bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular characterization of the residual disease after neoadjuvant endocrine therapy in ER+/HER2- breast cancer uncovers biomarkers of tumour response
Authors: López-Velazco Joanna I. , Manzano Sara , Elorriaga Kepa , Otaño Maria , Lahuerta Ainhara , Álvarez Luis , Etxabe Inge , Huarte Miren , Buch Elvira , Gimenez Julia , Quiroga Vanesa , Fernandez Marta , Aragón Sofía , Paré Laia , Prat Aleix , Alvarez Isabel , Caffarel Maria M. , Urruticoechea Ander 
Published: April 2024

Abstract

Background Neoadjuvant endocrine therapy (NET) in oestrogen receptor-positive (ER+) /HER2-negative (HER2-) breast cancer (BC) allows an in vivo evaluation of treatment sensitivity by the monitoring of tumour response and offers the opportunity of personalized BC therapy. However, the lack of reproducible biomarkers to assess response and long-term prognosis after NET, beyond Ki67 levels and preoperative endocrine prognostic index score (mPEPI), is a significant barrier to increase its indications.
Methods In this study we searched clinically relevant molecular reporters of NET response and prognosis in a multicentre population of ER+/HER2- BC patients by using: PAM50 gene expression panel, protein evaluation of key proteins involved in tumorigenesis and HER2-Low status evaluation.
Results On a cohort of 131 patients our results show that PAM50 categorization (Luminal A vs Luminal B and ROR high vs ROR Low) predicts response to NET, with Luminal A and low ROR score tumours showing better response and prognosis than Luminal B and high ROR score. Moreover, tumours changing from Luminal A to Normal-like after NET presented a significant larger decrease in Ki67 levels at surgery, lower mPEPI score and a lower tumour cellularity size than those with persistent Luminal A status. In addition, we identify that the percentage of p53 positive cells in pre- and post-NET samples are associated with response or prognosis to NET.
Conclusion Our findings highlight the change of intrinsic subtype to normal-like after NET as a putative biomarker characterizing a population that benefit highly from NET. If considered conjointly with the pathologic evaluation of response, we could characterize a tumour population benefiting most from endocrine approach and bearing a potential very good prognosis.
Blood ammonia concentration measurement – effects of sampling site and cirrhosis during induced hyperammonaemia
Authors: Djernes Lars , Vilstrup Hendrik , Ott Peter , Eriksen Peter Lykke 
Published: April 2024

Abstract

Background: Ammonia is implicated in hepatic encephalopathy (HE) and prognostic in cirrhosis. Venous ammonia concentration, yielding similar correlation with HE grades as arterial, has become the preferred practise but comparative data are limited.
Aim: To quantify effect of sampling site on ammonia concentration in healthy persons and patients with cirrhosis.
Methods: Ammonia concentrations were measured by arterial and femoral venous blood sampling in ten healthy men and ten male patients with cirrhosis before and during hyperammonaemia induced by ammonia infusion. Cubital vein samples were included during the infusion.
Results: At baseline, arterial-venous concentration gaps were similar (p=0.15) in healthy persons [14 (10–19) and 8 (4–12) µmol/L] and patients with cirrhosis [53 (32–74) and 40 (23–57) µmol/L]. Ammonia infusion increased arterial-venous concentration gaps in both groups [115 (97–133) and 61 (31–90) vs. 175 (123–227) and 134 (65–203) µmol/L]. Mean ammonia concentration difference between groups during hyperammonaemia was 72 (42–103) μmol/L (p<0.001) and independent of sampling site. Cubital and femoral vein concentrations were comparable (p = 0.26). In cirrhosis, calculated upper limit normal values (ULN) were comparable for arterial and venous blood at baseline [2.0 (1.2–2.8) and 2.1 (1.2–3.0), p=0.74] and during hyperammonaemia [6.7 (4.7–8.7) and 6.2 (4.4– 8.1), p=0.44].
Conclusions: We found clinically meaningful intra-individual arterial-venous concentration gaps in both healthy persons and patients with cirrhosis at any ammonia concentration. Inter-group concentration differences after induced hyperammonaemia were relatively constant across sampling sites which supports clinical use of venous sampling. ULN-normalised ammonia concentrations were valid for both arterial and venous sampling.
Sexual Harassment Policy at a Higher Education Institution: Knowledge and Perceptions of Undergraduate Students
Authors: Mbatha S , Steyn Jean 
Published: April 2024

