bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Comparison of the Bilateral Axillo-breast Approach (BABA) Robotic and Open Thyroidectomy for Papillary Thyroid Cancer After Propensity Score Matching
Authors: Paek Se Hyun , Kwon Hyungju , Kang Kyung Ho 
Published: August 2022

Background:
We aimed to investigate the potential advantages of bilateral axillo-breast approach (BABA) robotic thyroidectomy over conventional open surgery and to determine whether it is a safe and complete surgical procedure compared with open surgery in patients with papillary thyroid cancer.

Patients and Methods:
We retrospectively reviewed the records of 315 consecutive patients (robotic, n=54; open, n=261) who underwent total thyroidectomy and central neck dissection for papillary thyroid cancer from March 2013 to June 2014. Postoperative complication rate and surgical completeness were analyzed between patients who underwent BABA robotic thyroidectomy (robotic group) and those who chose open thyroidectomy (open group) after propensity score matching according to age, sex, body mass index, tumor size, extrathyroidal extension, and lymph node (LN) metastasis.

Results:
Transient hypoparathyroidism was higher in the open group than in the robotic group (13.0% vs. 1.9%; P=0.029). No difference was observed in the mean number of retrieved LNs and metastatic LNs. The mean level of stimulated thyroglobulin was acceptably low in both groups, and there was no difference in the proportion of patients who had stimulated thyroglobulin levels <1 ng/mL between the groups (P=0.543).

Conclusions:
Our results show that the outcomes of BABA robotic thyroidectomy may be comparable to those of conventional open thyroidectomy, with possibly better preservation of blood supply to the parathyroid glands, without sacrificing surgical completeness.
Efficient Initial Eradication of Large Esophageal Varices by Balloon-compression Endoscopic Injection Sclerotherapy
Authors: Zhang Qianqian , Wu Wenyue , Mei Xuecan , Zhang Fumin , Ren Xiaofei , Kong Derun 
Published: August 2022

Background:
The management of large esophageal varices (EVs) remains challenging because of the difficulty of endoscopic variceal ligation and fatal post-endoscopic variceal ligation bleeding ulcers. The current study evaluated the efficacy and safety of balloon-compression endoscopic injection sclerotherapy (bc-EIS) in the treatment of large EVs.

Materials and Methods:
This retrospective study included 105 patients with cirrhosis exhibiting large EVs (64 in the bc-EIS group and 41 in the EIS group). Primary outcomes included the initial rate of variceal eradication and intraoperative bleeding signs. Secondary outcomes included incidences of rebleeding, mortality, complications, and optimal time of balloon-compression (bc).

Results:
The initial rate of variceal eradication in the bc-EIS group was significantly higher than that in the EIS group (46.9 vs. 24.4%; P=0.021). The incidence of intraoperative bleeding, which was represented as oozing and spurting, in the bc-EIS group was markedly lower than that in the EIS group (43.8 vs. 61.0% and 9.4 vs. 39.0%, respectively; P=0.043). Patients in the bc-EIS group showed a significantly lower incidence of rebleeding (0.0 vs. 17.1%; P=0.001). However, no significant difference in mortality rate was observed between different groups. Chest pain or discomfort tended to be more common in the EIS group than in the bc-EIS group (58.5 vs. 17.2%; P=0.001). The cut-off value of 11.5-minutes appeared to have a maximum combined sensitivity and specificity of 80.0% and 58.8%, respectively. The area under the curve was 0.708 (95% confidence interval =0.576-0.839; P=0.004).

Conclusion:
bc-EIS could achieve a higher variceal eradication rate and milder intraoperative bleeding signs in large EVs. Furthermore, 11.5-minutes appeared to be the optimal compression time in bc-EIS.
Interobserver agreement for the Chest Wall Injury Society taxonomy of rib fractures using computed tomography images
Authors: Van Wijck Suzanne F.M. , Curran Christian , Sauaia Angela , Van Lieshout Esther M.M. , Whitbeck SarahAnn S. , Edwards John G. , Pieracci Fredric M. , Wijffels Mathieu M.E. 
Published: August 2022

BACKGROUND
In 2020, a universal nomenclature for rib fractures was proposed by the international Chest Wall Injury Society taxonomy collaboration. The purpose of this study is to validate this taxonomy. We hypothesized that there would be at least moderate agreement, regardless of the observers' background.

