bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethics rounds in the ambulance service: a qualitative evaluation
Authors: Frank Catharina , Rantala Andreas , Svensson Anders , Sterner Anders , Green Jessica , Bremer Anders , Holmberg Bodil
Published: January 2024

Background

It is a common ethical challenge for ambulance clinicians to care for patients with impaired decision-making capacities while assessing and determining the degree of decision-making ability and considering ethical values. Ambulance clinicians’ ethical competence seems to be increasingly important in coping with such varied ethical dilemmas. Ethics rounds is a model designed to promote the development of ethical competence among clinicians. While standard in other contexts, to the best of our knowledge, it has not been applied within the ambulance service context. Thus, the aim of this study was to describe ambulance clinicians’ experiences of participating in ethics rounds.

Methods

This was a qualitative descriptive study, evaluating an intervention. Data were collected through sixteen interviews with ambulance clinicians who had participated in an intervention involving ethics rounds. The analysis was performed by use of content analysis.

Results

Two themes describe the participants’ experiences: (1) Reflecting freely within a given framework, and (2) Being surprised by new insights. The following categories form the basis of the themes; 1a) Gentle guidance by the facilitator, 1b) A comprehensible structure, 2a) New awareness in the face of ethical problems, and 2b) Shared learning through dialogue.

Conclusion

Incorporating structured ethics rounds seems to create a continuous development in ethical competence that may improve the quality of care in the ambulance service. Structured guidance and facilitated group reflections offer ambulance clinicians opportunities for both personal and professional development. An important prerequisite for the development of ethical competence is a well-educated facilitator. Consequently, this type of ethics rounds may be considered a useful pedagogical model for the development of ethical competence in the ambulance service.
“Hospitals respond to demand. Public health needs to respond to risk”: health system lessons from a case study of northern Queensland’s COVID-19 surveillance and response
Authors: Edelman Alexandra , Allen Tammy , Devine Susan , Horwood Paul F. , McBryde Emma S. , Mudd Julie , Warner Jeffrey , Topp Stephanie M
Published: January 2024

Background

The vast region of northern Queensland (NQ) in Australia experiences poorer health outcomes and a disproportionate burden of communicable diseases compared with urban populations in Australia. This study examined the governance of COVID-19 surveillance and response in NQ to identify strengths and opportunities for improvement.

Methods

The manuscript presents an analysis of one case-unit within a broader case study project examining systems for surveillance and response for COVID-19 in NQ. Data were collected between October 2020–December 2021 comprising 47 interviews with clinical and public health staff, document review, and observation in organisational settings. Thematic analysis produced five key themes.

Results

Study findings highlight key strengths of the COVID-19 response, including rapid implementation of response measures, and the relative autonomy of NQ’s Public Health Units to lead logistical decision-making. However, findings also highlight limitations and fragility of the public health system more generally, including unclear accountabilities, constraints on local community engagement, and workforce and other resourcing shortfalls. These were framed by state-wide regulatory and organisational incentives that prioritise clinical health care rather than disease prevention, health protection, and health promotion. Although NQ mobilised an effective COVID-19 response, findings suggest that NQ public health systems are marked by fragility, calling into question the region’s preparedness for future pandemic events and other public health crises.

Conclusions

Study findings highlight an urgent need to improve governance, resourcing, and political priority of public health in NQ to address unmet needs and ongoing threats.
Rethinking the pros and cons of randomized controlled trials and observational studies in the era of big data and advanced methods: a panel discussion
Authors: Fernainy Pamela , Cohen Alan A. , Murray Eleanor , Losina Elena , Lamontagne Francois , Sourial Nadia
Published: January 2024

Randomized controlled trials (RCTs) have traditionally been considered the gold standard for medical evidence. However, in light of emerging methodologies in data science, many experts question the role of RCTs. Within this context, experts in the USA and Canada came together to debate whether the primacy of RCTs as the gold standard for medical evidence, still holds in light of recent methodological advances in data science and in the era of big data. The purpose of this manuscript, aims to raise awareness of the pros and cons of RCTs and observational studies in order to help guide clinicians, researchers, students, and decision-makers in making informed decisions on the quality of medical evidence to support their work. In particular, new and underappreciated advantages and disadvantages of both designs are contrasted. Innovations taking place in both of these research methodologies, which can blur the lines between the two, are also discussed. Finally, practical guidance for clinicians and future directions in assessing the quality of evidence is offered.
Hospitalized acute exacerbation in chronic obstructive pulmonary disease – impact on long-term renal outcomes
Authors: Kwok Wang Chun , Tam Terence C. C. , Ho James C. M. , Lam David C. L. , Ip Mary S. M. , Yap Desmond Y. H.
Published: January 2024

Introduction

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common and preventable event in patients with chronic obstructive pulmonary disease (COPD). Data regarding the impact of AECOPD on short- and long-term renal outcomes are lacking.

Methods

We included all COPD patients who were followed at Queen Mary Hospital (QMH) in year 2015 and reviewed their clinical/renal outcomes in subsequent five years. Relationships between AECOPD and adverse renal outcomes were evaluated.

