bluuebunny/crossref_metadata_2025 huggingface dataset:
Accuracy of MRI in predicting deep myometrial invasion in endometrial cancer and the influence of leiomyoma, adenomyosis and the microcystic elongated and fragmented tumour pattern
Authors: Liyanage Anuja , Cardoza Supriya , Kasabia Darshna , Moore Helen
Published: February 2024

Introduction

The most common form of endometrial cancer is Type 1 endometrioid adenocarcinoma. Depth of myometrial invasion is the most important prognostic factor correlating with overall patient survival. The objective was to investigate how accurate magnetic resonance imaging (MRI) is in predicting the depth of myometrial invasion in preoperative assessment, and the influence of leiomyoma and/or adenomyosis, or microcystic, elongated and fragmented (MELF) pattern of invasion on MRI diagnostic performance.

Method

Retrospective audit of 235 endometrial cancer patients from the regional Gynaecology Oncology multidisciplinary meeting at Auckland City Hospital, between January 2020 and January 2021. Radiologist assigned stage was compared to histopathology. Presence of leiomyoma, adenomyosis and MELF pattern evaluated followed by analysis under a Biostatistician's supervision.

Results

Overall MRI diagnostic accuracy for depth of myometrial invasion was 86%. For deep myometrial invasion, MRI had a sensitivity of 72% and specificity 91%. Out of the misreported 32/235 cases, 16 demonstrated fibroids and/or adenomyosis leading to a sensitivity of 57% and specificity 93% for deep invasion, compared with 94% and 74% respectively in the population without, demonstrating statistical significance. Thirty seven cases with MELF pattern of invasion showed a sensitivity of 81% and specificity 80% for deep invasion, compared with 63% and 92% respectively in the group without, demonstrating no statistical significance.

Conclusion

MRI assessment of the depth of myometrial invasion in endometrial cancer has high accuracy. In the presence of background uterine fibroids/adenomyosis, pre‐operative MRI accuracy of evaluating deep invasion shows a statistically significant reduction.
HuR‐positive stress granules: Potential targets for age‐related osteoporosis
Authors: Huai Ying , Wang Xue , Mao Wenjing , Wang Xuehao , Zhao Yipu , Chu Xiaohua , Huang Qian , Ru Kang , Zhang Ling , Li Yu , Chen Zhihao , Qian Airong
Published: February 2024

Aging impairs osteoblast function and bone turnover, resulting in age‐related bone degeneration. Stress granules (SGs) are membrane‐less organelles that assemble in response to stress via the recruitment of RNA‐binding proteins (RBPs), and have emerged as a novel mechanism in age‐related diseases. Here, we identified HuR as a bone‐related RBP that aggregated into SGs and facilitated osteogenesis during aging. HuR‐positive SG formation increased during osteoblast differentiation, and HuR overexpression mitigated the reduction in SG formation observed in senescent osteoblasts. Moreover, HuR positively regulated the mRNA stability and expression of its target β‐catenin by binding and recruiting β‐catenin into SGs. As a potential therapeutic target, HuR activator apigenin (API) enhanced its expression and thus aided osteoblasts differentiation. API treatment increased HuR nuclear export, enhanced the recruitment of β‐catenin into HuR‐positive SGs, facilitated β‐catenin nuclear translocation, and contributed osteogenesis. Our findings highlight the roles of HuR and its SGs in promoting osteogenesis during skeletal aging and lay the groundwork for novel therapeutic strategies against age‐related skeletal disorders.
MicroRNA mediated regulation of oxidative stress and cytokines in Chlamydia trachomatis‐infected recurrent spontaneous abortion: A case‐control study
Authors: Ray Ankita , Pradhan Dibyabhaba , Siraj Fouzia , Arora Renu , Rastogi Sangita
Published: February 2024

Problem

Increased oxidative stress (OS) and inflammatory responses are major underlying factors behind Chlamydia trachomatis‐associated recurrent spontaneous abortion (RSA). miRNAs are known to regulate inflammation and OS and their dysregulation has been associated with compromised pregnancies. Therefore, aim of this study was to investigate the expression/correlation of OS biomarkers, cytokines and miRNAs in C. trachomatis‐associated RSA.

Method of Study

Urine and non‐heparinized blood samples were collected from RSA patients with history of >3 consecutive abortions (cases) and non‐pregnant women with history of >2 successful deliveries (controls) attending Department of Obstetrics and Gynaecology, Safdarjung hospital, New Delhi. C. trachomatis detection was done in urine by PCR. miRNA expression was studied by microarray analysis and validated by real time‐PCR. Evaluation of cytokines and antioxidant genes expression were done by real‐time PCR. Level of OS biomarkers 8‐hydroxy guanosine (8‐OHdG) and 8‐isporostane (8‐IP) were measured by ELISA.

Results

Fifty circulating miRNAs were differentially expressed in infected patients compared with controls. Of these, four were overexpressed and 46 downregulated. Thirteen differentially expressed circulating miRNAs were selected to validate microarray results. miRs‐8069, ‐3663‐3p showed maximum upregulation/downregulation in infected versus control group. Expression of cytokines (IL‐8, TNF‐α, IFN‐γ), antioxidant genes SOD2 and OS biomarkers (8‐OHdG,8‐IP) were increased while SOD1 was decreased in infected patients. miR‐8069 showed significant positive correlation with cytokines, SOD2, 8‐OHdG and 8‐IP. miR‐3663‐3p showed significant positive correlation with SOD1.

