bluuebunny/crossref_metadata_2025 huggingface dataset:
Addressing ovarian cancer research gaps in under-resourced settings using individual initiatives: The OVANORDEST pilot project in Morocco.
Authors: El Bairi Khalid
Published: August 2024

183

Background: In Morocco, ovarian cancer (OC) is a neglected women’s cancer. To bridge this gap, early-career cancer researchers might develop and engage in individual initiatives to enhance research outcomes. In this perspective, I recently launched the OVANORDEST project as an individual initiative. This plan outlines a three-step strategy designed to promote OC research, highlighting specific milestones. This abstract presents the findings from the initial feasibility study, which focuses on real-world evidence, implementing inexpensive precision medicine approaches, supporting women in oncology, and enhancing meta-research. Methods: Initially, a bibliometric study was conducted to find research gaps in the field of OC in Morocco. A 16-year real-world retrospective study was conducted at the Hassan II Oncology Center (October 2005-June 2020). To implement precision medicine approaches, quality evidence on several potentially inexpensive blood-based biomarkers such as Pan-Immune Inflammation-Value (PIIV) were explored using a PROSPERO-registered umbrella systematic review and then investigated in an original cohort. Cox regression analyses were applied to identify the effects of different biomarkers on survival outcomes. Meta-research was developed by publishing two special thematic issues and one edited book on OC biomarkers. The project also included a mentorship program designed to empower women oncologists. Results: A total of 258 patients with OC were included. Most patients had advanced FIGO stages at diagnosis. The median overall survival (OS) for the entire cohort was 32 months, with a median progression-free survival (PFS) of 14.6 months. CA-125 positivity, advanced disease stage, and presence of residual disease after surgery were prognostic factors that adversely affected survival. In the multivariable analysis after adjustment for the FIGO stage, high PIIV was an independent predictive factor of OS (HR= 1.83; 95% CI: 1.18-2.84, p=0.007). Two specialized thematic issues were published alongside a book dedicated to ovarian cancer biomarkers. Additionally, careers of a group of women oncologists were boosted and a local patient advocacy group was supported in adopting supportive strategies for patients. Conclusions: Engaging early-career cancer researchers through individual initiatives in under-resourced settings may considerably improve research outcomes. In this context, I propose that sharing this experience, which has been successfully applied in Morocco, could empower health systems and facilitate the generation of research outputs in low- and middle-income countries.
A phase 2, open-label, single-arm study evaluating the combination of pembrolizumab (pembro), lenvatinib, and chemotherapy in patients (pts) with metastatic non-small cell lung cancer (NSCLC) harbouring a targetable mutation who experienced disease progression on standard tyrosine kinase inhibitors (TKIs).
Authors: Chan Hoi Wai , Tse Chris Chun Long , Li Yu-Chung , Leung Roland Ching-Yu , Wong Jeffrey Sum Lung , Kwok Gin Wai , Li Hoi Lam , Tsang Wing Yan Josephine , Li Cho Wing , Lo Jenny WY , Tang Vikki , Hui Rina , Yau Thomas , Ho James CM , Chiu Joanne W
Published: August 2024

198

Background: Pts with metastatic NSCLC harbouring a targetable mutation who progressed on standard TKIs often receive chemotherapy as the next line of treatment. We report efficacy and safety of a novel combination of pembro, lenvatinib and chemotherapy for these pts. Methods: This was a phase 2, open-label, single-centre, single-arm study enrolling pts with metastatic NSCLC with sensitizing EGFR, ALK or ROS1 mutation who progressed on standard TKIs. Eligible pts had measurable disease, no untreated brain metastasis and ECOG PS ≤1. Pts received pembro 200 mg, pemetrexed 500 mg/m2 and carboplatin AUC 5 every 3 weeks for 4 cycles plus lenvatinib 8 mg QD. The maintenance regimen without carboplatin was continued as tolerated for up to 2 years. The primary endpoint was objective response rate (ORR) by independent radiology review (IRR) as per RECIST 1.1. The secondary endpoints were PFS, overall survival (OS) and safety. Results: At the data cutoff date (2nd February 2024), 24 pts were screened and 19 were enrolled: median age 64 years (range 29–77); 10 (53%) female. Four pts were excluded at screening due to untreated brain metastasis. All enrolled pts were evaluated for safety while 15 pts were evaluable for response. All pts had adenocarcinoma with targetable mutation: EGFR mutation in 18 (95%) pts and ALK fusion in 1 (5%) pt. The median follow-up time was 11.3 months. Treatment was ongoing in 8 pts on the date of analysis, while 6 pts permanently discontinued due to disease progression and 1 pt permanently discontinued due to a treatment-related adverse event (TRAE). The ORR was 40% (6/15, 95% CI 19.8%–64.3%). All responses were partial responses. The median PFS was 11.9 months (range 3.5–20.3). The OS was not reached. TRAEs of any grade (Gr) occurred in 74% (14/19) of the pts. Most of the TRAEs were Gr 1–2, which occurred in 63% (12/19) of the pts. The most common TRAEs were hypothyroidism (31.6%), nausea (26.3%), neutropenia (26.3%), thrombocytopenia (26.3%), anorexia (21.1%), hypertension (15.8%), anaemia (10.5%), pruritus (10.5%) and rash (10.5%). G1 diarrhoea was reported in 1 pt (5.3%) and G1 adrenal insufficiency in 1 pt (5.3%). Gr 3 TRAEs were neutropenia in 2 pts, anaemia in 1 pt and thrombocytopenia in 1 pt. The only Gr 4 TRAE was thrombocytopenia. No treatment related death was observed. Conclusions: The combination of pembro, lenvatinib and chemotherapy demonstrated a favourable ORR and safety in treating metastatic NSCLC pts with a targetable mutation who progressed on standard TKIs. Clinical trial information: NCT04989322 .
Effect of heterozygosity loss of HLA-I on immune evasion and promotion of non-small cell lung cancer brain metastasis and immunotherapy resistance.
Authors: Han Jiefei , Lin Yi , Li Wenbin
Published: August 2024

