bluuebunny/crossref_metadata_2025 huggingface dataset:
SMCVdb: a database of experimental cellular toxicity information for drug candidate molecules
Authors: Pandey Abhay Deep , Sharma Ghanshyam , Sharma Anshula , Vrati Sudhanshu , Nair Deepak T
Published: October 2024

Many drug discovery exercises fail because small molecules that are effective inhibitors of target proteins exhibit high cellular toxicity. Early and effective assessment of toxicity and pharmacokinetics is essential to accelerate the drug discovery process. Conventional methods for toxicity profiling, including in vitro and in vivo assays, are laborious and resource-intensive. In response, we introduce the Small Molecule Cell Viability Database (SMCVdb), a comprehensive resource containing toxicity data for over 24 000 compounds obtained through high-content imaging (HCI). SMCVdb seamlessly integrates chemical descriptions and molecular weight data, offering researchers a holistic platform for toxicity data aiding compound prioritization and selection based on biological and economic considerations. Data collection for SMCVdb involved a systematic approach combining HCI toxicity profiling with chemical information and quality control measures ensured data accuracy and consistency. The user-friendly web interface of SMCVdb provides multiple search and filter options, allowing users to query the database based on compound name, molecular weight range, or viability percentage. SMCVdb empowers users to access toxicity profiles, molecular weights, compound names, and chemical descriptions, facilitating the exploration of relationships between compound properties and their effects on cell viability. In summary, the database provides experimentally derived cellular toxicity information for over 24 000 drug candidate molecules to academic researchers, and pharmaceutical companies. The SMCVdb will keep growing and will prove to be a pivotal resource to expedite research in drug discovery and compound evaluation.

Database URL: http://smcvdb.rcb.ac.in:4321/
Pacemaker lead extraction saved a severe lead-induced tricuspid regurgitation: a case report
Authors: Chai YuLiang , Liu Qiang , Chen Zhiwen , Zhang Wenjing , Liu Yuanqing
Published: October 2024

Background

Pacemaker lead-induced tricuspid regurgitation is a common complication after cardiac implantable electronic device (CIED) implantation. Cardiac implantable electronic device lead removal is a challenge procedure.

Case summary

A 72-year-old lady was admitted due to worsening heart failure. She had a history of permanent atrial fibrillation and had a permanent single-chamber pacemaker implanted 8 years ago due to complete heart block. Transthoracic echocardiography identified severe lead-related tricuspid regurgitation. The patient underwent successful lead extraction and received a new implantation of left bunch bundle area pacing. Transthoracic echocardiographic examination 2 days after the procedure showed a significant decrease of the tricuspid regurgitation. The patient also reported an improvement in heart failure symptoms.

Discussion

Pacemaker lead-related tricuspid regurgitation introduces negative haemodynamic overload, carrying high risk for the development of heart failure and worse outcome. The present case shows a rapid relief of symptom and improvement of echocardiography findings, indicating the significance of mechanistic approach in the treatment of lead-related tricuspid mechanical interference.
‘A Matter of Joint Decision’: The Origins of British Nuclear Retaliation Procedures and the Murphy–Dean Agreement of 1958
Authors: Jones Matthew
Published: October 2024

Formally concluded by the British prime minister, Harold Macmillan, and the US president, Dwight D. Eisenhower, in June 1958, the Murphy–Dean Agreement was an important aspect of the Anglo-American nuclear relationship during the Cold War but has not yet been the subject of any detailed historical scholarship. Updated and reaffirmed by a succession of prime ministers and presidents, the Agreement’s sensitive but now declassified contents outlined the consultation procedures that would have to be followed if ever a decision was to be taken to use US nuclear forces based in the United Kingdom, or British forces equipped with US nuclear warheads. Based on new documentary evidence, this article offers the first analysis of the origins and background to the Murphy–Dean Agreement. It explains how the Agreement was rooted in the British government’s need to draw up its own initial set of nuclear retaliation procedures, which are outlined here for the first time; shows how the government was subjected to parliamentary pressure to conclude an agreement on consultation with the Americans; and argues that the eventual Agreement was highly significant in revealing the nature of the UK’s purported nuclear ‘independence’ in the late 1950s.
Understanding trends in social fluidity in Western Europe: class structural change and the OED triangle
Authors: Bukodi Erzsébet , Goldthorpe John H
Published: October 2024

We start from a general theory of intergenerational class mobility previously proposed as an alternative to the ‘liberal’ theory. In further evaluating these theories, we report empirical analyses of relations within the origins–education–destinations (OED) triangle, drawing on data for individuals born 1923–1977 in 17 European societies. In contrast with earlier research, we treat education in relative terms. We find that the tendency for fluidity to increase within class structures after World War II, rather than being the expression of a ‘worldwide secular trend’, was restricted to a distinctive historical period of rapid economic growth and class structural change. Furthermore, in accounting for this increasing fluidity, the role of education may easily be exaggerated. The weakening of the ‘direct’ OD association is of at least comparable importance to changes in the OE and ED associations. Consistently with the proposed theory, class structural change, insofar as it promotes greater upward mobility, would also appear to provide a favourable context for increasing fluidity. Where downward mobility increases, the growing motivation and the capacity of more advantaged parents to protect their children against déclassement constitutes a powerful source of resistance to change in endogenous mobility regimes.
A transcription factor, PbWRKY24, contributes to russet skin formation in pear fruits by modulating lignin accumulation
Authors: Wang Jialong , Wang Dong , Zhao Mingrui , Yu Mengyuan , Zheng Xiaodong , Tian Yike , Sun Zhijuan , Liu Xiaoli , Wang Caihong , Ma Changqing
Published: October 2024

