bluuebunny/crossref_metadata_2025 huggingface dataset:
HER3 (ERBB3) amplification in liposarcoma - a putative new therapeutic target?
Authors: Becker Ann-Katharina , Puladi Behrus , Xie Kunpeng , Cassataro Angela , Götzl Rebekka , Hölzle Frank , Beier Justus P. , Knüchel-Clarke Ruth , Braunschweig Till
Published: May 2024

Background

Liposarcomas are among the most common mesenchymal malignancies. However, the therapeutic options are still very limited and so far, targeted therapies had not yet been established. Immunotherapy, which has been a breakthrough in other oncological entities, seems to have no efficacy in liposarcoma. Complicating matters further, classification remains difficult due to the diversity of morphologies and nonspecific or absent markers in immunohistochemistry, leaving molecular pathology using FISH or sequencing as best options. Many liposarcomas harbor MDM2 gene amplifications. In close relation to the gene locus of MDM2, HER3 (ERBB3) gene is present and co-amplification could occur. Since the group of HER/EGFR receptor tyrosine kinases and its inhibitors/antibodies play a role in a broad spectrum of oncological diseases and treatments, and some HER3 inhibitors/antibodies are already under clinical investigation, we hypothesized that in case of HER3 co-amplifications a tumor might bear a further potential therapeutic target.

Methods

We performed FISH analysis (MDM2, DDIT3, HER3) in 56 archived cases and subsequently performed reclassification to confirm the diagnosis of liposarcoma.

Results

Next to 16 out of 56 cases needed to be re-classified, in 20 out of 54 cases, a cluster-amplification of HER3 could be detected, significantly correlating with MDM2 amplification. Our study shows that the entity of liposarcomas show specific molecular characteristics leading to reclassify archived cases by modern, established methodologies. Additionally, in 57.1% of these cases, HER3 was cluster-amplified profusely, presenting a putative therapeutic target for targeted therapy.

Conclusion

Our study serves as the initial basis for further investigation of the HER3 gene as a putative therapeutic target in liposarcoma.
Protecting effects of 4-octyl itaconate on neonatal hypoxic-ischemic encephalopathy via Nrf2 pathway in astrocytes
Authors: Yang Yanping , Li Yang , Yang Wenyi , Yang Xueying , Luo Man , Qin Ling , Zhu Junchao
Published: May 2024

Background

Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the most common neurological problems occurring in the perinatal period. However, there still is not a promising approach to reduce long-term neurodevelopmental outcomes of HIE. Recently, itaconate has been found to exhibit anti-oxidative and anti-inflammatory effects. However, the therapeutic efficacy of itaconate in HIE remains inconclusive. Therefore, this study attempts to explore the pathophysiological mechanisms of oxidative stress and inflammatory responses in HIE as well as the potential therapeutic role of a derivative of itaconate, 4-octyl itaconate (4OI).

Methods

We used 7-day-old mice to induce hypoxic-ischemic (HI) model by right common carotid artery ligation followed by 1 h of hypoxia. Behavioral experiments including the Y-maze and novel object recognition test were performed on HI mice at P60 to evaluate long-term neurodevelopmental outcomes. We employed an approach combining non-targeted metabolomics with transcriptomics to screen alterations in metabolic profiles and gene expression in the hippocampal tissue of the mice at 8 h after hypoxia. Immunofluorescence staining and RT-PCR were used to evaluate the pathological changes in brain tissue cells and the expression of mRNA and proteins. 4OI was intraperitoneally injected into HI model mice to assess its anti-inflammatory and antioxidant effects. BV2 and C8D1A cells were cultured in vitro to study the effect of 4OI on the expression and nuclear translocation of Nrf2. We also used Nrf2-siRNA to further validate 4OI-induced Nrf2 pathway in astrocytes.

Results

We found that in the acute phase of HI, there was an accumulation of pyruvate and lactate in the hippocampal tissue, accompanied by oxidative stress and pro-inflammatory, as well as increased expression of antioxidative stress and anti-inflammatory genes. Treatment of 4OI could inhibit activation and proliferation of microglial cells and astrocytes, reduce neuronal death and relieve cognitive dysfunction in HI mice. Furthermore, 4OI enhanced nuclear factor erythroid-2-related factor (Nfe2l2; Nrf2) expression and nuclear translocation in astrocytes, reduced pro-inflammatory cytokine production, and increased antioxidant enzyme expression.

Conclusion

Our study demonstrates that 4OI has a potential therapeutic effect on neuronal damage and cognitive deficits in HIE, potentially through the modulation of inflammation and oxidative stress pathways by Nrf2 in astrocytes.
The intersection between migration, HIV, and contraceptive use in Uganda: a cross-sectional population-based study
Authors: Namusisi Prossy , Yeh Ping Teresa , Ssekubugu Robert , Chang Larry William , Lutalo Tom , Zimmerman Linnea , Grabowski Mary Kathryn
Published: May 2024

Background

Low use of modern methods of contraception has been linked to HIV seropositivity and to migration, but few studies have evaluated the intersection of both risk factors with contraceptive use.

