Creating Climate-Resilient Crops by Increasing Drought, Heat, and Salt Tolerance.

Over the years, the changes in the agriculture industry have been inevitable, considering the need to feed the growing population. As the world population continues to grow, food security has become challenged. Resources such as arable land and freshwater have become scarce due to quick urbanization in developing countries and anthropologic activities; expanding agricultural production areas is not an option. Environmental and climatic factors such as drought, heat, and salt stresses pose serious threats to food production worldwide. Therefore, the need to utilize the remaining arable land and water effectively and efficiently and to maximize the yield to support the increasing food demand has become crucial. It is essential to develop climate-resilient crops that will outperform traditional crops under any abiotic stress conditions such as heat, drought, and salt, as well as these stresses in any combinations. This review provides a glimpse of how plant breeding in agriculture has evolved to overcome the harsh environmental conditions and what the future would be like.

Engagement and factors associated with annual anal human papillomavirus screening among sexual and gender minority individuals.

Objectives: Annual screening with a provider has been recommended for groups at highest risk for anal cancer. Anal self-sampling could help address screening barriers, yet no studies have examined annual engagement with this method. Methods: The Prevent Anal Cancer Self-Swab Study recruited sexual and gender minority individuals 25 years and over who have sex with men in Milwaukee, Wisconsin to participate in an anal cancer screening study. Participants were randomized to a home or clinic arm. Home-based participants were mailed an anal human papillomavirus self-sampling kit at baseline and 12 months, while clinic-based participants were asked to schedule and attend one of five participating clinics at baseline and 12 months. Using Poisson regression, we conducted an intention-to-treat analysis of 240 randomized participants who were invited to screen at both timepoints. Results: 58.8% of participants completed annual (median=370 days) anal screening. When stratified by HIV status, persons living with HIV had a higher proportion of home (71.1%) versus clinic (22.2%) annual screening ( p <0.001). Non-Hispanic Black participants had a higher proportion of home-based annual anal screening engagement (73.1%) compared to annual clinic screening engagement (31.6%) ( p =0.01). Overall, annual screening engagement was significantly higher among participants who had heard of anal cancer from an LGBTQ organization, reported "some" prior anal cancer knowledge, preferred an insertive anal sex position, and reported a prior cancer diagnosis. Annual screening engagement was significantly lower for participants reporting a medical condition. Conclusions: Annual screening engagement among those at disproportionate anal cancer risk was higher in the home arm.

Association analysis between an epigenetic risk score and blood pressure.

Background: Epigenome-wide association studies have revealed multiple DNA methylation sites (CpGs) associated with alcohol consumption, an important lifestyle risk factor for cardiovascular diseases. Results: We generated an alcohol consumption epigenetic risk score (ERS) based on previously reported 144 alcohol-associated CpGs and examined the association of the ERS with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension (HTN) in 3,898 Framingham Heart Study (FHS) participants. We found an association of alcohol intake with the ERS in the meta-analysis with 0.09 units higher ERS per drink consumed per day (p < 0.0001). Cross-sectional analyses in FHS revealed that a one-unit increment of the ERS was associated with 1.93 mm Hg higher SBP (p = 4.64E-07), 0.68 mm Hg higher DBP (p = 0.006), and an odds ratio of 1.78 for HTN (p < 2E-16). Meta-analysis of the cross-sectional association of the ERS with BP traits in eight independent external cohorts (n = 11,544) showed similar relationships with blood pressure levels, i.e., a one-unit increase in ERS was associated with 0.74 (p = 0.002) and 0.50 (p = 0.0006) mm Hg higher SBP and DBP, but could not confirm the association with hypertension. Longitudinal analyses in FHS (n = 3,260) and five independent external cohorts (n = 4,021) showed that the baseline ERS was not associated with a change in blood pressure over time or with incident HTN. Conclusions: Our findings provide proof-of-concept that utilizing an ERS is a useful approach to capture the recent health consequences of lifestyle behaviors such as alcohol consumption.