Skin color is one of the major traits of fruit appearance quality in pear (Pyrus) that affects the fruit commodity value. Russet skin protects pear fruits from environmental stresses and its formation process is closely linked to lignin accumulation. However, the molecular regulatory networks underlying russet skin formation in pear fruits involve complex secondary metabolic pathways and remain elusive. Here, we explored the regulatory mechanisms underlying lignin accumulation in pear skin based on transcriptome sequencing, co-expression network analysis, and gene expression profiling. We identified a WRKY transcription factor gene, PbWRKY24, that regulates russet skin formation in pear fruits. The relative expression of PbWRKY24 in russet pear skin was significantly correlated with lignin content. We then verified the function of PbWRKY24 in lignin accumulation via genetic transformation. DNA affinity purification sequencing revealed that PbWRKY24 directly binds to the promoter of a lignin biosynthesis gene, PbPRX4. This binding was confirmed by yeast one-hybrid, dual-luciferase, and electrophoretic mobility shift assays. Overexpression of PbPRX4 in pear skin stimulated lignin accumulation and consequently promoted russet skin formation. This study provides a glimpse into the intricate lignin biosynthesis mechanisms during russet skin formation in pear fruits, which is of practical significance to pear breeding for fruit quality.
Legal Mobilization Networks and the LGBT Rights Revolution in Colombia (1992–2022): Using Litigation and Amicus Curiae Briefs in Rights Struggles
Authors: Jaramillo Juliana
Published: October 2024

Identifying what actors drive social change through the courts has been a central pursuit in the socio-legal literature. This article studies Colombia’s LGBT rights revolution (1992–2022) by focusing on the broad legal mobilization network that promoted these rights through litigation and amicus curiae briefs. While legal mobilization scholarship has traditionally explained significant legal reforms by focusing on social movements and their support structures, this study adopts a network approach to capture the diversity of both civil society and state actors involved in court-based rights struggles. Based on an original database of 133 rulings, interviews, and network analysis, this work shows the emergence of a broad and dense pro-LGBT network that played a crucial role in advancing LGBT rights and countering conservative-religious mobilization by exerting sustained pressure on judges, providing valuable information, and lending legitimacy to legal claims. This research demonstrates that a network approach contributes to developing a more comprehensive theory of the different actors, resources, and mobilizing structures that influence legal change.
Multidimensional analysis of matched primary and recurrent glioblastoma identifies contributors to tumor recurrence influencing time to relapse
Authors: Shekarian Tala , Ritz Marie-Françoise , Hogan Sabrina , Martins Tomás A , Schmassmann Philip , Gerber Alexandra , Roux Julien , Kaymak Deniz , Durano Célia , Burger Bettina , Matter Matthias , Hutter Gregor
Published: October 2024

Glioblastoma (GBM) is a lethal brain tumor without effective treatment options. This study aimed to characterize longitudinal tumor changes in order to find potentially actionable targets to prevent GBM relapse. We extracted RNA and proteins from fresh frozen tumor samples from patient-matched IDHwt WHO grade 4 primary (pGBM) and recurrent (rGBM) tumors for transcriptomics and proteomics analysis. A tissue microarray containing paired tumor samples was processed for spatial transcriptomics analysis. Differentially expressed genes and proteins between pGBM and rGBM were involved in synapse development and myelination. By categorizing patients into short (STTR) and long (LTTR) time-to-lapse, we identified genes/proteins whose expression levels positively or negatively correlated with TTR. In rGBM, expressions of Fcγ receptors (FCGRs) and complement system genes were negatively correlated with TTR, whereas expression of genes involved in DNA methylation was positively correlated with TTR. Spatial transcriptomics of the tumor cells showed enrichment of oligodendrocytes in rGBM. Besides, we observed changes in the myeloid compartment such as a switch from quiescent to activated microglia and an enrichment in B and T cells in rGBM with STTR. Our results uncover a role for activated microglia/macrophages in GBM recurrence and suggest that interfering with these cells may hinder GBM relapse.
Surgical treatment of coexisting intra and extralobar sequestration in an infant
Authors: Saleh Ahmad , Awwad Adam , Bhattacharyya Ratul , Bhattacharyya Nishith
Published: October 2024

Pulmonary sequestration is a rare congenital malformation in which a nonfunctional segment of lung tissue has no communication with the tracheobronchial tree and does not participate in gas exchange. We present a rare case of a 20-month old female with extralobar pulmonary sequestration that was diagnosed at birth. The patient was also found to have a coexisting intralobar sequestration, found during surgery.
Molecular line lists for the singlet states in gaseous YN at high temperature
Authors: Farhat Ayman , Hammoud Sami
Published: October 2024

