bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of the safety and efficacy of combination chemotherapy and PD-1/PD-L1 inhibitor treatment of breast cancer: A meta-analysis
Authors: Qian Da , Xu Yuhao , Wu Yihao , Qiu Jie , Hong Weimin , Meng Xuli 
Published: June 2023

Abstract

Background:
As the efficacy of programmed cell death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors combined with chemotherapy in curing breast cancer is still controversial, this meta-analysis compares the efficacy and safety of PD-1/PD-L1 inhibitors combined with chemotherapy and chemotherapy alone in the treatment of breast cancer, which provides guidance for the clinical treatment.

Methods:
Relevant studies published as of April 2022 in the various databases including EMBASE, PubMed, and Cochrane Library were selected. Randomized controlled trials (RCTs) in which control patients underwent chemotherapy alone and experimental group patients underwent combination chemotherapy and PD-1/PD-L1 inhibitor treatment were included in this investigation. Investigations without complete information, researches from which information could not be extracted, duplicate articles, animal studies, review articles, and systematic reviews were excluded. STATA 15.1 was employed for all statistical analyses.

Results:
In total, eight eligible studies were identified, revealing that combination chemotherapy and PD-1/PD-L1 inhibitor treatment was linked to significant increases in progression-free survival (PFS) relative to chemotherapy alone (hazard ratio [HR] = 0.83, 95% confidence interval [CI]: 0.70–0.99, P = 0.032) but not overall survival (HR = 0.92, 95% CI: 0.80–1.06, P = 0.273). Pooled adverse event rates were also increased within the group of combination treatment relative to the chemotherapy group (risk ratio [RR] = 1.08, 95% CI: 1.03–1.14, P = 0.002). Specifically, nausea rates were lesser within the group of combination treatment relative to the group of chemotherapy (RR = 0.48, 95% CI: 0.25–0.92, P = 0.026). Subgroup analyses indicated that the PFS of patients who underwent combination atezolizumab or pembrolizumab and chemotherapy treatment were substantially longer than those of patients who underwent chemotherapy alone (HR = 0.79, 95% CI: 0.69–0.89, P ≤0.001; HR = 0.79, 95% CI: 0.67–0.92, P = 0.002).

Conclusions:
The pooled results suggest that combination chemotherapy and PD-1/PD-L1 inhibitor treatment approaches help prolong PFS in breast cancer patients, but have no statistically significant effect on overall survival (OS). Additionally, combination therapy can significantly improve complete response rate (CRR) compared with chemotherapy alone. However, combination therapy was associated with greater rates of adverse events.
H19 recruited N6-methyladenosine (m6A) reader YTHDF1 to promote SCARB1 translation and facilitate angiogenesis in gastric cancer
Authors: Bai Rumeng , Sun Miaomiao , Chen Yuanyuan , Zhuo Shuaishuai , Song Guoxin , Wang Tianjun , Zhang Zhihong 
Published: June 2023

Abstract

Background:
Angiogenesis is described as a complex process in which new microvessels sprout from endothelial cells of existing vasculature. This study aimed to determine whether long non-coding RNA (lncRNA) H19 induced the angiogenesis of gastric cancer (GC) and its possible mechanism.

Methods:
Gene expression level was determined by quantitative real-time polymerase chain reaction and western blotting. Cell counting kit-8, transwell, 5-Ethynyl-2′-deoxyuridine (EdU), colony formation assay, and human umbilical vein endothelial cells (HUVECs) angiogenesis assay as well as Matrigel plug assay were conducted to study the proliferation, migration, and angiogenesis of GC in vitro and in vivo. The binding protein of H19 was found by RNA pull-down and RNA Immunoprecipitation (RIP). High-throughput sequencing was performed and next Gene Ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted to analyze the genes that are under H19 regulation. Methylated RIP (me-RIP) assay was used to investigate the sites and abundance among target mRNA. The transcription factor acted as upstream of H19 was determined through chromatin immunoprecipitation (ChIP) and luciferase assay.