Racial and Socioeconomic Disparities Exist in Patients Pursuing Peanut Oral Immunotherapy.

BACKGROUND: Oral immunotherapy (OIT) is a promising treatment for food allergy. Prior studies demonstrate significant differences among food allergic individuals across race, ethnicity, and socioeconomic groups. Disparities in OIT have not been evaluated. OBJECTIVE: We assessed disparities in the use of OIT in patients with peanut allergy based on race, ethnicity, and socioeconomic status at a single academic medical center. METHODS: We identified 1028 peanut allergic patients under 18 years of age receiving care in the University of Michigan food allergy clinics. 148 patients undergoing peanut OIT (treatment group) were compared to the 880 patients avoiding peanut (control group). Pertinent demographic and socioeconomic characteristics were compared. RESULTS: There were no differences in gender or ethnicity between the OIT and control groups. However, Black patients comprised 18% of the control group but only 4.1% of the OIT treatment group (p<0.0001). The proportion of patients with private insurance was significantly higher in the treatment group compared to control group, 93.2% vs 82.2% (p=0.0004). Finally, the Neighborhood Affluence Index, a Census-based measure of the relative socioeconomic prosperity of a neighborhood, was significantly higher in the OIT group vs. the control group (0.51±0.18 vs 0.47±0.19) (p=0.015), while the Neighborhood Disadvantage Index, a Census-based measure of the relative socioeconomic disadvantage of a neighborhood, was significantly lower (0.082±0.062 vs 0.10±0.093) (p=0.020). CONCLUSION: Significant racial and economic disparities exist at our institution between peanut allergic individuals who receive OIT and those who do not. Efforts to understand the basis for these disparities are important to ensure patients have equitable access to OIT.

Aire mediates tolerance to insulin through thymic trimming of high-affinity T cell clones.

Insulin is a central autoantigen in the pathogenesis of T1D, and thymic epithelial cell expression of insulin under the control of the Autoimmune Regulator (Aire) is thought to be a key component of maintaining tolerance to insulin. In spite of this general working model, direct detection of this thymic selection on insulin-specific T cells has been somewhat elusive. Here, we used a combination of highly sensitive T cell receptor transgenic models for detecting thymic selection and sorting and sequencing of Insulin-specific CD4+ T cells from Aire-deficient mice as a strategy to further define their selection. This analysis revealed a number of unique t cell receptor (TCR) clones in Aire-deficient hosts with high affinity for insulin/major histocompatibility complex (MHC) ligands. We then modeled the thymic selection of one of these clones in Aire-deficient versus wild-type hosts and found that this model clone could escape thymic negative selection in the absence of thymic Aire. Together, these results suggest that thymic expression of insulin plays a key role in trimming and removing high-affinity insulin-specific T cells from the repertoire to help promote tolerance.

Comparison of the ScreenFire and Xpert HPV assays for the detection of human papillomavirus and cervical precancer among women living with HIV in Malawi.

Background: The World Health Organization (WHO) recommends human papillomavirus (HPV) testing for primary cervical cancer screening, including among women living with HIV (WLWH). Low-and-middle-income countries (LMICs) account for 85% of the cervical cancer burden globally, yet have limited access to HPV-based screening, largely due to cost. This study aims to compare the performance of a rapid, isothermal amplification HPV assay (ScreenFire) to that of the Xpert HPV assay for the detection of HPV and cervical precancer among WLWH in Malawi. Methods: We utilized stored self- and provider-collected specimens from a prospective cohort study of WLWH in Malawi from July 2020 to February 2022. Specimens were tested with both Xpert and ScreenFire HPV assays. The overall and within-channel non-hierarchical agreement between ScreenFire and Xpert was determined for both self- and provider-collected specimens. Hierarchical ScreenFire HPV positivity by channel was compared to Xpert for each histological diagnosis - cervical intraepithelial neoplasia grade 2 or worse (CIN2+) compared to

Cadherin-11 targeted cell-specific liposomes enabled skin fibrosis treatment by inducing apoptosis.

