bluuebunny/crossref_metadata_2025 huggingface dataset:
A learning health systems approach to scaling up an evidence-based intervention for integrated primary mental healthcare case finding and referral in South Africa
Authors: Janse van Rensburg André , Hongo Nikiwe , Mthethwa Londiwe , Grant Merridy , Kathree Tasneem , Luvuno Zamasomi , Leung Alim , Bhana Arvin , Rao Deepa , Petersen Inge
Published: October 2024

Despite progress in the development and evaluation of evidence-based primary mental health interventions in low-income and middle-income countries, implementation and scale-up efforts have had mixed results. Considerable gaps remain in the effective translation of research knowledge into routine health system practices, largely due to real-world contextual constraints on implementation and scale-up efforts. The Southern African Research Consortium for Mental Health Integration (S-MhINT) programme used implementation research to strengthen the implementation of an evidence-based integrated collaborative depression care model for primary healthcare (PHC) services in South Africa. To facilitate the scale-up of this model from a testing site to the whole province of KwaZulu-Natal, a capacity building programme was embedded within the Alliance for Health Policy and Systems Research (AHPSR) learning health systems (LHS) approach. The paper discusses efforts to scale up and embed case finding and referral elements of the S-MhINT package within routine PHC. Data from semistructured interviews, a focus group discussion, proceedings from participatory workshops and outputs from the application of continuous quality improvement (CQI) cycles were thematically analysed using the AHPSR LHS framework. Learning particularly occurred through information sharing at routine participatory workshops, which also offered mutual deliberation following periods of applying CQI tools to emergent problems. Individual-level, single-loop learning seemed to be particularly observable elements of the AHPSR LHS framework. Ultimately, our experience suggests that successful scale-up requires strong and sustained relationships between researchers, policy-makers and implementers, investments into learning platforms and organisational participation across all levels to ensure ownership and acceptance of learning processes.
Clinical outcomes of antifungal therapy on Candida pulmonary colonisation in immunocompetent patients with invasive ventilation: a systematic review and meta-analysis
Authors: Li Linqi , Su Shan , Yang Hongzhong , Xie He-Bin
Published: October 2024

Objective

This study aimed to use systematic review and meta-analysis to establish the influence of antifungal therapy on pulmonaryCandidacolonisation of patients with mechanical ventilation (MV).

Design

Systematic review and meta-analysis.

Data sources

An extensive search was undertaken on publications from inception to 25 July 2023, through PubMed, Web of Science, Medline, Embase, China National Knowledge Infrastructure, Wanfang Data and VIP Databases.

Eligibility criteria for selecting studies

Randomised trials, cohort studies and case-control studies comparing the efficacy of antifungal treatment in immunocompetent patients with pulmonaryCandidacolonisation after invasive ventilation.

Data extraction and synthesis

Two reviewers independently extracted the data and assessed the quality of studies. Dichotomous outcomes were expressed as ORs with 95% CIs. Continuous outcomes were expressed as standardised mean differences (SMD) with 95% CIs.

Primary and secondary outcome measures

The primary outcomes included intensive care unit (ICU), hospital, 28-day, and 90-day mortality. The secondary outcomes included ICU length of stay, MV duration and ventilator-associated pneumonia (VAP).

Results

Nine high-quality studies were included. According to the data collected from these nine studies, there is no significant evidence showing a difference between the therapy group treated with antifungal drugs and the control group without antifungal drugs in clinical outcomes, including ICU mortality (OR: 1.37; 95% CI 0.84 to 2.22), hospital mortality (OR: 1.17; 95% CI 0.57 to 2.38), 28-day mortality (OR: 0.71; 95% CI 0.45 to 1.14), 90-day mortality (OR: 0.76; 95% CI 0.35 to 1.63), ICU length of stay (SMD: −0.15; 95% CI −0.88 to 0.59), MV duration (SMD: 0.11; 95% CI −0.88 to 1.10) and VAP (OR: 1.54; 95% CI 0.56 to 4.20). Subgroup analysis of different treatment types indicates that the combined effect size is stable and unaffected by different treatment types including inhalation (OR: 2.32; 95% CI 0.30 to 18.09) and intravenous (OR: 0.65; 95% CI 0.13 to 3.34).

Conclusion

The application of antifungal treatment did not improve clinical outcomes in patients with MV. We do not suggest initiating antifungal treatment in patients withCandidapulmonary colonisation after invasive ventilation.

Trial registration number

International Prospective Register of Systematic Reviews, CRD42020161138.
Prevalence of teenage pregnancy and associated factors in Uganda: a meta-analysis and systematic reviews protocol
Authors: Aremu Abdulmujeeb Babatunde , Afolabi Ismail Bamidele , Awunor Nyemike Simeon , Sumayah Nakitende , Mujeeb Salaam , Mahjub Atiku Saad
Published: October 2024

Introduction

Teenage pregnancy is a major public health problem with huge consequences for maternal health and pregnancy outcomes. More than 90% of these live births are estimated to occur in developing countries. The objective of this review is to estimate the prevalence of teenage pregnancy and its associated factors in Uganda.

Methods and analysis

This review protocol will be registered with the PROSPERO database and will be designed following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. A literature search will be conducted in PubMed, African Journals OnLine, Science Direct and Google Scholar in December 2023. Observational studies that report the prevalence of teenage pregnancy will be included. Studies will be assessed for the risk of bias in duplicate. The data will be pooled using random-effects models to estimate the prevalence of teenage pregnancy, with a 95% CI and I2statistic capturing heterogeneity.