METHODS
An international group of independent observers evaluated axial, coronal, and sagittal computed tomography images on an online platform from 11 rib fractures for location (anterior, lateral, or posterior), type (simple, wedge, or complex), and displacement (undisplaced, offset, or displaced) of rib fractures. The multirater κ and Gwet's first agreement coefficient (AC1) were calculated to estimate agreement among the observers.

RESULTS
A total of 90 observers participated, with 76 complete responses (84%). Strong agreement was found for the classification of fracture location (κ = 0.83 [95% confidence interval (CI) 0.69–0.97]; AC1, 0.84 [95% CI, 0.81–0.88]), moderate for fracture type (κ = 0.46 [95% CI, 0.32–0.59]; AC1, 0.50 [95% CI, 0.45–0.55]), and fair for rib fracture displacement (κ = 0.38 [95% CI, 0.21–0.54], AC1, 0.38 [95% CI, 0.34–0.42]).

CONCLUSION
Agreement on rib fracture location was strong and moderate for fracture type. Agreement on displacement was lower than expected. Evaluating strategies such as comprehensive education, additional imaging techniques, or further specification of the definitions will be needed to increase agreement on the classification of rib fracture type and displacement as defined by the Chest Wall Injury Society taxonomy.

LEVEL OF EVIDENCE
Diagnostic Test or Criteria; Level IV.
Predicting Early Allograft Function After Normothermic Machine Perfusion
Authors: Watson Christopher J.E. , Gaurav Rohit , Fear Corrina , Swift Lisa , Selves Linda , Ceresa Carlo D.L. , Upponi Sara S. , Brais Rebecca , Allison Michael , Macdonald-Wallis Corrie , Taylor Rhiannon , Butler Andrew J. 
Published: August 2022

Background.Normothermic ex situ liver perfusion is increasingly used to assess donor livers, but there remains a paucity of evidence regarding criteria upon which to base a viability assessment or criteria predicting early allograft function.Methods.Perfusate variables from livers undergoing normothermic ex situ liver perfusion were analyzed to see which best predicted the Model for Early Allograft Function score.Results.One hundred fifty-four of 203 perfused livers were transplanted following our previously defined criteria. These comprised 84/123 donation after circulatory death livers and 70/80 donation after brain death livers. Multivariable analysis suggested that 2-h alanine transaminase, 2-h lactate, 11 to 29 mmol supplementary bicarbonate in the first 4 h, and peak bile pH were associated with early allograft function as defined by the Model for Early Allograft Function score. Nonanastomotic biliary strictures occurred in 11% of transplants, predominantly affected first- and second-order ducts, despite selection based on bile glucose and pH.Conclusions.This work confirms the importance of perfusate alanine transaminase and lactate at 2-h, as well as the amount of supplementary bicarbonate required to keep the perfusate pH > 7.2, in the assessment of livers undergoing perfusion. It cautions against the use of lactate as a sole indicator of viability and also suggests a role for cholangiocyte function markers in predicting early allograft function.
Impact of Older Donor Age on Recipient and Graft Survival After LDLT: The US Experience
Authors: Kanneganti Mounika , Olthoff Kim M. , Bittermann Therese 
Published: August 2022

Background.
The impact of selecting older donors for living donor liver transplantation (LDLT) in the United States is incompletely studied, particularly in light of the recent expansion of LDLT nationally.

Methods.
Adult LDLTs from January 01, 2005 to December 31, 2019 were identified using the United Network for Organ Sharing database. Multivariable Cox models evaluated living donor (LD) age as a predictor of LDLT recipient and graft survival. The impact of increasing donor age on recipient outcomes was compared between LD and deceased donor recipients. Donor postoperative outcomes were evaluated.

Results.
There were 3539 LDLTs at 65 transplant centers during the study period. Despite the recent expansion of LDLT, the proportion of LDs aged ≥50 y was stable. There were no clinically significant differences in recipient or donor characteristics by LD age group. LD age ≥50 y was associated with an adjusted hazard ratio of 1.49 (P = 0.012) for recipient survival and 1.61 (P < 0.001) for graft survival (vs LDs aged 18–29 y). The negative impact of increasing donor age on graft survival was more profound after LDLT than deceased donor liver transplantation (interaction P = 0.019). There was a possible increased rate of early donor biliary complications for donors >55 y (7.1% versus 3.1% for age <40 y; P = 0.156).

