bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV-1 Treatment Failure, Drug Resistance, and Clinical Outcomes in Perinatally Infected Children and Adolescents Failing First-Line Antiretroviral Therapy in Western Kenya
Authors: Nyandiko Winstone , Holland Sabina , Vreeman Rachel , DeLong Allison K. , Manne Akarsh , Novitsky Vladimir , Sang Festus , Ashimosi Celestine , Ngeresa Anthony , Chory Ashley , Aluoch Josephine , Orido Millicent , Jepkemboi Eslyne , Sam Soya S. , Caliendo Angela M. , Ayaya Samuel , Hogan Joseph W. , Kantor Rami ,   for the Resistance in a Pediatric Cohort (RESPECT) Study
Published: November 2021

Background:Long-term impact of drug resistance in perinatally infected children and adolescents living with HIV (CALWH) is poorly understood. We determined drug resistance and examined its long-term impact on failure and mortality in Kenyan CALWH failing first-line non-nucleoside reverse transcriptase inhibitor–based antiretroviral therapy (ART).Setting:Academic Model Providing Access to Healthcare, western Kenya.Methods:Participants were enrolled in 2010–2013 (timepoint 1) and a subsample re-enrolled after 4–7 years (timepoint 2). Viral load (VL) was performed on timepoint 1 samples, with genotyping of those with detectable VL. Primary endpoints were treatment failure (VL >1000 copies/mL) at and death before timepoint 2. Multinomial regression analysis was used to characterize resistance effect on death, failure, and loss-to-follow-up, adjusting for key variables.Results:The initial cohort (n = 480) was 52% (n = 251) female, median age 8 years, median CD4% 31%, 79% (n = 379) on zidovudine/abacavir + lamivudine + efavirenz/nevirapine for median 2 years. Of these, 31% (n = 149) failed at timepoint 1. Genotypes at timepoint 1, available on n = 128, demonstrated 93% (n = 119) extensive resistance, affecting second line. Of 128, 22 failed at timepoint 2, 17 died, and 32 were lost to follow-up before timepoint 2. Having >5 resistance mutations at timepoint 1 was associated with higher mortality [relative risk ratio (RRR) = 8.7, confidence interval (CI) 2.1 to 36.3] and loss to follow-up (RRR = 3.2, CI 1.1 to 9.2). Switching to second line was associated with lower mortality (RRR <0.05, CI <0.05 to 0.1) and loss to follow-up (RRR = 0.1, CI <0.05 to 0.3).Conclusion:Extensive resistance and limited switch to second line in perinatally infected Kenyan CALWH failing first-line ART were associated with long-term failure and mortality. Findings emphasize urgency for interventions to sustain effective, life-long ART in this vulnerable population.
The Role of Interleukin 10 in Keloid Therapy
Authors: Harsono Anastasia Dessy , Prasetyono Theddeus Octavianus Hari , Dilogo Ismail Hadisoebroto 
Published: November 2021

Introduction
Keloids are pathological wound healing responses to dermal injuries. These scars may lead to considerable morbidity, but treatments remain challenging for physicians. Interleukin 10 (IL-10), a potent anti-inflammatory cytokine, plays a prominent role in fetal scarless regenerative healing; therefore, it may become a more targeted and effective therapy for keloids. This review aimed to obtain an overview of the background of keloid and IL-10 functions as its promising forthcoming treatment.

Materials and Methods
Studies were sought from Pubmed, ScienceDirect, PLOS, and Clinical Key. Keywords are interleukin 10, keloid, and wound healing as Medical Subject Headings terms.

Results and Discussion
Keloids and fetal scarless healing represent 2 opposing ends of the tissue repair spectrum. Promising multiple animal models have demonstrated successful regenerative healing promotion through IL-10 overexpression by its ability to minimize inflammatory wound microenvironment, downregulate transforming growth factor β/SMAD signaling pathway, increase extracellular matrix breakdown, and regulate extracellular matrix. These results have led to the development of clinical trials investigating human recombinant IL-10.