Our aim in this study is to investigate the electronic structure of the gaseous YN molecule and provide an accurate molecular line list of spectroscopic transitions between the five lowest singlet states. The calculations were done by using large basis set for yttrium aug-cc-pVQZ-PP with relativistic effective core potentials at the spin-free level. We first used the method of complete active space self-consistent field, which was followed by the multireference singles and doubles configuration interaction. Potential energy curves and permanent and transition dipole moments were calculated at the internuclear distance range of 1.3–2.96 Å. For each state, we calculated the spectroscopic constants (Te, ωe, ωexe, ωeye, Be, αe, Re). The calculated values of the spectroscopic constants are in excellent agreement with the experimental constants available, with a relative difference of less than 5 cm−1. We further calculated the transition intensities of allowed transitions, and we provided the absorption spectra up to a temperature of 4000 K. The computed molecular line list contains 2.6 million transitions calculated between almost 18 186 vibro-rotational energy levels. It covers the frequency range between 0 and 30 000 cm−1. The effect of temperature on the spectra of hot YN was investigated with partition functions calculated between 298 and 4000 K. This study should help in identifying the singlet state spectrum of the hot YN molecule, which is possibly found in the atmospheres of cool stars and hot rocky super-Earths.
Generalized linear model study of the T90–T50 relation of gamma-ray bursts
Authors: Dutta Sourav , Sunanda  , Moharana Reetanjali , Kumar Manish
Published: October 2024

Gamma-ray bursts (GRBs) can be studied with their linearly dependent parameters alongside the standard $T_{90}$ distribution. The generalized linear model (GLM) identifies the number of linear dependences in a two-parameter space. Classically, GRBs are classified into two classes by the presence of bimodality in the histogram of $T_{90}$. However, additional classes and different features of GRBs are fascinating topics to explore. In this work, we investigate GRB features in the $T_{90} {-}T_{50}$ plane using the GLM for three major catalogues: Swift, the Fermi Gamma-ray Burst Monitor (GBM), and the Burst And Transient Source Experiment (BATSE). This study shows five linear features for the Fermi GBM catalogue and four linear features for the BATSE catalogue, directing us towards the possibility of non-Gaussianity in the light curves of GRBs.
A two-minute burst of highly polarized radio emission originating from low Galactic latitude
Authors: Dobie Dougal , Zic Andrew , Oswald Lucy S , Pritchard Joshua , Lower Marcus E , Wang Ziteng , Qiu Hao , Hurley-Walker Natasha , Wang Yuanming , Lenc Emil , Kaplan David L , Anumarlapudi Akash , Auchettl Katie , Bailes Matthew , Cameron Andrew D , Cooke Jeffrey , Deller Adam , Driessen Laura N , Freeburn James , Murphy Tara , Shannon Ryan M , Stewart Adam J
Published: October 2024

Several sources of repeating coherent bursts of radio emission with periods of many minutes have now been reported in the literature. These ‘ultralong period’ (ULP) sources have no clear multiwavelength counterparts and challenge canonical pulsar emission models, leading to debate regarding their nature. In this work, we report the discovery of a bright, highly polarized burst of radio emission at low Galactic latitude as part of a wide-field survey for transient and variable radio sources. ASKAP J175534.9$-$252749.1 does not appear to repeat, with only a single intense two-minute $\sim$200-mJy burst detected from 60 h of observations. The burst morphology and polarization properties are comparable to those of classical pulsars but the duration is more than one hundred times longer, analogous to ULPs. Combined with the existing ULP population, this suggests that these sources have a strong Galactic latitude dependence and hints at an unexplored population of transient and variable radio sources in the thin disc of the Milky Way. The resemblance of this burst with both ULPs and pulsars calls for a unified coherent emission model for objects with spin periods from milliseconds to tens of minutes. However, whether or not these are all neutron stars or have the same underlying power source remains open for debate.
Effectiveness and Safety of Bictegravir/Emtricitabine/Tenofovir Alafenamide in Late-Presenting People With HIV-1 Infection
Authors: Yang Xiaoyan , Xie Xiaoxin , Fu Yanhua , Gan Lin , Ma Shujing , Long Hai
Published: October 2024

Background

The efficacy and safety of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) have been demonstrated in treatment-naive clinical trials. However, real-world evidence for this regimen in late-presenting patients with HIV-1 (PWH) is lacking. We investigated the virologic and safety outcomes of BIC/FTC/TAF in late-presenting PWH.

Methods

This retrospective cohort analysis consisted of late-presenting PWH who initiated an antiretroviral regimen of BIC/FTC/TAF between June 2021 and June 2023. Treatment effectiveness, defined as HIV-1 RNA <50 copies/mL, was analyzed. Changes in immunologic, metabolic, liver, and renal parameters were evaluated. Late-presenting PWH were defined as surviving PWH with CD4 <200 cells/μL or surviving patients who met the criteria for AIDS-defining conditions with a CD4 ranging from 200 to 499 cells/μL.

Results

A total of 130 participants were included in the study. At week 48, 93.8% (122/130) of the patients achieved HIV-1 RNA levels <50 copies/mL. CD4 increased by 150.0 cells/μL, and CD4/CD8 increased by 0.16 (P < .001). Sixteen (12.3%) participants experienced adverse events, and 6 (4.6%) experienced drug-related adverse events. None of the participants discontinued treatment due to either a lack of effectiveness or adverse events.

