bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromoplexy Is a Frequent Early Clonal Event in EWSR1-Rearranged Round Cell Sarcomas That Can Be Detected Using Clinically Validated Targeted Sequencing Panels
Authors: Dermawan Josephine K. , Slotkin Emily , Tap William D. , Meyers Paul , Wexler Leonard , Healey John , Vanoli Fabio , Vanderbilt Chad M. , Antonescu Cristina R.
Published: February 2024

Chromoplexy is a phenomenon defined by large-scale chromosomal chained rearrangements. A previous study observed chromoplectic events in a subset of Ewing sarcomas (ES), which was linked to an increased relapse rate. Chromoplexy analysis could potentially facilitate patient risk stratification, particularly if it could be detected with clinically applied targeted next-generation sequencing (NGS) panels. Using DELLY, a structural variant (SV) calling algorithm that is part of the MSK-IMPACT pipeline, we characterized the spectrum of SVs in EWSR1-fused round cell sarcomas, including 173 ES and 104 desmoplastic small round cell tumors (DSRCT), to detect chromoplexy and evaluate its association with clinical and genomic features. Chromoplectic events were detected in 31% of the ES cases and 19% of the DSRCT cases. EWSR1 involvement accounted for 76% to 93% of these events, being rearranged with diverse noncanonical gene partners across the genome, involving mainly translocations but also intrachromosomal deletions and inversions. A major breakpoint cluster was located on EWSR1 exons 8–13. In a subset of cases, the SVs disrupted adjacent loci, forming deletion bridges. Longitudinal sequencing and breakpoint allele fraction analysis showed that chromoplexy is an early event that remains detectable throughout disease progression and likely develops simultaneously with the driver fusion. The presence of chromoplexy was validated in an external ES patient cohort with whole exome sequencing. Chromoplexy was significantly more likely to be present in cases that were metastatic at presentation. Together, this study identifies chromoplexy as a frequent genomic alteration in diverse EWSR1-rearranged tumors that can be captured by targeted NGS panels.

Significance:

Chromoplexy is detectable using targeted NGS in a substantial portion of EWSR1-rearranged round cell sarcomas as an early and persistent clonal event, expanding the genomic complexity of fusion-associated sarcomas.
Development of Chromosome 1q+ Specific Treatment for Highest Risk Pediatric Posterior Fossa Ependymoma
Authors: Griesinger Andrea M. , Calzadilla Annaliese J. , Grimaldo Enrique , Donson Andrew M. , Amani Vladimir , Pierce Angela M. , Steiner Jenna , Kargar Soudabeh , Serkova Natalie J. , Bertrand Kelsey C. , Wright Karen D. , Vibhakar Rajeev , Hankinson Todd , Handler Michael , Lindsay Holly B. , Foreman Nicholas K. , Dorris Kathleen
Published: February 2024

Purpose:

There are no effective treatment strategies for children with highest-risk posterior fossa group A ependymoma (PFA). Chromosome 1q gains (1q+) are present in approximately 25% of newly diagnosed PFA tumors, and this number doubles at recurrence. Seventy percent of children with chromosome 1q+ PFA will die because of the tumor, highlighting the urgent need to develop new therapeutic strategies for this population.

Experimental Design:

In this study, we utilize 1q+ PFA in vitro and in vivo models to test the efficacy of combination radiation and chemotherapy in a preclinical setting.

Results:

5-fluorouracil (5FU) enhances radiotherapy in 1q+ PFA cell lines. Specifically, 5FU increases p53 activity mediated by the extra copy of UCK2 located on chromosome 1q in 1q+ PFA. Experimental downregulation of UCK2 resulted in decreased 5FU sensitivity in 1q+ PFA cells. In in vitro studies, a combination of 5FU, retinoid tretinoin (ATRA), and radiation provided the greatest reduction in cellular proliferation and greatest increase in markers of apoptosis in 1q+ PFA cell lines compared with other treatment arms. Similarly, in vivo experiments demonstrated significant enhancement of survival in mice treated with combination radiation and 5FU and ATRA.

Conclusions:

These results are the first to identify a chromosome 1q+ specific therapy approach in 1q+ PFA. Existing phase I studies have already established single-agent pediatric safety and dosages of 5FU and ATRA, allowing for expedited clinical application as phase II trials for children with high-risk PFA.
Tumor Burden Dictates the Neoantigen Features Required to Generate an Effective Cancer Vaccine
Authors: Garzia Irene , Nocchi Linda , Avalle Lidia , Troise Fulvia , Leoni Guido , Seclì Laura , Antonucci Laura , Cotugno Gabriella , Allocca Simona , Romano Giuseppina , Conti Laura , Caiazza Carmen , Mallardo Massimo , Poli Valeria , Scarselli Elisa , D'Alise Anna Morena
Published: February 2024

