Analysis of NIH K99/R00 awards and the career progression of awardees.

Many postdoctoral fellows and scholars who hope to secure tenure-track faculty positions in the United States apply to the National Institutes of Health (NIH) for a Pathway to Independence Award. This award has two phases (K99 and R00) and provides funding for up to 5 years. Using NIH data for the period 2006-2022, we report that ~230 K99 awards were made every year, representing up to ~$250 million annual investment. About 40% of K99 awardees were women and ~89% of K99 awardees went on to receive an R00 award annually. Institutions with the most NIH funding produced the most recipients of K99 awards and recruited the most recipients of R00 awards. The time between a researcher starting an R00 award and receiving a major NIH award (such as an R01) ranged between 4.6 and 7.4 years, and was significantly longer for women, for those who remained at their home institution, and for those hired by an institution that was not one of the 25 institutions with the most NIH funding. Shockingly, there has yet to be a K99 awardee at a historically Black college or university. We go on to show how K99 awardees flow to faculty positions, and to identify various factors that influence the future success of individual researchers and, therefore, also influence the composition of biomedical faculty at universities in the United States.

Science Communication Training Imparts Confidence and Influences Public Engagement Activity.

The impacts of science are felt across all socio-ecological levels, ranging from the individual to societal. In order to adapt or respond to scientific discoveries, novel technologies, or biomedical or environmental challenges, a fundamental understanding of science is necessary. However, antiscientific rhetoric, mistrust in science, and the dissemination of misinformation hinder the promotion of science as a necessary and beneficial component of our world. Scientists can promote scientific literacy by establishing dialogues with nonexperts, but they may find a lack of formal training as a barrier to public engagement. To address this, the American Society for Biochemistry and Molecular Biology (ASBMB) launched the Art of Science Communication course in 2015 in order to provide scientists at all career stages with introductory science communication training. In 2020, we conducted a retrospective survey of former participants to evaluate how the course had impacted participants' science communication behaviors and their confidence engaging with nonexperts, as well as other benefits to their professional development. We found that scientists were significantly more likely to communicate with nonexpert audiences following the course compared to before (77% versus 51%; P < 0.0001). In addition, quantitative and qualitative data suggested that scientists were more confident in their ability to communicate science after completing the course (median of 8, standard deviation [SD] of 0.98 versus median of 5, SD of 1.57; P < 0.0001). Qualitative responses from participants supported quantitative findings. This suggested that the Art of Science Communication course is highly effective at improving the confidence of scientists to engage with the public and other nonexpert audiences regardless of career status. These data-driven perspectives provide a rationale for the implementation of broadly accessible science communication training programs that promote public engagement with science.

Evaluation of Professional Setbacks and Resilience in Biomedical Scientists During the COVID-19 Pandemic.

This survey study evaluates whether resilience was associated with professional and career setbacks among biomedical scientists during the COVID-19 pandemic.

Physician and Biomedical Scientist Harassment on Social Media During the COVID-19 Pandemic.

This survey study assesses the frequency and nature of harassment on social media experienced by physicians, biomedical scientists, and trainees during the COVID-19 pandemic.

Analysis of NIH K99/R00 Awards and the Career Progression of Awardees.

Many postdoctoral fellows and scholars who hope to secure tenure-track faculty positions in the United States apply to the National Institutes of Health (NIH) for a Pathway to Independence Award. This award has two phases (K99 and R00) and provides funding for up to five years. Using NIH data for the period 2006-2022, we report that ~230 K99 awards were made every year, representing up to ~$250 million annual investment. About 40% of K99 awardees were women and ~89% of K99 awardees went on to receive an R00 award annually. Institutions with the most NIH funding produced the most recipients of K99 awards and recruited the most recipients of R00 awards. The time between a researcher starting an R00 award and receiving a major NIH award (such as an R01) ranged between 4.6 and 7.4 years, and was significantly longer for women, for those who remained at their home institution, and for those hired by an institution that was not one of the 25 institutions with the most NIH funding. Shockingly, there has yet to be a K99 awardee at a historically Black college or university. We go on to show how K99 awardees flow to faculty positions, and to identify various factors that influence the future success of individual researchers and, therefore, also influence the composition of biomedical faculty at universities in the US.

