bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender income differences among general practitioners with compulsory services in early career stage in underdeveloped areas: evidence from a prospective cohort study in China
Authors: Tang Haoqing , Li Mingyue , Zheng Huixian , Zhang Xiaotian , Liu Xiaoyun
Published: June 2024

Background

Gender equality and the gender income gap in medicine are long-standing global problems. Although gender-related differences have been widely studied in developed countries, they remain unclear in underdeveloped regions. In 2010, China initiated a national compulsory service program (CSP) to train qualified general practitioners in rural and remote areas. This study aimed to evaluate gender income differences for early career CSP and non-CSP (NCSP) graduates in underdeveloped areas.

Methods

A cohort study was conducted with 3620 CSP and NCSP graduates from four medical universities in Central and Western China. Baseline surveys and six follow-up surveys were conducted between 2015 and 2022. Incomes, including monthly mean income and proportion of performance-based income, were measured as the key outcome variables. Multivariate linear regression models were used to identify the gender income gap.

Results

NCSP graduates had higher average monthly incomes than CSP graduates. In the seventh year after graduation, the average monthly income for NCSP graduates was 7859 CNY while was 5379 CNY for CSP graduates. After controlling for demographic characteristics, the gender monthly income gap for CSP graduates was expanded from the fourth year (3.0%) to the sixth year (5.9%) after graduation, and that for NCSP graduates was expanded from the fifth year (11.9%) to the seventh year (16.3%) after graduation. Regarding performance-based income, it was 58.9% for NCSP graduates and 45.8% for CSP graduates in the seventh year after graduation. After controlling for performance-based income proportion, the gender income gap was reduced from 5.9 to 4.0% in the sixth year after graduation for CSP graduates, and from 16.3 to 14.4% for NCSP graduates in the seventh year after graduation.

Conclusion

An extensive and ever-increasing gender income gap exists among young doctors in the early stages of their careers in underdeveloped areas of China. The high proportion of performance-based income among men is one of the main explanations for the observed difference. A more explicit compensation system must be established to enhance support for female health workers.
The RNA binding protein IGF2BP2/IMP2 alters the cargo of cancer cell-derived extracellular vesicles supporting tumor-associated macrophages
Authors: Mashayekhi Vida , Schomisch Annika , Rasheed Sari , Aparicio-Puerta Ernesto , Risch Timo , Yildiz Daniela , Koch Marcus , Both Simon , Ludwig Nicole , Legroux Thierry M. , Keller Andreas , Müller Rolf , Fuhrmann Gregor , Hoppstädter Jessica , Kiemer Alexandra K.
Published: June 2024

Background

Tumor cells release extracellular vesicles (EVs) that contribute to the polarization of macrophages towards tumor-associated macrophages (TAMs). High expression levels of the RNA binding protein IGF2BP2/IMP2 are correlated with increased tumor cell proliferation, invasion, and poor prognosis in the clinic. However, there is a lack of understanding of whether IMP2 affects the cargo of cancer cell-derived EVs, thereby modulating macrophage polarization.

Methods

EVs were isolated from IMP2-expressing HCT116 parental cells (WT) and CRISPR/Cas9 IMP2 knockout (KO) cells. EVs were characterized according to MISEV guidelines, microRNA cargo was assessed by microRNA-Seq, and the protein cargo was analyzed by proteomics. Primary human monocyte-derived macrophages (HMDMs) were polarized by EVs, and the expression of genes and surface markers was assessed using qPCR and flow cytometry, respectively. Morphological changes of macrophages, as well as the migratory potential of cancer cells, were assessed by the Incucyte® system and macrophage matrix degradation potential by zymography. Changes in the metabolic activity of macrophages were quantified using a Seahorse® analyzer. For in vivo studies, EVs were injected into the yolk sac of zebrafish larvae, and macrophages were isolated by fluorescence-activated cell sorting.

Results

EVs from WT and KO cells had a similar size and concentration and were positive for 25 vesicle markers. The expression of tumor-promoting genes was higher in macrophages polarized with WT EVs than KO EVs, while the expression of TNF and IL6 was reduced. A similar pattern was observed in macrophages from zebrafish larvae treated in vivo. WT EV-polarized macrophages showed a higher abundance of TAM-like surface markers, higher matrix degrading activity, as well as a higher promotion of cancer cell migration. MicroRNA-Seq revealed a significant difference in the microRNA composition of WT and KO EVs, particularly a high abundance of miR-181a-5p in WT EVs, which was absent in KO EVs. Inhibitors of macropinocytosis and phagocytosis antagonized the delivery of miR-181a-5p into macrophages and the downregulation of the miR-181a-5p target DUSP6. Proteomics data showed differences in protein cargo in KO vs. WT EVs, with the differentially abundant proteins mainly involved in metabolic pathways. WT EV-treated macrophages exhibited a higher basal oxygen consumption rate and a lower extracellular acidification rate than KO EV-treated cells.

Conclusion

Our results show that IMP2 determines the cargo of EVs released by cancer cells, thereby modulating the EVs' actions on macrophages. Expression of IMP2 is linked to the secretion of EVs that polarize macrophages towards a tumor-promoting phenotype.
Multiomic analysis of monocyte-derived alveolar macrophages in idiopathic pulmonary fibrosis
Authors: Zhang Miaomiao , Zhang Jinghao , Hu Haisheng , Zhou Yuan , Lin ZhiWei , Jing Hui , Sun Baoqing
Published: June 2024

Background

Monocyte-derived alveolar macrophages (Mo_AMs) are increasingly recognised as potential pathogenic factors for idiopathic pulmonary fibrosis (IPF). While scRNAseq analysis has proven valuable in the transcriptome profiling of Mo_AMs, the integration analysis of multi-omics may provide additional dimensions of understanding of these cellular populations.

