bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Serum Bicarbonate Level with Mortality in Patients with Acute Kidney Injury: A Retrospective Cohort Study
Authors: Ling Xiaojing , Liu Linchang , Gao Zhuo , Yu Ying , Gu Junhui , Shan Jing , Qiu Dejun , Cui Yu , Lu Xiaomeng , Liu Dong 
Published: April 2024

ABSTRACT

Background:
Metabolic acidosis due to a decreased level of serum bicarbonate in patients with chronic kidney disease is associated with increased mortality, but the association of serum bicarbonate with outcomes in patients with acute kidney injury (AKI) is uncertain. We investigated the association of serum bicarbonate level with mortality in patients with AKI.

Methods:
The study cohort consisted of 4800 patients diagnosed with AKI at multiple hospitals between September 17, 2013, and April 14, 2014. Smooth curve fitting, threshold effect analysis, and multiple regression analysis were used to assess the relationship between serum bicarbonate and 14-day mortality (primary outcome) and with intensive care unit (ICU) admission, length of hospitalization, and total hospital costs (secondary outcomes).

Results:
Multiple regression analysis, adjusting for confounding factors, demonstrated a U-shaped association between serum bicarbonate levels and AKI mortality. The lowest mortality rate was observed in patients with a bicarbonate level of 26.9 mmol/L, while greater rates were observed in those with lower and higher levels. Additionally, patients with AKI exhibiting high serum bicarbonate levels (> 26.9 mmol/L) had a significantly lower rate of ICU admission and a shorter hospital stay compared to those with low serum bicarbonate levels (< 26.9 mmol/L).

Conclusion:
A serum bicarbonate level of 26–29 mmol/L in patients with AKI is associated with a lower 14-day mortality rate, with the lowest rate observed at a serum bicarbonate level of 26.9 mmol/L. Prospective clinical studies are needed to determine whether optimizing the serum bicarbonate level can decrease mortality in this population.
Development and validation of models for predicting mortality in intertrochanteric fracture surgery patients with perioperative blood transfusion: a prospective multicenter cohort study
Authors: Guo Junfei , Geng Qian , Xu Ke , Jing Wensen , Li Zheng , He Jinwen , Pan Ying , Li Yanan , Wang Tao , Long Yubin , Hou Zhiyong , Xu Xin , Xu Peng 
Published: April 2024

Background:
The association between allogenic blood transfusions and all-cause mortality in surgically treated hip fracture patients with perioperative transfusion (STHFPT) remained unknown. The authors aim to introduce transfusion-related factors, new variables to develop, and validate models to predict mortality in these patients.

Methods:
A prospective multicenter cohort study was conducted with STHFPT hospitalized during January 2018 and June 2021. The database was divided into training cohort and validation cohort in a ratio of 70–30% using the randomization method. All participants received a minimum of 2-year follow-up and all participants’ overall and eight time-specific survival status were recorded. Prediction models were developed using multivariate logistic regression and Cox regression for variable selection. Model performance was measured by determining discrimination, calibration, overall model performance or precision, and utility. Sensitivity analyses were performed to test robustness of the results.

Results:
A total of 7074 consecutive patients were prospectively screened and assessed for eligibility to participate. Finally, 2490 patients met our inclusion and exclusion criteria and 1743 (70%) patients were randomized to the training cohort and 747 (30%) to the validation cohort. The median duration of follow-up was 38.4 months (IQR 28.0–62.0). Our novel models highlight that preoperative transfusion is of significance for short-term mortality while mid-term outcomes are predominantly determined by severe complications, pulmonary complications, and advanced age. Our models showed high discriminative power, good calibration, and precision for mortality prediction in both training and validation cohorts, especially in short-term mortality prediction.

Conclusions:
The authors introduce transfusion-related factors, new variables to develop, and validate models to predict mortality with STHFPT. The models can be further tested and updated with the ultimate goal of assisting in optimizing individual transfusion strategy.
Endoscopic Submucosal Dissection Criteria for Differentiated-type Early Gastric Cancer Are Applicable to Mixed-type Differentiated Predominant
Authors: Yang Zhen , Yan Jin , Qian Hai-Sheng , Zhong Zi-Hang , Yang Ruo-Yun , Li Ke-Dong , Chen Han , Zhao Yu-Han , Gao Xin , Kong Zi-Hao , Zhang Guo-Xin , Wang Yun 
Published: April 2024

Background:
There is a lack of sufficient evidence on whether mixed-type differentiated predominant early gastric cancer (MD-EGC) can be treated endoscopically by referring to the criteria for differentiated-type early gastric cancer (EGC). This study aims to evaluate the efficacy of endoscopic submucosal dissection (ESD) in MD-EGC.

