bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unsolved mystery of Fas: mononuclear cells may have trouble dying in patients with Sjögren’s syndrome
Authors: Lindrova Irena , Kolackova Martina , Svadlakova Tereza , Vankova Radka , Chmelarova Marcela , Rosecka Michaela , Jozifkova Eva , Sembera Martin , Krejsek Jan , Slezak Radovan 
Published: June 2023

Abstract
Background
Patients with Sjögren’s syndrome, like other patients with autoimmune disorders, display dysregulation in the function of their immune system. Fas and Fas Ligand (FasL) are among the dysregulated proteins.

Methods
We studied Fas and FasL on IL-2Rα+ cells and in serum of patients with Sjögren’s syndrome (n = 16) and healthy individuals (n = 16); both from same ethnic and geographical background. We used flow cytometry and enzyme-linked immunosorbent for this purpose. We also measured the expression of Bcl-2 and Bax by reverse transcription quantitative real-time PCR (RT-qPCR) and percentage of apoptotic and dead cells using Annexin V and 7-AAD staining in lymphocytes.

Results
FasL was increased in patients’ T and B cells while Fas was increased in patients’ monocytes, T and B cells. No signs of increased apoptosis were found. sFas and sFasL in patients’ serum were increased, although the increase in sFasL was not significant. We suspect an effect of non-steroidal anti-inflammatory therapy on B cells, explaining the decrease of the percentage Fas+ B cells found within our samples. In healthy individuals, there was a noticeable pattern in the expression of FasL which mutually correlated to populations of mononuclear cells; this correlation was absent in the patients with Sjögren’s syndrome.

Conclusions
Mononuclear cells expressing IL-2Rα+ had upregulated Fas in Sjögren’s syndrome. However, the rate of apoptosis based on Annexin V staining and the Bcl-2/Bax expression was not observed in mononuclear cells. We suspect a functional role of abnormal levels of Fas and FasL which has not been cleared yet.
Data quality in an HIV vaccine efficacy clinical trial in South Africa: through natural disasters and with discipline
Authors: Laher Fatima , Malahleha Mookho , Ramirez Shelly , Brumskine William , Otwombe Kennedy , Moodie Zoe , Allen Mary 
Published: June 2023

Abstract
Background
To produce quality data that informs valid clinical trial results and withstands regulatory inspection, trial sites should adhere to many complex and dynamic requirements. Understanding non-conformance to requirements informs the emerging field of improvement science. We describe protocol deviations in South Africa’s largest HIV vaccine efficacy trial.

Methods
We analysed data from the HVTN 702 trial using mixed methods. We obtained descriptive statistics, from protocol deviation case report forms collected from 2016–2022, of deviation by participant, trial site, and time to site awareness. We thematically analysed text narratives of deviation descriptions, corrective and preventive actions, generating categories, codes and themes which emerged from the data.

Results
For 5407 enrollments, 4074 protocol deviations were reported (75 [95% CI: 73.0–77.6] deviations per 100 enrolments). There was a median of 1 protocol deviation per participant (IQR 1–2). Median time from deviation to site awareness was 31 days (IQR 0–146). The most common category of deviation type was omitted data and/or procedures (69%), and 54% of these omissions were stated to have arisen because of the national lockdown at the beginning of the COVID-19 pandemic. The ratio of protocol deviations to cumulative enrolments was highest in the year 2020 (0.34). Major themes of deviations were: COVID-19 and climate disasters giving rise to deviation trends, subroutines introducing an opportunity for deviation, and document fragmentation (such as requirements dispersed across multiple guidance documents) as an obstacle. Preventive action categories were: no preventive measures; discipline, training and/or awareness; quality review, checking and verifying and changing the process and/or implementation tools. Major themes of preventive actions were that systems-based actions are unusual, with people-based actions dominating, and that root cause analysis was rarely mentioned.

Conclusions
In the age of infectious and climate disaster risks, trials may benefit from simple study designs and trial-related documents. To optimise protocol adherence, sponsors and sites should consider ongoing training, and routinely review deviation reports with a view to adjusting processes. These data quality lessons may inform future trial design, training and implementation.

