bluuebunny/crossref_metadata_2025_split huggingface dataset:
Point/Counterpoint #1
Authors: Kumar Abhishek , Palta Manisha , Jia Jingquan 
Published: July 2024

Abstract
For decades, the standard neoadjuvant therapy regimen for locally advanced rectal cancer consisted of chemoradiation, surgical resection, and consideration of adjuvant systemic therapy. Additional data have emerged suggesting neoadjuvant systemic therapy as a reasonable alternative to chemoradiation in selected patients. In addition, a total neoadjuvant therapy approach integrating both chemotherapy and chemoradiation results in superior cancer outcomes and the potential for consideration of nonoperative management in patients with a clinical complete response. Despite a multitude of therapeutic pathways for the management of rectal cancer, what is clear, however, is the importance of a multidisciplinary approach with shared patient and provider decision-making.
The Use of Frailty Scores for Screening the Surgical Risk Benefits
Authors: Ballacchino Madison M. , McQuestion Chloe C. , Giuca Matthew S. , Dosluoglu Hasan H. , Nader Nader D. 
Published: July 2024

Objective:
Our study aims to examine the role of multi-disciplinary surgical pause committees (MDSPC) in perioperative planning to reduce adverse postoperative events and mortality rates.

Summary Background Data:
Frail patients could benefit from preoperative MDSPCs when utilizing risk-benefit ratios for the proposed surgical plan. We examined whether MDSPCs improved clinical outcomes by developing individualized care plans and stratifying patients based on their level of frailty and ability to overcome external stressors.

Methods:
We retrospectively collected patient information after MDSPC evaluation, at our medical center for 12 years since 2011. Patient’s frailty risk assessment index (RAI) scores were calculated, and survival status was updated. MDSPCs plans were put into the following categories: proceed with the planned surgery (G1), proceed after medical optimization (G2), reduce invasiveness of surgery or anesthesia plan (G3), or adopt a non-surgical approach (G4). Chi-square and independent t-tests were used for categorical and numerical data, respectively. Survival analysis for 30-day (primary endpoint), one-year, and overall mortality rates used Kaplan-Meier. The alpha was set at 0.05.

Results:
Clinical information was accessed from 12 women and 382 men. The average age was 71±11 years. 87.3% of planned surgical operations were stratified as ASA class III and IV. RAI scores were 36.4±9.6 (G1), similar to 37.4±10.8 (G2) but lower than 41.4±9.3 (G3) and 44.2±9.7 (G4) (P<0.001). Average survival duration was 35 months (G1), 35 months (G2), both significantly longer than 20 months (G3) and 18 months (G4) (P<0.001).

Conclusion:
Medical optimization improved overall survival and reduced death within 30 days and one year to be comparable to G1. Additionally, reducing the surgical invasiveness only improved survival advantage for six months, after which it was comparable to those in G4 with the worst outcome. RAI scoring is an excellent tool to predict the outcome of surgery, and it was used successfully in critically ill patients.
Multi-proxy bioarchaeological analysis of skeletal remains shows genetic discontinuity in a Medieval Sicilian community
Authors: Monnereau Aurore , Ughi Alice , Orecchioni Paola , Hagan Richard , Talbot Helen M. , Nikita Efthymia , Hamilton Derek , Le Roux Petrus , Molinari Alessandra , Carver Martin , Craig Oliver E. , Speller Camilla F. , Alexander Michelle M. , Wales Nathan 
Published: July 2024

The medieval period in Sicily was turbulent, involving successive regime changes, from Byzantine (Greek Christian), Aghlabid (Sunni Muslim), Fatimid (Shīʿa Muslim), to Normans and Swabians (Latin Christian). To shed new light on the local implications of regime changes, we conducted a multidisciplinary analysis of 27 individuals buried in adjacent Muslim and Christian cemeteries at the site of Segesta, western Sicily. By combining radiocarbon dating, genome-wide sequencing, stable and radiogenic isotopic data, and archaeological records, we uncover genetic differences between the two communities but find evidence of continuity in other aspects of life. Historical and archaeological evidence shows a Muslim community was present by the 12th century during Norman governance, with the Christian settlement appearing in the 13th century under Swabian governance. A Bayesian analysis of radiocarbon dates from the burials finds the abandonment of the Muslim cemetery likely occurred after the establishment of the Christian cemetery, indicating that individuals of both faiths were present in the area in the first half of the 13th century. The biomolecular results suggest the Christians remained genetically distinct from the Muslim community at Segesta while following a substantially similar diet. This study demonstrates that medieval regime changes had major impacts beyond the political core, leading to demographic changes while economic systems persisted and new social relationships emerged.
Ex vivo model of breast cancer cell invasion in live lymph node tissue
Authors: Morgaenko Katerina , Arneja Abhinav , Ball Alexander G. , Putelo Audrey M. , Munson Jennifer M. , Rutkowski Melanie R. , Pompano Rebecca R. 
Published: July 2024

