and 2024 were found, 13 of them with medical indication for suspension of treatment, and 4 by own decision. At the time of discontinuation, the supervised group had an average disease duration of 7.04 years [4.89 - 11.83], while the other group had 8.16 years [3.78 - 10.49]. The following results were obtained: Of the 13 patients in protocol, 69.2% (9 patients) remained under observation without loss of molecular response. Of the 4 patients without treatment by their own decision, only 25% (1) remained under observation.
Besides, the average time to restart treatment due to loss of molecular response in the protocol group was 4.81 months [2.73 - 7 months), while for the unauthorized group it was 11.8 months [5.6 - 16.4 months]. At the time of completing the registry, the average treatment-free remission (TFR) time for the within-protocol group was 26.9 months, and 96 months for the only patient in the opposite group.

CONCLUSION
At our hospital, patients with Chronic Myeloid Leukemia who initiated treatment discontinuation within a protocol are a small population yet, although, doing so in a supervised setting generates better opportunities to maintained without therapy by a better selection of suitable patients. Furthermore, the results of this study allow us to keep this measure which is really usefull especially in countries with limited resources for diseases requiring long term therapies.
Detecting departures from the conditional independence assumption in diagnostic latent class models: a simulation study
Authors: Okkaoglu Yasin , Welton Nicky J. , Jones Hayley E. 
Published: December 2024

Abstract
Background
Latent class models can be used to estimate diagnostic accuracy without a gold standard test. Early studies often assumed independence between tests given the true disease state, however this can lead to biased estimates when there are inter-test dependencies. Residual correlation plots and chi-squared statistics have been commonly utilized to assess the validity of the conditional independence assumption and, when it does not hold, identify which test pairs are conditionally dependent. We aimed to assess the performance of these tools with a simulation study covering a wide range of scenarios.

Methods
We generated data sets from a model with four tests and a dependence between tests 1 and 2 within the diseased group. We varied sample size, prevalence, covariance, sensitivity and specificity, with 504 combinations of these in total, and 1000 data sets for each combination. We fitted the conditional independence model in a Bayesian framework, and reported absolute bias, coverage, and how often the residual correlation plots, $${G}^{2}$$

G

2

and $${\chi }^{2}$$

χ

2

statistics indicated lack-of-fit globally or for each test pair.

Results
Across all settings, residual correlation plots, pairwise $${G}^{2}$$

G

2

and $${\chi }^{2}$$

χ

2

detected the correct correlated pair of tests only 12.1%, 10.3%, and 10.3% of the time, respectively, but incorrectly suggested dependence between tests 3 and 4 64.9%, 49.7%, and 49.5% of the time. We observed some variation in this across parameter settings, with these tools appearing to perform more as intended when tests 3 and 4 were both much more accurate than tests 1 and 2. Residual correlation plots, $${G}^{2}$$

G

2

and $${\chi }^{2}$$

χ

2

statistics identified a lack of overall fit in 74.3%, 64.5% and 67.5% of models, respectively. The conditional independence model tended to overestimate the sensitivities of the correlated tests (median bias across all scenarios 0.094, 2.5th and 97.5th percentiles -0.003, 0.397) and underestimate prevalence and the specificities of the uncorrelated tests.

Conclusions
Residual correlation plots and chi-squared statistics cannot be relied upon to identify which tests are conditionally dependent, and also have relatively low power to detect lack of overall fit. This is important since failure to account for conditional dependence can lead to highly biased parameter estimates.
Relationship between evaluation factors and star ratings for Japanese community healthcare institutions in electronic word-of-mouth reviews: an observational study
Authors: Maita Hiroki , Kanezaki Yuki , Akimoto Takashi , Kobayashi Tadashi , Hirano Takahiro , Kato Hiroyuki 
Published: December 2024

Abstract
Background
Internet reviews have become increasingly crucial for both healthcare providers and patients. Electronic word-of-mouth (eWOM) reviews on internet sites often comprise textual content with numerical ratings. In this study, we aimed to identify the evaluation factors of community healthcare institutions regarding eWOM reviews and the impact of each evaluation factor on the institution’s ratings.