Conclusions

Overall results indicate circulating miRNAs are involved in pathogenesis of C. trachomatis‐associated RSA and are potential modulators of cytokine signalling and OS in infected RSA.
Pregnant individuals with uncomplicated pregnancies display pro‐inflammatory immune changes when exposed to the COVID‐19 pandemic
Authors: Bernier Elsa , Brien Marie‐Eve , Girard Sylvie
Published: February 2024

Problem

The COVID‐19 pandemic has been shown to have a detrimental impact on the mental health of pregnant individuals, and chronic stress can alter the immune profile. However, the effects of the COVID‐19 pandemic on the immune system in pregnancy are still poorly understood. We aimed to evaluate the impact of pandemic exposure on the maternal immune profile in uncomplicated pregnancies.

Method of study

We collected blood and placenta samples from pregnant individuals exposed and unexposed to the pandemic to compare their immune and inflammatory profiles. We performed co‐culture with circulating maternal immune cells and endothelial cells to assess endothelial activation. Statistical analysis was performed using unpaired t‐test, Mann‐Whitney, or Fisher's exact test as appropriate.

Results

In exposed individuals, we observed a decreased proportion of Th2 cells (p < .0001) and Treg/Th17 ratio (p < .05), as well as an increased Th1/Th2 ratio (p < .0001). Levels of IL‐1β (p < .01) and IL‐18 (p < .01) were increased in the circulation of exposed participants, whilst other mediators were significantly decreased (IFNγ, IL‐8, MCP‐1, amongst others). Furthermore, we observed increased production of ICAM, hallmark of endothelial activation, when we co‐cultured endothelial cells with immune cells from exposed individuals. Vaccination status impacted the cellular profile with increased proportions of Th1 and B cells in vaccinated participants.

Conclusion

Overall, we observed a pro‐inflammatory bias in the circulation of pregnant individuals exposed to the COVID‐19 pandemic, with otherwise uncomplicated pregnancies. Our work also supports an association between the increased risk of endothelial activation/hypertension and SARS‐CoV2 infection, which might be driven in part by exposure to the pandemic and associated stressors.
Uncertainty in crisis bargaining with multiple policy options
Authors: Kenkel Brenton , Schram Peter
Published: February 2024

Formal models commonly characterize interstate bargaining as dichotomous, ending in either war or peace. But there are many forms of coercion—including supporting rebel groups, sanctions, and cyberattacks. How does the availability of intermediate policy options affect the incidence of war and peace? We present an analysis of crisis bargaining models with intermediate policy options that challenges conventional results about the relationship between private information and negotiation outcomes. In our “flexible‐response” modeling framework, unlike in traditional crisis bargaining models, we find that greater private war payoffs may be associated with a lower probability of war or worse settlement values. When intermediate options are available, the relationship between the private efficacy of war and the private efficacy of these other options largely determines equilibrium outcomes. By utilizing the tools of mechanism design, we derive game‐form–free results on how private information shapes international conflict, regardless of the precise negotiating protocol.
Working towards 2030 road safety targets, the need for specific rural and remote children strategies
Authors: Koh Soonho , Kenji Doma , Franklin Richard
Published: February 2024

Introduction

Despite the importance of child road traffic death, the knowledge about rural child road traffic death in Australia is limited.

Objective

To explore the difference of child road traffic death between urban and rural areas.

Design

This study was a retrospective analysis of road traffic death in Australia among children and adolescents aged 0–19 registered between 1 January 2009 and 30 June 2019.

Results

During the study period, there were 1757 child road traffic death in Australia, and the crude mortality rate was 2.96 per 100 000 population. The crude mortality rate in remote (8.83 per 100 000 population) and very remote (11.08 per 100 000 population) areas was much higher than major cities (1.83 per 100 000 population), inner regional (5.14 per 100 000 population) and outer regional (5.91 per 100 000 population).

Conclusions

Specific targets are needed to address the burden of child road traffic death in Australia around rurality, as it is a significant risk factor of child road traffic death.
Testicular biopsies in men with testicular microlithiasis and additional risk factors for cancer: A case series
Authors: Frandsen Rasmus Hassing , Durukan Emil , von Rohden Elena , Jensen Christian Fuglesang S. , Thamsborg Andreas Key Milan , Azawi Nessn , Fode Mikkel
Published: February 2024

Background

Testicular microlithiasis is the presence of small calcifications in the testicular parenchyma. The association between testicular microlithiasis and germ cell neoplasia in situ, a precursor to testicular cancer, is still unclear.

Objectives

To determine the incidence of germ cell neoplasia in situ in men with testicular microlithiasis and evaluate the indication for testicular biopsy according to risk factors in the form of male infertility/reduced semen quality, testicular atrophy, and history of cryptorchidism.

Materials and methods

This retrospective case series included all patients diagnosed with testicular microlithiasis who underwent testicular biopsies at three hospitals in Denmark between 2007 and 2021. The medical records of 167 patients were reviewed, and data on patient demographics, testicular microlithiasis characteristics, risk factors, histological findings, and treatments were collected. The main outcome measure was the incidence of germ cell neoplasia in situ in relation to each risk factor. The data were analyzed using descriptive statistics. Logistic regression was used to examine the odds ratio of germ cell neoplasia in situ in patients with testicular microlithiasis and testicular atrophy.

