bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Maternal Hepatitis B Virus Infection on Congenital Heart Disease Risk in Offspring: A National Cohort Study
Authors: Park Yewan , Heo Jihye , Kang Danbee , Gwak Geum‐Youn
Published: November 2024

Maternal hepatitis B virus (HBV) infection influence both maternal and fetal health. Recent studies reported increased congenital anomalies in offspring of HBV‐infected mothers. This study investigated whether maternal HBV infection was associated with higher risk of congenital heart disease (CHD) in children. With the Korean National Health Insurance Service (K‐NHIS) database, this retrospective cohort study included live births from 2005 to 2019, born to women under 40. Propensity score matching with a 1:3 ratio was conducted to compare HBV‐infected mother's children with HBV‐uninfected mother's children while adjusting for various maternal and pregnancy‐related factors. Logistic regression models were used to estimate the risk. Of 2,673,059 eligible participants, 263,904 children were born to HBV‐infected mothers. Risk estimation in this group showed a modestly increased risk of CHD (OR = 1.05, 95% CI = 1.02, 1.09). Notably, when pregnant mothers were treated with antiviral medication, there was an indication of reduced CHD risk, although this result was not statistically significant. The highest risk of CHD was observed in children who were themselves infected with HBV. The study indicates an association between maternal HBV infection and an increased CHD risk in offspring. The findings suggest the need to re‐evaluate the timing of antiviral treatment during pregnancy to align more closely with early stages of fetal cardiac development. Further research is needed to understand the biological mechanisms of this association and to redefine clinical guidelines for managing HBV infection in pregnancy.
Challenges and Opportunities for Treating Hepatitis C Amongst People Who Use Drugs: Experience of an Integrated Mobile Clinic in Baltimore City
Authors: Rosecrans Amanda , Harris Robert , Clair Anne St , Rice Molly , Zoltick Meredith , Willman Catherine , King Anne , Kerr Meredith , Page Kathleen R.
Published: November 2024

Progress in treating chronic hepatitis C virus (HCV) infection has been slow amongst people who use drugs (PWUD). This study describes the HCV treatment cascade amongst people accessing a mobile clinic offering integrated low‐threshold buprenorphine and infectious disease services in Baltimore City. From May 1, 2021, to December 31, 2022, 560 people had a rapid HCV antibody test, of whom 201 (36%) had a positive result and amongst those, 117 (58%) had an HCV RNA test performed, 81 (40%) had a documented positive RNA, 45 (22%) were prescribed medication, 42 (21%) started medication, 32 (16%) completed medication, 22 (11%) had blood work to assess for sustained virologic response and 20 (10%) had a documented cure. Challenges including housing instability, insurance barriers and lack of venous access limit progress in this cascade. Providing integrated care models to meet the needs of PWUD in the community is necessary but not sufficient to make progress in improving HCV treatment. Removal of insurance restrictions, availability of point‐of‐care HCV RNA testing, development of rapid HCV treatment guidelines and development of long‐acting injectable HCV treatment are needed to move towards a same‐day, one‐time test and treat model of care.
Cucumber Green Mottle Mosaic Virus Coat Protein Hijacks Mitochondrial ATPδ to Promote Viral Infection
Authors: Yang Xue , Jiang Xing‐Lin , Fu Han , Yu Lian‐Wei , Ai Niu , Shi Ya‐Juan , Lu Yu‐Wen , Xia Zi‐Hao , Li Hong‐Lian , Shi Yan
Published: November 2024

The production and scavenging of reactive oxygen species (ROS) are critical for plants to adapt to biotic and abiotic stresses. In this study, we investigated the interaction between the coat protein (CP) of cucumber green mottle mosaic virus (CGMMV) and ATP synthase subunit δ (ATPδ) in mitochondria. Silencing of ATPδ by tobacco rattle virus‐based virus‐induced gene silencing impeded CGMMV accumulation in Nicotiana benthamiana leaves. Both the overexpression of ATPδ in transgenic plants and transient expression promoted CGMMV infection. Nitro blue tetrazolium (NBT) and 3,3′‐diaminobenzidine (DAB) staining revealed that ATPδ inhibited O2− production but not H2O2 production. The treatment of CGMMV‐infected leaves with the ROS inhibitor diphenylene iodonium (DPI) induced a ROS burst that inhibited CGMMV infection. Reverse transcription‐quantitative PCR and superoxide dismutase (SOD) activity assays showed that ATPδ, CGMMV infection, and CP expression specifically induced NbFeSOD3/4 expression and SOD activity, and silencing NbFeSOD3/4 inhibited CGMMV infection. We speculate that CGMMV CP interacts with ATPδ and hijacks it, thereby enhancing O2− quenching by upregulating NbFeSOD expression and, in turn, SOD activity.
A glioneuronal tumor with neurocytic rosettes harboring FGFR1 internal tandem duplication – A report of a unique case
Authors: Soukup Jiri , Hajkova Nikola , Hajkova Veronika , Svajdler Marian , Netuka David , Majovsky Martin
Published: November 2024

Rosette‐forming glioneuronal tumors (RGNTs) with FGFR1 tyrosine kinase domain internal tandem duplication (FGFR1 ITD) is exceedingly rare, with only a few cases reported in the literature. Hereby we present a case of a tumor with RGNT morphology occurring in area of septum pellucidum of 43‐year‐old male. The tumor showed FGFR1 ITD, no PIK3CA, PIK3R1 or NF1 alterations and inconclusive methylation profile with match for class of “low‐grade glial/glioneuronal/neuroepithelial tumors”. No areas characteristic of dysembryoplastic neuroepithelial tumor were identified. A brief review of literature on discrepancies between morphological diagnosis of RGNT and molecular profile of the entity is provided.
Profile of Inflammatory Cytokines in Gingival Crevicular Fluid and Plasma in Patients With Grade C Periodontitis During Orthodontic Treatment: A Longitudinal Case Series Report
Authors: Xin Tian‐yi , Zhu Zi‐lu , Chen Liu‐jing , Han Bin , Yang Rui‐li , Shi Jie
Published: November 2024

Aim

To examine the immune responses in patients diagnosed as grade C periodontitis during orthodontic treatment.