Continuous and aberrant activation of myofibroblasts is the hallmark of pathological fibrosis (e.g., abnormal wound healing). The deposition of excessive extracellular matrix (ECM) components alters or increases the stiffness of tissue and primarily accounts for multiple organ dysfunctions. Among various proteins, Cadherin-11 (CDH11) has been reported to be overexpressed on myofibroblasts in fibrotic tissues. Anti-apoptotic proteins such as (B cell lymphoma-2) (BCL-2) are also upregulated on myofibroblasts. Therefore, we hypothesize that CDH11 could be a targeted domain for cell-specific drug delivery and targeted inhibition of BCL-2 to ameliorate the development of fibrosis in the skin. To prove our hypothesis, we have developed liposomes (LPS) conjugated with CDH11 neutralizing antibody (antiCDH11) to target cell surface CDH11 and loaded these LPS with a BCL-2 inhibitor, Navitoclax (NAVI), to induce apoptosis of CDH11 expressing fibroblasts. The developed LPS were evaluated for physicochemical characterization, stability, in vitro therapeutic efficacy using dermal fibroblasts, and in vivo therapeutic efficacy in bleomycin-induced skin fibrosis model in mice. The findings from in vitro and in vivo studies confirmed that selectivity of LPS was improved towards CDH11 expressing myofibroblasts, thereby improving therapeutic efficacy with no indication of adverse effects. Hence, this novel research work represents a versatile LPS strategy that exhibits promising potential for treating skin fibrosis.

The Effects of a Single-Session Virtual Rumination Intervention to Enhance Cognitive Functioning in Veterans With Subjective Cognitive Symptoms: Multimethod Pilot Study.

BACKGROUND: Subjective cognitive concerns (SCCs) entail perceived difficulties in thinking or memory, often reported without substantial objective evidence of cognitive impairment. These concerns are prevalent among individuals with a history of brain injuries, neurological conditions, or chronic illnesses, contributing to both psychological distress and functional limitations. They are increasingly considered to be a risk factor for future objective decline. A considerable number of individuals reporting SCCs also exhibit mental health symptoms, such as a history of trauma, depression, or anxiety. Interventions that address modifiable emotional and cognitive factors related to SCC could improve functioning and quality of life. Therefore, the use of emotion regulation strategies, especially those directed at minimizing rumination, could serve as a promising focus for interventions aimed at mitigating subjective cognitive concerns in veteran populations. OBJECTIVE: This pilot study explored the feasibility, acceptability, and preliminary efficacy of a brief, 1-session emotion regulation intervention called "Worry Less, Remember More." The Worry Less, Remember More intervention was designed to reduce rumination and improve subjective cognitive functioning in veterans with subjective cognitive changes (N=15). METHODS: We randomized 15 veterans to either the active telehealth condition or waitlist control and completed the intervention. Participants were aged between 31 and 67 (mean 49.5, SD 10.1) years, and the sample was primarily male (12/15, 83%) and White (10/15, 67%). The most common diagnoses were posttraumatic stress disorder and depression. Following the intervention, veteran input was sought through semistructured interviews with a subset of 12 participants, examining feasibility, acceptability, and perceived efficacy. Preliminary efficacy was also measured using pre- and postintervention self-report measures. RESULTS: Veterans reported that this intervention was acceptable, with 92% (11/12) of the sample reporting that they benefited from the intervention and would recommend the intervention to others with similar difficulties. Semistructured interviews revealed difficulties with feasibility, including problems with the remote consenting process, forgetting appointments, and needing additional strategies to remember to consistently use the interventions. The intervention improved self-reported cognitive symptoms on quantitative measures but did not improve self-reported rumination. CONCLUSIONS: This pilot study establishes the preliminary feasibility, acceptability, and efficacy of the Worry Less, Remember More intervention for veterans with subjective cognitive symptoms. Future iterations of the intervention may benefit from simplifying the electronic consent process, providing reminders for appointments, and incorporating compensatory cognitive strategies to assist with using the telehealth system, as well as applying the strategies learned in the intervention. While future research is needed with larger samples, including nonveteran populations, the intervention may also be a useful clinical tool to bridge care between neuropsychology clinics and mental health treatment.

