bluuebunny/crossref_metadata_2025_split huggingface dataset:
Out of balance: conflicts of interest persist in food chemicals determined to be generally recognized as safe
Authors: Matouskova Klara , Neltner Thomas G. , Maffini Maricel V. 
Published: September 2023

AbstractManufacturers of chemicals added to food are responsible for determining that the use of their products is safe. There are two major legal definitions of chemicals in food: (1) food additives which includes ingredients and chemicals indirectly entering food from packaging and processing equipment, and (2) generally recognized as safe (GRAS) substances mostly used as ingredients. The law requires food additives to undergo approval by the U.S. Food and Drug Administration (FDA) before they are sold, but it GRAS substances are exempted from pre-market approval. In 1997, FDA created a voluntary program for manufacturers to submit their chemical’s safety determination in the form of a GRAS notice to the agency. Manufacturers make GRAS determinations regardless of whether they voluntarily submit a notice to FDA for review. They rely on their own employees, the employee of a hired consulting firm or a panel of experts, known as GRAS panel, to review the safety information. Because this process determines whether a chemical is safe for use in food, conflicts of interest and biases need to be avoided or minimized to credibly ensure food is safe. Recently, FDA has published guidance for industry on best practices to convene GRAS panels to manage conflicts of interest and reduce biases that have plagued the process. Here, we perform a qualitative assessment of the compliance of GRAS panels with basic elements of FDA’s guidance. We assessed 403 GRAS notices filed by FDA between 2015 and 2020 and identified whether a GRAS panel was convened and by whom, its members, affiliations, and relationships between panelists and panel conveners. Then, we compared FDA’s recommendations against the information included in the notices voluntarily submitted by manufacturers. We found no evidence that GRAS panels have adhered to FDA’s guidance. Panels are populated from a very small pool of professionals; we found that seven panel members alone occupied almost half of all available panel positions and that they often serve together. Against guidance recommendations, ad-hoc panels have been substituted by panels with recurring members in hired consulting firms’ payroll. The widespread persistence of conflicts of interest, appearance of conflict and bias in GRAS determinations continue to put the health of Americans at risk and undermine confidence in the safety of food ingredients in the US market. FDA should require notice for all GRAS determinations including how the financial conflicts of interest of those who make these determinations are minimized.
Pathways of lymph node metastasis and prognosis after right hemicolectomy for cecal cancer: results from a retrospective single center
Authors: Yu Liang , Liu Zhun , Chen Zhifen , Wang Xiaojie , Xu Zongbin , Jiang Weizhong , Huang Ying , Lin Huiming , Chi Pan 
Published: September 2023

Abstract
Background
The recommended operation for cecum cancer (CC) is right hemicolectomy (RH) in some Western countries while the principle of D3 lymphadenectomy in Japan recommends resecting approximately 10 cm from the tumor edge. Therefore, the optimal surgical approach for cecum cancer (CC) remains controversial. We conducted this retrospective study to explore the pattern of lymph node metastasis and better surgical procedures for CC.

Methods
A total of 224 cecum cancer patients from January 1, 2014, to December 31, 2021, were retrospectively included in the final study. The pattern of lymph node metastasis (LNM) was investigated.

Results
A total of 113 (50.4%, 113/224) patients had pathologically confirmed LNM. The most frequent metastatic site was no. 201 lymph node (46%, 103/224), while 20 (8.9%, 20/224) patients had LNM in no. 202 lymph node, and 8 (3.6%, 8/224) patients had LNM in no. 203 lymph node. Only 1 (0.4%, 1/224) patient had LNM in no. 221 lymph node, four (1.8, 4/224%) patients had LNM in no. 223 lymph node, and no patients had LNM in no. 222 lymph node. LNM in no. 223 lymph node was significantly associated with a poor prognosis. Multivariate analysis indicated that LNM in no. 223 lymph node (HR = 4.59, 95% CI 1.18–17.86, P = 0.028) was the only independent risk factor associated with worse disease-free survival (DFS).

