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Soft, Skin-Interfaced Wireless Electrogoniometry Systems For Continuous Monitoring Of Finger And Wrist Joints, Hee-Sup Shin, Jihye Kim, Nicholas Fadell, Logan B Pewitt, Yusuf Shaaban, Claire Liu, Min-Seung Jo, Josif Bozovic, Andreas Tzavelis, Minsu Park, Kelly Koogler, Jin-Tae Kim, Jae-Young Yoo, John A Rogers, Mitchell A Pet May 2025

Soft, Skin-Interfaced Wireless Electrogoniometry Systems For Continuous Monitoring Of Finger And Wrist Joints, Hee-Sup Shin, Jihye Kim, Nicholas Fadell, Logan B Pewitt, Yusuf Shaaban, Claire Liu, Min-Seung Jo, Josif Bozovic, Andreas Tzavelis, Minsu Park, Kelly Koogler, Jin-Tae Kim, Jae-Young Yoo, John A Rogers, Mitchell A Pet

2020-Current year OA Pubs

Continuous kinematic biofeedback during exercise interventions can lead to improved therapeutic outcomes in hand and wrist rehabilitation. Conventional methods for measuring joint kinematics typically allow only static measurements performed by specially trained therapists. This paper introduces skin-conformal, wearable wireless systems designed to continuously and accurately capture the angles of target joints, specifically in hand and wrist. Supported by a computer vision-based calibration protocol run on a smart device, these magnetometer-based standalone systems provide patients and clinicians with continuous, real-time data on joint angles and ranges of motion through an intuitive graphical interface. Human trials in healthy volunteers demonstrate the accuracy …


Genome-Wide Analyses Identify 30 Loci Associated With Obsessive-Compulsive Disorder, Nora I. Strom, Arpana Agrawal, Kathleen K. Bucholz, Et Al. May 2025

Genome-Wide Analyses Identify 30 Loci Associated With Obsessive-Compulsive Disorder, Nora I. Strom, Arpana Agrawal, Kathleen K. Bucholz, Et Al.

2020-Current year OA Pubs

No abstract provided.


White Matter Connections Within The Central Sulcus Subserving The Somato-Cognitive Action Network, Georgios P Skandalakis, Evan M Gordon, Nico U F Dosenbach, Et Al. May 2025

White Matter Connections Within The Central Sulcus Subserving The Somato-Cognitive Action Network, Georgios P Skandalakis, Evan M Gordon, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

The somato-cognitive action network (SCAN) consists of three nodes interspersed within Penfield's motor effector regions. The configuration of the somato-cognitive action network nodes resembles the one of the 'plis de passage' of the central sulcus: small gyri bridging the precentral and postcentral gyri. Thus, we hypothesize that these may provide a structural substrate of the somato-cognitive action network. Using microdissections of 16 human hemispheres, we consistently identified a chain of three distinct plis de passage with increased underlying white matter in locations analogous to the somato-cognitive action network nodes. We mapped localizations of plis de passage into standard stereotactic space …


Augmented Reality Microscopy To Bridge Trust Between Ai And Pathologists, Sunil Badve, Xiuli Liu, Et Al. May 2025

Augmented Reality Microscopy To Bridge Trust Between Ai And Pathologists, Sunil Badve, Xiuli Liu, Et Al.

2020-Current year OA Pubs

Diagnostic certainty is the cornerstone of modern medicine and critical for maximal treatment benefit. When evaluating biomarker expression by immunohistochemistry (IHC), however, pathologists are hindered by complex scoring methodologies, unique positivity cut-offs and subjective staining interpretation. Artificial intelligence (AI) can potentially eliminate diagnostic uncertainty, especially when AI "trustworthiness" is proven by expert pathologists in the context of real-world clinical practice. Building on an IHC foundation model, we employed pathologists-in-the-loop finetuning to produce a programmed cell death ligand 1 (PD-L1) CPS AI Model. We devised a multi-head augmented reality microscope (ARM) system overlayed with the PD-L1 CPS AI Model to assess …


Phase Ii Study Of Venetoclax Added To Bendamustine And Obinutuzumab In Patients With High-Risk Follicular Lymphoma As Front-Line Therapy: Pre0403, Craig A Portell, Opeyemi A Jegede, Nina Wagner-Johnston, Grzegorz S Nowakowski, Christopher Fletcher, Jonathon B Cohen, Andrew M Evens, Lori J Rosenstein, Jeffrey W Craig, Nishitha Reddy, Brad S Kahl May 2025

