bluuebunny/crossref_metadata_2025_split huggingface dataset:
CFT8634, a Clinical Stage BRD9 Bi DAC™ Degrader, Is Active in a Subset of Multiple Myeloma Cell Line Models and Synergistic When Combined with Pomalidomide
Authors: Poling Laura L , Cocozziello David , He Minsheng , Hurh Eunju , Lobbardi Riadh , Jackson Katrina L , Fisher Stewart L , Pollock Roy M 
Published: December 2023

Recent literature has shown that loss-of-function of BRD9, a component of the noncanonical SWI/SNF (ncSWI/SNF) complex, mediated either by RNA interference or by BRD9 tool degrader compounds can inhibit multiple myeloma (MM) cell lines and primary MM cell proliferation in vitro, as well as inhibit mouse MM xenograft tumor growth in vivo. Additionally, in vitro synergy in MM proliferation assays was observed when a tool BRD9 degrader was combined with the standard of care (SoC) agents, dexamethasone or pomalidomide. Given the continued unmet need of the MM patient population, we explored the therapeutic potential of CFT8634 in this indication. CFT8634, a potent and selective oral BiDAC™ degrader of BRD9, is currently in a Phase 1/2 clinical trial (NCT05355753) for the treatment of SMARCB1-perturbed cancers, including synovial sarcoma and SMARCB1-null tumors. Pharmacokinetic and pharmacodynamic data to date from the ongoing trial of CFT8634 has demonstrated dose-proportional human plasma exposure and robust BRD9 degradation in patient tumor samples thereby establishing proof of mechanism in patients.
Here we show that CFT8634 has anti-proliferative activity in a subset of MM cell lines that translates into tumor growth inhibition in MM xenograft models at clinically relevant CFT8634 exposures. We observe that cell lines less sensitive to pomalidomide tend to be significantly more sensitive to CFT8634 treatment. As pomalidomide is a SoC treatment in MM, we interrogated the ability to combine CFT8634 and pomalidomide. CFT8634 demonstrates synergy with pomalidomide in MM cell lines where CFT8634 is anti-proliferative as a single agent. We further show that clinically relevant exposures of CFT8634 demonstrate synergy with pomalidomide in vivo in the NCI-H929 mouse xenograft model (Figure 1). This model is relatively unresponsive to pomalidomide alone, suggesting that CFT8634 can render otherwise recalcitrant MM tumors sensitive to the effects of pomalidomide in combination. Pharmacokinetic and pharmacodynamic analyses show that in combination, CFT8634 and pomalidomide do not interfere with the ability to degrade each other's targets (BRD9 and IKZF1/3, respectively) despite both utilizing the E3 ligase cereblon.
In conclusion, we demonstrate in vitro and in vivo activity in an expanded set of MM models using the clinical oral BRD9 degrader CFT8634 as a single agent and show in vivo synergy between CFT8634 and pomalidomide at clinically relevant doses. Our findings suggest that combining CFT8634 with pomalidomide may be a viable therapeutic strategy in treating MM patients.
Preliminary Results from a Phase I/II Study of Pomalidomide Plus Rituximab, Ifosfamide, Carboplatin, and Etoposide for Relapsed or Refractory Diffuse Large B-Cell Lymphoma (PRIDE)
Authors: Xu Pengpeng , Li Wang , Cheng Shu , Zhao Wei Li 
Published: December 2023