Trial registration
HVTN 702 was registered with the South African National Clinical Trials Register (DOH-27–0916-5327) and ClinicalTrials.gov (NCT02968849).
Effects of real-time remote cardiac rehabilitation on exercise capacity and quality of life: a quasi-randomised controlled trial
Authors: Fukuta Yoshitatsu , Arizono Shinichi , Tanaka Shinichiro , Kawaguchi Tomonori , Tsugita Natsumi , Fuseya Takahiro , Magata Junichi , Tawara Yuichi , Segawa Tomonori 
Published: June 2023

AbstractBackgroundThe impact of real-time remote cardiac rehabilitation (CR) on health and disability-related outcomes and its correlation with physical function are unknown. We compared the effectiveness of real-time remote CR with that of hospital-based CR on physical function improvement and physical functions of improvement (Δ) to clarify the relationship between health and disability at baseline.MethodsPatients with cardiovascular diseases (CVDs) were enrolled (n = 38) in this quasi-randomised controlled trial and underwent 4 weeks of hospital-based CR, followed by 12 weeks of remote or hospital-based CR based on quasi-randomised allocation. Patients were assessed at baseline and after 12 weeks of remote or hospital-based CR using the shortened version of the World Health Organization (WHO) Quality of Life scale (WHOQOL-BREF) for subjective satisfaction, WHO Disability Assessment Schedule (WHODAS2.0-J) for objective performance, and cardiopulmonary exercise test for physical function and peak oxygen uptake (peak VO2). The trends in measured variables from baseline to the post-CR stage were analysed.ResultsSixteen patients (mean age, 72.2 ± 10.4 years) completed remote CR, and 15 patients (mean age, 77.3 ± 4.8 years) completed hospital-based CR. The post-CR physical function differed significantly between the groups (ΔpeakVO2, 2.8 ± 3.0 versus 0.84 ± 1.8 mL·min−1·kg−1;p < 0.05). The differences in post-CR changes in the WHOQOL-BREF scores between the groups were insignificant. The post-CR changes in the WHODAS2.0-J scores were significantly lower in the remote CR group than in the hospital-based CR group (ΔWHODAS2.0-J score, –8.56 ± 14.2 versus 2.14 ± 7.6;p < 0.01). Forward multiple stepwise regression analysis using overall data showed that the intervention method (β = 0.339,p < 0.05), baseline cognition (β =  − 0.424,p < 0.05), and social interaction level (β = 0.658,p < 0.01; WHODAS2.0-J) were significant independent contributors to Δpeak VO2(r2 = 0.48, F = 8.13,p < 0.01).ConclusionsRemote CR considerably improved physical function and objective performance in patients with CVDs. Remote CR can be used to effectively treat stable patients who cannot visit hospitals.Trial registrationThis interventional trial was registered at the UMIN-CTR registry (trial title: Development of remote programme for cardiac rehabilitation using wearable electrocardiograph; trial ID: UMIN000041746; trial URL:https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046564; registration date: 2020/09/09).
Comparison of guideline concordant antibiotic prophylaxis in Veterans Affairs and non-Veterans Affairs dental settings among those with cardiac conditions or prosthetic joints
Authors: Ramanathan Swetha , Evans Charlesnika T. , Hershow Ronald C. , Calip Gregory S. , Rowan Susan , Hubbard Colin , Suda Katie J. 
Published: June 2023

Abstract
Background
No research has been conducted to assess whether antibiotic prophylaxis prescribing differs by dental setting. Therefore, the goal of this study was to compare the prescribing of antibiotic prophylaxis in Veterans Affairs (VA) and non-Veterans Affairs settings.

Methods
This was a retrospective study of veteran and non-veteran dental patients with cardiac conditions or prosthetic joints between 2015–2017. Multivariable log binomial regression analysis was conducted to compare concordant prescribing by setting with a sub-analysis for errors of dosing based on antibiotic duration (i.e., days prescribed).

Results
A total of 61,124 dental visits that received a prophylactic antibiotic were included. Most were male (61.0%), and 55 years of age or older (76.2%). Nearly a third (32.7%) received guideline concordant prophylaxis. VA dental settings had a lower prevalence of guideline concordant prescribing compared to non-VA settings in unadjusted results (unadjusted prevalence ratio [uPR] = 0.92, 95% CI: 0.90–0.95). After adjustment, prevalence of guideline concordant prescribing was higher in those with prosthetic joints in the VA setting (adjusted prevalence ratio [aPR] = 1.73, 95% CI: 1.59–1.88), with no difference identified in those without a prosthetic joint (aPR = 0.99, 95% CI: 0.96–1.01). Concordance of dosing was higher in VA compared to non-VA settings (aPR = 1.11, 95% CI: 1.07–1.15).