209

Background: HLA-I play a crucial role in T cell recognition and killing of tumor cells as well as in PD-1/PD-L1 immunotherapy. Loss of heterozygosity (LOH) of HLA-I alleles has been found to be common in lung cancer patients and influences immune escape during tumor evolution. This study aims to explore the incidence of HLA-I LOH in intracranial metastases of advanced non-small cell lung cancer patients with brain metastasis and its impact on the efficacy of immunotherapy. Methods: A total of 29 patients with non-small cell lung cancer brain metastasis were included in this study. All enrolled patients underwent either percutaneous biopsy or surgical resection of intracranial metastases and had tissue specimens from the primary lung lesions. Whole-exome sequencing was performed on all primary/metastatic lesions to determine HLA-I typing/LOH and calculate tumor mutation burden (TMB). Additionally, we assessed the expression levels of CD8 T cells in the tumor immune microenvironment. Among the enrolled patients, 20 received PD-1/PD-L1 treatment. Results: Among the enrolled patients, 82.8% (24/29) had heterozygous HLA-I typing, with HLA-I LOH present in 25% (6/24) of patients' primary lesions and 58.3% (14/24) in brain metastatic lesions. Analysis of TMB in different lesions revealed a median TMB of 7.8 mut/Mb in lesions with intact HLA-I and 11.4 mut/Mb in lesions with HLA-I LOH. Notably, the median TMB in brain metastatic lesions with HLA-I LOH was 13.2 mut/Mb, higher than that in HLA-I LOH primary lung lesions (10.1 mut/Mb). Immunohistochemistry demonstrated that CD8 T cell expression levels were lowest in brain metastatic lesions with HLA-I LOH and highest in intact HLA-I primary lung lesions. Among patients who received immunotherapy, four cases exhibited inconsistent lesion responses, with stable or regressing primary lesions but progressive intracranial metastases. Survival analysis revealed that patients with HLA-I LOH in brain metastases had significantly lower PFS compared to those without (4.1 months vs. 6.9 months, P < 0.05), with no significant difference in OS. Conclusions: This study indicates that the incidence of HLA-I LOH in brain metastases of lung cancer is higher than that in primary lung lesions, accompanied by higher TMB, possibly due to the ineffective presentation of tumor antigens resulting in the accumulation of mutations in lost HLA-I. Moreover, tumors with HLA-I LOH have reduced levels of CD8 T cell infiltration, suggesting impaired tumor antigen presentation impedes immune cytotoxicity. These phenomena contribute to the poorer efficacy of immunotherapy in such patients. In conclusion, HLA-I LOH may be one of the important mechanisms of immune escape in lung cancer brain metastases.
Racial impact of secondary metastasis in patients with lung cancer: Evidence of US hospitals in 2020.
Authors: Suenghataiphorn Thanathip , Kulthamrongsri Narathorn , Saowapa Sakditad , Naunsilp Piengpitch , Xanthavanij Nutchapon , Osataphan Soravis Alm
Published: August 2024

213

Background: Lung cancer patient often encounter disparities in health outcomes, especially in difference racial and ethnic groups. Metastasis is the primary cause of cancer morbidity and mortality. However, data on the metastasis risks and clinical outcomes on hospitalized individuals with lung cancer is still limited. Therefore, we aim to assess the association between metastatic lung cancer and racial differences. Methods: We analyzed the 2020 U.S. National Inpatient Sample (NIS) to explore patients who have lung cancer as the primary diagnosis. Additionally, we identified evidence of metastasis, as recorded by ICD-10-CM. Adjusted odds ratios (aORs) for specified outcomes were calculated through multivariable logistic and linear regression analyses. The primary outcome was racial differences in organ metastasis and secondary outcomes included mortality and length of stay. Statistical significance was established at p-value of 0.05. Results: We identified 103,335 patients with primary diagnosis of lung and bronchus cancer at discharge. The mean age was 68.9 years; 50.5% were female. Caucasians accounted for 74.3%, with African Americans at 12.1% and Hispanics at 4.6%. 10% of the patients had brain metastasis, whereas 14% had bone metastasis. In a multivariate analysis adjusting for patient, COVID-19, chemotherapy usage and hospital factors, African Americans had higher risk of brain metastasis (aOR 1.18; 95%CI (1.02, 1.37), p = 0.002), higher risk of bone metastasis (aOR 1.16; 95%CI (1.02, 1.33), p = 0.025), higher risk of mortality (aOR 1.21; 95% CI (1.01, 1.45), p = 0.039) and longer length of stay (b = 0.85; 95%CI (0.55, 1.16), p = 0.001). Hispanics also had higher risk of brain (aOR 1.36, p < 0.05) and prolonged length of stay (b 0.79, p < 0.005). We observed an increase in risk of metastasis and mortality but non-statistically significant in some parameters and races, as shown in table provided. Conclusions: In conclusion, our study revealed that racial difference is associated with higher risk of metastasis, as well as other outcomes. Further longitudinal research is necessary to establish a causal relationship between races, metastasis, and mortality in patients with lung cancer. [Table: see text]
Prognostic and immunological significance of tertiary lymphoid structures in nasopharyngeal carcinoma.
Authors: Huang Daofeng , Liu Xu , Li Hui , Zheng Zi-Qi , Du Juan , Ma Jun
Published: August 2024

