bluuebunny/crossref_metadata_2025 huggingface dataset:
Fried. Krupp’s ‘Chinese Trade’ prior to the First World War, 1895–1914
Authors: Skřivan Aleš , Skřivan Aleš
Published: July 2024

The German arms company Fried. Krupp exported weapons and military material to China beginning in the early 1870s. It achieved marked success during the 1880s and 1890s. The Sino-Japanese War (1894/95) represented an important milestone for the company’s ‘Chinese trade’. Because the Chinese government had to pay war reparations to Japan, it did not have the funds for purchasing weapons. As a result, not even the posting of German advisors to China saw particularly positive results. Following the Boxer Rebellion (1899–1901), an embargo on the import of weapons to China was declared. After the embargo was revoked in 1903, the German manufacturer never again achieved the results it had attained in 1884 and 1894. The Germans were negatively affected by the rise of Japanese influence in China following Japan’s victory in its war with Russia. Additionally, some of China’s plans were not in line with Krupp’s capabilities. The Essen company’s managers, for example, considered entirely unrealistic China’s plan to form thirty-six new divisions equipped with modern weapons, which Krupp would supply, by funding the construction of a huge munitions factory in Central China. Although China remained a major purchaser primarily of Krupp’s guns until the First World War, it was no longer one of its main customers. The outbreak of the First World War marked an end to Krupp’s activities in China and the entire Far East.
Patterns of Multidimensional Social Exclusion Among Older Home Care Services Recipients
Authors: Ristolainen Hanna , Van Regenmortel Sofie , De Donder Liesbeth , Vercauteren Toon , Lehtiö Johanna , Tiilikainen Elisa
Published: July 2024

Objectives

The guiding principle of current aging policies has been to promote older adults to live in their private homes, but little attention has been paid to social exclusion of older adults receiving home-based care. The aim of this study is to increase understanding on different patterns of multidimensional social exclusion among older adults receiving formal home care services, and through this to shed light on the possible challenges of current aging-in-place policies.

Methods

The survey data were collected in 2022 among older adults aged 65 to 102 years receiving home care services in Finland and merged with administrative data (n = 733). A latent class analysis was used to identify different types of social exclusion. Multinomial logistic regression modeling examined factors associated with different social exclusion types.

Results

Four social exclusion types were identified: (1) not excluded (16.9%), (2) homebound economically excluded (40.1%), (3) excluded from social relations (28.6%), and (4) multidimensionally excluded (14.3%). Poor self-rated health and poor functional ability significantly increase the risk of being multidimensionally excluded or homebound economically excluded. The group using home care and medical services the most are the most multidimensionally excluded. The group living in urban areas are more likely to be excluded from social relations.

Discussion

Different types of social exclusion should be acknowledged when addressing social exclusion among home care clients. Enhanced measures should be developed to support older adults using home and healthcare services the most, as they are at high risk of severe exclusion.
Beyond Hypertension: Examining Variable Blood Pressure’s Role in Cognition and Brain Structure
Authors: Morrison Cassandra , Oliver Michael D , Kamal Farooq , Dadar Mahsa
Published: July 2024

Objectives

Hypertension or high blood pressure (BP) is one of the 12 modifiable risk factors that contribute to 40% of dementia cases that could be delayed or prevented. Although hypertension is associated with cognitive decline and structural brain changes, less is known about the long-term association between variable BP and cognitive/brain changes. This study examined the relationship between variable BP and longitudinal cognitive, white matter hyperintensity (WMH), gray matter (GM), and white matter (WM) volume change over time and postmortem neuropathology.

Methods

A total of 4,606 participants (32,776 follow-ups) from RADC Research Resource Sharing Hub (RUSH) and 2,114 participants (9,827 follow-ups) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were included. Participants were divided into 1 of 3 groups: normal, high, or variable BP. Linear-mixed models investigated the relationship between BP and cognition, brain structure, and neuropathology.

Results

Older adults with variable BP exhibited the highest rate of cognitive decline followed by high and then normal BP. Increased GM volume loss and WMH burden were also observed in variable compared to high and normal BP. In postmortem neuropathology, both variable and high BP had increased rates compared to normal BP. Results were consistent across the RUSH and ADNI participants, supporting the generalizability of the findings.

Discussion

Damages potentially associated with variable BP may reduce resilience to future dementia-related pathology and increased the risk of dementia more than that caused by high BP. Improved treatment and management of variable BP may help reduce cognitive decline in the older adult population.
Contestation from Below: Status and Revisionism in Hierarchy
Authors: Lin Alex Yu-Ting
Published: July 2024

Existing scholarship suggests that rising powers can become revisionist powers when they are dissatisfied with their status. What causes such dissatisfaction? Conventional wisdom holds that rising powers become dissatisfied when established powers refuse to recognize them as equals. However, if status informs patterns of superiority and inferiority, then rising powers can also become dissatisfied when smaller states do not defer to them. In fact, I argue that there is a life cycle as to how status dissatisfaction develops: status disputes between rising powers and smaller states can be especially frequent early in the power transition, before status disputes between rising powers and established powers become more prevalent. Through text analysis of an original dataset of statements from China’s Ministry of Foreign Affairs from 1978 to 2018, supplemented by survey and archival evidence, I demonstrate that contestations from smaller states trigger the majority of China’s status grievances, and China-smaller states status disputes are especially prevalent early on. Thus, status-driven revisionism can emerge via bottom-up processes, and it can happen earlier than currently theorized. My analysis highlights the agency of smaller states in shaping power transitions and hierarchies, as well as how and when the US–China competition unfolds.
The appropriateness of empirical antibiotic therapy in the management of symptomatic urinary tract infection patients—a cross-sectional study in Nairobi County, Kenya
Authors: Onyango Hellen A , Sloan Derek J , Keenan Katherine , Kesby Mike , Ngugi Caroline , Gitonga Humphrey , Hammond Robert
Published: July 2024

Background

In low- and middle-income countries, symptomatic urinary tract infection (UTI) patients are often prescribed antibiotics without microbiological confirmation. UTIs caused by antibiotic-resistant bacteria are increasingly common, and this heightens the risk of empirical treatment failure. This study evaluates the appropriateness of empirical antibiotic therapy to UTI patients in Nairobi County, Kenya.