Conclusions

BIC/FTC/TAF demonstrated robust virologic suppression and tolerability in patients presenting late in the course of HIV infection.
TRANSPARENT TESTA 16 collaborates with the MYB-bHLH-WD40 transcriptional complex to produce brown fiber cotton
Authors: Li Yuanxue , Yao Tian , Fu Chao , Wang Nian , Xu Zhiyong , Yang Ningyu , Zhang Xianlong , Wen Tianwang , Lin Zhongxu
Published: October 2024

Naturally colored cotton (NCC; Gossypium spp.) does not require additional chemical dyeing and is an environmentally friendly textile material with great research potential and applications. Our previous study using linkage and association mapping identified TRANSPARENT TESTA 2 (Gh_TT2) as acting on the proanthocyanin synthesis pathway. However, limited information is available about the genetic regulatory network of NCC. Here, we verified the effectiveness of Gh_TT2 and the roles of Gh_TT2 and red foliated mutant gene (Re) in pigment formation and deposition of brown fiber cotton (BFC). Variations in Gh_TT2 derived from interspecific hybridization between Gossypium barbadense acc. Pima 90-53 and Gossypium hirsutum acc. Handan208 resulted in gene expression differences, thereby causing phenotypic variation. Additionally, the MYB-bHLH-WD complex was found to be negatively modulated by TRANSPARENT TESTA 16/ARABIDOPSIS BSISTER (TT16/ABS). RNA-seq suggested that differential expression of homologous genes of key enzymes in the proanthocyanin synthesis pathway strongly contributes to the color rendering of natural dark brown and light brown cotton. Our study proposes a regulatory model in BFC, which will provide theoretical guidance for the genetic improvement of NCC.
Role of Embolic Protection in Percutaneous Coronary Intervention Without Saphenous Venous Graft Lesions in ST-Segment–Elevation Myocardial Infarction: A Systematic Review and Meta-Analysis
Authors: Maliha Maisha , Satish Vikyath , Chi Kuan Yu , Zeas Diego Barzallo , Kharawala Amrin , Shama Nishat , Abittan Nathaniel , Nandy Sneha , Osabutey Anita , Madan Nidhi , Singh Prabhjot , Gashi Eleonora
Published: October 2024

Introduction:

Embolic protection devices (EPDs) are catheter-based devices that can be used to capture atherosclerotic remnants released during percutaneous coronary intervention (PCI). We aim to study the efficacy and safety of EPDs in PCIs without saphenous vein grafts (SVGs) in ST-segment–elevation myocardial infarction (MI).

Methods:

Three electronic databases of MEDLINE, Web of Science, and Embase were searched from inception to April 10, 2024, to identify relevant randomized controlled trials that compared outcomes of patients subjected to EPD during PCI with a control group where EPDs were not utilized. The primary outcome was 30-day all-cause mortality. Secondary outcomes were major adverse cardiovascular and cerebrovascular events at 30 days, post-PCI thrombolysis in MI grade 3 flow attainment, ST-segment resolution at 90 minutes post-procedure, and postprocedure angiographically detectable signs of distal embolization. The effect estimates of outcomes were assessed using risk ratio (RR) with a 95% confidence interval (CI). Random-effects meta-analysis was conducted using the restricted maximum likelihood method, given that the interstudy variance was inevitable.

Results:

We included 3 randomized controlled trials enrolling 741 patients (age, 61.6 ± 12.15 years; 22% females) undergoing PCI without SVG lesions. As opposed to the control group, the use of EPD did not yield a significant effect on all-cause mortality [RR, 0.76 (95% CI, 0.31–1.86); I2 = 0%], major adverse cardiovascular and cerebrovascular events [RR, 0.66 (95% CI, 0.34–1.27); I2 = 0%], post-PCI thrombolysis in MI 3 flow [RR, 1.18 (95% CI, 0.86–1.62); I2 = 77%], and ST-segment resolution at 90 minutes post-procedure [RR, 1.05 (95% CI, 0.90–1.22); I2 = 0%]. However, EPD significantly decreased angiographically detectable signs of distal embolization [RR, 0.60 (95% CI, 0.36–0.99); I2 = 0%].

Conclusions:

EPD significantly reduced angiographically detectable signs of distal embolization in PCI without SVG lesions in ST-segment–elevation MI though there were no clinical signs of improved flow or mortality. Further trials are necessary to thoroughly evaluate the potential benefits and requirements of EPD usage in such procedures.
Economics of risk stratification for skin cancer screening in solid organ transplant recipients
Authors: McAuliffe Dominic L. , Griffith Cynthia F. , Korzeniowski Pamela
Published: October 2024

Background:

Solid organ transplant recipients (SOTRs) have different risks of developing skin cancer depending on patient characteristics. However, there is currently no widely used tool to stratify skin cancer risk in these patients. The Skin and Ultraviolet Neoplasia Transplant Risk Assessment Calculator (SUNTRAC) is an attempt to stratify skin cancer risk in SOTRs and guide screening recommendations for those patients.

Materials and methods:

It was assumed that the 2022 solid organ transplant population in the United States would follow the same distribution of skin cancer risk as the population in the study that led to the development of the SUNTRAC. The total number of skin cancer screening visits and the total cost of those visits over 10 years were determined utilizing the screening recommendations in the SUNTRAC.

Results:

If all SOTRs received yearly skin cancer screens, 428,870 office visits would be conducted over 10 years for a total cost of $94,780,270. If the SUNTRAC were utilized, 336,666 office visits would be conducted for a 10-year cost of $74,403,186.

