Digital Commons Network^™

Therapies In Stiff-Person Syndrome: Advances And Future Prospects Based On Disease Pathophysiology, Marinos Dalakas

Department of Neurology Faculty Papers

Among the glutamic acid decarboxylase (GAD)-antibody-spectrum disorders, the most common phenotypic subset is the stiff-person syndrome (SPS), caused by impaired GABAergic inhibitory neurotransmission and autoimmunity characterized by very high titers of GAD antibodies and increased GAD-IgG intrathecal synthesis. If not properly treated or untreated because of delayed diagnosis, SPS progresses leading to disability; it is therefore fundamental to apply the best therapeutic schemes from the outset. This article is focused on the rationale of specific therapeutic strategies based on the SPS pathophysiology targeting both the impaired reciprocal GABAergic inhibition to symptomatically improve the main clinical manifestations of stiffness in the …

From The Private Submissive Sphere To Public Intellectual Resistance: American Female Playwrights’ Contributions To Dramaturgy And Feminism, S. M. Al-Shraah, M. A. Alnwairan, A. A. Alkhawaldeh

Information Sciences Letters

This article joins a vibrant conversation in American literary studies about the contribution of female playwrights to dramaturgy as well as the feminist movement in the early twentieth century. In addition to assessing their contribution to American drama, the article extends the discussion to study how these female dramatists reflected the status of women in contemporary societies. We argue that the selected works of Susan Glaspell’s Trifles (1916) and Bernice (1917), Lorraine Hansberrys A Raisin in the Sun (1959), and Rachel Crothers’ A Mans World (1910) reveal a process, a transformation, a theatrical presentation of the development of female awareness …

Hica Toxin-Based Counterselection Marker For Allelic Exchange Mutations In Fusobacterium Nucleatum, Bibek Gc, Peng Zhou, Chenggang Wu

Faculty, Staff and Student Publications

The study of fusobacterial virulence factors has dramatically benefited from the creation of various genetic tools for DNA manipulation, including galK-based counterselection for in-frame deletion mutagenesis in Fusobacterium nucleatum, which was recently developed. However, this method requires a host lacking the galK gene, which is an inherent limitation. To circumvent this limitation, we explored the possibility of using the hicA gene that encodes a toxin consisting of a HicAB toxin-antitoxin module in Fusobacterium periodonticum as a new counterselective marker. Interestingly, the full-length hicA gene is not toxic in F. nucleatum, but a truncated hicA gene version lacking the first …

Large Multi-Ethnic Genetic Analyses Of Amyloid Imaging Identify New Genes For Alzheimer Disease, Muhammad Ali, Priyanka Gorijala, Daniel Western, Jigyasha Timsina, Maria V Fernández, Gengsheng Chen, Brian Gordon, Tammie L S Benzinger, Chengjie Xiong, John C Morris, Randall J Bateman, Celeste M Karch, Eric Mcdade, Yun Ju Sung, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Amyloid PET imaging has been crucial for detecting the accumulation of amyloid beta (Aβ) deposits in the brain and to study Alzheimer's disease (AD). We performed a genome-wide association study on the largest collection of amyloid imaging data (N = 13,409) to date, across multiple ethnicities from multicenter cohorts to identify variants associated with brain amyloidosis and AD risk. We found a strong APOE signal on chr19q.13.32 (top SNP: APOE ɛ4; rs429358; β = 0.35, SE = 0.01, P = 6.2 × 10

Parental Perspectives On The Social Communication Between Adolescent Females Diagnosed With High Functioning Autism Spectrum Disorder And Their Typically Developing Older Siblings: A Case Study, Victoria Suzette Paxton

Doctoral Dissertations and Projects

Verbal social communication and nonverbal social communication have been documented as a source of deficiency in adolescents with high-functioning (H-F) autism. Likewise, adolescent females with autism reported an increase in social communication difficulties as they aged into adolescence. While the positive impact on social communication in children with autism by older siblings has been documented, there is no such research that has investigated the nonverbal and verbal social communication characteristics among adolescent females with high-functioning autism and their typically developing older siblings (Ben-Itzchak et al., 2016). In the following research study, parental perspectives on the social communication between female adolescents …

The Lived Experiences Of Challenges Faced By Female Stem Degree Holders While In Their Programs: A Phenomenological Study, Rebecca Keeter-Lee