Materials and Methods

Our study included seven orthodontic patients with grade C periodontitis and measured their levels of inflammatory cytokines in gingival crevicular fluid and plasma before orthodontic treatment, during the alignment and levelling phase, and during the detailing and finishing phase. The key signal pathways in the orthodontic process of patients with periodontitis were detected by KEGG analysis.

Results

Studies have shown that orthodontic treatment brings great improvement to patients with grade C periodontitis, and most of the local/systemic inflammatory cytokines can be reduced after orthodontic treatment. Simultaneously, orthodontic treatment can reduce the percentage of IFN‐γ+ Th1 cells in patients with grade C periodontitis. Through KEGG analysis, the IL‐17 signalling pathway and TNF signalling pathway are closely interrelated in the orthodontic treatment of patients diagnosed with grade C periodontitis (p‐value < 0.001).

Conclusion

Orthodontic treatment can effectively control the local and system levels of inflammation in patients with grade C periodontitis, with IL‐17A and TNF‐α as potential distinctive inflammatory markers for orthodontic‐periodontal combined treatment in individuals with periodontitis.
Disciplined Comparison in the Undergraduate Theory and Method Classroom
Authors: Jensen Christopher
Published: November 2024

This article details the author's reimagining of the undergraduate theory and method course, in which intentional, disciplined comparison is employed to challenge and problematize traditional narratives about Religious Studies as an academic discipline. Doing so helps to answer calls to decolonize our curricula, not only by critiquing historical theorists, but also by including non‐Western perspectives as sources of theory (as opposed to mere data to be studied). Such an approach is additionally pertinent in the author's Canadian institutional context, where traditional definitions of “religion” have been used to oppress Canada's Indigenous populations: a useful case study for explaining why such theorization matters.
Risk factors for vasovagal reactions in blood donors: A systematic review and meta‐analysis
Authors: Wu Yaning , Qi Hongchao , Di Angelantonio Emanuele , Kaptoge Stephen , Wood Angela M. , Kim Lois G.
Published: November 2024

Background

While blood donation is generally safe, some donors experience vasovagal reactions (VVRs) that may lead to injury and reduce likelihood of future donation. Several risk factors for VVRs have been identified, but the consistency, magnitude, and validity of their associations have not been systematically evaluated. Therefore, this systematic review and meta‐analysis synthesized evidence for VVR risk factors.

Methods

Database searches identified English‐language studies published before February 2024 describing VVR risk factors in voluntary whole blood donors. Study characteristics, VVR and risk factor assessment methods, and effect sizes were extracted. Random‐effects models pooled estimates across all studies and subgroups of geographical context, study quality, donation experience, and outcome severity. Inconsistently and infrequently reported risk factors were narratively synthesized.

Results

Totally 71 studies reporting a total of 19 million total donations were included. Female sex, new donor status, younger age, smaller blood volume, and lower blood pressure were positively associated with higher VVR risk. Donation‐related fear, anxiety, and disgust were associated with higher VVR risk in narrative syntheses. Substantial between‐study heterogeneity (I2 > 90%) was observed for the majority of risk factors, while there was no clear evidence of subgroup variability and small study effects.

Conclusion

This systematic review and meta‐analysis provides a comprehensive synthesis of risk factors for VVRs across wide‐ranging blood service contexts and symptom severities, reinforcing evidence for previously identified factors. The heterogeneous associations of several risk factors motivate large‐scale studies that enable comprehensive multivariable adjustment to evidence donor selection criteria and preventative intervention allocation.
Inner Race Dynamics of a High-Speed Ball Bearing With Elastic Ring Squeeze Film Damper
Authors: Jiang Bingzhen , Yang Xiaomin , Xu Bensheng , Geng Ruiguang , Li Baochen
Published: November 2024

This paper aims at the inner race dynamics of a high-speed ball bearing incorporated with Elastic Ring Squeeze Film Damper (ERSFD). A dynamic model of the inner race with three degrees-of-freedom (DOFs) is established in an ERSFD-integrated ball bearing. The ball contact force and operating contact angle are characterized using an improved quasi-static model, which includes the motion of the outer race when establishing the geometric relationship between bearing displacement and contact elastic deformation. Numerical simulations were performed for bearings with or without ERSFD. The model was validated using Campbell diagram and measured displacement response and center trajectory of the inner race at different rotor speeds. The results show that the ERSFD provides adequate stable traction on the ball and limits excessive increase in the inner race contact angle. Such load-carrying condition benefits for decrease in ball orbital revolution skid at high rotor speeds. The ERSFD enables rotor's unbalance force to dominate bearing motion, resulting in stable periodic motion of the inner race at high rotor speeds. For ball bearings without ERSFD, the inner race possesses stable motion at low and moderate rotor speeds, but is more prone to instability at high rotor speeds.
Associations Between Match Running Performance and Environmental Temperatures in 4 Professional Football Leagues
Authors: Schwarz Edgar , Duffield Rob , Novak Andrew R. , Görres Tom , Meyer Tim
Published: November 2024

