bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Presence of Blood in a Strain Gauge Pressure Transducer Has a Clinical Effect on the Accuracy of Intracranial Pressure Readings
Authors: Nairon Emerson B. , Joseph Jeslin , Kamal Abdulkadir , Busch David R. , Olson DaiWai M. 
Published: May 2024

IMPORTANCE:
Patients admitted with cerebral hemorrhage or cerebral edema often undergo external ventricular drain (EVD) placement to monitor and manage intracranial pressure (ICP). A strain gauge transducer accompanies the EVD to convert a pressure signal to an electrical waveform and assign a numeric value to the ICP.

OBJECTIVES:
This study explored ICP accuracy in the presence of blood and other viscous fluid contaminates in the transducer.

DESIGN:
Preclinical comparative design study.

SETTING:
Laboratory setting using two Natus EVDs, two strain gauge transducers, and a sealed pressure chamber.

PARTICIPANTS:
No human subjects or animal models were used.

INTERVENTIONS:
A control transducer primed with saline was compared with an investigational transducer primed with blood or with saline/glycerol mixtures in mass:mass ratios of 25%, 50%, 75%, and 100% glycerol. Volume in a sealed chamber was manipulated to reflect changes in ICP to explore the impact of contaminates on pressure measurement.

MEASUREMENTS AND MAIN RESULTS:
From 90 paired observations, ICP readings were statistically significantly different between the control (saline) and experimental (glycerol or blood) transducers. The time to a stable pressure reading was significantly different for saline vs. 25% glycerol (< 0.0005), 50% glycerol (< 0.005), 75% glycerol (< 0.0001), 100% glycerol (< 0.0005), and blood (< 0.0005). A difference in resting stable pressure was observed for saline vs. blood primed transducers (0.041).

CONCLUSIONS AND RELEVANCE:
There are statistically significant and clinically relevant differences in time to a stable pressure reading when contaminates are introduced into a closed drainage system. Changing a transducer based on the presence of blood contaminate should be considered to improve accuracy but must be weighed against the risk of introducing infection.
Combination treatment with PD1/PDL-1 inhibitors for sarcomas: state of the art, next questions
Authors: Martin-Broto Javier , Hindi Nadia , Moura David S. 
Published: May 2024

Purpose of review
Only a small fraction of sarcomas exhibit recognized parameters of immune sensitivity, such as tumor mutational burden, PDL-1 expression, or microsatellite instability. Combined strategies aimed to modulate tumor microenvironment to increase the efficacy of PD1/PDL-1 inhibitors in sarcoma. Most explored prospective studies were based on combinations of PD1/PDL-1 inhibitors with antiangiogenics, other immune checkpoints, or chemotherapy.

Recent findings
Results on 6-month PFS rate, median PFS, and ORR in trials using PD1/PDL-1 inhibitors plus antiangiogenics ranged respectively as 46.9–55%, 4.7–7.8 months and 21–36.7%. In combination with other immune checkpoint inhibitors, the results of median PFS and ORR ranged from 2.8–4.1 months and 10–16%, respectively. In combination with chemotherapy, the best results were obtained with doxorubicin-based regimens compared to other agents. Duplet-based chemotherapy plus anti-PD1/PDL-1 obtained the highest ORR (56.2%) compared with doxorubicin (19–36.7%). Currently, the most robust predictive biomarker for anti-PD1/PDL-1 efficacy is the presence of tertiary lymphoid structures (TLS) with mature dendritic cells.

Summary
Even when direct comparisons between PD1/PDL-1 inhibitor-based combinations and single agents have not been performed yet in sarcoma, some combinations appear promising. Studies controlling heterogeneity by biomarker or histotype selection contribute to an increase in efficacy or knowledge crucial for future comparative trials.
Sarculator: how to improve further prognostication of all sarcomas
Authors: Borghi Alessandra , Gronchi Alessandro 
Published: May 2024

Purpose of review
Prognostication of soft tissue sarcomas is challenging due to the diversity of prognostic factors, compounded by the rarity of these tumors. Nomograms are useful predictive tools that assess multiple variables simultaneously, providing estimates of individual likelihoods of specific outcomes at defined time points. Although these models show promising predictive ability, their use underscores the need for further methodological refinement to address gaps in prognosis accuracy.