Conclusions
VA has a higher prevalence of guideline concordant prescribing among those with prosthetic joints and when assessing dosing errors. Though the presence of an integrated electronic health record (EHR) may be contributing to these differences, other system or prescriber-related factors may be responsible. Future studies should focus on to what extent the integrated EHR may be responsible for increased guideline concordant prescribing in the VA setting.
Oscillometric pulse wave analysis for detecting low flow arteriovenous fistula
Authors: Busch Veit , Streis Joachim , Müller Sandra , Mueller Niklas , Seibert Felix S. , Felderhoff Thomas , Westhoff Timm H. 
Published: June 2023

Abstract
Background
Pulse wave analysis may be useful to assess fistula function. We aimed to prospectively evaluate if convenient oscillometric devices are applicable to detect flow below 500 ml/min in a real life clinical setting.

Methods
Pulse waves were recorded ambilaterally with the vicorder® device at the brachial artery in 53 patients on haemodialysis with native fistula. Primary variables consisted of the mean slope between the systolic maximum and the diacrotic notch (Slope2), the sum of the mean slopes in the four characteristic sections of pulse waves (Slope∑) and the amplitude of relative volumetric change in the measuring cuff at the upper arm (AMP). Fistula flow was measured with the use of duplex sonography using a standardized approach.

Results
Parameter values above or below the median indicated measurement at the non-fistula side, with sensitivities/specificities of 0.79/0.79 (p < 0.001) for Slope 2, 0.64/0.64 (p = 0.003) for Slope∑ and 0.81/0.81 (p < 0.001) for AMP if measurements at the fistula and non-fistula arm were considered. ROC-analyses of parameter values measured at the fistula to detect low flow demonstrated AUCs (with CI) of 0.652 (0.437–0.866, p = 0.167) for Slope2, 0.732 (0.566–0.899, p = 0.006) for Slope∑ and 0.775 (0.56–0.991, p = 0.012) for AMP. The point with maximal youden’s index was regarded as optimal cut-off, which corresponded to sensitivities and specificities of 0.8/0.56 for slope2, 0.86/ 0.56 for Slope∑ and 0.93/0.78 for AMP.

Conclusion
Functional surveillance with oscillometry is a promising clinical application to detect a low fistula flow. Among all investigated pulse wave parameters AMP revealed the highest diagnostic accuracy.

Graphical Abstract
Enacting person-centred care: a multi-perspective study of practices in clinical encounters for people living with chronic kidney disease
Authors: Cotta Amie , Kristiansen Maria 
Published: June 2023

Abstract
Background
There is growing emphasis on the need for ensuring person-centred care for patients living with chronic kidney disease as this will benefit patients, providers, and healthcare systems alike. Nevertheless, less emphasis is given to how this complex concept is practiced in clinical encounters and how it is experienced by patients. This qualitative multi-perspective study investigates how person-centred care for people living with chronic kidney disease is practiced and experienced by patients in clinical encounters at a nephrological ward at a hospital in the capital region of Denmark.

Methods
The study builds upon qualitative methodologies, including field notes from observations of clinical encounters between clinicians and patients in an out-patient clinic (n = ~ 80) and in-person interviews with patients in peritoneal dialysis (n = 4). Key themes from field notes and interview transcripts were identified through thematic analysis. Analyses were informed by practice theory.

Results
Findings illustrate that person-centred care is practiced in a relational and situational encounter between patients and clinicians as dialogues about choice of treatment modality, which is shaped by the individual’s life circumstances, preferences, and values. The practice of person-centred care appeared to be complex and interlinked with a range of factors, individual to each patient. We identified three themes of relevance for practices and experiences related to person-centred care: (1) Patients’ perceptions of living with chronic kidney disease. Perceptions differed according to medical history, life situation and prior experiences with treatment in the healthcare system. These patient-related factors were perceived to be important for person-centred care to unfold; (2) Relations between patients and healthcare professionals were important for patients’ experiences of trust and appeared fundamental for the practice and experiences of person-centred care; and (3) Decision-making on treatment modality that is the best fit for each patient’s everyday life, appear to be shaped by the patient’s need for knowledge about treatment modalities and level of self-determination in the decision-making.

Conclusions
The context of clinical encounters influences the practices and experiences of person-centred care, where health policies and lack of embodiment are identified as barriers for providing and experiencing person-centred care.
Effects of tolvaptan discontinuation in patients with autosomal dominant polycystic kidney disease: a post hoc pooled analysis
Authors: Lioudis Michael , Zhou Xiaolei , Davenport Eric , Nunna Sasikiran , Krasa Holly B. , Oberdhan Dorothee , Fernandes Ancilla W. 
Published: June 2023

Abstract
Background
Tolvaptan slows kidney function decline in patients with autosomal dominant polycystic kidney disease (ADPKD) who are at risk of rapid progression. Given that treatment requires commitment to long-term use, we evaluated the effects of tolvaptan discontinuation on the trajectory of ADPKD progression.