Ethics and dissemination

This review will not require ethical approval. The findings from the data synthesis will be published in relevant peer-reviewed journals and conferences targeting adolescent and reproductive health.

PROSPERO registration number

CRD42023486460
IQGAP3 signalling mediates intratumoral functional heterogeneity to enhance malignant growth
Authors: Shimura Mitsuhiro , Matsuo Junichi , Pang ShuChin , Jangphattananont Nawaphat , Hussain Aashiq , Rahmat Muhammad Bakhait , Lee Jung-Won , Douchi Daisuke , Tong Jasmine Jie Lin , Myint Khine , Srivastava Supriya , Teh Ming , Koh Vivien , Yong Wei Peng , So Jimmy Bok Yan , Tan Patrick , Yeoh Khay-Guan , Unno Michiaki , Chuang Linda Shyue Huey , Ito Yoshiaki
Published: October 2024

Background

The elevation of IQGAP3 expression in diverse cancers indicates a key role for IQGAP3 in carcinogenesis. Although IQGAP3 was established as a proliferating stomach stem cell factor and a regulator of the RAS-ERK pathway, how it drives cancer growth remains unclear.

Objective

We define the function of IQGAP3 in gastric cancer (GC) development and progression.

Design

We studied the phenotypic changes caused by IQGAP3 knockdown in three molecularly diverse GC cell lines by RNA-sequencing. In vivo tumorigenesis and lung metastasis assays corroborated IQGAP3 as a mediator of oncogenic signalling. Spatial analysis was performed to evaluate the intratumoral transcriptional and functional differences between control tumours and IQGAP3 knockdown tumours.

Results

Transcriptomic profiling showed that IQGAP3 inhibition attenuates signal transduction networks, such as KRAS signalling, via phosphorylation blockade. IQGAP3 knockdown was associated with significant inhibition of MEK/ERK signalling-associated growth factors, including TGFβ1, concomitant with gene signatures predictive of impaired tumour microenvironment formation and reduced metastatic potential. Xenografts involving IQGAP3 knockdown cells showed attenuated tumorigenesis and lung metastasis in immunodeficient mice. Accordingly, immunofluorescence staining revealed significant reductions of TGFβ/SMAD signalling and αSMA-positive stromal cells; digital spatial analysis indicated that IQGAP3 is indispensable for the formation of two phenotypically diverse cell subpopulations, which played crucial but distinct roles in promoting oncogenic functions.

Conclusion

IQGAP3 knockdown suppressed the RAS-TGFβ signalling crosstalk, leading to a significant reduction of the tumour microenvironment. In particular, IQGAP3 maintains functional heterogeneity of cancer cells to enhance malignant growth. IQGAP3 is thus a highly relevant therapy target in GC.
Lacosamide in palliative medicine: a retrospective chart review
Authors: Rimmer Adam , Howard Paul , Curtin John
Published: October 2024

Objectives

To investigate the efficacy and safety of oral (PO) and subcutaneous (SC) lacosamide for refractory symptoms in the palliative setting.

Methods

We conducted a retrospective chart review of the use of lacosamide since it was introduced in our palliative care service 1½ years ago. All clinical notes, medication administration records and infusion monitoring documentation were examined to ascertain therapeutic aim, efficacy, and tolerability.

Results

Lacosamide was administered to 91 patients; 90% had cancer. The most common indication was neuropathic pain (97%); there appeared to be a significant improvement in 35%; this was sometimes apparent within a few hours of an SC loading ‘test’ dose. Many recipients (44%) were in their last month of life. 59% received one or more SC doses; switching from PO to SC lacosamide was straightforward and it appeared compatible with a range of other palliative medications. Lacosamide appeared well tolerated; adverse effects were identified in 11% (10/91), half of whom (5%, 5/91) discontinued treatment. Of 59 admixtures infused SC, one mild SC site reaction occurred that resolved with the addition of dexamethasone.

Conclusions

Lacosamide appears to be a promising option for refractory symptoms warranting further study; SC administration is an advantage when the PO route is lost.
A comprehensive framework to evaluate the financial impacts of genetic improvement on wood products from planted forests
Authors: Chagnon Catherine , Moreau Guillaume , Soro André , Bombardier-Cauffopé Christine , Baby-Bouchard Emmanuelle , Chamberland Vincent , Barrette Julie , Gélinas Nancy , Duchesne Isabelle , Lenz Patrick , Bousquet Jean , Achim Alexis
Published: October 2024

Increasing the productivity of planted forests may efficiently provide an important part of the world’s growing demand for wood while protecting natural forests. In this study, we developed an integrated modelling framework to evaluate the financial impacts of improving productivity of planted forests by tree breeding. Using this framework, we compared three genetic improvement scenarios of white spruce plantations, a key reforestation species in North America, and evaluated the differences in the derived wood product assortments in terms of quantity, quality, and revenues. Favouring the production of wood volume appears as the best way to enhance financial gains from white spruce plantations in the current market. The scenario that focused on increasing tree height produced a greater volume of wood products and larger lumber pieces, which resulted in the greatest revenues. In comparison, favouring wood stiffness over volume led to poorer results, as the increased product quality was not sufficient to surpass the financial gain associated with greater wood volumes. While we successfully provided an evaluation of the product assortments derived from genetically improved plantations, the proposed framework would benefit from more data input to help maximize financial gains from a range of tree breeding strategies.
Small area estimators in a simulation test
Authors: Kangas Annika , Myllymäki Mari , Packalen Petteri
Published: October 2024

