Search

Abstract 5‐Fluorouracil (5‐FU) has been used for chemotherapy for colorectal and other cancers for over 50 years. The prevailing view of its mechanism of action is inhibition of thymidine synthase leading to defects in DNA replication and repair. However, 5‐FU is also incorporated into RNA causing defects in RNA metabolism, inhibition of pseudouridine modification, and altered ribosome function. We examined the impact of 5‐FU on post‐transcriptional small RNA modifications (PTxMs) and the expression and export of RNA into small extracellular vesicles (sEVs). EVs are secreted by all cells and contain a variety of proteins and RNAs that can function in cell‐cell communication. We found that treatment of colorectal cancer (CRC) cells with 5‐FU represses sEV export of miRNA and snRNA‐derived RNAs, but promotes export of snoRNA‐derived RNAs. Strikingly, 5‐FU treatment significantly decreased the levels of pseudouridine on both cellular and sEV small RNA profiles. In contrast, 5‐FU exposure led to increased levels of cellular small RNAs containing a variety of methyl‐modified bases. These unexpected findings show that 5‐FU exposure leads to altered RNA expression, base modification, and aberrant trafficking and localization of small RNAs.

ABSTRACT Introduction We present a relationship‐centred shared‐decision‐making (RCSDM) process model to explicate factors that shape decision‐making processes during physical medicine and rehabilitation (PMR) encounters among patients, their care partners and practitioners. Existing shared decision‐making (SDM) models fall short in addressing the everyday decisions routinely made regarding persons with chronic disabilities who require high levels of support, their care partners and rehabilitation practitioners. In PMR, these everyday decisions are small scale, immediate and in service to a larger therapeutic goal. They can be thought of as micro‐decisions and involve multiple practitioners, care partners and patients. How micro‐decisions are made in this context is contingent on multiple roles and relationships among these relevant parties. Our model centres on micro‐decisions among patients, their care partners and practitioners based on our disorders of consciousness (DoC) research. Methods To develop our model, we examined peer‐reviewed literature in SDM in PMR, chronic disability and person‐centeredness; formed collaborations and co‐created our constructs with rehabilitation practitioners and with care partners who have lived experience of caring for persons with DoC; analysed emerging empirical data and vetted early versions with expert scientific and clinical audiences. Our model builds from the core tenets of relational autonomy, and scholarship and activism of disability advocates. Findings Our model conceptualizes four non‐hierarchical levels of analysis to understand the process of micro‐decision‐making in chronic disability and medical rehabilitation: social forces (historical and sociological); roles and relationships (multiple and intersecting); relational dimensions (interactional and contextual) and micro‐decision moments (initiation, response and closure). Discussion Relationships among patients, their care partners and practitioners are the intersubjective milieu within which decisions are made. Our conceptual model explicates the process of micro‐decision‐making in PMR. Patient or Public Contribution Care partners (or caregivers) and rehabilitation practitioners are active members of our team. We work together to develop research projects, collect, analyse and disseminate data. The conceptual model we present in this manuscript was co‐created—input from care partners and practitioners on previously collected data became the impetus to develop the RCSDM process model and share co‐authorship in this manuscript.

Abstract Purpose Healthy cancer survivorship involves patients' active engagement with preventative health behaviors and follow‐up care. While clinicians and patients have typically held dual responsibility for activating these behaviors, transitioning some clinician effort to technology and health coaches may enhance guideline implementation. This paper reports on the acceptability of the Shared Healthcare Actions & Reflections Electronic systems in survivorship (SHARE‐S) program, an entirely virtual multicomponent intervention incorporating e‐referrals, remotely‐delivered health coaching, and automated text messages to enhance patient self‐management and promote healthy survivorship. Methods SHARE‐S was evaluated in single group hybrid implementation‐effectiveness pilot study. Patients were e‐referred from the clinical team to health coaches for three health self‐management coaching calls and received text messages to enhance coaching. Semi‐structured qualitative interviews were conducted with 21 patient participants, 2 referring clinicians, and 2 health coaches to determine intervention acceptability (attitudes, appropriateness, suitability, convenience, and perceived effectiveness) and to identify important elements of the program and potential mechanisms of action to guide future implementation. Results SHARE‐S was described as impactful and convenient. The nondirective, patient‐centered health coaching and mindfulness exercises were deemed most acceptable; text messages were less acceptable. Stakeholders suggested increased flexibility in format, frequency, timing, and length of participation, and additional tailored educational materials. Patients reported tangible health behavior changes, improved mood, and increased accountability and self‐efficacy. Conclusions SHARE‐S is overall an acceptable and potentially effective intervention that may enhance survivors' self‐management and well‐being. Alterations to tailored content, timing, and dose should be tested to determine impact on acceptability and outcomes.

