Clinical Guidance Research Articles

Synthesizing regulatory guidance for demonstrating preclinical efficacy and translating promising cell therapies to early phase clinical trials: a scoping review

BackgroundRegulatory applications for cell therapy face more objections compared to conventional small molecule or biological drugs, leading to delays in market approval and clinical adoption. Increased regulatory objections frequently relate to issues regarding preclinical evidence, such as experimental design of animal studies, selection of animal models, endpoints, and determination of mechanism of action. Synthesis and clarification of the preclinical evidence necessary to demonstrate treatment efficacy and advance into early-phase clinical trials is needed to help researchers avoid regulatory objections.MethodsWe conducted a scoping review in which we searched repositories of the International Council for Harmonisation and all national member organizations (N = 38) for documents related to preclinical studies of cell therapies. Active guidance documents related to cell therapy were included, with no restrictions based on the year or language of publication. Data extraction was conducted in duplicate with conflicts resolved through consensus discussion.ResultsFrom 1215 identified documents, a total of 182 were included and analyzed, with 71% originating from ten major regulatory agencies. The most prevalent preclinical item addressed was the mechanism of action (n = 161, 88% of documents), underscoring its importance in bridging preclinical findings to clinical application. Most documents (n = 140, 77%) emphasized the importance of using clinically relevant preclinical models, though specific recommendations on models of disease were less common (n = 81, 45%). Selection of clinically relevant intervention parameters (n = 136, 75%) and outcome measures (n = 121, 66%) were also frequently recommended, but selection of relevant comparator groups appeared less frequently (n = 35, 19%). Furthermore, robust study design elements such as randomization and blinding were less frequently recommended, appearing in 31% of documents (n = 57). Comparison with clinical trial guidance revealed a significant gap in the rigor of study design recommendations for preclinical research.ConclusionsRegulatory guidance for preclinical efficacy studies often recommends a strong emphasis on the clinical relevance of animal models, intervention parameters, outcomes, and mechanism of action. Incorporating these recommendations into early preclinical studies should improve the acceptability of preclinical evidence for approval by the relevant national regulators and can be used as a guide to ensure that all evidence that regulators say they expect is efficiently assembled into new clinical trial applications.

Guía de práctica clínica para la toma de muestra de sangre venosa en pacientes adultos en México

More than 70 % of medical decisions are based on the results of diagnostic tests from the clinical laboratory. To establish and standardize procedures and technical resources that allow for the generalization of optimal samples obtained by phlebotomy, a multidisciplinary group of experts gathered and developed Guía de práctica clínica para la toma de muestra de sangre venosa en pacientes adultos en México (Clinical Practice Guide for Venous Blood Sampling in Adult Patients in Mexico). This guide includes recommendations on requesting the exam, preparing the area, the patient's preanalytical conditions, required supplies, sample identification, use of the tourniquet, selection and disinfection of the puncture site, extraction and collection of the blood sample, recommendations for phlebotomy in patients with difficult venous access,among other procedures.

Prognosis prediction of head and neck squamous cell carcinoma through the basement membrane-related lncRNA risk model.

Head and neck squamous cell carcinoma (HNSCC) ranks among the most widespread and significantly heterogeneous malignant tumors globally. Increasing evidence suggests that the basement membrane (BM) and associated long non-coding RNAs (lncRNA) are correlated with the onset of HNSCC and its prognosis. Our study aims to construct a basement membrane-associated lncRNAs (BMlncRNAs) marker to accurately predict the prognosis of HNSCC patients and find novel immunotherapy targets. The Cancer Genome Atlas (TCGA) database was accessed to acquire the transcriptome expression matrices, somatic mutation data, and clinical follow-up data of HNSCC patients. Utilizing co-expression analysis, the BMlncRNAs were identified and the differentially expressed lncRNAs (DEBMlncRNA) were then filtered, The filtering thresholds are FDR<0.05 and |log2FC|≥1. Furthermore, univariate analysis, least absolute shrinkage and selection operator (LASSO), and multivariable Cox regression were utilized to develop the risk model. The model then underwent thorough evaluation across diverse perspectives, encompassing tumor immune infiltration, tumor mutation burden (TMB), functional enrichment, and chemotherapy sensitivity. The risk assessment model consists of 14 BMlncRNA pairs. The acquired data is indicative of the reliability of the risk score in its capacity as a prognostic factor. Individuals at high risk exhibited a poorer prognosis, and a statistically significant variance was noted in TMB and tumor immune infiltration compared to the low-risk group. Additionally, heightened sensitivity to paclitaxel and docetaxel was evident in the patients at high risk. We have established a BMLncRNA-based prognostic model that can provide clinical guidance for future laboratory and clinical studies of HNSCC.

