bluuebunny/crossref_metadata_2025_split huggingface dataset:
Examining multiple funding flows to public healthcare providers in low- and middle-income countries — results from case studies in Burkina Faso, Kenya, Morocco, Nigeria, Tunisia and Vietnam
Authors: Dkhimi Fahdi , Honda Ayako , Hanson Kara , Mbau Rahab , Onwujekwe Obinna , Phuong Hoang Thi , Mathauer Inke , Akhnif El Houcine , Jaouadi Imen , Kiendrébéogo Joël Arthur , Ezumah Nkoli , Kabia Evelyn , Barasa Edwine 
Published: November 2023

Abstract
Provider payment methods are traditionally examined by appraising the incentive signals inherent in individual payment mechanisms. However, mixed payment arrangements, which result in multiple funding flows from purchasers to providers, could be better understood by applying a systems approach that assesses the combined effects of multiple payment streams on healthcare providers. Guided by the framework developed by Barasa et al. (2021) (Barasa E, Mathauer I, Kabia E et al. 2021. How do healthcare providers respond to multiple funding flows? A conceptual framework and options to align them. Health Policy and Planning 36: 861–8.), this paper synthesizes the findings from six country case studies that examined multiple funding flows and describes the potential effect of multiple payment streams on healthcare provider behaviour in low- and middle-income countries. The qualitative findings from this study reveal the extent of undesirable provider behaviour occurring due to the receipt of multiple funding flows and explain how certain characteristics of funding flows can drive the occurrence of undesirable behaviours. Service and resource shifting occurred in most of the study countries; however, the occurrence of cost shifting was less evident. The perceived adequacy of payment rates was found to be the strongest driver of provider behaviour in the countries examined. The study results indicate that undesirable provider behaviours can have negative impacts on efficiency, equity and quality in healthcare service provision. Further empirical studies are required to add to the evidence on this link. In addition, future research could explore how governance arrangements can be used to coordinate multiple funding flows, mitigate unfavourable consequences and identify issues associated with the implementation of relevant governance measures.
Antibody-Mediated Suppression Regulates the Humoral Immune Response to Influenza Vaccination in Humans
Authors: Lu Xiuhua , Liu Feng , Tzeng Wen-Ping , York Ian A , Tumpey Terrence M , Levine Min Z 
Published: November 2023

Abstract

Background
Preexisting immunity, including memory B cells and preexisting antibodies, can modulate antibody responses to influenza in vivo to antigenically related antigens. We investigated whether preexisting hemagglutination inhibition (HAI) antibodies targeting the K163 epitope on the hemagglutinin (K163 antibodies) could affect antibody responses following vaccination with A/California/07/2009-like A(H1N1)pdm09 influenza viruses in humans.

Methods
Pre- and postvaccination sera collected from 300 adults (birth years, 1961–1998) in 6 seasons (2010–2016) were analyzed by HAI assays with 2 reverse genetics viruses and A(H1N1) viruses circulated from 1977 to 2018. Antibody adsorption assays were used to verify the preexisting K163 antibody–mediated suppression effect.

Results
Preexisting K163 antibody titers ≥80 affected HAI antibody responses following influenza vaccination containing A/California/07/2009-like antigens. At high K163 antibody concentrations (HAI antibody titers ≥160), all HAI antibody responses were suppressed. However, at moderate K163 antibody concentrations (HAI antibody titer, 80), only K163 epitope–specific antibody responses were suppressed, and novel HAI antibody responses targeting the non-K163 epitopes were induced by vaccination. Novel antibodies targeting non-K163 epitopes cross-reacted with newly emerging A(H1N1)pdm09 strains with a K163Q mutation rather than historic 1977–2007 A(H1N1) viruses.