Conclusions.
Increasing LD age is associated with decreased recipient and graft survival, although older donors still largely yield acceptable outcomes. Donor outcomes were not clearly impacted by increasing age, though this warrants further study.
Receptor binding domain (RBD) antibodies contribute more to SARS-CoV-2 neutralization when target cells express high levels of ACE2
Authors: Farrell Ariana Ghez , Dadonaite Bernadeta , Greaney Allison J. , Eguia Rachel , Loes Andrea N. , Franko Nicholas M. , Logue Jennifer , Carreño Juan Manuel , Abbad Anass , Chu Helen Y. , Matreyek Kenneth A. , Bloom Jesse D. 
Published: August 2022

AbstractNeutralization assays are experimental surrogates for the effectiveness of infection- or vaccine-elicited polyclonal antibodies and therapeutic monoclonal antibodies targeting SARS-CoV-2. However, the measured neutralization can depend on details of the experimental assay. Here we systematically assess how ACE2 expression in target cells affects neutralization by antibodies to different spike epitopes in lentivirus pseudovirus neutralization assays. For high ACE2-expressing target cells, receptor binding domain (RBD) antibodies account for nearly all neutralizing activity in polyclonal human sera. But for lower ACE2-expressing target cells, antibodies targeting regions outside the RBD make a larger (although still modest) contribution to serum neutralization. These serum-level results are mirrored for monoclonal antibodies: N-terminal domain (NTD) antibodies and RBD antibodies that do not compete for ACE2 binding incompletely neutralize on high ACE2-expressing target cells, but completely neutralize on cells with lower ACE2 expression. Our results show that ACE2 expression level in the target cells is an important experimental variable, and that high ACE2 expression emphasizes the role of a subset of RBD-directed antibodies.
Primate Social Organization Evolved from a Flexible Pair-Living Ancestor
Authors: Olivier Charlotte-Anaïs , Martin Jordan S. , Pilisi Camille , Agnani Paul , Kauffmann Cécile , Hayes Loren , Jaeggi Adrian V. , Schradin C. 
Published: August 2022

AbstractExplaining the evolution of primate social organization has been fundamental to understand human sociality and social evolution more broadly. It has often been suggested that the ancestor of all primates was solitary and that other forms of social organization evolved later. However, previous research included the assumption that many understudied primate species were solitary, then finding transitions to more complex social systems being driven by various life history traits and ecological factors. Here we show that when intra-specific variation is accounted for, the ancestral social organization of primates was variable, with the most common social organization being pair-living but with approximatively 15-20% of social units of the ancestral population deviating from this pattern by being solitary living. We built a detailed database from primary field studies quantifying the number of individuals (social units) expressing different social organizations in each population. We used Bayesian phylogenetic models to infer the probability of each social organization, conditional on several socio-ecological predictors, in ancestral populations. Body size and activity patterns had large effects on transitions between types of social organizations. Our results challenge the assumption that ancestral primates were solitary and that pair-living evolved afterwards. Moreover, our results emphasize the importance of focusing on field data and accounting for intra-specific variation. Pair-living is evolutionary ancient, likely caused by reproductive benefits such as access to partners and reduced intra-sexual competition, with more complex social structure (pair-bonding) and care systems (biparental and allo-parental care) evolving later.Significance StatementWas the ancestor of all primates a solitary-living species? Did more social forms of primate societies evolve from this basic and simple society? The dogma has been that the answer is yes. We used a modern statistical analysis, including variations within species, to show that the ancestral primate social organization was most likely variable. Most lived in pairs, and only 15-20% of individuals were solitary. Living in pairs was likely ancient and caused by reproductive benefits, like access to partners and reduced competition with the sexes. More complex social elaborations like pair-bonds, and biparental and allo-parental care, probably evolved later.
Chemically synthesized guide RNAs can direct CRISPR-CasRx cleavage of circRNAs with high efficiency and specificity
Authors: Rahimi Karim , Andersen Maria Schertz , Seeler Sabine , Hansen Thomas Birkballe , Kjems Jørgen 
Published: August 2022