A Dual-Mode Optical Sensing Strategy for Rapid Detection of D-Penicillamine in Pharmaceutical Formulations

Accurate, rapid, and quantitative detection of D-penicillamine (D-PA) in pharmaceutical formulations is imperative for drug quality and clinical medication guidance. Various colorimetric and fluorescent assays have been constructed for D-PA based on nanomaterials. However, the reliable and rapid detection of D-PA in pharmaceutical formulations remains a challenge because these methods suffer from shortcomings such as time-consuming procedures, poor uniformity, and complicated nanomaterial preparation. In this work, an effective and facile homogeneous dual-mode optical sensing strategy was established based on the strong complexation between D-PA and Cu2+ and catalyzed the oxidation of O-phenylenediamine. This platform displayed a sensitive response to D-PA from 5 to 100 µmol/L, with a detection limits of 0.54 µmol/L (fluorescence) and 0.76 µmol/L (colorimetry). As expected, the method was successfully applied to the determination of D-PA in pharmaceutical formulations with satisfactory results. Overall, this developed strategy provides a facile and rapid dual-mode optical platform for D-PA and has great potential in D-PA-related pharmaceutical quality control.

Survival comparison between open and thoracoscopic esophagectomy for node-negative esophageal squamous cell cancer: an ambispective cohort study.

It is controversial whether there is a survival difference between open esophagectomy (OE) and thoracoscopic esophagectomy (TE) for esophageal cancer (EC). Therefore, this study aimed to compare the differences in survival and safety between two surgical approaches in patients with node-negative esophageal squamous cell carcinoma (ESCC). This ambispective cohort study included 1104 patients with node-negative ESCC who received OE or TE treatment at a Grate-A tertiary hospital in Henan Province between January 2015 and December 2016. The primary endpoint was 5-year overall survival (OS) and disease-free survival (DFS), and the secondary endpoint was surgical safety. Multivariable Cox regression analysis was used to analyze the effect of surgical approaches on OS and DFS, and propensity score matching (PSM) was performed to match confounding factors between two groups. Patients were followed up ranged from 1.03 to 91.60months, with a median follow-up time of 67.37months. Kaplan-Meier survival analysis showed statistically significant differences between OE and TE in OS (70.05% vs 83.73%, P < 0.001) and DFS (67.15% vs 77.76%, P < 0.001). Furthermore, multivariate Cox regression analysis also demonstrated significant differences in long-term survival between the two groups (OS, HR (95%CI): 0.54 (0.41,0.70); DFS, HR (95% CI): 0.68 (0.54, 0.86)). TE was associated with a reduction in intraoperative bleeding (median: 100ml vs. 200ml, P < 0.001), and an increase in the number of lymph nodes dissection (median: 23 vs. 28, P < 0.001). Similar results were found after PSM. In a selected cohort of patients with node-negative ESCC, TE surgical treatment was safer and had better long-term survival outcomes compared to OE. This provided corresponding clinical guidance to enhance survival benefits for patients. In the future, we hope to further explore the reasons for TE achieving higher survival rates.

Use of neonatal lung ultrasound in European neonatal units: a survey by the European Society of Paediatric Research

ObjectiveRegarding the use of lung ultrasound (LU) in neonatal intensive care units (NICUs) across Europe, to assess how widely it is used, for what indications and how its implementation might...

A qualitative exploratory study into medical, nursing and allied health professional experiences of elective withdrawal of non-invasive ventilation in a motor neurone disease cohort.

