bluuebunny/crossref_metadata_2025 huggingface dataset:
Coacervation-triggered hierarchically assembled hydrogels with application as surgical sealant
Authors: Guo Zhongwei , Wei Zunghang , Sun Wei
Published: June 2023

Adhesive hydrogels possess great potential to be explored as tissue adhesives, surgical sealants, and hemostats. However, it has been a great challenge to develop hydrogels that can function rapidly and controllably on wet, dynamic biological tissues. Inspired by polyphenol chemistry, we introduce a coacervation-triggered shaping strategy that enables the hierarchical assembly of recombinant human collagen (RHC) and tannic acid (TA). The conformation of the RHC and TA aggregates is controlled to evolve from granular to web-like states, accompanied by the significant enhancement of mechanical and adhesion performance. The coacervation and assembly process is driven by intermolecular interactions, especially hydrogen bonding between RHC and TA. Benefitting from the multifaceted nature of polyphenol chemistry, the hierarchically assembled hydrogels revealed excellent properties as surgical sealing materials, including fast gelation time (within 10 s), clotting time (within 60 s), ultrastretchability (strain >10 000%), and tough adhesion (adhesive strength >250 kPa). In vivo experiments demonstrated complete sealing of severely leaking heart and liver tissues with the assistance of in situ formed hydrogels during 7 d of follow-up. This work presents a highly promising hydrogel-based surgical sealant in wet and dynamic biological environments for future biomedical applications.
Bordered Floer homology for manifolds with torus boundary via immersed curves
Authors: Hanselman Jonathan , Rasmussen Jacob , Watson Liam
Published: June 2023

This paper gives a geometric interpretation of bordered Heegaard Floer homology for manifolds with torus boundary. If

M
M

is such a manifold, we show that the type D structure

C
F
D

^

(
M
)

\widehat {CFD}(M)

may be viewed as a set of immersed curves decorated with local systems in

∂
M

\partial M

. These curves-with-decoration are invariants of the underlying three-manifold up to regular homotopy of the curves and isomorphism of the local systems. Given two such manifolds and a homeomorphism

h
h

between the boundary tori, the Heegaard Floer homology of the closed manifold obtained by gluing with

h
h

is obtained from the Lagrangian intersection Floer homology of the curve-sets. This machinery has several applications: We establish that the dimension of

H
F

^

\widehat {HF}

decreases under a certain class of degree one maps (pinches) and we establish that the existence of an essential separating torus gives rise to a lower bound on the dimension of

H
F

^

\widehat {HF}

. In particular, it follows that a prime rational homology sphere

Y
Y

with

H
F

^

(
Y
)
>
5

\widehat {HF}(Y)>5

must be geometric. Other results include a new proof of Eftekhary’s theorem that L-space homology spheres are atoroidal; a complete characterization of toroidal L-spaces in terms of gluing data; and a proof of a conjecture of Hom, Lidman, and Vafaee on satellite L-space knots.
Infinite divisibility of the Whittaker distribution
Authors: Assefa Genet , Baricz Árpád
Published: June 2023

In this paper, by using an integral representation of Ismail and Kelker for the quotient of Tricomi hypergeometric functions, we investigate the infinite divisibility and self-decomposability of the recently defined four-parameter lifetime Whittaker distribution, which is a natural extension of the classical gamma, exponential, chi-square, generalized Lindley, Lindley, beta prime, and Lomax distributions. We also show that the Whittaker distribution belongs to the class of hyperbolically completely monotone distributions and generalized gamma convolutions, and it is a super-Gaussian distribution. By using some results for the moments of the Whittaker distribution, we also deduce some Turán type inequalities for the Whittaker functions of the second kind and as an application we show that the effective variance of the Whittaker distribution is bounded from below.
Some properties of 𝑝-limited sets
Authors: Galindo Pablo , Miranda Vinícius
Published: June 2023