Conclusions
The LNM in no. 223 lymph node for cecum cancer was rare. Therefore, standard right hemicolectomy excision is too extensive for most CC cases.
Incidence of anti-platelet factor4/polyanionic antibodies, thrombocytopenia, and thrombosis after COVID-19 vaccination with ChAdOx1 nCoV-19 in Thais
Authors: Boonyawat Kochawan , Phojanasenee Tichayapa , Noikongdee Phichchapha , Police Pornnapa , Chantrathammachart Pichika , Niparuck Pimjai , Puavilai Teeraya , Phuphuakrat Angsana , Angchaisuksiri Pantep 
Published: September 2023

Abstract
Background
The prevalence of anti-platelet factor 4 (PF4)/polyanionic antibodies occurring after vaccination with ChAdOx1 nCoV-19 is low. Most of these antibodies are not associated with vaccine-induced thrombotic thrombocytopenia. It remains unknown whether these antibodies are preexisting or occur as a result of vaccination. In this study, we demonstrated the incidence of anti-PF4/polyanionic antibodies, thrombocytopenia, and thrombosis after vaccination with ChAdOx1 nCoV-19 in a large cohort of Thais.

Methods
We conducted a prospective study in a cohort of health care workers and members of the general population who received COVID-19 vaccination with ChAdOx1 nCoV-19. Blood collection for complete blood count, D-dimer, and anti-PF4/polyanionic antibodies was performed before vaccination (day 0), day 10, and day 28 after vaccination. Anti-PF4/polyanionic antibodies were detected using enzyme-link immunosorbent assay (ELISA). Functional assay was performed for all positive ELISA tests.

Results
A total of 720 participants were included in the study. 214 participants received both the first and second doses, 91 participants received only the first, 51 received only the second, and 364 received the third booster dose of ChAdOx1 nCoV-19. Median age was 42 years (IQR, 34–53). 67% of participants were female. Three participants developed seroconversion, yielding an incidence of vaccination-induced anti-PF4/polyanionic antibodies of 0.42% (95% confidence interval 0.08, 1.23). Fourteen (1.9%) participants had preexisting anti-PF4/polyanionic antibodies before the vaccination but their optical density of anti-PF4/polyanionic antibodies did not significantly increase over time. None of the anti-PF4/polyanionic positive sera induced platelet aggregation. Abnormal D-dimer levels following vaccination were not different among the positive and negative anti-PF4/polyanionic groups (11.8% vs. 13.2%, p = 0.86). Thrombocytopenia occurred in one person with negative anti-PF4/polyanionic antibodies. No clinical thrombosis or bleeding occurred.

Conclusion
We found a low incidence of seroconversion of anti-PF4/polyanionic antibodies after vaccination with ChAdOx1 nCoV-19 in Thais. Most of the anti-PF4/polyanionic antibodies were preexisting and did not significantly increase after vaccination with ChAdOx1 nCoV-19. Following vaccination, some participants with anti-PF4/polyanionic antibodies had elevated D-dimer levels, while only one developed thrombocytopenia and no thrombotic events were observed.
Evaluating the scaling up of an effective implementation intervention (PACE) to increase the delivery of a mandatory physical activity policy in primary schools
Authors: Hall Alix , Lane Cassandra , Wolfenden Luke , Wiggers John , Sutherland Rachel , McCarthy Nicole , Jackson Rebecca , Shoesmith Adam , Lecathelinais Christophe , Reeves Penny , Bauman Adrian , Gillham Karen , Boyer James , Naylor Patti-Jean , Kerr Nicola , Kajons Nicole , Nathan Nicole 
Published: September 2023

Abstract
Background
Physically Active Children in Education (PACE) is an effective implementation intervention for increasing the number of minutes classroom teachers schedule physical activity each week. To date, evaluations of PACE have included a smaller number of schools from only one region in New South Wales Australia. If PACE is to have population-wide benefits we must be able to deliver this support to a larger number of schools across multiple regions. This study aimed to evaluate the scale-up of PACE.

Methods
An uncontrolled before and after study, with 100 schools from three regions was conducted. Participating schools received PACE for approximately 12 months. We assessed the following outcomes: delivery of the evidence-based intervention (EBI) (i.e. minutes of physical activity scheduled by classroom teachers per week); delivery of the implementation strategies (i.e. reach, dose delivered, adherence and indicators of sustainability); and key determinants of implementation (i.e. acceptability of strategies and cost). Data were collected via project officer records, and principal and teacher surveys. Linear mixed models were used to assess EBI delivery by evaluating the difference in the mean minutes teachers scheduled physical activity per week from baseline to follow-up. Descriptive data were used to assess delivery of the implementation strategies and their perceived acceptability (i.e. PACE). A prospective, trial-based economic evaluation was used to assess cost.