Methods

We analyzed cross-sectional data from sexually active female participants aged 15 to 49 years in the Rakai Community Cohort Study (RCCS) between 2011 and 2013. The RCCS is an open population-based census and individual survey in south-central Uganda. Recent in-migrants (arrival within approximately 1.5 years) into RCCS communities were identified at time of household census. The primary outcome was unsatisfied demand for a modern contraceptive method (injectable, oral pill, implant, or condom), which was defined as non-use of a modern contraceptive method among female participants who did not want to become pregnant in the next 12 months. Poisson regression models with robust variance estimators were used to identify associations and interactions between recent migration and HIV serostatus on unsatisfied contraceptive demand.

Results

There were 3,417 sexually active participants with no intention of becoming pregnant in the next year. The mean age was 30 (± 8) years, and 17.3% (n = 591) were living with HIV. Overall, 43.9% (n = 1,500) were not using any modern contraceptive method. Recent in-migrants were somewhat more likely to have unsatisfied contraceptive demand as compared to long-term residents (adjusted prevalence risk ratio [adjPRR] = 1.14; 95% confidence interval [95%CI]: 1.02–1.27), whereas participants living with HIV were less likely to have unsatisfied contraceptive demand relative to HIV-seronegative participants (adjPRR = 0.80; 95%CI = 0.70–0.90). When stratifying on migration and HIV serostatus, we observed the highest levels of unsatisfied contraceptive demand among in-migrants living with HIV (48.7%); however, in regression analyses, interaction terms between migration and HIV serostatus were not statistically significant.

Conclusions

Unsatisfied contraceptive demand was high in this rural Ugandan setting. Being an in-migrant, particularly among those living with HIV, was associated with higher unsatisfied contraceptive demand.
The neutrophil to lymphocyte ratio associates with markers of Alzheimer’s disease pathology in cognitively unimpaired elderly people
Authors: Jacobs Tovia , Jacobson Sean R. , Fortea Juan , Berger Jeffrey S. , Vedvyas Alok , Marsh Karyn , He Tianshe , Gutierrez-Jimenez Eugenio , Fillmore Nathanael R. , Gonzalez Moses , Figueredo Luisa , Gaggi Naomi L. , Plaska Chelsea Reichert , Pomara Nunzio , Blessing Esther , Betensky Rebecca , Rusinek Henry , Zetterberg Henrik , Blennow Kaj , Glodzik Lidia , Wisniweski Thomas M. , de Leon Mony J. , Osorio Ricardo S. , Ramos-Cejudo Jaime ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: May 2024

Background

An elevated neutrophil–lymphocyte ratio (NLR) in blood has been associated with Alzheimer’s disease (AD). However, an elevated NLR has also been implicated in many other conditions that are risk factors for AD, prompting investigation into whether the NLR is directly linked with AD pathology or a result of underlying comorbidities. Herein, we explored the relationship between the NLR and AD biomarkers in the cerebrospinal fluid (CSF) of cognitively unimpaired (CU) subjects. Adjusting for sociodemographics, APOE4, and common comorbidities, we investigated these associations in two cohorts: the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the M.J. de Leon CSF repository at NYU. Specifically, we examined associations between the NLR and cross-sectional measures of amyloid-β42 (Aβ42), total tau (t-tau), and phosphorylated tau181 (p-tau), as well as the trajectories of these CSF measures obtained longitudinally.

Results

A total of 111 ADNI and 190 NYU participants classified as CU with available NLR, CSF, and covariate data were included. Compared to NYU, ADNI participants were older (73.79 vs. 61.53, p < 0.001), had a higher proportion of males (49.5% vs. 36.8%, p = 0.042), higher BMIs (27.94 vs. 25.79, p < 0.001), higher prevalence of hypertensive history (47.7% vs. 16.3%, p < 0.001), and a greater percentage of Aβ-positivity (34.2% vs. 20.0%, p = 0.009). In the ADNI cohort, we found cross-sectional associations between the NLR and CSF Aβ42 (β = -12.193, p = 0.021), but not t-tau or p-tau. In the NYU cohort, we found cross-sectional associations between the NLR and CSF t-tau (β = 26.812, p = 0.019) and p-tau (β = 3.441, p = 0.015), but not Aβ42. In the NYU cohort alone, subjects classified as Aβ + (n = 38) displayed a stronger association between the NLR and t-tau (β = 100.476, p = 0.037) compared to Aβ- subjects or the non-stratified cohort. In both cohorts, the same associations observed in the cross-sectional analyses were observed after incorporating longitudinal CSF data.

Conclusions

We report associations between the NLR and Aβ42 in the older ADNI cohort, and between the NLR and t-tau and p-tau in the younger NYU cohort. Associations persisted after adjusting for comorbidities, suggesting a direct link between the NLR and AD. However, changes in associations between the NLR and specific AD biomarkers may occur as part of immunosenescence.
Epidemiology of work-related injuries, musculoskeletal disorders and dermatitis among hospital food service workers in a tertiary hospital in Asia
Authors: Leong Kenneth Bao Ren , Ng Qin Xiang , Gan Wee Hoe , Ng Wee Tong , Lim John Wah
Published: May 2024

Background

Despite the relative importance, the prevalence of workplace safety and health issues in hospital food service workers is not well studied. This study describes the epidemiology of work-related injuries and occupational diseases among hospital food service workers (FSWs) in a tertiary hospital in Singapore.