Recent findings
Ongoing efforts focus on improving prognostic tools by either enhancing existing models based on established parameters or integrating novel prognostic markers, such as radiomics, genomic, proteomic, and immunologic factors. Artificial intelligence is a new field that is starting to be explored, as it has the capacity to combine and analyze vast and intricate amounts of relevant data, ranging from multiomics information to real-time patient outcomes.

Summary
The integration of these innovative markers and methods could enhance the prognostic ability of nomograms such as Sarculator and ultimately enable more accurate and individualized healthcare. Currently, clinical variables continue to be the most significant and effective factors in terms of predicting outcomes in patients with STS. This review firstly introduces the rationale for developing and employing nomograms such as Sarculator, secondly, reflects on some of the latest and ongoing methodological refinements, and provides future perspectives in the field of prognostication of sarcomas.
Secular trend and projection of overweight and obesity among Chinese children and adolescents aged 7–18 years from 1985 to 2019: Rural areas are becoming the focus of investment
Authors: Dang Jiajia , Liu Yunfei , Cai Shan , Zhong Panliang , Shi Di , Chen Ziyue , Zhang Yihang , Dong Yanhui , Ma Jun , Song Yi 
Published: May 2024

Abstract

Background:
The urban–rural disparities in overweight and obesity among children and adolescents are narrowing, and there is a need for long-term and updated data to explain this inequality, understand the underlying mechanisms, and identify priority groups for interventions.

Methods:
We analyzed data from seven rounds of the Chinese National Survey on Students Constitution and Health (CNSSCH) conducted from 1985 to 2019, focusing on school-age children and adolescents aged 7–18 years. Joinpoint regression was used to identify inflection points (indicating a change in the trend) in the prevalence of overweight and obesity during the study period, stratified by urban/rural areas and sex. Annual percent change (APC), average annual percent change (AAPC), and 95% confidence interval (CI) were used to describe changes in the prevalence of overweight and obesity. Polynomial regression models were used to predict the prevalence of overweight and obesity among children and adolescents in 2025 and 2030, considering urban/rural areas, sex, and age groups.

Results:
The prevalence of overweight and obesity in urban boys and girls showed an inflection point of 2000, with AAPC values of 10.09% (95% CI: 7.33–12.92%, t = 7.414, P <0.001) and 8.67% (95% CI: 6.10–11.30%, t = 6.809, P <0.001), respectively. The APC for urban boys decreased from 18.31% (95% CI: 4.72–33.67%, t = 5.926, P = 0.027) to 4.01% (95% CI: 1.33–6.75%, t = 6.486, P = 0.023), while the APC for urban girls decreased from 13.88% (95% CI: 1.82–27.38%, t = 4.994, P = 0.038) to 4.72% (95% CI: 1.43–8.12%, t = 6.215, P = 0.025). However, no inflection points were observed in the best-fit models for rural boys and girls during the period 1985–2019. The prevalence of overweight and obesity for both urban and rural boys is expected to converge at 35.76% by approximately 2027. A similar pattern is observed for urban and rural girls, with a prevalence of overweight and obesity reaching 20.86% in 2025.

Conclusions:
The prevalence of overweight and obesity among Chinese children and adolescents has been steadily increasing from 1985 to 2019. A complete reversal in urban–rural prevalence is expected by 2027, with a higher prevalence of overweight and obesity in rural areas. Urgent action is needed to address health inequities and increase investments, particularly policies targeting rural children and adolescents.
Radiotherapy enhances efficacy of PD-1 inhibitors in advanced hepatocellular carcinoma: A propensity-matched real-world study
Authors: Hsu Shujung , Chao Yencheng , Hu Yong , Zhang Yang , Hong Weifeng , Chen Yixing , Chen Rongxin , Zeng Zhaochong , Du Shisuo 
Published: May 2024

Abstract

Background:
To address the need for immunotherapy in patients with advanced primary hepatocellular carcinoma (HCC), combination with radiotherapy (RT) has emerged as a promising strategy. In preclinical studies, irradiated tumors released tumor antigens to synergistically increase the antitumor effect of immunotherapy. Hence, we investigated whether RT enhances the efficacy of anti-programmed death receptor-1 (PD-1) inhibitors in advanced HCC in real-world practice.