Doctoral Dissertations and Projects

The purpose of this hermeneutic phenomenological research study was to describe the challenges female higher education students (FHESs) experience in their science, technology, engineering, or mathematics (STEM) degree program. The central research question guiding the study was: How do female higher education STEM research participants describe their lived experiences while in their degree programs? Sub-Question one was, How do female higher education students describe the influence their personal history had on their choice to pursue a higher education STEM degree? Sub-question two was: How do female higher education students in STEM program describe their reality versus their expectation going into …

Barriers To Care In Juvenile Localized And Systemic Scleroderma: An Exploratory Survey Study Of Caregivers’ Perspectives, Leigh A Stubbs, Andrew M Ferry, Danielle Guffey, Christina Loccke, Erin Moriarty Wade, Pamela Pour, Kaveh Ardalan, Peter Chira, Ingrid M Ganske, Daniel Glaser, Gloria Higgins, Nadia Luca, Katharine F Moore, Vidya Sivaraman, Katie Stewart, Natalia Vasquez-Canizares, Raegan D Hunt, Renata S Maricevich, Kathryn S Torok, Suzanne C Li, Childhood Arthritis, Rheumatology Research Alliance (Carra) Scleroderma Workgroup

Faculty, Staff and Students Publications

BACKGROUND: Juvenile localized scleroderma (LS) and systemic sclerosis (SSc) are rare pediatric conditions often associated with severe morbidities. Delays in diagnosis are common, increasing the risk for permanent damage and worse outcomes. This study explored caregiver perspectives on barriers they encountered while navigating diagnosis and care for their child's scleroderma.

METHODS: In this cross-sectional study, caregivers of juvenile LS or SSc patients were recruited from a virtual family scleroderma educational conference and a juvenile scleroderma online interest group. The survey queried respondents about their child's condition and factors affecting diagnosis and treatment.

RESULTS: The response rate was 61% (73/120), with …

Nk Cell-Derived Extracellular Granzyme B Drives Epithelial Ulceration During Hsv-2 Genital Infection, Ying Shiang Lim, Aisha G Lee, Xiaoping Jiang, Jason M Scott, Adjoa Cofie, Sandeep Kumar, Dania Kennedy, David J Granville, Haina Shin

2020-Current year OA Pubs

Genital herpes is characterized by recurrent episodes of epithelial blistering. The mechanisms causing this pathology are ill defined. Using a mouse model of vaginal herpes simplex virus 2 (HSV-2) infection, we show that interleukin-18 (IL-18) acts upon natural killer (NK) cells to promote accumulation of the serine protease granzyme B in the vagina, coinciding with vaginal epithelial ulceration. Genetic loss of granzyme B or therapeutic inhibition by a specific protease inhibitor reduces disease and restores epithelial integrity without altering viral control. Distinct effects of granzyme B and perforin deficiency on pathology indicates that granzyme B acts independent of its classic …

From Natchitoches To Nuremberg: The Life Of Legal Pioneer Lyria Dickason, Todd C. Peppers

Scholarly Articles

Lyria was one of a small handful of women who graduated from a Louisiana law school in the 1930’s. Despite the employment barriers facing female attorneys, she went on to become one of the first female law clerks in both the federal and state judiciary. To date, Lyria’s story has not been told. I have recently discovered, however, that Lyria’s children and grandchildren preserved her letters to her family. They are a treasure trove of information about a woman whose career took her from rural Louisiana to Louisiana’s highest court as well as the post-war ruins of Nazi Germany. The …

Modifiable Risk Factors In Women At High Risk Of Breast Cancer: A Systematic Review, Sarah Y Cohen, Carolyn R Stoll, Akila Anandarajah, Michelle Doering, Graham A Colditz

2020-Current year OA Pubs

BACKGROUND: Modifiable risk factors (alcohol, smoking, obesity, hormone use, and physical activity) affect a woman's breast cancer (BC) risk. Whether these factors affect BC risk in women with inherited risk (family history, BRCA1/2 mutations, or familial cancer syndrome) remains unclear.

METHODS: This review included studies on modifiable risk factors for BC in women with inherited risk. Pre-determined eligibility criteria were used and relevant data were extracted.