Abstract Pasteurised donor human milk is recommended for very low birthweight infants who do not have access to their mother's milk. Although the use of donor milk continues to increase, little is known about the donation experiences of milk bank donors. We aimed to describe and compare enablers, barriers and patterns of human milk donation and identify factors predicting donation volume in a convenience sample of approved milk bank donors in the United Kingdom and the United States. A cross‐sectional online survey was conducted from August 2022 to December 2022. Approved milk bank donors (n = 556) from three milk banks in the United States (n = 369, Mothers' Milk Bank of Florida, Mother's Milk Bank of North Texas and Northwest Mothers Milk Bank) and one milk bank in the United Kingdom (n = 187, Hearts Milk Bank) completed the survey. A substantial portion of donors in both settings reported participating in other forms of milk exchange (51% of U.S. donors vs. 39% of UK donors, p = 0.009). Top donation barriers reported in both settings were completing the serological screening and having enough space to store collected milk. Most donors started donating when their infant was 3 months old or older and reported donating mature milk. The most common source of information related to milk banking in each setting was the internet (United Kingdom–70% vs. United States ‐ 63%, p = 0.112). Variables that predicted lifetime donation volume differed between the United States and the United Kingdom, highlighting the importance of setting‐specific milk banking research.

Abstract Quantitative analysis of complex mixtures, including compounds having similar chemical properties, is demonstrated using an automatic and high throughput approach to microcrystal electron diffraction (MicroED). Compositional analysis of organic and inorganic compounds can be accurately executed without the need of diffraction standards. Additionally, with sufficient statistics, small amounts of compounds in mixtures can be reliably detected. These compounds can be distinguished by their crystal structure properties prior to structure solution. In addition, if the crystals are of good quality, the crystal structures can be generated on the fly, providing a complete analysis of the sample. MicroED is an effective method for analyzing the structural properties of sub‐micron crystals, which are frequently found in small‐molecule powders. By developing and using an automatic and high throughput approach to MicroED, and with the use of SerialEM for data collection, data from thousands of crystals allow sufficient statistics to detect even small amounts of compounds reliably.

Abstract Where a mother's own milk is not available or is insufficient, donor human milk (DHM) processed by a human milk bank (HMB) is the recommended next best alternative. HMBs exist in over 65 countries. However, most countries have yet to establish national policies or programmes that support the provision of DHM. In July 2019, a group of international experts in fields relevant to human milk banking gathered at a meeting organised by the Institute of Biomedical Ethics, University of Zurich, and co‐sponsored by the World Health Organisation. Prompted by the growing interest globally in creating and sustaining HMBs and addressing current safety and ethical concerns and standards, the aims of the meeting were to define knowledge gaps, determine the need for and scope of global guidelines and provide recommendations on steps that need to be taken at the international level. Following wide‐ranging discussions that included the integration of milk banks into health care systems, strategy and policy, quality and safety, the use of DHM and associated ethical considerations, the overall conclusion of the meeting was that in the absence of global recommendations on the implementation, operation and regulation of HMBs, evidence‐based guidance is urgently needed.

Abstract This paper explores the legislative and operational commonalities and differences in Medical Products of Human Origin (MPHO) programs, including blood, hematopoietic cells, tissues and reproductive cells and human milk banking. The analysis includes ethical principles in donation and utilization, policies and legislation, public awareness and education, registries, guidelines in donor selection, safety and quality assurance, operational models and funding, infrastructure and human resources and biovigilance and evaluation of outcomes. Unlike other MPHO, the need for donor human milk (DHM) may be greatly reduced, that is, by ensuring optimal support for maternal lactation and breastfeeding. This should not be lost in the drive for wider and improved service provision. Nevertheless, increased overall demand for DHM is expected as a result of forthcoming international recommendations and also its increased use as the first‐choice supplement to a mother's own milk both within and beyond preterm, low‐birthweight and sick infant populations. Insight into current human milk banking highlights differences and gaps in practices that can benefit from further exploration and harmonization. Strong similarities with the ethical and operational principles underpinning donation and processing of the diverse MPHO suggest that legislating human milk banks within similar MPHO frameworks may bring additional safety and facilitate improved product quality. Moreover, that MPHO‐inspired models operating within attainable regulatory requirements may contribute to sustainable human milk banking activity and growth.

Key Clinical Message While intermittent hemodialysis (HD) is the most efficient method of removing lithium in patients with lithium toxicity, continuous renal replacement therapy is an acceptable alternative in the setting of intradialytic hypotension. This form of dialysis can reduce the need for vasopressors during HD, which increases mortality.

