The Protective Effect of Virus Capsids on RNA and DNA Virus Genomes in Wastewater.

Virus concentrations measured in municipal wastewater help inform both the water treatment necessary to protect human health and wastewater-based epidemiology. Wastewater measurements are typically PCR-based, and interpreting gene copy concentrations requires an understanding of the form and stability of the nucleic acids. Here, we study the persistence of model virus genomes in wastewater, the protective effects provided by the virus capsids, and the relative decay rates of the genome and infectious viruses. In benchtop batch experiments in wastewater influent at 25 °C, extraviral (+)ssRNA and dsDNA amplicons degraded by 90% within 15-19 min and 1.6-1.9 h, respectively. When encapsidated, the T90 for MS2 (+)ssRNA increased by 424× and the T90 for T4 dsDNA increased by 52×. The (+)ssRNA decay rates were similar for a range of amplicon sizes. For our model phages MS2 and T4, the nucleic acid signal in untreated wastewater disappeared shortly after the viruses lost infectivity. Combined, these results suggest that most viral genome copies measured in wastewater are encapsidated, that measured concentrations are independent of assay amplicon sizes, and that the virus genome decay rates of nonenveloped (i.e., naked) viruses are similar to inactivation rates. These findings are valuable for the interpretation of wastewater virus measurements.

Reactivity of Viral Nucleic Acids with Chlorine and the Impact of Virus Encapsidation.

Free chlorine disinfection is widely applied to inactivate viruses by reacting with their biomolecules, which include nucleic acids, proteins, and lipids. Knowing the reactivities of viral genomes with free chlorine and the protection that encapsidation provides would ultimately help predict virus susceptibility to the disinfectant. The relative reactivities of different viral genome types and the impact of viral higher order structure with free chlorine are poorly characterized. Here, we studied the reactivity of viral genomes representing four genome types from virus particles with diverse structures, namely, (+)ssRNA (MS2), dsRNA (φ6), ssDNA (φX174), and dsDNA (T3) with free chlorine. We compared the reactivities of these viral nucleic acids when they were suspended in phosphate buffer solutions (naked forms) and when they were in the native virus particles (encapsidated forms). The reactivities of nucleic acids were tracked by polymerase chain reaction (PCR)-based assays. The naked dsDNA of T3 was the least reactive with free chlorine, with an average second order rate constant normalized by the number of bases in the measured regions (in M-1 s-1 b-1) that was 34×, 65×, and 189× lower than those of the dsRNA of φ6, ssRNA of MS2, and ssDNA of φX174, respectively. Moreover, different regions in the ssRNA genome of MS2 and the dsRNA genome of φ6 exhibited statistically different reaction kinetics. The genomes within virus particles reacted slower than the naked genomes overall, but the extent of these differences varied among the four viruses. The results on viral nucleic acid reactivity help explain different susceptibilities of viruses to inactivation by free chlorine and also provide a valuable comparison of the susceptibilities of different nucleic acids to oxidants.

Improving our departmental reporting of thyroid cytology specimens against national guidelines: A two-cycle retrospective audit.

INTRODUCTION: In the UK, guidelines from the Royal College of Pathologists (RCPath) facilitate consistent and reproducible reporting and classification of fine needle aspiration cytology (FNAC) thyroid specimens. The aim was to audit our department against RCPath guidelines to refine and improve our reporting process. METHODS: Two-cycle retrospective observational audit of all patients undergoing thyroid FNAC over a 2-year period (1 year for each cycle). Final histology was correlated. The positive predictive value (PPV) for malignant neoplastic lesions was calculated; for Thy1, Thy1c, Thy2 and Thy2c all cases without final histology were assumed to be benign, while for Thy3a, Thy3f, Thy4 and Thy5 samples the PPV calculation was based only on those cytology samples with corresponding histology. False positive and false negative cases were reviewed. RESULTS: In total, 288 cytology samples were included in the first cycle; 96 (33.3%) had corresponding histology. There were 287 samples included in the second cycle; 119 (41.5%) had follow-up histology. The rate of non-diagnostic samples (Thy1/1c) decreased from 39.6% to 30.0%. The PPV for malignant neoplastic lesions was Thy1/1c 2.6%, Thy2/2c 0.0%, Thy3a 40.0%, Thy3f 19.4%, Thy4 75.0%, Thy5 100.0% (first cycle); Thy1/1c 4.7%, Thy2/2c 0.7%, Thy3a 13.3%, Thy3f, 7.7%, Thy4, 50.0%, Thy5 100.0% (second cycle). CONCLUSIONS: Our department was able to reduce the rate of non-diagnostic FNAC samples and improve the diagnostic accuracy of FNAC. Auditing local outcomes helps refine and improve the reporting process. Review of false positive and false negative cases helps examine potential pitfalls of cytology.

