Clonal evolution dissection reveals that a high MSI2 level promotes chemoresistance in T-cell acute lymphoblastic leukemia.

ABSTRACT: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer with resistant clonal propagation in recurrence. We performed high-throughput droplet-based 5' single-cell RNA with paired T-cell receptor (TCR) sequencing of paired diagnosis-relapse (Dx_Rel) T-ALL samples to dissect the clonal diversities. Two leukemic evolutionary patterns, "clonal shift" and "clonal drift" were unveiled. Targeted single-cell DNA sequencing of paired Dx_Rel T-ALL samples further corroborated the existence of the 2 contrasting clonal evolution patterns, revealing that dynamic transcriptional variation might cause the mutationally static clones to evolve chemotherapy resistance. Analysis of commonly enriched drifted gene signatures showed expression of the RNA-binding protein MSI2 was significantly upregulated in the persistent TCR clonotypes at relapse. Integrated in vitro and in vivo functional studies suggested that MSI2 contributed to the proliferation of T-ALL and promoted chemotherapy resistance through the posttranscriptional regulation of MYC, pinpointing MSI2 as an informative biomarker and novel therapeutic target in T-ALL.

The transcriptional hub SHORT INTERNODES1 integrates hormone signals to orchestrate rice growth and development.

Plants have evolved sophisticated mechanisms to coordinate their growth and stress responses via integrating various phytohormone signaling pathways. However, the precise molecular mechanisms orchestrating integration of the phytohormone signaling pathways remain largely obscure. In this study, we found that the rice (Oryza sativa) short internodes1 (shi1) mutant exhibits typical auxin-deficient root development and gravitropic response, brassinosteroid (BR)-deficient plant architecture and grain size as well as enhanced abscisic acid (ABA)-mediated drought tolerance. Additionally, we found that the shi1 mutant is also hyposensitive to auxin and BR treatment but hypersensitive to ABA. Further, we showed that OsSHI1 promotes the biosynthesis of auxin and BR by activating the expression of OsYUCCAs and D11, meanwhile dampens ABA signaling by inducing the expression of OsNAC2, which encodes a repressor of ABA signaling. Furthermore, we demonstrated that 3 classes of transcription factors, AUXIN RESPONSE FACTOR 19 (OsARF19), LEAF AND TILLER ANGLE INCREASED CONTROLLER (LIC), and OsZIP26 and OsZIP86, directly bind to the promoter of OsSHI1 and regulate its expression in response to auxin, BR, and ABA, respectively. Collectively, our results unravel an OsSHI1-centered transcriptional regulatory hub that orchestrates the integration and self-feedback regulation of multiple phytohormone signaling pathways to coordinate plant growth and stress adaptation.

A congenital hydrocephalus-causing mutation in Trim71 induces stem cell defects via inhibiting Lsd1 mRNA translation.

Congenital hydrocephalus (CH) is a major cause of childhood morbidity. Mono-allelic mutations in Trim71, a conserved stem-cell-specific RNA-binding protein, cause CH; however, the molecular basis for pathogenesis mediated by these mutations remains unknown. Here, using mouse embryonic stem cells as a model, we reveal that the mouse R783H mutation (R796H in human) alters Trim71's mRNA substrate specificity and leads to accelerated stem-cell differentiation and neural lineage commitment. Mutant Trim71, but not wild-type Trim71, binds Lsd1 (Kdm1a) mRNA and represses its translation. Specific inhibition of this repression or a slight increase of Lsd1 in the mutant cells alleviates the defects in stem cell differentiation and neural lineage commitment. These results determine a functionally relevant target of the CH-causing Trim71 mutant that can potentially be a therapeutic target and provide molecular mechanistic insights into the pathogenesis of this disease.

CircularSTAR3D: a stack-based RNA 3D structural alignment tool for circular matching.