Results
Delivery of the EBI was successful: teachers increas their average minutes of total physical activity scheduled across the school week by 26.8 min (95% CI: 21.2, 32.4, p < 0.001) after receiving PACE. Indicators for delivery of implementation strategies were high: 90% of consenting schools received all strategies and components (reach); 100% of strategies were delivered by the provider (dose); >50% of schools adhered to the majority of strategies (11 of the 14 components); and acceptability was > 50% agreement for all strategies. The incremental cost per additional minute of physical activity scheduled per week was $27 per school (Uncertainty Interval $24, $31).

Conclusions
PACE can be successfully delivered across multiple regions and to a large number of schools. Given the ongoing and scalable benefits of PACE, it is important that we continue to extend and improve this program while considering ways to reduce the associated cost.
Application of radiomics-based multiomics combinations in the tumor microenvironment and cancer prognosis
Authors: Kang Wendi , Qiu Xiang , Luo Yingen , Luo Jianwei , Liu Yang , Xi Junqing , Li Xiao , Yang Zhengqiang 
Published: September 2023

AbstractThe advent of immunotherapy, a groundbreaking advancement in cancer treatment, has given rise to the prominence of the tumor microenvironment (TME) as a critical area of research. The clinical implications of an improved understanding of the TME are significant and far-reaching. Radiomics has been increasingly utilized in the comprehensive assessment of the TME and cancer prognosis. Similarly, the advancement of pathomics, which is based on pathological images, can offer additional insights into the panoramic view and microscopic information of tumors. The combination of pathomics and radiomics has revolutionized the concept of a “digital biopsy”. As genomics and transcriptomics continue to evolve, integrating radiomics with genomic and transcriptomic datasets can offer further insights into tumor and microenvironment heterogeneity and establish correlations with biological significance. Therefore, the synergistic analysis of digital image features (radiomics, pathomics) and genetic phenotypes (genomics) can comprehensively decode and characterize the heterogeneity of the TME as well as predict cancer prognosis. This review presents a comprehensive summary of the research on important radiomics biomarkers for predicting the TME, emphasizing the interplay between radiomics, genomics, transcriptomics, and pathomics, as well as the application of multiomics in decoding the TME and predicting cancer prognosis. Finally, we discuss the challenges and opportunities in multiomics research. In conclusion, this review highlights the crucial role of radiomics and multiomics associations in the assessment of the TME and cancer prognosis. The combined analysis of radiomics, pathomics, genomics, and transcriptomics is a promising research direction with substantial research significance and value for comprehensive TME evaluation and cancer prognosis assessment.
CBX3 promotes clear cell renal carcinoma through PI3K/AKT activation and aberrant immunity
Authors: Chen Jiasheng , Lin Yuxin , zheng Shukai , Chen Qingshan , Tang Shijie , Zhong Xiaoping 
Published: September 2023

Abstract
Background
A chromobox homologue 3 (CBX3) is elevated in various cancers and significantly contributes to the promotion of malignant behavior; despite this, its exact involvement in clear cell renal cell carcinoma (ccRCC) is yet unknown.

Methods
The Cancer Genome Atlas database served to evaluate CBX3 production and its connection to survival in patients with ccRCC. Our team evaluated the effects of knockdown of CBX3 levels in ccRCC cell populations using in vitro together with in vivo models. CBX3, proteins related to death, and epithelial-to-mesenchymal transition (EMT)-related proteins were measured in ccRCC cells using western blotting and immunohistochemical assays. Through the analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) and GeneOntology (GO) and Gene Set Enrichment Analysis (GSEA), the biological processes and signal pathways related to CBX3 expression were identified. Immune-related activity reduced by CBX3 was assessed using various online tools.

Results
Both genomic and protein expression showed that CBX3 was upregulated in ccRCC. Further functional analyses revealed that CBX3 played a crucial role in enhancing cell growth, migration, and EMT in vitro along with in vivo. Moreover, the study results provided distinct mechanistic evidence that CBX3 exerts its pathological functions in ccRCC by activating the PI3K/AKT pathway. Finally, immunoassays revealed that CBX3, a possible biomarker of ccRCC, was significantly associated with immunity.

