bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of patients with R/R B-cell NHL and limited (<5 sites) pre-CART disease bridged with or without radiotherapy
Authors: Saifi Omran , Breen William G. , Lester Scott C. , Rule William G. , Stish Bradley J. , Rosenthal Allison , Munoz Javier , Lin Yi , Bansal Radhika , Hathcock Matthew A. , Johnston Patrick B. , Ansell Stephen M. , Paludo Jonas , Khurana Arushi , Villasboas Jose C. , Wang Yucai , Iqbal Madiha , Alhaj Moustafa Muhamad , Murthy Hemant S. , Ayala Ernesto , Kharfan-Dabaja Mohamed A. , Hoppe Bradford S. , Peterson Jennifer L.
Published: July 2024

Unirradiated patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) who undergo anti-CD19 chimeric antigen receptor T-cell therapy (CART) have a predominant localized pattern of relapse, the significance of which is heightened in individuals with limited/localized disease before CART. This study reports on the outcomes of patients with R/R NHL and limited (<5 involved sites) disease bridged with or without radiotherapy. A multicenter retrospective review of 150 patients with R/R NHL who received CART with <5 disease sites before leukapheresis was performed. Bridging treatment, if any, was administered between leukapheresis and CART infusion. Study end points included relapse-free survival (RFS), event-free survival (EFS), and overall survival. Before CART infusion, 48 patients (32%) received bridging radiotherapy (BRT), and 102 (68%) did not. The median follow-up was 21 months. After CART infusion, BRT patients had higher objective response (92% vs 78%; P = .046) and sustained complete response rates (54% vs 33%; P = .015). Local relapse in sites present before CART was lower in the BRT group (21% vs 46%; P = .003). BRT patients had improved 2-year RFS (53% vs 44%; P = .023) and 2-year EFS (37% vs 34%; P = .039) compared with patients who did not receive BRT. The impact of BRT was most prominent in patients who had ≤2 pre-CART involved disease sites, with 2-year RFS of 62% in patients who received BRT compared with 42% in those who did not (P = .002). BRT before CART for patients with limited (<5 involved disease sites) R/R NHL improves response rate, local control, RFS, and EFS without causing significant toxicities.
Some virulence genes are associated with antibiotic susceptibility in Enterobacter cloacae complex
Authors: Mosaffa Fatemeh , Saffari Fereshteh , Veisi Mahin , Tadjrobehkar Omid
Published: July 2024

Background

Enterobacter cloacae complex (ECC) including different species are isolated from different human clinical samples. ECC is armed by many different virulence genes (VGs) and they were also classified among ESKAPE group by WHO recently. The present study was designed to find probable association between VGs and antibiotic susceptibility in different ECC species.

Methods

Forty-five Enterobacter isolates that were harvested from different clinical samples were classified in four different species. Seven VGs were screened by PCR technique and antibiotic susceptibility assessment was performed by disk-diffusion assay.

Result

Four Enterobacter species; Enterobacter cloacae (33.3%), Enterobacter hormaechei (55.6%), Enterobacter kobei (6.7%) and Enterobacter roggenkampii (4.4%) were detected. Minimum antibiotic resistance was against carbapenem agents and amikacin even in MDR isolates. 33.3% and 13.3% of isolates were MDR and XDR respectively. The rpoS (97.8%) and csgD (11.1%) showed maximum and minimum frequency respectively. Blood sample isolated were highly virulent but less resistant in comparison to the other sample isolates. The csgA, csgD and iutA genes were associated with cefepime sensitivity.

Conclusion

The fepA showed a predictory role for differentiating of E. hormaechei from other species. More evolved iron acquisition system in E. hormaechei was hypothesized. The fepA gene introduced as a suitable target for designing novel anti-virulence/antibiotic agents against E. hormaechei. Complementary studies on other VGs and ARGs and with bigger study population is recommended.
Comprehensive analysis of PHF5A as a potential prognostic biomarker and therapeutic target across cancers and in hepatocellular carcinoma
Authors: Cheng Qianqian , Ji Wenbin , Lv Zhenyu , Wang Wei , Xu Zhaiyue , Chen Shaohua , Zhang Wenting , Shao Yu , Liu Jing , Yang Yan
Published: July 2024

Objective

Cancer is a predominant cause of death globally. PHD-finger domain protein 5 A (PHF5A) has been reported to participate in various cancers; however, there has been no pan-cancer analysis of PHF5A. This study aims to present a novel prognostic biomarker and therapeutic target for cancer treatment.

Methods

This study explored PHF5A expression and its impact on prognosis, tumor mutation burden (TMB), microsatellite instability (MSI), functional status and tumor immunity across cancers using various public databases, and validated PHF5A expression and its correlation with survival, immune evasion, angiogenesis, and treatment response in hepatocellular carcinoma (HCC) using bioinformatics tools, qRT-PCR and immunohistochemistry (IHC).