Karn and Sinha [Glasg. Math. J. 56 (2014), pp. 427–437] introduced the

p
p

-limited (

1
≤
p
>
∞

1 \leq p > \infty

) sets (see the definition below). We show that

p
p

-limited sets are preserved by continuous polynomials as well as by the projective tensor product and that scalar-valued polynomials are

p
p

-summable on

p
p

-limited sets. Considering the notion of

p
p

-limited set from the

ℓ
p

\ell _p

-valued operators point of view, we introduce in Section \ref{sec:3} two weaker types of

p
p

-limitedness in the setting of Banach lattices and study their basic properties.
Stationary phase method, powers of functions, and applications to functional analysis
Authors: Queffélec H. , Zarouf R.
Published: June 2023

The utility of the (weighted) van der Corput inequalities or of the stationary phase method is illustrated with various examples borrowed from: differentiability issues (Riemann’s function and related); functional analysis on Banach spaces or algebras of analytic functions (composition operators); and local Banach space geometry (Schäffer’s problem).
Death Penalty Abolitionism from the Enlightenment to Modernity
Authors: Jouet Mugambi
Published: June 2023

The modern movement to abolish the death penalty in the United States stresses that this punishment cannot be applied fairly and effectively. The movement does not emphasize that killing prisoners is inhumane per se. Its focus is almost exclusively on administrative, procedural, and utilitarian issues, such as recurrent exonerations of innocents, incorrigible racial discrimination, endemic arbitrariness, lack of deterrent value, and spiraling financial costs. By comparison, modern European law recognizes any execution as an inherent violation of human rights rooted in dignity. This humanistic approach is often assumed to be “European” in nature and foreign to America, where distinct sensibilities lead people to concentrate on practical problems surrounding executions. This Article demonstrates that, in reality, the significant transatlantic divergence on abolitionism is a relatively recent development. By the late eighteenth century, abolitionists in Europe and America recurrently denounced the inhumanity of executions in language foreshadowing modern human rights norms. Drawing on sources overlooked by scholars, including the views of past American and French abolitionists, the Article shows that reformers previously converged in employing a polyvalent rhetoric blending humanistic and practical objections to executions. It was not until the 1970s and 1980s that a major divergence materialized. As America faced an increasingly punitive social climate leading to the death penalty’s resurgence and the rise of mass incarceration, abolitionists largely abandoned humanistic claims in favor of practical ones. Meanwhile, the opposite generally occurred as abolitionism triumphed in Europe. These findings call into question the notion that framing the death penalty as a human rights abuse marks recent shifts in Western Europe or international law. While human rights have indeed become the official basis for abolition in modern Europe, past generations of European and U.S. abolitionists defended similar moral and political convictions. These humanistic norms reflect a long-term evolution traceable to the Renaissance and Enlightenment. But for diverse social transformations, America may have kept converging with Europe in gradually adopting humanistic norms of punishment.
Gender disparity in Canadian Institutes of Health Research grant funding decisions among recipients from dermatology departments: a retrospective study
Authors: Tao Brendan , Ding Jeffrey , Joseph Marissa , Tien Chi-Wei , Chawla Sahil , Khan Waleed , Khosa Faisal
Published: June 2023

We investigated the extent of gender disparity among dermatologists awarded Canadian Institutes of Health Research (CIHR) grants. Our results indicate that, between 2008 and 2022, CIHR grant recipients were disproportionately male, thereby substantiating the influence of system-level barriers during research funding decision-making.
2-Reflective Lattices of Signature (n, 2) withn≥8
Authors: Wang Haowu
Published: June 2023

An even lattice $M$ of signature $(n,2)$ is called $2$-reflective if there is a non-constant modular form for the orthogonal group of $M$, which vanishes only on quadratic divisors orthogonal to $2$-roots of $M$. In 2017, Ma [ 25] proved that there are only finitely many $2$-reflective lattices of signature $(n,2)$ with $n\geq 7$. In this paper, we extend the finiteness result of Ma to $n\geq 5$ and show that there are exactly forty-two $2$-reflective lattices of signature $(n,2)$ with $n\geq 8$.
Molecular diagnostic tools for the World Health Organization (WHO) 2021 classification of gliomas, glioneuronal and neuronal tumors; an EANO guideline
Authors: Sahm Felix , Brandner Sebastian , Bertero Luca , Capper David , French Pim J , Figarella-Branger Dominique , Giangaspero Felice , Haberler Christine , Hegi Monika E , Kristensen Bjarne W , Kurian Kathreena M , Preusser Matthias , Tops Bastiaan B J , van den Bent Martin , Wick Wolfgang , Reifenberger Guido , Wesseling Pieter
Published: June 2023

