bluuebunny/crossref_metadata_2025_split huggingface dataset:
Double Arterialized Scapular Tip Free Flap for Mandibular Reconstruction
Authors: Arcuri Francesco , Laganà Francesco , Bianchi Bernardo , Ferrari Silvano , Ferri Andrea 
Published: July 2023

Introduction:
Scapular tip free flap (STFF) has become today one of the workhorse flaps for maxillary reconstruction; recently, the possibility of extending the vascular supply by adding to the angular branch of the circumflex pedicle up to its periosteal entrance in the lateral border of the scapula has been proposed as a reliable technique to improve the length of perfused bone when STFF is used for mandibular reconstruction. The purpose of this study was to evaluate the patients who had received microvascular reconstruction of the mandible with STFF vascularized by both the circumflex scapular artery via the periosteal branch and the thoracodorsal artery via the angular artery.

Methods:
A retrospective chart review was conducted for all patients who underwent reconstruction with an STFF for mandibular defect between January 2016 and December 2020 at the University Hospital of Parma. The outcome was evaluated by assessing dietary intake (unrestricted, soft, liquid, and tube feed) and speech (normal, intelligible, partially intelligible, and unintelligible).

Results:
The final study sample included 9 patients (5 men and 4 women). The average patient age was 68.9 years (range, 59.9–74.8 y) at the time of surgery. There was no flap loss. A 1-year postoperative computed tomography scan revealed full osteointegration of the flap.

Conclusions:
Our results show that the STFF is a valuable reconstructive option, especially in patients with complex head and neck defects requiring soft and hard tissues.
The Effect of Different Types of Collagen Membranes on Peri-Implant Dehiscence Defects
Authors: Dogan Kaplan Aylin , Cinar Ihsan Caglar , Gultekin Bahattin Alper , Avci Kupeli Zehra , Ozfirat Eren Can , Yalcin Serdar 
Published: July 2023

Aim:
This experimental study aimed to compare the bone-implant contact (BIC) following guided bone regeneration with 3 bioabsorbable collagen membranes on peri-implant dehiscence defects.

Methods:
Forty-eight standard dehiscence defects were created in the sheep iliac bone crest, and dental implants were placed into the defects. With the guided bone regeneration technique, the autogenous graft was placed into the defect and covered with different types of membranes: Geistlich Bio-Gide, Ossix Plus, and Symbios Prehydrated were covered. One group was left without a membrane as the control group (C) by applying only an autogenous graft. After recovery periods of 3 and 6 weeks, the experimental animals were sacrificed. Histologic sections were prepared by a nondecalcified method, and BIC was examined.

Results:
There was no statistically important difference between groups in the third week (P>0.05). A statistically significant difference between groups was found in the sixth week (P<0.01). Bone-implant contact values of the C group were significantly lower than those of the Geistlich Bio-Gide and Ossix Plus groups (P<0.05). There was no statistically significant difference between control and Symbios Prehydrated groups (P>0.05). In all sections, osseointegration was observed, with no signs of inflammation, necrosis, or foreign body reaction.

Conclusion:
In our study, it has been concluded that the resorbable collagen membranes used in treating peri-implant dehiscence defects might affect the BIC, and the success varies according to the type of membrane used.
An integrative literature review examining the key elements of bereavement follow-up interventions in critical care
Authors: Labram Aileen H. , Johnston Bridget , McGuire Margaret 
Published: July 2023

Purpose of review
The aim of this review is to examine bereavement follow-up intervention studies in critical care, with the purpose of integrating results on the timing, content, aims and outcomes of interventions. The impact of a death in critical care is well documented, and bereavement follow-up is recognised as an important topic, but there is limited research with little consensus on the content and structure of interventions.

Recent findings
A total of 18 papers were selected; 11 are intervention studies, with only one randomised control trial. Six papers were from national surveys and are not the focus of this review. Bereavement follow-up mainly consisted of information giving, condolence interventions, telephone calls and meetings with families. The timing, content, aims and outcomes depended on the intervention and were influenced by the design of the study.