Phase Ii Study Of Venetoclax Added To Bendamustine And Obinutuzumab In Patients With High-Risk Follicular Lymphoma As Front-Line Therapy: Pre0403, Craig A Portell, Opeyemi A Jegede, Nina Wagner-Johnston, Grzegorz S Nowakowski, Christopher Fletcher, Jonathon B Cohen, Andrew M Evens, Lori J Rosenstein, Jeffrey W Craig, Nishitha Reddy, Brad S Kahl

2020-Current year OA Pubs

Over-expression of BCL-2 defines follicular lymphoma (FL). Venetoclax (VEN), a selective BCL-2 inhibitor, has previously been evaluated with bendamustine-based chemoimmunotherapy. VEN was given continuously, resulting in promising efficacy but unacceptable toxicity. The Phase II PrE0403 study was designed to evaluate intermittent dosing of VEN (10 days per cycle) combined with obinutuzumab and bendamustine (VEN-OB) in untreated FL subjects with high-risk features defined as a FLIPI-1 score of ≥3 and/or high tumor burden by GELF criteria. A total of 56 subjects were planned to be accrued with a goal of having 51 subjects eligible to improve the historical 50% CR rate …


A Scoping Review Of Remote And Unsupervised Digital Cognitive Assessments In Preclinical Alzheimer's Disease, Sarah E Polk, Fredrik Öhman, Jason Hassenstab, Alexandra König, Kathryn V Papp, Michael Schöll, David Berron May 2025

A Scoping Review Of Remote And Unsupervised Digital Cognitive Assessments In Preclinical Alzheimer's Disease, Sarah E Polk, Fredrik Öhman, Jason Hassenstab, Alexandra König, Kathryn V Papp, Michael Schöll, David Berron

2020-Current year OA Pubs

Characterizing subtle cognitive changes in preclinical Alzheimer's disease (AD) is difficult using traditional neuropsychological assessments. Remote and unsupervised digital assessments can improve scalability, measurement reliability, and ecological validity, enabling the capture of subtle changes. We evaluate such tools for use in preclinical AD, or cognitively unimpaired individuals with abnormal levels of AD pathology. We screened 1904 reports for studies remotely assessing cognition in preclinical AD samples. Twenty-three tools were identified, and their usability, reliability, and validity, including construct and criterion validity based on in-person neuropsychological and Aβ/tau measures, was reported. We present a necessary update to a rapidly evolving field, …


Optimizing Peptide Nucleic Acid-Based Pretargeting For Enhanced Targeted Radionuclide Therapy, Mohamed Altai, Ábel Nagy, Pauline Granit, Wahed Zedan, Myriam Cerezo-Magaña, Julie Park, Katharina Lückerath, Susanne Geres, Marie Sydoff, Daniel L J Thorek, Kristina Westerlund, David Ulmert, Amelie Eriksson Karlström May 2025

Optimizing Peptide Nucleic Acid-Based Pretargeting For Enhanced Targeted Radionuclide Therapy, Mohamed Altai, Ábel Nagy, Pauline Granit, Wahed Zedan, Myriam Cerezo-Magaña, Julie Park, Katharina Lückerath, Susanne Geres, Marie Sydoff, Daniel L J Thorek, Kristina Westerlund, David Ulmert, Amelie Eriksson Karlström

2020-Current year OA Pubs

Radiolabeled targeting agents have emerged as valuable tools for the treatment of disseminated cancer. Monoclonal antibodies (mAbs) are widely employed as carriers for diagnostic and therapeutic radionuclides due to their exceptional specificity and affinity. However, their prolonged circulatory half-life can diminish diagnostic efficacy and increase radiation exposure to non-target tissues in therapeutic applications, resulting in dose-limiting toxicities. To overcome this limitation, pretargeting technologies emerge as promising strategies to enhance tumor-to-background ratio and reduce radiation exposure of healthy tissues. Our previous work introduced a pretargeting concept leveraging the specific interaction between two peptide nucleic acid (PNA) probes, HP1 and HP2, as …


Molecular Basis Of Trpv3 Channel Blockade By Intracellular Polyamines, Jingying Zhang, Peng Yuan, Colin G Nichols, Grigory Maksaev May 2025

Molecular Basis Of Trpv3 Channel Blockade By Intracellular Polyamines, Jingying Zhang, Peng Yuan, Colin G Nichols, Grigory Maksaev

