bluuebunny/crossref_metadata_2025 huggingface dataset:
Review on obesity management: diet, exercise and pharmacotherapy
Authors: Peri Katya , Eisenberg Mark
Published: December 2024

Currently, obesity is one of the largest risk factors for cardiometabolic disease in North American adults. Over the past few years, the prevalence of this disease has been steadily increasing. This article is the second article in a three-part series of reviews exploring current clinical guidelines and management strategies used in practice to mitigate the spread of obesity. Guidelines to help physicians manage patients with obesity have been released in Canada and Europe. They outline proper management and treatment for overweight and obese patients. Examples include changes in diet and exercise, behavioural therapy and the administration of antiobesity medications as first-line and second-line treatments. Management of obesity takes on a tiered approach, where first-line therapies include lifestyle changes such as diet and exercise and second-line therapies include the use of antiobesity medications.
Oral β-GPA induces daily torpor in the mouse
Authors: Jansujwicz Eliza A. , Swoap Steven J.
Published: December 2024

In response to caloric deficit and a cool environment, mice ( Mus musculus Linnaeus, 1758) employ daily torpor, a physiological state characterized by metabolic rate depression and bradycardia, followed by a decrease in body temperature. Although some heat is generated during arousal from torpor via uncoupling-protein 1 (UCP1)-dependent activity, there is also evidence of UCP1-independent mechanisms. We hypothesized that mice utilize futile creatine cycling as a UCP1-independent mechanism for generating heat during arousal from torpor, and thus interference with this cycle would result in longer arousal times. β-Guanidinopropionic acid (β-GPA), a creatine analog shown to decrease cellular creatine levels, was used to assess the role of the futile creatine cycle in arousal from torpor. Mice consuming a standard 1% β-GPA diet lost body weight and, unexpectedly, experienced drops in body temperature that appear “torpor-like” in nature. Behavioral (body position) and physiological (body temperature dynamics, heart rate dynamics and variability, surface tail temperature) assessments were used to distinguish between torpor-like bouts induced by 1% β-GPA feeding and natural torpor. Our analysis suggests that the torpor-like bouts induced during feeding of 1% β-GPA should be considered daily torpor. Contrary to our initial hypothesis, the rate of arousal from these bouts was not significantly affected by β-GPA treatment. Still, the utilization of torpor by mice in a fed state is an unusual finding, and one of the few cases where food consumption does not inhibit daily torpor in the mouse.
Neoproterozoic-early Paleozoic tectonic evolution of Oman revisited: implications for the consolidation of Gondwana
Authors: Gómez-Pérez Irene , Morton A.
Published: December 2024

Implications of a new tectonic evolution model that puts Oman at the eastern margin of the Mozambique Ocean during the Neoproterozoic are wide and regionally significant. This model helps understanding the Neoproterozoic tectonics and paleogeography of Gondwana, the closure of the Mozambique Ocean, the paleogeography of the world-renowned Cryogenian and Ediacaran successions of Oman, and the petroleum systems of Oman and the rest of Arabia.

The proposed evolution model implies that the basement of Oman formed at the margin of Neoproterozoic India, and that the Cryogenian-Ediacaran sedimentary succession of Oman, and its early tectonic evolution, whose structural trends influenced tectonics through its geological history, were separate from those of the Arabian-Nubian Shield to the west*, as they were on opposite sides of the Mozambique Ocean up to the early Cambrian. It also implies that the final Gondwanan suture lies somewhere along, or just west of, the Western Deformation Front, an early Cambrian orogenic belt now found in the subsurface of Oman and in outcrops of north and south Oman. Its development is related to Malagasy-Angudan Orogeny, and it separates two realms: the juvenile Ediacaran basement and active margin sedimentary successions of the Arabian-Nubian Shield, and the Tonian igneous and metamorphic basement, Cryogenian rift deposits and Ediacaran passive margin deposits of Oman/Neoproterozoic India. The Precambrian hydrocarbon systems of Oman do therefore not extend to western Arabia, but to India and Pakistan instead. Sediment provenance studies using zircon geochronology and facies maps of the Neoproterozoic successions help to understand the tectonic setting during deposition and the distribution of reservoir rocks in shallow water settings in northeast Oman, and source rocks in deep basinal settings in south and west Oman.
Training and Support Practices and Insights in the Sustainability of mHealth Implementations in Sub-Saharan Africa
Authors: Babirye Diana , Anderson Richard
Published: December 2024

We conducted an interview-based study to understand the training and support practices and insights that influence sustainable implementations of mHealth projects of varying mHealth technologies. The qualitative assessment was inspired by the Consolidated Framework for Implementation Research adapted with the recommended questions for guiding the implementation of training programs. Participants in the study (N = 16) were both international and in-country researchers managing projects in sub-Saharan Africa. We chose to focus on training and support, as it is often the interface between international and in-country components of these projects. Participants agreed on the central role of training in the implementation of mHealth projects and are following best practices. There was often a division in the responsibility of training between international and in-country researchers reflecting the distinction between project management and local implementation adaptions. One of the main findings is the importance of individualized continuous retraining to make deployments robust with respect to changing conditions with technology and personnel, an aspect that has been managed a bit differently with varying mHealth technologies as presented in this article.
AIS: An Active Idleness I/O Scheduler to Reduce Buffer-Exhausted Degradation of Solid-State Drives
Authors: Zhan Yekang , Yang Xiangrui , Hu Haichuan , Cao Qiang , Zhang Yifan , Yao Jie
Published: December 2024