Summary
Overall, bereavement follow-up is acceptable for relatives but outcomes are mixed. Calls for more research are valid, but how do we utilise the current research to better inform the critical care community? Researchers suggest that bereavement follow-up interventions need to be designed with specific aims and outcomes, in collaboration with bereaved families that are appropriate to the intervention.
The VanS sensor histidine kinase from type-B VRE recognizes vancomycin directly
Authors: Maciunas Lina J. , Rotsides Photis , D’Lauro Elizabeth J. , Brady Samantha , Beld Joris , Loll Patrick J. 
Published: July 2023

AbstractVancomycin-resistantenterococci (VRE) are among the most common causes of nosocomial infections and have been prioritized as targets for new therapeutic development. Many genetically distinct types of VRE have been identified; however, they all share a common suite of resistance genes that function together to confer resistance to vancomycin. Expression of the resistance phenotype is controlled by the VanRS two-component system. This system senses the presence of the antibiotic, and responds by initiating transcription of resistance genes. VanS is a transmembrane sensor histidine kinase, and plays a fundamental role in antibiotic resistance by detecting vancomycin or its effects; it then transduces this signal to the VanR transcription factor, thereby alerting the organism to the presence of the antibiotic. Despite the critical role played by VanS, fundamental questions remain about its function, and in particular about how it senses vancomycin. Here, we focus on a purified VanRS system from one of the most clinically prevalent forms of VRE, type B. We show that in a native-like membrane environment, the autokinase activity of type-B VanS is strongly stimulated by vancomycin. We additionally demonstrate that this effect is mediated by a direct physical interaction between the antibiotic and the type-B VanS protein, and localize the interacting region to the protein’s periplasmic domain. This represents the first time that a direct sensing mechanism has been confirmed for any VanS protein.Significance StatementWhenvancomycin-resistantenterococci (VRE) sense the presence of vancomycin, they remodel their cell walls to block antibiotic binding. This resistance phenotype is controlled by the VanS protein, a histidine kinase that senses the antibiotic or its effects and signals for transcription of resistance genes. However, the mechanism by which VanS detects the antibiotic has remained unclear, with no consensus emerging as to whether the protein interacts directly with vancomycin, or instead detects some downstream consequence of vancomycin’s action. Here, we show that for one of the most clinically relevant types of VRE, type B, VanS is activated by direct binding of the antibiotic. Such mechanistic insights will likely prove useful in circumventing vancomycin resistance.
Trabectedin derails transcription-coupled nucleotide excision repair to induce DNA breaks in highly transcribed genes
Authors: Son Kook , Takhaveev Vakil , Mor Visesato , Yu Hobin , Dillier Emma , Zilio Nicola , Püllen Nikolai J.L. , Ivanov Dmitri , Ulrich Helle D. , Sturla Shana J. , Schärer Orlando D. 
Published: July 2023

ABSTRACTMost genotoxic anticancer agents fail in tumors with intact DNA repair. Therefore, trabectedin, a unique agent more toxic to cells with active DNA repair, specifically transcription-coupled nucleotide excision repair (TC-NER), provides new therapeutic opportunities. To unlock the potential of trabectedin and inform its application in precision oncology, a full mechanistic understanding of the drug’s TC-NER-dependent toxicity is needed. Here, we determined that abortive TC-NER of trabectedin-DNA adducts forms persistent single-strand breaks (SSBs) as the adducts block the second of the two sequential NER incisions. We mapped the 3’-hydroxyl groups of SSBs originating from the first NER incision at trabectedin lesions, recording TC-NER on a genome-wide scale. We showed that trabectedin-induced SSBs primarily occur in transcribed strands of active genes and peak near transcription start sites. Frequent SSBs were also found outside gene bodies, connecting TC-NER to divergent transcription from promoters. This work advances the use trabectedin for precision oncology and for studying TC-NER and transcription.
Where in the brain do internally generated and externally presented visual information interact?
Authors: Alho Jussi , Gotsopoulos Athanasios , Silvanto Juha 
Published: July 2023