2020-Current year OA Pubs

ThermoTRPV1-4 channels are involved in the regulation of multiple physiological processes, including thermo- and pain perception, thermoregulation, itch, and nociception and therefore tight control of their activity is a critical requirement for correct perception of noxious stimuli and pain. We previously reported a voltage-dependent inhibition of TRPV1-4 channels by intracellular polyamines that could be explained by high affinity spermine binding in, and passage through, the permeation path. Here, using electrophysiology and cryo-electron microscopy, we elucidate molecular details of TRPV3 blockade by endogenous spermine and its analog NASPM. We identify a high-affinity polyamine interaction site at the intracellular side of the …


Recombinant Interleukin-7 Treatment Of Refractory Refractory Mycobacterium Avium Complexlung Disease (Impulse-7): A Pilot Phase Ii, Single-Center, Randomized, Clinical Trial, Carlos Mejia-Chew, Andrej Spec, Andrew H Walton, Alina Ulezko Antonova, Alexandra Dram, Sanjeev Bhalla, Marco Colonna, Michel Morre, Richard Hotchkiss May 2025

Recombinant Interleukin-7 Treatment Of Refractory Refractory Mycobacterium Avium Complexlung Disease (Impulse-7): A Pilot Phase Ii, Single-Center, Randomized, Clinical Trial, Carlos Mejia-Chew, Andrej Spec, Andrew H Walton, Alina Ulezko Antonova, Alexandra Dram, Sanjeev Bhalla, Marco Colonna, Michel Morre, Richard Hotchkiss

2020-Current year OA Pubs

BACKGROUND: Nontuberculous mycobacteria disease is an emerging opportunistic infection that is often refractory to therapy. Interleukin 7 (IL-7) is a pleiotropic cytokine with broad-ranging effects that enhance immunity and augment monocyte/macrophage anti-

OBJECTIVES: This study evaluated IL-7 in patients with refractory

DESIGN: Prospective, single-center, randomized, study of IL-7 in patients with refractory MAC-LD.

METHODS: Randomization (two sets of 4 weekly IL-7 injections) was stratified based on the presence of pulmonary cavities. The primary outcome was sputum culture conversion to negative within 6 months. Exploratory outcomes included investigation of potential molecular mechanisms of immunosuppression via single-cell RNA sequencing (scRNA-seq).

RESULTS: Of …


Outcomes Of 1,021 Consecutive Cases Utilizing A Triple Tapered Collared Stem And Automated Broaching System, Ravi R Agrawal, Maria T Schwabe, Helena F Barber, Ethan Blum, Joseph T Gibian, Ryan M Nunley, Ilya Bendich May 2025

Outcomes Of 1,021 Consecutive Cases Utilizing A Triple Tapered Collared Stem And Automated Broaching System, Ravi R Agrawal, Maria T Schwabe, Helena F Barber, Ethan Blum, Joseph T Gibian, Ryan M Nunley, Ilya Bendich

2020-Current year OA Pubs

No abstract provided.


Multi-Parametric Quantitative Evaluation Of Murine Cervical Remodeling During Pregnancy And Postpartum, Yan Yan, Jose Galaz, Joshua Marvald, Tanzy Love, Steven Yellon, Nardhy Gomez-Lopez, Mohammad Mehrmohammadi May 2025

Multi-Parametric Quantitative Evaluation Of Murine Cervical Remodeling During Pregnancy And Postpartum, Yan Yan, Jose Galaz, Joshua Marvald, Tanzy Love, Steven Yellon, Nardhy Gomez-Lopez, Mohammad Mehrmohammadi

2020-Current year OA Pubs

Cervical remodeling during pregnancy is a critical process that, if untimely, can lead to complications such as preterm birth (PTB). This study introduces a novel multi-parametric approach combining non-invasive imaging modalities to quantify cervical tissue changes during pregnancy and postpartum in a murine model. By integrating ultrasound-based measurements of cervical length, photoacoustic imaging of the collagen-to-water ratio, and elastography for tissue elasticity alongside histological assessments, this method provides a comprehensive evaluation of cervical remodeling. The findings reveal that combining these parameters significantly improves the accuracy of gestational age prediction compared to individual measurements, with a tri-parametric model achieving 85.3% prediction …


High-Throughput Echocardiography-Guided Induction Of Myocardial Ischemia/Reperfusion In Mice, Florian Sicklinger, Niklas Hartmann, Attila Kovacs, Carla Weinheimer, Jess Nigro, Junedh M. Amrute, Kory J. Lavine, Et Al. May 2025

High-Throughput Echocardiography-Guided Induction Of Myocardial Ischemia/Reperfusion In Mice, Florian Sicklinger, Niklas Hartmann, Attila Kovacs, Carla Weinheimer, Jess Nigro, Junedh M. Amrute, Kory J. Lavine, Et Al.