Abstract Background Traditionally, weight loss (WL) trials utilize dual energy X‐ray absorptiometry (DXA) to measure lean mass. This method assumes lean mass, as the sum of all non‐bone and non‐fat tissue, is a reasonable proxy for muscle mass. In contrast, the D3‐creatine (D3Cr) dilution method directly measures whole body skeletal muscle mass, although this method has yet to be applied in the context of a geriatric WL trial. The purpose of this project was to (1) describe estimates of change and variability in D3Cr muscle mass in older adults participating in an intentional WL intervention and (2) relate its change to other measures of body composition as well as muscle function and strength. Methods The INVEST in Bone Health trial (NCT04076618), used as a scaffold for this ancillary pilot project, is a three‐armed, 12‐month randomized, controlled trial designed to determine the effects of resistance training or weighted vest use during intentional WL on a battery of musculoskeletal health outcomes among 150 older adults living with obesity. A convenience sample of 24 participants (n = 8/arm) are included in this analysis. At baseline and 6 months, participants were weighed, ingested a 30 mg D3Cr tracer dose, provided a fasted urine sample 3–6 days post‐dosage, underwent DXA (total body fat and lean masses, appendicular lean mass) and computed tomography (mid‐thigh and trunk muscle/intermuscular fat areas) scans, and performed 400‐m walk, stair climb, knee extensor strength, and grip strength tests. Results Participants were older (68.0 ± 4.4 years), mostly White (75.0%), predominantly female (66.7%), and living with obesity (body mass index: 33.8 ± 2.7 kg/m2). Six month total body WL was −10.3 (95% confidence interval, CI: −12.7, −7.9) kg. All DXA and computed tomography‐derived body composition measures were significantly decreased from baseline, yet D3Cr muscle mass did not change [+0.5 (95% CI: −2.0, 3.0) kg]. Of muscle function and strength measures, only grip strength significantly changed [+2.5 (95% CI: 1.0, 4.0) kg] from baseline. Conclusions Among 24 older adults, significant WL with or without weighted vest use or resistance training over a 6‐month period was associated with significant declines in all bioimaging metrics, while D3Cr muscle mass and muscle function and strength were preserved. Treatment assignment for the trial remains blinded; therefore, full interpretation of these findings is limited. Future work in this area will assess change in D3Cr muscle mass by parent trial treatment group assignment in all study participants.

Abstract This study evaluated the effect of the Certified Child Life Specialist (CCLS) on pediatric pain and pain management during routine immunization administration in the pediatric primary care clinic. Children 4–12 years of age (n = 125) presenting for a well child physical examination at a rural primary care clinic were selected to receive standard nursing care or standard nursing care plus CCLS support during routine immunization administration. Patient reported pain was measured using the Faces Pain Scale‐Revised (FPS‐R), and patient behavioral responses were measured during immunization administration using the Children's Emotional Manifestation Scale (CEMS). The performance of psychosocial interventions and administration of topical pain‐relieving interventions were measured between both groups. CCLS support was associated with fewer negative emotional behaviors during immunization administration among 7‐ to 12‐year‐old children and a significantly higher provision of psychosocial interventions and topical pain‐relieving interventions among all ages. This study demonstrates that the presence of a CCLS can increase the provision of psychosocial and pain‐relieving interventions and reduce distress during immunization administration in a busy pediatric primary care clinic.

Abstract The Veterans Affairs (VA) medical centers provide care for millions of Veterans at high risk of cardiovascular disease and accurate BP measurement in this population is vital for optimal BP control. Few studies have examined terminal digit preference (TDP), a marker of BP measurement bias, clinician perceptions of BP measurement, and BP control in VA medical centers. This mixed methods study examined BP measurements from Veterans aged 18 to 85 years with hypertension and a primary care visit within 8 VA medical centers. TDP for all clinic BP measurements was examined using a goodness of fit test assuming 10% frequency for each digit. Interviews were also conducted with clinicians from 3 VA medical centers to assess perceptions of BP measurement. The mean age of the 98,433 Veterans (93% male) was 68.5 years (SD 12.7). BP was controlled (

Abstract Introduction Initial cancer survivorship care planning efforts focused on information sharing demonstrated limited impact on patient health outcomes. We designed the Shared Healthcare Actions & Reflections Electronic Systems in survivorship (SHARE‐S) program to enhance survivorship guideline implementation by transitioning some effort from clinicians to technology and patients through supporting health self‐management (e.g., healthy lifestyles). Methods We conducted a single‐group hybrid implementation‐effectiveness pilot study. SHARE‐S incorporated three strategies: (1) e‐referral from the clinical team for patient engagement, (2) three health self‐management coach calls, and (3) text messages to enhance coaching. Our primary implementation measure was the proportion of patients e‐referred who enrolled (target >30%). Secondary implementation measures assessed patient engagement. We also measured effectiveness by describing changes in patient health outcomes. Results Of the 118 cancer survivor patients e‐referred, 40 engaged in SHARE‐S (proportion enrolled = 34%). Participants had a mean age of 57.4 years (SD = 15.7), 73% were female, 23% were Black/African American, and 5 (12.5%) were from a rural location. Patient‐level adherence to coach calls was >90%. Changes from baseline to follow‐up showed at least a small effect (Cohen's d = 0.2) for improvements in: mindful attention, alcohol use, physical activity, fruit and vegetable intake, days of mindfulness practice, depressive symptoms, ability to participate in social roles and activities, cancer‐specific quality of life, benefits of having cancer, and positive feelings. Conclusion The SHARE‐S program successfully engaged cancer survivor patients. Once enrolled, patients showed promising improvements in health outcomes. Supporting patient self‐management is an important component of optimizing delivery of cancer survivorship care.

