bluuebunny/crossref_metadata_2025 huggingface dataset:
p53 inhibits CTR1-mediated cisplatin absorption by suppressing SP1 nuclear translocation in osteosarcoma
Authors: Yong Lei , Shi Yan , Wu Hai-Long , Dong Qi-Yuan , Guo Jing , Hu Li-Sheng , Wang Wen-Hao , Guan Zhi-Ping , Yu Bin-Sheng
Published: January 2023

Background

Osteosarcoma (OS) is a malignant bone tumor mainly affecting children and young adolescents. Cisplatin is a first-line chemotherapy drug for OS, however, drug resistance severely limits the survival of OS. Nevertheless, cellular factors in cisplatin resistance for OS remain obscure. In this study, the function and potential mechanism of p53 in cisplatin absorption were explored in OS cells.

Methods

The CRISPR-Cas9 gene editing technology was performed to obtain p53 gene knock-out U2OS cells. The p53 over-expression 143B cell line was established by lentivirus-mediated virus infection. Moreover, the functions of p53 and CTR1 in cisplatin absorption were assessed by inductively coupled plasma mass spectrometry (ICP-MS) through CTR1 over-expression and knock-down. Further, the DNA binding activity of SP1 on CTR1 gene promoter was determined by dual-luciferase assay and chromatin immunoprecipitation (ChIP) assay. The functional regulation of p53 on SP1 was studied by nucleocytoplasmic separation assay and electrophoretic mobility shift assay (EMSA). The interaction between p53 and SP1 was verified by Co-Immunoprecipitation assay.

Results

Under cisplatin treatment, p53 knock-out promoted CTR1 expression and cisplatin uptake, while p53 overexpression inhibited CTR1 expression and cisplatin uptake. Moreover, p53 regulated CTR1 level not by binding to CTR1 promoter directly but by suppressing the nuclear translocation of transcription factor specificity protein 1 (SP1). It was verified that SP1 is directly bound with CTR1 promoter. SP1 overexpression stimulated CTR1 expression, and SP1 knock-down attenuated CTR1 expression.

Conclusion

The p53 might function as a negative regulator in CTR1 mediated cisplatin absorption, and the p53-SP1-CTR1 axis is a target for cisplatin resistance.
The role of transplantation in Hodgkin lymphoma
Authors: Maranzano Michael , Mead Monica
Published: January 2023

Despite the success of frontline anthracycline-based chemotherapy for classical Hodgkin Lymphoma (cHL), approximately 15% of patients do not achieve an adequate response and require further therapy. For transplant-eligible patients, additional treatment followed by high-dose chemotherapy and autologous hematopoietic stem cell transplantation (autoHCT) provides a durable response in 50% of patients. The most refractory patients, including those requiring multiple lines of therapy to achieve a response or those relapsing after an autoHCT, may achieve long-term survival with allogeneic hematopoietic stem cell transplant (alloHCT). Contemporary salvage regimens used as a bridge to transplant have expanded to include not only non-cross resistant chemotherapy, but also brentuximab vedotin (BV) and checkpoint inhibitors (CPI). As the management of relapsed/refractory (R/R) cHL evolves with the introduction of novel agents, so too does the role of transplantation. The paradigm of chemosensitivity as a predictor for autoHCT efficacy is being challenged by favorable post- autoHCT outcomes in heavily pre-treated CPI-exposed patients. Contemporary supportive care measures, validated comorbidity assessments, and an increased donor pool with haploidentical donors have broadened the application of transplantation to an increasingly older and diverse patient population. Despite the introduction of increasingly effective treatment options for R/R cHL, transplantation continues to play an important role in the management of these patients. In this review, we explore the impact of salvage therapy on autoHCT, conditioning regimens, maintenance therapy and the diminishing role of alloHCT for patients with cHL.
Permanent stoma after sphincter preservation for rectal cancer. A situation that occurs more often than you might think
Authors: Thomas Flavie , Menahem Benjamin , Lebreton Gil , Bouhier-Leporrier Karine , Dejardin Olivier , Alves Arnaud
Published: January 2023

Objectives

This study aimed: (i) to assess the cumulative incidence of permanent stoma (PS) after sphincter-preserving surgery (SPS) for rectal cancer (RC): (ii) to analyze associated risk factors for primary and secondary PS; and (iii) to compare the long-term survival of patients according to the stoma state.

Methods

We conducted a retrospective single-center cohort study based on a prospectively maintained database of SRC patients undergoing SPS from January 2007 to December 2017. Incidence of both primary (no reversal of defunctioning stoma) and secondary (created after closure of defunctioning stoma) PS were investigated. Associations between potential risk factors and PS were analyzed using a logistic regression model. Cumulative survival curve was drawn by Kaplan-Meier method.

Results

Of the 257 eligible patients, 43 patients (16.7%) had a PS (16 primary PS and 27 secondary PS) after a median follow-up of 4.8 years. In multivariate analysis, the independent risk factors for primary PS were severe post-operative complications (OR 3.66; 95% CI, 1.19-11.20, p=0.022), and old age (OR 1.11; 95% CI 1.04-1.18, p=0.001) and those for secondary PS were local recurrence (OR 38.07; 95% CI 11.07-130.9, p<0.0001), anastomotic leakage (OR 7.01; 95% CI, 2.23-22.04, p=0.009), and severe post-operative complications (OR 3.67; 95% CI, 1.22-11.04, p=0.02), respectively. Both overall survival (OS) and disease-free survival (DFS) were significantly lower in patients with a PS compared with patients with SPS (p < 0.01).