Results

PHF5A was differentially expressed between tumor and corresponding normal tissues and was correlated with prognosis in diverse cancers. Its expression was also associated with TMB, MSI, functional status, tumor microenvironment, immune infiltration, immune checkpoint genes and tumor immune dysfunction and exclusion (TIDE) score in diverse malignancies. In HCC, PHF5A was confirmed to be upregulated by qRT-PCR and IHC, and elevated PHF5A expression may promote immune evasion and angiogenesis in HCC. Additionally, multiple canonical pathways were revealed to be involved in the biological activity of PHF5A in HCC. Moreover, immunotherapy and transcatheter arterial chemoembolization (TACE) worked better in the low PHF5A expression group, while sorafenib, chemotherapy and AKT inhibitor were more effective in the high expression group.

Conclusions

This study provides a comprehensive understanding of the biological function of PHF5A in the carcinogenesis and progression of various cancers. PHF5A could serve as a tumor biomarker related to prognosis across cancers, especially HCC, and shed new light on the development of novel therapeutic targets.
Phenotypic characteristics and rehabilitation effect of children with regressive autism spectrum disorder: a prospective cohort study
Authors: Hu Chaoqun , Yang Ting , Chen Jie , Dai Ying , Wei Hua , Wu Qionghui , Chen Hongyu , Long Dan , Feng Yuru , Wei Qiuhong , Zhang Qian , Chen Li , Li Tingyu
Published: July 2024

Background

In this prospective cohort study, we determined the phenotypic characteristics of children with regressive autism spectrum disorder (ASD) and explored the effects of rehabilitation.

Methods

We recruited 370 children with ASD aged 1.5–7 years. Based on the Regression Supplement Form, the children were assigned to two groups: regressive and non-regressive. The core symptoms and neurodevelopmental levels of ASD were assessed before and after 1 year of behavioral intervention using the Autism Diagnostic Observation Schedule (ADOS), Social Response Scale (SRS), Children Autism Rating Scale (CARS), and Gesell Developmental Scale (GDS).

Results

Among the 370 children with ASD, 28.38% (105/370) experienced regression. Regression was primarily observed in social communication and language skills. Children with regressive ASD exhibited higher SRS and CARS scores and lower GDS scores than those with non-regressive ASD. After 1 year of behavioral intervention, the symptom scale scores significantly decreased for all children with ASD; however, a lesser degree of improvement was observed in children with regressive ASD than in those with non-regressive ASD. In addition, the symptom scores of children with regressive ASD below 4 years old significantly decreased, whereas the scores of those over 4 years old did not significantly improve. Children with regressive ASD showed higher core symptom scores and lower neurodevelopmental levels. Nevertheless, after behavioral intervention, some symptoms exhibited significant improvements in children with regressive ASD under 4 years of age.

Conclusion

Early intervention should be considered for children with ASD, particularly for those with regressive ASD.
“We chose PrEP because I wanted to be sure that this child my wife was going to conceive was indeed mine.” Factors influencing the choice of safer conception methods and experiences with its use: a qualitative study among HIV sero-discordant couples in Zimbabwe
Authors: Brown Joelle M. , Musara Petina , Gitome Serah , Chitukuta Miria , Mataveke Bismark , Chirenda Thandiwe , Mgodi Nyaradzo , Mutero Prisca , Matubu Allen , Chareka Gift , Chasakara Charles , Murombedzi Caroline , Makurumure Tinei , Hughes Carolyn Smith , Bukusi Elizabeth , Cohen Craig R. , Shiboski Stephen , Darbes Lynae , Rutherford George W. , Chirenje Z. Michael , Mhlanga Felix
Published: July 2024

Background

Safer conception services are needed to minimize HIV transmission among HIV sero-discordant couples desiring pregnancy. Few studies have evaluated the choices couples make when they are offered multiple safer conception methods or real-world method acceptability. This paper addresses an important knowledge gap regarding factors that influence the choice of safer conception methods, couples' actual experiences using safer conception methods, and why some couples switch safer conception methods.

Methods

Between February and June 2019, we conducted semi-structured in-depth interviews among 14 men and 17 women, representing 17 couples who exited the SAFER study—a pilot safer conception study for HIV sero-discordant couples in Zimbabwe that offered couples a choice of ART with monthly viral load monitoring (ART/VL), oral PrEP, vaginal insemination, and semen washing. All couples in SAFER had used at least two safer conception methods.

Results

We found that safer conception method choice often centered around a desire for intimacy, condomless sex, and certainty in the conception process, particularly for men. Method-related attributes such as familiarity, perceived ease of use, side effects, and perceived level of effectiveness in preventing HIV and achieving pregnancy influenced method choice, switching, and satisfaction. Concerns were expressed about each safer conception method and couples were willing to try different methods until they found method(s) that worked for them. The majority of participants reported having positive experiences using safer conception, especially those using ART/VL + PrEP, citing that they were able to attempt pregnancy for the first time with peace of mind and experienced joy and satisfaction from being able to achieve pregnancy safely.

