bluuebunny/crossref_metadata_2025 huggingface dataset:
KIFC1 overexpression promotes pancreatic carcinoma progression via the BUB1/WNT/β- catenin pathway
Authors: Cui Ao , Yu Ying-Xue , Wang Ji-Yang , Zou Ye-Qing , Zhu Ya-Qiong , Ran Long-Jian , Zhang yu , Liu Rui-Xiang , Dong Ming-Yi , Wang Hui , Fang Lu , Fu Xiao-Wei
Published: September 2024

Background: Pancreatic cancer (PC) is a highly lethal tumor of the gastrointestinal tract. New molecular targets are urgently needed for its treatment. Kinesin family member C1 (KIFC1) is implicated in the development and progression of several types of cancer. Previously, our studies indicated that KIFC1 is overexpressed in hepatocellular carcinoma and activates the malignant behavior of hepatocellular carcinoma through the PI3K/AKT pathway. However, the molecular and functional mechanisms of KIFC1
in PC have not been investigated.
Methods: In this study, high-throughput sequencing technology was utilized to characterize differential gene expression profiles in patients with PC. KIFC1 was revealed by screening up-regulated genes from our sequenced data and the Gene Expression Omnibus (GEO) database. Sixty-two PC tissues were analyzed to determine
the correlation of KIFC1 expression with the clinicopathological features and prognosis
of patients. The role of KIFC1 in proliferation, migration and invasion in PC was verified both in vitro and in vivo. Bioinformatics analysis, coimmunoprecipitation (CoIP), and western blotting were performed to identify proteins that interact with KIFC1and further affect the downstream pathway.
Results: According to high-throughput sequencing and the GEO database, KIFC1 is highly expressed in PC. KIFC1 is highly expressed in PC tissues and cells and is positively correlated with poor patient prognosis and malignant cellular behavior. Silencing KIFC1 inhibited the proliferation, migration, and invasion of PC cells, and
overexpression of KIFC1 had the opposite effect. Protein‒protein interaction (PPI) and
Co-IP analyses indicated that KIFC1 interacts with and regulates BUB1. Overexpression of BUB1 can also promote the proliferation, migration, and invasion of PC cells. BUB1 acts as an intermediary in the activation of the Wnt/β-catenin pathway by KIFC1, leading to an increase in the malignant behaviors of PC cells. The reversal of Wnt/β-catenin activation and increase in cellular malignant behavior induced by KIFC1 overexpression are achieved by silencing BUB1. These biological functions of KIFC1 in PC were also confirmed in a nude mouse xenograft model.
Conclusions: Our experiments demonstrated for the first time that KIFC1 can influence PC progression by regulating BUB1 to activate the Wnt/β-catenin pathway. Therefore, KIFC1 shows promise as an attractive therapeutic target for PC in the future.
Diagnostic and Prognostic Value of SCN4B in ccRCC
Authors: Yang Hongwei , Yi Faxian
Published: September 2024

Background
The role of the voltage-gated sodium channel β4 subunit (SCN4B) gene in clear cell renal cell carcinoma (ccRCC) remains ambiguous. Utilizing the Cancer Genome Atlas (TCGA) database, we undertook a bioinformatics analysis to delineate SCN4B's function in ccRCC.
Methods
Data from 541 ccRCC patients and 72 normal individuals were extracted from the TCGA database. The Kruskal–Wallis test and logistic regression analysis were used to assess the relationship between SCN4B expression and clinicopathological characteristics. Cox regression and Kaplan–Meier analyses were performed to evaluate the prognostic value of SCN4B. Single-sample gene set enrichment analysis (ssGSEA) was employed to explore associations between SCN4B expression and immune infiltration levels in ccRCC.
Results
SCN4B was significantly overexpressed in ccRCC (P < 0.001) and effectively distinguished tumor tissue (area under the curve = 0.835) from normal tissue. SCN4B was notably associated with pathological T stage (odds ratio (OR) = 0.429 (0.298–0.616), P < 0.001) and pathological M stage (odds ratio (OR) = 0.424 (0.256–0.704), P < 0.001). Kaplan–Meier survival analysis revealed that patients with high SCN4B expression had better overall survival (hazard ratio (HR) = 0.57, P < 0.001) and progression-free interval (hazard ratio (HR) = 0.50, P < 0.001). Cox regression analysis indicated that pathological M stage was a risk factor for progression-free interval (HR = 4.062 (2.439–6.765), P < 0.001). Using ssGSEA, SCN4B expression was positively correlated with the abundance of NK cells (R = 0.415, P < 0.001), mast cells (R = 0.405, P < 0.001), and plasmacytoid dendritic cells (pDC) (R = 0.381, P < 0.001).
Conclusion
SCN4B may serve as a crucial biomarker for predicting ccRCC prognosis and could represent a viable target for immunotherapy related to immune infiltration.
A Constant Contact Community-Based Epidemiological Investigation (C3EI) for Malaria Elimination in Mandla District, Madhya Pradesh, India
Authors: Singh Mrigendra P , Rajvanshi Harsh , Bharti Praveen K , Sahu Ram S , Jayswar Himanshu , Nisar Sekh , Anvikar Anup R , Lal Altaf A.
Published: September 2024

