bluuebunny/crossref_metadata_2025_split huggingface dataset:
The tumor immune microenvironment remodeling and response to HER2‐targeted therapy in HER2‐positive advanced gastric cancer
Authors: Jiang Lei , Zhao Xingwang , Li Yilin , Hu Yajie , Sun Yu , Liu Shengde , Zhang Zizhen , Li Yanyan , Feng Xujiao , Yuan Jiajia , Li Jian , Zhang Xiaotian , Chen Yang , Shen Lin 
Published: December 2023

AbstractCombination therapy with anti‐HER2 agents and immunotherapy has demonstrated significant clinical benefits in gastric cancer (GC), but the underlying mechanism remains unclear. In this study, we used multiplex immunohistochemistry to assess the changes of the tumor microenvironment in 47 advanced GC patients receiving anti‐HER2 therapy. Additionally, we performed single‐cell transcriptional sequencing to investigate potential cell‐to‐cell communication and molecular mechanisms in four HER2‐positive GC baseline samples. We observed that post‐treated the infiltration of NK cells, CD8+ T cells, and B lymphocytes were significantly higher in patients who benefited from anti‐HER2 treatment than baseline. Further spatial distribution analysis demonstrated that the interaction scores between NK cells and CD8+ T cells, B lymphocytes and M2 macrophages, B lymphocytes and Tregs were also significantly higher in benefited patients. Cell–cell communication analysis from scRNA sequencing showed that NK cells utilized CCL3/CCL4‐CCR5 to recruit CD8+ T cell infiltration. B lymphocytes employed CD74‐APP/COPA/MIF to interact with M2 macrophages, and utilized TNF‐FAS/ICOS/TNFRSR1B to interact with Tregs. These cell–cell interactions contribute to inhibit the immune resistance of M2 macrophages and Tregs. Our research provides potential guidance for the use of anti‐HER2 therapy in combination with immune therapy.
Revisiting the analysis of matched‐pair and stratified experiments in the presence of attrition
Authors: Bai Yuehao , Hsieh Meng Hsuan , Liu Jizhou , Tabord‐Meehan Max 
Published: December 2023

AbstractIn this paper, we revisit some common recommendations regarding the analysis of matched‐pair and stratified experimental designs in the presence of attrition. Our main objective is to clarify a number of well‐known claims about the practice of dropping pairs with an attrited unit when analyzing matched‐pair designs. Contradictory advice appears in the literature about whether or not dropping pairs is beneficial or harmful, and stratifying into larger groups has been recommended as a resolution to the issue. To address these claims, we derive the estimands obtained from the difference‐in‐means estimator in a matched‐pair design both when the observations from pairs with an attrited unit are retained and when they are dropped. We find limited evidence to support the claims that dropping pairs helps recover the average treatment effect, but we find that it may potentially help in recovering a convex‐weighted average of conditional average treatment effects. We report similar findings for stratified designs when studying the estimands obtained from a regression of outcomes on treatment with and without strata fixed effects.
Heterogeneity of weight loss and transcriptomic signatures in pancreatic ductal adenocarcinoma
Authors: Riner Andrea N. , Herremans Kelly M. , Vudatha Vignesh , Han Song , Qu Xufeng , Liu Jinze , Mukhopadhyay Nitai , Freudenberger Devon C. , George Thomas J. , Judge Sarah M. , Judge Andrew R. , Hughes Steven J. , Trevino Jose G. 
Published: December 2023