ABSTRACTLymph nodes (LNs) are common sites of metastatic invasion in breast cancer, often preceding spread to distant organs and serving as key indicators of clinical disease progression. However, the mechanisms of cancer cell invasion into LNs are not well understood. Existing in vivo models struggle to isolate the specific impacts of the tumor-draining lymph node (TDLN) milieu on cancer cell invasion due to the co-evolving relationship between TDLNs and the upstream tumor. To address these limitations, we used live ex vivo LN tissue slices with intact chemotactic function to model cancer cell spread within a spatially organized microenvironment. After showing that BRPKp110 breast cancer cells were chemoattracted to factors secreted by naïve LN tissue in a 3D migration assay, we demonstrated that ex vivo LN slices could support cancer cell seeding, invasion, and spread. This novel approach revealed dynamic, preferential cancer cell invasion within specific anatomical regions of LNs, particularly the subcapsular sinus (SCS) and cortex, as well as chemokine-rich domains of immobilized CXCL13 and CCL1. While CXCR5 was necessary for a portion of BRPKp110 invasion into naïve LNs, disruption of CXCR5/CXCL13 signaling alone was insufficient to prevent invasion towards CXCL13-rich domains. Finally, we extended this system to pre-metastatic TDLNs, where the ex vivo model predicted a lower invasion of cancer cells. The reduced invasion was not due to diminished chemokine secretion, but it correlated with elevated intranodal IL-21. In summary, this innovative ex vivo model of cancer cell spread in live LN slices provides a platform to investigate cancer invasion within the intricate tissue microenvironment, supporting time-course analysis and parallel read-outs. We anticipate that this system will enable further research into cancer-immune interactions and allow isolation of specific factors that make TDLNs resistant to cancer cell invasion, which are challenging to dissect in vivo.
Graphene-based micro-electrodes with reinforced interfaces and tunable porous structures for improved neural recordings
Authors: Dong Miheng , Yang Junjun , Zhen Fangzheng , Du Yu , Ding Siyuan , Yu Aibing , Zou Ruiping , Qiu Ling , Guo Zhijun , Coleman Harold A. , Parkington Helena C. , Fallon James B. , Forsythe John S. , Liu Minsu 
Published: July 2024

AbstractInvasive neural electrodes prepared from materials with miniaturized geometrical size could improve the longevity of implants by reducing the chronic inflammatory response. Graphene-based microfibers with tunable porous structures have a large electrochemical surface area (ESA)/geometrical surface area (GSA) ratio that has been reported to possess low impedance and high charge injection capacity (CIC), yet the control of the porous structure remains to be fully investigated. In this study, we introduce wet-spun graphene-based electrodes with pores tuned by sucrose concentrations in the coagulation bath. The electrochemical properties of thermally reduced rGO were optimized by adjusting the ratio of rGO to sucrose, resulting in significantly lower impedance, higher CIC, and higher charge storage capacity (CSC) than platinum microwires. Tensile and insertion tests confirmed that optimized electrodes had sufficient strength to ensure a 100% insertion success rate with low angle shift, thus allowing precise implantation without the need for additional mechanical enhancement. Acutein-vivorecordings from the auditory cortex found low impedance benefits from the recorded amplitude of spikes, leading to an increase in the signal-to-noise ratio (SNR).Ex-vivorecordings from hippocampal brain slices demonstrate that it is possible to record and/or stimulate with graphene-based electrodes with good fidelity compared with conventional electrodes.
Multiple Independent Genetic Code Reassignments of the UAG Stop Codon in Phyllopharyngean Ciliates
Authors: McGowan Jamie , Richards Thomas A. , Hall Neil , Swarbreck David 
Published: July 2024