Methods

A hospital-based, cross-sectional study was conducted in Nairobi County, Kenya, amongst symptomatic adult and child patients. UTI was defined as a monoculture growth with colony counts of ≥104 cfu/mL. Antimicrobial susceptibility testing was performed by the Kirby–Bauer disc diffusion method. Empirical therapy was considered appropriate if the pathogen isolated was susceptible to the prescribed antibiotic and inappropriate if the pathogen was resistant to the prescribed antibiotic.

Results

A total of 552 participants were enrolled with a median age of 29 years (interquartile range: 24–36). The majority were female, 398 (72%). Of the 552, 274 (50%) received empirical antibiotic therapy, and 95/274 (35%) were confirmed to have UTI by culture. The antibiotics most frequently prescribed were fluoroquinolones [ciprofloxacin in 80 (30%) and levofloxacin 43 (16%)], amoxicillin–clavulanic acid in 48 (18%) and nitrofurantoin in 32 (12%). Amongst the 95 patients with bacteriological confirmation of UTI, 50 (53%) received appropriate empirical antibiotic therapy, whilst for 38 (40%) participants, the therapy was inappropriate.

Conclusions

The complexity of appropriate empirical treatment for UTIs is compounded by high levels of resistance in UTI pathogens. Antimicrobial resistance surveillance strategies that could help in designing appropriate empirical regimens in resource constrained settings should be adopted for optimal empiric therapy.
First report of Enterocytozoon bieneusi in Erinaceus europaeus and Hemiechinus auritus hedgehogs from recovery centers of Portugal
Authors: Gomes-Gonçalves Sara , Santos-Silva Sérgio , Cruz Andreia V S , Rodrigues Clarisse , Soeiro Vanessa , Barradas Patrícia , Mesquita João R
Published: July 2024

Enterocytozoon bieneusi microsporidia are emerging pathogens infecting a wide range of vertebrate and invertebrate hosts, known to have zoonotic features since they infect both wild and domestic animals, and humans. Despite their significance, there is very limited epidemiological data on microsporidia in hedgehogs, especially European hedgehogs (Erinaceus europaeus) and long-eared hedgehogs (Hemiechinus auritus), the former known as synantropic hedgehogs, and the latter suited as pets. As such, the present study aimed to assess the presence of E. bieneusi in hedgehogs from Portugal. For this purpose, fecal samples from 110 hedgehogs of three species—E. europaeus (n = 106), H. auritus (n = 1), and Atelerix albiventris (n = 3)—were collected and tested for E. bieneusi by PCR targeting the internal transcribed spacer region and the flanking small and large subunits of the rRNA. We found an overall occurrence of 22.7% (25/110; 95% confidence interval [CI]: 15.28–31.70), with 22.6% (24/106; 95% [CI]: 15.08–31.79) in E. europaeus, 100% (1/1) in H. auritus, and 0% in A. albiventris. Interestingly, three novel genotypes were identified, all belonging to the potentially zoonotic Group 1. Our findings highlight the importance of hedgehogs as potential reservoirs for E. bieneusi and emphasize the need for further research to understand their role in transmission dynamics and assess the associated risks to public and veterinary health.
The JWST weather report from the nearest brown dwarfs I: multiperiod JWST NIRSpec + MIRI monitoring of the benchmark binary brown dwarf WISE 1049AB
Authors: Biller Beth A , Vos Johanna M , Zhou Yifan , McCarthy Allison M , Tan Xianyu , Crossfield Ian J M , Whiteford Niall , Suarez Genaro , Faherty Jacqueline , Manjavacas Elena , Chen Xueqing , Liu Pengyu , Sutlieff Ben J , Limbach Mary Anne , Molliere Paul , Dupuy Trent J , Oliveros-Gomez Natalia , Muirhead Philip S , Henning Thomas , Mace Gregory , Crouzet Nicolas , Karalidi Theodora , Morley Caroline V , Tremblin Pascal , Kataria Tiffany
Published: July 2024

