bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health-related quality of life and experience measures, to assess patients’ experiences of peripheral intravenous catheters: a secondary data analysis
Authors: Larsen Emily N. , Marsh Nicole , Rickard Claire M. , Mihala Gabor , Walker Rachel M. , Byrnes Joshua 
Published: January 2024

Abstract
Background
Peripheral intravenous catheters (PIVCs) are essential for successful administration of intravenous treatments. However, insertion failure and PIVC complications are common and negatively impact patients’ health-outcomes and experiences. We aimed to assess whether generic (not condition-specific) quality of life and experience measures were suitable for assessing outcomes and experiences of patients with PIVCs.

Methods
We undertook a secondary analysis of data collected on three existing instruments within a large randomised controlled trial, conducted at two adult tertiary hospitals in Queensland, Australia. Instruments included the EuroQol Five Dimension - Five Level (EQ5D-5L), the Functional Assessment of Chronic Illness Therapy – Treatment Satisfaction – General measure (FACIT-TS-G, eight items), and the Australian Hospital Patient Experience Question Set (AHPEQS, 12 items). Responses were compared against two clinical PIVC outcomes of interest: all-cause failure and multiple insertion attempts. Classic descriptives were reported for ceiling and floor effects. Regression analyses examined validity (discrimination). Standardised response mean and effect size (ES) assessed responsiveness (EQ5D-5L, only).

Results
In total, 685 participants completed the EQ5D-5L at insertion and 526 at removal. The FACIT-TS-G was completed by 264 and the AHPEQS by 262 participants. Two FACIT-TS-G items and one AHPEQS item demonstrated ceiling effect. Instruments overall demonstrated poor discrimination, however, all-cause PIVC failure was significantly associated with several individual items in the instruments (e.g., AHPEQS, ‘unexpected physical and emotional harm’). EQ5D-5L demonstrated trivial (ES < 0.20) responsiveness.

Conclusions
Initial investigation of an existing health-related quality of life measure (EQ5D-5L) and two patient-reported experience measures (FACIT-TS-G; AHPEQS) suggest they are inadequate (as a summary measure) to assess outcomes and experiences for patients with PIVCs. Reliable instruments are urgently needed to inform quality improvement and benchmark standards of care.
Follitropin delta combined with menotropin in patients at risk for poor ovarian response during in vitro fertilization cycles: a prospective controlled clinical study
Authors: Duarte-Filho Oscar Barbosa , Miyadahira Eduardo Hideki , Matsumoto Larissa , Yamakami Lucas Yugo Shiguehara , Tomioka Renato Bussadori , Podgaec Sergio 
Published: January 2024

Abstract
Background
The maximum daily dose of follitropin delta for ovarian stimulation in the first in vitro fertilization cycle is 12 μg (180 IU), according to the algorithm developed by the manufacturer, and based on patient’s ovarian reserve and weight. This study aimed to assess whether 150 IU of menotropin combined with follitropin delta improves the response to stimulation in women with serum antimullerian hormone levels less than 2.1 ng/mL.

Methods
This study involved a prospective intervention group of 44 women who received 12 μg of follitropin delta combined with 150 IU of menotropin from the beginning of stimulation and a retrospective control group of 297 women who received 12 μg of follitropin delta alone during the phase 3 study of this drug. The inclusion and exclusion criteria and other treatment and follow-up protocols in the two groups were similar. The pituitary suppression was achieved by administering a gonadotropin-releasing hormone (GnRH) antagonist. Ovulation triggering with human chorionic gonadotropin or GnRH agonist and the option of transferring fresh embryos or using freeze-all strategy were made according to the risk of developing ovarian hyperstimulation syndrome.

Results
Women who received follitropin delta combined with menotropin had higher estradiol levels on trigger day (2150 pg/mL vs. 1373 pg/mL, p < 0.001), more blastocysts (3.1 vs. 2.4, p = 0.003) and more top-quality blastocysts (1.8 vs. 1.3, p = 0.017). No difference was observed in pregnancy, implantation, miscarriage, and live birth rates after the first embryo transfer. The incidence of ovarian hyperstimulation syndrome did not differ between the groups. However, preventive measures for the syndrome were more frequent in the group using both drugs than in the control group (13.6% vs. 0.6%, p < 0.001).