Methods

We performed multi-omics analysis on 116 scRNAseq, 119 bulkseq and five scATACseq lung tissue samples from IPF. We built a large-scale IPF scRNAseq atlas and conducted the Monocle 2/3 as well as the Cellchat to explore the developmental path and intercellular communication on Mo_AMs. We also reported the difference in metabolisms, tissue repair and phagocytosis between Mo_AMs and tissue-resident alveolar macrophages (TRMs). To determine whether Mo_AMs affected pulmonary function, we projected clinical phenotypes (FVC%pred) from the bulkseq dataset onto the scRNAseq atlas. Finally, we used scATATCseq to uncover the upstream regulatory mechanisms and determine key drivers in Mo_AMs.

Results

We identified three Mo_AMs clusters and the trajectory analysis further validated the origin of these clusters. Moreover, via the Cellchat analysis, the CXCL12/CXCR4 axis was found to be involved in the molecular basis of reciprocal interactions between Mo_AMs and fibroblasts through the activation of the ERK pathway in Mo_AMs. SPP1_RecMacs (RecMacs, recruited macrophages) were higher in the low-FVC group than in the high-FVC group. Specifically, compared with TRMs, the functions of lipid and energetic metabolism as well as tissue repair were higher in Mo_AMs than TRMs. But, TRMs may have higher level of phagocytosis than TRMs. SPIB (PU.1), JUNB, JUND, BACH2, FOSL2, and SMARCC1 showed stronger association with open chromatin of Mo_AMs than TRMs. Significant upregulated expression and deep chromatin accessibility of APOE were observed in both SPP1_RecMacs and TRMs.

Conclusion

Through trajectory analysis, it was confirmed that SPP1_RecMacs derived from Monocytes. Besides, Mo_AMs may influence FVC% pred and aggravate pulmonary fibrosis through the communication with fibroblasts. Furthermore, distinctive transcriptional regulators between Mo_AMs and TRMs implied that they may depend on different upstream regulatory mechanisms. Overall, this work provides a global overview of how Mo_AMs govern IPF and also helps determine better approaches and intervention therapies.
Acceptability of artificial intelligence for cervical cancer screening in Dschang, Cameroon: a qualitative study on patient perspectives
Authors: Sachdeva Malika , Datchoua Alida Moukam , Yakam Virginie Flore , Kenfack Bruno , Jonnalagedda-Cattin Magali , Thiran Jean-Philippe , Petignat Patrick , Schmidt Nicole Christine
Published: June 2024

Background

Cervical cancer is the fourth most frequent cancer among women, with 90% of cervical cancer-related deaths occurring in low- and middle-income countries like Cameroon. Visual inspection with acetic acid is often used in low-resource settings to screen for cervical cancer; however, its accuracy can be limited. To address this issue, the Swiss Federal Institute of Technology Lausanne and the University Hospitals of Geneva are collaborating to develop an automated smartphone-based image classifier that serves as a computer aided diagnosis tool for cancerous lesions. The primary objective of this study is to explore the acceptability and perspectives of women in Dschang regarding the usage of a screening tool for cervical cancer relying on artificial intelligence. A secondary objective is to understand the preferred form and type of information women would like to receive regarding this artificial intelligence-based screening tool.

Methods

A qualitative methodology was employed to gain better insight into the women’s perspectives. Participants, aged between 30 and 49 were invited from both rural and urban regions and semi-structured interviews using a pre-tested interview guide were conducted. The focus groups were divided on the basis of level of education, as well as HPV status. The interviews were audio-recorded, transcribed, and coded using the ATLAS.ti software.

Results

A total of 32 participants took part in the six focus groups, and 38% of participants had a primary level of education. The perspectives identified were classified using an adapted version of the Technology Acceptance Model. Key factors influencing the acceptability of artificial intelligence include privacy concerns, perceived usefulness, and trust in the competence of providers, accuracy of the tool as well as the potential negative impact of smartphones.

Conclusion

The results suggest that an artificial intelligence-based screening tool for cervical cancer is mostly acceptable to the women in Dschang. By ensuring patient confidentiality and by providing clear explanations, acceptance can be fostered in the community and uptake of cervical cancer screening can be improved.

Trial registration

Ethical Cantonal Board of Geneva, Switzerland (CCER, N°2017–0110 and CER-amendment n°4) and Cameroonian National Ethics Committee for Human Health Research (N°2022/12/1518/CE/CNERSH/SP). NCT: 03757299.
The impact of insurance status on patient placement into inpatient and outpatient orthopaedic surgical centers
Authors: Tallapaneni Jetha , Harrington Michael , Troiani Zach , Venturino Luciano , Rosenbaum Andrew
Published: June 2024

Background

Innovation has fueled the shift from inpatient to outpatient care for orthopaedic joint arthroplasty. Given this transformation, it becomes imperative to understand what factors help assign care-settings to specific patients for the same procedure. While the comorbidities suffered by patients are important considerations, recent research may point to a more complex determination. Differences in reimbursement structures and patient characteristics across various insurance statuses could potentially influence these decisions.

Methods

Retrospective binary logistic and ordinary least square (OLS) regression analyses were employed on de-identified inpatient and outpatient orthopaedic arthroplasty data from Albany Medical Center from 2018 to 2022. Data elements included surgical setting (inpatient vs. outpatient), covariates (age, sex, race, obesity, smoking status), Elixhauser comorbidity indices, and insurance status.