220

Background: Tertiary lymphoid structures (TLSs) are ectopic lymphoid tissues found in non-lymphoid organs, characterized by the presence of CD20+ B cell follicles adjacent to a T cell zone. Their presence has been associated with improved survival in various tumor types. However, the role of TLSs in nasopharyngeal carcinoma (NPC) remains unclear. In this study, we investigated the prognostic and immunological significance of TLSs in NPC patients. Methods: The investigation involved a discovery cohort (n = 145) comprising NPC patients diagnosed at Sun Yat-sen University Cancer Center between July 2010 and December 2016, with pretreatment primary tumor samples collected. An independent validation cohort included 150 NPC patients with gene expression profiles, among whom Hematoxylin & Eosin (H&E)-stained slides were available for 95 patients. The primary endpoint of this study is overall survival, defined as the duration of time from diagnosis until death from any cause. The presence of TLSs was assessed on H&E and CD20-stained slides. Analyses of tumor-infiltrating immune cell subsets, differentially expressed genes, and BCR/TCR clonotypes were performed to explore the association between TLSs and the anti-tumor immune response. A molecular definition of TLSs was proposed and assessed for its prognostic value across multiple cohorts. Results: The presence of TLSs was independently associated with a favorable overall survival (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.07-0.94; log-rank p = 0.04), surpassing the significance of B cell density in multivariate analysis (HR, 0.83; 95% CI, 0.38-1.79, log-rank p = 0.63). These findings were corroborated in the independent validation cohort. TLSs positively correlated with multiple immune-related pathways and a higher proportion of functionally mature immune cells. Notably, the counts of BCR and TCR clonotypes showed a significant positive correlation with the TLSs score. We proposed a TLSs gene signature and demonstrated its prognostic relevance across multiple cohorts, including patients treated with immune checkpoint blockade. Conclusions: TLSs exhibit heightened immune activity and indicate improved survival outcomes in NPC patients. A TLSs gene signature was proposed and demonstrated its prognostic relevance across multiple cohorts, indicating potential guidance for treatment decisions in cancer.
Tissue of origin detection for cancer tumor using low-depth cfDNA samples through combination of tumor-specific methylation atlas and genome-wide methylation density in graph convolutional neural networks.
Authors: Doan Nhu Nhat Tan , Nguyen Trong Hieu , Tran Trung Hieu , Nguyen Thi Hue Hanh , Nguyen Van Thien Chi , Giang Hoa , Tran Le Son , Phan Minh Duy
Published: August 2024

224

Background: Cell free DNA (cfDNA)-based assays hold great potential in detecting early cancer signals yet determining the tissue-of-origin (TOO) for cancer signals remains a challenging task. Here, we investigated the contribution of a methylation atlas to TOO detection in low depth cfDNA samples. Methods: We constructed a tumor-specific methylation atlas (TSMA) using whole-genome bisulfite sequencing (WGBS) data from five types of tumor tissues (breast, colorectal, gastric, liver and lung cancer) and paired white blood cells (WBC). TSMA was used with a non-negative least square matrix factorization (NNLS) deconvolution algorithm to identify the abundance of tumor tissue types in a WGBS sample. We showed that TSMA worked well with tumor tissue but struggled with cfDNA samples due to the overwhelming amount of WBC-derived DNA. To construct a model for TOO, we adopted the multi-modal strategy and used as inputs the combination of deconvolution scores from TSMA with other features of cfDNA. Results: Our final model comprised of a graph convolutional neural network using deconvolution scores and genome-wide methylation density features, which achieved an accuracy of 69% in a held-out validation dataset of 239 low-depth cfDNA samples. Conclusions: In conclusion, we have demonstrated that our TSMA in combination with other cfDNA features can improve TOO detection in low-depth cfDNA samples.
Prognostic value of immuno-nutritional status in patients with cancer treated by immune checkpoint inhibitors.
Authors: Kuo Ming-Chun
Published: August 2024