With absence of a cure, the mainstay of management for patients with motor neurone disease (MND) is holistic supportive care and symptom control. Non-invasive ventilation (NIV) can provide relief from distressing dyspnoea which often accompanies progressive respiratory muscle weakness. Some patients using NIV will become dependent on it, with a small proportion of these patients going on to request withdrawal. Despite being legal in the UK, elective withdrawal of NIV can be emotionally and ethically challenging for the staff involved. To guide the process of symptom-controlled withdrawal, in 2015 the Association for Palliative Medicine (APM) released clinical guidance. The aim of this study is to explore the experiences of the multi-disciplinary team (MDT) involved in elective withdrawal of NIV in an MND cohort following the publication of this guidance. A qualitative, semi-structured interview study of eight NHS qualified staff members (three Doctors, four Nurses, one Allied Health Professional). Clinicians were asked questions relating to their experiences of the withdrawals. After full transcription, data was analysed thematically. Four main themes were identified, offering insight into how the withdrawals affected staff's well-being and summarised via an 'enablers and barriers' model. The setting was important, as was the depth and longevity of the clinician's investment in the patient. Positive influences on staff's well-being arose from the sense of fulfilling the patient's wishes, good teamwork, presence of an experienced clinician and awareness of the APM (2015) Guidance. Conversely, barriers to well-being were expressed through the unpredictability of each scenario, moral and ethical uncertainties, external pressures on time, mismatched expectations, poor communication and the emotional intensity of the act. Elective withdrawal is highly emotive, simultaneously positively and negatively influencing staff well-being. By addressing the potential mitigating factors, the overall impact on staff's mental health and well-being maybe improved and thus, subsequently, patient care.

Double umbilical artery converging into a single umbilical artery: A case report.

The normal structure and Doppler parameters of the umbilical cord are closely related to many diseases, including fetal infection, chromosomal abnormalities, hypoxia, and growth and development restrictions. We report a case of bilateral umbilical artery confluence resulting in the formation of a single umbilical artery in the free segment of the fetal umbilical cord, diagnosed at 24 weeks and 4 days gestation. The fetus was born prematurely after premature membrane rupture at 31 weeks and 3 days gestation. The Toxoplasma, Others, Rubellavirus, Cytomegalovirus, Herpesvirus test showed positive results for Toxoplasma gondii, rubella virus, and herpes simplex virus IgG antibodies. A 36-year-old woman had vaginal discharge for > 1 hour at 31 weeks + 3 days gestation and came to our obstetrics department for treatment. The pregnant woman sought treatment due to premature membrane rupture and vaginal discharge for > 1 hour. The vaginal discharge was caused by Escherichia coli. After cesarean section, the Toxoplasma, Others, Rubellavirus, Cytomegalovirus, Herpesvirus test revealed positive results for the following: T gondii, rubella virus, and herpes simplex virus IgG antibodies. The patient underwent 2 ultrasound examinations and was diagnosed with umbilical artery malformation (the free segment of the umbilical cord on the fetal side converged into a single umbilical artery), which may have been related to fetal infection. The patient received anti-inflammatory and fetal lung maturation treatment for 2 days before undergoing a cesarean section. The mother and newborn received anti-inflammatory, symptomatic, and supportive treatment and were discharged after 1 week of improvement. After 1 month, 6 months, and 1 year of follow-up after birth, the growth and development of the infant (height and weight) were significantly lower than those of her peers, and her responses to sound and light were slightly delayed. Umbilical artery malformation is extremely rare and may be related to intrauterine parasitic and viral infections. Ultrasound has the advantages of being noninvasive and cost-effective and can be used to dynamically observe umbilical artery structure. An abnormal change in umbilical artery structure found during ultrasound examination can indicate intrauterine infection risk, which provides clinical guidance for further examination of pregnant women, early diagnosis, timely targeted treatment, and fetal prognosis improvement.

Paediatric opioid poisoning in the UK: a retrospective analysis of clinical enquiries to the National Poisons Information Service

ObjectiveTo evaluate a decade of reported paediatric opioid poisoning cases in the UK.MethodsThe National Poisons Information Service (NPIS) telephone enquiries database (UK Poisons Information Database) was searched for calls regarding...

Transformer-Integrated Hybrid Convolutional Neural Network for Dose Prediction in Nasopharyngeal Carcinoma Radiotherapy.