In the 5th edition of the WHO CNS tumor classification (CNS5, 2021), multiple molecular characteristics became essential diagnostic criteria for many additional CNS tumor types. For those tumors, an integrated, “histomolecular” diagnosis is required. A variety of approaches exists for determining the status of the underlying molecular markers. The present guideline focuses on the methods that can be used for assessment of the currently most informative diagnostic and prognostic molecular markers for the diagnosis of gliomas, glioneuronal and neuronal tumors. The main characteristics of the molecular methods are systematically discussed, followed by recommendations and information on available evidence levels for diagnostic measures. The recommendations cover DNA and RNA next-generation-sequencing, methylome profiling, and select assays for single/limited target analyses, including immunohistochemistry. Additionally, because of its importance as a predictive marker in IDH-wildtype glioblastomas, tools for the analysis of MGMT promoter methylation status are covered. A structured overview of the different assays with their characteristics, especially their advantages and limitations, is provided, and requirements for input material and reporting of results are clarified. General aspects of molecular diagnostic testing regarding clinical relevance, accessibility, cost, implementation, regulatory, and ethical aspects are discussed as well. Finally, we provide an outlook on new developments in the landscape of molecular testing technologies in neuro-oncology.
Assessing Electronic Nicotine Delivery Systems Device Type Accurately in Surveys
Authors: Kaplan Bekir , Crespi Elizabeth , Hardesty Jeffrey J , Cohen Joanna E
Published: June 2023

Introduction

The electronic nicotine delivery systems (ENDS) market is highly heterogeneous and changing rapidly in the United States, making classification of devices complicated, especially for surveys. We assessed the percentage of concordant responses between self-reported device type and device type reported by manufacturer/retailer sites for three ENDS brands.

Aims and Methods

Population Assessment of Tobacco and Health Study wave 5 (2018–2019) asked adult ENDS users about their ENDS device type with the following multiple-choice question: “What kind of electronic nicotine product [is/was] it?” with response options: (1) A disposable device, (2) A device that uses replaceable prefilled cartridges, (3) A device with a tank that you refill with liquids (4) A mod system, and (5) Something else. Participants using only one ENDS device and reporting brands of JUUL (n = 579), Markten (n = 30), or Vuse (n = 47) were included. Responses were dichotomized as “concordant=1” (prefilled cartridge for these three brands) and “discordant = 0” (other responses) to assess the concordance.

Results

The overall concordance between self-reports and manufacturer/retail sites was 81.8% (n = 537). This percentage was 82.7% (n = 37) among Vuse users, 82.6% (n = 479) among JUUL users, and 69.1% (n = 21) among Markten users. Almost one in three people who use Markten did not indicate that their device uses replaceable prefilled cartridges.

Conclusions

While at least 70% concordance could be acceptable, collecting more information about device type (eg, liquid container (pod/cartridge/tank), refillability; and submitting pictures) may improve the accuracy of the information.

Implications

This study is particularly relevant for researchers analyzing smaller samples for example when examining disparities. Monitoring the characteristics of ENDS accurately in population-based studies is critical for regulatory authorities to understand ENDS toxicity, addiction, health effects, and use behaviors at the population level. There is evidence that higher concordance can be achieved with other questions- and methods. Adjusting survey questions about ENDS device type (eg, more descriptive response options, inclusion of separate questions asking about tank, pod, cartridge) and potentially including photos of participants’ devices may help to classify ENDS device types more accurately.
Hyperuricemia: A key contributor to endothelial dysfunction in cardiovascular diseases
Authors: Wei Xin , Zhang Mao , Huang Shian , Lan Xiaozhong , Zheng Jing , Luo Hui , He Yuan , Lei Wei
Published: June 2023

