bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of thoracic radiotherapy in extensive-stage small-cell lung cancer patients receiving first-line immunotherapy plus chemotherapy: a propensity score matched multicentre retrospective analysis
Authors: Yao Yueyuan , Li Butuo , Song Ruiting , Yang Linlin , Zou Bing , Wang Linlin
Published: February 2024

Background

Platinum-etoposide chemotherapy combined with immune checkpoint inhibitors (ICIs) has been recommended as the first-line standard treatment for extensive-stage small-cell lung cancer (ES-SCLC). However, the effect of thoracic radiotherapy (TRT) on these patients is still unknown. This study aimed to evaluate the efficacy and safety of TRT for ES-SCLC patients who responded to first-line ICIs and chemotherapy (CHT).

Methods

Patients who received 4 to 6 cycles of ICIs and CHT as first-line therapy at three hospitals between 2018 and 2022 were included in the analysis. All patients were divided into two groups based on whether they received TRT as first-line treatment, and propensity score matching (PSM) was performed to ensure that the characteristics of two groups were well-balanced. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was toxic effects.

Results

A total of 276 patients were included, and the median follow-up time was 22.3 (range, 4.0-53.73) months. After PSM, 197 patients were further analysed, and 99 of whom received TRT. The baseline characteristics were well-balanced between patients in the TRT and non-TRT groups. There were significant differences in PFS between the TRT and non-TRT groups, with the median PFS of 10.76 and 7.63 months, respectively (P = 0.014). Significantly improved OS was observed in the TRT group (21.67 vs. 16.6 months, P = 0.009). In addition, the use of TRT was an independent prognostic factor for PFS and OS of ES-SCLC patients receiving ICIs plus CHT. In terms of safety, no significant increase of any grades adverse event (AE) (P = 0.874) and G3-4 AE (P = 0.909) was observed for patients receiving TRT. Radiation esophagitis, gastrointestinal and hematologic toxicities were the most common AEs in TRT group, which were tolerable. And high-dose radiotherapy was associated with higher incidence of pneumonitis.

Conclusion

Addition of TRT showed significant survival benefits and well tolerability in ES-SCLC patients receiving platinum-etoposide CHT and ICIs, which could be a feasible first-line treatment strategy for ES-SCLC patients.
Recombinations, chains and caps: resolving problems with the DCJ-indel model
Authors: Bohnenkämper Leonard
Published: February 2024

One of the most fundamental problems in genome rearrangement studies is the (genomic) distance problem. It is typically formulated as finding the minimum number of rearrangements under a model that are needed to transform one genome into the other. A powerful multi-chromosomal model is the Double Cut and Join (DCJ) model.While the DCJ model is not able to deal with some situations that occur in practice, like duplicated or lost regions, it was extended over time to handle these cases. First, it was extended to the DCJ-indel model, solving the issue of lost markers. Later ILP-solutions for so called natural genomes, in which each genomic region may occur an arbitrary number of times, were developed, enabling in theory to solve the distance problem for any pair of genomes. However, some theoretical and practical issues remained unsolved. On the theoretical side of things, there exist two disparate views of the DCJ-indel model, motivated in the same way, but with different conceptualizations that could not be reconciled so far. On the practical side, while ILP solutions for natural genomes typically perform well on telomere to telomere resolved genomes, they have been shown in recent years to quickly loose performance on genomes with a large number of contigs or linear chromosomes. This has been linked to a particular technique, namely capping. Simply put, capping circularizes linear chromosomes by concatenating them during solving time, increasing the solution space of the ILP superexponentially. Recently, we introduced a new conceptualization of the DCJ-indel model within the context of another rearrangement problem. In this manuscript, we will apply this new conceptualization to the distance problem. In doing this, we uncover the relation between the disparate conceptualizations of the DCJ-indel model. We are also able to derive an ILP solution to the distance problem that does not rely on capping. This solution significantly improves upon the performance of previous solutions on genomes with high numbers of contigs while still solving the problem exactly and being competitive in performance otherwise. We demonstrate the performance advantage on simulated genomes as well as showing its practical usefulness in an analysis of 11 Drosophila genomes.
An innovative lab-scale production for a novel therapeutic DNA vaccine candidate against rheumatoid arthritis
Authors: Long Juan , Zhao Xiao , Liang Fei , Zeng Yang , Liu Nan , Sun Yuying , Xi Yongzhi
Published: February 2024

Background

Recent therapeutic-plasmid DNA vaccine strategies for rheumatoid arthritis (RA) have significantly improved. Our pcDNA-CCOL2A1 vaccine is the most prominent and the first antigen-specific tolerising DNA vaccine with potent therapeutic and prophylactic effects compared with methotrexate (MTX), the current “gold standard” treatment for collagen-induced arthritis (CIA). This study developed a highly efficient, cost-effective, and easy-to-operate system for the lab-scale production of endotoxin-free supercoiled plasmids with high quality and high yield. Based on optimised fermentation culture, we obtained a high yield of pcDNA-CCOL2A1 vaccine by PEG/MgCl2 precipitation and TRION-114. We then established a method for quality control of the pcDNA-CCOL2A1 vaccine. Collagen-induced arthritis (CIA) model rats were subjected to intramuscular injection of the pcDNA-CCOL2A1 vaccine (300 μg/kg) to test its biological activity.