Conclusions
Interleukin 10 has the potential to become a more targeted and promising therapy of keloids owing to its pleiotropic effects.
Plastic Surgery Away Rotations During the Coronavirus Disease Pandemic
Authors: Tucker A. Blake , Pakvasa Mikhail , Shakir Afaaf , Chang David W. , Reid Russell R. , Silva Amanda K. 
Published: November 2021

Background
Plastic surgery has traditionally been a specialty that places a strong emphasis on away rotations during the final year of medical school. These rotations allow the program and residency candidates to become better acquainted and are often crucial, as a large portion of applicants match at programs where they rotated. The coronavirus disease 2019 (COVID-19) pandemic forced many institutions to modify their educational curriculums when away rotations were canceled. We present our experience creating and implementing a virtual plastic surgery rotation.

Methods
Our virtual program was designed to mirror the in-person away rotations as much as possible. Prerotation and postrotation surveys from the students as well as feedback interviews with the students, residents, and faculty were used to gather information on the experience.

Results
We created a 2-week curriculum including approximately 20 hours of lecture time, 28 hours of operating room time, 2.5 hours of one-on-one mentorship, and 3 hours of social opportunities. Students reported that they learned more about plastic surgery and the residency program, but in contrast to this, some found it difficult to make an impression.

Conclusions
We developed a novel 2-week virtual curriculum that provided visiting medical students from across the country an opportunity to learn more about plastic surgery and our residency program. Virtual learning is becoming a vital part of education, and our study provides pearls and pitfalls when structuring these experiences.
Extended Scalp Expansion for Larger Defects During Staged Cranioplasty
Authors: Dinis Jacob , Junn Alexandra , Kahle Kristopher , Alperovich Michael 
Published: November 2021

Background:
Secondary cranioplasty is often required following trauma, infection, radiation, or oncologic care, but is complicated by soft-tissue deficits with limited regional options. Scalp tissue expanders can provide hair-bearing, vascularized tissue for tension- free closure yielding optimal aesthetic results. However, the upper limit of safe scalp expansion has not been explored. This study sought to evaluate the efficacy of extended scalp tissue expansion for challenging cranioplasties in a consecutive series.

Methods:
Patients who underwent scalp tissue expansion before cranioplasty were retrospectively identified from a single institution between the years 2017 and 2020. Patient demographics, tissue expansion characteristics, and complications during expansion and after cranioplasty were collected.

Results:
Six patients were identified who underwent staged scalp expansion for cranioplasty; 5 were male (83.3%) with a mean age of 43.8 ± 12.5 years. Indications for cranioplasty included 2 epilepsy- related procedures, 1 oligodendroglioma, 2 infectious processes, and 1 traumatic incident. A single expander was used in 5 cases, whereas 2 were used in the remaining case. The average expander fill volume was 434.3 ± 115 ccs with a mean expansion time of 3.3 ± 1.4  months. Expander infection occurred in 1 case and expander exposure in another, but adequate scalp expansion was still achieved in both. Successful closure over cranioplasty was obtained in 5 cases (83.3%); 1 patient ultimately required free flap reconstruction for soft-tissue coverage.

Conclusions:
In cases of extended scalp defects, scalp tissue expansion remains the preferred method for recruiting large quantities of like tissue before implant cranioplasty.
Vocal modulation in human mating and competition
Authors: Hughes Susan M. , Puts David A. 
Published: November 2021

The human voice is dynamic, and people modulate their voices across different social interactions. This article presents a review of the literature examining natural vocal modulation in social contexts relevant to human mating and intrasexual competition. Altering acoustic parameters during speech, particularly pitch, in response to mating and competitive contexts can influence social perception and indicate certain qualities of the speaker. For instance, a lowered voice pitch is often used to exert dominance, display status and compete with rivals. Changes in voice can also serve as a salient medium for signalling a person's attraction to another, and there is evidence to support the notion that attraction and/or romantic interest can be distinguished through vocal tones alone. Individuals can purposely change their vocal behaviour in attempt to sound more attractive and to facilitate courtship success. Several findings also point to the effectiveness of vocal change as a mechanism for communicating relationship status. As future studies continue to explore vocal modulation in the arena of human mating, we will gain a better understanding of how and why vocal modulation varies across social contexts and its impact on receiver psychology.
This article is part of the theme issue ‘Voice modulation: from origin and mechanism to social impact (Part I)’.
Singers show enhanced performance and neural representation of vocal imitation
Authors: Waters Sheena , Kanber Elise , Lavan Nadine , Belyk Michel , Carey Daniel , Cartei Valentina , Lally Clare , Miquel Marc , McGettigan Carolyn 
Published: November 2021

