tbuckley/cabot-search huggingface dataset:
Transformable Carbonate Apatite Chains as a Novel Type of Bone Graft
Authors: Koichiro Hayashi, Ryo Kishida, Akira Tsuchiya, Kunio Ishikawa
Journal: Advanced Healthcare Materials (2024)

The aging global population is generating an ever-increasing demand for bone regeneration. Various materials, including blocks, granules, and sponges, are developed for bone regeneration. However, blocks require troublesome shaping and exhibit poor bone-defect conformities; granules migrate into the surrounding tissues during and after filling of the defect, causing handling difficulties and complications; and sponges contain polymers that are subject to religious restrictions, lack osteoconductivity, and may cause inflammation and allergies. Herein, carbonate apatite chains that overcome the limitations of conventional materials are presented. Although carbonate apatite granules migrate, causing inflammation and ectopic calcification, the chains remain in the defects without causing any complications. The chains conform to the defect shape and transform into 3D porous structures, resulting in faster bone regeneration than that observed using granules. Thus, these findings indicate that even traditional calcium phosphates materials can be converted to state-of-the-art materials via shape control.
Endoscopic recanalization of complete fibrotic colorectal anastomosis using an endoscopic ultrasound-guided hybrid approach
Authors: Jianbo Ni, Linlin Zhang, Yuqing Mao, Shengzheng Luo, Xiaoyuan Gong, Baiwen Li
Journal: Endoscopy (2024)

Complete benign anastomotic obstructions post-colorectal surgery traditionally demand surgical intervention [1] [2]. We report the successful recanalization of a completely fibrotic rectal anastomosis using an unprecedented endoscopic ultrasound (EUS)-guided hybrid approach, which offers a less invasive alternative to surgery.
Salvage technique for covered metal stent migration during endoscopic reintervention after endoscopic ultrasound-guided hepaticogastrostomy
Authors: Yuki Ikeda, Daichi Watanabe, Ginji Oomori, Shota Yamada, Toshinori Okuda, Shinya Minami
Journal: Endoscopy (2024)

Endoscopic ultrasound (EUS)-guided hepaticogastrostomy (EUS-HGS) is an alternative drainage method for malignant biliary obstruction (MBO) when endoscopic retrograde cholangiopancreatography (ERCP) has failed [1]. A partially covered self-expandable metal stent (PCSEMS) is often used for EUS-HGS, but it cannot be removed. A new metal or plastic stent is therefore placed as endoscopic reintervention following EUS-HGS [2] [3] [4]; however, troubleshooting after endoscopic reintervention remains problematic because of a paucity of reported cases.
Ecological Diversification in an Adaptive Radiation of Plants: The Role of De Novo Mutation and Introgression
Authors: Benjamin W Stone, Carolyn A Wessinger
Journal: Molecular Biology and Evolution (2024)

Abstract Adaptive radiations are characterized by rapid ecological diversification and speciation events, leading to fuzzy species boundaries between ecologically differentiated species. Adaptive radiations are therefore key systems for understanding how species are formed and maintained, including the role of de novo mutations versus preexisting variation in ecological adaptation and the genome-wide consequences of hybridization events. For example, adaptive introgression, where beneficial alleles are transferred between lineages through hybridization, may fuel diversification in adaptive radiations and facilitate adaptation to new environments. In this study, we employed whole-genome resequencing data to investigate the evolutionary origin of hummingbird-pollinated flowers and to characterize genome-wide patterns of phylogenetic discordance and introgression in Penstemon subgenus Dasanthera, a small and diverse adaptive radiation of plants. We found that magenta hummingbird-adapted flowers have apparently evolved twice from ancestral blue-violet bee-pollinated flowers within this radiation. These shifts in flower color are accompanied by a variety of inactivating mutations to a key anthocyanin pathway enzyme, suggesting that independent de novo loss-of-function mutations underlie the parallel evolution of this trait. Although patterns of introgression and phylogenetic discordance were heterogenous across the genome, a strong effect of gene density suggests that, in general, natural selection opposes introgression and maintains genetic differentiation in gene-rich genomic regions. Our results highlight the importance of both de novo mutation and introgression as sources of evolutionary change and indicate a role for de novo mutation in driving parallel evolution in adaptive radiations.
Plastic stents: silenced by the LAMS?
Authors: Timothy B. Gardner
Journal: Endoscopy (2024)