Impact of Stress on Menstrual Cyclicity During the Coronavirus Disease 2019 Pandemic: A Survey Study.

Background: The coronavirus disease 2019 (COVID-19) pandemic has introduced acute and persistent psychosocial stressors for many individuals, with emerging gender differences that suggest women may be at greater risk for poorer mental health outcomes. This may have unintended consequences for women's overall health and well-being, including disruptions to reproductive function as elevated stress is often associated with menstrual cycle irregularities. The objective of this study was to determine if and how the COVID-19 pandemic and its related stressors have impacted women's menstrual cyclicity. Materials and Methods: An online survey instrument designed to capture self-reported information on menstrual cycle changes and perceived stress levels was distributed between July and August 2020. A total of 210 women between the ages of 18-45 years met stringent inclusion and exclusion criteria and completed the survey. Results: Of the 210 respondents, more than half (54%) reported changes in their menstrual cycles. These included changes in menstrual cycle length (50%), the duration of menses (34%), and changes in premenstrual symptoms (50%). Respondents with high perceived stress scale (PSS) scores during Covid were more likely to experience a longer duration of menses (p < 0.001) and heavier bleeding during menses (p = 0.028) compared with those with moderate Covid PSS scores. Conclusions: By uncovering a trend in increased menstrual cycle irregularities during the early months of the COVID-19 pandemic, this study contributes to our understanding of the implications that the pandemic may have on women's reproductive health.

Sex and Gender Bias in Covid-19 Clinical Case Reports.

Clinical case reports circulate relevant information regarding disease presentation and describe treatment protocols, particularly for novel conditions. In the early months of the Covid-19 pandemic, case reports provided key insights into the pathophysiology and sequelae associated with Covid-19 infection and described treatment mechanisms and outcomes. However, case reports are often subject to selection bias due to their singular nature. To better understand how selection biases may have influenced Covid-19-releated case reports, we conducted a bibliometric analysis of Covid-19-releated case reports published in high impact journals from January 1 to June 1, 2020. Case reports were coded for patient sex, country of institutional affiliation, physiological system, and first and last author gender. Of 494 total case reports, 45% (n = 221) of patients were male, 30% (n = 146) were female, and 25% (n = 124) included both sexes. Ratios of male-only to female-only case reports varied by physiological system. The majority of case reports had male first (61%, n = 302) and last (70%, n = 340) authors. Case reports with male last authors were more likely to describe male patients [X 2 (2, n = 465) = 6.6, p = 0.037], while case reports with female last authors were more likely to include patients of both sexes [OR = 1.918 (95% CI = 1.163-3.16)]. Despite a limited sample size, these data reflect emerging research on sex-differences in the physiological presentation and impact of Covid-19 and parallel large-scale trends in authorship patterns. Ultimately, this work highlights potential biases in the dissemination of clinical information via case reports and underscores the inextricable influences of sex and gender biases within biomedicine.

COVID-19 Threatens Progress Toward Gender Equity Within Academic Medicine.

Women remain underrepresented within academic medicine despite past and present efforts to promote gender equity. The authors discuss how the COVID-19 pandemic could stymie progress toward gender parity within the biomedical workforce and limit the retention and advancement of women in science and medicine. Women faculty face distinct challenges as they navigate the impact of shelter-in-place and social distancing on work and home life. An unequal division of household labor and family care between men and women means women faculty are vulnerable to inequities that may develop in the workplace as they strive to maintain academic productivity and professional development without adequate assistance with domestic tasks and family care. Emerging data suggest that gender differences in academic productivity may be forthcoming as a direct result of the pandemic. Existing gender inequities in professional visibility, networking, and collaboration may be exacerbated as activities transition from in-person to virtual environments and create new barriers to advancement. Meanwhile, initiatives designed to promote gender equity within academic medicine may lose key funding due to the economic impact of COVID-19 on higher education. To ensure that the gender gap within academic medicine does not widen, the authors call upon academic leaders and the broader biomedical community to support women faculty through deliberate actions that promote gender equity, diversity, and inclusion. The authors provide several recommendations, including faculty needs assessments; review of gender bias within tenure-clock-extension offers; more opportunities for mentorship, sponsorship, and professional recognition; and financial commitments to support equity initiatives. Leadership for these efforts should be at the institutional and departmental levels, and leaders should ensure a gender balance on task forces and committees to avoid overburdening women faculty with additional service work. Together, these strategies will contribute to the development of a more equitable workforce capable of transformative medical discovery and care.