Conclusions
In women with serum antimullerian hormone levels less than 2.1 ng/mL, the administration of 150 IU of menotropin combined with 12 μg of follitropin delta improved the ovarian response, making it a valid therapeutic option in situations where ovulation triggering with a GnRH agonist and freeze-all embryos strategy can be used routinely.

Trial registration
U1111-1247-3260 (Brazilian Register of Clinical Trials, available at https://ensaiosclinicos.gov.br/rg/RBR-2kmyfm).
Long pentraxin 3 and vitamin D receptor mRNA expression pattern of cumulus granulosa cells isolated from PCOS oocytes at different stages of nuclear maturation
Authors: Ersahin Aynur , Celik Onder , Gungor Nur D. , Celik Nilufer , Melil Sureyya , Yardim Meltem , Dalkilic Semih , Ersahin Cenk , Dogukargin Ece , Celik Sudenaz , Akkoc Ramazan F. 
Published: January 2024

Abstract
Background
A fine-tuned pro-inflammatory and anti-inflammatory balance in the follicular unit is essential for cumulus expansion and successful ovulation. While the long pentraxin 3 (PTX3) gene is required for the expansion of cumulus cells (CCs), ovulation, resumption of meiosis and fertilization, the vitamin D receptor gene (VDR-X2) is required for intra-follicle redox balance. This study was planned to determine the expression pattern of VDR-X2 and PTX3 mRNA in CCs isolated from germinal vesicle (GV), metaphase I (MI), and metaphase II (MII) oocytes of PCOS patients with ovulatory dysfunction.

Methods
The relative expression of CC-PTX3 and CC-VDR-X2 mRNA were evaluated using qRT-PCR in a total of 79 CC samples collected from individual cumulus-oocyte complex of 40 infertile patients (20 PCOS and 20 non-PCOS normal responders) who underwent ovarian stimulation with the GnRH antagonist protocol.

Results
Relative PTX3 mRNA expressions of CCMI-control and CCMII-control showed 3- and 9-fold significant upregulation compared to CCGV-control, respectively. The relative PTX3 mRNA expression of CCMII-control increased approximately three fold compared to CCMI-control. Compared to CCGV-pcos, a 3-fold increase was noted in the relative PTX3 mRNA expression of CCMI-pcos and an approximately 4-fold increase in the PTX3 mRNA expression of CCMII-pcos. Relative PTX3 mRNA expression values of CCMII-pcos and CCMI-pcos were similar. A 6-fold upregulation of relative PTX3 mRNA and a 4-fold upregulation of VDR-X2 mRNA were detected in CCMII-control compared to CCMII-pcos. CC-VDR-X2 expression patterns of the PCOS and control groups overlapped with the CC-PTX3 pattern. Fertilization rates of the PCOS group exhibiting failed transcript expression were similar to normal responders.

Conclusion
The fact that relative CC-PTX3 and CC-VDR mRNA expression does not increase during the transition from MI to MII stage in PCOS as in normal responders suggests that PTX3 and VDR expression may be defective in cumulus cells of PCOS patients with ovulatory dysfunction.
The efficacy and safety of direct oral anticoagulants compared with vitamin K antagonist in patients with hypertrophic cardiomyopathy and atrial fibrillation
Authors: Lyu Si-qi , Zhu Jun , Wang Juan , Wu Shuang , Zhang Han , Shao Xing-hui , Yang Yan-min 
Published: January 2024

Abstract
Background
The benefit-risk profile of direct oral anticoagulants (DOAC) therapy in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF) has not been well established yet. This study aimed to evaluate the efficacy and safety of DOAC compared with vitamin K antagonists (VKA) in patients with HCM and AF.

Methods
PubMed, EMBASE, the Cochrane Library, and clinicaltrials.gov were searched to identify studies comparing DOAC with VKA in patients with HCM and AF. The primary endpoint was thromboembolic events. The relative risks and standard errors were pooled by random-effect models using the generic inverse variance method.

Results
Seven observational studies involving 9395 patients were included in this meta-analysis. Compared to the VKA group, the DOAC group displayed a similar risk of thromboembolic events [RR (95%CI): 0.93 (0.73–1.20), p = 0.59] and ischemic stroke [RR (95%CI): 0.65 (0.33–1.28), p = 0.22]. The incidence of major bleeding was comparable between the two groups [RR (95%CI): 0.75 (0.49–1.15), p = 0.19]. Meanwhile, DOAC therapy was superior to VKA therapy in reducing the incidences of all-cause death [RR (95%CI): 0.44 (0.35–0.55), p < 0.001], cardiovascular death [RR (95%CI): 0.41 (0.22–0.75), p = 0.004], and intracranial hemorrhage [RR (95%CI): 0.42 (0.24–0.74), p = 0.003].

