bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatosplenic T-Cell Lymphoma: A SEER Stat Review of Epidemiology
Authors: Ali Hassan , Durugu Satya R , Desai Krishna , Bajwa Shammas , Sinha Shrishti , Batool Humera , Hassan Muhammad , Thirumaran Rajesh , Agrawal Shubham
Published: December 2024

Background:

Hepatosplenic T-cell Lymphoma (HSTCL), historically known as hepatosplenic gamma/delta T cell lymphoma, is an extremely rare and highly aggressive subtype of peripheral T-cell lymphomas. Characterized by malignant proliferation of cytotoxic T cells, usually expressing gamma/delta T cell receptors but infrequently alpha/beta receptors as well, HSTCL presents with hepatosplenomegaly, thrombocytopenia, or systemic B symptoms. The aim of this study is to investigate epidemiology and survival outcomes based on independent prognostic factors in adult patients with HSTCL over the last two decades.

Method:

The data was collected from Surveillance, Epidemiology and End Result database Research Plus Data, 17 Registries, Nov 2023 Sub (2000-2021). We extracted cases of Hepatosplenic T-cell lymphoma in adults of age 20 years and above, using the ICD code 9716/3. The data was stratified on the basis of age, gender, race, primary site labelled, stage, treatment types, and median household income inflation adjusted to 2022. The analysis was further completed by comparing survival using the Log-rank test (GraphPad Prism).

Results:

From 2000 to 2021, 163 cases of HSTCL were identified in adults of age 20 years and above. 63.8% of the reported cases were males and 36.2% were females. Race-specific distribution observed in descending order was: Caucasian (57.69%), Black (20.86%), Asian/Pacific Islander (11.66%), Hispanic (9.20%) and Native American/Alaskan (0.61%). The median age of diagnosis was 48 years. Further comparison of the survival curves based on age, gender, race, primary site labelled, stage, and inflation adjusted-median household income showed no statistical significance. Survival analysis calculated for chemotherapy and radiation therapy (XRT), as the primary treatment modality, also didn't show any significant association. The sole prognostic factor in our study that showed statistically significant association with survival outcomes was surgical management. The MoS compared for surgery was 22 months and no-surgery was 7 months (CI: 2.138 - 4.621, HR 0.6412, p value 0.0207).

Conclusion:

Hepatosplenic T-cell lymphoma is an ultra-rare malignancy, accounting for <1% of all non-Hodgkins lymphomas. This aggressive tumor has poor outcomes, even with standard-of-care treatment approaches. HSTCL is most commonly observed in male gender and Caucasian race. Our study showed no influence on survival outcomes based on age, race, gender, primary site labelled, stage and income. While improved survival was observed in patients treated surgically, chemotherapy/XRT had no impact on MoS. More studies are needed to better understand and aid in management of this rare but hostile neoplasm.
Venous Thromboembolism in Transgender Individuals Receiving Hormone Replacement Therapy in Alberta, Canada
Authors: Shyian Melissa , Wu Cynthia M. , Wynick Chris J
Published: December 2024

Background:

Hormone therapy is a key component of gender-affirming care for transgender individuals. Estrogen, testosterone, and progestin therapy have been associated with a higher risk of venous thromboembolism (VTE). However, this is largely based on use of these medications in hypogonadism, birth control, and hormone replacement therapy (HRT). There is a lack of information regarding their relation to VTE risk in transgender persons. The aim of this study is to retrospectively examine VTE events for transgender individuals in Alberta, Canada, and their potential association with hormone therapy.

Methods:

Chart review of adult (≥ 18 years of age) transgender individuals was completed using electronic medical records between 2002 and 2021. A list of individuals for the study was provided by a psychiatrist who specializes in transgender care at the Gender Program in Edmonton, Canada. Population included those who were referred for gender affirming surgery. Data collected included age, affirmed gender, VTE events, thrombophilia history, anticoagulation use, and hormone therapy. All data was anonymized prior to analysis. This study was approved by the Alberta Health Ethics Research Board (Pro00114160).

Results:

Fifty-six individuals were identified for this study. Median age as of December 31, 2021 was 27.5 years (range 18-73). Affirmed gender in this cohort included 36 affirmed females (64%), 13 affirmed males (23%), and 7 non-binary individuals (13%). None of the individuals had a history of thrombotic events prior to the study, nor did any have known genetic or acquired thrombophilia. Two of the affirmed female individuals (ages 69 and 73) were on anticoagulation for atrial fibrillation during the study. There were no VTE events (DVT or PE) documented in this cohort.

In terms of HRT, 46 of 56 individuals (82%) were on HRT at some point in the study, including 32/36 affirmed females (89%), 10/13 affirmed males (77%), and 4/7 non-binary individuals (57%). 18/36 of affirmed females (50%) were on combined estradiol and progesterone at some point in the study.

Limitations of this study include the small numbers, retrospective nature and incomplete documentation. Furthermore, transgender individuals must go out of province for gender affirming surgery, and documentation around this strong provoking event was not included as was not accessible in this chart review.

Conclusion:

While there is a known association between hormone supplementation and VTE, there were no documented VTE events in this cohort. Further prospective studies would be ideal to fully characterize other VTE risk factors in this cohort and to monitor for VTE events.
Risk of Venous Thromboembolism in Hospitalized Patients with Chronic Lymphocytic Leukemia Complicated with Autoimmune Hemolytic Anemia
Authors: Eltaher Basant , Mahmoud Amir , Shah Purva
Published: December 2024

Introduction: Autoimmune hemolytic anemia is a recognized complication of chronic lymphocytic leukemia (CLL). Even though venous thromboembolism (VTE) is a potential complication in CLL patients with superimposed autoimmune hemolytic anemia (AIHA), there are not enough studies on anticoagulation guidelines in these patients including prophylaxis.