AbstractThe translation of nucleotide sequences into amino acid sequences, governed by the genetic code, is one of the most conserved features of molecular biology. The standard genetic code, which uses 61 sense codons to encode one of the 20 standard amino acids and 3 stop codons (UAA, UAG, and UGA) to terminate translation, is used by most extant organisms. The protistan phyla Ciliophora (the ‘ciliates’) are an unusual exception to this norm, exhibiting the greatest diversity of non-canonical nuclear genetic code variants and evidence of repeated changes in code. In this study, we report the discovery of multiple independent genetic code changes within the Phyllopharyngea class of ciliates. By mining publicly available ciliate genome datasets, we discovered that three ciliate species from the TARA Oceans eukaryotic metagenome dataset use the UAG codon to putatively encode leucine. We identified novel suppressor tRNA genes in two of these genomes. Phylogenomics analysis revealed that these three uncultivated taxa form a monophyletic lineage within the Phyllopharyngea class. Expanding our analysis by reassembling published phyllopharyngean genome datasets led to the discovery that the UAG codon had also been reassigned to putatively code for glutamine inHartmannula sinicaandTrochilia petrani. Phylogenomics analysis suggests that this occurred via two independent genetic code change events. These data demonstrate that the reassigned UAG codons have widespread usage as sense codons within the phyllopharyngean ciliates. Furthermore, we show that the function of UAA is firmly fixed as the preferred stop codon. These findings shed light on the evolvability of the genetic code in understudied microbial eukaryotes.
Waves of Colonization and Gene Flow in a Great Speciator
Authors: Gyllenhaal Ethan F. , Brady Serina S. , DeCicco Lucas H. , Naikatini Alivereti , Hime Paul M. , Manthey Joseph D. , Kelly John , Moyle Robert G. , Andersen Michael J. 
Published: July 2024

AbstractSecondary contact between previously allopatric lineages offers a test of reproductive isolating mechanisms that may have accrued in isolation. Such instances of contact can produce stable hybrid zones—where reproductive isolation can further develop via reinforcement or phenotypic displacement—or result in the lineages merging. Ongoing secondary contact is most visible in continental systems, where steady input from parental taxa can occur readily. In oceanic island systems, however, secondary contact between closely related species of birds is relatively rare. When observed on sufficiently small islands, relative to population size, secondary contact likely represents a recent phenomenon. Here, we examine the dynamics of a group of birds whose apparent widespread hybridization influenced Ernst Mayr’s foundational work on allopatric speciation: the whistlers of Fiji (Aves:Pachycephala). We demonstrate two clear instances of secondary contact within the Fijian archipelago, one resulting in a hybrid zone on a larger island, and the other resulting in a wholly admixed population on a smaller, adjacent island. We leveraged low genome-wide divergence in the hybrid zone to pinpoint a single genomic region associated with observed phenotypic differences. We use genomic data to present a new hypothesis that emphasizes rapid plumage evolution and post-divergence gene flow.
Identification of targetable vulnerabilities of PLK1-overexpressing cancers by synthetic dosage lethality
Authors: Cunningham Chelsea E. , Vizeacoumar Frederick S. , Zhang Yue , Kyrylenko Liliia , Gao Peng , Maranda Vincent , Dong He , Price Jared DW , Ganapathysamy Ashtalakshmi , Hari Rithik , Denomy Connor , Both Simon , Wagner Konrad , Wu Yingwen , Khan Faizaan , Mosley Shayla , Chen Angie , Katrii Tetiana , Zoller Ben G. E. , Rajamanickam Karthic , Walke Prachi , Gong Lihui , Patel Hardikkumar , Lazell-Wright Mary , Morales Alain Morejon , Bhanumathy Kalpana K. , Elhasasna Hussain , Dahiya Renuka , Abuhussein Omar , Dmitriev Anton , Freywald Tanya , Munhoz Erika Prando , Krishnan Anand , Ruppin Eytan , Lee Joo Sang , Rox Katharina , Toosi Behzad , Koebel Martin , Kinloch Mary , Hopkins Laura , Lee Cheng Han , Datla Raju , Yadav Sunil , Wu Yuliang , Baker Kristi , Empting Martin , Kiemer Alexandra K. , Freywald Andrew , Vizeacoumar Franco J. 
Published: July 2024

