Electric vehicle battery chemistry affects supply chain disruption vulnerabilities.

We examine the relationship between electric vehicle battery chemistry and supply chain disruption vulnerability for four critical minerals: lithium, cobalt, nickel, and manganese. We compare the nickel manganese cobalt (NMC) and lithium iron phosphate (LFP) cathode chemistries by (1) mapping the supply chains for these four materials, (2) calculating a vulnerability index for each cathode chemistry for various focal countries and (3) using network flow optimization to bound uncertainties. World supply is currently vulnerable to disruptions in China for both chemistries: 80% [71% to 100%] of NMC cathodes and 92% [90% to 93%] of LFP cathodes include minerals that pass through China. NMC has additional risks due to concentrations of nickel, cobalt, and manganese in other countries. The combined vulnerability of multiple supply chain stages is substantially larger than at individual steps alone. Our results suggest that reducing risk requires addressing vulnerabilities across the entire battery supply chain.

KARR-seq reveals cellular higher-order RNA structures and RNA-RNA interactions.

RNA fate and function are affected by their structures and interactomes. However, how RNA and RNA-binding proteins (RBPs) assemble into higher-order structures and how RNA molecules may interact with each other to facilitate functions remain largely unknown. Here we present KARR-seq, which uses N3-kethoxal labeling and multifunctional chemical crosslinkers to covalently trap and determine RNA-RNA interactions and higher-order RNA structures inside cells, independent of local protein binding to RNA. KARR-seq depicts higher-order RNA structure and detects widespread intermolecular RNA-RNA interactions with high sensitivity and accuracy. Using KARR-seq, we show that translation represses mRNA compaction under native and stress conditions. We determined the higher-order RNA structures of respiratory syncytial virus (RSV) and vesicular stomatitis virus (VSV) and identified RNA-RNA interactions between the viruses and the host RNAs that potentially regulate viral replication.

Direct RNA sequencing coupled with adaptive sampling enriches RNAs of interest in the transcriptome.

Abundant cellular transcripts occupy most of the sequencing reads in the transcriptome, making it challenging to assay for low-abundant transcripts. Here, we utilize the adaptive sampling function of Oxford Nanopore sequencing to selectively deplete and enrich RNAs of interest without biochemical manipulation before sequencing. Adaptive sampling performed on a pool of in vitro transcribed RNAs resulted in a net increase of 22-30% in the proportion of transcripts of interest in the population. Enriching and depleting different proportions of the Candida albicans transcriptome also resulted in a 11-13.5% increase in the number of reads on target transcripts, with longer and more abundant transcripts being more efficiently depleted. Depleting all currently annotated Candida albicans transcripts did not result in an absolute enrichment of remaining transcripts, although we identified 26 previously unknown transcripts and isoforms, 17 of which are antisense to existing transcripts. Further improvements in the adaptive sampling of RNAs will allow the technology to be widely applied to study RNAs of interest in diverse transcriptomes.

The Role of Human-Centered Design in Healthcare Innovation: a Digital Health Equity Case Study.

Healthcare delivery has become more complicated, particularly with the addition of digital tools and advanced technologies that can further exacerbate existing disparities. New approaches to solve complex, multi-faceted problems are needed. Human-centered design (HCD), also known as design thinking, is an innovative set of methods to develop solutions to these types of issues using collaborative, team-based, and empathetic approaches focused on end user experiences. Originally advanced in technology sectors, HCD has garnered growing attention in quality improvement, healthcare redesign, and public health and medical education. During the COVID-19 pandemic, our healthcare organization recognized notable differences in utilization of virtual (video-based) services among specific patient populations. In response, we mobilized, and using HCD, we collectively brainstormed ideas, rapidly developed prototypes, and iteratively adapted solutions to work toward addressing this digital divide and clinic and systems-level struggles with improving and maintaining digital health access. HCD approaches create a cohesive team-based structure that permits the dismantling of organizational hierarchies and departmental silos. Here we share lessons learned on implementing HCD into clinical care settings and how HCD can result in the development of site-specific, patient-centered innovations to address access disparities and to improve digital health equity.

Outpatient Management of COVID-19: Rapid Evidence Review.