Conclusions

This present study suggests that one out of 6 patients has a PS, 5 years after rectal resection with SPS for SRC.
New panel of biomarkers to discriminate between amelanotic and melanotic metastatic melanoma
Authors: Militaru Ioana V. , Rus Alina Adriana , Munteanu Cristian V.A. , Manica Georgiana , Petrescu Stefana M.
Published: January 2023

Melanoma is a form of skin cancer that can rapidly invade distant organs. A distinctive feature of melanomas is their pigmentation status, as melanin is present in most skin melanomas, whilst many metastatic tumors could become amelanotic. Besides the obvious malfunction of the key genes of the melanin pathway, the amelanotic tumors could bear a characteristic molecular signature accounting for their aggressivity. Using mass spectrometry-based proteomics we report here a distinctive panel of biomarkers for amelanotic aggressive melanoma that differ from the less invasive pigmented cells. The developed method allows the label-free quantification of proteins identified by LC-MS/MS analysis. We found a set of proteins comprising AHNAK, MYOF, ANXA1, CAPN2, ASPH, EPHA2, THBS1, TGM2, ACTN4 along with proteins involved in cell adhesion/migration (integrins, PLEC, FSCN1, FN1) that are highly expressed in amelanotic melanoma. Accompanying the down regulation of pigmentation specific proteins such as tyrosinase and TYRP1, these biomarkers are highly specific for a type of highly invasive melanoma. Interestingly, the LC-MS/MS proteomics analysis in hypoxia revealed that the abundance of this specific set of proteins found in normoxia was rather unaltered in these conditions. These biomarkers could therefore predict a metastatic behaviour for the amelanotic cells in the early stages of the tumor development and thus serve in melanoma prognostic. Applying this algorithm to related databases including melanoma samples published by independent laboratories/public databases we confirm the specificity of the newly found signatures. Overall, we begin to unravel the molecular alterations in the amelanotic melanoma and how basic proteomics offers insights into how to assess the clinical, pathological and misdiagnosis differences between the main subtypes of melanoma.
Pleiotropic effects of the COX-2/PGE2 axis in the glioblastoma tumor microenvironment
Authors: Dean Phillip T. , Hooks Shelley B.
Published: January 2023

Glioblastoma (GBM) is the most common and aggressive form of malignant glioma. The GBM tumor microenvironment (TME) is a complex ecosystem of heterogeneous cells and signaling factors. Glioma associated macrophages and microglia (GAMs) constitute a significant portion of the TME, suggesting that their functional attributes play a crucial role in cancer homeostasis. In GBM, an elevated GAM population is associated with poor prognosis and therapeutic resistance. Neoplastic cells recruit these myeloid populations through release of chemoattractant factors and dysregulate their induction of inflammatory programs. GAMs become protumoral advocates through production a variety of cytokines, inflammatory mediators, and growth factors that can drive cancer proliferation, invasion, immune evasion, and angiogenesis. Among these inflammatory factors, cyclooxygenase-2 (COX-2) and its downstream product, prostaglandin E2 (PGE2), are highly enriched in GBM and their overexpression is positively correlated with poor prognosis in patients. Both tumor cells and GAMs have the ability to signal through the COX-2 PGE2 axis and respond in an autocrine/paracrine manner. In the GBM TME, enhanced signaling through the COX-2/PGE2 axis leads to pleotropic effects that impact GAM dynamics and drive tumor progression.
Safety and efficacy of the pan-FGFR inhibitor erdafitinib in advanced urothelial carcinoma and other solid tumors: A systematic review and meta-analysis
Authors: Zheng Xinyi , Wang Hang , Deng Junyue , Yao Minghe , Zou Xiuhe , Zhang Fan , Ma Xuelei
Published: January 2023

Objective

This review aimed to comprehensively analyze the safety and efficacy of erdafitinib in treating advanced and metastatic urothelial carcinoma and other solid tumors.

Methods

PubMed, Embase, and ClinicalTrials.gov were searched until 10 February 2022. The safety outcome as adverse events and efficacy outcomes, including objective response rate, stable disease rates, and progressive disease rates, were selected and analyzed by comprehensive meta-analysis version 3.0 and STATA 15.0.

Results

The most common all-grade adverse events were hyperphosphatemia, dry mouth, stomatitis, diarrhea, and dysgeusia. The occurrence of ≥3 adverse events was relatively low, and stomatitis and hyponatremia were the most common. Moreover, eye disorders could not be ignored. Efficacy in urothelial carcinoma patients was obviously better than in other solid tumor patients, with a higher objective response rate (0.38 versus 0.10) and lower progressive disease rate (0.26 versus 0.68). All responses occurred in patients with fibroblast growth factor receptor (FGFR) alteration. In those patients, a specific FGFR alteration (FGFR3-TACC3) was observed to have a maximum response.