Humans have a remarkable capacity to finely control the muscles of the larynx, via distinct patterns of cortical topography and innervation that may underpin our sophisticated vocal capabilities compared with non-human primates. Here, we investigated the behavioural and neural correlates of laryngeal control, and their relationship to vocal expertise, using an imitation task that required adjustments of larynx musculature during speech. Highly trained human singers and non-singer control participants modulated voice pitch and vocal tract length (VTL) to mimic auditory speech targets, while undergoing real-time anatomical scans of the vocal tract and functional scans of brain activity. Multivariate analyses of speech acoustics, larynx movements and brain activation data were used to quantify vocal modulation behaviour and to search for neural representations of the two modulated vocal parameters during the preparation and execution of speech. We found that singers showed more accurate task-relevant modulations of speech pitch and VTL (i.e. larynx height, as measured with vocal tract MRI) during speech imitation; this was accompanied by stronger representation of VTL within a region of the right somatosensory cortex. Our findings suggest a common neural basis for enhanced vocal control in speech and song.
This article is part of the theme issue ‘Voice modulation: from origin and mechanism to social impact (Part I)’.
Biological Insights Knowledge Graph: an integrated knowledge graph to support drug development
Authors: Geleta David , Nikolov Andriy , Edwards Gavin , Gogleva Anna , Jackson Richard , Jansson Erik , Lamov Andrej , Nilsson Sebastian , Pettersson Marina , Poroshin Vladimir , Rozemberczki Benedek , Scrivener Timothy , Ughetto Michael , Papa Eliseo 
Published: November 2021

AbstractThe use of knowledge graphs as a data source for machine learning methods to solve complex problems in life sciences has rapidly become popular in recent years. Our Biological Insights Knowledge Graph (BIKG) combines relevant data for drug development from public as well as internal data sources to provide insights for a range of tasks: from identifying new targets to repurposing existing drugs. Besides the common requirements to organisational knowledge graphs such as being able to capture the domain precisely and give the users the ability to search and query the data, the focus on handling multiple use cases and supporting use case-specific machine learning models presents additional challenges: the data models must also be streamlined for the performance of downstream tasks; graph content must be easily customisable for different use cases; different projections of the graph content are required to support a wider range of different consumption modes. In this paper we describe our main design choices in implementation of the BIKG graph and discuss different aspects of its life cycle: from graph construction to exploitation.
Global transcriptome analysis reveals partial estrogen-like effects of karanjin in MCF-7 breast cancer cells
Authors: Bhatt Gaurav , Gupta Akshita , Rangan Latha , Limaye Anil Mukund 
Published: November 2021