Identifying and characterizing high-risk populations in pilot malaria elimination districts in Madagascar: a mixed-methods study.

BACKGROUND: In Madagascar, the districts of Antsirabe II, Faratsiho and Antsiranana I have relatively low malaria incidence rates and have been selected by the National Malaria Control Programme for pilot elimination strategies. The districts have residual transmission despite increasing coverage and quality of malaria services. This study sought to identify priority subpopulations at highest risk for malaria and collect information on intervention preferences and methods that will inform subnational tailoring of malaria service delivery. METHODS: This mixed methods study employed (i) a quantitative malaria risk factor assessment in Antsirabe II and Faratsiho comprising a test-negative frequency matched case-control study and a qualitative risk factor assessment in Antsiranana I; and (ii) a qualitative formative assessment in all three districts. For the case-control study, a mixed effects logistic regression was used with age, sex and district included as fixed effects and health facility included as a random effect. The qualitative risk factor assessment used semi-structured interview guides and key informant interviews. For the qualitative formative assessment in the three districts, a summary report was generated following semi-structured interviews and focus group discussions with high-risk populations (HRPs) and stakeholders. RESULTS: In Antsirabe II and Faratsiho districts, rice agriculture workers, outdoor/manual workers, particularly miners, and those with jobs that required travel or overnight stays, especially itinerant vendors, had higher odds of malaria infection compared to other (non-rice) agricultural workers. In Antsiranana I, respondents identified non-rice farmers, mobile vendors, and students as HRPs. Risk factors among these groups included overnight stays and travel patterns combined with a lack of malaria prevention tools. HRPs reported treatment cost and distance to the health facility as barriers to care and expressed interest in presumptive treatment and involvement of gatekeepers or people who have influence over intervention access or participation. CONCLUSIONS: The study results illustrate the value of in-depth assessments of risk behaviours, access to services and prevention tools, surveillance and prevention strategies, and the involvement of gatekeepers in shaping subnational tailoring to reach previously unreached populations and address residual transmission in elimination settings.

Barriers to Cervical Cancer Screening by Sexual Orientation Among Low-Income Women in North Carolina.

We sought to examine cervical cancer screening barriers by sexual orientation among low-income women in North Carolina. The MyBodyMyTest-3 Trial recruited low-income women (< 250% of federal poverty level) aged 25-64 years who were 1+ year overdue for cervical cancer screening. We compared perceptions of cervical cancer screening among those who self-identified as lesbian, gay, bisexual, or queer (LGBQ; n = 70) to straight/heterosexual women (n = 683). For both LGBQ and straight respondents, the greatest barriers to screening were lack of health insurance (63% and 66%) and cost (49% and 50%). LGBQ respondents were more likely than straight respondents to report forgetting to screen (16% vs. 8%, p = .05), transportation barriers (10% vs. 2%, p = .001), and competing mental or physical health problems (39% vs. 27%, p = .10). Addressing access remains important for improving cervical cancer screening among those under-screened. For LGBQ women, additional attention may be needed for reminders, co-occurring health needs, and transportation barriers.

Triage-initiated intranasal fentanyl for hip fractures in an Emergency Department - Results from introduction of an analgesic guideline.