AbstractConscious experiences normally result from the flow of external input into our sensory systems. However, we can also create conscious percepts independently of sensory stimulation. These internally generated percepts are referred to as mental images, and they have many similarities with real visual percepts. Consequently, mental imagery is often referred to as “seeing in the mind’s eye”. While the neural basis of imagery has been widely studied, the interaction between internal and external sources of visual information has received little interest. Here we examined this question by using fMRI to record brain activity of healthy human volunteers while they were performing visual imagery that was distracted with a concurrent presentation of a visual stimulus. Multivariate pattern analysis (MVPA) was used to identify the brain basis of this interaction. Visual imagery was reflected in several brain areas in ventral temporal, lateral occipitotemporal, and posterior frontal cortices, with a left-hemisphere dominance. The key finding was that imagery content representations in the left lateral occipitotemporal cortex were disrupted when a visual distractor was presented during imagery. Our results thus demonstrate that the representations of internal and external visual information interact in brain areas associated with the encoding of visual objects and shapes.
RNA G-quadruplexes forming scaffolds for α-synuclein aggregation lead to progressive neurodegeneration
Authors: Matsuo Kazuya , Asamitsu Sefan , Maeda Kohei , Kawakubo Kosuke , Komiya Ginji , Kudo Kenta , Sakai Yusuke , Hori Karin , Ikenoshita Susumu , Usuki Shingo , Funahashi Shiori , Kawata Yasushi , Mizobata Tomohiro , Shioda Norifumi , Yabuki Yasushi 
Published: July 2023

AbstractSynucleinopathies, including Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy, are triggered by the aggregation of α-synuclein, leading to progressive neurodegeneration1,2,3,4,5,6,7,8. However, the intracellular mechanism of α-synuclein aggregation remains unclear. Here we show that assembly of RNA G-quadruplexes forming scaffolds for α-synuclein aggregation, contributing to neurodegeneration. Purified α-synuclein binds RNA G-quadruplexes directly through the N-terminus. RNA G-quadruplex itself undergoes phase separation and assembly by Ca2+, accelerating the sol–gel phase transition of α-synuclein. In α-synuclein preformed fibrils-treated neurons, RNA G-quadruplexes assembly composed of synaptic mRNAs co-aggregates with α-synuclein upon Ca2+excess influx into cytoplasm, eliciting synaptic dysfunction. Forced assembly of RNA G-quadruplexes using an optogenetic approach evokes α-synuclein aggregation, neuronal dysfunction and neurodegeneration. Administration of 5-aminolevulinic acid, a prodrug of protoporphyrin IX that prevents phase separation of RNA G-quadruplexes9, attenuating α-synuclein aggregation, neurodegeneration, and progressive motor deficits in α-synuclein preformed fibrils-injected synucleinopathy mice. Together, assembly of RNA G-quadruplexes due to dysregulation of intracellular Ca2+homeostasis accelerates α-synuclein phase transition and aggregation may contribute to pathogenesis of synucleinopathies.
Suppressive might of a few: T follicular regulatory cells impede auto-reactivity despite being outnumbered in the germinal centres
Authors: Schips Marta , Mitra Tanmay , Bandyopadhyay Arnab , Meyer-Hermann Michael 
Published: July 2023