Methods: National Inpatient Sample (NIS) ICD-10 codes were used between 2016-2020 to create a cohort of hospitalized patients with CLL and AIHA. Data was analyzed using STAT BE software. We implemented descriptive analysis and logistic regression analysis to examine the risk and outcome of VTE in this patient population. Additionally, we adjusted for confounding factors including hypertension, diabetes, end-stage renal disease, hyperlipidemia, and thrombophilia.

Results: Our analysis included 78,974 hospitalized patients with CLL. The mean age was 75 years, with men (60%) and white race (83%) making up the majority of our cohort. 1,866 hospitalized patients with CLL had AIHA, 13.5% of whom had VTE (Vs 10.3% in patients without AIHA). Pulmonary embolism occurred in 6.8% of CLL patients with AIHA (Vs 4.6% in patients without AIHA). The logistic regression model revealed that CLL patients with AIHA were strongly associated with an increased likelihood of VTE (OR 1.3, 95% CI, 1.2-1.5). Additionally, underlying thrombophilia was associated with a significantly increased risk of VTE (OR 6, 95% CI, 5-7.2), even though they comprised around 0.6% of patients with CLL (Vs 0.9% in CLL patients with AIHA). Patients with CLL and underlying comorbid conditions such as congestive heart failure, end-stage renal disease and thrombophilia significantly increased risk of mortality. However, the presence of AIHA didn't have a significant association with the risk of death.

Conclusion: CLL patients with AIHA have an increased likelihood of developing VTE in comparison to CLL patients without AIHA. This data warrants further investigation regarding anticoagulation in these patients.
Impact of Acute Renal Failure on Clinical Outcomes in Bone Marrow Transplant Patients: A Nationwide Analysis
Authors: Uttam Chandani Kanishka , Agrawal Siddharth pravin , Raval Maharshi , Lotia Dev , Nadeem Ahmed
Published: December 2024

Introduction:

Acute renal failure (ARF) complicates bone marrow transplant (BMT) procedures and significantly affects clinical outcomes. This study examines the impact of ARF on mortality, resource use, and other key outcomes in a nationwide cohort of BMT patients.

Methods:

Data were extracted from the National Inpatient Sample (NIS) database, which includes BMT hospitalizations from 2016 to 2021. Patients were classified into two groups: those with ARF (BMT+ ARF+) and those without ARF (BMT+ ARF-). The analysis compared demographic characteristics, baseline health conditions, and clinical outcomes between these groups. Multivariate logistic regression was employed to analyze outcomes adjusting for potential confounders.

Results:

Among the 139,085 BMT hospitalizations, 32,205 patients were identified with ARF. Patients with ARF were older, with a mean age of 55.58 years compared to 46.49 years for those without ARF. Gender distribution differed between groups, with a higher proportion of males in the ARF group (60.47% vs. 55.30%). Racial composition also varied; ARF patients had a larger proportion of White individuals (69.01% vs. 66.41%) and a smaller proportion of Hispanic individuals (10.93% vs. 13.61%) compared to the non-ARF group.

ARF patients had an odds ratio (OR) of 5.42 for mortality (95% CI 4.77-6.16, p < 0.001). The likelihood of requiring transfusions was increased with an OR of 1.61 (95% CI 1.48-1.75, p < 0.001). Additionally, ARF patients had higher odds of bleeding (OR = 1.63, 95% CI 1.48-1.79, p < 0.001), sepsis (OR = 2.92, 95% CI 2.73-3.13, p < 0.001), and septic shock (OR = 6.97, 95% CI 6.22-7.80, p < 0.001). The odds of myocardial infarction were also elevated (OR = 1.64, 95% CI 1.38-1.93, p < 0.001), while arrhythmia had an OR of 1.32 (95% CI 1.07-1.63, p = 0.01). The risk of BMT infection and BMT failure was higher with ORs of 2.16 (95% CI 1.14-4.08, p = 0.017) and 1.39 (95% CI 1.09-1.79, p = 0.008), respectively. Although the odds of BMT rejection were not significantly different (OR = 1.22, 95% CI 0.77-1.94, p = 0.39). ARF patients also experienced longer hospital stays (mean 11.53 days vs. 6.79 days) and incurred higher total healthcare charges ($202,288 vs. $99,901).

Conclusion:

ARF is associated with worse clinical outcomes in BMT patients, with increased mortality, extended hospital stays, and higher healthcare costs. The study also highlights notable differences in gender and racial composition between ARF and non-ARF patients, suggesting that demographic factors may influence the impact of ARF. These findings underscore the need for tailored management strategies to address ARF effectively and to reduce disparities in care. Further research is necessary to refine these strategies and optimize care for this high-risk population.
FLT3 Inhibitors As Maintenance Therapy Post Allogenic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia Patients with FLT3 Mutations; A Systematic Review and Meta-Analysis
Authors: Ansar Sadia , Keen Mahnoor Asghar , Sukaina Mahnoor , Saeed Muhammad , Rehman Zarlish , Rehman Roshaan , Wahab Qazi Muhammad Farooq , Masaud Faryal , Mumtaz Aqsa , Jatwani Karan , Faisal Muhammad Salman
Published: December 2024

INTRODUCTION

Approximately 20-30% of adult patients with acute myeloid leukemia (AML) have an FMS-like tyrosine kinase 3 (FLT3) mutation, which falls in the intermediate risk category for relapse and overall survival per ELN 2022 classification, and eligible patients undergo allogeneic hematopoietic cell transplantation (allo-HCT). FLT3 inhibitors (FLT3i) are used in induction and relapsed settings, but recent studies suggest that FLT3i may reduce the risk of post-transplant relapse. We performed this systematic review and meta-analysis to evaluate the efficacy of FLT3i as post-transplant maintenance therapy in AML patients.