Conclusion
In patients with HCM and AF, DOAC therapy was similar to VKA therapy in reducing the risk of thromboembolic events, without increasing bleeding risk. In addition, the DOAC group displayed significant advantages in reducing mortality and intracranial hemorrhage compared with the VKA group. Further randomized controlled trials are needed to provide more evidence for DOAC therapy in this population.
CXXC5 mitigates P. gingivalis-inhibited cementogenesis by influencing mitochondrial biogenesis
Authors: Ma Li , Wang Huiyi , Huang Xin , Huang Hantao , Peng Yan , Liu Heyu , Wang Xiaoxuan , Cao Zhengguo 
Published: January 2024

Abstract
Background
Cementoblasts on the tooth-root surface are responsible for cementum formation (cementogenesis) and sensitive to Porphyromonas gingivalis stimulation. We have previously proved transcription factor CXXC-type zinc finger protein 5 (CXXC5) participates in cementogenesis. Here, we aimed to elucidate the mechanism in which CXXC5 regulates P. gingivalis-inhibited cementogenesis from the perspective of mitochondrial biogenesis.

Methods
In vivo, periapical lesions were induced in mouse mandibular first molars by pulp exposure, and P. gingivalis was applied into the root canals. In vitro, a cementoblast cell line (OCCM-30) was induced cementogenesis and submitted for RNA sequencing. These cells were co-cultured with P. gingivalis and examined for osteogenic ability and mitochondrial biogenesis. Cells with stable CXXC5 overexpression were constructed by lentivirus transduction, and PGC-1α (central inducer of mitochondrial biogenesis) was down-regulated by siRNA transfection.

Results
Periapical lesions were enlarged, and PGC-1α expression was reduced by P. gingivalis treatment. Upon apical inflammation, Cxxc5 expression decreased with Il-6 upregulation. RNA sequencing showed enhanced expression of osteogenic markers, Cxxc5, and mitochondrial biogenesis markers during cementogenesis. P. gingivalis suppressed osteogenic capacities, mitochondrial biogenesis markers, mitochondrial (mt)DNA copy number, and cellular ATP content of cementoblasts, whereas CXXC5 overexpression rescued these effects. PGC-1α knockdown dramatically impaired cementoblast differentiation, confirming the role of mitochondrial biogenesis on cementogenesis.

Conclusions
CXXC5 is a P. gingivalis-sensitive transcription factor that positively regulates cementogenesis by influencing PGC-1α-dependent mitochondrial biogenesis.
Liver damage profile in COVID-19 pregnant patients
Authors: Januszewski Marcin , Ziuzia-Januszewska Laura , Kudan Michal , Pluta Kamil , Klapaczyński Jakub , Wierzba Waldemar , Maciejewski Tomasz , Jakimiuk Alicja A. , Jakimiuk Artur J. 
Published: January 2024

Abstract
Introduction
SARS-CoV-2 unsparingly impacts all areas of medicine. Pregnant women are particularly affected by the pandemic and COVID-19 related liver damage seems to be another threat to maternal and fetal health. The aim of this study is to define liver damage profile including bile acids serum levels in COVID-19 pregnant patients and to determine predictors of disease aggravation and poor obstetrics outcomes.

Methods
This study has been carried out in the Obstetrics and Gynecology Department, at the National Medical Institute in Warsaw, Poland between 01.02.2021 and 01.11.2022 The study cohort comprises 148 pregnant patients with COVID-19 and 102 pregnant controls who has been tested negative for SARS-CoV-2.

Results
COVID-19 pregnant patients presented liver involvement at admission in 41,9%. Hepatotoxic damage accounted for 27 (19.85%), cholestatic type was diagnosed in 11 (8.09%) and mixed type of liver injury was presented in 19 (13.97%) of patients. Higher serum levels of AST, ALT, GGT, total bilirubin and bile acids as well as mixed type of liver injury at admission were correlated with severe form of an illness. AST and ALT above upper reference limit as well as hepatotoxic type of liver damage predisposed pregnant patients with COVID-19 to poor obstetrics outcomes.