AbstractThe selection of high-affinity B cells and the production of high-affinity antibodies are mediated by T follicular helper cells (Tfhs) within germinal centres (GCs). Therein, somatic hypermutation and selection enhance B cell affinity but risk the emergence of self-reactive B cell clones. Despite being outnumbered compared to their helper counterpart, the ablation of T follicular regulatory cells (Tfrs) results in enhanced dissemination of self-reactive antibody-secreting cells (ASCs). The specific mechanisms by which Tfrs exert their regulatory action on self-reactive B cells are largely unknown. We developed computer simulations to investigate how Tfrs regulate either selection or differentiation of B cells to prevent auto-reactivity. We observed that Tfr-induced apoptosis of self-reactive B cells during the selection phase impedes self-reactivity with physiological Tfr numbers, especially when Tfrs can access centrocyte-enriched GC areas. While this aided in selecting non-self-reactive B cells by restraining competition, higher Tfr numbers distracted non-self-reactive B cells from receiving survival signals from Tfhs. Thus, the location and number of Tfrs must be regulated to circumvent suchTfr distractionand avoid disrupting GC evolution. In contrast, when Tfrs regulate differentiation of selected centrocytes by promoting recycling to the dark zone phenotype of self-reactive GC resident pre-plasma cells (GCPCs), higher Tfr numbers were required to impede the circulation of self-reactive ASCs (s–ASCs). On the other hand, Tfr-engagement with GCPCs and subsequent apoptosis of s–ASCs can control self-reactivity with low Tfr numbers, but does not confer selection advantage to non-self-reactive B cells. The simulations predict that to restrict auto-reactivity, natural redemption of self-reactive B cells is insufficient and that Tfrs should increase the mutation probability of self-reactive B cells.
In-Silicoanalysis of Human Insulin Gene for Mirror repeat sequences
Authors: Yadav Manisha , Sehrawat Barkha , Yadav Pooja , Kumari Jyoti , Yadav Priyanka , Yadav Shivani , Yadav Rachna , Singh Amrita , Yadav Sandeep 
Published: July 2023

AbstractThe genetic material contains all the instructions necessary for the development, functioning & regulation of biological processes. This is also considering as a regulatory molecule. The structure constitute by its unique pattern of bases make it unique for every living being consider from bacteria to human. The varied pattern of bases in genomes or genes represents different types of repeats. These repeats types constitute the major fraction of the genomes. Among varied types Mirror repeats (MR’s) play crucial roles in the genome especially in formation of H-DNA structure by Non Watson pairing. Some studies suggest that mirror sequences responsible for neurological diseases also. Now days in modern era of technologyin silicotechniques were develop to extract any type of repeat sequences from any gene or genome. The major focus of current work is on identification of mirror repeats (MR’s) from human insulin gene sequence using anin silicoapproach. The approach is refer to as FPCB (FASTA Parallel Complement Analysis) were utilized to extract MR sequences. From the current study a total no of 210 MR sequenced were identified in Human insulin gene. The identified repeats vary in their length and majority of them are imperfect in nature. The maximum no of MR were reported in the region 3 & minimum is in the region 8 (8). In the remaining regions the no of MR sequences were lies in between maximum & minimum values. These sequences may be helpful in many molecular level studies.
Bursts of novel composite gene families at major nodes in animal evolution
Authors: Mulhair Peter O. , Moran Raymond J. , Pathmanathan Jananan S. , Sussfeld Duncan , Creevey Christopher J. , Siu-Ting Karen , Whelan Fiona J. , Pisani Davide , Constantinides Bede , Pelletier Eric , Lopez Philippe , Bapteste Eric , McInerney James O. , O’Connell Mary J. 
Published: July 2023