Tumor neoantigens (nAg) represent a promising target for cancer immunotherapy. The identification of nAgs that can generate T-cell responses and have therapeutic activity has been challenging. Here, we sought to unravel the features of nAgs required to induce tumor rejection. We selected clinically validated Great Ape–derived adenoviral vectors (GAd) as a nAg delivery system for differing numbers and combinations of nAgs. We assessed their immunogenicity and efficacy in murine models of low to high disease burden, comparing multi-epitope versus mono-epitope vaccines. We demonstrated that the breadth of immune response is critical for vaccine efficacy and having multiple immunogenic nAgs encoded in a single vaccine improves efficacy. The contribution of each single neoantigen was examined, leading to the identification of 2 nAgs able to induce CD8+ T cell–mediated tumor rejection. They were both active as individual nAgs in a setting of prophylactic vaccination, although to different extents. However, the efficacy of these single nAgs was lost in a setting of therapeutic vaccination in tumor-bearing mice. The presence of CD4+ T-cell help restored the efficacy for only the most expressed of the two nAgs, demonstrating a key role for CD4+ T cells in sustaining CD8+ T-cell responses and the necessity of an efficient recognition of the targeted epitopes on cancer cells by CD8+ T cells for an effective antitumor response. This study provides insight into understanding the determinants of nAgs relevant for effective treatment and highlights features that could contribute to more effective antitumor vaccines.

See related Spotlight by Slingluff Jr, p. 382.
The Siren Song of Synergy
Authors: Bhola Patrick D. , Letai Anthony
Published: February 2024

In ancient Greek mythology, sirens were creatures of stunning beauty whose mystical songs led sailors to sail their boats onto hidden rocks and into total destruction. In this issue, Mason-Osann and colleagues present data in the context of acute myelogenous leukemia to suggest that while synergy may show initial attractions in drug combinations, it may carry with it hazards previously unforeseen.

See related article by Mason-Osann et al., p. 95 (1).
The Association between High-Dose Allopurinol and Erythropoietin Hyporesponsiveness in Advanced Chronic Kidney Disease: JOINT-KD Study
Authors: Oikawa Megumi , Nishiwaki Hiroki , Hasegawa Takeshi , Sasaki Sho , Yazawa Masahiko , Miyazato Hitoshi , Saka Yosuke , Shimizu Hideaki , Fujita Yoshiro , Murakami Minoru , Uchida Daisuke , Kawarazaki Hiroo , Omiya Shinya , Sasai Fumihiko , Koiwa Fumihiko ,   JOINT-KD Investigators
Published: February 2024

Introduction: The aim of the study was to explore the association between urate-lowering agents and reduced response to erythropoietin-stimulating agents in patients suffering from chronic kidney disease G5. Methods: We conducted a cross-sectional, multicenter study in Japan between April and June 2013, enrolling patients aged 20 years or older with an estimated glomerular filtration rate of ≤15 mL/min/1.73 m2. Exclusion criteria encompassed patients with a history of hemodialysis, peritoneal dialysis, or organ transplantation. The patients were categorized into four groups based on the use of urate-lowering drugs: high-dose allopurinol (>50 mg/day), low-dose allopurinol (≤50 mg/day), febuxostat, and no-treatment groups. We used a multivariable logistic regression model, adjusted for covariates, to determine the odds ratio (OR) for erythropoietin hyporesponsiveness, defined by an erythropoietin resistance index (ERI) of ≥10, associated with urate-lowering drugs. Results: A total of 542 patients were included in the analysis, with 105, 36, 165, and 236 patients in the high-dose allopurinol, low-dose allopurinol, febuxostat, and no-treatment groups, respectively. The median and quartiles of ERIs were 6.3 (0, 12.2), 3.8 (0, 11.2), 3.4 (0, 9.8), and 4.8 (0, 11.2) in the high-dose allopurinol, low-dose allopurinol, febuxostat, and no-treatment groups, respectively. The multivariate regression model showed a statistically significant association between the high-dose allopurinol group and erythropoietin hyporesponsiveness, compared to the no-treatment group (OR = 1.98, 95% confidence interval: 1.10–3.57). Conclusions: Our study suggests that the use of high-dose allopurinol exceeding the optimal dose may lead to hyporesponsiveness to erythropoiesis-stimulating agents.
Prognostic Nutritional Index after Introduction of Atezolizumab with Bevacizumab Predicts Prognosis in Advanced Hepatocellular Carcinoma: A Multicenter Study
Authors: Suzuki Takanori , Matsuura Kentaro , Suzuki Yuta , Okumura Fumihiro , Nagura Yoshihito , Sobue Satoshi , Kato Daisuke , Kusakabe Atsunori , Koguchi Hiroki , Hasegawa Izumi , Matoya Sho , Miyaki Tomokatsu , Kimura Yoshihide , Tanaka Yoshito , Kondo Hiromu , Ozasa Atsushi , Kawamura Hayato , Kuno Kayoko , Fujiwara Kei , Nojiri Shunsuke , Kataoka Hiromi ,   Sakurayama Liver Study Group
Published: February 2024