The functions of non-coding RNAs usually depend on their 3D structures. Therefore, comparing RNA 3D structures is critical in analyzing their functions. We noticed an interesting phenomenon that two non-coding RNAs may share similar substructures when rotating their sequence order. To the best of our knowledge, no existing RNA 3D structural alignment tools can detect this type of matching. In this article, we defined the RNA 3D structure circular matching problem and developed a software tool named CircularSTAR3D to solve this problem. CircularSTAR3D first uses the conserved stacks (consecutive base pairs with similar 3D structures) in the input RNAs to identify the circular matched internal loops and multiloops. Then it performs a local extension iteratively to obtain the whole circular matched substructures. The computational experiments conducted on a non-redundant RNA structure dataset show that circular matching is ubiquitous. Furthermore, we demonstrated the utility of CircularSTAR3D by detecting the conserved substructures missed by regular alignment tools, including structural motifs and conserved structures between riboswitches and ribozymes from different classes. We anticipate CircularSTAR3D to be a valuable supplement to the existing RNA 3D structural analysis techniques.

Analysis of PROS1 mutations and clinical characteristics in three Chinese families with hereditary protein S deficiency.

We report three heterozygous PROS1 mutations that caused type I protein S deficiency in three unrelated Chinese families. We measured protein S activity and antigen levels for all participants, screened them for mutations in the PROS1 gene. And we employed the calibrated automated thrombin generation (CAT) method to investigate thrombin generation. Numerous bioinformatics tools were utilized to analyze the conservation, pathogenicity of mutation, and spatial structure of the protein S. Phenotyping analysis indicated that all three probands exhibited simultaneous reduced levels of PS:A, TPS:Ag, and FPS:Ag. Genetic testing revealed that proband A harbored a heterozygous c.458_458delA (p.Lys153Serfs*6) mutation in exon 5, proband B carried a heterozygous c.1687C>T (p.Gln563stop) mutation in exon 14, and proband C exhibited a heterozygous c.200A>C (p.Glu67Ala) mutation in exon 2. Bioinformatic analysis predicted that the p.Lys153Serfs*6 frameshift mutation and the p.Gln563stop nonsense mutation in the protein S were classified as "disease-causing." The identification of the novel mutation p.Lys153Serfs*6 in PROS1 enriches the Human Genome Database. Our research suggests that these three mutations (p.Lys153Serfs*6, p.Gln563stop, and p.Glu67Ala) are possibly responsible for the decreased level of protein S in the three families. Furthermore, the evidence also supports the notion that individuals who are asymptomatic but have a family history of PSD can benefit from genetic analysis of the PROS1 gene.

Cut-off values of haemoglobin and clinical outcomes in incident peritoneal dialysis: the PDTAP study.

BACKGROUND: To explore the cut-off values of haemoglobin (Hb) on adverse clinical outcomes in incident peritoneal dialysis (PD) patients based on a national-level database. METHODS: The observational cohort study was from the Peritoneal Dialysis Telemedicine-assisted Platform (PDTAP) dataset. The primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and modified MACE (MACE+). The secondary outcomes were the occurrences of hospitalization, first-episode peritonitis and permanent transfer to haemodialysis (HD). RESULTS: A total of 2591 PD patients were enrolled between June 2016 and April 2019 and followed up until December 2020. Baseline and time-averaged Hb <100 g/l were associated with all-cause mortality, MACE, MACE+ and hospitalizations. After multivariable adjustments, only time-averaged Hb <100 g/l significantly predicted a higher risk for all-cause mortality {hazard ratio [HR] 1.83 [95% confidence interval (CI) 1.19-281], P = .006}, MACE [HR 1.99 (95% CI 1.16-3.40), P = .012] and MACE+ [HR 1.77 (95% CI 1.15-2.73), P = .010] in the total cohort. No associations between Hb and hospitalizations, transfer to HD and first-episode peritonitis were observed. Among patients with Hb ≥100 g/l at baseline, younger age, female, use of iron supplementation, lower values of serum albumin and renal Kt/V independently predicted the incidence of Hb <100 g/l during the follow-up. CONCLUSION: This study provided real-world evidence on the cut-off value of Hb for predicting poorer outcomes through a nation-level prospective PD cohort.

