bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of platelet-rich fibrin (PRF) versus freeze-dried bone allograft (FDBA) used in alveolar ridge preservation on the peri-implant soft and hard tissues: a randomized clinical trial
Authors: Azangookhiavi Hassan , Habibzadeh Sareh , Zahmatkesh Houyar , Mellati Ehsan , Mosaddad Seyed Ali , Dadpour Yalda 
Published: June 2024

AbstractBackgroundThe effectiveness of alveolar ridge preservation on bone regeneration and tissue healing has been thoroughly documented in the literature. This study aimed to evaluate the peri-implant soft and hard tissue changes after alveolar ridge preservation using either platelet-rich fibrin (PRF) or freeze-dried bone allograft (FDBA) over a 12-month period following the prosthetic loading of implants.MethodsIn this randomized clinical trial, 40 individuals were recruited for alveolar ridge preservation using (1) FDBA or (2) PRF in incisal/premolar areas. At two follow-up sessions (six- and 12-months post-implant insertion), radiographic imaging and clinical examinations assessed marginal bone loss and soft tissue factors, including gingival recession and bleeding on probing. The differences between study groups were analyzed using Generalized estimating Equations, the Binary logistic regression model, and Cochran’s Q test.ResultsThere was a statistically significant difference regarding gingival recession at both follow-up evaluations; values in the PRF group were considerably lower compared to the FDBA group (p < 0.05). The mean values for vertical marginal bone loss and bleeding on probing showed no significant differences between the two study groups (p > 0.05).ConclusionsExcept for gingival recession, applying PRF yielded comparable clinical results to FDBA after one year of implant loading and could be recommended as a potential biomaterial for alveolar ridge preservation following tooth extractions.Clinical trial registrationThe research protocol was registered in the Protocol Registration and Results System on 13/08/2021, available athttps://clinicaltrials.gov/(NCT05005377).
Associations of clinical context-specific ambiguity tolerance with burnout and work engagement among Japanese physicians: a nationwide cross-sectional study
Authors: Fujikawa Hirohisa , Aoki Takuya , Ando Takayuki , Haruta Junji 
Published: June 2024

Abstract
Purpose
Ambiguity tolerance specific to the clinical context – in contrast to ambiguity tolerance as a personality trait – may vary with experience and has received considerable attention. Although this tolerance appears to be related to burnout and work engagement, few studies have examined this association among physicians. Thus, we aimed to examine the relationships between clinical context-specific ambiguity tolerance, burnout, and work engagement among physicians in Japan.

Methods
We conducted a nationwide cross-sectional study in Japan. We invited family physicians from 14 family medicine residency programs and physicians with specialties other than family medicine from monitors of an Internet survey company to participate in the study. We measured ambiguity tolerance in the clinical context using the Japanese version of the Tolerance of Ambiguity in Medical Students and Doctors (J-TAMSAD) scale, burnout using the Japanese version of the Burnout Assessment Scale (BAT-J), and work engagement using the Utrecht Work Engagement Scale (UWES). We performed a multivariable linear regression analysis to determine whether the J-TAMSAD scale score was associated with the BAT-J and UWES scores.

Results
383 respondents were included in the analysis. After adjustment for possible confounders, clinical context-specific ambiguity tolerance showed a dose-dependent negative association with burnout (adjusted mean difference  -0.39, 95% confidence interval (CI) -0.56 to -0.22 for the highest J-TAMSAD score quartile compared with the lowest). Ambiguity tolerance in the clinical context also showed a dose-dependent positive association with work engagement (adjusted mean difference 0.83, 95% CI 0.49 to 1.16 for the highest J-TAMSAD score quartile compared with the lowest).

Conclusions
Our study showed that tolerance for ambiguity in the clinical context was negatively associated with burnout, and positively associated with work engagement. These findings will be useful in developing interventions aimed at preventing burnout and promoting work engagement among physicians.
ALKBH5 promotes non-small cell lung cancer progression and susceptibility to anti-PD-L1 therapy by modulating interactions between tumor and macrophages
Authors: Hua Xin , Xu Qiuli , Wu Ranpu , Sun Wei , Gu Yanli , Zhu Suhua , Liu Xin , Lv Tangfeng , Song Yong 
Published: June 2024

Abstract
Background
Understanding the mechanisms that mediate the interaction between tumor and immune cells may provide therapeutic benefit to patients with cancer. The N6-methyladenosine (m6A) demethylase, ALKBH5 (alkB homolog 5), is overexpressed in non-small cell lung cancer. However, its role in the tumor microenvironment is unknown.