Gene Graphics: a genomic neighborhood data visualization web application.

Summary: The examination of gene neighborhood is an integral part of comparative genomics but no tools to produce publication quality graphics of gene clusters are available. Gene Graphics is a straightforward web application for creating such visuals. Supported inputs include National Center for Biotechnology Information gene and protein identifiers with automatic fetching of neighboring information, GenBank files and data extracted from the SEED database. Gene representations can be customized for many parameters including gene and genome names, colors and sizes. Gene attributes can be copied and pasted for rapid and user-friendly customization of homologous genes between species. In addition to Portable Network Graphics and Scalable Vector Graphics, produced representations can be exported as Tagged Image File Format or Encapsulated PostScript, formats that are standard for publication. Hands-on tutorials with real life examples inspired from publications are available for training. Availability and implementation: Gene Graphics is freely available at https://katlabs.cc/genegraphics/ and source code is hosted at https://github.com/katlabs/genegraphics. Contact: katherinejh@ufl.edu or remizallot@ufl.edu. Supplementary information: Supplementary data are available at Bioinformatics online.

Evidence that COG0325 proteins are involved in PLP homeostasis.

Pyridoxal 5'-phosphate (PLP) is an essential cofactor for nearly 60 Escherichia coli enzymes but is a highly reactive molecule that is toxic in its free form. How PLP levels are regulated and how PLP is delivered to target enzymes are still open questions. The COG0325 protein family belongs to the fold-type III class of PLP enzymes and binds PLP but has no known biochemical activity although it occurs in all kingdoms of life. Various pleiotropic phenotypes of the E. coli COG0325 (yggS) mutant have been reported, some of which were reproduced and extended in this study. Comparative genomic, genetic and metabolic analyses suggest that these phenotypes reflect an imbalance in PLP homeostasis. The E. coli yggS mutant accumulates the PLP precursor pyridoxine 5'-phosphate (PNP) and is sensitive to an excess of pyridoxine but not of pyridoxal. The pyridoxine toxicity phenotype is complemented by the expression of eukaryotic yggS orthologs. It is also suppressed by the presence of amino acids, specifically isoleucine, threonine and leucine, suggesting the PLP-dependent enzyme transaminase B (IlvE) is affected. These genetic results lay a foundation for future biochemical studies of the role of COG0325 proteins in PLP homeostasis.

Delay discounting demonstrates lower impulsivity linked to a higher likelihood of succeeding at smoking cessation.

Sixty-eight percent of smokers want to quit, but only one in 10 are successful at smoking cessation. Recently, impulsivity has been studied in relation to smoking cessation with measures like the delay discounting task (DDT). We aimed to build on the robust literature that has already revealed the association between impulsivity and smoking cessation, as well as look at the differences between sexes for which there is conflicting evidence. We hypothesized that lower impulsivity would be positively associated with cessation success. In the parent cessation trial, participants were randomized to 12 weeks of progesterone or placebo. Participants were asked to quit smoking, and their smoking status was monitored via expired carbon monoxide throughout the study. Participants completed a DDT at screening, week 4, and week 8 using the 27-item Monetary Choice Questionnaire, where participants decided between a small immediate reward or a larger delayed reward (LDR). The effective delay 50 (ED50), which is the delay at which the LDR loses half its value, was analyzed. To estimate the association between ED50 and cessation, a logistic mixed model with a participant random intercept was fit, controlling for study week, randomization, sex, and age. For the 181 participants, a doubling of the ED50 was associated with an 18% increase in the odds of tobacco cessation (95% confidence interval: 0.2-38% increase; p=0.05). In agreement with our hypothesis, lower impulsivity correlated to greater tobacco cessation success. Our study also showed no evidence of sex differences in the association between ED50 and smoking cessation.

Approach to machine learning for extraction of real-world data variables from electronic health records.