Conclusions:

Utilizing the SUNTRAC to guide skin cancer screening recommendations in SOTRs has the potential to minimize over-screening and lower the total cost of skin cancer screening visits for SOTRs. Initial studies into the applicability of the SUNTRAC have found similar risk distribution in different populations of SOTRs. Utilizing this model to guide skin cancer screening recommendations will better allocate resources to the highest risk patients while also avoiding unnecessary health care costs.
Plan of Care Visits
Authors: Masiano Steven P. , Rose Susannah , Wolfe Judith , Albert Nancy M. , Milinovich Alex , Jurecko Leslie , Ridgeway Beri , Kattan Michael W. , Misra-Hebert Anita D.
Published: October 2024

Background:

Plan of Care of Visits (POCV), including the patient, nurse, and hospital provider were implemented across an integrated health system to improve provider-patient communication during hospitalization and patient outcomes.

Objectives:

To assess POCV adoption after implementation, patient characteristics assosites were classified as teachsites were classified as teachsites were classified as teachsites were classified as ciated with POCV completion, and association of POCV with 30-day readmissions.

Methods:

This retrospective cohort study utilized electronic medical record (EMR) data of 237,430 adult patients discharged to home from 11 hospitals from January 2020 to December 2022. POCV completion was a discrete EMR variable. POCV adoption was estimated monthly by hospital as proportion of patients with at least 1 POCV during hospitalization, with variation among hospitals measured using the Variance Partition Coefficient (VPC). Multivariable logistic regressions assessed factors associated with POCV completion and POCV association with 30-day readmission.

Results:

POCV adoption increased from 69% to 94% (2020–2022) and varied by 50% across hospitals (VPC 0.50, 95% CI: 0.29–0.70). Odds of a discharge-day POCV were lower among older patients (≥65 vs. 18–34 y, OR 0.81, CI: 0.79–0.83), and higher among female (OR 1.06; CI: 1.04–1.07), Asian (vs. White, OR 1.13; CI: 1.06–1.21), Hispanic (OR 1.09; CI: 1.05–1.13), and surgical patients (vs. medical, OR 1.33; CI: 1.30–1.35). Patients completing discharge-day POCV had lower 30-day readmission odds (2022 OR 0.76, CI: 0.73–0.79). Patients with POCV on ≥75% of hospital days had similar readmission odds trends.

Conclusions:

POCV implementation was successful, and POCV completion was associated with fewer 30-day readmissions. Future work should focus on increasing POCV adoption while reducing hospital variation.
The current state of tolerance induction in vascularized composite allotransplantation
Authors: Blades Caitlin M. , Huang Christene A. , Mathes David W.
Published: October 2024

Purpose of review

Significant advancements have been made in the field of vascularized composite allotransplantation (VCA); however, like solid organ transplantation, bypassing the recipient's immune response remains a significant obstacle to long-term allograft survival. Therefore, strategies to overcome acute and chronic rejection and minimize immunosuppressive therapy are crucial for the future of VCA. This review highlights recent attempts to induce tolerance in VCA and discusses key findings through a clinical lens.

Recent findings

Promising VCA tolerance protocols are being investigated, with five recent studies illustrating various successes. These preclinical approaches demonstrate a correlation between the presence of donor-derived T cells and VCA tolerance, the importance of using clinically available reagents within preclinical protocols, and the ability to induce sustained tolerance through nonmyeloablative methods. Furthermore, environmental factors, such as NB-UVB light are being investigated for their immunomodulation properties and may influence VCA graft rejection.

To widen the scope of VCA, minimization of immunosuppression is needed. Overall, tolerance induction protocols should have a low-toxicity level, minimally invasive induction therapies, and utilize short-term immunosuppressive medications. By examining the milestones of recent studies, researchers can gain new technical approaches to immune modulation and make data-driven amendments to tolerance protocols in preparation for clinical translation.
The paradox of Helicobacter pylori: how does H. pylori infection protect against esophageal cancer?
Authors: Banisefid Erfan , Nasiri Ehsan , Pourebrahimian Leilabadi Seyedyashar , Hamzehzadeh Sina , Akbarzadeh Mohammad Amin , Hosseini Mohammad-Salar
Published: October 2024

Helicobacter pylori is a microaerophilic gram-negative bacterium infecting around half of the world’s population. Despite its well-known role in gastric malignancies, its impact on esophageal cancer comes with a complex paradox. Several mechanisms have been proposed to explain its observed lack of carcinogenic activity in the esophagus, including the trigger of anti-inflammatory pathways, promoting atrophic gastritis, and esophageal microbiome modulation. However, recent studies have highlighted a significantly more complicated interplay, where H. pylori, typically considered a pathogen, may even deliver a protective effect against esophageal carcinogenesis. This paper aims to evaluate the prevalence of H. pylori infection among patients with esophageal carcinoma, discussing the underlying mechanisms of the paradoxical effects of H. pylori on esophageal cancer.
Mechanical thrombectomy by stent retriever for the treatment of arterial ischemic stroke in a pediatric patient with acute lymphoblastic leukemia: a case report
Authors: Khameneh Bagheri Arash , Khalili Mitra , Alavi Samin , Khaffafpour Zahra , Aghapour Mehdi , Zamani Alireza , Mirmoghaddam Paniz
Published: October 2024

Introduction:

Arterial ischemic stroke (AIS) caused by occlusion of large vessels in childhood is a devastating rare condition that can contribute to long-term disabilities. Childhood leukemia is identified as a recognized risk factor for ischemic strokes. Mechanical thrombectomy is the standard of care for large vessel occlusions in adults. However, there are still no definite recommendations regarding the application and outcomes of endovascular thrombectomy and the devices used for pediatric patients with arterial ischemic stroke.