Conclusions
K163 antibody–mediated suppression shapes antibody responses to A(H1N1)pdm09 vaccination. Understanding how preexisting antibodies suppress and redirect vaccine-induced antibody responses is of great importance to improve vaccine effectiveness.
3D hydrodynamics simulations of a 3 M⊙ core helium burning star
Authors: Blouin Simon , Herwig Falk , Mao Huaqing , Denissenkov Pavel , Woodward Paul R 
Published: November 2023

ABSTRACT
The inner structure of core helium burning (CHeB) stars remains uncertain due to the yet unknown nature of mixing at the boundary of their cores. Large convective cores beyond a bare Schwarzschild model are favoured both from theoretical arguments and from asteroseismological constraints. However, the exact nature of this extra mixing, and in particular the possible presence of semiconvective layers, is still debated. In this work, we approach this problem through a new avenue by performing the first full-sphere 3D hydrodynamics simulations of the interiors of CHeB stars. We use the ppmstar explicit gas dynamics code to simulate the inner 0.45$\, {\rm M}_{\odot }$ of a 3 M⊙ CHeB star. Simulations are performed using different Cartesian grid resolutions (7683, 11523, and 17283) and heating rates. We use two different initial states, one based on mesas's predictive mixing scheme (which significantly extends the core beyond the Schwarzschild boundary) and one based on the convective premixing approach (which exhibits a semiconvective interface). The general behaviour of the flow in the convective core and in the stable envelope (where internal gravity waves are observed) is consistent with our recent simulations of core convection in massive main-sequence stars, and so are the various luminosity scaling relations. The semiconvective layers are dominated by strong internal gravity waves that do not produce measurable species mixing, but overshooting motions from the convective core gradually homogenize the semiconvective interface. This process can possibly completely erase the semiconvective layers, which would imply that CHeB stars do not harbour a semiconvection zone.
Synthesis of peptide–siRNA conjugates via internal sulfonylphosphoramidate modifications and evaluation of their in vitro activity
Authors: Smidt Jakob Melgaard , Lykke Lennart , Stidsen Carsten Enggaard , Pristovšek Nuša , Gothelf Kurt V 
Published: November 2023

Abstract
Conjugates of therapeutic oligonucleotides (ONs) including peptide conjugates, provide a potential solution to the major challenge of specific tissue delivery faced by this class of drugs. Conjugations are often positioned terminal at the ONs, although internal placement of other chemical modifications are known to be of critical importance. The introduction of internal conjugation handles in chemically modified ONs require highly specialized and expensive nucleoside phosphoramidites. Here, we present a method for synthesizing a library of peptide–siRNA conjugates by conjugation at internal phosphorous positions via sulfonylphosphoramidate modifications incorporated into the sense strand. The sulfonylphosphoramidate modification offers benefits as it can be directly incorporated into chemically modified ONs by simply changing the oxidation step during synthesis, and furthermore holds the potential to create multifunctionalized therapeutic ONs. We have developed a workflow using a novel pH-controlled amine-to-amine linker that yields peptide–siRNA conjugates linked via amide bonds, and we have synthesized conjugates between GLP1 peptides and a HPRT1 siRNA as a model system. The in vitro activity of the conjugates was tested by GLP1R activity and knockdown of the HPRT1 gene. We found that conjugation near the 3′-end is more favorable than certain central internal positions and different internal conjugation strategies were compared.
Cistrome Data Browser: integrated search, analysis and visualization of chromatin data
Authors: Taing Len , Dandawate Ariaki , L’Yi Sehi , Gehlenborg Nils , Brown Myles , Meyer Clifford A 
Published: November 2023

Abstract
The Cistrome Data Browser is a resource of ChIP-seq, ATAC-seq and DNase-seq data from humans and mice. It provides maps of the genome-wide locations of transcription factors, cofactors, chromatin remodelers, histone post-translational modifications and regions of chromatin accessible to endonuclease activity. Cistrome DB v3.0 contains approximately 45 000 human and 44 000 mouse samples with about 32 000 newly collected datasets compared to the previous release. The Cistrome DB v3.0 user interface is implemented as a single page application that unifies menu driven and data driven search functions and provides an embedded genome browser, which allows users to find and visualize data more effectively. Users can find informative chromatin profiles through keyword, menu, and data-driven search tools. Browser search functions can predict the regulators of query genes as well as the cell type and factor dependent functionality of potential cis-regulatory elements. Cistrome DB v3.0 expands the display of quality control statistics, incorporates sequence logos into motif enrichment displays and includes more expansive sample metadata. Cistrome DB v3.0 is available at http://db3.cistrome.org/browser.
Genome-wide transformation reveals extensive exchange across closely related Bacillus species
Authors: Förster Mona , Rathmann Isabel , Yüksel Melih , Power Jeffrey J , Maier Berenike 
Published: November 2023