A 10-year follow-up study of sex inclusion in the biological sciences.

In 2016, to address the historical overrepresentation of male subjects in biomedical research, the US National Institutes of Health implemented a policy requiring investigators to consider sex as a biological variable. In order to assess the impact of this policy, we conducted a bibliometric analysis across nine biological disciplines for papers published in 34 journals in 2019, and compared our results with those of a similar study carried out by Beery and Zucker in 2009. There was a significant increase in the proportion of studies that included both sexes across all nine disciplines, but in eight of the disciplines there was no change in the proportion studies that included data analyzed by sex. The majority of studies failed to provide rationale for single-sex studies or the lack of sex-based analyses, and those that did relied on misconceptions surrounding the hormonal variability of females. Together, these data demonstrate that while sex-inclusive research practices are more commonplace, there are still gaps in analyses and reporting of data by sex in many biological disciplines.

Gender-Specific Conferences and Symposia: A Putative Support Structure for Female Physicians.

Objective: To determine the impact of gender-specific conferences or symposia as it relates to medical professional development. Materials and Methods: An online survey instrument was distributed nationally through social media and shared by respondents. The survey assessed participants' demographics, attendance at gender-specific conferences or symposia, motivations or barriers to attendance, and perceived benefits of attendance. Results: Of 792 respondents, 34% had attended a conference or symposia for women in medicine, whereas 66% had not. Attendees were significantly more likely to hold a leadership position (68% vs. 43%, p < 0.0001), an academic faculty position (74% vs. 56%, p < 0.0001), and have received a professional accolade within the past year (42% vs. 28%, p < 0.0001). Nonattendees were significantly more likely to be the primary caregiver for children or seniors (64% vs. 56%, p = 0.042). Respondents indicated that an interest in discussion topics, a sense of community, and growth of professional network were key motivators in attendance. The majority of respondents indicated that attendance improved their self-advocacy, self-image, and leadership skills. Of those who did not attend, 51% were unaware of such conferences or symposia. Those who were aware, but unable to attend, cited lack of time as the major barrier to participation. Conclusions: The results of this study provide preliminary data surrounding gender-specific conferences or symposia for women in medicine and highlight opportunities for increased engagement. While not causative, attendees share attributes of professional success and report personal and professional benefits. Lack of awareness and access to child/family care are likely major barriers to participation, which can be addressed through strategic initiatives.

Implementation of the NIH Sex-Inclusion Policy: Attitudes and Opinions of Study Section Members.

OBJECTIVE: On January 25th, 2016, the National Institutes of Health (NIH) implemented a policy requiring investigators to consider sex as a biological variable (SABV) within their grant submissions. We surveyed NIH study section members in 2016 and 2017 to determine their attitudes toward the policy and their perceptions regarding its implementation. MATERIALS AND METHODS: Members of standing study sections and special emphasis panels who met in May, June, or July of 2016 and 2017, and had a publicly accessible e-mail address, were invited to participate in the survey (n = 4376 and n = 4710, respectively). The survey assessed participant demographics, knowledge and awareness of the SABV policy, and opinions regarding its utility and implementation. RESULTS: A combined total of 1161 study section members participated in the survey for a response rate of 10.2% in 2016 and 15.1% in 2017. Respondents thought it was important for NIH-funded research to consider SABV (63% vs. 68%, p = 0.141) and that it will improve rigor and reproducibility (54% vs. 58%, p = 0.208). In terms of implementation, respondents indicated that the percentage of grants, which have successfully addressed and incorporated the policy, has significantly increased over time (p < 0.0001 for all endpoints). However, open-ended comments revealed concern for federal research funding, the overuse of experimental animals, and uncertainty surrounding grant scoring, as it relates to the SABV policy. CONCLUSIONS: In this study, we show improving attitudes toward the sex-inclusive policy at NIH and that a statistically significant number of grants are addressing sex as a biological variable appropriately in their submissions. These data suggest the policy is becoming more well accepted, and it is thus anticipated that the reproducibility of scientific reports will increase over time and new discoveries using sex as a biological variable are on the horizon.

Structural basis for light control of cell development revealed by crystal structures of a myxobacterial phytochrome.