Targeted phytogenic compounds against Vibrio parahaemolyticus biofilms.

As one of main culprit of seafood-associated human illness, Vibrio parahaemolyticus can readily accumulate on biotic or abiotic surfaces to form biofilms in the seafood processing environment. Biofilm formation on various surfaces can provide a protective barrier for viable bacterial cells that are resistant to most traditional bacteriostatic measures. This underscores the necessity and urgency of developing effective alternative strategies to control V. parahaemolyticus biofilms. Plants have always provided an extensive and infinite source of biologically active compounds for "green" antibiofilm agents. This review summarizes recent developments in promising multitargeted phytogenic compounds against V. parahaemolyticus biofilms. This review provides valuable insights into potential research targets that can be pursued further to identify potent natural antibiofilm agents in the food industry.

Utilizing metagenomic next-generation sequencing for pathogen detection and diagnosis in lower respiratory tract infections in real-world clinical practice.

BACKGROUND: Infectious etiologies of lower respiratory tract infections (LRTIs) by the conventional microbiology tests (CMTs) can be challenging. Metagenomic next-generation sequencing (mNGS) has great potential in clinical use for its comprehensiveness in identifying pathogens, particularly those difficult-to-culture organisms. METHODS: We analyzed a total of 205 clinical samples from 201 patients with suspected LRTIs using mNGS in parallel with CMTs. mNGS results were used to guide treatment adjustments for patients who had negative CMT results. The efficacy of treatment was subsequently evaluated in these patients. RESULTS: mNGS-detected microorganisms in 91.7% (188/205) of the clinical samples, whereas CMTs demonstrated a lower detection rate, identifying microorganisms in only 37.6% (77/205) of samples. Compared to CMT results, mNGS exhibited a detection sensitivity of 93.5% and 95.4% in all 205 clinical samples and 180 bronchoalveolar lavage fluid (BALF) samples, respectively. A total of 114 patients (114/201; 56.7%) showed negative CMT results, among which 92 received treatment adjustments guided by their positive mNGS results. Notably, 67.4% (62/92) of patients demonstrated effective treatment, while 25% (23/92) experienced a stabilized condition. Subgroup analysis of cancer patients revealed that 41.9% (13/31) exhibited an effective response to treatment, and 35.5% (11/31) maintained a stable condition following medication adjustments guided by mNGS. CONCLUSION: mNGS demonstrated great potential in identifying microorganisms of clinical significance in LRTIs. The rapid turnaround time and reduced susceptibility to the impact of antimicrobial administration make mNGS a valuable supplementary tool for diagnosis and treatment decision-making for suspected LRTIs in clinical practice.

Excessive dietary iron exposure increases the susceptibility of largemouth bass (Micropterus salmoides) to Aeromonas hydrophila by interfering with immune response, oxidative stress, and intestinal homeostasis.

Iron is an essential cofactor in the fundamental metabolic pathways of organisms. Moderate iron intake can enhance animal growth performance, while iron overload increases the risk of pathogen infection. Although the impact of iron on the pathogen-host relationship has been confirmed in higher vertebrates, research in fish is extremely limited. The effects and mechanisms of different levels of iron exposure on the infection of Aeromonas hydrophila in largemouth bass (Micropterus salmoides) remain unclear. In this study, experimental diets were prepared by adding 0, 800, 1600, and 3200 mg/kg of FeSO4∙7H2O to the basal feed, and the impact of a 56-day feeding period on the mortality rate of largemouth bass infected with A. hydrophila was analyzed. Additionally, the relationships between mortality rate and tissue iron content, immune regulation, oxidative stress, iron homeostasis, gut microbiota, and tissue morphology were investigated. The results showed that the survival rate of largemouth bass infected with A. hydrophila decreased with increasing iron exposure levels. Excessive dietary iron intake significantly increased iron deposition in the tissues of largemouth bass, reduced the expression and activity of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, increased the content of lipid peroxidation product malondialdehyde, and thereby induced oxidative stress. Excessive iron supplementation could influence the immune response of largemouth bass by upregulating the expression of pro-inflammatory cytokines in the intestine and liver, while downregulating the expression of anti-inflammatory cytokines. Additionally, excessive iron intake could also affect iron metabolism by inducing the expression of hepcidin, disrupt intestinal homeostasis by interfering with the composition and function of the gut microbiota, and induce damage in the intestinal and hepatic tissues. These research findings provide a partial theoretical basis for deciphering the molecular mechanisms underlying the influence of excessive iron exposure on the susceptibility of largemouth bass to pathogenic bacteria.