Results

Germ cell neoplasia in situ was found in 13 out of 167 patients (7.8% [95% confidence interval: 4.3, 13.2]). Eleven of these had testicular atrophy resulting in a significantly higher incidence in this group than other risk factors (odds ratio 9.36 [95% confidence interval: 2.41, 61.88]; p = 0.004).

Discussion

The study comprises the largest cohort to date of men who have undergone testicular biopsies because of testicular microlithiasis and additional risk factors. Limitations include its retrospective design, and relatively low absolute numbers of patients with germ cell neoplasia in situ on biopsies.

Conclusion

This study found that men with testicular microlithiasis and testicular atrophy are at an increased risk of germ cell neoplasia in situ. Additionally, our results indicate that biopsies should be considered in men with a combination of subfertility and bilateral testicular microlithiasis. Our findings do not support testicular biopsies for men with testicular microlithiasis and other risk factors.
Producing the post‐postmodern flâneur: An assemblage analysis of Macau's Cotai Strip
Authors: Sun Zhen
Published: February 2024

Macau, an internationally renowned gambling city, has experienced rapid growth in casino space expansion and tourism since 2002 when the new Macau SAR government liberalised gambling. Despite the impact of COVID‐19 on the city's economy over the past three years, infrastructure construction and remodelling of casino resorts continue. This study focuses on the spatial production of casino resorts and tourist identity in Macau's Cotai Strip. Methodologically, the study conducts an assemblage analysis to interpret the data collected mainly through participant observation and in‐depth interviews. The research findings show that the Cotai Strip homogenises the human and non‐human elements through the repetitive rhythms of buildings and multi‐tiered enclosed territorialisation. The identity of Macau casino tourists emerges from their interactions with other components within the Strip assemblage. The emerging identity is defined as a post‐postmodern flâneur, characterised by their programmed and controlled tourist activities and their intensified visual sensations and photographic gazes.
Craft making: Traditional and creative trajectories in Jingdezhen, China
Authors: Liu Fangfang , Xu Honggang
Published: February 2024

Debates surrounding craft‐making have long centred on the intricate relationship among the head, hand and the materials. While studies have typically differentiated between traditional craft and creative crafts by focusing on specific aspect of the relationship, the co‐existence and interdependence of these elements remained largely unexplored. This research focuses on ceramic craft making in Jingdezhen, where traditional and creative crafts coexist. We employ ethnographic research to comprehend the connotation of traditional and creative crafts, examining them from the perspectives of engagement and detachment. In doing so, this study challenges oversimplified narratives that undervalue the making role of traditional craft and position creative craft as a means for self‐expression and resistance against alienation. Instead, we emphasise the complex relationship between the two, characterised by mutual dependence and mutual detriment. These findings partly stem from the predominance of detachment in traditional crafts, which prioritise the act of making and, to some extent, maximising efficiency. They also relate to the prevalence of engagement in creative craft, where the pursuit of creativity is supported by traditional crafts.
Eculizumab dose tapering should take into account the nonlinearity of its pharmacokinetics
Authors: Le Tilly Olivier , Gatault Philippe , Semlali Saida , Sberro‐Soussan Rebecca , Passot Christophe , Bertrand Dominique , Desvignes Céline , Caillard Sophie , Paintaud Gilles , Halimi Jean‐Michel , Ternant David
Published: February 2024

Aims

Eculizumab is a monoclonal antibody targeting complement protein C5 used in renal diseases. As recommended dosing regimen leads to unnecessarily high concentrations in some patients, tailored dosing therapeutic drug monitoring was proposed to reduce treatment cost. The objectives of the present work were (i) to investigate the target‐mediated elimination of eculizumab and (ii) whether a pharmacokinetic model integrating a nonlinear elimination allows a better prediction of eculizumab concentrations than a linear model.

Methods

We analysed 377 eculizumab serum concentrations from 44 patients treated for atypical haemolytic uraemic syndrome and C3 glomerulopathy with a population pharmacokinetic approach. Critical concentrations (below which a non‐log‐linear decline of concentration over time is evidenced) were computed to estimate the relevance of the target‐mediated elimination. Simulations of dosing regimens were then performed to predict probabilities of target attainment (i.e. trough >100 mg/L).

Results

Pharmacokinetics of eculizumab was nonlinear and followed a mixture of first‐order (CL = 1.318 mL/day/kg) and Michaelis–Menten elimination (Vmax = 26.07 mg/day, Km = 24.06 mg/L). Volume of distribution (72.39 mL/kg) and clearance were weight‐dependent. Critical concentrations (Vmax/CL) ranged from 144.7 to 759.7 mg/L and were inversely related to body weight (P = .013). Nonlinearity was thus noticeable at therapeutic concentrations. Simulations predicted that 1200 mg of eculizumab every 21 days would allow 85% and 76% of patients to maintain a therapeutic exposure, for 50 or 90 kg body weight, respectively.

Conclusions

Our study investigates the nonlinear elimination of eculizumab and discusses the importance of accounting for eculizumab target‐mediated elimination in therapeutic drug monitoring.
The prevalence of impostor phenomenon and its association with burnout amongst urologists
Authors: Jefferson Francis A. , Fadel Anthony , Findlay Bridget L. , Robinson Maraika O. , Seyer Amanda K. , Koo Kevin , Granberg Candace F. , Boorjian Stephen A. , Anderson Katherine T.
Published: February 2024

Objectives

To characterise the prevalence of impostor phenomenon (IP; tendency for high‐achieving individuals to perceive themselves as fraudulent in their successes) amongst attending staff in urology, to identify variables that predict more severe impostorism, and to study the association of IP with burnout.