Results

An average yield of 11.81 ± 1.03 mg purified supercoiled plasmid was obtained from 1 L of fermentation broth at 670.6 ± 57.42 mg/L, which was significantly higher than that obtained using anion exchange column chromatography and a commercial purification kit. Our supercoiled plasmid had high purity, biological activity, and yield, conforming to the international guidelines for DNA vaccines.

Conclusion

The proposed innovative downstream process for the pcDNA-CCOL2A1 vaccine can not only provide a large-scale high-quality supercoiled plasmid DNA for preclinical research but also facilitate further pilot-scale and even industrial-scale production of pcDNA-CCOL2A1 vaccine.
Organoids as a biomarker for personalized treatment in metastatic colorectal cancer: drug screen optimization and correlation with patient response
Authors: Smabers Lidwien P. , Wensink Emerens , Verissimo Carla S. , Koedoot Esmee , Pitsa Katerina-Chara , Huismans Maarten A. , Higuera Barón Celia , Doorn Mayke , Valkenburg-van Iersel Liselot B. , Cirkel Geert A. , Brousali Anneta , Overmeer René , Koopman Miriam , Braat Manon N. , Penning de Vries Bas , Elias Sjoerd G. , Vries Robert G. , Kranenburg Onno , Boj Sylvia F. , Roodhart Jeanine M.
Published: February 2024

Background

The inability to predict treatment response of colorectal cancer patients results in unnecessary toxicity, decreased efficacy and survival. Response testing on patient-derived organoids (PDOs) is a promising biomarker for treatment efficacy. The aim of this study is to optimize PDO drug screening methods for correlation with patient response and explore the potential to predict responses to standard chemotherapies.

Methods

We optimized drug screen methods on 5–11 PDOs per condition of the complete set of 23 PDOs from patients treated for metastatic colorectal cancer (mCRC). PDOs were exposed to 5-fluorouracil (5-FU), irinotecan- and oxaliplatin-based chemotherapy. We compared medium with and without N-acetylcysteine (NAC), different readouts and different combination treatment set-ups to capture the strongest association with patient response. We expanded the screens using the optimized methods for all PDOs. Organoid sensitivity was correlated to the patient’s response, determined by % change in the size of target lesions. We assessed organoid sensitivity in relation to prior exposure to chemotherapy, mutational status and sidedness.

Results

Drug screen optimization involved excluding N-acetylcysteine from the medium and biphasic curve fitting for 5-FU & oxaliplatin combination screens. CellTiter-Glo measurements were comparable with CyQUANT and did not affect the correlation with patient response. Furthermore, the correlation improved with application of growth rate metrics, when 5-FU & oxaliplatin was screened in a ratio, and 5-FU & SN-38 using a fixed dose of SN-38. Area under the curve was the most robust drug response curve metric. After optimization, organoid and patient response showed a correlation coefficient of 0.58 for 5-FU (n = 6, 95% CI -0.44,0.95), 0.61 for irinotecan- (n = 10, 95% CI -0.03,0.90) and 0.60 for oxaliplatin-based chemotherapy (n = 11, 95% CI -0.01,0.88). Median progression-free survival of patients with resistant PDOs to oxaliplatin-based chemotherapy was significantly shorter than sensitive PDOs (3.3 vs 10.9 months, p = 0.007). Increased resistance to 5-FU in patients with prior exposure to 5-FU/capecitabine was adequately reflected in PDOs (p = 0.003).

Conclusions

Our study emphasizes the critical impact of the screening methods for determining correlation between PDO drug screens and mCRC patient outcomes. Our 5-step optimization strategy provides a basis for future research on the clinical utility of PDO screens.
ITC-net-audio-5: an audio streaming dataset for application identification in network traffic classification
Authors: Nikbakht Mohammad , Teimouri Mehdi
Published: February 2024

Objectives

An essential aspect of network traffic classification is application identification. This involves capturing and analyzing the traffic patterns of applications. There are a few publicly available datasets that specifically capture streaming data from network-based applications. Therefore, our objective is to generate an up-to-date dataset with a focus on audio streaming data. This dataset can be a valuable resource for identifying audio streaming applications in the field of network traffic classification.

Data description

The dataset contains network traffic captured during audio streaming communications on five trending applications: Google Meet, Skype, Telegram, WhatsApp, and SoundCloud. It includes 500 files in PCAP format captured by Wireshark and PCAPdroid tools during voice calls and online music playback. The concurrent utilization of these tools facilitates the avoidance of capturing background traffic.
Identifying Hmga2 preserving visual function by promoting a shift of Müller glia cell fate in mice with acute retinal injury
Authors: Yin Zhiyuan , Ge Lingling , Cha Zhe , Gao Hui , A Luodan , Zeng Yuxiao , Huang Xiaona , Cheng Xuan , Yao Kai , Tao Zui , Xu Haiwei
Published: February 2024

Background

Unlike in lower vertebrates, Müller glia (MG) in adult mammalian retinas lack the ability to reprogram into neurons after retinal injury or degeneration and exhibit reactive gliosis instead. Whether a transition in MG cell fate from gliosis to reprogramming would help preserve photoreceptors is still under exploration.

Methods

A mouse model of retinitis pigmentosa (RP) was established using MG cell lineage tracing mice by intraperitoneal injection of sodium iodate (SI). The critical time point for the fate determination of MG gliosis was determined through immunohistochemical staining methods. Then, bulk-RNA and single-cell RNA seq techniques were used to elucidate the changes in RNA transcription of the retina and MG at that time point, and new genes that may determine the fate transition of MG were screened. Finally, the selected gene was specifically overexpressed in MG cells through adeno-associated viruses (AAV) in the mouse RP model. Bulk-RNA seq technique, immunohistochemical staining methods, and visual function testing were used to elucidate and validate the mechanism of new genes function on MG cell fate transition and retinal function.