Background: As artificial intelligence (AI) continues to advance with breakthroughs in natural language processing (NLP) and machine learning (ML), such as the development of models like OpenAI's ChatGPT, new opportunities are emerging for efficient curation of electronic health records (EHR) into real-world data (RWD) for evidence generation in oncology. Our objective is to describe the research and development of industry methods to promote transparency and explainability. Methods: We applied NLP with ML techniques to train, validate, and test the extraction of information from unstructured documents (e.g., clinician notes, radiology reports, lab reports, etc.) to output a set of structured variables required for RWD analysis. This research used a nationwide electronic health record (EHR)-derived database. Models were selected based on performance. Variables curated with an approach using ML extraction are those where the value is determined solely based on an ML model (i.e. not confirmed by abstraction), which identifies key information from visit notes and documents. These models do not predict future events or infer missing information. Results: We developed an approach using NLP and ML for extraction of clinically meaningful information from unstructured EHR documents and found high performance of output variables compared with variables curated by manually abstracted data. These extraction methods resulted in research-ready variables including initial cancer diagnosis with date, advanced/metastatic diagnosis with date, disease stage, histology, smoking status, surgery status with date, biomarker test results with dates, and oral treatments with dates. Conclusion: NLP and ML enable the extraction of retrospective clinical data in EHR with speed and scalability to help researchers learn from the experience of every person with cancer.

Gender Differences in the Psychosocial Determinants Underlying the Onset and Maintenance of Alcohol Use Disorder.

A large number of different mechanisms have been linked to Alcohol Use Disorder (AUD), including psychosocial, neurocognitive, affective, and neurobiological factors. Gender has been shown to impact the presentation and progression of AUD; yet, little work has been done to parse the different mechanisms underlying AUD within the lens of gender differences. A review of the literature on adolescence revealed that psychosocial factors, in particular lack of family social support and interactions with peers, drive the onset of alcohol use more strongly in girls relative to boys. However, research done on gender differences in disease progression in adults remains limited. Our gender-specific analysis of the mechanisms underlying AUD in adults revealed that lack of social support was causally linked to negative affect, mental health symptoms, and AUD symptom severity in women, but not men. These novel results suggest that psychosocial factors may play a gender-specific role not only in the onset of use in adolescence, but also in the maintenance of addiction in adults. If confirmed, this suggests the need for investigating gender-specific recovery trajectories. In this perspective piece, we review the literature regarding gender differences in the onset and maintenance of AUD and present original data that support unique risk factors in women.

Quantifying Karenia brevis bloom severity and respiratory irritation impact along the shoreline of Southwest Florida.

Nearly all annual blooms of the toxic dinoflagellate Karenia brevis (K. brevis) pose a serious threat to coastal Southwest Florida. These blooms discolor water, kill fish and marine mammals, contaminate shellfish, cause mild to severe respiratory irritation, and discourage tourism and recreational activities, leading to significant health and economic impacts in affected communities. Despite these issues, we still lack standard measures suitable for assessing bloom severity or for evaluating the efficacy of modeling efforts simulating bloom initiation and intensity. In this study, historical cell count observations along the southwest Florida shoreline from 1953 to 2019 were used to develop monthly and annual bloom severity indices (BSI). Similarly, respiratory irritation observations routinely reported in Sarasota and Manatee Counties from 2006 to 2019 were used to construct a respiratory irritation index (RI). Both BSI and RI consider spatial extent and temporal evolution of the bloom, and can be updated routinely and used as objective criteria to aid future socioeconomic and scientific studies of K. brevis. These indices can also be used to help managers and decision makers both evaluate the risks along the coast during events and design systems to better respond to and mitigate bloom impacts. Before 1995, sampling was done largely in response to reports of discolored water, fish kills, or respiratory irritation. During this timeframe, lack of sampling during the fall, when blooms typically occur, generally coincided with periods of more frequent-than-usual offshore winds. Consequently, some blooms may have been undetected or under-sampled. As a result, the BSIs before 1995 were likely underestimated and cannot be viewed as accurately as those after 1995. Anomalies in the frequency of onshore wind can also largely account for the discrepancies between BSI and RI during the period from 2006 to 2019. These findings highlighted the importance of onshore wind anomalies when predicting respiratory irritation impacts along beaches.

Knowledge, Attitudes, and Beliefs about Relapse Prevention Research Involving Bupropion among Current and Former Pregnant Individuals Who Smoke.