Background: Relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) patients have limited treatment options and are associated with poor prognosis. Outcomes are particularly poor following immunochemotherapy failure or relapse within 12 months of induction. The addition of the immunomodulatory agent lenalidomide (Len) to rituximab plus ifosfamide-carboplatin-etoposide (RICE) was shown to be feasible with promising efficacy in some studies. Pomalidomide (Pom) is a third-generation immunomodulatory drug that has shown excellent therapeutic activity against relapsed/refractory primary central nervous system lymphoma (PCNSL) with an acceptable toxicity profile. We conducted a phase I/II study combining Pom with RICE (PRICE) as a salvage regimen in first-relapse or primary refractory DLBCL (ChiCTR2100049327). Here we report the phase I results of the study.
Methods: In phase I of the study, patients receive escalating doses of pomalidomide (2 mg, 3 mg, or 4 mg daily on d1-10) along with R-ICE therapy every 21 days by 3+3 design. Patients with CR or PR but not eligible for ASCT receive continuous pomalidomide as maintenance therapy for 12 months. The primary objective was to determine the maximum tolerated dose (MTD) or recommended dose, based on the occurrence of treatment-related DLTs. Secondary objectives included tumor response and safety.
Results: At data cut-off (July 11, 2023), 14 patients were screened and 10 eligible patients were enrolled. 9 patients had been treated in the first 2 dose-escalation cohorts: 6 patients at 2 mg and 6 patients at 3 mg. Patient characteristics at baseline are shown in Table I. DLT was observed in two patients in the 3 mg cohort (grade 4 thrombocytopenia and grade 4 rash). MTD was determined as 2 mg. Grade (G) ≥ 3 TRAEs were leukopenia (4 patients), lymphopenia (3 patients), thrombocytopenia (3 patients), neutropenia (3 patients), rash (1 patient) and myelosuppression (1 patient). No death was related to the treatment. Five patients (55.6%) achieved an objective response including four patients (44.4%) with CR. ORR for the MTD dose level was (4/6) 66.7% with 3 CR and 1 PR. Notably, among the 7 patients with MYD88 mutations, which are associated with enhanced NF-κB activity, 4 achieved CR and 1 achieved PR.
Conclusion: The addition of pomalidomide to the widely used RICE salvage regimen is feasible, and results in promising response rates in this DLBCL population that mostly with non-GCB subtype and double expression. MTD was reached and RP2D was determined to be 2 mg. Further studies are needed to evaluate the efficacy of this regimen, particularly in patients with MYD88 mutations.
Using infrared cameras in drones to detect bleeding events
Authors: West Christoph , Kaus Bernhard , Sullivan Sean O’ , Schneider Henning , Seifert Oskar 
Published: December 2023

Abstract
Background
Hemorrhage is one of the main causes of death in trauma. Critical bleeding in patients needs to be detected as soon as possible to save the patient. Drones are gaining increasing importance in emergency services and can support rescue forces in accident scenarios such as a mass casualty incident.

Methods
In this study, a simulated pelvic hemorrhage was detected using a drone from 7 m above the ground over a time span of 30 s.

Results
The results allow a good detection of the pelvic hemorrhage. Nevertheless, the simulated blood cools down quickly. After 30 s, there was no significant temperature difference compared to the rest of the body. At this point, further assessment is only possible via the RGB image.

Conclusion
The findings suggest that bleeding from an open and continuously bleeding wound would most likely be detectable using the drone’s thermal imaging camera, even over a longer period of time.
Association between gestational exposure and risk of orofacial clefts: a systematic review and meta-analysis
Authors: Huang ZhiMeng , Wu JinZhun , Qiu Yue , Lin Jiayan , Huang Wanting , Ma Xiaohui , Zhang Huifen , Yang Xiaoqing 
Published: December 2023

Abstract
Background
The occurrence of orofacial Clefts (OFCs) is a congenital disease caused by many factors. According to recent studies, air pollution has a strong correlation with the occurrence of OFCs. However, there are still some controversies about the current research results, and there is no relevant research to review the latest results in recent years.

Objective
In this paper, the authors conducted a systematic review and meta-analysis to explore the correlation between ambient air pollution and the occurrence of neonatal OFCs deformity.

Methods
We searched Pubmed, Web of science, and Embase databases from the establishment of the database to May 2023. We included observational studies on the relationship between prenatal exposure to fine particulate matter 2.5 (PM2.5), fine particulate matter 10 (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), carbon monoxide (CO) and the risk of cleft lip (CL), cleft palate (CP), cleft lip with or without palate (CL/P). the Newcastle-Ottawa quality assessment scale (NOS) was used to evaluate the quality of the literature. Funnel plot and Egger’s regression were used to verify the publication bias. Random effect model or fixed effect model was used to estimate the combined relative risk (RR) and 95% confidence interval (95%CI).

Results
A total of eleven studies were included in this study, including four cohort studies and seven case-control studies, including 22,453 cases of OFCs. Ten studies had low risk of bias and only one study had high risk of bias. Three studies reported that PM2.5 was positively correlated with CL and CP, with a combined RR and 95%CI of 1.287(1.174,1.411) and 1.267 (1.105,1.454). Two studies reported a positive correlation between O3 and CL, with a combined RR and 95%CI of 1.132(1.047,1.225). Two studies reported a positive correlation between PM10 and CL, with a combined RR and 95%CI of 1.108 (1.017,1.206). No association was found between SO2, CO, NO2 exposure during pregnancy and the risk of OFCs.