Results

Here, we found the critical time point for MG gliosis fate determination was 3 days post SI injection. Hmga2 was screened out as a candidate regulator for the cell fate transition of MG. After retinal injury caused by SI, the Hmga2 protein is temporarily and lowly expressed in MG cells. Overexpression of Hmga2 in MG down-regulated glial cell related genes and up-regulated photoreceptor related genes. Besides, overexpressing Hmga2 exclusively to MG reduced MG gliosis, made MG obtain cone’s marker, and retained visual function in mice with acute retinal injury.

Conclusion

Our results suggested the unique reprogramming properties of Hmga2 in regulating the fate transition of MG and neuroprotective effects on the retina with acute injury. This work uncovers the reprogramming ability of epigenetic factors in MG.
Preventing lipophilic aggregation in cosolvent molecular dynamics simulations with hydrophobic probes using Plumed Automatic Restraining Tool (PART)
Authors: Beyens Olivier , De Winter Hans
Published: February 2024

Cosolvent molecular dynamics (MD) simulations are molecular dynamics simulations used to identify preferable locations of small organic fragments on a protein target. Most cosolvent molecular dynamics workflows make use of only water-soluble fragments, as hydrophobic fragments would cause lipophilic aggregation. To date the two approaches that allow usage of hydrophobic cosolvent molecules are to use a low (0.2 M) concentration of hydrophobic probes, with the disadvantage of a lower sampling speed, or to use force field modifications, with the disadvantage of a difficult and inflexible setup procedure. Here we present a third alternative, that does not suffer from low sampling speed nor from cumbersome preparation procedures. We have built an easy-to-use open source command line tool PART (Plumed Automatic Restraining Tool) to generate a PLUMED file handling all intermolecular restraints to prevent lipophilic aggregation. We have compared restrained and unrestrained cosolvent MD simulations, showing that restraints are necessary to prevent lipophilic aggregation at hydrophobic probe concentrations of 0.5 M. Furthermore, we benchmarked PART generated restraints on a test set of four proteins (Factor-Xa, HIV protease, P38 MAP kinase and RNase A), showing that cosolvent MD with PART generated restraints qualitatively reproduces binding features of cocrystallised ligands.
Asymmetric division of stem cells and its cancer relevance
Authors: Chao Shanshan , Yan Huiwen , Bu Pengcheng
Published: February 2024

Asymmetric division is a fundamental process for generating cell diversity and maintaining the stem cell population. During asymmetric division, proteins, organelles, and even RNA are distributed unequally between the two daughter cells, determining their distinct cell fates. The mechanisms orchestrating this process are extremely complex. Dysregulation of asymmetric division can potentially trigger cancer progression. Cancer stem cells, in particular, undergo asymmetric division, leading to intra-tumoral heterogeneity, which contributes to treatment refractoriness. In this review, we delve into the cellular and molecular mechanisms that govern asymmetric division and explore its relevance to tumorigenesis.
Pharmacokinetics and bioequivalence evaluation of two oral formulations of cotrimoxazole tablets in healthy Chinese volunteers under fasting conditions
Authors: Zuo Xu , Zhao Xin , Shi Jinjin , Zhang Tiandong
Published: February 2024

This bioequivalence study was conducted to evaluate two oral formulations of cotrimoxazole tablets in healthy Chinese subjects. All 26 subjects recruited to this study were randomly and evenly classified into two groups and received a single dose (sulfamethoxazole: 400 mg and trimethoprim: 80 mg) of test cotrimoxazole tablets (generic drug) or reference cotrimoxazole tablets (branded drug). After a 7-day washout period, these subjects received one dose of reference drug or test drug. Blood samples were collected from participants before and up to 48 h after dosing to assess the concentration of sulfamethoxazole (SMX) and trimethoprim (TMP) in plasma and a plasma concentration-time curve was drawn. Then, the pharmacokinetics parameters were calculated accordingly. Our data revealed that there were no significant differences observed in the maximum plasma concentration (Cmax), area under the curve from time 0 to the last measurable concentration (AUC0-t), and area under the curve from time 0 to infinity (AUC0-∞) between the two formulations. For SMX, the 90% confidence intervals (CI) of the geometric mean ratio for Cmax, AUC0-t, and AUC0-∞ were 104.03-113.92%, 100.46-103.70%, and 100.41-103.81%, respectively. Similarly, for Trimethoprim (TMP), the 90% CI ranged from 98.54 to 106.95% for Cmax, from 99.31 to 107.68% for AUC0-t, and from 99.49 to 107.55% for AUC0-∞. Importantly, all these 90% CI values fell within the range of 80.00–125.00%, indicating that the test drug is bioequivalent to the reference drug. Furthermore, throughout the entire trial, no suspected serious adverse events were reported, indicating the safety profile of the newly developed generic cotrimoxazole. In summary, our study demonstrates that the newly developed generic formulation of cotrimoxazole is bioequivalent to the branded formulation under fasting conditions.
Exploring graphene structure, material properties, and electrochemical characteristics through laser-induced temperature analysis
Authors: Yang Na-Kyoung , Shin Yoo-Kyum , Park Saeyoung , Kim Sang-Min , Koo Bon-Jae , Jeong Joonsoo , Seo Min-Ho
Published: February 2024