Introduction:
In India, an increase in malaria cases by 21% (223,961 cases) has been reported between 2022 and 2023. Madhya Pradesh ranks 10th in malaria burden, with Mandla district selected for the Malaria Elimination Demonstration Project (MEDP) to demonstrate the feasibility of malaria elimination in a hard-to-reach, tribal-dominated, and hilly forested district. A Constant Contact Community-Based Epidemiological Investigation (C3EI) was undertaken by continuous engagement with the community for real-time data collection, mapping of malaria cases, identification of risk factors, monitoring of intervention outcomes designed to drive effective strategies for malaria elimination.
Methods
The study mapped 1,143,126 individuals from 248,825 households in the year 2017 in Mandla district for constant contact surveillance. Fortnightly household visits were conducted to inquire about febrile episodes, with on-spot diagnosis and treatment. Data collection was done using the SOCH mobile application, and analysis using R.
Results
The constant contact household surveillance revealed that out of 956,795 individuals, 230,780 (24.12%) unique individuals reported one or more febrile episodes, with a total of 322,577 febrile episodes and 490 malaria episodes (RDT positive). Males had a higher risk of malaria infection than females (OR = 2.62; p < 0.0001). The cumulative incidence of malaria was highest among children aged 5–15 years and pregnant women. Multiple episodes of malaria infections were more common in adults over 30 years. The incidence of malaria gradually declined from 26.13 in 2018 to 11.18 in 2020, with the highest incidence during the monsoon season.
Conclusion
The C3EI presents a new surveillance strategy suitable for disease elimination programs. Implementing C3EI-type longitudinal studies in elimination projects holds promise for generating data to expedite malaria elimination efforts because the unit of observation is a ‘household’. Such comprehensive approach allows identification in the gaps in case management for prompt interventions at the household-level.
Predictive Factors and Risk Scoring System for Acute Kidney Injury (AKI) in Sick Neonates-A Prospective Cohort Study
Authors: Ramya Kagnur , Mukhopadhyay Kanya , Kumar Jogender
Published: September 2024

Background
Neonatal AKI (Acute kidney injury) is an underreported entity in sick neonates associated with significant morbidity and mortality.
Methods
It was a prospective cohort study, to study the incidence, risk factors, and outcomes of AKI among sick neonates. We included sick inborn neonates admitted at a level III neonatal intensive care unit. Neonates with congenital anomalies and who died within 72 hours of life were excluded. AKI was defined and categorized as per KDIGO guidelines.
Results
Two hundred and seventy-six neonates were enrolled over 1 year, of which 115(42%) had AKI. AKI was higher in the first week of life as compared to beyond the first week n = 103/115 (89%) vs. n = 12/115 (7%), p = < 0.01). The incidence of AKI was highest n = 27/38 (71%) among extremely preterm (< 28 weeks) infants. On Cox regression analysis, sepsis, invasive ventilation, acidosis, and perinatal asphyxia were significantly associated with AKI with a hazard ratio (95% CI) of 4 (1.21–13.42), 2.3 (1.32–4.03), 1.9 (1.13–3.36), and 1.5 (1.04–2.31), respectively. The risk prediction model, using the 4 predictors mentioned above, had good diagnostic accuracy (area under the curve- 83.6%) with a sensitivity and specificity of 77% and 80%, respectively. Infants with AKI have significantly higher mortality, compared to those who did not have AKI n = 45/115(39%) vs. n = 5/161 (3%), p < 0.01.
Conclusion
Nearly half of sick neonates admitted to NICU have AKI, and is maximum in extremely preterm infants. Sepsis, invasive ventilation, acidosis, and perinatal asphyxia have good diagnostic accuracy in identifying neonates likely to develop AKI.
Clinical Outcome and Prognosis of Differentiated Thyroid Carcinoma with Distant Metastasis
Authors: Shan Chanchan , Xu Shichen , Cai Gangming , Li Mengdi , Wang Tingting , Li Aoshuang , Zhong Aisheng , Zhang Jian
Published: September 2024

Objective
To investigate the risk and prognostic factors of Radioactive iodide (RAI)-refractory (RAIR) in distant metastatic (DM) differentiated thyroid cancer (DTC).
Methods
DM-DTC patients who received iodine-131 radiation therapy were enrolled in this cohort study. After exclusion, 75 DTC radioiodine therapy resistant patients and 53 treatment effective patients were finally included. The clinical data, BRAFV600E and TERT promoter mutations were compared between these two groups to predict the risks of RAIR. Patients with RAIR-DM-DTC were followed up to further explore the risk factors for disease progression after iodine refractory.
Results
Univariate analysis showed that TERTp mutation, age at diagnosis, mean maximum tumor diameter, lymph node metastasis, synchronous metastasis or heterochronous metastasis, mean cumulative dose of RAI and preoperative Tg (pre-Tg) were statistically different between the RAIR and RAIE (radioiodine efficient) groups. Logistic regression analysis further found that the TERTp mutation may be risk factors for iodine refractory occurrence. During the follow-up of RAIR-DM-DTC patients, 41 patients developed disease progression and 24 patients had good disease control.
Conclusions
We found that TERTp mutation was correlated with the poor curative effect of RAI therapy in DM-DTC. Once iodine refractory occurs, patients aged 55 years or older are more likely to develop disease progression.
Eicosapentaenoic acid administration ameliorates the progression of liver fibrosis after laparoscopic Kasai portoenterostomy
Authors: Sumida Wataru , Tainaka Takahisa , Shirota Chiyoe , Makita Satoshi , Amano Hizuru , Yasui Akihiro , Maeda Takuya , Kato Daiki , Goda Yosuke , Ishii Hiroki , Ota Kazuki , Yaohui Guo , Jiahui Liu , Hinoki Akinari , Uchida Hiroo
Published: September 2024