Modern solid-state drives (SSDs) continue to boost storage density and I/O bandwidth at the cost of flash-access I/O latency, especially for write, hence prevalently deploy a build-in buffer to absorb incoming writes. However, when the buffer is used up, the applications suffer from a sudden and long performance declines, i.e., buffer-exhausted degradation (BED). To holistically understand BED and recovery, we design an automated testing toolset (SSDTest) to measure six commodity NVMe SSDs and find: 1) the occurrence of the BED strictly relies on the written-data amount, 2) BED dramatically increases I/O latency of SSDs, especially write and read-after-write, 3) BED can be conditionally reduced and recovered only after a period of idle time, and 4) a read without preceding writes is largely immune to BED, but prolongs the required idle time to recover the available buffer. Furthermore, we build a black-box SSD buffer-recovery model to quantitatively characterize the idleness-recovery behaviors and design an SSD BED predictor to make BED occurrence and buffer recovery predictable. Leveraging this model, we further design an Active Idleness I/O Scheduler (AIS) with small-sized auxiliary storage to actively regulate the I/O idle-intervals to maximize the internal buffer recovery of SSD. AIS adaptively steers incoming data to the auxiliary storage to 1) strategically keep SSD idle to reduce the occurrence of BED and 2) mitigate the tail latency of SSDs caused by read-after-writes during BED. We perform extensive evaluations under a variety of workloads. The results show that AIS improves average, 99th, 99.9th and 99.99th-percentile latencies of SSDs by up to 29.3%, 37.3%, 78.7% and 67.2% respectively, with up to 512MB auxiliary storage.
Addressing Limitations of the Endpoint Slippage Analysis
Authors: Rodrigues Marco-Tulio F.
Published: December 2024

Some rate of oxidation and reduction side-reactions will inevitably coexist in most rechargeable batteries. While parasitic reduction traps electrons, parasitic oxidation donates electrons to the cell’s inventory and may cause temporary capacity gain. Consequently, capacity measurements can provide unreliable information about the total extent of side-reactions occurring in the cell. The most widely used method to determine the rate of both these parasitic processes involves analyzing the slippage of endpoints, which consists in tracking the termination of cell charge and discharge when data is represented along a cumulative capacity axis. Here, we argue that this approach could lead to inaccuracies when applied to certain systems, which includes Si electrodes in Li-ion batteries and hard carbon in Na-ion batteries. This inaccuracy originates from the smooth nature of the voltage profiles of these materials at low and high alkali-ion content, causing the termination of charge and discharge to be dictated by voltage changes at both the positive and negative electrodes. We analyze this issue in quantitative terms and propose equations that can provide true rates of parasitic processes from experimental endpoint slippage data. This work shows that, in battery science, well-established analytical approaches may not be directly transferrable to new electrode systems.
Evaluating Allyl and Vinyl-Modified Boronium Ionic Liquids for Energy Storage Applications
Authors: Stachurski Christopher D. , Cho Whirang , Kinnaman Conner M. , Zeller Matthias , Davis James H. , Larm Nathaniel E. , Trulove Paul C. , Durkin David P.
Published: December 2024

This work investigates two polymerizable boronium ionic liquids (BILs) that were identified as candidates for solid or pseudo-solid electrolytes in energy storage applications. The cation structures, [(1-v-imid)N111BH2]+ and [(1-a-pyrr)N111BH2]+, were chosen to bolster high performing BILs from past studies with polymerizable functionality capable of producing solid or pseudo-solid state electrolytes. The second cation ([(1-a-pyrr)N111BH2]+) has not yet been reported in the literature. Ultimately, two polyBILs with the bis(trifluoromethanesulfonyl)imide anion were prepared and characterized using a suite of characterization techniques including nuclear magnetic resonance spectroscopy, X-ray diffractometry, thermal gravimetric analysis, differential scanning calorimetry, cyclic voltammetry, and electrochemical impedance spectroscopy.
Review—Challenges in Lab-to-Clinic Translation of 5th/6th Generation Intelligent Nanomaterial-enabled Biosensors
Authors: Talreja Rishi Kumar , Sable Harsh , Chaudhary Vikash , Kadian Sachin , Singh Mamta , Kumar Manish , Kishore Jugal , Chaudhary Vishal , Khosla Ajit
Published: December 2024

Conventional diagnostic platforms often lack point-of-care, simple, economical, prompt and personalized detection features, whereas nanomaterial-supported intelligent biosensors belonging to the 5th/6th generation are vital vectors in medical diagnostics. The tunable and enhanced physicochemical properties of nanomaterials such as surface area, surface chemistry, band gap, and flexibility, nano-biosensors exhibit high sensitivity, specificity, and prompt and accurate detection. Despite substantial research and an exponentially growing market, projected to reach $46.4 billion by 2028, biosensors face considerable challenges in clinical implementation. This article underlines the manifold translational challenges, such as regulatory barriers, safety and toxicity concerns related to nanomaterials, technical and manufacturing issues, hesitancy in adopting new tools, and economic constraints. Besides discussing the perspectives of material scientists, medical doctors, data scientists, and public health professionals, this article presents a comprehensive overview of the current state and prospects of integrating next-generation nanomaterial-based artificial intelligence-supported biosensors into clinical practice. It emphasizes the need to address these barriers, which can enhance early disease detection, improve patient outcomes, and reduce the overall burden on healthcare systems. Their applications can be extended to one health management team with dedicated collaborations to achieve sustainable development goals.
IGF-1 LR3 does not promote growth in late-gestation growth-restricted fetal sheep
Authors: White Alicia , Stremming Jane , Wesolowski Stephanie R. , Al-Juboori Saif I. , Dobrinskikh Evgenia , Limesand Sean W. , Brown Laura D. , Rozance Paul J.
Published: December 2024

IGF-1 LR3 treatment administered directly into growth-restricted fetal sheep circulation did not improve fetal growth or attenuate circulating insulin or fetal GSIS. Importantly, IGF-1 LR3 treatment reduced circulating amino acids, notably branched-chain amino acids, which have been shown to potentiate GSIS and protein accretion supporting fetal growth.
Hepatocyte HIF-2α aggravates NAFLD by inducing ferroptosis through increasing extracellular iron
Authors: Luo Shunkui , Lu Zhanjin , Wang Lingling , Li Yun , Zeng Yingjuan , Lu Hongyun
Published: December 2024

The experiment demonstrated that HIF-2α increased extracellular iron. In LO2 cells overexpressing HIF-2α, FFAs not only increased cellular lipid and triglyceride levels but also induced key features of ferroptosis, such as reduced GSH and GPX4 levels and increased LPO, despite the absence of cellular iron overload. These effects were reversed by lowering extracellular iron with DFO. Furthermore, DFO treatment increased β-oxidation protein expression and improved lipid deposition in hepatocytes, potentially through the PI3K/AKT pathway.
The Bacterial Biofilms: Formation, Impacts, and Possible Management Targets in the Healthcare System
Authors: Omwenga Eric Omori , Awuor Silas Onyango
Published: December 2024

Introduction: The persistent increase in multidrug‐resistant pathogens has catalyzed the creation of novel strategies to address antivirulence and anti‐infective elements. Such methodologies aim to diminish the selective pressure exerted on bacterial populations, decreasing the likelihood of resistance emergence. This review explores the role of biofilm formation as a significant virulence factor and its impact on the development of antimicrobial resistance (AMR).