Subjects and Methods

A survey composed of the Clance Impostor Phenomenon Scale (CIPS), demographic information, practice details, and burnout levels was e‐mailed to urologists via urological subspecialty societies. Survey results were analysed to identify associations between IP severity, survey respondent characteristics, and symptoms of professional burnout. This study was conducted in the United States of America.

Results

A total of 614 survey responses were received (response rate 11.0%). In all, 40% (n = 213) of responders reported CIPS scores qualifying as either ‘frequent’ or ‘intense’ impostorism (i.e., scores of 61–100). On multivariable analysis, female gender, fewer years in practice (i.e., 0–2 years), and lower academic rank were all independently associated with higher CIPS scores (adjusted P < 0.05). Regarding burnout, 46% of responders reported burnout symptoms. On multivariable analysis, increase in CIPS score was independently associated with higher odds of burnout (odds ratio 1.06, 95% confidence interval 1.04–1.07; P < 0.001).

Conclusion

Impostor phenomenon is prevalent in the urological community and is experienced more severely in younger and female urologists. IP is also independently associated with burnout. Increased female representation may improve IP amongst our female colleagues. More work is needed to determine strategies that are effective in mitigating feelings of IP and professional burnout amongst urologists, particularly those earlier in their careers.
Genetic and phenotypic landscape of pediatric‐onset epilepsy in 142 Indian families: Counseling and therapeutic implications
Authors: Majethia Purvi , Kaur Namanpreet , Mascarenhas Selinda , Rao Lakshmi Priya , Pande Shruti , Narayanan Dhanya Lakshmi , Bhat Vivekananda , Nayak Shalini S. , Nair Karthik Vijay , Prasannakumar Adarsh Pooradan , Chaurasia Ankur , Hunakunti Bhagesh , Jadhav Nalesh , Farooqui Sheeba , Yeole Mayuri , Kothiwale Vishaka , Naik Rohit , Bhat Veena , Aroor Shrikiran , Lewis Leslie , Purkayastha Jayashree , Bhat Y. Ramesh , Praveen B. K. , Yatheesha B. L. , Patil Siddaramappa J. , Nampoothiri Sheela , Kamath Nutan , Siddiqui Shahyan , Bielas Stephanie , Girisha Katta Mohan , Sharma Suvasini , Shukla Anju
Published: February 2024

The application of genomic technologies has led to unraveling of the complex genetic landscape of disorders of epilepsy, gaining insights into their underlying disease mechanisms, aiding precision medicine, and providing informed genetic counseling. We herein present the phenotypic and genotypic insights from 142 Indian families with epilepsy with or without comorbidities. Based on the electroclinical findings, epilepsy syndrome diagnosis could be made in 44% (63/142) of the families adopting the latest proposal for the classification by the ILAE task force (2022). Of these, 95% (60/63) of the families exhibited syndromes with developmental epileptic encephalopathy or progressive neurological deterioration. A definitive molecular diagnosis was achieved in 74 of 142 (52%) families. Infantile‐onset epilepsy was noted in 81% of these families (61/74). Fifty‐five monogenic, four chromosomal, and one imprinting disorder were identified in 74 families. The genetic variants included 65 (96%) single‐nucleotide variants/small insertion‐deletions, 1 (2%) copy‐number variant, and 1 (2%) triplet‐repeat expansion in 53 epilepsy‐associated genes causing monogenic disorders. Of these, 35 (52%) variants were novel. Therapeutic implications were noted in 51% of families (38/74) with definitive diagnosis. Forty‐one out of 66 families with monogenic disorders exhibited autosomal recessive and inherited autosomal dominant disorders with high risk of recurrence.
Multi‐gene panel sequencing in highly consanguineous families and patients with congenital forms of skeletal dysplasias
Authors: Kakar Naseebullah , Rehman Fazal ur , Kaur Ramandeep , Bhavani Gandham SriLakshmi , Goyal Manisha , Shah Hitesh , Kaur Karandeep , Sodhi Kushaljit Singh , Kubisch Christian , Borck Guntram , Panigrahi Inusha , Girisha Katta Mohan , Kornak Uwe , Spielmann Malte
Published: February 2024

Skeletal dysplasias (SKDs) are a heterogeneous group of more than 750 genetic disorders characterized by abnormal development, growth, and maintenance of bones or cartilage in the human skeleton. SKDs are often caused by variants in early patterning genes and in many cases part of multiple malformation syndromes and occur in combination with non‐skeletal phenotypes. The aim of this study was to investigate the underlying genetic cause of congenital SKDs in highly consanguineous Pakistani families, as well as in sporadic and familial SKD cases from India using multigene panel sequencing analysis. Therefore, we performed panel sequencing of 386 bone‐related genes in 7 highly consanguineous families from Pakistan and 27 cases from India affected with SKDs. In the highly consanguineous families, we were able to identify the underlying genetic cause in five out of seven families, resulting in a diagnostic yield of 71%. Whereas, in the sporadic and familial SKD cases, we identified 12 causative variants, corresponding to a diagnostic yield of 44%. The genetic heterogeneity in our cohorts was very high and we were able to detect various types of variants, including missense, nonsense, and frameshift variants, across multiple genes known to cause different types of SKDs. In conclusion, panel sequencing proved to be a highly effective way to decipher the genetic basis of SKDs in highly consanguineous families as well as sporadic and or familial cases from South Asia. Furthermore, our findings expand the allelic spectrum of skeletal dysplasias.
Patterns of recovery in extant and extirpated seabirds after the world's largest multipredator eradication
Authors: Bird Jeremy P. , Fuller Richard A. , Shaw Justine D.
Published: February 2024