Conclusions

The differences in method preferences and experiences voiced by participants in this study and in other studies from the region point to the importance of having a variety of safer conception options in the service delivery package and addressing concerns about paternity, intimacy, and method-related attributes to enable HIV sero-discordant couples to safely achieve their reproductive goals.
Perceptions of safety during everyday travel shaping older adults’ mobility in Bengaluru, India
Authors: Patil Divya Sussana , Bailey Ajay , George Sobin , Ashok Lena , Ettema Dick
Published: July 2024

Background

In the context of socially sustainable urban development, comfortable, safe, and accessible public transport is crucial to motivating people to travel more sustainably. Using the framework given by Masoumi and Fastenmeier (2016) to examine the concepts of safety and security, we explore how perceptions of safety about different transport modes shaped the mobility of older adults in Bengaluru, India.

Methods

In-depth telephonic interviews were conducted with 60 adults, aged 50 years and over, residing in urban Bengaluru, using a semi-structured in-depth interview guide to explore the perceptions of safety in different transport modes. Observations were conducted prior to the COVID-19 pandemic. Applying thematic analysis, we present how the perceptions of safety during their everyday travel shaped their mobility.

Results

According to our research, older adults’ perception of safety during their everyday travel is shaped by past negative experiences with accidents, pickpocketing, theft of mobile phones, and chain snatching. In addition, the Covid-19 pandemic exacerbated the already existing inequalities, further limiting older adults’ mobility to carry out regular activities such as buying groceries, socialising, making a hospital visit, or going to work due to the fear of getting infected.

Conclusion

Our findings indicate that the use of public transport needs to be encouraged among older adults by enhancing necessary safety features following the age-friendly cities framework. Furthermore, it can help policymakers develop transport polices, which suit the mobility needs of older adults.
Association between psychological stress and mandibular condyle structure: an analytical cross-sectional study
Authors: Ghasemzadeh Fatemeh , Mortazavi Nazanin , Mallahi Mysa , Gharib Mohammad Hadi , Behnampour Naser , Badeleh Mohammad Taghi , Asgari Negar
Published: July 2024

Objective

The potential influence of psychological factors on temporomandibular joint disorders has been clinically documented. To date, all research examining the impact of psychological stress on the temporomandibular joint has been conducted on animals. This study aims to explore the relationship between psychological stress and the structure of the human mandibular condyle.

Methods

This cross-sectional study was performed on individuals, who were referred to the radiology division of 5th Azar Hospital for head and neck Computed Tomography (CT) scans. All participants completed a perceived stress questionnaire to determine their level of stress. Bone density and cortical bone thickness were measured as indicators of mandibular condyle structure. Based on multi-slice CT scan data, bone density was calculated in the anterior, middle, and posterior mandibular condyle. The cortical bone thickness was also measured at the anterior and posterior mandibular condyle. Statistical analysis was performed in R 4.0.2 software.

Results

Seventy individuals, aged 18–59 years, participated in this study. The CT scans revealed a decrease in Hounsfield units (HU) and bone mineral density (BMD) in both the anterior and posterior regions. However, in the high-stress group, there was no significant difference in cortical bone thickness in the anterior and posterior regions of the condyle, nor in HU and BMD in the middle region of the condyle. An inverse correlation was observed between BMD and perceived stress in the anterior, middle, and posterior regions of both condyles.

Conclusion

The current findings indicate that recent psychological stress is associated with changes in the structure of the condyle.
Exploring the therapeutic potential of Thai medicinal plants: in vitro screening and in silico docking of phytoconstituents for novel anti-SARS-CoV-2 agents
Authors: Maikhunthod Bussayarat , Chaipayang Sukanya , Jittmittraphap Akanitt , Thippornchai Narin , Boonchuen Pakpoom , Tittabutr Panlada , Eumkeb Griangsak , Sabuakham Sahachai , Rungrotmongkol Thanyada , Mahalapbutr Panupong , Leaungwutiwong Pornsawan , Teaumroong Neung , Tanthanuch Waraporn
Published: July 2024

Background

The high virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVID-19), has triggered global health and economic concerns. The absence of specific antiviral treatments and the side effects of repurposed drugs present persistent challenges. This study explored a promising antiviral herbal extract against SARS-CoV-2 from selected Thai medicinal plants based on in vitro efficacy and evaluated its antiviral lead compounds by molecular docking.

Methods

Twenty-two different ethanolic-aqueous crude extracts (CEs) were rapidly screened for their potential activity against porcine epidemic diarrhea virus (PEDV) as a surrogate using a plaque reduction assay. Extracts achieving ≥ 70% anti-PEDV efficacy proceeded to the anti-SARS-CoV-2 activity test using a 50% tissue culture infectious dose method in Vero E6 cells. Molnupiravir and extract-free media served as positive and negative controls, respectively. Potent CEs underwent water/ethyl acetate fractionation to enhance antiviral efficacy, and the fractions were tested for anti-SARS-CoV-2 performance. The fraction with the highest antiviral potency was identified using liquid chromatography–high-resolution mass spectrometry (LC–HRMS). Molecular docking analyses of these compounds against the main protease (Mpro) of SARS-CoV-2 (6LU7) were performed to identify antiviral lead molecules. The top three hits were further evaluated for their conformational stability in the docked complex using molecular dynamics (MD) simulation.