Radiotherapy is recognized as the major treatment of nasopharyngeal carcinoma. Rapid and accurate dose prediction can improve the efficiency of the treatment planning process and the quality of radiotherapy plans. Currently, deep learning-based methods have been widely applied to dose prediction for radiotherapy treatment planning. However, it is important to note that existing models based on Convolutional Neural Networks (CNN) often overlook long-distance information. Although some studies try to use Transformer to solve the problem, it lacks the ability of CNN to process the spatial information inherent in images. Therefore, we propose a novel CNN and Transformer hybrid dose prediction model. To enhance the transmission ability of features between CNN and Transformer, we design a hierarchical dense recurrent encoder with a channel attention mechanism. Additionally, we propose a progressive decoder that preserves richer texture information through layer-wise reconstruction of high-dimensional feature maps. The proposed model also introduces object-driven skip connections, which facilitate the flow of information between the encoder and decoder. Experiments are conducted on in-house datasets, and the results show that the proposed model is superior to baseline methods in most dosimetric criteria. In addition, the image analysis metrics including PSNR, SSIM, and NRMSE demonstrate that the proposed model is consistent with ground truth and produces promising visual effects compared to other advanced methods. The proposed method could be taken as a powerful clinical guidance tool for physicists, significantly enhancing the efficiency of radiotherapy planning. The source code is available at https://github.com/CDUTJ102/THCN-Net .

Multi-omics insights into the microbiota-gut-brain axis and cognitive improvement post-bariatric surgery

BackgroundAlthough numerous studies have shown that bariatric surgery results in sustained weight loss and modifications in gut microbiota composition and cognitive function, the exact underlying mechanisms are unclear. This study aimed to investigate the effects of bariatric surgery on cognitive function through the microbiota-gut-brain axis (MGBA).MethodsDemographic data, serum samples, fecal samples, cognitive assessment scales, and resting-state functional connectivity magnetic resonance imaging (rs-fMRI) scans were obtained from 39 obese patients before and after (6 months) laparoscopic sleeve gastrectomy (LSG). PCA analysis, OPLS-DA analysis, and permutation tests were used to conduct fecal 16 S microbiota profiling, serum metabolomics, and neuroimaging analyses, and a bariatric surgery-specific rs-fMRI brain functional connectivity network was constructed. Spearman correlation analysis and Co-inertia analysis were employed to correlate significant alterations in cognitive assessment scales and resting-state functional connectivity difference networks with differential serum metabolites and 16 S microbiota data to identify key gut microbiota and serum metabolic factors.ResultsLSG significantly reduced the weight of obese patients, with reductions of up to 28%. Furthermore, cognitive assessment scale measurements revealed that LSG enhanced cognitive functions, including memory (HVLT, p = 0.000) and executive function (SCWT, p = 0.008). Also, LSG significantly altered gut microbiota composition (p = 0.001), with increased microbial abundance and diversity (p < 0.05). Moreover, serum metabolite levels were significantly altered, revealing intergroup differences in 229 metabolites mapped to 72 metabolic pathways (p < 0.05, VIP > 1). Spearman correlation analysis among cognitive assessment scales, gut microbiota species, and serum metabolites revealed correlations with 68 gut microbiota species and 138 serum metabolites (p < 0.05). Furthermore, pairwise correlations were detected between gut microbiota and serum metabolites (p < 0.05). Functional neuroimaging analysis revealed that LSG increased functional connectivity in cognitive-related frontotemporal networks (FPN, p < 0.01). Additionally, normalization of the default mode network (DMN) and salience network (SN) connectivity was observed after LSG (p < 0.001). Further canonical correlation and correlation analysis suggested that the cognitive-related brain network changes induced by LSG were associated with key gut microbiota species (Akkermansia, Blautia, Collinsella, Phascolarctobacterium, and Ruminococcus, p < 0.05) and neuroactive metabolites (Glycine, L-Serine, DL-Dopa, SM (d18:1/24:1(15Z), p < 0.05).ConclusionThese findings indicate the pathophysiological role of the microbiota-gut-brain axis in enhancing cognitive function after bariatric surgery, and the study provides a basis for clinical dietary adjustments, probiotic supplementation, and guidance for bariatric surgery, but further research is still needed.Trial registrationChinese Clinical Trial Registry, ChiCTR2100049403. Registered 02 August 2021, https://www.chictr.org.cn/.

Traumatic brain injury rehabilitation for warfighters with post-traumatic stress.

