Seeking Communal Emotions in Social Practices That Culturally Evolved to Evoke Emotions: Worship, Kitten Videos, Memorials, Narratives of Love, and More.

In many instances, emotions do not simply happen to people by chance; Often, people actively seek out an emotion by engaging in practices that have culturally evolved to evoke that emotion. Such practices tend to be perpetuated and spread if people want to experience the emotion, like to recall it and tell others about it, want to give the emotion to others and experience it together, and/or regard the emotion as a sign of something wonderful. We illustrate this with a newly delineated emotion, kama muta. Many social practices around the world are structured to evoke kama muta. In those culturally evolved practices, and outside them, what typically evokes kama muta is a sudden intensification of communal sharing, or a sudden shift of attention to a communal sharing relationship. It seems probable that other social-relational emotions are also evoked by sudden changes in relationships or the sudden salience of a relationship. This change or saliencing may be incorporated in social practices that are perpetuated because they evoke the sought-after emotion. We suggest that such practices, as well as sudden changes in relationships that occur elsewhere, are especially promising places to discover social-relational emotions.

Surgery or Endovascular Therapy for Chronic Limb-Threatening Ischemia.

Chronic limb-threatening ischemia is defined as ischemic rest pain or tissue loss (eg, ulceration/gangrene) that has been present for greater than 2 weeks. Workup includes a careful history, physical examination focused on evaluation of pulses and wounds, lower extremity noninvasive vascular studies (eg, ankle-brachial indices, toe pressures), saphenous vein mapping, and imaging of the lower extremity arterial anatomy (eg, computed tomography, magnetic resonance, or subtraction angiography) if a revascularization intervention is planned.

Demographic but not competitive time lags can transiently amplify climate-induced changes in vegetation carbon storage.

How terrestrial ecosystems will accumulate carbon as the climate continues to change is a major source of uncertainty in projections of future climate. Under growth-stimulating environmental change, time lags inherent in population and community dynamic processes have been posed to dampen, or alternatively amplify, short-term carbon gain in terrestrial vegetation, but these outcomes can be difficult to predict. To theoretically frame this problem, we developed a simple model of vegetation dynamics that identifies the stage-structured demographic and competitive processes that could govern the timescales of carbon storage and loss. We show that demographic lags associated with growth-stimulating environmental change can allow a rapid increase in population-level carbon storage that is lost back to the atmosphere in later years. However, this transient carbon storage only emerges when environmental change increases the transition of adult individuals into a larger size class that suffers markedly higher mortality. Otherwise, demographic lags simply slow carbon accumulation. Counterintuitively, an analogous tradeoff between maximum adult size and survivorship in two-species models, coupled with environmental change-driven replacement, does not generate the transient carbon gain seen in the single-species models. Instead lags in competitive replacement slow the approach to the eventual carbon trajectory. Together, our results suggest that time lags inherent in demographic and compositional turnover tend to slow carbon accumulation in systems responding to growth-stimulating environmental change. Only under specific conditions will lagged demographic processes in such systems drive transient carbon accumulation, conditions that investigators can examine in nature to help project future carbon trajectories.

Corrigendum: Magnetic resonance imaging prognostic factors for survival and relapse in dogs with meningoencephalitis of unknown origin.

[This corrects the article DOI: 10.3389/fvets.2024.1370882.].

Advancing Ki67 hotspot detection in breast cancer: a comparative analysis of automated digital image analysis algorithms.

AIM: Manual detection and scoring of Ki67 hotspots is difficult and prone to variability, limiting its clinical utility. Automated hotspot detection and scoring by digital image analysis (DIA) could improve the assessment of the Ki67 hotspot proliferation index (PI). This study compared the clinical performance of Ki67 hotspot detection and scoring DIA algorithms based on virtual dual staining (VDS) and deep learning (DL) with manual Ki67 hotspot PI assessment. METHODS: Tissue sections of 135 consecutive invasive breast carcinomas were immunohistochemically stained for Ki67. Two DIA algorithms, based on VDS and DL, automatically determined the Ki67 hotspot PI. For manual assessment; two independent observers detected hotspots and calculated scores using a validated scoring protocol. RESULTS: Automated hotspot detection and assessment by VDS and DL could be performed in 73% and 100% of the cases, respectively. Automated hotspot detection by VDS and DL led to higher Ki67 hotspot PIs (mean 39.6% and 38.3%, respectively) compared to manual consensus Ki67 PIs (mean 28.8%). Comparing manual consensus Ki67 PIs with VDS Ki67 PIs revealed substantial correlation (r = 0.90), while manual consensus versus DL Ki67 PIs demonstrated high correlation (r = 0.95). CONCLUSION: Automated Ki67 hotspot detection and analysis correlated strongly with manual Ki67 assessment and provided higher PIs compared to manual assessment. The DL-based algorithm outperformed the VDS-based algorithm in clinical applicability, because it did not depend on virtual alignment of slides and correlated stronger with manual scores. Use of a DL-based algorithm may allow clearer Ki67 PI cutoff values, thereby improving the clinical usability of Ki67.