Case presentation:

The authors report a 13-year-old female with acute lymphoblastic leukemia who developed AIS due to thrombosis in the left internal carotid and proximal middle cerebral artery in the induction phase of treatment. The patient underwent successful mechanical thrombectomy via Solumbra by using “Embolus Retriever with Interlinked Cages (ERIC)” stent retriever and Sofia plus catheter, which resulted in successful recanalization of ICA and MCA.

Discussion:

Selected pediatric patients with AIS due to large vessel occlusions can benefit from mechanical thrombectomy. Although the recently published literature demonstrated the efficacy and safety of MT in children, strong guideline recommendations are still absent. At present, the last AHA/ASA guidelines for early management of AIS recommends intravenous thrombolysis and endovascular therapy in adults, whereas controversy still exists in children. An urgent approach within the defined therapeutic time frame and a multidisciplinary team specialized in pediatric stroke with professionally trained interventional neuroradiologist is essential for achieving optimal results.

Conclusion:

Mechanical thrombectomy provides promising results with high rates of arterial recanalization and favorable outcomes in pediatric patients with AIS.
Nurses’ Perception of Firearm Safety
Authors: Cypress Brigitte S. , Caboral-Stevens Meriam , Rosario-Sim Maria G. , Sagar Priscilla L.
Published: October 2024

Background

Firearm or gun violence has become a significant and ongoing public health crisis in the United States. There is little evidence of the current practices of nurses in assessing, screening, and counseling patients and families on firearm ownership and safety.

Objectives

The purpose of this exploratory qualitative study was to explore the attitudes, perceptions, and current practices in assessing, screening, and counseling gun ownership and safety among registered nurses, with a secondary aim of identifying the facilitators and barriers to implementing the practice.

Method

An exploratory qualitative research study design was used. We recruited focus group participants via e-mail, social media blasts, referrals, and personal contact requests. Participants were interviewed using structured focus group questions via Zoom. Five focus groups included 32 registered and advanced practice nurses. The audio-recorded and transcribed data were analyzed using Braun and Clarke’s approach to thematic analysis.

Results

We identified four key themes. First, there was a significant need to educate and train nurses in the assessment, screening, and counseling about firearm safety. Second, there was a need to extend this education to patients, families, and the community. Third, there was a need to advocate for the creation and implementation of policies. Fourth, there was a need to implement mental health assessment as a standard practice before owning a gun, which emerged as a potential solution. Additionally, we found a need to address barriers to assessment and counseling on gun use. The creation of state laws and organizational policies, along with the provision of current data, emerged as other facilitators for assessment, screening, and counseling among nurses about firearms use and safety.

Discussion

Ours is one of the first studies to explore attitudes and perceptions about gun ownership and current practices in gun safety assessment, screening, and counseling among registered nurses. The findings lay some foundation for a focused, multifaceted approach and interventions to address gun violence and safety concerns.
Revolutionizing nurse well-being
Authors: Clough Amy L. , Breda Karen Lucas , Plaskonka Abby
Published: October 2024

This article describes an 8-week pilot project implementing virtual reality (VR) technology as a stress relief intervention for nurses at a rural hospital. It highlights how VR allowed nurses to temporarily disconnect from their stressful work environment and experience calming virtual scenarios during break times.
“Evaluation of palatal bone regeneration in cleft palate patients following a two-stage palatoplasty using a modified Furlow procedure”
Authors: Teblick Sofie , Van de Casteele Elke , Scheuermann Maria , Vanreusel Inne , Renier Lieven , Nadjmi Nasser
Published: October 2024

Background:

A palatal cleft can be reconstructed using various palatoplasty techniques. Many techniques use local mucoperiosteal flaps to close the hard palate cleft, without closing the underlying bone defect. The purpose of this study was to explore the possibility of spontaneous bone regeneration in the remaining bone defect following a two-stage palatoplasty. Furthermore, the effect of this bone regeneration on transverse maxillary growth was studied

Methods:

A retrospective study of unilateral cleft lip and palate patients was performed. Cleft size was measured at the hard-soft palate junction on plaster models obtained during palatoplasty. Residual bony cleft was evaluated at the time of alveolar process reconstruction using CBCT images. The presence of crossbites was evaluated through clinical photographs to evaluate transverse maxillary growth.

Results:

Forty-six patients were included in this study. Thirteen patients (28%) presented with complete ossification of the hard palate at the age of six years. Six patients (13%) had no ossification, while twenty-seven patients (59%) demonstrated partial closure, averaging 75% of the total hard palate length. All patients with complete closure and 89% of patients with partial closure presented without lateral crossbites. Statistical analysis revealed no significant correlation between lateral crossbites and the extent of hard palate ossification (p = 0.4314).

Conclusions:

87% of children presented with at least partial ossification of the hard palate after a two-stage palatoplasty, indicating the potential for spontaneous bone regeneration. Importantly, lateral crossbites demonstrated no correlation with palatal ossification (p = 0.1819), suggesting no detrimental impact of regenerated bone on transverse maxillary growth.
Comparing Innervated and Non-Innervated Glabrous Skin Flaps for Volar Digital Defects: Insights from Patient-Reported Outcomes
Authors: Huang Ren-Wen , Chi Mu-Chieh , Hsieh Yun-Huan , Hsu Chung-Chen , Lin Yu-Te , Lin Chih-Hung , Lin Cheng-Hung
Published: October 2024

Background:

Volar soft tissue defects in digits necessitate reconstructions that restore appearance sensation and minimize complications. This study compares innervated toe pulp (TP) and non-innervated medialis pedis (MP) flaps for reconstructing such defects, focusing on objective and subjective outcomes.