Abstract
Bacterial transformation is an important mode of horizontal gene transfer that helps spread genetic material across species boundaries. Yet, the factors that pose barriers to genome-wide cross-species gene transfer are poorly characterized. Here, we develop a replacement accumulation assay to study the effects of genomic distance on transfer dynamics. Using Bacillus subtilis as recipient and various species of the genus Bacillus as donors, we find that the rate of orthologous replacement decreases exponentially with the divergence of their core genomes. We reveal that at least 96% of the B. subtilis core genes are accessible to replacement by alleles from Bacillus spizizenii. For the more distantly related Bacillus atrophaeus, gene replacement events cluster at genomic locations with high sequence identity and preferentially replace ribosomal genes. Orthologous replacement also creates mosaic patterns between donor and recipient genomes, rearranges the genome architecture, and governs gain and loss of accessory genes. We conclude that cross-species gene transfer is dominated by orthologous replacement of core genes which occurs nearly unrestricted between closely related species. At a lower rate, the exchange of accessory genes gives rise to more complex genome dynamics.
HOCOMOCO in 2024: a rebuild of the curated collection of binding models for human and mouse transcription factors
Authors: Vorontsov Ilya E , Eliseeva Irina A , Zinkevich Arsenii , Nikonov Mikhail , Abramov Sergey , Boytsov Alexandr , Kamenets Vasily , Kasianova Alexandra , Kolmykov Semyon , Yevshin Ivan S , Favorov Alexander , Medvedeva Yulia A , Jolma Arttu , Kolpakov Fedor , Makeev Vsevolod J , Kulakovskiy Ivan V 
Published: November 2023

Abstract
We present a major update of the HOCOMOCO collection that provides DNA binding specificity patterns of 949 human transcription factors and 720 mouse orthologs. To make this release, we performed motif discovery in peak sets that originated from 14 183 ChIP-Seq experiments and reads from 2554 HT-SELEX experiments yielding more than 400 thousand candidate motifs. The candidate motifs were annotated according to their similarity to known motifs and the hierarchy of DNA-binding domains of the respective transcription factors. Next, the motifs underwent human expert curation to stratify distinct motif subtypes and remove non-informative patterns and common artifacts. Finally, the curated subset of 100 thousand motifs was supplied to the automated benchmarking to select the best-performing motifs for each transcription factor. The resulting HOCOMOCO v12 core collection contains 1443 verified position weight matrices, including distinct subtypes of DNA binding motifs for particular transcription factors. In addition to the core collection, HOCOMOCO v12 provides motif sets optimized for the recognition of binding sites in vivo and in vitro, and for annotation of regulatory sequence variants. HOCOMOCO is available at https://hocomoco12.autosome.org and https://hocomoco.autosome.org.
m6A epitranscriptome analysis reveals differentially methylated transcripts that drive early chemoresistance in bladder cancer
Authors: Hodara Emmanuelle , Mades Aubree , Swartz Lisa , Iqbal Maheen , Xu Tong , Bsteh Daniel , Farnham Peggy J , Rhie Suhn K , Goldkorn Amir 
Published: November 2023