Methods
Datasets and tissue samples were used to determine the relationship between ALKBH5 expression and immunotherapy efficacy. Bioinformatic analysis, colorimetric assay to determine m6A RNA methylation, dual luciferase reporter assay, RNA/m6A-modified RNA immunoprecipitation, RNA stability assay, and RNA sequencing were used to investigate the regulatory mechanism of ALKBH5 in non-small cell lung cancer. In vitro and in vivo assays were performed to determine the contribution of ALKBH5 to the development of non-small cell lung cancer.

Results
ALKBH5 was upregulated in primary non-small cell lung cancer tissues. ALKBH5 was positively correlated with programmed death-ligand 1 expression and macrophage infiltration and was associated with immunotherapy response. JAK2 was identified as a target of ALKBH5-mediated m6A modification, which activates the JAK2/p-STAT3 pathway to promote non-small cell lung cancer progression. ALKBH5 was found to recruit programmed death-ligand 1-positive tumor-associated macrophages and promote M2 macrophage polarization by inducing the secretion of CCL2 and CXCL10. ALKBH5 and tumor-associated macrophage-secreted IL-6 showed a synergistic effect to activate the JAK2/p-STAT3 pathway in cancer cells.

Conclusions
ALKBH5 promotes non-small cell lung cancer progression by regulating cancer and tumor-associated macrophage behavior through the JAK2/p-STAT3 pathway and the expression of CCL2 and CXCL10, respectively. These findings suggest that targeting ALKBH5 is a promising strategy of enhancing the anti-tumor immune response in patients with NSCLC and that identifying ALKBH5 status could facilitate prediction of clinical response to anti-PD-L1 immunotherapy.
Effectiveness of remote risk-based monitoring and potential benefits for combination with direct data capture
Authors: Yamada Osamu , Chiu Shih-Wei , Nakazawa Toru , Tsuda Satoru , Yoshida Mitsuhide , Asano Toshifumi , Kokubun Taiki , Hashimoto Kazuki , Takata Munenori , Ikeda Suzuka , Kawabe Yosuke , Tamura Yuko , Yamaguchi Takuhiro 
Published: June 2024

Abstract
Background
In recent years, alternative monitoring approaches, such as risk-based and remote monitoring techniques, have been recommended instead of traditional on-site monitoring to achieve more efficient monitoring. Remote risk-based monitoring (R2BM) is a monitoring technique that combines risk-based and remote monitoring and focuses on the detection of critical data and process errors. Direct data capture (DDC), which directly collects electronic source data, can facilitate R2BM by minimizing the extent of source documents that must be reviewed and reducing the additional workload on R2BM. In this study, we evaluated the effectiveness of R2BM and the synergistic effect of combining R2BM with DDC.

Methods
R2BM was prospectively conducted with eight participants in a randomized clinical trial using a remote monitoring system that uploaded photographs of source documents to a cloud location. Critical data and processes were verified by R2BM, and later, all were confirmed by on-site monitoring to evaluate the ability of R2BM to detect critical data and process errors and the workload of uploading photographs for clinical trial staff. In addition, the reduction of the number of uploaded photographs was evaluated by assuming that the DDC was introduced for data collection.

Results
Of the 4645 data points, 20.9% (n = 973, 95% confidence interval = 19.8–22.2) were identified as critical. All critical data errors corresponding to 5.4% (n = 53/973, 95% confidence interval = 4.1–7.1) of the critical data and critical process errors were detectable by R2BM. The mean number of uploaded photographs and the mean time to upload them per visit per participant were 34.4 ± 11.9 and 26.5 ± 11.8 min (mean ± standard deviation), respectively. When assuming that DDC was introduced for data collection, 45.0% (95% confidence interval = 42.2–47.9) of uploaded photographs for R2BM were reduced.