Methods

Using a total population sampling approach, a cross-sectional self-administered questionnaire was distributed to all FSWs employed at a major tertiary hospital in Singapore.

Results

The response rate was 98.4% (n = 125). The overall prevalence of workplace injuries and musculoskeletal symptoms was 35% (n = 43) and 53% (n = 65) respectively. The most common workplace injuries were cuts/lacerations (35.8%), muscle strain (25.4%) and burns (19.4%). The prevalence of workplace injuries among staff performing food preparation duties was higher at 56.3% as compared to 21.6% among staff with no food preparation duties (p < 0.01). The prevalence of workplace injuries among staff performing cooking duties was also higher at 47.5%, compared to 29.3% among staff with no cooking duties (p = 0.05). Staff performing food preparation duties had a higher prevalence of musculoskeletal symptoms at 66.7% as compared to 44.6% among staff with no food preparation duties (p = 0.02). Obese staff had a higher prevalence of musculoskeletal symptoms at 78.9%, compared to overweight staff at 53.8% and staff with normal weight at 43.1% (p = 0.03).

Conclusion

FSWs with jobs involving cooking and preparation of food, and those with obesity, are at higher risk of sustaining workplace injuries or musculoskeletal symptoms. Targeted interventions should be implemented for injury prevention and to mitigate these risks.
Same job, same working conditions? A cross-sectional study to examine the similarities and differences of the working situation in ambulatory and residential youth welfare workers
Authors: Kersten Maren , Vincent-Höper Sylvie , Wirth Tanja , Gregersen Sabine , Nienhaus Albert
Published: May 2024

Background

Employees in social work exhibit high rates of sick leave due to mental health issues. Additionally, work-related demands in youth welfare have increased in recent years. Particularly in light of the escalating shortage of skilled professionals in this field, this trend becomes especially critical. The aim of this study is to systematically examine health-relevant working conditions, coping strategies, and health indicators in youth welfare. A special focus is placed on a differentiated analysis of job-related characteristics in the context of outpatient and residential youth welfare.

Methods

Mean values, standard deviations and the reliability of scales are measured. In addition to descriptive statistics, t-tests for analyzing mean differences, as well as correlation analyses and odds ratios as measures of association, are computed.

Results

A total of N = 1044 employees in youth welfare participated in the online survey. Among them, 671 individuals belonged to the field of residential youth welfare, and 373 to outpatient youth welfare. The results indicate that, in youth welfare in general, a variety of emotional, social, qualitative, and quantitative demands exhibit high levels. The comparison between outpatient and residential youth welfare reveals differences in half of the demands. The significant differences are observed for social demands and aggression from clients, which are statistically significant higher in the residential setting. Regarding resources, the most significant difference is observed for autonomy, which is higher in the outpatient setting. Overall, the association patterns reveals more similarities than differences between outpatient and residential settings. In both settings working conditions seem to have deteriorated during the pandemic.

Conclusions

In conclusion, the identified job-related characteristics in outpatient and residential youth welfare exhibit more similarities than differences. Nevertheless, the identified differences provide insights into the specific features of each work context, offering valuable starting points for targeted health promotion in practice.

Trial registration

This trial is recorded at the Hamburg University Ethics Committee (AZ 2022_027).
Preoperative assessment of bone density for dental implantation: a comparative study of three different ROI methods
Authors: Wang Shiuan-Hui , Fuh Lih-Jyh , Chen Michael Y. C. , Tsai Ming-Tzu , Huang Heng-Li , Peng Shin-Lei , Hsu Jui-Ting
Published: May 2024

Background

Dental cone beam computed tomography (CBCT) is commonly used to evaluate cancellous bone density before dental implant surgery. However, to our knowledge, no measurement approach has been standardized yet. This study aimed to evaluate the relationship between three different regions of interest (ROI) methods on cancellous bone density at the dental implant site using dental CBCT images.

Methods

Patients’ dental CBCT images (n = 300) obtained before dental implant surgery were processed using Mimics (Materialise, Leuven, Belgium). At the potential implant sites, the rectangle, cylinder, and surrounding cylinder ROI methods were used to measure bone density. Repeated measures one-way analysis of variance was performed to compare the three ROI methods in terms of measurement results. Pearson correlation analysis was performed to identify the likely pair-wise correlations between the three ROI methods.

Results

The density value obtained using the surrounding cylinder approach (grayscale value [GV],523.56 ± 228.03) was significantly higher than the values obtained using the rectangle (GV, 497.04 ± 236.69) and cylinder (GV,493 ± 231.19) ROI methods in terms of results. Furthermore, significant correlations were noted between the ROI methods (r > 0.965; p < 0.001).

Conclusions

The density measured using the surrounding cylinder method was the highest. The choice of method may not influence the trends of measurement results.