Laser-induced graphene (LIG) is a three-dimensional graphene structure fabricated through the irradiation of a polymer substrate with laser energy (or fluence, equivalently). This methodology offers a cost-effective and facile means of producing 3D nanostructures, yielding graphene materials characterized by extremely high surface area and superior electrical properties, rendering them advantageous for various electrochemical applications. Nonetheless, it is imperative to acknowledge that the structures and material properties of LIG are subject to substantial variations contingent upon processing parameters, thereby underscoring the necessity for systematic inquiry and systematic comprehension of processing conditions, such as fluence and multi-passing, and resultant outcomes. Herein, we explored the impact of different laser fluence levels on the structural and material properties of LIG. We, especially, focused on how laser fluence affected substrate temperature and found that it caused polyimide (PI) substrate pyrolysis, resulting in changes in 3D structures and material density to LIG properties. We also investigated the effects of a multi-passing process on 3D LIG structures and material qualities, varying fluences, and temperature fluctuations. Lastly, we assessed electrochemical properties using LIGs produced under different conditions as working electrodes, leading to distinct impedance profiles and cyclic voltammetry (CV) curves. These variations were linked to the unique structural and material characteristics of the LIG samples.
Rethinking our world: a perspective on a cleaner globe emerging from reduced anthropogenic activities
Authors: Nguyen Kim-Anh , Liou Yuei-An
Published: February 2024

Stringent measures, such as lockdowns, were implemented to curb the virus's spread, leading to reduced pollution levels and environmental improvements at various geographic scales, from cities to regions and nations. Such positive effects have been found and reported for regional scales, but not for a global scale till nowadays. This study aims to fill the gap by uncovering the modifications of global spatiotemporal eco-environmental vulnerability patterns between pre-pandemic (2016) and amid-pandemic (2020) periods. By analyzing various factors influencing the eco-environmental health or geo-health, such as human activities, climate change, and ecological dynamics, we seek to understand the intricate relationships and dynamics within these influential factors. We examined six categories of environmental vulnerability, which encompassed socioeconomics, land resources, natural hazards, hydrometeorology, and topography, using a five-dimensional stressor framework. Our analysis revealed a significant decrease in vulnerability levels across all categories, except for the very low level increased by 78.5% globally. These findings emphasize the detrimental impact of human activities on the global environment. They underscore the urgency of implementing spatial management strategies that prioritize sustainable geo-health development and foster a more resilient Earth.
Knee Biomechanics During Neurocognitively Challenged Drop Landings in Male Elite Soccer Players with Anterior Cruciate Ligament Reconstruction
Authors: Gholipour Aghdam Ghazal Mohammad , Alizadeh Mohammad Hossein , Minoonejad Hooman , Shirzad Elham , Wilke Jan
Published: February 2024

Background

Reactive decision-making during athletic movement has been demonstrated to evoke unfavorable biomechanics associated with anterior cruciate ligament (ACL) rupture. However, the current evidence is based on assessments of healthy individuals. We aimed to investigate unplanned jump landing kinetics and knee kinematics in ACL-reconstructed (ACLR) and non-injured athletes.

Methods

A total of 30 male professional soccer players (n = 15 ACLR after return to play, n = 15 matched controls) performed six drop landings onto a force plate. As a neurocognitive challenge requiring decision-making, a diode flashing in randomly selected colors indicated the requested landing location. Knee joint kinematics (flexion, valgus and tibial rotation angles) assessed with a 10-camera motion capture system, vertical ground reaction force (vGRF), time to stabilization (TTS) and length of the center of pressure (COP) trace (all analyzed from force plate data) were calculated. Cognitive function was assessed using the CNS Vital Signs battery.

Results

The ACLR group produced lower knee flexion angles than the control group (median [interquartile range] 50.00° [6.60] vs. 55.20° [4.45], p = .02). In addition, path length of the center of pressure (379 mm [56.20] vs. 344 mm [37.00], p = .04) and ground reaction force (3.21 N/kg [0.66] vs. 2.87 N/kg [0.48], p = .01) were higher for the ACLR group. No differences were found for knee valgus (p = .96), tibial rotation (p = .83) and TTS (p = .82). ACLR participants scored lower for reaction time (p = .02) and processing speed (p = .01). Unfavorable knee biomechanics were more often related to cognitive function in the ACLR group than in the control group (p < .05).

Conclusions

Impaired reactive decision-making during athletic movement may contribute to the high re-injury risk in individuals with ACLR. Prospective studies confirming potential cause-effect relationships are warranted.
Protocol for a single-arm, pilot trial of creatine monohydrate supplementation in patients with Alzheimer’s disease
Authors: Taylor Matthew K. , Burns Jeffrey M. , Choi In-Young , Herda Trent J. , Lee Phil , Smith Aaron N. , Sullivan Debra K. , Swerdlow Russell H. , Wilkins Heather M.
Published: February 2024

Background

Impaired brain bioenergetics is a pathological hallmark of Alzheimer’s disease (AD) and is a compelling target for AD treatment. Patients with AD exhibit dysfunction in the brain creatine (Cr) system, which is integral in maintaining bioenergetic flux. Recent studies in AD mouse models suggest Cr supplementation improves brain mitochondrial function and may be protective of AD peptide pathology and cognition.