Purpose:
Biliary atresia (BA) poses a persistent challenge characterized by ongoing liver inflammation and subsequent fibrosis even after the clearance of jaundice (COJ). This study aimed to evaluate the therapeutic potential of eicosapentaenoic acid (EPA) in alleviating liver inflammation and limiting fibrosis during the post-COJ phase of BA.
Methods:
Among the BA patients undergoing laparoscopic Kasai portoenterostomy (lapKP) between December 2016 and October 2021, EPA (20–40 mg/kg/day) was administered orally to those whose parents consented. The study included patients from January 2014 to October 2021, classifying them into two groups: EPA-treated (Group E) and untreated (Group N). Their liver fibrosis and clinical course at 1 and 2 years post-lapKP were compared.
Results:
Group E consisted of 25 patients, while Group N comprised 32 patients. Twenty-one patients in Group E and 25 patients in Group N achieved COJ (p = 0.74). Among jaundice-free patients at 1 and 2 years post-lapKP, Group E exhibited significantly lower M2BPGi levels and platelet counts, and Group E showed a significant reduction in Aminotransferase-to-Platelet Ratio Index (APRI) at 2 years post-lapKP.
Conclusion:
Although EPA administration did not improve COJ, it attenuated the progression of liver fibrosis during the 2 years following lapKP in jaundice-free patients.
Discriminatory value and validation of a risk prediction model of serum cytokines in pediatric acute appendicitis: a single-center experience of 483 cases
Authors: Zhou Jiajia , Liu Guobin , Song Xiaofeng , Kang Quan
Published: September 2024

Objectives: Pediatric acute appendicitis (AA) is one of the most prevalent acute abdomens in the department of pediatric surgery. Children with complicated AA may need timely decisions on surgery and have a worse prognosis. We explored the risk factors and developed a predictive model for complicated AA in children.
Methods: A retrospective analysis was conducted on patient information from those hospitalized for acute appendicitis confirmed by post-surgery pathological results at Children's Hospital of Chongqing Medical University between September 2022 and October 2023. Lasso regression was performed to identify risk factors and multivariate logistic regression analysis was used for model establishment.
Results: Serum levels of IFN-γ, IL-5, IL-6, IL-8, and IL-10 before surgery are useful in the classification of acute appendicitis in children. IL-6, IL-8, and IL-10, on their own, had high predictive values for CA in children. Independent risk factors for CA were age, IL-10, and IFN-γ. A multifactorial logistic regression prediction model was so established, and it demonstrated good predictive efficacy. Its predictive sensitivity was 70.0%, and specificity was 73.9%, with an AUC of 0.7949. Furthermore, the results of the external validation indicated that the model's accuracy was good with an AUC of 0.8567.
Conclusions: It's imperative to identify CA early and make clinical decisions. Prediction models based on age, IL-10, and IFN-γ may be reliable and accurate in predicting the incidence of CA, which may lead to better clinical outcomes for kids with AA.
Assessment of the utility of two-dimensional shear wave elastography and superb microvascular imaging in postoperative patients with biliary atresia
Authors: Oita Satoru , Toma Miki , Hirono Koji , Masuko Takayuki , Shimizu Toru , Shimizu Sakika , Miyajima Kojiro , Asai Nobuyoshi , Yanai Toshihiro
Published: September 2024

Purpose
We aimed to investigate whether prediction of liver fibrosis using two-dimensional shear wave elastography (2D-SWE) and vascular tree grading using superb microvascular imaging (SMI) are useful for postoperative follow-up in patients with biliary atresia (BA).
Methods
We retrospectively collected data from medical records of 134 patients who underwent ultrasound examination with 2D-SWE or SMI, including 13 postoperative patients with BA and 121 non-BA patients. We investigated the distribution of liver stiffness values with SWE and vascular tree grading with SMI and evaluated correlations between these findings and biochemical indices of liver fibrosis in postoperative BA patients.
Results
The SWE values of the BA group were not significantly different from that of any other disease groups in non-BA patients. In postoperative BA patients, SWE values correlated significantly with aspartate aminotransferase to platelet ratio index (Spearman rank correlation coefficient [rs] = 0.6380, p = 0.0256) and with the Fib-4 index (rs=0.6526, p = 0.0214). SMI vascular tree grading of the BA group was significantly higher than that of the choledochal cyst group (p = 0.0008) and other hepatobiliary disorder group (p = 0.0030). In postoperative BA patients, SMI vascular tree grading was not positively correlated with any biochemical marker of fibrosis.
Conclusion
2D-SWE appears to be useful for follow-up in postoperative BA patients.
Role of arachidonic acid metabolism in osteosarcoma prognosis by integrating WGCNA and bioinformatics analysis
Authors: Wang Yaling , HSU Peichun , Lin Feng , Hu Haiyan , Wei Xiaokang
Published: September 2024

Background Osteosarcoma is a rare tumor with poor clinical outcomes. New therapeutic targets are urgently needed. Previous research indicates that genes abnormally expressed in osteosarcoma are significantly involved in the arachidonic acid (AA) metabolic pathway. However, the role of arachidonic acid metabolism-related genes (AAMRGs) in osteosarcoma prognosis remains unknown. Methods Osteosarcoma samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were classified into high-score and low-score groups based on AAMRGs scores obtained through ssGSEA analysis. The intersecting genes were identified from weighted gene co-expression network analysis (WGCNA), DEGs (osteosarcoma vs normal) and DE-AAMRGs (high- vs low-score). An AA metabolism predictive model of the five AAMRGs were established by Cox regression and the LASSO algorithm. Model performance was evaluated using Kaplan-Meier survival and receiver operating characteristic (ROC) curve analysis. In vitro experiments of the AA related biomarkers was validated. Results Our study constructed an AAMRGs prognostic signature (CD36, CLDN11, STOM, EPYC, PANX3). K-M analysis indicated that patients in the low-risk group showed superior overall survival to high-risk group (p<0.05). ROC curves showed that all AUC values in the prognostic model exceeded 0.76. By ESTIMATE algorithms, we discovered that patients in high-risk groups had lower immune score, stromal score, and estimate score. Correlation analysis showed the strongest positive correlation between STOM and natural killer cells, and the highest negative association between PANX3 and central memory CD8 T cells. An AAMRGs prognostic signature was constructed for osteosarcoma prognosis. Conclusion The study suggested that a high level of AAMRGs might serve as a biomarker for poor prognosis in osteosarcoma and offers a potential explanation for the role of cyclooxygenase inhibitors in cancer. The five biomarkers (CD36, CLDN11, EPYC, PANX3, and STOM) were screened to construct an AAMRGs risk model with prognostic value, providing a new reference for the prognosis and treatment of osteosarcoma.
Factors predicting the need for liver transplantation in biliary atresia patients after 18 years of age
Authors: Takahashi Yoshiaki , Matsuura Toshiharu , Maeda Shohei , Uchida Yasuyuki , Kajihara Keisuke , Toriigahara Yukihiro , Kawakubo Naonori , Nagata Kouji , Tajiri Tatsuro
Published: September 2024