Conclusions
R2BM can detect 100% of the critical data and process errors without on-site monitoring. Combining R2BM with DDC reduces the workload of R2BM and further improves its efficiency.
Simulation of gravity field estimation of Phobos for Martian Moon eXploration (MMX)
Authors: Yamamoto Keiko , Matsumoto Koji , Ikeda Hitoshi , Senshu Hiroki , Willner Konrad , Ziese Ramona , Oberst Jürgen 
Published: June 2024

AbstractWe study the dynamic orbit about Phobos of the Martian Moon eXploration (MMX) spacecraft and simulate gravity field estimation using Doppler, image landmarks, and LIght Detection And Ranging (LIDAR) data based on a mission plan of MMX and investigate whether the differences in the internal density structure of Phobos can be detected through this mission. Degree 2 Stokes coefficients of the Phobos gravity field, $${\overline{C} }_{20}$$

C
¯

20

and $${\overline{C} }_{22}$$

C
¯

22

, which are necessary to obtain the moment of inertia by combining with the libration amplitude, could be determined with an accuracy within the order of 0.1% using datasets from two-dimensional (2D) quasi-satellite orbits (QSOs). If observations from 3D-QSO could be realized at low altitude, coefficients up to degree and order 5 could be estimated, which could be used to detect regional density anomalies. Moreover, the observation data from the ascending trajectory after landing on the Phobos surface can be used to detect local density anomalies around the landing site, which could help interpret the origin of the samples and understand the internal structure of Phobos.
Graphical Abstract
Exploring the utilization and perceptions of pre-travel health consultations in primary care settings in Saudi Arabia: a cross-sectional study
Authors: AlAmer Naheel A. , AlQarni Amani M. 
Published: June 2024

Abstract
Background
International travel exposes individuals to diverse health risks, necessitating proactive pre-travel health preparations. Saudi Arabia has witnessed increased outbound travel. This study addresses a critical gap in knowledge by investigating the utilization and perceptions of pre-travel health consultations among adults in the Eastern Province of Saudi Arabia.

Methods
This cross-sectional study surveyed patients at the Family and Community Medicine Center of Imam Abdulrahman Bin Faisal University during January 2024 to explore perceptions of pre-travel health consultations among the Saudi Arabian population. Adults aged 18 years or older in the waiting area were invited to complete a self-administered questionnaire.

Results
Of the 772 participants, 624 (80.8%) engaged in international travel within the last year. However, 593 (76.8%) had never sought pre-travel health consultations. Age, gender, and education level significantly influenced the pursuit of pre-travel health advice, with older individuals, females, and those with higher educational attainment more likely to seek consultations. Participants perceived vaccination recommendations (597, 77.4%) and disease prevention information (678, 87.8%) as crucial parts of pre-travel health consultations. However, barriers to seeking advice included perceived low risk (445, 74.8%), lack of awareness (215, 36.3%), time constraints (128, 21.6%), and cost concerns (92, 15.5%).

Conclusion
The low prevalence of pre-travel health consultations among travelers highlights the need for targeted educational campaigns and the integration of travel health services into primary healthcare. Addressing the identified barriers and leveraging preferred information sources are crucial steps towards enhancing the uptake of pre-travel health consultations, ultimately improving the health and safety of international travelers from the region.
Safety and efficacy of CyberKnife radiosurgery plus anlotinib hydrochloride in patients with recurrent glioblastoma: A prospective phase II single-arm study.
Authors: Guan Yun , Zhu Huaguang , Li Jing , Zou Wei , Pan Li , Wang Yang , Liu Ying , Wang Enmin , Wang Xin 
Published: June 2024