Conclusion

Erdafitinib has satisfactory clinical activity for metastatic urothelial carcinoma and other solid tumors, while the toxicity is acceptable. With more RCTs and combination therapy trials published, erdafitinib will be applied widely.
Quality improvements in radiation oncology clinical trials
Authors: Smith Koren , Ulin Kenneth , Knopp Michael , Kry Stephan , Xiao Ying , Rosen Mark , Michalski Jeff , Iandoli Matthew , Laurie Fran , Quigley Jean , Reifler Heather , Santiago Juan , Briggs Kathleen , Kirby Shawn , Schmitter Kate , Prior Fred , Saltz Joel , Sharma Ashish , Bishop-Jodoin Maryann , Moni Janaki , Cicchetti M. Giulia , FitzGerald Thomas J.
Published: January 2023

Clinical trials have become the primary mechanism to validate process improvements in oncology clinical practice. Over the past two decades there have been considerable process improvements in the practice of radiation oncology within the structure of a modern department using advanced technology for patient care. Treatment planning is accomplished with volume definition including fusion of multiple series of diagnostic images into volumetric planning studies to optimize the definition of tumor and define the relationship of tumor to normal tissue. Daily treatment is validated by multiple tools of image guidance. Computer planning has been optimized and supported by the increasing use of artificial intelligence in treatment planning. Informatics technology has improved, and departments have become geographically transparent integrated through informatics bridges creating an economy of scale for the planning and execution of advanced technology radiation therapy. This serves to provide consistency in department habits and improve quality of patient care. Improvements in normal tissue sparing have further improved tolerance of treatment and allowed radiation oncologists to increase both daily and total dose to target. Radiation oncologists need to define a priori dose volume constraints to normal tissue as well as define how image guidance will be applied to each radiation treatment. These process improvements have enhanced the utility of radiation therapy in patient care and have made radiation therapy an attractive option for care in multiple primary disease settings. In this chapter we review how these changes have been applied to clinical practice and incorporated into clinical trials. We will discuss how the changes in clinical practice have improved the quality of clinical trials in radiation therapy. We will also identify what gaps remain and need to be addressed to offer further improvements in radiation oncology clinical trials and patient care.
Adjuvant immunotherapy in early-stage resectable non–small cell lung cancer: A new milestone
Authors: Tang Wen-Fang , Ye Hong-Yu , Tang Xuan , Su Jian-Wei , Xu Kang-Mei , Zhong Wen-Zhao , Liang Yi
Published: January 2023

Currently, chemotherapy is the standard adjuvant treatment for early-stage non-small cell lung cancer (NSCLC). However, adjuvant cisplatin-based chemotherapy after surgery has been shown to improve 5-year survival rates by only 4−5%. Immunotherapy using immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced NSCLC, there is a growing interest in the role of immunotherapy in early-stage NSCLC. Here, we summarize the rationale for adjuvant immunotherapy, including the postoperative immunosuppressive environment and immunological effects of platinum chemotherapy. Many ongoing clinical trials and the related progress in adjuvant immunotherapy in early-stage resectable NSCLC are discussed. Furthermore, we highlight several unresolved challenges, including markers predictive of treatment benefit, the efficacy of treatment for some oncogene-addicted tumors, the optimal combination therapy, the duration of adjuvant immunotherapy, and optimal selection between neoadjuvant and adjuvant immunotherapy. Early findings in some clinical trials are promising, and updated overall survival results will be useful for validating the current role of adjuvant immunotherapy, particularly in the context of perioperative strategy.
Oral health in HPV-positive and HPV-negative patients with oropharyngeal squamous cell carcinoma
Authors: Kanzow Philipp , Mielke Katharina , Hrasky Valentina , Wiegand Susanne , Schliephake Henning , Beutner Dirk , Wiegand Annette
Published: January 2023

This study compared oral health in oropharyngeal squamous cell carcinoma (OPSCC) patients with positive or negative human papillomavirus (HPV) status and analysed whether oral health was associated with survival. Patients referred for dental assessment prior to radio(chemo)therapy between 2009 and 2019 were included. Patient-related risk factors for OPSCC (alcohol, tobacco, HPV status), age, sex, treatment (primary treatment, intent), performance status, tumor/node/metastasis (TNM) staging, and oral health parameters (DMFT, periodontal status, teeth with/without root canal treatment and with/without periodontitis apicalis) were compared between HPV-negative and HPV-positive patients. Survival was assessed using Kaplan-Meier statistics. The effect of patient-related risk factors and oral health parameters was analysed by cox regression analyses (α=5%). A total of 119 patients (n=50 HPV-negative, n=69 HPV-positive) was included. HPV-positive patients showed more present teeth, a higher number of filled teeth, were less often edentulous and presented a lower DMFT compared to HPV-negative patients (padj.≤0.003). Among dentulous patients, HPV-positive patients showed more present teeth and fewer teeth with periodontitis apicalis lacking a root canal treatment (padj.≤0.036). Survival probability differed between groups (p=0.006) and trended towards being associated with HPV status, tobacco exposure, performance status, T stage, N stage, and the number of missing or filled teeth as well as the number of root canal treated teeth with periodontitis apicalis and the number of teeth with periodontitis apicalis lacking a root canal treatment (p≤0.077). However, only tobacco exposure, performance status, and the number of teeth with periodontitis apicalis lacking a root canal treatment in dentulous patients remained significant in the multivariate analyses (p≤0.047). HPV-negative patients with OPSCC showed a poorer oral health compared to HPV-positive patients, but survival was not associated with oral health.
Sulforaphane: An emergent anti-cancer stem cell agent
Authors: Coutinho Leandro de Lima , Junior Tharcísio Citrangulo Tortelli , Rangel Maria Cristina
Published: January 2023