Objective The study objective was to prioritize topics for future patient‐centered research to increase uptake of common vaccines, such as for pneumococcal pneumonia, influenza, herpes zoster, human papillomavirus, and severe acute respiratory syndrome coronavirus 2, among adults living with autoimmune conditions. Methods A steering committee (SC) was formed that included clinicians, patients, patient advocates, and researchers associated with rheumatic diseases (psoriatic arthritis, rheumatoid arthritis, vasculitis), inflammatory bowel disease, and multiple sclerosis. Through a scoping review and discussions, SC members identified research topics regarding vaccine uptake and/or hesitancy for prioritization. A larger multistakeholder alliance that included patients and patient advocates, clinicians, researchers, policy makers, regulators, and vaccine manufacturers conducted a modified Delphi exercise online with three rating rounds and one ranking round. Frequency analysis and comparisons across stakeholder groups were conducted. A weighted ranking score was generated for each item in the ranking round for final prioritization. Results Through the Delphi process, 33 research topics were identified, of which 13 topics were rated as critical by more than 70% of all stakeholders (n = 31). The two highest ranked critical topics per the full stakeholder group were “How well a vaccine works for adults with autoimmune conditions” and “How beliefs about vaccine safety affect vaccine uptake.” Conclusion A multistakeholder group identified key topics as critically important priorities for future research to decrease vaccine hesitancy and improve uptake of vaccines for adults with autoimmune conditions.

Abstract Introduction Polypharmacy is a growing phenomenon associated with adverse effects in older adults. We assessed the potential confounding effects of cumulative anticholinergic burden (ACB) in patients who were hospitalized with falls. Methods A noninterventional, prospective cohort study of unselected, acute admissions aged ≥ 65 years. Data were derived from electronic patient health records. Results were analyzed to determine the frequency of polypharmacy and degree of ACB and their relationship to falls risk. Primary outcomes were polypharmacy, defined as prescription of 5 or more regular oral medications, and ACB score. Key Results Four hundred eleven (411) consecutive subjects were included, mean age 83.8 ± 8.0 years: 40.6% men. There were 38.4% patients who were admitted with falls. Incidence of polypharmacy was 80.8%, (88.0% and 76.3% among those admitted with and without fall, respectively). Incidence of ACB score of 0, 1, 2, ≥ 3 was 38.7%, 20.9%, 14.6%, and 25.8%, respectively. On multivariate analysis, age [odds ratio (OR) = 1.030, 95% CI:1.000 ~ 1.050, P = 0.049], ACB score (OR = 1.150, 95% CI:1.020 ~ 1.290, P = 0.025), polypharmacy (OR = 2.140, 95% CI:1.190 ~ 3.870, P = 0.012), but not Charlson Comorbidity Index (OR = 0.920, 95% CI:0.810 ~ 1.040, P = 0.172) were significantly associated with higher falls rate. Of patients admitted with falls, 29.8% had drug‐related orthostatic hypotension, 24.7% had drug‐related bradycardia, 37.3% were prescribed centrally acting drugs, and 12.0% were taking inappropriate hypoglycemic agents. Conclusion Polypharmacy results in cumulative ACB and both are significantly associated with falls risk in older adults. The presence of polypharmacy and each unit rise in ACB score have a stronger effect of increasing falls risk compared to age and comorbidities.

Abstract Aim To describe adults' health‐related experiences with chronic cough. Design Survey and interviews. Methods Participants completed questionnaires and interviews, to explore chronic cough's impact and management. Data Sources Patients aged 18–85 years with at least three cough‐related encounters within 56–120 days. Results Forty‐one patients were surveyed. Mean cough severity was 4.5 (scale 0–9). Chronic cough‐related problems included embarrassment (66%), fatigue (56%), and anxiety or depression (49%). Testing was judged insufficient by 44%. Only 28% were satisfied with treatment; 20% reported abandoning treatment due to ineffectiveness. Interview themes (N = 30) included frustration with diagnostic uncertainty, and feelings of therapeutic futility. Some reported psychological distress. Work and socializing were commonly disrupted. Conclusion Diagnostic uncertainty, perceived limitations of testing, and treatment failures suggest needs for better approaches to evaluating and treating chronic cough. Special attention to identifying and addressing mental health issues appears warranted.

Mobile devices (e.g., tablets and smartphones) have been rapidly integrated into the lives of children and have impacted how children engage with digital media. The portability of these devices allows for sporadic, on-demand interaction, reducing the accuracy of self-report estimates of mobile device use. Passive sensing applications objectively monitor time spent on a given device but are unable to identify who is using the device, a significant limitation in child screen time research. Behavioral biometric authentication, using embedded mobile device sensors to continuously authenticate users, could be applied to address this limitation. This study examined the preliminary accuracy of machine learning models trained on iPad sensor data to identify the unique user of the device in a sample of children ages 6 to 11. Data was collected opportunistically from nine participants (8.2 ± 1.75 years, 5 female) in the sedentary portion of two semistructured physical activity protocols. SensorLog was downloaded onto study iPads and collected data from the accelerometer, gyroscope, and magnetometer sensors while the participant interacted with the iPad. Five machine learning models, logistic regression (LR), support vector machine, neural net (NN), k-nearest neighbors (k-NN), and random forest (RF), were trained using 57 features generated from the sensor output to perform multiclass classification. A train-test split of 80%–20% was used for model fitting. Model performance was evaluated using F1 score, accuracy, precision, and recall. Model performance was high, with F1 scores ranging from 0.75 to 0.94. RF and k-NN had the highest performance across metrics, with F1 scores of 0.94 for both models. This study highlights the potential of using existing mobile device sensors to continuously identify the user of a device in the context of screen time measurement. Future research should explore the performance of this technology in larger samples of children and in free-living environments.