2020-Current year OA Pubs

BACKGROUND: Mouse models of myocardial ischemia with subsequent heart failure are common approaches to examine heart failure pathology and possible treatment strategies. We sought to establish a high-throughput approach for echocardiography-guided induction of myocardial ischemia/reperfusion (IR) in mice.

METHODS: After visualization of the left coronary artery with high-resolution ultrasound imaging and echocardiographic definition of the level of coronary occlusion, the left anterior descending artery was temporarily occluded with 2 micromanipulator-controlled needles. Functional and molecular changes were assessed and compared with commonly performed surgical techniques.

RESULTS: Echocardiography-guided induction of myocardial IR enabled standardized induction of myocardial IR injury with subsequent left …


Psma-Expressing, Fluciclovine-Negative Vertebral Hemangioma, Azadeh Eslambolchi, Amin Haghighat Jahromi May 2025

Psma-Expressing, Fluciclovine-Negative Vertebral Hemangioma, Azadeh Eslambolchi, Amin Haghighat Jahromi

2020-Current year OA Pubs

BACKGROUND: False-positive findings in Prostate-Specific Membrane Antigen Positron Emission Tomography-Computed Tomography (PSMA PET-CT) can complicate accurate staging of prostate cancer, especially in cases such as vertebral hemangiomas, a benign lesion of the spinal column. These ambiguities may result in unnecessary biopsies in patients with prostate cancer when PSMA PET findings are inconclusive.

CASE PRESENTATION: We present the case of a 68-year-old male with prostate cancer who had a PSMA-expressing, fluciclovine-negative vertebral hemangioma.

CONCLUSION: This case highlights the role of fluciclovine PET-CT in distinguishing benign vertebral hemangiomas from prostate cancer metastases, improving diagnostic accuracy specifically in positive cases of PSMA PET-CT.


Sirt6 Deficiency Promotes Senescence And Age-Associated Intervertebral Disc Degeneration In Mice, Pranay Ramteke, Bahiyah Watson, Mallory Toci, Victoria A Tran, Shira Johnston, Maria Tsingas, Ruteja A Barve, Ramkrishna Mitra, Richard F Loeser, John A Collins, Makarand V Risbud May 2025

Sirt6 Deficiency Promotes Senescence And Age-Associated Intervertebral Disc Degeneration In Mice, Pranay Ramteke, Bahiyah Watson, Mallory Toci, Victoria A Tran, Shira Johnston, Maria Tsingas, Ruteja A Barve, Ramkrishna Mitra, Richard F Loeser, John A Collins, Makarand V Risbud

2020-Current year OA Pubs

Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain. While the etiological factors for disc degeneration vary, age is still one of the most important risk factors. Recent studies have shown the promising role of SIRT6 in mammalian aging and skeletal tissue health, however its role in the intervertebral disc health remains unexplored. We investigated the contribution of SIRT6 to disc health by studying the age-dependent spinal phenotype of mice with conditional deletion of Sirt6 in the disc (Acan


Estradiol Protects Against Pain-Facilitated Fentanyl Use Via Suppression Of Opioid-Evoked Dopamine Activity In Males, Jessica A Higginbotham, Julian G Abt, Rachel H Teich, Joanna J Dearman, Tania Lintz, Jose A Morón May 2025

Estradiol Protects Against Pain-Facilitated Fentanyl Use Via Suppression Of Opioid-Evoked Dopamine Activity In Males, Jessica A Higginbotham, Julian G Abt, Rachel H Teich, Joanna J Dearman, Tania Lintz, Jose A Morón

2020-Current year OA Pubs

Pain relief is the most frequently reported motivation for opioid misuse, but it remains unclear how pain alters reward pathway function contributing to maladaptive opioid use and whether these neuroadaptations occur in a sex-specific manner. Here, we show that persistent inflammatory pain leads to augmented fentanyl self-administration in male, not female, rats. Wireless in vivo fiber photometry recordings and chemogenetic manipulations indicate that pain-facilitated fentanyl use is mediated by enhanced ventral tegmental area dopamine (VTA


Barriers And Facilitators Of The Implementation Of Mammography Screening In The Brazilian Public Health System: Scoping Review, Danila Cristina Paquier Sala, Oswaldo Yoshimi Tanaka, Reginaldo Adalberto Luz, Alexandre Pazetto Balsanelli, Sonia Isoyama Venancio, Marília Cristina Prado Louvison, Ana A Baumann May 2025