AbstractCircular RNAs (circRNAs) are characterized by a covalently closed circular structure, formed from pre-mRNAs through an alternative splicing mechanism named back-splicing. CircRNAs have been shown to play a regulatory role in the development of eukaryotic organisms and to be implicated in human diseases. However, the extensive sequence-overlap between circRNAs and their linear RNA counterparts makes it technically difficult to deplete circRNAs without affecting their linear host, which complicates functional studies. Therefore, it is important to identify the most efficient and specific strategy for circRNA depletion. In this study, we demonstrate that CRISPR/RfxCas13d (CasRx)-mediated circRNA depletion is, for the circRNAs studied, more efficient than Argonaute 2-dependent short hairpin RNA (agoshRNA)-mediated depletion and with fewer off-target effects on the linear host RNAs. Furthermore, we show that synthetic guide RNAs (syn-gRNAs) can be used in combination with CasRx to efficiently deplete circRNA, ciRS-7. Finally, none of the knockdown (KD) strategies tested (pre-gRNA, gRNA, syn-gRNA and agoshRNA) showed any significant off-target effects on the global transcriptome. Taken together, CasRx-mediated circRNA KD strategies, using either vector-based or syn-gRNA, are useful tools for future studies on circRNA functions.
β-catenin interacts with the TAZ1 and TAZ2 domains of CBP/p300 to activate gene transcription
Authors: Brown Alexandra D. , Cranstone Connor , Dupré Denis J. , Langelaan David N. 
Published: August 2022

AbstractThe transcriptional co-regulator β-catenin is a critical effector of the canonical Wnt-signalling pathway, which plays a crucial role in regulating cell fate and maintaining tissue homeostasis. Deregulation of the Wnt/β-catenin pathway is characteristic in the development of major types of cancer, where accumulation of β-catenin promotes cancer cell proliferation and renewal. β-catenin gene expression is facilitated through recruitment of co-activators such as histone acetyltransferases CBP/p300; however, the mechanism of their interaction is not fully understood. Here we investigate the interaction between the C-terminal transactivation domain of β-catenin and CBP/p300. Using a combination of pulldown assays, isothermal titration calorimetry, and nuclear resonance spectroscopy we determine the disordered C-terminal region of β-catenin binds promiscuously to the TAZ1 and TAZ2 domains of CBP/p300. We then map the interaction site of the C-terminal β-catenin transactivation domain onto TAZ1 and TAZ2 using chemical-shift perturbation studies. Luciferase-based gene reporter assays indicate Asp750-Leu781 is critical to β-catenin gene activation, and mutagenesis revealed that acidic and hydrophobic residues within this region are necessary to maintain TAZ1 binding. These results provide a mechanistic understanding of Wnt/β-catenin gene regulation that underlies cell development and provide a framework to develop methods to block β-catenin dependent signalling in the future.
A confinable female-lethal population suppression system in the malaria vector, Anopheles gambiae
Authors: Smidler Andrea L. , Pai James J. , Apte Reema A. , Sánchez C. Héctor M. , Corder Rodrigo M. , Gutiérrez Eileen Jeffrey , Thakre Neha , Antoshechkin Igor , Marshall John M. , Akbari Omar S. 
Published: August 2022

AbstractMalaria is among the world’s deadliest diseases, predominantly affecting sub-Saharan Africa, and killing over half a million people annually. Controlling the principal vector, the mosquito Anopheles gambiae, as well as other anophelines, is among the most effective methods to control disease spread. Here we develop an innovative genetic population suppression system termed Ifegenia (Inherited Female Elimination by Genetically Encoded Nucleases to Interrupt Alleles) in this deadly vector. In this bicomponent CRISPR-based approach, we disrupt a female-essential gene, femaleless (fle), demonstrating complete genetic sexing via heritable daughter gynecide. Moreover, we show that Ifegenia males remain reproductively viable, and can load both fle mutations and CRISPR machinery to induce fle mutations in subsequent generations, resulting in sustained population suppression. Through modeling, we demonstrate that iterative releases of non-biting Ifegenia males can act as an effective, confinable, controllable, and safe population suppression and elimination system.
Resolving the origins of secretory products and anthelmintic responses in a human parasitic nematode at single-cell resolution
Authors: Henthorn Clair R. , Airs Paul M. , Neumann Emma K. , Zamanian Mostafa 
Published: August 2022