The Finnish National Forest Inventory produces municipality level results either with an indirect model-based K-nearest neighbor (K-NN) estimator or a direct design-based post-stratification estimator. Design-based approach is unbiased, but not always feasible due to low number of field plots. The K-NN estimator is lacking an analytical estimator for the variance. A composite estimator combining the indirect and direct estimates could be an attractive solution. In this article, estimators for small-area estimation are analyzed in a simulation experiment with varying size small areas and varying quality auxiliary data. The potential of estimators is assessed based on the true standard errors and RMSEs in the simulation experiment. Direct estimators and composite estimators work reasonably well with varying quality models, but the performance of indirect estimators is dependent on the quality of the model used. The performance of different estimators also depends on the size of the small areas. Linear models in which the weight of plots outside the target domain is smaller than those within the target domain, performed better than an unweighted model, suggesting that localizing the models for the small areas is beneficial. EBLUP approach also performed well, both in connection of a K-NN model and a linear model.
A polar diatomic molecule under a high-frequency laser field: classical analytical solution
Authors: Kryukov N. , Oks E.
Published: October 2024

Dynamics of a polar diatomic molecule (represented as the oscillating rotator model) under external fields is the most fundamental problem and the testbed in molecular physics—analogously to the dynamics of hydrogenic atom (represented as the model of an electron in the Coulomb field) under external fields being the most fundamental problem and the testbed in atomic physics. We present the classical analytical study of the dynamical Stark effect in the oscillating rotator under a high-frequency laser field. We obtain the analytical results by using the method of effective potentials. We demonstrate that under the laser field, the rotation frequency increases, while the oscillation frequency decreases, and the amplitude of the oscillations increases. More significantly, the laser field causes the generation of the second harmonic in the oscillations of this system. This is an important, counterintuitive result in studying this fundamental physical system. We also drew attention to some flaws in the literature on this subject.
Microwave versus Radiofrequency Ablation in Treating Predominantly Solid Benign Thyroid Nodules: A Randomized Controlled Trial
Authors: Chen Sitong , Dou Jianping , Cang Yuancheng , Che Ying , Dong Gang , Zhang Chunlai , Xu Dong , Long Qinxian , Yu Jie , Liang Ping
Published: October 2024

Both microwave and radiofrequency ablation can be effective in treating predominantly solid benign thyroid nodules, yielding significant improvements in both symptoms and aesthetics.
Evaluating the Performance and Bias of Natural Language Processing Tools in Labeling Chest Radiograph Reports
Authors: Santomartino Samantha M. , Zech John R. , Hall Kent , Jeudy Jean , Parekh Vishwa , Yi Paul H.
Published: October 2024

Natural language processing tools for chest radiograph report annotation show high overall accuracy but exhibit age-related bias, with poorer performance in older patients.
Study on Oxygen Plasma-Based Copper Etching Process
Authors: Su Jia Quan , Kuo Yue
Published: October 2024

A plasma-based, room-temperature copper etch process using the chlorine- or bromine-containing feed gas was reported. This simple process could potentially replace the chemical mechanical polishing method in preparing copper interconnects. However, the chlorine- and bromine-containing gases are corrosive and must be handled with expensive equipment following stringent safety procedures. In this paper, the oxygen plasma-based copper etch process is presented. The copper film was converted into a porous and polycrystalline copper oxide film which was subsequently dissolved in a dilute hydrochloric acid solution. The copper film was expanded when converted into an oxide film. The oxidation precursors, i.e., oxygen radicals and ions, were generated in the plasma phase and then transported through the oxide layer to the underneath copper film where the oxidation reaction proceeded. The oxide growth rate is affected by plasma parameters, such as pressure and power, and the kinetics of the oxidation reaction. This new oxygen plasma-based process is a simple solution for preparing copper interconnects for nano and microelectronic products.
Effects of Frequency on the Performance of Ultrasonic Vibration Assisted Chemical Mechanical Polishing for Sapphire
Authors: Zhou Mufang , Zhong Min , Xu Wenhu , Li Xiaobing , Yi Meirong , Chen Jianfeng
Published: October 2024

Sapphire (Al2O3) is renowned for its exceptional properties, yet its unique natural presents a surface processing challenge. To enhance the polishing quality and efficiency, the sapphire ultrasonic vibration assisted chemical mechanical polishing (UV-CMP) has been proposed. This paper employs computational fluid dynamics (CFD) simulation and polishing experiments to investigate the action and mechanism of ultrasonic frequency on sapphire UV-CMP. The CFD simulation reveals that an increase in frequency can effectively elevate the fluid velocity, pressure, and cavitation. The enhancement in pressure, Z-direction, and resultant velocity has a positive impact on the cutting ability and utilization rate of nano-abrasives. A high frequency can enhance the physical fields of slurry, but it suppresses the growth of cavitation bubbles, and is detrimental to the number and size of abrasive particles. The best processing performance of sapphire UV-CMP is obtained at 40 kHz due to coordinated physicochemical interactions. X-ray photoelectron spectroscpy proves the product of solid-solid chemical reaction between nano-SiO2 and sapphire is softer Al2Si2O7 instead of Al2SiO5, which is beneficial to the material removal. This article provides theoretical and practical guidance for sapphire UV-CMP.
Effect of Substrate Thinning on Temperature Rise in Ga2O3 Rectifiers
Authors: Chiang Chao-Ching , Li Jian-Sian , Wan Hsiao-Hsuan , Ren Fan , Pearton Stephen J.
Published: October 2024

