A brainstem peptide system activated at birth protects postnatal breathing.

Among numerous challenges encountered at the beginning of extrauterine life, the most celebrated is the first breath that initiates a life-sustaining motor activity1. The neural systems that regulate breathing are fragile early in development, and it is not clear how they adjust to support breathing at birth. Here we identify a neuropeptide system that becomes activated immediately after birth and supports breathing. Mice that lack PACAP selectively in neurons of the retrotrapezoid nucleus (RTN) displayed increased apnoeas and blunted CO2-stimulated breathing; re-expression of PACAP in RTN neurons corrected these breathing deficits. Deletion of the PACAP receptor PAC1 from the pre-Bötzinger complex-an RTN target region responsible for generating the respiratory rhythm-phenocopied the breathing deficits observed after RTN deletion of PACAP, and suppressed PACAP-evoked respiratory stimulation in the pre-Bötzinger complex. Notably, a postnatal burst of PACAP expression occurred in RTN neurons precisely at the time of birth, coinciding with exposure to the external environment. Neonatal mice with deletion of PACAP in RTN neurons displayed increased apnoeas that were further exacerbated by changes in ambient temperature. Our findings demonstrate that well-timed PACAP expression by RTN neurons provides an important supplementary respiratory drive immediately after birth and reveal key molecular components of a peptidergic neural circuit that supports breathing at a particularly vulnerable period in life.

Building Capacity for Research on Community Doula Care: A Stakeholder-Engaged Process in California.

PURPOSE: In an effort to address persistent inequities in maternal and infant health, policymakers and advocates have pushed to expand access to doula care. Several states, including California, now cover doula services through Medicaid. As coverage expands, research on the impact of doula care will likely increase. To develop best practices for research, it is critical to engage community doulas, clients, and other key stakeholders. DESCRIPTION: Our overarching goal was to build capacity for future doula- and client-centered research on community doula care. First, we established a Steering Committee with members from seven relevant stakeholder groups: community doulas, former or potential doula clients, clinicians, payers, advocates, researchers, and public health professionals. Second, we conducted a needs assessment to identify and understand stakeholders' needs and values for research on community doula care. Findings from the needs assessment informed our third step, conducting a research prioritization to develop a shared research agenda related to community doula care with the Steering Committee. We adapted the Research Prioritization by Affected Communities protocol to guide this process, which resulted in a final list of 21 priority research questions. Lastly, we offered a training to increase capacity among community doulas to engage in research on community doula care. ASSESSMENT: Our findings provide direction for those interested in conducting research on doula care, as well as policymakers and funders. CONCLUSION: The findings of our stakeholder-engaged process provide a roadmap that will lead to equity-oriented research centering clients, doulas, and their communities.

A conceptual model of vulnerability to care delay among women at risk for endometrial cancer.

OBJECTIVE: Care delay may allow for cancer progression prior to treatment initiation. However, in endometrial cancer, quantitative data to support this hypothesis is mixed. Factors that cuase delay prior to clinical presentation are present among Black women, however the whether and how they present among White women, and thus how they may drive racial disparity is unknown. METHODS: In this qualitative study, from June 2019 to March 2020, we conducted in-depth semi-structured interviews among 17 White women with EC (34-73 years), living in the Northwest (11), West (2), Midwest (1), Southwest (1), and Northeast (2) U.S. regions, including six with high-risk and/or advanced stage endometrial cancer. An exploratory and descriptive content analysis was performed using iterative rounds of inductive coding, case summaries, and additional interviews to confirm emergent themes, followed by synthetic analysis of themes from a prior qualitative study conducted among Black women, which we analyzed for overlap and distinctions. RESULTS: There were critical points of overlap and distinction between Black and White women in four delay factors identified: menopause and endometrial cancer knowledge, prior negative healthcare experiences, prior/concurrent reproductive conditions, and healthcare provider response. Conceptualizing the care journey as a circular path demonstrates the potential for accumulation of delay that is dependent on underlying risk. CONCLUSION: We have identified four areas of vulnerability that are often unrecognized and difficult to assess in quantitative investigations of overall quality and co-occurring disparities in endometrial cancer care. With the addition of epidemiologic risk, we present a unified model of vulnerability to care delay in endometrial cancer that can be applied to future quantitative studies and ongoing clinical care.

Population Pharmacodynamics of Amphotericin B Deoxycholate for Disseminated Infection Caused by Talaromyces marneffei.

