Publications by authors named "Multani A"

Cytomegalovirus (CMV) infection in solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients may increase the risk of rejection or allograft dysfunction, other infection(s), and morbidity and mortality. Treatment can be challenging due to medication-associated toxicities. Maribavir (MBV) is a promising option for the treatment of resistant or refractory (R/R) CMV infection in lieu of foscarnet (FOS), which has long been the recommended therapy for (val)ganciclovir-resistant infection.

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Aneuploid epithelial cells are common in breast cancer; however, their presence in normal breast tissues is not well understood. To address this question, we applied single-cell DNA sequencing to profile copy number alterations in 83,206 epithelial cells from the breast tissues of 49 healthy women, and we applied single-cell DNA and assay for transposase-accessible chromatin sequencing co-assays to the samples of 19 women. Our data show that all women harboured rare aneuploid epithelial cells (median 3.

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There is an increased risk of infection in patients with cancer that results in higher morbidity and mortality. Several risk factors can predispose these patients to infectious complications. Some such factors include immunocompromised states like neutropenia, allogeneic hematopoietic cell transplantation, and graft-versus-host disease, while others include immunosuppressive agents like corticosteroids, purine analogs, monoclonal antibodies, and other emerging cancer therapeutics like CAR T-cell therapy.

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  • - The study examined anal cancer screening practices among high-risk populations, including people living with HIV, those with HPV-related issues, and organ transplant recipients, using clinical data from an academic medical system between 2015 and 2022.
  • - Results showed that only 6.3% of the 7,654 patients had anal cytology screening, with significantly lower rates among women and Black patients, who were 73% and 46% less likely to be screened respectively.
  • - The findings highlight the need for improved and equitable screening strategies, as only 21.7% of people living with HIV received screening, while other high-risk groups had even lower rates.
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  • Cyclin E, particularly its low-molecular weight isoforms (LMW-E), plays a crucial role in cell cycle regulation and is frequently expressed in triple-negative breast cancer (TNBC), where it correlates with poor patient outcomes.
  • The study reveals that LMW-E enhances the stability and expression of PKMYT1, which inhibits CDK1 and affects mitotic timing, making it a potential therapeutic target for TNBC.
  • The selective inhibitor RP-6306 shows promise in treating LMW-E-expressing tumors by promoting tumor cell death and enhancing immune responses, suggesting that the LMW-E/PKMYT1/CDK1 pathway could be an effective target for therapy in aggressive breast cancers.
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  • Mucorales infections lead to high morbidity and mortality rates in immunocompromised patients, such as those receiving solid organ or hematopoietic cell transplants, despite advances in diagnosis and treatment.!* -
  • A study analyzed 43 patients with Mucorales infections, finding that most developed the infection around 184 days post-transplant, with a 64% overall mortality rate; fatalities were mainly linked to Mucormycosis and common in disseminated disease.!* -
  • The findings highlight a gap in effective prophylaxis and treatment strategies, indicating that improved data post-transplant can aid in managing Mucormycosis and emphasizing the need for further research on antifungal treatments.!
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  • Anti-HER2 therapies like trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) have improved outcomes for patients with HER2+ metastatic breast cancer, but resistance to these treatments poses a significant challenge without established follow-up therapies.
  • The study examined genetic changes in breast cancer patients after anti-HER2 therapy and developed resistant cancer cell lines to explore mechanisms of resistance and identify potential targets to boost the effectiveness of T-DXd.
  • It was discovered that resistance might occur due to reduced HER2 expression and increased activity of DNA repair genes, suggesting that targeting DNA repair pathways could enhance the efficacy of T-DXd in resistant cases.
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Background: A myriad of risk factors and comorbidities have been determined to influence COVID-19 mortality rates; among these is pneumonia. This study considers pneumonia as a risk factor for increased mortality in patients admitted with COVID-19 in a rural healthcare system. We predicted that the presence of pneumonia of any kind would increase mortality rates in patients admitted with COVID-19.

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Despite their relatively short lifespan, neutrophils are tasked with counteracting pathogens through various functions, including phagocytosis, production of reactive oxygen species, neutrophil extracellular traps (NETs), and host defense peptides. Regarding the latter, small cationic cathelicidins present a conundrum in neutrophil function. Although primarily recognized as microbicides with an ability to provoke pores in microbial cell walls, the ability of cathelicidin to modulate key neutrophil functions is also of great importance, including the release of chemoattractants, cytokines, and reactive oxygen species, plus prolonging neutrophil lifespan.

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  • Inactivating TP53 mutations disrupt p53 function and can lead to gain-of-function (GOF) activities of mutant p53 proteins, which contribute to tumor growth and spread.
  • The study reveals that GOF mutp53 interacts with components of the minichromosome maintenance complex (MCMs), causing replication stress and chromosomal instability (CIN), which intensifies cancer cell behavior.
  • This interaction triggers a series of signaling pathways, including cGAS-STING-NC-NF-κB, that promote tumor metastasis and create an immunosuppressive tumor environment by dampening interferon responses and enhancing inflammation-related gene expression.
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  • - The 2022 mpox outbreak primarily impacted men who have sex with men (MSM), leading sexual health institutions like Fenway Health in Boston to take charge of the response, including diagnosis and vaccination.
  • - Fenway Health diagnosed its first mpox case in June 2022, began treatment with tecovirimat, and administered the Jynneos vaccine shortly after under Emergency Use Authorization, ultimately providing over 6,300 vaccine doses by late October 2022.
  • - Of the 69 confirmed mpox cases at Fenway Health, about 62.3% identified as male and 58% reported being gay or bisexual, highlighting the community's significance in targeting future health strategies during outbreaks. *
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Remdesivir is the first FDA-approved drug for treating severe SARS-CoV-2 infection and targets RNA-dependent RNA polymerase (RdRp) that is required for viral replication. To monitor for the development of mutations that may result in remdesivir resistance during prolonged treatment, we sequenced SARS-CoV-2 specimens collected at different treatment time points in two transplant patients with severe COVID-19. In the first patient, an allogeneic hematopoietic stem cell transplant recipient, a transient RdRp catalytic subunit mutation (nsp12:A449V) was observed that has not previously been associated with remdesivir resistance.