Conclusion
The results of this study showed that there was a significant statistical correlation between exposure to PM10, PM2.5, O3 and the risk of OFCs in the second month of pregnancy. Exposure assessment, research methods and mechanisms need to be further explored.
CYP4B1 polymorphisms and the risk of breast cancer in Chinese women: a case-control study
Authors: Yin Yanhai , Tong Liangqian , Wan Zhenling , Sui Yanfang , Li Fen , Huang Qian , Zhao Xinhan 
Published: December 2023

Abstract
Background
Breast cancer (BC) is one of the malignant diseases threatening the life and health of women worldwide. The CYP4B1 gene was abnormally expressed in BC and was associated with the prognosis of BC patients. This study aimed to explore the relationship between CYP4B1 single nucleotide polymorphisms (SNPs) and BC risk in Chinese women.

Methods
A case-control study of 1,143 women (571 patients and 572 healthy individuals) was conducted. Rs2297813 G/T, rs12142787 G/A, and rs3766197 C/T in CYP4B1 were selected and genotyped by MassARRAY system. The relationships between these SNPs and the risk of BC were assessed by logistic regression analysis. In addition, multi-factor dimensionality reduction (MDR) was used to analyze SNP-SNP interactions.

Results
CYP4B1 rs2297813 had a risk-increasing effect on BC in women with body mass index (BMI) ≤ 24 kg/m2 (OR = 1.72, p = 0.026). CYP4B1 rs12142787 was associated with an increased BC risk in smokers (AA: OR = 1.32, p = 0.045). Among non-drinkers, rs2297813 (OR = 1.69, p = 0.009) and rs12142787 (OR = 1.51, p = 0.020) were related to an increased incidence of BC. CYP4B1 rs3766197 (OR = 1.61p = 0.031) was associated with a higher risk of advanced stages (III/IV stage) of BC. Besides, the contributions of CYP4B1 rs2297813 (OR = 1.55, p = 0.021) and rs12142787 (OR = 1.53, p = 0.033) to BC risk might be associated with more than one birth in patients with BC. The three-locus model consisting of rs2297813, rs12142787, and rs3766197 was regarded as the best predictive model for BC risk.

Conclusion
CYP4B1 SNPs were associated with BC risk in Chinese women, especially in patients with BMI ≤ 24 kg/m2, smokers, non-drinkers, patients in advanced stages (III/IV stage), and patients who reproduced once. These findings shed light on the relationship between CYP4B1 SNPs and BC risk in Chinese women.
Construction and validation of a nomogram to predict the overall survival of small cell lung cancer: a multicenter retrospective study in Shandong province, China
Authors: Song Ziqian , Ma Hengmin , Sun Hao , Li Qiuxia , Liu Yan , Xie Jing , Feng Yukun , Shang Yuwang , Ma Kena , Zhang Nan , Wang Jialin 
Published: December 2023

Abstract
Background
Patients diagnosed with small cell lung cancer (SCLC) typically experience a poor prognosis, and it is essential to predict overall survival (OS) and stratify patients based on distinct prognostic risks.

Methods
Totally 2309 SCLC patients from the hospitals in 15 cities of Shandong from 2010 − 2014 were included in this multicenter, population-based retrospective study. The data of SCLC patients during 2010–2013 and in 2014 SCLC were used for model development and validation, respectively. OS served as the primary outcome. Univariate and multivariate Cox regression were applied to identify the independent prognostic factors of SCLC, and a prognostic model was developed based on these factors. The discrimination and calibration of this model were assessed by the time-dependent C-index, time-dependent receiver operator characteristic curves (ROC), and calibration curves. Additionally, Decision Curve Analysis (DCA) curves, Net Reclassification Improvement (NRI), and Integrated Discriminant Improvement (IDI) were used to assess the enhanced clinical utility and predictive accuracy of the model compared to TNM staging systems.

Results
Multivariate analysis showed that region (Southern/Eastern, hazard ratio [HR] = 1.305 [1.046 − 1.629]; Western/Eastern, HR = 0.727 [0.617 − 0.856]; Northern/Eastern, HR = 0.927 [0.800 − 1.074]), sex (female/male, HR = 0.838 [0.737 − 0.952]), age (46–60/≤45, HR = 1.401 [1.104 − 1.778]; 61–75/≤45, HR = 1.500 [1.182 − 1.902]; >75/≤45, HR = 1.869 [1.382 − 2.523]), TNM stage (II/I, HR = 1.119[0.800 − 1.565]; III/I, HR = 1.478 [1.100 − 1.985]; IV/I, HR = 1.986 [1.477 − 2.670], surgery (yes/no, HR = 0.677 [0.521 − 0.881]), chemotherapy (yes/no, HR = 0.708 [0.616 − 0.813]), and radiotherapy (yes/no, HR = 0.802 [0.702 − 0.917]) were independent prognostic factors of SCLC patients and were included in the nomogram. The time-dependent AUCs of this model in the training set were 0.699, 0.683, and 0.683 for predicting 1-, 3-, and 5-year OS, and 0.698, 0.698, and 0.639 in the validation set, respectively. The predicted calibration curves aligned with the ideal curves, and the DCA curves, the IDI, and the NRI collectively demonstrated that the prognostic model had a superior net benefit than the TNM staging system.