Results:
In this study, we found that hypoxia-induced factor (HIF)-1α could bind to the promoter region of H19, leading to H19 overexpression. High expression of H19 was correlated with angiogenesis in GC, and H19 knocking down could inhibit cell proliferation, migration and angiogenesis. Mechanistically, the oncogenic role of H19 was achieved by binding with the N6-methyladenosine (m6A) reader YTH domain-containing family protein 1 (YTHDF1), which could recognize the m6A site on the 3′-untransated regions (3′-UTR) of scavenger receptor class B member 1 (SCARB1) mRNA, resulting in over-translation of SCARB1 and thus promoting the proliferation, migration, and angiogenesis of GC cells.

Conclusion:
HIF-1α induced overexpression of H19 via binding with the promoter of H19, and H19 promoted GC cells proliferation, migration and angiogenesis through YTHDF1/SCARB1, which might be a beneficial target for antiangiogenic therapy for GC.
Antibody interventions in HIV: broadly neutralizing mAbs in children
Authors: Ajibola Gbolahan , Masheto Gaerolwe , Shapiro Roger 
Published: June 2023

Purpose of review
Treatment strategies for children with HIV are evolving, with considerations beyond plasma viremic control that raise the possibility of reducing or eliminating latent reservoirs to achieve posttreatment control. Novel strategies that maintain HIV viral suppression and allow time off small molecule antiretroviral therapy (ART) are of high priority. Trials with broadly neutralizing mAbs (bNAbs) have begun in children and may become a viable alternative treatment option. Recent bNAb treatment studies in adults indicate that bNAbs may be associated with a reduction in viral reservoirs, providing optimism that these agents may provide a pathway towards posttreatment control that rarely occurs with small molecule ART.

Recent findings
Children with HIV provide an ideal opportunity to study bNAbs as an alternative treatment strategy that reduces direct ART toxicities during critical periods of growth and development, allows time off ART and takes advantage of the distinct features of the developing immune system in children that could facilitate induction of more potent autologous cellular and humoral immune responses against HIV-1. To date, paediatric bNAb studies with reported results include IMPAACT P1112, IMPAACT 2008, IMPAACT P1115 and the Tatelo study, and these results will be reviewed.

Summary
In this review, we summarize the current and planned paediatric bNAb studies, with an emphasis on trial results available to date. We highlight the potential benefits of immune-based therapies for the maintenance of viral suppression and its potential for achieving viral remission in children living with HIV.
Predictors of 6-year event-free survival in Alagille syndrome patients treated with maralixibat, an ileal bile acid transporter inhibitor
Authors: Sokol Ronald J. , Gonzales Emmanuel M. , Kamath Binita M. , Baker Alastair , Vig Pamela , Mogul Douglas B. , Garner Will , Hansen Bettina E. , Jacquemin Emmanuel , Thompson Richard J. 
Published: June 2023

Background and Aims:Refractory pruritus and other complications of cholestasis are indications for liver transplantation (LT) in patients with Alagille syndrome (ALGS). We evaluated predictors of event-free survival and transplant-free survival in patients with ALGS treated with maralixibat (MRX), an ileal bile acid transporter inhibitor.Approach and Results:We assessed patients with ALGS from 3 clinical trials of MRX with up to 6 years of follow-up. Event-free survival was defined as the absence of LT, surgical biliary diversion, hepatic decompensation, or death; transplant-free survival was the absence of LT or death. Forty-three potential predictors were evaluated, including age, pruritus (ItchRO[Obs] 0–4 scale), biochemistries, platelets, and serum bile acids. Harrell’s concordance statistic assessed goodness-of-fit, and then, Cox proportional hazard models confirmed the statistical significance of the predictors identified. A further analysis was performed to identify cutoffs using a grid search. Seventy-six individuals met the criteria of receiving MRX for ≥48 weeks with laboratory values available at week 48 (W48). The median duration of MRX was 4.7 years (IQR: 1.6–5.8); 16 had events (10 LT, 3 decompensation, 2 death, and 1 surgical biliary diversion). The 6-year event-free survival improved with a clinically meaningful >1-point ItchRO(Obs) reduction from baseline to W48 (88% vs. 57%;p= 0.005), W48 bilirubin < 6.5 mg/dL (90% vs. 43%;p< 0.0001), and W48 serum bile acid < 200 µmol/L (85% vs. 49%;p= 0.001). These parameters were also predictive of 6-year transplant-free survival.Conclusions:Improvement in pruritus by 48 weeks, and lower W48 bilirubin and serum bile acid levels were associated with fewer events. These data may help identify potential markers of disease progression for ALGS patients treated with MRX.
Reimplantation of Implantable Cardiac Devices—An Ethical Controversy?
Authors: Astărăstoae Vasile , Rogozea Liliana M. 
Published: June 2023