SummaryTumor heterogeneity poses a significant challenge in combating treatment resistance. Despite Polo-like kinase 1 (PLK1) being universally overexpressed in cancers and contributing to chromosomal instability (CIN), direct PLK1 inhibition hasn’t yielded clinical progress. To address this, we utilized the synthetic dosage lethality (SDL) approach, targeting PLK1’s genetic interactions for selective killing of overexpressed tumor cells while mitigating heterogeneity-associated challenges. Employing computational methods, we conducted a genome-wide shRNA screen, identifying 105 SDL candidates. Further in vivo CRISPR screening in a breast cancer xenograft model and in vitro CRISPR analysis validated these candidates. Employing Perturb-seq revealed IGF2BP2/IMP2 as a key SDL hit eliminating PLK1-overexpressing cells. Suppression of IGF2BP2, genetically or pharmacologically, downregulated PLK1 and limited tumor growth. Our findings strongly propose targeting PLK1’s genetic interactions as a promising therapeutic approach, holding broad implications across multiple cancers where PLK1 is overexpressed.
How do we imagine a speech? A triple network model for situationally simulated inner speech
Authors: Gao Xiaowei , Yang Junjie , Li Chaoqun , Guo Xiaolin , Wang Yaling , Qu Zhiheng , Li Wanchun , Liu Jiaxuan , Li Zhongqi , Li Wanjing , Hu Zhe , Li Junjing , Huang Yien , Chen Jiali , Wen Hao , Zhao Zehao , Kaiser Daniel , Wei Tao , Yuan Binke 
Published: July 2024

AbstractInner speech is a silent verbal experience and plays central roles in human consciousness and cognition. Despite impressive studies over the past decades, the neural mechanisms of inner speech remain largely unknown. In this study, we adopted an ecological paradigm called situationally simulated inner speech. Unlike mere imaging speech of words, situationally simulated inner speech involves the dynamic integration of contextual background, episodic and semantic memories, and external events into a coherent structure. We conducted dynamic activation and network analyses on fMRI data, where participants were instructed to engage in inner speech prompted by cue words across 10 different contextual backgrounds. Our seed-based co-activation pattern analyses revealed dynamic involvement of the language network, sensorimotor network, and default mode network in situationally simulated inner speech. Additionally, frame-wise dynamic conditional correlation analysis uncovered four temporal-reoccurring states with distinct functional connectivity patterns among these networks. We proposed a triple network model for deliberate inner speech, including language network for a truncated form of overt speech, sensorimotor network for perceptual simulation and monitoring, and default model network for integration and ‘sense-making’ processing.HighlightsIn ten contextual backgrounds, subjects were instructed to perform situationally simulated inner speech based on cue words.The ventral parts of the bilateral somatosensory areas and middle superior temporal gyrus were as centers for seed-based co-activation pattern analyses.A triple network model of language network, sensorimotor network, and default mode network was proposed for deliberate inner speech.
Initial TCR Signal Strength Imprints GATA3 and Tbet Expression Driving T-helper Cell Fate Decisions
Authors: Al-Aghbar Mohammad Ameen , Khan Taushif , Guarch Meritxell Espino , Palmer Douglas C , van Panhuys Nicholas 
Published: July 2024