METHODS

A comprehensive search was conducted across PubMed, Embase, Cochrane Library, and Clinicaltrials.gov from inception to March 29, 2024. Studies were included that evaluated response [overall survival (OS), relapse-free survival (RFS), and leukemia-free survival (LFS)], in comparisons between FLT3i and control groups. RevMan version 5.4.1 was used for statistical analysis. A random effect model with inverse variance as the statistical method was used for hazard ratio (HR) and 95% confidence interval (CI).

RESULTS

Of 1698 included studies, the data consists of 13 observational studies, comprising 4402 patients (52% males and 48% females), who met the inclusion criteria. Of the sample size, 36% of patients received FLT3i therapy, while the control group comprised 63.9% of patients. Patient age ranged from 14 to 78 years (median 49 years in intervention). AML subtypes included de novo (29%), secondary to antecedent hematological disorder (AHD) (1.7%), secondary to therapy (0.8%), and unspecified (68.5%). The follow-up period extended from 5.7 to 47.7 months. Nine out of thirteen studies reported cytogenetic risk. The type of FLT3i regimen used was reported as 54% Sorafenib followed by 15% Midostaurin, and only 8% Gilteritinib and Quizartinib. FLTi as maintenance in post-transplant patients significantly improved OS [ HR; 0.56] 95% CI [0.46-0.68], P< 0.00001, I2 31%], RFS [HR 0.56; 95% CI (0.50-0.64), P< 0.00001, I2 0%] and LFS [HR 0.47; 95% CI (0.38-0.57), P< 0.00001, I2 0%] as compared to control.

CONCLUSION

This meta-analysis demonstrates the efficacy of FLT3i as a post-transplant maintenance therapy for preventing relapse in AML patients.
Exploratory Analysis of Biomarkers for Quality Control of Cell Cultures and Prediction of Response to CART Cell Therapy
Authors: Su Guoai , Wu Tong
Published: December 2024

The factors affecting the curative effect of autologous CART cells, derived from the patients' lymphocyte function and activity themselves, plays a very important role.

We were analyzed retrospectively 20 cases treated with autologous CART cells of the blood system of malignant tumor patients, including B - NHL and multiple myeloma, from March-22 to July-31 in 2024; Combined with peripheral blood flow cytometry before the cytological examination related indicators, CART cell activity and the safety of function and the doping after amplification and curative effect of forecast analysis.

The results of multivariate analysis showed that PD1+TIM3+CD4+ exhausted T cells %, PD1+TIM3+CD8+ exhausted T cells %, CD8 Tcm CD45RA-CCR7+CD27+%, TIM3+ % of total T cells %. Initial CD27 + CD45RA + killer T cells when the CCR7 + % of T cell and the living rate of the CART cells and is directly related to the inside-body amplification.

Conclusions: In order to ensure the success rate of CART preparation, and to predict the maximum curative effect, patients after multi-line treatments or influence T cell function related anti-tumor medicine, can use the PD1 + TIM3 + % of the depletion of CD4 + T cells, PD1 + % depleting the TIM3 + CD8 + T cells, Tcm CD45RA - when the CCR7 CD8 + CD27 + %, TIM3 + % of total T cell, and the initial killer T cells CD27 + CD45RA + CCR7 + % of T cells as predict factors and we need to set up subsequently predictive model, data validation and prospective study.
Feasibility of Co-Administration of Autologous NK Cells and Anti-CD38 Monoclonal Antibody Isatuximab, in Multiple Myeloma Post-Autologous HSCT in a Randomized Phase 2 Clinical Trial
Authors: Lund Johan , Meinke Stephan , Kashif Muhammad , Bohlin Anna , Hellstrom Lindberg Eva , Ljunggren Hans-Gustaf , Alici Evren
Published: December 2024

Background: Autologous natural killer (NK) cells have been administered as consolidation therapy in multiple myeloma patients following autologous hematopoietic stem cell transplantation (HSCT). Our primary aim was to evaluate the detectability and phenotypic characteristics of transferred NK cells, with a specific focus on CD38 expression.

Methods: NK cells were isolated, expanded as previously described (https://doi.org/10.1016/j.xcrm.2022.100508), and infused into multiple myeloma patients post-HSCT. Phenotypic analysis was performed to assess CD38 expression on the transferred NK cells. Results indicated retention of reduced CD38 expression on the infused NK cells. Based on initial findings, a clinical trial was initiated to investigate the co-administration of autologous NK cells with isatuximab. To date, 18 patients have been enrolled in which 8 patients received a combination therapy of isatuximab and NK cells and 10 patients received isatuximab only. NK cells were administered in three consecutive doses, every other week during every other week isatuximab administration regimen. First two NK cell doses were 30 million cells/kg, and the last dose was up to 100 million cells/kg. Isatuximab treatment was initiated within 103 days after autologous stem cell transplantation (Range 54-103 days). The retention and phenotype of NK cells following anti-CD38 mAb administration was monitored.