AbstractKaranjin, an abundantly occurring furanoflavonoid in edible and non-edible legumes, exerts diverse biological effectsin vivo, andin vitro. Its potential as an anticancer agent is also gaining traction following recent demonstrations of its anti-proliferative, cell cycle inhibitory, and pro-apoptotic effects. However, the universality of its anticancer potential is yet to be scrutinized, particularly so because flavonoids can act as selective estrogen receptor modulators (SERMs). Even the genomic correlates of its biological activities are yet to be examined in hormone responsive cells. This paper presents the early and direct transcriptomic footprint of 10 μM karanjin in MCF-7 breast cancer cells, using next generation sequencing technology (RNA-seq). We show that karanjin-modulated gene-expression repertoire is enriched in several hallmark gene sets, which include early estrogen-response, and G2/M checkpoint genes. Genes modulated by karanjin overlapped with those modulated by 1 nM 17β-estradiol (E2), or 1 μM tamoxifen. Karanjin altered the expression of selected estrogen-regulated genes in a cell-type, and concentration dependent manner. It downmodulated the expression of ERα protein in MCF-7 cells. Furthermore, ERα knockdown negatively impacted karanjin’s ability to modulate the expression of selected E2 target genes. Our data suggest that karanjin exerts its effects on ERα-positive breast cancer cells, at least in part, via ERα. The apparent SERM-like effects of karanjin pose a caveat to the anticancer potential of karanjin. In-depth studies on cell-type and concentration-dependent effects of karanjin may bring out its true potential in endocrine therapies.
Multi-attribute Glycan Identification and FDR Control for Glycoproteomics
Authors: Polasky Daniel A. , Geiszler Daniel J. , Yu Fengchao , Nesvizhskii Alexey I. 
Published: November 2021

AbstractRapidly improving methods for glycoproteomics have enabled increasingly large-scale analyses of complex glycopeptide samples, but annotating the resulting mass spectrometry data with high confidence remains a major bottleneck. We recently introduced a fast and sensitive glycoproteomics search method in our MSFragger search engine, which reports glycopeptides as a combination of a peptide sequence and the mass of the attached glycan. In samples with complex glycosylation patterns, converting this mass to a specific glycan composition is not straightforward, however, as many glycans have similar or identical masses. Here, we have developed a new method for determining the glycan composition of N-linked glycopeptides fragmented by collision or hybrid activation that uses multiple sources of information from the spectrum, including observed glycan B- (oxonium) and Y-type ions and mass and precursor monoisotopic selection errors to discriminate between possible glycan candidates. Combined with false discovery rate estimation for the glycan assignment, we show this method is capable of specifically and sensitively identifying glycans in complex glycopeptide analyses and effectively controls the rate of false glycan assignments. The new method has been incorporated into the PTM-Shepherd modification analysis tool to work directly with the MSFragger glyco search in the FragPipe graphical user interface, providing a complete computational pipeline for annotation of N-glycopeptide spectra with FDR control of both peptide and glycan components that is both sensitive and robust against false identifications.
Removing Inter-Experimental Variability from Functional Data in Systems Neuroscience
Authors: Gonschorek Dominic , Höfling Larissa , Szatko Klaudia P. , Franke Katrin , Schubert Timm , Dunn Benjamin A. , Berens Philipp , Klindt David A. , Euler Thomas 
Published: November 2021

AbstractIntegrating data from multiple experiments is common practice in systems neuroscience but it requiresinter-experimental variabilityto be negligible compared to the biological signal of interest. This requirement is rarely fulfilled; systematic changes between experiments can drastically affect the outcome of complex analysis pipelines. Modern machine learning approaches designed to adapt models across multiple data domains offer flexible ways of removing inter-experimental variability where classical statistical methods often fail. While applications of these methods have been mostly limited to single-cell genomics, in this work, we develop a theoretical framework for domain adaptation in systems neuroscience. We implement this in an adversarial optimization scheme that removes inter-experimental variability while preserving the biological signal. We compare our method to previous approaches on a large-scale dataset of two-photon imaging recordings of retinal bipolar cell responses to visual stimuli. This dataset provides a unique benchmark as it contains biological signal from well-defined cell types that is obscured by large inter-experimental variability. In a supervised setting, we compare the generalization performance of cell type classifiers across experiments, which we validate with anatomical cell type distributions from electron microscopy data. In an unsupervised setting, we remove inter-experimental variability from data which can then be fed into arbitrary downstream analyses. In both settings, we find that our method achieves the best trade-off between removing inter-experimental variability and preserving biological signal. Thus, we offer a flexible approach to remove inter-experimental variability and integrate datasets across experiments in systems neuroscience. Code available athttps://github.com/eulerlab/rave.
The socio-economic difference in the prevalence and treatment of diarrheal disease in children under five years across the geo-political zones in Nigeria
Authors: Awoniyi Fatima Badmus , Neupane Subas 
Published: November 2021