Aims

The Creatine to Augment Bioenergetics in Alzheimer’s disease (CABA) study is designed to primarily assess the feasibility of supplementation with 20 g/day of creatine monohydrate (CrM) in patients with cognitive impairment due to AD. Secondary aims are designed to generate preliminary data investigating changes in brain Cr levels, cognition, peripheral and brain mitochondrial function, and muscle strength and size.

Methods

CABA is an 8-week, single-arm pilot study that will recruit 20 patients with cognitive impairment due to AD. Participants attend five in-person study visits: two visits at baseline to conduct screening and baseline assessments, a 4-week visit, and two 8-week visits. Outcomes assessment includes recruitment, retention, and compliance, cognitive testing, magnetic resonance spectroscopy of brain metabolites, platelet and lymphocyte mitochondrial function, and muscle strength and morphology at baseline and 8 weeks.

Discussion

CABA is the first study to investigate CrM as a potential treatment in patients with AD. The pilot data generated by this study are pertinent to inform the design of future large-scale efficacy trials.

Trial registration

ClinicalTrials.gov, NCT05383833, registered on 20 May 2022.
A scoping review of In-the-loop paradigms in the energy sector focusing on software-in-the-loop
Authors: Clausen Christian Skafte Beck , Jørgensen Bo Nørregaard , Ma Zheng Grace
Published: February 2024

Software-in-the-Loop (SIL) testing is an approach used for verification and validation in the energy sector. However, there is no comprehensive overview of the application, potential, and challenges of SIL within this sector. Therefore, this paper conducts a thorough scoping review of the existing literature within the scope of SIL and related in-the-loop approaches in the energy sector. A total of 88 full-text articles from four significant databases ACM, IEEE Xplore, Scopus, and Web of Science are analyzed and categorized to map the purpose, methods, architecture, interoperability and protocols, technologies, challenges, and limitations. The results present a grand perspective of in-the-loop across several domains followed by an analysis of SIL in the energy sector. The application domains carry characteristics from complex systems, systems-of-systems, cyber-physical systems, critical systems, real-time systems, and sociotechnical systems. The energy sector and the automotive industry are amongst the most applied domains. Within energy- and electricity systems, hardware-based in-the-loop paradigms are mostly applied for testing low-level signaling, and SIL is used for control strategy testing, optimization, dispatching, and experimentation. The examined SIL architectures have distributed-, real-time, and closed-loop properties, and are constrained by specialized simulation power hardware. Future research should address how to systematically develop SIL testing environments with guiding principles to support application development for the future digitalized energy system.
A novel N7-methylguanosine-associated feature predicts prognosis in gastric cancer
Authors: Zhao Shixing , Zhao Wenbo , Yao Chunxia , Tian Yunxiao
Published: February 2024

Background

Despite substantial advancements in gastric cancer treatment in recent years, our understanding of the disease’s pathophysiology and progression processes remains limited, and the prognosis for gastric cancer patients remains poor. This study investigated potential prognostic indicators based on m7G-associated long non-coding RNA (lncRNA) and its relationship with gastric cancer (STAD).

Methods

The researchers used RNA-seq and prognostic data from TCGA, employing Cox regression, co-expression network analysis, and multivariate Cox regression to identify relevant lncRNAs. We compiled four m7G-related lncRNAs into a single signature.

Results

We found it may be used as a prognostic indicator for gastric cancer. The m7G-related lncRNA profile had an area under the curve of 0.710, significantly more diagnostic than clinicopathological markers. The study also found that the TMB and tumor microenvironment were associated with gastric cancer risk, highlighting their signature’s potential utility for personalized treatment and disease monitoring.

Conclusions

This study provides a novel signature of m7G-related lncRNAs that can be used as a prognostic indicator for gastric cancer and may help guide the development of targeted immunotherapy for the condition.
A mixed-methods evaluation of organization and individual factors influencing provider intentions to use caregiver coaching in community-based early intervention
Authors: Pellecchia Melanie , Mandell David S. , Tomczuk Liza , Marcus Steven C. , Stewart Rebecca , Stahmer Aubyn C. , Beidas Rinad S. , Rieth Sarah R. , Lawson Gwendolyn M.
Published: February 2024

Background

Most psycho-social interventions contain multiple components. Practitioners often vary in their implementation of different intervention components. Caregiver coaching is a multicomponent intervention for young autistic children that is highly effective but poorly implemented in community-based early intervention (EI). Previous research has shown that EI providers’ intentions, and the determinants of their intentions, to implement caregiver coaching vary across components. Organizational culture and climate likely influence these psychological determinants of intention by affecting beliefs that underlie attitudes, norms, and self-efficacy to implement an intervention. Research in this area is limited, which limits the development of theoretically driven, multilevel implementation strategies to support multi-component interventions. This mixed methods study evaluated the relationships among organizational leadership, culture and climate, attitudes, norms, self-efficacy, and EI providers’ intentions to implement the components of caregiver coaching.

Methods

We surveyed 264 EI providers from 37 agencies regarding their intentions and determinants of intentions to use caregiver coaching. We also asked questions about the organizational culture, climate, and leadership in their agencies related to caregiver coaching. We used multilevel structural equation models to estimate associations among intentions, psychological determinants of intentions (attitudes, descriptive norms, injunctive norms, and self-efficacy), and organizational factors (implementation climate and leadership). We conducted qualitative interviews with 36 providers, stratified by strength of intentions to use coaching. We used mixed-methods analysis to gain an in-depth understanding of the organization and individual-level factors.