(Purpose) We aimed to identify factors predicting the need for future liver transplantation (LT) at 18 years of age in patients with biliary atresia (BA).
(Methods) BA patients with native liver survival at >18 years of age were retrospectively reviewed. The clinical characteristics, outcomes, hepatobiliary function, and liver fibrosis markers of native liver survivors (NLS group) were compared with patients who subsequently underwent LT (LT group).
(Results) The study population included 48 patients (NLS, n=34; LT, n=14). The male-to-female ratio, age at Kasai procedure, and type of BA in the two groups did not differ to a statistically significant extent. There was no significant difference in the MELD scores between the groups at 18 years of age. The aspartate aminotransferase-to-platelet ratio index (APRI), albumin-bilirubin (ALBI), and BA liver fibrosis (BALF) scores at 18 years of age were significantly higher in the LT group. The AUCs for APRI, ALBI, and BALF were 0.91, 0.79, and 0.85, respectively.
(Conclusion) Adult BA patients have limited options for LT owing to the lack of donor candidates and the low prevalence of deceased donors. The elucidation of prognostic factors for LT in adulthood is important. APRI was the most useful marker in this study.
The combination of ALPPS, interventional hepatoma therapy, targeted therapy, and immunotherapy: A novel conversion therapy model for unresectable HCC
Authors: Chen Zhu , Hu Haiyang , Chen Xingyu , Chen Kai , Xiao Heng , Du Chengyou , Lan Xiang
Published: September 2024

Purpose
We aimed to report a new conversion therapy model, which was the combination of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), interventional hepatoma therapy, targeted therapy, and immunotherapy (AITI), to provide more radical resection opportunities for patients with initially unresectable liver cancer.
Methods
Between September 2021 and April 2024, patients treated with the AITI model conversion therapy in our hospital were retrospectively analyzed. ALPPS for patients with insufficient residual liver volume but expected to be resected after physician evaluation was chose to perform. Interventional hepatoma therapy, targeted therapy, and immunotherapy was used before first-stage ALPPS or between stages.
Results
Five patients underwent AITI model conversion therapy. Three patients underwent traditional conversion therapy between the two stages of the ALPPS and achieved satisfactory hypertrophy, while two patients achieved radical resection through ALPPS following suboptimal conversion therapy. Among all patients, the mean residual volume before the first stage surgery was 580 ± 245 mL, and before the second stage surgery, it was 701 ± 295 mL. The mean duration of the first stage surgery was 175.00 ± 17.32 minutes with a blood loss of 210.00 ± 124.50 mL. For the second stage surgery, the mean duration was 234.00 ± 25.35 minutes with a blood loss of 400.00 ± 70.71 mL. The average duration of treatment was 136.8 ± 98.3 days. No recurrences and no metastasis were observed as of April,2024.
Conclusion
The AITI model conversion therapy is safe and affective. This approach can provide more opportunities for unresectable patients to achieve radical resection.
Evaluating perioperative stresses in children by noninvasive modalities using salivary cortisol and autonomic reactivity
Authors: Adachi Ayaka , Fujiwara Kentaro , Watayo Hiroko , Hu Ailing , Yamaguchi Takuji , Iida Hisae , Ishiyama Asuka , Shimizu Masahiro , Nojiri Shuko , Koga Hiroyuki , Kobayashi Hiroyuki , Lane Geoffrey J. , Yamataka Atsuyuki , Suda Kazuto
Published: September 2024

Purpose
Salivary cortisol (SalC) and low to high pulse ratio (LHR) were used for evaluating perioperative stresses in children.
Methods
Children aged 6 months-16 years having elective general (thoracic/abdominal) or minor (open/minimally invasive: MI) procedures underwent pulse monitoring during AM (08:00–12:00) and PM (17:00–21:00) saliva collections from the day before surgery (S-1) to 3 days after surgery (S + 3). SalC/LHR were correlated with age, sex, caregiver attendance, operative time, and surgical site/approach using mixed model analysis and face/numeric pain rating scales (FRS/NRS).
Results
Mean ages (years): minor-open (n = 31) 4.7 ± 2.0, thoracic-open (n = 2) 8.7 ± 4.9, thoracic-MI (n = 6) 9.6 ± 6.1, abdominal-open (n = 14) 4.3 ± 4.1, and abdominal-MI (n = 32) 8.0 ± 5.0. Postoperative SalC increased rapidly and decreased to preoperative levels by S + 3 (p < 0.001). LHR increased slightly without decreasing (p = 0.038). SalC correlated positively with operative time (p = 0.036) and open surgery (p = 0.0057), and negatively with age (p < 0.0001) and caregiver attendance (p < 0.001). SalC correlated positively with FRS (n = 51) at S + 2(PM) (p = 0.023), S + 3(AM) (p < 0.001), S + 3(PM) (p = 0.012) and NRS (n = 34) at S + 1(AM) (p = 0.031), S + 3(AM) (p < 0.044). LHR positively correlated with age (p = 0.0072), female sex (p = 0.0047), and caregiver attendance (p = 0.0026). Postoperative SalC after robotic-assisted MI was significantly lower than after open surgery at S + 2(AM) (p = 0.020).
Conclusions
SalC correlated with pain. Caregiver attendance effectively alleviated stress.
Inhibition of DNA ligase IV affects the DNA damage repair pathway and decreases the sensitivity of olaparib to platinum-sensitive BRCA wild-type ovarian cancer
Authors: Gu Yupeng , Pan Yichen , Wang Yue , Jiang Kui
Published: September 2024