Results: Transferred NK cells were detectable in all patients and characterized by low CD38 expression (MFIR: 0.2) This suggested potential compatibility with anti-CD38 mAb therapy. In this clinical trial, co-administration of autologous NK cells with anti-CD38 mAb was well tolerated in all included patients. NK cells were retained up to one month after administration, indicating that the anti-CD38 mAb did not adversely affect infused autologous NK cells' persistence. Only one patient had a grade 3 treatment emergent adverse event, hemolysis, that was attributed to COVID and RSV infections. Infused cells retained their proliferative capacity with a fluctuating receptor profile, including CD16, following isatuximab administrations.

Conclusion: The co-administration of autologous ex vivo expanded and activated NK cells and Isatuximab is feasible and does not result in the loss of NK cells. These findings support further exploration of this combination therapy to enhance consolidation treatment in multiple myeloma patients post-HSCT.
Racial and Socioeconomic Disparities in Survival Outcomes of Mantle Cell Lymphoma: An Analysis of the Surveillance, Epidemiology, and End Results (SEER) Database from 2000 to 2021
Authors: Ogedegbe Oboseh John , Cheema Asfand Yar , Sukhera Ahmed Bashir , Unlu Serhan , Rodriguez Vazquez Jorge , Erazo Gloria , Tabowei Godfrey
Published: December 2024

Introduction

Mantle Cell Lymphoma (MCL) is a rare class of B-cell non-Hodgkin lymphomas (NHL) characterized by an (11,14) translocation resulting in overexpression of the cyclin D1 (CCND1) gene. Mantle cell lymphoma often follows a difficult clinical course and challenging prognosis. Age and performance status play a role in overall prognosis. There needs to be more data on racial and socioeconomic disparities in the survival outcomes of MCL. Our analysis involved comparing survival outcomes of patients with mantle cell lymphoma based on race, rural-urban, and income.

Methods

Data from the Surveillance, Epidemiology, and End Results (SEER) database program was utilized to obtain the survival analysis data of Mantle Cell Lymphoma. Patient characteristics were expressed in proportions (%). Kaplan-Meier methods were used to estimate 5-year survival rates. Cox proportional hazards regression was used for multivariable modelling of the survival database. The difference between the observed number of events between each group was compared using a log-rank statistical test.

Results

We identified 11,450 patients with complete survival data who were analyzed by our study. 90.4% were whites, 4.1% were blacks, 0.7% were American Indian/Alaska Native, and 4.7% were Asian/Pacific Islander. The one and five-year survival by race/ethnicity were whites (83.6%, 60.3%), Blacks (83.8%, 61.3%), American Indian/Alaska Native (75.8%, 56.4%), Asian or Pacific Islander (82.5%, 60.3%). Urban residency was coded by counties in metropolitan areas with a population greater than 250,000, while non-metropolitan counties coded rural residency. The one and five-year survival by urban (83.8%,61.0%) and rural (82.3%,56.6%) was analyzed. The one and five-year survival by $40,000-$79,999 income (82.9%-58.5%) and >$80,000 income (84.5%, 63.1%) was also calculated. Race was a predictor of worse outcome, Black HR 0.98(95% CI; 0.87-1.1, p = 0.72), American Indian/Alaska Native HR 1.36 (95% CI; 1.02-1.8, p = 0.035), Asian or Pacific Islander HR 0.90 (95% CI; 0.79-1.0, p = 0.075). There was survival disparity by sex, Male (CI 95%; 1.06, 1.00-1.1)

Conclusion

Race and socioeconomic factors play a pertinent role in survival outcomes in patients with mantle cell lymphoma. A survival disparity by sex has also been noted. American Indian/Alaska Natives demonstrated a statistically significant higher hazard ratio compared to Whites, which was the reference.
Advantages of a genomic DNA-based next-generation sequencing assay for detection of mutant NPM1 measurable residual disease in AML
Authors: Vonk Christian M. , Grob Tim , Rijken Melissa , Kavelaars François G. , Konijnenburg Jolinda M. L. , Ossenkoppele Gert J. , Manz Markus G. , Havelange Violaine , Fløisand Yngvar , Löwenberg Bob , Valk Peter J. M.
Published: December 2024

Mutations in the nucleophosmin-1 (NPM1) gene are among the most common molecular aberrations in acute myeloid leukemia (AML). Various studies have established mutant NPM1 (mNPM1) as a faithful molecular measurable residual disease (MRD) marker with prognostic significance. Assessment of prognostic mNPM1 is included in the European LeukemiaNet recommendations on MRD detection in AML. Because of recent advancements of promising drugs targeting mNPM1 AML, monitoring of mNPM1 MRD has gained interest, and is generally done by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). However, these RT-qPCR assays use complementary DNA (cDNA) as input, are based on gene expression levels of mNPM1, and are generally limited to specific mNPM1 gene variants. The main advantages of next-generation sequencing (NGS) using genomic DNA as input are stability, independence of gene expression levels, and the ability to detect any NPM1 variant in a single assay. Here, we comprehensively investigated the applicability of NGS on DNA to detect mNPM1 MRD in a cohort of 119 (cDNA) and 310 (DNA) patients with mNPM1 AML in complete remission after 2 cycles of induction chemotherapy. We demonstrate high correlations in levels and prognostic value between RT-qPCR/cDNA and NGS/DNA approaches, postulating NGS/DNA as an attractive alternative to RT-qPCR. We report that the 2% mNPM1/ABL1 threshold by RT-qPCR/cDNA corresponds to an NGS/DNA variant allele frequency of 0.01%. The NGS/DNA threshold of >0.01% after 2 cycles of induction chemotherapy identifies significantly more patients with AML with an increased relapse risk than current RT-qPCR/cDNA assays. The prognostic significance of mNPM1 MRD appears greatest in patients with AML with FLT3-internal tandem duplications.
Extracorporeal photopheresis for the prevention of rejection after lung transplantation: a prospective randomised controlled trial
Authors: Benazzo Alberto , Cho Ara , Auner Sophia , Schwarz Stefan , Kovacs Zsofia , Ramazanova Dariga , Kolovratova Vera , Branka Manuela , Muraközy Gabriela , Hielle-Wittmann Elisabeth , Aigner Clemens , Hoetzenecker Konrad , Wekerle Thomas , Worel Nina , Knobler Robert , Jaksch Peter
Published: December 2024