AbstractWith the exception of the T-helper 2 (Th2) subset, cytokine driven pathways provide a robust mechanistic explanation for the observed outcomes of CD4+ T-cell differentiation. Using a quantitative model of activation, we studied the integration of TCR-signal-strength with cytokine signalling during Th2 differentiation. Upon the initial activation of Th-naïve cells, TCR signalling was found to set early expression levels for the master regulators of differentiation Tbet and GATA3, independent of the presence of polarizing cytokines.Subsequently cytokine stimuli modulated transcription factor (TF) expression levels to tune the outcome of differentiation. Here, weak TCR signalling was sufficient to drive the early upregulation of GATA3 and induce Th2 differentiation, in an IL-4 independent manner. Th1 differentiation was however shown to require additional cytokine signalling input, either in the form of autocrine IFNγ or exogenous IL-12. Using mathematical modelling we demonstrate that T-helper differentiation occurs along a continuum of states. Set by the relative co-expression of regulatory TFs, where effector cytokine production is controlled in a probabilistic manner determined by the relative levels GATA3 and Tbet expressed.Together, our data indicate TCR signalling inputs drive an early bifurcation in the T-helper differentiation pathway. Together, the integration of TCR signal strength with cytokine inputs act as a mechanism for the detection of immuno-evasive parasitic infections, whilst providing an additional checkpoint to prevent aberrant Th1 associated immunopathology.
Association between genetic clades and cancer prevalence suggested by French-wide study of oncogenic small ruminant beta-retroviruses diversity
Authors: Benjamin Riocreux-Verney , Marie Verneret , Rémi Diesler , Christine Dolmazon , Barbara Gineys , Jean-Luc Cadoré , Jocelyn Turpin , Caroline Leroux 
Published: July 2024

AbstractENTV (Enzootic Nasal Tumor Virus) and JSRV (Jaagsiekte Sheep Retrovirus) are β-retroviruses responsible for respiratory cancers in sheep and goats. In this study, we analyzed the genetic features of the sheep and goat β-retrovirus (29 JSRV and 24 ENTV strains) circulating in France to identify molecular signatures associated with disease severity in flocks. We developed a highly specific PCR to amplify and sequence exogenous targeted regions or near full length proviruses based on limited discriminating motifs along their genomes. The phylogenetic reconstructions based on the LTR andenvregions suggest that one major strain is circulating on the French territory for ENTV-1 and ENTV-2 while not clustering with already published Spanish, Canadian or Chinese strains. JSRV strains circulating in French sheep flocks were distributed in 2 distinct genetic clades clustering with sequences originating from North America, Africa and United-Kingdom. JSRV clade I was found to be associated with a higher incidence of cancer in French flocks. Specific motifs spanning the entire JSRV genome particularly in the LTRs and in the intracytoplasmic domain of the envelope were detected between the two genetic subtypes.This work represents the first nationwide study describing the circulation of the three closely related β-oncogenic retrovirus JSRV, ENTV-1 and ENTV-2 in French sheep and goat flocks. Better characterization of strain genetics is a critical step in monitoring circulating β retrovirus, especially those associated with higher cancer incidence in small ruminants.
Ru(II)-Photoactive Agents for Targeting ER Stress and Immunogenic Cell Death
Authors: Denison Madeline , Ullrich Alexander , Herroon Mackenzie K. , Mecca Shane , Turro Claudia , Podgorski Izabela , Gibson Heather , Kodanko Jeremy J. 
Published: July 2024

AbstractImmunotherapy has emerged as a promising avenue for cancer treatment by bolstering the immune system’s ability to recognize and attack cancer cells. Photodynamic therapy shows potential in enhancing antitumor immunity, though the mechanisms behind its success are not fully understood. In this manuscript, we investigate two previously reported green light activated PCT/PDT agents where compound2- [Ru(tpy)(Me2bpy)(3)]2+, (tpy = 2,2’:6’,2’’- terpyridine, Me2bpy = 6,6’-dimethyl-2,2’-bipyridine,3= pyridyl-BODIPY-I2,) - shows remarkable photoselectivity in assays containing both 2D cancer cells and 3D cocultures containing BALB/c macrophages and 4T1 murine breast cancer cells. Through flow cytometry and protein analysis, we found complex2displays superior evidence of induced endoplasmic reticulum (ER) stress markers and indicators of immunogenic cell death (ICD) compared to its ligand3, despite its weaker photoselectivity. Most importantly, these results were supported byin vivostudies where2produced anti-tumor immunity against the 4T1 tumor model in BALB/c mice. Complete tumor elimination was achieved in 2/8 mice, and these mice were both protected against a subsequent contralateral rechallenge and showed increasedex vivoperipheral tumor antigen-specific recall, suggesting memory T cells are induced by2. Signatures of M1 macrophage polarization were also evident in tumor tissue from the remaining 6/8 mice treated with2compared to untreated tumors.These findings demonstrate Ru(II) complexation plays a critical role in ER targeting which triggers ICD, highlighting the potential of Ru(II) agents as futurein situtumor vaccines.