As an end product of purine metabolism, uric acid (UA) is a major endogenous antioxidant in humans. However, impaired UA synthesis and excretion can lead to hyperuricemia (HUA), which may in turn induce endothelial dysfunction (ED) and contribute to the pathogenesis of cardiovascular diseases (CVDs; e.g., atherosclerosis and hypertension). In this review, we discuss recent advances and novel insights into the effects exerted by HUA conditions in ED and related underlying mechanisms focusing on impaired UA metabolism, reduction in the synthesis and bioavailability of nitric oxide, endothelial cell injury, the endothelial‐to‐mesenchymal transition, insulin resistance, procoagulant activity, and acquisition of an inflammatory phenotype. We additionally discuss intervention strategies for HUA‐induced ED and the paradoxical roles of UA in endothelial function. We summarize major conclusions and perspectives: the deleterious effects of HUA contribute to the initiation and progression of CVD‐related ED. However, the treatment strategies (in addition to urate‐lowering therapy) for increasing endothelial function are limited because the majority of literature on pharmacological and pathophysiological mechanisms underlying HUA‐induced ED solely describes in vitro models. Therefore, a better understanding of the mechanisms involved in HUA‐induced ED is critical to the development of novel therapies for preventing and treating CVD‐HUA comorbidities.
CYP eicosanoid pathway mediates colon cancer‐promoting effects of dietary linoleic acid
Authors: Zhang Jianan , Yang Jun , Duval Caroline , Edin Matthew L. , Williams Andrea , Lei Lei , Tu Maolin , Pourmand Elham , Song Renhua , Graves Joan P. , DeGraff Laura M. , Wong Justin J.‐L. , Wang Yige , Sun Quancai , Sanidad Katherine Z. , Wong Siu , Han Yanhui , Zhang Zhenyu , Lee Kin Sing Stephen , Park Yeonhwa , Xiao Hang , Liu Zhenhua , Decker Eric A. , Cui Wei , Zeldin Darryl C. , Zhang Guodong
Published: June 2023

Human and animal studies support that consuming a high level of linoleic acid (LA, 18:2ω‐6), an essential fatty acid and key component of the human diet, increases the risk of colon cancer. However, results from human studies have been inconsistent, making it challenging to establish dietary recommendations for optimal LA intake. Given the importance of LA in the human diet, it is crucial to better understand the molecular mechanisms underlying its potential colon cancer‐promoting effects. Using LC‐MS/MS‐based targeted lipidomics, we find that the cytochrome P450 (CYP) monooxygenase pathway is a major pathway for LA metabolism in vivo. Furthermore, CYP monooxygenase is required for the colon cancer‐promoting effects of LA, since the LA‐rich diet fails to exacerbate colon cancer in CYP monooxygenase‐deficient mice. Finally, CYP monooxygenase mediates the pro‐cancer effects of LA by converting LA to epoxy octadecenoic acids (EpOMEs), which have potent effects on promoting colon tumorigenesis via gut microbiota‐dependent mechanisms. Overall, these results support that CYP monooxygenase‐mediated conversion of LA to EpOMEs plays a crucial role in the health effects of LA, establishing a unique mechanistic link between dietary fatty acid intake and cancer risk. These results could help in developing more effective dietary guidelines for optimal LA intake and identifying subpopulations that may be especially vulnerable to LA's negative effects.
A Qualitative Study on Using Telemedicine for Precepting and Teaching in the Academic Setting
Authors: Raffa Brittany J. , Muellers Kimberly A. , Andreadis Katerina , Ancker Jessica S. , Flower Kori B. , Horowitz Carol R. , Kaushal Rainu , Lin Jenny J.
Published: June 2023

Purpose

To examine the impact of telemedicine use on precepting and teaching among preceptors and patients during the COVID-19 pandemic.