Case Presentation: The ability of bacteria to form a superstructure—biofilm—has made resistance cases in the microbial world a big concern to public health and other sectors as it is a crucial virulence factor that causes difficulties in the management of infections, hence enhancing chronic infection occurrence. Biofilm formation dates to about 3.4 billion years when prokaryotes were discovered to be forming them and since then due to evolution and growth in science, they are more understood.

Management and Outcome: The unique microenvironments within bacterial biofilms diminish antibiotic effectiveness and help bacteria evade the host immune system. Biofilm production is a widespread capability among diverse bacterial species. Biofilm formation is enhanced by quorum sensing (QS), reduction of nutrients, or harsh environments for the bacteria.

Conclusion: The rise of severe, treatment‐resistant biofilm infections poses major challenges in medicine and agriculture, yet much about how these biofilms form remains unknown.
Supplementary Methods from Selective Enhancer Gain-of-Function Deregulates MYC Expression in Multiple Myeloma
Authors: Rahmat Mahshid , Clement Kendell , Alberge Jean-Baptiste , Sklavenitis-Pistofidis Romanos , Kodgule Rohan , Fulco Charles P. , Heilpern-Mallory Daniel , Nilsson Katarina , Dorfman David , Engreitz Jesse M. , Getz Gad , Pinello Luca , Ryan Russell J.H. , Ghobrial Irene M.
Published: December 2024

Supplementary Methods
Table S4 from Combined Autophagy Inhibition and Dendritic Cell Recruitment Induces Antitumor Immunity and Enhances Immune Checkpoint Blockade Sensitivity in Pancreatic Cancer
Authors: Oyama Koki , Nakata Kohei , Tsutsumi Chikanori , Hayashi Masataka , Zhang Bo , Mochida Yuki , Shinkawa Tomohiko , Hirotaka Kento , Zhong Pingshan , Date Satomi , Luo Haizhen , Kubo Akihiro , Higashijima Nobuhiro , Yamada Yutaka , Abe Toshiya , Ideno Noboru , Koikawa Kazuhiro , Iwamoto Chika , Ikenaga Naoki , Ohuchida Kenoki , Onishi Hideya , Morisaki Takashi , Kuba Keiji , Oda Yoshinao , Nakamura Masafumi
Published: December 2024

Gene lists and sources of each gene sets used in the analysis of public PDAC patient scRNA-seq data
Table S1 from Combined Autophagy Inhibition and Dendritic Cell Recruitment Induces Antitumor Immunity and Enhances Immune Checkpoint Blockade Sensitivity in Pancreatic Cancer
Authors: Oyama Koki , Nakata Kohei , Tsutsumi Chikanori , Hayashi Masataka , Zhang Bo , Mochida Yuki , Shinkawa Tomohiko , Hirotaka Kento , Zhong Pingshan , Date Satomi , Luo Haizhen , Kubo Akihiro , Higashijima Nobuhiro , Yamada Yutaka , Abe Toshiya , Ideno Noboru , Koikawa Kazuhiro , Iwamoto Chika , Ikenaga Naoki , Ohuchida Kenoki , Onishi Hideya , Morisaki Takashi , Kuba Keiji , Oda Yoshinao , Nakamura Masafumi
Published: December 2024

Key Resources
Figure S9 from Combined Autophagy Inhibition and Dendritic Cell Recruitment Induces Antitumor Immunity and Enhances Immune Checkpoint Blockade Sensitivity in Pancreatic Cancer
Authors: Oyama Koki , Nakata Kohei , Tsutsumi Chikanori , Hayashi Masataka , Zhang Bo , Mochida Yuki , Shinkawa Tomohiko , Hirotaka Kento , Zhong Pingshan , Date Satomi , Luo Haizhen , Kubo Akihiro , Higashijima Nobuhiro , Yamada Yutaka , Abe Toshiya , Ideno Noboru , Koikawa Kazuhiro , Iwamoto Chika , Ikenaga Naoki , Ohuchida Kenoki , Onishi Hideya , Morisaki Takashi , Kuba Keiji , Oda Yoshinao , Nakamura Masafumi
Published: December 2024

Triplet therapy comprising CQ, Flt3L, and aLAG3 markedly suppresses tumor growth
Figure S8 from Combined Autophagy Inhibition and Dendritic Cell Recruitment Induces Antitumor Immunity and Enhances Immune Checkpoint Blockade Sensitivity in Pancreatic Cancer
Authors: Oyama Koki , Nakata Kohei , Tsutsumi Chikanori , Hayashi Masataka , Zhang Bo , Mochida Yuki , Shinkawa Tomohiko , Hirotaka Kento , Zhong Pingshan , Date Satomi , Luo Haizhen , Kubo Akihiro , Higashijima Nobuhiro , Yamada Yutaka , Abe Toshiya , Ideno Noboru , Koikawa Kazuhiro , Iwamoto Chika , Ikenaga Naoki , Ohuchida Kenoki , Onishi Hideya , Morisaki Takashi , Kuba Keiji , Oda Yoshinao , Nakamura Masafumi
Published: December 2024

scRNA-seq analysis and immunofluorescence images revealed that CD8+ T cells in KPC-shATG7 tumors express high LAG3 levels
Supplementary Table S1 from Induction of the TEAD Coactivator VGLL1 by Estrogen Receptor–Targeted Therapy Drives Resistance in Breast Cancer
Authors: Gemma Carolina , Lai Chun-Fui , Singh Anup K. , Belfiore Antonino , Portman Neil , Milioli Heloisa Z. , Periyasamy Manikandan , Raafat Sara , Nicholls Alyssa J. , Davies Claire M. , Patel Naina R. , Simmons Georgia M. , Fan Hailing , Nguyen Van T.M. , Magnani Luca , Rakha Emad , Martin Lesley-Ann , Lim Elgene , Coombes R. Charles , Pruneri Giancarlo , Buluwela Laki , Ali Simak
Published: December 2024