Results

The water fraction of mulberry (Morus alba Linn.) leaf CE (WF-MLCE) exhibited the most potent anti-SARS-CoV-2 efficacy with low cytotoxicity profile (CC50 of ~ 0.7 mg/mL), achieving 99.92% in pre-entry mode and 99.88% in postinfection treatment mode at 0.25 mg/mL. Flavonoids and conjugates were the predominant compounds identified in WF-MLCE. Molecular docking scores of several flavonoids against SARS-CoV-2 Mpro demonstrated their superior antiviral potency compared to molnupiravir. Remarkably, myricetin-3-O-β-D-galactopyranoside, maragrol B, and quercetin 3-O-robinobioside exhibited binding energies of ~  − 9 kcal/mol. The stability of each ligand–protein complex of these compounds with the Mpro system showed stability during MD simulation. These three molecules were pronounced as antiviral leads of WF-MLCE. Given the low cytotoxicity and high antiviral potency of WF-MLCE, it holds promise as a candidate for future therapeutic development for COVID-19 treatment, especially considering its economic and pharmacological advantages.
Validation of malaria-attributed deaths using verbal autopsy studies: a systematic review
Authors: Carshon-Marsh Ronald , Bondy Susan , Witek Theodore , Jha Prabhat
Published: July 2024

Background

Malaria contributes substantially to the persistent burden of child deaths in sub-Saharan Africa. Accurate and comprehensive malaria mortality data are crucial to monitor the progress in reducing malaria incidence and mortality. Verbal Autopsy (VA) ascertains the cause of death despite its limitations leading to misclassification errors. Minimally Invasive Tissue Sampling (MITS) is being conducted in some settings as an alternative to Complete Diagnostic Autopsy (CDA). The present study examines the validity of malaria-related deaths comparing VA diagnoses with those obtained through MITS and/or CDA.

Methods

A comprehensive literature search for original studies in English language using Ovid MEDLINE, Ovid Embase, CINAHL via EBSCO, Scopus, The Cochrane Library via Wiley, Google Scholar and searching the MITS Surveillance Alliance papers was carried out. The reference period was January 1, 1990–March 31, 2024. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were adopted.

Results

Among 71 articles identified in the databases, 21 matched the eligibility criteria. Qualitative syntheses showed that malaria Cause Specific Mortality Fractions (CSMFs) across various studies ranged from 2 to 31%.Plasmodium falciparumwas mostly responsible for these deaths and the most common complications were anaemia and cerebral malaria. The sensitivity and specificity of the VA validation studies ranged from 18.4% to 33% and from 86.6% to 97%, respectively, and there was a high level of misclassification for both InSilico and Expert Algorithm VA for malaria compared to MITS. The overall concordance rates between MITS and CDA diagnoses ranged from 68 to 90%, with the highest concordance seen in deaths due to infectious diseases and malignant tumours. Clinical data increased diagnostic coincidence between MITS blind to clinical data and the gold standard CDA by 11%.

Conclusions

The comprehensive review finds that MITS demonstrated better accuracy compared to VA in diagnosing malaria-attributed deaths, particularly in hospital settings. The high specificity of malaria in VA diagnosis suggests population-based estimates of the proportion of deaths due to malaria are broadly plausible.
How collider bias affects the relationship between skin color and heart attack using directed acyclic graphs, propensity scores, and stepwise approaches
Authors: Menezes-Júnior Luiz Antônio Alves , Barbosa Bruna Carolina Rafael , do Carmo Parajára Magda , Vidigal Mariana Cassemira Aparecida , de Oliveira Wanessa Cecília , Bouzada Deisyane Fumian , de Oliveira Taciana , Duarte Rafael Vieira
Published: July 2024

Background

Statistical methods are essential in epidemiology research, but they can generate erroneous estimates when selecting variables based only on statistical criteria. The use of directed acyclic graphs (DAG) helps to understand the causal relationships between variables and to avoid biases.

Objective

Compare the estimate of the effect of skin color on heart attack obtained from three data analysis techniques: a stepwise approach based on statistical criteria, a propensity score technique, and a graphical approach based on causal criteria.

Methods

Population-based cross-sectional study using data from the second National Health and Nutrition Examination Survey (NHANES). The exposure variable was skin color (black or non-black) and the outcome was heart attack (yes or no). Multivariable logistic regressions were carried out using the stepwise, propensity score techniques and the DAG-based approach to identify the association between the variables. In the stepwise technique, all variables potentially related to the outcome were included in the model and a forward or backward algorithm was used. The propensity score was applied, estimating the probability of exposure based on the covariates and helping to create balanced groups for comparison. Different possible causal models were developed between the variables in the DAG-based approach, identifying confounding, mediation, and collision factors. The models were created considering self-rated health as a confounding or collider variable, and the modeling results were verified.

Results

A total of 10,351 adults were evaluated, the majority female (52.1%), aged 20 to 39 years (48.5%), and with non-black skin color (90.4%). The prevalence of heart attacks was 3.0%, and 17% rated their health as fair or poor. Using different modeling techniques, no association was found between skin color and heart attack (p > 0.05), except when self-rated health, a collider variable, was included in the stepwise models. In this case, there was an inverse and biased association between the two variables, indicating a collision bias (stepwise-backward-OR 0.48; 95%CI 0.33–0.70; stepwise-forward-OR 0.64; 95%CI 0.44–0.94).

