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- Volume 76, 2025
Annual Review of Medicine - Volume 76, 2025
Volume 76, 2025
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Lessons from the Use of Monoclonal Antibodies to SARS-CoV-2 Spike Protein During the COVID-19 Pandemic
Vol. 76 (2025), pp. 1–12More LessMonoclonal antibodies (mAbs) targeting the SARS-CoV-2 Spike protein were deployed during the COVID-19 pandemic. While all of the clinically authorized mAbs were eventually defeated by SARS-CoV-2 variants, they were highly effective in preventing disease progression when given early in the course of the disease. The experience with mAbs to SARS-CoV-2 offers important lessons for the use of mAbs in future infectious disease emergencies, such as choosing mAbs that target conserved epitopes and designing cocktails to reduce the emergence of escape variants. Planning for future use must include the creation of infusion centers and the development of strategies to minimize the emergence of escape variants.
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New Approaches to Respiratory Syncytial Virus Prevention and Treatment
Vol. 76 (2025), pp. 13–28More LessThere have been several recent advances in the prevention of lower respiratory tract disease (LRTD) due to respiratory syncytial virus (RSV) infection in older adults and young children. Three different vaccines are now approved for use in older adults; one of these vaccines is also approved for use in pregnant individuals for the prevention of LRTD due to RSV in their infants. In addition, a new monoclonal antibody is available to prevent RSV LRTD in infants born during or entering their first RSV season and in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. Despite these advances in prevention efforts, specific antiviral treatment options for RSV infection remain limited. Several promising compounds remain in development.
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Global Elimination of Hepatitis C Virus
Vol. 76 (2025), pp. 29–41More LessHepatitis C virus (HCV) is predominantly transmitted through parenteral exposures to infectious blood or body fluids. In 2019, approximately 58 million people worldwide were infected with HCV, and 290,000 deaths occurred due to hepatitis C–related conditions, despite hepatitis C being curable. There are substantial barriers to elimination, including the lack of widespread point-of-care diagnostics, cost of treatment, stigma associated with hepatitis C, and challenges in reaching marginalized populations, such as people who inject drugs. The World Health Organization (WHO) has set goals to eliminate hepatitis C by 2030. Several countries, including Australia, Egypt, Georgia, and Rwanda, have made remarkable progress toward hepatitis C elimination. In the United States, the Biden–Harris administration recently issued a plan for the national elimination of hepatitis C. Global progress has been uneven, however, and will need to accelerate considerably to reach the WHO's 2030 goals. Nevertheless, the global elimination of hepatitis C is within reach and should remain a high public health priority.
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Update on HIV Chemoprevention
Vol. 76 (2025), pp. 43–56More LessDespite rapid advances in the field of HIV prevention and treatment, unacceptably high global HIV incidence rates highlight the ongoing need for effective HIV prevention interventions for populations at risk for HIV acquisition. This article provides an updated review of the current data surrounding HIV prevention strategies, including treatment as prevention (TasP), preexposure prophylaxis (PrEP), and postexposure prophylaxis (PEP), as well as advances in sexually transmitted infection biomedical prevention. This review provides an overview of the multiple PrEP modalities that are available globally, such as oral PrEP, injectable cabotegravir, and the dapivirine vaginal ring, and describes their respective clinical trials, efficacies, and regulatory approvals. We also discuss ongoing research into novel PrEP agents, such as broadly neutralizing antibodies, and efforts toward HIV vaccine development.
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Candida auris: Epidemiology and Antifungal Strategy
Vol. 76 (2025), pp. 57–67More LessCandida auris is a recently emerged fungal pathogen that causes severe infections in healthcare settings around the globe. A feature that distinguishes C. auris from other fungal pathogens is its high capacity to colonize skin, leading to widespread outbreaks in healthcare facilities via patient-to-patient transmission. C. auris can persist on skin or in the surrounding environment for extended periods of time, and it exhibits greater antifungal resistance than other Candida species. These factors pose major obstacles for the prevention and treatment of C. auris infection. Recent reports have identified frequently colonized skin sites, risk factors for developing invasive infection, and patterns of antifungal resistance among C. auris strains, all of which help guide therapeutic options. In this review, we highlight key studies of C. auris epidemiology and antifungal resistance, discussing how these factors influence healthcare-associated transmission and treatment outcomes.