Introduction: While many individuals quit smoking during pregnancy, most relapse within one year postpartum. Research into methods to decrease smoking relapse postpartum has been hampered by difficulties with recruitment. Method: We conducted individual interviews with pregnant women (N = 22) who were interested in quitting smoking while pregnant about their attitudes regarding smoking and quitting during pregnancy, clinical trial participation, and smoking cessation medication use. Results: Participants were aware of the risks of smoking while pregnant. Many wanted to quit smoking before delivery. Few used empirically supported treatments to quit. While research was viewed positively, interest in taking on new commitments postpartum and taking a medication to prevent relapse was low. Medication concerns were evident among most participants, especially among those planning to breastfeed. Further, several women noted medication was unnecessary, as they did not believe they would relapse postpartum. Financial incentives, childcare, and fewer and/or remote visits were identified as facilitators to participating in research. However, these factors did not outweigh women's concerns about medication use and time commitments. Conclusions: Women are aware that quitting smoking during pregnancy and remaining smoke-free postpartum are important. However, beliefs that personal relapse risk is low and that medications are dangerous reduced enthusiasm for taking medication for postpartum relapse prevention. Future medication trials should educate women about the high likelihood of relapse, prepare to answer detailed questions about risks of cessation medications, and connect with participants' clinicians. For new mothers, studies conducted remotely with few scheduled appointments would reduce barriers to participation.

Effect of exogenous progesterone administration on smoking topography.

INTRODUCTION: Progesterone has been implicated as protective against drug taking behaviors, including combustible cigarettes. While prior research indicates higher endogenous progesterone levels are associated with a reduction in smoking intensity (as measured by smoking topography), it is unknown if exogenous delivery of progesterone may have the same effect. METHODS: This double-blind, counterbalanced, cross-over randomized trial enrolled women between the ages of 18 and 40 who smoked at least five cigarettes per day and were currently using oral contraceptives. After overnight abstinence participants attended two topography lab sessions. One lab session was conducted during progesterone (200 mg twice per day) treatment and the other was during placebo treatment. Analyses included linear mixed effect models to examine the effect of exogenous progesterone administration and endogenous progesterone values on topography outcomes. RESULTS: Participants (n = 43) were 23.8 (standard deviation [SD] ± 4.5) years old, smoked 10.5 (SD ± 3.7) cigarettes per day. Compared to placebo administration, progesterone administration reduced cumulative puff volume by 300 mL (95% confidence interval [CI]: -536, -65; p-value = 0.01) with additional trends indicating possible reductions in the number of puffs, average puff volume, and average flow. There were no significant effects of endogenous progesterone on smoking topography outcomes. CONCLUSIONS: Progesterone administration has the potential to reduce smoking intensity after overnight abstinence in women of reproductive age. Additional research is needed to explore how this may relate to smoking cessation outcomes in women of reproductive age.

Bupropion for postpartum smoking relapse: A remote protocol for a two-arm, double-blind, placebo-controlled randomized clinical trial.

Cigarette smoking among postpartum women remains a significant public health problem despite known health risks to women and their newborns. It is estimated that over 50% of women quit smoking during pregnancy but 90% relapse by one year. Safe and effective postpartum relapse prevention strategies are urgently needed. In an attempt to address this deficit, we will investigate the efficacy of bupropion vs. placebo as a smoking relapse prevention aid in postpartum women. The objective of this paper is to detail an approach to investigate bupropion's efficacy for preventing postpartum smoking relapse among women who quit smoking during pregnancy. Specifically, we designed a two-arm, double-blind, placebo-controlled randomized trial testing the efficacy of bupropion vs. placebo as a relapse prevention tool. Mothers of healthy infants who quit smoking while pregnant will be stratified based on current or past history of major depressive disorder or persistent depressive disorder and randomized to receive either active (bupropion XL 300 mg/day) or placebo medication for 12 weeks. To respond to safety concerns associated with participant and staff exposure to COVID-19, we revised our original protocol and present procedures which allow our trial to be conducted entirely remotely. Primary and secondary outcomes will be assessed at weeks 12, 24, 36 and 52 post-randomization. The primary outcome is 7-day point prevalence abstinence at 24 weeks. Results of this work have the potential to positively impact women and their children by promoting lifelong cessation, eliminating secondhand smoke exposure, and modelling of abstinence to children.

Validation of N95 Filtering Facepiece Respirator Decontamination Methods Available at a Large University Hospital.