I well remember the first time I deployed a lumen-apposing metal stent (LAMS). It was about a decade ago and I went to a demonstration of the new technology sponsored by the stent manufacturer at a national gastroenterology meeting. After a brief instructional tutorial and using a plastic cyst model, I successfully deployed the stent in what I remember being about 30 seconds. Among the many takeaways from that experience was that this new disruptive technology would soon render the standard laborious cystenterostomy technique obsolete.
Novel clip method for endoscopic submucosal dissection defect closure reducing submucosal dead space in antithrombotic gastric patients
Authors: Taisuke Inada, Yorinobu Sumida, Hitoshi Homma, Kosuke Maehara, Kazuo Shiotsuki, Shin-ichiro Fukuda, Hirotada Akiho
Journal: Endoscopy (2024)

Wound suture after endoscopic submucosal dissection (ESD) is anticipated to be beneficial in the stomach, particularly for patients taking antithrombotic medications, as they face an increased risk of posterior bleeding [1] [2]. However, defect closure in the stomach presents challenges due to its relatively thick mucosa and muscular layer [3]. This was achieved without leaving any submucosal dead space by using a novel clip that features sharp claws at the tip for a strong grasping force ([Fig. 1]). The video shows the procedure ([Video 1]).
Testosterone Treatment and Fractures in Men with Hypogonadism
Authors: Peter J Snyder, Douglas C Bauer, Susan S Ellenberg, Jane A Cauley, Kevin A Buhr, Shalender Bhasin, Michael G Miller, Nader S Khan, Xue Li, Steven E Nissen
Journal: New England Journal of Medicine (2024)

BackgroundTestosterone treatment in men with hypogonadism improves bone density and quality, but trials with a sufficiently large sample and a sufficiently long duration to determine the effect of testosterone on the incidence of fractures are needed.MethodsIn a subtrial of a double-blind, randomized, placebo-controlled trial that assessed the cardiovascular safety of testosterone treatment in middle-aged and older men with hypogonadism, we examined the risk of clinical fracture in a time-to-event analysis. Eligible men were 45 to 80 years of age with preexisting, or high risk of, cardiovascular disease; one or more symptoms of hypogonadism; and two morning testosterone concentrations of less than 300 ng per deciliter (10.4 nmol per liter), in fasting plasma samples obtained at least 48 hours apart. Participants were randomly assigned to apply a testosterone or placebo gel daily. At every visit, participants were asked if they had had a fracture since the previous visit. If they had, medical records were obtained and adjudicated.Download a PDF of the Research Summary.ResultsThe full-analysis population included 5204 participants (2601 in the testosterone group and 2603 in the placebo group). After a median follow-up of 3.19 years, a clinical fracture had occurred in 91 participants (3.50%) in the testosterone group and 64 participants (2.46%) in the placebo group (hazard ratio, 1.43; 95% confidence interval, 1.04 to 1.97). The fracture incidence also appeared to be higher in the testosterone group for all other fracture end points.ConclusionsAmong middle-aged and older men with hypogonadism, testosterone treatment did not result in a lower incidence of clinical fracture than placebo. The fracture incidence was numerically higher among men who received testosterone than among those who received placebo. (Funded by AbbVie and others; TRAVERSE ClinicalTrials.gov number, NCT03518034.) Quick Take Testosterone Treatment and Fractures in Hypogonadism 2m 0s
Dynamics and persistence of antimicrobial resistance genes and gut microbiome after travel
Authors: Cong Shen, Li Luo, Jinxiang Zeng, Hongyun Zhou, Bin Huang, Cha Chen
Journal: The Lancet Microbe (2024)