Background:
Cardiovascular diseases are an important public health problem, the main cause of death in both men and women, with a continuous increasing prevalence and consequences upon morbidity in economic, physical, and psychological terms.
The new technology have made possible the development of innovative devices, which have increased the possibility of therapeutic interventions today, extending the life of the population with cardiovascular pathology, transforming the patient care, and providing a complex, personalized therapeutic approach.

Fields of Uncertainty:
The aim of the study was to evaluate from an ethical perspective the need, feasibility, and safety of reusing cardiac pacemakers to revise the legal terms and requirements.
In recent years, the problem of accessibility to cardiovascular drugs has been increasingly accompanied by the accessibility to technology, interventional cardiology advancing recently, and becoming an increasingly important standard of care.

Data Sources:
A review of the specialized literature was performed in March 2023, using keywords such as implantable cardiac devices, reuse, ethics from PubMed, Scopus, Web of Science, and Google Scholar, as well as official documents issued at the international level (World Health Organization).

Ethics and Therapeutic Advances:
An ethical analysis assesses the extent to which a medical act (PM reimplantation) is covered by the 4 universally accepted principles: nonmaleficence, beneficence, autonomy (respect for the person), and social justice, the analysis addressing to the risk–benefit ratio based on studies that analyzed the phenomenon over the past 50 years. The ethical analyzed issues start from the fact that although 80% of pacemakers, most of them working perfectly, with a battery life of more than 7 years are buried with their owners, while approximately 3 million patients die annually due to the lack of access to these devices in undeveloped and developing countries.
But beyond the ethical issues, legal practice has meant that in many countries, reusing of these devices is prohibited, mostly being single-use devices. Low-income countries continue to accept this practice as the only one economically accessible to them, considering the prohibition of reusing them to be an economic rather than a medical issue.

Conclusions:
Reusing implantable cardiac devices is of great interest because of the costs, being in certain situations, the only possibility that certain people can have access to a therapeutic method that ensures their health recovery and increases their quality of life. But this is not possible without clear procedures, without clear criteria on how sterilization should be performed, how the technique should be performed, without obtaining a truly informed consent, and especially without a proper patient's follow-up.
The Effect of Health Insurance on Pediatric Cancer Survival: An Analysis of Children Evaluated for Radiation Therapy in Diverse Multicenter Health Systems
Authors: Fine Jessica R. , Ransdell Justine M. , Pinheiro Paulo S. , Kwon Deukwoo , Reis Isildinha M. , Barredo Julio C. , Isrow Derek M. 
Published: June 2023

Background:
Understanding the role of health insurance in cancer survival in a diverse population of pediatric radiation oncology patients could help to identify patients at risk of adverse outcomes.

Materials and Methods:
Data were collected from cancer patients evaluated for radiation therapy, age <19, diagnosed from January 1990 to August 2019. Predictors of recurrence-free survival (RFS) and overall survival (OS) were analyzed by univariable and multivariable Cox regression. Variables included health insurance, diagnosis type, sex, race/ethnicity, and socioeconomic status deprivation index.

Results:
The study included 459 patients with a median diagnosis age of 9 years. Demographic breakdown was 49.5% Hispanic, 27.2% non-Hispanic White, and 20.7% non-Hispanic Black. There were 203 recurrences and 86 deaths observed over a median follow-up of 2.4 years. Five-year RFS was 59.8% (95% CI, 51.6, 67.0) versus 36.5% (95% CI, 26.6, 46.6), and 5-year OS was 87.5% (95% CI, 80.9, 91.9) versus 71.0% (95% CI, 60.3, 79.3) in private pay insurance versus Medicaid/Medicare, respectively. Multivariable showed Medicaid/Medicare patients experienced a 54% higher risk of recurrence (hazard ratio: 1.54, 95% CI, 1.08, 2.20) and 79% higher risk of death (hazard ratio: 1.79, 95% CI, 1.02, 3.14) than privately insured patients.