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Hidradenitis Suppurativa
Vol. 76 (2025), pp. 69–80More LessHidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by the formation of nodules, abscesses, and fistulae at intertriginous sites. Pain, pruritus, malodor, and suppuration have a significant impact on quality of life for HS patients. Prevalence figures vary greatly in the literature from 0.05% to 4.1%, and HS is more common in females. The current understanding of the etiology and pathogenesis of HS is incomplete; numerous hypotheses concern the interplay of lifestyle factors, skin microbiota, genetics, and a dysregulated immune system. Due to its phenotypic heterogeneity and multifactorial pathogenesis, HS is a complex disease that can prove challenging to manage. Two approved biologic therapies for the management of HS have led to clinical response in approximately 50% of treated patients. New therapies targeting the interleukin (IL)-1, IL-17, IL-36, and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways are in ongoing clinical trials, and preliminary data offer hope for greater clinical efficacy in HS in the future.
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Transformative Therapies for Depression: Postpartum Depression, Major Depressive Disorder, and Treatment-Resistant Depression
Vol. 76 (2025), pp. 81–93More LessDepressive disorders present an enormous global public health burden. A notable treatment gap exists between the prevalence of depression and our ability to provide rapid-acting, effective treatment that achieves remission. Brexanolone and zuranolone, the first US Food and Drug Administration–approved drugs for postpartum depression, signify a critical advancement in addressing the unmet needs of a vulnerable patient population. Psilocybin shows promise for treatment-resistant depression and for those who have struggled to find relief with existing treatments. This review discusses transformative therapies that represent significant advancements in postpartum depression, major depressive disorder, and treatment-resistant depression.
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Normal Gut Microbiomes in Diverse Populations: Clinical Implications
Vol. 76 (2025), pp. 95–114More LessThe human microbiome is a sensor and modulator of physiology and homeostasis. Remarkable tractability underpins the promise of therapeutic manipulation of the microbiome. However, the definition of a normal or healthy microbiome has been elusive. This is in part due to the underrepresentation of minority groups and major global regions in microbiome studies to date. We review studies of the microbiome in different populations and highlight a commonality among health-associated microbiome signatures along with major drivers of variation. We also provide an overview of microbiome-associated therapeutic interventions for some widespread, widely studied diseases. We discuss sources of bias and the challenges associated with defining population-specific microbiome reference bases. We propose a roadmap for defining normal microbiome references that can be used for population-customized microbiome therapeutics and diagnostics.
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Healthy and Unhealthy Aging and the Human Microbiome
Vol. 76 (2025), pp. 115–127More LessAn altered gut microbiome is a feature of many multifactorial diseases, and microbiome effects on host metabolism, immune function, and possibly neurological function are implicated. Increased biological age is accompanied by a change in the gut microbiome. However, age-related health loss does not occur uniformly across all subjects but rather depends on differential loss of gut commensals and gain of pathobionts. In this article, we summarize the known and possible effects of the gut microbiome on the hallmarks of aging and describe the most plausible mechanisms. Understanding and targeting these factors could lead to prolonging health span by rationally maintaining the gut microbiome.
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Probiotics in Health Care: A Critical Appraisal
Vol. 76 (2025), pp. 129–141More LessConsumption of probiotic products continues to increase, perhaps driven by an interest in gut health. However, the field is filled with controversy, inconsistencies, misuse of terminology, and poor communication. While the probiotic concept is biologically plausible and in some cases mechanistically well established, extrapolation of preclinical results to humans has seldom been proven in well-conducted clinical trials. With noteworthy exceptions, clinical guidance has often been derived not from large, adequately powered clinical trials but rather from comparisons of disparate, small studies with insufficient power to identify the optimal strain. The separation of probiotics from live biotherapeutic products has brought some clarity from a regulatory perspective, but in both cases, consumers should expect scientific rigor and strong supporting evidence for health claims.
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Emerging Long-Term Risks of the Use of Proton Pump Inhibitors and Potassium-Competitive Acid Blockers
Vol. 76 (2025), pp. 143–153More LessAcid-related disorders represent a significant global health burden. Pharmacological treatment of these conditions has at times been challenged and limited by incomplete effectiveness, antibiotic resistance, adverse medication effects and/or interactions, and disease recurrence. Since the early 1990s, the mainstay of treatment has been proton pump inhibitors (PPIs). Recently, the US Food and Drug Administration issued a clearance for vonoprazan, a potassium-competitive acid blocker (PCAB). PCABs are a new class of acid-suppressing agents that may overcome some of these challenges. The aim of this review is to evaluate and compare the emerging long-term risks of PPI and PCAB therapies.