Cancer is a major public health concern worldwide responsible for high morbidity and mortality rates. Alternative therapies have been extensively investigated, and plant-derived compounds have caught the attention of the scientific community due to their chemopreventive and anticancer effects. Sulforaphane (SFN) is one of these naturally occurring agents, and studies have shown that it is able to target a specific cancer cell population displaying stem-like properties, known as cancer stem cells (CSCs). These cells can self-renewal and differentiate to form highly heterogeneous tumor masses. Notably, most of the conventional chemotherapeutic agents cannot target CSCs once they usually exist in a quiescent state and overall, the available cytotoxic drugs focus on highly dividing cells. This is, at least in part, one of the reasons why some oncologic patients relapse after standard therapy. In this review we bring together studies supporting not only the chemopreventive and anticancer properties of SFN, but especially the emerging anti-CSCs effects of this natural product and its potential to be used with conventional antineoplastic drugs in the clinical setting.
Progress of research on tumor organoids: A bibliometric analysis of relevant publications from 2011 to 2021
Authors: Shuoxin Yin , Shuping Wang , Xinyue Zhang , Tao Zhang , Yuanneng Chen
Published: January 2023

Background

Research on tumor organoids has developed rapidly over the past 20 years, but a systematic analysis of current research trends is lacking. Researchers in the field need relevant references and knowledge of current research hot spots. Bibliometric analysis and visualization is a systematic method of acquiring an in-depth understanding of the status of research on tumor organoids.

Methods

CiteSpace, VOSviewer and the Bibliometric Online Analysis Platform from the Web of Science Core Collection were used to analyze and predict publishing trends and research hot spots worldwide in the field of tumor organoids.

Results

A total of 3,666 publications on tumor organoids were retrieved, and 2,939 eligible articles were included in the final analysis. The number of publications has grown significantly, with the United States of America as the leading country for research on tumor organoids. Among journals, Cancers published the largest number of articles. Harvard Medical School published the highest number of articles among all institutions. The Chinese Academy of Sciences was ranked highest among all contributing institutions on the importance of their publications. A trend in multi-disciplinary collaboration was observed in studies on tumor organoids. Keywords indicated that the current research largely concentrated on optimizing the construction of organoid models to use for medication development and screening in the clinical setting, and to provide patients with individualized treatment for gastric cancer and colorectal cancer, which are newly emerging research hotspots. Gastric and colorectal cancers were the top two tumors that have received increasing attention and have become the focal points of recent studies.

Conclusion

This study analyzed 2,939 publications covering the topic of tumor organoids. Although optimizing the construction of organoid models has always been a hot topic in this field, the application of tumor organoids to the development of medications and screenings will foster individualized treatment for patients, which is another emerging hot spot in this field of research.
Bibliometric analysis of global research on physical activity and sedentary behavior in the context of cancer
Authors: Gu Jialin , Hu Miao , Chen Yonglin , Yu Jialin , Ji Yi , Wei Guoli , Huo Jiege
Published: January 2023

Objective

Numerous studies focusing on sedentary behavior (SB) and physical activity (PA) in the context of cancer have been reported in recent years. We analyzed and visualized studies on SB and PA in patients with cancer over the last 20 years using scientometric methods, to provide insights on gaps and deficiencies in the literature, and to inform future research guidelines.

Methods

All relevant studies in the field from 2001 to October 2022 were reviewed using bibliometric tools, including VOSviewer, Bibliometric online analysis platform, and biblioshiny, to determine the most influential countries, institutions, journals, and authors. We explored current research hotpots and potential research trends, based on keyword clustering and dynamic changes. Our research focuses on PA, SB, and cancer across the entire cancer continuum, from primary prevention to treatment to cancer survivorship.

Results

Scientometric analysis identified 4,382 relevant manuscripts on SB and PA in the context of cancer, with a 10-fold increase in articles over the past 20 years. The United States, Canada, and Australia were the most influential countries. The journal, Supportive Care in Cancer, had the highest number of publications, while Clinical Oncology had the highest H-index. K.S. Courneya was the most influential author in this field, with the highest number of publications, total citations, and H-index. Keyword analysis revealed that current research is focused on PA and SB in patients with breast cancer, quality of life, and aerobic exercise. Future frontiers include cancer prehabilitation programs and cardiorespiratory fitness, and remote intervention and social support.

Conclusion

By using bibliometrics, we conducted a comprehensive review of SB and PA in cancer-related studies. The current research focused on exercise and sedentariness in breast cancer patients and the role of PA in improving quality of life in survivorship. Emerging research foci were generally around cancer prehabilitation programs and remote intervention issues for PA. In addition, some publication deficits are noted: studies of PA and SB in less common cancers; the recommended doses and intensities of exercise for cancer; the timing of interventions for prehabilitation and the establishment of individualized exercise protocols. These deficiencies align with the needs for future research topics.
Combining neoadjuvant chemotherapy with PD-1/PD-L1 inhibitors for locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma: A systematic review and meta-analysis
Authors: Yuan Zhen , Cui Hao , Wang Shuyuan , Liang Wenquan , Cao Bo , Song Liqiang , Liu Guibin , Huang Jun , Chen Lin , Wei Bo
Published: January 2023

Background

Immune checkpoint inhibitors (ICIs) have shown promising prospects in locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC) immunotherapy, but their efficacy in neoadjuvant settings remains unclear. This study aimed to assess the efficacy and safety of integrating programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors into neoadjuvant chemotherapy (NACT) of GC/GEJC treatment.