Purpose: This study investigated associations between environmental temperatures and match running performance in 4 professional football leagues. Methods: Running performance indicators including total, high-speed, and sprint distances were collated from 1610 matches from the German Bundesliga 1 and 2, Japanese J-League, and Turkish SüperLig. Environmental data for each of these matches were obtained for dry-bulb and wet-bulb globe temperatures (WBGT) retrospectively from public sources. Linear regressions were used to determine relationships between running performance indicators and both temperature and WBGT for individual leagues. Furthermore, linear mixed models were used to determine associations across all 4 leagues, accounting for differences between them as random effects. Bonferroni corrections were applied to account for multiple tests. Results: Overall, combined-league data showed that total distance (95% CI, −0.50 to 0.37; β: −0.36), number of high-speed runs (95% CI, −4.57 to 2.93; β: −0.29), high-speed distances (95% CI, −0.07 to 0.05; β: −0.28), number of sprints (95% CI, −2.72 to 2.07; β: −0.39), and sprint distances (95% CI, −0.05 to 0.03; β: −0.22) were all lower when WBGT was higher (P < .001), whereas the peak speed recorded per match (95% CI, 0.01 to 0.03; β: 0.18) was higher when WBGT was higher (P < .001). Models with temperature instead of WBGT derived similar results. Conclusion: Warmer environmental conditions were associated with lower total, high-speed, and sprint distances covered. These responses may result from an increased thermoregulatory load or indirectly from an adapted individual or team-tactical pacing strategy in warmer conditions. Teams should consider strategies to counter such effects to avoid lower distances covered at high intensities that are related to success in football.
Insights into antibiotic resistance promoted by quinolone exposure
Authors: Bush Natassja G. , Diez-Santos Isabel , Sankara Krishna Pilla , Clavijo Bernardo , Maxwell Anthony
Published: November 2024

Quinolone-induced antibiotic resistance (QIAR) refers to the phenomenon by which bacteria exposed to sublethal levels of quinolones acquire resistance to non-quinolone antibiotics. We have explored this in
Escherichia coli
MG1655 using a variety of compounds and bacteria carrying a quinolone-resistance mutation in gyrase, mutations affecting the SOS response, and mutations in error-prone polymerases. The nature of the antibiotic-resistance mutations was determined by whole-genome sequencing. Exposure to low levels of most quinolones tested led to mutations conferring resistance to chloramphenicol, ampicillin, kanamycin, and tetracycline. The mutations included point mutations and deletions and could mostly be correlated with the resistance phenotype. QIAR depended upon DNA gyrase and involved the SOS response but was not dependent on error-prone polymerases. Only moxifloxacin, among the quinolones tested, did not display a significant QIAR effect. We speculate that the lack of QIAR with moxifloxacin may be attributable to it acting via a different mechanism. In addition to the concerns about antimicrobial resistance to quinolones and other compounds, QIAR presents an additional challenge in relation to the usage of quinolone antibacterials.
Identification of determinants that allow maintenance of high-level fluoroquinolone resistance in
Acinetobacter baumannii
Authors: Hamami Efrat , Huo Wenwen , Hernandez-Bird Juan , Castaneda Arnold , Bai Jinna , Syal Sapna , Ortiz-Marquez Juan C. , van Opijnen Tim , Geisinger Edward , Isberg Ralph R.
Published: November 2024

Acinetobacter baumannii
is associated with multidrug-resistant infections in healthcare settings, with fluoroquinolones such as ciprofloxacin being currently ineffective. Clinical isolates largely harbor mutations in the GyrA and TopoIV fluoroquinolone targets, as well as mutations that increase expression of drug resistance-nodulation-division (RND) efflux pumps. Factors critical for maintaining fitness levels of pump overproducers are uncharacterized despite their prevalence in clinical isolates. We, here, identify proteins that contribute to the fitness of fluoroquinolone-resistant (FQR) strains overexpressing three known RND systems using high-density insertion mutagenesis. Overexpression of the AdeFGH efflux pump caused hypersensitization to defects in outer membrane homeostatic regulation, including lesions that reduced lipooligosaccharide (LOS) biosynthesis and blocked production of the major
A. baumannii
porin. In contrast, AdeAB pump hyperexpression, in the absence of elevated
adeC
expression (the outer membrane component of the pump), was relatively tolerant to loss of these functions, consistent with the outer membrane protein being the primary disruptive component. Surprisingly, overexpression of proton-transporting efflux pumps had little impact on cytosolic pH, consistent with a compensatory response to pump activity. The most striking transcriptional changes were associated with AdeFGH pump overexpression, including the activation of the phenylacetate (PAA) degradation regulon. Disruption of the PAA pathway resulted in cytosolic acidification and defective expression of genes involved in protection from oxidative stress. These results indicate that RND efflux pump overproduction is compensated by maintenance of outer membrane integrity in
A. baumannii
to facilitate fitness of FQR isolates.