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Endoscopic Approaches for Managing Small Intestinal Disease
Vol. 76 (2025), pp. 155–165More LessThe endoscopic evaluation and management of small intestinal diseases continue to evolve and expand. The advent of small bowel wireless capsule endoscopy and deep enteroscopy with either a double- or single-balloon enteroscope now allows complete endoscopic visualization of the entire small intestine and enables access for endoscopic interventions such as biopsies or hemostasis for most of the small bowel. New endoscopic techniques are available to treat proximal malignant small bowel obstruction, including intraluminal stents and endoscopic gastrojejunal stents. Emerging technologies also aim to improve weight loss and diabetes management via small bowel endoscopic interventions.
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Approach to Therapy for Chronic Pouchitis
Maia Kayal, and Brigid BolandVol. 76 (2025), pp. 167–173More LessChronic pouchitis (CP) occurs in approximately 20% of patients with ulcerative colitis after total proctocolectomy with ileal pouch anal anastomosis and is categorized as antibiotic dependent, antibiotic refractory, or Crohn's disease–like. The management of CP is challenging because of limited evidence and few randomized controlled trials. In this review, we discuss the medical management of CP and its supporting data delineated by type of therapy.
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New Therapeutic Options for BRCA Mutant Patients
Vol. 76 (2025), pp. 175–187More LessPathogenic variants in BRCA1 and BRCA2 are associated with significantly elevated lifetime risks of breast, ovarian, pancreatic, and prostate cancer. These genes are critical in double-strand break repair through homologous recombination. An understanding of the biology of BRCA1 and BRCA2 led to the development of targeted therapeutics, specifically poly(ADP-ribose) polymerase (PARP) inhibitors, which are approved by the US Food and Drug Administration for multiple BRCA1/2-associated cancers. Here, we discuss the development of PARP inhibitors, mechanisms of resistance, and the potential utility of these drugs beyond canonical BRCA1/2 tumors, and we describe novel agents under study.
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Application and Expectations for Immune Checkpoint Blockade of LAG3 and TIGIT
Vol. 76 (2025), pp. 189–205More LessImmune checkpoint blockade targeting the novel targets of the lymphocyte activation gene 3 (LAG3) and the T cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibition motif domains (TIGIT) has marked a significant advancement in oncology, offering new therapeutic opportunities to fight diverse malignancies. This review covers the biological basis and clinical application of LAG3 and TIGIT inhibitors, highlighting pivotal trials and therapeutic outcomes. We underscore the use of dual therapy immune checkpoint blockade in enhancing antitumor immunity, particularly in settings where monotherapy has shown limited efficacy. Additionally, we address the emerging challenges such as treatment resistance and adverse effects. We explore the strategic integration of LAG3 and TIGIT blockade within the broader immunotherapy landscape, emphasizing innovative combinations and the quest for predictive biomarkers to optimize patient selection and treatment efficacy.
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Circulating Tumor DNA: A Pan-Cancer Biomarker in Solid Tumors with Prognostic and Predictive Value
Vol. 76 (2025), pp. 207–223More LessCirculating tumor DNA (ctDNA), often referred to as a liquid biopsy, represents a promising biomarker in the management of both localized and advanced solid tumors. It has garnered significant attention due to its potential to inform prognosis and guide therapeutic decisions. The clinical utility of ctDNA spans early cancer detection, minimal residual disease identification, recurrence surveillance, treatment monitoring, and precision oncology treatment decision-making in the advanced setting. Unlike conventional radiological assessments, the short half-life of ctDNA allows for more timely insights into disease dynamics. Several technological approaches are available to measure ctDNA, including next-generation sequencing and droplet digital polymerase chain reaction, although their clinical accuracy depends on multiple biological and technical factors. This review evaluates current evidence surrounding ctDNA's utility in early and advanced solid tumors.
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Care Models for Cancer Survivors
Vol. 76 (2025), pp. 225–241More LessThe population of cancer survivors is on the rise due to an increase in cancer incidence and a decline in cancer mortality. This growing survivor population creates a number of challenges. Although there have been improvements in care planning for cancer survivors, our healthcare system still lacks the delivery of coordinated care between primary care physicians and specialists. Understanding the needs of cancer survivors can help improve the current care models. In this review we describe existing survivorship care models. We also describe emerging models using some programs at the Cleveland Clinic to highlight various potential approaches.