Supplementary Table S1
Supplementary Table 3 from Induction of the TEAD Coactivator VGLL1 by Estrogen Receptor–Targeted Therapy Drives Resistance in Breast Cancer
Authors: Gemma Carolina , Lai Chun-Fui , Singh Anup K. , Belfiore Antonino , Portman Neil , Milioli Heloisa Z. , Periyasamy Manikandan , Raafat Sara , Nicholls Alyssa J. , Davies Claire M. , Patel Naina R. , Simmons Georgia M. , Fan Hailing , Nguyen Van T.M. , Magnani Luca , Rakha Emad , Martin Lesley-Ann , Lim Elgene , Coombes R. Charles , Pruneri Giancarlo , Buluwela Laki , Ali Simak
Published: December 2024

Supplementary Table 3
Data from Combined Autophagy Inhibition and Dendritic Cell Recruitment Induces Antitumor Immunity and Enhances Immune Checkpoint Blockade Sensitivity in Pancreatic Cancer
Authors: Oyama Koki , Nakata Kohei , Tsutsumi Chikanori , Hayashi Masataka , Zhang Bo , Mochida Yuki , Shinkawa Tomohiko , Hirotaka Kento , Zhong Pingshan , Date Satomi , Luo Haizhen , Kubo Akihiro , Higashijima Nobuhiro , Yamada Yutaka , Abe Toshiya , Ideno Noboru , Koikawa Kazuhiro , Iwamoto Chika , Ikenaga Naoki , Ohuchida Kenoki , Onishi Hideya , Morisaki Takashi , Kuba Keiji , Oda Yoshinao , Nakamura Masafumi
Published: December 2024

Abstract
The effect of immune checkpoint inhibitors is extremely limited in patients with pancreatic ductal adenocarcinoma (PDAC) due to the suppressive tumor immune microenvironment. Autophagy, which has been shown to play a role in antitumor immunity, has been proposed as a therapeutic target for PDAC. In this study, single-cell RNA sequencing of autophagy-deficient murine PDAC tumors revealed that autophagy inhibition in cancer cells induced dendritic cell (DC) activation. Analysis of human PDAC tumors substantiated a negative correlation between autophagy and DC activation signatures. Mechanistically, autophagy inhibition increased the intracellular accumulation of tumor antigens, which could activate DCs. Administration of chloroquine, an autophagy inhibitor, in combination with Flt3 ligand–induced DC infiltration inhibited tumor growth and increased tumor-infiltrating T lymphocytes. However, autophagy inhibition in cancer cells also induced CD8+ T-cell exhaustion with high expression of immune checkpoint LAG3. A triple-therapy comprising chloroquine, Flt3 ligand, and an anti-LAG3 antibody markedly reduced tumor growth in orthotopic syngeneic PDAC mouse models. Thus, targeting autophagy in cancer cells and activating DCs sensitize PDAC tumors to immune checkpoint inhibitor therapy, warranting further development of this treatment approach to overcome immunosuppression in pancreatic cancer.

Significance: Inhibiting autophagy in pancreatic cancer cells enhances intracellular accumulation of tumor antigens to induce dendritic cell activation and synergizes with immunotherapy to markedly inhibit the growth of pancreatic ductal adenocarcinoma.
Supplementary Table S2 from Large-Scale Comparative Analysis of Canine and Human Osteosarcomas Uncovers Conserved Clinically Relevant Tumor Microenvironment Subtypes
Authors: Patkar Sushant , Mannheimer Joshua , Harmon Stephanie A. , Ramirez Christina J. , Mazcko Christina N. , Choyke Peter L. , Brown Gregory Thomas , Turkbey Baris , LeBlanc Amy K. , Beck Jessica A.
Published: December 2024

QuPath (v0.5.0) T cell density (number of CD3 positive cells per mm2) outputs for each case that passed quality review.
Supplementary Table S6 from Spatial Dynamics of T- and B-Cell Responses Predicts Clinical Outcome of Resectable and Unresectable Hepatocellular Carcinoma
Authors: Kurebayashi Yutaka , Sugimoto Katsutoshi , Tsujikawa Hanako , Matsuda Kosuke , Nomura Rui , Ueno Akihisa , Masugi Yohei , Yamazaki Ken , Effendi Kathryn , Takeuchi Hirohito , Itoi Takao , Hasegawa Yasushi , Abe Yuta , Kitago Minoru , Ojima Hidenori , Sakamoto Michiie
Published: December 2024

Table S6. Clinicopathological findings in autopsy cases.
Supplementary Table S3 from Spatial Dynamics of T- and B-Cell Responses Predicts Clinical Outcome of Resectable and Unresectable Hepatocellular Carcinoma
Authors: Kurebayashi Yutaka , Sugimoto Katsutoshi , Tsujikawa Hanako , Matsuda Kosuke , Nomura Rui , Ueno Akihisa , Masugi Yohei , Yamazaki Ken , Effendi Kathryn , Takeuchi Hirohito , Itoi Takao , Hasegawa Yasushi , Abe Yuta , Kitago Minoru , Ojima Hidenori , Sakamoto Michiie
Published: December 2024

Table S3. Multivariate analysis for DFS in Cohort 1 + 2 (n = 268)
Supplementary Figure S1 from Histology-Specific Clinical Trial of Lenvatinib and Pembrolizumab in Patients with Sarcoma
Authors: Movva Sujana , Seier Kenneth , Avutu Viswatej , Banks Lauren B. , Chan Jason , Chi Ping , Dickson Mark A. , Gounder Mrinal M. , Kelly Ciara M. , Keohan Mary L. , Maki Robert , Rosenbaum Evan , Salcito Tiffany , Rodriguez Kaithleen , Dempsey Rebecca , Meyers Paul A. , Cohen Seth M. , Hensley Martee L. , Konner Jason A. , Schram Alison M. , Lefkowitz Robert A. , Erinjeri Joseph P. , Qin Li-Xuan , Tap William D. , D’Angelo Sandra P.
Published: December 2024