Results

Patients insured by Medicare were significantly more likely to be placed in inpatient care-settings for total hip, knee, and ankle arthroplasty when compared to their privately insured counterparts even after Centers for Medicare and Medicaid Services (CMS) removed each individual surgery from its inpatient-only-list (1.65 (p < 0.05), 1.27 (p < 0.05), and 12.93 (p < 0.05) times more likely respectively). When compared to patients insured by the other payers, Medicare patients did not have the most comorbidities (p < 0.05).

Conclusions

Medicare patients were more likely to be placed in inpatient care-settings for hip, knee, and ankle arthroplasty. However, Medicaid patients were shown to have the most comorbidities. It is of value to note Medicare patients billed for outpatient services experience higher coinsurance rates.

Level of evidence

III.
Retrograde cerebral embolism and pulmonary embolism caused by patent ductus arteriosus: a case report
Authors: Li Jian , Liu Tihua , Rong Qinfeng
Published: June 2024

Background

Although rare, paradoxical embolism sometimes occurs with patent ductus arteriosus (PDA). This study presents a case of PDA-associated paradoxical embolism with acute ischemic stroke (AIS) and pulmonary embolism (PE) following thoracoscopic surgery.

Case Presentation

A 65-year-old woman developed acute-onset aphasia and right hemiparesis on the third day following thoracoscopic resection for a right lung tumor. Brain magnetic resonance imaging revealed multiple infarcts, and lower extremity venous Doppler ultrasound revealed deep vein thrombosis. The patient subsequently developed dyspnea, tachycardia, and hypoxemia. PE was confirmed by percutaneous transfemoral venous selective pulmonary angiography, which meanwhile demonstrated a PDA lesion. The patient, after receiving catheter-directed thrombolysis and inferior vena cava filter placement, improved in both neurological and respiratory status.

Conclusion

For an uncommon but potentially fatal case with PDA-induced paradoxical embolism causing AIS and PE, early recognition and treatment are vital. Further studies are warranted to determine the optimal management and prognosis of patients with PDA-related embolic events.
Advances in the localization of pulmonary nodules: a comprehensive review
Authors: Wang Yafang , Chen Enguo
Published: June 2024

In recent years, with the widespread use of chest CT, the detection rate of pulmonary nodules has significantly increased (Abtin and Brown, J Clin Oncol 31:1002-8, 2013). Video-assisted thoracoscopic surgery (VATS) is the most commonly used method for suspected malignant nodules. However, for nodules with a diameter less than 1 cm, or located more than 1.5 cm from the pleural edge, especially ground-glass nodules, it is challenging to achieve precise intraoperative localization by manual palpation (Ciriaco et al., Eur J Cardiothorac Surg 25:429-33, 2004). Therefore, preoperative accurate localization of such nodules becomes a necessary condition for precise resection. This article provides a comprehensive review and analysis of the research progress in pulmonary nodule localization, focusing on four major localization techniques: Percutaneous puncture-assisted localization, Bronchoscopic preoperative pulmonary nodule localization, 3D Printing-Assisted Localization, and intraoperative ultrasound-guided pulmonary nodule localization.
Large-scale performance assessment of the BG-Counter 2 used with two different mosquito traps
Authors: Rauhöft Leif , Șuleșco Tatiana , Martins Afonso Sara M. , Schmidt-Chanasit Jonas , Jöst Hanna , Sauer Felix G. , Lühken Renke
Published: June 2024

Background

Mosquitoes are important vectors of pathogens. They are usually collected with CO2-baited traps and subsequently identified by morphology. This procedure is very time-consuming. Automatic counting traps could facilitate timely evaluation of the local risk for mosquito-borne pathogen transmission or decision-making on vector control measures, but the counting accuracy of such devices has rarely been validated in the field.

Methods

The Biogents (BG)-Counter 2 automatically counts mosquitoes by discriminating the size of captured objects directly in the field and transmits the data to a cloud server. To assess the accuracy of this counting device, 27 traps were placed at 19 sampling sites across Germany and used in daily, weekly or bimonthly intervals from April until October 2021. The BG-Counter 2 was attached to a CO2-trap (BG-Pro trap = CO2-Pro) and the same trap was converted to also attract gravid mosquitoes (upside-down BG-Pro trap with a water container beneath = CO2-Pro-gravid). All captured mosquitoes were identified by morphology. The number of females (unfed and gravid), mosquito diversity and the number of identified specimens in relation to the counting data of the BG-Counter were compared between the two trapping devices to evaluate sampling success and counting accuracy.

Results

In total 26,714 mosquitoes were collected during 854 trap days. The CO2-Pro-gravid trap captured significantly more mosquitoes per trap day for all specimens, gravid females and non-gravid females, while there was no difference in the mosquito diversity. The linear model with the captured mosquitoes as a response and the counted specimens as a predictor explained only a small degree of the variation within the data (R2 = 0.16), but per individual trap the value could reach up to 0.62 (mean R2 = 0.23). The counting accuracy for the daily samples had a significant positive correlation with sample size, resulting in higher accuracy for the CO2-Pro-gravid trap and higher accuracy for sites and sampling months with high mosquito abundance.

Conclusions

While the accuracy of the BG-Counter 2 is quite low, the device is able to depict mosquito phenology and provide information about local population dynamics.

Graphical Abstract
Spontaneous pneumomediastinum and surgical emphysema presenting as rhinolalia following ecstasy ingestion: a case report
Authors: Prada Caterina , Ross Max
Published: June 2024

Background

We present a unique case of rhinolalia as the first recognizable sign of spontaneous pneumomediastinum and surgical emphysema following drug use.