2050 Background: Glioblastoma (GBM) is a tumor known for its highly vascular nature and limited treatment options upon disease recurrence. While Bevacizumab which target VEGF-A has gained approval for treating recurrent glioblastoma, the multi-target tyrosine kinase inhibitor Anlotinib has the ability to directly target Vascular Endothelial Growth Factor Receptor (VEGFR), Platelet-Derived Growth Factor Receptor (PDGFR), and Fibroblast Growth Factor Receptor (FGFR). Theoretically, its anti-angiogenic effect may exceed that of Bevacizumab, and preliminary studies have shown its therapeutic efficacy in recurrent GBM (rGBM), indicating promising treatment potential. This study aims to present findings regarding the effectiveness and safety of combining Anlotinib with stereotactic radiosurgery (SRS) in treating patients with rGBM. Methods: Patients who underwent surgery, standard radiotherapy, and temozolomide chemotherapy and were diagnosed with recurrence based on Response Assessment in Neuro-Oncology (RANO) criteria and/or biopsy were eligible for inclusion. Each patient underwent CyberKnife SRS (25Gy/5fx) in combination with oral administration of Anlotinib (12 mg, daily, days 1–14/3 weeks) until encountering disease progression or experiencing intolerable adverse effects. The primary objective was the investigator-assessed median overall survival (OS) using the Response Assessment in Neuro-Oncology (RANO) criteria. Results: Between December 2019 and July 2023, 22 patients (median age: 55 years; range: 28–70) were included. According to RANO criteria, 21 patients exhibited tumor response, with 6 achieving complete response, resulting in an objective response rate of 95.5%. Additionally, one patient maintained stable disease without progression. Median progression-free survival (PFS) was 9.1 months (95% CI, 7.5–24.7), with a 6-month PFS rate of 85.7% (95% CI, 71.9–100.0). Median overall survival was 19.5 months (95% CI, 10.6–46.8). Common adverse events included hand-foot skin reactions (40.9%), hypercholesterolemia (27.3%), and hypertension (22.7%). Four patients experienced grade 3 adverse events, accounting for an 18.2% incidence rate. Therapy discontinuation due to ischemic stroke (grade 3) occurred in one patient. No grade 4 events or treatment-related deaths were reported. Conclusions: The combination of salvage SRS with Anlotinib demonstrated promising outcomes and manageable toxicity in managing recurrent GBM. Currently, a phase II randomized controlled trial, supported by the Shanghai Municipal Commission of Health, is underway. This trial aims to compare the efficacy of Anlotinib combined with radiosurgery against Bevacizumab combined with radiosurgery for the treatment of rGBM patients, further exploring this therapeutic regimen. Clinical trial information: NCT04197492 .
A phase 1 study of the small-molecule PD-L1 inhibitor INCB099280 in select advanced solid tumors: Updated safety, efficacy, and pharmacokinetics (PK) results.
Authors: Prenen Hans , Daniel Jeannie , Ebiana Victoria , Howe Jason , Gong Xiaohua , Spitz Susan , Italiano Antoine 
Published: June 2024

2608 Background: INCB099280 has shown preliminary efficacy and acceptable safety in an ongoing phase 1, open-label, multicenter study in patients (pts) with advanced solid tumors (1). Here we present updated results and PK data. Methods: Eligible pts were ≥18 years of age with ECOG PS ≤1 and disease progression after available treatment (tx) or were ineligible for/without access to standard tx. Study started with dose escalation (100 mg qd to 800 mg bid), followed by dose expansion in 3 cohorts (IO-naive; IO-naive, MSI-H/dMMR tumors; anti–PD-1 previously treated). Primary endpoints are safety, tolerability, and determination of pharmacologically active dose/MTD. PK, objective response rate (ORR) per RECIST v1.1, and pharmacologic biomarkers were also analyzed. Results: As of January 14, 2023, 179 pts had received INCB099280 at doses from 100 mg qd to 800 mg bid (median age, 63 years [range, 21-86]; ≥2 prior lines of tx, 65.4%; prior IO, 16.2%). MTD was not reached. Overall, 96.6% of pts had ≥1 tx-emergent adverse events (TEAEs). Immune-related (ir) TEAEs occurred in 23.5% of pts. Best antitumor activity was noted with 400 mg bid (ORR, 17.8%) in pts with mixed tumor types. Updated clinical data will be presented. PK exposures increased proportionally as dose increased up to 800 mg bid (Table). Steady-state PK was achieved by cycle 1 day 8, with an accumulation ratio of 2-3. Inter-individual PK variability was high, but similar to that of healthy participants. Steady-state trough concentrations exceeded IC90 across 300-800 mg bid doses. In preliminary analyses correlating exposure with clinical outcomes, increased exposure was associated with a moderate trend of higher ORR and incidence of serious and/or ir-TEAEs. Preliminary electrocardiogram data suggested that large QTc effects (>20 ms) can be excluded at doses up to 800 mg bid. No association was detected between PK exposure and ctDNA change at cycle 4 day 1 or end-of-tx vs baseline, but decreased ctCNA was seen in all complete responders (n=2) and 6 partial responders (n=11). Conclusions: INCB099280 was generally well tolerated at all doses tested and showed promising antitumor activity. INCB099280 PK was dose proportional up to 800 mg bid, with high variability; steady-state trough exposure exceeded IC90 for ≥300 bid doses. These data support further development of INCB099280 as monotherapy and in combination regimens for solid tumors. Phase 2 studies are ongoing. 1. Prenen, ESMO-IO 2023; NCT04242199. Clinical trial information: NCT04242199 . [Table: see text]
A phase 2a study of NT-I7 (efineptakin alfa), a long-acting IL-7, and pembrolizumab to evaluate efficacy, including overall survival, in hard-to-treat gastrointestinal tumors.
Authors: Kim Richard D. , Mamdani Hirva , Barve Minal A. , Johnson Melissa Lynne , Murphy Julie A. , Trogun Lauren , Ferrando-Martinez Sara , Lee Byung Ha , Yang Se Hwan , Chaney Marya F. , Naing Aung 
Published: June 2024