The low thermal conductivity of β-Ga2O3 is a concern for the high-power switching applications envisaged for this ultra-wide bandgap semiconductor. In this work, we examine the effect of substrate thinning to reduce the temperature rise in rectifiers under high power conditions and also reduce the on-resistance. The Ga2O3 substrates on which the rectifiers were fabricated were thinned from the original thickness of 630 μm to a lowest value of 50 μm and transferred to a brass heat sink. Experimentally, we observed that the on-resistance was reduced from 5.66 to 5.17 mΩ.cm2 when thinning to 50 μm, in excellent agreement with simulations. The calculated peak temperature rise was roughly halved for rectifiers on such thin substrates over a broad range of power densities (500–1500 W.cm2), a result supported by thermal imaging.
Artificial intelligence and omics in malignant gliomas
Authors: Tambi Richa , Zehra Binte , Vijayakumar Aswathy , Satsangi Dharana , Uddin Mohammed , Berdiev Bakhrom K.
Published: October 2024

Glioblastoma multiforme (GBM) is one of the most common and aggressive type of malignant glioma with an average survival time of 12–18 mo. Despite the utilization of extensive surgical resections using cutting-edge neuroimaging, and advanced chemotherapy and radiotherapy, the prognosis remains unfavorable. The heterogeneity of GBM and the presence of the blood-brain barrier further complicate the therapeutic process. It is crucial to adopt a multifaceted approach in GBM research to understand its biology and advance toward effective treatments. In particular, omics research, which primarily includes genomics, transcriptomics, proteomics, and epigenomics, helps us understand how GBM develops, finds biomarkers, and discovers new therapeutic targets. The availability of large-scale multiomics data requires the development of computational models to infer valuable biological insights for the implementation of precision medicine. Artificial intelligence (AI) refers to a host of computational algorithms that is becoming a major tool capable of integrating large omics databases. Although the application of AI tools in GBM-omics is currently in its early stages, a thorough exploration of AI utilization to uncover different aspects of GBM (subtype classification, prognosis, and survival) would have a significant impact on both researchers and clinicians. Here, we aim to review and provide database resources of different AI-based techniques that have been used to study GBM pathogenesis using multiomics data over the past decade. We summarize different types of GBM-related omics resources that can be used to develop AI models. Furthermore, we explore various AI tools that have been developed using either individual or integrated multiomics data, highlighting their applications and limitations in the context of advancing GBM research and treatment.
Prediction of Crack Propagation Directions in Dissimilar Metal‐Welded Joints Using Phase‐Field Models and Discussion of Its Mechanisms
Authors: Zhao Lingyan , Yang Bin , Wang Zheng
Published: October 2024

Stress corrosion cracking (SCC) in dissimilar metal‐welded joints (DMWJs) poses a significant threat to the safe operation of nuclear power plants. This study employs the phase‐field method to analyze crack propagation paths at various positions in DMWJs of nuclear power safety ends. A user‐defined material (UMAT) subroutine was implemented to characterize the mechanical heterogeneity of the heat‐affected zone (HAZ) and fusion zone (FZ). The effects of Young’s modulus (E), critical energy release rate (GC), and mechanical heterogeneity on crack propagation paths were investigated. Results indicate that E has minimal impact on crack propagation paths, while GC significantly influences them. Mechanical heterogeneity in local regions, particularly in the HAZ and FZ, substantially affects crack propagation paths, with the HAZ having the most pronounced effect. Interface crack propagation is identified as the most hazardous. Notably, cracks in 316L/52Mw are less affected by mechanical heterogeneity compared to those in SA508/52Mb.
Medical Malpractice Stress Syndrome and Defensive Medicine in Obstetricians and Gynecologists in Turkey
Authors: Gunenc O. , Kulhan N. G. , Geyik Bayman M. , Celik C. , Bilgi A. , Colluoglu C. , Kulhan M.
Published: October 2024

Background: Medical malpractice is a significant global issue affecting various aspects of healthcare, including ethical, legal, and managerial perspectives. Defensive medicine, where physicians engage in excessive practices to avoid malpractice lawsuits, is prevalent. In Turkey, the impact of malpractice fears on obstetricians and gynecologists (OB/GYNs) has not been extensively studied. This study aims to investigate the frequency of medical malpractice lawsuits, defensive medicine practices, the prevalence of medical malpractice stress syndrome (MMSS), and potential preventive measures among OB/GYNs in Turkey.

Methods: A cross‐sectional survey was conducted with 212 OB/GYNs in Turkey, following ethical approval. Participants completed a questionnaire on their experiences with malpractice, defensive practices, and MMSS. The survey included sociodemographic questions, standardized scales for defensive medicine practices, and MMSS‐related questions. Data were analyzed using SPSS 18 with a 95% confidence level.

Results: The majority of participants were experienced professionals aged 30–39, predominantly female, and working in the public sector with limited subspecialty training. Defensive medicine was widespread, with 95.5% of participants engaging in such practices, and 79.2% reported altering their practice due to malpractice fears. Older age, female gender, extensive experience, private sector employment, and specific subspecialties were associated with higher defensive practices and MMSS.