Methods:

Between 1998 and 2017, 101 free glabrous skin flap reconstructions were performed at our institution for volar digital soft tissue injuries, comprising 75 TP and 26 MP flaps. Follow-up assessments included the Michigan Hand Outcomes Questionnaire, Disabilities of the Arm, Shoulder and Hand Questionnaire, Foot and Ankle Disability Index, and sensory testing (static and moving two-point discrimination, Semmes-Weinstein monofilament test). Data analysis utilized the Mann-Whitney U test and Pearson correlation coefficients.

Results:

The study cohort included 29 participants (15 TP, 14 MP) with an average follow-up of 106 months. Functional and sensory outcomes revealed no significant differences between TP and MP flaps. Both flap types achieved satisfactory function and sensibility, with no statistically significant distinctions in patient-reported outcomes. Subjective complaints were similarly distributed across both groups, with a few reports of cold intolerance and discomfort at the donor site in the TP group.

Conclusions:

TP and MP flaps provide adequate coverage and sensory outcomes for volar digital defects without significant differences between innervated and non-innervated flap transfers. The flap choice should be tailored to individual patient needs and defect characteristics, emphasizing the importance of patient-centered decision-making in reconstructive surgery. Further research is required to explore the long-term outcomes of these reconstruction methods, especially for larger defects.
A Stepped-Wedge, Cluster-Randomized, Multisite Study of Text Messaging Plus Peer Navigation to Improve Adherence and Viral Suppression Among Youth on Antiretroviral Therapy
Authors: Taiwo Babafemi O. , Kuhns Lisa. M. , Agbaji Oche , David Agatha , Akanmu Sulaimon , Akinbami Akinyinka , Omigbodun Olayinka , Adekanmbi Folashade , Yiltok Esther , Ezemelue Priscilla , Akintan Patricia , Sodipo Olujimi , Awolude Olutosin , Kuti Kehinde , Mautin Gbenayon , Badru Titilope , Cervantes Marbella , Janulis Patrick , Okonkwor Ogochuckwu , Berzins Baiba , Garofalo Robert
Published: October 2024

Background:

To address the need for improved virologic suppression among youth living with HIV (YLH) on antiretroviral treatment (ART), we evaluated peer navigation plus TXTXT daily text message ART reminders.

Setting:

YLH aged 15–24 years on ART for at least 3 months at 6 research sites in 4 Nigerian cities.

Methods:

Using a stepped-wedge design, cluster 1 was nonrandomized, whereas clusters 2 and 3 were randomized to sequences of routine care (control period) and 48 weeks of the combination intervention (intervention period). The primary end point was viral suppression (HIV-1 RNA <200 copies/mL) at week 48 of the intervention. Secondary end points included adherence measured by self-report (

90% considered adherent). Post hoc analysis assessed virologic control at <50 copies per milliliter and <1000 copies per milliliter. Generalized estimating equations determined the difference between intervention and control periods in the intention-to-treat population.

Results:

We enrolled 558 YLH and followed 541 over time, mean age 18 years, 53.8% female, 71.7% perinatally infected, and 38.6% virologically nonsuppressed at enrollment. For the primary end point, the intervention periods displayed a small, nonsignificant increase in viral suppression < 200 copies per milliliter [odds ratio (OR) = 1.16 (0.88–1.54), P = 0.297]. There was a significant effect of the combination intervention on virologic control <1000 copies per milliliter (OR = 1.42 [1.03–1.94], P = 0.030). Self-reported adherence also improved (OR = 2.07 [1.46–2.95], P < 0.001).

Conclusions:

Peer navigation plus daily text message ART reminders demonstrated limited benefit among ART-experienced, predominantly perinatally infected YLH, with no significant effect on viral suppression below 200 copies per milliliter despite improvement in self-reported adherence.
Prevalence and Clinical Correlates of Endometriosis in Patients With IC/BPS
Authors: Namugosa Mary , El Haraki Amr , Ritts Rory , Ferrara Kaylee , Badlani Gopal , Evans Robert , Walker Stephen J.
Published: October 2024

Importance

Interstitial cystitis/bladder pain syndrome (IC/BPS) presents as a complex heterogeneous disorder that poses a significant clinical challenge both for diagnosis and treatment. The identification of patient subgroups with significant overlap in their nonurological associated symptoms, including endometriosis, may enable a more targeted therapeutic approach.

Objective

This study investigated the prevalence, clinical correlates, and clinical sequelae associated with concurrent endometriosis in patients with IC/BPS.

Study Design

Demographic, clinical, surgical, and questionnaire data from female patients (n = 533) with a diagnosis of IC/BPS were evaluated in this retrospective cohort study. Surgical history was obtained from patient electronic medical records, using Current Procedural Terminology (CPT) and International Classification of Diseases (ICD) codes. Data from participants with and without concurrent endometriosis were compared using univariate analysis, followed by binary logistic regression to identify associated variables.