Method

The authors conducted a secondary analysis of a qualitative study focusing on providers’ and patients’ experiences with and attitudes toward telemedicine at 4 academic health centers. Teaching and precepting were emergent codes from the data and organized into themes. Themes were mapped to domains from the 2009 Consolidated Framework for Implementation Research (CFIR), a framework that assists with effective implementation and consists of 5 domains: intervention characteristics, outer settings, inner settings, characteristics of individuals, and process.

Results

In total, 86 interviews were conducted with 65 patients and 21 providers. Nine providers and 3 patients recounted descriptions related to teaching and precepting with telemedicine. Eight themes were identified, mapping across all 5 CFIR domains, with the majority of themes (n = 6) within the domains of characteristics of individuals, processes, and intervention characteristics. Providers and patients described how a lack of prepandemic telemedicine experience and inadequate processes in place to precept and teach with telemedicine affected the learning environment and perceived quality of care. They also discussed how telemedicine exacerbated existing difficulties in maintaining resident continuity. Providers described ways communication changed with telemedicine use during the pandemic, including having to wear masks while in the same room as the trainee and sitting closely to remain within range of the camera, as well as the benefit of observing trainees with the attending’s camera off. Providers expressed a lack of protected structure and time for teaching and supervising with telemedicine, and a general view that telemedicine is here to stay.

Conclusions

Efforts should focus on increasing knowledge of telemedicine skills and improving processes to implement telemedicine in the teaching setting in order to best integrate it into undergraduate and graduate medical education.
Emotions and Psychological Mechanisms of Listening to Music in Cochlear Implant Recipients
Authors: Yüksel Mustafa , Sarlik Esra , Çiprut Ayça
Published: June 2023

Objectives:

Music is a multidimensional phenomenon and is classified by its arousal properties, emotional quality, and structural characteristics. Although structural features of music (i.e., pitch, timbre, and tempo) and music emotion recognition in cochlear implant (CI) recipients are popular research topics, music-evoked emotions, and related psychological mechanisms that reflect both the individual and social context of music are largely ignored. Understanding the music-evoked emotions (the “what”) and related mechanisms (the “why”) can help professionals and CI recipients better comprehend the impact of music on CI recipients’ daily lives. Therefore, the purpose of this study is to evaluate these aspects in CI recipients and compare their findings to those of normal hearing (NH) controls.

Design:

This study included 50 CI recipients with diverse auditory experiences who were prelingually deafened (deafened at or before 6 years of age)—early implanted (N = 21), prelingually deafened—late implanted (implanted at or after 12 years of age—N = 13), and postlingually deafened (N = 16) as well as 50 age-matched NH controls. All participants completed the same survey, which included 28 emotions and 10 mechanisms (Brainstem reflex, Rhythmic entrainment, Evaluative Conditioning, Contagion, Visual imagery, Episodic memory, Musical expectancy, Aesthetic judgment, Cognitive appraisal, and Lyrics). Data were presented in detail for CI groups and compared between CI groups and between CI and NH groups.

Results:

The principal component analysis showed five emotion factors that are explained by 63.4% of the total variance, including anxiety and anger, happiness and pride, sadness and pain, sympathy and tenderness, and serenity and satisfaction in the CI group. Positive emotions such as happiness, tranquility, love, joy, and trust ranked as most often experienced in all groups, whereas negative and complex emotions such as guilt, fear, anger, and anxiety ranked lowest. The CI group ranked lyrics and rhythmic entrainment highest in the emotion mechanism, and there was a statistically significant group difference in the episodic memory mechanism, in which the prelingually deafened, early implanted group scored the lowest.

Conclusion:

Our findings indicate that music can evoke similar emotions in CI recipients with diverse auditory experiences as it does in NH individuals. However, prelingually deafened and early implanted individuals lack autobiographical memories associated with music, which affects the feelings evoked by music. In addition, the preference for rhythmic entrainment and lyrics as mechanisms of music-elicited emotions suggests that rehabilitation programs should pay particular attention to these cues.
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

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

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.