Results

The associations among intentions, psychological determinants of intentions, and organizational factors varied across core components of caregiver coaching. Qualitative interviews elucidated how providers describe the importance of each component. For example, providers’ attitudes toward coaching caregivers and their perceptions of caregivers’ expectations for service were particularly salient themes related to their use of caregiver coaching.

Conclusion

Results highlight the importance of multi-level strategies that strategically target individual intervention components as well as organization-level and individual-level constructs. This approach holds promise for improving the implementation of complex, multicomponent, psychosocial interventions in community-based service systems.
The “D&I Bridge”: introducing a teaching tool to define the D, the I, and the why
Authors: Becker Sara J. , DiClemente-Bosco Kira , Scott Kelli , Helseth Sarah A. , Patel-Syed Zabin , Li Dennis H.
Published: February 2024

Interest in learning dissemination and implementation (D&I) science is at an all-time high. As founding faculty and fellows of a new center focused on D&I science, we have found that non-specialist researchers and newcomers to D&I science often express confusion around the difference between the D and the I. Relatedly, they struggle to identify what their specific D&I projects target to impact public health within the amorphous “black box” that is the singular, loosely defined “research-to-practice gap.” To improve conceptual clarity and enhance engagement with D&I science, we developed a graphic—the D&I Bridge—and an accompanying glossary of terms to use as a teaching and framing tool. The D&I Bridge depicts D&I science as bridging what we know from public health knowledge to what we do in public health practice with intention and equity, and it spans over four distinct, inter-related gaps: the public health supply gap, the public health demand gap, the methodological/scientific gap, and the expertise capacity gap. The public health supply gap is addressed by implementation strategies, whereas the public health demand gap is addressed by dissemination strategies. The methodological/scientific gap is addressed by producing generalizable knowledge about D&I, and the expertise capacity gap is addressed by developing the multi-disciplinary workforce needed to advance D&I. Initial practice feedback about the D&I Bridge has been positive, and this conceptualization of D&I science has helped inform our center’s D&I training, D&I project consultations, and strategic planning. We believe the D&I Bridge provides a useful heuristic for helping non-specialists understand the differential scopes of various D&I science projects as well as specific gaps that may be addressed by D&I methods.
Outcomes of endoscopic management of benign maxillary sinus lesions 5-year experience, non-randomized clinical trials
Authors: Gad Mohamed Omar A. , Ibrahim Ahmed Ali , Aleem Ahmed Abdel , Mohamed Shimaa Ibrahim
Published: February 2024

Background

When medical therapy fails to control maxillary sinus (MS) disease, surgery is required. There are many advanced MS endoscopic approaches, each one with its anatomical limitations and possible complications. This study aimed to review the outcomes of three endoscopic approaches to the MS (middle meatal antrostomy approach (MMAA), prelacrimal recess approach (PLRA), and canine fossa approach (CFA)) to manage benign MS lesions.

Methods

Sixty-three patients with diseased MS require surgery. Endoscopic MS approaches used include MMAA, PLRA, and CFA. Each approach was used in 21 patients. The outcome of each approach was measured regarding lesion accessibility and clearance, complications (intraoperative or postoperative), and recurrence.

Results

The maxillary sinus posterior wall was accessible in all approaches. Other walls and different recesses were also accessible in the case of PLRA and CFA with statistically significant difference between the three approaches. There was no significant difference between patients operated by PLRA and CFA regarding accessibility to different walls and recesses of the MS. Endoscopic and radiological recurrence were found in three (15%) patients who were operated by MMAA. There was no evidence of recurrence in patients operated by the other approaches. Complications like crustations, fascial pain, fascial welling, and fascial hypoesthesia occurred in a few patients.

Conclusion

By using a suitable endoscopic approach, the different walls and recesses of the MS were completely accessible, so benign MS lesions that required open surgical approaches can be managed endoscopically while preserving the sinus structure and function.
Path-BigBird: An AI-Driven Transformer Approach to Classification of Cancer Pathology Reports
Authors: Chandrashekar Mayanka , Lyngaas Isaac , Hanson Heidi A. , Gao Shang , Wu Xiao-Cheng , Gounley John
Published: February 2024

PURPOSE

Surgical pathology reports are critical for cancer diagnosis and management. To accurately extract information about tumor characteristics from pathology reports in near real time, we explore the impact of using domain-specific transformer models that understand cancer pathology reports.

METHODS

We built a pathology transformer model, Path-BigBird, by using 2.7 million pathology reports from six SEER cancer registries. We then compare different variations of Path-BigBird with two less computationally intensive methods: Hierarchical Self-Attention Network (HiSAN) classification model and an off-the-shelf clinical transformer model (Clinical BigBird). We use five pathology information extraction tasks for evaluation: site, subsite, laterality, histology, and behavior. Model performance is evaluated by using macro and micro F1 scores.

RESULTS

We found that Path-BigBird and Clinical BigBird outperformed the HiSAN in all tasks. Clinical BigBird performed better on the site and laterality tasks. Versions of the Path-BigBird model performed best on the two most difficult tasks: subsite (micro F1 score of 72.53, macro F1 score of 35.76) and histology (micro F1 score of 80.96, macro F1 score of 37.94). The largest performance gains over the HiSAN model were for histology, for which a Path-BigBird model increased the micro F1 score by 1.44 points and the macro F1 score by 3.55 points. Overall, the results suggest that a Path-BigBird model with a vocabulary derived from well-curated and deidentified data is the best-performing model.