Conclusion

Skin color was not associated with heart attack when controlling for appropriate confounding factors. However, when adjusting for self-rated health in stepwise techniques, a colliding variable, there was an inverse and distorted association between the two variables, indicating a collider bias. The DAG-based approach and propensity score can avoid this bias by correctly identifying confounding factors and colliders.
Adaptive radiotherapy for muscle invasive bladder cancer: a retrospective audit of two bladder filling protocols
Authors: Guel Diana Nohemi Briceño , Laverick Nicola , MacLaren Linda , MacLeod Nicholas , Glegg Martin , Lamb Gillian , Houston Peter , Carruthers Ross , Grocutt Laura , Valentine Ronan M.
Published: July 2024

Background

Radical radiotherapy for muscle-invasive bladder cancer (MIBC) is challenging due to large variations in bladder shape, size and volume during treatment, with drinking protocols often employed to mitigate geometric uncertainties. Utilising adaptive radiotherapy together with CBCT imaging to select a treatment plan that best fits the bladder target and reduce normal tissue irradiation is an attractive option to compensate for anatomical changes. The aim of this retrospective study was to compare a bladder empty (BE) protocol to a bladder filling (BF) protocol with regards to variations in target volumes, plan of the day (PoD) selection and plan dosimetry throughout treatment.

Methods

Forty patients were included in the study; twenty were treated with a BE protocol and twenty with a BF protocol to a total prescribed dose of 55 Gy in 20 fractions. Small, medium and large bladder plans were generated using three different CTV to PTV margins. Bladder (CTV) volumes were delineated on planning CTs and online pre-treatment CBCTs. Differences in CTV volumes throughout treatment, plan selection, PTV volumes and resulting dose metrics were compared for both protocols.

Results

Mean bladder volume differed significantly on both the planning CTs and online pre-treatment CBCTs between the protocols (p < 0.05). Significant differences in bladder volumes were observed between the planning CT and pre-treatment CBCTs for BF (p < 0.05) but not for BE (p = 0.11). Both protocols saw a significant decrease in bladder volume between first and final treatment fractions (p < 0.05). Medium plans were preferentially selected for BE whilst when using the BF protocol the small plan was chosen most frequently. With no significant change to PTV coverage between the protocols, the volume of body receiving 25.0–45.8 Gy was found to be significantly smaller for BE patients (p < 0.05).

Conclusions

This work provides evidence in favour of a BE protocol compared to a BF protocol for radical radiotherapy for MIBC. The smaller treatment volumes observed in the BE protocol led to reduced OAR and total body doses and were also observed to be more consistent throughout the treatment course. These results highlight improvements in dosimetry for patients who undergo a BE protocol for MIBC.
A retrospective analysis of lymph node dissection in Siewert II adenocarcinoma of the esophagogastric junction
Authors: Tian Yang , Lv Hiulai , Wang Mingbo , Tian Ziqiang
Published: July 2024

Background

Analyze the pattern of lymph node metastasis in Siewert II adenocarcinoma of the esophagogastric junction (AEG) and provide a basis for the principles of surgical access.

Methods

The clinical data of 112 Siewert type II AEG patients admitted to the Fifth Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University from 2020 to 2022 were retrospectively collected. The probability of lymph node metastasis in each site and the clearance rate of lymph nodes in each site by different surgical approaches were analyzed.

Results

The lymph node metastasis rates in the middle and upper mediastinum group, the lower mediastinum group, the upper perigastric + supra pancreatic group, and the lower perigastric + hepatoduodenal group were 0.0%, 5.4%, 61.6%, and 17.1%, (P < 0.001). The number of lymph nodes cleared in the middle and upper mediastinum group was 0.00, 0.00, 4.00 in the transabdominal approach (TA), left thoracic approach (LT), and Ivor-Lewis (IL) group, (P < 0.001); The number of lymph nodes cleared in the lower mediastinal group was 0.00, 2.00, 2.00, (P < 0.001); The number of lymph node dissection in the perigastric + hepatoduodenal group was 3.00, 0.00, and 8.00, (P < 0.001). The overall complication rates were 25.7%, 12.5%, and 36.4%, (P = 0.058).

Conclusion

Siewert II AEG has the highest rate of lymph node metastasis in the upper perigastric + supra-pancreatic region, followed by the lower perigastric + hepatoduodenal, lower mediastinal, middle, and upper mediastinal regions. Ivor-Lewis can be used for both thoracic and abdominal lymph node dissection and does not increase the incidence of postoperative complications.
Acetylation model predicts prognosis of patients and affects immune microenvironment infiltration in epithelial ovarian carcinoma
Authors: Wang Xuan , Li Xiaoning , Wei Li , Yu Yankun , Hazaisihan Yeernaer , Tao Lin , Jia Wei
Published: July 2024

Background

Epithelial ovarian carcinoma (EOC) is a prevalent gynaecological malignancy. The prognosis of patients with EOC is related to acetylation modifications and immune responses in the tumour microenvironment (TME). However, the relationships between acetylation-related genes, patient prognosis, and the tumour immune microenvironment (TIME) are not yet understood. Our research aims to investigate the link between acetylation and the tumour microenvironment, with the goal of identifying new biomarkers for estimating survival of patients with EOC.