IMPORTANCE

Acinetobacter baumannii
is a pathogen that often causes multidrug-resistant infections in healthcare settings, presenting a threat to the efficacy of known therapeutic interventions. Fluoroquinolones such as ciprofloxacin are currently ineffective against a majority of clinical
A. baumannii
isolates, many of which express pumps that remove this antibiotic class from within the bacterium. Three of these pumps can be found in most clinical isolates, with one of the three often hyperproduced at all times. In this study, we identify proteins that are necessary for the fitness of pump hyperproducers. The identified proteins are necessary to stabilize the outer membrane and allow the cytoplasm to tolerate the accumulation of ions as a consequence of excess pump activity. These results point to strategies for developing therapies that combine known antibiotics with drugs that target proteins important for survival of strains hyper-expressing efflux pumps.
Clinical performance of two commercially available rapid antigen tests for influenza, RSV, and SARS-CoV-2 diagnostics
Authors: Savolainen Laura E. , Peltola Joanna , Hilla Risto , Åman Tapio , Broas Markku , Junttila Ilkka S.
Published: November 2024

Rapid antigen tests (RATs) might provide rapid, low-cost, and easy-to-perform choice to nucleic-acid amplification methods (NAAT) in point-of-care (POC) diagnostics of respiratory infections. The clinical performance of two commercial combo-RATs for influenza A and B, respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) POC diagnostics, was assessed. RAT and real-time-PCR (RT-PCR) analysis were performed on 620 patients admitted to the emergency department due to respiratory symptoms. The sensitivity and specificity of the RATs compared with RT-PCR results were studied. The sensitivity of the RATs with respect to symptom duration was also estimated. The tested RAT1 showed sensitivities of 98.68%, 73,53%, and 44.44% for SARS-CoV-2, influenza A, and RSV, respectively, when the cycle threshold (Ct) values were <25 and 95.45%, 68.42%, 40.0% with Ct values <30. In RAT2 analysis, respective sensitivities for influenza A and RSV in samples with Ct <25 were 85% and 100% and in samples with Ct <30 respective sensitivities dropped to 69.23% and 66.67%. Positive SARS-CoV-2 cases during the RAT2 testing period and influenza B cases during both the RAT1 and RAT2 testing periods were scarce, so they were omitted from the statistical analysis. The specificity of both tested RATs was high and varied between 99.48% and 100%. The clinical use of RATs should be carefully considered due to the possibility of insufficient sensitivity. Because the specificity of the tests is high, the use of such tests might provide added value, for example, in emergency units, particularly when the prevalence of these infections is high. However, an option to confirm negative RAT by NAAT should be available.

IMPORTANCE

Rapid diagnostics of respiratory viruses is essential for clinical management, infection control, and epidemiological surveillance. Our results showed that due to the high specificity and still inadequate sensitivity, rapid antigen tests (RATs) might be useful for influenza, respiratory syncytial virus, and severe acute respiratory syndrome coronavirus 2 point-of-care diagnostics when correctly used. The results provide useful information for laboratory and infectious disease control professionals to support decision-making when implementation of the RATs in clinical use is planned.
Oesophageal overlap motility disorders: beyond Chicago classification V.4.0
Authors: Gopal Prashant , Dahale Amol , Karad Abhijeet , Bade Yogesh
Published: November 2024

Patients with oesophageal motility disorders may present with dysphagia, regurgitation or chest pain. High-resolution manometry (HRM) is the current gold-standard modality for the diagnosis of oesophageal motility disorders. The data from HRM are analysed and interpreted to form a diagnosis based on the Chicago classification. However, the Chicago classification is a work in progress, and a few cases can present with features beyond the scope of the current Chicago classification. We present two such cases with distinctive manometric features of an elevated distal contractile integral and increased integrated relaxation pressure but no intrabolus pressurisation or decreased distal latency. As such, they do not fit into any pattern described in the current Chicago classification V.4.0 and can be best described as overlap motility disorders or mixed motor disorders. Patients with such findings warrant further evaluation and long-term follow-up to understand if they evolve to fit into any disorder currently described in the Chicago classification.
Physical activity interventions implemented for older people in Sub-Saharan Africa: a scoping review
Authors: Naidoo Shane , Otoo Samuel , Naidoo Niri
Published: November 2024

Background

Sub-Saharan Africa mirrors global patterns with an expanding elderly demographic, frequently characterised by a high incidence of non-communicable diseases (NCDs), manifesting as multimorbidity. Physical activity (PA) is a validated intervention for managing the increasing prevalence of NCDs in this demographic.

Objective

This review aimed to elucidate the extent of PA interventions implemented in Sub-Saharan Africa for managing NCDs in older people (OP).

Eligibility criteria

This review synthesised randomised controlled trials published in English since 2010, focusing on PA interventions for managing NCDs or associated risk factors in OP in Sub-Saharan Africa.

Sources of evidence

The Joanna Briggs Institute methodology for scoping reviews was implemented with searches in the following databases: PubMed, EBSCOhost (Academic Search Premier AfricaWide Information, CINAHL, Health Sources Premier Academic/Nursing), Scopus and ProQuest.

Charting methods

Extraction and reporting adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses-Scoping Reviews framework, ensuring rigorous and systematic synthesis.

Results

A total of 3754 studies were initially identified, with 67 studies ultimately included after applying the exclusion criteria. The synthesised trials tested primarily supervised structured PA interventions (n=30), education on PA and lifestyle (n=30) and combined structured PA with lifestyle education (n=7). A structured supervised PA regimen combining aerobic exercise at 60–80% of maximum heart rate (three 45–60 min sessions per week) and resistance training starting at 50% of one-repetition maximum (3 weekly sessions of three sets with 10–12 repetitions per muscle group), progressively increasing to 60%, was the most effective in reducing risk factors associated with NCDs in this cohort.