CONCLUSION

The Path-BigBird pathology transformer model improves automated information extraction from pathology reports. Although Path-BigBird outperforms Clinical BigBird and HiSAN, these less computationally expensive models still have utility when resources are constrained.
Microvascular Disease, Cardiovascular Health, and Risk of Coronary Heart Disease in Type 2 Diabetes: A UK Biobank Study
Authors: Chen Guo-Chong , Hukportie Daniel Nyarko , Liu Yu-Jie , Wang Hai-Peng , Qin Li-Qiang , Fan Wei-Dong , Li Fu-Rong , Wu Xian-Bo
Published: February 2024

Context

The interplay between cardiovascular health metrics (CVHMs) and microvascular disease (MVD) in relation to the risk of incident coronary heart disease (CHD) among individuals with type 2 diabetes mellitus (T2DM) remains to be evaluated.

Objective

To investigate the role of MVD and CVHMs in the development of CHD among T2DM.

Design

We included 19 664 participants with T2DM from the UK Biobank who had CVHM data and were free of CHD during recruitment. CVHMs were defined based on 5 behavioral (body mass index, diet, sleep duration, smoking, and regular exercise) and 3 biological (glycemic control, hyperlipidemia, and hypertension) factors. MVD was defined as the presence of retinopathy, peripheral neuropathy, or chronic kidney disease. Hazard ratio (HR) and 95% CI of CHD were estimated by multivariable Cox regression models.

Results

There were 3252 incident cases of CHD recorded after a median follow-up of 12.3 years. After multivariable adjustment, each MVD was separately associated with risk of CHD, and those who had 1 or ≥ 2 MVD had a 27% and an 87% increased risk of developing CHD, respectively. Each unfavorable CVHM was associated with a higher risk of CHD. As compared with MVD-free participants who had ideal CVHMs, those who had ≥ 2 MVD and had poor CVHMs were at particularly high risk of incident CHD (HR = 4.58; 95% CI: 3.58, 5.86), similarly when considering behavioral CVH or biological CVH separately. On an additive scale, there was a positive statistically significant interaction between number of MVD and CVHMs.

Conclusion

Coexistence of multiple MVDs was associated with a substantially higher risk of CHD among individuals with T2DM. Such association may be amplified by unfavorable CVHMs.
High hsCRP Concentration Is Associated With Acute Pancreatitis in Multifactorial Chylomicronemia Syndrome
Authors: Guay Simon-Pierre , Paquette Martine , Blais Chantal , Fortin Andréanne , Bernard Sophie , Baass Alexis
Published: February 2024

Background

Multifactorial chylomicronemia syndrome (MCS) is a severe form of hypertriglyceridemia (hyperTG) associated with an increased risk of acute pancreatitis. However, the risk of acute pancreatitis is very heterogenous in MCS. Previous studies suggested that inflammation might promote disease progression in hyperTG-induced acute pancreatitis.

Objective

To determine if low-grade inflammation is associated with acute pancreatitis in MCS.

Methods

This study included 102 subjects with MCS for whom high-sensitivity C-reactive protein (hsCRP) concentration was measured at their first visit at the Montreal Clinical Research Institute.

Results

Patients with MCS who had a previous history of acute pancreatitis had a significant higher hsCRP concentration (4.62 mg/L vs 2.61 mg/L; P = .003), and high hsCRP concentration (≥ 3 mg/L) was independently associated with acute pancreatitis prevalence (P < .05). Up to 64% of the variability in acute pancreatitis prevalence was explained by the maximal triglycerides (TG) concentration, hsCRP concentration, the presence of rare variants in TG-related genes, and fructose intake, based on a stepwise multivariate regression model (P < .0001).

Conclusion

This retrospective study showed for the first time that hsCRP concentration is strongly associated with acute pancreatitis prevalence in MCS. It also suggests that low-grade inflammation may be a driver of acute pancreatitis in severe hypertriglyceridemia. Prospective studies could help determine the causality of this association and assess whether medication known to reduce low-grade inflammation could help prevent acute pancreatitis in individuals with severe hypertriglyceridemia.
Can Ethanol Ablation Achieve Durable Control of Neck Nodal Recurrences in Adults With Stage I Papillary Thyroid Cancer?
Authors: Hay Ian D , Lee Robert A , Reading Carl C , Charboneau J William
Published: February 2024

Objective

Results of ethanol ablation (EA) for controlling neck nodal metastases (NNM) in adult patients with papillary thyroid carcinoma (APTC) beyond 6 months have rarely been reported. We now describe outcome results in controlling 71 NNM in 40 node-positive stage I APTC patients followed for 66 to 269 months.

Methods

All 40 patients were managed with bilateral thyroidectomy and radioiodine therapy and followed with neck ultrasound (US) for >48 months after EA. Cumulative radioiodine doses ranged from 30 to 550 mCi; pre-EA 27 patients (67%) had 36 additional neck surgeries. Cytologic diagnosis of PTC in 71 NNM selected for EA was confirmed by US-guided biopsy. EA technique and follow-up protocol were as previously described.

Results

The 40 patients had 1 to 4 NNM; 67/71 NNM (94%) received 2 to 4 ethanol injections (total median volume 0.8 cc). All ablated 71 NNM shrank (mean volume reduction of 93%); nodal hypervascularity was eliminated. Thirty-eight NNM (54%) with initial volumes of 12-1404 mm3 (median 164) disappeared on neck sonography. Thirty-three hypovascular foci from ablated NNM (pre-EA volume range 31-636 mm3; median 147) were still identifiable with volume reductions of 45% to 97% observed (median 81%). There were no complications and no postprocedure hoarseness. Final results were considered to be ideal or near ideal in 55% and satisfactory in 45%. There was no evidence of tumor regrowth after EA.