Introduction: Atezolizumab plus bevacizumab (Atez/Bev) is the preferred treatment for advanced hepatocellular carcinoma (HCC). However, biomarkers of therapeutic efficacy have remained unclear. We took a retrospective approach to explore the role of prognostic nutritional index (PNI) for predicting the outcomes of Atez/Bev treatment. Methods: One hundred 25 HCC patients were enlisted; these patients received Atez/Bev treatment and underwent dynamic computerized tomography/magnetic resonance imaging to determine the treatment response on at least one occasion between October 2020 and January 2023, and their PNI before treatment and at the beginning of the second cycle (PNI-2c) was evaluated. Results: During the initial evaluation, 2 (2%), 28 (22%), 70 (56%), and 25 (20%) patients exhibited a complete response, partial response, stable disease, and progressive disease (PD), respectively. Patients with non-PD tended to have higher PNI at baseline and PNI-2c than those with PD (p = 0.245 and 0.122, respectively), with optimal baseline PNI and PNI-2c cut-off values of 42.6 and 40.4, respectively. PNI at baseline could not be used to predict overall survival (OS) or progression-free survival (PFS). However, PNI-2c predicted OS and PFS (PNI-2c ≥ 40.4 vs. < 40.4: 25.3 vs. 16.2 months, p = 0.008 for OS; 12.7 vs. 8.4 months, p = 0.036 for PFS). A multivariate analysis showed a significant association between PNI-2c and OS. Conclusions: PNI-2c is a predictor of prognosis in HCC patients treated with Atez/Bev therapy.
A Prognostic Model for Survival in Patients with Gastric Signet Ring Cell Carcinoma
Authors: Shao Xiao-Xiao , Li Xi-Chen , Lin Zi-Jian , Ruan Ye-Jiao , Lu Guang-Rong , Wang Wei-Zhong , Huang He
Published: February 2024

Introduction: The objective of our study was to develop a nomogram to predict overall survival (OS) and cancer-specific survival (CSS) in patients with gastric signet ring cell carcinoma (GSRCC). Methods: A total of 3,408 GSRCC patients between 1975 and 2017 were screened from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided into training and validation cohorts. Univariate and multivariate Cox analyses were conducted to identify independent prognostic factors for the construction of a nomogram. The performance of the model was then assessed by the concordance index (C-index), calibration plot, and area under the receiver operating characteristic curve (AUC). Then, the novel nomogram was further assessed by 64 GSRCC patients from our hospital as the external cohort. Results: We identified age, tumor lymph node metastasis (TNM) staging system, surgery, and chemotherapy as significant independent elements of prognosis. On this basis, a nomogram was constructed, with a C-index of OS in the training and validation cohorts of 0.763 (95% CI: 0.751–0.774) and 0.766 (95% CI: 0.748–0.784) and a C-index of CSS of 0.765 (95% CI: 0.753–0.777) and 0.773 (95% CI: 0.755–0.791), respectively. The AUCs of the nomogram for predicting 2- and 5-year OS were 0.848 and 0.885, respectively, and those for predicting CSS were 0.854 and 0.899, respectively, demonstrating the excellent predictive value of the constructed nomogram compared to the traditional AJCC staging system. Similar results were also observed in both the internal and external validation sets. Conclusion: The nomogram provided an accurate tool to predict OS and CSS in patients with GSRCC, which can assist clinicians in making predictions about individual patient survival.
Diagnostische Bronchoskopien: Auch Spätkomplikationen sind bedeutsam
Authors: Hagmeyer Lars
Published: February 2024

Background and objective: Limited data exist regarding the adverse events of advanced diagnostic bronchoscopy, with most of the available information derived from retrospective datasets that primarily focus on early complications. Methods: We conducted a 15-month prospective cohort study among consecutive patients undergoing endosonography and/or guided bronchoscopy under general anesthesia. We evaluated the 30-day incidence of severe complications, any complication, unplanned hospital encounters, and deaths. Additionally, we analyzed the time of onset (immediate, within 1 h of the procedure; early, 1 h–24 h; late, 24 h–30 days) and identified risk factors associated with these events. Results: Thirty-day data were available for 697 out of 701 (99.4%) enrolled patients, with 85.6% having suspected malignancy and multiple comorbidities (median Charlson Comorbidity Index (IQR): 4 (2–5)). Severe complications occurred in only 17 (2.4%) patients, but among them, 10 (58.8%) had unplanned hospital encounters and 2 (11.7%) died within 30 days. A significant proportion of procedure-related severe complications (8/17, 47.1%); unplanned hospital encounters (8/11, 72.7%); and the two deaths occurred days or weeks after the procedure. Low-dose attenuation in the biopsy site on computed tomography was independently associated with any complication (OR: 1.87; 95% CI 1.13–3.09); unplanned hospital encounters (OR: 2.17; 95% CI 1.10–4.30); and mortality (OR: 4.19; 95% CI 1.74–10.11).
Relationship between Lipoprotein Lipase Derived from Subcutaneous Adipose Tissue and Cardio-Ankle Vascular Index in Japanese Patients with Severe Obesity
Authors: Saiki Atsuhito , Takahashi Yuka , Nakamura Shoko , Yamaoka Shuhei , Abe Kazuki , Tanaka Sho , Watanabe Yasuhiro , Yamaguchi Takashi , Nagayama Daiji , Ohira Masahiro , Oshiro Takashi , Tatsuno Ichiro , Shirai Kohji
Published: February 2024