Methods:
Between August 2018 and June 2021, 172 patients with advanced primary HCC were enrolled in the tertiary center (Zhongshan Hospital of Fudan University); 95 were treated with a combination of RT and the inhibitor of PD-1 (RT-PD1 cohort), and 77 were administered anti-PD-1 therapy (PD1 cohort). The first cycle of PD-1 inhibitors was administered within 60 days or concurrently with RT. Propensity score matching for bias reduction was used to evaluate the clinical outcomes.

Results:
Among 71 propensity-matched pairs, median progression-free survival was 5.7 months in the RT-PD1 cohort vs. 2.9 months in the PD1 cohort (P <0.001). Median overall survival was 20.9 months in the RT-PD1 cohort vs. 11.2 months in the PD1 cohort (P = 0.018). Compared with patients in the PD1 cohort, patients in the RT-PD1 cohort had significantly higher objective response rates (40.8%, 29/71 vs. 19.7%, 14/71, P = 0.006) and disease control rates (62.0%, 44/71 vs. 31.0%, 22/71, P <0.001). The incidences of toxic effects were not significantly different between the two cohorts.

Conclusions:
RT plus anti-PD-1 therapy is well tolerated. RT enhances the efficacy of anti-PD-1 therapy in patients with advanced primary HCC by improving survival outcomes without increased toxic effects.
CYP1A2 Polymorphism and Drug Co-administration Affect the Blood Levels and Adverse Effects of Pirfenidone
Authors: Yang Xuerong , Wei Jingxia , Yang Yong , He Yuanyuan , Guo Lu , He Xing , Zhang Lijuan , Chen Lu 
Published: May 2024

Background:
Mutations in metabolic enzymes and co-administration of drugs may affect the blood concentration of pirfenidone effective in pulmonary fibrosis. To provide a basis for the precise clinical use of pirfenidone, the authors analyzed the correlation between steady-state pirfenidone trough concentration and adverse drug reactions (ADRs) and examined the impact of CYP1A2*1C (rs2069514) and *1F (rs762551) variants and co-administration on pirfenidone blood concentrations and ADRs.

Methods:
Forty-four patients were enrolled. The blood concentration of pirfenidone was determined using high-performance liquid chromatography. CYP1A2*1C and *1F genotypes were determined using direct SNP sequencing. Additional information related to drug associations was collected to screen factors affecting drug metabolism.

Results:
The highest predictive value of ADRs was observed when the steady-state trough concentration of pirfenidone was 3.18 mcg·mL−1 and the area under the receiver operating characteristic curve was 0.701 (P = 0.024). The pirfenidone concentration-to-dose ratio (C/D) in CYP1A2*1F homozygous AA mutants was lower than that in C carriers (CC+AC) (1.28 ± 0.85 vs. 2.03 ± 1.28 mcg·mL−1; P = 0.036). Adverse drug reaction (ADR) incidence in the homozygous AA mutant group (28.0%) was significantly lower than that in the C carriers (CC+AC) (63.2%; P = 0.020), and ADR incidence in the A carriers (AC+AA) was considerably lower than that in the CC group (85.7%; P = 0.039). The C/D value of the combined lansoprazole/rabeprazole group was lower than that of the noncombination group (P < 0.05).

Conclusions:
The ADR incidence was positively correlated with pirfenidone blood concentration. The CYP1A2 (rs762551) AA genotype is associated with lower pirfenidone concentrations and fewer ADRs. Lansoprazole/rabeprazole co-administration reduced pirfenidone concentrations. Randomized controlled trials should further explore personalized dosing of pirfenidone and combination therapies.
A polygenic risk score for alcohol-associated cirrhosis among heavy drinkers with European ancestry
Authors: Schwantes-An Tae-Hwi , Whitfield John B. , Aithal Guruprasad P. , Atkinson Stephen R. , Bataller Ramon , Botwin Greg , Chalasani Naga P. , Cordell Heather J. , Daly Ann K. , Darlay Rebecca , Day Christopher P. , Eyer Florian , Foroud Tatiana , Gawrieh Samer , Gleeson Dermot , Goldman David , Haber Paul S. , Jacquet Jean-Marc , Lammert Craig S. , Liang Tiebing , Liangpunsakul Suthat , Masson Steven , Mathurin Philippe , Moirand Romain , McQuillin Andrew , Moreno Christophe , Morgan Marsha Y. , Mueller Sebastian , Müllhaupt Beat , Nagy Laura E. , Nahon Pierre , Nalpas Bertrand , Naveau Sylvie , Perney Pascal , Pirmohamed Munir , Seitz Helmut K. , Soyka Michael , Stickel Felix , Thompson Andrew , Thursz Mark R. , Trépo Eric , Morgan Timothy R. , Seth Devanshi ,   for the GenomALC Consortium
Published: May 2024

