bluuebunny/crossref_metadata_2025_split huggingface dataset:
FGFR4 and EZH2 inhibitors synergistically induce hepatocellular carcinoma apoptosis via repressing YAP signaling
Authors: Yang Yiqi , Zhang Yibo , Cao Jieqiong , Su Zijian , Li Fu , Zhang Peiguang , Zhang Bihui , Liu Rongzhan , Zhang Linhao , Xie Junye , Li Jingsheng , Zhang Jinting , Chen Xiaojia , Hong An 
Published: April 2023

Abstract
Background
Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide, but current treatment options remain limited and cause serious life-threatening side effects. Aberrant FGFR4 signaling has been validated as an oncogenic driver of HCC, and EZH2, the catalytic subunit of the PRC2 complex, is a potential factor that contributes to acquired drug resistance in many tumors, including HCC. However, the functional relationship between these two carcinogenic factors, especially their significance for HCC treatment, remains unclear. In this study, we systematically evaluated the feasibility of a combination therapy targeting FGFR4 and EZH2 for HCC.

Methods
RNA sequencing data of patients with Liver hepatocellular carcinoma (LIHC) from The Cancer Genome Atlas (TCGA) were analyzed to determine FGFR4 and EZH2 expression and their interaction with prognosis. Moreover, the HCC cell lines, zebrafish/mouse HCC xenografts and zebrafish HCC primary tumors were treated with FGFR4 inhibitor (Roblitinib) and/or EZH2 inhibitor (CPI-169) and then subjected to cell proliferation, viability, apoptosis, and tumor growth analyses to evaluate the feasibility of combination therapy for HCC both in vitro and in vivo. Furthermore, RNA-Seq was performed in combination with ChIP-Seq data analysis to investigate the critical mechanism underlying the combination treatment with Roblitinib and CPI-169.

Results
EZH2 accumulated through the non-canonical NF-kB signaling in response to FGFR4 inhibitor treatment, and the elevated EZH2 levels led to the antagonism of HCC against Roblitinib (FGFR4 inhibitor). Notably, knockdown of EZH2 sensitized HCC cells to Roblitinib, while the combination treatment of Roblitinib and CPI-169 (EZH2 inhibitor) synergistically induced the HCC cell apoptosis in vitro and suppressed the zebrafish/mouse HCC xenografts and zebrafish HCC primary tumors development in vivo. Moreover, Roblitinib and CPI-169 synergistically inhibited HCC development via repressing YAP signaling.

Conclusions
Collectively, our study highlighted the potential of the therapeutic combination of FGFR4 and EZH2 inhibitors, which would provide new references for the further development of clinical treatment strategies for HCC.
Knockdown of heat shock protein family D member 1 (HSPD1) promotes proliferation and migration of ovarian cancer cells via disrupting the stability of mitochondrial 3-oxoacyl-ACP synthase (OXSM)
Authors: Duan Yaoyun , Yu Juan , Chen Miaojuan , Lu Qinsheng , Ning Fen , Gan Xiaowen , Liu Hanbo , Ye Yixin , Lu Shenjiao , Lash Gendie E. 
Published: April 2023

Abstract
Background
Heat shock protein 60 (HSP60) is essential for the folding and assembly of newly imported proteins to the mitochondria. HSP60 is overexpressed in most types of cancer, but its association with ovarian cancer is still in dispute. SKOV3 and OVCAR3 were used as experimental models after comparing the expression level of mitochondrial HSP60 in a normal human ovarian epithelial cell line and four ovarian cancer cell lines.

Results
Low HSPD1 (Heat Shock Protein Family D (HSP60) Member 1) expression was associated with unfavorable prognosis in ovarian cancer patients. Knockdown of HSPD1 significantly promoted the proliferation and migration of ovarian cancer cells. The differentially expressed proteins after HSPD1 knockdown were enriched in the lipoic acid (LA) biosynthesis and metabolism pathway, in which mitochondrial 3-oxoacyl-ACP synthase (OXSM) was the most downregulated protein and responsible for lipoic acid synthesis. HSP60 interacted with OXSM and overexpression of OXSM or LA treatment could reverse proliferation promotion mediated by HSPD1 knockdown.