Supplementary Figure 1. Progression-free survival by histology.
Supplementary Figure S7 from Spatial Dynamics of T- and B-Cell Responses Predicts Clinical Outcome of Resectable and Unresectable Hepatocellular Carcinoma
Authors: Kurebayashi Yutaka , Sugimoto Katsutoshi , Tsujikawa Hanako , Matsuda Kosuke , Nomura Rui , Ueno Akihisa , Masugi Yohei , Yamazaki Ken , Effendi Kathryn , Takeuchi Hirohito , Itoi Takao , Hasegawa Yasushi , Abe Yuta , Kitago Minoru , Ojima Hidenori , Sakamoto Michiie
Published: December 2024

Figure S7. CD68+ and CD169+ macrophages in TA/TLS
Supplementary Figure S5 from Spatial Dynamics of T- and B-Cell Responses Predicts Clinical Outcome of Resectable and Unresectable Hepatocellular Carcinoma
Authors: Kurebayashi Yutaka , Sugimoto Katsutoshi , Tsujikawa Hanako , Matsuda Kosuke , Nomura Rui , Ueno Akihisa , Masugi Yohei , Yamazaki Ken , Effendi Kathryn , Takeuchi Hirohito , Itoi Takao , Hasegawa Yasushi , Abe Yuta , Kitago Minoru , Ojima Hidenori , Sakamoto Michiie
Published: December 2024

Figure S5. Intratumoral distribution of NK cells
Supplementary Table S3 from Phase Ib Study of the Immunocytokine Simlukafusp Alfa (FAP-IL2v) in Combination with Cetuximab in Patients with Head and Neck Squamous Cell Carcinoma
Authors: Hansen Aaron R. , Gomez-Roca Carlos A. , Robbrecht Debbie G. J. , Verlingue Loic , Italiano Antoine , Bauman Julie E. , Steeghs Neeltje , Prenen Hans , Fayette Jérôme , Spicer James , Niu Jiaxin , Habigt Christin , Schneider Meike , Evers Stefan , Sleiman Nassim , Dejardin David , Ardeshir Caroline , Schmid Daniela , Boetsch Christophe , Charo Jehad , Kraxner Anton , Teichgräber Volker , Keshelava Nino , Bonomi Marcelo R.
Published: December 2024

Supplementary Table S3. Characterization of patients with partial response.
Figure 3 from First-in-Human Dose-Escalation Study of Fianlimab, an Antilymphocyte Activation Gene-3 Antibody, with Cemiplimab in Patients with Advanced Malignancies
Authors: Lakhani Nehal J. , Papadopoulos Kyriakos P. , Johnson Melissa Lynne , Park Haeseong , Wang Ding , Yap Timothy A. , Dowlati Afshin , Maki Robert G. , Ulahannan Susanna , Lynce Filipa , Kelly Karen , Williamson Stephen , Malhotra Jyoti , Chen Shuquan , Gonzalez Ortiz Ana , Jankovic Vladimir , Paccaly Anne , Masinde Sheila , Mani Jayakumar , Lowy Israel , Gullo Giuseppe , Sims Tasha , Kroog Glenn
Published: December 2024

Analysis of T-cell subset proliferation subsequent to initiation of fianlimab as monotherapy or in combination with cemiplimab in (A) CD4 effector memory T cells and (B) CD8 effector memory T cells. Representative dot plots of CD4 and CD8+ T-cell memory subpopulations expressing Ki67+, LAG3+, HLA-DR+, PD-1+, or PD-L1+. Pharmacodynamic assay data from the 40 mg/kg dose cohort could not be generated due to poor quality of samples. DL, dose level; IV, intravenous; Q3W, every 3 weeks.
Figure 2 from Circulating Chromogranin A as a Surveillance Biomarker in Patients with Carcinoids—The CASPAR Study
Authors: Meng Qing H. , Halfdanarson Thorvardur R. , Bornhorst Joshua A. , Jann Henning , Shaheen Shagufta , Shi Run Zhang , Schwabe Andrej , Stade Katrin , Halperin Daniel M.
Published: December 2024

A, ROC curves for diagnosis of tumor progression in the intention-to-diagnose population with corresponding AUC. B, Box plots of continuous ΔCgA, simple ΔCgA, and CgA concentrations are shown with log-scaled axes. Strata of follow-up visits of the intention-to-diagnose population: no progression (blue) and progression (red). The horizontal gray lines show the prespecified cut-off 50% for ΔCgA.
Supplementary Appendix S1 from Efficacy, Safety, and Influence on the Tumor Microenvironment of Neoadjuvant Pembrolizumab plus Ramucirumab for PD-L1–Positive NSCLC: A Phase II Trial (EAST ENERGY)
Authors: Aokage Keiju , Koyama Shohei , Kumagai Shogo , Nomura Kotaro , Shimada Yoshihisa , Yoh Kiyotaka , Wakabayashi Masashi , Fukutani Miki , Furuya Hideki , Miyoshi Tomohiro , Tane Kenta , Samejima Joji , Taki Tetsuro , Hayashi Takuo , Matsubayashi Jun , Ishii Genichiro , Nishikawa Hiroyoshi , Ikeda Norihiko , Tsuboi Masahiro
Published: December 2024

Supplementary Appendix S1: EAST_ENERGY_Protocol_v7.
Data from Oxygen-Enhanced MRI Detects Incidence, Onset, and Heterogeneity of Radiation-Induced Hypoxia Modification in HPV-Associated Oropharyngeal Cancer
Authors: Dubec Michael J. , Price James , Berks Michael , Gaffney John , Little Ross A. , Porta Nuria , Sridharan Nivetha , Datta Anubhav , McHugh Damien J. , Hague Christina J. , Cheung Susan , Manoharan Prakash , van Herk Marcel , Choudhury Ananya , Matthews Julian C. , Parker Geoff J.M. , Buckley David L. , Harrington Kevin J. , McPartlin Andrew , O’Connor James P.B.
Published: December 2024