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.
Assessing Life's Essential 8 and Adverse Childhood Experiences in Grandparent-Grandchild Co-residing Dyads
Authors: Song MinKyoung , Bessette Hannah C. , Musil Carol M. , Lyons Karen S. , Winters-Stone Kerri M. , Hayman Laura L.
Published: June 2023

We assessed a subset of behavioral indicators from the American Heart Association Life's Essential 8 cardiovascular health (CVH) construct—diet, physical activity, sleep, and nicotine exposure—and quantified associations in scores between members of 12 grandparent-grandchild dyads (grandparents, 52–70 years old; children, 7–12 years old). We also assessed the number of adverse childhood experiences from the dyads. Using the Life's Essential 8 scoring algorithm (0–100, with 100 as optimal), we calculated averages and used Spearman's ρ correlation to quantify associations. Mean score was 67.5 (±12.4) for grandparents and 63.0 (±11.2) for grandchildren. Mean scores for the dyad members were significantly correlated (r = 0.66, P < .05). The mean numbers of adverse childhood experiences were 7.0 and 5.8 for the grandparents and grandchildren, respectively. The results indicate that CVH in these dyads was suboptimal and interrelated. Adverse childhood experiences in this analysis surpass levels reported as high risk for poor CVH. Our findings suggest that dyadic-based interventions to improve CVH are warranted.
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.
Adoption of alternative life cycles in a parasitic trematode is linked to microbiome differences
Authors: Salloum Priscila M. , Jorge Fátima , Dheilly Nolwenn M. , Poulin Robert
Published: June 2023

For parasites with complex multi-host life cycles, the facultative truncation of the cycle represents an adaptation to challenging conditions for transmission. However, why certain individuals are capable of abbreviating their life cycle while other conspecifics are not remains poorly understood. Here, we test whether conspecific trematodes that either follow the normal three-host life cycle or skip their final host by reproducing precociously (via progenesis) in an intermediate host differ in the composition of their microbiomes. Characterization of bacterial communities based on sequencing of the V4 hypervariable region of the 16S SSU rRNA gene revealed that the same bacterial taxa occur in both normal and progenetic individuals, independent of host identity and temporal variation. However, all bacterial phyla recorded in our study, and two-thirds of bacterial families, differed in abundance between the two morphs, with some achieving higher abundance in the normal morph and others in the progenetic morph. Although the evidence is purely correlative, our results reveal a weak association between microbiome differences and intraspecific plasticity in life cycle pathways. Advances in functional genomics and experimental microbiome manipulation will allow future tests of the significance of these findings.
Single-cell Ca
2+
parameter inference reveals how transcriptional states inform dynamic cell responses
Authors: Wu Xiaojun , Wollman Roy , MacLean Adam L.
Published: June 2023

Single-cell genomic technologies offer vast new resources with which to study cells, but their potential to inform parameter inference of cell dynamics has yet to be fully realized. Here we develop methods for Bayesian parameter inference with data that jointly measure gene expression and Ca
2+
dynamics in single cells. We propose to share information between cells via transfer learning: for a sequence of cells, the posterior distribution of one cell is used to inform the prior distribution of the next. In application to intracellular Ca
2+
signalling dynamics, we fit the parameters of a dynamical model for thousands of cells with variable single-cell responses. We show that transfer learning accelerates inference with sequences of cells regardless of how the cells are ordered. However, only by ordering cells based on their transcriptional similarity can we distinguish Ca
2+
dynamic profiles and associated marker genes from the posterior distributions. Inference results reveal complex and competing sources of cell heterogeneity: parameter covariation can diverge between the intracellular and intercellular contexts. Overall, we discuss the extent to which single-cell parameter inference informed by transcriptional similarity can quantify relationships between gene expression states and signalling dynamics in single cells.
COMSE: Analysis of Single-Cell RNA-seq Data Using Community Detection Based Feature Selection
Authors: Luo Qinhuan , Chen Yaozhu , Lan Xun
Published: June 2023

Single-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

Context

Surface 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.

Method

We 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.

Results

We 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

Midbrain 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

Glucose 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.