Conclusions
Our results suggest that the overexpression of CBX3 promotes ccRCC advancement through PI3K/AKT activation and even immunological dysregulation, making it a potentially viable and beneficial therapeutic target.
A favorable suture method for size-mismatched nerve transfer: comparison with standard perineural suture in an experimental rat study
Authors: Iwabuchi Sho , Hara Yuki , Yoshii Yuichi , Ikumi Akira , Mishima Hajime , Yamazaki Masashi 
Published: September 2023

Abstract
Background
In nerve transfer for peripheral nerve injury, it is sometimes necessary to suture size-mismatched nerves. In 1993, a favorable suture method called the Ochiai suture method for size-mismatched nerve transfer was reported. However, there is currently a lack of substantial evidence beyond the original report. Therefore, this study aimed to verify the advantages of using the Ochiai suture method for size-mismatched nerve transfer.

Methods
A total of 18 rats were evaluated in this study and randomly divided into two groups. All rats underwent femoral to sciatic nerve transfer. Specifically, group A (n = 10) underwent the Ochiai suture method, while group B (n = 8) underwent the perineural suture method. After 12 weeks postoperatively, we conducted the sciatic functional index (SFI) test, measured muscle wet-weight, and performed histological evaluations. All data were compared between the two groups, with Welch’s t test for normally distributed data and Mann-Whitney's U test for non-normally distributed data. Statistical significance was set at p < 0.05.

Results
The mean number of axons was significantly greater in group A than in group B at 5 mm distal to the stump (p = 0.04). Additionally, the average axonal diameter was significantly greater in group A than in group B at 5 mm and 10 mm distal to the stump (p < 0.01 and p < 0.01, respectively). However, the SFI test and measured muscle wet-weight values showed no significant differences between the two groups.

Conclusions
Our study revealed that the Ochiai suture method for size-mismatched nerve transfer in rats increases the regenerative axon numbers and diameters. These findings suggest that the Ochiai suture method could be a valuable approach for achieving effective motor function restoration in cases of size-mismatched nerve transfer.
Accuracy of augmented reality with computed tomography-based navigation in total hip arthroplasty
Authors: Hasegawa Masahiro , Naito Yohei , Tone Shine , Sudo Akihiro 
Published: September 2023

Abstract
Background
Augmented reality (AR) provides the surgeon with direct visualization of radiological images by overlaying them on the patient. This study aimed to evaluate the accuracy of cup placement using a computed tomography (CT)-based AR navigation system.

Methods
Sixty-five prospectively enrolled patients underwent primary cementless total hip arthroplasty (THA) in a supine position using this novel AR navigation system, and changes in pelvic flexion angle (PFA) were evaluated. Absolute navigation errors were defined as the absolute differences between angles in the intraoperative navigation record and those measured on postoperative CT. Factors affecting the absolute navigation error in cup alignment were determined.

Results
Mean absolute change in PFA between preoperative CT and reduction was 2.1° ± 1.6°. Mean absolute navigation errors were 2.5° ± 1.7° in radiographic inclination (RI) and 2.5° ± 2.2° in radiographic anteversion (RA). While no factors significantly affecting absolute navigation error were found for RI, absolute change in PFA between preoperative CT and reduction correlated significantly with the absolute navigation error for RA.

Conclusion
This CT-based navigation system with AR enabled surgeons to place the cup more accurately than was possible by freehand placement during THA in a supine position.
Incidence and root causes of surgery cancellations at an academic medical center in Iran: a retrospective cohort study on 29,978 elective surgical cases
Authors: Naderi-Boldaji Vida , Banifatemi Mahsa , Zandi Raheleh , Eghbal Mohammad Hossein , Nematollahi Milad , Sahmeddini Mohammad Ali 
Published: September 2023

Abstract
Introduction
Canceling scheduled surgeries on the day of surgery places a heavy burden on healthcare providers and has psychological, social, and financial consequences on patients and their families. This study aimed to investigate the main reasons for cancellations of elective procedures and provide appropriate recommendations to reduce the rate of such avoidable cancellations.