Abstract Human milk (HM) is a highly evolutionary selected, complex biofluid, which provides tailored nutrition, immune system support and developmental cues that are unique to each maternal–infant dyad. In the absence of maternal milk, the World Health Organisation recommends vulnerable infants should be fed with screened donor HM (DHM) from a HM bank (HMB) ideally embedded in local or regional lactation support services. However, demand for HM products has arisen from an increasing awareness of the developmental and health impacts of the early introduction of formula and a lack of prioritisation into government‐funded and nonprofit milk banking and innovation. This survey of global nonprofit milk bank leaders aimed to outline the trends, commonalities and differences between nonprofit and for‐profit HM banking, examine strategies regarding the marketing and placement of products to hospital and public customers and outline the key social, ethical and human rights concerns. The survey captured information from 59 milk bank leaders in 30 countries from every populated continent. In total, five companies are currently trading HM products with several early‐stage private milk companies (PMCs). Products tended to be more expensive from PMC than HMB, milk providers were financially remunerated and lactation support for milk providers and recipients was not a core function of PMCs. Current regulatory frameworks for HM vary widely, with the majority of countries lacking any framework, and most others placing HM within food legislation, which does not include the support and care of milk donors and recipient prioritisation. Regulation as a Medical Product of Human Origin was only in place to prevent the sale of HM in four countries; export and import of HM was banned in two countries. This paper discusses the safety and ethical concerns raised by the commodification of HM and the opportunities policymakers have globally and country‐level to limit the potential for exploitation and the undermining of breastfeeding.

Abstract The nutritional adequacy of human milk (HM) from vegan/vegetarian mothers has been a matter of debate, and a variety of recommendations regarding the eligibility of these mothers as human milk donors exists. According to the latest evidence, HM from vegans/vegetarians is similar in its composition to that from omnivores, however, some differences may be observed regarding vitamin B12 and omega‐3 fatty acids concentrations. Maternal supplementation of these compounds has been proven effective in increasing their HM concentration. With this survey, we aimed to explore the practices currently in use in European human milk banks (HMBs) regarding potential donors following vegan/vegetarian diets. The online survey was distributed to European HMBs between January and July 2022. A total of 188 HMBs were contacted, and 118 replied (response rate 63%). Vegan and vegetarian mothers were recommended supplements of vitamin B12 to be accepted as donors in 27% and 26% of HMBs, respectively. Additional omega‐3 fatty acid supplementation was required in 8% HMBs. In the remaining HMBs, these mothers were either systematically excluded or included regardless of supplementation. The dosage of the recommended supplements was extremely variable. Fifty‐one percent of HMBs were following recommendations to guide their practice, national or local recommendations mainly. Great variability in European HMBs practices towards potential donors following vegan/vegetarian diets exists. Some of these practices can result in loss of donors and/or in potential nutritional deficiencies. Standardised evidence‐based recommendations on this issue and their implementation in daily HMB practice are needed.

Abstract Understanding the costs and benefits of climate change mitigation and adaptation options is crucial to justify and prioritize future decarbonization pathways to achieve net zero. Here, we quantified the co‐benefits of decarbonization for air quality and public health under scenarios that aim to limit end‐of‐century warming to 2°C and 1.5°C. We estimated the mortality burden attributable to ambient PM2.5 exposure using population attributable fractions of relative risk, incorporating projected changes in population demographics. We found that implementation of decarbonization scenarios could produce substantial global reductions in population exposure to PM2.5 pollution and associated premature mortality, with maximum health benefits achieved in Asia around mid‐century. The stringent 1.5ºC‐compliant decarbonization scenario (SSP1‐1.9) could reduce the PM2.5‐attributable mortality burden by 29% in 2050 relative to a middle‐of‐the‐road scenario (SSP2‐4.5), averting around 2.9 M annual deaths worldwide. While all income groups were found to benefit from improved air quality through a combination of decarbonization and air pollution controls, the smallest health benefits are experienced by the low‐income population. The disparity in PM2.5 exposure across income groups is projected to reduce by 2100, but a 30% disparity between high‐ and low‐income groups persists even in the strongest mitigation scenario. Further, without additional and targeted air quality measures, low‐ and lower‐middle‐income populations (predominantly in Africa and Asia) will continue to experience PM2.5 exposures that are over three times the World Health Organization Air Quality Guideline.