RESULTS: The literature search resulted in 93 eligible studies. For women with family history, most studies indicated that modifiable risk factors had no association with BC and some indicated decreased (physical activity) or increased …

Association Of Radiotherapy Duration With Clinical Outcomes In Patients With Esophageal Cancer Treated In Nrg Oncology Trials: A Secondary Analysis Of Nrg Oncology Randomized Clinical Trials, Christopher L. Hallemeier, Jennifer Moughan, Michael G. Haddock, Arnold M. Herskovic, Bruce D. Minsky, Mohan Suntharalingam, Kenneth L. Zeitzer, Madhur K. Garg, Bruce D. Greenwald, Ritsuko U. Komaki, Lindsay L. Puckett, Hyun Kim, Shane Lloyd, David A. Bush, Harold E. Kim, Thomas E. Lad, Joshua E. Meyer, Gordon S. Okawara, Adam Raben, Tracey E. Schefter, Jerry L. Barker, Carla I. Falkson, Gregory M.M. Videtic, Rojymon Jacob, Kathryn A. Winter, Christopher H. Crane

Einstein Health Papers

IMPORTANCE: For many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes.

OBJECTIVE: To analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT).

DESIGN, SETTING, AND PARTICIPANTS: This study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy Oncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute-sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology …

Moderate To Vigorous-Intensity Continuous Training Versus High-Intensity Interval Training For Improving Vo2max In Women: A Systematic Review And Meta-Analysis, Robert Lindner, Isaac Selva Raj, Angela W. H. Yang, Shadman Zaman, Brianna Larsen, Joshua Denham

Research outputs 2022 to 2026

Traditional continuous training and high-intensity interval training (HIIT) can increase maximal oxygen uptake (VO2max). However, there is conflicting evidence regarding which form of training demonstrates the greatest improvements to VO2max, and data in women is sparse. We conducted a systematic review and meta-analyses to assess whether moderate to vigorous-intensity continuous training (MVICT) or HIIT was superior at improving VO2max in women. Randomised controlled and parallel studies examined the influence of MVICT and/or HIIT on VO2max in women. There was no statistical difference in VO2max improvements after training between women in the MVICT and HIIT cohorts (mean difference [MD]: −0.42, 95%CI: …

Head-To-Head Comparison Of 10 Plasma Phospho-Tau Assays In Prodromal Alzheimer's Disease, Shorena Janelidze, Nicolas R Barthélemy, Yingxin He, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Plasma phospho-tau (p-tau) species have emerged as the most promising blood-based biomarkers of Alzheimer's disease. Here, we performed a head-to-head comparison of p-tau181, p-tau217 and p-tau231 measured using 10 assays to detect abnormal brain amyloid-β (Aβ) status and predict future progression to Alzheimer's dementia. The study included 135 patients with baseline diagnosis of mild cognitive impairment (mean age 72.4 years; 60.7% women) who were followed for an average of 4.9 years. Seventy-one participants had abnormal Aβ-status (i.e. abnormal CSF Aβ42/40) at baseline; and 45 of these Aβ-positive participants progressed to Alzheimer's dementia during follow-up. P-tau concentrations were determined in baseline …

Comorbidities And Risk Factors Associated With Insomnia In The Elderly Population., Neil Mookerjee, Nicole Schmalbach, Gianna Antinori, Subhadra Thampi, Dylan Windle-Puente, Amy Gilligan, Ha Huy, Megha Andrews, Angela Sun, Roshni Gandhi, William Benedict, Austin Chang, Ben Sanders, Justin Nguyen, Maanika Reddy Keesara, Janet Aliev, Aneri Patel, Isaiah Hughes, Ian Millstein, Krystal Hunter, Satyajeet Roy

Cooper Medical School of Rowan University Departmental Research

INTRODUCTION/OBJECTIVES: Sleep disorders affect around 50 to 70 million Americans, with chronic insomnia being the most common, especially in the elderly population. With an 11-fold increase in the US office visits due to insomnia, from 0.8 to 9.4 million, between 1993 and 2015, it is imperative to identify the modifiable risk factors. The aim of our study was to examine the association of risk factors and comorbid medical conditions with insomnia in patients 65 years, and older.