Conclusion
The nomogram using SCLC patients in Shandong surpassed the TNM staging system in survival prediction accuracy and enabled the stratification of patients with distinct prognostic risks based on nomogram scores.
The predictive roles of parental stress and intolerance of uncertainty on psychological well-being of parents with a newborn in neonatal intensive care unit: a hierarchical linear regression analysis
Authors: Rambod Masoume , Pasyar Nilofar , Mazarei Zeinab , Soltanian Mitra 
Published: December 2023

AbstractBackgroundHospitalization of newborns in neonatal intensive care units (NICU) exposes parents to considerable stress. This study aimed to determine the predictive role of parental stress and intolerance of uncertainty on the psychological well-being of parents with a newborn in NICU using hierarchical linear regression analysis.MethodsThis cross-sectional study included 130 parents of newborns hospitalized in the NICU. Data were collected using Parental Stress Scale, Intolerance of Uncertainty Scale, and Psychological Wellbeing Scale. The data were analyzed in SPSS v.26 using hierarchical linear regression analysis.ResultsThe mean scores of the parents’ psychological well-being, parental stress, and intolerance of uncertainty were 79.08 (SD = 11.70), 63.06 (SD = 26.71), and 75.38 (SD = 19.40), respectively. The result of the hierarchical linear regression analysis revealed that, in step 1, academic education had a significant proportion of the variance of parents’ psychological well-being (β = 0.26, P = 0.005). In step 2, it was shown that academic education (β=-0.25, P = 0.006) and parental stress (β=-0.25, P = 0.006) had a significant proportion of the variance of parents’ psychological well-being. According to step 2, education levels, parental stress, and intolerance of uncertainty explained 22% of the changes in parents’ psychological well-being.ConclusionThere was a significant association between the parents’ psychological well-being and education levels, intolerance of uncertainty, and parental stress. Academic education and parental stress were the predictors of parents’ psychological well-being. Based on these findings, early detection of parents’ education and stress are important for their psychological well-being.
Comparison of accidental findings of brain magnetic resonance imaging of patients with obsessive-compulsive disorder and healthy controls
Authors: Kapıcı Olga Bayar , Kapıcı Yaşar , Tekin Atilla 
Published: December 2023

Abstract
Background
Abnormalities in brain magnetic resonance imaging (MRI) have been reported in drug-naive and chronic patients with obsessive-compulsive disorder (OCD). The Fazekas scale is a method used to categorize and grade the severity of white matter hyperintensities (WMH) in brain MRI. These lesions can be indicative of various neurological conditions, particularly small vessel disease or cerebrovascular pathology.

Methods
Brain MRIs of patients followed up with the diagnosis of OCD were retrospectively analyzed. 58 OCD (36 females, 22 males) and 58 healthy controls (HC) (30 females, 28 males) were included in the study. Age, gender, and brain MRI findings of the participants were recorded.

Results
The mean ages of the OCD and HC groups were 33.4 ± 10.6 and 35.9 ± 9.3. There was no difference between the groups in terms of mean ages and gender distribution (p = 0.180 and p = 0.260, accordingly). Generalized cerebral atrophy was more common in patients with OCD than in HC (p = 0.008). Fazekas grade 1 was detected in 17.2% of the patients with OCD and 1.7% of HC. Accordingly, it was significantly more common in Fazekas grade 1 OCD patients (p = 0.002). Fazekas grade 2 was detected in only 2 patient with OCD. CVI was present in 20.7% of the patients with OCD and 1.7% of HC. There was a significant difference between the groups regarding CVI (p = 0.001). Ethmoidal thickening was more common in patients with OCD than in HC (p = 0.004). The YBOCS scores and ages of OCD patients with Fazekas grade 1 and 2 were significantly higher than those of patients with Fazekas grade 0. Likewise, the YBOCS scores and ages of OCD patients with generalized cerebral atrophy were significantly higher than those of patients without atrophy.