Trial registration

This study was approved by the Institutional Review Board of China Medical University Hospital, No. CMUH111-REC3-205. Informed consent was waived by the Institutional Review Board of China Medical University Hospital, CMUH111-REC3-205, owing to the retrospective nature of the study.
Clinical applications of metagenomic next-generation sequencing in the identification of pathogens in periprosthetic joint infections: a retrospective study
Authors: Shi Tengfei , Chen Huiyu , Liu Yinhuan , Wu Yexin , Lin Feitai
Published: May 2024

Background

This study aimed to evaluate the application of metagenomic next-generation sequencing (mNGS) technology to identify pathogens in periprosthetic joint infection (PJI).

Methods

A retrospective analysis was conducted on 65 patients suspected of having PJI between April 2020 and July 2023. The patients were categorized into PJI (46 patients) and non-PJI (19 patients) groups based on the 2018 International Consensus Meeting criteria. Clinical data were collected, and both conventional bacterial culture and mNGS were performed. The diagnostic performance of the two methods was compared and analyzed.

Results

mNGS exhibited a sensitivity of 89.13%, a specificity of 94.74%, a positive predictive value of 97.62%, a negative predictive value of 78.26%, and an overall diagnostic accuracy of 90.77%. Compared to microbial culture, mNGS demonstrated superior diagnostic sensitivity while maintaining similar specificity. A total of 48 pathogens were successfully identified using mNGS, with Coagulase-negative staphylococci, Streptococci, Staphylococcus aureus, and Cutibacterium acnes being the most common infectious agents. Notably, mNGS was used to identify 17 potential pathogens in 14 culture-negative PJI samples, highlighting its ability to detect rare infectious agents, including Cutibacterium acnes (n = 5), Granulicatella adiacens (n = 1), Mycobacterium tuberculosis complex (n = 1), and Coxiella burnetii (n = 1), among others, which are not detectable by routine culture methods. However, mNGS failed to detect the pathogen in 4 culture-positive PJI patients, indicating its limitations. Among the 46 PJI patients, 27 had positive culture and mNGS results. The results of mNGS were concordant with those of culture at the genus level in 6 patients with PJI and at the species level in 18 patients. Furthermore, the present study revealed a significantly greater proportion of Staphylococcus aureus in the sinus tract group (45.45%) than in the non-sinus tract group (14.29%), indicating the association of this pathogen with sinus formation in PJI (P = 0.03). Additionally, there was no significant difference in the occurrence of polymicrobial infections between the sinus tract group (27.27%) and the non-sinus tract group (33.33%) (P = 0.37).

Conclusions

Metagenomic next-generation sequencing can serve as a valuable screening tool in addition to traditional culture methods to improve diagnostic accuracy through optimized culture strategies.
Fatty Liver Index (FLI) is the best score to predict MASLD with 50% lower cut-off value in women than in men
Authors: Crudele Lucilla , De Matteis Carlo , Novielli Fabio , Di Buduo Ersilia , Petruzzelli Stefano , De Giorgi Alessia , Antonica Gianfranco , Berardi Elsa , Moschetta Antonio
Published: May 2024

Background

Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined by the presence of hepatic steatosis, detected on ultrasonography (US) imaging or histology, and at least one of criteria for Metabolic Syndrome diagnosis. Simple non-invasive tests (NITs) have been proposed as an acceptable alternative when US and biopsy are not available or feasible but have not been validated for MASLD. In this observational study, we investigated the reliability of NITs for MASLD detection and whether sex-differences in screening methods should be considered.

Methods

We included 1069 individuals (48% males and 52% females) who underwent their first clinical examination for Metabolic Syndrome in the period between January 2015 and December 2022. Liver steatosis was detected through US and anthropometric and clinical parameters were recorded.

Results

Liver steatosis was detected in 648 patients and MASLD was diagnosed in 630 subjects (355 males; 275 females). Women with MASLD showed better metabolic profile and lower prevalence of Metabolic Syndrome criteria than men. Among NITs, Fatty Liver Index (FLI) showed the best ability for detection of MASLD, with a cut-off value of 44 (AUC = 0.82). When considering the two sexes for MASLD detection via FLI, despite no substantial differences regarding FLI correlations with metabolic biomarkers except for age, women showed marked lower FLI cut-off value (32; AUC = 0.80) than men (60; AUC = 0.80).

Conclusions

In this study, we found that FLI is the best non-invasive predictor of both liver steatosis and MASLD. The finding that in women FLI cut-off value for MASLD detection is 50% lower than in men suggests the need of a sex-specific personalized program of screening and prevention of dysmetabolism-related liver diseases, despite outwardly healthy biomarkers profile.
‘Atawhai’: a primary care provider-led response to family violence in Aotearoa New Zealand
Authors: Gear Claire , Koziol-McLain Jane , Eppel Elizabeth , Rolleston Anna , Timutimu Ngareta , Ahomiro Hori , Kelly Eunice , Healy Clare , Isham Claire
Published: May 2024

Background

As a key determinant of ill-health, family violence is inadequately responded to within Aotearoa New Zealand health policy and practice. Without adequate system support, health professionals can often be unsure of what to do, or how to help. Developed in response to this system gap, ‘Atawhai’ aims to make it easier for primary care professionals to respond to family violence.