Haplotype-specific MAPK3 expression in 16p11.2 deletion contributes to variable neurodevelopment.

Recurrent proximal 16p11.2 deletion (16p11.2del) is a risk factor for diverse neurodevelopmental disorders with incomplete penetrance and variable expressivity. Although investigation with human induced pluripotent stem cell models has confirmed disruption of neuronal development in 16p11.2del neuronal cells, which genes are responsible for abnormal cellular phenotypes and what determines the penetrance of neurodevelopmental abnormalities are unknown. We performed haplotype phasing of the 16p11.2 region in a 16p11.2del neurodevelopmental disorders cohort and generated human induced pluripotent stem cells for two 16p11.2del families with distinct residual haplotypes and variable neurodevelopmental disorder phenotypes. Using transcriptomic profiles and cellular phenotypes of the human induced pluripotent stem cell-differentiated cortex neuronal cells, we revealed MAPK3 to be a contributor to dysfunction in multiple pathways related to early neuronal development, with altered soma and electrophysiological properties in mature neuronal cells. Notably, MAPK3 expression in 16p11.2del neuronal cells varied on the basis of a 132 kb 58 single nucleotide polymorphism (SNP) residual haplotype, with the version composed entirely of minor alleles associated with reduced MAPK3 expression. Ten SNPs on the residual haplotype were mapped to enhancers of MAPK3. We functionally validated six of these SNPs by luciferase assay, implicating them in the residual haplotype-specific differences in MAPK3 expression via cis-regulation. Finally, the analysis of three different cohorts of 16p11.2del subjects showed that this minor residual haplotype is associated with neurodevelopmental disorder phenotypes in 16p11.2del carriers.

Fecal calprotectin: A novel predictor of ulcerated esophageal injury after atrial fibrillation catheter ablation.

BACKGROUND: Atrial esophageal fistula (AEF) is a lethal complication that can occur post atrial fibrillation (AF) ablation. Esophageal injury (EI) is likely to be the initial lesion leading to AEF. Endoscopic examination is the gold standard for a diagnosis of EI but extensive endoscopic screening is invasive and costly. This study was conducted to determine whether fecal calprotectin (Fcal), a marker of inflammation throughout the intestinal tract, may be associated with the existence of esophageal injury. METHODS: This diagnostic study was conducted in a cohort of 166 patients with symptomatic AF undergoing radiofrequency catheter ablation from May 2020 to June 2021. Fcal tests were performed 1-7 days after ablation. All patients underwent endoscopic ultrasonography 1 or 2 days after ablation. RESULTS: The levels of Fcal were significantly different between the EI and non-EI groups (404.9 µg/g (IQR 129.6-723.6) vs. 40.4 µg/g (IQR 15.0-246.2), p < .001). Analysis of ROC curves revealed that a Fcal level of 125 µg/g might be the optimal cut-off value for a diagnosis of EI, giving a 78.8% sensitivity and a 65.4% specificity. The negative predictive value of Fcal was 100% for ulcerated EI. CONCLUSIONS: The level of Fcal is associated with EI post AF catheter ablation. 125 µg/g might be the optimal cut-off value for a diagnosis of EI. Negative Fcal could predict the absence of ulcerated EI, which could be considered a precursor to AEF.