METHODS: We performed a retrospective electronic medical record review of the patients aged 65 years and older, who visited our suburban internal medicine …

Extended Analysis Of Hiv Infection In Cisgender Men And Transgender Women Who Have Sex With Men Receiving Injectable Cabotegravir For Hiv Prevention: Hptn 083, Mark A Marzinke, Jessica M Fogel, Zhe Wang, Estelle Piwowar-Manning, Ryan Kofron, Amber Moser, Pradip Bhandari, Ryann Gollings, Lane R Bushman, Lei Weng, Elias K Halvas, John Mellors, Peter L Anderson, Deborah Persaud, Craig W Hendrix, Marybeth Mccauley, Alex R Rinehart, Marty St Clair, Susan L Ford, James F Rooney, Adeola Adeyeye, Suwat Chariyalertsak, Kenneth Mayer, Roberto C Arduino, Myron S Cohen, Beatriz Grinsztejn, Brett Hanscom, Raphael J Landovitz, Susan H Eshleman

Faculty, Staff and Student Publications

HPTN 083 demonstrated that injectable cabotegravir (CAB) was superior to oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for HIV prevention in cisgender men and transgender women who have sex with men. We previously analyzed 58 infections in the blinded phase of HPTN 083 (16 in the CAB arm and 42 in the TDF-FTC arm). This report describes 52 additional infections that occurred up to 1 year after study unblinding (18 in the CAB arm and 34 in the TDF-FTC arm). Retrospective testing included HIV testing, viral load testing, quantification of study drug concentrations, and drug resistance testing. The new CAB arm infections …

Zoster-Associated Prothrombotic Plasma Exosomes And Increased Stroke Risk, Andrew N Bubak, Christina Coughlan, Janelle Posey, Anthony J Saviola, Christy S Niemeyer, Serena W R Lewis, Sara Bustos Lopez, Adriana Solano, Stephen K Tyring, Cassidy Delaney, Keith B Neeves, Ravi Mahalingam, Kirk C Hansen, Maria A Nagel

Faculty, Staff and Student Publications

Herpes zoster (HZ; shingles) caused by varicella zoster virus reactivation increases stroke risk for up to 1 year after HZ. The underlying mechanisms are unclear, however, the development of stroke distant from the site of zoster (eg, thoracic, lumbar, sacral) that can occur months after resolution of rash points to a long-lasting, virus-induced soluble factor (or factors) that can trigger thrombosis and/or vasculitis. Herein, we investigated the content and contributions of circulating plasma exosomes from HZ and non-HZ patient samples. Compared with non-HZ exosomes, HZ exosomes (1) contained proteins conferring a prothrombotic state to recipient cells and (2) activated platelets …

Interspecies Interactions Within The Host: The Social Network Of Group B Streptococcus, Marlyd E Mejia, Clare M Robertson, Kathryn A Patras

Faculty, Staff and Students Publications

Group B Streptococcus (GBS) is a pervasive neonatal pathogen accounting for a combined half a million deaths and stillbirths annually. The most common source of fetal or neonatal GBS exposure is the maternal microbiota. GBS asymptomatically colonizes the gastrointestinal and vaginal mucosa of 1 in 5 individuals globally, although its precise role in these niches is not well understood. To prevent vertical transmission, broad-spectrum antibiotics are administered to GBS-positive mothers during labor in many countries. Although antibiotics have significantly reduced GBS early-onset neonatal disease, there are several unintended consequences, including an altered neonatal microbiota and increased risk for other microbial …

Female Emotion In The Holy Quran, The Story Of Umm Musa As A Model, A Study In The Structure Of Language, Anwar Aziz Jalil Al-Asadi

Uruk Journal of Human Sciences

The voices rose until they reached the level of axioms that passion is a woman, and a woman is passion, as evidenced by the story of Umm Musa in the Almighty’s saying: {And the heart of Umm Musa became empty if she would have expressed it had it not been for We tied her heart so that she would be among the believers_ Al Qasas: 10}, and the judgment became through This verse is absolutely to judge women with passion. I wish it was a praiseworthy ruling, but rather this ruling robbed the woman of many rights under the pretext …

Anthracycline-Containing And Taxane-Containing Chemotherapy For Early-Stage Operable Breast Cancer: A Patient-Level Meta-Analysis Of 100 000 Women From 86 Randomised Trials, Early Breast Cancer Trialists’ Collaborative Group (Ebctcg)

Faculty, Staff and Student Publications

BACKGROUND: Anthracycline-taxane chemotherapy for early-stage breast cancer substantially improves survival compared with no chemotherapy. However, concerns about short-term and long-term side-effects of anthracyclines have led to increased use of taxane chemotherapy without anthracycline, which could compromise efficacy. We aimed to better characterise the benefits and risks of including anthracycline, and the comparative benefits of different anthracycline-taxane regimens.