Methods

PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and main oncology conference databases were systematically searched up to 19 November 2022, and randomized controlled trials (RCTs) and cohort studies that evaluated the efficacy and safety of PD-1/PD-L1 inhibitors plus NACT were included. The main outcomes were pathological complete response (pCR), major pathological response (MPR), R0 resection rate, and treatment-related adverse events (TRAEs).

Results

A total of 753 patients from 20 prospective studies were included in this meta-analysis. The pooled pCR and MPR rates from studies reporting were 21.7% [95% confidence interval (CI), 18.1%–25.5%] and 44.0% (95% CI, 34.1%–53.8%), respectively. The pooled incidence rate of total TRAEs was 89.1% (95% CI, 82.7%–94.3%), and the incidence rate of grade 3 to 4 TRAEs was 34.4% (95% CI, 17.8%–66.5%). The pooled R0 resection rate was reported to be 98.9% (95% CI, 97.0%–99.9%). Subgroup analysis has not found significant differences in efficacy and safety among different PD-1/PD-L1 inhibitors. Moreover, the efficacy in patients with positive PD-L1 expression (combined positive score ≥1) was comparable with that in the entire study population [pCR, 22.5% vs. 21.2% (p > 0.05); MPR, 48.6% vs. 43.7% (p > 0.05)].

Conclusion

This systematic review and meta-analysis found that PD-1/PD-L1 inhibitors combined with NACT for locally advanced GC/GEJC were well tolerated and may confer therapeutic advantages. The integration of ICIs into NACT has shown the potential for application in any PD-L1 expression population.
Long-term stable disease with mFOLFOX6 chemotherapy plus cetuximab for bone marrow metastasis from rectal cancer: A case report
Authors: Fan Xiumei , Li Fang , Xiao Chong , Cai Yi , You Fengming
Published: January 2023

Bone marrow metastasis from rectal cancer is a rare but severe disease associated with a poor prognosis due to limited treatment options. There is no consensus on therapeutic strategies, and better-tolerated and more effective treatment options are urgently needed. We report a case that one patient with rectal cancer developed pancytopenia 15 months after completion of radical surgery and chemotherapy and was diagnosed with bone marrow metastasis. The patient was treated with mFOLFOX6 chemotherapy plus cetuximab, considering both his poor bone marrow function and a genetic test showing a wild-type of KRAS/NRAS/PIK3CA/BRAF. Twelve cycles were successfully completed with dose modifications and supportive measures. The patient’s condition improved markedly based on a comprehensive assessment that included computed tomography images, blood cell counts, tumor markers, and clinical symptoms. The patient remains alive for 11 months at the last follow up. The patient treated with mFOLFOX6 chemotherapy plus cetuximab attained long-term stable disease, suggesting its promising efficacy and safety for bone marrow metastasis from rectal cancer and may hold promise as a treatment strategy for this specific patient population. Consideration can be given to the inclusion of mFOLFOX6 chemotherapy plus cetuximab in first-line treatment regimen for bone marrow metastasis from rectal cancer.
Optimal age of surgery for children with thyroglossal duct cysts: A single-institution retrospective study of 340 patients
Authors: Wang Yingli , Yang Gang
Published: January 2023

Objective

The recommended age of surgery for thyroglossal duct cysts (TGDCs) in children is inconclusive. This study aimed to explore the optimal age of surgery by analyzing the natural history of the disease and the association between the age of surgery and postoperative complications.

Methods

All TGDC patients who underwent a modified Sistrunk procedure at our hospital between March 2010 and May 2022 were reviewed retrospectively. The evaluation focused on the age of preoperative symptomatic cystic infection, pathological inflammation, postoperative wound infection, and recurrence.

Results

Of the 340 patients included in the study, the median age of surgery was 47.5 months (IQR, 24.1–61.6). Preoperative symptomatic cystic infection and pathological inflammation frequencies were 27.1% (n = 92) and 48.5% (n = 165), respectively. The cumulative hazard of symptomatic cystic infection and pathological inflammation increased steadily with age. The ages of 50% cumulative incidence of symptomatic cystic infection and pathological inflammation were 97 months and 71 months, respectively. Postoperative wound infection was higher in patients of younger age (OR = 0.96, 95% CI, 0.93–0.98, P < 0.001) and with symptomatic cystic infection (OR = 8.16, 95% CI, 2.54–36.86, P = 0.002). There was no significant association between the age of surgery and recurrence.