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Background: Situs inversus totalis (SIT) is a rare genetic anomaly involving the mirror-image transposition of organs. This transposition can potentially make surgical treatments difficult because of the reversed anatomy and intraoperative confusion. The aim of this systematic review is to compare the perioperative outcomes and safety of robotic and laparoscopic gastrectomy in patients with SIT.

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The field of transplant infectious diseases is rapidly evolving, presenting a challenge for clinical practice and trainee education. Here we describe the construction of transplantid.net, a free online library, crowdsourced and continuously updated for the dual purpose of point-of-care evidence-based management and teaching.

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  • The human adrenal cortex has distinct zones responsible for steroid hormone production, but how these zones differentiate into functionally distinct cells is not well understood.
  • The study introduces a new Human Adrenocortical Adenoma (HAA1) cell line that can exit a dormant state and express steroidogenic genes when treated with histone deacetylase inhibitors (HDACis).
  • Gene analysis shows that the HAA1 cells mimic the gene expression of their original adrenal layer, and treatment with HDACis not only boosts steroid gene expression but also activates the Tumor Necrosis Factor (TNF) alpha pathway, aiding understanding of adrenal development and function.
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  • Low-molecular-weight cyclin E (LMW-E) is a truncated form of cyclin E found in breast cancer, linked to poor patient survival and associated with genomic instability in early tumors.
  • LMW-E helps cancer cells tolerate replication stress by enhancing DNA repair processes, contrasting with full-length cyclin E, which inhibits cell proliferation through DNA damage.
  • Targeting specific pathways related to DNA damage repair in LMW-E-overexpressing cells shows potential for new treatment strategies in breast cancer.
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The structure of the genome shapes the distribution of genetic diversity and sequence divergence. To investigate how the relationship between chromosome size and recombination rate affects sequence divergence between species, we combined empirical analyses and evolutionary simulations. We estimated pairwise sequence divergence among 15 species from three different mammalian clades-Peromyscus rodents, Mus mice, and great apes-from chromosome-level genome assemblies.

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Background: Mycoplasma hominis can cause significant infections after solid organ transplantation (SOT). Treatment should be guided by susceptibility testing, but conventional lab methods are laborious with prolonged turnaround time (TAT). This case series compares the phenotypic and genotypic susceptibility profiles of M.

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Introduction: Most studies of solid organ transplant (SOT) recipients with COVID-19 focus on outcomes within one month of illness onset. Delayed mortality in SOT recipients hospitalized for COVID-19 has not been fully examined.

Methods: We used data from a multicenter registry to calculate mortality by 90 days following initial SARS-CoV-2 detection in SOT recipients hospitalized for COVID-19 and developed multivariable Cox proportional-hazards models to compare risk factors for death by days 28 and 90.

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Despite efforts in understanding its underlying mechanisms, the etiology of chromosomal instability (CIN) remains unclear for many tumor types. Here, we identify CIN initiation as a previously undescribed function for APOBEC3A (A3A), a cytidine deaminase upregulated across cancer types. Using genetic mouse models of pancreatic ductal adenocarcinoma (PDA) and genomics analyses in human tumor cells we show that A3A-induced CIN leads to aggressive tumors characterized by enhanced early dissemination and metastasis in a STING-dependent manner and independently of the canonical deaminase functions of A3A.

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Unlabelled: Focal amplifications (FA) can mediate targeted therapy resistance in cancer. Understanding the structure and dynamics of FAs is critical for designing treatments that overcome plasticity-mediated resistance. We developed a melanoma model of dual MAPK inhibitor (MAPKi) resistance that bears BRAFV600 amplifications through either extrachromosomal DNA (ecDNA)/double minutes (DM) or intrachromosomal homogenously staining regions (HSR).

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-activating mutations are the most frequent driver mutations in papillary thyroid cancer (PTC). Targeted inhibitors such as dabrafenib have been used in advanced -mutated PTC; however, acquired resistance to the drug is common and little is known about other effectors that may play integral roles in this resistance. In addition, the induction of PTC dedifferentiation into highly aggressive -driven anaplastic thyroid cancer (ATC) has been reported.

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Mortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020-June 19, 2020) and late 2020 (June 20, 2020-December 31, 2020).

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Purpose: Diabetes mellitus (DM) is common among recipients of heart transplantation (HTx) but its impact on clinical outcomes is unclear. We evaluated the associations between pretransplant DM and posttransplant DM (PTDM) and outcomes among adults receiving HTx at a single center.

Methods: We performed a retrospective study (range 01/2008 - 07/2018), n = 244.

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Measles is a worldwide viral disease that can cause fatal complications in immunocompromised hosts such as hematopoietic cell transplant (HCT) recipients. The live attenuated measles, mumps, and rubella (MMR) vaccine is generally contraindicated post-HCT due to the risk for vaccine-associated measles. This, combined with decreasing vaccination rates due to vaccine hesitancy and the coronavirus disease 2019 pandemic, raises significant concerns for a measles resurgence that could portend devastating consequences for immunocompromised hosts.

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