Introduction: Cardio-ankle vascular index (CAVI) is an arterial stiffness index that correlates inversely with body mass index (BMI) and subcutaneous fat area. Lipoprotein lipase (LPL) that catalyzes the hydrolysis of serum triglycerides is produced mainly in adipocytes. Serum LPL mass reflects LPL expression in adipose tissue, and its changes correlate inversely with changes in CAVI. We hypothesized that LPL derived from subcutaneous adipose tissue (SAT) suppresses the progression of arteriosclerosis and examined the relationship of LPL gene expression in different adipose tissues and serum LPL mass with CAVI in Japanese patients with severe obesity undergoing laparoscopic sleeve gastrectomy (LSG). Methods: This study was a single-center retrospective database analysis. Fifty Japanese patients who underwent LSG and had 1-year postoperative follow-up data were enrolled (mean age 47.5 years, baseline BMI 46.6 kg/m2, baseline HbA1c 6.7%). SAT and visceral adipose tissue (VAT) samples were obtained during LSG surgery. LPL gene expression was analyzed by real-time PCR. Serum LPL mass was measured by ELISA using a specific monoclonal antibody against LPL. Results: At baseline, LPL mRNA expression in SAT correlated positively with serum LPL mass, but LPL mRNA expression in VAT did not. LPL mRNA expression in SAT was correlated, and serum LPL mass tended to correlate inversely with the number of metabolic syndrome symptoms, but LPL mRNA expression in VAT did not. LPL mRNA expression in SAT and CAVI tended to correlate inversely in the group with visceral-to-subcutaneous fat ratio of 0.4 or higher, which is considered metabolically severe. Serum LPL mass increased 1 year after LSG. Change in serum LPL mass at 1 year after LSG tended to be an independent factor inversely associated with change in CAVI. Conclusions: Serum LPL mass reflected LPL mRNA expression in SAT in Japanese patients with severe obesity, and LPL mRNA expression in SAT was associated with CAVI in patients with visceral obesity. The change in serum LPL mass after LSG tended to independently contribute inversely to the change in CAVI. This study suggests that LPL derived from SAT may suppress the progression of arteriosclerosis.
Circulating Dipeptidyl Peptidase 3 Modulates Systemic and Renal Hemodynamics Through Cleavage of Angiotensin Peptides
Authors: Picod Adrien , Placier Sandrine , Genest Magali , Callebert Jacques , Julian Nathan , Zalc Maxime , Assad Noma , Nordin Hugo , Santos Karine , Gaudry Stéphane , Chatziantoniou Christos , Mebazaa Alexandre , Azibani Feriel
Published: February 2024

BACKGROUND:

High circulating DPP3 (dipeptidyl peptidase 3) has been associated with poor prognosis in critically ill patients with circulatory failure. In such situation, DPP3 could play a pathological role, putatively via an excessive angiotensin peptides cleavage. Our objective was to investigate the hemodynamics changes induced by DPP3 in mice and the relation between the observed effects and renin–angiotensin system modulation.

METHODS:

Ten-week-old male C57Bl/6J mice were subjected to intravenous injection of purified human DPP3 or an anti-DPP3 antibody (procizumab). Invasive blood pressure and renal blood flow were monitored throughout the experiments. Circulating angiotensin peptides and catecholamines were measured and receptor blocking experiment performed to investigate the underlying mechanisms.

RESULTS:

DPP3 administration significantly increased renal blood flow, while blood pressure was minimally affected. Conversely, procizumab led to significantly decreased renal blood flow. Angiotensin peptides measurement and an AT1R (angiotensin II receptor type 1) blockade experiment using valsartan demonstrated that the renovascular effect induced by DPP3 is due to reduced AT1R activation
via
decreased concentrations of circulating angiotensin II, III, and IV. Measurements of circulating catecholamines and an adrenergic receptor blockade by labetalol demonstrated a concomitant catecholamines release that explains blood pressure maintenance upon DPP3 administration.

CONCLUSIONS:

High circulating DPP3 increases renal blood flow due to reduced AT1R activation via decreased concentrations of circulating angiotensin peptides while blood pressure is maintained by concomitant endogenous catecholamines release.
Neptunus and To Løver: An Archaeological, Archival, and Dendrochronological Survey of Two Danish Prize Ships, Scuttled in the Stockholm Archipelago in 1659
Authors: Daly Aoife , Eriksson Niklas , Hansson Jim
Published: February 2024

We report the archaeological survey, dendrochronological analysis, and archival research concerning two shipwrecks located in shallow waters outside Vaxholm in the Stockholm Archipelago, Baltic Sea. According to oral tradition, the two wrecks are the remains of Neptunus and To Løver, two former Danish warships that were taken as prizes at the battle of Fehmarn in 1644. The Swedish navy then used the two ships until 1659, when they were reportedly scuttled as a blockage along the sea route towards Stockholm. Before being intentionally scuttled, the two ships drifted away and sank. The work presented in this article confirms the substance of the tradition and reports that substantial portions of the two ships are preserved. Moreover, the two wrecks shed light on the scuttling process and the construction of an underwater barrier.
Correlation of detrended fluctuation analysis alpha 1 with blood lactate concentration in field standardised exercise tests in sport horses
Authors: Murphy K. , Solomon C. , Stefanovski D. , Lorello O. , Robinson M. , Haughan J. , Navas de Solis C.
Published: February 2024