Abstract Extracellular vesicle (EV)‐carried miRNAs can influence gene expression and functional phenotypes in recipient cells. Argonaute 2 (Ago2) is a key miRNA‐binding protein that has been identified in EVs and could influence RNA silencing. However, Ago2 is in a non‐vesicular form in serum and can be an EV contaminant. In addition, RNA‐binding proteins (RBPs), including Ago2, and RNAs are often minor EV components whose sorting into EVs may be regulated by cell signaling state. To determine the conditions that influence detection of RBPs and RNAs in EVs, we evaluated the effect of growth factors, oncogene signaling, serum, and cell density on the vesicular and nonvesicular content of Ago2, other RBPs, and RNA in small EV (SEV) preparations. Media components affected both the intravesicular and extravesicular levels of RBPs and miRNAs in EVs, with serum contributing strongly to extravesicular miRNA contamination. Furthermore, isolation of EVs from hollow fiber bioreactors revealed complex preparations, with multiple EV‐containing peaks and a large amount of extravesicular Ago2/RBPs. Finally, KRAS mutation impacts the detection of intra‐ and extra‐vesicular Ago2. These data indicate that multiple cell culture conditions and cell states impact the presence of RBPs in EV preparations, some of which can be attributed to serum contamination.

Abstract Diffuse large B‐cell lymphoma (DLBCL) arising in the spleen, also known as primary splenic DLBCL (PS‐DLBCL), is a rare form of malignant lymphoma. It is defined as a lymphoma confined to the spleen or involving splenic hilar lymph nodes. Here we report a case of PS‐DLBCL with CD30. The patient was a 62‐year‐old who presented with 2 weeks of left flank pain, chills, and abdominal distension. Computed tomography identified an 8‐cm splenic mass with central necrosis interpreted as an abscess. A drain was placed, yielding purulent necrotic material; cytologically, only neutrophils were identified. However, purulent drainage continued for 28 days without resolution, prompting splenectomy. Pathological dissection revealed a multinodular mass with central necrosis. Microscopic examination revealed extensive karyorrhexis, abundant ghosts of large cells, and scattered large cells with pleomorphic, multilobated, and vesicular nuclei with moderately abundant cytoplasm. Immunohistochemical staining revealed large, atypical cells positive for CD20, CD30, CD45, PAX5, MYC (>40%), MUM1 (>30%), and p53 (focally). The large cells were negative for CD3 (polyclonal), CD4, CD5, CD8, CD10, CD15, CD34, BCL2, BCL6, AE1/AE3, S100, HHV8, and ALK. The Ki‐67 proliferation rate was approximately 80% in large cells. Notably, this PS‐DLBCL was positive for CD30, an unusual finding among non‐Hodgkin B‐cell lymphomas, which, coupled with the Reed‐Sternberg‐like morphology, raised the possibility of classic Hodgkin lymphoma. Therefore, we reviewed the literature to confirm the unique features of this large B‐cell lymphoma, its abscess‐like appearance, and its expression of CD30.

Abstract The use of donor human milk (DHM) where there is a shortfall of maternal milk can benefit both infant and maternal outcomes but DHM supply is not always assured. This study aimed to understand current DHM usage in UK neonatal units and potential future demand to inform service planning. An online survey was disseminated to all UK neonatal units using Smart Survey or by telephone between February and April 2022 after development alongside neonatal unit teams. Surveys were completed by 55.4% of units (108/195) from all 13 Operational Delivery Networks. Only four units reported not using DHM, and another two units only if infants are transferred on DHM feeds. There was marked diversity in DHM implementation and usage and unit protocols varied greatly. Five of six units with their own milk bank had needed to source milk from an external milk bank in the last year. Ninety units (84.9%) considered DHM was sometimes (n = 35) or always (n = 55) supportive of maternal breastfeeding, and three units (2.9%) responded that DHM was rarely supportive of breastfeeding. Usage was predicted to increase by 37 units (34.9%), and this drive was principally a result of parental preference, clinical trials and improved evidence. These findings support the assumption that UK hospital DHM demand will increase after updated recommendations from the World Health Organization (WHO) and the British Association of Perinatal Medicine. These data will assist service delivery planning, underpinned by an ongoing programme of implementation science and training development, to ensure future equity of access to DHM nationally.

Abstract Premise Field images are important sources of information for research in the natural sciences. However, images that lack photogrammetric scale bars, including most iNaturalist observations, cannot yield accurate trait measurements. We introduce FieldPrism, a novel system of photogrammetric markers, QR codes, and software to automate the curation of snapshot vouchers. Methods and Results Our photogrammetric background templates (FieldSheets) increase the utility of field images by providing machine‐readable scale bars and photogrammetric reference points to automatically correct image distortion and calculate a pixel‐to‐metric conversion ratio. Users can generate a QR code flipbook derived from a specimen identifier naming hierarchy, enabling machine‐readable specimen identification for automatic file renaming. We also developed FieldStation, a Raspberry Pi–based mobile imaging apparatus that records images, GPS location, and metadata redundantly on up to four USB storage devices and can be monitored and controlled from any Wi‐Fi connected device. Conclusions FieldPrism is a flexible software tool designed to standardize and improve the utility of images captured in the field. When paired with the optional FieldStation, researchers can create a self‐contained mobile imaging apparatus for quantitative trait data collection.