Conclusion: Defensive medicine is common among Turkish OB/GYNs, driven by malpractice fears. The study highlights the need for improved support systems, better legal protections, and educational interventions to address defensive practices and reduce malpractice‐related stress.
Cervical Chylous Leakage Combined With Chylothorax: A Case Report of a Rare Complication Postretroperitoneal Surgery and Its Management
Authors: Zhou Yao , Ding Mingde , Shi Qiang , Wang Jing , Liu Guanghai , Zhang Qianqian
Published: October 2024

Chylous leakage is an uncommon and serious clinical condition, especially occurring after retroperitoneal operations. Here, we report a case of cervical chylous leakage combined with chylothorax in a 57‐year‐old woman postretroperitoneal surgery, and our conservative approach led to resolution/clinical improvement. The causes of this rare complication are discussed. We considered that the venous thrombosis, the increased intra‐abdominal pressure, or the patient positioning during the surgery may lead to the chylous particles leakage and chylothorax. Because of its rarity, we hope this case report will improve clinicians’ understanding of cervical chylous leakage combined with chylothorax and provide suitable treatment options for future clinical reference.
A Comprehensive Review of the Phytochemical Constituents and Bioactivities of Ocimum tenuiflorum
Authors: Bhattarai Keshab , Bhattarai Rabin , Pandey Ram Darash , Paudel Babita , Bhattarai Hari Datta
Published: October 2024

Ocimum tenuiflorum, commonly known as Tulsi, is revered in Ayurveda for its extensive medicinal properties. However, there is a need to consolidate current knowledge on its phytochemical constituents and their pharmacological activities to identify potential areas for further research and drug development. This review aims to bridge this gap by providing a comprehensive analysis of the bioactive secondary metabolites found in O. tenuiflorum, such as rosmarinic acid, oleanolic acid, luteolin, ursolic acid, and limonene, and their associated therapeutic effects. The review will highlight the pharmacological importance of these metabolites, which exhibit antioxidant, neuroprotective, anticancer, and anti‐inflammatory properties. Additionally, this study will explore the plant’s wide range of beneficial qualities, including anti‐inflammatory, antioxidant, anticholinergic, pain‐relieving, antimicrobial, stress‐reducing, antidiabetic, anticancer, liver‐protective, ulcer‐inhibiting, antifungal, and wound‐healing attributes. Furthermore, this review focuses on the plant’s potential in treating conditions such as asthma, persistent fever, tuberculosis, malaria, skin discoloration, itching, digestive issues, hemorrhoids, bone fractures, gout, urinary tract infection, and diabetes. By reviewing the current literature, the aim is to identify the gaps in the existing research and propose directions for future studies. This comprehensive review will serve as a valuable resource for researchers in the development and investigation of novel drugs derived from O. tenuiflorum.
SOS1 Inhibition Enhances the Efficacy of KRASG12C Inhibitors and Delays Resistance in Lung Adenocarcinoma
Authors: Daley Brianna R. , Sealover Nancy E. , Finniff Bridget A. , Hughes Jacob M. , Sheffels Erin , Gerlach Daniel , Hofmann Marco H. , Kostyrko Kaja , LaMorte Joseph P. , Linke Amanda J. , Beckley Zaria , Frank Andrew M. , Lewis Robert E. , Wilkerson Matthew D. , Dalgard Clifton L. , Kortum Robert L.
Published: October 2024

The clinical effectiveness of KRASG12C inhibitors (G12Ci) is limited both by intrinsic and acquired resistance, necessitating the development of combination approaches. Here, we identified targeting proximal receptor tyrosine kinase signaling using the SOS1 inhibitor (SOS1i) BI-3406 as a strategy to improve responses to G12Ci treatment. SOS1i enhanced the efficacy of G12Ci and limited rebound receptor tyrosine kinase/ERK signaling to overcome intrinsic/adaptive resistance, but this effect was modulated by SOS2 protein levels. G12Ci drug-tolerant persister (DTP) cells showed up to a 3-fold enrichment of tumor-initiating cells (TIC), suggestive of a sanctuary population of G12Ci-resistant cells. SOS1i resensitized DTPs to G12Ci and inhibited G12C-induced TIC enrichment. Co-mutation of the tumor suppressor KEAP1 limited the clinical effectiveness of G12Ci, and KEAP1 and STK11 deletion increased TIC frequency and accelerated the development of acquired resistance to G12Ci, consistent with clinical G12Ci resistance seen with these co-mutations. Treatment with SOS1i both delayed acquired G12Ci resistance and limited the total number of resistant colonies regardless of KEAP1 and STK11 mutational status. Together, these data suggest that targeting SOS1 could be an effective strategy to both enhance G12Ci efficacy and prevent G12Ci resistance regardless of co-mutations.

Significance: The SOS1 inhibitor BI-3406 both inhibits intrinsic/adaptive resistance and targets drug tolerant persister cells to limit the development of acquired resistance to clinical KRASG12C inhibitors in lung adenocarcinoma cells.
Supplementary Methods from Incorporating Alternative Polygenic Risk Scores into the BOADICEA Breast Cancer Risk Prediction Model
Authors: Mavaddat Nasim , Ficorella Lorenzo , Carver Tim , Lee Andrew , Cunningham Alex P. , Lush Michael , Dennis Joe , Tischkowitz Marc , Downes Kate , Hu Donglei , Hahnen Eric , Schmutzler Rita K. , Stockley Tracy L. , Downs Gregory S. , Zhang Tong , Chiarelli Anna M. , Bojesen Stig E. , Liu Cong , Chung Wendy K. , Pardo Monica , Feliubadaló Lidia , Balmaña Judith , Simard Jacques , Antoniou Antonis C. , Easton Douglas F.
Published: October 2024

Supplementary Methods provides details of methodology
Figure 1 from Incorporating Alternative Polygenic Risk Scores into the BOADICEA Breast Cancer Risk Prediction Model
Authors: Mavaddat Nasim , Ficorella Lorenzo , Carver Tim , Lee Andrew , Cunningham Alex P. , Lush Michael , Dennis Joe , Tischkowitz Marc , Downes Kate , Hu Donglei , Hahnen Eric , Schmutzler Rita K. , Stockley Tracy L. , Downs Gregory S. , Zhang Tong , Chiarelli Anna M. , Bojesen Stig E. , Liu Cong , Chung Wendy K. , Pardo Monica , Feliubadaló Lidia , Balmaña Judith , Simard Jacques , Antoniou Antonis C. , Easton Douglas F.
Published: October 2024