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New Oral Selective Estrogen Receptor Degraders Redefine Management of Estrogen Receptor–Positive Breast Cancer
Vol. 76 (2025), pp. 243–255More LessOral selective estrogen receptor degraders (SERDs) are pure estrogen receptor antagonists that have the potential to overcome common resistance mechanisms to endocrine therapy in estrogen receptor–positive breast cancer. There are currently five oral SERDs in published and ongoing clinical trials—elacestrant, camizestrant, giredestrant, imlunestrant, and amcenestrant—with more in development. They offer a reasonably well-tolerated oral therapy option with low discontinuation rates in studies. This review summarizes the currently available literature on this new class of drugs.
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CD70: An Emerging Anticancer Target in Renal Cell Carcinoma and Beyond
Vol. 76 (2025), pp. 257–266More LessCD70 is an emerging target for anticancer therapies. It is an ideal antigen target given its limited expression in normal physiologic tissues and propensity to be aberrantly expressed in a variety of malignancies, thus limiting off-target toxicities. It is also heavily involved in immune homeostasis, and disruption of this pathway can help overcome tumor-related immune cell exhaustion. Recent phase I/II trials using cellular therapies targeting CD70, such as chimeric antigen receptor-T cells, have shown promising effectiveness and safety in treating relapsed or refractory renal cell carcinoma. Noncellular therapies targeting CD70, such as antibody-drug conjugates, monoclonal antibodies, radionuclides, and cytokines, are currently under investigation, with early data showing encouraging results as well. Efforts are already underway to further improve and optimize CD70-based therapies.
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Medical Therapy Alone, Percutaneous Coronary Intervention, or Coronary Artery Bypass Grafting for Treatment of Coronary Artery Disease
Vol. 76 (2025), pp. 267–281More LessIn this review, we describe how the management of coronary artery disease (CAD) has become increasingly complex due to the rapid evolution of pharmacotherapy and procedural techniques. The expanding array of treatment options has driven researchers to investigate the optimal combination of therapies; while the findings offer invaluable insights, the sheer volume and occasional contradictions can foster confusion. Given the diverse spectrum of CAD and its manifestations, a tailored treatment decision is critical for each patient. We hope to demonstrate that by integrating the key messages from clinical trials and prioritizing patient comprehension and preference, healthcare providers can guide their patients toward appropriate treatment options, ultimately leading to enhanced care.
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Previous Volumes
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Volume 76 (2025)
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Volume 75 (2024)
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Volume 74 (2023)
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Volume 73 (2022)
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Volume 72 (2021)
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Volume 71 (2020)
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Volume 70 (2019)
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Volume 69 (2018)
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Volume 68 (2017)
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Volume 67 (2016)
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Volume 66 (2015)
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Volume 65 (2014)
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Volume 64 (2013)
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Volume 63 (2012)
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Volume 62 (2011)
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Volume 61 (2010)
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Volume 60 (2009)
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Volume 59 (2008)
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Volume 58 (2007)
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Volume 57 (2006)
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Volume 56 (2005)
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Volume 55 (2004)
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Volume 54 (2003)
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Volume 53 (2002)
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Volume 52 (2001)
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Volume 51 (2000)
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Volume 50 (1999)
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Volume 49 (1998)
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Volume 48 (1997)
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Volume 47 (1996)
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Volume 46 (1995)
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Volume 45 (1994)
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Volume 44 (1993)
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Volume 43 (1992)
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Volume 42 (1991)
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Volume 41 (1990)
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Volume 40 (1989)
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Volume 39 (1988)
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Volume 38 (1987)
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Volume 37 (1986)
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Volume 36 (1985)
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Volume 35 (1984)
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Volume 34 (1983)
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Volume 33 (1982)
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Volume 32 (1981)
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Volume 31 (1980)
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Volume 30 (1979)
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Volume 29 (1978)
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Volume 28 (1977)
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Volume 27 (1976)
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Volume 26 (1975)
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Volume 25 (1974)
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Volume 24 (1973)
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Volume 23 (1972)
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Volume 22 (1971)
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Volume 21 (1970)
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Volume 20 (1969)
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Volume 19 (1968)
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Volume 18 (1967)
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Volume 17 (1966)
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Volume 16 (1965)
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Volume 15 (1964)
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Volume 14 (1963)
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Volume 13 (1962)
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Volume 12 (1961)
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Volume 11 (1960)
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Volume 10 (1959)
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Volume 9 (1958)
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Volume 8 (1957)
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Volume 7 (1956)
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Volume 6 (1955)
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Volume 5 (1954)
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Volume 4 (1953)
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Volume 3 (1952)
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Volume 2 (1951)
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Volume 1 (1950)
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Volume 0 (1932)