Results

371 COPD patients were included. 169 patients had hospitalized AECOPD in past one year (HAE group) while 202 patients did not (non-HAE group). 285 patients (76.8%) had renal progression/death and 102 (27.5%) patients developed acute kidney injury (AKI). HAE group showed a more rapid eGFR decline than non-HAE group (-4.64 mL/min/1.73m2/year vs. -2.40 mL/min/1.73m2/year, p = 0.025). HAE group had significantly higher risk for renal progression/death at 5 years [adjusted OR (aOR) 2.380 (95% CI = 1.144–4.954), p = 0.020]. The frequency of hospitalized AECOPD in past 3 years, any AECOPD in past 3 years, hospitalized AECOPD in past 3 years were also predictive of renal progression/death at 5 years [aOR were 1.176 (95% CI = 1.038– 1.331), 2.998 (95% CI = 1.438–6.250) and 2.887 (95% CI = 1.409–5.917) respectively; p = 0.011, 0.003 and 0.004]. HAE group also showed significantly higher risk of AKI [adjusted HR (aHR) 2.430; 95% CI = 1.306–4.519, p = 0.005].

Conclusions

AECOPD, in particular HAE, was associated with increased risk of renal progression/death and AKI. Prevention of AECOPD, especially HAE, may potentially improve short- and long-term renal outcomes in COPD patients.
Glycylglycine promotes the solubility and antigenic utility of recombinant HCV structural proteins in a point-of-care immunoassay for detection of active viremia
Authors: Shawky Heba , Tabll Ashraf A. , Elshenawy Reem M. , Helmy Naiera M. , Moustafa Rehab I. , Elesnawy Yasser K. , Abdelghany Marwa M. , El-Abd Yasmine S.
Published: January 2024

Background

Although E. coli is generally a well-opted platform for the overproduction of recombinant antigens as heterologous proteins, the optimization of expression conditions to maximize the yield of functional proteins remains empirical. Herein, we developed an optimized E. coli (BL21)-based system for the overproduction of soluble immunoreactive HCV core/envelope proteins that were utilized to establish a novel immunoassay for discrimination of active HCV infection.

Methods

The core/E1-E2 genes were amplified and expressed in E. coli BL21 (DE3) in the absence/presence of glycylglycine. The antigenic performance of soluble proteins was assessed against 63 HCV-seronegative (Ab−) sera that included normal and interferent sera (HBV and/or chronic renal failure), and 383 HCV-seropositive (Ab+) samples that included viremic (chronic/relapsers) and recovered patients’ sera. The color intensity (OD450) and S/Co values were estimated.

Results

The integration of 0.1–0.4M glycylglycine in the growth media significantly enhanced the solubility/yield of recombinant core and envelope proteins by ~ 225 and 242 fold, respectively. This was reflected in their immunoreactivity and antigenic performance in the developed immunoassay, where the soluble core/E1/E2 antigen mixture showed 100% accuracy in identifying HCV viremic sera with a viral RNA load as low as 3800 IU/mL, without cross-reactivity against normal/interferent HCV-Ab−sera. The ideal S/Co threshold predicting active viremia (> 2.75) showed an AUC value of 0.9362 (95% CI: 0.9132 to 0.9593), with 87.64, 91.23% sensitivity and specificity, and 94.14, 82.11% positive and negative predictive values, respectively. The different panels of samples assayed with our EIA showed a good concordance with the viral loads and also significant correlations with the golden standards of HCV diagnosis in viremic patients. The performance of the EIA was not affected by the immunocompromised conditions or HBV co-infection.

Conclusion

The applicability of the proposed platform would extend beyond the reported approach, where glycylglycine, low inducer concentration and post-induction temperature, combined with the moderately-strong constitutive promoter enables the stable production of soluble/active proteins, even those with reported toxicity. Also, the newly developed immunoassay provides a cost-effective point-of-care diagnostic tool for active HCV viremia that could be useful in resource-limited settings.
The roles and molecular mechanisms of non-coding RNA in cancer metabolic reprogramming
Authors: Li Shizhen , Peng Mingjing , Tan Shiming , Oyang Linda , Lin Jinguan , Xia Longzheng , Wang Jiewen , Wu Nayiyuan , Jiang Xianjie , Peng Qiu , Zhou Yujuan , Liao Qianjin
Published: January 2024

One of the key features of cancer is energy metabolic reprogramming which is tightly related to cancer proliferation, invasion, metastasis, and chemotherapy resistance. NcRNAs are a class of RNAs having no protein-coding potential and mainly include microRNAs, lncRNAs and circRNAs. Accumulated evidence has suggested that ncRNAs play an essential role in regulating cancer metabolic reprogramming, and the altered metabolic networks mediated by ncRNAs primarily drive carcinogenesis by regulating the expression of metabolic enzymes and transporter proteins. Importantly, accumulated research has revealed that dysregulated ncRNAs mediate metabolic reprogramming contributing to the generation of therapeutic tolerance. Elucidating the molecular mechanism of ncRNAs in cancer metabolic reprogramming can provide promising metabolism-related therapeutic targets for treatment as well as overcome therapeutic tolerance. In conclusion, this review updates the latest molecular mechanisms of ncRNAs related to cancer metabolic reprogramming.
Microglia-mediated drug substance transfer promotes chemoresistance in brain tumors: insights from an in vitro co-culture model using GCV/Tk prodrug system
Authors: Wu Sheng-Yan , Yu Wen-Jui , Chien Ting-Yi , Ren Yu-An , Chen Chi-Shuo , Chiang Chi-Shiun
Published: January 2024

Background

It is well known that tumor-associated macrophages (TAMs) play essential roles in brain tumor resistance to chemotherapy. However, the detailed mechanisms of how TAMs are involved in brain tumor resistance are still unclear and lack a suitable analysis model.