Abstract

Background
‘University of uThukela is a placebo name used to protect the identity of the institution.’
Sexual harassment in higher education institutions appears to be an ongoing deplorable and dreadful matter for students. This study seeks to establish a rich understanding of the knowledge and perceptions that students at the ‘University of uThukela’ have on sexual harassment and its policies, and the role played by the policy in the institution in educating students about sexual harassment, with the intent to prevent and deter sexual harassment.
Methods
The study used a Qualitative exploratory design, focusing on the Interpretivist paradigm in understanding issues of sexual harassment. More specifically, the study used semi-structured individual interviews to sexual harassment staff members responsible for sexual harassment implementation within the ‘University of uThukela’ and external experts. Furthermore, focus group discussions, and a knowledge test to undergraduate students in two departments as measuring instruments. Self-selection (volunteer) and snowball sampling were used to identify the research participants.
Results
This study has revealed that sexual harassment is prevalent in the ‘University of uThukela’. Student participants indicated general knowledge of sexual harassment. However, they showed poor knowledge of the institution’s policy. Findings further revealed that the institution lacks sufficiently trained individuals receiving cases of sexual harassment. According to the interviewed support specialists, findings show that the latter impacted students’ academic performance, health, and social life.
Conclusion
It is recommended that the institution educates students about sexual harassment policies, the definitions, and types of sexual harassment. Ensuring consistent training and implementation of personnel policies and practices, to further create a safe and inclusive learning environment.
FAM111B knockdown attenuates tumorigenesis of ovarian cancer via the down regulation of MYC
Authors: Yu Guoyu , Wei Fang , Li Wanying , Guo Qiuyun , Zhang Lihong 
Published: April 2024

Abstract

Background Ovarian cancer, a prevalent malignancy with the highest fatality rate among gynecological cancers, continues to face challenges in the development of effective targeted therapy approaches. While the FAM111B gene has been implicated in various cancer types, its specific role in ovarian cancer remains poorly understood.
Methods The ES2 and A2780 ovarian cell lines were used to explore the cellular proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in FAM111B knockdown experiments. The mouse tumor model was constructed to investigate the impact of FAM111B silencing in vivo. Tissue microarray was used to explore the prognostic value of different FAM111B expression level. Western blotting assay, MYC overexpression rescue experiments, protein transcriptomics and bioinformatics analysis were employed to explore the downstream molecular mechanism of FAM111B.
Results The in vitro experiments indicated that the inhibition of FAM111B resulted in decreased cellular proliferation, migration, invasion, and EMT in ovarian cancer cell lines. The suppression of FAM111B resulted in the suppression of tumor growth in a mouse xenograft model. Immunohistochemistry analyses conducted on tissue-microarray samples obtained from patients with serous ovarian cancer indicated that elevated levels of FAM111B expression were associated with unfavorable prognostic outcomes. The silencing of FAM111B mechanistically suppressed MYC expression, with subsequent MYC overexpression reversing the phenotypic suppression caused by FAM111B silencing. Additionally, protein transcriptomics analysis indicated that FAM111B is implicated in genetic information processing via the MYC pathway, underscoring its central role in ovarian cancer tumorigenesis.
Conclusions These findings suggest that FAM111B may serve as a novel biomarker and potential therapeutic target for ovarian cancer.
Effectiveness and safety of remimazolam tosilate versus propofol in patients undergoing painless gastrointestinal endoscopy: A randomized controlled trial.
Authors: Li Dong-Bin , Wang Yu , Xing Yang , Zhao Zi-Cen , Chang Li-Ya , Leng Yu-Fang 
Published: April 2024