While there is extensive empirical support and clinical guidance for the treatment of mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) individually, less is known about treating the comorbid presentation of both conditions. The purpose of this review article is to provide information on the mental health treatment needs of service members (SMs) engaged in traumatic brain injury (TBI) rehabilitation. It also aims to offer a framework for an integrated treatment approach to address the cognitive and psychological health needs of warfighters. We review the prevalence and outcomes associated with comorbid TBI and PTSD and present relevant access to care considerations. Additionally, we identify an integrated approach to TBI treatment which takes psychological trauma into consideration. We introduce a trauma-informed care (TIC) model with specified diagnostic and treatment considerations for the service member and veteran (SM/V) communities. TIC is a strengths-based framework that raises the system-wide awareness of treatment facilities to the impact of psychological trauma on behavioral health. A comprehensive diagnostic approach is recommended with considerations for symptom etiology. Clinical considerations derived from available guidelines are identified to meet critical treatment needs for SM/Vs presenting for TBI treatment with a remote history of mTBI and psychological trauma or known PTSD. Clinical practice guidelines are used to inform an integrated TBI treatment model and maximize rehabilitation efforts for warfighters. Given the prevalence of comorbid TBI and PTSD among SM/Vs and its impact on outcomes, this review presents the integration of appropriate diagnostics and treatment practices, including the incorporation of CPGs into TBI rehabilitation.

Evaluating Speech-Language Pathologists' Knowledge of Functional Speech Disorders

Purpose: The purpose of this article is to offer an evaluation of speech-language pathologists' (SLPs') experiences with and knowledge of functional speech disorders. Functional speech disorders occur as a part of functional neurological disorders, a complex disorder that is often overlooked and misdiagnosed. Through an assessment of experience with and common myths about functional speech disorders among SLPs, the importance of providing education to SLPs about this patient population is discussed. Method: As a part of the presentation about functional speech disorders during the 2023 American Speech-Language-Hearing Association Health Care Summit, 122 participants were asked to anonymously respond to a series of questions that outlined their demographics, training in functional speech disorders, and experiences with this patient population. Descriptive data are presented. Results and Conclusions: Among attendees, 58% were exposed to functional speech disorders in graduate school while 75% had seen a patient with a functional speech disorder, most of whom had also diagnosed the patients' communication disorder. This study highlights the role of the SLP in identifying and managing functional speech disorders and the increased attention this patient population has received over time, as well as the work yet to be done. Functional speech disorders are a legitimate clinical entity, for which a diagnosis can be made based on positive clinical features (i.e., is not a diagnosis of exclusion). The call to action includes guidance for clinicians, educators, and academic training programs to support this patient population. See the Appendix for a plain language summary.

Perioperative immunotherapy for non-small cell lung cancer: consensus and controversy (2024 edition)

Lung cancer is the malignant tumour with the highest morbidity and mortality rate in China, among which non-small cell lung cancer (NSCLC) is the main pathological type of lung cancer, accounting for about 80% to 85%. Radial surgery is the standard treatment for early-stage NSCLC, but postoperative recurrence is an inevitable problem in clinical practice. Adding perioperative chemotherapy to surgery can only increase the 5-year overall survival rate by about 5%. There is an urgent need for better systemic treatments. In recent years, immunotherapeutic drugs, represented by PD-1/PD-L1 monoclonal antibodies, have brought breakthroughs from subsequent-line treatment to front-line treatment for NSCLC. Several Phase III studies on perioperative immunotherapy have shown that adding immunotherapy during the neoadjuvant and adjuvant treatment can significantly improve survival outcomes for patients, leading to the development of a new standard treatment for resectable NSCLC. In January 2024, the first PD-1 monoclonal antibodies (Toripalimab) were approved for perioperative treatment of NSCLC in China, starting a new era of perioperative immunotherapy. At present, there is still a lack of unified consensus on the application of perioperative immunotherapy at all levels of medical institutions. In order to privide diagnostic and treatment guidance for clinicians, promote the standardization of clinical practice for immunotherapy in resectable NSCLC, and clarify the controversial opinions regarding perioperative immunotherapy, Lung Cancer Expert Committee of the Chinese Anti-Cancer Association, Chinese Thoracic Oncology Group, Lung Cancer Expert Committee of the Chinese Medical Association Oncology Society jointly published this Consensus and Controversy to provide a guidance for the standardized management of perioperative immunotherapy for NSCLC.