Abstract
N 6-Methyladenosine (m6A) RNA modifications dynamically regulate messenger RNA processing, differentiation and cell fate. Given these functions, we hypothesized that m6A modifications play a role in the transition to chemoresistance. To test this, we took an agnostic discovery approach anchored directly to chemoresistance rather than to any particular m6A effector protein. Specifically, we used methyl-RNA immunoprecipitation followed by sequencing (MeRIP-seq) in parallel with RNA sequencing to identify gene transcripts that were both differentially methylated and differentially expressed between cisplatin-sensitive and cisplatin-resistant bladder cancer (BC) cells. We filtered and prioritized these genes using clinical and functional database tools, and then validated several of the top candidates via targeted quantitative polymerase chain reaction (qPCR) and MeRIP-PCR. In cisplatin-resistant cells, SLC7A11 transcripts had decreased methylation associated with decreased m6A reader YTHDF3 binding, prolonged RNA stability, and increased RNA and protein levels, leading to reduced ferroptosis and increased survival. Consistent with this, cisplatin-sensitive BC cell lines and patient-derived organoids exposed to cisplatin for as little as 48 h exhibited similar mechanisms of SLC7A11 upregulation and chemoresistance, trends that were also reflected in public cancer survival databases. Collectively, these findings highlight epitranscriptomic plasticity as a mechanism of rapid chemoresistance and a potential therapeutic target.
Clinical Predictors of Survival in Patients With BRAFV600-Mutated Metastatic Melanoma Treated With Combined BRAF and MEK Inhibitors After Immune Checkpoint Inhibitors
Authors: Kahn Adriana M , Perry Curtis J , Etts Katrina , Kluger Harriet , Sznol Mario 
Published: November 2023

Abstract
Prospective and between trial comparisons indicate that first-line treatment with immune checkpoint inhibitors improves survival outcomes compared to first-line therapy with combined BRAF and MEK inhibitors in metastatic melanoma containing BRAFV600E/K mutations. Long-term outcomes for BRAF/MEK inhibition after progression on immunotherapy have not been reported. Moreover, clinical variables associated with outcome from treatment with combined BRAF/MEK inhibition were previously identified in the first-line setting but have not been investigated when targeted therapies are administered after progression on immune therapy. We performed a retrospective single institution analysis of 40 metastatic melanoma patients receiving combined BRAF/MEK inhibitors after progression on an anti-PD-1 or ipilimumab plus nivolumab to assess response rate by RECIST 1.1, progression-free and overall survival (PFS and OS). Pretreatment clinical variables were analyzed for association with OS. Ipilimumab/nivolumab was the first-line immunotherapy regimen in 39 patients (97.5%), and BRAFV600E/K mutations were present in 33 (83%) and 7 (17%) patients, respectively. The median OS from start of BRAF/MEK inhibitors was 20.3 months (1.73-106.4+, 95% CI of median 13.3-30.7). Clinical characteristics associated with worse survival prior to starting BRAF/MEK inhibitors included age &gt; 60 years (median OS 14 vs. 28 months; HR 2.5; 95% CI 0.91-6.87, P = .023), ECOG-PS &gt; 2 (median OS 7 vs. 33 months; HR 2.89; 95% CI 0.78-10.76, P = .018), and presence of bone metastases (median OS 9 vs. 52 months; HR 3.17; 95% CI 1.33-7.54, P = .002). These associations with shorter survival maintained their significance on multivariate analysis. If confirmed in larger cohorts, the identified prognostic variables can be used for stratification of patients in future randomized trials.
Type II metacaspase mediates light-dependent programmed cell death in Chlamydomonas reinhardtii
Authors: Lambert Lou , de Carpentier Félix , André Phuc , Marchand Christophe H , Danon Antoine 
Published: November 2023

Abstract
Among the crucial processes that preside over the destiny of cells from any type of organism are those involving their self-destruction. This process is well characterized and conceptually logical to understand in multicellular organisms; however, the levels of knowledge and comprehension of its existence are still quite enigmatic in unicellular organisms. We use Chlamydomonas (Chlamydomonas reinhardtii) to lay the foundation for understanding the mechanisms of programmed cell death (PCD) in a unicellular photosynthetic organism. In this paper, we show that while PCD induces the death of a proportion of cells, it allows the survival of the remaining population. A quantitative proteomic analysis aiming at unveiling the proteome of PCD in Chlamydomonas allowed us to identify key proteins that led to the discovery of essential mechanisms. We show that in Chlamydomonas, PCD relies on the light dependence of a photosynthetic organism to generate reactive oxygen species and induce cell death. Finally, we obtained and characterized mutants for the 2 metacaspase genes in Chlamydomonas and showed that a type II metacaspase is essential for PCD execution.
Characteristics of Japanese physician influencers on Twitter during the COVID-19 pandemic and fact-checking their tweets on COVID-19-related drugs
Authors: Suzuki Tomoya , Tanimoto Tetsuya , Kamamoto Sae , Ozaki Akihiko , Torii Hiroyuki A , Hase Daisuke , Murayama Anju , Yoshimura Hiroki , Uno Kazuko 
Published: November 2023