Methods

Underpinned by indigenous Māori customs, Atawhai combines complexity theory and participatory research methodologies to be responsive to the complexity involved in family violence. We worked with 14 primary care professionals across ten whakawhitiwhiti kōrero wānanga (meetings for deliberate dialogue) to identify and develop primary care system pathways and tools for responding to family violence. This paper focuses on the development of Atawhai through wānanga and observation methods. Methods used to capture change will be reported separately.

Findings

Atawhai is a relational response to family violence, focused on developing a network of trusted relationships between health and social care professionals to support safe responses to those accessing care. This study identified four key health system pathways to responsiveness and developed associated tools to support health care responsiveness to family violence. We found the quality of relationships, both among professionals and with those accessing care, coupled with critical reflection on the systems and structures that shape policy and practice are essential in generating change within primary care settings.

Conclusions

Atawhai is a unique health care response to family violence evidenced on empirical knowledge of primary care professionals. Our theoretical lens calls attention to parts of the system often obscured by current health care responses to family violence. Atawhai presents an opportunity to develop a grassroots-informed, long-term response to family violence that evolves in response to needs.
Modeling the distribution of Aloe ankoberensis and A. debrana under different climate change scenarios in North Shewa Zone, Amhara National Regional State, Ethiopia
Authors: Abebe Haile , Desta Anteneh Belayneh , Dejene Sintayehu Workneh
Published: May 2024

Background

Aloeankoberensis M.G. Gilbert & Sebsebe and A.debrana Christian are Ethiopian endemic species currently classified as endangered and least concern, respectively under International Union for Conservation of Nature (IUCN) categories. Recent studies indicate that climate change is anticipated to significantly influence the distribution of plant species. Therefore, this study aimed to model the distribution of A.ankoberensis and A.debrana under different climate change scenarios in the North Shewa Zone, Amhara National Regional State of Ethiopia. Thirty-six and 397 georeferenced presence points for A.ankoberensis and A.debrana, respectively, and 12 environmental variables were used to simulate their current and future distributions. The ensemble model approach was used to examine the current and future (2050 and 2070) climatic suitability for both species under three shared socio-economic pathway (SSP) climate scenarios (SSP 2.6, 4.5 and 8.5).

Results

The performance of ensemble model was excellent for A.ankoberensis with score of area under curve (AUC) 0.96 and true skill statistics (TSS) 0.88, and good for A.debrana with score of AUC 0.87 and TSS 0.63. The main variables that affected the species' distributions were mean diurnal range of temperature, annual precipitation, and elevation. According to the model, under the current climate conditions, 98.32%, 1.01%, 0.52%, and 0.15% were not suitable, lowly, moderately, and highly suitable areas, respectively for A.ankoberensis, and 63.89%, 23.35%, 12.54%, and 0.21% were not suitable, lowly, moderately and highly suitable areas, respectively for A.debrana. Under future climate scenarios, suitable habitats of these species could shrink. In addition, under all climate change scenarios, it is anticipated that highly suitable areas for both species and moderately suitable areas for A.ankoberensis will be lost completely in the future unless crucial interventions are done on time.

Conclusions

The results indicate that the future may witness a decline in suitable habitat for A.ankoberensis and A.debrana, which leads to increasing threat of extinction. Therefore, it is crucial to develop a conservation plan and enhance climate change adaptation strategies to mitigate the loss of suitable habitats for these highland and sub-Afroalpine endemic Aloe species.
Analysis of CD20 and PD-L1 levels on small extracellular vesicles (sEV) produced by DLBCL cells and EBV-transformed B cells, and potential role in T cell inhibition
Authors: Akil Hussein , Bentayeb Hafidha , Aitamer Marine , Vignoles Chantal , Abraham Julie , Gachard Nathalie , Olivrie Agnès , Guyot Anne , Gobbo Jessica , Feuillard Jean , Shirvani Hamasseh , Troutaud Danielle
Published: May 2024

Increasing evidence supports a role for small extracellular vesicles (sEV, including exosomes) in Diffuse Large B-cell lymphoma (DLBCL) progression and resistance to treatment. CD20 and PD-L1 are found on DLBCL-derived sEV, but little is known about their patient-level heterogeneity. Moreover, the capacity of PD-L1+ sEV to modulate T cells needs to be clarified. Herein we analyzed sEV produced by human DLBCL cell lines and EBV-transformed B cell-lymphoblastoid cell lines (LCLs), a model allowing autologous T cell co-cultures. We determined CD20 and PD-L1 levels on plasma sEV from patient samples vs healthy volunteers (HV). sEV functional relevance was also investigated on CD4+ and CD8+ T cells. sEV derived from all cell lines showed an enrichment of CD20 and a high glycosylated PD-L1 expression when compared to cell lysates. High PD-L1 expression on LCL-derived sEV was associated with higher CD4+ and CD8+ T cell apoptosis. In patients, plasma sEV concentration was higher vs HV. Compared to sEV-CD20 level that seemed higher in patients, PD-L1 level in sEV was not different from those of HV. A high glycosylated PD-L1 level was shown in sEV from both patients and HV plasma samples, that was associated with the same inhibiting effect on activated T cells. We conclude that sEV derived from EBV-transformed B cells realize an immunosuppressive role that involved cell–cell interaction and probably at least PD-L1. Furthermore, our findings suggest the potential of circulating sEV as a source of biomarkers in DLBCL, notably to have information on immunotherapeutic target levels of parental tumor cells.
Changes in interoceptive accuracy related to emotional interference in somatic symptom disorder
Authors: Lee Deokjong , Kim Se Joo , Cheon Jooah , Jung Young-Chul , Kang Jee In
Published: May 2024

Objective

The somatic symptom disorder (SSD) is characterized by one or more distressing or disabling somatic symptoms accompanied by an excessive amount of time, energy and emotion related to the symptoms. These manifestations of SSD have been linked to alterations in perception and appraisal of bodily signals. We hypothesized that SSD patients would exhibit changes in interoceptive accuracy (IA), particularly when emotional processing is involved.