Methods to determine exercise intensity thresholds, such as the aerobic and anaerobic threshold, that separate different exercise intensities in exercising horses in the field setting or on the treadmill often require equipment, standardised conditions and/or blood sampling. Detrended fluctuation analysis (DFA) is a heart rate variability variable proposed as a non-invasive tool for exercise intensity monitoring and with a potential association with exercise intensity thresholds and fatigue. The objectives of this study were to (1) describe the first component of DFA (DFA-α1) during standardised field incremental exercise tests in sport horses in active Eventing competition and in sport horses ridden without the goal of participating in competitions, and (2) to determine if DFA-α1 is associated with blood lactate concentration. Null hypotheses of the study were that (1) DFA-α1 is not correlated with blood lactate concentration measurements and (2) the correlation between DFA-α1 and blood lactate concentration is not stronger than the one between blood lactate concentration and heart rate or blood lactate concentration and speed. An in vivo observational study was performed analysing exercising electrocardiograms obtained in 59 standardised exercise tests in the field. DFA-α1 was significantly and moderately correlated with blood lactate concentration (, ). A strong correlation was observed between blood lactate concentration and speed (, ), as well as between blood lactate concentration and heart rate (, ). DFA-α1 correlation with blood lactate concentration was moderate but weaker than the correlation of blood lactate concentration and heart rate or blood lactate concentration and speed. DFA-α1 was not a useful surrogate of blood lactate concentration in field incremental standardised tests used for sport horses in this setting.
The Case for Spirit Realism: A Reply to Fales
Authors: Van Eyghen Hans
Published: February 2024

In this article, I respond to some criticisms raised in Evan Fales’ review of my book The Epistemology of Spirit Beliefs that was published in this journal. The points I will address are the following: (i) Fales’ complaint about unclarity in my epistemological position, (ii) his complaint about my insufficient presentation of alternative explanations, and (iii) his complaint about my use of the terms ‘naturalism’ and ‘naturalistic explanation’.
A Brief Intervention in Primary Care to Improve Parents’ Discipline Practices and Reach Other Caregivers
Authors: Scholer Seth J. , Martin Hannah K. , Adams LauraBeth , Dietrich Mary S.
Published: February 2024

Parents (N = 599) of 6-month-old to 10-year-old children were given a handbook intervention that educates about healthy discipline in a pediatric clinic serving low-income families in Nashville, Tennessee. A research assistant spent approximately 1 minute introducing the intervention. A total of 440 parents (73.4%) responded to a follow-up survey 2 to 4 months later. Most parents (88%) who completed the follow-up survey had read at least part of the handbook. Of parents who received the handbook, 63% reported that the handbook helped them discipline their children. Half of parents reported specific changes they made because of the handbook. The most frequently reported changes were more talking/explaining/communicating (25%), more redirecting (7.8%), more patience/listening (6.0%), less anger/yelling (10.8%), and less spanking (7.5%). 42% of parents reported that they shared the handbook with other caregivers, friends, relatives, and children. A brief clinic intervention improves parents’ discipline practices and reaches other caregivers.
How Institutional Logics Inform Emotional Labour: An Ethnography of Junior Doctors
Authors: Vedi Priyanka , Korczynski Marek , Bishop Simon
Published: February 2024

Sociological analysis of emotional labour can be aided by considering how institutional logics inform the performance of emotional labour. We consider the link between institutional logics and emotional labour by conducting an in-depth case study of junior doctors in a large UK hospital. We point to three key institutional logics – bureaucratic, consumerist and professional logics – and show how they inform the emotional labour of junior doctors. We also consider how doctors respond to these logics through enactment processes of choice, resistance and negotiation. In this way, we make an important theoretical contribution by identifying the way that institutional logics relate to the performance of emotional labour. We also make an important empirical contribution by contributing to a growing body of ethnographies on the emotional labour of doctors.
Granulin in renal tubular epithelia is associated with interstitial inflammation and activates the TLR9-IFN-α pathway in lupus nephritis
Authors: Huang Lanting , Dai Yijun , Geng Zhenbo , He Hongyan , Hong Fuyuan
Published: February 2024

Objective

This study aimed to investigate the possible role of granulin (GRN) in activating the TLR9-IFN-α pathway in renal tubular epithelial cells (RTECs) and explore clues that RTECs regulate the micro-environment of inflammatory response in lupus nephritis (LN).

Methods

Renal sections from 57 LN patients and 30 non-LN patients were sampled for histological study, and GRN overexpression RTECs were applied for cytological study.

Results

In the histological study, GRN is highly expressed in LN RTECs with tubulointerstitial inflammation (TII) and well co-localized with TLR9. ROC analysis suggested a potential relationship between GRN expression in RTECs and therapeutic response. Moreover, IFN-α also highly expressed in LN RTECs with TII, and the intensity of IFN-α is positively correlated with the co-localization intensity of GRN and TLR9. In the cytological study, LN serum, especially serum from LN with TII, activates the expression of TLR9 in RTECs, and GRN engages the interaction of TLR9 to activate the expression of IFN-α in RTECs. While TLR9 inhibitors can suppress the expression of IFN-α in RTECs, the degree of inhibition is dose-dependent.

Conclusion

The expression of GRN in RTECs is associated with interstitial inflammation and therapeutic response. GRN may mediate the activation of the TLR9-IFN-α pathway in RTECs and involve in the micro-environment of inflammatory response in LN.
Immunogenicity and safety of BNT162b2 vaccination in adolescents with systemic lupus erythematosus
Authors: Piyaphanee Nuntawan , Charuvanij Sirirat , Thepveera Sutheera , Toh Zheng Quan , Licciardi Paul V. , Pattaragarn Anirut , Wongprompitak Patimaporn , Boonnak Kobporn , Pheerapanyawaranun Chatkamol , Chokephaibulkit Kulkanya
Published: February 2024

Objectives

We evaluated the immunogenicity and safety of BNT162b2 vaccination in adolescents with systemic lupus erythematosus (adoSLE) receiving either high- or low-dose immunosuppressant (High-IS and Low-IS).