We report results from 8 h of JWST/MIRI low resolution spectroscopic (LRS) monitoring directly followed by 7 h of JWST/NIRSpec prism spectroscopic monitoring of the benchmark binary brown dwarf WISE 1049AB, the closest, brightest brown dwarfs known. We find water, methane, and CO absorption features in both components, including the 3.3 μm methane absorption feature and a tentative detection of small grain ($\lt $ 1μm) silicate absorption at $\gt $8.5 μm in WISE 1049A. Both components vary significantly ($\gt 1~{{\rm per\ cent}}$), with WISE 1049B displaying larger variations than WISE 1049A. Using K-means clustering, we find three main transition points in wavelength for both components of the binary: (1) change in behaviour at $\sim$2.3 μm coincident with a CO absorption bandhead, (2) change in behaviour at 4.2 μm, close to the CO fundamental band at $\lambda \gt $ 4.4 µm, and (3) change in behaviour at 8.3–8.5 µm, potentially corresponding to silicate absorption. We interpret the light curves observed with both NIRSpec and MIRI as likely stemming from (1) a deep pressure level driving the double-peaked variability seen in WISE 1049B at wavelengths $\lt $2.3 and $\gt $8.5 µm, (2) an intermediate pressure level shaping the light-curve morphology between 2.3 and 4.2 µm, and (3) a higher altitude pressure level producing single-peaked and plateaued light-curve behaviour between 4.2 and 8.5 µm.
Properties of supernova remnants in SIGNALS galaxies – I. NGC 6822 and M33
Authors: Duarte Puertas Salvador , Drissen Laurent , Robert Carmelle , Rousseau-Nepton Laurie , Martin René Pierre , Amram Philippe , Martin Thomas
Published: July 2024

We present a spatially resolved study of the kinematical properties of known supernova remnants (SNRs) in the nearest galaxies of the SIGNALS survey, namely NGC 6822 (one object) and M33 (163 objects), based on data obtained with the SITELLE imaging Fourier transform spectrometer at the Canada–France–Hawaii Telescope. The purpose of this paper is to provide a better scheme of identification for extragalactic SNRs and, in particular, to distinguish between H ii regions and SNRs. For that we have used diagrams which involve both the [S ii]/H$\alpha$ ratio and the velocity dispersion ($\sigma$). We also introduce a new parameter, $\xi = {[\rm S\, {\small II}] \over H\alpha } \times \sigma$, which enhances still the contrast between SNRs and the rest of the ionized gas. More than 90 per cent of the SNRs in our entire sample show an integrated [S ii]/H$\alpha$ ratio larger than the canonical value (0.4). 86 per cent of the SNRs present in our field show a significant velocity dispersion. The spectral resolution of our observations allows us to observe the complex velocity structure of some SNRs.
Hyponatraemia—treatment standard 2024
Authors: Spasovski Goce
Published: July 2024

Hyponatraemia is the most common electrolyte disorder in hospital patients associated with increased morbidity, mortality, hospital stay and financial burden. The speed of a correction with 3% sodium chloride as a 100- to 150-ml intravenous bolus or continuous infusion depends on the severity and persistence of the symptoms and needs frequent biochemical monitoring. The rapid intermittent administration of hypertonic saline is preferred for treatment of symptomatic hyponatraemia. In asymptomatic mild hyponatraemia, an adequate solute intake with an initial fluid restriction (FR) of 500 ml/day adjusted according to the serum sodium (sNa) levels is preferred. Almost half of the syndrome of inappropriate antidiuretic hormone (SIADH) patients do not respond to FR as first-line therapy. At present, urea and tolvaptan are considered the most effective second-line therapies in SIADH. However, the evidence for guidance on the choice of second-line therapy of hypotonic hyponatraemia is lacking. Oral urea is considered to be a very effective and safe treatment. Mild and asymptomatic hyponatraemia is treated with adequate solute intake (salt and protein) and initial FR with adjustments based on sNa levels. Specific treatment with vaptans may be considered in either euvolaemic or hypervolaemic patients with high ADH activity. In order to ensure optimal patient outcome, close monitoring and readiness for administration of either hypotonic fluids or desmopressin may be crucial in the decision-making process for specific treatment and eventual overcorrection consequences. According to the guidelines, gradual correction and clinical evaluation is preferable over rapid normalization of sNa towards the laboratory reference ranges.
Evaluation of Microseismic Motion at the KAGRA Site Based on Ocean Wave Data
Authors: Hoshino S , Fujikawa Y , Ohkawa M , Washimi T , Yokozawa T
Published: July 2024

Microseismic motion, ambient ground vibration caused by ocean waves, affects ground-based gravitational wave detectors. In this study, characteristics of the ocean waves including seasonal variations and correlation coefficients were investigated to obtain the significant wave heights at 13 coasts in Japan. The relationship between the ocean waves and the microseismic motion at the KAGRA site was also evaluated. As a result, it almost succeeded in explaining the microseismic motion at the KAGRA site by the principal components of the ocean wave data. One possible application of this study is microseismic forecasting, an example of which is also presented.
The size-dependence and reversibility of polystyrene nanoplastics-induced hepatic pyroptosis in mice through TXNIP/NLRP3/GSDMD pathway
Authors: Lu Yan-Yang , Hua Weizhen , Lu Lu , Tian Meiping , Huang Qingyu
Published: July 2024

As emerging environmental contaminants, nanoplastics (NPs) are progressively accumulating in terrestrial and aquatic ecosystems worldwide, posing a potential threat to human health. The liver is considered as one of the primary organs targeted by NPs accumulation in living organisms. However, there remains a large knowledge gap concerning NPs-induced hepatotoxicity. In this study, we examined the impact of chronic exposure to environmentally relevant doses of polystyrene (PS) NPs on hepatic pyroptosis in mice. The results demonstrated that both particle sizes of PS-NPs (100 nm and 500 nm) significantly triggered pyroptosis in the mouse liver, as evidenced by the upregulation of GSDMD-N protein levels; moreover, this pyroptotic effect induced by 100 nm PS-NPs was more pronounced compared to that of 500 nm PS-NPs. Mechanistically, exposure to 100 nm and 500 nm PS-NPs resulted in an upregulation of TXNIP protein expression, thereby activating NLRP3 inflammasome and subsequently inducing inflammatory responses and pyroptosis. Notably, following the termination of PS-NPs exposure and a subsequent recovery period of 50 days, PS-NPs-mediated inflammation and pyroptosis via TXNIP/NLRP3 pathway were effectively ameliorated, even returning to levels close to the baseline. Collectively, our findings provide novel evidence for the size-dependence and reversibility of NPs-induced hepatic pyroptosis through TXNIP/NLRP3/GSDMD pathway in vivo.
Functional Characterization of the Histone Acetyltransferase FcElp3 in Lotus Rhizome Rot-Causing Fungus Fusarium commune
Authors: Ye Lifang , Kuang Weigang , Zhang Lianhu , Lin Yachun , Zhang Yifan , Sun Xiaotang , Cui Ruqiang
Published: July 2024