Amphotericin B deoxycholate (DAmB) is a first-line agent for the initial treatment of talaromycosis. However, little is known about the population pharmacokinetics and pharmacodynamics of DAmB for talaromycosis. Pharmacokinetic data were obtained from 78 patients; among them, 55 patients had serial fungal CFU counts in blood also available for analysis. A population pharmacokinetic-pharmacodynamic model was fitted to the data. The relationships between the area under the concentration-time curve (AUC)/MIC and the time to blood culture sterilization and the time to death were investigated. There was only modest pharmacokinetic variability in the average AUC, with a mean ± standard deviation of 11.51 ± 3.39 mg·h/liter. The maximal rate of drug-induced kill was 0.133 log10 CFU/ml/h, and the plasma concentration of the DAmB that induced the half-maximal rate of kill was 0.02 mg/liter. Fifty percent of patients sterilized their bloodstreams by 83.16 h (range, 13 to 264 h). A higher initial fungal burden was associated with a longer time to sterilization (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.36 to 0.70; P < 0.001). There was a weak relationship between AUC/MIC and the time to sterilization, although this did not reach statistical significance (HR, 1.03; 95% CI, 1.00 to 1.06, P = 0.091). Furthermore, there was no relationship between the AUC/MIC and time to death (HR, 0.97; 95% CI, 0.88 to 1.08; P = 0.607) or early fungicidal activity {slope = log[(0.500 - 0.003·(AUC/MIC)]; P = 0.319} adjusted for the initial fungal burden. The population pharmacokinetics of DAmB are surprisingly consistent. The time to sterilization of the bloodstream may be a useful pharmacodynamic endpoint for future studies. (This study has been registered at the ISRCTN registry under no. ISRCTN59144167.).

Development and evaluation of a real-time polymerase chain reaction assay for the rapid detection of Talaromyces marneffei MP1 gene in human plasma.

Penicilliosis caused by Talaromyces marneffei is a common AIDS-defining illness in South and Southeast Asia. Diagnosis is based on culture which can take up to 14 days for identification, leading to treatment delay and increased mortality. We developed a TaqMan real-time PCR assay targeting the MP1 gene encoding an abundant cell wall protein specific to T. marneffei. The assay's performance was evaluated in MP1-containing plasmids, clinical isolates, and plasma from HIV-infected patients with and without penicilliosis. The assay consistently detected 10 copies of MP1-containing plasmids per reaction and 100 T. marneffei yeast cells per millilitre plasma. There were no amplification with seven other Penicillium species and six other HIV-associated fungal pathogens tested. The assay was evaluated in 70 patients with AIDS: 50 patients with culture-confirmed penicilliosis and 20 patients with opportunistic infections other than penicilliosis. The diagnostic sensitivity was 70.4% (19/27, 95% CI: 51.5-84.1%) and 52.2% (12/23, 95% CI: 33.0-70.8%) in plasma samples collected prior to and within 48 h of antifungal therapy respectively. The diagnostic specificity was 100% (20/20, 95% CI: 83.9-100%). This assay provides a useful tool for the rapid diagnosis of T. marneffei infection and has the potential to improve the management of patients with penicilliosis.

Comparison of the BD Veritor System for Flu A+B with the Alere BinaxNOW influenza A&B card for detection of influenza A and B viruses in respiratory specimens from pediatric patients.

The performance characteristics of two commercially available rapid tests for influenza, the BD Veritor System for Flu A+B (BD) and the Alere BinaxNOW influenza A&B card (BN), were evaluated using 200 frozen clinical specimens collected from January 2011 to June 2012 from pediatric patients. Real-time reverse transcriptase PCR (RT-PCR) was used as the gold standard to evaluate the results obtained by the two different assays. Of the 200 specimens tested, real-time RT-PCR assay detected influenza A or B virus in 116 samples, while BD detected 104 samples and BN detected 84 samples as positive. The overall sensitivity and specificity for detection of both influenza A and B virus in comparison to those of real-time RT-PCR were 89.6% (95% confidence interval [CI], 82.2 to 94.3) and 98.8% (95% CI, 92.6 to 99.9) for BD Veritor and 72.4% (95% CI, 63.2 to 80.0) and 100% (95% CI, 94.5 to 100.0) for BinaxNOW. Workflow analysis indicated that overall processing times for a batch size of 10 specimens were virtually identical between both systems. Overall, these results indicate that the BD Veritor assay was more sensitive than the BinaxNOW assay in detection of influenza A and B viruses in respiratory specimens from pediatric patients.

