bluuebunny/crossref_metadata_2025_split huggingface dataset:
Test-retest reliability and validity of vagally-mediated heart rate variability to monitor internal training load in older adults: a within-subjects (repeated-measures) randomized study
Authors: Manser Patrick , de Bruin Eling D. 
Published: June 2024

Abstract
Background
Vagally-mediated heart rate variability (vm-HRV) shows promise as a biomarker of internal training load (ITL) during exergame-based training or motor-cognitive training in general. This study evaluated the test-retest reliability of vm-HRV during exergaming in healthy older adults (HOA) and its validity to monitor ITL.

Methods
A within-subjects (repeated-measures) randomized study was conducted that included baseline assessments and 4 measurement sessions. Participants played 5 exergames at 3 standardized levels of external task demands (i.e., “easy”, “challenging”, and “excessive”) in random order for 90 s. Test-retest reliability was assessed on the basis of repeated-measures analyses of variance (ANOVA), intraclass correlation coefficients (ICC3,1), standard errors of measurement (SEM), and smallest detectable differences (SDD). Validity was determined by examining the effect of game level on vm-HRV in the ANOVA.

Results
Fourty-three HOA (67.0 ± 7.0 years; 58.1% females (25 females, 18 males); body mass index = 23.7 ± 3.0 kg·m−2) were included. Mean R-R time intervals (mRR) and parasympathetic nervous system tone index (PNS-Index) exhibited mostly good to excellent relative test-retest reliability with no systematic error. Mean SEM% and SDD% were 36.4% and 100.7% for mRR, and 44.6% and 123.7% for PNS-Index, respectively. Significant differences in mRR and PNS-Index were observed between standardized levels of external task demands, with mostly large effect sizes (mean r = 0.847). These results persisted irrespective of the type of neurocognitive domain trained and when only motoric and cognitive demands were manipulated while physical intensity was kept constant. The remaining vm-HRV parameters showed inconsistent or poor reliability and validity.

Conclusion
Only mRR and PNS-Index demonstrated reliable measurement and served as valid biomarkers for ITL during exergaming at a group level. Nonetheless, the presence of large SEMs hampers the detection of individual changes over time and suggests insufficient precision of these measurements at the individual level. Future research should further investigate the reliability and validity of vm-HRV with a specific focus on comparing different measurement methodologies and exercise conditions, particularly focusing on ultra-short-term HRV measurements, and investigate the potential implications (i.e., superiority to other markers of ITL or monitoring strategies?) of using vm-HRV as a biomarker of ITL.
PANX1-mediated ATP release confers FAM3A’s suppression effects on hepatic gluconeogenesis and lipogenesis
Authors: Hu Cheng-Qing , Hou Tao , Xiang Rui , Li Xin , Li Jing , Wang Tian-Tian , Liu Wen-Jun , Hou Song , Wang Di , Zhao Qing-He , Yu Xiao-Xing , Xu Ming , Liu Xing-Kai , Chi Yu-Jing , Yang Ji-Chun 
Published: June 2024

Abstract
Background
Extracellular adenosine triphosphate (ATP) is an important signal molecule. In previous studies, intensive research had revealed the crucial roles of family with sequence similarity 3 member A (FAM3A) in controlling hepatic glucolipid metabolism, islet β cell function, adipocyte differentiation, blood pressure, and other biological and pathophysiological processes. Although mitochondrial protein FAM3A plays crucial roles in the regulation of glucolipid metabolism via stimulating ATP release to activate P2 receptor pathways, its mechanism in promoting ATP release in hepatocytes remains unrevealed.

Methods
db/db, high-fat diet (HFD)-fed, and global pannexin 1 (PANX1) knockout mice, as well as liver sections of individuals, were used in this study. Adenoviruses and adeno-associated viruses were utilized for in vivo gene overexpression or inhibition. To evaluate the metabolic status in mice, oral glucose tolerance test (OGTT), pyruvate tolerance test (PTT), insulin tolerance test (ITT), and magnetic resonance imaging (MRI) were conducted. Protein–protein interactions were determined by coimmunoprecipitation with mass spectrometry (MS) assays.