Fusarium commune is the main pathogen of lotus rhizome rot, which causes the wilt of many plants. Histone acetyltransferase plays a critical part in the growth and virulence of fungi. In the present study, we identified an FcElp3 in F. commune homologous to histone acetyltransferase Elp3. We further constructed a mutant strain of F. commune to determine the function of FcElp3 in fungal growth and pathogenicity. The results showed that the deletion of FcElp3 resulted in reduced mycelial growth and sporulation. Compared with the wild type, the Δ FcElp3 strain showed more tolerance to osmotic stress and cell wall stress responses but was highly sensitive to oxidative stress. The subcellular localization results indicated that FcElp3 was distributed in both the cytoplasm and nucleus. Western blotting showed that FcElp3 was important for acetylation of H3K14 and H4K8. RNA sequencing analysis showed significant transcriptional changes in the Δ FcElp3 mutant, with 3,098 genes upregulated and 5,770 genes downregulated. Peroxisome was the most significantly enriched metabolic pathway for downregulated genes. This led to a significant decrease in the expression of the core transcription factor Fcap1 involved in the oxidative stress response. Pathogenicity tests revealed that the Δ FcElp3 mutant's pathogenicity on lotus was significantly decreased. Together, these findings clearly demonstrated that FcElp3 was involved in fungal growth, development, stress response, and pathogenicity via the direct regulation of multiple target genes.
Revolutionizing Mental Health Nursing Education: Virtual Reality Simulation for Understanding and Intervening in Major Depressive Disorder and Suicidal Thoughts
Authors: Bruce Cody , Wells-Beede Elizabeth , Seo Jinsil Hwaryoung , Han Gang , Thai Lauren
Published: July 2024

Utilizing Healthcare Simulation Standards of Best Practice™, a virtual reality (VR) platform was created to meet American Association of Colleges of Nursing Essential and Quad Council Public Health competencies. The scenario, involving major depressive disorder with suicidal ideation and alcohol dependency, engages learners in assessing suicide risk, recognizing symptoms, and recommending treatment. Eighty-four prelicensure nursing students have taken part in this mental health VR simulation since spring 2023. Although no significant difference was observed between pre-post knowledge, learners appreciated the VR experience. Student ratings were lowest for how physically demanding the task was and highest for their focus and interest in successfully doing the simulation.
A Novel, Mutually Beneficial Student-Faculty Partnership to Develop Real-Time Formative Assessments Aligning With the Preclinical Undergraduate Medical Curriculum
Authors: Schwartzman William E. , Paul Samuel N. , Amsterdam Chloe , Bustamante Galo , Vemulapalli Vamsee , Quinn Melissa M. , Pierson Christopher R.
Published: July 2024

Problem

A shortage of curriculum-aligned formative multiple-choice questions (FMCQs) remains despite their known learning benefits in preclinical medical education due to limitations on teaching faculty time and other reasons. In response, students often use extramural resources such as commercial or collaborative question banks; however, these options are often expensive and cannot be aligned with the content of each school’s unique curriculum. In addition, students need feedback on their learning in a manner that parallels the format of summative assessments. In this pilot, the authors aimed to enhance student learning by creating an intramural formative practice resource that was developed as the curriculum unfolded under the direction of the faculty leading the concurrently running curricular units.

Approach

The authors developed a workflow known as Professor-Reviewed Exam Practice (PREP) in 2023. PREP partnered with preclinical medical students and faculty to create vignette-style, single-best-response FMCQs with feedback for every lecture and self-guided learning module in multiple preclinical blocks of The Ohio State University College of Medicine undergraduate medical curriculum.

Outcomes

PREP established a sustainable, student-led, faculty-guided workflow that created high-quality, curriculum-aligned FMCQs for student use in the preclinical medical curriculum over a 14-month period. Usage rates were high across multiple preclinical blocks, reflecting high student demand for FMCQs of this nature and their value as a study aid. Survey data showed faculty agreed that their time commitment and role in the PREP workflow was appropriate.

Next Steps

Future work will evaluate the benefits of PREP to students by exploring the potential impact of PREP FMCQs on summative assessment performance and if writing FMCQs confers benefits to PREP team members. Faculty survey indicated that performance data from PREP FMCQs could be used to tailor upcoming teaching and learning methods, which is an area for future inquiry.
Development and Videographic Evaluation of a Vascular Access Simulation-Based Curriculum for Surgical and Medical Trainees
Authors: Pendleton Alaska , Bellomo Tiffany R. , Lella Srihari K. , Jogerst Kristen , Stefanescu Ada , Drachman Douglas , Zacharias Nikolaos , Dua Anahita
Published: July 2024

Background:

There is a paucity of data evaluating femoral arterial access training, despite significant morbidity/mortality associated with incorrect femoral arterial access. The aim of this study was to develop and evaluate a novel 2-component simulation-based curriculum to address a lack of standardized access training and identify the most frequent errors in access.