226

Background: The treatment efficacy of immune checkpoint inhibitors (ICIs) may relate to tumor factors or host factors, such as systemic inflammation status or nutritional status. In this study, we investigated the prognostic value of immuno-nutritional status in cancer patients treated by ICIs, and develop nomogram models for predicting overall survival (OS). Methods: We used Chang Gung Research Database to retrospectively evaluate cancer patients who received ICIs during January 2015 to December 2021. Patients had double cancer or received only one cycle of ICI were excluded. All patients were divided into a training cohort and a validation cohort. The training cohort was used to analyze the risk factors and develop nomogram models. The models were validated by the validation cohort. The univariate analysis, stepwise multivariate analysis, receiver operator characteristics (ROC) analysis were used to find out the independent risk factors. The calibration plot were used to evaluate the reliability of the models. Results: All patients (3219 cases) could be categorized into lung cancer (22.1%), genitourinary cancer (14.9%), upper gastrointestinal tract cancer (8.1%), colorectal cancer (3.1%), hepatocellular carcinoma (24.6%), pancreatobiliary cancer (3.8%), head and neck cancer (12.9%), melanoma (4.0%), breast cancer (1.9%) and lymphoma (0.5%). 80.2% of patients received anti-PD1, 19.8% of patients received anti-PD-L1. In training cohort, the cut-off value was set for neutrophil-to-lymphocyte ratio (NLR), total lymphocyte count (TLC), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), prognostic nutrition index (PNI) and hemoglobin-albumin-lymphocyte-platelet (HALP) score. The above risk factors showed significant difference in median OS in validation cohort respectively (Table). The multivariate analysis demonstrated that NLR, PNI and HALP score were independent risk factors in predicting OS. The hazard ratio were 1,439 (95% CI 1.149-1.801), 0.689 (95% CI 0.549-0.865) and 0.784 (95% CI 0.626-0.982) respectively. Conclusions: We developed nomogram models to investigate the immuno-nutritional status and predict the OS of cancer patients who received ICIs therapy. High NLR, low PNI and low HALP score were associated with worse OS. [Table: see text]
Unsupervised clustering of brain tumor leukocytes to reveal atypical lymphoid cell subsets.
Authors: Hermelo Ismaïl , Virtanen Tuomo , Salonen Iida , Nätkin Reetta , Keitaanniemi Sofia , Tiihonen Aliisa , Lehtipuro Suvi , Kummola Laura , Nordfors Kristiina , Haapasalo Hannu , Rauhala Minna , Kesseli Juha , Nykter Matti , Haapasalo Joonas , Rautajoki Kirsi
Published: August 2024

25

Background: The brain tumor immune microenvironment (TiME) is characterised by suppression of tumor-infiltrating leukocytes. The lymphocyte niche activity is particularly downregulated within this TiME milieu. Methods: Here, using data-driven approaches in flow cytometry and RNA sequencing analysis, we aimed at dissecting leukocyte cell types infiltrating human brain tumor TiME. Results: Unsupervised clustering provided T lymphocyte subsets including double-negative (CD3+CD4- CD8-) T cells (DNT). Our DNT phenotype was validated with an independent dataset, suggesting DNT to be compatible with γδ T cell phenotype. In our cohort, myeloid immune cell frequencies were associated with malignancy type as previously reported, while a gliosarcoma notably presented unexpectedly high lymphocyte frequencies. Consistently, double-positive (CD4+ CD8+) T cells (DPT) had higher frequency in the gliosarcoma than other tumors. The flow cytometry results were supported by transcriptome patterns and the activity of immune-related genes in these tumors. Conclusions: Our findings feature the benefit of data-driven approaches for brain TiME lymphocyte analysis, and show that primary brain tumors can entail atypical lymphocyte subsets like DNTs and DPT cells. Unbiased lymphocyte characterisation can potentially outline novel targets for immune checkpoint blockade therapy.
Challenges of liquid panel in genomic profiling of esophageal squamous cell carcinoma (ESCC): Insights from an analysis of over 1000 cases.
Authors: Morita Ryuichi , Ishikawa Takeshi , Itani Junichiro , Sone Daiki , Iwai Naoto , Doi Toshifumi , Iwasaku Masahiro , Inoue Ken , Dohi Osamu , Yoshida Naohisa , Uchiyama Kazuhiko , Takagi Tomohisa , Konishi Hideyuki , Horiguchi Go , Takayama Koichi , Itoh Yoshito
Published: August 2024

86

Background: Genomic analysis of ctDNA from cancer patients can allow identification of actionable alterations of tumor without an invasive biopsy. ctDNA analysis has been reported to be superior for global summary of tumor heterogeneity and a short turnaround time compared to tissue analysis,however, there are potential issues including the detection sensitivity, threshold to determine TMB-H, and clonal hematopoiesis of indeterminate potential (CHIP). In order to elucidate the impact of ctDNA analysis on personalized cancer treatment, we decided to examine the genetic landscape and clinical outcomes of ESCC cohort registered in the C-CAT database. Methods: We retrospectively analyzed data from 1059 cases of ESCC registered in the C-CAT from June 2019 to February 2024. Clinical characteristics, TMB status, pathological gene variants, and time to treatment failure (TTF) of first-line treatment were examined. Results: The panels applied to eligible patients consisted of 925 tumor tissue panels (87.3%) and 134 liquid panels (12.7%). Pathological gene mutations were detected in 924 cases (99.8%) in tissue panels and 133 cases (99.2%) in liquid panels. The top 10 detected genes were TP53 (93.4%), CDKN2A (57.8%), CDKN2B (45.5%), CCND1 (43.9%), FGF19 (41.0%), PIK3CA (29.0%), NFE2L2 (28.3%), BCL6 (16.5%), NOTCH1 (13.5%), and KMT2D (12.2%). The detection rate for these genes excluding NOTCH1 and KMT2D were significantly higher in tissue panels than in liquid panels (P≤0.01). The median TMB was 5.00 Muts/Mb for both. In first-line treatment, the TTF for immune checkpoint inhibitors (ICIs) and chemotherapy was significantly longer in TMB-H (≧10 Muts/Mb) compared to TMB-L (3.1M vs. 1.9M, P<0.01) in patients evaluated by tissue panels, but it was not proven in patients evaluated by liquid panels (P=0.38). Furthermore, the results suggest that patients with CDKN2A, CCND1, and FGF19 variants benefit more by adding ICIs to chemotherapy than patients without these variants and while the opposite was true for BCL6 and NOTCH1 and KMT2D. Conclusions: In this ESCC cohort, detection rates in the liquid panels were generally lower than in the tissue panels, suggesting that sufficient ctDNA could not be obtained in many cases. The appropriate patient selection for the liquid panels and the timing of blood collection should be discussed. Furthermore, the ideal threshold for determining TMB-H in the liquid panels needs to be further investigated.
Routine Symptom Screening to Address Supportive Care Needs
Authors: Hannon Breffni , Zimmermann Camilla
Published: August 2024