Methods

Using data downloaded from the tumour genome atlas (TCGA), genotypic tissue expression (GTEx), and gene expression master table (GEO), we comprehensively evaluated acetylation-related genes in 375 ovarian cancer specimens and identified molecular subtypes using unsupervised clustering. The prognosis, TIME, stem cell index and functional concentration analysis were compared among the three groups. A risk model based on differential expression of acetylation-related genes was established through minimum absolute contraction and selection operator (LASSO) regression analysis, and the predictive validity of this feature was validated using GEO data sets. A nomogram is used to predict a patient's likelihood of survival. In addition, different EOC risk groups were evaluated for timing, tumour immune dysfunction and exclusion (TIDE) score, stemness index, somatic mutation, and drug sensitivity.

Results

We used the mRNA levels of the differentially expressed genes related to acetylation to classify them into three distinct clusters. Patients with increased immune cell infiltration and lower stemness scores in cluster 2 (C2) exhibited poorer prognosis. Immunity and tumourigenesis-related pathways were highly abundant in cluster 3 (C3). We developed a prognostic model for ten differentially expressed acetylation-related genes. Kaplan–Meier analysis demonstrated significantly worse overall survival (OS) in high-risk patients. Furthermore, the TIME, tumour immune dysfunction and exclusion (TIDE) score, stemness index, tumour mutation burden (TMB), immunotherapy response, and drug sensitivity all showed significant correlations with the risk scores.

Conclusions

Our study demonstrated a complex regulatory mechanism of acetylation in EOC. The assessment of acetylation patterns could provide new therapeutic strategies for EOC immunotherapy to improve the prognosis of patients.
Email recruitment for chronic pain clinical trials: results from the LAMP trial
Authors: Ferguson John E. , Hagel Campbell Emily , Bangerter Ann , Cross Lee J. S. , Allen Kelli D. , Behrens Kimberly , Branson Mariah , Calvert Collin , Friedman Jessica K. , Hennessy Sierra , Meis Laura A. , Taylor Brent C. , Burgess Diana J.
Published: July 2024

Background

Recruitment for clinical trials and large-scale studies is challenging, especially for patients with complex conditions like chronic pain. Email recruitment has the potential to increase efficiency, to reduce costs, and to improve access for underrepresented patient populations. The objective of this study was to examine the effectiveness, efficiency, and equitability of email versus postal mail recruitment for the Learning to Apply Mindfulness to Pain (LAMP) study, a three-site clinical trial of mindfulness-based interventions for chronic pain.

Methods

Patients with chronic pain diagnoses were recruited from three United States Department of Veterans Affairs (VA) facilities using the VA electronic health record (EHR). Recruitment materials were sent using either postal mail (n = 7986) or email (n = 19,333). Patients in the email recruitment group were also mailed introductory postcards before any emails. Mailing addresses and email addresses were obtained from the EHR. Effectiveness was measured by the response rate of patients who logged into the secure LAMP study website. Efficiency was measured by the number of days from when the recruitment materials were sent to when patients logged into the LAMP portal as well as the estimated costs of each recruitment approach. To assess equitability, we examined whether email recruitment was less effective for underrepresented populations, based on demographic information from the EHR.

Results

Effectiveness—unadjusted response rates were greater for email versus postal-mail recruitment (18.9% versus 6.3%), and adjusted response rates were over three times greater for email recruitment (RR = 3.5, 95% CI 3.1–3.8) based on a multivariable analysis controlling for age, gender, race, ethnicity, rurality, and site. Efficiency—email recruitment had a significantly lower mean response time (1 day versus 8 days) and a lower cost. Equity—email recruitment led to higher response rates for all subpopulations, including older, non-White, Hispanic, rural, and female Veterans.

Conclusions

Email recruitment is an effective, efficient, and equitable way to recruit VA patients to large-scale, chronic pain clinical trials.

Trial registration

Clinical Trial Registration Number: NCT04526158. Patient enrollment began on December 4, 2020.
Translated and culturally adapted internet-delivered cognitive therapy for social anxiety disorder in Japanese clinical settings: study protocol for a randomised controlled trial
Authors: Yoshinaga Naoki , Thew Graham R. , Hayashi Yuta , Tanoue Hiroki , Nakai Michikazu , Clark David M.
Published: July 2024

Background

Cognitive therapy for social anxiety disorder (CT-SAD) has extensive empirical support and is recommended in several national guidelines. However, ensuring access to evidence-based psychological therapies such as CT-SAD remains a global challenge. An internet-delivered version of this treatment protocol (iCT-SAD) has recently been developed in the UK as a way to overcome this challenge, demonstrating comparable outcomes to face-to-face CT-SAD whilst requiring less therapist time per client. Initial findings also suggest its cross-cultural transferability, but the previous studies in other cultural settings used the English language programme and only included English-fluent participants as a second language. It is not yet known what outcomes can be achieved once the programme has been translated and adapted for a different cultural context. Therefore, this trial aims to evaluate the clinical efficacy of Japanese iCT-SAD when combined with treatment as usual (TAU) in clients with SAD.