Methods
An observational study was conducted to qualitatively and quantitatively analyse eWOM data posted on Google for randomly selected healthcare institutions in Hirosaki, Japan from September to October 2022. For qualitative data, the authors repeatedly read the eWOM text, coded it, and categorised related sections. For quantitative analysis, a multivariate analysis using a linear regression model was conducted with the categorised factors from the qualitative analysis as explanatory variables and eWOM ratings as response variables.

Results
Twenty medical institutions (two hospitals and 18 clinics) were randomly extracted from the registry. A total of 147 eWOM texts from each institution were analysed, and coding was performed for 474 segments in the texts. In the qualitative analysis, the evaluated factors in eWOM texts for medical institutions were categorised as communication (evaluation factor for communication with healthcare providers), clinical practice (evaluation factor for the clinical practice of healthcare providers), and medical institution (evaluation factor for the characteristics of medical institutions). According to the multiple regression analysis, the partial regression coefficients for the explanatory variables of positive communication, clinical practice, and medical institution evaluations were 1.04 (95% confidence interval 0.70 to 1.39), 0.65 (95% confidence interval 0.27 to 1.04), and 0.75 (95% confidence interval 0.35 to 1.15), respectively, with the number of ratings as the response variable. Partial regression coefficients for the explanatory variables of negative communication, clinical practice, and medical institution evaluations were − 1.52 (95% confidence interval − 1.88 to -1.16), -0.90 (95% confidence interval − 1.28 to -0.52), and − 0.24 (95% confidence interval − 0.60 to 0.12), respectively.

Conclusion
We quantitatively and qualitatively analysed the eWOM reviews and ratings of healthcare institutions posted on Google. Three evaluation factors were identified: communication, clinical practice, and medical institution. Our study revealed that communication significantly impacts ratings.
Glycemic control and associated factors in patients with type 2 diabetes in Southwest Ethiopia: a prospective observational study
Authors: Garedo Aster Wakjira , Tesfaye Gorfineh Teshome , Tamrat Rahel , Wynendaele Evelien 
Published: December 2024

Abstract
Background
Diabetes, a known syndrome marked by hyperglycemia and glucose intolerance, is increasing at an alarming rate worldwide. Over half a billion people worldwide have DM, and most live in low- and middle-income countries. Poor glycemic control is a public health concern in type 2 diabetes mellitus. Glycemic control and identifying factors associated with poor glycemic control can help healthcare providers design programs that improve glycemic control and the quality of services provided to patients.

Objectives
This study was designed to assess the level of glycemic control and associated factors in patients with type 2 diabetes in Jimma Medical Center, Southwest Ethiopia.

Methods
This institution-based prospective observational study was conducted among 420 patients with type 2 diabetes at Jimma Medical Center’s diabetic clinics. A pretested structured interviewer-administered questionnaire was used to collect data, and a checklist was used to assess patient documents. The data were analyzed using SPSS version 26. The variables linked to poor glycemic control were investigated using binary logistic regression. Variables with p values less than 0.05 were considered statistically significant.

Results
Six-month follow-ups were conducted among 420 patients with type 2 diabetes, among whom 220 (52.38%) were women. The median age of the participants was 54(IQR = 40–60 years old). The proportion of respondents with uncontrolled fasting blood glucose was 58.1%. Sex (AOR = 2.576, 95% CI [2.80-11.479], P = 0.001), age(≥ 60) (AOR = 2.024, 95% CI [1.794–4.646], P = 0.002), diabetes duration > 10 years (AOR = 3.036, 95% CI [2.616–8.306], P = 0.003), type 2 diabetes mellitus on insulin + oral antidiabetic (OADs) (AOR = 2.08, 95% CI [298-3.918], P = 0.004), obesity (AOR = 2.18, 95% CI [(1.218–4.218)], P = 0.003), diabetic complications (AOR = 3.193, 95% CI [2.324–6.05], p = 0.002) and poor self-care practices (AOR = 3.034, 95% CI [5.821–7.02], P = 0.005) were found to be significantly associated with poor glycemic control.

Conclusion
At the Jimma Medical Center, the prevalence of poor glycemic control was high. Based on these findings, teaching and counseling provided by healthcare providers should focus on improving diabetes self-care activities, weight reduction, and diabetic complications to achieve good glycemic control.

Clinical trial number
Not applicable.