Methods

A BV2 microglial cells with ALTS1C1 astrocytoma cells in vitro co-culture system was used to mimic the microglia dominating tumor stroma in the tumor invasion microenvironment and explore the interaction between microglia and brain tumor cells.

Results

Our result suggested that microglia could form colonies with glioma cells under high-density culturing conditions and protect glioma cells from apoptosis induced by chemotherapeutic drugs. Moreover, this study demonstrates that microglia could hijack drug substances from the glioma cells and reduce the drug intensity of ALTS1C1 via direct contact. Inhibition of gap junction protein prevented microglial-glioma colony formation and microglia-mediated chemoresistance.

Conclusions

This study provides novel insights into how glioma cells acquire chemoresistance via microglia-mediated drug substance transferring, providing a new option for treating chemo-resistant brain tumors.
Multiple Anopheles species complicate downstream analysis and decision-making in a malaria pre-elimination area in southern Mozambique
Authors: Máquina Mara , Opiyo Mercy A. , Cuamba Nelson , Marrenjo Dulcisária , Rodrigues Maria , Armando Sarmento , Nhate Sheila , Luis Fabião , Saúte Francisco , Candrinho Baltazar , Lobo Neil F. , Paaijmans Krijn P.
Published: January 2024

Background

Different anopheline species (even within a species group/complex) can differ in their feeding and resting behaviours, which impact both malaria transmission patterns as well as the efficacy of vector control interventions. While morphological identification of sampled specimens is an important first step towards understanding species diversity and abundance, misidentification can result in the implementation of less effective vector control measures, and consequently smaller reductions in the number of local malaria cases. Focusing on southern Mozambique, a malaria pre-elimination area where malaria remains persistent, the aims of this preliminary study were to use molecular identification (CO1 and ITS2 barcoding) to (1) validate the results from the morphological identification (with a particular focus on Anopheles pharoensis and Anopheles squamosus), and (2) have a closer look at the Anopheles coustani group (which includes Anopheles tenebrosus and Anopheles ziemanni).

Methods

Female anopheline mosquitoes (n = 81) were identified morphologically and subsequently sequenced at the ribosomal DNA internal transcribed spacer region 2 (ITS2) and/or cytochrome oxidase subunit 1 (CO1) loci towards species determination.

Results

Out of the 62 specimens that were identified morphologically to species, 4 (6.5%) were misidentified. Regarding the An. coustani group, morphological identification showed that several members are present in southern Mozambique, including An. coustani sensu lato (s.l.), An. ziemanni and An. tenebrosus. However, based on both ITS2 and CO1 sequences, the exact species remains unknown for the latter two members until voucher sequences are available for comparison.

Conclusion

The reason(s) for morphological misidentification of anopheline mosquitoes need to be mitigated. This is usually related to both the capacity (i.e. training) of the microscopist to identify anopheline species, and the information provided in the dichotomous identification key. As the An. coustani complex contributes to (residual) malaria transmission in sub-Saharan Africa, it may play a role in the observed persistent malaria in southern Mozambique. A better baseline characterizing of the local anophelines species diversity and behaviours will allow us to improve entomological surveillance strategies, better understand the impact of vector control on each local vector species, and identify new approaches to target those vector species.
Cost of illness studies in COVID-19: a scoping review
Authors: Nakhaee Majid , Khandehroo Masoud , Esmaeili Reza
Published: January 2024

Background

Human communities suffered a vast socioeconomic burden in dealing with the pandemic of coronavirus disease 2019 (COVID-19) globally. Real-word data about these burdens can inform governments about evidence-based resource allocation and prioritization. The aim of this scoping review was to map the cost-of-illness (CoI) studies associated with COVID-19.

Methods

This scoping review was conducted from January 2019 to December 2021. We searched cost-of-illness papers published in English within Web of Sciences, PubMed, Google Scholar, Scopus, Science Direct and ProQuest. For each eligible study, extracted data included country, publication year, study period, study design, epidemiological approach, costing method, cost type, cost identification, sensitivity analysis, estimated unit cost and national burden. All of the analyses were applied in Excel software.

Results

2352 records were found after the search strategy application, finally 28 articles met the inclusion criteria and were included in the review. Most of the studies were done in the United States, Turkey, and China. The prevalence-based approach was the most common in the studies, and most of studies also used Hospital Information System data (HIS). There were noticeable differences in the costing methods and the cost identification. The average cost of hospitalization per patient per day ranged from 101$ in Turkey to 2,364$ in the United States. Among the studies, 82.1% estimated particularly direct medical costs, 3.6% only indirect costs, and 14.3% both direct and indirect costs.

Conclusion

The economic burden of COVID-19 varies from country to country. The majority of CoI studies estimated direct medical costs associated with COVID-19 and there is a paucity of evidence for direct non-medical, indirect, and intangible costs, which we recommend for future studies. To create homogeneity in CoI studies, we suggest researchers follow a conceptual framework and critical appraisal checklist of cost-of-illness (CoI) studies.
Hypoxia-induced P4HA1 overexpression promotes post-ischemic angiogenesis by enhancing endothelial glycolysis through downregulating FBP1
Authors: Xu Yating , Xia Di , Huang Kai , Liang Minglu
Published: January 2024

Background

Angiogenesis is essential for tissue repair in ischemic diseases, relying on glycolysis as its primary energy source. Prolyl 4-hydroxylase subunit alpha 1 (P4HA1), the catalytic subunit of collagen prolyl 4-hydroxylase, is a glycolysis-related gene in cancers. However, its role in glycolysis-induced angiogenesis remains unclear.