Background

Lung transplant recipients have the worst long-term outcomes of all solid organs due to acute rejection and chronic lung allograft dysfunction (CLAD). Our objective was to investigate the efficacy of extracorporeal photopheresis (ECP) as a prophylactic treatment to prevent acute cellular rejection (ACR), cytomegalovirus (CMV) infections and reduce the risk of CLAD.

Methods

This was a single-centre prospective randomised controlled trial conducted at the Medical University of Vienna (Vienna, Austria) between 2018 and 2020. It included 31 COPD recipients per group. The treatment group underwent ECP in addition to a standard triple-drug immunosuppression protocol after lung transplantation. The control group received standard triple-drug immunosuppressive therapy. The primary outcome was a composite outcome defined as incidence of high-grade ACR, CMV infection or CLAD within 24 months after lung transplantation.

Results

In the control group, 19 patients (61.3%) achieved the primary combined end-point compared with only six patients (19.4%) in the treatment group (p<0.001). Freedom from high-grade ACR was significantly greater in the ECP group (p=0.045). Cumulative A scores were significantly lower in the ECP group than in the control group at 3 months (0.18±0.44versus0.56±0.94; p<0.05) and at 12 months (0.25±0.48versus1.0±1.45; p=0.002). The rate of infections was lower in the ECP group with five cases and 67 cumulative hospital days compared with 22 cases and 309 days in the control group (p=0.002). Freedom from CLAD at 3 years was significantly greater in the ECP group (p=0.015).

Conclusion

Adding ECP to standard triple immunosuppression resulted in a significant reduction of the number of ACR episodes and significantly lower incidence of CLAD.
Immunomodulatory dynamics in the porcine myometrium: global transcriptome analysis, including the effects of PPARγ ligands
Authors: Kurzynska Aleksandra , Mierzejewski Karol , Golubska Monika , Jastrzebski Jan Pawel , Bogacka Iwona
Published: December 2024

Background

The myometrium is involved in many processes during pregnancy and the estrous/menstrual cycle. Peroxisome proliferator-activated receptors (PPARs) can be regulators of the processes occurring in the myometrium. In the present study, we determined the global transcriptome profile of the porcine myometrium during the peri-implantation period and the late luteal phase of the estrous cycle. In addition, we investigated for the first time the influence of PPARγ ligands on the transcriptome profile.

Results

The myometrium of gilts (n = 3) was collected on days 10–11 and 14–15 of pregnancy and on the corresponding days of the estrous cycle. The expression of PPARγ was confirmed in the tissue. Based on the mRNA level, further studies were conducted on myometrial explants obtained from pigs at days 14–15 of pregnancy and the corresponding days of the estrous cycle. The tissue sections were incubated in vitro for 6 h in the presence of a PPARγ agonist, pioglitazone (P; 10 µM), or antagonist, T0070907 (T; 1 µM). To identify the transcription profile of the myometrium, RNA-Seq was performed on the NovaSeq 6000 Illumina platform. This study identified 1082 differentially expressed genes (DEGs; 609 upregulated and 473 downregulated) in the porcine myometrium on days 14–15 of pregnancy compared with the corresponding days of the estrous cycle. During pregnancy, we detected 6 and 80 DEGs related to PPARγ agonist and antagonist, respectively. During the estrous cycle, we identified 4 and 17 DEGs for P and T vs. the control, respectively.

Conclusions

The results indicate that the DEGs are involved in a number of processes, including the immune response, prostaglandin synthesis, cell differentiation and communication. In addition, the role of PPARγ activity in regulating the expression of genes related to the immune response and hormone synthesis in the porcine myometrium has been demonstrated.
Measures of social connectedness in adult populations: a systematic review
Authors: Plackett Ruth , Hulin Joe , Mukuria Clara , Clowes Mark , Ramsay Sheena E. , Spencer Liam , Adams Emma A. , Dykxhoorn Jennifer , Walters Kate , Osborn David P. J. , Zamperoni Victoria , Jones Oliver , Weich Scott
Published: December 2024

Background

Poor social connectedness has been identified as a risk factor for poor mental health but there is a lack of standardisation in how it is measured. This systematic review aimed to identify suitable measures of social connectedness for use in UK adult general populations.

Methods

Searches were undertaken in two stages to identify: (1) measures of social connectedness from review articles and grey literature and (2) studies reporting on the psychometric properties of the identified measures. Grey literature and five databases were searched: MEDLINE, Embase and PsycINFO; CINAHL and Web of Science. Studies based on UK adult general populations (16–65 years) or other English language speaking countries with similar cultures (US, Canada, Ireland, Australia and New Zealand) were included. Psychometric evidence was extracted relating to six general domains: conceptual model, content validity, reliability, construct validity, scoring and interpretability, and respondent burden and presentation. A narrative synthesis summarised these psychometric properties.