Gastroesophageal reflux disease and atrial fibrillation: a bidirectional Mendelian randomization study.

Background: In observational studies, gastroesophageal reflux disease (GERD) is linked to atrial fibrillation (AF). It is uncertain whether the relationship is due to GERD-induced AF or GERD caused by AF, or confusion with factors related to GERD and AF such as obesity and sleep-disordered breathing. We applied bidirectional Mendelian randomization (MR), in which genetic variations are used as instrumental variables to resolve confounding and reverse causation issues, to determine the causal effect between GERD and AF. Methods: Using summary data from the GERD and AF genome-wide association study (GWAS), a bidirectional MR was performed to estimate the causative impact of GERD on AF risk and AF on GERD risk. The GWAS of GERD meta-analysis comprised 78707 cases and 288734 controls. GWAS summary data for AF, including 45766 AF patients and 191924 controls, were used to genetically predicted AF. The inverse variance weighted (IVW) method was the major MR approach used. MR-PRESSO was implemented to detect heterogeneity and correct the effect of outliers. Weighted median and MR-Egger regression were applied to test heterogeneity and pleiotropy. Results: The genetic instruments of GERD related to increasing the risk of AF, with an OR of 1.339 (95% CI: 1.242-1.444, p < 0.001). However, after removing the outlier 8 SNPs, genetically predicted AF was not associated with an elevated risk of GERD (p = 0.351). Conclusions: Our result suggested that GERD had a causal effect on AF. However, no evidence was identified that AF elevated the risk of GERD.

Pre- and postpartum fear of childbirth and its predictors among rural women in China.

BACKGROUND: Fear of childbirth (FOC) can influence both maternal and child health. Research on FOC in China is scarce, especially on rural women. This study aimed to assess pre- and postpartum FOC and its predictors among Chinese rural women. METHODS: This was a prospective correlation study. A total of 569 women completed the prenatal questionnaire in the third trimester, and 477 of them completed the postpartum questionnaire within three days after childbirth. Maternal socio-demographic information, clinical information, childbirth self-efficacy and prenatal and postpartum FOC were investigated. FOC was evaluated using the Wijma Childbirth Expectancy/ Experience Questionnaire (WDEQ). Descriptive, bivariate, multivariate linear regression analysis, univariate and multivariate logistic regression analyses were performed. RESULTS: The mean pre- and postpartum FOC scores were 64.5 (standard deviation: 25.1) and 64.3 (standard deviation: 23.9), respectively, with 20.8% of women reporting severe fear before childbirth and 18.2% after childbirth. Multivariate linear regression analysis revealed predictors for higher levels of prenatal FOC including higher education level, nullipara, higher monthly household income, lower family support, and lower childbirth self-efficacy (p < 0.05) and the predictors for higher levels of postpartum FOC included unemployed status, lower childbirth self-efficacy, and higher prenatal FOC (p < 0.05). Multivariate logistic regression showed that higher childbirth self-efficacy reduced the likelihood of severe prenatal FOC (OR: 0.99, p < 0.001), while severe prenatal FOC increased the likelihood of severe postpartum FOC (OR: 3.57, p < 0.001). CONCLUSION: The rural women have high levels of FOC before and after childbirth, with approximately 20% experiencing severe FOC during both periods. Higher education level, nullipara, higher monthly household income, lower family support, and lower childbirth self-efficacy are predictors of heightened prenatal FOC. Unemployed status, lower childbirth self-efficacy, and higher prenatal FOC are predictors of heightened postpartum FOC. Notably, enhancing childbirth self-efficacy emerges as crucial in mitigating severe prenatal FOC, while severe prenatal FOC significantly increases the likelihood of severe postpartum FOC. The development of targeted intervention strategies for the above factors can help reduce women's FOC level and improve their overall pregnancy and childbirth experience.

Current status of electronic health literacy among pregnant women with gestational diabetes mellitus and their perceptions of online health information: a mixed-methods study.