Methods

P4HA1 expression was modulated using adenoviruses. Endothelial angiogenesis was evaluated through 5-ethynyl-2′-deoxyuridine incorporation, transwell migration, and tube formation assays in vitro. In vivo experiments measured blood flow and capillary density in the hindlimb ischemia (HLI) model. Glycolytic stress assays, glucose uptake, lactate production, and quantitative reverse transcription-polymerase chain reaction (RT-PCR) were employed to assess glycolytic capacity. Transcriptome sequencing, validated by western blotting and RT-PCR, was utilized to determine underlying mechanisms.

Results

P4HA1 was upregulated in endothelial cells under hypoxia and in the HLI model. P4HA1 overexpression promoted angiogenesis in vitro and in vivo, while its knockdown had the opposite effect. P4HA1 overexpression reduced cellular α-ketoglutarate (α-KG) levels by consuming α-KG during collagen hydroxylation. Downregulation of α-KG reduced the protein level of a DNA dioxygenase, ten–eleven translocation 2 (TET2), and its recruitment to the fructose-1,6-biphosphatase (FBP1) promoter, resulting in decreased FBP1 expression. The decrease in FBP1 enhanced glycolytic metabolism, thereby promoting endothelial angiogenesis.

Conclusions

Hypoxia-induced endothelial P4HA1 overexpression enhanced angiogenesis by promoting glycolytic metabolism reprogramming through the P4HA1/α-KG/TET2/FBP1 pathway. The study’s findings underscore the significance of P4HA1 in post-ischemic angiogenesis, suggesting its therapeutic potential for post-ischemic tissue repair.
Comparative study of locking neutralization plate construct versus tension band wiring with a cannulated screw for patella fractures: experimental and finite element analysis
Authors: Kim Sunjung , Mungalpara Nirav , Wangikar Rohan , Tarabichi Majd , Karam Joseph , Bedi Asheesh , Koh Jason , Amirouche Farid
Published: January 2024

Transverse patella fractures, accounting for approximately 1% of Orthopedic injuries, pose intricate challenges due to their vital role in knee mechanics. This study aimed to compare the biomechanical performance of a construct, integrating cannulated screws and an anterior locking neutralization plate, with the conventional tension band wiring technique for treating these fractures. Experimental testing and Finite Element Analysis were employed to evaluate the constructs and gain profound insights into their mechanical behavior. Sixteen cadaveric knees were prepared, and transverse patella fractures were induced at the midpoints using a saw. The plate construct and tension band wire fixation were randomly assigned to the specimens. A cyclic test evaluated the implants' durability and stability, simulating knee movement during extension and flexion. Tensile testing assessed the implants' maximum failure force after cyclic testing, while Finite Element Analysis provided detailed insights into stress distribution and deformation patterns. Statistical analysis was exclusively performed for the experimental data. Results showed the plate enhanced stability with significantly lower deformation (0.09 ± 0.12 mm) compared to wire fixation (0.77 ± 0.54 mm) after 500 cycles (p = 0.004). In tensile testing, the construct also demonstrated higher failure resistance (1359 ± 21.53 N) than wire fixation (780.1 ± 22.62N) (p = 0.007). Finite Element Analysis highlighted distinct stress patterns, validating the construct's superiority. This research presents a promising treatment approach for transverse patella fractures with potential clinical impact and future research prospects. This study presents a promising advancement in addressing the intricate challenges of transverse patella fractures, with implications for refining clinical practice. The construct's improved stability and resistance to failure offer potential benefits in postoperative management and patient outcomes.
Structure-primed embedding on the transcription factor manifold enables transparent model architectures for gene regulatory network and latent activity inference
Authors: Tjärnberg Andreas , Beheler-Amass Maggie , Jackson Christopher A. , Christiaen Lionel A. , Gresham David , Bonneau Richard
Published: January 2024

Background

Modeling of gene regulatory networks (GRNs) is limited due to a lack of direct measurements of genome-wide transcription factor activity (TFA) making it difficult to separate covariance and regulatory interactions. Inference of regulatory interactions and TFA requires aggregation of complementary evidence. Estimating TFA explicitly is problematic as it disconnects GRN inference and TFA estimation and is unable to account for, for example, contextual transcription factor-transcription factor interactions, and other higher order features. Deep-learning offers a potential solution, as it can model complex interactions and higher-order latent features, although does not provide interpretable models and latent features.

Results

We propose a novel autoencoder-based framework, StrUcture Primed Inference of Regulation using latent Factor ACTivity (SupirFactor) for modeling, and a metric, explained relative variance (ERV), for interpretation of GRNs. We evaluate SupirFactor with ERV in a wide set of contexts. Compared to current state-of-the-art GRN inference methods, SupirFactor performs favorably. We evaluate latent feature activity as an estimate of TFA and biological function in S. cerevisiae as well as in peripheral blood mononuclear cells (PBMC).