Abstract

Background
Remimazolam tosilate and propofol are commonly used sedatives. However, there are few reports that compare the effectiveness and safety of remimazolam with those of propofol combined with alfentanil.
Aim
This trial compared the effectiveness and safety of remimazolam with those of propofol in patients undergoing painless gastrointestinal endoscopy.
Methods
One hundred and sixty-six eligible patients who underwent painless gastrointestinal endoscopy under intravenous anaesthesia were randomly divided into 2 groups: the propofol control group (Group P) and the remimazolam group (Group R). The primary outcomes were perioperative haemodynamic variables. The secondary outcomes included induction and awakening time, patient satisfaction, operator satisfaction, drug injection pain, hypoxemia, hypotension, bradycardia, limb movement, hiccups, postoperative nausea and vomiting, and 4 times or more drug additions.
Results
Compared with those in Group P, the SBP in Group R was significantly higher at T1, T2, T3, and T6 (P < 0.05); the DBP and MAP were significantly higher at T1, T2, T3, T5, and T6 (P < 0.05); the HR was significantly faster at T1 to T6 (P < 0.05); the SpO2 was significantly higher at T1 to T4 (P < 0.05); the incidences of intraoperative hypoxemia, hypotension, and drug injection pain were significantly lower in Group R (P < 0.05); the incidence of intraoperative hiccups was higher (P < 0.05); the awakening time was shorter in Group R (P < 0.05); and the operator satisfaction score was high (P < 0.05).
Conclusions
Remimazolam, in combination with alfentanil, is utilized for painless gastrointestinal endoscopy,which has a short awakening time, minimal circulatory and respiratory effects, and low incidence of adverse events.
Clinical trial registration
This trial protocol was registered in the Chinese Clinical Trial Registry (ChiCR2300077252, date: 2023 11 02)
Physiological Targets for Orthostatic Hypotension: Improving Nonpharmacological Interventions in Patients with Orthostatic Cerebral Hypoperfusion
Authors: Criado José R. , Kalafut Mary A. 
Published: April 2024

Abstract

Orthostatic hypotension (OH) is a form of orthostatic intolerance (OI) and a key physiological indicator of autonomic dysfunction that is associated with an increased risk of major cerebrocardiovascular events. Symptoms of cerebral hypoperfusion have been reported in patients with OH, which worsens symptoms and increases the risk of syncope. Since pharmacological interventions increase blood pressure (BP) independent of posture and do not restore normal baroreflex control, nonpharmacological treatments are considered the foundation of OH management. While reductions in cerebral blood flow velocity (CBFv) during orthostatic stress are associated with a decrease in end-tidal CO2 (EtCO2) and hypocapnia in patients with OI, their contribution to the severity of OH is not well understood. These measures have been physiological targets in a wide variety of biofeedback interventions. This study explored the relationship between cardiovascular autonomic control, EtCO2 and cerebral hypoperfusion in patients (N=71) referred for OI. Patients with systolic OH were more likely to be male, older, demonstrate reduced adrenal and vagal baroreflex sensitivity, and reduced cardiovagal control during head-up tilt (HUT) than patients without systolic OH. Greater reduction in CBFv during HUT was associated with a larger reduction in ETCO2 and systolic BP during HUT. While deficits in cardiovascular autonomic control played a more important role in systolic OH, reduced EtCO2 was a major contributor to orthostatic cerebral hypoperfusion. These findings suggest that biofeedback treatments targeting both the autonomic nervous system and EtCO2 should be part of nonpharmacological interventions complementing the standard of care in OH patients with symptoms of cerebral hypoperfusion.
Study on the Mechanism of Competing Endogenous Network of 'Scutellaria barbata D.Don-Houttuynia cordata- Radix Scutellariae' in the Treatment of NSCLC based on Bioinformatics, Molecular Dynamics and Experimental Verification
Authors: Wu Lulu , Xu Bo , Qi Yu , Yuan Changjin 
Published: April 2024

Introduction:
Non-small cell lung cancer (NSCLC) is the most common type of lung
cancer. Traditional Chinese medicine, known for its multi-target and multi-pathway characteristics,
offers a potential treatment approach for NSCLC.

Objective:
This study aimed to explore the mechanism of the competitive endogenous network
of 'Scutellaria barbata D.Don-Houttuynia cordata-Radix Scutellariae' in treating NSCLC
through bioinformatics analysis and in vitro experiments.

objective:
This study aimed to explore the mechanism of the competitive endogenous network of 'Scutellaria barbata D.Don-Houttuynia cordata-Radix Scutellariae' in treating NSCLC through bioinformatics analysis and in vitro experiments.