Ovarian cancer is one of the most common gynecologic malignancies, and the mortality rate has always been the highest among gynecologic malignancies. Currently, the initial treatment mode after the first diagnosis of ovarian cancer is tumor cytoreductive surgery, platinum-based chemotherapy, and targeted drug maintenance therapy. Although PARP inhibitors are an important approach to maintenance therapy, relapse occurs in patients after a period of treatment. PARP inhibitors mainly exert anti-tumor effects by inhibiting the repair of tumor cell DNA damage to achieve synthetic lethality. After DNA damage, repair primarily occurs through two pathways: homologous recombination (HR) and non-homologous end joining (NHEJ). DNA ligase IV, as a crucial enzyme in NHEJ, plays a role in connecting DNA fragments during the DNA repair process. Through bioinformatics analysis, we found that the use of olaparib in platinum-sensitive BRCA wild-type ovarian cancer cells leads to a decrease in the expression levels of DNA ligase IV in patients. Furthermore, cell experiments revealed that the expression levels of DNA ligase IV affect the sensitivity of ovarian cancer cells to olaparib. Specifically, when the expression levels of DNA ligase IV are reduced, the sensitivity of ovarian cancer to olaparib decreases. This suggests that BRCA wild-type ovarian cancer patients with low expression of DNA ligase IV may not respond well to PARP inhibitors. Through comet assays and other methods, it was discovered that a decrease in DNA ligase IV levels makes DNA less susceptible to damage in platinum-sensitive BRCA wild-type cells. Additionally, alterations in DNA ligase IV affect the related pathway genes of DNA damage repair in platinum-sensitive BRCA ovarian cancer, resulting in changes in DNA damage repair mechanisms. Therefore, the changes in NHEJ caused by DNA ligase IV may be one of the reasons for the sensitivity of BRCA wild-type ovarian cancer cells to PARP inhibitors. In the future, it may be possible to improve the efficacy of PARP inhibitors in BRCA wild-type ovarian cancer patients by influencing changes in the expression levels of DNA ligase IV.
Pulmonary function tests for identifying pathological invasive stage I lung adenocarcinoma: A multiple-center retrospective cohort study
Authors: Liu Yu , Tan Xueyun , Ma Guanzhou , Zhao Dong , Cao Yaqi , Liang Mengyuan , Tang Jian , Yu Hongyin , Chang Yan , Guo Mengfei , Wang Sufei , Jin Yang
Published: September 2024

Background Preoperative biopsy can hardly be used to diagnose lung cancer invasion; therefore, supplementary methods to estimate pathological tumor invasiveness are needed to identify candidates for limited resection. We aim to ascertain the risk factors and create and verify a model for predicting lung cancer invasion likelihood. Methods A nomogram was trained and validated on retrospectively collected data of patients with primary lung cancer whose pulmonary function was examined within 3 months before surgery. Least absolute shrinkage and selection operator logistic regression were used for important factor selection. The nomogram was established by combining preoperative pulmonary function tests (PFTs) and clinical factors. The area under the receiver operating characteristic curve and decision curve analysis (DCA) were used to evaluate the model’s predictive performance and clinical utility, respectively. Results Lung function impairment was detected in 508 patients (38.72%, 508/1312). The prediction model, which included age (odds ratio [OR] = 1.02), tumor size (OR = 1.31), lung function (OR = 3.10), basophils (OR = 0.51), and direct bilirubin levels (OR = 1.15), showed good performance in both sets. The areas under the curve for predicting lung cancer invasion were 0.820 (95% confidence interval [CI]: 0.781–0.858), 0.758 (95% CI: 0.659–0.858), and 0.838 (95% CI: 0.797–0.879) in the training, internal validation, and external validation sets, respectively, indicating good performance. In the multivariable analysis, patients with restrictive ventilation impairment (OR 2.86 [95% CI 1.43–5.69]) and diffusion capacity impairment (OR 4.23 [95% CI 1.00-17.84]) had high tumor invasion risks. Conclusions Lung function impairment could potentially serve as a biomarker for stage I lung adenocarcinoma invasion.
Angiomyolipomatous Lesions of the Nasal Cavity (Sinonasal Angioleiomyoma with Adipocytic Differentiation): A Multi-Institutional Immunohistochemical and Molecular Study
Authors: Jones Victoria M. , Thompson Lester D. R. , Pettus Jason R. , Green Donald C. , Lefferts Joel A. , Shah Parth S. , Tsongalis Gregory J. , Sajed Dipti P. , Guilmette Julie M. , Lewis James S. , Fisch Adam S. , Tafe Laura J. , Kerr Darcy A.
Published: September 2024