Methods:
Patients with differentiated-type EGC treated with ESD first from January 2015 to June 2021 were reviewed, including MD-EGC and pure differentiated-type EGC (PD-EGC). Clinical data, including the clinicopathological characteristics, resection outcomes of ESD, and recurrence and survival time, were collected, and the difference between MD-EGC and PD-EGC was tested.

Results:
A total of 48 patients (48 lesions) with MD-EGC and 850 patients (890 lesions) with PD-EGC were included. Compared with PD-EGC, MD-EGC had a higher submucosal invasion rate (37.5% vs. 13.7%, P<0.001) and lymphatic invasion rate (10.4% vs. 0.4%, P<0.001). The rates of complete resection (70.8% vs. 92.5%, P<0.001) and curative resection (54.2% vs. 87.4%, P<0.001) in MD-EGC were lower than those of PD-EGC. Multivariate analysis revealed that MD-EGC (OR 4.26, 95% CI, 2.22-8.17, P<0.001) was an independent risk factor for noncurative resection. However, when curative resection was achieved, there was no significant difference in the rates of recurrence (P=0.424) between the 2 groups, whether local or metachronous recurrence. Similarly, the rates of survival(P=0.168) were no significant difference.

Conclusions:
Despite the greater malignancy and lower endoscopic curative resection rate of MD-EGC, patients who met curative resection had a favorable long-term prognosis.
Impact of a Professional Development Course for Doctoral Nurses and Students on Genomic Conceptual Knowledge and Competencies
Authors: Kronk Rebecca , Kalarchian Melissa , Lutz Calvin 
Published: April 2024

Background:
Universally, nurses’ limited educational opportunities to expand their genomic literacy may have implications on patient care management, research, and training.

Purpose:
To evaluate the impact of a self-paced online course on genomic knowledge and competency acquisition in a sample of nurses possessing a doctoral degree and doctoral students.

Methods:
Pre- and postcourse data were collected using the “Genomic Nursing Concept Inventory” (GNCI) (N = 129) and a self-report survey based on the Essential Genetic and Genomic Competencies for Nurses with Graduate Degrees (N = 131).

Results:
GNCI scores in all 4 topical categories and in 9 of the 16 domains significantly improved. All Genetic Competency scores significantly improved. Significant correlations were observed between Genetic Competency self-ratings and GNCI scores precourse and change of scores.

Conclusions:
The positive outcomes should encourage the development of more accessible educational opportunities for nurses and other healthcare professionals to improve genomic literacy and competency.
Topical Application of TT-10 Ameliorates Impaired Wound Healing
Authors: Liu Yangdan , Ho Chiakang , Wen Dongsheng , Zhou Zhiyuan , Tsai Tingyu , Sun Jiaming , Liu Yuxin , Gao Ya , Li Qingfeng , Zhang Yifan 
Published: April 2024

Background:
In recent decades, chronic wounds have become an increasingly significant clinical concern because of their increasing morbidity and socioeconomic toll. However, there is currently no product available on the market that specifically targets this intricate process. One clear indicator of delayed wound repair is the inhibition of reepithelialization. Yes-associated protein (YAP), which is a potential focal point for tissue repair and regeneration, has been shown to be prominent in several studies. In this context, the authors have identified the pharmacologic product TT-10, which is a YAP activator, as a potential candidate for the treatment of various forms of chronic wounds.

Methods:
The role of TT-10 in regulating YAP activity and subcellular localization was determined by Western blotting and immunofluorescence staining. The effect of TT-10 on the biological functions of keratinocytes was assessed by proliferation, wound healing, and apoptosis assays. The impairment of YAP activity in chronic wounds was measured in human and mouse tissues. The in vivo efficacy of TT-10 was examined by gross examination; hematoxylin and eosin staining; and measuring wound areas and gaps in normal, diabetic, and ischemic wounds.

Results:
The authors’ findings suggest that TT-10 facilitates the nuclear transport of YAP, consequently increasing YAP activity, which in turn increases the proliferation and migration of keratinocytes. Moreover, the authors showed that intracutaneous injection of TT-10 along the wound periphery promoted reepithelialization by means of YAP activation in the epidermis, culminating in accelerated wound closure in several chronic wound healing models.