Conclusion

Our results demonstrate that for patients with American Joint Committee on Cancer stage I APTC, who do not wish further surgery or radioiodine, and are uncomfortable with active surveillance, EA can achieve durable control of recurrent NNM.
Characterizing Chronic Pain and Adverse Childhood Experiences in the Lesbian, Gay, Bisexual, Transgender, or Queer Community
Authors: Shirsat Nikita , Finney Nicole , Strutner Sami , Rinehart Joseph , Higgins K. Elliott , Shah Shalini
Published: February 2024

BACKGROUND:

Childhood adversity is associated with chronic pain in adulthood. Additionally, individuals identifying as lesbian, gay, bisexual, transgender, or queer (LGBTQ+) report a greater prevalence of chronic pain and increased adverse childhood experiences (ACEs). While the LGTBQ+ community has a disproportionately high chronic disease burden, limited research has been conducted on the associations between chronic pain conditions or intensity and childhood adversity in this population.

METHODS:

In this cross-sectional study, participants were 18 years or older, LGBTQ+ identifying, and reported chronic pain. Surveys were electronically distributed from August to November 2022 via LGBTQ+ organization email listservs and social media platforms. The survey included demographics and validated questionnaires measuring chronic pain (The Chronic Pain Questionnaire) and childhood adversity (ACE score). In analysis, ACE scores of 4 or more were defined as high.

RESULTS:

Responses from 136 individuals (average age of 29 ± 7.4 years) were analyzed. The mean for participants’ average pain rating in the last 6 months was 5.9 of 10. Participants’ worst pain was rated at least a 7 of 10 for 80% of respondents. Half (47%) had high ACE scores, and high ACE scores were significantly associated with higher average pain scores (6.27 ± 1.79, mean difference = −2.22, P = .028, 95% confidence interval [CI], –1.2 to −0.0), and higher perceived current pain ratings (4.53 ± 2.16, mean difference = −2.78, P = .007, 95% CI, –1.9 to −0.3). Transgender and gender diverse (TGD) participants (n = 75) had higher ACE scores (3.91 ± 1.78) and current pain scores compared to cisgender individuals (3.9 ± 1.8 vs 3.0 ± 1.9, P = .009, 95% CI, 0.0–0.3). History of any sexual trauma was prevalent in 36.7% and was associated with chronic pain located in the pelvic region (P = .016, effect size estimate 0.21). Specific histories of forced sexual and touch encounters were associated with a specific diagnosis of fibromyalgia (P = .008, effect size estimate 0.31 and P = .037, effect size estimate 0.31, respectively).

CONCLUSIONS:

Childhood adversity and chronic pain’s dose-dependent relationship among our LGBTQ+ sample indicates a need to explore trauma’s role in perceived pain. Given sexual trauma’s association with pain location and diagnosis, type of trauma may also be crucial in understanding chronic pain development. Research into the relationships between childhood adversity, sexuality, gender identity, and chronic pain could improve chronic pain prevention and management for the LGBTQ+ community.
Repeated Ultrasound-Guided Percutaneous Intercostal Cryoneurolysis for the Management of Chronic Postmastectomy Pain Syndrome: A Case Report
Authors: Gabriel Rodney A. , Kestenholz Renè , Filipovski Igor
Published: February 2024

Ultrasound-guided percutaneous cryoneurolysis of the intercostal nerves is an effective analgesic modality for the management of postmastectomy pain syndrome. The duration of analgesia provided by intercostal cryoneurolysis for chronic postmastectomy pain syndrome may vary. Furthermore, limited studies have described the repeated use of cryoneurolysis to manage chronic pain in these patients. In this case report, we describe the repeated use of ultrasound-guided cryoneurolysis of the intercostal nerves to manage chronic postmastectomy pain for 2.5 years. No adverse events or long-term neurologic sequelae were reported.
TBXT dose sensitivity and the decoupling of nascent mesoderm specification from EMT progression in 2D human gastruloids
Authors: Bulger Emily A. , Muncie-Vasic Ivana , Libby Ashley R. G. , McDevitt Todd C. , Bruneau Benoit G.
Published: February 2024

In the nascent mesoderm, TBXT expression must be precisely regulated to ensure that cells exit the primitive streak and pattern the anterior-posterior axis, but how varying dosage informs morphogenesis is not well understood. In this study, we define the transcriptional consequences of TBXT dosage reduction during early human gastrulation using human induced pluripotent stem cell models of gastrulation and mesoderm differentiation. Multi-omic single-nucleus RNA and single-nucleus ATAC sequencing of 2D gastruloids comprising wild-type, TBXT heterozygous or TBXT null human induced pluripotent stem cells reveal that varying TBXT dosage does not compromise the ability of a cell to differentiate into nascent mesoderm, but instead directly influences the temporal progression of the epithelial-to-mesenchymal transition with wild type transitioning first, followed by TBXT heterozygous and then TBXT null. By differentiating cells into nascent mesoderm in a monolayer format, we further illustrate that TBXT dosage directly impacts the persistence of junctional proteins and cell–cell adhesions. These results demonstrate that epithelial-to-mesenchymal transition progression can be decoupled from the acquisition of mesodermal identity in the early gastrula and shed light on the mechanisms underlying human embryogenesis.