METHODS: We did an individual patient-level meta-analysis of randomised trials comparing taxane regimens with versus without anthracycline, and updated our previous meta-analysis of anthracycline regimens with versus without taxane, as well as analysing 44 trials in six related comparisons. We searched databases, including …

Phase Ii Study Of Palbociclib (Pd-0332991) In Ccnd1, 2, Or 3 Amplification: Results From The Nci-Match Ecog-Acrin Trial (Eay131) Subprotocol Z1b, Amy S Clark, Fangxin Hong, Richard S Finn, Angela M Demichele, Edith P. Mitchell, James Zwiebel, Fernanda I Arnaldez, Robert J Gray, Victoria Wang, Lisa M Mcshane, Larry V Rubinstein, David Patton, P Mickey Williams, Stanley R Hamilton, Mehmet S Copur, Samer S Kasbari, Ravneet Thind, Barbara A Conley, Carlos L Arteaga, Peter J O'Dwyer, Lyndsay N Harris, Alice P Chen, Keith T Flaherty

Department of Medical Oncology Faculty Papers

Purpose: Cyclin D/CDK4/6 is critical in controlling the G1 to S checkpoint. CCND, the gene encoding cyclin D, is known to be amplified in a variety of solid tumors. Palbociclib is an oral CDK4/6 inhibitor, approved in advanced breast cancer in combination with endocrine therapy. We explored the efficacy of palbociclib in patients with nonbreast solid tumors containing an amplification in CCND1, 2, or 3.

Patients and methods: Patients with tumors containing a CCND1, 2, or 3 amplification and expression of the retinoblastoma protein were assigned to subprotocol Z1B and received palbociclib 125 mg once daily for 21 days of …

Pertuzumab, Trastuzumab, And An Aromatase Inhibitor For Her2-Positive And Hormone Receptor-Positive Metastatic Or Locally Advanced Breast Cancer: Pertain Final Analysis, Grazia Arpino, Juan De La Haba Rodríguez, Jean-Marc Ferrero, Sabino De Placido, C Kent Osborne, Dirk Klingbiel, Valentine Revelant, Christine Wohlfarth, Raf Poppe, Mothaffar F Rimawi

Faculty, Staff and Students Publications

PURPOSE: In PERTAIN's primary analysis (31 months' median follow-up), adding pertuzumab to trastuzumab and an aromatase inhibitor (AI) with/without chemotherapy significantly improved progression-free survival (PFS) in patients with previously untreated HER2-positive and hormone receptor-positive metastatic or locally advanced breast cancer (M/LABC). A potentially enhanced treatment effect was observed in patients with no induction chemotherapy. We present the final analysis (>6 years' median follow-up).

PATIENTS AND METHODS: Patients (N = 258) were randomized 1:1 to pertuzumab (loading/maintenance: 840/420 mg) plus trastuzumab (loading/maintenance: 8/6 mg/kg) every 3 weeks and an AI (1 mg anastrozole or 2.5 mg letrozole daily; Arm A), …

Myocardial Infarction Signs And Symptoms: Females Vs. Males., Kyle J. Schulte, Harvey N. Mayrovitz

HPD Articles

Cardiovascular disease is the number one killer of females in the United States today, and myocardial infarction (MI) plays a role in many of these deaths. Females also present with more "atypical" symptoms than males and appear to have differences in pathophysiology underlying their MIs. Despite both differences in symptomology and pathophysiology being present in females versus males, a possible link between the two has not been studied extensively. In this systematic review, we analyzed studies examining differences in symptoms and pathophysiology of MI in females and males and evaluated possible links between the two. A search was performed for …