Conclusion:
The authors’ research highlights the potential of TT-10 to treat chronic wounds, which is a persistent challenge in tissue repair.

Clinical Relevance Statement:
The authors’ research identifies TT-10, a small molecule YAP activator, as a novel therapeutic candidate that enhances keratinocyte function and promotes reepithelialization, offering plastic surgeons an innovative approach to addressing chronic wound challenges.
“Loss of Bone Signal” on 99mTc-Labeled Pyrophosphate Scintigraphy in a Patient With Wild-Type Transthyretin Amyloidosis
Authors: Takahashi Koji , Sasaki Daisuke , Iwamura Takaaki , Sakaue Tomoki , Okura Takafumi 
Published: April 2024

Abstract

99mTc-3,3-diphosphono-1,2-propanedicarboxylic acid (DPD) scintigraphy and 99mTc-pyrophosphate (PYP) scintigraphy are highly sensitive modalities for imaging both myocardial and extracardiac amyloid transthyretin in patients with wild-type transthyretin (ATTRwt) amyloidosis. “Loss of bone signal” on planar imaging of 99mTc-DPD scintigraphy, in which the tracer uptake in bone is obscured by marked tracer uptake in the overlying skeletal muscles, is reported. However, this phenomenon has not yet been documented on 99mTc-PYP scintigraphy. We describe an 89-year-old woman with ATTRwt amyloidosis in whom “loss of bone signal” together with marked tracer uptake into the skeletal muscles was clearly demonstrated on 99mTc-PYP scan.
Genomic and Transcriptomic Landscape of RET Wild-Type Medullary Thyroid Cancer and Potential Use of Mitogen-Activated Protein Kinase-Targeted Therapy
Authors: Darabi Sourat , Adeyelu Tolulope , Elliott Andrew , Sukari Ammar , Hodges Kurt , Abdulla Farah , Zuazo Carlos E , Wise-Draper Trisha , Wang Thomas , Demeure Michael J 
Published: April 2024

BACKGROUND:
About 75% of medullary thyroid cancers (MTCs) are sporadic with 45% to 70% being driven by a RET mutation. Selpercatinib is an approved treatment for RET-mutated (mutRET) MTC; however, treatments are needed for wild-type RET MTC (wtRET). Genomic alterations and transcriptomic signatures of wtRET MTC may reveal new therapeutic insights.

STUDY DESIGN:
We did a retrospective analysis of MTC samples submitted for DNA/RNA sequencing and programmed cell death ligand 1 expression using immunohistochemistry at a Clinical Laboratory Improvement Amendments/College of American Pathologists-certified laboratory. Tumor microenvironment immune cell fractions were estimated using RNA deconvolution (quanTIseq). Transcriptomic signatures of inflammation and MAP kinase pathway activation scores were calculated. Mann-Whitney U, chi-square, and Fisher’s exact tests were applied (p values adjusted for multiple comparisons).

RESULTS:
The 160-patient cohort included 108 mutRET and 52 wtRET MTC samples. wtRET tumors frequently harbored mitogen-activated protein kinase (MAPK) pathway mutations, including HRAS (42.31%), KRAS (15.7%), NF1 (6.7%), and BRAF (2%), whereas only 1 MAPK pathway mutation (NF1) was identified among mutRET MTC. Recurrent mutations seen in wtRET MTC included MGA, VHL, APC, STK11, and NFE2L2. Increased transcriptional activation of the MAPK pathway was observed in patients with wtRET harboring mutations in MAPK genes. Although the frequency of programmed cell death ligand 1 expression was similar in wtRET and mutRET (10.2% vs 7%, p = 0.531), wtRET tumors were more often tumor mutational burden high (7.7% vs 0%, p = 0.011), and wtRET MTC exhibited higher expression of immune checkpoint genes.