Eradicating invasive predators from islands can result in substantial recovery of seabirds, but the mechanisms that drive population changes remain poorly understood. Meta‐analyses have recently revealed that immigration is surprisingly important to the recovery of philopatric seabirds, but it is not known whether dispersal and philopatry interact predictably to determine rates of population growth and changes of distribution. We used whole‐island surveys and long‐term monitoring plots to study the abundance, distribution, and trends of 4 burrowing seabird species on Macquarie Island, Australia, to examine the legacy impacts of invasive species and ongoing responses to the world's largest eradication of multiple species of vertebrates. Wekas (Gallirallus australis) were eradicated in 1988; cats (Felis catus) in 2001; and rabbits (Oryctolagus cuniculus), black rats (Rattus rattus), and mice (Mus mus) in 2011–2014. We compared surveys from 1976–1979 and 2017–2018 and monitoring from the 1990s and 2000s onward. Antarctic prions (Pachyptila desolata) and white‐headed petrels (Pterodroma lessonii) increased ∼1% per year. Blue petrels (Halobaena caerulea) and gray petrels (Procellaria cinerea) recolonized following extirpation from the main island in the 1900s but remained spatially and numerically rare in 2018. However, they increased rapidly at 14% and 10% per year, respectively, since cat eradication in 2001. Blue and gray petrel recolonization occurred on steep, dry, west‐facing slopes close to ridgelines at low elevation (i.e., high‐quality petrel habitat). They overlapped <5% with the distribution of Antarctic prion and white‐headed petrels which occurred in suboptimal shallow, wet, east‐facing slopes at high elevation. We inferred that the speed of population growth of recolonizing species was related to their numerically smaller starting size compared with the established species and was driven by immigration and selection of ideal habitat.
Tixagevimab/cilgavimab for the prevention of COVID‐19 in solid organ transplant recipients
Authors: Eribes Emily , Votruba Cassandra , Tinkham Tyler , Huang Angela , Ilges Dan , Kunze Katie , Hudson Madeline
Published: February 2024

Tixagevimab/cilgavimab (tix/cil) received emergency use authorization in December 2021 for pre‐exposure prophylaxis against COVID‐19 in moderately to severely immunocompromised patients. Our study aimed to describe the incidence of COVID‐19 infection and assess the immunologic risks associated with tix/cil in kidney, pancreas, liver, and heart transplant recipients. Retrospective chart review was completed to provide descriptive analysis. Outcomes data included COVID‐19 infection, severity of COVID‐19 infection, graft function, and rejection. Safety outcomes included cardiovascular (CV) and hypersensitivity events post tix/cil administration. A total of 410 transplant patients were included in the analysis: 20 heart, 92 liver, 243 kidney, 25 simultaneous pancreas/kidney, 23 simultaneous liver/kidney, and seven simultaneous heart/kidney. Twenty‐seven (6.5%) patients tested positive for COVID‐19 via PCR or antigen test post tix/cil. No apparent difference was observed in patients testing positive for COVID‐19 by type of organ transplant (p = .122). Twenty‐five of the 27 patients testing positive for COVID‐19 reported symptomatic infection, only nine of whom were hospitalized. No patients were mechanically ventilated and no deaths due to COVID‐19 occurred. No significant changes in graft function were observed. Clinically significant rejection was diagnosed and treated in four patients. COVID‐19 breakthrough infection rates remained low in immunocompromised solid organ transplant recipients who received tix/cil. No significant immunologic risks were observed.
De novo hepatitis B infection following liver transplantation with core antibody positive grafts: The role of surface antibody status in guiding long‐term prophylaxis
Authors: Busebee Brad , Myhre Laura , Mara Kristin , Aqel Bashar , Taner Timucin , Watt Kymberly D.
Published: February 2024

Liver transplantation (LT) with hepatitis B core antibody (anti‐HBc) positive grafts to hepatitis B surface‐antigen (HBsAg) negative recipients is safe and has likely contributed to improvements in organ access over the years. The incidence of de novo hepatitis B infection (HBV) in these instances is low with appropriate prophylaxis and is affected by recipient immunologic status. There is debate as to whether hepatitis B surface antibody (anti‐HBs) positivity may safely inform prophylaxis discontinuation post‐LT. In this retrospective study of all hepatitis B surface antigen (HBsAg) negative recipients of anti‐HBc positive organs at three large academic centers between January 2014 and December 2019, nine LT recipients discontinued prophylaxis after developing anti‐HBs antibodies 1 year or later post‐LT. Three of the nine patients (33%) developed de novo HBV, defined by positive HBsAg or hepatitis B virus (HBV) DNA, during the study period. The remaining six patients had no evidence of HBV infection after a mean follow‐up of 37 months. The patients without de novo HBV had higher anti‐HBs titers at the time of prophylaxis discontinuation and were less likely to have negative anti‐HBs at the time of transplant or negative anti‐HBc at any time point. These results suggest that quantitative anti‐HBs titer thresholds rather than qualitative anti‐HBs positivity at 1 year or later after LT should be used to identify patients at decreased risk of de novo infection and help guide prophylaxis duration.
Cannabis use is associated with reduced access to kidney transplantation and an increased risk of acute rejection post‐transplant
Authors: Rodríguez‐Ramírez Sonia , Tang Evan , Li Yanhong , Famure Olusegun , Mucsi Istvan , Kim Sang Joseph
Published: February 2024

Background

The association between cannabis use and access to waitlisting, transplantation, and post‐transplant outcomes remains uncertain.