New COVID-19 variants of concern continue to develop. Incubation period, transmissibility, immune escape, and treatment effectiveness differ by variants of concern. Physicians should be aware that the characteristics of the predominant variants of concern determine aspects of diagnosis and treatment. Multiple testing modalities exist; the most appropriate testing strategy varies depending on the clinical scenario, with factors of test sensitivity, turnaround time, and the expertise required for specimen collection. Three types of vaccines are available in the United States, and all people six months and older should be encouraged to receive one because vaccination is effective in reducing the incidence of and hospitalizations and deaths associated with COVID-19. Vaccination may also reduce the incidence of post-acute sequelae of SARS-CoV-2 infection (i.e., long COVID). Consider medications, such as nirmatrelvir/ritonavir, as first-line treatment for eligible patients diagnosed with COVID-19 unless logistical or supply constraints occur. National Institutes of Health guidelines and local health care partner resources can be used to determine eligibility. Long-term health effects of having COVID-19 are under investigation.

The Carbon Footprint and Cost of Virtual Residency Interviews.

Background: The shift from in-person to virtual residency interviews may impact greenhouse gas emissions (GHGE) and costs but the direction and amount of this change is not yet clear. Objective: To estimate GHGE and financial impacts of virtual interviews among applicants and programs. Methods: In 2020-2021 we sent a postinterview survey to 1429 applicants from 7 residency programs and 1 clinical psychology program at 1 institution. The survey collected origin of travel and transit type if in-person interviews had been held and excluded responses if the applicant would not have participated in an in-person interview, or if travel type or original city was missing. We used the International Civil Aviation Organization calculator to estimate flight-related GHGE in metric tons of carbon dioxide equivalent (MTCO2e) and Google Maps to estimate ground travel, with a standard CO2e per mile. Flight, hotel, and airport taxi costs were estimated using Expedia.com, Hotels.com, Uber, and Lyft. We aggregated these data and calculated median and interquartile ranges (IQRs) for applicant GHGE and cost savings, and assumed no cost or GHGE from virtual interviews. We used Wilcoxon signed rank sum tests to compare in-person 2019-2020 and virtual 2020-2021 GME program interview budgets. Results: The survey response rate was 565, or 40% of applicants; 543 remained after the exclusion criteria were applied. Reduction in applicant travel due to virtual interviews led to median estimated GHGE savings of 0.47 (IQR 0.30-0.61) MTCO2e and $490 (IQR $392-$544) per applicant, per interview. Programs savings ranged from $7,615 to $33,670 for the interview season. Conclusions: Virtual interviews in 8 GME programs were associated with lower estimated GHGE and costs, for applicants and programs, compared with in-person interviews.

Patient-Facing Clinical Decision Support for High Blood Pressure Control: Patient Survey.

BACKGROUND: High blood pressure (HBP) affects nearly half of adults in the United States and is a major factor in heart attacks, strokes, kidney disease, and other morbidities. To reduce risk, guidelines for HBP contain more than 70 recommendations, including many related to patient behaviors, such as home monitoring and lifestyle changes. Thus, the patient's role in controlling HBP is crucial. Patient-facing clinical decision support (CDS) tools may help patients adhere to evidence-based care, but customization is required. OBJECTIVE: Our objective was to understand how to adapt CDS to best engage patients in controlling HBP. METHODS: We conducted a mixed methods study with two phases: (1) survey-guided interviews with a limited cohort and (2) a nationwide web-based survey. Participation in each phase was limited to adults aged between 18 and 85 years who had been diagnosed with hypertension. The survey included general questions that assessed goal setting, treatment priorities, medication load, comorbid conditions, satisfaction with blood pressure (BP) management, and attitudes toward CDS, and also a series of questions regarding A/B preferences using paired information displays to assess perceived trustworthiness of potential CDS user interface options. RESULTS: We conducted 17 survey-guided interviews to gather patient needs from CDS, then analyzed results and created a second survey of 519 adults with clinically diagnosed HBP. A large majority of participants reported that BP control was a high priority (83%), had monitored BP at home (82%), and felt comfortable using technology (88%). Survey respondents found displays with more detailed recommendations more trustworthy (56%-77% of them preferred simpler displays), especially when incorporating social trust and priorities from providers and patients like them, but had no differences in action taken. CONCLUSIONS: Respondents to the survey felt that CDS capabilities could help them with HBP control. The more detailed design options for BP display and recommendations messaging were considered the most trustworthy yet did not differentiate perceived actions.

Translocation detection from Hi-C data via scan statistics.

Recent Hi-C technology enables more comprehensive chromosomal conformation research, including the detection of structural variations, especially translocations. In this paper, we formulate the interchromosomal translocation detection as a problem of scan clustering in a spatial point process. We then develop TranScan, a new translocation detection method through scan statistics with the control of false discovery. The simulation shows that TranScan is more powerful than an existing sophisticated scan clustering method, especially under strong signal situations. Evaluation of TranScan against current translocation detection methods on realistic breakpoint simulations generated from real data suggests better discriminative power under the receiver-operating characteristic curve. Power analysis also highlights TranScan's consistent outperformance when sequencing depth and heterozygosity rate is varied. Comparatively, Type I error rate is lowest when evaluated using a karyotypically normal cell line. Both the simulation and real data analysis indicate that TranScan has great potentials in interchromosomal translocation detection using Hi-C data.