Results
In livers of individuals and mice with steatosis, the expression of ATP-permeable channel PANX1 was increased (P < 0.01). Hepatic PANX1 overexpression ameliorated the dysregulated glucolipid metabolism in obese mice. Mice with hepatic PANX1 knockdown or global PANX1 knockout exhibited disturbed glucolipid metabolism. Restoration of hepatic PANX1 rescued the metabolic disorders of PANX1-deficient mice (P < 0.05). Mechanistically, ATP release is mediated by the PANX1-activated protein kinase B-forkhead box protein O1 (Akt-FOXO1) pathway to inhibit gluconeogenesis via P2Y receptors in hepatocytes. PANX1-mediated ATP release also activated calmodulin (CaM) (P < 0.01), which interacted with c-Jun N-terminal kinase (JNK) to inhibit its activity, thereby deactivating the transcription factor activator protein-1 (AP1) and repressing fatty acid synthase (FAS) expression and lipid synthesis (P < 0.05). FAM3A stimulated the expression of PANX1 via heat shock factor 1 (HSF1) in hepatocytes (P < 0.05). Notably, FAM3A overexpression failed to promote ATP release, inhibit the expression of gluconeogenic and lipogenic genes, and suppress gluconeogenesis and lipid deposition in PANX1-deficient hepatocytes and livers.

Conclusions
PANX1-mediated release of ATP plays a crucial role in maintaining hepatic glucolipid homeostasis, and it confers FAM3A’s suppressive effects on hepatic gluconeogenesis and lipogenesis.
Integrating phylogenetic, phylogeographic, and morphometric analyses to reveal cryptic lineages within the genus Asaccus (Reptilia: Squamata: Phyllodactylidae) in Iran
Authors: Kamali Kamran , Nazarizadeh Masoud , Fatemizadeh Faezeh , Salmabadi Saeed , Hung Chih–Ming , Kaboli Mohammad 
Published: June 2024

AbstractThe Middle Eastern endemic genus Asaccus comprises Southwest Asian leaf-toed geckos. To date, this genus includes 19 species of leaf-toed geckos (seven in Arabia and 12 in the Zagros Mountains). Despite a recent study on the taxonomy and phylogeny of Asaccus species in Iran, controversies still remain surrounding the phylogeny and phylogeography of the genus. Here, we used an integrative approach to determine the phylogeny and phylogeography of Asaccus species using two mitochondrial genes (12 S and Cyt b), and one nuclear gene (c-mos). Our results uncovered 22 distinct lineages, demonstrating a significant cryptic diversity that challenges the current morphological classifications of these species. Phylogenetic analyses reinforce the monophyly of the Asaccus group, positioning A. montanus as a basal lineage, which supports a deep evolutionary divergence dating back to the Late Oligocene, approximately 27.94 million years ago. This genetic diversity also highlights the impact of historical climatic and geographical changes on species diversification. The findings advocate for an integrative approach combining both molecular and morphological data to resolve species identities accurately, thereby enhancing conservation strategies to protect these genetically distinct lineages.
Proactive patient safety: enhancing hospital readiness through simulation-based clinical systems testing and healthcare failure mode and effect analysis
Authors: Hazwani Tarek , Hamam Heba , Caswell Angela , Madkhaly Azza , Al Saif Saif , Al Hassan Zahra , Al Sweilem Reem , Arabi Asma 
Published: June 2024

Abstract
Background
Recognizing and identifying latent safety threats (LSTs) before patient care commences is crucial, aiding leaders in ensuring hospital readiness and extending its impact beyond patient safety alone. This study evaluated the effectiveness of a combination of Simulation-based Clinical Systems Testing (SbCST) with Healthcare Failure Mode and Effect Analysis (HFMEA) with regard to mitigating LSTs within a newly constructed hospital.