Conclusions:
Significant disadvantages in RFS and OS were identified in radiation oncology patients with Medicaid/Medicare insurance, even after adjusting for clinical and demographic variables.
COMSE: Analysis of Single-Cell RNA-seq Data Using Community Detection Based Feature Selection
Authors: Luo Qinhuan , Chen Yaozhu , Lan Xun 
Published: June 2023

AbstractSingle-cell RNA sequencing enables studying cells individually, yet high gene dimensions and low cell numbers challenge the analysis. And only a subset of the genes detected are involved in the biological processes underlying cell-type specific functions. We present COMSE, an unsupervised feature selection framework using community detection to capture informative genes from scRNA-seq data. COMSE identified cell substates with high resolution, as demonstrated by its capacity in distinguishing cells at different stages of the cell cycle. Evaluations based on real and simulated scRNA-seq datasets showed COMSE outperformed methods even at high dropout rates in cell clustering. We also demonstrate that by identifying communities of genes associated with batch effects, COMSE differentiates biological differences from batch effects, thereby enabling integrated analysis of scRNA-seq datasets generated with different platforms.
Movement Recognition via Channel-Activation-Wise sEMG Attention
Authors: Zhang Jiaxuan , Matsuda Yuki , Fujimoto Manato , Suwa Hirohiko , Yasumoto Keiichi 
Published: June 2023

ABSTRACTContextSurface electromyography (sEMG) signals contain rich information recorded from muscle movements and therefore reflect the user’s intention. sEMG has seen dominant applications in reha-bilitation, clinical diagnosis as well as human engineering, etc. However, current feature extraction methods for sEMG signals have been seriously limited by its stochasticity, transiency, non-stationarity.Objective:Our objective is to combat the difficulties induced by the aforementioned downsides of sEMG and thereby extract representative features for various downstream movement recognition.MethodWe propose a novel 3-axis view of sEMG features composed of temporal, spatial, and channel-wise summary. We leverage the state-of-the-art architecture Transformer to enforce efficient parallel search and to get rid of limitations imposed by previous work in gesture classification.ResultsWe compared the proposed method against existing methods on two Ninapro datasets consisting of data from both healthy people and amputees. Experimental results show the proposed method attains the state-of-the-art (SOTA) accuracy on both datasets. We further show that the proposed method enjoys strong generalization ability: a new SOTA is achieved by pretraining the model on a different dataset followed by fine-tuning it on the target dataset.
Transcriptomic atlas of midbrain dopamine neurons uncovers differential vulnerability in a Parkinsonism lesion model
Authors: Yaghmaeian Salmani Behzad , Lahti Laura , Gillberg Linda , Jacobsen Jesper Kjaer , Mantas Ioannis , Svenningsson Per , Perlmann Thomas 
Published: June 2023

AbstractMidbrain dopamine (mDA) neurons comprise diverse cells with unique innervation targets and functions. This is illustrated by the selective sensitivity of mDA neurons of the substantia nigra compacta (SNc) in patients with Parkinson’s disease, while those in the ventral tegmental area (VTA) are relatively spared. Here we used single nuclei RNA sequencing (snRNA-seq) of approximately 70,000 mouse midbrain cells to build a high-resolution atlas of mouse mDA neuron diversity at the molecular level. The results showed that differences between mDA neuron groups could best be understood as a continuum without sharp differences between subtypes. Thus, we assigned mDA neurons to several “territories” and “neighborhoods” within a shifting gene expression landscape where boundaries are gradual rather than discrete. Based on the enriched gene expression patterns of these territories and neighborhoods, we were able to localize them in the adult mouse midbrain. Moreover, because the underlying mechanisms for the variable sensitivities of diverse mDA neurons to pathological insults are not well understood, we analyzed surviving neurons after partial 6-hydroxydopamine (6-OHDA) lesions to unravel gene expression patterns that correlate with mDA neuron vulnerability and resilience. Together, this atlas provides a basis for further studies on the neurophysiological role of mDA neurons in health and disease.
Isolation of the murine Glut1 deficient thalamocortical circuit: wavelet characterization and reverse glucose dependence of low and gamma frequency oscillations
Authors: Solis Elysandra M. , Good Levi B. , Vázquez Rafael Granja , Patnaik Sourav , Hernandez-Reynoso Ana G. , Ma Qian , Angulo Gustavo , Dobariya Aksharkumar , Cogan Stuart F. , Pancrazio Joseph J. , Pascual Juan M. , Jakkamsetti Vikram 
Published: June 2023