Effect Of Angiotensin-Converting Enzyme Inhibitor And Angiotensin Receptor Blocker Initiation On Organ Support-Free Days In Patients Hospitalized With Covid-19: A Randomized Clinical Trial, Patrick R Lawler, Lennie P G Derde, Frank L Van De Veerdonk, Bryan J Mcverry, David T Huang, Lindsay R Berry, Elizabeth Lorenzi, Roland Van Kimmenade, Frank Gommans, Muthiah Vaduganathan, David E Leaf, Rebecca M Baron, Edy Y Kim, Claudia Frankfurter, Slava Epelman, Yvonne Kwan, Richard Grieve, Stephen O'Neill, Zia Sadique, Michael Puskarich, John C Marshall, Alisa M Higgins, Paul R Mouncey, Kathryn M Rowan, Farah Al-Beidh, Djillali Annane, Yaseen M Arabi, Carly Au, Abi Beane, Wilma Van Bentum-Puijk, Marc J M Bonten, Charlotte A Bradbury, Frank M Brunkhorst, Aidan Burrell, Adrian Buzgau, Meredith Buxton, Maurizio Cecconi, Allen C Cheng, Matthew Cove, Michelle A Detry, Lise J Estcourt, Justin Ezekowitz, Mark Fitzgerald, David Gattas, Lucas C Godoy, Herman Goossens, Rashan Haniffa, David A Harrison, Thomas Hills, Christopher M Horvat, Nao Ichihara, Francois Lamontagne, Kelsey M Linstrum, Daniel F Mcauley, Anna Mcglothlin, Shay P Mcguinness, Zoe Mcquilten, Srinivas Murthy, Alistair D Nichol, David R J Owen, Rachael L Parke, Jane C Parker, Katrina M Pollock, Luis Felipe Reyes, Hiroki Saito, Marlene S Santos, Christina T Saunders, Christopher W Seymour, Manu Shankar-Hari, Vanessa Singh, Alexis F Turgeon, Anne M Turner, Ryan Zarychanski, Cameron Green, Roger J Lewis, Derek C Angus, Scott Berry, Anthony C Gordon, Colin J Mcarthur, Steve A Webb

Faculty, Staff and Student Publications

IMPORTANCE: Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.

OBJECTIVE: To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non-critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).

INTERVENTIONS: Patients were randomized to receive open-label initiation of an ACE inhibitor …

Upper Age Limits For Us Male Human Papillomavirus Vaccination For Oropharyngeal Cancer Prevention: A Microsimulation-Based Modeling Study, Rebecca Landy, Gregory Haber, Barry I Graubard, Nicole G Campos, Stephen Sy, Jane J Kim, Emily A Burger, Li C Cheung, Hormuzd A Katki, Maura L Gillison, Anil K Chaturvedi

Faculty, Staff and Student Publications

BACKGROUND: Human papillomavirus (HVP)-positive oropharyngeal cancer is the most common HPV-associated cancer in the United States. The age at acquisition of oral HPV infections that cause oropharyngeal cancer (causal infections) is unknown; consequently, the benefit of vaccination of US men aged 27-45 years remains uncertain.

METHODS: We developed a microsimulation-based, individual-level, state-transition model of oral HPV16 and HPV16-positive oropharyngeal cancer among heterosexual US men aged 15-84 years, calibrated to population-level data. We estimated the benefit of vaccination of men aged 27-45 years for prevention of oropharyngeal cancer, accounting for direct- and indirect effects (ie, herd effects) of male and female …

Rank Is A Poor Prognosis Marker And A Therapeutic Target In Er-Negative Postmenopausal Breast Cancer, Marina Ciscar, Eva M Trinidad, Gema Perez-Chacon, Mansour Alsaleem, Maria Jimenez, Maria J Jimenez-Santos, Hector Perez-Montoyo, Adrian Sanz-Moreno, Andrea Vethencourt, Michael Toss, Anna Petit, Maria T Soler-Monso, Victor Lopez, Jorge Gomez-Miragaya, Clara Gomez-Aleza, Lacey E Dobrolecki, Michael T Lewis, Alejandra Bruna, Silvana Mouron, Miguel Quintela-Fandino, Fatima Al-Shahrour, Antonio Martinez-Aranda, Angels Sierra, Andrew R Green, Emad Rakha, Eva Gonzalez-Suarez

Faculty, Staff and Students Publications

Despite strong preclinical data, the therapeutic benefit of the RANKL inhibitor, denosumab, in breast cancer patients, beyond the bone, is unclear. Aiming to select patients who may benefit from denosumab, we hereby analyzed RANK and RANKL protein expression in more than 2,000 breast tumors (777 estrogen receptor-negative, ER- ) from four independent cohorts. RANK protein expression was more frequent in ER- tumors, where it associated with poor outcome and poor response to chemotherapy. In ER- breast cancer patient-derived orthoxenografts (PDXs), RANKL inhibition reduced tumor cell proliferation and stemness, regulated tumor immunity and metabolism, and improved response to chemotherapy. Intriguingly, tumor …