Barriers And Facilitators Of The Implementation Of Mammography Screening In The Brazilian Public Health System: Scoping Review, Danila Cristina Paquier Sala, Oswaldo Yoshimi Tanaka, Reginaldo Adalberto Luz, Alexandre Pazetto Balsanelli, Sonia Isoyama Venancio, Marília Cristina Prado Louvison, Ana A Baumann

2020-Current year OA Pubs

BACKGROUND: There are high incidence and mortality rates of breast cancer in Brazil. Brazilian's social and economic disparities, along with complexities of its health system pose challenges to the appropriate implementation of mammography screening as a public policy for the population. In 2015, the Ministry of Health updated the recommendations for the early detection of breast cancer, which had, until then, been based on specialists' consensus, maintaining biennial screening mammography for women aged 50-69 years. However, the screening coverage did not exceed 25% of the expected number of exams for the Brazilian population who use the public health system. The …


Human Papilloma Virus Infection Drives Unique Metabolic And Immune Profiles In Head And Neck And Cervical Cancers: Implications For Targeted Therapies And Prognostic Markers, Saira Hamid, Mohd Shahnawaz Khan, Meraj Alam Khan, Naoshad Muhammad, Mayank Singh, Ammira S Al-Shabeeb Akil, Ajaz A Bhat, Muzafar A Macha May 2025

Human Papilloma Virus Infection Drives Unique Metabolic And Immune Profiles In Head And Neck And Cervical Cancers: Implications For Targeted Therapies And Prognostic Markers, Saira Hamid, Mohd Shahnawaz Khan, Meraj Alam Khan, Naoshad Muhammad, Mayank Singh, Ammira S Al-Shabeeb Akil, Ajaz A Bhat, Muzafar A Macha

2020-Current year OA Pubs

Human papillomavirus (HPV) is a key driver of head and neck squamous cell carcinoma (HNSCC) and cervical squamous cell carcinoma (CESC). Yet, these cancers exhibit distinct molecular and clinical features influenced by HPV status. This study utilizes RNA sequencing data from The Cancer Genome Atlas (TCGA). It employs bioinformatics tools, including DESeq2 for differential gene expression, CIBERSORT for immune profiling, and Kaplan-Meier survival analysis to investigate these differences. Differential expression analysis revealed distinct molecular signatures, with HPV-positive tumors enriched in immune-related pathways such as cytokine-cytokine receptor interactions. In contrast, HPV-negative tumors exhibited upregulation of metabolic pathways, including PPAR signaling. Metaflux …


Rag Suppresses Group 2 Innate Lymphoid Cells, Aaron M Ver Heul, Madison Mack, Lydia Zamidar, Masato Tamari, Ting-Lin Yang, Anna M Trier, Do-Hyun Kim, Hannah Janzen-Meza, Steven J Van Dyken, Chyi-Song Hsieh, Jenny M Karo, Joseph C Sun, Brian S Kim May 2025

Rag Suppresses Group 2 Innate Lymphoid Cells, Aaron M Ver Heul, Madison Mack, Lydia Zamidar, Masato Tamari, Ting-Lin Yang, Anna M Trier, Do-Hyun Kim, Hannah Janzen-Meza, Steven J Van Dyken, Chyi-Song Hsieh, Jenny M Karo, Joseph C Sun, Brian S Kim

2020-Current year OA Pubs

Antigen specificity is the central trait distinguishing adaptive from innate immune function. Assembly of antigen-specific T cell and B cell receptors occurs through V(D)J recombination mediated by the Recombinase Activating Gene endonucleases RAG1 and RAG2 (collectively called RAG). In the absence of RAG, mature T and B cells do not develop and thus RAG is critically associated with adaptive immune function. In addition to adaptive T helper 2 (Th2) cells, group 2 innate lymphoid cells (ILC2s) contribute to type 2 immune responses by producing cytokines like Interleukin-5 (IL-5) and IL-13. Although it has been reported that RAG expression modulates the …


Identifying Genetic Errors Of Immunity Due To Mosaicism, Elizabeth G Schmitz, Malachi Griffith, Obi L Griffith, Megan A Cooper May 2025

Identifying Genetic Errors Of Immunity Due To Mosaicism, Elizabeth G Schmitz, Malachi Griffith, Obi L Griffith, Megan A Cooper

2020-Current year OA Pubs

Inborn errors of immunity are monogenic disorders of the immune system that lead to immune deficiency and/or dysregulation in patients. Identification of precise genetic causes of disease aids diagnosis and advances our understanding of the human immune system; however, a significant portion of patients lack a molecular diagnosis. Somatic mosaicism, genetic changes in a subset of cells, is emerging as an important mechanism of immune disease in both young and older patients. Here, we review the current landscape of somatic genetic errors of immunity and methods for the detection and validation of somatic variants.