Conclusion

This analysis confirms that a structured PA regimen paired with lifestyle education significantly mitigates NCDs in Sub-Saharan Africa’s elderly population. Furthermore, it highlights the imperative for further investigation into non-pharmacological strategies, especially those targeting hypertension, diabetes and cognitive health disorders.
Birth preparedness, complication readiness and associated factors among pregnant women attending public health facilities in Chelia District, Central Ethiopia (2022): a cross-sectional study
Authors: Tafasa Segni Mulugeta , Bekuma Debela , Fikadu Worku , Gelassa Firaol Regea , Jebena Desalegn Emana , Zerihun Ebisa , Willi Wakeshe , Chaka Eshetu Ejeta
Published: November 2024

Background

Birth preparedness and complication readiness (BPCR) are essential components of maternal health that encourage proactive planning and decision-making during pregnancy and childbirth. However, there is limited information available regarding the status of BPCR, particularly in our study area. Therefore, this study aimed to assess birth preparedness, complication readiness and associated factors among pregnant women attending public health facilities in the Chelia District.

Methods

A facility-based cross-sectional study was conducted among 410 pregnant women at public health facilities, using a systematic random sampling method. Descriptive statistics, such as frequencies, and summary statistics were calculated for the relevant variables. Bivariate and multivariate binary logistic regression analyses were performed to evaluate the relationship between dependent and independent variables. The strength of the association was measured using an OR with a 95% CI. Statistical significance was determined at a p value of 0.05.

Results

A total of 406 mothers participated in the study, resulting in a 99% response rate. The study found that 245 (60.3%) respondents were well-prepared for birth and complication readiness. Several factors such as: family size (adjusted odds ratios (AOR)=0.18; 95% CI (0.09 to 0.35)), decision-making with husbands (AOR=2.43, 95% CI (1.44 to 3.32)), parity (AOR=0.32; 95% CI (0.16 to 0.62)), lack of awareness about birth preparedness (AOR=0.30; 95% CI (0.16 to 0.57)), not knowing about the existence of a waiting home (AOR=0.31; 95% CI (0.19 to 0.48)) and not participating in a pregnant women’s conference (AOR=0.50; 95% CI (0.32 to 0.79)) were significantly associated with BPCR.

Conclusion

The study found that the level of BPCR is low in the study area. Family size, decision-making with husbands, awareness of maternity waiting homes, participation in pregnant women’s conferences, knowledge about BPCR and parity were significantly associated with BPCR. Therefore, strengthening pregnant women’s conferences, encouraging husband involvement in decision-making and ensuring maternity waiting homes at health facilities are important.
Outcomes of traumatically injured patients after nighttime transfer from the intensive care unit
Authors: Howk Amy , Clegg Devin John , Balmer Jacob C , Foster Natalie G , Gerard Justin , Rowe Anthony S , Daley Brian
Published: November 2024

Background

Prior studies have associated nighttime transfer of patients from the intensive care unit (ICU) with increased morbidity. This study sought to examine this relationship in traumatically injured patients, as this has not been previously performed.

Methods

A retrospective review of traumatically injured patients admitted to a Level I Trauma Center’s ICU from January 2021 to September 2022 was performed. “Day shift” (DS) was defined as 07:00 to 19:00 and “night shift” (NS) as 19:01 to 06:59. The time of transfer completion was based on the time of the patient arrival at the destination unit. The univariate analysis compared patients with completed transfers during DS and NS. Multivariate logistic regression was performed to predict readmission to the ICU.

Results

A total of 1,800 patients were included in the analysis, with 608 patients that had completed transfers during NS, and 1,192 during DS. Both groups were similar, with no significant differences in age, sex, Injury Severity Score (ISS), mechanism of injury, or median total comorbidities. The NS group had a longer median time to transfer completion (10.1 (IQR 5.5–13.6) hours vs 5.1 (IQR 2.9–8.4) hours; p<0.001). A significantly higher proportion of the NS group had a readmission to the ICU (60 (10.0%) vs 86 (7.0%); p=0.03) or a major complication (72 (11.9%) vs 107 (9.0%); p=0.048). When controlling for age, comorbidities, ISS, time to bed assignment and to transfer completed, and ICU length of stay, transfer completion during NS was associated with 1.56 times higher odds of having an ICU readmission (OR 1.56 (95% CI 1.05, 2.33); p=0.03).

Conclusions

Trauma patients transferred from the ICU during NS experienced longer delays, readmission to the ICU, and major complications significantly more often. With increasing hospital bed shortages, patient transfers must be analyzed to minimize worsened outcomes, especially in traumatically injured patients.

Level of evidence

Level III, therapeutic/care management.
Preparing the future combat surgeon: a survey of the military general surgery trainee GME experience
Authors: Baird Emily W , Dilday Joshua , Lammers Daniel , Tadlock Matthew D , Gurney Jennifer M. , Jansen Jan O , Holcomb John B
Published: November 2024

Introduction

Graduate medical education (GME) lacks a standardized military training program for general surgery residents, and concern exists that they may not be prepared to serve as combat surgeons on training completion. The purpose of this study was to assess military surgery trainee satisfaction with their programs. Our hypothesis was that military residents were not completely confident to care for combat casualties on completion of current GME training.

Methods

We surveyed US Army, Navy, and Air Force general surgery residents and fellows between November 2023 and March 2024 to assess their confidence in managing combat injuries. Queried residents further rate their overall satisfaction with surgical training, perceived level of deployment preparedness and curriculum elements which they thought would be most beneficial to their training.

Results

The survey yielded an overall 43% response rate (132/305) with a response rate of 42% (61/147) from the Army, 56% (44/79) from the Navy, and 34% (27/79) from the Air Force. Most trainees were trained in military medical treatment facility residency programs (n=91, 68.9%) and nearly half of respondents (n=64, 49%) were senior trainees (postgraduate year (PGY)4, PGY5, and fellows). Among all trainees, only two-thirds (n=88, 67%,) thought they were adequately prepared to deploy and operate on military combat casualties by the end of residency but 114 (86%) were satisfied with the training they received during general surgery residency in adult trauma, 103 (78%) in critical care, and 112 (85%) in acute care surgery. However, more than half were unsatisfied with the training they received in obstetric/gynecologic and urologic emergencies (n=72, 55%; and n=67, 51%, respectively).