Conclusions
HSP60 interacted with OXSM and maintained its stability. Knockdown of HSPD1 could promote the proliferation and migration of SKOV3 and OVCAR3 via lowering the protein level of OXSM and LA synthesis.
Treatment for ovarian clear cell carcinoma with combined inhibition of WEE1 and ATR
Authors: Chien Wenwen , Tyner Jeffrey W. , Gery Sigal , Zheng Yueyuan , Li Li-Yan , Gopinatha Pillai Mohan Shankar , Nam Chehyun , Bhowmick Neil A. , Lin De-Chen , Koeffler H. Phillip 
Published: April 2023

Abstract
Background
Standard platinum-based therapy for ovarian cancer is inefficient against ovarian clear cell carcinoma (OCCC). OCCC is a distinct subtype of epithelial ovarian cancer. OCCC constitutes 25% of ovarian cancers in East Asia (Japan, Korea, China, Singapore) and 6–10% in Europe and North America. The cancer is characterized by frequent inactivation of ARID1A and 10% of cases of endometriosis progression to OCCC. The aim of this study was to identify drugs that are either FDA-approved or in clinical trials for the treatment of OCCC.

Results
High throughput screening of 166 compounds that are either FDA-approved, in clinical trials or are in pre-clinical studies identified several cytotoxic compounds against OCCC. ARID1A knockdown cells were more sensitive to inhibitors of either mTOR (PP242), dual mTOR/PI3K (GDC0941), ATR (AZD6738) or MDM2 (RG7388) compared to control cells. Also, compounds targeting BH3 domain (AZD4320) and SRC (AZD0530) displayed preferential cytotoxicity against ARID1A mutant cell lines. In addition, WEE1 inhibitor (AZD1775) showed broad cytotoxicity toward OCCC cell lines, irrespective of ARID1A status.

Conclusions
In a selection of 166 compounds we showed that inhibitors of ATR and WEE1 were cytotoxic against a panel of OCCC cell lines. These two drugs are already in other clinical trials, making them ideal candidates for treatment of OCCC.
Hypertonic sodium lactate infusion reduces vasopressor requirements and biomarkers of brain and cardiac injury after experimental cardiac arrest
Authors: Annoni Filippo , Su Fuhong , Peluso Lorenzo , Lisi Ilaria , Caruso Enrico , Pischiutta Francesca , Gouvea Bogossian Elisa , Garcia Bruno , Njimi Hassane , Vincent Jean-Louis , Gaspard Nicolas , Ferlini Lorenzo , Creteur Jacques , Zanier Elisa R. , Taccone Fabio Silvio 
Published: April 2023

Abstract
Introduction
Prognosis after resuscitation from cardiac arrest (CA) remains poor, with high morbidity and mortality as a result of extensive cardiac and brain injury and lack of effective treatments. Hypertonic sodium lactate (HSL) may be beneficial after CA by buffering severe metabolic acidosis, increasing brain perfusion and cardiac performance, reducing cerebral swelling, and serving as an alternative energetic cellular substrate. The aim of this study was to test the effects of HSL infusion on brain and cardiac injury in an experimental model of CA.

Methods
After a 10-min electrically induced CA followed by 5 min of cardiopulmonary resuscitation maneuvers, adult swine (n = 35) were randomly assigned to receive either balanced crystalloid (controls, n = 11) or HSL infusion started during cardiopulmonary resuscitation (CPR, Intra-arrest, n = 12) or after return of spontaneous circulation (Post-ROSC, n = 11) for the subsequent 12 h. In all animals, extensive multimodal neurological and cardiovascular monitoring was implemented. All animals were treated with targeted temperature management at 34 °C.

Results
Thirty-four of the 35 (97.1%) animals achieved ROSC; one animal in the Intra-arrest group died before completing the observation period. Arterial pH, lactate and sodium concentrations, and plasma osmolarity were higher in HSL-treated animals than in controls (p < 0.001), whereas potassium concentrations were lower (p = 0.004). Intra-arrest and Post-ROSC HSL infusion improved hemodynamic status compared to controls, as shown by reduced vasopressor requirements to maintain a mean arterial pressure target > 65 mmHg (p = 0.005 for interaction; p = 0.01 for groups). Moreover, plasma troponin I and glial fibrillary acid protein (GFAP) concentrations were lower in HSL-treated groups at several time-points than in controls.