Graph of BOADICEA parameter alpha (αRL) versus log-OR per 1 SD. Graph of BOADICEA parameter alpha (αRL) versus log-OR per 1 SD for PRS313 and alternative PRS. αRL were estimated using the retrospective likelihood method as described in Materials and Methods and Supplementary Methods.
Metabolic Tumor Volume Assessed by 18F FDG–PET CT Scan as a Predictive Biomarker for Immune Checkpoint Blockers in Advanced NSCLC and Its Biological Correlates
Authors: Dall’Olio Filippo G. , Zrafi Wael , Roelants Veronique , Ambrosini Valentina , Fourquet Aloyse , Mitea Cristina , Passiglia Francesco , Bauckneht Matteo , Bonardel Gerald , Conci Nicole , Benitez Jose Carlos , Arena Vincenzo , Namour Céline , Naigeon Marie , Monnet Isabelle , Beshiri Kristi , Hoton Delphine , Dursun Safiye , Danlos François Xavier , Argalia Giulia , Aldea Mihaela , Rovera Guido , Derosa Lisa , Iebba Valerio , Gietema Hester A. , Gounant Valerie , Lacroix Valérie , Remon Jordi , Gautheret Daniel , Chaput Nathalie , Job Bastien , Kannouche Patricia L. , Velasco-Nuño Monica , Zitvogel Laurence , Cella Eugenia , Chícharo de Freitas José Reinaldo , Vasseur Damien , Bettaieb Mohamed Aymen , Tagliamento Marco , Hendriks Lizza , Italiano Antoine , Planchard David , Marabelle Aurelien , Barlesi Fabrice , Novello Silvia , De Andreis Desiree , Aboubakar Nana Frank , Ardizzoni Andrea , Zalcman Gerard , Garcia Camilo , Besse Benjamin
Published: October 2024

Purpose:

This study aimed to explore metabolic tumor volume (MTV) as assessed by 18F-fluorodeoxyglucose positron emission tomography–computed tomography (18F-FDG–PET/CT) and understand its biological meaning in patients with non–small cell lung cancer (NSCLC) exposed to immune checkpoint blockers (ICB).

Experimental Design:

In this study, patients with advanced NSCLC and a positive PET scan within 42 days of first-line treatment were enrolled in 11 institutions across four countries. Total MTV (tMTV) was analyzed, with a 42% maximum standardized uptake value threshold. Survival was analyzed according to high tMTV (≥median). Plasma proteomic profile, whole exome, transcriptome, and other analyses were performed on monocentric cohorts to explore its biological correlates.

Results:

Of the 518 patients included, 167 received ICBs, 257 had chemotherapy plus ICBs, and 94 had chemotherapy. Median tMTV was 99 cm3. Median overall survival (OS) for patients with high tMTV treated with ICBs was 11.4 vs. 29.6 months (P < 0.0012) for those with low tMTV. In patients who received chemotherapy–ICB, tMTV did not correlate with OS (P = 0.099). In patients with programmed death-ligand 1 (PD-L1) ≥1% and high tMTV, chemotherapy–ICB combination was associated with longer OS compared with ICBs alone (20 vs. 11.4 months; P = 0.026), while no survival differences were observed in the low tMTV group. High tMTV correlated (and its detrimental effect seems to be driven) with a specific proteomic profile and increase in genomic instability.

Conclusions:

Our analysis indicates high tMTV is linked to an increase in systemic inflammation, specific cytokines production, and chromosomal instability. tMTV may serve as one of the biomarkers to select the best upfront strategy in patients with PD-L1–positive advanced NSCLC.
First-in-Human Dose-Escalation Study of the First-in-Class PDE3A–SLFN12 Complex Inducer BAY 2666605 in Patients with Advanced Solid Tumors Coexpressing SLFN12 and PDE3A
Authors: Papadopoulos Kyriakos P. , McKean Meredith , Goldoni Silvia , Genvresse Isabelle , Garrido Marine F. , Li Rui , Wilkinson Gary , Kneip Christoph , Yap Timothy A.
Published: October 2024

Purpose:

The study aims to evaluate the safety, tolerability, and pharmacokinetics of BAY 2666605, a velcrin that induces complex formation between the phosphodiesterase PDE3A and the protein Schlafen 12 (SLFN12), leading to a cytotoxic response in cancer cells.

Patients and Methods:

This was a first-in-human phase I study of BAY 2666605 (NCT04809805), an oral, potent first-in-class PDE3A–SLFN12 complex inducer, with reduced PDE3A inhibition. Adults with advanced solid tumors that coexpress SLFN12 and PDE3A received BAY 2666605 at escalating doses starting at 5 mg once daily in 28-day cycles. Forty-seven patients were prescreened for SLFN12 and PDE3A overexpression, and five biomarker-positive patients received ≥1 BAY 2666605 dose.

Results:

The most common adverse event was grade 3 to 4 thrombocytopenia in three of the five patients treated. The long half-life (>360 hours) and associated accumulation of BAY 2666605 led to the selection of an alternative schedule consisting of a loading dose with a once-daily maintenance dose. The maximum tolerated dose was not established as the highest doses of both schedules were intolerable. No objective responses were observed. Due to the high expression of PDE3A in platelets compared with tumor tissues, the ex vivo dose-dependent inhibitory effect of BAY 2666605 on megakaryocytes, and the pharmacokinetic profile of the compound, alternative schedules were not predicted to ameliorate the mechanism-based thrombocytopenia.