BACKGROUND: Pain relief is a priority for patients with hip fractures who present to Emergency Departments (EDs). Intranasal fentanyl (INF) is an ideal option for nurse initiated analgesia as it does not require intravenous access and can expedite care prior to examination by a physician. LOCAL PROBLEM: Pain relief in patients with hip fractures is delayed during episodes of ED crowding. METHODS: A retrospective medical record review was conducted following introduction of an INF guideline in an adult ED in 2018. Patients were included over a 4-month period during which the guideline was introduced. Historical and concurrent control groups receiving usual care were compared to patients receiving INF. INTERVENTIONS: This quality improvement initiative investigated whether an INF analgesia at triage guideline would decrease time to analgesic administration in adults with hip fracture in ED. RESULTS: This study included 112 patients diagnosed with fractured hips of which 16 patients received INF. Background characteristics were similar between groups. Mean time to analgesic administration (53 v 110 minutes), time to x-ray (46 v 75 minutes), and ED length of stay (234 v 298 minutes) were significantly decreased in the intervention group. Inadequate documentation was a limiting factor in determining improved efficacy of analgesia. CONCLUSION: Use of triage-initiated INF significantly decreased time to analgesic administration, time to imaging and overall length of stay in ED.

Circuit mechanism underlying fragmented sleep and memory deficits in 16p11.2 deletion mouse model of autism.

Sleep disturbances are prevalent in children with autism spectrum disorder (ASD) and have a major impact on the quality of life. Strikingly, sleep problems are positively correlated with the severity of ASD symptoms, such as memory impairment. However, the neural mechanisms underlying sleep disturbances and cognitive deficits in ASD are largely unexplored. Here, we show that non-rapid eye movement sleep (NREMs) is highly fragmented in the 16p11.2 deletion mouse model of ASD. The degree of sleep fragmentation is reflected in an increased number of calcium transients in the activity of locus coeruleus noradrenergic (LC-NE) neurons during NREMs. Exposure to a novel environment further exacerbates sleep disturbances in 16p11.2 deletion mice by fragmenting NREMs and decreasing rapid eye movement sleep (REMs). In contrast, optogenetic inhibition of LC-NE neurons and pharmacological blockade of noradrenergic transmission using clonidine reverse sleep fragmentation. Furthermore, inhibiting LC-NE neurons restores memory. Rabies-mediated unbiased screening of presynaptic neurons reveals altered connectivity of LC-NE neurons with sleep- and memory regulatory brain regions in 16p11.2 deletion mice. Our findings demonstrate that heightened activity of LC-NE neurons and altered brain-wide connectivity underlies sleep fragmentation in 16p11.2 deletion mice and identify a crucial role of the LC-NE system in regulating sleep stability and memory in ASD.

Two Randomized Controlled Trials of Nudges to Encourage Referrals to Centralized Pharmacy Services for Evidence-Based Statin Initiation in High-Risk Patients: Rationale and Design of the SUPER LIPID Program.