AbstractBackgroundPancreatic ductal adenocarcinoma (PDAC) is highly associated with cachexia and weight loss, which is driven by the tumour's effect on the body. Data are lacking on differences in these metrics based on PDAC anatomic location. We hypothesize that the primary tumour's anatomic region influences the prevalence and severity of unintentional weight loss.MethodsTreatment naïve patients with PDAC who underwent pancreatectomy at a single institution between 2012 and 2020 were identified retrospectively. Patients with pancreatic head or distal tumours were matched by sex, age, N and T stage. Serologic and anthropometric variables were obtained at the time of diagnosis. Skeletal muscle index (SMI), muscle radiation attenuation (MRA) and adiposity were measured. The primary outcome was presence of significant weight loss [>5% body weight (BW) loss in past 6 months]. Signed rank tests, Cochran Mantel Haenszel tests and Kaplan–Meier survival analysis are presented. RNA‐seq of tumours was performed to explore enriched pathways related to cachexia and weight loss.ResultsPancreatic head tumours (n = 24) were associated with higher prevalence (70.8% vs. 41.7%, P = 0.081) and degree of weight loss (7.9% vs. 2.5%, P = 0.014) compared to distal tumours (n = 24). BMI (P = 0.642), SMI (P = 0.738) and MRA (P = 0.478) were similar between groups. Combining BW loss, SMI and MRA into a composite score, patients with pancreatic head cancers met more criteria associated with poor prognosis (P = 0.142). Serum albumin (3.9 vs. 4.4 g/dL, P = 0.002) was lower and bilirubin (4.5 vs. 0.4 mg/dL, P < 0.001) were higher with pancreatic head tumours. Survival differed by tumour location (P = 0.014) with numerically higher median overall survival with distal tumours (11.1 vs. 21.8 months; P = 0.066). Transcriptomic analysis revealed inactivation of appetite stimulation, weight regulation and nutrient digestion/metabolism pathways in pancreatic head tumours.ConclusionsResectable pancreatic head PDAC is associated with higher prevalence of significant weight loss and more poor prognosis features. Pancreaticobiliary obstruction and hypoalbuminemia in patients with head tumours suggests compounding effects of nutrient malabsorption and systemic inflammation on molecular drivers of cachexia, possibly contributing to shorter survival. Therefore, PDAC‐associated cachexia is a heterogenous syndrome, which may be influenced by the primary tumour location. Select patients with resectable pancreatic head tumours may benefit from nutritional rehabilitation to improve outcomes.
Marked irregular myofiber shape is a hallmark of human skeletal muscle ageing and is reversed by heavy resistance training
Authors: Soendenbroe Casper , Karlsen Anders , Svensson Rene B. , Kjaer Michael , Andersen Jesper L. , Mackey Abigail L. 
Published: December 2023

AbstractBackgroundAge‐related loss of strength is disproportionally greater than the loss of mass, suggesting maladaptations in the neuro‐myo‐tendinous system. Myofibers are often misshaped in aged and diseased muscle, but systematic analyses of large sample sets are lacking. Our aim was to investigate myofiber shape in relation to age, exercise, myofiber type, species and sex.MethodsVastus lateralis muscle biopsies (n = 265) from 197 males and females, covering an age span of 20–97 years, were examined. The gastrocnemius and soleus muscles of 11 + 22‐month‐old male C57BL/6 mice were also examined. Immunofluorescence and ATPase stainings of muscle cross‐sections were used to measure myofiber cross‐sectional area (CSA) and perimeter. From these, a shape factor index (SFI) was calculated in a fibre‐type‐specific manner (type I/II in humans; type I/IIa/IIx/IIb in mice), with higher values indicating increased deformity. Heavy resistance training (RT) was performed three times per week for 3–4 months by a subgroup (n = 59). Correlation analyses were performed comparing SFI and CSA with age, muscle mass, maximal voluntary contraction (MVC), rate of force development and specific force (MVC/muscle mass).ResultsIn human muscle, SFI was positively correlated with age for both type I (R2 = 0.20) and II (R2 = 0.38) myofibers. When subjects were separated into age cohorts, SFI was lower for type I (4%, P < 0.001) and II (6%, P < 0.001) myofibers in young (20–36) compared with old (60–80) and higher for type I (5%, P < 0.05) and II (14%, P < 0.001) myofibers in the oldest old (>80) compared with old. The increased SFI in old muscle was observed in myofibers of all sizes. Within all three age cohorts, type II myofiber SFI was higher than that for type I myofiber (4–13%, P < 0.001), which was also the case in mice muscles (8–9%, P < 0.001). Across age cohorts, there was no difference between males and females in SFI for either type I (P = 0.496/0.734) or II (P = 0.176/0.585) myofibers. Multiple linear regression revealed that SFI, after adjusting for age and myofiber CSA, has independent explanatory power for 8/10 indices of muscle mass and function. RT reduced SFI of type II myofibers in both young and old (3–4%, P < 0.001).ConclusionsHere, we identify type I and II myofiber shape in humans as a hallmark of muscle ageing that independently predicts volumetric and functional assessments of muscle health. RT reverts the shape of type II myofibers, suggesting that a lack of myofiber recruitment might lead to myofiber deformity.
Untangling the nexus between marketization, crop diversity, farmers' wealth and nutrition: The case of Uzbekistan
Authors: Lombardozzi Lorena 
Published: December 2023