Purpose
Mesenchymal neoplasms composed of vascular, smooth muscle, and adipocytic components are uncommon in the nasal cavity. While angioleiomyoma (AL) is a smooth muscle tumor in the Head & Neck WHO classification, it is considered of pericytic origin in the Skin as well as Soft Tissue and Bone classifications. For nasal AL with an adipocytic component, the terms AL with adipocytic differentiation and angiomyolipoma (AML) have been applied, among others. AML is a type of perivascular epithelioid cell tumor (PEComa), most often arising in the kidney, sometimes associated with the tuberous sclerosis complex (TSC). It is uncertain whether nasal cavity AML and AL are best considered hamartomas or neoplasms, as their genetics are largely unexplored.
Methods
We performed a multi-institutional retrospective study of nasal cavity mesenchymal lesions. Patient demographics, clinical histories, and histologic and immunohistochemical findings were collected. DNA and RNA were extracted from formalin-fixed, paraffin-embedded tissue and analyzed by SNP-based chromosomal microarray, targeted RNA fusion sequencing, and whole-exome sequencing.
Results
Fifteen lesions (3 to 42 mm) were identified predominantly in male (87%) patients with a median age of 60. Patients typically presented with obstructive symptoms, and none had a history of TSC. One AL was a recurrence from six years prior; 11 cases showed no recurrence (median 4.7 years, range: 0.88–12.4). Morphologically, 11 AMLs contained 30–80% smooth muscle, 10–25% vasculature, and 2–60% adipose tissue, while four ALs contained 70–80% smooth muscle and 20–30% vasculature. Other histologic observations included surface ulceration, vascular thrombosis, chronic inflammation, and myxoid change; no well-developed epithelioid cell morphology was identified. Immunohistochemically, all cases were positive for smooth muscle markers (actin and/or desmin) and negative for melanocytic markers. Molecular analysis revealed loss of 3p and 11q in a single AML. No other known pathogenic copy number or molecular alterations were seen, including in TSC1/2, TFE3, or NOTCH2.
Conclusion
Nasal cavity AML lacks morphologic, immunophenotypic, and genetic features of PEComa family AMLs. The significant histologic overlap between nasal AML and AL without distinguishing molecular features in either entity suggests “sinonasal angioleiomyoma with adipocytic differentiation” may be the most appropriate terminology for hybrid vascular and smooth muscle lesions containing adipocytic components.
Morphological changes in the biliary mucosa in pediatric patients with congenital biliary dilatation are more influenced by the duration of amylase exposure than by amylase levels in the gallbladder
Authors: Korai Takahiro , Nui Akihiro , Nishibori Shigeki , Yokoyama Shinichiro , Hashimoto Satsuki , Ishimura Riku , Hamada Hiromi
Published: September 2024

Purpose
We investigated the relationship between bile amylase (AMY) levels and biliary epithelial changes in pancreaticobiliary maljunction (PBM), a congenital anomaly characterized by pancreaticobiliary reflux due to duct fusion outside the duodenal wall
Methods
We enrolled 43 children with congenital biliary dilatation (CBD) of Todani types Ia, Ic, and IVa who underwent surgery at the Hokkaido Medical Center for Child Health and Rehabilitation between November 2007 and June 2023. We defined total AMY exposure in bile as bile AMY levels multiplied by the patient's age (months), representing amount of estimated AMY exposure until surgery. We retrospectively investigated the relationships between bile AMY levels and clinicopathological findings.
Results
All patients exhibited hyperplasia in the gallbladder and bile duct epithelium, with dysplasia observed in 13 cases, but no carcinoma. Exposure to bile AMY ≥ 662,400 IU/L×months was an independent risk factor for dysplasia.
Conclusion
The amount of estimated AMY exposure in bile rather than AMY levels in the bile is an independent risk factor for dysplasia in the biliary mucosa.
Exploring Familial Hypospadias: Genetic Insights from Copy Number Variants in a Quad Family
Authors: Kumar Sourabh , Sharma Jyoti , Gupta Dinesh , Sardar Rahila , Lal Preeti , Jain Vishesh , Dhua Anjan Kumar , Yadav Devendra Kumar , Agarwala Sandeep , Shamsi Monis Bilal , Almaramhy Hamdi Hameed , Singh Harpreet , Kumar Neeta , Goel Prabudh
Published: September 2024

The genetic aetiology of hypospadias is likely to be oligogenic with possible interactions between multiple genetic variants and contributory environmental factors. A pathogenic copy number variant (CNV) is usually harboured by 3–14% of patients with rare developmental disorders. With this background, a landscape of CNVs in a family with multiple affected and unaffected progeny is presented with an investigation into the potentially responsible, molecular pathways underlying the etiopathogenesis of hypospadias. The family consists of both parents, two sons with hypospadias, and two unaffected sons (whole exome data unavailable for one unaffected son). CNVkit pipeline was executed and the structural variant files were annotated. The identified CNVs were studied for distribution within the family, inheritance, gene-composition and correlated with available information for potential relevance to the phenotype. Cumulative analysis (F:father, M:mother, P1-P2:affected progeny, U:unaffected progeny) identified 152 unique CNVs[size:1.49 kb–6.53 Mb) comprising 139 deletions and 13 duplications. P1 & P2 have been represented by 29(of 52) & 22(of 50) de novo CNVs respectively. P1 & P2 have 16 common deletion CNVs:8/16 CNVs are absent in U (inherited:6, de novo:2); de novo CNVs: chr6:29100942:29306930:DEL & chr16:11379821:11441076:D. de novo CNVs encompass OR2J1 and OR14J1 genes expressed in testis and spermatozoa as major histocompatibility complex (MHC)-linked olfactory receptors. CNVs encompassing GREM1, RRN3, KIAA0753 and HNF1B genes relevant to hypospadias were identified. The landscape of CNVs in familial hypospadias has been presented to enhance the understanding of their distribution, frequency and impact on the development of hypospadias and a database has been generated for future research.
Formative Development of InTSHA: Interactive Transition Support for Adolescents with HIV using Social Media
Authors: Zanoni Brian C. , Archary Moherndran , Sibaya Thobekile , Goldstein Madeleine H. , Bergam Scarlett , Psaros Christina , Marconi Vincent C. , Haberer Jessica E.
Published: September 2024