AbstractPurpose:
Hypoxia mediates treatment resistance in solid tumors. We evaluated if oxygen-enhanced MRI–derived hypoxic volume (HVMRI) is repeatable and can detect radiotherapy-induced hypoxia modification in human papillomavirus–associated oropharyngeal head and neck squamous cell cancer.
Experimental Design:
A total of 27 patients were recruited prospectively between March 2021 and January 2024. HVMRI was measured in primary and nodal tumors prior to standard-of-care (chemo)radiotherapy and then at weeks 2 and 4 (W2 and W4) into therapy. Two pretreatment scans assessed biomarker within-subject coefficient of variation and repeatability coefficient (RC). Cohort treatment response was measured using mixed-effects modeling. Responding lesions were identified by comparing HVMRI change with RC limits of agreement.
Results:
Oxygen-enhanced MRI identified hypoxia in all lesions. The HVMRI within-subject coefficient of variation was 24.6%, and RC limits of agreement were −45.7% to 84.1%. A cohort median pretreatment HVMRI of 11.3 cm3 reduced to 6.9 cm3 at W2 and 5.9 cm3 at W4 (both P < 0.001). HVMRI was reduced in 54.5% of individual lesions by W2 and in 88.2% by W4. All lesions with W2 hypoxia reduction showed persistent modification at W4. HVMRI reduced in some lesions that showed no overall volume change. Hypoxia modification was discordant between primary and nodal tumors in 50.0% of patients.
Conclusions:
Radiation-induced hypoxia modification can occur as early as W2, but onset varies between patients and was not necessarily associated with overall size change. Half of all patients had discordant changes in primary and nodal tumors. These findings have implications for patient selection and timing of dose de-escalation strategies in human papillomavirus–associated oropharyngeal carcinoma.

See related commentary by Mason, p. 5503
HMGA2 Expression Predicts Subtype, Survival, and Treatment Outcome in Pancreatic Ductal Adenocarcinoma
Authors: Yamamoto Naomi , Dobersch Stephanie , Loveless Ian , Samraj Annie N. , Jang Gun Ho , Haraguchi Miki , Kang Liang-I. , Ruzinova Marianna B. , Vij Kiran R. , Mudd Jacqueline L. , Walsh Thomas , Safyan Rachael A. , Chiorean Elena Gabriela , Hingorani Sunil R. , Bolton Nathan M. , Li Li , Fields Ryan C. , DeNardo David G. , Notta Faiyaz , Crawford Howard C. , Steele Nina G. , Kugel Sita
Published: December 2024

Purpose:

The purpose of this study was to establish HMGA2 as a marker of basal-like disease in pancreatic ductal adenocarcinoma (PDAC) and explore its use as a biomarker for prognosis and treatment resistance.

Experimental Design:

We identified high-mobility group A2 (HMGA2) protein expression in basal PDAC cells in a single-cell RNA sequencing (RNA-seq) atlas of 172 patient samples. We then analyzed HMGA2 expression, along with expression of the classic marker GATA-binding factor 6 (GATA6), in a cohort of 580 PDAC samples with multiplex IHC. We further supplemented these data with an additional 30 diverse patient samples and multiple independent single-cell RNA-seq databases.

Results:

We found that expression of HMGA2, but not previously described basal markers cytokeratins 5 or 17, predicted overall survival in our cohort. Combining HMGA2 and GATA6 statuses allowed for the identification of two key study groups: an HMGA2+/GATA6− cohort with worse survival, low tumor-infiltrating CD8+ T cells, increased FAP+ fibroblasts, and poorer response to gemcitabine-based chemotherapies (n = 94, median survival = 11.2 months after surgery) and an HMGA2−/GATA6+ cohort with improved survival, increased CD8+ T-cell infiltrate, decreased FAP+ fibroblasts, and improved survival with gemcitabine-based chemotherapy (n = 198, median survival = 21.7 months after surgery). HMGA2 was also prognostic for overall survival in RNA-seq from an independent cohort.

Conclusions:

IHC stratification of primary tumors by HMGA2 and GATA6 statuses in pancreatic cancer is associated with differential outcomes, survival following chemotherapy, and tumor microenvironments. As a nuclear marker for basal disease, HMGA2 complements GATA6 to identify disease subtypes in PDAC.
Human Papilloma Virus Circulating Cell-Free DNA Kinetics in Patients with Cervical Cancer Undergoing Definitive Chemoradiation
Authors: Seo Aaron , Xiao Weihong , Gjyshi Olsi , Yoshida-Court Kyoko , Wei Peng , Swanson David , Cisneros Napravnik Tatiana , Grippin Adam , Venkatesan Aradhana M. , Jacobsen Megan C. , Fuentes David T. , Lynn Erica , Sammouri Julie , Jhingran Anuja , Joyner Melissa , Lin Lilie L. , Colbert Lauren E. , Gillison Maura L. , Klopp Ann H.
Published: December 2024

Purpose:

Human papillomavirus (HPV) is a significant cause of cervical cancer. We hypothesized that detecting viral cell-free HPV DNA (cfDNA) before, during, and after chemoradiation (chemoRT) could provide insights into disease extent, clinical staging, and treatment response.

Experimental Design:

A total of 66 patients with locally advanced cervical cancer were enrolled between 2017 and 2023, with 49 receiving standard-of-care treatment and 17 participating in a clinical trial combining a therapeutic HPV vaccine (PDS0101; IMMUNOCERV). Plasma was collected at baseline, weeks 1, 3, and 5 of chemoRT, and 3 to 4 months after chemoRT. HPV cfDNA was quantified using droplet digital PCR targeting the HPV E6/E7 oncogenes of 13 high-risk types. MRI was performed at baseline and before brachytherapy.