BACKGROUND: Due to unprecedented shortages in N95 filtering facepiece respirators, healthcare systems have explored N95 reprocessing. No single, full-scale reprocessing publication has reported an evaluation including multiple viruses, bacteria, and fungi along with respirator filtration and fit. METHODS: We explored reprocessing methods using new 3M 1860 N95 respirators, including moist (50%-75% relative humidity [RH]) heat (80-82°C for 30 minutes), ethylene oxide (EtO), pulsed xenon UV-C (UV-PX), hydrogen peroxide gas plasma (HPGP), and hydrogen peroxide vapor (HPV). Respirator samples were analyzed using 4 viruses (MS2, phi6, influenza A virus [IAV], murine hepatitis virus [MHV)]), 3 bacteria (Escherichia coli, Staphylococcus aureus, Geobacillus stearothermophilus spores, and vegetative bacteria), and Aspergillus niger. Different application media were tested. Decontaminated respirators were evaluated for filtration integrity and fit. RESULTS: Heat with moderate RH most effectively inactivated virus, resulting in reductions of >6.6-log10 MS2, >6.7-log10 Phi6, >2.7-log10 MHV, and >3.9-log10 IAV and prokaryotes, except for G stearothermohphilus. Hydrogen peroxide vapor was moderately effective at inactivating tested viruses, resulting in 1.5- to >4-log10 observable inactivation. Staphylococcus aureus inactivation by HPV was limited. Filtration efficiency and proper fit were maintained after 5 cycles of heat with moderate RH and HPV. Although it was effective at decontamination, HPGP resulted in decreased filtration efficiency, and EtO treatment raised toxicity concerns. Observed virus inactivation varied depending upon the application media used. CONCLUSIONS: Both moist heat and HPV are scalable N95 reprocessing options because they achieve high levels of biological indicator inactivation while maintaining respirator fit and integrity.

Factors limiting data quality in the expanded programme on immunization in low and middle-income countries: A scoping review.

Few public health interventions can match the immense achievements of immunization in terms of mortality and morbidity reduction. However, progress in reaching global coverage goals and achieving universal immunization coverage have stalled; with key stakeholders concerned about the accuracy of reported coverage figures. Incomplete and incorrect data has made it challenging to obtain an accurate overview of immunization coverage, particularly in low- and middle-income countries (LMIC). To date, only one literature review concerning immunization data quality exists. However, it only included articles from Gavi-eligible countries, did not go deep into the characteristics of the data quality problems, and used a narrow 'data quality' definition. This scoping review builds upon that work; exploring the "state of data quality" in LMIC, factors affecting data quality in these settings and potential means to improve it. Only a small volume of literature addressing immunization data quality in LMIC was found and definitions of 'data quality' varied widely. Data quality was, on the whole, considered poor in the articles included. Coverage numerators were seen to be inflated for official reports and denominators were inaccurate and infrequently adjusted. Numerous factors related to these deficiencies were reported, including health information system fragmentation, overreliance on targets and poor data management processes. Factors associated with health workers were noted most frequently. Authors suggested that data quality could be improved by ensuring proper data collection tools, increasing workers' capacities and motivation through training and supervision, whilst also ensuring adequate and timely feedback on the data collected. The findings of this scoping review can serve as the basis to identify and address barriers to good quality immunization data in LMICs. Overcoming said barriers is essential if immunization's historic successes are to continue.

Response to nicotine following overnight smoking abstinence during short-term progesterone treatment in women.

Preclinical and clinical literature suggest that sex hormones impact tobacco use behaviors in women. The goal of this double-blind crossover laboratory study was to examine the effect of oral exogenous progesterone (200 mg twice per day) versus placebo on nicotine response using measures of motor speed and cognitive function in women following overnight smoking abstinence. We hypothesized that increased progesterone would blunt the nicotine response whereby producing less change in motor speed and cognition in response to nicotine exposure. Female smokers, age 18-35, were randomized to participate in two 9-day crossover testing weeks. Participants completed a lab session following overnight abstinence where they were administered nicotine nasal spray and asked to complete measures of immediate memory (IMT), delayed memory (DMT), word recall (WR), and finger tapping speed (FT). After the first 9-day testing week, participants resumed smoking and returned the following month to complete the identical lab session in the crossover condition. Forty-seven women were included in this analysis (n = 47). We found no differences in the magnitude of response for IMT, DMT, and WR between conditions. For FT, women had a blunted response to nicotine during the placebo condition. When examining the association between hormone levels and relative performance, we found increases in DMT, WR, and FT but decreases in IMT during the progesterone condition. We observed differences between progesterone versus placebo in relative change in some measures of nicotine response following overnight abstinence. Future studies are needed to further characterize this response. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Benzalkonium chloride alters phenotypic and genotypic antibiotic resistance profiles in a source water used for drinking water treatment.