Characterization of a novel chicken γδ TCR-specific marker.

Chickens are a species with a high number of γδ T cells in various tissues. Despite their abundance, γδ T cells are poorly characterized in chickens, partially due to a lack of specific reagents to characterize these cells. Up until now, the TCR1 clone has been the only γδ T cell-specific monoclonal antibody (mAb) in chickens and additional reagents for γδ T cell subsets are needed. In order to address this issue, new mAb were generated in our laboratory by immunizing mice with in vitro cultured γδ T cells. In an initial flow cytometric screen a new mAb, clone "8D2", displayed an interesting staining pattern that mirrored γδ TCR up- and downregulation in the γδ T cell line D4 over time, prompting us to characterize this antibody further. We compared the expression of the unknown 8D2 epitope in combination with TCR1 staining across various primary cells. In splenocytes, peripheral blood lymphocytes and intestinal epithelial cells, 8D2 consistently labeled a subset of TCR1+ cells. To determine, whether specific γδ T cell receptors were recognized by 8D2, we sorted γδ T cells according to their 8D2 and TCR1 expression and analyzed their TCR V(D)J gene usage by TCR profiling. Strikingly, sorted 8D2+ cells preferentially expressed Vγ3 genes, whereas the TCR Vγ genes used by TCR1+ 8D2- cells were more variable. γδ TCR in 8D2+ cells were most frequently comprised of gamma chain VJ genes TRGV3-8 and TRGJ3, and delta chain VDJ genes TRDV1-2, TRDD2, TRDJ1. To confirm binding of 8D2 to specific γδ TCR, the preferentially utilized combination of TRG and TRD was expressed in HEK293 cells in combination with CD3, demonstrating surface binding of the 8D2 mAb to this Vγ3 γδ TCR-expressing cell line. Conversely, HEK293 cells expressing either Vγ1 or Vγ2 TCR did not react with 8D2. In conclusion, 8D2 is a novel tool for identifying specific Vγ3 bearing γδ T cells.

Brazilian Peppertree: Watch Out for This Lesser-Known Relative of Poison Ivy.

Brazilian peppertree (Schinus terebinthifolia), a member of the Anacardiaceae family, has invaded territory throughout the world, including the southeastern and western United States. Similar to fellow family members poison ivy and poison oak, Brazilian peppertree causes allergic contact dermatitis (ACD) in susceptible individuals. As this pest increases its range, dermatologists living in endemic areas should familiarize themselves with Brazilian peppertree, its effects on the skin, and how to treat any associated ACD.

Top Ten Tips Palliative Care Clinicians Should Know About Caring for Patients with Myeloproliferative Neoplasms.

Myeloproliferative neoplasms (MPNs) are a group of rare chronic progressive blood cancers that vary widely in clinical presentation, yet all patients have a risk of disease progression and thrombotic complications. Diseases include primary myelofibrosis, polycythemia vera, and essential thrombocythemia. With current treatment approaches, most patients live a prolonged life, but many experience a complex of symptoms that negatively influence their functional status and quality of life. Although significant advances have been made in preventing arterial and venous complications while mitigating inflammatory processes, comprehensive palliative care can help address unmet complex physical and psychosocial needs on a long-term basis. This article, created by a multidisciplinary group of providers, offers an overview of MPNs so palliative care clinicians can better support patients with these hematologic cancers.

Designing Patient-Reported Measures of Fertility: Cognitive Interview Findings from Adolescents and Young Adults with Cancer.