Phytochromes are red-light photoreceptors that were first characterized in plants, with homologs in photosynthetic and non-photosynthetic bacteria known as bacteriophytochromes (BphPs). Upon absorption of light, BphPs interconvert between two states denoted Pr and Pfr with distinct absorption spectra in the red and far-red. They have recently been engineered as enzymatic photoswitches for fluorescent-marker applications in non-invasive tissue imaging of mammals. This article presents cryo- and room-temperature crystal structures of the unusual phytochrome from the non-photosynthetic myxo-bacterium Stigmatella aurantiaca (SaBphP1) and reveals its role in the fruiting-body formation of this photomorphogenic bacterium. SaBphP1 lacks a conserved histidine (His) in the chromophore-binding domain that stabilizes the Pr state in the classical BphPs. Instead it contains a threonine (Thr), a feature that is restricted to several myxobacterial phytochromes and is not evolutionarily understood. SaBphP1 structures of the chromophore binding domain (CBD) and the complete photosensory core module (PCM) in wild-type and Thr-to-His mutant forms reveal details of the molecular mechanism of the Pr/Pfr transition associated with the physiological response of this myxobacterium to red light. Specifically, key structural differences in the CBD and PCM between the wild-type and the Thr-to-His mutant involve essential chromophore contacts with proximal amino acids, and point to how the photosignal is transduced through the rest of the protein, impacting the essential enzymatic activity in the photomorphogenic response of this myxobacterium.

EP24.15 as a Potential Regulator of Kisspeptin Within the Neuroendocrine Hypothalamus.

The neuropeptide kisspeptin (Kiss1) is integral to the advent of puberty and the generation of cyclical LH surges. Although many complex actions of Kiss1 are known, the mechanisms governing the processing/regulation of this peptide have not been unveiled. The metallo enzyme, endopeptidase 24.15 (thimet oligopeptidase), has been demonstrated to play a key role in the processing and thus the duration of action of the reproductive neuropeptide, GnRH, which signals downstream of Kiss1. Initial in silico modeling implied that Kiss1 could also be a putative substrate for EP24.15. Coincubation of Kiss1 and EP24.15 demonstrated multiple cleavages of the peptide predominantly between Arg29-Gly30 and Ser47-Phe48 (corresponding to Ser5-Phe6 in Kiss-10; Kiss-10 as a substrate had an additional cleavage between Phe6-Gly7) as determined by mass spectrometry. Vmax for the reaction was 2.37±0.09 pmol/min · ng with a Km of 19.68 ± 2.53µM, which is comparable with other known substrates of EP24.15. EP24.15 immunoreactivity, as previously demonstrated, is distributed in cell bodies, nuclei, and processes throughout the hypothalamus. Kiss1 immunoreactivity is localized primarily to cell bodies and fibers within the mediobasal and anteroventral-periventricular hypothalamus. Double-label immunohistochemistry indicated coexpression of EP24.15 and Kiss1, implicating that the regulation of Kiss1 by EP24.15 could occur in vivo. Further studies will be directed at determining the precise temporal sequence of EP24.15 effects on Kiss1 as it relates to the control of reproductive hormone secretion and treatment of fertility issues.

Femto- to Microsecond Photodynamics of an Unusual Bacteriophytochrome.

A bacteriophytochrome from Stigmatella aurantiaca is an unusual member of the bacteriophytochrome family that is devoid of hydrogen bonding to the carbonyl group of ring D of the biliverdin (BV) chromophore. The photodynamics of BV in SaBphP1 wild type and the single mutant T289H reintroducing hydrogen bonding to ring D show that the strength of this particular weak interaction determines excited-state lifetime, Lumi-R quantum yield, and spectral heterogeneity. In particular, excited-state decay is faster in the absence of hydrogen-bonding to ring D, with excited-state half-lives of 30 and 80 ps for wild type and the T289H mutant, respectively. Concomitantly, the Lumi-R quantum yield is two times higher in wild type as compared with the T289H mutant. Furthermore, the spectral heterogeneity in the wild type is significantly higher than that in the T289H mutant. By extending the observable time domain to 25 µs, we observe a new deactivation pathway from the Lumi-R intermediate in the 100 ns time domain that corresponds to a backflip of ring D to the original Pr 15Za isomeric state.