Case presentation

This case presents a 17-year-old white male experiencing rhinolalia following ecstasy ingestion at a rave. Subsequent chest X-ray revealed extensive surgical emphysema, along with a continuous diaphragm sign indicative of pneumomediastinum. Computed tomography confirmed the diagnosis. The patient was managed conservatively with strict monitoring and 6 hourly electrocardiograms. Follow-up computed tomography on day 3 showed resolution of pneumomediastinum and surgical emphysema, and the patient was safely discharged. Notably, the patient experienced a temporary rhinolalia during the acute phase, which resolved spontaneously as his condition improved.

Conclusions

This case underscores the importance of considering spontaneous pneumomediastinum and surgical emphysema in the differential diagnosis of young individuals presenting with acute symptoms after drug use.
Causal relationship between primary sclerosing cholangitis and systemic lupus erythematosus: a bidirectional Mendelian randomization study
Authors: Pan Ziwen , Zhang Weijie
Published: June 2024

Background

Observational studies have found a link between two autoimmune diseases, namely, primary sclerosing cholangitis (PSC) and systemic lupus erythematosus (SLE). However, the relationship remains unclear.

Methods

Bidirectional Mendelian randomization (MR) analysis and statistical methods, including inverse variance weighting, weighted median, and MR-Egger tests, were performed using data from genome-wide association studies to detect a causal relationship between PSC and SLE. Sensitivity analyses were subsequently performed to assess the robustness of the results. Univariate MR methods were also investigated.

Results

Results of MR analysis suggested that PSC was associated with an increased risk for SLE (odds ratio: 1.33, 95% confidence interval: 1.10–1.61, P=0.0039) However, SLE had no significant causal relationship with PSC.

Conclusion

Results of MR analysis revealed that patients with PSC were at an increased risk for SLE, which provides new insights into the relationship between these two autoimmune diseases.
Adolescents’ short-form video addiction and sleep quality: the mediating role of social anxiety
Authors: Jiang Li , Yoo Yizoon
Published: June 2024

Background

Adolescence is a critical period for individual growth and development. Insufficient sleep adversely affects adolescents’ physical development, blood pressure, vision, and cognitive function. This study examined the effect of short-form video addiction on adolescents’ sleep quality, as well as the mediating role of social anxiety, to identify methods for improving adolescents’ sleep quality in the Internet era.

Methods

A questionnaire survey was conducted in this cross-sectional study on 1629 adolescents recruited from three high schools. Their short-form video addiction, social anxiety, and sleep quality were evaluated using corresponding scales. Pearson correlation analysis was carried out to analyze the relationships among short‐form video addiction, sleep quality, and social anxiety. Mediating effect analysis was constructed using AMOS 20.0 statistical software.

Results

Participants’ sleep quality score is 6.12 ± 3.29 points. The detection rate of sleep quality among them is 31.06%. Short‐form video addiction, sleep quality, and social anxiety are significantly correlated (r = 0.439, 0.404, 0.457, P < 0.001). The direct effect of short-form video addiction on sleep quality is 0.248, accounting for 62.4% of the total effect. The indirect effect exerted through social anxiety is 0.149, accounting for 37.6%.

Conclusions

Sleep disorders are very common among Chinese adolescents. Short‐form video addiction is positively correlated with adolescents’ sleep quality and social anxiety. Social anxiety partially mediates the relationship between short-form video addiction and sleep quality. The adverse effects of short-form video addiction and social anxiety on the sleep quality of this group must be minimized. Schools are recommended to implement measures to promote sleep quality among adolescents.
The social factors behind the mask: contextual effects on trait impressions from faces wearing a face mask
Authors: Tumino Matilde , Carraro Luciana , Castelli Luigi
Published: June 2024

The presence of face masks can significantly impact processes related to trait impressions from faces. In the present research, we focused on trait impressions from faces either wearing a mask or not by addressing how contextual factors may shape such inferences. In Study 1, we compared trait impressions from faces in a phase of the COVID-19 pandemic in which wearing masks was a normative behavior (T1) with those assessed one year later when wearing masks was far less common (T2). Results at T2 showed a reduced positivity in the trait impressions elicited by faces covered by a mask. In Study 2, it was found that trait impressions from faces were modulated by the background visual context in which the target face was embedded so that faces wearing a mask elicited more positive traits when superimposed on an indoor rather than outdoor visual context. Overall, the present studies indicate that wearing face masks may affect trait impressions from faces, but also that such impressions are highly flexible and can significantly fluctuate across time and space.
Efficacy of entomopathogenic nematodes in laboratory and field conditions of Cicer arietinum against cotton bollworm, Helicoverpa armigera Hübner (Lepidoptera: Noctuidae)
Authors: Mengal Maqbool Ahmed , Javed Salma , Majeed Saima
Published: June 2024

Background

The chickpea Cicer arietinum (Fabaceae) field has suffered significant economic losses due to the presence of cotton bollworm, Helicoverpa armigera Hübner (Lepidoptera: Noctuidae). Attempts to control the larval population through chemical pesticides led to some reduction but also resulted in the development of resistance among the larvae. Consequently, the H. armigera population experienced a rapid resurgence in the field. Given the substantial losses caused by Helicoverpa larvae, there is now a growing interest in adopting eco-friendly methods for management. The application of biocontrol agents has emerged as a promising solution for effectively managing the infestation.