Conclusion

Here we present a framework for structure-primed inference and interpretation of GRNs, SupirFactor, demonstrating interpretability using ERV in multiple biological and experimental settings. SupirFactor enables TFA estimation and pathway analysis using latent factor activity, demonstrated here on two large-scale single-cell datasets, modeling S. cerevisiae and PBMC. We find that the SupirFactor model facilitates biological analysis acquiring novel functional and regulatory insight.
Association between left ventricular systolic function parameters and myocardial injury, organ failure and mortality in patients with septic shock
Authors: Blixt Patrik Johansson , Nguyen Maxime , Cholley Bernard , Hammarskjöld Fredrik , Toiron Alois , Bouhemad Belaid , Lee Shaun , De Geer Lina , Andersson Henrik , Aneq Meriam Åström , Engvall Jan , Chew Michelle S.
Published: January 2024

Background

Left ventricular ejection fraction (LVEF) is inconsistently associated with poor outcomes in patients with sepsis. Newer parameters such as LV longitudinal strain (LVLS), mitral annular plane systolic excursion (MAPSE) and LV longitudinal wall fractional shortening (LV-LWFS) may be more sensitive indicators of LV dysfunction, but are sparsely investigated. Our objective was to evaluate the association between five traditional and novel echocardiographic parameters of LV systolic function (LVEF, peak tissue Doppler velocity at the mitral valve (s´), LVLS, MAPSE and LV-LWFS) and outcomes in patients admitted to the Intensive Care Unit (ICU) with septic shock.

Methods

A total of 152 patients admitted to the ICU with septic shock from two data repositories were included. Transthoracic echocardiograms were performed within 24 h of ICU admission. The primary outcome was myocardial injury, defined as high-sensitivity troponin T ≥ 45 ng/L on ICU admission. Secondary outcomes were organ support-free days (OSFD) and 30-day mortality. We also tested for the prognostic value of the systolic function parameters using multivariable analysis.

Results

LVLS, MAPSE and LV-LWFS, but not LVEF and s´, differed between patients with and without myocardial injury. After adjustment for age, pre-existing cardiac disease, Simplified Acute Physiology (SAPS3) score, Sequential Organ Failure Assessment (SOFA) score, plasma creatinine and presence of right ventricular dysfunction, only MAPSE and LV-LWFS were independently associated with myocardial injury. None of the systolic function parameters were associated with OSFD or 30-day mortality.

Conclusions

MAPSE and LV-LWFS are independently associated with myocardial injury and outperform LVEF, s´ and LVLS. Whether these parameters are associated with clinical outcomes such as the need for organ support and short-term mortality is still unclear.

Trial registration NCT01747187 and NCT04695119.
Robotic spleen-preserving distal pancreatectomy using the first domestic surgical robot platform (the hinotori™ Surgical Robot System): a case report
Authors: Tomihara Kazuki , Ide Takao , Ito Kotaro , Tanaka Tomokazu , Noshiro Hirokazu
Published: January 2024

Background

Robotic pancreatectomy has been performed worldwide mainly using the da Vinci® Surgical System (Intuitive Surgical, Inc., Sunnyvale, CA, USA). Recently, because of the death of some patents related to the da Vinci® system, new surgical robot systems have been introduced that are characterized by unique technical refinements. In Japan, the hinotori™ Surgical Robot System (Medicaroid Corporation, Kobe, Japan) was approved for use in gastroenterological surgery in October 2022. Since then, we have attempted complicated procedures using this robot. In this report, we report our first experience performing spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein using this first Japanese domestic surgical robot.

Case presentation

The patient was a 58-year-old woman with a mass in the pancreatic tail identified during medical screening. Further examinations resulted in a diagnosis of a pancreatic neuroendocrine tumor. The patient consented to surgical resection, and we planned robotic spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein, using the hinotori™. Five trocars, including one port for the assistant surgeon, were placed in the upper abdomen. The operating unit was rolled in from the patient’s right side. The pivot position was set for each robotic arm, and this setting was specific to the hinotori™. The cockpit surgeon performed all surgical procedures, excluding port placement and pancreatic transection. There were no unrecoverable device errors during the operation. The operation time was 531 min, and blood loss was 192 ml. The postoperative course was uneventful. We were able to safely perform this highly complicated surgery for a pancreatic tumor using the first Japanese domestic surgical robot platform.

Conclusions

The first Japanese domestic surgical robot platform, hinotori™, has different features from those of the da Vinci® and performed sufficiently as a surgical robot system in highly advanced pancreatic surgery.
A novel missense mutation (FGG c.1168G > T) in the gamma chain of fibrinogen causing congenital hypodysfibrinogenemia with bleeding phenotype
Authors: Xu Nuo , Zheng Liping , Dai Zhehao , Zhu Jun , Xie Peng , Yang Shun , Chen Fei
Published: January 2024

Background

Fibrinogen plays pivotal roles in multiple biological processes. Genetic mutation of the fibrinogen coding genes can result in congenital fibrinogen disorders (CFDs). We identified a novel heterozygous missense mutation, FGG c.1168G > T (NCBI NM_000509.6), and conducted expression studies and functional analyses to explore the influence on fibrinogen synthesis, secretion, and polymerization.