Methods
Three phases of the combined SbCST and HFMEA approach were implemented across all hospital settings. The scenarios tested system functionalities, team responses, and resource availability. The threats thus identified were categorized into system-related issues, human issues, and resource issues, after which they were prioritized and addressed using mitigation strategies. Reassessment confirmed the effectiveness of these strategies before hospital commissioning.

Results
More than 76% of the LSTs were mitigated through the combined approach. System-related issues, such as nonfunctional communication devices and faulty elevators, were addressed by leadership. Human issues such as miscommunication and nonadherence to hospital policy led to improvements in interprofessional communication and teamwork. Resource issues, including missing equipment and risks of oxygen explosion, were addressed through procurement, maintenance, and staff training for equipment preparation.

Conclusion
The SbCST and HFMEA were highly effective with regard to proactively identifying and mitigating LSTs across all aspects of hospital preparedness. This systematic and comprehensive approach offers a valuable tool for enhancing patient safety in new healthcare facilities, thereby potentially setting a new standard for proactive hazard identification and risk management in the context of healthcare construction and commissioning.
A case of gallbladder hemangioma detected in a patient with jaundice and suspected Klatskin tumor: case report and review of the literature
Authors: Karahan F. , Atay A. , Ekinci N. , Dilek O. N. 
Published: June 2024

Abstract
Background and objective
The diagnosis and treatment of benign tumors of the gallbladder and bile ducts are difficult due to their anatomical relationships with neighboring vital organs. Hemangiomas are non-epithelial benign tumors of the gallbladder. The gallbladder is an extremely rare localization for cavernous hemangiomas. To date, 7 cases of cavernous gallbladder hemangioma have been reported in the literature. Although it is seen very rarely, the main problem is that it mimics malignant lesions. Pre-operative diagnosis of gallbladder hemangiomas is difficult. Ultrasound (US), computed tomography (CT) magnetic resonance imaging(MRI), endoscopic ultrasound (EUS), and angiography are helpful in differential diagnosis.
Here, we aimed to present our case, which is the first case of cavernous gallbladder hemangioma and obstructive jaundice in the literature.

Case presentation
A 49-year-old female patient was admitted with the complaint of pain in the right upper quadrant of her abdomen. Bilirubin levels were high due to obstructive jaundice. Abdominal CT and MRI showed an appearance in favor of hemangioma in the gallbladder. There was an increase in bile duct wall thickness on MRCP, and it was evaluated as suspicious for malignant neoplasia. The patient was operated on, and extrahepatic bile duct resection + Roux-en-Y hepaticojejunostomy procedure was performed. As a result of histopathology, hemangioma was detected in the gallbladder. There was no malignancy in the bile ducts.

Conclusion
It should be kept in mind that the mass detected in the gallbladder in a patient with jaundice who is suspected of having a bile duct tumor may also be a hemangioma.
Translation, cross-cultural adaptation, and psychometric evaluation of the brief illness perception questionnaire into Yoruba language among persons with chronic low back pain
Authors: Fatoye Francis , Daramola Olusegun Joshua , Oyewole Olufemi Oyeleye , Falade Olatomiwa , Gebrye Tadesse , Idowu Opeyemi , Fatoye Clara , Mbada Chidozie 
Published: June 2024

Abstract
Background
Illness perception may influence the coping behaviors of patients. There is a lack of tools to measure this construct among Yoruba speakers. Therefore, we translate, cross-culturally adapt and determine the reliability and the validity of the Yoruba version of the Brief Illness Perception Questionnaire (BIPQ-Y).

Methods
The translation and cross-cultural adaptation process was according to Beaton criteria. The psychometric testing of the BIPQ-Y was carried out among 28 consenting patients with low back pain attending a university teaching hospital, while only 10 of them participated in the reliability test. The convergent and discriminant validity of the BIPQ-Y was carried out using the Fear Avoidance Belief Questionnaire and Quadruple Visual Analogue scale. Confirmatory factor analysis was to assess construct validity.