CONCLUSIONS:
We identified molecular alterations and immune-related features that distinguish wtRET from mutRET MTC. Although RET mutation drives MTC in the absence of other alterations, we showed that wtRET MTC frequently harbors MAPK pathway mutations. These findings may indicate a potential basis for MAPK-targeted therapy, possibly in combination with immuno-oncology agents for selected patients with wtRET MTC.
MPN Transformation Is Characterized By Heterogeneous Shifts In Lineage Character Resulting In Both HSC-Like And More Differentiated Lineage Signatures
Authors: Menghrajani Kamal , Dilip Deepika , Farnoud Noushin , Famulare Chris , McGovern Erin , Sirenko Maria , Mascarenhas John , Kosiorek Heidi , Hoffman Ronald , Levine Ross , Koche Richard , Rampal Raajit , Glass Jacob 
Published: April 2024

AbstractPhiladelphia chromosome-negative myeloproliferative neoplasms (MPNs) have a propensity to transform to an accelerated or blast phase (MPN-AP/BP). The resulting disease has clinically similar manifestations to Acute Myeloid Leukemia (AML) but worse clinical outcomes. Here we present the first comprehensive description of the transcriptomic characteristics of MPN-AP/BP. Our analysis incorporates data from 261 patients of the BeatAML cohort and 56 MPN-AP/BP patients, 11 of whom had paired samples from before and after transformation. We establish that transformed MPN is a transcriptionally distinct entity from de novo AML and chronic phase MPNs. Genomic pathways traditionally associated with MPN pathogenesis, such as IL2/STAT5 signaling, IL6/JAK/STAT3 signaling, and NUP98/HOXA9 fusions, were enriched in chronic-phase MPNs but are absent in transformed disease, suggesting JAK2 directed therapy may be less effective in this disease phase. We also discovered that gene expression signatures associated with doxorubicin resistance are highly enriched in transformed MPNs, which may explain the lack of efficacy of standard AML therapies. In addition, we identify that lineage composition at the time of transformation may define distinct subsets of MPN-AP/BP patients, which may assist in the future development of novel treatment strategies.Key Points-Accelerated- and blast-phase transformed MPNs are a transcriptionally entities which are distinct from de novo AML.-Transformed MPNs may be characterized by their lineage characteristics, which can drive clinical behavior and account for their inferior overall survival-Gene expression signatures associated with doxorubicin resistance were highly enriched in transformed MPNs, which may explain the lack of effectiveness of anthracycline-based therapies
Developing and testing Advance Choice Document implementation resources for Black African and Caribbean people with experience of compulsory psychiatric admission
Authors: Simpson Jonathan , Babatunde Abigail , Simpson Alan , Gilbert Steven , Ruck Keene Alex , Stephenson Lucy , Chua Kia-Chong , Owen Gareth , Crowe Fiona , Edwards Pauline , Galloway Selena , Fisher Megan , Schilderman Marcela , Bignell Anita , Smith Shubulade , Henderson Claire 
Published: April 2024

AbstractBackgroundAdvance Choice Documents (ACDs) have been recommended for use in England and Wales based on evidence from trials that show that they can reduce involuntary hospitalisation, which disproportionately affects Black African and Caribbean people. Our aim was therefore to develop and test ACD implementation resources and processes for Black people who have previously been involuntarily hospitalised and the people that support them.MethodsResource co-production workshops were held to inform the development of the ACD template and two types of training for all stakeholders, comprising a Recovery College course and simulation training. An ACD facilitator then used the ACD template developed through the workshops to create personalised ACDs with service users and mental health staff over a series of meetings. Interviews were then conducted with service user and staff participants and analysed to document their experience of the process and opinions on ACDs. Other implementation strategies were also employed alongside to support and optimise the creation of ACDs.ResultsNine ACDs were completed and were largely reported as appropriate, acceptable, and feasible to service users and staff. Both reported it being an empowering process that encouraged hope for better future treatment and therefore better wellbeing. Uncertainty was also expressed about the confidence people had that ACDs would be adhered to/honoured, primarily due to staff workload. The information provision training and the skills training were generally considered to be informative by trainees.ConclusionsThe project has developed an ACD creation resource that was reported as agreeable to all stakeholders; however, the generalisability of the findings is limited due to the small sample size. The project also highlights the importance of staff and ACD facilitator capacity and good therapeutic relationships in ACD completion. Further research is needed to determine the adjustments needed for large scale use, including for those under age 18 and those under the care of forensic mental health services; and how to include carers/supporters more in the process.
Can Large Language Models Provide Emergency Medical Help Where There Is No Ambulance? A Comparative Study on Large Language Model Understanding of Emergency Medical Scenarios in Resource-Constrained Settings
Authors: Mensah Paulina Boadiwaa , Quao Nana Serwaa , Dagadu Sesinam ,   Cohort 2, Project Genie Clinician Evaluation Group
Published: April 2024