We read with interest an Article published in The Lancet Microbe by Colin J Worby and colleagues.1 They examined the changes in gut microbiome and antimicrobial resistant organisms in a cohort of US travellers before and after international travel. They found that the travellers frequently acquired Enterobacteriaceae and antimicrobial resistance genes (ARGs), aligning with our findings and those of other studies.2–5 Nevertheless, they were unable to determine the persistence of acquired antimicrobial resistant organisms, as they obtained only pre-travel and post-travel samples.
Endoscopic submucosal dissection of early gastric angle cancer by using a simplified robot-assisted device for traction
Authors: Can Cui, Xuefeng Lu, Xiu-Li Zuo, Rui Ji
Journal: Endoscopy (2024)

Endoscopic submucosal dissection (ESD) is the standard technique for resection of gastric superficial tumors. However, in difficult locations of the stomach, a vertical approach toward the muscular layer is always unavoidable and results in a higher risk of damage [1]. To help address these issues, we designed a flexible auxiliary single-arm transluminal endoscopic robot (FASTER). The operator can utilize its external control system to precisely manipulate the grasping forceps, exerting a controlled pulling force in multiple directions away from the gastric wall ([Fig. 1]) [2].
Complete occlusion of an ascending colon varix and its contributors using endoscopic cyanoacrylate glue injection
Authors: Anastasios C. Manolakis, Dimitrios Chougias, Stelios Kyriakidis, Ioannis Hatzoudis, Eirini Deligianni, Georgios Gelas, Andreas Kapsoritakis
Journal: Endoscopy (2024)

Bleeding from colonic varices is a rare occurrence [1], lacking uniform management and usually treated with radiology interventions at the expense of hepatic encephalopathy aggravation [2]. Endoscopic cyanoacrylate glue injection is used for gastric variceal bleeding [3], however its use for ascending colon varices is hindered by the complexity of collaterals, scarcity of cases, cumbersome accessibility, injection needle occlusion, and risk of embolic events [1] [2] [3]. Herein, we report a case of successful complete obliteration of a large ascending colon varix and its contributors through a single-puncture endoscopic cyanoacrylate glue injection.
Case 2-2024: A 57-Year-Old Woman with Melanoma and Fever
Authors: Amir M Mohareb, Jiyoon Kang, Kamaneh Montazeri, Stuti G Shroff
Journal: New England Journal of Medicine (2024)

A 57-year-old woman with resected stage IIIC melanoma was admitted because of fever and hypotension. Treatment with BRAF–MEK inhibitors had been started 4 weeks earlier. A diagnosis was made.
TMEM106B core deposition associates with TDP-43 pathology and is increased in risk SNP carriers for frontotemporal dementia
Authors: Jordan D. Marks, Virginia Estades Ayuso, Yari Carlomagno, Mei Yue, Tiffany W. Todd, Ying Hao, Ziyi Li, Zachary T. McEachin, Anantharaman Shantaraman, Duc M. Duong, Lillian M. Daughrity, Karen Jansen-West, Wei Shao, Anna Calliari, Jesus Gonzalez Bejarano, Michael DeTure, Bailey Rawlinson, Monica Castanedes Casey, Meredith T. Lilley, Megan H. Donahue, Vidhya Maheswari Jawahar, Bradley F. Boeve, Ronald C. Petersen, David S. Knopman, Björn Oskarsson, Neill R. Graff-Radford, Zbigniew K. Wszolek, Dennis W. Dickson, Keith A. Josephs, Yue A. Qi, Nicholas T. Seyfried, Michael E. Ward, Yong-Jie Zhang, Mercedes Prudencio, Leonard Petrucelli, Casey N. Cook
Journal: Science Translational Medicine (2024)