Results
The mean age of the respondents was 47 ± 15.3 years. The concurrent validity of the BIPQ-Y was excellent (r = 0.996) for the total score of BIPQ-Y while the internal consistency was moderate (α = 0.52). The test–retest of BIPQ-Y yielded excellent results with item intra-class correlation coefficient (ICC) ranging between 0.833 and 0.973 and an overall ICC of 0.889. For the confirmatory analysis of the BIPQ-Y, the factor loading for the eight items ranged from − 0.071 to 0.799 and the composite reliability was good with a score of 0.68.

Conclusion
The BIPQ-Y demonstrated excellent psychometric properties that are satisfactory with standards, and it is recommended for assessing illness perceptions of patients with chronic low back pain among the Yoruba-speaking populations.
Is “green” ammonia a misnomer? Unpacking the green label from a food-water-energy nexus perspective in water-scarce regions
Authors: Simha Prithvi , van der Merwe Gert 
Published: June 2024

AbstractThe term ‘green ammonia’ can be misleading. For fertilisers to merit a green label, the industry must adopt a planetary boundaries framework that includes reducing carbon emissions and circular management of nutrients. It should seek to achieve net reductions in reactive nitrogen and phosphorus fluxes to terrestrial and marine ecosystems.
Investigation of missense mutation-related type 1 diabetes mellitus through integrating genomic databases and bioinformatic approach
Authors: Pakha Dyonisa Nasirochmi , Yudhani Ratih Dewi , Irham Lalu Muhammad 
Published: June 2024

AbstractThough genes are already known to be responsible for type 1 diabetes mellitus (T1DM), the knowledge of missense mutation of that disease gene has still to be under covered. A genomic database and a bioinformatics-based approach are integrated in the present study in order to address this issue. Initially, nine variants associated with T1DM were retrieved from the GWAS catalogue. Different genomic algorithms such as PolyPhen2.0, SNPs and GTEx analyser programs were used to study the structural and functional effects of these mutations. Subsequently, SNPnexus was also employed to understand the effect of these mutations on the function of the expressed protein. Nine missense variants of T1DM were identified using the GWAS catalogue database. Among these nine SNPs, three were predicted to be related to the progression of T1DM disease by affecting the protein level. TYK2 gene variants with SNP rs34536443 were thought to have a probably damaging effect. Meanwhile, both COL4A3 and IFIH1 genes with SNPs rs55703767 and rs35667974, respectively, might alter protein function through a possibly damaging prediction. Among the variants of the three genes, the TYK2 gene with SNP rs34536443 had the strongest contribution in affecting the development of T1DM, with a score of 0.999. We sincerely hope that the results could be of immense importance in understanding the genetic basis of T1DM.
Phase I trial of aurora kinase A (AURKA) inhibitor VIC-1911 plus osimertinib for TKI-resistant, EGFR-mutant non-small cell lung cancer (NSCLC).
Authors: Zhao Shen , Zhao Hongyun , Zhang Li , Sun Yuping , Zhuang Wu , Dong Xiaorong , Zhou Jianying , Li Mingjun , Li Xiaoyan , xi yuqin , Zhang Jintao , Xu Wen , Li Ao , Chen Qianrong , Paradiso Linda J. , Myers Thomas J. , Zhang Lei 
Published: June 2024