Results

In the laboratory experiment, the entomopathogenic nematodes (EPNs) Steinernema pakistanense NNRC-NB.14, S. balochiense NNRC-NB.23, and S. abbasi NNRC-NB.33 were evaluated for their infectivity and mortality effects on mature cotton bollworm at various concentrations. The study demonstrated that the highest mortality rates were achieved at a concentration of 250 infective juveniles (IJs) per larva after 72 h. Steinernema pakistanense and S. balochiense exhibited higher mortality rates (95–98%) compared to S. abbasi (77%) at higher application concentrations. The field trial results reinforced the laboratory findings, demonstrating a significant decrease in H. armigera larval populations when employing EPN strains, particularly NNRC-NB.14 and NNRC-NB.33, compared to NNRC-NB.23. Despite the initial applications showing relatively low mortality percentages, the most effective larval control occurred after the third application of EPNs. The field trials revealed that, following the third spray, mortality percentages significantly increased from the initial range of 20–32% to a more substantial 70–90%. This cumulative impact highlights the importance of multiple applications in achieving optimal pest control.

Conclusion

The findings of these studies highlight the promising potential of EPN as an eco-friendly and sustainable method for controlling the cotton bollworm. However, the successful implementation of EPN-based control strategies in agricultural systems requires careful consideration of factors such as nematode species selection, application methods, environmental conditions, and integration with other pest management practices. Further research is needed to optimize the efficacy and practicality of using EPN on a larger scale, addressing issues such as nematode production, formulation, and compatibility with existing farming practice.
Study of P wave dispersion in patients with paroxysmal atrial fibrillation and its role in prediction of atrial fibrillation recurrence
Authors: Gomaa Mohammed Magdy Mohammed , Elsafty Eman Elsayed Ali , Gomaa Hend Magdy Mohamed , Abdulrahim Mona Malek , Eladawy Ahmed Hassan Hosny
Published: June 2024

Background

It has been known that increased P wave duration and P wave dispersion reflect prolongation of intra-atrial and interatrial conduction time and the inhomogeneous propagation of sinus impulses, which are well-known electrophysiologic characteristics in patients with atrial arrhythmias and especially paroxysmal atrial fibrillation. The objective of this study was assessment of P wave dispersion value in cases with paroxysmal atrial fibrillation and its role in predicting recurrence.

Results

Forty-eight patients with documented paroxysmal AF were subjected to clinical evaluation, electrocardiogram and routine Doppler echocardiogram. We found that a statistically significant association was detected between P wave dispersion and older age, diabetic and hypertensive cases with positive correlation also detected with left atrial dimension (LAD), left ventricle size and diastolic dysfunction grade. Mean corrected P wave dispersion and corrected QT interval were higher among cases using sotalol, ca channel blockers, among cases using nitrates and among cases with Morris index > 0.04. Higher mean value of corrected QT was associated with biphasic P v1 shape. Old age, female sex, P wave dispersion and QT wave dispersion are statistically significant predictors of PAF recurrence.

Conclusion

P wave dispersion in patients with paroxysmal atrial fibrillation was strongly correlated to older age, diabetic and hypertensive patients and also with left atrial dimension (LAD), left ventricle size and diastolic dysfunction grade. Also, mean corrected P wave dispersion can predict atrial fibrillation recurrence in patients with Morris index > 0.04, old age, female sex, and QT wave dispersion.
Synthesizing a realistic seismic training data set incorporating prior geologic patterns and seismic imaging features for supervised convolutional neural network-based intracratonic strike-slip fault detection
Authors: Jing Jiankun , Yan Zhe , Gong Wei , Li Haiying , Zhang Zheng , Gu Hanming
Published: June 2024

Intracratonic strike-slip faults play a vital role in hydrocarbon migration and accumulation, making their accurate detection crucial for subsurface structure interpretation and reservoir characterization. Although numerous approaches have been developed for automatic fault interpretation, they are still unable to fully recognize intracratonic strike-slip faults with subtle reflection variations in seismic images. We develop a supervised convolutional neural network (CNN) to automatically and precisely delineate these faults in 3D seismic images. The primary obstacle in using a CNN for this task is the lack of diverse seismic training samples and corresponding high-quality labels. To address this, we develop an efficient two-step workflow for automatically generating a tremendous amount of 3D seismic training sample pairs: (1) guided by the prior geologic structure patterns of the study area, we use parameterized vector fields to simulate various velocity models with accurate fault labels incorporating realistic intracratonic strike-slip faulting features, such as the transtensional, transpressional, and strike-slip translational types and (2) following seismic imaging laws, we synthesize seismic training samples from simulated velocity models through the point-spread function-based convolution method. One synthetic and two field examples demonstrate that the CNN trained with this seismic data set containing prior geologic patterns and seismic imaging features outperforms the conventional fault detection approaches in accurately and continuously delineating intracratonic strike-slip faults.
Barriers and Challenges to Implementing a Quality Improvement Program: Political and Administrative Challenges
Authors: Carbonell Chantelle , Adegbulugbe Abisola , Cheung Winson , Ruff Paul
Published: June 2024