Results

Stage (1) 2,396 studies were retrieved and, 24 possible measures of social connectedness were identified; stage (2) 6,218 studies were identified reporting on psychometrics of identified measures and 22 studies were included. These studies provided psychometric evidence for 10 measures, and we did not find psychometric studies for the other identified measures. Six measures (6/10, 60%) reported assessing loneliness and four (4/10, 40%) reported assessing social support but there was a degree of overlap between the assessments of each concept. There was good evidence of reliability across measures, 90% (9/10) had adequate internal consistency, but evidence of content validity was only available for one scale. Five measures (5/10, 50%) reported on at least half of the psychometric criteria, and these were: UCLA-3 (for loneliness), and MSPSS, F-SozU K-6, SPS-10 and SPS-5 (for social support).

Conclusions

This review identified ten social connectedness measures, and identified UCLA-3, MSPSS, F-SozUK-6, SPS-10, and SPS-5 as having the most robust psychometric properties for the UK adult population. Further testing is required to establish content validity, and to clarify the definition and conceptualisation of social connectedness, to enable standardisation in the approach to measuring social connectedness.
Same patient but different worlds: A state-of-the-art review translating best practice psychosocial care from musculoskeletal care to the orthopaedic context
Authors: March Marie K. , Roberts Katharine E.
Published: December 2024

Background

Individuals with chronic musculoskeletal conditions experience persistent pain and disability that has deleterious impacts on physical function, psychological health, social engagement, relationships, and work participation. This impact is greater in people with psychosocial risk factors, and best practice musculoskeletal care recommends a biopsychosocial approach to management. Orthopaedic surgery is often an effective management approach for chronic musculoskeletal conditions, but research has only recently explored the links between differing patient outcomes after orthopaedic surgery and psychosocial risk factors. Implementing biopsychosocial approaches to musculoskeletal care has taken great strides in the primary care setting however, implementation of the biopsychosocial approach in orthopaedic surgery brings complexity as the context changes from primary care to hospital based secondary care. The aim of this review therefore is to explore implementation of psychosocial care in the elective orthopaedic surgery context, informed by evidence in musculoskeletal care.

Assessment and management of psychosocial factors

Several composite screening tools for psychosocial factors or ‘yellow flags’ are recommended for use in primary care for musculoskeletal conditions alongside a comprehensive patient interview. However, in the orthopaedic surgery context, composite measures have focused on discharge destination, and there is not a universal approach to comprehensive patient interview incorporating a biopsychosocial approach. A range of biopsychosocial approaches to musculoskeletal conditions have been developed for the primary care setting, yet few have been explored in the context of orthopaedic surgery.

Implementation of psychosocial care

Implementing best practice psychosocial care into the orthopaedic context has enormous potential for all stakeholders, but several barriers exist at the level of the individual patient and practitioner, workforce, health service and society. We have discussed key considerations for implementation including workforce composition, patient-centred care and shared decision making, health literacy, continuity of care, and consideration of preferences for women and culturally diverse communities.

Conclusion

This review considers current literature exploring implementation of psychosocial care into the orthopaedic surgery context, informed by current research in musculoskeletal care. This presents a critical opportunity for orthopaedic surgery to provide optimised, equitable, high-value, patient-centred care.
How to evaluate lifelong learning skills of healthcare professionals: a systematic review on content and quality of instruments for measuring lifelong learning
Authors: Verkooijen Monica H. M. , van Tuijl Anne A. C. , Calsbeek Hiske , Fluit Cornelia R. M. G. , van Gurp Petra J.
Published: December 2024

Background

Having lifelong learning skills is a necessity for healthcare professionals. To evaluate these skills, sound instruments are needed. Those working in healthcare of medical educating looking for a suitable instrument to evaluate lifelong learning (LLL) skills in healthcare professionals are faced with a multitude of definitions and operationalizations of the concept of LLL. A systematic review was performed to analyze the methodological quality and content of instruments measuring LLL for professionals.

Methods

A systematic search of literature published until October 2023 in the electronic databases MEDLINE, CINAHL, PsycINFO, ERIC, Sociological Abstracts, EMBASE, and Web of Science was conducted. English articles describing the development, validation or use of an instrument measuring lifelong learning for professionals working in a professional context were included. A data extraction form was developed to evaluate the content and methodological quality of the instruments. The STORIES statement was used to support reporting this review.

Results

The search revealed 85 articles on 18 questionnaires, no qualitative instruments were found. The instruments covered a range of settings, for example the Jefferson Scale of Physician LLL (JSPLL) covered healthcare and the Effective LLL Inventory (ELLI) covered education. Most instruments provided evidence on content validity and internal consistency, other aspects of validity were examined less frequently. Furthermore, the way that LLL was defined varied greatly, also great variety in the constructs that were defined in the instruments was found. Most instruments lacked a clear description of how the dimensions and items were formalized.

Conclusions

There is a need for LLL instruments that provide more evidence on their validity and put greater emphasis on the development of the definition and operationalization of LLL. Furthermore, there is a need for a better understanding of how to interpret and use the results of the instruments. It is recommended to take a critical look at these constructs before selecting an instrument. This will help all those involved in the training and working environment of healthcare professionals in evaluating lifelong learning skills in their context.