Materials and Methods:
Various databases and ceRNA networks were utilized to collect and
screen components and target genes, molecular docking and molecular dynamics simulations to
determine the binding ability of ligand-receptor complexes. In vitro experiments were conducted
to validate the effects of active ingredients of 'Scutellaria barbata D.Don-Houttuynia cordata-
Radix Scutellariae' on non-small cell lung cancer cell line A549.

method:
Various databases and ceRNA networks were utilized to collect and screen components and target genes, molecular docking and molecular dynamics simulations to determine the binding ability of ligand-receptor complexes. In vitro experiments were conducted to validate the effects of active ingredients of 'Scutellaria barbata D.Don-Houttuynia cordata-Radix Scutellariae' on non-small cell lung cancer cell line A549.

Results:
The key target proteins CCL2, EDN1, MMP9, PPARG, and SPP1 were docked well
with their corresponding TCM ligands. Among the ligand-receptor complexes, MMP9-Luteolin
and MMP9-Quercetin demonstrated the weaking binding force, while the SPP1-Quercetin complex,
associated with NSCLC prognosis, exhibited stable structure formation through hydrogen
bond interaction during MD simulation. In vitro experiments confirmed the inhibitory effect of
Quercetin on SPP1 expression, as well as the proliferation and migration of A549 cells.

Conclusion:
The findings suggest that 'Scutellaria barbata D.Don-Houttuynia cordata-Radix
Scutellariae' may potentially treat lung cancer by suppressing the expression of SPP1. This
study provides valuable insights and novel research directions for understanding the mechanism
of traditional Chinese medicine in combating lung cancer.
Digital Remote Monitoring Using an mHealth Solution for Survivors of Cancer: Protocol for a Pilot Observational Study
Authors: Innominato Pasquale F , Macdonald Jamie H , Saxton Wendy , Longshaw Laura , Granger Rachel , Naja Iman , Allocca Carlo , Edwards Ruth , Rasheed Solah , Folkvord Frans , de Batlle Jordi , Ail Rohit , Motta Enrico , Bale Catherine , Fuller Claire , Mullard Anna P , Subbe Christian P , Griffiths Dawn , Wreglesworth Nicholas I , Pecchia Leandro , Fico Giuseppe , Antonini Alessio 
Published: April 2024

Background
Healthy lifestyle interventions have a positive impact on multiple disease trajectories, including cancer-related outcomes. Specifically, appropriate habitual physical activity, adequate sleep, and a regular wholesome diet are of paramount importance for the wellness and supportive care of survivors of cancer. Mobile health (mHealth) apps have the potential to support novel tailored lifestyle interventions.

Objective
This observational pilot study aims to assess the feasibility of mHealth multidimensional longitudinal monitoring in survivors of cancer. The primary objective is to test the compliance (user engagement) with the monitoring solution. Secondary objectives include recording clinically relevant subjective and objective measures collected through the digital solution.

Methods
This is a monocentric pilot study taking place in Bangor, Wales, United Kingdom. We plan to enroll up to 100 adult survivors of cancer not receiving toxic anticancer treatment, who will provide self-reported behavioral data recorded via a dedicated app and validated questionnaires and objective data automatically collected by a paired smartwatch over 16 weeks. The participants will continue with their normal routine surveillance care for their cancer. The primary end point is feasibility (eg, mHealth monitoring acceptability). Composite secondary end points include clinically relevant patient-reported outcome measures (eg, the Edmonton Symptom Assessment System score) and objective physiological measures (eg, step counts). This trial received a favorable ethical review in May 2023 (Integrated Research Application System 301068).

Results
This study is part of an array of pilots within a European Union funded project, entitled “GATEKEEPER,” conducted at different sites across Europe and covering various chronic diseases. Study accrual is anticipated to commence in January 2024 and continue until June 2024. It is hypothesized that mHealth monitoring will be feasible in survivors of cancer; specifically, at least 50% (50/100) of the participants will engage with the app at least once a week in 8 of the 16 study weeks.

Conclusions
In a population with potentially complex clinical needs, this pilot study will test the feasibility of multidimensional remote monitoring of patient-reported outcomes and physiological parameters. Satisfactory compliance with the use of the app and smartwatch, whether confirmed or infirmed through this study, will be propaedeutic to the development of innovative mHealth interventions in survivors of cancer.