Conclusion

Although the majority of military surgical residents surveyed are satisfied with their training in adult trauma, critical care, and emergency general surgery, a large number of trainees thought they would not be ready to deploy and manage combat casualties.

Level of evidence

Prognostic and epidemiological, Level IV.
Chern–Simons-like formulation of exotic massive 3D gravity models
Authors: Dedeoğlu Büşra , Ozkan Mehmet , Sarıoğlu Özgür
Published: November 2024

We investigate the Chern–Simons-like formulation of exotic general massive gravity models within the framework of third-way to three-dimensional gravity. We classify our construction into two main approaches: one using torsional cosmological Einstein and exotic massive gravity equations, and the other a torsion-free approach. The former approach, while mathematically appealing, precludes the construction of critical exotic models where the central charges vanish. In contrast, the latter approach has a wider parameter space and allows for the construction of critical models. An explicit example of an exotic general model is provided to illustrate both methods. Our methodology represents the first step towards establishing the most general Chern–Simons-like formulation of third-way to three-dimensional gravity, which would enable the study of identifying its bulk/boundary unitary sector.
A Singular Case Analysis: Lamotrigine‐Associated Stevens–Johnson Syndrome
Authors: Joshi Albin , Palikhe Anjula , Acharya Santosh , Kunwor Puskar
Published: November 2024

Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) is an immune complex–mediated hypersensitivity reaction linked as an adverse side effect to many drugs. There have been case reports of similar incidences in Nepal related to various medications. Here, we present a case of a 29‐year‐old lady who developed a generalized erythematous rash over her body and erosion of the oral mucous membrane. Two weeks back she gave a history of initiation of lamotrigine, olanzapine, and sertraline. Given the strong association between SJS and lamotrigine, and the usual presentation being within the first 8 weeks of exposure to susceptible medications; she was diagnosed as SJS/TEN induced by lamotrigine. On April 1, 2024, she was admitted to the ICU at KIST MCTH. All the medicines were withheld, and she was managed with corticosteroids and antihistamines. She improved significantly within 7 days. Early identification of SJS, discontinuation of triggering medicines, and prompt initiation of supportive therapy improved the prognosis.
Comparison of the Long‐Term Efficacy of Targeting the Subthalamic Nucleus Versus the Globus Pallidus Interna for Deep Brain Stimulation Treatment of Motor Dysfunction in Patients With Parkinson’s Disease: A Meta‐Analysis Study
Authors: Huhn Makenna , Prewett Matthew , Rossignol Julien , Dunbar Gary L.
Published: November 2024

A cardinal symptom of Parkinson’s disease (PD) is motor dysfunction, including bradykinesia and tremors, which is quantified in the Unified PD Rating Scale (UPDRS). Although some medications provide palliative treatments for these motor deficits, their efficacy wanes and can produce unwanted side effects, such as dyskinesia. Deep‐brain stimulation (DBS) has provided an alternative treatment strategy that can benefit many patients, but optimal target structures for DBS and its long‐term efficacy are not fully understood. The present study represents a meta‐analysis of the long‐term (> 5 years) effects of DBS on the two most common targets, the subthalamic nucleus (STN) and the globus pallidus interna (GPi), on scores of motor performance using the UPDRS‐III. The initial search of PubMed, Cochrane Library, and Clinical Trials resulted in 197 articles, of which 28 met the criteria for our analysis. Of the 1321 patients included, 1179 received STN DBS group and 142 received GPi DBS. UPDRS‐III scores for both target groups were analyzed at baseline and at either 5–8 or 10–15 years later for both on‐ and off‐medication phases. The results indicated that the STN stimulation is effective at reducing motor symptoms during off‐medication treatment for up to 15 years and that the GPi stimulation can be effective for up to at least 8 years. Our findings further suggest that STN‐ and GPi‐targeted DBS may wear off during the on‐medication phase between 5 and 10 years of treatment. This study supports findings that both DBSs of either the STN or GPi have long‐term efficacy, especially during off‐medication periods.
Research on Vibration Reduction Performance of Series Bistable Nonlinear Energy Sink
Authors: Jia XiaoMin , Chang XiaoTong , Xue GuoDing
Published: November 2024

The vibration reduction performance of NES is extremely sensitive to the excitation intensity. When the excitation intensity is low, target energy transfer cannot occur, and the vibration reduction performance is significantly reduced. When the excitation intensity is too high, bifurcation occurs, forming a high branching response and the performance of the NES is also significantly reduced, even leading to vibration deterioration. In response to the above issues, this paper proposes a series bistable nonlinear energy sink (SBNES), which improve the vibration reduction performance under low disturbances through chaotic response between wells, and reduce the generation of high branches within a certain range through mass configuration. The vibration reduction performance of the proposed SBNES was analyzed using analytical and numerical methods, and the results showed that it had better vibration reduction performance than CNES under both impact and harmonic excitations.
Table S5 from Spatial Context of Immune Checkpoints as Predictors of Overall Survival in Patients with Resectable Colorectal Cancer Independent of Standard Tumor–Node–Metastasis Stages
Authors: Kong Hao , Yang Qingxin , Wu Chunwei , Wu Xiangji , Yan Xinrui , Huang Li-Bin , Chen Lu , Zhou Zong-Guang , Wang Ping , Jiang Hong
Published: November 2024