Methods

Patients referred for kidney transplant (KT) to the University Health Network from January 1, 2003, to June 30, 2020, and followed until December 31, 2020, were included. Predictors of reported cannabis use were examined using a logistic regression model. The association between cannabis use and time to clearance for KT, undergoing KT, and post‐transplant outcomes was evaluated using Cox proportional hazards models.

Results

Among 3734 patients, the prevalence of reported cannabis use was 11.8%. Cannabis use was associated with a lower likelihood of KT clearance (adjusted hazard ratio [aHR] .82 [95% confidence interval (CI): .72, .94]). Once cleared for KT, cannabis use did not predict the subsequent receipt of KT (aHR .92, [95% CI: .79, 1.08]). Among 2091 KT recipients, cannabis use was associated with a higher likelihood of biopsy‐proven acute rejection (aHR 1.55, [95% CI: 1.06, 2.27]). The relative hazard of death‐censored graft failure was similarly elevated (aHR 1.60 [95% CI: .95, 2.72]). Cannabis use did not predict total graft failure (aHR 1.33 [95% CI: .90, 1.96]), death with graft function (aHR 1.06 [95% CI: .59, 1.89]), or hospital readmission in the first‐year post‐transplant (aHR 1.26 [95% CI: .95, 1.68]).

Conclusions

Cannabis users have less access to transplantation and an increased risk of acute rejection, possibly leading to more graft loss. Further studies are warranted to understand possible mechanisms for the increased risk of allograft immune injury among cannabis users.
Upper gastrointestinal haemorrhage patients' survival: A causal inference and prediction study
Authors: Deng Fuxing , Cao Yaoyuan , Zhao Shuangping
Published: February 2024

Background

Upper gastrointestinal (GI) bleeding is a common medical emergency. This study aimed to develop models to predict critically ill patients with upper GI bleeding in‐hospital and 30‐day survival, identify the correlation factor and infer the causality.

Methods

A total of 2898 patients with upper GI bleeding were included from the Medical Information Mart for Intensive Care‐IV and eICU‐Collaborative Research Database, respectively. To identify the most critical factors contributing to the prognostic model, we used SHAP (SHapley Additive exPlanations) for machine learning interpretability. We performed causal inference using inverse probability weighting for survival‐associated prognostic factors.

Results

The optimal model using the light GBM (gradient boosting algorithm) algorithm achieved an AUC of .93 for in‐hospital survival, .81 for 30‐day survival in internal testing and .87 for in‐hospital survival in external testing. Important factors for in‐hospital survival, according to SHAP, were SOFA (Sequential organ failure assessment score), GCS (Glasgow coma scale) motor score and length of stay in ICU (Intensive critical care). In contrast, essential factors for 30‐day survival were SOFA, length of stay in ICU, total bilirubin and GCS verbal score. Our model showed improved performance compared to SOFA alone.

Conclusions

Our interpretable machine learning model for predicting in‐hospital and 30‐day mortality in critically ill patients with upper gastrointestinal bleeding showed excellent accuracy and high generalizability. This model can assist clinicians in managing these patients to improve the discrimination of high‐risk patients.
miR‐619‐5p and cardiogenic shock in patients with ST‐segment elevation myocardial infarction
Authors: Escate Rafael , Padró Teresa , Suades Rosa , Sans‐Roselló Jordi , Devaux Yvan , Lakkisto Päivi , Harjola Veli‐Pekka , Sionis Alessandro , Badimon Lina
Published: February 2024

Background

Cardiogenic shock (CS) is a severe myocardial dysfunction secondary to various cardiac conditions including ST‐segment elevation acute myocardial infarction (STEMI) and associated with a high risk of death. Little is known on epigenetic determinants in CS. Here, we investigated plasma miRNAs in relation to CS stratification in STEMI‐patients.

Methods

STEMI‐patients (n = 49), with (CS, n = 25) and without CS (non‐CS, n = 24) fulfilling inclusion criteria were included from HSCSP‐cohort (Derivation‐cohort). CS‐miRNAs were analysed by Affymetrix‐microarray and RT‐PCR. Results were validated in a second cohort of CS‐patients (CardShock: n = 35) with similar inclusion/exclusion criteria as the derivation cohort. In silico analysis were performed to identify potential miRNA target genes.

Results

Of the 5‐miRNA signature obtained from microarray analysis, miR‐619‐5p showed higher levels in CS than in Non‐CS patients (p = .003) and discriminating power for CS by ROC (AUC: .752, p = .003). miR‐619‐5p directly associated with risk scores [GRACE, p = .001; CardShock, p < .001]. Furthermore, miR‐619‐5p showed discrimination power for death in CS. Thus, miRNA levels were significantly higher in patients with mortality outcome both in the Derivation HSCSP‐cohort (p = .02; AUC: .78 ± .095) and the Validation CardShock‐cohort (p = .017; AUC: .737 ± .086) By in silico analysis, miR‐619‐5p target genes and TNF‐alpha were involved in the regulation of inflammation. miR‐619‐5p and TNF‐alpha levels discriminated mortality outcome in CS‐patients during 30‐day follow‐up (Validation‐Cohort: ROC: .812, p = .002; HR: 9.99, p = .003).