Results

Of 533 participants, 108 (20.3%) reported a history of endometriosis. Those with concurrent endometriosis were younger, had a larger bladder capacity, and had a higher number of nonurological associated symptoms. Patients with concurrent endometriosis were less likely to have a history of cystectomy (the surgical removal of the bladder) and report allergies but more prone to report comorbidities such as chronic pelvic pain, chronic fatigue, fibromyalgia, migraines, and pelvic floor dysfunction. Binary logistic regression identified a positive association between endometriosis and chronic pelvic pain, and a negative association between allergies and low bladder capacity for those with concurrent endometriosis.

Conclusions

Endometriosis is common in younger female patients with IC/BPS and is associated with a non–bladder-centric (ie, systemic pain disorder) phenotype.
In Vitro Experiment Present ROCK2 Inhibition Promotes the Therapeutic of Bevacizumab in Treatment of Glioblastoma Multiforme
Authors: Lai Jun , Zhang Xiaojing , Liang Kaixin
Published: October 2024

Objective

Gliomas are a general designation for neuroepithelial tumors derived from the glial cells of the central nervous system. According to the histopathological and immunohistochemical features, the World Health Organization classifies gliomas into four grades. Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor that has been approved for the treatment of glioblastoma multiforme (GBM) as a second-line therapy. However, its efficacy remains limited. Rho/Rho-associated kinase (ROCK) is a downstream molecule of small guanosine triphosphatases (GTPases) that regulates multiple cellular processes, including motility, migration, and proliferation. Thus, ROCK has been regarded as a therapeutic target for cardiovascular diseases, neurological diseases, immune diseases, and cancer, and ROCK inhibitors have high potential clinical value.

Methods

Viability rate of cells was detected using MTT assay, and apoptosis of cells was detected using FACS. Expression of target genes and proteins was detected using qPCR and western blotting analysis. Concentration of cytokines was detected using ELISA methods.

Results

Viability and migration of GBM cells were reduced after bevacizumab treatment and that these effects were enhanced by ROCK2 inhibition. We further found that ROCK2 inhibition promoting the effect of bevacizumab was mainly mediated by the RhoA/ROCK2 pathway, further inducing apoptosis in GBM cells. In addition, we found that angiogenesis and degradation of cellular matrix-related cytokines were reduced by ROCK2 inhibition.

Conclusions

ROCK2 inhibition contributes to the therapeutic effects of bevacizumab.
Bridging biomolecular modalities for knowledge transfer in bio-language models
Authors: Prakash Mangal , Moskalev Artem , DiMaggio Peter A. , Combs Steven , Mansi Tommaso , Scheer Justin , Liao Rui
Published: October 2024

In biology, messenger RNA (mRNA) plays a crucial role in gene expression and protein synthesis. Accurate predictive modeling of mRNA properties can greatly enhance our understanding and manipulation of biological processes, leading to advancements in medical and biotechnological applications. Utilizing bio-language foundation models allows for leveraging large-scale pretrained knowledge, which can significantly improve the efficiency and accuracy of these predictions. However, mRNA specific foundation models are notably limited posing challenges for efficient predictive modeling in mRNA-focused tasks. In contrast, DNA and protein modalities have numerous general-purpose foundation models trained on billions of sequences. This paper explores the potential for adaptation of existing DNA and protein bio-language models for mRNA-focused tasks. Through experiments using various mRNA datasets curated from both public domain and internal proprietary database, we demonstrate that pre-trained DNA and protein models can be effectively transferred for mRNA-focused tasks using various adaptation techniques such as probing, full-rank, and low-rank finetuning. In addition, we identify key factors that influence successful adaptation, offering guidelines on when general-purpose DNA and protein models are likely to perform well for mRNA-focused tasks. We further assess the impact of model size on adaptation efficacy, finding that medium-scale models often outperform larger ones for cross-modal knowledge transfer. We conclude that by leveraging the interconnectedness of DNA, mRNA, and proteins, as outlined by the central dogma of molecular biology, the knowledge in foundation models can be effectively transferred across modalities, significantly enhancing the repertoire of computational tools available for mRNA analysis.
Stereotype of mouse social competency and status revealed by a novel competition paradigm in combination with available paradigms
Authors: Liu Meiqiu , Chen Yue , Chen Rongqing
Published: October 2024

With the acceleration of urbanization process, psychological, behavioral and biological studies on social organization and competition are boosting. The mouse has been recognized as valuable and economic model animal for biomedical research in social behaviors, but the application of reliable, valid and easily executable social competition paradigm for mouse is still limited. Moreover, discrepant paradigms containing different competitive factors such as muscular confrontation, threatening level, boldness or timidity tendency might lead to task-specific win-or-lose outcomes and confusing rankings. Here, we developed a convenient mouse competition behavioral paradigm in which contenders were a pair of mice eager to take over the same food pellet hidden under a movable block in the middle of a narrow chamber where they were separated to the either right or left side. Our design mentality of this food pellet competition test (FPCT) avoids the direct violent competition between mice and facilitates to expose the psychological motivation of the contenders. Application of FPCT in combination with typically available paradigms, tube test and warm spot test (WST), discovered a stereotypic property of mouse social organization and competitivity in a given society of either males or females that were raised in an either 2– or 3-member cage, indicating that hierarchical sense of animals might be part of a comprehensive identify of self-recognition of individuals in an established society. More importantly, FPCT may largely facilitate the researches regarding the social organization and competition due to its reliability, validity and easy operability.