Conclusion

Although wound infection was weakly associated with younger age, the symptomatic cystic infection increasing with age has a more remarkable impact on wound infection after the Sistrunk procedure. The recurrence rate did not increase in young patients receiving surgery. Therefore, the Sistrunk procedure was safe and effective at a young age, and prompt operation in children with TGDC once diagnosed was reasonable.
Case report: Morphological changes evident after manual therapy in two cases of late-diagnosed developmental dysplasia of the hip
Authors: Fludder Christian J. , Keil Braden G. , Neave Melissa J.
Published: January 2023

Background

Late diagnosed Developmental Dysplasia of the Hip (DDH) is the detection of DDH after 3 months of age and is associated with significantly poorer outcomes than when diagnosed and managed early. Late diagnosed DDH has lower rates of success with bracing, higher rates of surgery and higher rates of complications, including avascular necrosis of the femoral head and early osteoarthritis of the hip. We describe two cases of late-diagnosed DDH which demonstrated changes in femoroacetabular joint morphology on radiographic interpretation after a 6-month trial period of manual therapy.

Case Presentation

Two cases (13 and 30 months of age) with late-diagnosed DDH presented to a private chiropractic clinic for conservative, non-bracing management. One case had unilateral DDH and the other bilateral DDH. A trial of manual therapy was utilized over a 6-month period. Both cases demonstrated changes to femoroacetabular morphology as well as improvements in gross motor activity and lower extremity muscle tone.

Conclusion

Manual therapy, as an adjunct or alternative to static bracing, may be of benefit in individuals with late-diagnosed DDH not responding to bracing, and prior to more invasive interventions. Additional cases of manual therapy-based management of this condition are required to inform the design of future trials to investigate this hypothesis.
Multicenter review of a tadalafil suspension formulation for infants and children with pulmonary hypertension: A North American experience
Authors: Youssef David Edward , Handler Stephanie S. , Richards Susan Marjorie , Sheppard Catherine Anne , Smith Jenna , Tillman Kathryn , Pietrosanu Matthew , Kirkpatrick Edward , Bates Angela
Published: January 2023

Introduction

Phosphodiesterase type 5 (PDE5) inhibitors, with sildenafil the earliest among them, are widely used in the management of pediatric pulmonary arterial hypertension (PAH). Tadalafil is a PDE5 inhibitor with a long half life (16 h), stable pharmacokinetics and pharmacodynamics, and minimal adverse effects. However, the utility of tadalafil suspensions in this setting has not been widely explored due to a lack of clinical experience. We present a multicenter experience that details the safety and tolerability of a tadalafil suspension, either alone or in combination with another vasodilator, for the management of pediatric pulmonary hypertension (PH).

Methods and materials

This is a retrospective chart review of infants and children at Children's Wisconsin and the Stollery Children's Hospital enrolled in pediatric PH programs between December 2013 and April 2022 managed with a tadalafil suspension. Patients aged six years of age and under who were treated with a tadalafil suspension were included. Demographics, clinical information, echocardiographic and hemodynamic measurements, and laboratory data were collected before and six months after tadalafil initiation.

Results

Over the study period, 154 children with a median age of 1.0 (range 0.0–6.9) years were treated with tadalafil therapy. Of these, 39 (25.3%) were in group 1 (PAH), 79 (51.3%) were in group 3 (lung disease), and 33 (21.4%) were in group 5 (pulmonary hypertensive vascular disease). The median initial dose of tadalafil was 1.0 mg/kg once daily. Eleven (7.1%) patients in the cohort were established on tadalafil therapy de novo. The suspension formulation was necessary for 103 (66.9%) patients due to an inability to take enteral tablets and for 49 (31.8%) due to a need for feeding via gastric or jejunal tubes. We observed a statistically significant increase in tricuspid annular plane systolic excursion as well as significant decreases in right-ventricular systolic pressure and NT-proBNP. Tadalafil therapy was well tolerated over the six-month period: at six months, no adverse effects were reported aside from gastrointestinal disturbances by 2 (1.3%) patients.

Conclusion

Tadalafil, a long-acting PDE5 inhibitor, when administered in a suspension formulation, has a safe and tolerable adverse effect profile. Following six months of therapy, our cohort showed improvements in clinical parameters, echocardiographic measurements, and laboratory results. Patient compliance was good and adverse effects were rare, minor, and manageable with nonpharmacological means.
Greater alteration of gut microbiota occurs in childhood obesity than in adulthood obesity
Authors: Yu Zhongjia , Yu Xiang-Fang , Zhao Xiu , Su Zhe , Ren Pei-Gen
Published: January 2023

The children's gut microbiota, associated with the development of obesity, is in maturation. The impact of obesity on the gut microbiota in childhood could have a more significant effect than on adulthood and eventually be lifelong lasting, but it has been rarely studied. Aimed to discover the difference in gut microbiota between children and adults with obesity, we collected published amplicon sequencing data from National Center for Biotechnology Information (NCBI) and re-analyzed them using a uniform bioinformatic pipeline, as well as predicted the obesity using gut microbiota based on the random forest model. Summarizing common points among these cohorts, we found that the gut microbiota had a significant difference between children with and without obesity, but this difference was not observed in adult cohorts. Based on the random forest model, it was more challenging to predict childhood obesity using gut microbiota than adulthood obesity. Our results suggest that gut microbiota in childhood is more easily affected than in adulthood. Early intervention for childhood obesity is essential to improve children's health and lifelong gut microbiota-related health.
Immune checkpoint inhibitor-induced aplastic anaemia: Case series and large-scale pharmacovigilance analysis
Authors: Guo Qian , Zhao Jin Ning , Liu Ting , Gao Jian , Guo Hui , Cheng Jing Min
Published: January 2023

Introduction: Impressive advances in immunotherapy especially immune checkpoint inhibitors have made great progress in treating multiple cancers but can also cause serious even incurable immune-related adverse events, mostly found in colitis, dermatitis, hepatitis, and thyroiditis patients. Rare autoimmune hematologic toxicities have been reported in the literature, but are poorly described. Aplastic anaemia induced by immune checkpoint inhibitors is a life-threatening autoimmune disease; however, only a few cases have been reported in the literature.