Results:

The median follow-up was 23 months, with recurrence-free survival (RFS) of 78.4% at 2 years. Baseline nodal disease extent correlated with HPV cfDNA levels. HPV cfDNA levels peaked in week 1 of radiation and decreased through treatment. Patients receiving the PDS0101 vaccine had a higher rate of undetectable HPV type 16 cfDNA compared with those who received standard-of-care therapy. HPV cfDNA clearance correlated with better 2-year RFS (92.9% vs. 30%, log-rank; P = 0.0067). The strongest predictor of RFS was HPV cfDNA clearance in follow-up achieving a concordance index score of 0.83, which improved when combined with MRI response (concordance index, 0.88).

Conclusions:

HPV cfDNA levels change dynamically during chemoRT. HPV cfDNA levels at follow-up predict RFS, and delivery of therapeutic HPV vaccine with chemoRT was linked to rapid HPV cfDNA decline. Monitoring HPV cfDNA during and after chemoRT may guide tailoring of personalized treatment.
Alcohol Consumption Does not Modify the Polygenic Risk Score–Based Genetic Risk of Breast Cancer in Postmenopausal Women: Atherosclerosis Risk in Communities Study
Authors: Zhang Minghui , Ru Meng , Zhang Jingning , Wang Ziqiao , Lu Jiayun , Butler Kenneth R. , Chatterjee Nilanjan , Couper David J. , Prizment Anna E. , Soori Mehrnoosh M. , Visvanathan Kala , Zahnow Cynthia A. , Joshu Corinne E. , Platz Elizabeth A.
Published: December 2024

High genetic risk and alcohol consumption ≥1 drink/day are associated with increased breast cancer risk. However, the interaction between alcohol and genetics on breast cancer risk is poorly understood, including in populations not enriched with daily drinkers. We prospectively studied 5,651 White and Black postmenopausal women in the Atherosclerosis Risk in Communities study. Alcohol intake was assessed by a food frequency questionnaire. The 313-SNP polygenic risk score (PRS) was calculated. Breast cancer cases were ascertained primarily by cancer registry linkage through 2015. Multivariable Cox regression was used to estimate HRs and 95% confidence intervals (CI) for the association of PRS and current ethanol intake with breast cancer, and their interaction. Of these individuals, 50.6% were current drinkers, and of them, 50.8% drank <1 drink/week and 12.8% drank >7 drinks/week. A higher PRS was associated with a higher breast cancer risk among White (HR1-SD, 1.48; 95% CI, 1.34–1.65) and Black (HR1-SD, 1.15; 95% CI, 0.96–1.38) women. Positive associations were not observed between current ethanol intake and breast cancer risk (White: HR13 g/week, 1.00; 95% CI, 0.98–1.03; Black: HR, 0.83; 95% CI, 0.69–1.00). Among both White and Black women, PRS generally seemed to be positively associated with risk in drinkers and nondrinkers. There was no evidence of a PRS–ethanol intake interaction among White or Black women. Patterns in Black women were similar when using an 89-SNP PRS developed among African ancestry women. In conclusion, in a prospective analysis of White and Black postmenopausal women in a study population not enriched with daily drinkers, our findings suggest that alcohol drinking does not modify the PRS-based genetic risk of breast cancer.

Prevention Relevance: Although our findings suggest that alcohol drinking does not modify the PRS-based genetic risk of breast cancer among White and Black women with lower alcohol intake, nevertheless, women should consider limiting alcohol consumption as a general cancer prevention strategy, as indicated in dietary guidelines.
The Tumor Immune Microenvironment and Therapeutic Efficacy of Trastuzumab Deruxtecan in Gastric Cancer
Authors: Koganemaru Shigehiro , Koyama Shohei , Suto Fumitaka , Koga Makito , Inaki Koichiro , Kuwahara Yusuke , Arita Takeo , Hirata Tsuyoshi , Goto Hiroki , Wada Naoya , Kobayashi Maki , Shibutani Tomoko , Okabayashi Tatsuya , Nakamaru Kenji , Kawazoe Akihito , Togashi Yousuke , Nishikawa Hiroyoshi , Shitara Kohei
Published: December 2024

Trastuzumab deruxtecan (T-DXd), an anti-HER2 antibody–drug conjugate with a topoisomerase I inhibitor connected by a cleavable linker, has been approved for patients with HER2-positive gastric or gastroesophageal junction tumors. This biomarker study assessed HER2 expression and immune cell infiltration in relation to the therapeutic response to T-DXd. This retrospective analysis included samples from patients treated with T-DXd in three clinical trials. We performed RNA sequencing and multiplex IHC on archival tumor samples obtained at baseline, during treatment, and after treatment. Flow cytometry was performed on tumor-infiltrating immune cells freshly isolated from tumor tissues. Samples from 28 patients were included in this study. ERBB2 mRNA levels and CD20+ cell infiltration in tumors were significantly higher at baseline in responders than in nonresponders. Patients were classified into three biological groups based on their baseline tumor/stroma-infiltrating immune cell densities. Two groups reported similar response rates, but a trend was observed toward a shorter progression-free survival in the group with more immunosuppressive regulatory T cells and PD-L1 expression at baseline. T-DXd treatment tended to increase the levels of tumor-infiltrating CD8+ T cells and PD1+CD8+ T cells, particularly in responders. Gene expression signatures of CTL and Th cells increased during treatment, whereas signatures related to hypoxia, MYC targets, collagen formation, and IL-10 were downregulated. Our data suggest that HER2 expression levels and baseline tumor microenvironment characteristics correlate with T-DXd efficacy. Furthermore, this treatment may modulate tumor microenvironment immune profiles. Further validation using a larger sample size is warranted.