Genetic variation at the transmembrane protein 106B gene ( TMEM106B) has been linked to risk of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) through an unknown mechanism. We found that presence of the TMEM106B rs3173615 protective genotype was associated with longer survival after symptom onset in a postmortem FTLD-TDP cohort, suggesting a slower disease course. The seminal discovery that filaments derived from TMEM106B is a common feature in aging and, across a range of neurodegenerative disorders, suggests that genetic variants in TMEM106B could modulate disease risk and progression through modulating TMEM106B aggregation. To explore this possibility and assess the pathological relevance of TMEM106B accumulation, we generated a new antibody targeting the TMEM106B filament core sequence. Analysis of postmortem samples revealed that the TMEM106B rs3173615 risk allele was associated with higher TMEM106B core accumulation in patients with FTLD-TDP. In contrast, minimal TMEM106B core deposition was detected in carriers of the protective allele. Although the abundance of monomeric full-length TMEM106B was unchanged, carriers of the protective genotype exhibited an increase in dimeric full-length TMEM106B. Increased TMEM106B core deposition was also associated with enhanced TDP-43 dysfunction, and interactome data suggested a role for TMEM106B core filaments in impaired RNA transport, local translation, and endolysosomal function in FTLD-TDP. Overall, these findings suggest that prevention of TMEM106B core accumulation is central to the mechanism by which the TMEM106B protective haplotype reduces disease risk and slows progression.
Antibodies targeting the fusion peptide on the HIV envelope provide protection to rhesus macaques against mucosal SHIV challenge
Authors: Amarendra Pegu, Sarah E. Lovelace, Megan E. DeMouth, Michelle D. Cully, Daniel J. Morris, Yingying Li, Keyun Wang, Stephen D. Schmidt, Misook Choe, Cuiping Liu, Xuejun Chen, Elise Viox, Ariana Rowshan, Justin D. Taft, Baoshan Zhang, Kai Xu, Hongying Duan, Li Ou, John-Paul Todd, Rui Kong, Hui Li, George M. Shaw, Nicole A. Doria-Rose, Peter D. Kwong, Richard A. Koup, John R. Mascola
Journal: Science Translational Medicine (2024)

The fusion peptide (FP) on the HIV-1 envelope (Env) trimer can be targeted by broadly neutralizing antibodies (bNAbs). Here, we evaluated the ability of a human FP-directed bNAb, VRC34.01, along with two vaccine-elicited anti-FP rhesus macaque mAbs, DFPH-a.15 and DF1W-a.01, to protect against simian-HIV (SHIV) BG505 challenge. VRC34.01 neutralized SHIV BG505 with a 50% inhibitory concentration (IC 50 ) of 0.58 μg/ml, whereas DF1W-a.01 and DFPH-a.15 were 4- or 30-fold less potent, respectively. VRC34.01 was infused into four rhesus macaques at a dose of 10 mg/kg and four rhesus macaques at a dose of 2.5 mg/kg. The animals were intrarectally challenged 5 days later with SHIV BG505 . In comparison with all 12 control animals that became infected, all four animals infused with VRC34.01 (10 mg/kg) and three out of four animals infused with VRC34.01 (2.5 mg/kg) remained uninfected. Because of the lower potency of DF1W-a.01 and DFPH-a.15 against SHIV BG505 , we infused both Abs at a higher dose of 100 mg/kg into four rhesus macaques each, followed by SHIV BG505 challenge 5 days later. Three of four animals that received DF1W-a.01 were protected against infection, whereas all animals that received DFPH-a.15 were protected. Overall, the protective serum neutralization titers observed in these animals were similar to what has been observed for other bNAbs in similar SHIV infection models and in human clinical trials. In conclusion, FP-directed mAbs can thus provide dose-dependent in vivo protection against mucosal SHIV challenges, supporting the development of prophylactic vaccines targeting the HIV-1 Env FP.
Splicing neoantigen discovery with SNAF reveals shared targets for cancer immunotherapy
Authors: Guangyuan Li, Shweta Mahajan, Siyuan Ma, Erin D. Jeffery, Xuan Zhang, Anukana Bhattacharjee, Meenakshi Venkatasubramanian, Matthew T. Weirauch, Emily R. Miraldi, H. Leighton Grimes, Gloria M. Sheynkman, Tamara Tilburgs, Nathan Salomonis
Journal: Science Translational Medicine (2024)