Conclusions:

Despite the decreased PDE3A enzymatic inhibition profile of BAY 2666605, the occurrence of thrombocytopenia in treated patients, an on-target effect of the compound, precluded the achievement of a therapeutic window, consequently leading to trial termination.
Spontaneous Regression of an Inflammatory Myofibroblastic Tumor: A Case Report and a Review of the Literature
Authors: Medici Bianca , Caffari Eugenia , Salati Massimiliano , Spallanzani Andrea , Garajova Ingrid , Piacentini Federico , Dominici Massimo , Gelsomino Fabio
Published: October 2024

Introduction: Spontaneous tumor regression is the volumetric reduction or complete disappearance of a primary tumor or metastatic sites (single or multiple) without the administration of treatments. This rare phenomenon occurs most commonly in certain types of neoplasms. Case Presentation: In this manuscript, we describe a spontaneous tumor regression in an adult patient followed at the Modena Cancer Center and affected by retroperitoneal inflammatory myofibroblastic tumor, an ultra-rare subtype of sarcoma. Finally, we will provide a concise review of the literature and try to explain the mechanisms underlying the tumor regression described in the clinical case. Conclusion: The etiopathogenetic mechanisms for spontaneous tumor regression are not yet fully understood and likely involve a complex interplay among immunological mechanisms, growth factors, cytokines, and hormonal factors.
Ketone Management in Pediatric Diabetes Centers in the USA: Current Practices and a Call for Improved Standardization
Authors: Marks Brynn E. , Meighan Seema , Fivekiller Emily E. , Escobar Estella , Berget Cari
Published: October 2024

Introduction: Diabetic ketoacidosis (DKA) is the leading cause of mortality among youth with type 1 diabetes (T1D). Guidelines for DKA prevention exist; however, specific guidance about when to check ketones and how to manage youth using insulin pumps and automated insulin delivery (AID) systems is lacking. Methods: A 35-item online survey exploring clinical ketone management practices for youth with T1D in the USA was distributed to diabetes healthcare professionals (HCPs). Survey responses, including multiple-choice and Likert scale questions, were summarized and rates of agreement and disagreement (Likert scale 4, 5 vs. 1, 2, 3) are reported. Results: In total, 123 HCPs (51% physicians, 26% diabetes educators, 19% nurse practitioners) from 47 institutions completed the survey. Seventy percent worked at academic specialty centers. Ninety-seven percent reported >50% continuous glucose monitoring use in their clinic and 72% reported >50% insulin pump use. Although 79% reported having ketone management protocols, the level and duration of hyperglycemia at which ketone monitoring was advised ranged from >200 to 350 mg/dL and from 0 min to >6 h of duration. While 72% had distinct ketone management protocols for pump users, only 29% had specific protocols for AID. Sixty-two percent agreed that DKA due to infusion site failure was a significant problem in their practice, and 70% agreed there was a need to standardize ketone management guidelines. Conclusions: The preventable nature and high incidence of DKA highlight the need to build consensus for clinical ketone management and to develop tools to facilitate management, especially as the use of diabetes technologies continues to increase.
Chinese Expert Consensus on the Whole-Course Management of Hepatocellular Carcinoma (2023 Edition)
Authors: Yang Yu , Sun Juxian , Cai Jianqiang , Chen Minshan , Dai Chaoliu , Wen Tianfu , Xia Jinglin , Ying Mingang , Zhang Zhiwei , Zhang Xuewen , Fang Chihua , Shen Feng , An Ping , Cai Qingxian , Cao Jingyu , Zeng Zhen , Chen Gang , Chen Juan , Chen Ping , Chen Yongshun , Shan Yunfeng , Dang Shuangsuo , Guo Wei-Xing , He Jiefeng , Hu Heping , Huang Bin , Jia Weidong , Jiang Kexiang , Jin Yan , Jin Yongdong , Jin Yun , Li Gong , Liang Yun , Liu Enyu , Liu Hao , Peng Wei , Peng Zhenwei , Peng Zhiyi , Qian Yeben , Ren Wanhua , Shi Jie , Song Yusheng , Tao Min , Tie Jun , Wan Xueying , Wang Bin , Wang Jin , Wang Kai , Wang Kang , Wang Xin , Wei Wenjing , Wu Fei-Xiang , Xiang Bangde , Xie Lin , Xu Jianming , Yan Mao-Lin , Ye Yufu , Yue Jinbo , Zhang Xiaoxun , Zhang Yu , Zhang Aibin , Zhao Haitao , Zhao Weifeng , Zheng Xin , Zhou Hongkun , Zhou Huabang , Zhou Jun , Zhou Xinmin , Cheng Shu-Qun , Li Qiu ,   on behalf of Chinese Association of Liver Cancer and Chinese Medical Doctor Association
Published: October 2024

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. Most HCC patients have the complications of chronic liver disease and need overall consideration and whole-course management, including diagnosis, treatment, and follow-up. To develop a reasonable, long-term, and complete management plan, multiple factors need to be considered, including the patient’s general condition, basic liver diseases, tumor stage, tumor biological characteristics, treatment requirements, and economic cost. Summary: To better guide the whole-course management of HCC patients, the Chinese Association of Liver Cancer and the Chinese Medical Doctor Association has gathered multidisciplinary experts and scholars in relevant fields to formulate the “Chinese Expert Consensus on The Whole-Course Management of Hepatocellular Carcinoma (2023).” Key Messages: This expert consensus, based on the current clinical evidence and experience, proposes surgical and nonsurgical HCC management pathways and involves 18 recommendations, including perioperative treatment, systematic treatment combined with local treatment, conversion treatment, special population management, symptomatic support treatment, and follow-up management.
Optimizing warehouse management system with blockchain and machine learning predictive data analytics
Authors: Hande Kapil N. , Chandak Manoj B.
Published: October 2024