Quality improvement (QI) programs have rapidly grown in health care over recent years. Despite increasing evidence of successful QI initiatives resulting in improved outcomes, the adoption and implementation of QI programs remain a challenge worldwide. This paper briefly describes political and administrative barriers that impede the implementation of QI programs, including political and ideological factors, socioeconomic and educational barriers, and barriers related to data collection, privacy, and security. Key political and administrative barriers identified include resource limitations due to inadequate public funding, stringent laws, and change resistance. Potential solutions include support and commitment from regional and national authorities, consultation of all involved parties during QI program development, and financial incentives. The barrier of limited resources is starker among low- and middle-income countries (LMICs) compared with high-income countries (HICs) due to the absence of adequate infrastructure, personnel equipped with QI-oriented skills, and analytical technology. Solutions that have facilitated QI programs in some LMICs include outreach and collaboration with other health centers and established QI programs in HICs. The lack of QI-specific training and education in medical curricula challenges QI implementation but can be mitigated through the provision of QI promotion webinars, QI-specific project opportunities, and formalized QI training modules. Finally, barriers related to data collection, privacy, and security include laws hindering the availability of quality data, inefficient data collection and processes, and outdated clinical information systems. Access to high-quality data, organized record-keeping, and alignment of data collection processes will help alleviate these barriers to QI program implementation. The multidimensional nature of these barriers means that proposed solutions will require coordination from multiple stakeholders, government support, and leaders across multiple fields.
Comparing the somatic, germline, and immune landscapes of upper tract urothelial carcinoma (UTUC) and UC of the bladder (UCB).
Authors: Yuen Kit L. , Meagher Margaret F. , Mercer Jacob , Yilma Binyam , Stoppler Melissa Conrad , Fragkogianni Stamatina , Mar Nataliya , Rezazadeh Arash , Gupta Shilpa , Grivas Petros , Bagrodia Aditya , McKay Rana R. , Stewart Tyler F. , Salmasi Amirali
Published: June 2024

4520

Background: Molecular characterization of anatomically distinct UCs has been limited by the rarity of UTUC; however, recent advances in real-world data curation have enabled larger UTUC cohort generation. Here, we investigated the somatic, germline, and immunologic landscapes of UTUC compared to UCB. Methods: From the Tempus Database, we retrospectively analyzed de-identified next-generation sequencing data from 505 UTUC (224 ureter, 281 renal pelvis) and 2,416 UCB cases (2,379 bladder, 37 urethra). Tumors were sequenced with the Tempus xT DNA and xR RNA assays. Pathogenic somatic mutations, immune cell infiltration predicted from gene expression patterns, TMB, PD-L1 from IHC, MSI, and mismatch repair (MMR) were evaluated. Incidental germline alterations were assessed in 46 genes for patients with tumor/normal-matched (T/N) sequencing (UTUC n=285, UCB n=1,359). Chi-squared, Fisher's exact, and Wilcoxon rank-sum tests were used to assess statistical significance (p<0.05, q<0.05 for false discovery rate correction for multiple testing). Results: Median age of the UTUC and UCB cohort were 73 and 70 years, respectively (p=0.003). The UCB cohort had significantly more males (75% vs 56%, p<0.001) and ever smokers (59% vs 46%, p<0.001).Alterations in TERT, TP53, CDK12, RB1, ERBB2, and CDKN1A were more frequent in UCB, while KMT2D, FGFR3, BRIP1, CDKN2B, KRAS, and MYC more frequent in UTUC (Table). Additionally, FGFR3 fusions were more frequent in UTUC. Germline variants were found in 7.1% of UCB and 7.0% of UTUC cases, with trends towards higher prevalence of alterations in lynch-associated genes ( MLH1, MSH2, MSH6, PMS2) in UTUC (0.6% vs 1.8%, p=0.059). The prevalence of TMB ≥ 10 mut/Mb was higher in UCB vs UTUC (17% vs 11%, p<0.001). UCB had increased PD-L1 positivity (p=0.013), whereas UTUC had more MSI-high (UTUC = 3.2% vs UCB = 1%, p=0.001) and deficient MMR (p=0.020) cases. There were similar proportions of total immune infiltrates in UCB and UTUC. However, UTUC harbored a higher percentage of CD4+ T cells (p<0.001), while UCB had a higher proportion of regulatory T and NK cells (p<0.001). Conclusions: Via comprehensive molecular characterization of UC, we observed distinct DNA alteration and tumor microenvironment patterns in UTUC and UCB. The germline results underline how T/N testing can identify patients with UTUC and/or UCB who can benefit from dedicated germline testing. Further research is warranted to elucidate the clinical implications of these findings. [Table: see text]
Tumor-specific MHC class II upregulation associated with response to anti-PD-L1 therapy in patients with urothelial cancer.
Authors: Hasakioğulları İlayda , Kockx Mark , Szabados Bernadett , Young Matthew , Powles Thomas
Published: June 2024

4584

Background: The mechanism of response and resistance to immune checkpoint inhibition (ICI) remains to be defined in urothelial cancer. Methods: The abacus study explored neo-adjuvant atezolizumab prior to cystectomy in muscle-invasive bladder cancer (MIBC, NCT02662309). In this post hoc exploratory analysis, we utilized samples from the Abacus. Nanostring GeoMx Digital Spatial Profiler (DSP), a spatial transcriptomics platform enabling comprehensive characterization of the entire human transcriptome while preserving spatial information, was performed on Formalin Fixed Paraffin Embedded (FFPE) tissue from 12 paired biopsies (3 pCR, 3 MPR, and 6 relapse tumors). To guide region selection and tissue segmentation on the GeoMx DSP, we utilized SYTO 13, PanCK, CD45, and CD3 markers. Subsequently, we quantified the entire transcriptome in selected regions and conducted differential gene expression analysis using the DSP data analysis suite and BioTuring Lens platforms. Results: Tumor cells of the MPR samples showed upregulation of MHC class II genes (log2FC >1.52, q < 5.5E-04, p< 9.7E-07). pCR samples showed numerous tertiary lymphoid structures (TLS) in the remaining tumor bed. We then performed MHC class II (HLA-DR) immunohistochemistry staining to confirm this transcriptome-level finding on available FFPE samples from Abacus. The MPR response group (n=4) had significantly higher levels of MHC class II expression on tumor cells after the treatment than relapse (n=12) and stable disease (n=15) patients ( p < 0.001). Conclusions: Upregulation of MHC class II on tumor cells in anti-PD-L1 responding patients is a novel finding. Together with the TLS presence, they offer insights into potential mechanisms underlying treatment response, thus aiding in identifying predictive biomarkers for ICI therapy in MIBC.
Survival outcomes of small cell variant bladder cancer: Analysis from nationwide study.
Authors: Ganiyani Mohammad Arfat , Khosla Atulya Aman , Ahmad Shahzaib , Jatwani Karan , Bellur Shreyas S , Aziz Nouman , Rubens Muni , Roy Mukesh , Bastos Bruno R. , Ozambela Manuel , Eldefrawy Ahmed , Manoharan Murugesan , Garje Rohan
Published: June 2024