Methods
This was a post hoc analysis of pooled data from two clinical trials of tolvaptan (TEMPO 2:4 [NCT00413777] and TEMPO 3:4 [NCT00428948]), an extension trial (TEMPO 4:4 [NCT01214421]), and an observational study (OVERTURE [NCT01430494]) that enrolled patients from the other trials. Individual subject data were linked longitudinally across trials to construct analysis cohorts of subjects with a tolvaptan treatment duration > 180 days followed by an off-treatment observation period of > 180 days. For inclusion in Cohort 1, subjects were required have ≥ 2 outcome assessments during the tolvaptan treatment period and ≥ 2 assessments during the follow-up period. For Cohort 2, subjects were required to have ≥ 1 assessment during the tolvaptan treatment period and ≥ 1 assessment during the follow-up period. Outcomes were rates of change in estimated glomerular filtration rate (eGFR) and total kidney volume (TKV). Piecewise-mixed models compared changes in eGFR or TKV in the on-treatment and post-treatment periods.

Results
In the Cohort 1 eGFR population (n = 20), the annual rate of eGFR change (in mL/min/1.73 m2) was -3.18 on treatment and -4.33 post-treatment, a difference that was not significant (P = 0.16), whereas in Cohort 2 (n = 82), the difference between on treatment (-1.89) and post-treatment (-4.94) was significant (P < 0.001). In the Cohort 1 TKV population (n = 11), TKV increased annually by 5.18% on treatment and 11.69% post-treatment (P = 0.06). In Cohort 2 (n = 88), the annual TKV growth rates were 5.15% on treatment and 8.16% post-treatment (P = 0.001).

Conclusions
Although limited by small sample sizes, these analyses showed directionally consistent acceleration in measures of ADPKD progression following the discontinuation of tolvaptan.
Predictive role of pre-thrombolytic hs-CRP on the safety and efficacy of intravenous thrombolysis in acute ischemic stroke
Authors: Cheng Xu-Dong , Wang Duo-Zi , Zhang Qi , Wang Jian-Hong , Li Bing-Hu , Zhang Xin , Zhang Jing , Zhou Sen , Jia Li-Jun , Wang Li-Rong , Yu Neng-Wei 
Published: June 2023

Abstract
Purpose
To investigate the predictive role of pre-thrombolytic high sensitivity C-reactive protein (hs-CRP) on the safety and efficacy of intravenous thrombolysis in patients with acute ischemic stroke (AIS).

Methods
Patients with AIS who underwent intravenous thrombolysis with recombinant plasminogen activator (rtPA) or urokinase without endovascular therapy from June 2019 to June 2022 were retrospectively analysed. All patients were grouped into two groups (high or low hs-CRP group) according to the median value of hs-CRP before intravenous thrombolysis. The baseline NIHSS, NIHSS changes before and after thrombolysis (ΔNIHSS), the rate of good thrombolysis response (NIHSS decreased ≥ 2 points from baseline), the rate of any intracranial hemorrhage, age, sex, hypertension, diabetes, uric acid and platelet count were compared between the two groups. Logistic regression analysis was performed to identify possible prognostic factors for a good thrombolysis response.

Results
A total of 212 patients were included in the analysis, with a mean age of 66.3 ± 12.5 years. In total, 145 patients received rtPA, and 67 patients received urokinase. Patients were divided into a high hs-CRP group (> 1.60 mg/L) and a low hs-CRP group (≤ 1.60 mg/L) according to the median hs-CRP level (1.60 mg/L). The ΔNIHSS of the high hs-CRP group was significantly smaller than that of the low hs-CRP group (0 [-1 ~ 0] vs. -1 [-2 ~ 0], P < 0.05). The good rate of thrombolysis response in the high hs-CRP group was significantly lower than that in the low hs-CRP group (21.9% vs. 36.5%, P < 0.05). Similar results were shown in the rtPA subgroup between the high and low hs-CRP groups but not in the urokinase subgroup. Logistic regression analysis showed that hs-CRP > 1.60 mg/L was negatively correlated with a good thrombolysis response rate (OR = 0.496, 95% CI = 0.266–0.927, P = 0.028).