Methods:

The femoral arterial access curriculum was developed through a multi-disciplinary collaboration and utilized in-person simulation sessions in conjunction with online and in-person didactic training. Access errors and curriculum efficacy were assessed using mixed-methodology evaluation of video recordings of trainee arterial access pre- and postcurriculum. All recordings were reviewed and scored by 2 blinded, independent investigators.

Results:

Twenty-six participants completed the curriculum with pre- and postcurriculum recordings. Sixteen participants (62%) were in their first year of residency training. Fifteen participants (58%) belonged to general surgery residency, 9 (35%) to emergency medicine, 1 to vascular surgery, and 1 to interventional radiology residency programs. The global rating for the overall ability to obtain femoral arterial access under ultrasound guidance (0 = fail, 4 = excellent) improved following the curriculum (0.87 ± 0.15, 2.79 ± 1.26, P < 0.0001). Fourteen participants (54%) were unable to independently complete the procedure before training, compared to only 2 participants (8%) following the curriculum. Procedural completion time decreased from 7.14 ± 4.26 to 3.81 ± 2.53 minutes (P < 0.001). Most frequent errors, determined through qualitative analysis, included difficulty using the ultrasound and unsafe maneuvers.

Conclusions:

Before the curriculum, there were significant frequent errors in junior resident femoral arterial access with major patient safety concerns. A novel simulation-based femoral arterial access curriculum resulted in improved procedural skills across all metrics.
Value of sentinel node ultrastaging and pathologic techniques in tumoral detection
Authors: Viveros-Carreño David , Mora-Soto Nathalia , Pareja René
Published: July 2024

Purpose of review

Sentinel lymph node assessment is an option for patients with clinically early-stage vulvar cancer, endometrial cancer, cervical cancer, and, more recently, ovarian cancer. However, although ultrastaging is mandatory as part of the node evaluation, universally accepted pathology protocols are lacking. This review focuses on the current evidence for the most relevant aspects of sentinel lymph node evaluation, as well as some controversial topics like frozen section or one-step nucleic acid amplification.

Recent findings

The diagnostic accuracy of sentinel lymph node detection algorithms for patients with gynecologic neoplasms is high. However, the heterogeneity among the published studies and the absence of clear recommendations from most guidelines make it challenging to recommend one protocol over another. The minimum requirement from ultrastaging protocols (regarding the number of levels to be assessed, among others) to get the highest accuracy with a minor cost is unknown.

Sentinel lymph node evaluation is now part of the surgical management for most early-stage gynecologic neoplasms. However, a universally accepted ultrastaging pathology protocol is lacking in literature and clinical practice. This gap requires significant effort from the gynecologic oncology and pathology community to be closed and then to allow advancements in surgical management for early-stage gynecologic tumors to go forward.
Different tracers for sentinel node detection in gynecologic oncology
Authors: Laufer Joel , Scasso Santiago , Papadia Andrea
Published: July 2024

Purpose of review

In the past decade, sentinel lymph node (SLN) mapping has progressively substituted full lymphadenectomies in gynecologic oncology. In this article, we review the most relevant and the latest literature on this topic

Recent findings

In endometrial and cervical cancer, the current evidence further support the value of indocyanine green (ICG) as tracer of choice for SLN mapping. Experience in vulvar cancer is more limited, with ICG used together with technetium-99 m (Tc-99m) as a dual tracer but ICG, so far, has not been a game changer in this setting as it has been for cervical and endometrial cancer.

For most gynecologic cancers, ICG fluorescence imaging is considered now a days the tracer of choice for lymphatic mapping. However, in early-stage vulvar cancer, SLN biopsy with radioactive tracer continues to be the standard-of-care in lymph node status assessment.
HES6 Mediates Oxidative Phosphorylation Pathway to Promote Immune Infiltration of CD8+ T Cells in Lung Adenocarcinoma
Authors: Chen Zhoumiao , Wang Yongliang , Tang Weijian , Xu Shaohua , Yu Hao , Chen Zhao
Published: July 2024

Tumor immunotherapy has recently gained popularity as a cancer treatment strategy. The molecular mechanism controlling immune infiltration in lung adenocarcinoma (LUAD) cells, however, is not well characterized. Investigating the immune infiltration modulation mechanism in LUAD is crucial. LUAD patient samples were collected, and HES6 expression and immune infiltration level of CD8+ T cells in patient tissues were analyzed. Bioinformatics was utilized to identify binding relationship between E2F1 and HES6, and enrichment pathway of HES6. The binding of E2F1 to HES6 was verified using dual-luciferase and ChIP experiments. HES6 and E2F1 expression in LUAD cells was detected. LUAD cells were co-cultured with CD8+ T cells, and the CD8+ T cell killing level, IFN-γ secretion, and CD8+ T-cell chemotaxis level were measured. Expression of key genes involved in oxidative phosphorylation was detected, and the oxygen consumption rate of LUAD cells was assessed. A mouse model was constructed to assay Ki67 expression and apoptosis in tumor tissue. High expression of HES6 promoted CD8+ T-cell infiltration and enhanced T-cell killing ability through oxidative phosphorylation. Further bioinformatics analysis, molecular experiments, and cell experiments verified that E2F1 negatively regulated HES6 by oxidative phosphorylation, which suppressed CD8+ T-cell immune infiltration. In addition, in vivo assays illustrated that silencing HES6 repressed tumor cell immune evasion. E2F1 inhibited HES6 transcription, thereby mediating oxidative phosphorylation to suppress immune infiltration of CD8+ T cells in LUAD. The biological functions and signaling pathways of these genes were analyzed, which may help to understand the possible mechanisms regulating immune infiltration in LUAD.
In Situ Protein Expression Analysis of Melanocyte Differentiation Antigen TRP1 (Tyrosinase-Related Protein-1)
Authors: Chen Joyce M. , Hernandez Enmily , Frosina Denise , Ruh Peter A. , Ariyan Charlotte , Busam Klaus J. , Jungbluth Achim A.
Published: July 2024