BACKGROUND: Women diagnosed with gestational diabetes mellitus often rely on internet-based health information for managing their condition. This study aims to investigate the present state of electronic health literacy among women with gestational diabetes mellitus, analyze the influencing factors, and explore their experiences regarding accessing, comprehending, evaluating, and applying online health information pertinent to gestational diabetes mellitus. METHODS: A sequential explanatory mixed methods research design was adopted in this study. Initially, 235 women with gestational diabetes mellitus participated in a cross-sectional survey. The research tools included general information and the Chinese version of the electronic Health Literacy Scale (eHEALS). Descriptive analyses were conducted to describe the characteristics of the sample, and multiple linear regression analyses were used to explore the factors influencing electronic health literacy among women with gestational diabetes mellitus. Secondly, 11 women with gestational diabetes mellitus joined semi-structured in-depth interviews to obtain their perceptions about online health information. The data were analyzed using inductive content analysis to develop themes. RESULTS: The median score of eHEALS in the Chinese version among 235 women diagnosed with gestational diabetes mellitus was 29 (interquartile range [IQR], 26 to 32). Factors influencing electronic health literacy among these women included accessing health information from medical professionals (ß = 0.137, p = 0.029) and utilizing health information from applications (ß = 0.159, p = 0.013). From the qualitative phase of the study, four thematic categories emerged: reasons and basis for accessing health information from the Internet; address barriers to accessing and applying online health information; desires for a higher level of online health information services; outcomes of accessing and applying online health information. CONCLUSION: The electronic health literacy of women diagnosed with gestational diabetes mellitus remains suboptimal and warrants improvement. The sources of access to health information affect electronic health literacy in women with gestational diabetes mellitus. Moreover, women facing gestational diabetes encounter numerous impediments when attempting to access health-related information online, underscoring the necessity for enhanced online health information services to meet their needs.

Effect of Bright Light Therapy on Perinatal Depression: A Systematic Review and Meta-Analysis: Effet de la luminothérapie sur la dépression périnatale: une revue systématique et une méta-analyse.

OBJECTIVE: This study represents the inaugural attempt to systematically review and analyse the efficacy of bright light therapy on depression among women experiencing major depressive disorder or depressive symptoms during the perinatal period, encompassing its efficacy on depression scores, remission rates, and response rates. METHODS: We searched 10 databases for randomized controlled trials examining bright light therapy's efficacy on perinatal depression up to January 2024. Data extraction was performed independently by 2 investigators. The Cochrane Handbook guidelines appraised the study quality, and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach assessed evidence certainty. RESULTS: We incorporated 6 studies, encompassing 151 participants. When contrasted with dim light therapy, bright light therapy did not significantly alter depression scores (standard mean difference = -0.29, 95% confidence interval [CI], -0.62 to 0.04, P = 0.08, I² = 34%) or response rates (risk ratio [RR] = 1.56, 95% CI, 0.98 to 2.49, P = 0.06, I² = 0%) in women experiencing perinatal depression. Conversely, bright light therapy was associated with a substantial increase in remission rates (RR = 2.63, 95% CI, 1.29 to 5.38, P = 0.008, I² = 2%). CONCLUSION: Bright light therapy did not show efficacy in treating perinatal depression in terms of depression scores and response rates. However, regarding the remission rate, bright light did show efficacy compared to control conditions. Due to the limited sample size in the included studies, type II err or may occur. To obtain more conclusive evidence, future studies must employ larger sample sizes.

Expression patterns and pathogenesis of Semaphorin class 4 subfamily proteins in solid tumors.