4606

Background: Small cell carcinoma of bladder (SCB) is a rare and aggressive histological subtype. While the survival impact of various treatment modalities for the classic urothelial bladder cancer has been well-researched, limited studies exists on the survival outcomes of these treatment modalities in patients with SCB, primarily due to the exclusion of these patients from clinical trials. This study aims to explore the impact of different treatment modalities on the survival outcome of patients with SCB using data from a large nationwide registry. Methods: This retrospective study queried the National Cancer Database from 2004 to 2020 and followed STROBE guidelines. The primary analytic cohort included patients diagnosed with locoregional SCB based on the TNM stage (T1-T4, N0-N3, M0). Treatment modalities comprised perioperative systemic therapy combined with definitive surgery (PST), concurrent chemoradiation (CR), surgery only (S), Radiation therapy only (RT) and systemic therapy only (ST). This study utilized Kaplan-Meier survival analysis and the Cox Proportional regression. Results: The study included 4,658 patients with locoregional SCB. The analysis revealed 236 (4.82%) patients with SCB received PST, 752 (15.36%) got CR, 612 (12.50%) underwent S, 3,029 (61.85%) received ST, and 268 (5.47%) had RT. The median overall survival was 64.49 months (CI: 41.4-75.1, P < 0.001) with PST, 29.27 months (CI: 22.9-35.88), with CR, 14.13 months (CI: 9.92-21.65) with S alone, 21.29 months (CI: 18.53-23.69) with ST, and 7.82 months (CI: 6.24-9.53) with RT alone. In the multivariate analysis, combining perioperative systemic therapy with surgery led to a 54% reduction in hazards of death (HR: 0.46; CI: 0.37-0.58) compared to surgery alone, whereas CCR achieved a 41.16% (HR: 0.59; CI: 0.47-0.73) decrease in hazard, illustrating the effectiveness of multimodal treatment for SCB. Conclusions: Treatment approaches with either systemic therapy combined with definitive surgery or concurrent chemoradiation enhanced survival outcomes, highlighting the significance of a multimodal approach for patients with SCB. [Table: see text]
Real-world data based on PD-L1 expression in early-stage NSCLC in an east-Asian patient population: A 10-year follow-up study.
Authors: Hong Ji Hyung , Ko Elaine Yee-Ling , Lee Young Sub , Moon Youngkyu , Kim Seoung Joon , Lecoultre Marc , Shih David Jen-Hao , Lee Victor Ho-Fun , Hui Rina , Hong Sook-Hee , EL Helali Aya
Published: June 2024

8019

Background: Recent studies on the perioperative treatment of Non-Small Cell Lung Cancer (NSCLC) have often excluded patients with stage IA. To address this issue and bridge the knowledge gap, we aim to investigate the impact of PD-L1 and EGFR status on survival in stage IA NSCLC. Methods: Our study aimed to determine the impact of PD-L1 expression on overall survival (OS) in patients with resectable stage IA-IIIB NSCLC who underwent curative resection between May 2010 and April 2020. We analyzed survival and clinicopathological data and categorized patients based on PD-L1 tumor proportion score (TPS). PD-L1 TPS ≥ 50% were categorized as PD-L1 high and < 50% as PD-L1 negative/low. Our primary objective was to assess the association between PD-L1 expression status and OS in resectable NSCLC patients. We also investigated the relationships between OS, PD-L1 expression, EGFR status, and tumor stage. Results: Among the 386 patients recruited, those with PD-L1 negative/low and high had a 5-year OS of 82% and 63%, respectively ( p = 0.00011). Among patients with stage IA NSCLC, those with PD-L1 negative/low demonstrated the most favorable 5-year OS (96%) compared to the other subgroups (stage IA PD-L1 high 63%, stage IB-IIIB PD-L1 negative/low 67% and stage IB-IIIB PD-L1 high 62%, p < 0.0001). Stage IA EGFR mutant NSCLC showed a significantly better 5-year OS compared to EGFR wildtype (97% versus 84%, p= 0.0028). In comparison, survival in stage IB-IIIB NSCLC was similar regardless of EGFR status (stage IB-IIIB/EGFR mutant 66% vs EGFR wildtype 65%, p= 0.13). Next, we addressed the impact of the co-occurrence of an EGFR mutation and PD-L1 expression on survival in stage IA. In stage IA, the PD-L1 high EGFR mutant and wildtype subgroups demonstrated a 5-year OS of 83% and 56%, respectively, while in the PD-L1 negative/low subgroup, the EGFR mutant and wildtype had a 98% and 93% OS ( p< 0.0001), respectively. Conclusions: Stage IA NSCLC patients with PD-L1 high and EGFR wildtype, surprisingly, were associated with poorer survival outcomes. These findings highlight the urgent need for clinical trials investigating perioperative management strategies in this population.
Surgical outcomes in patients with non-small cell lung cancer receiving neoadjuvant chemoimmunotherapy versus chemotherapy alone: A systematic review and meta-analysis.
Authors: Aburaki Riona , Fujiwara Yu , Chida Kohei , Horita Nobuyuki , Nagasaka Misako
Published: June 2024