Melanocyte differentiation antigens refer to molecules expressed in cells of melanocytic lineage such as gp100/PMEL, tyrosinase, and Melan-A. Corresponding antibodies such as HMB45, T311, and A103 have become key immunohistochemical tools in surgical pathology for the diagnosis of pigmented and related lesions. Little is known about tyrosinase-related protein 1 (TRP1), another melanocyte differentiation antigen, which is an enzymatic component of melanogenesis and known as the brown locus in mice. In this study, we tested several commercial reagents to TRP1 and identified one clone, EPR13063, which we further characterized by testing its specificity and usefulness for surgical pathology. Subsequently, we analyzed the expression of TRP1 in panels of normal tissues and tumors. TRP1 is regularly expressed in normal skin and in cutaneous nevi predominantly present in junctional and to a lesser extent in dermal nevocytes. In melanoma, TRP1 is present in 100% and 44% of primary and metastatic melanomas, respectively. TRP1 was absent in 5 desmoplastic melanomas but heterogeneously present in 9 of 11 PEComas/angiomyolipomas. No TRP1 was found in neoplasms of nonmelanocytic lineage. We demonstrate that EPR13063 is a valuable reagent for the analysis of TRP1 expression in archival surgical pathology material. The TRP1 expression pattern in melanocytic and related lesions appears to parallel other melanocyte differentiation antigens with a higher incidence in primary and a lower incidence in metastatic melanomas.
Reactive Lobular Panniculitis in the Setting of Mpox (Monkeypox) Infection
Authors: Forouzan Parnia , Raffi Jodie , Doan Linda T. , Min Michelle S.
Published: July 2024

Mpox, previously referred to as monkeypox, was recently deemed a public health emergency in 2022. Our understanding of potential secondary cutaneous manifestations in the setting of this infection is still evolving. We report a rare case of a man who presented with erythematous, painful subcutaneous nodules on his extremities in the setting of recent mpox infection. Biopsy of a lesion from the lower legs revealed a lobular panniculitis with lupus panniculitis-like features on pathology. He was ultimately diagnosed with a unique case of reactive panniculitis secondary to mpox.
A comparative study of ultrasonography (USG) and computed tomography for detecting ureteric calculi in patients with acute flank pain, and analysis of factors influencing ultrasound detection rates
Authors: Khatiwada Bishnu , Mahat Asim , Yadav Gopal Kumar , Duwadi Bikash , Mishra Upama , Bhusal Amrit , Yadav Priti , Khadka Hensan
Published: July 2024

Introduction:

Urolithiasis, a frequent urologic issue, often relies on computed tomography (CT) scans, the preferred imaging technique. However, in low-income countries like Nepal, access to CT scans is limited. The authors’ study focused on comparing ultrasound (US) and CT for assessing ureteric calculi in patients with acute flank pain and examined factors influencing US detection rates in these patients.

Methods:

The authors conducted a cross-sectional study using purposive sampling, involving 87 participants who presented with acute flank pain at a tertiary hospital in Nepal. Ethical clearance was obtained from the institutional review board.

Results:

Among the 87 patients presenting with acute flank pain, the majority were male (51, 58.62%). Of the 78 cases with CT-detected ureteric calculi, the most common locations were distal ureter (23/78, 29.49%), followed by proximal ureter (21/78, 26.92%), and pelvic-ureteric junction (PUJ) (20/78, 25.64%). Ultrasound demonstrated varying sensitivities for detecting ureteric calculi: 95.00% for PUJ, 100.00% for vesicoureteric junction (VUJ), 66.67% for proximal ureter, and 56.52% for distal ureter calculi. The highest sensitivity was observed for calculi greater than 15 mm (100%), followed by 10.1–15 mm (77.7%). Overall, ultrasound exhibited a sensitivity of 76.92%, a specificity of 100%, and an accuracy rate of 79.31% in detecting calculi. Notably, patients with hematuria had significantly higher odds of ultrasound-detected ureteric calculi (odds ratio: 36.68, 4.54–296.26, P<0.01) than those without hematuria. However, age, hydronephrosis, calculi location, and laterality were not found to be significantly associated with ultrasound detection.