Introduction:
Using human-centered design strategies and a strong theoretical framework, we describe the formative development of a mobile-phone-based intervention: InTSHA (Interactive Transition Support for Adolescents with HIV).
Methods
We performed in-depth, semi-structured interviews with adolescents (n = 20), caregivers (n = 10), and healthcare providers (n = 10) to develop an intervention based on modifiable factors within the Socioecological Model for Adolescent and young Adult Readiness Transition (SMART) and delivered through social media. We then created a preliminary digital, interactive intervention based on modifiable factors in the SMART along with existing transition protocols and adolescent support group curricula to be delivered through mobile phones. We then theatre-tested the intervention with new groups of adolescents (n = 19), caregivers (n = 10), and healthcare providers (n = 7) to obtain feedback on content, delivery, and redesign.
Results
Participants expressed that moderated, small, mixed-gender, closed group chats with focused content facilitated weekly through WhatsApp would likely increase peer support and connection to clinical staff. Separate, closed group chat discussions among only caregivers of the adolescents in the InTSHA group could improve communication with their adolescents. Major concerns included internet and phone security, cost of data plans, and potential accidental disclosure of HIV status. Individual messaging with healthcare providers was seen as potentially beneficial; however, some healthcare providers voiced concern about procedures in the event of disclosure of medical and/or psychiatric emergencies.
Conclusion
The preliminary InTSHA intervention was developed through human-centered design focused on adolescents with HIV during transition to adult care that will use group WhatsApp chats to improve engagement in care.
Comparison of CT and MRI findings of different types of pancreatic Serous cystic neoplasm: combined with histopathology
Authors: Li Guangmang , Lei Aichun , Niu Shangfu , Wang Peng , Ji Guanghai , Han Xiao , Li Peng , Li Bo
Published: September 2024

Objectives
A comparative analysis of the imaging findings across different types Serous Cystic Neoplasm（SCN）was conducted, the objective is to delineate distinct image characteristics, thus enhancing diagnostic accuracy.
Methods
The retrospective analysis involved 65 patients diagnosed with Serous Cystic Neoplasm (SCN) confirmed by pathology. Patients were categorised into macrocystic, microcystic, mixed, and solid types based on morphology. A comparative analysis of the imaging findings across different SCN types was conducted, elucidating their respective imaging characteristics. Additionally, microscopic pathological observations were juxtaposed to discern disparities among the various SCN types.
Results
Age, lesion location, clinical symptoms, and underlying diseases did not exhibit significant differences among the various types of Serous Cystic Neoplasm (SCN) (P > 0.05). However, the volume of lesions in the mixed type was notably larger than that in the microcystic type (P < 0.05). Additionally, the CT values of the mixed and microcystic types were higher than those of the macrocystic type in precontrast scans (P < 0.05). The enhancement degree of the macrocystic type significantly differed from that of the mixed and microcystic types (P < 0.05). Notably, central fibrous scars were evident in mixed and microcystic SCN interiors, contrasting with the absence of such scars in macrocystic types (P < 0.05). While the proportion of calcification and pancreatic duct dilatation was higher in mixed and microcystic types. Electron microscopic revealed that macrocystic types featured large cyst cavities with thin fiber separation and few blood vessels, whereas microcystic types exhibited small cavities with a high number of fibers and visible scar tissue. Mixed types represented a combination of macrocystic and microcystic features. Solid types displayed very small cavities, high proportions of fibrous stroma, and rich blood vessels.
Conclusion
Differences in CT and MR findings among different types of SCN suggest a correlation with their pathological basis.
Causal Relationship between Serum Metabolites, Plasma Lipids, and Hemorrhoidal Disease: A Mendelian Randomization Study
Authors: Yu Hongkai , Yang Yingqi , You Chang , Zhao Jiayu , Wang Luyao , Sun Haohan , Li Yutong , Fan Yu , Jiang Xiaomeng
Published: September 2024

Hemorrhoidal Disease (HD) is a common anorectal disorder that significantly impacts patients' quality of life over the long term and imposes a substantial economic burden. However, the potential link between HD and serum metabolites and lipids has been scarcely studied, and its pathogenesis remains unclear. In this study, the causal relationship between serum metabolite traits, plasma lipids, and HD was evaluated using Mendelian Randomization (MR). Three methods were employed to estimate the causal effect of exposure on outcomes. The study identified 27 serum metabolic traits and 4 plasma lipids with significant causal effects on HD. Among these, 11 serum metabolic traits were identified as risk factors, and the top three ones exhibiting the most significant causal effects on the outcomes are Cortolone glucuronide (1) levels(OR=1.544, 95%CI=1.124-2.123,p=0.007), 3-methyl-2-oxobutyrate levels(OR=2.079, 95%CI=1.189-3.635,p=0.010), and Glycocholate levels(OR=1.405, 95%CI=1.063-1.857, p=0.017). Additionally, 16 serum metabolic traits were found to be protective factors, with lipids or lipoids and their metabolites comprising the largest proportion. In the Mendelian randomization analysis of plasma lipids and HD,Phosphatidylcholine (18:2_20:4) (OR=1.588,95%CI=1.097-2.299,p=0.014) and Phosphatidylcholine (O-16:1_16:0) (OR=1.676，95%CI=1.109-2.533,p=0.014) were identified as risk factors for HD.
Implementing a Healthcare-Associated Bloodstream Infection Surveillance Network in India: a Mixed-Methods Study on the Best Practices, Challenges and Opportunities, 2022
Authors: Vedachalam Srividya K. , Siromany Valan A. , VanderEnde Daniel , Malpiedi Paul , Vasquez Amber , Dikid Tanzin , Walia Kamini , Mathur Purva
Published: September 2024