Conclusion
Hepatic damage in pregnant women with COVID-19 is a common, mild, transaminase-dominant, or mixed type of injury, and often correlates with elevated inflammatory markers. SARS-CoV-2 test should be performed as a part of differential diagnosis in elevated liver function tests. Although bile acids serum levels were commonly elevated they seems to be clinically irrelevant in terms of pregnancy outcomes.
Transfer of cGAMP from neuron to microglia activates microglial type I interferon responses after subarachnoid hemorrhage
Authors: Chang Hanxiao , Li Zheng , Zhang Weiwei , Lin Chao , Shen Yuqi , Zhang Guangjian , Mao Lei , Ma Chencheng , Liu Ning , Lu Hua 
Published: January 2024

AbstractPrimary subarachnoid hemorrhage (SAH) is a type of acute stroke, accounting for approximately 10% of cases, with high disability and mortality rate. Early brain injury (EBI) is a critical factor in determining SAH mortality; however, there are no effective treatment interventions for EBI. Based on our results, the transmission of cyclic GMP-AMP (cGAMP) from neurons to microglia is a key molecular event that triggers type I interferon response, amplifies neuroinflammation, and leads to neuronal apoptosis. Abnormal intracytoplasmic mitochondrial DNA (mtDNA) is the initiating factor of the cGAS-cGAMP-STING signaling axis. Overall, the cGAS-cGAMP-STING signaling axis is closely associated with neuroinflammation after subarachnoid hemorrhage. Targeting cGAS triggered by cytoplasmic mtDNA may be useful for comprehensive clinical treatment of patients after SAH. Further studies targeting cGAS-specific antagonists for treating SAH are warranted.
Macrophages reprogramming driven by cancer-associated fibroblasts under FOLFIRINOX treatment correlates with shorter survival in pancreatic cancer
Authors: Hussain Zainab , Bertran Thomas , Finetti Pascal , Lohmann Eugenie , Mamessier Emilie , Bidaut Ghislain , Bertucci François , Rego Moacyr , Tomasini Richard 
Published: January 2024

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) remains a clinically challenging cancer, mainly due to limited therapeutic options and the presence of a highly prominent tumor microenvironment (TME), facilitating tumor progression. The TME is predominated by heterogeneous populations of cancer-associated fibroblasts (CAFs) and tumor associated macrophages (TAMs), in constant communication with each other and with tumor cells, influencing many tumoral abilities such as therapeutic resistance. However how the crosstalk between CAFs and macrophages evolves following chemotherapeutic treatment remains poorly understood, limiting our capacity to halt therapeutic resistance.

Methods
We combined biological characterization of macrophages indirectly cocultured with human PDAC CAFs, under FOLFIRINOX treatment, with mRNAseq analyses of such macrophages and evaluated the relevance of the specific gene expression signature in a large series of primary PDAC patients to search for correlation with overall survival (OS) after FOLFIRINOX chemotherapy.

Results
Firstly, we demonstrated that CAFs polarize naïve and M1 macrophages towards an M2-like phenotype with a specific increase of CD200R and CD209 M2 markers. Then, we demonstrated that CAFs counteract the pro-inflammatory phenotype induced by the FOLFIRINOX on Macrophages. Indeed, we highlighted that, under FOLFIRINOX, CAFs limit the FOLFIRINOX-induced cell death of macrophages and further reinforce their M2 phenotype as well as their immunosuppressive impact through specific chemokines production. Finally, we revealed that under FOLFIRINOX CAFs drive a specific macrophage gene expression signature involving SELENOP and GOS2 that correlates with shortened OS in FOLFIRINOX-treated PDAC patients.

Conclusion
Our study provides insight into the complex interactions between TME cells under FOLFIRINOX treatment. It suggests potential novel candidates that could be used as therapeutic targets in combination with FOLFIRINOX to prevent and alleviate TME influx on therapeutic resistance as well as biomarkers to predict FOLFIRINOX response in PDAC patients.
Characterization of gastric cancer-stimulated signaling pathways and function of CTGF in cancer-associated fibroblasts
Authors: Choi Kyoung-Min , Kim Boram , Lee Su-Min , Han Jisoo , Bae Ha-Song , Han Su-Bhin , Lee Dagyeong , Ham In-Hye , Hur Hoon , Kim Eunjung , Kim Jae-Young 
Published: January 2024

Abstract
Background
Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment (TME) that play an important role in cancer progression. Although the mechanism by which CAFs promote tumorigenesis has been well investigated, the underlying mechanism of CAFs activation by neighboring cancer cells remains elusive. In this study, we aim to investigate the signaling pathways involved in CAFs activation by gastric cancer cells (GC) and to provide insights into the therapeutic targeting of CAFs for overcoming GC.