8077 Background: ARUKA has been implicated in the emergence of resistance to osimertinib. VIC-1911 is a highly selective ARUKA inhibitor that has minimal activity in EGFR-mutant (mt) cell lines as a monotherapy. Preclinical data show synergy of VIC-1911 with osimertinib across in vitro and in vivo osimertinib-resistant models. Sustained tumor control after drug withdrawal is observed in both osimertinib-naïve and -resistant xenograft models. This trial evaluated the safety and efficacy of VIC-1911 plus osimertinib in patients with TKI-resistant, EGFRmt NSCLC (NCT05489731). Methods: This is a phase I trial with a 3+3 dose escalation stage and a dose expansion stage. Eligible patients should have advanced NSCLC with EGFR 19del/L858R and failure after ≥1 lines of EGFR-TKIs. Patients enrolled into the dose escalation stage were treated with VIC-1911 150mg or 200mg BID intermittently (4 days on, 3 days off) plus osimertinib 80 mg QD consecutively. Patients enrolled into the dose expansion stage were treated with VIC-1911 at the recommended phase 2 dose (RP2D) plus osimertinib 80 mg QD. Toxicity was assessed by the NCI CTCAE V5. Efficacy was evaluated per RECIST v1.1. Results: As of 18 December 2023, a total of 24 patients were treated. Median lines of prior treatment were 3 (range,1-8). Seven patients were enrolled during the dose escalation stage (150mg = 4, 200mg = 3). No DLT was observed and 200mg was selected as the RP2D. The most common AEs related to VIC-1911 at RP2D were diarrhea (52.3%), leucopenia (38.1%), neutropenia (33.3%), and thrombocytopenia (28.6%). Efficacy was evaluable in 23 patients. Among them, 10 patients were osimertinib-naïve (T790M-negative = 8,T790M-positive = 2) and 13 were osimertinib-resistant. For osimertinib-naïve patients, confirmed objective response rate (ORR) was 50% (5PRs, T790M-negative = 4, T790M-positive = 1) and disease control rate (DCR) was 80% (3SDs). For osimertinib-resistant patients, ORR was 0% and DCR was 53.8% (7SDs). Among patients with disease control, 66.7% (10/15) stayed on treatment as of data cutoff. The median follow-up duration was 5.5 months. Median duration of response (DOR) was not reached. The 6-month (6m) DOR rate was 50%. Median progression-free survival (PFS) was not reached and 4.3months for osimertinib- naïve and -resistant patients, respectively. The 6m PFS rate was 70.0% and 38.5%, respectively. Updated DOR and PFS data will be presented. Conclusions: VIC-1911 in combination of osimertinib is well-tolerated in previously-treated EGFRmt NSCLC. The combination demonstrates sustained antitumor activity, which indicates the potential of AURKA blockade in delaying the emergence of resistance to osimertinib. Clinical trial information: NCT05489731 .
EGFR-TKI as neoadjuvant treatment in patients with NSCLC with EGFR sensitive mutation: A retrospective real-world analysis.
Authors: Liu Sangtian , Liang Wenhua , He Jianxing 
Published: June 2024