Background Healthcare-associated bloodstream infections (BSI) threaten patient safety and are the third most common healthcare-associated infection (HAI) in low- and middle-income countries. An intensive-care-unit (ICU) based HAI surveillance network recording BSIs was started in India in 2017. We evaluated this surveillance network’s ability to detect BSI to identify best practices, challenges, and opportunities in its implementation.Methods We conducted a mixed-methods descriptive study from January to May 2022 using the CDC guidelines for evaluation. We focused on hospitals reporting BSI surveillance data to the HAI network from May 2017 to December 2021, and collected data through interviews, surveys, record reviews, and site visits. We integrated quantitative and qualitative results and present mixed methods interpretation.Results The HAI surveillance network included 39 hospitals across 22 states of India. We conducted 13 interviews, four site visits, and one focus-group discussion and collected 50 survey responses. Respondents included network coordinators, surveillance staff, data entry operators, and ICU physicians. Among surveyed staff, 83% rated the case definitions simple to use. Case definitions were correctly applied in 280/284 (98%) case reports. Among 21 site records reviewed, 24% reported using paper-based forms for laboratory reporting. Interviewees reported challenges, including funding, limited human resources, lack of digitalization, variable blood culture practices, and inconsistent information sharing.Conclusion Implementing a standardized HAI surveillance network reporting BSIs in India has been successful, and the case definitions developed were simple. Allocating personnel, digitalizing medical records, improving culturing practices, establishing feedback mechanisms, and funding commitment are crucial for its sustainability.
Global, regional, and national trends in prevalence and disability-adjusted life years (DALYs) for early-onset dementias, 1990-2021: Insights from the Global Burden of Disease Study 2021
Authors: Lin Chen-Ying , Zhai Ya-Jie , An Hao-Hua , Wu Fan , Qiu Hui-Na , Li Jing-Bo , Lin Jing-Na
Published: September 2024

Background This study aims to analyze temporal trends in the prevalence and disability-adjusted life year (DALY) burden of early-onset dementia (EOD) globally from 1990 to 2021 and assess the attributable burdens of modifiable risk factors.
Methods Data from the Global Burden of Disease Study (GBD) 2021 were used. EOD was defined as dementia in individuals aged 40-64. The analysis included case numbers with 95% uncertainty intervals (UIs), age-standardized prevalence rates (ASPRs), and DALY rates (ASDRs) with 95% confidence intervals (CIs), stratified by global, regional, and national levels, sociodemographic index (SDI), and sex. Joinpoint regression analysis evaluated the average annual percent change (AAPC). Population attributable fractions (PAFs) estimated the proportion of DALYs attributable to risk factors.
Results The global number of EOD cases and DALYs nearly doubled from 1990 to 2021, reaching 7.758 million cases (95% UI 5.827 to 10.081) and 3.774 million DALYs (95% UI 1.696 to 8.881) in 2021. ASPR and ASDR increased slightly to 355.9 (95% CI 267.2 to 462.8) and 173.3 (95% CI 77.9 to 407.7) per 100,000 in 2021. In 2021, the highest ASPR was in high-middle SDI countries at 387.6 per 100,000 (95% CI 291.1 to 506.8), while the highest ASDR was in middle SDI at 182.9 per 100,000 (95% CI 82.2 to 431). The fastest ASDR increase was in low and low-middle SDI countries from 2010 to 2021, with AAPCs of 0.42% (95% CI 0.34 to 0.50) and 0.36% (95% CI 0.33 to 0.39), respectively. A significant negative correlation was found between SDI and ASDR. During the COVID-19 pandemic (2019-2021), ASPR and ASDR in high-SDI countries declined, while other SDI regions saw an accelerated increase. In 2021, high fasting plasma glucose (FPG) was the most significant attributable risk factor for EOD-related DALYs globally, with PAFs for high body mass index and high FPG increasing in nearly all regions since 1990, while the PAF for smoking decreased.
Conclusions In 2021, EOD burden was highest in high-middle and middle SDI countries, particularly rising during the COVID-19 pandemic. The growing influence of metabolic risk factors underscores the need for targeted public health policies and resource allocation to mitigate the EOD burden.
Integrative single cell analysis to decode transcriptomic heterogeneity in pulmonary fibrosis across diverse pathologies
Authors: Bharat Ankit , Yan Yuanqing , Kaihou Taisuke , Lecuona Emilia , Shigemura Masahiko , Sun Haiying , Kurihara Chitaru , Gao Ruli , Budinger G.R.
Published: September 2024

Studies using single-cell transcriptional profiling of human samples have provided invaluable mechanistic insights into the development of various acute and chronic fibrotic lung states. However, the lack of data harmonization has impeded the comprehensive mapping of lung fibrosis, particularly for rarer etiologies with limited tissue availability. In this study, we performed new transcriptional analysis of human lungs with fibrotic disease states and integrated our data with approximately 1.3 million human cells from 15 studies, utilizing novel methods to address technical and batch effects. This integration allowed us to uncover common molecular signatures across different disease states including COVID-19 ARDS, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and interstitial lung disease, while identifying disease-specific transcriptomic profiles. Furthermore, our approach enabled the identification of a core gene signature for KRT17+KRT5- cells, a distinct subset implicated in pulmonary fibrosis across various etiologies which we validated using image-based spatial transcriptomics analyses. Additionally, our approach enabled us to deconvolute myeloid and stromal cell lineages in lung allografts from recipients with chronic lung allograft dysfunction, defining pathogenic transcriptional signatures and elucidating the intercellular crosstalk between donor- and recipient-derived cells in the allograft. Our approach provides a method to overcome the technical challenges in integrating single cell RNA-sequencing data from uncommon fibrotic lung diseases with extant datasets to define distinct and common molecular features and potential therapeutic targets.