Effectiveness of Virtual Residency Interviews: Interviewer Perspectives.

BACKGROUND AND OBJECTIVES: Virtual residency interviews were widely utilized during the COVID-19 pandemic. Little is known about the effectiveness, advantages, barriers, and acceptability of virtual interviews, casting uncertainty about how interviews should be conducted after the pandemic. We conducted a survey of interviewers to inform future decisions. METHODS: We developed and implemented an online postinterview survey of interviewers representing seven residency programs and two clinical psychology programs at one midsized academic medical center. We analyzed results using descriptive statistics. RESULTS: Of 312 interviewers, 136 completed the survey (44% response rate). A majority rated virtual interviews as very or extremely effective in creating a comfortable setting (79%), answering interviewee questions (86%), establishing a sense of connection (59%), evaluating interviewee strengths (64%), and communicating program culture (51%). About half felt virtual interviews were not effective at all or only slightly effective for evaluating interviewee strengths via informal interactions (51%). A similar portion agreed or strongly agreed that virtual tours (44%) and social environment (50%) information were adequate. The most frequent advantages were time efficiency (81%), reduced carbon footprint (61%) and cost savings (56%). Frequent disadvantages included technological issues (21%) and caregiving duties (18%). Most interviewers (91%) thought some form of virtual interviews should be incorporated postpandemic. CONCLUSIONS: Interviewers found virtual interviews to be effective in most aspects, and identified more advantages than barriers. The vast majority preferred incorporation of virtual interviews in the future. Virtual tours and social activities were areas for improvement.

Long COVID: Rapid Evidence Review.

Postacute sequelae of COVID-19, also known as long COVID, affects approximately 10% to 30% of the hundreds of millions of people who have had acute COVID-19. The Centers for Disease Control and Prevention defines long COVID as the presence of new, returning, or ongoing symptoms associated with acute COVID-19 that persist beyond 28 days. The diagnosis of long COVID can be based on a previous clinical diagnosis of COVID-19 and does not require a prior positive polymerase chain reaction or antigen test result to confirm infection. Patients with long COVID report a broad range of symptoms, including abdominal pain, anosmia, chest pain, cognitive impairment (brain fog), dizziness, dyspnea, fatigue, headache, insomnia, mood changes, palpitations, paresthesias, and postexertional malaise. The presentation is variable, and symptoms can fluctuate or persist and relapse and remit. The diagnostic approach is to differentiate long COVID from acute sequelae of COVID-19, previous comorbidities, unmasking of preexisting health conditions, reinfections, new acute concerns, and complications of prolonged illness, hospitalization, or isolation. Many presenting symptoms of long COVID are commonly seen in a primary care practice, and management can be improved by using established treatment paradigms and supportive care. Although several medications have been suggested for the treatment of fatigue related to long COVID, the evidence for their use is currently lacking. Holistic treatment strategies for long COVID include discussion of pacing and energy conservation; individualized, symptom-guided, phased return to activity programs; maintaining adequate hydration and a healthy diet; and treatment of underlying medical conditions.

Virtual Residency Interviews: Applicant Perceptions Regarding Virtual Interview Effectiveness, Advantages, and Barriers.

Background: Studies of the virtual interview format are needed to inform medical residency program leaders as they plan for future virtual interview seasons. Objective: In the current study, completed in 2021, we sought to assess applicant perspectives of virtual interview effectiveness, advantages, and barriers, including factors that might impact equity and inclusion. Methods: Interviewees applying to 7 residency programs and 2 clinical psychology programs at an academic medical center in the Pacific Northwest completed a post-interview survey. Results: A total of 565 of 1429 interviewees (40%) completed the survey. A vast majority (83%-96%) agreed virtual interviews were effective in each measured domain, except for learning institutional culture (352 of 565, 62%). Many also found information regarding social/living environments inadequate. Participants selected advantages to virtual interviews more frequently than disadvantages. Commonly selected advantages included cost savings, time efficiency, reduced burden of travel, and reduced carbon footprint. Disadvantages included time zone differences, access to an appropriate interview setting, and reliable access to internet. The majority of interviewees (84%, 456 of 542) desired to keep a component of virtual interviews in the future. There were no significant disparities in results based on gender, rural/suburban/urban location, race, or underrepresented minority status. Conclusions: Virtual interviews were perceived as effective, more advantageous than burdensome, and widely acceptable, with no disparities in these findings by included demographic characteristics.