Routine symptom screening may identify unmet needs, but must consider patient engagement and clinician workloads.
Thyroid Arteriovenous Malformation in Hereditary Hemorrhagic Telangiectasia: Insights on Successful Noninvasive Imaging
Authors: Goto Hisanori , Tanimura Iyo , Nakano Yujiro , Takeshita Yumie , Takamura Toshinari
Published: August 2024

Hereditary hemorrhagic telangiectasia (HHT) causes arteriovenous malformations (AVMs) in several organs. This report is the first to document and image a thyroid AVM complication in HHT.

A 72-year-old woman with HHT was referred for thyroid nodule evaluation. Ultrasonography showed a hypervascularized nodule in the right thyroid lobe which was initially suspected to be malignant. However, 3-dimensional computed tomography angiography demonstrated a thyroid AVM with abnormal anastomosis of the superior thyroid artery and the inferior thyroid vein.

In the formation of thyroid AVM, here, chronic thyroiditis and hypothyroidism complications may have been a second hit, due to the predisposing first-hit germline mutation.

This report sheds light on overlooked thyroid lesions in HHT and advocates a noninvasive imaging approach in diagnosing thyroid AVMs. Furthermore, this case suggests a potential mechanism of AVM formation in human HHT, possibly supporting the second-hit hypothesis.
Endoscopic Extended Transsphenoidal Surgery for Transbasal Tuberculum Sellae Meningioma: 2-Dimensional Operative Video
Authors: de Rosa Giorgia , Serioli Simona , Musarra Alessandra , Brancaleone Riccardo Maria , Rigante Mario , di Domenico Michele , Gessi Marco , Mattogno Pier Paolo , Lauretti Liverana , Arena Vincenzo , Olivi Alessandro , Doglietto Francesco
Published: August 2024

Transbasal meningiomas
1
are a rare group of tumors that grow intracranially, invade the skull base, and propagate extracranially; they are usually located at the level of the olfactory cribra and sphenoid wing.
1-4
Transbasal tuberculum sellae meningiomas are a subset of these tumors, which extend into the suprasellar and sphenoid regions. The traditional transcranial approach for some transbasal meningiomas has recently evolved toward the transnasal endoscopic approach, which allows the removal of both the intranasal and intracranial components, reducing the manipulation of the optic nerves and neurovascular structures. Nevertheless, specific anatomical criteria must be present; the knowledge of specific anatomy
5,6
and the surgeon's experience are fundamental for reaching the most favorable outcome.
7-11
In this video, we present the case of a 50-year-old woman with a history of progressive visual impairment and scotoma in the left inferotemporal quadrant. Radiological examinations suggested a transbasal tuberculum meningioma that extended into the suprasellar region, sphenoid sinus, and optic canals. An endoscopic transtuberculum approach with intraoperative visual-evoked potentials
12
was performed, allowing an early devascularization with the preservation of the superior hypophyseal arteries and the removal of the component extending in the medial portion of both optic canals. The postoperative MRI documented a gross total resection without complications. The patient reported an immediate improvement of the visual symptoms. Histopathology documented a meningioma (CNS World Health Organization grade 1) with bone invasion. The patient consented to the procedure and to the publication of her image; Institutional Review Board approval was not required for this single case report.
Preliminary Experience With Novel Straight 3-Fr Guiding Sheath for Transradial Access in Endovascular Treatment: Feasibility and Safety
Authors: Fuga Michiyasu , Sano Tohru , Hataoka Shunsuke , Ishibashi Toshihiro , Kan Issei , Aoki Ken , Tachi Rintaro , Kato Naoki , Nagayama Gota , Murayama Yuichi
Published: August 2024

BACKGROUND AND OBJECTIVES:

Radial artery diameter may limit whether a guiding sheath (GS) can be used via transradial artery access (TRA). A smaller GS may reduce the risk of access site–related complications. This study investigated the feasibility and safety of endovascular treatment (EVT) using a straight-shaped 3-Fr GS (Axcelguide; Medikit).

METHODS:

Patients who underwent EVT with a straight-shaped 3-Fr GS at 3 institutions between April 2022 and March 2024 were retrospectively reviewed. Patient background, anatomic and procedural factors, and complications were recorded.

RESULTS:

Twenty-six pathologies were treated with EVT using a 3-Fr GS. Median radial artery diameter was 1.9 mm, and distal TRA (73.1%) was selected more often than TRA (26.9%) as the access site. The breakdown of target pathologies and the role of the 3-Fr GS were as follows: 12 unruptured cerebral aneurysms for intra-aneurysmal coiling, with 5 dural arteriovenous fistulas, 5 brain or head and neck tumors, 2 chronic subdural hematoma, 1 arteriovenous malformation, and 1 hereditary hemorrhagic telangiectasia for transarterial embolization. A success rate of 96.2% was achieved, with no access site– or non–access site–related complications observed within 30 days.