Conclusion
hs-CRP > 1.6 mg/L may serve as a poor prognosis predictive factor for patients with AIS receiving intravenous thrombolysis. However, due to the small sample size of this study, further studies are needed to verify our results.
Development of machine learning models to predict gestational diabetes risk in the first half of pregnancy
Authors: Cubillos Gabriel , Monckeberg Max , Plaza Alejandra , Morgan Maria , Estevez Pablo A. , Choolani Mahesh , Kemp Matthew W. , Illanes Sebastian E. , Perez Claudio A. 
Published: June 2023

Abstract
Background
Early prediction of Gestational Diabetes Mellitus (GDM) risk is of particular importance as it may enable more efficacious interventions and reduce cumulative injury to mother and fetus. The aim of this study is to develop machine learning (ML) models, for the early prediction of GDM using widely available variables, facilitating early intervention, and making possible to apply the prediction models in places where there is no access to more complex examinations.

Methods
The dataset used in this study includes registries from 1,611 pregnancies. Twelve different ML models and their hyperparameters were optimized to achieve early and high prediction performance of GDM. A data augmentation method was used in training to improve prediction results. Three methods were used to select the most relevant variables for GDM prediction. After training, the models ranked with the highest Area under the Receiver Operating Characteristic Curve (AUCROC), were assessed on the validation set. Models with the best results were assessed in the test set as a measure of generalization performance.

Results
Our method allows identifying many possible models for various levels of sensitivity and specificity. Four models achieved a high sensitivity of 0.82, a specificity in the range 0.72–0.74, accuracy between 0.73–0.75, and AUCROC of 0.81. These models required between 7 and 12 input variables. Another possible choice could be a model with sensitivity of 0.89 that requires just 5 variables reaching an accuracy of 0.65, a specificity of 0.62, and AUCROC of 0.82.

Conclusions
The principal findings of our study are: Early prediction of GDM within early stages of pregnancy using regular examinations/exams; the development and optimization of twelve different ML models and their hyperparameters to achieve the highest prediction performance; a novel data augmentation method is proposed to allow reaching excellent GDM prediction results with various models.
Post-therapeutic circulating tumor cell-associated white blood cell clusters predict poor survival in patients with advanced driver gene-negative non-small cell lung cancer
Authors: Wang Ying , Liu Yanxia , Zhang Zhiyun , Lu Baohua , Gao Yuan , Tong Li , Hu Mingming , Lin Peter Ping , Li Baolan , Zhang Tongmei 
Published: June 2023

Abstract
Purpose
This study aimed to investigate the clinical utility of diverse aneuploid circulating tumor cell (CTC) subtypes and particularly CTC-associated white blood cell (CTC-WBC) clusters in predicting treatment response, prognosis and real-time monitoring disease progression in advanced driver gene-negative non-small lung cancer (NSCLC) patients.

Materials and methods
A total of 74 eligible patients were prospectively enrolled and serial blood samples were collected at pre-treatment(t0), after two cycles of therapy (t1) and at post-four-to-six treatment cycles (t2). Co-detection of diverse subtypes of aneuploid CTCs and CTC-WBC clusters was conducted in advanced NSCLC patients receiving first-line treatment.

Results
At baseline, CTCs were detected in 69 (93.24%) patients and CTC-WBC clusters were detected in 23 (31.08%) patients. Patients with CTCs < 5/6ml or with CTC-WBC clusters undetectable exhibited a better treatment response than patients with pre-therapeutic aneuploid CTCs ≥ 5/6ml or harboring CTC-WBC clusters (p = 0.034 and p = 0.012, respectively). Before treatment, patients bearing tetraploid CTCs ≥ 1/6ml showed significantly inferior progression-free survival (PFS) [hazard ratio (HR):2.420, 95% confidence interval (CI): 1.426–4.106; p = 0.001] and overall survival (OS) compared to patients with tetraploid CTCs < 1/6ml (HR:1.907, 95%CI: 1.119–3.251; p = 0.018). A longitudinal study demonstrated that post-therapeutic patients harboring CTC-WBC clusters displayed the reduced PFS and OS compared with those without CTC-WBC clusters, and subgroup analysis showed that the presence of CTC-WBC clusters indicated a worse prognosis in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. After adjusting for multiple significant factors, post-therapeutic CTC-WBC clusters were the only independent predictor of both PFS (HR:2.872, 95% CI: 1.539–5.368; p = 0.001) and OS (HR:2.162, 95% CI: 1.168–4.003; p = 0.014).

Conclusions
In addition to CTCs, longitudinal detection of CTC-WBC clusters provided a feasible tool to indicate initial treatment response, dynamically monitor disease progression and predict survival in driver gene-negative advanced NSCLC patients.