Methods

Twenty-three patients with SSD and 20 healthy controls were recruited. IA was assessed using the heartbeat perception task. The task was performed in the absence of stimuli as well as in the presence of emotional interference, i.e., photographs of faces with an emotional expression. IA were examined for correlation with measures related to their somatic symptoms, including resting-state heart rate variability (HRV).

Results

There was no significant difference in the absolute values of IA between patients with SSD and healthy controls, regardless of the condition. However, the degree of difference in IA without emotional interference and with neutral facial interference was greater in patients with SSD than in healthy controls (p = 0.039). The IA of patients with SSD also showed a significant correlation with low-frequency HRV (p = 0.004) and high-frequency HRV (p = 0.007).

Conclusion

SSD patients showed more significant changes in IA when neutral facial interference was given. These results suggest that bodily awareness is more affected by emotionally ambiguous stimuli in SSD patients than in healthy controls.
Assessment of abdominal lesions in pigs with wounded umbilical outpouchings transported to slaughter
Authors: Jørgensen Benjamin Meyer , Jensen Tina Birk , Becker Cecilie Brandt , Flyger Christoffer Kirkelund , Christensen Maja Vive , Birch Andreas , Jensen Henrik Elvang
Published: May 2024

Background

Umbilical outpouchings (UOs) in pigs are of welfare and production concern in Danish pig herds. One of the challenges is the transportation of these animals due to the size of the UOs and ulcerations on them. With certain precautions and an approval from a veterinarian, pigs with UOs may be transported, however, UOs are associated with several intra-abdominal lesions, e.g. peritonitis and incarceration, which may worsen during the process of transportation. The prevalence and characterization of intra-abdominal lesions associated with UOs following transportation has not been investigated. Therefore, the objective of the present study was to evaluate lesions associated with the intestines and peritoneum in slaughter pigs with wounded UOs following transportation to an abattoir.

Results

A cross-sectional study involving three conventional Danish pig herds was conducted comprising 96 slaughter pigs with wounded UOs transported to an abattoir. Following slaughter the UOs with accompanying intestines were examined pathologically. Three distinct morphological categories were present: hernia, enterocystoma and herniating enterocystoma. Intra-abdominal lesions were present in 72% of the animals, representing 65% (44/68) of the hernias, 77% (10/13) of the enterocystomas, and 100% (15/15) of the herniating enterocystomas. Several different lesions were found like bleedings, acute/chronic peritonitis and hypertrophy of the intestinal muscular layers.

Conclusions

The prevalence of intra-abdominal lesions in pigs transported with a wounded UO was found to be high independent of the underlying condition, and it is clear that these pigs possess a vulnerable group of animals, especially during physical stressful situations like transportation. More information is needed regarding the prevalence of intra-abdominal lesions in UO pigs without wounds on the UO. The results provide valuable knowledge, that can be used when examining and evaluating UO pigs before transportation.
Exploring the drivers of unmet need for contraception among adolescents and young women in Sierra Leone. a cross-sectional study
Authors: Osborne Augustus , James Peter Bai , Bangura Camilla , Kangbai Jia B.
Published: May 2024

Background

Sierra Leone grapples with a concerning reality: a high unmet need for contraception among adolescents and young women (AYW). This translates to a multitude of unintended pregnancies, jeopardising their health, education, and overall life trajectory. To effectively address this challenge, we aim to examine the factors associated with the unmet need for contraception among AYW in Sierra Leone.

Methods

The study analysed the 2019 Sierra Leone Demographic and Health Survey data. A total of 1,796 married and cohabiting AYW aged 15 to 24 years, representing the nationally representative sample, comprised the study. A multivariable binary regression analysis was used to explore the drivers of unmet needs for contraception. The regression results were presented using an adjusted odds ratio (AOR) with 95% confidence intervals (CI).

Results

The study found that 29% of Sierra Leonean AYW had an unmet need for contraception. AYW with three or more births(AOR = 6.80, 95% CI = 3.97, 11.65), two births (AOR = 4.11, 95% CI = 2.50, 6.76), one birth (AOR = 4.40, 95% CI = 2.81, 6.88), heard family planning on TV last few months (AOR = 1.94, 95% CI = 0.98, 3.83), and are cohabiting (AOR = 1.88, 95% CI = 1.29, 2.75) had higher odds of unmet need for contraception. AYW who read the newspaper or magazine at least once a week (AOR = 0.11, 95% CI = 0.01, 1.10) had lower odds of unmet need for contraception.