BACKGROUND: In patients with or at risk for atherosclerotic vascular disease, statins reduce the incidence of major adverse cardiovascular events, but the majority of U.S. adults with an indication for statin therapy are not prescribed statins at guideline-recommended intensity. Clinicians' limited time to address preventative care issues is cited as one factor contributing to gaps in statin prescribing. Centralized pharmacy services can fulfill a strategic role for population health management through outreach, education, and statin prescribing for patients at elevated ASCVD risk, but best practices for optimizing referrals of appropriate patients are unknown. STUDY DESIGN AND OBJECTIVES: SUPER LIPID (NCT05537064) is a program consisting of two pragmatic clinical trials testing the effect of nudges in increasing referrals of appropriate patients to a centralized pharmacy service for lipid management, conducted within 11 primary care practices in a large community health system. In both trials, patients were eligible for inclusion if they had an assigned primary care provider (PCP) in a participating practice and were not prescribed a high- or moderate-intensity statin despite an indication, identified via an electronic health record (EHR) algorithm. Trial #1 was a stepped wedge trial, conducted at a single practice with randomization at the PCP level, of an interruptive EHR message that appeared during eligible patients' visits and facilitated referral to the pharmacy service. For the first 3 months, no PCPs received the message; for the second 3 months, half were randomly selected to receive the message; and for the last 3 months, all PCPs received the message. Trial #2 was a cluster-randomized trial conducted at 10 practices, with randomization at the practice level. Practices were randomized to usual care or to have eligible patients automatically referred to centralized pharmacy services via a referral order placed in PCPs EHR inboxes for co-signature. In both trials, when a patient was referred to centralized pharmacy services, a pharmacist reviewed the patient's chart, contacted the patient, and initiated statin therapy if the patient agreed. The primary endpoint of both trials was the proportion of patients prescribed a statin; secondary endpoints include the proportion of patients prescribed a statin at guideline-recommended intensity, the proportion of patients filling a statin prescription, and serum low-density lipoprotein level. CONCLUSIONS: SUPER LIPID is a pair of pragmatic clinical trials assessing the effectiveness of two strategies to encourage referral of appropriate patients to a centralized pharmacy service for lipid management. The trial results will develop the evidence base for simple, scalable, EHR-based strategies to integrate clinical pharmacists into population health management and increase appropriate statin prescribing. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov; NCT05537064.

The influence of home versus clinic anal human papillomavirus sampling on high-resolution anoscopy uptake in the Prevent Anal Cancer Self-Swab Study.

Background Anal cancer disproportionately affects sexual and gender minority individuals living with HIV. High-resolution anoscopy (HRA) is an in-clinic procedure to detect precancerous anal lesions and cancer, yet prospective data on factors associated with HRA attendance are lacking. We examined whether anal HPV sampling at home versus in a clinic impacts HRA uptake and assessed HRA acceptability. Methods Sexual and gender minority individuals were randomised to home-based self-sampling or clinical sampling. All were asked to attend in-clinic HRA 1year later. We regressed HRA attendance on study arm using multivariable Poisson regression and assessed HRA acceptability using χ 2 tests. Results A total of 62.8% of 196 participants who engaged in screening attended HRA. Although not significant (P =0.13), a higher proportion of participants who engaged in clinic-based screening attended HRA (68.5%) compared to home-based participants (57.9%). Overall, HRA uptake was higher among participants with anal cytology history (aRR 1.40, 95% CI 1.07-1.82), and lower among participants preferring a versatile anal sex position versus insertive (aRR 0.70, 95% CI 0.53-0.91), but did not differ by race or HIV serostatus. In the clinic arm, persons living with HIV had lower HRA attendance (42.9%) versus HIV-negative participants (73.3%) (P =0.02) and Black non-Hispanic participants had lower HRA attendance (41.7%) than White non-Hispanic participants (73.1%), (P =0.04). No differences in attendance by race or HIV status were observed in the home arm. Conclusions HRA uptake differed significantly by race and HIV status in the clinic arm but not the home arm.

Methylation patterns associated with C-reactive protein in racially and ethnically diverse populations.

Systemic low-grade inflammation is a feature of chronic disease. C-reactive protein (CRP) is a common biomarker of inflammation and used as an indicator of disease risk; however, the role of inflammation in disease is not completely understood. Methylation is an epigenetic modification in the DNA which plays a pivotal role in gene expression. In this study we evaluated differential DNA methylation patterns associated with blood CRP level to elucidate biological pathways and genetic regulatory mechanisms to improve the understanding of chronic inflammation. The racially and ethnically diverse participants in this study were included as 50% White, 41% Black or African American, 7% Hispanic or Latino/a, and 2% Native Hawaiian, Asian American, American Indian, or Alaska Native (total n = 13,433) individuals. We replicated 113 CpG sites from 87 unique loci, of which five were novel (CADM3, NALCN, NLRC5, ZNF792, and cg03282312), across a discovery set of 1,150 CpG sites associated with CRP level (p < 1.2E-7). The downstream pathways affected by DNA methylation included the identification of IFI16 and IRF7 CpG-gene transcript pairs which contributed to the innate immune response gene enrichment pathway along with NLRC5, NOD2, and AIM2. Gene enrichment analysis also identified the nuclear factor-kappaB transcription pathway. Using two-sample Mendelian randomization (MR) we inferred methylation at three CpG sites as causal for CRP levels using both White and Black or African American MR instrument variables. Overall, we identified novel CpG sites and gene transcripts that could be valuable in understanding the specific cellular processes and pathogenic mechanisms involved in inflammation.