AbstractThe effects of marketization on crop diversity and dietary diversity is very contested. Therefore, more empirical work is needed to unpack the multidimensional factors that underpin these processes. This article expands the analytical understanding of the linkages between these dimensions by looking at the case of Uzbekistan. First, it uses quantitative methods to assess the hypotheses that (a) wealth leads to higher dietary diversity; (b) agricultural marketization leads to lower dietary diversity; and (c) crop diversity leads to higher dietary diversity. Regression analysis shows that only wealth is an independent determinant of dietary diversity. Second, the article uses qualitative data to argue that state policies and social norms, by influencing food availability, knowledge and nutritional values, are key to unpacking the relationships between marketization, crop diversity and dietary diversity.
Embracing ethical research: Implementing the 3R principles into fracture healing research for sustainable scientific progress
Authors: Anup Amritha , Dieterich Sandra , Oreffo Richard O. C. , Dailey Hannah L. , Lang Annemarie , Haffner‐Luntzer Melanie , Hixon Katherine R. 
Published: December 2023

AbstractAs scientific advancements continue to reshape the world, it becomes increasingly crucial to uphold ethical standards and minimize the potentially adverse impact of research activities. In this context, the implementation of the 3R principles—Replacement, Reduction, and Refinement—has emerged as a prominent framework for promoting ethical research practices in the use of animals. This article aims to explore recent advances in integrating the 3R principles into fracture healing research, highlighting their potential to enhance animal welfare, scientific validity, and societal trust. The review focuses on in vitro, in silico, ex vivo, and refined in vivo methods, which have the potential to replace, reduce, and refine animal experiments in musculoskeletal, bone, and fracture healing research. Here, we review material that was presented at the workshop “Implementing 3R Principles into Fracture Healing Research” at the 2023 Orthopedic Research Society (ORS) Annual Meeting in Dallas, Texas.
Nitrogen fixation of lablab and finger millet in South‐India
Authors: Mock Andrea , Ingold Mariko , Vazhacharickal Prem Jose , Sourav Suman Kumar , Dittert Klaus , Buerkert Andreas 
Published: December 2023

AbstractBackgroundIn a long‐term rotation experiment (2016–2022) with different nitrogen (N) fertilizer levels in subtropical South‐India, crop yields of low N plots were unexpectedly high. We therefore hypothesized that in the absence of mineral N application, these yields are largely due to N inputs by N2 fixation in the component crops. To assess the diazotrophic N2‐fixation of lablab (Lablab purpureus L. Sweet) and possible associative N2‐fixation of finger millet (Eleusine coracana L. Gaertn), a controlled experiment was conducted during the 2021 monsoon season within the above‐mentioned long‐term field study. Two approaches were used to estimate the quantity of N derived from the atmosphere (Ndfa): the dilution method using a 15N‐labeled fertilizer and the natural abundance method.MethodFor the 15N dilution method irrigated maize (Zea maize L.), finger millet and lablab were labeled with two split applications of 10% 15N fertilizer (50:50 15N‐urea and 15N‐ammonium sulfate) amounting to a total of 15 kg N ha−1. Maize was selected as the non‐fixing reference plant to estimate diazotrophic N2‐fixation. The entire aboveground biomass of the labeled plants was harvested at maturity and analyzed for total DM, N concentration, and the 15N isotope ratio.ResultsN2 fixation efficiency for lablab was 52%–69% depending on the calculation method, corresponding to 40–53 kg N ha−1. For finger millet, the natural abundance method resulted in an estimated N2‐fixation of 5 kg N ha−1, which was suggested by the results of the dilution method whereby the reference plant maize was only poorly labeled.ConclusionLabeling of maize might have been diluted due to unexpected associative N2‐fixation or N‐uptake from unlabeled deep soil N pools. The data underline the importance of symbiotic N2‐fixation in crop rotation systems of South‐India.
Hepatic extravasation of total parenteral nutrition following umbilical venous catheter insertion: A rare complication
Authors: Berger Tal David , Gavri Ayelet , Jesin Stuart , Strauss Tzipi , Weiss Batia 
Published: December 2023