Methods

This two-arm, parallel-group, superiority randomised controlled trial will recruit 60 Japanese participants with SAD, randomly assigning them to either Japanese iCT-SAD + TAU or TAU alone at a ratio of 1:1. The primary outcome measure is the self-report Liebowitz Social Anxiety Scale, and secondary.outcomes include other measures of social anxiety symptoms and processes, general mood and functioning, and response to treatment. We will also assess treatment acceptability and gather participant feedback. Assessments will take place at baseline (week 0), mid-treatment (week 8), and post-treatment (week 15), with a further 3-month follow-up (week 27) for the iCT-SAD + TAU arm. The primary analyses will be conducted on an intent-to-treat basis, comparing the primary and secondary outcome measures between groups using linear mixed-effect models, along with additional mediation analysis.

Discussion

Investigating the efficacy of translated and culturally adapted iCT-SAD in different cultural contexts is an important step in evaluating the global reach of internet interventions. This trial will provide valuable insights into the effects of iCT-SAD combined with usual care, and how this treatment could be delivered in routine clinical settings in Japan.

Trial registration

International Standard Randomized Controlled Trials (ISRCTN), ISRCTN82859645, registered on January 19, 2024. UMIN Clinical Trials Registry (UMIN-CTR), UMIN000052702, registered on November 6, 2023.
Exploring sources of inaccuracy and irreproducibility in the CDC bottle bioassay through direct insecticide quantification
Authors: Peard Evah F. , Luu Calvin , Hageman Kimberly J. , Sepesy Rose , Bernhardt Scott A.
Published: July 2024

Background

The Centers for Disease Control and Prevention (CDC) bottle bioassay is a commonly used susceptibility test for measuring insect response to insecticide exposure. However, inconsistencies and high variability in insect response when conducting CDC bottle bioassays have been reported in previous publications. We hypothesized that the CDC bottle bioassay results may be compromised when expected and actual insecticide concentrations in the bottles are not equivalent and that inadequate bottle cleaning and/or loss during insecticide introduction and bottle storage steps could be responsible. We explored this hypothesis by quantifying insecticides using gas chromatography tandem mass spectrometry (GC-MS/MS) in bottles that had been cleaned, prepared, and stored according to the CDC guidelines.

Methods

We investigated the bottle cleaning, preparation, and storage methods outlined in the CDC bottle bioassay procedure to identify sources of irreproducibility. We also investigated the effectiveness of cleaning bottles by autoclaving because this method is commonly used in insecticide assessment laboratories. The two insecticides used in this study were chlorpyrifos and lambda-cyhalothrin (λ-cyhalothrin). Insecticides were removed from glass bioassay bottles by rinsing with ethyl-acetate and n-hexane and then quantified using GC-MS/MS.

Results

The CDC bottle bioassay cleaning methods did not sufficiently remove both insecticides from the glass bottles. The cleaning methods removed chlorpyrifos, which has higher water solubility, more effectively than λ-cyhalothrin. Chlorpyrifos experienced significant loss during the bottle-coating process whereas λ-cyhalothrin did not. As for bottle storage, no significant decreases in insecticide concentrations were observed for 6 h following the initial drying period for either insecticide.

Conclusions

The CDC bottle bioassay protocol is susceptible to producing inaccurate results since its recommended bottle cleaning method is not sufficient and semi-volatile insecticides can volatilize from the bottle during the coating process. This can lead to the CDC bottle bioassay producing erroneous LC50 values. High levels of random variation were also observed in our experiments, as others have previously reported. We have outlined several steps that CDC bottle bioassay users could consider that would lead to improved accuracy and reproducibility when acquiring toxicity data.

Graphical Abstract
Dengue rhabdomyolysis successfully treated with hemoperfusion using CytoSorb® in combination with continuous renal replacement therapy: a case report
Authors: Samarasingha Piyum , Karunatilake Harindra , Jayanaga Ananda , Jayawardhana Hansani , Priyankara Dilshan
Published: July 2024

Background

Dengue fever is a mosquito-borne viral infection with a broad spectrum of clinical manifestations. Expanded dengue syndrome includes unusual manifestations that do not fall into the categories of dengue fever, dengue hemorrhagic fever, or dengue shock syndrome. Rhabdomyolysis causing acute renal failure in dengue is one such unusual manifestation, the pathophysiology of which is incompletely understood.

Case presentation

We describe a 21-year-old Sri Lankan man with dengue fever who developed severe rhabdomyolysis and acute kidney injury with extremely high creatinine phosphokinase levels (> 2 million U/L). Management of this patient was challenging as his creatinine phosphokinase kept rising with persistent anuria despite hydration, intermittent hemodialysis, and, later, continuous venovenous hemodiafiltration. Further therapeutic options were explored, and CytoSorb® adsorber was added as an adjunct to continuous venovenous hemodiafiltration, following which we observed a marked reduction in his creatinine phosphokinase and myoglobin levels over the next 12 hours and complete renal recovery over the next 5 weeks.