Methods

Patients aged 12–18 years diagnosed with SLE were enrolled. High-IS was defined as >7.5 mg/day prednisolone or with other immunosuppressant, while Low-IS was defined as only ≤7.5 mg/day of prednisolone and no immunosuppressant. Two doses of BNT162b2 vaccination were given 4 weeks apart, followed by a booster (third) dose at 4–6 months later. Anti-spike receptor binding domain (anti-RBD) IgG against Wuhan, neutralising antibody (NT) against Wuhan and Omicron variants, and cellular immune response by IFN-γ-ELISpot assay were evaluated following vaccination. Adverse events (AEs) and SLE flare were monitored.

Results

A total of 73 participants were enrolled, 40 and 33 in the High-IS and Low-IS group, respectively. At 4 weeks following the 2nd dose, overall anti-RBD IgG seropositivity was 97.3%, with no difference between the groups ( p = .498). AdoSLE on High-IS had lower anti-RBD IgG ( p < .001), Wuhan NT ( p < .001), and IFN-γ-ELISpot ( p = .022) than those on Low-IS. A 3rd dose induced significantly higher antibody responses than after the 2nd dose ( p < .001) in both groups and established seroconversion against Omicron variants, with persistent lower antibody levels in High-IS group. SELENA-SLEDAI scores within 12 weeks after 2-dose vaccination was higher than before vaccination (3.1 vs 2.5; p < .036); however, the occurrence of disease flare by SELENA-SLEDAI flare index was not different after vaccination compared to before vaccination, consistent across groups. Non-severe AEs occurred similarly in both groups.

Conclusion

AdoSLE on High-IS induced lower SARS-CoV-2 vaccine immune responses than Low-IS. Vaccination can increase disease activity and requires close monitoring for disease flare.
Effects of Mineral Chinese Medicine Chloriti Lapis on Gut Microbiota of Small Intestine in PTZ-kindling Epileptic Rats
Authors: Yuan Peng , Li Fengtao , Qian Xilong , Ma Yulu , Wang Xiuxiu , Zhao Qian , Zhu Xingyu , Yan Baofei , Zhou Liu , Yang Wei , Pan Yanqiong , Dai Shilin , Fang Fang , Zhao Jin , Liu Shengjin
Published: February 2024

Background

Epilepsy is a neurological disease, and its clinical treatment presents a significant medical challenge. Nevertheless, Chloriti Lapis (CL), a traditional Chinese Mineral Medicine, has been employed for centuries to address neurological disorders and has shown notable effectiveness.

Objectives

The objectives of this study are to further explore whether CL can modulate the abundance and diversity of the small intestinal flora in rats with epilepsy induced by pentylenetetrazol (PTZ) and to investigate the interrelationship among the flora.

Materials and Methods

Operational taxonomic units (OTUs), α diversity, β diversity, hierarchical clustering tree, and principal component analysis (PCA) were utilized to analyze the small intestinal flora of PTZ-kindled epileptic rats.

Results

The predominant bacterial groups in the small intestine mainly belonged to the phyla Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes. The administration of CL was found to effectively increase the abundance and diversity of the small intestinal flora, modify its structural composition, reduce the relative abundance of PTZ-elevated microflora, and enhance the abundance of Streptococcus, Staphylococcus, and Gemella Berger.

Conclusion

CL exhibits promising potential, reliability, and unique value in managing epilepsy through the regulation of intestinal flora.
“I Am Half of a Person”: Lived Experiences of Individuals Living With Ostomy After Surgery in Rural Haiti
Authors: Chery Maurice J. , Henderson Rebecca , Dubique Kobel , Camilus Adler , Eliacin Henry Claude , Pinard Jacquemine , Toussaint Eric , Clisbee Mary
Published: February 2024

Intestinal ostomy can have significant effects on lives and lived experiences. However, limited research exists on the experiences of persons with ostomy in low-resource settings, such as rural Haiti. This study aimed to explore the lived experiences of Haitians with an ostomy, focusing on the physical, psychological, and social aspects of their post-operative lives. We conducted 9 semi-structured, in-depth interviews with participants who had undergone ostomy surgery at the Hôpital Universitaire de Mirebalais in Haiti. Employing interpretative phenomenological analysis (IPA), we iteratively examined transcripts to identify convergent and divergent codes, which were then grouped into themes to better understand the participants’ experiences. Three themes emerged: (a) ostomy as a social disease, which has severe impacts on relationships and place in society; (b) ostomy as altering self-image, leading participants to reflect on their identity and the underlying causes of their condition and to reevaluate their necessities and abilities; and (c) ostomy as an arduous medical journey, characterized by pain, distress, uncertainty, and disillusionment, but also resiliency, improvisation, and hope. This study highlights the multifaceted experiences of persons with ostomy in the low-resource rural environment of Haiti and underscores the need for improved access to medical care, financial support, and psychosocial and caregiving resources for these individuals. Findings also emphasize the importance of medical providers’ improved understanding in making medical decisions, and cultural and socioeconomic factors in developing effective support strategies.
Business Model Innovation for Ambulance Systems in Low- and Middle-Income Countries: “Coordination and Competition”
Authors: Gernert Andreas K , Calmon Andre P , Romero Gonzalo , Van Wassenhove Luk N
Published: February 2024