Immunotherapy has emerged as a crucial strategy to combat cancer by “reprogramming” a patient’s own immune system. Although immunotherapy is typically reserved for patients with a high mutational burden, neoantigens produced from posttranscriptional regulation may provide an untapped reservoir of common immunogenic targets for new targeted therapies. To comprehensively define tumor-specific and likely immunogenic neoantigens from patient RNA-Seq, we developed Splicing Neo Antigen Finder (SNAF), an easy-to-use and open-source computational workflow to predict splicing-derived immunogenic MHC-bound peptides (T cell antigen) and unannotated transmembrane proteins with altered extracellular epitopes (B cell antigen). This workflow uses a highly accurate deep learning strategy for immunogenicity prediction (DeepImmuno) in conjunction with new algorithms to rank the tumor specificity of neoantigens (BayesTS) and to predict regulators of mis-splicing (RNA-SPRINT). T cell antigens from SNAF were frequently evidenced as HLA-presented peptides from mass spectrometry (MS) and predict response to immunotherapy in melanoma. Splicing neoantigen burden was attributed to coordinated splicing factor dysregulation. Shared splicing neoantigens were found in up to 90% of patients with melanoma, correlated to overall survival in multiple cancer cohorts, induced T cell reactivity, and were characterized by distinct cells of origin and amino acid preferences. In addition to T cell neoantigens, our B cell focused pipeline (SNAF-B) identified a new class of tumor-specific extracellular neoepitopes, which we termed ExNeoEpitopes. ExNeoEpitope full-length mRNA predictions were tumor specific and were validated using long-read isoform sequencing and in vitro transmembrane localization assays. Therefore, our systematic identification of splicing neoantigens revealed potential shared targets for therapy in heterogeneous cancers.
Commensal antimicrobial resistance mediates microbiome resilience to antibiotic disruption
Authors: Shakti K. Bhattarai, Muxue Du, Abigail L. Zeamer, Benedikt M. Morzfeld, Tasia D. Kellogg, Kaya Firat, Anna Benjamin, James M. Bean, Matthew Zimmerman, Gertrude Mardi, Stalz Charles Vilbrun, Kathleen F. Walsh, Daniel W. Fitzgerald, Michael S. Glickman, Vanni Bucci
Journal: Science Translational Medicine (2024)

Despite their therapeutic benefits, antibiotics exert collateral damage on the microbiome and promote antimicrobial resistance. However, the mechanisms governing microbiome recovery from antibiotics are poorly understood. Treatment of Mycobacterium tuberculosis , the world’s most common infection, represents the longest antimicrobial exposure in humans. Here, we investigate gut microbiome dynamics over 20 months of multidrug-resistant tuberculosis (TB) and 6 months of drug-sensitive TB treatment in humans. We find that gut microbiome dynamics and TB clearance are shared predictive cofactors of the resolution of TB-driven inflammation. The initial severe taxonomic and functional microbiome disruption, pathobiont domination, and enhancement of antibiotic resistance that initially accompanied long-term antibiotics were countered by later recovery of commensals. This resilience was driven by the competing evolution of antimicrobial resistance mutations in pathobionts and commensals, with commensal strains with resistance mutations reestablishing dominance. Fecal-microbiota transplantation of the antibiotic-resistant commensal microbiome in mice recapitulated resistance to further antibiotic disruption. These findings demonstrate that antimicrobial resistance mutations in commensals can have paradoxically beneficial effects by promoting microbiome resilience to antimicrobials and identify microbiome dynamics as a predictor of disease resolution in antibiotic therapy of a chronic infection.
Mycobacterium tuberculosis: a new hitchhiker in the etiopathogenesis of periodontitis
Authors: ArunSundar MohanaSundaram, Namra Vinay Gohil, Maudlyn O. Etekochay, Premalkumar Patel, Swathi Gurajala, Shanmugarajan Thukani Sathanantham, Mugisha Nsengiyumva, Santosh Kumar, Talha Bin Emran
Journal: International Journal of Surgery (2024)