Objective: To characterize and evaluate Aplastic anaemia associated with different ICI regimens in public database and review the literature.

Methods: We described a case series of patients experiencing Aplastic anaemia while on immune checkpoint inhibitors. We also mined the Food and Drug Administration’s Adverse Event Reporting System and used reporting odds ratio, the proportional reporting ratio, the Bayesian confidence propagation neural network and the multi-item gamma Poisson shrinker algorithms to achieve the data of the suspected adverse events of Aplastic anaemia-induced by immune checkpoint inhibitors between January 2011 and June 2022.

Results: Thirteen patients with Aplastic anaemia events while on immune checkpoint inhibitors were included in our case series, and seven of them had a fatal outcome. In FAERS, a total of 38 individual case safety reports (immune checkpoint inhibitors) with different ICI regimens were retrieved, of which 25 (65.79%) were reported as monotherapy and 13 (34.2%) had a fatal outcome. The reporting odds ratio was significant for nivolumab (reporting odds ratio 3.05, 95%CI 1.73–5.38), pembrolizumab (reporting odds ratio 2.33, 95%CI 1.16–4.67), avelumab (reporting odds ratio 12.63, 95%CI 3.15–50.62) and ipilimumab/nivolumab (ROR 2.57, 95%CI 1.15–5.72).

Conclusion: There is a significant reporting signal of Aplastic anaemia with several ICI agents. Clinicians should raise awareness and monitor this potentially fatal adverse event.
Orphan drugs’ clinical uncertainty and prices: Addressing allocative and technical inefficiencies in orphan drug reimbursement
Authors: Eichler Hans-Georg , Kossmeier Michael , Zeitlinger Markus , Schwarzer-Daum Brigitte
Published: January 2023

Legislations incentivising orphan drug development and scientific advances have made orphan drugs pharma’s high-end favourite for the past two decades. Currently, around 50% of new marketing authorizations are for orphan drugs. For third-party healthcare payers (“payers”) the rise of orphan drugs presents new challenges, including a high degree of uncertainty around clinical benefits and harms, a moderate effect size (for many orphan drugs), and a high price tag. The association of high clinical uncertainty and moderate effect sizes is not surprising in small target populations but in combination with high prices creates the risk of allocative and technical inefficiencies for payers. We here discuss and illustrate these risks. A combination of policies is needed for mitigation of allocative inefficiency: while there may be a rationale for higher prices for orphan than non-orphan drugs, a focus of pricing and reimbursement negotiations should include considerations of product profitability and of the consequences of orphan drug costs on the distribution inequality of medication costs for individual insured persons, coupled to knowledge generation from reimbursement contracts covering high-price orphan drugs that would benefit the wider patient community. Performance-based managed entry agreements could help to de-risk the economic consequences of clinical uncertainty and to mitigate technical inefficiency.
Acoustophoretic trapping of particles by bubbles in microfluidics
Authors: González Itziar , Candil Manuel , Luzuriaga Jon
Published: January 2023

We present in this paper a simple method to produce strategic acoustic particle capture sites in microfluidic channels in a controlled way. Air bubbles are intermittently injected into a micro-capillary with rectangular cross section during a flow motion of liquid suspensions containing micron-sized particles or particles to create bubble-defined “micro-gaps” with size close to 200 µm and spheroidal geometry. The establishment of a 3D standing acoustic wave inside the capillary at a frequency close to 1 MHz produces different radiation forces on solid particles and bubbles, and acoustic streaming around the bubble. While the sample flows, part of the particles collect along the acoustic pressure node established near the central axis and continue circulating aligned through the capillary until reaching the end, where are released enriched. Meanwhile, the bubble travels very fast toward positions of maximum pressure amplitude beside the channel wall, driven by Bjerkness forces, and attach to it, remaining immovable during the acoustic actuation. Some particles adhere to its membrane trapped by the acoustic streaming generated around the oscillating bubble. Changes of frequency were applied to analyze the influence of this parameter on the bubble dynamics, which shows a complete stability once attached to the channel wall. Only increasing the flow motion induces the bubble displacements. Once reached the open air at the end of the capillary, the bubble disappears releasing the trapped particles separated from their initial host suspension with a purity degree. The device presents a very simple geometry and a low-cost fabrication.
Construction of medical equipment maintenance network management platform based on big data
Authors: Li Jiansheng , Mao Yajie , Zhang Jin
Published: January 2023

Introduction: Medical equipment is an indispensable part of hospitals. It is the basic condition and guarantee for the hospital to carry out medical services, scientific research, teaching, and other activities, and it plays an irreplaceable role in the entire medical process of the hospital. Therefore, the maintenance management of equipment is also the focus of our attention. In the past, traditional management methods such as paper were mainly used for equipment maintenance management, and it was difficult to share data.