Methods
Alteration of receptor tyrosine kinase (RTK) activity in CAFs was analyzed using phospho-RTK array. The expression of CAFs effector genes was determined by RT-qPCR or ELISA. The migration and invasion of GC cells co-cultured with CAFs were examined by transwell migration/invasion assay.

Results
We found that conditioned media (CM) from GC cells could activate multiple receptor tyrosine kinase signaling pathways, including ERK, AKT, and STAT3. Phospho-RTK array analysis showed that CM from GC cells activated PDGFR tyrosine phosphorylation, but only AKT activation was PDGFR-dependent. Furthermore, we found that connective tissue growth factor (CTGF), a member of the CCN family, was the most pronouncedly induced CAFs effector gene by GC cells. Knockdown of CTGF impaired the ability of CAFs to promote GC cell migration and invasion. Although the PDGFR-AKT pathway was pronouncedly activated in CAFs stimulated by GC cells, its pharmacological inhibition affected neither CTGF induction nor CAFs-induced GC cell migration. Unexpectedly, the knockdown of SRC and SRC-family kinase inhibitors, dasatinib and saracatinib, significantly impaired CTGF induction in activated CAFs and the migration of GC cells co-cultured with CAFs. SRC inhibitors restored the reduced expression of epithelial markers, E-cadherin and Zonula Occludens-1 (ZO-1), in GC cells co-cultured with CAFs, as well as CAFs-induced aggregate formation in a 3D tumor spheroid model.

Conclusions
This study provides a characterization of the signaling pathways and effector genes involved in CAFs activation, and strategies that could effectively inhibit it in the context of GC.
Development and content validity of an application to assess 24-hour movement behaviors in 0–4-year-old children involving end-users and key stakeholders: the My Little Moves app
Authors: Arts Jelle , Chinapaw Mai J. M. , Gubbels Jessica S. , Verhoeff Arnoud P. , Brons Annette , Veldman Sanne , Lettink Annelinde , Altenburg Teatske M. 
Published: January 2024

Abstract
Background
Recently, research focus has shifted to the combination of all 24-h movement behaviors (physical activity, sedentary behavior and sleep) instead of each behavior separately. Yet, no reliable and valid proxy-report tools exist to assess all these behaviors in 0–4-year-old children. By involving end-users (parents) and key stakeholders (researchers, professionals working with young children), this mixed-methods study aimed to 1) develop a mobile application (app)-based proxy-report tool to assess 24-h movement behaviors in 0–4-year-olds, and 2) examine its content validity.

Methods
First, we used concept mapping to identify activities 0–4-year-olds engage in. Parents (n = 58) and professionals working with young children (n = 21) generated a list of activities, sorted related activities, and rated the frequency children perform these activities. Second, using multidimensional scaling and cluster analysis, we created activity categories based on the sorted activities of the participants. Third, we developed the My Little Moves app in collaboration with a software developer. Finally, we examined the content validity of the app with parents (n = 14) and researchers (n = 6) using focus groups and individual interviews.

Results
The app has a time-use format in which parents proxy-report the activities of their child, using eight activity categories: personal care, eating/drinking, active transport, passive transport, playing, screen use, sitting/lying calmly, and sleeping. Categories are clarified by providing examples of children’s activities. Additionally, 1–4 follow-up questions collect information on intensity (e.g., active or calm), posture, and/or context (e.g., location) of the activity. Parents and researchers considered filling in the app as feasible, taking 10–30 min per day. The activity categories were considered comprehensive, but alternative examples for several activity categories were suggested to increase the comprehensibility and relevance. Some follow-up questions were considered less relevant. These suggestions were adopted in the second version of the My Little Moves app.

Conclusions
Involving end-users and key stakeholders in the development of the My Little Moves app resulted in a tailored tool to assess 24-h movement behaviors in 0–4-year-olds with adequate content validity. Future studies are needed to evaluate other measurement properties of the app.