Registration

PROSPERO registration number: CRD42019134804
Medical students’ understanding of clinical empathy – a qualitative exploratory interview study
Authors: Pohontsch Nadine Janis , Stark Anne , Scherer Martin
Published: December 2024

Background

Empathy plays an important role in the interaction and communication with patients. Physicians’ empathy has various positive patients’ and physicians’ outcomes. Despite the inclusion of empathy in medical curricula and the relevance of empathy in general and physicians’ concept of it to medical care, there is no common definition of empathy in the clinical context: definitions tend to be abstract and we do not know enough about medical students’ conceptualization of clinical empathy. A clear and consensual definition of empathy is needed to be able to teach and measure empathy adequately. We aimed to explore German medical students’ views and understanding of (clinical) empathy.

Methods

We interviewed 24 students from the second half of the 3rd year and in their final clinical year (six female and male students in each subgroup) using a semi-structured interview guide. Interviews were digitally recorded and transcribed verbatim. We analysed the transcripts using thematic synthesis (Braun & Clarke).

Results

We found three overarching themes: (1) empathy means perceiving and understanding patients’ needs and acting accordingly, (2) empathy as an interpersonal, intangible construct and (3) taking time for patients. Showing interests, impartiality and openness towards the patients as well as the need to take patients seriously, treating them with respect, having a holistic view on patients and generate some kind of closeness with patients are subthemes of the first overarching theme.

Conclusions

Although it is often stated that the various existing definitions of empathy are abstract or far from practice, German medical students seem to have a good idea how to define empathy. Their definition resembles definitions known from the literature and used in education. Further research is needed to compare concepts of empathy of medical students from different countries and cultural backgrounds to inform research and teaching. It would also be interesting to investigate how concepts of empathy change over the course of study and affect perceptions of empathy in third party assessments.
Exploring the value of arterial spin labeling and six diffusion MRI models in differentiating solid benign and malignant renal tumors
Authors: Gao Mengmeng , Li Shichao , Yuan Guanjie , Qu Weinuo , He Kangwen , Liao Zhouyan , Yin Ting , Chen Wei , Chu Qian , Li Zhen
Published: December 2024

Objective

To explore the value of three-dimensional arterial spin labeling (ASL) and six diffusion magnetic resonance imaging (MRI) models in differentiating solid benign and malignant renal tumors.

Methods

This retrospective study included 89 patients with renal tumors. All patients underwent ASL and ZOOMit diffusion-weighted imaging (DWI) examinations and were divided into three groups: clear cell renal cell carcinoma (ccRCC), non-ccRCC, and benign renal tumors (BRT). The mean and peak renal blood flow (RBFmean and RBFpeak) from ASL and fourteen diffusion parameters from mono-exponential DWI (Mono_DWI), intravoxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI), stretched exponential model (SEM), fractional order calculus (FROC), and continuous-time random-walk (CTRW) model were analyzed. Binary logistic regression was used to determine the optimal parameter combinations. The diagnostic performance of various MRI-derived parameters and their combinations was compared.

Results

Among the six diffusion models, the SEM model achieved the highest performance in differentiating ccRCC from non-ccRCC (area under the receiver operating characteristic curve [AUC] 0.880) and from BRT (AUC 0.891). IVIM model achieved the highest AUC (0.818) in differentiating non-ccRCC from BRT. Among all the MRI-derived parameters, RBFpeak combined with DKI_MK yielded the highest AUC (0.970) in differentiating ccRCC from non-ccRCC, and the combination of RBFpeak, SEM_DDC, and FROC_μ yielded the highest AUC (0.992) for differentiating ccRCC from BRT.

Conclusion

ASL and all diffusion models showed similar diagnostic performance in differentiating ccRCC from non-ccRCC or BRT, while the IVIM model performed better in distinguishing non-ccRCC from BRT. Combining ASL with diffusion models can provide additional value in predicting ccRCC.

Relevance statement

Considering the increasing detection rate of incidental renal masses, accurate discrimination of benign and malignant renal tumors is crucial for decision-making. Combining ASL with diffusion MRI models offers a promising solution to this clinical issue.

Key Points

All assessed models were effective for differentiating ccRCC from non-ccRCC or BRT.

ASL and all diffusion models showed similar performance in differentiating ccRCC from non-ccRCC or BRT.

Combining ASL with diffusion models significantly improved diagnostic efficacy in predicting ccRCC.

IVIM model could better differentiate non-ccRCC from BRT.

Graphical Abstract
Biocontrol ability of Arcopilus aureus YZXR against Fusarium fujikuroi causing leaf spot on Polygonatum odoratum
Authors: Xu Rui , Song Siqing , Wu Guichun , Hu Baishi , Xie Jin , Wang Xiaojiang , Xia Yuanqi , Zheng Sixiang , Peng Siwen , Yuan Ye , Cao Liang , Song Rong , Huang Yanning
Published: December 2024

Arcopilus aureus is a plant-beneficial fungal species showing remarkable biocontrol capabilities. We investigated the antifungal activity of A. aureus YZXR strain and found that it strongly suppressed Polygonatum odoratum leaf spot disease caused by Fusarium fujikuroi. However, the antifungal substances and antifungal mechanisms remain unknown. To identify the antifungal substances, we extracted the fermentation liquid with ethyl acetate and found that the antifungal activity was mainly in the organic phase. Using column chromatography, semi-preparative HPLC, and GC–MS assays, we analyzed the compounds in the ethyl acetate phase and identified phenylethyl alcohol and 3,5-dihydroxytoluene as two compounds showing antifungal activity. The phenylethyl alcohol completely inhibited the growth of F. fujikuroi at a concentration of 0.25% (v/v), whereas the inhibition rate of 10.00 mg/mL 3,5-dihydroxytoluene on fungal growth was 80.60%. The fermentation broth of strain YZXR efficiently inhibited mycelial growth and conidiation of F. fujikuroi. Thus, this study uncovered the antifungal metabolites of A. aureus and the potential of A. aureus as a biological fungicide for managing P. odoratum leaf spot disease, providing a foundation for further research on its biocontrol mechanisms and field applications.
Pattern of antibiotic use among children caregivers: a cross-sectional study
Authors: Ahmed Doaa S. , AboElela Asmaa M. , Ismail Samar S. , Hammour Zeinab E. , Fawaz Rasha A. , Abdelmoniem Marwa E.
Published: December 2024

Background

Antibiotic resistance, a major global health concern, is primarily caused by the irrational use of antibiotics. Parents play a crucial role in antibiotic use by children, directly impacting their clinical outcomes. This study aimed to assess the pattern of antibiotic use among parents and its related factors.