Transmission Pathways Of Campylobacter Jejuni Between Humans And Livestock In Rural Ethiopia Are Highly Complex And Interdependent, Nitya Singh, Cecilie A N Thystrup, Bahar Mummed Hassen, Menuka Bhandari, Gireesh Rajashekara, Tine M Hald, Mark J Manary, Sarah L Mckune, Jemal Yusuf Hassen, Helen L Smith, Jonathan C Marshall, Nigel P French, Arie H Havelaar, Caged Research Team Members May 2025

Transmission Pathways Of Campylobacter Jejuni Between Humans And Livestock In Rural Ethiopia Are Highly Complex And Interdependent, Nitya Singh, Cecilie A N Thystrup, Bahar Mummed Hassen, Menuka Bhandari, Gireesh Rajashekara, Tine M Hald, Mark J Manary, Sarah L Mckune, Jemal Yusuf Hassen, Helen L Smith, Jonathan C Marshall, Nigel P French, Arie H Havelaar, Caged Research Team Members

2020-Current year OA Pubs

BACKGROUND: Campylobacter jejuni and C. coli are the most common causes of bacterial enteritis worldwide whereas symptomatic and asymptomatic infections are associated with stunting in children in low- and middle-income countries. Little is known about their sources and transmission pathways in low- and middle-income countries, and particularly for infants and young children. We assessed the genomic diversity of C. jejuni in Eastern Ethiopia to determine the attribution of infections in infants under 1 year of age to livestock (chickens, cattle, goats and sheep) and other humans (siblings, mothers).

RESULTS: Among 287 C. jejuni isolates, 48 seven-gene sequence types (STs), including …


Antibiotic De-Escalation In The Intensive Care Unit: Rationale And Potential Strategies, Sarah Singer Matuszak, Lauren Kolodziej, Scott Micek, Marin Kollef May 2025

Antibiotic De-Escalation In The Intensive Care Unit: Rationale And Potential Strategies, Sarah Singer Matuszak, Lauren Kolodziej, Scott Micek, Marin Kollef

2020-Current year OA Pubs

Antibiotic de-escalation (ADE) is important to help optimize antibiotic use and balance the positive and negative effects of antimicrobial therapy. ADE should be performed promptly, and infections should be treated with the shortest course of antimicrobials as clinically feasible to avoid unnecessary use of broad-spectrum antimicrobials. Several tools have been developed to increase efficient ADE, including rapid diagnostic tests (ex. multiplex PCR), MRSA nasal PCR/culture, and biomarkers. Multiplex PCR and MRSA nasal PCR/culture have been associated with reductions in inappropriate antibiotic use. Procalcitonin, a biomarker, has been associated with shorter antimicrobial durations in some studies; however, widespread use may be …


Mrn-Ctip, Exo1, And Dna2-Wrn/Blm Act Bidirectionally To Process Dna Gaps In Parpi-Treated Cells Without Strand Cleavage, Isabelle M Seppa, Mithila Tennakoon, Jessica Jackson, Celia D Rouault, Sumedha Agashe, Vladislav O Sviderskiy, Mangsi Limbu, Erica Lantelme, Alice Meroni, Priyanka Verma, Alessandro Vindigni, Et Al. May 2025

Mrn-Ctip, Exo1, And Dna2-Wrn/Blm Act Bidirectionally To Process Dna Gaps In Parpi-Treated Cells Without Strand Cleavage, Isabelle M Seppa, Mithila Tennakoon, Jessica Jackson, Celia D Rouault, Sumedha Agashe, Vladislav O Sviderskiy, Mangsi Limbu, Erica Lantelme, Alice Meroni, Priyanka Verma, Alessandro Vindigni, Et Al.

2020-Current year OA Pubs

Single-stranded DNA (ssDNA) gaps impact genome stability and PARP inhibitor (PARPi) sensitivity, especially in BRCA1/2-deficient tumors. Using single-molecule DNA fiber analysis, electron microscopy, and biochemical methods, we found that MRN, CtIP, EXO1, and DNA2-WRN/BLM resect ssDNA gaps through a mechanism different from their actions at DNA ends. MRN resects ssDNA gaps in the 3'-to-5' direction using its pCtIP-stimulated exonuclease activity. Unlike at DNA ends, MRN does not use its endonucleolytic activity to cleave the 5'-terminated strand flanking the gap or the ssDNA. EXO1 and DNA2-WRN/BLM specifically resect the 5' end of the gap independent of MRN-CtIP. This resection process alters …


Selection Of Therapeutically Effective T-Cell Receptors From The Diverse Tumor-Bearing Repertoire, Leonie Rosenberger, Naresha Saligrama, Et Al. May 2025

Selection Of Therapeutically Effective T-Cell Receptors From The Diverse Tumor-Bearing Repertoire, Leonie Rosenberger, Naresha Saligrama, Et Al.