Abstract Premise Quantitative plant traits play a crucial role in biological research. However, traditional methods for measuring plant morphology are time consuming and have limited scalability. We present LeafMachine2, a suite of modular machine learning and computer vision tools that can automatically extract a base set of leaf traits from digital plant data sets. Methods LeafMachine2 was trained on 494,766 manually prepared annotations from 5648 herbarium images obtained from 288 institutions and representing 2663 species; it employs a set of plant component detection and segmentation algorithms to isolate individual leaves, petioles, fruits, flowers, wood samples, buds, and roots. Our landmarking network automatically identifies and measures nine pseudo‐landmarks that occur on most broadleaf taxa. Text labels and barcodes are automatically identified by an archival component detector and are prepared for optical character recognition methods or natural language processing algorithms. Results LeafMachine2 can extract trait data from at least 245 angiosperm families and calculate pixel‐to‐metric conversion factors for 26 commonly used ruler types. Discussion LeafMachine2 is a highly efficient tool for generating large quantities of plant trait data, even from occluded or overlapping leaves, field images, and non‐archival data sets. Our project, along with similar initiatives, has made significant progress in removing the bottleneck in plant trait data acquisition from herbarium specimens and shifted the focus toward the crucial task of data revision and quality control.

Abstract Introduction This study aimed to establish the indices of responsiveness for the Coma/Near‐Coma (CNC) scale without (8 items) and with (10 items) pain test stimuli. A secondary purpose was to examine whether the CNC 8 items and 10 items differ when detecting change in neurobehavioral function. Methods We analyzed CNC data from three studies of participants with disorders of consciousness: one observational study and two intervention studies. We generated Rasch person measures using the CNC 8 items and CNC 10 items for each participant at two time points 14 ± 2 days apart using Rasch Measurement Theory. We calculated the distribution‐based minimal clinically important difference (MCID) and minimal detectable change using 95% confidence intervals (MDC95). Results We used the Rasch transformed equal‐interval scale person measures in logits. For the CNC 8 items: Distribution‐based MCID 0.33 SD = 0.41 logits and MDC95 = 1.25 logits. For the CNC 10 items: Distribution‐based MCID 0.33 SD = 0.37 logits and MDC95 = 1.03 logits. Twelve and 13 participants made a change beyond measurement error (MDC95) using the CNC 8‐item and 10‐item scales, respectively. Conclusion Our preliminary evidence supports the clinical and research utility of the CNC 8‐item scale for measuring the responsiveness of neurobehavioral function, and that it demonstrates comparable responsiveness to the CNC 10‐item scale without administering the two pain items. The distribution‐based MCID can be used to evaluate group‐level changes while the MDC95 can support clinical, data‐driven decisions about an individual patient.

Abstract Background Despite robust weight loss and cardiometabolic benefit, lean mass loss following sleeve gastrectomy (SG) confers health risk. Bisphosphonates are a potential therapeutic agent for lean mass maintenance. Thus, our objective was to explore the effect of 6 months of risedronate (vs. placebo) on change in dual‐energy x‐ray absorptiometry (DXA)‐ and computed tomography (CT)‐derived lean mass metrics in the year following SG. Methods Twenty‐four SG patients were randomized to 6 months of 150‐mg oral risedronate or placebo capsules (NCT03411902). Body composition was assessed at baseline and 6 months with optional 12‐month follow‐up using whole‐body DXA and CT at the lumbar spine and mid‐thigh. Group treatment effects and 95% confidence intervals (CIs) were generated from a mixed model using contrast statements at 6 and 12 months, adjusted for baseline values. Results Of 24 participants enrolled [55.7 ± 6.7 years (mean ± SD), 79% Caucasian, 83% women, body mass index (BMI) 44.7 ± 6.3 kg/m2], 21 returned for 6‐month testing and 14 returned for 12‐month testing. Six‐month weight loss was −16.3 kg (−20.0, −12.5) and −20.9 kg (−23.7, −18.1) in the risedronate and placebo groups, respectively (P = 0.057). Primary analysis at 6 months revealed a non‐significant sparing of appendicular lean mass in the risedronate group compared with placebo [−1.2 kg (−2.3, −0.1) vs. −2.1 kg (−3.0, −1.2)]; P = 0.20. By 12 months, the risedronate group displayed no change in appendicular lean mass from baseline [−0.5 kg (−1.5, 0.6)]; however, the placebo group experienced significantly augmented loss [−2.9 kg (−3.6, −2.1)]. Conclusions Pilot data indicate that risedronate treatment may mitigate appendicular lean mass loss following SG. Further study is warranted.