Several low- and middle-income countries’ emergency transportation systems (ETSs) do not have a centralized emergency number. Instead, they have many independent ambulance providers, each with a small number of ambulances. As a result, ETSs in these contexts lack coordination and ambulances. Using a free-entry equilibrium model, we show that in such decentralized systems, the probability that any given call can be served by at least one ambulance, that is, its coverage, is at most 71.54%, regardless of the ETS’s profitability. We examine three business models that can address the ETS’s lack of coordination and ambulances: (i) a competitor-only business model, where an entrepreneur enters the ETS and acquires ambulances to compete with existing providers; (ii) a platform business model, where an entrepreneur coordinates existing providers; and (iii) an innovative platform-plus business model, where an entrepreneur combines (i) and (ii): setting-up a platform and acquiring platform-owned ambulances. We also examine a government-run platform that takes no commissions from providers. Using a game-theoretic approach, we find that it is optimal for all platform models to incentivize all providers to join. However, only the government-run platform may incentivize providers to acquire additional ambulances. Furthermore, a government-run platform offers higher coverage than a platform-plus only when the platform’s power to coordinate ambulance providers is moderate. Our results can help entrepreneurs and policymakers in LMICs navigate various tradeoffs in improving their countries’ ETS.
Flexural behavior of concrete beams hybrid-reinforced with glass fiber-reinforced polymer, carbon fiber-reinforced polymer, and steel rebars
Authors: Terzioglu Hilal , Eryilmaz Yildirim Meltem , Karagoz Omer , Unluoglu Esref , Dogan Mizan
Published: February 2024

The utilization of fiber-reinforced polymer (FRP) reinforcements in structural design is increasing due to their non-corrosive nature. However, the anisotropic features and linear elastic behavior of FRP rebars have led researchers to explore the use of hybrid combinations of FRP and steel reinforcements. Current codes and guidelines predominantly focus on the design of glass FRP (GFRP) reinforced structural elements, leaving a gap in incorporating the hybrid use of FRP-steel combinations and different types of FRP materials, such as carbon FRP (CFRP). This study conducted experimental investigations on concrete beams reinforced with GFRP, CFRP, and hybrid (GFRP-steel and CFRP-steel in combination) rebars, comparing the results with theoretical models. Ten full-scale beams were tested under monotonic loading. Test results revealed that existing codes overestimate GFRP reinforced beam displacements while underestimating CFRP reinforced beam displacements. A reduction factor is proposed for the effective moment of inertia expression given by ACI 440.11-22 to predict the deflections of CFRP reinforced and hybrid reinforced beams. The experimental data for CFRP and hybrid reinforced concrete beams align well with the predictions calculated using the proposed equations.
Denial from the other side: Experiences of racism as narrated by South Sudanese refugees in Australia
Authors: Hatoss Anikó
Published: February 2024

This paper discusses experiences of everyday racism as narrated by South Sudanese refugee-background informants living in Australia. The paper draws on accounts of verbal and physical attacks reported during a sociolinguistic interview about the refugee experience and adaptation to the Australian lifestyle. The study contributes to the exploration of features of refugee narratives, using the socio-interactional approach to narrative analysis. Selected stories about racism are explored using positioning theory, paying attention to the discursive strategies narrators use to position themselves in the interactional world of the interview setting as well as the story-world. Their narratives demonstrate that despite the harsh experiences of everyday racism, they position themselves as resilient and strong individuals. They do this by drawing on their refugee history and making references to harder times. However, the stories also reveal their mitigation strategies to soften the accounts and either downplay or deny racism. However, by sharing their stories and making explicit evaluative statements about social injustice, they mobilise their agency to make their story heard.
Menstrual cycle characteristics, hormonal contraceptive use and perceptions of related effects in resistance-trained athletes
Authors: SantaBarbara Kimberly , Helms Eric , Armour Mike , Harris Nigel
Published: February 2024

There has been an increased interest in the effects the menstrual cycle (MC) may have on sports performance. As a part of the MC, many females experience a wide range of symptoms related to hormonal fluctuations and menstrual bleeding, including physical pain and mood disturbances. Currently, there is a lack of data on the MCs of females who participate in resistance training. The dearth of information on the regular MC in female athletes may lead to poorly informed training recommendations which may be detrimental for female athletic advancement. The purpose of this survey was to determine the average MC characteristics, hormonal contraceptive (HC) use and perceived effects of the MC on training in resistance-trained athletes, and to determine if there are differences in these variables when comparing recreationally trained women to competitive-level athletes. A survey addressing questions about the MC, HC use and perceived effects of the MC was accessed by 906 participants who self-identified as resistance-trained athletes. Resistance-trained athletes, competitive or not, experience MCs similar to data on other exercising females and the general population. MC symptoms are widespread and, for some, can be quite severe and limiting. Competitive athletes were not more likely to experience MC irregularities than non-competitive females. Nearly half of the participants reported using HCs. Most participants perceived that their MC had a negative effect on their performance and that their MC caused reductions in training load or workout program adherence, although most competitive-level athletes did not withdraw from competitions due to MC symptoms.
Adipose tissue derived stem cell secretome induces motor and histological gains after complete spinal cord injury in Xenopus laevis and mice
Authors: Assunção-Silva Rita C , Pinho Andreia , Cibrão Jorge R , Pereira Inês M , Monteiro Susana , Silva Nuno A , Campos Jonas , Rebelo Ana L , Schlosser Gerhard , Pinto Luisa , Pandit Abhay , Salgado António J
Published: February 2024