Methods

A cross-sectional study was conducted among 400 parents randomly selected from the pediatric outpatient clinics of Al-Zahraa University Hospital, Cairo. Data were collected using a structured interview questionnaire about sociodemographic data, antibiotic use patterns, parental knowledge and attitudes, common sources of information, and reasons for self-prescribing antibiotics.

Results

Out of the 400 parents surveyed, 87.7% were mothers with a mean age of 31.9 ± 7 years, 76% were highly educated, almost half were not working, 63% came from urban areas, and 95.2% had sufficient income. As for their children, 57.5% had male children; their average age was 5.5 ± 3.7 years. The misuse of antibiotics was prevalent among 37.2% (95% CI = 32.5–42.2%) of parents. When assessing parents’ knowledge and attitude towards antibiotic use, 30.2% (95% CI = 25.8–35.0%) had good knowledge which was significantly more common among highly educated, working, and high-income parents, while the majority (72%, 95% CI = 67.3–76.3%) had a positive attitude. Having more and older children significantly increased the probability of antibiotic misuse, while a higher level of parental education and a positive attitude decreased the likelihood of such misuse (odds ratio (OR) was 1.31, 1.09, 0.52, and 0.11, respectively). Most parents obtained their information about antibiotics from physicians (92%) followed by experience from previous prescription (58.5%). Moreover, among inappropriate users, previous prescriptions and the parent’s perception of the child’s illness as a nonurgent condition were the most frequently cited reasons for the parents’ self-prescription of antibiotics (76.5% and 69.1%, respectively).

Conclusion

Approximately, one-third of surveyed parents demonstrated an inappropriate use of antibiotics. Despite possessing a highly positive attitude and a reasonable level of knowledge about antibiotics, parents often underestimate the potential adverse effects. Tailored measures to promote appropriate antibiotic use are therefore needed to combat the problem of antibiotic resistance.
Lima bean (Phaseolus lunatus L.) powder ameliorates pituitary-liver-axis regulation and anti-inflammatory activity in malnourished rats
Authors: Maliza Rita , Syaidah Rahimi , Rosdianto Aziiz Mardanarian , Tofrizal Allimuddin , Santoso Putra , Lesmana Ronny , Arya Bramadi , Rafi Mohamad
Published: December 2024

The endocrine system is critical for adapting to malnutrition, which can disrupt the pituitary-liver axis and induce inflammation, leading to health complications. Lima beans (Phaseolus lunatus L.), known for their high protein content and anti-inflammatory properties, present a potential nutritional intervention. This study investigated the effects of lima bean powder on pituitary-liver axis regulation and anti-inflammatory activity in malnourished rats. Rats were divided into four groups: Normal (N), Malnourished (MAL), MAL treated with 25% lima bean flour (MAL + 25% LB), and MAL treated with 50% lima bean flour (MAL + 50% LB) for 6 weeks. Proximate composition was determined to analysed its major nutrients and metabolites in the methanol extract were analysed through LC–MS/MS. Parameters such as weight gain, serum albumin, total protein levels, Growth Hormone (GH), Insulin-like Growth Factor 1 (IGF1), and liver inflammation markers were measured. Bioactive compounds such as L(-)-pipecolinic acid, choline, trigonelline, L-phenylalanine, and oleamide were identified, highlighting the nutritional and therapeutic potential of lima beans. Compared to the N group, the MAL group showed significant decreases in body weight gain, serum albumin, and total protein levels. However, both MAL + 25% LB and MAL + 50% LB groups demonstrated significant improvements in these parameters, approximating the levels observed in the N group. Lima bean supplementation appeared to regulate GH at both the cellular and mRNA levels, positively impacting the pituitary-liver axis. Additionally, the study revealed reduced liver inflammation in the MAL + 25% LB and MAL + 50% LB groups, suggesting the anti-inflammatory properties of lima beans. These findings indicate that lima bean flour supplementation can ameliorate disruptions in the pituitary-liver axis and reduce inflammation in malnourished rats.

Graphical Abstract
WISER: Multimodal variational inference for full-waveform inversion without dimensionality reduction
Authors: Yin Ziyi , Orozco Rafael , Herrmann Felix J.
Published: December 2024

We develop a semiamortized variational inference (VI) framework designed for computationally feasible uncertainty quantification in full-waveform inversion to explore the multimodal posterior distribution without dimensionality reduction. The framework is called full-waveform VI via subsurface extensions with refinements (WISER). WISER builds on top of a supervised generative artificial intelligence method that performs approximate amortized inference that is low-cost albeit showing an amortization gap. This gap is closed through nonamortized refinements that make frugal use of wave physics. Case studies illustrate that WISER is capable of full-resolution, computationally feasible, and reliable uncertainty estimates of velocity models and imaged reflectivities.