Antibiotic resistance is a major public health concern. Triclosan is an antimicrobial compound with direct links to antibiotic resistance that was widely used in soaps in the U.S. until its ban by the U.S. Food and Drug Administration. Benzalkonium chloride (BAC), a quaternary ammonium compound, has widely replaced triclosan in soaps marketed as an antibacterial. BAC has been detected in surface waters and its presence will likely increase following increased use in soap products. The objective of this study was to determine the effect of BAC on relative abundance of antibiotic resistance in a bacterial community from a surface water used as a source for drinking water treatment. Bench-scale microcosm experiments were conducted with microbial communities amended with BAC at concentrations ranging from 0.1 µg L-1 to 500 µg L-1. Phenotypic antibiotic resistance was quantified by culturing bacteria in the presence of different antibiotics, and genotypic resistance was determined using qPCR to quantify antibiotic resistance genes (ARGs). BAC at concentrations ranging from 0.1 µg L-1 to 500 µg L-1 was found to positively select for bacteria resistant to ciprofloxacin and sulfamethoxazole, and negatively select against bacteria with resistance to six other antibiotics. Exposure to BAC for 14 days increased the relative abundance of sul1 and blaTEM. This study re-highlights the importance of employing both culture and non-culture-based techniques to identify selection for antibiotic resistance. The widespread use of BAC will likely impact antibiotic resistance profiles of bacteria in the environment, including in source waters used for drinking water, wastewater treatment plants, and natural waterways.

Kikuchi-Fujimoto Disease and Prognostic Implications.

Kikuchi-Fujimoto disease (KFD) is a rare cause of lymphadenitis seen mostly in Asian populations (Kikuchi in Nippon Ketsueki Gakkai Zasshi 35:379-80, 1972). First described in 1972, KFD is a benign and self-limiting disease characterised by lymphadenopathy, mild fever, fatigue, and leukopenia (Fujimoto in Naika 30:920-7, 1972; Lin et al. in Otolaryngol Head Neck Surg 128(5): 650-3, 2003). We present a case of a 38-year-old woman with a 6-week history of cervical lymphadenopathy. Her ultrasound scan and fine needle aspiration cytology results were inconclusive. Excisional biopsy of the lymph node confirmed presence of KFD. The aetiology of KFD is unknown; however, there is strong association with systemic lupus erythematosus (SLE). Kucukardali reported 9% of European KFD patients and 28% of East Asian patients had concomitant SLE (Kucukardali et al. in Clin Rheumatol 26(1):50-4, 2007). We describe a follow-up algorithm for newly diagnosed KFD cases, based on the current literature. KFD is a rare cause of cervical lymphadenopathy. It is associated with increased risk of developing SLE, therefore early diagnosis and long-term follow-up are recommended.

Effect of exogenous progesterone administration on cigarette smoking-related symptomology in oral contraceptive users who smoke.

Cigarette smoking-related symptomatology (e.g., craving; SRS) is linked to relapse after a quit attempt. SRS varies by menstrual phase, possibly due to variations in sex hormones (e.g., progesterone), though much of the research to-date has relied on observations from the menstrual cycle acting as a proxy for hormone levels. The goal of this study was to examine the effect of exogenous progesterone on SRS during ad libitum smoking and following overnight abstinence. Oral contraceptive users who smoked completed two 9-day crossover testing periods (7 days of ad libitum smoking and 2 days following overnight abstinence) while taking double-blind active/placebo exogenous progesterone. Participants completed questionnaires to measure SRS. The effect of exogenous progesterone and endogenous hormones (progesterone, estradiol, and progesterone-to-estradiol [P/E2] ratio) on SRS was assessed with paired t-tests and linear mixed effect models. Participants (n = 53) were, on average, 24 years old and smoked 11 cigarettes per day. During ad libitum smoking, a doubling of the P/E2 ratio was associated with 0.09 points lower anticipated relief from negative affect (95% confidence interval [CI]: 0.03-0.15 points lower; p = 0.008) and 0.11 points lower psychological reward (95% CI: 0.03-0.18 points lower; p = 0.006). After correction for multiple testing, these associations were not statistically significant: anticipated relief from negative effect (p = 0.10) and psychological reward (p = 0.09). No other significant associations were observed. Although substantial previous literature indicates that progesterone influences SRS, exogenous progesterone administration did not alter SRS here. Additional research is needed to elucidate alternative mechanisms involved in menstrual phase effects on SRS.