Mesenchymal stem cell-based therapies have been studied for spinal cord injury (SCI) treatment due to their paracrine action upon damaged tissues. MSCs neuroregenerative role may relate to the contents of their secretome in anti-inflammatory cytokines and growth-permissive factors. We propose using the secretome of MSCs isolated from the adipose tissue—adipose tissue-derived stem cells (ASCs) as a cell-free based therapy for SCI. In vivo studies were conducted in two SCI models, Xenopus laevis and mice, after complete spinal cord transection. Our results on both models demonstrated positive impacts of ASC secretome on their functional recovery which were correlated with histopathological markers of regeneration. Furthermore, in our mice study, secretome induced white matter preservation together with modulation of the local and peripheral inflammatory response. Altogether, these results demonstrate the neuroregenerative and potential for inflammatory modulation of ASC secretome suggesting it as a good candidate for cell-free therapeutic strategies for SCI.
Rethinking the filter bubble? Developing a research agenda for the protective filter bubble
Authors: Erickson Jacob
Published: February 2024

Filter bubbles and echo chambers have received global attention from scholars, media organizations, and the general public. Filter bubbles have primarily been regarded as intrinsically negative, and many studies have sought to minimize their influence. The detrimental influence of filter bubbles is well-studied. Filter bubbles may, for example, create information silos, amplify misinformation, and promote hatred and extremism. However, comparatively few studies have considered the other side of the filter bubble; its protective benefits, particularly to marginalized communities and those living in countries with low levels of press freedom. Through a review of the literature on digital safe spaces and protective filter bubbles, this commentary suggests that there may be a need to rethink the filter bubble, and it proposes several areas for future research.
Accent Bias Training in Undergraduate Human Resource Management Education
Authors: O’Brien Mary Grantham , Le Thao-Nguyen Nina , Bodea Anamaria , Trofimovich Pavel , Shimada Masako
Published: February 2024

Accent bias, a type of linguistic bias that is based on a speaker’s pronunciation, is a source of partiality in hiring and retention decisions. This study sought to understand perspectives on linguistic diversity and accent bias among university instructors and students in undergraduate human resource management programs. Results point to a lack of coverage alongside stereotypical views about accents and accent bias among instructors and a desire for accent bias training among all participants. The discussion addresses misconceptions that arose, argues for greater focus on accent bias in business communication, and provides guidance for the development of accent bias training.
Foucault and Clinical Photography: An Analysis and Mitigation of the Clinical Gaze in Pediatric Craniofacial Plastic Surgery
Authors: (Johan) Han Lee John , Vercler Christian John
Published: February 2024

While objectification in medicine has been extensively critiqued as a philosophical concept dating back to the Ancient Greeks and contemporarily popularized by Michel Foucault, the impact of objectification through clinical photography in plastic surgery is often overlooked. Plastic surgery patients are by necessity subjected to the clinical gaze through clinical photography, which may lead to experiences of dehumanization and alienation from their physicians and surgeons. In this essay, we explore the concept of the clinical gaze in clinical photography from a structured philosophical lens, and offer one potential answer to this problem. First, we draw upon Foucault’s well-known and monumental critique of contemporary Western medical practice from Birth of the Clinic alongside a brief history of clinical photography to illustrate the problem of the “clinical gaze.” Then, we argue that mitigating the clinical gaze is critical for the flourishing of patients in general and plastic surgery patients in particular. Finally, we offer our attempt to mitigate the clinical gaze that was conducted by the Craniofacial Anomalies Program at the University of Michigan in 2014 as a demonstration of an upending of the power dynamic usually at play.
Complete genome sequence of Schaalia odontolytica isolated from subgingival biofilm
Authors: Jang Eun-Young , Chun Jeewan , Kwack Kyu Hwan , Moon Ji-Hoi , Lee Jae-Hyung
Published: February 2024

Objective

Recent advancements in genome-based taxonomic classification propose the reclassification of certain Actinomyces species into new genera, including Schaalia. Schaalia odontolytica, the type species within this genus, is frequently found in the human oral cavity and has been associated with actinomycotic lesions. Currently, only two complete genomes of S. odontolytica strains have been reported. Recognizing the limited research on subspecies-level variation of S. odontolytica, we conducted genome sequencing of strain KHUD_008, isolated from a Korean periodontitis patient’s subgingival biofilm. Additionally, we performed a comparative genome analysis using previously sequenced genomes of strain XH001 and strain FDAARGOS_732, both derived from the human oral cavity.

Data description

Pacific Biosciences Sequel II sequencing generated 15,904 and 76,557 raw sequencing sub-reads, which were integrated to assemble the de novo genome using the Microbial Genome Analysis pipeline in the Single-Molecule Real-Time Analysis. The genome assembly completeness, assessed by Benchmarking Universal Single-Copy Orthologs, reached 99.2%. The genome is 2,389,595 bp with a GC content of 66.37%, and contains 2,002 protein-coding genes, 9 rRNAs, and 48 tRNA. Comparative analysis with two previously sequenced strains revealed many strain-specific genes in KHUD_008, primarily related to envelope biogenesis and replication/recombination/repair processes.