8081 Background: This study aimed to evaluate the efficacy and outcome of Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) as preoperative neoadjuvant treatment in patients with NSCLC and EGFR sensitive mutation. Methods: A retrospective analysis was conducted. Patients with resectable stage I-III NSCLCs and received neoadjuvant treatment with any generation of EGFR-TKI before surgical resection were enrolled. The primary endpoint were major pathological response (MPR) and objective response rate (ORR), the second endpoints included diseases down staging, surgical outcomes, disease-free survival (DFS) and overall survival (OS). Results: A total of 58 patients were enrolled. Female accounted for 62.1% and most of them (77.6%) were never-smoker. Forty-five (77.6%) patients received the first generation of EGFR-TKI and 11 received the third. The median duration of EGFR-TKI before surgery was 3.6 months (0.7-19.5m). Nine (15.5%) patients achieved MPR and one patient (1.71%) achieved pathological complete response (pCR). The ORR was 60.3% (35/58) according to RECIST v1.1. Eighteen patients achieved TNM downstaging with T downstaging occurred in 44.8% of patients and N downstaging was about 32.8%. Majority of patients (96.6%) underwent thoracoscopic surgery and the rate of R0 resection was 82.8% (48/58). The DFS and OS of the whole cohort was 25.7months and not reached respectively. Patients with MPR had statistically improved outcomes than those without. What noticeable was that patients with tumor regression grade 3 (13/58) (residual viable tumor cells counts for 10% to 50%) also demonstrated a significant benefit from EGFR-TKI preoperative treatment than those with TRG4 or 5 (residual viable tumor cells>50%) (p = 0.01). We define patients with TRG1 to TRG3 as deep pathological regression (DPR) and the rest as non-DPR, and the DPR cohort showed significantly prolonged DFS than those with non-DPR (median DFS, 60.9 vs 16.7 months; HR, 0.29 (95%CI: 0.11-0.74), p = 0.006), the data of OS was not mature. Subgroup analysis validated DPR was an independent predictive factor for DFS. Conclusions: EGFR-TKI as neoadjuvant therapy had good effect on tumor pathological regression and disease downstaging, DPR patients were more likely to achieve long-term disease-free survival. Patients with NDPR should be closely followed up and appropriate adjuvant therapy was necessary after surgery due to the high risk of reccurence.
Health-related quality of life (HRQoL) with tepotinib in patients with MET exon 14 (METex14) skipping non-small cell lung cancer (NSCLC) with brain, liver, adrenal, or bone metastases in the phase II VISION trial.
Authors: Reinmuth Niels , Mazieres Julien , Popat Sanjay , Paz-Ares Luis G. , Hook Emma S , Hatswell Anthony , Vlassak Soetkin , Johne Andreas , Vioix Helene , Paik Paul K. 
Published: June 2024

8575 Background: Tepotinib, a highly selective MET inhibitor, showed robust and durable activity in patients with METex14 skipping NSCLC in the VISION trial (NCT02864992) (1). Systemic and intracranial activity was seen in patients with brain metastases. Secondary endpoints in the overall population showed stability in overall HRQoL, dyspnea and chest pain, with clinically meaningful improvement in cough. We analyzed HRQoL in patients with brain, liver, adrenal or bone metastases. Methods: Eligible patients (including patients with brain metastases if asymptomatic or neurologically stable on a stable steroid dose) received oral tepotinib 500 mg (450 mg active moiety) once daily. HRQoL was assessed at baseline and during follow-up using the EORTC QLQ-C30 Global Health Score (GHS), EQ-5D-5L visual analog scale (VAS), and EORTC QLQ-LC13 cough, dyspnea, and chest pain scores. Subgroup analyses evaluated patients with brain, liver, adrenal or bone metastases at baseline per independent review (data cut-off: November 20, 2022). Mean change from baseline across all visits was evaluated by linear mixed model regression in patients with baseline and ≥1 post-baseline score. Results: Of 313 enrolled patients, change from baseline in HRQoL was evaluable in 52 patients with brain (16.6%), 56 with liver (17.9%), 54 with adrenal (17.3%), and 86 with bone metastases (27.5%). At baseline, mean ± standard error (SE) EORTC QLQ-C30 GHS was worst in patients with bone metastases (49.90 ± 2.03), followed by patients with adrenal (51.85 ± 2.51), liver (58.33 ± 2.77), or brain metastases (59.94 ± 2.53). A similar pattern was observed for baseline EQ-5D-5L VAS (bone: 60.42 ± 1.94; adrenal: 63.06 ± 2.45; liver: 65.30 ± 2.46; brain: 66.75 ± 2.57). During tepotinib treatment, overall HRQoL (i.e. EORTC QLQ-C30 GHS and EQ-5D-5L VAS) remained stable in patients with brain, liver, adrenal or bone metastases (Table). Symptom scores in these patients showed trends for improvement in cough, with stability in dyspnea and chest pain. Conclusions: In the VISION trial in METex14 skipping NSCLC, patients with brain, liver, adrenal or bone metastases maintained overall HRQoL during tepotinib treatment, with trends for improvement in cough, consistent with results for the overall population. 1. Mazieres et al. JAMA Oncol 2023;9:1260–66. Clinical trial information: NCT02864992 . [Table: see text]