Conclusions
In this experimental CA model, HSL infusion was associated with reduced vasopressor requirements and decreased plasma concentrations of measured biomarkers of cardiac and cerebral injury.
Smell and taste of milk during tube feeding of preterm infants: neurodevelopmental follow-up of the randomized TASTE trial, study protocol
Authors: Beker Friederike , Hughes Ian P. , Jacobs Sue , Liley Helen G. , Bora Samudragupta , Simcock Gabrielle , Davis Peter G. 
Published: April 2023

Abstract
Background
The Taste And Smell To Enhance nutrition (TASTE) trial investigated the effects of smell and taste of milk with tube feeding compared to routine care on the growth of preterm infants. There was no difference between groups in growth (weight, head circumference, length) z-scores at discharge from the hospital. Infants in the intervention group had higher head circumference and length z-scores at 36 weeks postmenstrual age, both secondary outcomes. The objective of this follow-up study is to assess 2-year neurodevelopmental and growth outcomes after exposure of preterm infants to the smell and taste of milk with tube feeding compared to routine care.

Methods
This is a neurodevelopmental follow-up study of a two-center, placebo-controlled randomized trial. Infants born before 29 weeks postmenstrual age and/or with a birth weight of less than 1250 g were randomized to smell and taste of milk with each tube feed or routine care. The current follow-up assessed the 2-year neurodevelopmental and growth outcomes of participants of the TASTE trial discharged from the hospital (n = 334). The primary outcome is survival free of any major neurodevelopmental impairment comprising any moderate/severe cerebral palsy (Gross Motor Function Classification System score II–V), Bayley Scales of Infant and Toddler Development, Third/Fourth Edition (Bayley-III/Bayley-4) motor, cognitive, or language scores < -2SD, blindness, or deafness at 2 years of age. Other outcomes include death, breastfeeding within the first year, and respiratory support, oral feeding, and anthropometric parameters at 2 years of age. The Human Research Ethics Committees of Mater Misericordiae Limited and the Royal Women’s Hospital approved the TASTE trial including the neurodevelopmental follow-up described in this protocol.

Discussion
For patients and their families, the neurodevelopmental outcomes of preterm infants are of utmost importance. Consequently, they should be investigated following any interventional study performed during the newborn period. Furthermore, improved weight gain and head growth in the hospital are associated with better long-term neurodevelopmental outcomes. Smelling and tasting of milk is an uncomplicated and cost-effective intervention that may improve the growth and neurodevelopmental outcomes of preterm infants. Potential limitations affecting this follow-up study, caused by the COVID-19 pandemic, are anticipated and discussed in this protocol.

Trial registration
Name of the registry: Australian and New Zealand Clinical Trials Registry; Registration number: ACTRN12617000583347; Registration date: 26 April 2017.
A novel spectrophotometric approach relies on a charge transfer complex between atomoxetine with quinone-based π-acceptor. Application to content uniformity test
Authors: Abu-hassan Ahmed A. 
Published: April 2023

AbstractAtomoxetine (ATO) belongs to psychoanaleptic drugs and is utilized in attention-deficit hyperactivity syndrome treatment. In this study, two facile and selective approaches are implemented for the spectrophotometric analysis of atomoxetine. The two approaches rely on charge transfer formed between ATO base (n-donor) with p-chloranil and 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ; π-acceptor). The generated complexes exhibit absorption intensity maxima at 550 and 460 nm in acetonitrile for p-chloranil and DDQ in the order. Under the optimum reaction condition, Beer’s law was followed for p-chloranil and DDQ at concentrations of 30–320 and 10–80 µg mL− 1, respectively. The ICH guidelines were followed for work validation, and the outcomes were excellent and satisfactory. The assessment of ATO in pharmaceutical capsules using the suggested procedures was successful, and the results were contrasted with those obtained using a different published method to show accuracy and precision. Additionally, the two methods were used to assess the homogeneity of ATO content in the commercialized capsule.
Pilot study: validity and reliability of textile insoles used to measure the characteristics of landing tasks during rehabilitation and artistic gymnastics
Authors: Schümperlin Delia , Schärer Christoph , Kalberer Luzia , Ferguson Stephen J. , Lorenzetti Silvio R. 
Published: April 2023