AbstractThe capabilities of Large Language Models (LLMs) have advanced since their popularization a few years ago. The healthcare sector operates on, and generates a large volume of data annually and thus, there is a growing focus on the applications of LLMs within this sector. There are a few medicine-oriented evaluation datasets and benchmarks for assessing the performance of various LLMs in clinical scenarios; however, there is a paucity of information on the real-world usefulness of LLMs in context-specific scenarios in resourceconstrained settings. In this study, 16 iterations of a decision support tool for medical emergencies using 4 distinct generalized LLMs were constructed, alongside a combination of 4 Prompt Engineering techniques: In-Context Learning with 5-shot prompting (5SP), chain-of-thought prompting (CoT), self-questioning prompting (SQP), and a stacking of self-questioning prompting and chain-of-thought (SQCT). In total 428 model responses were quantitatively and qualitatively evaluated by 22 clinicians familiar with the medical scenarios and background contexts. Our study highlights the benefits of In-Context Learning with few-shot prompting, and the utility of the relatively novel self-questioning prompting technique. We also demonstrate the benefits of combining various prompting techniques to elicit the best performance of LLMs in providing contextually applicable health information. We also highlight the need for continuous human expert verification in the development and deployment of LLM-based health applications, especially in use cases where context is paramount.
Sequential and dynamic coding of water-sucrose categorization in rat gustatory cortices
Authors: Mendoza Germán , Fonseca Esmeralda , Merchant Hugo , Gutierrez Ranier 
Published: April 2024

SummaryThe gustatory system enables our conscious perception of sweetness, allowing us to distinguish sweet solutions from water. However, the neural mechanisms underlying this categorization process in rats remain poorly understood. We addressed this question by designing a novel sucrose categorization task in which rats classified varying sucrose concentrations against water. We found that in the anterior insular cortex (aIC) and orbitofrontal cortex (OFC), neural activity primarily encoded the categorical distinction between sucrose and water, rather than specific sucrose concentrations. Notably, aIC neurons encoded this distinction faster than OFC neurons. Conversely, the OFC slightly preceded the aIC in encoding choice information, although both cortices maintained parallel encoding of the rat’s choices. The encoding of sensory and categorical decisions was dynamic and sequential, forming a sequence of encoding neurons throughout the trial. These findings reveal that sucrose categorization relies on dynamic coding sequences in the neuronal activity of the aIC and OFC rather than static, long-lasting (sustained) neural representations. This dynamic coding, supported by single-cell population decoding and principal component analyses, suggests that the brain continuously updates its representation of sucrose categorization as new information emerges. Additionally, both the aIC and OFC rapidly encoded reward outcomes. Our data supports the notion that gustatory cortices employ sequential and dynamic coding to compute sensorimotor transformations, from taste detection to categorical taste decisions and reward processing.Graphical Abstract
Lightsheet microscopy integrates single-cell optical visco-elastography and fluorescence cytometry of 3D live tissues
Authors: Tomizawa Yuji , Wali Khadija H. , Surti Manav , Suhail Yasir , Kshitiz  , Hoshino Kazunori 
Published: April 2024

AbstractMost common cytometry methods, including flow cytometry, observe suspended or fixed cells and cannot evaluate their structural roles in 3D tissues. However, cellular physical interactions are critical in physiological, developmental, and pathological processes. Here, we present a novel optical visco-elastography that characterizes single-cellular physical interactions by applying in-situ micro-mechanical perturbation to live microtissues under 3D lightsheet microscopy. The 4D digital image correlation (DIC) analysis of ∼20,000 nodes tracked the compressive deformation of 3D tissues containing ∼500 cells. The computational 3D image segmentation allowed cell-by-cell qualitative observation and statistical analysis, directly correlating multi-channel fluorescence and viscoelasticity. To represent epithelia-stroma interactions, we used a 3D organoid model of maternal-fetal interface and visualized solid-like, well-aligned displacement and liquid-like random motion between individual cells. The statistical analysis through our unique cytometry confirmed that endometrial stromal fibroblasts stiffen in response to decidualization. Moreover, we demonstrated in the 3D model that interaction with placental extravillous trophoblasts partially reverses the attained stiffness, which was supported by the gene expression analysis. Placentation shares critical cellular and molecular significance with various fundamental biological events such as cancer metastasis, wound healing, and gastrulation. Our analysis confirmed existing beliefs and discovered new insights, proving the broad applicability of our method.