CONCLUSION:

The straight-shaped 3-Fr GS may be applicable for selected pathologies, allowing access even with RAs <2 mm in diameter and facilitating EVT without complications. Preliminary experience with the 3-Fr GS via TRA demonstrated excellent feasibility and safety.
The FAM114A proteins are adaptors for the recycling of Golgi enzymes
Authors: Welch Lawrence G. , Muschalik Nadine , Munro Sean
Published: August 2024

Golgi-resident enzymes remain in place while their substrates flow through from the endoplasmic reticulum to elsewhere in the cell. COPI-coated vesicles bud from the Golgi to recycle Golgi residents to earlier cisternae. Different enzymes are present in different parts of the stack, and one COPI adaptor protein, GOLPH3, acts to recruit enzymes into vesicles in part of the stack. Here, we used proximity biotinylation to identify further components of intra-Golgi vesicles and found FAM114A2, a cytosolic protein. Affinity chromatography with FAM114A2, and its paralogue FAM114A1, showed that they bind to Golgi-resident membrane proteins, with membrane-proximal basic residues in the cytoplasmic tail being sufficient for the interaction. Deletion of both proteins from U2OS cells did not cause substantial defects in Golgi function. However, a Drosophila orthologue of these proteins (CG9590/FAM114A) is also localised to the Golgi and binds directly to COPI. Drosophila mutants lacking FAM114A have defects in glycosylation of glue proteins in the salivary gland. Thus, the FAM114A proteins bind Golgi enzymes and are candidate adaptors to contribute specificity to COPI vesicle recycling in the Golgi stack.
Predictors of mortality for blunt trauma patients in intensive care: A retrospective cohort study
Authors: Jennings Michael , Booker James , Addison Amy , Egglestone Rebecca , Dushianthan Ahilanandan
Published: August 2024

Background: Major trauma places substantial demand on critical care services, is a leading cause of death in under 40-year-olds and causes significant morbidity and mortality across all age groups. Various factors influence patient outcome and predefining these could allow prognostication. The aim of this study was to identify predictors of mortality from major trauma in intensive care. Methods: This was a retrospective study of adult trauma patients admitted to general intensive care between January 2018 and December 2019. We assessed the impact on mortality of patient demographics, patterns of injury, injury scores (Glasgow Coma Score (GCS), Charlson’s comorbidity index (CCI), Acute Physiology and Health Evaluation II (APACHE II), Injury Severity Score (ISS) and Probability of Survival Score (Ps19)), number of surgeries and mechanism of injury using logistic regression. Results: A total of 414 patients were included with a median age of 54 years (IQR 34–72). Overall mortality was 18.6%. The most common mechanism of injury was traffic collision (46%). Non-survivors were older, had higher ISS scores with lower GCS on admission and probability of survival scores. Factors independently predictive of mortality were increasing age (OR 1.06, p <0.001) and GCS <15 on admission (OR 7.21, p <0.001). Ps19 was the best predictor of mortality (p <0.001 for each score category), with an AUROC of 0.90. Conclusions: The significant mortality predictors were age, fall from <2 metres, injury of head or limbs, GCS <15 and Ps19. Contrary to previous studies CCI and APACHE II did not significantly predict mortality. Although Ps19 was found to be the best current prognostic score, trauma prognostication would benefit from a single validated scoring system incorporating both physiological variables and injury patterns.
Laboratory findings predictive of critical illness in hospitalized COVID-19 patients in Tunisia
Authors: Belkhir Donia , Blibech Hana , Kaabi Line , Miladi Saoussen , Jebali Mohamed Aymen , Daghfous Jalloul , Mehiri Nadia , Laatar Ahmed , Ben Salah Nozha , Snene Houda , Louzir Bechir
Published: August 2024

Background COVID-19 disease has spread rapidly worldwide, causing high mortality. Accessible biomarkers capable of early identification of patients at risk of severe form are needed in clinical practice. The aim of the study was to determine the biological markers that predict a critical condition. Methods Retrospective study including patients with confirmed COVID-19 hospitalized between September 2020 and June 2021. The primary endpoint was progression to critical status within 7 days from admission. We defined two groups: Critical group: Patients who developed a critical condition or died or transferred to the ICU before or at 7th day. Non-critical group: Patients who remained in non-critical respiratory status until 7th day or discharged before or at 7th day. Results Our study included 456 patients, with a sex ratio of 1.32 and an average age of 62 years. At the 7th day of hospitalization, 115 (25.2%) patients were in the critical group and 341 (74.8%) patients were in the non-critical group. The univariate logistic regression indicated that laboratory findings between non-critical and critical groups showed that C-reactive protein (CRP) (p=0.047), D-Dimer (p=0.011), creatinine (0.026), creatine kinase (p=0.039), lactate dehydrogenase (p=0.04), and troponin (p=0.001) were all higher among patients in critical group. However, lymphocyte (p<0.001) and platelet (p<0.001) counts were significantly lower among the critical group. Multivariate logistic regression model, identified four independent risk factors: lymphopenia (OR=2.771, 95%CI=1.482-5.181, p=0.001), Neutrophil to Lymphocyte Ratio (OR=2.286, 95%CI=1.461-3.578, p<0.001), thrombocytopenia (OR=1.944, 95%CI=1.092-3.459, p=0.024), and CRP>71.5 (OR=1.598, 95% CI=1.042-2.45, p=0.032) were associated to critical group. Conclusions Our results show the predictive value of some biological markers to evaluate the prognosis of COVID-19 pneumonia. A prognostic score could be proposed for guiding clinical care and improving patient outcomes.
The genome sequence of a robberfly Leptogaster cylindrica (De Geer, 1776)
Authors: Sivell Olga , Sivell Duncan ,   Natural History Museum Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: August 2024