AbstractObjectivesArtistic gymnastics is a sport where most athletes start at an early age and training volumes are high. Hence, overuse and acute injuries are frequent due to the load endured during landing tasks. During landing, the ground reaction force (GRF) is up to 15.8 times the body weight and therefore reliable GRF measurements are crucial. The gold standard for GRF measurements are force plates. As force plates are mostly used in a constrained laboratory environment, it is difficult to measure the GRF in representative training settings. Textile insoles (novel GmbH, Munich, Germany) exist, which can be used to measure dynamic GRF. Hence, the motivation of this study is to test the validity and reliability of these insoles during landing tasks. GRF was measured during four different exercises, in two test subjects and compared to concurrent force plate data.ResultsTwelve out of 16 statistical parametric mapping plots showed no significant difference between the measured force curves of insoles and force plates. Across conditions, the root mean square error of the maximal vertical GRF was 21 N/kg and an impulse 0.4 Ns/kg. The intraclass correlation coefficient (ICC 2,1) ranged from 0.02 to 0.76 for maximal vertical GRF and from − 0.34 to 0.76 for impulse. The insoles are a valid measurement tool for GRF curve progression and impulse during landing but underestimate the maximal vertical GRF.
Bilateral distal Achilles tendon sleeve avulsion: a case report
Authors: Mohd Rothi Illina , Åkerback Mikael , Bister Ville 
Published: April 2023

Abstract
Background
While Achilles tendon rupture is a common injury sustained especially in sporting events, distal Achilles tendon rupture is less common. Even rarer is a bilateral traumatic distal Achilles tendon sleeve rupture, with outcomes of such injury unknown. The following case report describes this rare injury, not reported to date elsewhere.

Case
A 57-year-old Finnish man with no predisposing medical history had a traumatic bilateral distal Achilles tendon sleeve avulsion injury. Clinical and radiological evaluation confirmed the diagnosis. Treatment included suture anchors in a modified suture bridge style with customized rehabilitation protocol postoperatively. Symptoms continued to be relieved at 1 year postoperatively.

Conclusion
A modified suture bridge style and meticulous rehabilitation protocol including motivated patient contributed to very satisfying results in this very rare bilateral injury.
New tools for the investigation of muscle fiber-type spatial distributions across histological sections
Authors: Redmond Anna K. , Davies Tilman M. , Schofield Matthew R. , Sheard Philip W. 
Published: April 2023

Abstract
Background
The functional and metabolic properties of skeletal muscles are partly a function of the spatial arrangement of fibers across the muscle belly. Many muscles feature a non-uniform spatial pattern of fiber types, and alterations to the arrangement can reflect age or disease and correlate with changes in muscle mass and strength. Despite the significance of this event, descriptions of spatial fiber-type distributions across a muscle section are mainly provided qualitatively, by eye. Whilst several quantitative methods have been proposed, difficulties in implementation have meant that robust statistical analysis of fiber type distributions has not yielded new insight into the biological processes that drive the age- or disease-related changes in fiber type distributions.

Methods
We review currently available approaches for analysis of data reporting fast/slow fiber type distributions on muscle sections before proposing a new method based on a generalized additive model. We compare current approaches with our new method by analysis of sections of three mouse soleus muscles that exhibit visibly different spatial fiber patterns, and we also apply our model to a dataset representing the fiber type proportions and distributions of the mouse tibialis anterior.

Results
We highlight how current methods can lead to differing interpretations when applied to the same dataset and demonstrate how our new method is the first to permit location-based estimation of fiber-type probabilities, in turn enabling useful graphical representation.

Conclusions
We present an open-access online application that implements current methods as well as our new method and which aids the interpretation of a variety of statistical tools for the spatial analysis of muscle fiber distributions.
Feasibility of conducting qualitative research with persons living with dementia and their caregivers during a home-delivered meals pilot trial
Authors: Gadbois Emily A. , Bunker Jennifer N. , Hilgeman Michelle , Shield Renee , McAuliff Kathleen E. , Mills Whitney , Thomas Kali 
Published: April 2023

Abstract
Background
Among older adults, food insecurity is associated with poor health status and health outcomes; people living with dementia (PLWD) are at increased risk for insecurity. Approaches to addressing food insecurity among homebound older adults include two modes of home-delivered meals: (1) meals delivered daily to participants’ homes by a volunteer or paid driver who socializes with the client or (2) frozen meals that are mailed to participants’ homes. Research has not examined benefits of these meals for PLWD or their caregivers nor compared the effectiveness of these two approaches in reducing food insecurity. The objective of this study was to test the processes for recruiting and engaging in qualitative research with PLWD and caregivers in an effort to understand the context, implementation, and mechanisms of impact by which relationships between meal delivery and outcomes may be achieved in preparation for a larger, follow-on study.