AbstractBackgroundDiarrhoeal disease is one of the leading causes of mortality among under-5 children globally and affects the low socio-economic population.ObjectivesThis study aimed at evaluating the socioeconomic differences in the prevalence and its effect on the treatment of diarrheal disease in children in the different geopolitical zone in Nigeria.MethodsData of children under-5 from the 2018 Nigeria Demographic and Health Survey (NDHS) was used. A total of 30,068 women, that had at least a child under-5 years of age and answered diarrhoea specific questions were analysed for the prevalence, while data on 3885 children that reported symptoms of diarrhoea during the 2 weeks preceding the NDHS survey interview were analysed for treatment intervention offered during diarrhoea episodes. Logistic regression models adjusted for socio-demographic factors were used to study the association.ResultsThe overall prevalence of diarrhoea was 12.9% with the highest prevalence in the North East (24.7%), among the poor (17.1%) and the children of uneducated mothers (16.4%). Compared to South-West region, children in North-East (AOR 4.64, 95% CI 3.90, 5.51), North-West (AOR 2.34, 95% CI 1.97, 2.78) and North Central (AOR 2.02, 95% CI 1.69, 2.42) had a high likelihood of having diarrhoea. Children from a poor household (AOR 1.49, 95% CI 1.31, 1.70) had more chance of having diarrhoea. Children in North-East (AOR 2.11, 95% CI 1.49, 3.01) and North-West (AOR 2.52, 95% CI 1.77, 3.60) were more likely to receive treatment in a health care facility and also had less likely to receive more amount of drink and food during diarrhoea compared to South-West region.ConclusionsDiarrhoea prevalence is high in Nigeria with significant regional difference both in the prevalence and treatment of diarrheal disease which is also associated with household socio-economic status.
Quantifying the effects of non-pharmaceutical and pharmaceutical interventions against COVID-19 epidemic in the Republic of Korea: Mathematical model-based approach considering age groups and the Delta variant
Authors: Ko Youngsuk , Mendoza Victoria May P. , Seo Yubin , Lee Jacob , Kim Yeonju , Kwon Donghyok , Jung Eunok 
Published: November 2021

AbstractBackgroundEarly vaccination efforts and non-pharmaceutical interventions were insufficient to prevent a surge of coronavirus disease 2019 (COVID-19) cases triggered by the Delta variant. This study aims to understand how vaccination and variants contribute to the spread of COVID-19 so that appropriate measures are implemented.MethodsA compartment model that includes age, vaccination, and infection with the Delta or non-Delta variants was developed. We estimated the transmission rates using maximum likelihood estimation and phase-dependent reduction effect of non-pharmaceutical interventions (NPIs) according to government policies from 26 February to 8 October 2021. We extended our model simulation until 31 December considering the initiation of eased NPIs. Furthermore, we also performed simulations to examine the effect of NPIs, arrival timing of Delta variant, and speed of vaccine administration.ResultsThe estimated transmission rate matrices show distinct pattern, with the transmission rates of younger age groups (0 39 years) much larger than non-Delta. Social distancing (SD) level 2 and SD4 in Korea were associated with transmission reduction factors of 0.64 to 0.69 and 0.70 to 0.78, respectively. The easing of NPIs to a level comparable to SD2 should be initiated not earlier than 16 October to keep the number of severe cases below the capacity of Korea’s healthcare system. Simulation results also showed that a surge prompted by the spread of the Delta variant can be prevented if the number of people vaccinated daily was larger.ConclusionsSimulations showed that the timing of easing and intensity of NPIs, vaccination speed, and screening measures are key factors in preventing another epidemic wave.2Key MessagesMaximum likelihood estimation can be utilized to determine the transmission rates of the Delta and non-Delta variants.The phase-dependent NPIs implemented by the Korean government were effectively quantified in the modelling study.Even with fast vaccination, resurgence of cases is still possible if NPIs are eased too early or screening measures are relaxed.The model can be used as a guide for policy makers on deciding appropriate SD level that considers not only disease control, but also the socio-economic impact of maintaining strict measures.