Conclusions

The study found a high unmet need among AYW in Sierra Leone, which indicates a significant gap between desired and actual contraceptive use, leading to unintended pregnancies and potentially adverse health and socio-economic consequences. Parity, media exposure and cohabitation were associated with a higher unmet need for contraception and newspaper/magazine readership was associated with a lower unmet need for contraception. The study highlights the need to increase access to affordable and diverse contraceptive options, especially in rural areas. Expand educational campaigns beyond TV to include print media and community-based interventions. Provide AYWs with knowledge and authority to make well-informed decisions around their sexual and reproductive well-being.
A retrieval-augmented chatbot based on GPT-4 provides appropriate differential diagnosis in gastrointestinal radiology: a proof of concept study
Authors: Rau Stephan , Rau Alexander , Nattenmüller Johanna , Fink Anna , Bamberg Fabian , Reisert Marco , Russe Maximilian F.
Published: May 2024

Background

We investigated the potential of an imaging-aware GPT-4-based chatbot in providing diagnoses based on imaging descriptions of abdominal pathologies.

Methods

Utilizing zero-shot learning via the LlamaIndex framework, GPT-4 was enhanced using the 96 documents from the Radiographics Top 10 Reading List on gastrointestinal imaging, creating a gastrointestinal imaging-aware chatbot (GIA-CB). To assess its diagnostic capability, 50 cases on a variety of abdominal pathologies were created, comprising radiological findings in fluoroscopy, MRI, and CT. We compared the GIA-CB to the generic GPT-4 chatbot (g-CB) in providing the primary and 2 additional differential diagnoses, using interpretations from senior-level radiologists as ground truth. The trustworthiness of the GIA-CB was evaluated by investigating the source documents as provided by the knowledge-retrieval mechanism. Mann–Whitney U test was employed.

Results

The GIA-CB demonstrated a high capability to identify the most appropriate differential diagnosis in 39/50 cases (78%), significantly surpassing the g-CB in 27/50 cases (54%) (p = 0.006). Notably, the GIA-CB offered the primary differential in the top 3 differential diagnoses in 45/50 cases (90%) versus g-CB with 37/50 cases (74%) (p = 0.022) and always with appropriate explanations. The median response time was 29.8 s for GIA-CB and 15.7 s for g-CB, and the mean cost per case was $0.15 and $0.02, respectively.

Conclusions

The GIA-CB not only provided an accurate diagnosis for gastrointestinal pathologies, but also direct access to source documents, providing insight into the decision-making process, a step towards trustworthy and explainable AI. Integrating context-specific data into AI models can support evidence-based clinical decision-making.

Relevance statement

A context-aware GPT-4 chatbot demonstrates high accuracy in providing differential diagnoses based on imaging descriptions, surpassing the generic GPT-4. It provided formulated rationale and source excerpts supporting the diagnoses, thus enhancing trustworthy decision-support.

Key points

• Knowledge retrieval enhances differential diagnoses in a gastrointestinal imaging-aware chatbot (GIA-CB).

• GIA-CB outperformed the generic counterpart, providing formulated rationale and source excerpts.

• GIA-CB has the potential to pave the way for AI-assisted decision support systems.

Graphical Abstract
Clinical and economic burden of organ damage among patients with systemic lupus erythematosus in a real-world setting in Germany
Authors: Schultze Michael , Garal-Pantaler Elena , Pignot Marc , Levy Roger A , Carnarius Heike , Schneider Matthias , Gairy Kerry
Published: May 2024

Background

Systemic lupus erythematosus (SLE), a chronic multisystem autoimmune disease, carries high risk of organ damage and burden to healthcare systems. SLE disease modification aims to reduce disease activity with minimal treatment toxicity and preventing or minimizing organ damage development. This real-world study utilizing healthcare administrative claims data assessed organ damage development, associated costs and healthcare resource utilization (HCRU) in patients with SLE in Germany.

Methods

Claims data from January 1, 2007, to December 31, 2017, were obtained from the Betriebskrankenkassen German Sickness Fund Database. Adults (> 18 years) with a confirmed SLE diagnosis between January 1, 2009, and December 31, 2014, (inclusion period) were included. The index date was calculated based on the first recorded SLE diagnosis during this period. Patients were propensity score–matched (1:3) to a comparator cohort without SLE by age, sex, and comorbidities (Charlson comorbidity index). Organ damage was identified using an algorithm developed based on conditions described in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), using ICD-10-GM diagnostic codes, healthcare procedures, and/or treatments.

Results

2121 patients with SLE and 6308 comparator patients were included (mean follow-up time: 6.4 years). Organ damage prevalence increased from 60.5% at baseline to 83.0% during 6 years of follow-up in all patients with SLE, while 17.0% of patients with SLE did not develop organ damage. Patients with newly confirmed SLE diagnosis without organ damage at baseline were nearly twice as likely to develop organ damage within 5 years versus the comparator cohort (52.0% vs. 27.0%). Total annual costs per patient-year for patients with SLE with organ damage were more than double those of patients with SLE without organ damage; both the number of inpatient admissions and length of stay were higher.