AbstractUmbilical venous catheters are commonly inserted in critically ill newborns and can lead to severe complications when misplaced. We report a preterm female with a prenatal diagnosis of duodenal atresia who presented 2 days after the surgical repair with abdominal distension, hemodynamic instability, elevated liver enzymes with severe cholestatic jaundice, and a hepatic collection on abdominal sonography. An urgent explorative laparotomy demonstrated a large amount of white, milky‐appearing fluid in the abdominal cavity. Together with the sonographic findings, this led to the diagnosis of hepatic total parenteral nutrition extravasation. Upon removal of the umbilical venous catheter line, the infant's clinical state rapidly improved; however, cholestasis continued for months, with a very slow resolution. During follow‐up, the liver enzymes normalized, and a complete resolution of the liver collection was observed, without drainage.
Exploring the Role of Artificial Intelligence Chatbots in Preoperative Counseling for Head and Neck Cancer Surgery
Authors: Lee Jason C. , Hamill Chelsea S. , Shnayder Yelizaveta , Buczek Erin , Kakarala Kiran , Bur Andrés M. 
Published: December 2023

ObjectiveTo evaluate the potential use of artificial intelligence (AI) chatbots, such as ChatGPT, in preoperative counseling for patients undergoing head and neck cancer surgery.Study DesignCross‐Sectional Survey Study.SettingSingle institution tertiary care center.MethodsChatGPT was used to generate presurgical educational information including indications, risks, and recovery time for five common head and neck surgeries. Chatbot‐generated information was compared with information gathered from a simple browser search (first publicly available website excluding scholarly articles). The accuracy of the information, readability, thoroughness, and number of errors were compared by five experienced head and neck surgeons in a blinded fashion. Each surgeon then chose a preference between the two information sources for each surgery.ResultsWith the exception of total word count, ChatGPT‐generated pre‐surgical information has similar readability, content of knowledge, accuracy, thoroughness, and numbers of medical errors when compared to publicly available websites. Additionally, ChatGPT was preferred 48% of the time by experienced head and neck surgeons.ConclusionHead and neck surgeons rated ChatGPT‐generated and readily available online educational materials similarly. Further refinement in AI technology may soon open more avenues for patient counseling. Future investigations into the medical safety of AI counseling and exploring patients' perspectives would be of strong interest.Level of evidenceN/A. Laryngoscope, 134:2757–2761, 2024
Determination of internal target volume with Cine‐MRI sequence for prostate MRI‐Guided radiotherapy
Authors: Wei Ran , Liang Bin , Men Kuo , Qin Shirui , Gao Linrui , Lu Ningning , Dai Jianrong 
Published: December 2023

AbstractBackgroundIn prostate radiotherapy, the intrafractional target motion negatively affects treatment accuracy. Generating internal target volume (ITV) using four‐dimensional (4D) images may resolve the issue of intrafractional target motion induced by bladder filling and bowel movement. However, no 4D imaging techniques suitable for the prostate are currently available in clinical practice.PurposeThis study aimed to determine the ITV based on cine magnetic resonance imaging (MRI) sequence for intrafractional target motion management in prostate MRI‐guided radiotherapy.Materials and MethodsA reference ITV was generated in simulation process. Then, the reference ITV was adapted with cine MRI sequence before online planning in each fraction. Finally, the reference ITV was updated with the cine MRI sequence acquired during beam delivery after each fraction. Cine MRI sequences and positioning three‐dimensional (3D) MRI from 35 patients were retrospectively collected. Clinical target volume (CTV) coverage was computed according to the two‐dimensional contour of CTV and ITV on cine MRI images. Relative target size was calculated as the ratio of the volume of ITV and CTV. Isotropic planning target volume (PTV; 5 mm margin) and anisotropic PTV (3 mm margin in the posterior direction and 5 mm margin in other directions) were generated for comparison.ResultsThe CTV coverage rate of the proposed ITV had a mean value of 98.61% ± 0.51%, whereas the CTV coverage rates of the isotropic and anisotropic PTVs were 97.43% ± 0.41% and 96.58% ± 0.73%, respectively. The proposed ITV had a relative target size of 1.79 ± 0.17, whereas the anisotropic and isotropic PTVs had relative target sizes of 1.92 ± 0.12 and 2.21 ± 0.19, respectively. For both the CTV coverage rate and target relative size, significant differences were observed between the proposed ITV and the other two PTVs (p < 0.05).ConclusionThe ITV achieved higher CTV coverage with smaller size than conventional isotropic and anisotropic PTVs, indicating that it can effectively deal with the intrafractional movement of the prostate.
Technical note: hydrogel‐based mimics of prostate cancer with matched relaxation, diffusion and kurtosis for validating multi‐parametric MRI
Authors: Malyarenko Dariya , Ono Shigeto , Lynch Ted J. E. , Swanson Scott D. 
Published: December 2023