Semaphorins are originally described as regulators of nervous system development. Besides, members of the semaphorin family play important roles in the growth, metastasis, and angiogenesis of solid tumors. In contrast to the other semaphorin subclasses, semaphorin class 4 has both membrane-bound and active soluble forms. Soluble class 4 semaphorins in body fluids (blood and saliva) may serve as potential biomarkers for early diagnosis and prognosis prediction of specific cancers. The class 4 semaphorins also transduce signal in cancer cells in a cell membrane-bound form, thereby regulating cancer progression. In solid tumors, class 4 semaphorins can act as ligands in active soluble forms, regulating cancer progression via autocrine and paracrine to activate signal transduction in cancer cells or endothelial cells in the tumor microenvironment. Targeting class 4 semaphorins may be a novel strategy for specific cancer therapy. However, the expression of class 4 semaphorins in solid tumors and the responsive pathogenesis are still controversial. Therefore, this review summarizes the specific expression regulation of class 4 semaphorin members in different types of solid tumors and the mechanisms involved in cancer progression.

Obinutuzumab in untreated primary membranous nephropathy: An observational case series.

BACKGROUND: As an initial treatment for primary membranous nephropathy (PMN), there remains a significant proportion of patients for whom rituximab is not fully effective. Here, we aimed to assess the effectiveness and safety of obinutuzumab as initial treatment in patients with PMN. METHODS: In this observational case series, patients diagnosed with PMN and treated with obinutuzumab as initial treatment were included. Treatment response was assessed by 24-h urine total protein (24 h UTP) and serum albumin, and immunologic remission was assessed by phospholipase A2 receptor (PLA2R) antibodies. RESULTS: Twelve patients with PMN receiving obinutuzumab as initial treatment were included. Over 6 months, a statistically significant reduction in 24 h UTP levels (p = 0.003) and an increase in serum albumin levels were observed (p < 0.001). By the 6-month follow-up, two patients (16.7%) achieved complete remission, eight (66.6%) reached partial remission, and two (16.7%) showed no remission. Immunological remission was observed in 44.4% of evaluable patients (n = 9) after 3 months, increasing to 100% (6/6) at 6 months. Except for cases 1, 2, and 3, the total B cell counts in the remaining patients fell to less than 5 cells/µL before the administration of the second dose of obinutuzumab, including seven patients with counts as low as 0 cells/µL. Mild to moderate treatment-related adverse events (TRAEs) were reported in 58.3% (7/12) of the patients. No serious TRAEs were reported. CONCLUSIONS: Obinutuzumab demonstrates promising potential as an initial treatment for PMN, with good effectiveness and a manageable safety profile. Further large-scale prospective studies are needed to confirm these findings.

Development, validation and reliability testing of the hospice care environment scale.

BACKGROUND: WHO stated the environment is an important factor affecting the development of hospice care. The environment is the sum of factors affecting behavior besides the individual factors. Currently, a scale to comprehensively assess the hospice environment of nurse is still lacking. This study aimed to develop an instrument to investigate the environmental factors affecting hospice care of nurses. METHODS: Literature review and a semi-structured interview were conducted to form the items pool of the Hospice Care Environment Scale. Two rounds of Delphi expert consultation were conducted by 16 experts to revise the scale dimensions and entries to form the Hospice Care Environment Scale. A psychometric evaluation was then performed among 530 oncology nurses in a large tertiary oncology hospital in Hubei Province. The 500 valid questionnaires were randomly divided into two groups in a 1:1 ratio, sample 1 (n1 = 250) for item screening and sample 2 (n2 = 250) for quality evaluation of the resulting scale. Item analysis, reliability analysis, validity analysis and acceptability analysis were performed. RESULT: The Hospice Care Environment Scale consists of two dimensions and 13 entries. The Cronbach's α coefficient of the Hospice Care Environment Scale was 0.970, and the Cronbach's α coefficient of the two dimensions were 0.952 and 0.969, respectively, with the Item-content validity index and average Scale- content validity index of the scale was both 1.000. The validation factor analysis showed the standardized path coefficients of each item were basically above 0.5, and the factor structure model was stable and suitable. The average completion time of the scale was about 3 min, which had good feasibility. CONCLUSION: The Hospice Care Environment Scale to assess the environment of hospice care services, has good content and construct validity and reliability. This scale can provide guidance to evaluate the hospice care environment.