Methods: In today’s era of rapid development of information technology, we will use information technology to maintain and manage medical equipment. Through big data analysis and other technologies, the drawbacks of the existing traditional management methods are improved, so that medical equipment can be managed scientifically. By maximizing its functions, it can ensure the normal operation of medical facilities, improve the utilization rate and integrity rate of equipment, and reduce maintenance costs and unnecessary losses.

Results: According to the research findings, based on the background of big data, a de-Bayesian network is used for data mining to build a medical equipment maintenance platform. Through the data in the platform, we can better discover the distribution and reasons of equipment maintenance, and at the same time conduct an analysis to provide reference for the formulation of preventive maintenance plans, reduce equipment failure rate and maintenance costs and improve equipment utilization. Through the survey of medical staff, we can also find that at least 40% of the people feel that the work distribution is more reasonable, and 45% of the people feel that the equipment failure rate and the time required for maintenance have been greatly reduced.

Discussion: We can see that the network platform for medical equipment maintenance management built through big data is very feasible, which can help us work more effectively and improve work efficiency.
The applications of symbolic computation to exact wave solutions of two HSI-like equations in (2+1)-dimensional
Authors: Kuo Chun-Ku , Gunay B. , Juan Chieh-Ju
Published: January 2023

It is renowned that Hirota–Satsuma–Ito (HSI) equation is widely used to study wave dynamics of shallow water. In this work, two new HSI-like equations are investigated which could be extended to diversify problems in natural phenomena and give admirable contributions by applying the generalized exponential rational function method (GERFM). With the aid of symbolic calculations, various constraints on the free parameters are given, while classes of wave solutions are explicitly constructed from the coefficients of the combined non-linear and dissipative terms. After specifying values for free parameters, singular, periodic singular and anti-kink waves are demonstrated in 3D figures to exhibit different kinds of wave propagations. The fact that parameters directly influence the wave amplitude and speed of traveling waves is illustrated. The derived results are innovative and have important applications in the current field of mathematical physics research. Eventually, we show that generalized exponential rational function method is effective and straightforward to solve higher-order and high-dimensional non-linear evolution equations.
Joint DOD and DOA detection for MIMO radar based on signal subspace reconstruction and matching
Authors: Lv Yan , Mao Weiwei , Cui Ye
Published: January 2023

In this study, the Direction Of Departure (DOD) and Direction Of Arrival (DOA) of signals detection for Multi-Input Multi-Output (MIMO) radar is discussed. A novel signal subspace reconstruction model to match the signal subspace obtained based on the covariance matrix of the array output is developed to enhance the performance of the DOD and DOA detection. In the developed scheme, the technology of beamforming is first introduced to define an objective space in mathematics for the targets to be detected. By considering the orthogonality between the signal subspace and the noise subspace and defining a reconstruction index of the signal subspace, a multi-dimensional objective function of the DOD and DOA is established. Therefore, the problem of DOD and DOA detection is transformed into an optimization of the multi-dimensional objective function. Subsequently, the Quantum-Behaved Particle Swarm Optimization (QPSO) is employed to optimize the multi-dimensional objective function and to determine an optimal signal subspace. At the same time the DOD and DOA can be fast captured. A series of simulations demonstrate that the proposed method provides significant accuracy improvements in DOD and DOA detection, especially for low signal-to-noise ratio thresholds and small snapshots.
Virtual Fly Brain—An interactive atlas of the Drosophila nervous system
Authors: Court Robert , Costa Marta , Pilgrim Clare , Millburn Gillian , Holmes Alex , McLachlan Alex , Larkin Aoife , Matentzoglu Nicolas , Kir Huseyin , Parkinson Helen , Brown Nicolas H. , O’Kane Cahir J. , Armstrong J. Douglas , Jefferis Gregory S. X. E. , Osumi-Sutherland David
Published: January 2023

As a model organism,Drosophilais uniquely placed to contribute to our understanding of how brains control complex behavior. Not only does it have complex adaptive behaviors, but also a uniquely powerful genetic toolkit, increasingly complete dense connectomic maps of the central nervous system and a rapidly growing set of transcriptomic profiles of cell types. But this also poses a challenge: Given the massive amounts of available data, how are researchers to Find, Access, Integrate and Reuse (FAIR) relevant data in order to develop an integrated anatomical and molecular picture of circuits, inform hypothesis generation, and find reagents for experiments to test these hypotheses? The Virtual Fly Brain (virtualflybrain.org) web application & API provide a solution to this problem, using FAIR principles to integrate 3D images of neurons and brain regions, connectomics, transcriptomics and reagent expression data covering the whole CNS in both larva and adult. Users can search for neurons, neuroanatomy and reagents by name, location, or connectivity,viatext search, clicking on 3D images, search-by-image, and queries by type (e.g., dopaminergic neuron) or properties (e.g., synaptic input in the antennal lobe). Returned results include cross-registered 3D images that can be explored in linked 2D and 3D browsers or downloaded under open licenses, and extensive descriptions of cell types and regions curated from the literature. These solutions are potentially extensible to cover similar atlasing and data integration challenges in vertebrates.