Periodontitis, a chronic inflammatory disease of the gums affects both the ligament and alveolar bone. A severe form of periodontal disease affects a strikingly high number of one billion adults globally. The disease permutes both the soft and hard tissues of the oral cavity leading to localized and systemic diseases. Periodontitis has a deleterious impact on systemic health causing diabetes, cardiovascular diseases (CVD), and other disease. The cause of the enhanced inflammatory process is due to dysbiosis and an unregulated immune response. Innate immune response and T cells trigger uninhibited cytokine release causing an unwarranted inflammatory response. The RANK- RANKL interaction between osteoblasts, immune cells, and progenitor osteoclasts results in the maturation of osteoclasts, which promote bone resorption. It is well established that dysbiosis of the oral cavity has been implicated in periodontitis. But emerging reports suggest that the pulmonary pathogen, Mycobacterium tuberculosis (Mtb), causes extrapulmonary diseases such as periodontitis. Many clinical case reports advocate the involvement of Mtb in periodontitis, which poses a threat with the surge of tuberculosis in HIV and other immunocompromised individuals. Fostering a better understanding of the mechanism, causative agents and control on inflammatory response is imperative in the prevention and treatment of periodontitis.
C-C chemokine receptor type 7 (CCR7) regulates hepatic CD8+ T cell homeostasis and response to acute liver injury
Authors: Patricia Niemietz, Moritz Peiseler, Marlene Kohlhepp, Paul Horn, Kylie Matchett, Yuting Wang, Leon Haas, Tianjiao Zhang, Alix Bruneau, Adrien Guillot, Hilmar Berger, Anke Liepelt, Klaudia Warzecha, Catharina Demske, Diana Möckel, Twan Lammers, Neil Henderson, Felix Heymann, Frank Tacke
Journal: Hepatology (2024)

Background and Aims: Acute liver failure (ALF) is a rare but life-threatening condition, and DILI, particularly acetaminophen toxicity, is the leading cause of ALF. Innate immune mechanisms further perpetuate liver injury, while the role of the adaptive immune system in DILI-related ALF is unclear. Approach and Results: We analyzed liver tissue from 2 independent patient cohorts with ALF and identified hepatic T cell infiltration as a prominent feature in human ALF. CD8 + T cells were characterized by zonation toward necrotic regions and an activated gene expression signature. In murine acetaminophen-induced liver injury, intravital microscopy revealed zonation of CD8 + but not CD4 + T cells at necrotic areas. Gene expression analysis exposed upregulated C-C chemokine receptor 7 (CCR7) and its ligand CCL21 in the liver as well as a broadly activated phenotype of hepatic CD8 + T cells. In 2 mouse models of ALF, Ccr7 −/− mice had significantly aggravated early-phase liver damage. Functionally, CCR7 was not involved in the recruitment of CD8 + T cells, but regulated their activation profile potentially through egress to lymphatics. Ccr7 −/− CD8 + T cells were characterized by elevated expression of activation, effector, and exhaustion profiles. Adoptive transfer revealed preferential homing of CCR7-deficient CD8 + T cells to the liver, and depletion of CD8 + T cells attenuated liver damage in mice. Conclusions: Our study demonstrates the involvement of the adaptive immune system in ALF in humans and mice. We identify the CCR7-CCL21 axis as an important regulatory pathway, providing downstream protection against T cell–mediated liver injury.