Background:
Polygenic Risk Scores (PRS) based on results from genome-wide association studies offer the prospect of risk stratification for many common and complex diseases. We developed a PRS for alcohol-associated cirrhosis by comparing single-nucleotide polymorphisms among patients with alcohol-associated cirrhosis (ALC) versus drinkers who did not have evidence of liver fibrosis/cirrhosis.

Methods:
Using a data-driven approach, a PRS for ALC was generated using a meta-genome-wide association study of ALC (N=4305) and an independent cohort of heavy drinkers with ALC and without significant liver disease (N=3037). It was validated in 2 additional independent cohorts from the UK Biobank with diagnosed ALC (N=467) and high-risk drinking controls (N=8981) and participants in the Indiana Biobank Liver cohort with alcohol-associated liver disease (N=121) and controls without liver disease (N=3239).

Results:
A 20-single-nucleotide polymorphisms PRS for ALC (PRSALC) was generated that stratified risk for ALC comparing the top and bottom deciles of PRS in the 2 validation cohorts (ORs: 2.83 [95% CI: 1.82 -4.39] in UK Biobank; 4.40 [1.56 -12.44] in Indiana Biobank Liver cohort). Furthermore, PRSALC improved the prediction of ALC risk when added to the models of clinically known predictors of ALC risk. It also stratified the risk for metabolic dysfunction -associated steatotic liver disease -cirrhosis (3.94 [2.23 -6.95]) in the Indiana Biobank Liver cohort -based exploratory analysis.

Conclusions:
PRSALC incorporates 20 single-nucleotide polymorphisms, predicts increased risk for ALC, and improves risk stratification for ALC compared with the models that only include clinical risk factors. This new score has the potential for early detection of heavy drinking patients who are at high risk for ALC.
Patient-focused drug development in primary sclerosing cholangitis: Insights on patient priorities and involvement in clinical trials
Authors: Li Michael , Pai Ruth-Anne , Gomel Rachel , Vyas Mary , Callif Sarah Curup , Hatchett Joanne , Bowlus Christopher L. , Lai Jennifer C. 
Published: May 2024

Background:
According to the new AASLD Practice Guidance, all patients with primary sclerosing cholangitis (PSC) should be considered for participation in clinical trials. However, PSC’s rarity has posed challenges to characterizing patient interest in trial participation and identifying predictors of patient willingness to participate in drug trials.

Methods:
PSC Partners Seeking a Cure developed the “Our Voices” survey to inform the development of the Externally-Led Patient-Focused Drug Development Forum, an FDA initiative to capture patient experiences and perspectives on drug development.

Results:
Of 797 survey respondents from over 30 countries, 536 (67%) identified slowing disease progression as the most important outcome. Eighty-nine percent identified their hepatologist/gastroenterologist as someone they would approach for advice about trials. Although 61% reported being willing to participate in drug trials, only 26% had ever been asked to participate. Notable barriers to trial involvement included unknown long-term risks (71%), long travel times to the study center (32%), and a liver biopsy requirement (27%). On multivariable logistic regression, pruritus (OR 1.62, 95% CI: 1.09–2.40, p = 0.017) was positively associated with willingness to participate in disease-modifying therapy trials, while jaundice (OR 0.34, 95% CI: 0.19–0.61, p < 0.001) and inflammatory bowel disease (OR 0.64, 95% CI: 0.42–0.98, p = 0.038) were negatively associated. Pruritus (OR 2.25, 95% CI: 1.50–3.39, p < 0.001) was also independently associated with willingness to participate in symptom treatment trials.