Identification and quantification of chain-pairing variants or mispaired species of asymmetric monovalent bispecific IgG1 monoclonal antibody format using reverse-phase polyphenyl chromatography coupled electrospray ionization mass spectrometry.

Developing a knob-into-hole asymmetric bispecific IgG1 monoclonal antibody (mAb) poses manufacturing challenges due to the expression of chain pairing variants, also called mispaired species, in the desired product. The incorrect pairing of light and heavy chains could result in heterogeneous mispaired species of homodimers, heterodimers, light chain swapping, and low molecular weight species (LMWS). Standard chromatography, capillary electrophoretic, or spectroscopic methods poorly resolve these from the main variants. Here, we report a highly sensitive reverse-phase polyphenyl ultra-high-performance liquid chromatography (RP-UHPLC) method to accurately measure mispaired species of Duet mAb format, an asymmetric IgG1 bispecific mAb, for both process development and quality control analytical tests. Coupled with electrospray ionization mass spectrometry (ESI-MS), it enabled direct online characterization of mispaired species. This single direct assay detected diverse mispaired IgG-like species and LMWS. The method resolved eight disulfide bonds dissociated LMWS and three mispaired LMWS. It also resolved three different types of IgG-like mispaired species, including two homodimers and one heterodimer. The characterization and quantification simultaneously enabled the cell line selection that produces a lesser heterogeneity and lower levels of mispaired species with the desired correctly paired product. The biological activity assessment of samples with increased levels of these species quantified by the method exhibited a linear decline in potency with increasing levels of mispaired species in the desired product. We also demonstrated the utility of the technique for testing in-process intermediate materials to determine and assess downstream purification process capability in removing diverse mispaired IgG-like species and LMWS to a certain level during the downstream purification process. Our investigation demonstrates that adopting this method was vital in developing asymmetric bispecific mAb from the initial stage of cell line development to manufacturing process development. Therefore, this tool could be used in the control strategy to monitor and control mispaired species during manufacturing, thus improving the quality control of the final product.

Association analysis between an epigenetic alcohol risk score and blood pressure.

Background: Epigenome-wide association studies have revealed multiple DNA methylation sites (CpGs) associated with alcohol consumption, an important lifestyle risk factor for cardiovascular diseases. Results: We generated an alcohol consumption epigenetic risk score (ERS) based on previously reported 144 alcohol-associated CpGs and examined the association of the ERS with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension (HTN) in 3,898 Framingham Heart Study (FHS) participants. We found an association of alcohol intake with the ERS in the meta-analysis with 0.09 units higher ERS per drink consumed per day (p < 0.0001). Cross-sectional analyses in FHS revealed that a one-unit increment of the ERS was associated with 1.93 mm Hg higher SBP (p = 4.64E-07), 0.68 mm Hg higher DBP (p = 0.006), and an odds ratio of 1.78 for HTN (p < 2E-16). Meta-analysis of the cross-sectional association of the ERS with BP traits in eight independent external cohorts (n = 11,544) showed similar relationships with blood pressure levels, i.e., a one-unit increase in ERS was associated with 0.74 (p = 0.002) and 0.50 (p = 0.0006) mm Hg higher SBP and DBP, but could not confirm the association with hypertension. Longitudinal analyses in FHS (n = 3,260) and five independent external cohorts (n = 4,021) showed that the baseline ERS was not associated with a change in blood pressure over time or with incident HTN. Conclusions: Our findings provide proof-of-concept that utilizing an ERS is a useful approach to capture the recent health consequences of lifestyle behaviors such as alcohol consumption.