Facilitators and Barriers to Medicaid Doula Benefit Implementation in California: Perspectives From Managed Care Plans and Risk-Bearing Organizations.

INTRODUCTION: Medicaid coverage of doula services is increasing as a policy strategy to reduce maternal health inequities in the United States. However, early adopter states struggled to offer accessible, equitable Medicaid doula benefits when implementation began. California began covering doula services through its Medicaid program, Medi-Cal, in 2023. Managed care plans (MCPs) and risk-bearing organizations (RBOs) play an important role in ensuring pregnant and birthing people can access doula support through Medicaid benefits. MATERIALS AND METHODS: Between 2021 and 2022, we conducted 14 interviews with MCP and RBO staff (n = 20) representing a total of 14 MCPs and RBOs. Data were analyzed in two stages: 1) rapid assessment process and 2) using the Consolidated Framework for Implementation Research (CFIR) to identify specific facilitators and barriers to Medi-Cal doula benefit implementation. RESULTS: We identified 10 facilitators and 16 barriers across the five CFIR domains. Results indicate a general lack of familiarity with doula care and highlight the importance of relationship building with doulas and collaboration among plans. CONCLUSIONS: In California, these findings can help guide improvements to emerging implementation challenges and evaluation efforts. Our findings can also help other states in the planning and Medicaid doula benefit design process.

Advancing Synthetic Hydrogels through Nature-Inspired Materials Chemistry.

Synthetic extracellular matrix (ECM) mimics that can recapitulate the complex biochemical and mechanical nature of native tissues are needed for advanced models of development and disease. Biomedical research has heavily relied on the use of animal-derived biomaterials, which is now impeding their translational potential and convoluting the biological insights gleaned from in vitro tissue models. Natural hydrogels have long served as a convenient and effective cell culture tool, but advances in materials chemistry and fabrication techniques now present promising new avenues for creating xenogenic-free ECM substitutes appropriate for organotypic models and microphysiological systems. However, significant challenges remain in creating synthetic matrices that can approximate the structural sophistication, biochemical complexity, and dynamic functionality of native tissues. This review summarizes key properties of the native ECM, and discusses recent approaches used to systematically decouple and tune these properties in synthetic matrices. The importance of dynamic ECM mechanics, such as viscoelasticity and matrix plasticity, is also discussed, particularly within the context of organoid and engineered tissue matrices. Emerging design strategies to mimic these dynamic mechanical properties are reviewed, such as multi-network hydrogels, supramolecular chemistry, and hydrogels assembled from biological monomers.

Evaluation of the Impact of Meibomian Gland Dysfunction Using a Novel Patient-Reported Outcome Instrument.

Purpose: This study was intended to characterize the impact of meibomian gland dysfunction (MGD) on patients' quality of life. Methods: In this prospective, multicenter, noninterventional clinical study (NCT01979887), eligible individuals (age ≥40 years; absence of uncontrolled ocular/systemic disease) were categorized, based on composite grading of ocular symptoms, Schirmer score, and meibum quality, into (1) non-MGD, (2) mild/moderate MGD, or (3) severe MGD cohorts. The MGD Impact Questionnaire (MGD IQ), a 10-item patient-reported outcome measure, was self-administered at clinic visit on day 1, and readministered on day 22 to assess intervisit agreement regarding MGD IQ responses. Results: In total, 75 subjects were assigned to the study cohorts (25 per cohort). Across cohorts, MGD IQ item scores rose incrementally with increasing MGD severity. The severe MGD cohort experienced greater difficulty with reading and performance of leisure activities, greater time on eye care, and greater bother with eye care and eye appearance than the mild/moderate MGD cohort (all P < 0.05). Compared with the non-MGD cohort, the mild/moderate MGD cohort had greater difficulty working on computer, whereas the severe MGD cohort had greater difficulty reading, driving, and performing leisure activities, more frequent difficulty with outdoor activities, more time on eye care, and greater bother with eye care (all P < 0.05). Intervisit agreement between MGD IQ responses was fair to moderate (weighted kappa statistic 0.33‒0.58). Conclusions: Vision-related activities are negatively impacted by increasing severity of MGD. The MGD IQ instrument can help characterize disease severity and amplify the patient's voice in patient-centric clinical research. ClinicalTrials.gov NCT01979887.