2621 Background: Microsatellite-stable colorectal (MSS-CRC) and pancreatic cancer (PDAC) are immunologically cold tumors with null response to checkpoint inhibitors (CPI). NT-I7, a long-acting IL-7, in combination with pembrolizumab (pembro) has shown to significantly increase intratumoral T cell infiltration and elicit some tumor control in these hard-to-treat gastrointestinal indications. The original MSS-CRC and PDAC cohorts, enrolling 25 patients (pts) each, were expanded to 50 pts per indication. Here, we provide an updated analysis including the original and expansion cohorts. Methods: Open-label Phase 2a study in subjects with relapsed/refractory CPI-naïve MSS-CRC and PDAC; NT-I7 1200 µg/kg IM every 6 weeks (Q6W), pembro 200 mg IV Q3W. Antitumor activity assessed by RECIST v1.1/iRECIST. Results: As of 02OCT2023, 98 subjects were efficacy-evaluable (50 MSS-CRC, 48 PDAC); median age 61.0 years, all with baseline ECOG status 0-1. 95.9% (94/98) received study treatment ≥3rd line, with a median follow -up of 6.1 months. Safety profile for NT-I7 was similar to previous reports. In MSS-CRC pts, 1 pt and 3 pts achieved confirmed partial responses per RECIST and iRECIST, respectively; median duration of response (DOR/iDOR) was 13.1/13.0 months (mo) and 2 responders were alive with no progression at data cutoff. Disease control rate (DCR/iDCR) was 36.0% (18/50) / 38.0% (19/50), with a duration of response and stable disease (DORSD/iDORSD) of 3.2/14.5mo. Interestingly, iDCR was 71.4% (5/7) in MSS-CRC pts with primary tumor in the rectum, versus 30.8% (12/39) in pts with primary tumor in the colon. With 11 pts on follow up, progression free survival (PFS/iPFS) was 1.5/3.8 mo. Among PDAC pts, 2 and 3 pts achieved confirmed PR and iPR, with DOR/iDOR of NE/9.7 mo; 1 responder was alive with no progression at data cutoff. DCR/iDCR was 25.0% (12/48) / 27.1% (13/48), and DORSD/iDORSD was 2.9/9.8mo. With 11 pts on follow up, PFS/iPFS was 1.4/2.1 mo. Clinical benefit in MSS-CRC and PDAC was most evident by a notable median overall survival (mOS); 13.2 mo in MSS-CRC [95% CI 8.9 – 18.6 mo] and 11.1 mo in PDAC [95% CI 4.1 – 13.3 mo], compared to historical mOS for standard of care, 10.8 mo (MSS-CRC) and 6.1 mo (PDAC). Conclusions: NT-I7 and pembro treatment was associated with longer mOS relative to historical studies. Identification of predictive biomarkers that may define pts with higher likelihood of clinical benefit would be a promising step to maximizing potential of the NT-I7 + pembro treatment combination for pts with these indications. Research in this area is ongoing. Clinical trial information: NCT04332653 .