AbstractNematode excretory-secretory (ES) products are essential for the establishment and maintenance of infections in mammals and are valued as therapeutic and diagnostic targets. While parasite effector proteins contribute to host immune evasion and anthelmintics have been shown to modulate secretory behaviors, little is known about the cellular origins of ES products or the tissue distributions of drug targets. We leveraged single-cell approaches in the human parasiteBrugia malayito generate an annotated cell expression atlas of microfilariae. We show that prominent antigens are transcriptionally derived from both secretory and non-secretory cell and tissue types, and anthelmintic targets display distinct expression patterns across neuronal, muscular, and other cell types. While the major classes of anthelmintics do not affect the viability of isolated cells at pharmacological concentrations, we observe cell-specific transcriptional shifts in response to ivermectin. Finally, we introduce a microfilariae cell culture model to enable future functional studies of parasitic nematode cells. We expect these methods to be readily adaptable to other parasitic nematode species and stages.
Optimization of universal primer set for the identification of all Influenza A viruses using real-time PCR
Authors: Harkness Altrice , Matthews Qiana L , Smith Lula , Roberston Bokai , Wu Hongzhuan 
Published: August 2022

AbstractAvian Influenza Virus (AIV) occurs worldwide among aquatic wild and may mutate into a strain capable of efficient human-to-human transmission and cause a pandemic that could kill a large fraction of the human population. The purpose of this study is to efficiently identify and diagnose the virus for immediate treatment and prevention. Real-Time Reverse Transcription-Polymerase Chain Reaction (RRT-PCR or qPCR) was identified as the most efficient way to detect AIV in previous laboratory research, however only one pair of primers was used. In order to further optimize the test and make it commercially available in the future, we first tested an eight pair primer set via RRT-PCR by using standard AIV isolates from Dr.Gaimbrone’s lab (Auburn University). Using the AIV isolates, the optimal cDNA and primer concentrations were determined, this aided in the identification of the most sensitive primer set. Primers PA, HA, NP, and NA were able to detect the cDNA of positive AIV isolates at a low concentration of 0.0039 mg/ml. AIV cDNA were detected by primers M and HA at its lowest concentration of 0.0001 and 0.01 pmol/μl. In order to further test our lab results, 20 fecal samples from aquatic wild birds were collected from Alabama Shakespeare Park located in Montgomery, Alabama during the winter season. The samples were analyzed using RRT-PCR. HA primer set detected 10 positive samples for Avian Influenza and is the most sensitive primer set to be used in RRT-PCR. The field sample detection confirmed laboratory results and revealed that local aquatic birds are actively shedding low pathogenic avian influenza virus(LPAIV). The optimization of all primer sets used in this study will aid in disease surveillance, facilitate quick diagnosis of Influenza A viruses, and implement an effective prevention of flu pandemic.
Shared retinoic acid responsive enhancers coordinately regulate nascent transcription of Hoxb coding and non-coding RNAs in the developing mouse neural tube
Authors: Afzal Zainab , Lange Jeffrey , Nolte Christof , McKinney Sean , Wood Christopher , Paulson Ariel , De Kumar Bony , Unruh Jay , Slaughter Brian D. , Krumlauf Robb 
Published: August 2022

AbstractSignaling pathways regulate the patterns of Hox gene expression that underlie their functions in specification of axial identity. Little is known about the properties of cis-regulatory elements and underlying transcriptional mechanisms that integrate graded signaling inputs to coordinately control Hox expression. Here we optimized single molecule fluorescent in situ hybridization (smFISH) technique with probes spanning introns to evaluate how three shared retinoic acid response element (RARE)-dependent enhancers in the Hoxb cluster regulate patterns of nascent transcription in vivo at the level of single cells in wild type and mutant embryos. We predominately detect nascent transcription of only a single Hoxb gene in each cell, with no evidence for simultaneous co-transcriptional coupling of all or specific subsets of genes. Single and/or compound RARE mutations indicate each enhancer differentially impacts global and local patterns of nascent transcription, suggesting that selectivity and competitive interactions between these enhancers is important to robustly maintain the proper levels and patterns of nascent Hoxb transcription. This implies rapid and dynamic regulatory interactions potentiate transcription of genes through combined inputs from these enhancers in coordinating the RA response.