Abstract Background Psychological distress is associated with worsening symptoms during the active treatment period and lower quality of life in women with early‐stage breast cancer. Many studies have indicated risk for heightened psychological distress across the breast cancer trajectory. Purpose The aim of this review is to examine the literature for instruments used to measure psychological distress among women with breast cancer during chemotherapy. Methods This study used the Arksey and O’Malley framework of scoping reviews. Two databases, PubMed & CINAHL, were searched for peer‐reviewed original articles that were published within the last ten years, included participants with a diagnosis of breast cancer stages I to III, and receiving chemotherapy, English text articles, and studies that report psychological distress measures. Findings The initial screening yielded 529 relevant studies. After applying the exclusion criteria, a total of 17 studies concerning the assessment of psychological distress during chemotherapy were retained for the analysis of variables and measures of psychological distress. The instruments used to measure psychological distress varied, with a total of 21 measures. The most frequently utilized measure was the Hospital Anxiety and Depression Scale (n = 5), followed by the Impact of Event Scale (n = 2), the Distress Thermometer (n = 2), and the Perceived Stress Scale (n = 2). Conclusion This review identified the gaps related to inconsistencies in the operationalization and instruments used to measure psychological distress among breast cancer survivors during chemotherapy. Standardization of measures assessing psychological distress, along with conceptual clarity, is essential for measuring distress in research and clinical practice.

Abstract The movement of bacterial and viral pathogens through soil and vadose zone and subsequently into groundwater is a major public health concern. There are relatively few studies on the transport and fate of microbes through variably saturated vadose zone media compared with their transport in the soil and saturated groundwater zones. In this study, we investigated the transport of Escherichia coli, F‐RNA bacteriophage MS2, and a conservative solute tracer bromide through three intact vadose zone cores, under saturated (discharge rate ∼100 mm h−1) and unsaturated (discharge rate 10 and 0.5 mm h−1) flow conditions. The vadose zone media were sandy gravel overlying a sand lens in core 1, a heterogeneous SG mix in core 2, and SG with an open framework gravel lens through the middle of the core in core 3. The three flow regimes resulted in different transport characteristics through each of the cores. As expected, microbial transport through all cores was higher under saturated conditions, compared with unsaturated conditions. Overall, E. coli removal was consistently greater than that of MS2 phage irrespective of core media or flow conditions. There were relatively minor removals (factors of 1–2.5) of both microbes under saturated conditions, reductions of 2–3 orders of magnitude under the high flow unsaturated conditions, and almost complete removal (4 to >5 orders of magnitude) under the low flow unsaturated conditions. The much greater removal of microbes under unsaturated conditions has significant implications and potential benefits for land management decisions.

Abstract A critical step to evaluate the potential in vivo antiviral activity of a drug is to connect the in vivo exposure to its in vitro antiviral activity. The Anti–SARS‐CoV‐2 Repurposing Drug Database is a database that includes both in vitro anti–SARS‐CoV‐2 activity and in vivo pharmacokinetic data to facilitate the extrapolation from in vitro antiviral activity to potential in vivo antiviral activity for a large set of drugs/compounds. In addition to serving as a data source for in vitro anti–SARS‐CoV‐2 activity and in vivo pharmacokinetic information, the database is also a calculation tool that can be used to compare the in vitro antiviral activity with in vivo drug exposure to identify potential anti–SARS‐CoV‐2 drugs. Continuous development and expansion are feasible with the public availability of this database.

Abstract Changes in species distributions and disturbances have complex impacts on ecosystem functioning. In many subtropical coastal wetlands, plant identity and cover are changing, as salt marshes dominated by low‐stature herbaceous species transition to woody mangroves. These systems are also subject to frequent and potentially more intense hurricanes, which can alter a range of ecosystem structures and functions. We examined how changes in dominant plant species affected carbon processing in coastal wetlands following a hurricane. We experimentally manipulated cell‐scale (3 × 3 m) cover of black mangroves (Avicennia germinans) and salt marsh plants (e.g., Spartina alterniflora and Batis maritima) in fringe and interior locations of 10 plots (24 × 42 m) to create a gradient in mangrove cover in coastal Texas, USA. Hurricane Harvey made direct landfall over our site on 25 August 2017, uniformly decreasing soil nutrients and impacting the spatial patterns of total soil sulfide accumulation (δ34S). To test how mangrove cover affected carbon processing and retention after the hurricane, we measured litter breakdown rates (k) of A. germinans and S. alterniflora in surface soils and associated microbial respiration rates, and fast‐ and slow‐decomposing standard litter substrates (green and red tea, respectively) in subsurface soils (15 cm depth). Soil temperatures were lower in mangrove than marsh cells, and A. germinans litter k increased linearly with plot‐level mangrove cover. Breakdown rates of S. alterniflora and fast‐decomposing green tea litter increased nonlinearly with mangrove cover (highest k at intermediate % cover). Slow‐decomposing red tea had similar k in all plots and was highest where soil δ34S was greatest. Microbial respiration rates (R) did not change with plot‐level mangrove cover for either S. alterniflora or A. germinans litter. Respiration associated with S. alterniflora litter was highest in interior marsh cells, and R associated with A. germinans litter was similar between fringe and interior mangrove cells. Despite widespread declines in soil nutrient concentrations and increases in δ34S, all predicted to decrease R and k, post‐hurricane carbon processing increased with mangrove cover in coastal wetlands. Our results indicate that disturbances can reduce local plant identity effects and may enhance carbon loss.