Methods

Coagulation tests were performed on the patients to detect the fibrinogen concentration. Whole-exome sequencing (WES) and Sanger sequencing were employed to detect the novel mutation. Recombinant fibrinogen-producing Chinese hamster ovary (CHO) cell lines were built to examine the recombinant fibrinogen synthesis and secretion by western blotting and enzyme-linked immunosorbent assay (ELISA). The functional analysis of fibrinogen was performed by thrombin-catalyzed fibrin polymerization assay. In silico molecular analyses were carried out to elucidate the potential molecular mechanisms.

Results

The clinical manifestations, medical history, and laboratory tests indicated the diagnosis of hypodysfibrinogenemia with bleeding phenotype in two patients. The WES and Sanger sequencing revealed that they shared the same heterozygous missense mutation, FGG c.1168G > T. In the expression studies and functional analysis, the missense mutation impaired the recombinant fibrinogen's synthesis, secretion, and polymerization. Furthermore, the in silico analyses indicated novel mutation led to the hydrogen bond substitution.

Conclusion

The study highlighted that the novel heterozygous missense mutation, FGG c.1168G > T, would change the protein secondary structure, impair the “A: a” interaction, and consequently deteriorate the fibrinogen synthesis, secretion, and polymerization.
Resistance to biotic and abiotic stress in potato: the origin of the genes and corresponding molecular markers
Authors: Islam Saiful , Li Jiana , Rahman Mohammad Ataur , Xie Fangru , Song Botao , Nie Bihua
Published: January 2024

The integration of molecular markers in the realm of potato genetics has opened new avenues for accelerating genotype analysis and developing improved varieties. Many markers linked to important features have been discovered so far and are consistently distributed across 12 chromosomes (× = 12) of potato. Notably, the genes allied to disease resistance stand out as significant and prevalent. Molecular markers associated with these genes have revolutionized selection processes, making them faster and more effective. Besides, advanced technologies such as kompetitive allele-specific PCR, high-resolution melting assay, SNP-array, genotyping by sequencing, and genome-wide association study, are emphasizing the use of those molecular markers with greater accuracy to detect R genes aligning with the phenotypes. This review discusses advances in potato breeding for resistance against common stresses, focusing on progress made through molecular marker-assisted selection.
Molecular Tumor Board Improves Outcomes for Hispanic Patients With Advanced Solid Tumors
Authors: Sotelo-Rodríguez Carolina , Vallejo-Ardila Dora , Ruiz-Patiño Alejandro , Chamorro Diego F. , Rodríguez July , Moreno-Pérez Darwin A. , Carranza Hernán , Otero Jorge , Vargas Carlos , Archila Pilar , Rojas Leonardo , Zuluaga Jairo , Rubio Cladelis , Ordóñez-Reyes Camila , Garcia-Robledo Juan Esteban , Mejía Sergio , Jaller Elvira , Arrieta Oscar , Cardona Andrés F.
Published: January 2024

PURPOSE

Multidisciplinary molecular tumor boards (MTBs) decode complex genomic data into clinical recommendations. Although MTBs are well-established in the oncology practice in developed countries, this strategy needs to be better explored in developing countries. Herein, we describe the possible benefits and limitations of the first MTB established in Colombia.

METHODS

Demographic, clinical, and genomic information was collected between August 2020 and November 2021. By mid-2020, an MTB strategy was created to discuss clinical cases with one or more genomic alterations identified by next-generation sequencing using an open-access virtual platform. We characterized the patient population as benefiting from the recommended treatment option. We assessed the benefits and access to available targeted therapies that have the potential to change clinical management by making recommendations to treating oncologists on the basis of genomic profiling. However, we did not assess the treatment oncologists' compliance with MTB recommendations because they were not intended to replace clinical judgment/standard of care.

RESULTS

A total of 146 patients were included in the discussions of the MTB. The median age was 59 years, and 59.6% were women. Genomic results prompting a change in therapeutic decisions were obtained in 53.1% of patients (95% CI, 44.9 to 61.3). The most prevalent malignancy was non–small-cell lung cancer (51%). Other malignancies represented 60%, 50%, and 30% of patients with soft-tissue sarcomas, brain tumors, and breast cancer, respectively.

CONCLUSION

Using an open-access virtual platform, MTBs were feasible in low- and middle-income countries on the basis of the capability to provide the benefits and access to available targeted therapies that are not standard of care. Furthermore, MTB recommendations were made available to the treating oncologist in different locations across Colombia, providing the option to modify clinical management in most of these patients.
Cellular Mass Response to Therapy Correlates With Clinical Response for a Range of Malignancies
Authors: Stevens Mark M. , Kimmerling Robert J. , Olcum Selim , Vacha Madeleine , LaBella Rachel , Minnah Anthony , Katsis Katelin , Fujii Juanita , Shaheen Zayna , Sundaresan Srividya , Criscitiello Joseph , Niesvizky Ruben , Raje Noopur , Branagan Andrew , Krishnan Amrita , Jagannath Sundar , Parekh Samir , Sperling Adam S. , Rosenbaum Cara A. , Munshi Nikhil , Luskin Marlise R. , Tamrazi Anobel , Reid Clifford A.
Published: January 2024

PURPOSE

Cancer patients with advanced-stage disease have poor prognosis, typically having limited options for efficacious treatment, and genomics-based therapy guidance continues to benefit only a fraction of patients. Next-generation ex vivo approaches, such as cell mass-based response testing (MRT), offer an alternative precision medicine approach for a broader population of patients with cancer, but validation of clinical feasibility and potential impact remain necessary.