Conclusion

We report a rare case of significant rhabdomyolysis secondary to dengue infection leading to acute kidney injury. Continuous venovenous hemodiafiltration performed with the hemofilter Pecopen 140 was ineffective, and the addition of CytoSorb® adsorber as an adjunct therapy to continuous venovenous hemodiafiltration may have a potential benefit in removing high-molecular-weight proteins such as myoglobin.
Genome-scale CRISPR-Cas9 screening in stem cells: theories, applications and challenges
Authors: Zhou Heng , Ye Peng , Xiong Wei , Duan Xingxiang , Jing Shuili , He Yan , Zeng Zhi , Wei Yen , Ye Qingsong
Published: July 2024

Due to the rapid development of stem cell technology, there have been tremendous advances in molecular biological and pathological research, cell therapy as well as organoid technologies over the past decades. Advances in genome editing technology, particularly the discovery of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-related protein 9 (Cas9), have further facilitated the rapid development of stem cell researches. The CRISPR-Cas9 technology now goes beyond creating single gene editing to enable the inhibition or activation of endogenous gene loci by fusing inhibitory (CRISPRi) or activating (CRISPRa) domains with deactivated Cas9 proteins (dCas9). These tools have been utilized in genome-scale CRISPRi/a screen to recognize hereditary modifiers that are synergistic or opposing to malady mutations in an orderly and fair manner, thereby identifying illness mechanisms and discovering novel restorative targets to accelerate medicinal discovery investigation. However, the application of this technique is still relatively rare in stem cell research. There are numerous specialized challenges in applying large-scale useful genomics approaches to differentiated stem cell populations. Here, we present the first comprehensive review on CRISPR-based functional genomics screening in the field of stem cells, as well as practical considerations implemented in a range of scenarios, and exploration of the insights of CRISPR-based screen into cell fates, disease mechanisms and cell treatments in stem cell models. This review will broadly benefit scientists, engineers and medical practitioners in the areas of stem cell research.
The whole is greater than the sum of its parts: improving music source separation by bridging networks
Authors: Sawata Ryosuke , Takahashi Naoya , Uhlich Stefan , Takahashi Shusuke , Mitsufuji Yuki
Published: July 2024

This paper presents the crossing scheme (X-scheme) for improving the performance of deep neural network (DNN)-based music source separation (MSS) with almost no increasing calculation cost. It consists of three components: (i) multi-domain loss (MDL), (ii) bridging operation, which couples the individual instrument networks, and (iii) combination loss (CL). MDL enables the taking advantage of the frequency- and time-domain representations of audio signals. We modify the target network, i.e., the network architecture of the original DNN-based MSS, by adding bridging paths for each output instrument to share their information. MDL is then applied to the combinations of the output sources as well as each independent source; hence, we called it CL. MDL and CL can easily be applied to many DNN-based separation methods as they are merely loss functions that are only used during training and do not affect the inference step. Bridging operation does not increase the number of learnable parameters in the network. Experimental results showed that the validity of Open-Unmix (UMX), densely connected dilated DenseNet (D3Net) and convolutional time-domain audio separation network (Conv-TasNet) extended with our X-scheme, respectively called X-UMX, X-D3Net and X-Conv-TasNet, by comparing them with their original versions. We also verified the effectiveness of X-scheme in a large-scale data regime, showing its generality with respect to data size. X-UMX Large (X-UMXL), which was trained on large-scale internal data and used in our experiments, is newly available at https://github.com/asteroid-team/asteroid/tree/master/egs/musdb18/X-UMX.
Spatial distribution and pedigree age of intangible cultural heritage along the Grand Canal of China
Authors: Zhang Shuying , Zhang Xin , Liu Jiaming
Published: July 2024

Intangible cultural heritage is the carrier of national memory and a historical witness. Exploring the spatial distribution and chronological evolution of intangible cultural heritage is of great significance to understand the cultural integrity and historical continuity. Taking the intangible cultural heritage along the Grand Canal as an example, this study carries out spatial deconstruction based on the extent of the spread of intangible cultural heritage and reveales the aggregation pattern through spatial autocorrelation analysis. Then, the historical process and the spatial center of gravity are shown through an evolution tree model. The influencing factors are illustrated via the methods of Geodetector and qualitative analysis. The results are as follows: (1) The two ends of the canal exhibit obvious advantages in the number of intangible cultural heritage items; however, the existence of a spatial mismatch at the city–county level makes the southern endpoint occupy a dominant position. (2) Although there is a high–high aggregation pattern along the whole canal, 29.82% of the counties are distributed widely with low–low aggregation. (3) The spatial center of intangible cultural heritage items from different historical periods generally presents a changing path from north to south and returning north. (4) Intangible cultural heritage items are mainly distributed in areas with a prosperous culture, a high level of economic development, and strong policy and financial support from government. Changes in the natural environment, population migration, economic development, war disasters, and canal shipping have profound impacts over time. This study provides a new idea for the methodological advancement of spatial distribution of intangible cultural heritage, as well as studies on local cultural identity and regional consistency.