Behaviors and influencing factors of Chinese oncology nurses towards hospice care: a cross-sectional study based on social cognitive theory in 2022.

BACKGROUND: Although there is growing demand for hospice care in China due to its aging population and increasing cancer rates, the sector remains slow to expand. Oncology nurses are the primary providers of hospice care, but little is known about their behaviors towards hospice care and related factors. METHODS: This cross-sectional study conveniently sampled 933 oncology nurses from six grade A tertiary hospitals in Hubei Province between January to March 2022. The questionnaire was composed of seven parts: general information (including sociodemographic and work-related information), hospice care behaviors, hospice care knowledge, hospice care attitudes, hospice care self-efficacy, hospice care outcome expectancy, and hospice care environment. Data were analyzed using descriptive analysis, independent sample t-tests, one-way ANOVA, Pearson's correlation, multiple linear regression, random forest regression, and BP neural network model analysis. RESULTS: A total of 852 questionnaires were valid. The mean score of hospice care behaviors was 50.47 ± 10.56, with a mean item score of 3.61 ± 0.75. The three highest scoring behaviors were "pain assessment of patients (4.21 ± 0.91)", "satisfying the physical and mental needs of dying patients (4.04 ± 0.92)", and "creating good relationships between the medical staff and family members (4.02 ± 0.87)". The two lowest-scoring behaviors were "proactively recommending medical institutions for hospice care to terminally ill patients and their families (2.55 ± 1.10)" and "proactively talking to patients and families about death-related topics for patients who are critically ill and cannot be reversed (2.87 ± 1.03)." Multiple linear regression, random forest regression, and BP neural network models all showed that the frequency of sharing hospice care experiences with colleagues, hospice care attitudes, hospice care self-efficacy, and hospice care environments were positively associated with hospice care behaviors. CONCLUSIONS: The frequency of hospice care behaviors among Chinese oncology nurses is generally at a moderate to high level. The results provide a basis for promoting hospice care behaviors among oncology nurses in order to improve the quality of life for terminally ill cancer patients.

Comparative efficacy of telehealth interventions on promoting cancer screening: A network meta-analysis of randomized controlled trials.

BACKGROUND: Cancer screening is a pivotal method for reducing mortality from disease, but the screening coverage is still lower than expected. Telehealth interventions demonstrated significant benefits in cancer care, yet there is currently no consensus on their impact on facilitating cancer screening or on the most effective remote technology. DESIGN: A network meta-analysis was conducted to detect the impact of telehealth interventions on cancer screening and to identify the most effective teletechnologies. METHODS: Six English databases were searched from inception until July 2023 to yield relevant randomized controlled trials (RCTs). Two individual authors completed the literature selection, data extraction, and methodological evaluations using the Cochrane Risk of Bias tool. Traditional pairwise analysis and network meta-analysis were performed to identify the overall effects and compare different teletechnologies. RESULTS: Thirty-four eligible RCTs involving 131,644 participants were enrolled. Overall, telehealth interventions showed statistically significant effects on the improvement of cancer screening. Subgroup analyses revealed that telehealth interventions were most effective for breast and cervical cancer screening, and rural populations also experienced benefits, but there was no improvement in screening for older adults. The network meta-analysis indicated that mobile applications, video plus telephone, and text message plus telephone were associated with more obvious improvements in screening than other teletechnologies. CONCLUSION: Our study identified that telehealth interventions were effective for the completion of cancer screening and clarified the exact impact of telehealth on different cancer types, ages, and rural populations. Mobile applications, video plus telephone, and text message plus telephone are the three forms of teletechnologies most likely to improve cancer screening. More well-designed RCTs involving direct comparisons of different teletechnologies are needed in the future. CLINICAL RELEVANCE: Telehealth interventions should be encouraged to facilitate cancer screening, and the selection of the optimal teletechnology based on the characteristics of the population is also necessary.