Targeting The Mevalonate Pathway Suppresses Arid1a-Inactivated Cancers By Promoting Pyroptosis, Wei Zhou, Heng Liu, Zhe Yuan, Joseph Zundell, Martina Towers, Jianhuang Lin, Simona Lombardi, Hao Nie, Brennah Murphy, Tyler Yang, Chen Wang, Liping Liao, Aaron R Goldman, Toshitha Kannan, Andrew V Kossenkov, Ronny Drapkin, Luis J Montaner, Daniel T Claiborne, Nan Zhang, Shuai Wu, Rugang Zhang

Faculty, Staff and Student Publications

ARID1A, encoding a subunit of the SWI/SNF complex, is mutated in ∼50% of clear cell ovarian carcinoma (OCCC) cases. Here we show that inhibition of the mevalonate pathway synergizes with immune checkpoint blockade (ICB) by driving inflammasome-regulated immunomodulating pyroptosis in ARID1A-inactivated OCCCs. SWI/SNF inactivation downregulates the rate-limiting enzymes in the mevalonate pathway such as HMGCR and HMGCS1, which creates a dependence on the residual activity of the pathway in ARID1A-inactivated cells. Inhibitors of the mevalonate pathway such as simvastatin suppresses the growth of ARID1A mutant, but not wild-type, OCCCs. In addition, simvastatin synergizes with anti-PD-L1 antibody in a genetic OCCC …

Exploring Digital Interventions To Facilitate Coping And Discomfort For Nurses Experiencing The Menopause In The Workplace: An International Qualitative Study, Camille Cronin, Gemma Bidwell, Janene Carey, Sara Donevant Phd, Rn, Ccrn, Kerri-Ann Hughes, Marja Kaunonen, Jette Marcussen, Rhonda Wilson

Publications

INTRODUCTION: The global nursing workforce is predominantly female, with a large proportion working in the 45-55 age group. Menopause is a transition for all women, and; therefore needs recognition as it can impact work performance and consequently staff turnover. BACKGROUND: Women will go through the menopause, but not all women are affected. The menopause transition presents a range of signs and symptoms both physical and psychological which can impact the quality of life and individuals' work/life balance. The nursing workforce is predominantly women that will work through the menopause transition. OBJECTIVES: The study explored perspectives on digital health interventions as …

Bi-Allelic Snapc4 Variants Dysregulate Global Alternative Splicing And Lead To Neuroregression And Progressive Spastic Paraparesis, F Graeme Frost, Marie Morimoto, Prashant Sharma, Lyse Ruaud, Newell Belnap, Daniel G Calame, Yuri Uchiyama, Naomichi Matsumoto, Machteld M Oud, Elise A Ferreira, Vinodh Narayanan, Sampath Rangasamy, Matt Huentelman, Lisa T Emrick, Ikuko Sato-Shirai, Satoko Kumada, Nicole I Wolf, Peter J Steinbach, Yan Huang, Undiagnosed Diseases Network, Barbara N Pusey, Sandrine Passemard, Jonathan Levy, Séverine Drunat, Marie Vincent, Agnès Guet, Emanuele Agolini, Antonio Novelli, Maria Cristina Digilio, Jill A Rosenfeld, Jennifer L Murphy, James R Lupski, Gilbert Vezina, Ellen F Macnamara, David R Adams, Maria T Acosta, Cynthia J Tifft, William A Gahl, May Christine V Malicdan

Faculty, Staff and Students Publications

The vast majority of human genes encode multiple isoforms through alternative splicing, and the temporal and spatial regulation of those isoforms is critical for organismal development and function. The spliceosome, which regulates and executes splicing reactions, is primarily composed of small nuclear ribonucleoproteins (snRNPs) that consist of small nuclear RNAs (snRNAs) and protein subunits. snRNA gene transcription is initiated by the snRNA-activating protein complex (SNAPc). Here, we report ten individuals, from eight families, with bi-allelic, deleterious SNAPC4 variants. SNAPC4 encoded one of the five SNAPc subunits that is critical for DNA binding. Most affected individuals presented with delayed motor development …

Parp Inhibitors For The Treatment Of Brca1/2-Mutated Metastatic Breast Cancer: A Systematic Review And Meta-Analysis, Ranju Kunwor, Daniel P. Silver, Maysa Abu-Khalaf

Kimmel Cancer Center Faculty Papers

BACKGROUND: The PARP inhibitors (PARPis) olaparib and talazoparib are currently approved for the treatment of deleterious germline BRCA1/2-mutated (gBRCA+) metastatic breast cancer (MBC). These approvals were based on improvements in progression-free survival (PFS) observed in two randomized controlled trials (RCTs). Other PARPis, such as veliparib and niraparib, have also been studied. We conducted this meta-analysis of RCTs to assess the PFS and overall survival (OS) benefits of PARPis in gBRCA + MBC.