A Narrative Review on Broken Heart Syndrome: A Guide for Clinicians to Understand Takotsubo Cardiomyopathy

Abstract Takotsubo cardiomyopathy (TCM) is a transient and reversible cardiomyopathy which exhibits regional wall motion abnormalities in the absence of obstructive coronary artery disease. While TCM is a rare condition (incidence &lt;1%), its diagnosis has increased since its initial description in 1990. While many cases may follow an acute physical or emotional stressor, pathophysiology is likely multifactorial including factors such as catecholamine surges and microvascular dysfunction. On initial presentation, TCM often mimics acute coronary syndrome but may be differentiated with coronary angiography. Additional laboratory testing and imaging including transthoracic echocardiography may help with diagnosis and identification of complications such as left ventricular (LV) outflow obstruction and LV thrombus. Treatment is supportive, although medications such as angiotensin-converting enzyme inhibitors and beta-blockers have shown some benefit in improving long-term outcomes. Acute complications may include arrhythmia, LV or systemic thrombus, and cardiogenic shock, but most patients do well and experience rapid recovery. TCM continues to be an active area of research as there is still much to be learned regarding its pathogenesis, diagnosis, and treatment. This review analyzes the latest research to provide insight into the presentation, pathophysiology, diagnosis, and management of TCM.

Pancreatitis in Patients with Cancer Receiving Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis.

Immune checkpoint inhibitors (ICIs) occasionally cause immune-related adverse events (AEs), which pose challenges to the continuation of treatment. Although ICIs are widely used in patients with cancer, studies reporting immune-mediated pancreatitis remain scarce. We performed a systematic review and meta-analysis to address current knowledge gaps and provide clinical guidance for ICI-associated pancreatitis and lipase elevation. We searched PubMed/Medline, Embase, and Web of Science for phase 3 randomized controlled trials (RCTs) evaluating ICIs. The incidence of any-grade and grade 3-5 pancreatitis/lipase elevation was calculated. Then, we performed a random-effect model meta-analysis to pool the odds ratios (ORs) of these outcomes using RCTs evaluating the addition of an ICI to systemic therapy to assess the effect of ICIs on pancreatic AEs. A systematic review of the treatment of ICI-related pancreatitis was also conducted. The incidence analysis included 81 articles (79 RCTs) comprising 36,871 patients. The incidence of treatment-related pancreatitis was 0.68% (any-grade) and 0.32% (grade 3-5). Meta-analysis revealed that the addition of ICI therapy significantly increased any-grade (OR 2.12, 95% confidence interval [CI] 1.45-3.11, p < 0.001) and grade 3-5 pancreatitis (OR 1.76, 95% CI 1.01-3.08, p < 0.05) with low heterogeneity among ICI subtype subgroups (any-grade: I2 = 0%, p = 0.99; grade 3-5: I2 = 0%, p = 0.63). In analysis of treatment outcome among 146 patients from 53 articles, glucocorticoids were used in 80.6% (n = 108/134) and ICIs were discontinued in 76.5% (n = 101/132; permanent discontinuation: 62.5% [n = 35/56]). The overall rate of pancreatitis appears low, but the addition of ICI therapy significantly increased the incidence of pancreatitis. These findings provide insight into the incidence and treatment of pancreatitis associated with ICIs.

Is it time for international consensus clinical guidance development for digital papillary adenocarcinoma? : reply to Joshi et al.

Is it time for international consensus clinical guidance development for digital papillary adenocarcinoma? : reply to Joshi et al.

A systematic review of the effect of sandplay therapy on social communication deficits in children with autism spectrum disorder.