Conclusions:
Most patients with PSC report interest in participating in clinical trials, but few have been asked to participate. Referral of patients with PSC by their hepatologist/gastroenterologist to clinical trials and patient education on trial participation are vital to closing the gap between trial interest and participation. Pruritus may serve as a key indicator of patient interest in trial participation.
Characteristics of Prescreened Patients Who Did Not Participate in the Zoster Eye Disease Study
Authors: Maja Ayodele K. , Gu Darren , Ge Lily , Lopez-Jimenez Carlos , Cohen Elisabeth J. , Zegans Michael E. 
Published: May 2024

Purpose:
The Zoster Eye Disease Study (ZEDS) is a multicenter randomized clinical trial (RCT) funded by the National Eye Institute aiming to determine the efficacy of suppressive valacyclovir treatment in herpes zoster ophthalmicus (HZO) that enrolled fewer participants than planned (527/780, 67.6%). Understanding reasons for nonparticipation of likely eligible prescreened patients provides insights into patient populations that are not represented by ZEDS and barriers in clinical trials.

Methods:
In this retrospective cohort study, HZO adults likely eligible for ZEDS with a history of a typical rash and a medical record within the past year of an episode of epithelial or stromal keratitis or iritis were prescreened at activated Participating Clinical Centers from 2017 to 2022 using a standard prescreening log. De-identified data including demographic information, reasons for exclusion because of ineligibility, and patient refusal were retrospectively entered into REDCap and analyzed.

Results:
Prescreening logs with reasons for nonconsent (1244/1706, 72.9%) were included in the data set. Patients were excluded from the study (915/1244, 73.6%) because they did not meet all inclusion criteria (619/915, 67.7%) or met an exclusion criterion (296/915, 32.3%). Among the 12 exclusion criteria for the ZEDS study, immunocompromise (76/296, 25.7%) and renal insufficiency (50/296, 16.9%) were most frequently reported. Patient refusal to participate (327/1,244, 26.3%) was common.

Conclusion:
The most common reasons for ineligibility were immunocompromise and renal insufficiency. There may be benefits to long-term antiviral use in these populations not captured in ZEDS. A quarter (26.3%) of prescreened patients refused participation, showing the substantial impact of patient preferences on trial participation.
Lacrimal Obstruction in Craniosynostosis: Anatomical and Genetic Risk Factors
Authors: Landau-Prat Daphna , Taylor Jesse A. , Kalmar Christopher L. , Yu Yinxi , Ying Gui-Shuang , Bartlett Scott , Swanson Jordan , Revere Karen , Binenbaum Gil , Katowitz William R. , Katowitz James A. 
Published: May 2024

Purpose:
To investigate whether patients with craniosynostosis exhibit higher rates of nasolacrimal duct obstruction (NLDO) and to explore potential risk factors.

Methods:
Retrospective review including all craniosynostosis patients treated at both the Divisions of Ophthalmology and Plastic, Reconstructive, and Oral Surgery at The Children’s Hospital of Philadelphia between 2009 and 2020 was conducted. Synostosis characteristics, lacrimal disorders, and genetic data were collected. Main outcome measures were the rate of NLDO and associations with anatomical and syndromic/genetic risk factors.

Results:
The total of 767 participants had a mean age of 2.8 ± 3.8 years, 465 (60.6%) were males, 485 (63.2%) had no syndromic association; 631 (82.3%) had one major suture involved, 128 (17%) had involvement of 2 to 4 major sutures, and 429 (55.9%) underwent craniofacial surgery. Forty-eight (6.2%) patients had NLDO, which more prevalent in the genetic/syndromic group (11.0% vs. 3.5%, respectively, p < 0.001), with the highest prevalence observed in patients with Apert syndrome (n = 4, 30.8%). The genetic variants most associated with NLDO were EFNB1 (n = 1, 100%) and FGFR2 (n = 6, 19.4%). There was no association between NLDO and the number or types of sutures involved or a history of craniofacial surgery.

Conclusions:
Nasolacrimal duct obstruction is more common in patients with craniosynostosis compared to the general population. Having a putative syndrome or a putative genetic variant and female sex were risk factors for NLDO. Ophthalmic evaluations for all craniosynostosis patients and careful assessments of any symptoms of tearing are recommended.