Conclusions:

Due to its good sensitivity, ultrasound can serve as the first-line investigation for individuals experiencing acute flank pain, given its cost-effectiveness and radiation-free nature when compared to CT scans. CT scans should be reserved for patients exhibiting clinical symptoms of severe ureteric colic who have previously undergone a negative ultrasound (USG).
Preoperative Chemotherapy plus Immune Checkpoint Inhibitors as Conversion Therapy in Pancreatic Cancer Patients with Initially Unresectable Liver-limited Metastases: A Case Report
Authors: Xiao Li , Zhang Haoqi , Tan Chunlu , Liu Xubao , Zheng Zhenjiang
Published: July 2024

Pancreatic cancer (PC) is a lethal tumor, and overall survival (OS) is poor, especially for patients with liver metastases. Herein, we report a 55-year-old female who presented with right upper quadrant pain. Computed tomography (CT) of the upper abdomen revealed a large space-occupying lesion (5.5×5.2 cm) in the pancreatic neck with multiple liver metastases. After biopsy confirmation, the patient underwent conversion therapy consisting of doublet chemotherapy (gemcitabine 1,000 mg/m2 and nab-paclitaxel 125 mg/m2) and toripalimab (a novel PD-1 inhibitor, 240 mg). After six and a half cycles, radical pancreaticoduodenectomy combined with resection of liver metastases and portal vein replacement were performed successfully. The patient died from hemorrhage of the pancreaticojejunostomy anastomotic stoma four months after surgery. No recurrence or metastases were detected by CT until the patient died. This is the first study to report the results of conversion surgery in patients with metastatic PC limited to the liver after preoperative chemotherapy plus a PD-1 inhibitor. Stage IV PC should not be considered a general contraindication for surgical resection in well-selected patients. A multicenter randomized controlled study should be performed to investigate the efficacy and safety of this controversial treatment strategy.
Analysis of BK Virus Infection in Children After Hematopoietic Cell Transplantation: A Retrospective Single-center Study
Authors: Wei Ang , Jing Yuanfang , Zhu Guanghua , Wang Bin , Yang Jun , Jia Chenguang , Luo Yanhui , Yan Yan , Zheng Jie , Zhou Xuan , Qin Maoquan , Wang Tianyou
Published: July 2024

Background:

BK virus (BKV) is one of the most common causes of hemorrhagic cystitis (HC) in children undergoing hematopoietic stem cell transplantation (HSCT). Viruses can be found in urine and serum of immunocompromised patients.

Objective:

This study aimed to evaluate the incidence, clinical course, and risk factors for BKV infection in children undergoing HSCT.

Methods:

Retrospectively analyzed children who underwent HSCT at Beijing Children’s Hospital, Capital Medical University from June 2020 to June 2022. Data related to the clinical manifestations, engraftment, and prognosis were extracted from medical records. Patients were divided into the case group and the control group, according to the BKV infection or not after HSCT.

Results:

A total of 149 patients were enrolled in this study, and 61 (40.9%) patients developed BKV infection after HSCT. Among the 61 patients, BKV load was detected in all patients in urine samples and 22 patients in blood samples. The median value of BKV DNA copies in urine and plasma were 9.50×107 (5.37×102 to 6.84×109) copies/mL and 2.97×103 (9.96×102 to 3.58×108) copies/mL, respectively. The median time from beginning of the conditioning regimen to BKV infection was 23 (0 to 273) days, and the first positive time of urinary BKV was earlier than that of blood (13.5 d [0.0 to 123.0 d] vs. 30.5 d [7.0 to 165.0 d], P=0.003). Among the patients with BKV infection, 36 (59.0%) patients met the diagnosis of hemorrhagic cystitis (HC), and the incidence was higher than that in the control group (P<0.001). Similarly, 15 (24.6%) patients developed renal function damage in the case group and the proportion was higher than that in the control group. The median follow-up was 5.67 (0.03 to 24.90) months, and there was no significant difference in 1-year overall survival rate between the case group and the control group (84.2%±5.7% vs. 95.3%±2.3%, P=0.688), but the incidence of TA-TMA/VOD (31.1%) and diffuse alveolar hemorrhage (9.8%) in the case group was higher than that in the control group (P=0.002 and 0.038, respectively). Multivariate analysis showed that age above 5 years old (OR=9.039, 95% CI: 3.561-24.333, P<0.001) and use of MMF (OR=2.708, 95% CI: 1.041-7.044, P<0.05) were independent risk factors for BKV infection after HSCT.

Conclusion:

Among children after HSCT, the incidence of BKV infection was high and BKV infection was associated with an increased incidence of TA-TMA/VOD and diffuse alveolar hemorrhage. Patients older than 5 years of age at the time of HSCT and treated with MMF were more likely to develop BKV infection.
PD-L1 Expression and Its Modulating Factors in Anaplastic Thyroid Carcinoma
Authors: Agarwal Shipra , Jung Chan Kwon , Gaddam Pranitha , Hirokawa Mitsuyoshi , Higashiyama Takuya , Hang Jen-Fan , Lai Wei-An , Keelawat Somboon , Liu Zhiyan , Na Hee Young , Park So Yeon , Fukuoka Junya , Satoh Shinya , Mussazhanova Zhanna , Nakashima Masahiro , Kakudo Kennichi , Bychkov Andrey
Published: July 2024