MATERIALS AND METHODS

We evaluated the clinical feasibility and accuracy of using live-cell MRT to predict patient drug sensitivity. Using a unified measurement workflow with a 48-hour result turnaround time, samples were subjected to MRT after treatment with a panel of drugs in vitro. After completion of therapeutic course, clinical response data were correlated with MRT-based predictions of outcome. Specimens were collected from 104 patients with solid (n = 69) and hematologic (n = 35) malignancies, using tissue formats including needle biopsies, malignant fluids, bone marrow aspirates, and blood samples. Of the 81 (78%) specimens qualified for MRT, 41 (51%) patients receiving physician-selected therapies had treatments matched to MRT.

RESULTS

MRT demonstrated high concordance with clinical responses with an odds ratio (OR) of 14.80 ( P = .0003 [95% CI, 2.83 to 102.9]). This performance held for both solid and hematologic malignances with ORs of 20.67 ( P = .0128 [95% CI, 1.45 to 1,375.57]) and 8.20 ( P = .045 [95% CI, 0.77 to 133.56]), respectively. Overall, these results had a predictive accuracy of 80% ( P = .0026 [95% CI, 65 to 91]).

CONCLUSION

MRT showed highly significant correlation with clinical response to therapy. Routine clinical use is technically feasible and broadly applicable to a wide range of samples and malignancy types, supporting the need for future validation studies.
Detection of Copy-Number Variation in Circulating Cell-Free DNA in Patients With Uveal Melanoma
Authors: Sato Takuto , Montazeri Kamaneh , Gragoudas Evangelos S. , Lane Anne Marie , Aronow Mary Beth , Cohen Justine V. , Boland Genevieve M. , Banks Eric , Kachulis Christopher , Fleharty Mark , Cibulskis Carrie , Lawless Aleigha , Adalsteinsson Viktor A. , Sullivan Ryan J. , Kim Ivana K.
Published: January 2024

PURPOSE

Somatic chromosomal alterations, particularly monosomy 3 and 8q gains, have been associated with metastatic risk in uveal melanoma (UM). Whole genome-scale evaluation of detectable alterations in cell-free DNA (cfDNA) in UM could provide valuable prognostic information. Our pilot study evaluates the correlation between genomic information using ultra-low-pass whole-genome sequencing (ULP-WGS) of cfDNA in UM and associated clinical outcomes.

MATERIALS AND METHODS

ULP-WGS of cfDNA was performed on 29 plasma samples from 16 patients, 14 metastatic UM (mUM) and two non-metastatic, including pre- and post-treatment mUM samples from 10 patients treated with immunotherapy and one with liver-directed therapy. We estimated tumor fraction (TFx) and detected copy-number alterations (CNAs) using ichorCNA. Presence of 8q amplification was further analyzed using the likelihood ratio test (LRT).

RESULTS

Eleven patients with mUM (17 samples) of 14 had detectable circulating tumor DNA (ctDNA). 8q gain was detected in all 17, whereas monosomy 3 was detectable in 10 of 17 samples. TFx generally correlated with disease status, showing an increase at the time of disease progression (PD). 8q gain detection sensitivity appeared greater with the LRT than with ichorCNA at lower TFxs. The only patient with mUM with partial response on treatment had a high pretreatment TFx and undetectable on-treatment ctDNA, correlating with her profound response and durable survival.

CONCLUSION

ctDNA can be detected in mUM using ULP-WGS, and the TFx correlates with DS. 8q gain was consistently detectable in mUM, in line with previous studies indicating 8q gains early in primary UM and higher amplification with PD. Our work suggests that detection of CNAs by ULP-WGS, particularly focusing on 8q gain, could be a valuable blood biomarker to monitor PD in UM.
Tranexamic Acid Administration During Liver Transplantation Is Not Associated With Lower Blood Loss or With Reduced Utilization of Red Blood Cell Transfusion
Authors: Dehne Sarah , Riede Carlo , Feisst Manuel , Klotz Rosa , Etheredge Melanie , Hölle Tobias , Merle Uta , Mehrabi Arianeb , Michalski Christoph W. , Büchler Markus W. , Weigand Markus A. , Larmann Jan
Published: January 2024

BACKGROUND:

Current clinical guidelines recommend antifibrinolytic treatment for liver transplantation to reduce blood loss and transfusion utilization. However, the clinical relevance of fibrinolysis during liver transplantation is questionable, a benefit of tranexamic acid (TXA) in this context is not supported by sufficient evidence, and adverse effects are also conceivable. Therefore, we tested the hypothesis that use of TXA is associated with reduced blood loss.

METHODS:

We performed a retrospective cohort study on patients who underwent liver transplantation between 2004 and 2017 at Heidelberg University Hospital, Heidelberg, Germany. Univariable and multivariable linear regression analyses were used to determine the association between TXA administration and the primary end point intraoperative blood loss and the secondary end point intra- and postoperative red blood cell (RBC) transfusions. For further secondary outcome analyses, the time to the first occurrence of a composite end point of hepatic artery thrombosis, portal vein thrombosis, and thrombosis of the inferior vena cava were analyzed using a univariable and multivariable Cox proportional hazards model.