To explore the efficacy of sandplay therapy in intervening social communication deficits in children with autism spectrum disorders (ASD), and whether this efficacy is influenced by the age of the children and the dosage of sandplay therapy intervention. Following the PICOS principle, randomized controlled trials (RCTs) related to sandplay therapy for social communication deficits in ASD children were retrieved from seven databases: PubMed, WOS, The Cochrane Library, Embase, CNKI, Wanfang, and VIP, from the inception of each database to November 10, 2023. Two experimenters independently conducted study screening and excluded studies with concomitant diseases, incomplete data, unextractable data, and non-randomized controlled trials. The PEDro scale was used for methodological quality assessment, and the GRADEprofiler method was employed to evaluate the quality of evidence. Stata17 software was used for meta-analysis, subgroup analysis, sensitivity analysis, and publication bias testing. The standardized mean difference (SMD) and 95% confidence interval (CI) were used as the effect statistics. A total of 12 RCTs (791 cases) were included. Sandplay therapy had a positive impact on the social communication deficits of ASD children [SMD = -1.42, 95%CI (-1.79, -1.04), P < 0.001]. Subgroup analysis revealed that sandplay therapy administered during the early school age (449 cases, SMD = -1.44, P < 0.05), for a duration of 22-28 weeks (208 cases, SMD = 1.69, P < 0.05), and with a frequency of once per week (218 cases, SMD = -1.67, P < 0.05) was most effective in improving on social communication deficits of ASD children. The quality of evidence in this study was rated as high, with good methodological quality, including 12 studies with better quality and no detection of bias risk. The study had high heterogeneity, which was attributed to the measurement tools and intervention duration through subgroup analysis, with no inconsistency found. Additionally, no downgrade factors related to imprecision, publication bias, or indirectness were identified. In conclusion, sandplay therapy is an effective measure to improve social communication deficits in children with ASD, and current evidence recommends early intervention using an individual sandplay therapy or integrated sandplay therapy intervention program once a week for 22-28 weeks, which can serve as evidence-based clinical guidance. www.crd.york.ac.uk, identifier (CRD420234821750).

Differential associations between experiences of contraceptive care and subsequent contraceptive access and preferences among family planning patients by racial and ethnic identity: Evidence from Arizona, Iowa, and Wisconsin.

While many frameworks exist for building person-centered and equitable systems of contraceptive care, evidence indicates that the reality of patients' experiences of care is often not in alignment with these ideals. Historical and current contexts of racism in the healthcare system contribute to negative perceptions and experiences of care, as well as reduced care-seeking behavior, for those who identify as Black, Indigenous, and people of color (BIPOC). Our objective in this analysis is to examine whether people's past experiences of contraceptive care are a driver of subsequent barriers to contraceptive access, and whether this relationship differs across racial and ethnic identity. We draw on panel data from five waves of surveys collected between 2018-2023 among patients ages fifteen and older seeking family planning care at sites that receive public funding for these services in Arizona, Iowa, and Wisconsin. Overall and stratified by race/ethnicity, we examine cross-sectional and longitudinal associations between patients' experiences of high-quality, person-centered contraceptive care and three contraceptive access outcomes: use of preferred contraception, satisfaction with contraceptive method, and experience of no barriers to accessing preferred contraception. We find longitudinal associations between patients experiencing higher-quality, more person-centered contraceptive care and subsequent satisfaction with contraceptive methods. Among non-Hispanic white-identifying patients, we find similar associations between shifting to higher-quality contraceptive care and use of preferred contraception, but we find no statistical relationship between experiencing higher-quality care and subsequent contraceptive outcomes for patients who identify as Black, Indigenous, or Person of Color (BIPOC). Highlighting the dissonance between clinical guidance for quality contraceptive care and patient experiences of care, and especially whether similar experiences across racial and ethnic identity lead to differential outcomes, is a crucial step toward bringing contraceptive care systems into alignment with principles of sexual and reproductive health equity.

Microarray analysis points to LMNB1 and JUN as potential target genes for predicting metastasis promotion by etoposide in colorectal cancer

Etoposide is a second-line chemotherapy agent widely used for metastatic colorectal cancer. However, we discovered that etoposide treatment induced greater motility potential in four colorectal cancer cell lines. Therefore, we used microarrays to test the mRNA of these cancer cell lines to investigate the mechanisms of etoposide promoting colorectal cancer metastasis. Differentially expressed genes (DEGs) were identified by comparing the gene expression profiles in samples from etoposide-treated cells and untreated cells in all four colorectal cancer cell lines. Next, these genes went through the Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis. Among the top 10 genes including the upregulated and downregulated, eight genes had close interaction according to the STRING database: FAS, HMMR, JUN, LMNB1, MLL3, PLK2, STAG1 and TBL1X. After etoposide treatment, the cell cycle, metabolism-related and senescence signaling pathways in the colorectal cancer cell lines were significantly downregulated, whereas necroptosis and oncogene pathways were significantly upregulated. We suggest that the differentially expressed genes LMNB1 and JUN are potential targets for predicting colorectal cancer metastasis. These results provide clinical guidance in chemotherapy, and offer direction for further research in the mechanism of colorectal cancer metastasis.