Anti-PD immunotherapy is currently under investigation in anaplastic thyroid carcinoma (ATC). Tumor cell surface PD-L1 expression is considered predictive of therapeutic response. Although papillary thyroid carcinoma has been widely studied for PD-L1 expression, there are limited data on ATC. In this retrospective multi-institutional study involving 9 centers across Asia, 179 ATCs were assessed for PD-L1 expression using the SP263 (Ventana) clone. A tumor proportion score (TPS) ≥1% was required to consider a case PD-L1-positive. PD-L1 expression was compared with the histological patterns, the type of specimen (small or large), tumor molecular profile (BRAF V600E and TERT promoter mutation status), and patient outcome. PD-L1 expression in any co-existent differentiated thyroid carcinoma (DTC) was evaluated separately and compared with ATC. Most ATCs (73.2%) were PD-L1-positive. The median TPS among positive cases was 36% (IQR 11% to 75%; range 1% to 99%). A high expression (TPS ≥ 50%) was noted in 30.7%. PD-L1-negative cases were more likely to be small specimens (P=0.01). A negative result on small samples, hence, may not preclude expression elsewhere. ATCs having epithelioid and pleomorphic histological patterns were more likely to be PD-L1-positive with higher TPS than sarcomatoid (P<0.01). DTCs were more frequently negative and had lower TPS than ATC (P<0.01). Such PD-L1 conversion from DTC-negative to ATC-positive was documented in 71% of cases with co-existent DTC. BRAF V600E, but not TERT promoter mutations, correlated significantly with PD-L1-positivity rate (P=0.039), reinforcing the potential of combining anti-PD and anti-BRAF V600E drugs. PD-L1 expression, however, did not impact the patient outcome.
Habitual Caffeine Use Is Associated With Heightened Cortisol Reactivity to Lab-Based Stress in Two Samples
Authors: Cole Elli L. , Grillo Alessandra R. , Vrshek-Schallhorn Suzanne
Published: July 2024

Objective

Habitual caffeine consumption protects against depression but through unclear mechanisms. Although habitual caffeine use predicts cortisol release in response to other acute stressors (e.g., exercise), this is less examined with lab-based psychosocial stress in healthy adults. Furthermore, caffeine-induced cortisol increases may mask theory-predicted cortisol blunting to robust stress in people with elevated depression risk. In two samples, we tested whether acute (same-day) and habitual caffeine use would predict greater cortisol reactivity to lab-based stress, and whether caffeine would “mask” the effect of a depression risk factor, trait rumination, on blunted cortisol reactivity.

Method

In sample 1, N = 128 emerging adults completed one of three Trier Social Stress Test conditions: nonevaluative control, ambiguously evaluative intermediate, or explicit negative evaluative. In sample 2, N = 148 emerging adults completed either a control or negative evaluative condition.

Results

In both samples, multilevel growth curve modeling indicated that habitual caffeine use (t = −1.99, p = .048; t = −2.73, p = .007, samples 1 and 2, respectively) but not acute caffeine use predicted heightened cortisol reactivity as a function of condition. In sample 1, the relationship between condition, rumination, and blunted cortisol was evident only in caffeine nonusers, which differed from users (t = 2.82, p = .005), but in sample 2, the predicted blunting pattern was evident regardless of caffeine use.

Conclusion

The results provide evidence that habitual caffeine use is associated with greater cortisol release under psychosocial lab-based stress and may mask the influence of psychosocial variables; future research should examine whether habitual caffeine–induced cortisol release has behaviorally activating effects that protect against depression.
CT Quantification of Interstitial Lung Abnormality and Interstitial Lung Disease: From Technical Challenges to Future Directions
Authors: Choe Jooae , Hwang Hye Jeon , Lee Sang Min , Yoon Jihye , Kim Namkug , Seo Joon Beom
Published: July 2024

Interstitial lung disease (ILD) encompasses a variety of lung disorders with varying degrees of inflammation or fibrosis, requiring a combination of clinical, imaging, and pathologic data for evaluation. Imaging is essential for the noninvasive diagnosis of the disease, as well as for assessing disease severity, monitoring its progression, and evaluating treatment response. However, traditional visual assessments of ILD with computed tomography (CT) suffer from reader variability. Automated quantitative CT offers a more objective approach by using computer-based analysis to consistently evaluate and measure ILD. Advancements in technology have significantly improved the accuracy and reliability of these measurements. Recently, interstitial lung abnormalities (ILAs), which represent potential preclinical ILD incidentally found on CT scans and are characterized by abnormalities in over 5% of any lung zone, have gained attention and clinical importance. The challenge lies in the accurate and consistent identification of ILA, given that its definition relies on a subjective threshold, making quantitative tools crucial for precise ILA evaluation. This review highlights the state of CT quantification of ILD and ILA, addressing clinical and research disparities while emphasizing how machine learning or deep learning in quantitative imaging can improve diagnosis and management by providing more accurate assessments, and finally, suggests the future directions of quantitative CT in this area.
Thin inclusion at the junction of two elastic bodies: non-coercive case
Authors: Khludnev A. M.
Published: July 2024

This article addresses an analysis of the non-coercive boundary value problem describing an equilibrium state of two contacting elastic bodies connected by a thin elastic inclusion. Nonlinear conditions of inequality type are imposed at the joint boundary of the bodies providing a mutual non-penetration. As for conditions at the external boundary, they are Neumann type and imply the non-coercivity of the problem. Assuming that external forces satisfy suitable conditions, a solution existence of the problem analysed is proved. Passages to limits are justified as the rigidity parameters of the inclusion and the elastic body tend to infinity.

This article is part of the theme issue ‘Non-smooth variational problems with applications in mechanics’.
The homogenized dynamical model of a thermoelastic composite stitched with reinforcing filaments
Authors: Rudoy Evgeny M. , Sazhenkov Sergey A.
Published: July 2024

The dynamical problem of linear thermoelasticity for a body with incorporated thin rectilinear inclusions is studied. It is assumed that the inclusions (i.e. filaments and threads) are parallel to each other and the problem contains a small parameter

ϵ
>
0

, which characterizes the distance between two neighbouring inclusions. Using the two-scale convergence approach, we find the limiting problem as

ϵ
→
0

. As a result, we get a well-posed homogenized model of an anisotropic inhomogeneous body with effective characteristics inheriting thermomechanical properties of inclusions.

This article is part of the theme issue ‘Non-smooth variational problems with applications in mechanics’.