RESULTS:

Data from 779 transplantations were included in the final analysis. The median intraoperative blood loss was 3000 mL (1600–5500 mL). Intraoperative TXA administration occurred in 262 patients (33.6%) with an average dose of 1.4 ± 0.7 g and was not associated with intraoperative blood loss (regression coefficient B, −0.020 [−0.051 to 0.012], P = .226) or any of the secondary end points (intraoperative RBC transfusion; regression coefficient B, 0.023 [−0.006 to 0.053], P = .116), postoperative RBC transfusion (regression coefficient B, 0.007 [−0.032 to 0.046], P = .717), and occurrence of thrombosis (hazard ratio [HR], 1.110 [0.903–1.365], P = .321).

CONCLUSIONS:

Our data do not support the use of TXA during liver transplantation. Physicians should exercise caution and consider individual factors when deciding whether or not to administer TXA.
Care and Afterward: On Heidegger, Kafka, and Blanchot
Authors: Friedland Simon
Published: January 2024

Taking as its starting point Heidegger’s discussion in Being and Time (1927) of the Latin poet Hygenius’s fable about the formation of humankind by Cura, “Care,” this article opens the philosopher’s concept of care to a dialogue with literature. If Hygenius’s fable is, in Heidegger’s terms, a “pre-ontological testimony” to Dasein’s groundedness in care, Kafka’s story “The Cares of a Family Man” (1919) and Blanchot’s novel The Most High (1948) may be called “post-ontological testimonies” of care. Both texts thematize the slipping away of the temporal horizon of care, envisioning a world in which Dasein no longer takes center stage. Through an analysis of the Heideggerian grammar of care and its resonances in Kafka and Blanchot, this article offers a new appraisal of an influential concept in twentieth-century European philosophy and literature.
Imaging actin organisation and dynamics in 3D
Authors: Phillips Thomas A. , Marcotti Stefania , Cox Susan , Parsons Maddy
Published: January 2024

The actin cytoskeleton plays a critical role in cell architecture and the control of fundamental processes including cell division, migration and survival. The dynamics and organisation of F-actin have been widely studied in a breadth of cell types on classical two-dimensional (2D) surfaces. Recent advances in optical microscopy have enabled interrogation of these cytoskeletal networks in cells within three-dimensional (3D) scaffolds, tissues and in vivo. Emerging studies indicate that the dimensionality experienced by cells has a profound impact on the structure and function of the cytoskeleton, with cells in 3D environments exhibiting cytoskeletal arrangements that differ to cells in 2D environments. However, the addition of a third (and fourth, with time) dimension leads to challenges in sample preparation, imaging and analysis, necessitating additional considerations to achieve the required signal-to-noise ratio and spatial and temporal resolution. Here, we summarise the current tools for imaging actin in a 3D context and highlight examples of the importance of this in understanding cytoskeletal biology and the challenges and opportunities in this domain.
Matrix metalloproteinases at a glance
Authors: Hey Sven , Linder Stefan
Published: January 2024

Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases that belong to the group of endopeptidases or matrixins. They are able to cleave a plethora of substrates, including components of the extracellular matrix and cell-surface-associated proteins, as well as intracellular targets. Accordingly, MMPs play key roles in a variety of physiological and pathological processes, such as tissue homeostasis and cancer cell invasion. MMP activity is exquisitely regulated at several levels, including pro-domain removal, association with inhibitors, intracellular trafficking and transport via extracellular vesicles. Moreover, the regulation of MMP activity is currently being rediscovered for the development of respective therapies for the treatment of cancer, as well as infectious, inflammatory and neurological diseases. In this Cell Science at a Glance article and the accompanying poster, we present an overview of the current knowledge regarding the regulation of MMP activity, the intra- and extra-cellular trafficking pathways of these enzymes and their diverse groups of target proteins, as well as their impact on health and disease.
Environmental variation associated with overwintering elicits marked metabolic plasticity in a temperate salmonid, Salvelinus fontinalis
Authors: Middleton Ella K. , Gilbert Matthew J. H. , Landry Thomas , Lamarre Simon G. , Speers-Roesch Ben
Published: January 2024

Poleward winters commonly expose animals, including fish, to frigid temperatures and low food availability. Fishes that remain active over winter must therefore balance trade-offs between conserving energy and maintaining physiological performance in the cold, yet the extent and underlying mechanisms of these trade-offs are not well understood. We investigated the metabolic plasticity of brook char (Salvelinus fontinalis), a temperate salmonid, from the biochemical to whole-animal level in response to cold and food deprivation. Acute cooling (1°C day−1) from 14°C to 2°C had no effect on food consumption but reduced activity by 77%. We then assessed metabolic performance and demand over 90 days with exposure to warm (8°C) or cold winter (2°C) temperatures while fish were fed or starved. Resting metabolic rate (RMR) decreased substantially during initial cooling from 8°C to 2°C (Q10=4.2–4.5) but brook char exhibited remarkable thermal compensation during acclimation (Q10=1.4–1.6). Conversely, RMR was substantially lower (40–48%) in starved fish, conserving energy. Thus, the absolute magnitude of thermal plasticity may be masked or modified under food restriction. This reduction in RMR was associated with atrophy and decreases in in vivo protein synthesis rates, primarily in non-essential tissues. Remarkably, food deprivation had no effect on maximum oxygen uptake rates and thus aerobic capacity, supporting the notion that metabolic capacity can be decoupled from RMR in certain contexts. Overall, our study highlights the multi-faceted energetic flexibility of Salvelinus spp. that likely contributes to their success in harsh and variable environments and may be emblematic of winter-active fishes more broadly.