8020

Background: Neoadjuvant immune checkpoint blockade (ICB) including programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) blockade in combination with chemotherapy has been shown to improve survival outcomes in patients with early-stage non-small cell lung cancer (NSCLC). However, its impact on surgery has not been fully elucidated yet. We aimed to compare surgical outcomes between neoadjuvant chemoimmunotherapy with PD-1/PD-L1 blockade and chemotherapy alone in patients with resectable NSCLC. Methods: We performed a systematic search of PubMed and Embase for randomized-controlled trials (RCTs) that compared neoadjuvant chemoimmunotherapy to chemotherapy alone in patients with resectable NSCLC and reported surgical outcomes including surgical resection rates, R0 resection rates, postoperative complications, any-grade treatment-related adverse events (TRAEs), grade 3-5 TRAEs, serious AEs (SAEs), and AEs leading to cancellation of surgery. Meta-analysis was performed using the random-effects model to pool odds ratios (ORs) of these surgical and safety outcomes. Heterogeneity among the included studies for each outcome was assessed using I2 statistics and high heterogeneity was defined as I2 higher than 50%. Results: A systematic review identified 5 RCTs with 2,069 patients for a meta-analysis. All identified RCTs evaluated combination of neoadjuvant PD-1/ PD-L1 blockade with chemotherapy versus chemotherapy alone. Chemoimmunotherapy was associated with an improvement in R0 resection rates (OR 1.72, 95% CI 1.22 - 2.42; p = 0.002), whereas surgical resection rates were comparable between two groups (OR 1.51, 95% CI 0.90 - 2.51; p = 0.12). No significant difference was observed for complication rates, any-grade TRAEs, grade 3-5 TRAEs, SAEs, or AEs leading to cancellation of surgery. (Table). Conclusions: Although the surgical resection rate itself was not significantly different between neoadjuvant chemoimmunotherapy and chemotherapy alone, neoadjuvant chemoimmunotherapy was associated with increased R0 resection rates without an increase in the incidence of complications, TRAEs, and cancellation of surgery. This indicates that neoadjuvant chemoimmunotherapy can be safely administered with an increase in R0 resection rate, which potentially leads to improvement of survival outcomes in patients with resectable NSCLC. [Table: see text]
A phase II study of tislelizumab (TIS) and chemotherapy as neoadjuvant therapy for potentially resectable stage IIIA/IIIB non-small cell lung cancer (NSCLC).
Authors: Wang Ting , Li Lu , Huang Lin , Liu Jie Wei , Zhu Da Xing , Dong Jing Si , Deng Han Yu , Zheng Xi , Tian Long , Jiang Li Li , Wang Wei Ya , Zhou Ping , Su Ming Gang , Pu Dan , Cai Xu Yu , Feng Ming Yang , Ou Xue Jin , Wang Yongsheng , Zhou Qing Hua
Published: June 2024

8024

Background: Neoadjuvant immunotherapy and chemotherapy provide more surgical opportunities and survival benefits to potentially resectable locally advanced NSCLC remains unclear. Herein, we initiated a phase II study to evaluate the feasibility of neoadjuvant immunotherapy and chemotherapy in stage IIIA/IIIB NSCLC. We report the the updated analysis of the study. Methods: Patients (pts) with stage IIIA/IIIB EGFR/ALK/ROS wild-type NSCLC received 2 cycles of neoadjuvantchemoimmunotherapy (PD-1 inhibitor TIS, nab-paclitaxel, and cisplatin/carboplatin) and were reassessed for surgery.Thereafter, pts underwent surgery within 6 weeks and continued 2 cycles of TIS plus chemotherapy, followed by up to 15 cycles of TIS monotherapy. The primary endpoint was R0 resection rate, and secondary endpoints included major pathologic response (MPR), pathologic complete response (pCR), 1/2-year EFS rate, and overall survival, etc. Results: From Jan 2021 to Sep 2023, 33 pts were enrolled; 19 (58% ) pts with IIIA and 14 (42%) pts with IIIB disease, As of 14 Sep 2023, 27 pts completed neoadjuvant and 25 pts underwent resection. and 6 pts were on neoadjuvant. 2 pts downstaging had obvious downstaging after neoadjuvant treatment and were unwilling to surgery. 24 of 25 pts (96%) underwent successful R0 resection (Table). Of 25 pts who underwent resection,8 (32%) pts achieved pCR, 15 (60%) pts achieved pathologic response rate.Of the 7 pts who achieved MPR, 5 had only about 1% viable tumor cells in the resection specimen. The overall response rate (ORR) and disease control rate (DCR) were 88% (22/25) and 100 % (25/25), respectively. The clinical downstaging occurred in 22 of 25 pts (88%).The pathological downstaging occurred in 23 of 25 pts (92%).And The 1-year EFS rate 82.3% (95%CI 58.3-93.2), 2-year EFS rate 76.4% (95%CI 51.1-89.8). Conclusions: Neoadjuvant TIS plus chemotherapy increased surgical opportunities and survival benefits in potentially resectable locally advanced stage IIIA/IIIB NSCLC. [Table: see text]