Conclusions

The application of a recently developed algorithm allowed us to use claims data to elucidate SLE organ damage, and its associated high clinical and economic burden, in a large, representative sample in Germany. To our knowledge, this is the first European analysis of its kind involving a broad cohort of patients with SLE treated in the routine care setting.
AlphaFold-latest: revolutionizing protein structure prediction for comprehensive biomolecular insights and therapeutic advancements
Authors: Uzoeto Henrietta Onyinye , Cosmas Samuel , Bakare Toluwalope Temitope , Durojaye Olanrewaju Ayodeji
Published: May 2024

Breakthrough achievements in protein structure prediction have occurred recently, mostly due to the advent of sophisticated machine learning methods and significant advancements in algorithmic approaches. The most recent version of the AlphaFold model, known as “AlphaFold-latest,” which expands the functionalities of the groundbreaking AlphaFold2, is the subject of this article. The goal of this novel model is to predict the three-dimensional structures of various biomolecules, such as ions, proteins, nucleic acids, small molecules, and non-standard residues. We demonstrate notable gains in precision, surpassing specialized tools across multiple domains, including protein–ligand interactions, protein–nucleic acid interactions, and antibody–antigen predictions. In conclusion, this AlphaFold framework has the ability to yield atomically-accurate structural predictions for a variety of biomolecular interactions, hence facilitating advancements in drug discovery.
Selection of Germline Genetic Testing Panels in Patients With Cancer: ASCO Guideline
Authors: Tung Nadine , Ricker Charité , Messersmith Hans , Balmaña Judith , Domchek Susan , Stoffel Elena Martinez , Almhanna Khaldoun , Arun Banu , Chavarri-Guerra Yanin , Cohen Stephanie A. , Cragun Deborah , Crew Katherine D. , Hall Michael J. , Idos Gregory , Lopez Ghecemy , Pal Tuya , Pirzadeh-Miller Sara , Pritchard Colin , Rana Huma Q. , Swami Umang , Vidal Gregory A.
Published: May 2024

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines .

Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by providers and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases, or stages of diseases. Guidance is based on review and analysis of relevant literature and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and Appendix 2 ( online only) for more.

PURPOSE

To guide use of multigene panels for germline genetic testing for patients with cancer.

METHODS

An ASCO Expert Panel convened to develop recommendations on the basis of a systematic review of guidelines, consensus statements, and studies of germline and somatic genetic testing.

RESULTS

Fifty-two guidelines and consensus statements met eligibility criteria for the primary search; 14 studies were identified for Clinical Question 4.

RECOMMENDATIONS

Patients should have a family history taken and recorded that includes details of cancers in first- and second-degree relatives and the patient's ethnicity. When more than one gene is relevant based on personal and/or family history, multigene panel testing should be offered. When considering what genes to include in the panel, the minimal panel should include the more strongly recommended genes from Table 1 and may include those less strongly recommended. A broader panel may be ordered when the potential benefits are clearly identified, and the potential harms from uncertain results should be mitigated. Patients who meet criteria for germline genetic testing should be offered germline testing regardless of results from tumor testing. Patients who would not normally be offered germline genetic testing based on personal and/or family history criteria but who have a pathogenic or likely pathogenic variant identified by tumor testing in a gene listed in Table 2 under the outlined circumstances should be offered germline testing. Additional information is available at www.asco.org/molecular-testing-and-biomarkers-guidelines .
Street Evangelists and Transgender Saints
Authors: Greene-Hayes Ahmad
Published: May 2024

This article historicizes the religious fervor of the 1969 Stonewall riots—multiple direct actions against the anti-Black and homo- and transphobic NYPD and white-owned bars in Greenwich Village—by examining the political organizing of Marsha P. Johnson and Sylvia Rivera, cofounders of Street Transvestite Action Revolutionaries. This article queries and queers the field’s preoccupation with the cisgender and heterosexual regarding religious affiliation and the formation of liberation theologies, and probes at the heart of Johnson’s and Rivera’s critical absences in religious studies on the one hand, and the critical absence of their religious sensibilities in narrations of queer and trans politics on the other.
Christianity and Rationalism:
Authors: Papaoikonomou Antonis
Published: May 2024

Maximus the Confessor and René Descartes were influential thinkers in their respective historical and philosophical contexts, but their philosophical orientations and concerns were distinct. Maximus was primarily a Christian theologian who integrated faith and reason within a theological framework, while Descartes was a key figure in the development of modern philosophy, emphasizing individual reason and scepticism as foundational elements of his philosophical system. This paper aims to present some aspects of their philosophy and try to find common ground in their thought.
The fascination of the West and the ambivalence of the Byzantines towards it through the case of Demetrios Kydones
Authors: Tripoula Ioanna
Published: May 2024

This paper focuses on the case of the politician and scholar Demetrios Kydones as typical of the fascination that the West exerted on the Byzantines, but also of the ambivalence towards it. First, there is a brief overview of the events of his life, which encouraged his contact with the Latins. A more detailed reference was made to his translation, writing, and teaching. In our view, his provocative positions were the reason he had not received the recognition he deserved to this day. His most important value lies in the fact that, in an age of hostility, he sought to bring Byzantium closer to the West by presenting logical and valid arguments beyond petty political pursuits and prejudices.