Blockchain technology is proving to be a disruptive technology in many areas of supply chain, manufacturing, medical, agriculture, and so on. Warehouses are an inevitable part of the supply chain. Issues like space optimization, route optimization, quick item pick-up, demand forecasting, and transaction management are of importance to address in warehouse management systems (WMS). Traditional database systems have limitations of interoperability among different entities involved in warehouses. This paper presents an innovative application of blockchain technology and machine learning (ML) to build a smart warehouse management system in Web3 (SWMW3). We developed a decentralized application (DApp) using Web3.0 principles, integrating ReactJS for the frontend, express for the backend, and blockchain through smart contracts. This integration enhances security and transparency by storing WMS operational data in the blockchain and automating payments and verifications through smart contracts. Additionally, we implemented a ML model for predicting the total time from order receipt to delivery, leveraging historical data to optimize workflow, reduce delays, and improve overall efficiency. This combination of blockchain for secure transactions and ML for predictive analytics generates a robust, efficient, and optimized management system for the warehouse.
Transformer-based abstractive indonesian text summarization
Authors: Aurelia Miracle , Monica Sheila , Girsang Abba Suganda
Published: October 2024

The volume of data created, captured, copied, and consumed worldwide has increased from 2 zettabytes in 2010 to over 97 zettabytes in 2020, with an estimation of 181 zettabytes in 2025. Automatic text summarization (ATS) will ease giving points of information and will increase efficiency at the time consumed to understand the information. Therefore, improving ATS performance in summarizing news articles is the goal of this paper. This work will fine-tune the BART model using IndoSum, Liputan6, and Liputan6 augmented dataset for abstractive summarization. Data augmentation for Liputan6 will be augmented with the ChatGPT method. This work will also use r ecall-oriented understudy of gisting evaluation (ROUGE) as an evaluation metric. The data augmentation with ChatGPT used 10% of the clean news article from the Liputan6 training dataset and ChatGPT generated the abstractive summary based on that input, culminating in over 36 thousand data for the model’s fine-tuning. BART model that was finetuned using Indosum, Liputan6, and augmented Liputan6 dataset has the best ROUGE-2 score, outperforming ORACLE’s model although ORACLE still has the best ROUGE-1 and ROUGE-L score. This concludes that fine-tuning the BART model with multiple datasets will increase the performance of the model to do abstractive summarization tasks.
Machine learning-driven design and performance analysis of microstrip antennas for sub-6 GHz/mm Wave 5G networks
Authors: Prasanna Kumar Piske Laxmi , Padmasree Ramineni , Kiran Korra , Sudheer Banothu
Published: October 2024

In the realm of modern communication systems, antennas are crucial components, with the microstrip patch antenna being particularly notable for its low profile and seamless integration. Despite its widespread use, designing this antenna involves complex simulations to optimize parameters, requiring significant expertise and consuming considerable time and energy. To streamline this process, machine learning (ML) algorithms are being utilized. This paper introduces an innovative approach that employs ML techniques to design a rectangular microstrip patch antenna operating within the sub-6 GHz frequency range (1-6 GHz) and the millimeter frequency range (28-40 GHz). The antenna design maintains consistent patch dimensions positioned strategically at the center, with a thorough examination of patch length and width to enhance performance. Datasets are meticulously prepared, covering output parameters such as beam area, directivity, gain, and radiation efficiency across the specified frequency ranges. By employing various ML algorithms, this study conducts a comprehensive analysis to identify the most effective algorithm for accurately predicting antenna characteristics. The K-nearest neighbor (KNN) algorithm achieved high accuracy across all parameters: gain at 94.23% under sub-6 GHz and 95.93% under millimeter frequency range, directivity at 99.02% and 98.59%, radiation efficiency at 93.94% and 94.28%, and beam area at 99.07% and 98.59% respectively. These results optimize microstrip antenna designs and enhance understanding of the relationship between design parameters and performance outcomes with ML.
Revolutionizing agricultural efficiency with advanced coconut harvesting automation
Authors: Davincy R. Yona , Veemaraj Ebenezer , Edwin E. Bijolin , Kirubakaran S. Stewart , Thanka M. Roshni , Neola J. Dafny
Published: October 2024

The precision coconut harvesting system aims to develop an efficient system for accurately detecting coconuts in agricultural landscapes using advanced image processing techniques. Coconut cultivation is vital to many tropical economies and precise monitoring is essential for optimizing yield and resource utilization. Traditional methods of coconut detection are labor-intensive and time-consuming. The proposed computer vision-based approach automates and enhances coconut detection by analyzing high-resolution images of coconut plantations. Pre-processing techniques improve image quality and object detection algorithms such as convolutional neural networks (CNNs) identify coconut clusters. Challenges like lighting variations and background clutter are addressed using feature extraction and pattern recognition. A user-friendly interface visualizes detection results, aiding farmers in timely decision-making. Extensive testing on diverse datasets evaluates system effectiveness. This model aims to advance precision agriculture, enhancing productivity and informing coconut farmers' decision-making processes. Using a CNN model, the accuracy of coconut detection based on its ripeness was 98.8%.