Methods
This is a qualitative sub-study of a pilot, multisite, two-arm pragmatic feasibility trial comparing the effect of two modes of meal delivery on nursing home placement among 243 PLWD. In this sub-study, we tested recruitment and enrollment procedures and piloted interview guides among a subset of participants and caregivers.

Results
We recruited and conducted interviews with nine PLWD and seven caregivers. In testing the informed consent process, all participants were able to consent to be interviewed, and PLWD all demonstrated capacity to consent. We successfully used a cognitive screener to obtain scores of cognitive impairment for PLWD and observed scores indicating a broad range of function. Our interview guides successfully resulted in information about the context, implementation, and mechanisms of impact for meal delivery during the pilot.

Conclusions
In addition to establishing feasibility for the future trial, the substantive findings identified through the qualitative interviews provide an initial understanding of the contextual factors for meal delivery and the potential mechanisms of impact across meal delivery types that warrant further examination in a full-scale trial. Findings from our study provide crucial pilot data to support a follow-on trial to understand how to address food insecurity among PLWD.

Name of the registry
ClinicalTrials.gov

Trial registration
NCT04850781

Date of registration
April 20, 2021, retrospectively registered
https://clinicaltrials.gov/ct2/show/NCT04850781
Long-Term Outcomes of Parathyroid Autografts in Primary Hyperparathyroidism
Authors: Chuki Elias , Graf Akua , Ninan Anisha , Tora Rana , Abijo Tomilowo , Bliss Lynn , Nilubol Naris , Weinstein Lee S , Agarwal Sunita K , Simonds William F , Jha Smita 
Published: April 2023

Abstract

Context
Autologous implantation of parathyroid tissue is frequently utilized after parathyroidectomy in patients with heritable forms of primary hyperparathyroidism (PHPT). Data on long-term functional outcome of these grafts is sparse.

Objective
To investigate long-term outcomes of parathyroid autografts.

Methods
Retrospective study of patients with PHPT who underwent parathyroid autografts from 1991 to 2020.

Results
We identified 115 patients with PHPT who underwent 135 parathyroid autografts. Median follow-up duration since graft was 10 (4-20) years. Of the 111 grafts with known functional outcome, 54 (49%) were fully functional, 13 (12%) partially functional, and 44 (40%) nonfunctional at last follow-up. Age at time of graft, thymectomy prior to autograft, graft type (delayed vs immediate), or duration of cryopreservation did not predict functional outcome. There were 45 (83%) post-graft PHPT recurrences among 54 fully functional grafts at a median duration of 8 (4-15) years after grafting. Surgery was performed in 42/45 recurrences, but cure was attained in 18/42 (43%) only. Twelve of 18 (67%) recurrences were graft-related while remaining 6 (33%) had a neck or mediastinal source. Median time to recurrence was 16 (11-25) years in neck or mediastinal source vs 7 (2-13) years in graft-related recurrences. Median parathyroid hormone (PTH) gradient was significantly higher at 23 (20-27) in graft-related recurrence vs 1.3 (1.2-2.5) in neck or mediastinal source (P = .03).

Conclusions
Post-graft recurrence of PHPT occurs frequently within the first decade after graft and is challenging to localize. Time to recurrence after graft is significantly shorter and PTH gradient higher for graft-related recurrence.
Clinical Trial Number: NCT04969926
Flexibility is a hidden axis of biomechanical diversity in fishes
Authors: Jimenez Yordano E. , Lucas Kelsey N. , Long John H. , Tytell Eric D. 
Published: April 2023

ABSTRACT
Nearly all fish have flexible bodies that bend as a result of internal muscular forces and external fluid forces that are dynamically coupled with the mechanical properties of the body. Swimming is therefore strongly influenced by the body's flexibility, yet we do not know how fish species vary in their flexibility and in their ability to modulate flexibility with muscle activity. A more fundamental problem is our lack of knowledge about how any of these differences in flexibility translate into swimming performance. Thus, flexibility represents a hidden axis of diversity among fishes that may have substantial impacts on swimming performance. Although engineers have made substantial progress in understanding these fluid–structure interactions using physical and computational models, the last biological review of these interactions and how they give rise to fish swimming was carried out more than 20 years ago. In this Review, we summarize work on passive and active body mechanics in fish, physical models of fish and bioinspired robots. We also revisit some of the first studies to explore flexural stiffness and discuss their relevance in the context of more recent work. Finally, we pose questions and suggest future directions that may help reveal important links between flexibility and swimming performance.