Significance:

This biomarker study explored HER2 expression levels and immune cell characteristics that may affect response to T-DXd using tumor tissue samples collected from clinical trial participants. The results suggest that HER2 expression levels and tumor characteristics before the initiation of T-DXd may correlate with the efficacy of the drug.
Stereotactic Body Radiotherapy in a transplanted lung for a primary lung cancer: Case Report
Authors: Ferreira Pedro , Maia Dionísio , Abdulrehman Miriam
Published: December 2024

Background: Lung cancer in the transplanted organ is an extremely rare occurrence with very few cases reported. The use of stereotactic body radiotherapy (SBRT) for medically inoperable early-stage non-small cell lung cancer (NSCLC) is an option to treat an early-stage lung adenocarcinoma on a transplanted lung.
Case presentation: We report the case of a 63-year-old woman with a history of hypersensitivity pneumonitis, who underwent a right lung transplant in 2010 and developed pulmonary adenocarcinoma, stage IA2, in 2023. The patient was ineligible for surgical management and was referred for SBRT. The treatment was administered with a total dose of 48Gy in 4 fractions in December 2023. The nodule remained stable at 9 months follow-up, with post-radiogenic pneumonitis observed. Pulmonary function remained stable after treatment.
Conclusions: This case shows that SBRT on a transplanted lung cancer seems to be safe, even maintaining a standard SBRT fractionation, with good early local control. Careful consideration of dose, fractionation, and potential toxicities is essential in managing these complex cases, always in close cooperation with the transplant medical team.
Mentorstvo u prevenciji izgaranja kod medicinskih sestara
Authors: Ješić Valentina , Binaj Dafina
Published: December 2024

Uvod: Sindrom izgaranja čest je među medicinskim sestrama zbog kroničnog stresa na radnom mjestu. Karakterizira ga emocionalna iscrpljenost, depersonalizacija i smanjen osjećaj osobnog postignuća. Medicinske sestre svakodnevno se suočavaju s emocionalno i fizički zahtjevnim radnim uvjetima, što rezultira povećanim rizikom od izgaranja. Posljedice ovog sindroma narušavaju ne samo osobno blagostanje medicinskih sestara nego i kvalitetu skrbi koju pružaju pacijentima, smanjujući njihovu radnu učinkovitost i povećavajući rizik od grešaka. U tom kontekstu, mentorstvo se ističe kao ključna strategija za prevenciju izgaranja i način pružanja emocionalne podrške, poticanja profesionalnog razvoja i jačanja vještina za upravljanje stresom, što sve doprinosi većem zadovoljstvu poslom i boljoj kvaliteti skrbi.Metode: Pregledana je relevantna literatura o mentorstvu u prevenciji izgaranja kod medicinskih sestara putem baza Medline, PubMed, ScienceDirect i CINAHL koristeći ključne riječi „mentorship“, „nurses“, „burnout prevention“, „emotional support“ i „professional development“. Uključeni su radovi iz razdoblja 2009.–2024. godine koji proučavaju utjecaj mentorstva na blagostanje i razvoj sestara u bolničkim uvjetima. Isključeni su nerecenzirani i nerelevantni radovi, kao i radovi na jezicima osim engleskog i hrvatskog. Pretraga je usmjerena na strukturirane programe mentorstva i njihove učinke na smanjenje izgaranja te poboljšanje ravnoteže između posla i privatnog života.Rezultati i rasprava: Mentorstvo ima ključnu ulogu u pružanju emocionalne podrške, razvoju vještina suočavanja sa stresom te unapređenju profesionalnog razvoja. Iskusni mentori pomažu medicinskim sestrama razviti emocionalnu inteligenciju, prepoznati stresore i primijeniti strategije suočavanja, čime se smanjuje stopa izgaranja i povećava zadovoljstvo poslom. Mentorstvo također doprinosi jačanju profesionalnog identiteta i ravnoteži između privatnog i profesionalnog života.Zaključak: Strukturirani programi mentorstva ključni su za smanjenje izgaranja kod medicinskih sestara i poboljšanje njihove emocionalne stabilnosti i radnog zadovoljstva, što ima pozitivan utjecaj na kvalitetu skrbi koju pružaju pacijentima.
Transfer i kontratransfer u terapijskom odnosu medicinska sestra – bolesnik
Authors: Vuletin Gović Natali
Published: December 2024

Terapijski odnos medicinska sestra – bolesnik jedinstven je i predstavlja izazov u radu svake medicinske sestre. Svojim interpersonalnim vještinama i razumijevanjem ljudskog ponašanja, medicinska sestra ima izravan utjecaj na smanjivanje anksioznosti kod bolesnika, usredotočuje se na psihološke potrebe bolesnika i primjenjuje empatičnu skrb. Za razvijanje terapijskog odnosa vrlo je važna pojavnost transfera i kontratransfera. Pravovremenim prepoznavanjem transfera i kontratransfera te uključivanjem empatije u sestrinsku praksu moguće je razviti pozitivan predznak transfera i kontratransfera, što u obrnutoj situaciji neprepoznavanja može predstavljati kraj terapijskog odnosa. Usporedba psihoanalitičkog koncepta i koncepta interpersonalnih odnosa ukazuje na važnost holističkog pristupa u suvremenom terapijskom odnosu, kao i na model partnerskog odnosa između bolesnika i medicinske sestre.
Sestrinska uloga u procesu palijativne zdravstvene njege pedijatrijskih onkoloških pacijenata
Authors: Šalov Ana
Published: December 2024

Unatoč sve većem napretku u liječenju malignih bolesti kod djece, neke bolesti ipak nije moguće izliječiti i smrtni je ishod neminovan. Razvojne osobitosti djece te ovisnost o roditeljima zahtijevaju potpuno drugačiji pristup skrbi u odnosu na odrasle pacijente. Iako se palijativna skrb za odrasle i za djecu temelji na istim načelima ublažavanja patnje i usmjerenosti na kvalitetu života, važno je osvijestiti različitost potreba odraslih i djece te im adekvatno pristupiti. Medicinska sestra kao član multidisciplinarnog tima koji je tijekom 24 sata uz pacijenta ima krucijalnu ulogu u prepoznavanju fizičkih i emocionalnih simptoma bolesti i njihovom upravljanju uporabom različitih metoda i alata. Osim za dijete, dijagnoza maligne bolesti vrlo je stresna i za cijelu obitelj djeteta. Važno je da medicinska sestra koja sudjeluje u skrbi ima dobro razvijene komunikacijske vještine udružene s empatijom kako bi adekvatno mogla pružati podršku obitelji oboljelog djeteta tijekom trajanja bolesti i nakon djetetove smrti. Uz emocionalnu inteligenciju i kompetencije koje ima, važno je da medicinska sestra „ide ukorak s vremenom“ kako bi na svojem radnom mjestu pružala visokokvalitetnu skrb pomoću najnovijih smjernica i tehnologija.