Septins provide microenvironment sensing and cortical actomyosin partitioning in motile amoeboid T lymphocytes.

The all-terrain motility of lymphocytes in tissues and tissue-like gels is best described as amoeboid motility. For amoeboid motility, lymphocytes do not require specific biochemical or structural modifications to the surrounding extracellular matrix. Instead, they rely on changing shape and steric interactions with the microenvironment. However, the exact mechanism of amoeboid motility remains elusive. Here, we report that septins participate in amoeboid motility of T cells, enabling the formation of F-actin and α-actinin-rich cortical rings at the sites of cell cortex-indenting collisions with the extracellular matrix. Cortical rings compartmentalize cells into chains of spherical segments that are spatially conformed to the available lumens, forming transient "hourglass"-shaped steric locks onto the surrounding collagen fibers. The steric lock facilitates pressure-driven peristaltic propulsion of cytosolic content by individually contracting cell segments. Our results suggest that septins provide microenvironment-guided partitioning of actomyosin contractility and steric pivots required for amoeboid motility of T cells in tissue-like microenvironments.

Examining the Vietnamese Montreal cognitive assessment in healthy and moderate-to-severe traumatic brain injury populations.

Objective: There have been attempts to modify the Montreal Cognitive Assessment (MoCA), a brief cognitive screening tool, for use across several Asian countries, but evidence to support the utility of these translations has been limited, particularly for the Vietnamese translation of the MoCA (MoCA-V). This two-part study aimed to evaluate the MoCA-V in a Vietnamese sample. Methods: In the first stage, we examined the relationships between the MoCA-V subscales and common neuropsychological tests among healthy Vietnamese adults (n = 129) and individuals with moderate-to-severe traumatic brain injury (n = 80). In the second stage, we explored the relationship of TBI status (TBI vs non-TBI) and demographic variables to MoCA-V performance and investigated the optimal cut-off score of the MoCA-V using the two samples combined. Results: The MoCA-V Attention, Language, and Executive Function subscales were correlated with the Digit Span Test, Verbal Fluency Test, and Trail Making Test, respectively, across healthy participants and participants with TBI. Global performance on the MoCA-V was predicted by TBI status, education, and age. Our ROC analysis revealed that a cut-off score of 22 offered the best sensitivity (76.3%) and specificity (71.3%) trade-off for identifying cognitive impairment as measured by the MoCA-V. Conclusions: In addition to identifying a cut-off score for cognitive screening, the findings provide support for the validity of the examined MoCA-V subscales and for the MoCA-V's ability to distinguish TBI survivors vs controls. These results may pave the way for larger-scale investigations of the MoCA-V and for the development of more neuropsychological batteries in Vietnamese.

Exploring Signs and Symptoms Associated with Meibomian Gland Dysfunction for Use as Clinical Trial Endpoints.

Purpose: Dry eye disease is attributed to impaired tear production and/or evaporative dry eye. Evaporative dry eye is frequently associated with meibomian gland dysfunction (MGD). The objective of this study was to identify clinical study endpoints related to MGD. Methods: This 22-day, noninterventional, case-control clinical study involved three cohorts with increasing MGD severity: no MGD, mild/moderate MGD, and severe MGD. Symptoms were assessed with an ocular symptom questionnaire grading blurred vision, eye burning, eye dryness, eye pain, light sensitivity, eye itching, eye foreign body sensation, and overall ocular discomfort. Sign assessments included the maximum meibum quality score (MMQS), tear breakup time, Schirmer tear tests, biomicroscopy, and corneal staining. Signs and symptoms were compared between cohorts and study visits. Results: Seventy-five study participants were assigned to the cohorts (25 per cohort). MMQS scores increased with increasing MGD severity, reflecting the selection criteria for the cohorts. Between-visit scores showed a weighted kappa statistic of 0.72 indicating substantial agreement. Mean scores of all assessed symptoms increased with increasing MGD severity. Scores for symptoms showed moderate (κ = 0.41-0.60) to substantial (κ = 0.61-0.80) agreement between visits. Overall ocular discomfort demonstrated the strongest correlation with the MMQS. Conclusion: The MMQS was a reproducible sign of MGD showing good agreement with ocular symptoms. Overall ocular discomfort was well correlated with typical dry eye symptoms and could potentially be used as a single measure of MGD symptoms. The findings from this observational study may inform endpoints for future clinical trials. ClinicalTrials.gov NCT01979887.