Multimodal single-cell analysis of cutaneous T-cell lymphoma reveals distinct subclonal tissue-dependent signatures.

Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of mature T-cell neoplasms characterized by the accumulation of clonal malignant CD4+ T cells in the skin. The most common variant of CTCL, mycosis fungoides (MF ), is confined to the skin in early stages but can be accompanied by extracutaneous dissemination of malignant T cells to the blood and lymph nodes in advanced stages of disease. Sézary syndrome (SS), a leukemic form of disease, is characterized by significant blood involvement. Little is known about the transcriptional and genomic relationship between skin- and blood-residing malignant T cells in CTCL. To identify and interrogate malignant clones in matched skin and blood from patients with leukemic MF and SS, we combine T-cell receptor clonotyping with quantification of gene expression and cell surface markers at the single cell level. Our data reveal clonal evolution at a transcriptional and genetic level within the malignant populations of individual patients. We highlight highly consistent transcriptional signatures delineating skin- and blood-derived malignant T cells. Analysis of these 2 populations suggests that environmental cues, along with genetic aberrations, contribute to transcriptional profiles of malignant T cells. Our findings indicate that the skin microenvironment in CTCL promotes a transcriptional response supporting rapid malignant expansion, as opposed to the quiescent state observed in the blood, potentially influencing efficacy of therapies. These results provide insight into tissue-specific characteristics of cancerous cells and underscore the need to address the patients' individual malignant profiles at the time of therapy to eliminate all subclones.

Improving oligo-conjugated antibody signal in multimodal single-cell analysis.

Simultaneous measurement of surface proteins and gene expression within single cells using oligo-conjugated antibodies offers high-resolution snapshots of complex cell populations. Signal from oligo-conjugated antibodies is quantified by high-throughput sequencing and is highly scalable and sensitive. We investigated the response of oligo-conjugated antibodies towards four variables: concentration, staining volume, cell number at staining, and tissue. We find that staining with recommended antibody concentrations causes unnecessarily high background and amount of antibody used can be drastically reduced without loss of biological information. Reducing staining volume only affects antibodies targeting abundant epitopes used at low concentrations and is counteracted by reducing cell numbers. Adjusting concentrations increases signal, lowers background, and reduces costs. Background signal can account for a major fraction of total sequencing and is primarily derived from antibodies used at high concentrations. This study provides new insight into titration response and background of oligo-conjugated antibodies and offers concrete guidelines to improve such panels.

Launching a Statewide COVID-19 Primary Care Hotline and Telemedicine Service.

To respond to the COVID-19 pandemic and recover from its aftermath, primary care teams will face waves of overwhelming demand for information and the need to significantly transform care delivery. INNOVATION: Oregon Health & Science University's primary care team envisioned and implemented the COVID-19 Connected Care Center, a statewide telephone "hotline" service. RESULTS: The hotline has taken more than 5825 calls from patients in 33 of Oregon's 36 counties in less than 3 months. In preliminary survey data, 86% of patients said their questions were answered during the call, 90% would recommend this service, and 70% reported a reduction in stress levels about coronavirus. In qualitative interviews, patients reported their questions answered, short wait times, nurses spent time as needed, and appropriate follow-up was arranged. CONCLUSION: Academic health centers may have the capacity to leverage their extensive resources to rapidly launch a multiphased pandemic response that meets peoples' need for information and access to primary care, while minimizing risk of infection and emergency department use and rapidly supporting primary care teams to make the necessary operational changes to do the same in their communities. Such efforts require external funding in a fee-for-service payment model.

Direct DNA crosslinking with CAP-C uncovers transcription-dependent chromatin organization at high resolution.

Determining the spatial organization of chromatin in cells mainly relies on crosslinking-based chromosome conformation capture techniques, but resolution and signal-to-noise ratio of these approaches is limited by interference from DNA-bound proteins. Here we introduce chemical-crosslinking assisted proximity capture (CAP-C), a method that uses multifunctional chemical crosslinkers with defined sizes to capture chromatin contacts. CAP-C generates chromatin contact maps at subkilobase (sub-kb) resolution with low background noise. We applied CAP-C to formaldehyde prefixed mouse embryonic stem cells (mESCs) and investigated loop domains (median size of 200 kb) and nonloop domains (median size of 9 kb). Transcription inhibition caused a greater loss of contacts in nonloop domains than loop domains. We uncovered conserved, transcription-state-dependent chromatin compartmentalization at high resolution that is shared from Drosophila to human, and a transcription-initiation-dependent nuclear subcompartment that brings multiple nonloop domains in close proximity. We also showed that CAP-C could be used to detect native chromatin conformation without formaldehyde prefixing.