2020-Current year OA Pubs

BACKGROUND: The development of T-cell receptor (TCR)-based T-cell therapies is hampered by the difficulties in identifying therapeutically effective tumor-specific TCRs from the natural repertoire of a patient's cancer-specific T cells.

METHODS: Here, we mimic experimentally near-patient conditions to analyze the T-cell repertoire in euthymic tumor-bearing mice responding to the H-2K

RESULTS: We found that mp68-specific TCRs isolated from either tumor-infiltrating T cells or spleens of mice immunized with mp68-expressing cancer cells are diverse and not inherently therapeutic when introduced into peripheral T cells and used for adoptive therapy of established tumors. While measuring short-term T-cell responses in vitro was unreliable …


Treatment And Improved Outcomes Of Three Adult Patients With Guanidinoacetate Methyltransferase (Gamt) Deficiency, Angela Lee, Judith Weisenberg, Elizabeth Toolan, Marwan Shinawi May 2025

Treatment And Improved Outcomes Of Three Adult Patients With Guanidinoacetate Methyltransferase (Gamt) Deficiency, Angela Lee, Judith Weisenberg, Elizabeth Toolan, Marwan Shinawi

2020-Current year OA Pubs

Guanidinoacetate methyltransferase (GAMT) deficiency is a creatine synthesis disorder caused by biallelic pathogenic variants in


"They Gave Me One Star?" An Analysis Of Online Reviews Of Hand Surgeons, Stephen J Demartini, Brendan J Navarro, Christopher J Dy May 2025

"They Gave Me One Star?" An Analysis Of Online Reviews Of Hand Surgeons, Stephen J Demartini, Brendan J Navarro, Christopher J Dy

2020-Current year OA Pubs

PURPOSE: Measures of patient satisfaction are growing in importance. Patients can use online review websites as opportunities to both praise and criticize their physicians and health care experience. We examined "one star" reviews of American Society for Surgery of the Hand (ASSH) members, with the hypothesis that the types of complaints would differ based on patient management and physician gender (based on social identity).

METHODS: We assembled a list of ASSH members in the Midwest region using the ASSH "Find a Hand Surgeon" tool. We then screened three online physician rating websites, including Yelp.com, Healthgrades.com, and Vitals.com, for physician profiles …


Perianal Fistulizing Crohn's Disease-Associated Anorectal And Fistula Cancers: Systematic Review And Expert Consensus, Serre-Yu Wong, Parakkal Deepak, David H Ballard, Et Al. May 2025

Perianal Fistulizing Crohn's Disease-Associated Anorectal And Fistula Cancers: Systematic Review And Expert Consensus, Serre-Yu Wong, Parakkal Deepak, David H Ballard, Et Al.

2020-Current year OA Pubs

BACKGROUND & AIMS: Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and consequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of these cancers. To inform clinical practice, we developed consensus guidelines on PFCD-associated anorectal and fistula cancers by multidisciplinary experts from the international TOpClass consortium.

METHODS: We conducted a systematic review by standard methodology, using the Newcastle-Ottawa Scale quality assessment tool. We subsequently developed consensus statements using a Delphi consensus approach.

RESULTS: Of 561 articles identified, …


Regulation Of Tfeb In Human Placental Cytotrophoblasts And Syncytiotrophoblasts, A Mathew, J S Trausch-Azar, C Azar, M Schuetz, M R Mahjoub, A L Schwartz May 2025

Regulation Of Tfeb In Human Placental Cytotrophoblasts And Syncytiotrophoblasts, A Mathew, J S Trausch-Azar, C Azar, M Schuetz, M R Mahjoub, A L Schwartz