Continuing education in diversity and multicultural factors: Current state psychology board requirements and a call to action.

Objective: A growing body of literature shows the unequivocal importance of incorporating diversity-related factors into the practice of clinical neuropsychology. Thus, it is imperative that we continue to seek and obtain updated training and knowledge on how culture and diversity intersect with our clinical roles throughout our careers, not merely to satisfy initial coursework requirements. Although most professional organizations pertaining to clinical psychology - and thereby neuropsychology - strongly encourage the pursuit of training in diversity-related factors, explicit requirements for such training across one's career are minimal. Method: The Asian Neuropsychological Association Advocacy Committee reviewed continuing education (CE) requirements for all US states. Results: We found that only 8 states mandated CE credits pertaining to diversity-related factors for the renewal of licensure. Discussion: Given how inseparable cultural competence is from any aspect of clinical work (and the harm that can be done if culture is not considered), it is essential that our field shift from aspirational guidance to firm requirements with regard to cultural competence and diversity-related training in psychology. Requiring CE units devoted to diversity-related factors represents one avenue to pursue this goal. This commentary outlines the current status of diversity-related CE for psychology licensure renewal and offers future directions for incorporating such training as a part of continuing professional development and education.

Single Administration of Bimatoprost Implant: Effects on 24-Hour Intraocular Pressure and 1-Year Outcomes.

PURPOSE: To evaluate the effects of a single bimatoprost implant administration on 24-hour intraocular pressure (IOP) lowering at 8 weeks, and 1-year IOP-lowering efficacy and safety outcomes. DESIGN: Multicenter, open-label, 12-month, phase 3b study (NCT04285580). PARTICIPANTS: Adults with open-angle glaucoma or ocular hypertension. METHODS: Participants (n = 31) received 10-µg bimatoprost implant in the study eye on day 1; IOP (sitting and/or supine) was measured with pneumatonometry every 2 hours throughout a 24-hour period at baseline and week 8. IOP was measured by Goldmann applanation tonometry (GAT) at hour 0 (8 am ± 1 hour) at baseline, weeks 8 and 16, and months 6, 9, and 12. MAIN OUTCOME MEASURES: The primary endpoint was the week-8 hour-matched change from baseline in habitual position IOP over 24 hours assessed with pneumatonometry. Hour 0 IOP change from baseline measured with GAT in study eyes that received no additional (rescue) IOP-lowering treatment, treatment-emergent adverse events (TEAEs), and central corneal endothelial cell density (CECD) were evaluated through 12 months. RESULTS: The mean (standard deviation [SD]) baseline IOP at hour 0 was 24.2 (2.70) mmHg and 25.3 (7.15) mmHg by GAT and pneumatonometry, respectively. Pneumatonometer measurements of IOP taken over 24 hours at week 8 with the participant in habitual position (sitting from 8 am to 10 pm, supine from 12 am to 6 am) showed consistent IOP lowering through the day and night and reduced fluctuation in IOP. The range in IOP measurements over 24 hours was reduced from baseline by a mean (SD) of -1.6 (2.98) mmHg. All 31 bimatoprost implant-treated participants completed the 12-month study; 23 (74%) required no rescue IOP-lowering treatment. The mean (SD) IOP reduction from baseline at month 12 in nonrescued eyes was -4.3 (3.35) mmHg. The most common TEAE was conjunctival hyperemia (incidence 35.5%, 11/31). No implant-treated eye had a ≥ 15% loss in CECD from baseline. CONCLUSIONS: A single intracameral administration of the bimatoprost implant lowered IOP in the habitual position consistently throughout the day and night at week 8. The majority of participants continued to have reduced IOP for 1 year without additional therapy. The 1-year safety profile was favorable. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Supporting Birthing People and Supporting Doulas: The Impact of the COVID-19 Pandemic on a Community-Based Doula Organization in San Francisco.