AbstractGlucose represents the principal brain energy source. Thus, not unexpectedly, genetic glucose transporter 1 (Glut1) deficiency (G1D) manifests with encephalopathy. G1D seizures, which constitute a prominent disease manifestation, often prove refractory to medications but may respond to therapeutic diets. These seizures are associated with aberrant thalamocortical oscillations as inferred from human electroencephalography and functional imaging. Mouse electrophysiological recordings indicate that inhibitory neuron failure in thalamus and cortex underlies these abnormalities. This provides the motivation to develop a neural circuit testbed to characterize the mechanisms of thalamocortical synchronization and the effects of known or novel interventions. To this end, we used mouse thalamocortical slices on multielectrode arrays and characterized spontaneous low frequency oscillations and less frequent 30-50 Hz or gamma oscillations under near-physiological bath glucose concentration. Using the cortical recordings from layer IV, we quantified oscillation epochs via an automated wavelet-based algorithm. This method proved analytically superior to power spectral density, short-time Fourier transform or amplitude-threshold detection. As expected from human observations, increased bath glucose reduced the lower frequency oscillations while augmenting the gamma oscillations, likely reflecting strengthened inhibitory neuron activity. This approach provides anex vivomethod for the evaluation of mechanisms, fuels, and pharmacological agents in a crucial G1D epileptogenic circuit.
RNA-induced allosteric coupling drives viral capsid assembly in bacteriophage MS2
Authors: Hamilton Sean , Modi Tushar , Šulc Petr , Ozkan Banu 
Published: June 2023

AbstractUnderstanding the mechanisms by which single-stranded RNA viruses regulate capsid assembly around their RNA genomes has become increasingly important for the development of both antiviral treatments and drug delivery systems. Here, we investigate the effects of RNA-induced allostery in a single-stranded RNA virus —Levivirusbacteriophage MS2 — using the computational methods of the Dynamic Flexibility Index (DFI) and the Dynamic Coupling Index (DCI). We show that asymmetric binding of RNA to a symmetric MS2 coat protein dimer increases the flexibility of the distant FG-loop and induces a conformational change to an asymmetric dimer that is essential for proper capsid formation. We also show that a point mutation W82R in the FG-loop creates an assembly-deficient dimer in which RNA-binding has no significant effect on FG-loop flexibility. Lastly, we show that the highly flexible disordered FG-loop of the RNA bound asymmetric dimer not only becomes the controller of the rigid FG-loop but enhances its dynamic coupling with all the distal positions in the dimer. This strong dynamic coupling allows highly regulated communication and unidirectional signal transduction that drives the formation of the experimentally observed capsid intermediates.Author summaryThe final stage of an RNA virus’ life cycle is the assembly of a protein shell encapsulating the viral genome prior to release from the host organism. Despite rapid advancements in both experimental and theoretical biology since the mid-20th century, little is still known about the underlying mechanisms of viral capsid assembly. However, understanding the biophysical principles of viral capsid assembly would bring us one step closer to developing new biotechnologies such as antivirals that inhibit this critical stage of the life cycle or artificial capsids for targeted drug/vaccine delivery. Although we limit the present study to one simple RNA virus that infects bacteria, we propose that the physical implications can extend to other RNA viruses including the human coronavirus SARS-CoV-2. We also propose that the allosteric regulation by specific protein-RNA interactions might be a general mechanism exploited by many other ribonucleoprotein complexes, such as CRISPR-Cas9, spliceosome or ribosome.