Conclusions

Up‐regulation of miR‐619‐5p is found in the plasma of STEMI‐patients with CS and mortality outcome. These findings highlight the specificity of epigenetic regulation of inflammation on the disease severity of MI.
Investigation of the early apical release from endodontic hydrogels: A 3D printed model
Authors: Leveque Marianne , Bekhouche Mourad , Farges Jean‐Christophe , Richert Raphaël , Ducret Maxime
Published: February 2024

Aim

Regenerative Endodontic Procedures (REPs) using new materials such as hydrogels aim to replace current endodontic treatments, but numerous limitations are to overcome. Apical release was little explored in previous studies, especially regarding hydrogels that incorporate molecules, such as growth factors and antibiotics. Apical release is a key mechanism in achieving regeneration, as it could regulate disinfection or cell colonization. Few models exist for apical release, limiting the transfer of these devices from bench to bedside. This study aims to design a simple and standardized model to identify parameters that influence the early apical release kinetic of molecules from endodontic hydrogels.

Methodology

Endodontic Release Inserts (ERI) were designed to mimic the situation of an immature incisor using three different diameters (Ø 0.5 to 2 mm) and to allow the study of the early release from a hydrogel in a 96‐well plate. ERI was produced with a 3D printing machine. The kinetic release was investigated using 2 fluorescent, hydrophobic (BDP‐500) and hydrophilic (Fluorescein) molecules, in different hydrogels (fibrin and agarose) and in various media (PBS or serum). The release kinetics were estimated by measuring the fluorescence at different time points (1 to 24 h).

Results

ERI use made it possible to report that apical diameters increase from 500 to 1000 μm was associated with an increase in release from 4.02 ± 1.63% to 11.53 ± 2.38% over 24 h. It also allowed us to report that bottom solution composition change from PBS to human serum was associated with an increase in the release of fatty acid molecules, whilst a decrease in the hydrogel concentration was associated with a variation in release kinetics. Moreover, nano‐encapsulation of a molecule was associated with a decreased release over the first 24 h from 5.25 to 0%.

Conclusion

ERI use enables investigation of the parameters influencing release kinetics from endodontic hydrogels. Further investigations are necessary to evaluate the interaction of these parameters with each other, in animal models and clinic.
Against the tide: A case of industrial relations transformation in the Indian coal sector
Authors: Talluri Surendra Babu , Balasubramanian Girish , Sarkar Santanu
Published: February 2024

Although the scholarly debate on industrial relations (IR) transformation is inclined toward the conclusion that the IR transformation is bound to take place with changes in the surrounding business environment, we observe a few exceptions in each economy. The current study investigates one of such curious IR contexts, that is, the Indian coal sector. We rely on the ‘logic of the action’ framework and the IR transformation measures to assess the sector at an aggregate and micro level. The coal sector in India consists of a mix of both permanent and informal workforce. With respect to the permanent workforce, we analysed the collective bargaining agreements spanned over five decades (1975–2021). For the informal workforce, we analysed the recommendations of the HPC on wages and working conditions, the provisions of relevant legislation, internal circulars of coal companies and important judicial pronouncements. Our analyses revealed vast differences in wages and working conditions between the permanent and informal workforce. Despite a significant decline in the permanent workforce, they could negotiate better terms as the growing size of the informal workforce was yet to form a collective bargaining mechanism for better wages and working conditions. These results are indicative of a paradox which needs to be explored further. Our study advances the thesis of adaptive state capitalism in the coal sector through functional and numerical flexibility despite a politicised multi‐union model in India.
Identification of genomic regions and pathways associated with traits related to rumen acidosis in feedlot Nellore cattle
Authors: Estevam Daniela D. , Souza Johnny M. , Rey Fernando S. B. , Martins Cyntia L. , Stafuzza Nedenia B. , Espigolan Rafael , Millen Danilo D. , Arrigoni Mario D. B.
Published: February 2024

There may be an increased risk of metabolic disorders, such as rumen acidosis, in cattle fed high‐concentrate diets, particularly those from Bos taurus indicus genotypes, which have shown to be more sensitive to ruminal acidification. Therefore, this study aimed to estimate (co)variance components and identify genomic regions and pathways associated with ruminal acidosis in feedlot Nellore cattle fed high‐concentrate diets. It was utilized a dataset containing a total of 642 Nellore bulls that were genotyped from seven feedlot nutrition studies. The GGP Indicus 35k panel was used with the single step genome‐wide association study methodology in which the effects of the markers were obtained from the genomic values estimated by the GBLUP model. A bivariate model to estimate genetic correlations between the economically important traits and indicator traits for acidosis was used. The traits evaluated in this study that were nutritionally related to rumen acidosis included average daily gain (ADG), final body weight, time spent eating (TSE), time spent ruminating, rumenitis score (RUM), rumen absorptive surface area (ASA), rumen keratinized layer thickness (KER) and hot carcass weight (HCW). The identified candidate genes were mainly involved in the negative or non‐regulation of the apoptotic process, salivary secretion, and transmembrane transport. The genetic correlation between HCW and ASA was low positive (0.27 ± 0.23), and between ADG and ASA was high moderate (0.58 ± 0.59). A positive genetic correlation between RUM and all performance traits was observed, and TSE correlated negatively with HCW (−0.33 ± 0.21), ASA (−0.75 ± 0.48), and KER (−0.40 ± 0.27). The genetic association between economically important traits and indicator traits for acidosis suggested that Nellore cattle may be more sensitive to acidosis in feedlot systems.
Injury patterns and demographics in older adult abuse and falls: A comparative study in emergency department settings
Authors: Khurana Bharti , Bayne Haley N. , Prakash Jaya , Loder Randall T.
Published: February 2024