International Registered Report Identifier (IRRID)
PRR1-10.2196/52957
Finite Element Analysis of Pelvic Floor Biomechanical Models to Elucidate the Mechanism for Improving Urination and Defecation Dysfunction in Older Adults: Protocol for a Model Development and Validation Study
Authors: Wang Rui , Liu Guangtian , Jing Liwei , Zhang Jing , Li Chenyang , Gong Lichao 
Published: April 2024

Background
The population is constantly aging, and most older adults will experience many potential physiological changes as they age, leading to functional decline. Urinary and bowel dysfunction is the most common obstacle in older people. At present, the analysis of pelvic floor histological changes related to aging has not been fully elucidated, and the mechanism of improving intestinal control ability in older people is still unclear.

Objective
The purpose of this study is to describe how the finite element method will be used to understand the mechanical characteristics of and physiological changes in the pelvic cavity during the rehabilitation process, providing theoretical support for the mechanism for improving urination and defecation dysfunction in older individuals.

Methods
We will collect magnetic resonance imaging (MRI) and computed tomography (CT) data of the pelvic cavity of one male and one female volunteer older than 60 years and use the finite element method to construct a 3D computer simulation model of the pelvic cavity. By simulating different physiological states, such as the Valsalva maneuver and bowel movement, we will verify the accuracy of the constructed model, investigate the effects of different neuromuscular functional changes, and quantify the impact proportions of the pelvic floor muscle group, core muscle group, and sacral nerve.

Results
At present, we have registered the study in the Chinese Clinical Trial Registry and collected MRI and CT data for an older male and an older female patient. Next, the construction and analysis of the finite element model will be accomplished according to the study plan. We expect to complete the construction and analysis of the finite element model by July 2024 and publish the research results by October 2025.

Conclusions
Our study will build finite element models of the pelvic floor of older men and older women, and we shall elucidate the relationship between the muscles of the pelvic floor, back, abdomen, and hips and the ability of older adults to control bowel movements. The results of this study will provide theoretical support for elucidating the mechanism for improving urination and defecation dysfunction through rehabilitation.

Trial Registration
Chinese Clinical Trial Registry ChiCTR2400080749; https://www.chictr.org.cn/showproj.html?proj=193428

International Registered Report Identifier (IRRID)
DERR1-10.2196/56333
Comparison of methods for diagnosing sarcopenia in patients with rheumatoid arthritis
Authors: Stoika I. , Yatsyshyn R. , Drohomeretska O. , Popadynets I. , Babenko O. , Shapoval O. 
Published: April 2024

Background. Sarcopenia in patients with rheumatoid arthritis (RA) occurs in connection with the chronic inflammatory process, hormonal therapy, and limitation of physical activity due to pain syndrome. For RA patients, it is important to preserve muscle mass and function to reduce the risk of disability and improve quality of life. The research purposed to assess muscle mass and function in RA patients with a comparison of me­thods for determining skeletal muscle mass recommended by ­EWCSOP2. ­Materials and methods. A total of 44 persons were exa­mined, 32 were patients with RA, and 12 ones were healthy persons (the control group). The following methods were used in the study: the SARC-F questionnaire, the determination of the appendicular mass of skeletal muscles using dual-photon X-ray absorptiometry (DXA), the percentage of muscle and fat tissue using bioimpe­dancemetry, the determination of the cross-sectional area of the lumbar muscle using computer tomography (CT), physical performance tests. Patients with RA were divided into 3 groups: group A (11 persons) — questionnaire (SARC-F), assessment of skeletal muscle strength and determination of muscle mass using DXA was performed; group B (11 patients) — questionnaire (SARC-F), assessment of skeletal muscle strength and determination of muscle mass using bioimpedancemetry; group C (10 persons) — questionnaire (SARC-F), assessment of skeletal muscle strength and determination of muscle mass using CT. Results. All indices of physical performance tests and instrumental methods of assessing muscle mass were significantly worse in patients with RA compared to the control group. Sarcopenia was diagnosed in 50 % of patients with RA, 6 cases in group A (the average value of appendicular lean mass was 15.7 kg in them, in the control group — 21 kg), 5 in group B (the average values of the proportion of muscle mass were 21.2 compared to 29.3 % in the control group) and 5 in group C (the average percentage of muscle mass was 49.46 %, in the control group 58.32 %). ­Conclusions. Each of the methods of assessing the mass of skeletal muscles has proven its ability in the diagnosis of sarcopenia. Improving the efficiency of diagnosing sarcopenia in patients with RA will improve the response to the treatment of the underlying disease and improve the quality of life of patients.