Advancing Telemedicine Within Family Medicine's Core Values.

Telemedicine adoption has been gradual but accelerated during the COVID-19 pandemic. It is important for us to pause and consider how this impacts family medicine. How do we ground ourselves so that we use technology to enhance our practice while maintaining fundamental family medicine values? In this article, we explore how telemedicine interacts with five family medicine tenants: contextual care, continuity of care, access to care, comprehensive care, and care coordination. Keeping this framework in mind and using a health equity lens can help us retain fundamental family medicine values as we adapt to rapid technological change.

Outpatient Management of COVID-19: Rapid Evidence Review.

Common presenting symptoms of coronavirus disease 2019 include fever, dry cough, shortness of breath, and fatigue. However, patients may have a wide range of symptoms representing a spectrum of mild to severe illness. Symptoms in children tend to be milder and may include fever, cough, and feeding difficulty. The incubation period is two to 14 days, although symptoms typically appear within five days of exposure. Multiple testing modalities exist, but infection should be confirmed by polymerase chain reaction testing using a nasopharyngeal swab. There are no evidence- based treatments appropriate for use in the outpatient setting; management is supportive and should include education about isolation. In hospitalized patients, remdesivir should be considered to reduce time to recovery, and low-dose dexamethasone should be considered in patients who require supplemental oxygen. Overall, 85% of patients have mild illness, whereas 14% have severe disease requiring hospitalization, including 5% who require admission to an intensive care unit. Predictors of severe disease include increasing age, comorbidities, lymphopenia, neutrophilia, leukocytosis, low oxygen saturation, and increased levels of C-reactive protein, d-dimer, transaminases, and lactate dehydrogenase.

Redesigning Primary Care to Address the COVID-19 Pandemic in the Midst of the Pandemic.

During a pandemic, primary care is the first line of defense. It is able to reinforce public health messages, help patients manage at home, and identify those in need of hospital care. In response to the COVID-19 pandemic, primary care scrambled to rapidly transform itself and protect clinicians, staff, and patients while remaining connected to patients. Using the established public health framework for addressing a pandemic, we describe the actions primary care needs to take in a pandemic. Recommended actions are based on observed experiences of the authors' primary care practices and networks. Early in the COVID-19 pandemic, tasks focused on promoting physical distancing and encouraging patients with suspected illness or exposure to self-quarantine. Testing was not available and contract tracing was not possible. As the pandemic spread, in-person care was converted to virtual care using telehealth. Practices remained connected to patients using registries to reach out to those at risk for infection, with uncontrolled chronic conditions, or were socially vulnerable. Practices managed most patients with suspected COVID-19 at home. As the pandemic decelerates, practices are now preparing to address the direct and indirect consequences-complications from COVID-19 infections, missed treatment for acute problems, inadequate prevention, uncontrolled chronic disease, mental illness, and greater social needs. Throughout, practices bore tremendous financial burden, laying off staff or even closing at a time when most needed. Primary care must learn from this experience and be ready for the next pandemic. Policymakers and payers cannot fail primary care during their next time of need.

Effects of Clinic First Educational Interventions on Resident Wellness and Engagement.

BACKGROUND AND OBJECTIVES: Tensions between clinical and hospital training, along with dysfunctional family medicine training clinics, have resulted in continuity clinic being the least favorite part of training for some residents. These factors are all contributors to burnout. We hypothesized that following Clinic First action steps to prioritize and enhance outpatient clinic would positively affect resident wellness and clinic engagement. This study describes our interventions and their effects within the Oregon Health & Science University (OHSU) Family Medicine 4-year Portland residency program. METHODS: In July 2017 the Oregon Health & Science University Family Medicine Portland residency program implemented scheduling and curricular interventions inspired by the Clinic First model. We conducted a mixed-methods cross-sectional study using focus groups and surveys to understand the effects of these interventions on resident wellness and engagement. RESULTS: Clinic First-inspired interventions, particularly a 2+2 scheduling model, decreased transitions within the day, and a clinic immersion month were associated with improved residents' perception of wellness. These interventions had variable effects on clinic engagement. Eighty-eight percent of interns surveyed about the month-long clinic orientation in the beginning of residency reported that they felt prepared managing continuity patients in the clinic setting and their upcoming rotations. CONCLUSIONS: This study demonstrates that Clinic First-inspired structural changes can be associated with improvement in resident perceptions of wellness and aspects of clinic engagement. This can give educators a sense of hope as well as tangible steps to take to improve these difficult and important issues.