METHODS: We performed a systematic search for RCTs using the Cochrane Library, PubMed, Embase, and Web of Science databases up to March 2021. Only phase II and III …

Large-Scale Analysis Of Structural Brain Asymmetries In Schizophrenia Via The Enigma Consortium, Dick Schijven, Merel C Postema, Masaki Fukunaga, Junya Matsumoto, Kenichiro Miura, Sonja M C De Zwarte, Neeltje E M Van Haren, Wiepke Cahn, Hilleke E Hulshoff Pol, René S Kahn, Rosa Ayesa-Arriola, Víctor Ortiz-García De La Foz, Diana Tordesillas-Gutierrez, Javier Vázquez-Bourgon, Benedicto Crespo-Facorro, Dag Alnæs, Andreas Dahl, Lars T Westlye, Ingrid Agartz, Ole A Andreassen, Erik G Jönsson, Peter Kochunov, Jason M Bruggemann, Stanley V Catts, Patricia T Michie, Bryan J Mowry, Yann Quidé, Paul E Rasser, Ulrich Schall, Rodney J Scott, Vaughan J Carr, Melissa J Green, Frans A Henskens, Carmel M Loughland, Christos Pantelis, Cynthia Shannon Weickert, Thomas W Weickert, Lieuwe De Haan, Katharina Brosch, Julia-Katharina Pfarr, Kai G Ringwald, Frederike Stein, Andreas Jansen, Tilo T J Kircher, Igor Nenadić, Bernd Krämer, Oliver Gruber, Theodore D Satterthwaite, Juan Bustillo, Daniel H Mathalon, Adrian Preda, Vince D Calhoun, Judith M Ford, Steven G Potkin, Jingxu Chen, Yunlong Tan, Zhiren Wang, Hong Xiang, Fengmei Fan, Fabio Bernardoni, Stefan Ehrlich, Paola Fuentes-Claramonte, Maria Angeles Garcia-Leon, Amalia Guerrero-Pedraza, Raymond Salvador, Salvador Sarró, Edith Pomarol-Clotet, Valentina Ciullo, Fabrizio Piras, Daniela Vecchio, Nerisa Banaj, Gianfranco Spalletta, Stijn Michielse, Therese Van Amelsvoort, Erin W Dickie, Aristotle N Voineskos, Kang Sim, Simone Ciufolini, Paola Dazzan, Robin M Murray, Woo-Sung Kim, Young-Chul Chung, Christina Andreou, André Schmidt, Stefan Borgwardt, Andrew M Mcintosh, Heather C Whalley, Stephen M Lawrie, Stefan Du Plessis, Hilmar K Luckhoff, Freda Scheffler, Robin Emsley, Dominik Grotegerd, Rebekka Lencer, Udo Dannlowski, Jesse T Edmond, Kelly Rootes-Murdy, Julia M Stephen, Andrew R Mayer, Linda A Antonucci, Leonardo Fazio, Giulio Pergola, Alessandro Bertolino, Covadonga M Díaz-Caneja, Joost Janssen, Noemi G Lois, Celso Arango, Alexander S Tomyshev, Irina Lebedeva, Simon Cervenka, Carl M Sellgren, Foivos Georgiadis, Matthias Kirschner, Stefan Kaiser, Tomas Hajek, Antonin Skoch, Filip Spaniel, Minah Kim, Yoo Bin Kwak, Sanghoon Oh, Jun Soo Kwon, Anthony James, Geor Bakker, Christian Knöchel, Michael Stäblein, Viola Oertel, Anne Uhlmann, Fleur M Howells, Dan J Stein, Henk S Temmingh, Ana M Diaz-Zuluaga, Julian A Pineda-Zapata, Carlos López-Jaramillo, Stephanie Homan, Ellen Ji, Werner Surbeck, Philipp Homan, Simon E Fisher, Barbara Franke, David C Glahn, Ruben C Gur, Ryota Hashimoto, Neda Jahanshad, Eileen Luders, Sarah E Medland, Paul M Thompson, Jessica A Turner, Theo G M Van Erp, Clyde Francks

Faculty, Staff and Students Publications

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small …