Background: Beginning in March 2020, health care systems in the United States restricted the number of support people who could be present during pregnancy-related care to reduce the spread of COVID-19. We aimed to describe how SisterWeb, a community-based doula organization that employs Black, Pacific Islander, and Latinx doulas in San Francisco, California, adapted to the COVID-19 pandemic. Methods: As part of process and outcome evaluations conducted through an academic-community partnership, we interviewed SisterWeb doulas, mentors, and leaders in 2020, 2021, and 2022 (n=26 interviews). We identified preliminary themes using the Rapid Assessment Process and then conducted thematic analysis of data related to COVID-19. Results: SisterWeb leadership remained committed to safeguarding doulas by shifting to virtual support until doulas were onboarded as benefitted employees. Doulas reported hospital policies impacted clients' pregnancy-related care. Initially, doulas adapted to virtual support by connecting with clients more frequently through phone and text. When permitted to meet in person, doulas adjusted to client preference. Finally, as the pandemic impacted doulas' well-being, they turned to mentors for emotional support. Discussion and Health Equity Implications: This analysis contributes to a growing body of literature describing doulas' experiences during the pandemic. By shifting to virtual support, SisterWeb leaders prioritized the health, safety, and financial stability of doulas, who were members of communities disproportionately impacted by COVID-19. Our findings suggest that public health guidance, organizational COVID-19 precautions, and hospital policies hindered SisterWeb's goal of ensuring clients receive equitable medical care. In addition, we found that emotional support for doulas is vital to their work.

A Light-Promoted Innate Trifluoromethylation of Pyridones and Related N-Heteroarenes.

We report a practical, light-mediated perfluoroalkylation using Langlois' reagent (sodium trifluoromethylsulfinate) that proceeds in the absence of any photocatalyst or additives. This method has allowed for the facile functionalization of pyridones and related N-heteroarenes such as azaindole. This protocol is operationally simple, uses readily available materials, and is tolerable for electron-neutral and -rich functional pyridones. Cyclic voltammetry was utilized as a mechanistic probe, and preliminary data suggest the reaction may involve an electrophilic radical mechanism.

Dynamic and functional linkage between von Willebrand factor and ADAMTS-13 with aging: an Atherosclerosis Risk in Community study.

BACKGROUND: von Willebrand factor (VWF) is a multimeric glycoprotein critically involved in hemostasis, thrombosis, and inflammation. VWF function is regulated by its antigen levels, multimeric structures, and the state of enzymatic cleavage. Population studies in the past have focused almost exclusively on VWF antigen levels in cross-sectional study designs. OBJECTIVE: To identify subjects in the Atherosclerosis Risk in Community study who had persistently low and high VWF antigen over 10 years and to quantify longitudinal changes in the biological activities and cleavage of VWF in these subjects. METHODS: We measured VWF antigen, propeptide, adhesive activities, and cleavage by ADAMTS-13 quantified using a mass spectrometry method that detected the cleaved VWF peptide EQAPNLVY, as well as coagulation factor VIII activity. RESULTS: We determined the mean subject-specific increase in VWF to be 22.0 International Units (IU)/dL over 10 years, with 95% between -0.3 and 59.7 IU/dL. This aging-related increase was also detected in VWF propeptide levels, ristocetin cofactor activity, and VWF binding to collagen. We identified 4.1% and 25.0% of subjects as having persistently low (<50 IU/dL) and high (>200 IU/dL) VWF antigen, respectively. Subjects with persistently low VWF had enhanced ristocetin cofactor activity, whereas those with persistently high VWF had elevated levels of ADAMTS-13, resulting in a comparable rate of VWF cleavage between the 2 groups. CONCLUSIONS: These results provide new information about the effects of aging on VWF antigens and adhesive activity and identify a functional coordination between VWF and the rate of its cleavage by ADAMTS-13.

Dynein-Powered Cell Locomotion Guides Metastasis of Breast Cancer.

Metastasis is a principal cause of death in cancer patients, which remains an unresolved fundamental and clinical problem. Conventionally, metastatic dissemination is linked to the actomyosin-driven cell locomotion. However, locomotion of cancer cells often does not strictly line up with the measured actomyosin forces. Here, we identify a complementary mechanism of metastatic locomotion powered by the dynein-generated forces. These forces that arise within a non-stretchable microtubule network drive persistent contact guidance of migrating cancer cells along the biomimetic collagen fibers. We also show that dynein-powered locomotion becomes indispensable during invasive 3D migration within a tissue-like luminal network between spatially confining hydrogel microspheres. Our results indicate that the complementary contractile system of dynein motors and microtubules is always necessary and in certain instances completely sufficient for dissemination of metastatic breast cancer cells. These findings advance fundamental understanding of cell locomotion mechanisms and expand the spectrum of clinical targets against metastasis.