Spatial phenotypes of CD8+ T cells
Figure S6 from Spatial Context of Immune Checkpoints as Predictors of Overall Survival in Patients with Resectable Colorectal Cancer Independent of Standard Tumor–Node–Metastasis Stages
Authors: Kong Hao , Yang Qingxin , Wu Chunwei , Wu Xiangji , Yan Xinrui , Huang Li-Bin , Chen Lu , Zhou Zong-Guang , Wang Ping , Jiang Hong
Published: November 2024

Immune cell status changes after αPD-1 + αTIM-3 treatment
Figure S4 from Spatial Context of Immune Checkpoints as Predictors of Overall Survival in Patients with Resectable Colorectal Cancer Independent of Standard Tumor–Node–Metastasis Stages
Authors: Kong Hao , Yang Qingxin , Wu Chunwei , Wu Xiangji , Yan Xinrui , Huang Li-Bin , Chen Lu , Zhou Zong-Guang , Wang Ping , Jiang Hong
Published: November 2024

Analysis of immune cell statuses across different tumor locations in training and validation cohorts.
Figure 4 from Spatial Context of Immune Checkpoints as Predictors of Overall Survival in Patients with Resectable Colorectal Cancer Independent of Standard Tumor–Node–Metastasis Stages
Authors: Kong Hao , Yang Qingxin , Wu Chunwei , Wu Xiangji , Yan Xinrui , Huang Li-Bin , Chen Lu , Zhou Zong-Guang , Wang Ping , Jiang Hong
Published: November 2024

TIM-3 and PD-1 dual blockade reverses T-cell exhaustion and enhances the antitumor immune response. A, Tumor volume. A measure of 2.5 × 105 CT26 cells were injected subcutaneously into BALB/C mice, followed by treatment with isotype or αPD-1 (RMP1-14) and αTIM-3 (RMT3-23) antibodies (10 mg/kg) every 4 days (isotype: n = 6 mice per arm; αPD-1 + αTIM-3: n = 7 mice per arm). Data are presented as the mean ± SEM and determined by two-way ANOVA. B, Representative images of multiplex immunofluorescence staining (CD8, red; Ki67, white; PD-1, cyan; TIM-3, yellow; and TOX, green) in isotype or αPD-1 + αTIM-3 treatment tumor. C, mIHC quantification of PD-1+CD8+ T cells, TIM-3+CD8+ T cells, TOX+CD8+ T cells, PD-1+TIM-3+CD8+ T cells, PD-1+TIM-3+TOX+CD8+ T cells, and PD-1−TIM-3−TOX−CD8+ T cells as a percentage of CD8+ cells. Data are presented as the mean ± SEM and determined by a two-tailed unpaired t test. D, T-cell panel gating strategy. E, FACS quantification of PD-1+CD8+ T cells, TIM-3+CD8+ T cells, and PD-1+TIM-3+CD8+ T cells as a percentage of CD8+ T cells. Data are presented as the mean ± SEM and determined by a two-tailed unpaired t test. F, FACS quantification of PD-1+CD4+ T cells, TIM-3+CD4+ T cells, and PD-1+TIM-3+CD4+ T cells as a percentage of CD4+ cells. Data are presented as the mean ± SEM and determined by a two-tailed unpaired t test. G, Myeloid cell panel gating strategy. H, FACS quantification of dendritic cells, macrophages, and myeloid-derived suppressor cells as a percentage of CD45+ cells in the αPD-1 + αTIM-3 experiment. Data are presented as the mean ± SEM and determined by a two-tailed unpaired t test. DC, dendritic cell; MDSC, myeloid-derived suppressor cell.
Figure 1 from Spatial Context of Immune Checkpoints as Predictors of Overall Survival in Patients with Resectable Colorectal Cancer Independent of Standard Tumor–Node–Metastasis Stages
Authors: Kong Hao , Yang Qingxin , Wu Chunwei , Wu Xiangji , Yan Xinrui , Huang Li-Bin , Chen Lu , Zhou Zong-Guang , Wang Ping , Jiang Hong
Published: November 2024

Schematic approach and different infiltration patterns of T cells among colorectal cancer tumors. A, Selection of patients with colorectal cancer and workflow of the present study. B, Representative images of multiplex immunofluorescence staining (PanCK, green; CD8, red; PD-1, cyan; and TIM-3, yellow) and phenotype map. C, Representative images of tissue segmentation and phenotype maps of high and low CD8+ T-cell infiltration. Blue lines represent tumor core area boundaries. DAPI, x; FFPE, formalin-fixed paraffin-embedded.
Data from Spatial Context of Immune Checkpoints as Predictors of Overall Survival in Patients with Resectable Colorectal Cancer Independent of Standard Tumor–Node–Metastasis Stages
Authors: Kong Hao , Yang Qingxin , Wu Chunwei , Wu Xiangji , Yan Xinrui , Huang Li-Bin , Chen Lu , Zhou Zong-Guang , Wang Ping , Jiang Hong
Published: November 2024