Methods
Data were collected retrospectively from all consecutive elective cases scheduled for various elective surgeries from January 1, 2020 to March 31, 2022 at Namazi Teaching Hospital, a major referral center in southern Iran with a capacity of 938 beds. Daily data were collected on the number of planned electives, cancellations, and reasons for cancellations. Surgical cancellation reasons were categorized as patient-related, surgeon-related, hospital/system-related, and anesthesia-related. Data were expressed as frequency (percentage) and analyzed with SPSS version 19 software.

Results
The cancellation rate on surgery day for elective procedures in all fields was 6.3%. The highest cancellation rate was related to minor surgeries (19%), followed by urology (8%), pediatrics (7%), and plastic surgery (7%). The most common reasons for cancellation were patients not suitable for the procedure (37%), followed by patients who did not follow instructions (10%), lack of time (10.5%), and equipment/supplies problems (10%), and refusal to consent (6%).

Conclusions
According to this study, patients’ unsuitability for surgery, non-compliance with instructions, lack of time, and problems with equipment/supplies are the main reasons for canceling surgery. Proper preoperative assessment and preparation of patients and improved communication between medical teams and patients reduce the cancellation of booked surgeries.
A methylation- and immune-related lncRNA signature to predict ovarian cancer outcome and uncover mechanisms of chemoresistance
Authors: Chen Lu , Gao Wujiang , Lin Li , Sha Chunli , Li Taoqiong , Chen Qi , Wei Hong , Yang Meiling , Xing Jie , Zhang Mengxue , Zhao Shijie , Xu Wenlin , Li Yuefeng , Long Lulu , Zhu Xiaolan 
Published: September 2023

AbstractTumor-associated lncRNAs regulated by epigenetic modification switches mediate immune escape and chemoresistance in ovarian cancer (OC). However, the underlying mechanisms and concrete targets have not been systematically elucidated. Here, we discovered that methylation modifications played a significant role in regulating immune cell infiltration and sensitizing OC to chemotherapy by modulating immune-related lncRNAs (irlncRNAs), which represent tumor immune status. Through deep analysis of the TCGA database, a prognostic risk model incorporating four methylation-related lncRNAs (mrlncRNAs) and irlncRNAs was constructed. Twenty-one mrlncRNA/irlncRNA pairs were identified that were significantly related to the overall survival (OS) of OC patients. Subsequently, we selected four lncRNAs to construct a risk signature predictive of OS and indicative of OC immune infiltration, and verified the robustness of the risk signature in an internal validation set. The risk score was an independent prognostic factor for OC prognosis, which was demonstrated via multifactorial Cox regression analysis and nomogram. Moreover, risk scores were negatively related to the expression of CD274, CTLA4, ICOS, LAG3, PDCD1, and PDCD1LG2 and negatively correlated with CD8+, CD4+, and Treg tumor-infiltrating immune cells. In addition, a high-risk score was associated with a higher IC50 value for cisplatin, which was associated with a significantly worse clinical outcome. Next, a competing endogenous RNA (ceRNA) network and a signaling pathway controlling the infiltration of CD8+ T cells were explored based on the lncRNA model, which suggested a potential therapeutic target for immunotherapy. Overall, this study constructed a prognostic model by pairing mrlncRNAs and irlncRNAs and revealed the critical role of the FTO/RP5-991G20.1/hsa-miR-1976/MEIS1 signaling pathway in regulating immune function and enhancing anticancer therapy.
Unilateral diaphragmatic palsy and pleuropericarditis in a patient with granulomatosis with polyangiitis: a case report
Authors: Risal Ujjwol Prasad , Pangeni Raju Prasad , Pandey Rakshya , Regmi Pradeep Raj , Karki Aditi , Shah Avish 
Published: September 2023

Abstract
Background
Granulomatosis with polyangiitis (GPA) is a rare small vessel vasculitis predominantly affecting upper and lower respiratory tract and kidneys. Unilateral diaphragmatic palsy could be a rare manifestation of GPA. Here we report a case of GPA in a 45-year-old male with unilateral diaphragmatic palsy with pleuropericarditis.

Case presentation
We report a case of a 45-year-old Khas male who presented with acute onset chest pain and shortness of breath who had elevated right hemidiaphragm, bilateral pleural effusion and pericardial effusion who was later diagnosed as GPA.

Conclusions
GPA should be suspected in all patients with diaphragmatic palsy and pleuropericarditis with appropriate clinical and laboratory picture.