AbstractA molecular level perspective on how novel phenotypes evolve is contingent on our understanding of how genomes evolve through time, and of particular interest is how novel elements emerge or are lost. Mechanisms of protein evolution such as gene duplication have been well established. Studies of gene fusion events show they often generate novel functions and adaptive benefits. Identifying gene fusion and fission events on a genome scale allows us to establish the mode and tempo of emergence of composite genes across the animal tree of life, and allows us to test the repeatability of evolution in terms of determining how often composite genes can arise independently. Here we show that ∼5% of all animal gene families are composite, and their phylogenetic distribution suggests an abrupt, rather than gradual, emergence during animal evolution. We find that gene fusion occurs at a higher rate than fission (73.3% vs 25.4%) in animal composite genes, but many gene fusions (79% of the 73.3%) have more complex patterns including subsequent fission or loss. We demonstrate that nodes such as Bilateria, Euteleostomi, and Eutheria, have significantly higher rates of accumulation of composite genes. We observe that in general deuterostomes have a greater amount of composite genes as compared to protostomes. Intriguingly, up to 41% of composite gene families have evolved independently in different clades showing that the same solutions to protein innovation have evolved time and again in animals.Significance statementNew genes emerge and are lost from genomes over time. Mechanisms that can produce new genes include, but are not limited to, gene duplication, retrotransposition,de novogene genesis, and gene fusion/fission. In this work, we show that new genes formed by fusing distinct homologous gene families together comprise a significant portion of the animal proteome. Their pattern of emergence through time is not gradual throughout the animal phylogeny - it is intensified on nodes of major transition in animal phylogeny. Interestingly, we see that evolution replays the tape frequently in these genes with 41% of gene fusion/fission events occurring independently throughout animal evolution.
A large sensory and multi-omics evaluation unraveled chemical and genetic basis of orange flavor
Authors: Fan Zhen , Jeffries Kristen A. , Sun Xiuxiu , Olmedo Gabriela , Zhao Wei , Mattia Matthew R. , Stover Ed , Manthey John A. , Baldwin Elizabeth A. , Lee Seonghee , Gmitter Frederick G. , Plotto Anne , Bai Jinhe 
Published: July 2023

AbstractSweet orange (Citrus sinensis) exhibits limited genetic diversity and high susceptibility to Huanglongbing (HLB). New HLB-tolerant orange-like hybrids are promising alternatives. However, the genetic control of key flavor compounds in oranges remains unknown. Evaluating 179 juice samples, including oranges, mandarins,Poncirus trifoliataand hybrids, distinct volatile compositions were found. A random forest model predicted untrained samples with 78% accuracy and identified 26 compounds crucial for orange flavor. Notably, seven esters—methyl hexanoate, ethyl hexanoate, ethyl 3-hydroxyhexanoate, ethyl octanoate, methyl butanoate, ethyl butanoate, and ethyl 2-methylbutanoate—differentiated orange from mandarin. Cluster analysis showed six esters with shared genetic control. Differential gene expression analysis identifiedCsAAT1, analcohol acyltransferaseresponsible for ester production in orange. Its activity was validated through overexpression assays. A SNP-based DNA marker in the CDS region accurately predicted phenotypes. This study enhances our understanding of orange flavor compounds, their biosynthetic pathways, and expands breeding options for orange-like cultivars.
OrgaMapper: A robust and easy-to-use workflow for analyzing organelle positioning
Authors: Schmied Christopher , Ebner Michael , Ferré Paula Samsó , Haucke Volker , Lehmann Martin 
Published: July 2023

AbstractEukaryotic cells are highly compartmentalized by a variety of organelles that carry out specific cellular processes. The position of these organelles within the cell is elaborately regulated and vital for their function. For instance, the position of lysosomes relative to the nucleus controls their degradative capacity and is altered in pathophysiological conditions. The molecular components orchestrating the precise localization of organelles remain incompletely understood. A confounding factor in these studies is the fact that organelle positioning is surprisingly non-trivial to address. E.g., perturbations that affect the localization of organelles often lead to secondary phenotypes such as changes in cell or organelle size. These phenotypes could potentially mask effects or lead to the identification of false positive hits. To uncover and test potential molecular components at scale, accurate and easy to use analysis tools are required that allow robust measurements of organelle positioning.Here, we present an analysis workflow for the faithful, robust, and quantitative analysis of organelle positioning phenotypes. Our workflow consists of an easy to use Fiji plugin and an R Shiny App. These tools enable users without background in image or data analysis to (1) segment single cells and nuclei and to detect organelles, (2) to measure cell size and the distance between detected organelles and the nucleus, (3) to measure intensities in the organelle channel plus one additional channel, and (4) to plot the results in informative graphs. Using simulated data and immunofluorescent images of cells in which the function of known factors for lysosome positioning has been perturbed, we show that the workflow is robust against common problems for the accurate assessment of organelle positioning such as changes of cell shape and size, organelle size and background.