Abstract
Although immune checkpoint blockade therapy has shown promising results in a small subset of patients with colorectal cancer with high microsatellite instability, the majority of patients with colorectal cancer do not respond to immune checkpoint blockade therapy. The main obstacle to the success of immunotherapy in cancer treatment is the exhaustion of tumor-infiltrating lymphocytes (TIL). Elucidating the spatial organization of immune checkpoints within the tumor microenvironment (TME) could pave the way for the development of novel prognostic tools and therapeutic strategies to enhance antitumor immune responses. To clarify the spatial and functional diversity of TILs in the colorectal TME, we performed multiplexed IHC to examine the exhaustion of TILs in the TME, the expression of PD-1 and T-cell immunoglobulin and mucin domain–containing protein 3 (TIM-3), which are major biomarkers of T-cell exhaustion, and least absolute shrinkage and selection operator method–Cox analyses of the correlation between colorectal cancer prognosis and TME features. For proof of concept, the antitumor efficacy of TIM-3 and PD-1 dual blockade in colorectal cancer was further evaluated in a CT26 s.c. tumor model of human colorectal cancer. We found that the spatial context of PD-1 and TIM-3 successfully predicted the overall survival of patients with colorectal cancer independent of tumor–node–metastasis stage. Dual targeting of PD-1 and TIM-3 in mouse tumor models inhibited tumor progression and reduced T-cell exhaustion, indicating a potential strategy for improving the clinical treatment of colorectal cancer.
Significance:
The identification of specific spatial patterns of immune checkpoint expression that correlate with overall survival in patients with colon cancer suggests a potential prognostic tool for risk stratification and treatment selection. These findings pave the way for the development of novel therapeutic strategies to enhance antitumor immune responses.
Construction of a Hybrid Vaccine Based on Der f 35-Derived Peptides with Reduced Allergenicity
Authors: Hu Haoyang , Qin Qiao-Zhi , Zheng Wei , Xu Zhi-Qiang , Chen Xiang
Published: November 2024

Introduction: House dust mite is the primary trigger of allergic respiratory diseases worldwide, and allergen-specific immunotherapy (AIT) is the only disease-modifying treatment in the clinic. The use of allergen molecules instead of extracts is a promising strategy in AIT. In this study, we constructed a peptide hybrid vaccine against the major mite allergen Der f 35 and verified its hypoallergenicity, making it to be a promising candidate for AIT of mite allergy. Methods: The gene encoding Der f 35 was retrieved and synthesized. The hypoallergenic peptide fragments derived from the B-cell epitopes were synthesized based on the predicted profiles of B-cell or T helper-cell epitopes in Der f 35, they were verified by immunoglobulin E (IgE)-reaction test and fused to non-allergenic protein carrier to form the hybrid vaccine. Both the wild-type Der f 35 and the designed vaccine were expressed in Escherichia coli and purified by chromatography; their IgE-binding activity was compared by indirect enzyme-linked immunosorbent assay (ELISA), Western blot, inhibition ELISA, and basophil activation test (BAT). The blocking immunoglobulin G (IgG) against the designed vaccine was raised in rabbits and its ability to inhibit IgE binding of Der f 35 was evaluated by ELISA. The vaccine’s effects on peripheral blood mononuclear cells (PBMCs) were investigated. Results: A total of 29 out of 60 (48.33%) IgE-positive sera against Der f 35 were screened. Five peptide fragments (residue 39–42, 60–67, 73–107, 111–118, 126–143) from Der f 35 were selected as candidates, in which four peptides exhibited almost no IgE reactivity and the fragment 73–107 had weak reactions. Only 5.98–24.02% inhibition rates could be achieved by the peptides when compared with Der f 35 (97.32%). The designed vaccine migrated at approximately 30 kDa by SDS-PAGE. The IgE-ELISA revealed a significant reduction in IgE-binding activity to the vaccine when compared to wild-type Der f 35 (p < 0.0001); the decreased allergenicity was further confirmed by IgE-Western blot, inhibition ELISA, and BAT, respectively. The IgE-reactivity of Der f 35 could be blocked by the vaccine-induced IgG (p < 0.01). The levels of IL-5 and IL-13 from PBMCs were significantly decreased after stimulation by the vaccine than that by Der f 35 (p < 0.05). Conclusion: The designed B-cell epitope vaccine of Der f 35 showed greatly diminished allergenicity and Th2 activity. It could be an effective and safe candidate to prevent allergic adverse reactions during the immunotherapy of mite allergy and merits the further study.
Atypical Bilateral Acute Iris Transillumination: A Case Report
Authors: Hu Ying , Xie Yuan , Liu Mugen , Fan Junyu , Zhang Yang , Qiao Chunyan
Published: November 2024

Introduction: Bilateral acute iris transillumination (BAIT) is characterized by acute bilateral onset of intense pigment dispersion in the anterior chamber, diffuse iris transillumination, and mydriatic atonic pupils, accentuated pigment deposition in the angle of anterior chamber, and elevated intraocular pressure (IOP). Herein, we report an unusual case of a Chinese patient with BAIT presented to our hospital with no iris transillumination defect. Case Presentation: A 37-year-old male patient presented to our settings with bilateral photophobia, redness, and blurry vision. The symptoms began acutely following a respiratory illness, for which he was treated with moxifloxacin. The patient demonstrated a profound thick layer of pigment deposition on the anterior surface of the lens, corneal endothelial pigment dusting, and trabecular meshwork hyperpigmentation. He was previously diagnosed with acute anterior uveitis with accentuated IOP rise, and was subsequently treated with topical corticosteroids, cycloplegic, and IOP-lowering medications. Despite aggressive medical treatment, IOP remained refractory. The retinal nerve fiber layer severely restricted in both eyes (OU). He was then referred to our glaucoma consultant practice. Although low-energy Selective Laser Trabeculoplasty (SLT) (Quantel, USA) was then performed, it elicited no favorable response, a result that was different compared to previous reports on Caucasian patients. Finally, we performed binocular trabeculectomy combined with mitomycin application, resulting in the optimal IOP control. Conclusion: BAIT in Chinese patients has atypical characteristics, which can highly contribute to misdiagnosis and therapeutic delay with significant consequences. Simultaneously, it is essential to differentiate BAIT from iridocyclitis and pigment dispersion syndrome.