2020-Current year OA Pubs

While cellular proteins exist in a dynamic state maintained by the balance of synthesis and degradation, there is a paucity of information on these processes in placental trophoblasts, including within cytotrophoblasts which differentiate into multi-nucleate syncytiotrophoblasts. TFEB, a transcription factor with a myriad of cellular activities, is one of the most abundant genes expressed in syncytiotrophoblasts compared to cytotrophoblasts. TFEB is localized to the nucleus of human BeWo differentiated syncytiotrophoblasts and to the cytoplasm of the undifferentiated cytotrophoblasts. Within both the cytotrophoblasts and syncytiotrophoblasts, TFEB exists in subcellular compartments as both phosphorylated and unphosphorylated forms and translocates between cytoplasm and …


Elevated P16ink4a Expression Enhances Tau Phosphorylation In Neurons Differentiated From Human-Induced Pluripotent Stem Cells, Kristopher Holloway, Kashfia Neherin, Yingduo Song, Kazuhito Sato, Andrew Houston, Feng Chen, Li Ding, Hong Zhang May 2025

Elevated P16ink4a Expression Enhances Tau Phosphorylation In Neurons Differentiated From Human-Induced Pluripotent Stem Cells, Kristopher Holloway, Kashfia Neherin, Yingduo Song, Kazuhito Sato, Andrew Houston, Feng Chen, Li Ding, Hong Zhang

2020-Current year OA Pubs

Increased expression of the cyclin-dependent kinase inhibitor p16Ink4a (p16) is detected in neurons of human Alzheimer's disease (AD) brains and during normal aging. Importantly, selective eliminating p16-expressing cells in AD mouse models attenuates tau pathologies and improves cognition. But whether and how p16 contributes to AD pathogenesis remains unclear. To address this question, we tested whether induction of p16 expression in neurons exacerbates AD pathologies. We created a doxycycline-inducible system to trigger p16 up-regulation in human-induced pluripotent stem cells (iPSCs) and neurons differentiated from iPSCs. We demonstrated that up-regulated p16 expression in iPSCs reduces cell proliferation, down-regulates cell cycle genes, …


Post-Below-Knee Amputation Venous Thromboembolism And Mortality In United States Veterans, Khanh P Nguyen, Joshua B Gruber, Megan L Mertzel, Cecelia Madison, Reid Thompson, Kenneth Gundle, Scott Damrauer, Kristen M Sanfilippo May 2025

Post-Below-Knee Amputation Venous Thromboembolism And Mortality In United States Veterans, Khanh P Nguyen, Joshua B Gruber, Megan L Mertzel, Cecelia Madison, Reid Thompson, Kenneth Gundle, Scott Damrauer, Kristen M Sanfilippo

2020-Current year OA Pubs

BACKGROUND: Patients who undergo below-knee surgical amputation (BKA) are at risk of postoperative venous thromboembolism (VTE). Limited prior studies quantified the rate of VTE post-BKA or the association of VTE with survival in this population.

OBJECTIVES: We aimed to assess the incidence of post-BKA VTE and the association with all-cause mortality in a cohort of United States veterans.

METHODS: This was a retrospective cohort study of veterans who underwent surgical BKA between October 2016 and January 2023. We identified VTE within 90 days post-BKA using a previously validated algorithm combining International Classification of Diseases codes with a new anticoagulant prescription, …


Assessing Hypersight Iterative Cbct For Dose Calculation In Online Adaptive Radiotherapy For Pelvis And Breast Patients Compared To Synthetic Ct, Jingwei Duan, Joel A Pogue, Dennis N Stanley, Sui Shen, Natalie N Viscariello, Carlos E Cardenas, Richard A Popple, Joseph Harms May 2025

Assessing Hypersight Iterative Cbct For Dose Calculation In Online Adaptive Radiotherapy For Pelvis And Breast Patients Compared To Synthetic Ct, Jingwei Duan, Joel A Pogue, Dennis N Stanley, Sui Shen, Natalie N Viscariello, Carlos E Cardenas, Richard A Popple, Joseph Harms

2020-Current year OA Pubs

PURPOSE/OBJECTIVES: Recent technological advancements have increased efficiency for clinical deliverability of online-adaptive-radiotherapy (oART). Previous cone-beam-computed-tomography (CBCT) generations lacked the ability to provide reliable Hounsfield-units (HU), thus requiring oART workflows to rely on synthetic-CT (sCT) images derived through deformable-image-registration (DIR) between the planning CT (pCT) and the daily CBCT. These sCTs are prone to errors stemming from DIR, potentially contributing to dosimetric errors. This study aims to evaluate the capability of direct dose calculation using a novel CBCT platform, HyperSight (Varian-Medical-Systems), as an alternative for sCT.

METHODS/MATERIALS: To validate the HyperSight iterative CBCT (HS-iCBCT) HU accuracy, 125 kV and 140 kV …