Abstract

Background
During the coronavirus disease-2019 (COVID-19) pandemic, segments of the public relied on social media platforms such as Twitter for medical information shared by medical personnel. Although physicians are likely to disseminate more accurate information on Twitter than non-medical individuals, it cannot be taken for granted. As such, tweets written by physicians in Japan should also be scrutinized for accuracy.

Purpose
The purpose of this study was to create a profile of the most popular physician influencers on Twitter in Japan, and to do a fact-check of their tweets regarding COVID-19-related drugs.

Design
This is a retrospective observational study.

Methods
We purchased Twitter data for Japan for the initial 9 months of the COVID-19 pandemic (from January 2020 to September 2020), and extracted tweets with keywords related to COVID-19 at a sampling rate of 3%. The most popular physicians were identified and selected consecutively by searching for the top 1000 accounts using Twitter’s search function. These top accounts were considered influencers and their tweets and retweets concerning COVID-19-related drugs were fact-checked against scientific literature.

Results
We identified 21 physician influencers with real names: most were male in their 40s and 50s working at private medical facilities. The contents of their tweets were mainly sourced from scientific publications that were current at that time. The fact-check revealed that only one of 50 tweets was not correct while the others had no identifiable inaccuracies.

Conclusions
Except for one tweet, tweets written and retweeted by Japanese physician influencers concerning the COVID-19-related drugs contained predominantly accurate information.
Repayment Flexibility and Risk Taking: Experimental Evidence from Credit Contracts
Authors: Battaglia Marianna , Gulesci Selim , Madestam Andreas 
Published: November 2023

Abstract
A widely held view is that small firms in developing countries are prevented from making profitable investments by lack of access to credit and insurance markets. One solution is to provide repayment flexibility in credit contracts. Repayment flexibility eases both the credit constraint, as it allows for increased spending during the start-up phase, and offers insurance, in case of fluctuations in income. In a field experiment among traditional microfinance clients and larger collateralized borrowers in Bangladesh, we randomly assign the option to delay up to 2 monthly repayments at any point during a 12-month loan cycle. The flexible contract leads to substantial improvements in the traditional microfinance clients’ business outcomes, driven by borrowers in the upper tail of the distribution. In addition, we find a significant impact on socio-economic status, combined with lower default rates. We show theoretically and empirically that these effects are induced by an increase in entrepreneurial risk taking, implying that the primary mechanism is insurance provision. Repayment flexibility also attracts less risk-averse borrowers interested in business expansion. At the same time, the effects for the larger loan are much more modest. Our findings suggest that lack of insurance is an important constraint for small firms but that a simple financial product that increases repayment flexibility can be an effective tool for enabling enterprise growth.
Social processing modulates the initial allocation of attention towards angry faces: evidence from the N2pc component
Authors: Wirth Benedikt Emanuel , Wentura Dirk 
Published: November 2023

Abstract
Previous research has shown that attentional bias towards angry faces is moderated by the activation of a social processing mode. More specifically, reliable cueing effects for angry face cues in the dot-probe task only occurred when participants performed a task that required social processing of the target stimuli. However, cueing effects are a rather distal measure of covert shifts in spatial attention. Thus, it remains unclear whether the social processing mode modulates initial allocation of attention to or attentional disengagement from angry faces. In the present study, we used the N2pc, an event-related potential component, as an index of attentional shifts towards angry faces. Participants performed a dot-probe task with two different target conditions while the electroencephalogram (EEG) was recorded. In the social target condition, target stimuli were socially meaningful (schematic faces), and in the non-social target condition, they were meaningless (scrambled schematic faces). The amplitude of the N2pc component elicited by angry face cues was significantly larger in the social target condition than in the non-social target condition. This pattern also occurred for behavioural cueing effects. These results suggest that the activation of a social processing mode due to current task demands affects the initial allocation of attention towards angry faces.