We present a genome assembly from an individual female Leptogaster cylindrica (robberfly; Arthropoda; Insecta; Diptera; Asilidae). The genome sequence spans 196.60 megabases. Most of the assembly is scaffolded into 5 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 18.0 kilobases in length. Gene annotation of this assembly on Ensembl identified 10,816 protein-coding genes.
The genome sequence of a braconid wasp, Aleiodes leptofemur van Achterberg & Shaw, 2016
Authors: Broad Gavin R. ,   Natural History Museum Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: August 2024

We present a genome assembly from an individual male Aleiodes leptofemur (braconid wasp; Arthropoda; Insecta; Hymenoptera; Braconidae). The genome sequence spans 271.20 megabases. Most of the assembly is scaffolded into 15 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 32.28 kilobases in length.
The genome sequence of the western European hedgehog, Erinaceus europaeus Linnaeus, 1758
Authors: Allen Simon ,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: August 2024

We present a genome assembly from an individual female Erinaceus europaeus (the western European hedgehog; Chordata; Mammalia; Eulipotyphla; Erinaceidae). The genome sequence spans 2,720.70 megabases. Most of the assembly is scaffolded into 24 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 17.43 kilobases in length.
The genome sequence of a dance fly, Rhamphomyia laevipes (Fallén, 1816)
Authors: Falk Steven ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: August 2024

We present a genome assembly from a male dance fly, Rhamphomyia laevipes (Arthropoda; Insecta; Diptera; Empididae). The genome sequence has a length of 394.50 megabases. Most of the assembly is scaffolded into 7 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 18.04 kilobases in length.
The genome sequence of the small yellow-legged robberfly, Dioctria linearis (Fabricius, 1787)
Authors: Crowley Liam M. , Garland Steven , Akinmusola Ruth Y. ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: August 2024

We present a genome assembly from an individual female small yellow-legged robberfly, Dioctria linearis (Arthropoda; Insecta; Diptera; Asilidae). The genome sequence has a total length of 1,613.20 megabases. Most of the assembly is scaffolded into 5 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 18.4 kilobases in length. Gene annotation of this assembly on Ensembl identified 12,074 protein-coding genes.
ANALYSIS OF HOP DRYER PERFORMANCE WITH PARTIAL THERMAL ENERGY RECOVERY
Authors: Vasilev Aleksandr , Andreev Roman , Egorov Kirill , Kalimullin Marat
Published: August 2024

Drying is an integral part of the technological process of commercial hop production. Depending on the production volume and the level of automation of the process, there are several ways to dry hop cones, including convective, microwave and sublimation. At the same time, dryers have different ratios of quality and productivity. Reducing energy costs for drying hops is an important area in the development of hop growing. In this regard, modernization and analysis of the productivity of hop dryers is a pressing issue in the current conditions of rising production costs. The aim of the research is to analyze the productivity of the MXS-25 hop dryer, modernized by installing a heat pump in the air circulation circuit and having adjustable heat recovery. The air temperature in the drying chamber was successfully controlled in the range of 60 ± 2 ° C. The preheating time required to achieve the air temperature was approximately 0.5 hours, which corresponds to approximately 5% of the total hop drying time. Comparison of the measured and calculated energy consumption values showed that the experimental values were in the range of 10.2 kWh to 11.5 kWh, averaging approximately 10.85 kWh during the experiment. Accordingly, the calculated values were in the range of 8.9 kWh and 10.2 kWh, averaging 9.55 kWh. A series of experiments comparing the drying performance using partial recovery showed that with an increase in the ambient temperature to 24 °C, the maximum relative moisture separation rate reached 6.23 kg/(kWh) with a bypass ratio of 0.86, which was higher than that of 5.54 kg/(kWh) for drying with full recovery. The partial heat recovery system is superior to the full recovery system in terms of energy efficiency and increased hop drying performance.
TO THE CALCULATION OF LIQUID DISC SEPARATORS WITH PARABOLIC INSERTS
Authors: Ibyatov Ravil , Ziganshin Bulat , Galeev Damir
Published: August 2024

The object of the study is liquid disk separators with curvilinear inserts, which are described by equations of the type . The study was conducted to study the effect of the insert shape on the intensity of the centrifugal force on the liquid flow, as well as on the length of the sedimentation path (or float) of dispersed medium particles. The efficiency of clarification of dispersed media is predetermined by two design characteristics of the device - the length of the particle sedimentation path and the direction of the centrifugal force relative to the walls of the curved channel. For parabolic inserts, the distance between them and the angle of inclination of the walls are variable quantities. To calculate these quantities, nonlinear equations are constructed and an algorithm for numerical calculations is proposed. The calculation results are presented as graphical dependencies of the above parameters along the channel length. The calculations were performed for paraboloids of revolution with degrees m=2, 3 and 4 at coefficient a=2, 3 and 4. As the coefficient a increases, the distance between the inserts decreases. The influence of the exponent m on the gap between the paraboloids of revolution is more complex. The gap size along the channel length decreased from 3 cm to several millimeters. The angle of inclination of the walls relative to the rotation axis decreased in the range from 70 to 10 degrees. As the parameters a and m increase, this angle decreases, therefore, the component of the centrifugal force directed perpendicular to the channel wall increases. The equations of motion of the liquid system were solved by the method of equal flow surfaces, according to which the flow is represented as several layers with their own velocities. At the inlet section, the velocity diagram develops from a flat profile to a parabolic form. As a result of the action of the centrifugal force, an asymmetry of the velocity profile is observed. The obtained results can be used to justify the geometric characteristics of a plate separator with parabolic inserts and to coordinate them with the flow regime parameters.
Conditional Lead-Time Flexibility in an Assemble-to-Order System
Authors: Yu Yi , Deng Tianhu , Song Jing-Sheng
Published: August 2024