Conclusion
It is understood from the present study’s findings that CVI, a neurodevelopmental malformation, is more common in patients with OCD. Due to the potential relationship of this anomaly with neuronal migration, it would be appropriate to pay attention to OCD symptoms in individuals with CVI and to perform white matter examination on brain imaging. In future studies, Fazekas grade can be evaluated in drug-naive OCD patients, and data on the pre-disease period can be obtained.
Minimally invasive percutaneous screw internal fixation under robot navigation for the treatment of a hamate bone fracture
Authors: Jie Fang , Hui Zhu , Dawei Zheng , Guiqian Liu , Rongjian Shi , Weiya Qi 
Published: December 2023

Abstract
Purpose
Hamate fractures are rare fractures of the wrist and there is still no consensus on the optimal treatment for these fractures, especially hook of hamate fractures. Herein, the authors present a case study of a series of patients who were treated with closed reduction and minimally invasive percutaneous fixation under robot navigation.

Methods
This retrospective study reviewed 14 patients who had nondisplaced or minimally displaced hamate fractures on computerized tomography images and were treated using the treatment in our centre from November 1, 2019, to October 31, 2022. At the final follow-up, the flexion-extension and radial-ulnar range of motion of the wrist were measured, and the grip strength and pinch strength were measured. The pain of the wrist was assessed using the visual analogue scale (VAS). The Mayo wrist score reflected the recovery of the wrist.

Results
The mean total operative duration was 40.1 min. All the fractures showed union at a mean of 3.0 months. At a mean follow-up of 23.3 months (range 6–36 months), the mean VAS score was 0.7, the average Mayo wrist score was 95, and the mean pinch strength and grip strength were 11.3 and 38.7 kg, respectively. The flexion-extension arc was 138.3°, the mean radial and ulnar deviation arc was 63.8°, and the mean pronation-supination arc was 172.3°. And the time of return to the original occupation was mean 4 months (3~6 months). There were no complications, such as infection or nerve paralysis.

Conclusions
This study suggests that nondisplaced or minimally displaced hamate hook fractures can be successfully treated by closed reduction and internal fixation with a headless compression screw with the assistance of robot navigation, and the small fragment of fracture can be accurately fixed with minimal iatrogenic injury.
Effect of different application duration of a venous foot pump on prevention of venous thromboembolism after hip and knee arthroplasty: a multicenter prospective clinical trial
Authors: Gu Siqi , Chen Yu-e , Lei Mingxing , Li Jiahui , Li Wanying , Zhang Meihong , Zhu Hongxia , Ma Mengying , Kong Dan , Gao Yuan 
Published: December 2023

Abstract
Objective
To investigate the optimal duration of applying a venous foot pump (VFP) in the prevention of venous thromboembolism (VTE) following hip and knee arthroplasty.

Methods
A total of 230 patients undergoing hip and knee arthroplasty between March 2021 and March 2022 in orthopaedic departments of four major teaching hospitals were prospectively enrolled. Patients were randomly divided into five groups based on the duration of the VFP application. Postoperative deep vein thromboses (DVT), including proximal, distal, and intermuscular DVT, were recorded for analysis. Postoperative blood coagulation examinations, such as D-dimer and active partial thromboplastin time (APTT), pain outcome, and degree of comfort were also collected.

Results
Two of the 230 patients withdrew due to early discharge from the hospital, and 228 patients were included in the final analysis. The mean age was 60.38 ± 13.33 years. The baseline characteristics were comparable among the five groups. Compared with the other groups, patients treated with 6-hour VFP had the lowest incidence of DVT (8.7%, 4/46), followed by those treated with 1-hour VFP (15.2%, 7/46), 12-hour VFP (15.6%, 7/45), 18-hour VFP(17.8%, 8/45) and 20-hour VFP(21.7%, 10/46), but with no significant difference (P = 0.539). Regarding postoperative blood coagulation examinations, patients treated with 6-hour VFP had the lowest D-dimer (P = 0.658) and the highest APTT (P = 0.262) compared with the other four groups. 6-hour VFP also had the lowest pain score (P = 0.206) and the highest comfort score (P = 0.288) compared with the other four groups.

Conclusions
Six hours may be the optimal duration of applying VFP for the prevention of VTE in patients undergoing hip and knee arthroplasty in terms of VTE incidence, postoperative blood coagulation examinations, pain outcomes, and comfort scores.