Background

Falls and interpersonal violence pose significant threats to older adults, leading to injuries, hospitalizations, and emergency department (ED) visits. This study investigates the demographics and injury patterns in older adults (aged 60 and above) who sought ED care due to assaults, comparing them with those who experienced falls to gain a deeper understanding of older adult abuse patterns.

Method

This study utilizes data from the National Electronic Injury Surveillance System (NEISS) All Injury Program (2005–2019) to examine injuries among older adults aged 60 years and above. Participants were categorized into two groups: older adult abuse and injuries due to falls. The differences between the groups by demographics, injury locations, patterns, and temporal trends were analyzed using statistical methods accounting for the weighted stratified nature of the data. Cosinor analysis and Joinpoint regression were used for temporal analysis.

Results

Over 15 years, there were an estimated 307,237 ED visits for older adult abuse and 39,477,217 for falls. Older adults experiencing abuse were younger and had lower hospital admission rates compared to fall patients. Injuries associated with abuse included contusions/abrasions, penetrating injuries, and fractures to the head/neck, fingers, toes, ribs, and lower extremities. In contrast, fall patients had higher admission rates, with more fractures, including cervical spine and hip fractures. Temporal patterns showed a higher rate of assaults during the summer, whereas abuse demonstrated bimodal peaks in the summer and fall.

Conclusions

Injuries associated with abuse such as facial, upper trunk, and upper extremity fractures should raise suspicion even in the absence of severe symptoms. These findings emphasize the importance of early identification to connect older adults with support resources, as patients experiencing abuse often get discharged from the ED.
A widely targeted metabolite modificomics strategy for modified metabolites identification in tomato
Authors: Yang Jun , Chen Ridong , Wang Chao , Li Chun , Ye Weizhen , Zhang Zhonghui , Wang Shouchuang
Published: February 2024

The structural and functional diversity of plant metabolites is largely created via chemical modification of a basic backbone. However, metabolite modifications in plants have still not been thoroughly investigated by metabolomics approaches. In this study, a widely targeted metabolite modificomics (WTMM) strategy was developed based on ultra‐high performance liquid chromatography‐quadrupole‐linear ion trap (UHPLC‐Q‐Trap) and UHPLC‐Q‐Exactive‐Orbitrap (UHPLC‐QE‐Orbitrap), which greatly improved the detection sensitivity and the efficiency of identification of modified metabolites. A metabolite modificomics study was carried out using tomato as a model, and over 34,000 signals with MS2 information were obtained from approximately 232 neutral loss transitions. Unbiased metabolite profiling was also performed by utilizing high‐resolution mass spectrometry data to annotate a total of 2,118 metabolites with 125 modification types; of these, 165 modified metabolites were identified in this study. Next, the WTMM database was used to assess diseased tomato tissues and 29 biomarkers were analyzed. In summary, the WTMM strategy is not only capable of large‐scale detection and quantitative analysis of plant‐modified metabolites in plants, but also can be used for plant biomarker development.
Rural–urban disparities and trends in utilization of palliative care services among US patients with metastatic breast cancer
Authors: Freeman Jincong Q. , Scott Adam W. , Akhiwu Ted O.
Published: February 2024

Purpose

To assess trends and rural–urban disparities in palliative care utilization among patients with metastatic breast cancer.

Methods

We analyzed data from the 2004–2019 National Cancer Database. Palliative care services, including surgery, radiotherapy, systemic therapy, and/or other pain management, were provided to control pain or alleviate symptoms; utilization was dichotomized as “yes/no.” Rural–urban residence, defined by the US Department of Agriculture Economic Research Service's Rural–Urban Continuum Codes, was categorized as “rural/urban/metropolitan.” Multivariable logistic regression was used to examine rural–urban differences in palliative care use. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were calculated.

Findings

Of 133,500 patients (mean age 62.4 [SD = 14.2] years), 86.7%, 11.7%, and 1.6% resided in metropolitan, urban, and rural areas, respectively; 72.5% were White, 17.0% Black, 5.8% Hispanic, and 2.7% Asian. Overall, 20.3% used palliative care, with a significant increase from 15.6% in 2004–2005 to 24.5% in 2008–2019 (7.0% increase per year; p‐value for trend <0.001). In urban areas, 23.3% received palliative care, compared to 21.0% in rural and 19.9% in metropolitan areas (p < 0.001). After covariate adjustment, patients residing in rural (AOR = 0.84; 95% CI: 0.73–0.98) or metropolitan (AOR = 0.85, 95% CI: 0.80–0.89) areas had lower odds of having used palliative care than those in urban areas.

Conclusions

In this national, racially diverse sample of patients with metastatic breast cancer, the utilization of palliative care services increased over time, though remained suboptimal. Further, our findings highlight rural–urban disparities in palliative care use and suggest the potential need to promote these services while addressing geographic access inequities for this patient population.