Problem definition: We introduce and formalize a concept termed conditional lead-time flexibility (CLF), which refers to the industry practice where a manufacturer requests that its upstream suppliers dynamically adjust the pipeline orders’ remaining lead times. Over a finite horizon, an assemble-to-order manufacturer makes joint decisions on inventory replenishment and lead-time adjustment to minimize the total discounted expected cost. Methodology/results: The problem is formulated as a multiperiod dynamic programming with an enlarged state space to track the adjustable pipeline orders. The replenishment and lead-time adjustment decisions are made sequentially in each period. The analysis reveals that (i) the optimal cost-to-go function is both convex and additively separable, that (ii) both the optimal replenishment and lead-time adjustment decisions follow general base-stock policies, and that (iii) the convexity and additive separability allow us to perform a derivative analysis on the optimality equations and design an efficient algorithm. Managerial implications: Using real industry data, we numerically find that (i) CLF achieves notable cost savings over a wide range of parameters, that (ii) the value of CLF comes from both the order expediting and deferring, and that (iii) CLF outperforms dual sourcing when the unit adjustment cost is less than 40% of the unit ordering cost from the express source. Our findings underscore the importance of CLF.

Funding: T. Deng acknowledges financial support from the National Key Research and Development Program of China [Grant 2022YFB3305602] and the National Natural Science Foundation of China (NSFC) [Grant 72188101].

Supplemental Material: The electronic companion is available at https://doi.org/10.1287/msom.2023.0520 .
Loss of support for deaf children
Authors: Hayes Derren
Published: August 2024

Report reveals shortage of teachers for deaf pupils due to funding cuts is harming children's education
New era for inspection begins
Authors: Hayes Derren
Published: August 2024

Children's services ratings have improved but reforms to system present new challenges say leaders
Chin and jawline augmentation: a frontier of aesthetic medicine
Authors: Ramadan Francesca
Published: August 2024

The heightened public interest in and usage of non-invasive cosmetic procedures has translated to the practice of jawline and chin augmentation. Implants have historically been a cornerstone of chin augmentation; however, more recently, as non-invasive procedural techniques and modalities develop, questions have been raised as to whether there is still a need for implants. Francesca Ramadan explores the innovative options available to address even the most acute patient concerns.
Confronting EHS Challenges
Authors: Fanning Paul
Published: August 2024

An in-depth look at RS’s recent Health & Safety report finds there is “room for improvement” in attitudes to health and safety in the manufacturing sector.
Enhancing self-power broadband photodetection performance of Co3O4/ZnCo2O4/ZnO heterojunction via graphene oxide modification
Authors: Wang Hang , Peng Shaolong , Zhou Longjie , Li Lihua , Gu Yongjun , Kim Bok-Hee , Huang Jinliang
Published: August 2024

In today’s field of optoelectronic devices, high-performance, self-power broadband responsive photodetectors hold significant application prospects and can find wide-ranging utility in areas such as optical communication, biomedical imaging, and environmental monitoring. This study investigates a series of samples with varying graphene oxide (GO) content, obtained through detailed characterization and optoelectronic performance testing. An appropriate amount of GO modification can form a thin film covering the brush-like Co3O4/ZnCo2O4/ZnO heterojunction surface, creating a conductive network. However, excessive content leads to GO aggregation on the heterojunction surface, affecting detection performance. Density functional theory (DFT) calculations elucidate the electron structure and transport mechanism at the interface between ZnO and GO, demonstrating graphene oxide’s efficacy as an electron transfer channel, thus enhancing the material’s optoelectronic detection performance. By employing the most suitable amount of GO modification, the optoelectronic detection performance of the Co3O4/ZnCo2O4/ZnO heterojunction is further improved. The maximum responsivity and detectivity under monochromatic light reach 193.33 mA/W and 3.68×1013 Jones, respectively. This work provides significant insights for the design and manufacturing of optoelectronic devices, with crucial scientific significance and practical value.
High-efficiency simulation of coherent beam combining using a scaled angular spectrum method
Authors: Abedi M. , Saghafifar H. , Rahimi L.
Published: August 2024

Efficient and accurate modeling of coherent beam combining (CBC) was achieved using the scaled angular spectrum method (Sc-ASM) with graphic processing unit (GPU) acceleration. This approach simulates the propagation and combination of Gaussian beams while accounting for the spectral phase effects in ultrashort femtosecond pulses, including various orders of dispersion. Given the high costs of CBC systems, pre-experimental simulations are crucial. The integration of GPU acceleration significantly enhances the computational speed, making large-scale CBC system simulations feasible. This framework provides valuable insights into the experimental implementation and design of high-power laser systems.