Outcomes of severely injured pregnant trauma patients: a multicenter analysis.

Nearly 10% of pregnant women suffer traumatic injury. Clinical outcomes for pregnant trauma patients (PTPs) with severe injuries have not been well studied. We sought to describe outcomes for PTPs presenting with severe injuries, hypothesizing that PTPs with severe injuries will have higher rates of complications and mortality compared to less injured PTPs. A post-hoc analysis of a multi-institutional retrospective study at 12 Level-I/II trauma centers was performed. Patients were stratified into severely injured (injury severity score [ISS] > 15) and not severely injured (ISS < 15) and compared with bivariate analyses. From 950 patients, 32 (3.4%) had severe injuries. Compared to non-severely injured PTPs, severely injured PTPs were of similar maternal age but had younger gestational age (21 vs 26 weeks, p = 0.009). Penetrating trauma was more common in the severely injured cohort (15.6% vs 1.4%, p < 0.001). The severely injured cohort more often underwent an operation (68.8% vs 3.8%, p < 0.001), including a hysterectomy (6.3% vs 0.3%, p < 0.001). The severely injured group had higher rates of complications (34.4% vs 0.9%, p < 0.001), mortality (15.6% vs 0.1%, p < 0.001), a higher rate of fetal delivery (37.5% vs. 6.0%, p < 0.001) and resuscitative hysterotomy (9.4% vs. 0%, p < 0.001). Only approximately 3% of PTPs were severely injured. However, severely injured PTPs had a nearly 40% rate of fetal delivery as well as increased complications and mortality. This included a resuscitative hysterotomy rate of nearly 10%. Significant vigilance must remain when caring for this population.

Estimating the size of populations at risk for malaria: a case study in cattle herders and agricultural workers in Northern Namibia.

Cattle herders and agricultural workers have been identified has key high-risk populations for malaria in northern Namibia. Population size estimates for these groups are lacking but are important for planning, monitoring and evaluating the effectiveness of targeted strategies towards malaria elimination in the region. In this analysis, we extend population size estimation methods routinely used in HIV research, specifically social mapping and multiple source capture-recapture, to the context of malaria to estimate how many cattle herders and agricultural workers lived in two regions of northern Namibia over the course of the 2019-2020 malaria season. Both methods estimated two to three times more agricultural workers than cattle herders but size estimates based on the multiple source capture-recapture method were two to three times greater than the mapping-based, highlighting important methodological considerations to apply such methods to these highly mobile populations. In particular, we compared open versus closed populations assumptions for the capture-recapture method and assessed the impact of sensitivity analyses on the procedure to link records across multiple data sources on population size estimates. Our results are important for national control programs to target their resources and consider integrating routine population size estimation of high risk populations in their surveillance activities.

A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats.

The seventh iteration of the reference genome assembly for Rattus norvegicus-mRatBN7.2-corrects numerous misplaced segments and reduces base-level errors by approximately 9-fold and increases contiguity by 290-fold compared with its predecessor. Gene annotations are now more complete, improving the mapping precision of genomic, transcriptomic, and proteomics datasets. We jointly analyzed 163 short-read whole-genome sequencing datasets representing 120 laboratory rat strains and substrains using mRatBN7.2. We defined ∼20.0 million sequence variations, of which 18,700 are predicted to potentially impact the function of 6,677 genes. We also generated a new rat genetic map from 1,893 heterogeneous stock rats and annotated transcription start sites and alternative polyadenylation sites. The mRatBN7.2 assembly, along with the extensive analysis of genomic variations among rat strains, enhances our understanding of the rat genome, providing researchers with an expanded resource for studies involving rats.