AbstractBackgroundProtocol standardization and optimization for clinical translation of emerging quantitative multiparametric (mp)MRI biomarkers of high‐risk prostate cancer requires imaging references that mimic realistic tissue value combinations for bias assessment in derived relaxation and diffusion parameters.PurposeThis work aimed to develop a novel class of hydrogel‐based synthetic materials with simultaneously controlled quantitative relaxation, diffusion, and kurtosis parameters that mimic in vivo prostate value combinations in the same spatial compartment and allow stable assemblies of adjacent structures.MethodsA set of materials with tunable T2, diffusion, and kurtosis were assembled to create quantitative biomimetic (mp)MRI references. T2 was controlled with variable agarose concentration, monoexponential diffusion by polyvinylpyrrolidone (PVP), and kurtosis by addition of lamellar vesicles. The materials were mechanically stabilized by UV cross‐linked polyacrylamide gels (PAG) to allow biomimetic morphologies. The reference T2 were measured on a 3T scanner using multi‐echo CPMG, and diffusion kurtosis—with multi‐b DWI.ResultsAgarose concentration controls T2 values which are nominally independent of PVP or vesicle concentration. For agarose PVP hydrogels, monoexponential diffusion values are a function of PVP concentration and independent of agarose concentration. Compared to free vesicles, for agarose‐PAG combined with vesicles, diffusion was predominantly controlled by vesicles and PAG, while kurtosis was affected by agarose and vesicle concentration. Both hydrogel classes achieved image voxel parameter values (T2, Da, Ka) for relaxation (T2: 65–255 ms), apparent diffusion (Da: 0.8−1.7 μm2/ms), and kurtosis (Ka: 0.5–1.25) within the target literature ranges for normal prostate zones and cancer lesions. Relaxation and diffusion parameters remained stable for over 6 months for layered material assemblies.ConclusionA stable biomimetic mpMR reference based on hydrogels has been developed with a range of multi‐compartment diffusion and relaxation parameter combinations observed in cancerous and healthy prostate tissue.
Diaphragmatic ultrasonography as a predictor of respiratory muscle fatigue in myasthenia gravis
Authors: Ma Jing , Zhang Huiqiu , Pang Xiaomin , Zhang Jing , Zhao Rongjuan , Wang Juan , Chang Xueli , Guo Junhong , Zhang Wei 
Published: December 2023

AbstractIntroduction/AimsEasy fatigability, the clinical hallmark of generalized myasthenia gravis (GMG), cannot be detected in a dynamic way. The aim of this study was to assess respiratory function dynamically through diaphragmatic ultrasonography (DUS) in GMG patients.MethodsGMG patients and controls were recruited in a 1:1 ratio. DUS was performed during one quiet breath and 15 consecutive deep breaths. The diaphragm thicknesses were measured at different positions. Diaphragm thickening fraction (TFdi) and the maximal change in diaphragm thickness (Tmax) during 15 consecutive deep breaths were calculated and transformed to normality, named N‐TFdi and N‐Tmax, respectively. The percentages of changes in TFdi and Tmax compared with baseline were named ΔTFdi and ΔTmax, respectively. The diagnostic parameter for respiratory muscle fatigue was chosen from ΔTFdi and ΔTmax at different deep breath times according to their ability to distinguish GMG patients from controls and the interrater reliability of TFdi and Tmax.ResultsThirty‐four GMG patients and 30 healthy controls were enrolled. N‐TFdi and N‐Tmax significantly changed as the number of deep breaths increased (p < .001) in GMG patients, but not in controls. ΔTmax of the 15th deep breath (ΔTmax15) was selected as the diagnostic parameter for respiratory muscle fatigue. There were no significant differences in percentage of predicted values of forced vital capacity and arterial partial pressure of carbon dioxide between patients with normal and abnormal ΔTmax15.DiscussionDUS could identify diaphragm fatiguability in GMG patients, which may be more reliable and sensitive in assessment of diaphragm fatigue than conventional methods.