Purpose: Fertility concerns (FC) are central to the well-being of many adolescent and young adult (AYA) cancer survivors. Clinical conversations about FC and fertility preservation are suboptimal, increasing patient distress. The goal of this project was to establish content validity and comprehensibility of self-report questions on FCs for AYAs with cancer. Methods: Following best practices, we conducted: (1) item identification, refinement, and generation; (2) translatability and reading level review; and (3) cognitive interviews. Items were reviewed by five AYAs in each round of cognitive interviews. Results: A systematic search yielded 63 measures and 873 items. Fifty items were subsequently modified to enhance clarity and relevance, representing subdomains of psychological and social/relational FC. Flesch-Kincaid analysis found 31 items written above the 6th grade level, which were subsequently revised. Translatability review resulted in the modification of 3 items. During cognitive interviews, 76% of AYAs found items easy to answer with 52% describing them as "very easy" and 24% as "somewhat easy." Sixty percent of participants indicated the items captured their experiences. The majority of those who reported items only somewhat reflected or did not reflect their experiences suggested items were simply not applicable for their particular case. Conclusion: This study is a critical step toward the foundation for an FC measurement system that is reliable, flexible, developmentally appropriate, comprehensible, translatable, and interpretable. Subsequent steps include psychometric testing to examine the construct validity and reliability of the FC items and calibration to enable the application of computer-adaptive testing and short form development. The evaluation will include potential item response bias by age range, gender identity, and race/ethnicity.

Select Dietary Components Are Associated With Better Global Cognition in Adults With HIV.

ABSTRACT: People with HIV (PWH) are at an increased risk for cognitive impairment. Lifestyle factors can have protective effects on cognition; little work has examined diet and cognitive function in PWH. In this cross-sectional pilot study, 86 PWH (mean age 56 years) completed diet recalls and a neurocognitive assessment. Correlations were conducted between diet and cognitive function, adjusting for total calories, sex, and education (multiple comparison correction p values are reported). Diet quality of the sample was poor. Greater calories per day (r = 0.28, p =.08) and greater percentage of calories from saturated fatty acids (SFAs; r = 0.26, p = 0.08) were associated with better cognition. Higher intake of SFAs (rs 0.30-0.31, ps = 0.07), amino acids (rs = 0.27, ps = 0.08), and phosphorus (r = 0.29, p = .07) and magnesium (r = 0.25, p = .08) were associated with better cognition. A diet reflecting higher protein and fat relative to carbohydrates was associated with better cognition. Targeting individual nutrients, improving diet quality, and adequate caloric intake may preserve cognition in PWH.

Does preoperative forward elevation weakness affect clinical outcomes in anatomic or reverse total shoulder arthroplasty patients with glenohumeral osteoarthritis and intact rotator cuff?

Background: This study sought to determine if preoperative forward elevation (FE) weakness affects outcomes of anatomic (aTSA) and reverse total shoulder arthroplasty (rTSA) for patients with rotator cuff-intact glenohumeral osteoarthritis (RCI-GHOA). Methods: A retrospective review of a single institution's prospectively collected shoulder arthroplasty database was performed between 2007 and 2020, including 333 aTSAs and 155 rTSAs for primary RCI-GHOA with a minimum 2-year follow-up. Defining preoperative weakness as FE strength ≤4.9 pounds, three cohorts were matched 1:1:1 by age, sex, and follow-up: weak (n=82) to normal aTSAs, weak (n=44) to normal rTSAs, and weak aTSAs (n=61) to weak rTSAs. Compared outcomes included range of motion, outcome scores, and complication and revision rates at latest follow-up. Results: Weak aTSAs and weak rTSAs achieved similar postoperative outcome measures to normal aTSAs and normal rTSAs, respectively (P>0.05). Compared to weak rTSAs, weak aTSAs achieved superior postoperative passive (P=0.006) and active external rotation (ER) (P=0.014) but less favorable postoperative Shoulder Pain and Disability Index (P=0.032), American Shoulder and Elbow Surgeons (P=0.024), and University of California, Los Angeles scores (P=0.008). Weak aTSAs achieved the minimal clinically important difference (MCID) and substantial clinical benefit at a lower rate for abduction (P=0.045 and P=0.003) and FE (P=0.011 and P=0.001). Weak aTSAs had a higher revision rate (P=0.025) but a similar complication rate (P=0.291) compared to weak rTSAs. Conclusions: Patients with RCI-GHOA and preoperative FE weakness obtain postoperative outcomes similar to patients with normal preoperative strength after either aTSA or rTSA. Preoperatively, weak aTSAs achieved greater ER but lower rates of clinically relevant improvement in overhead motion compared to weak rTSAs. Level of evidence: III.

["Who cares about us?" Results of a cross-sectional study on the psychosocial health of obstetricians and midwives after traumatic birth experiences]. / "Wer kümmert sich um uns?" Ergebnisse einer Querschnittsuntersuchung zur psychosozialen Gesundheit von Geburtshelfer*innen und Hebammen nach traumatischen Geburtserlebnissen.

BACKGROUND: Traumatic births not only cause emotional stress for expectant parents but can also affect the psychosocial health of midwives and obstetricians due to their professional demands. AIM: To evaluate the impact of traumatic birth experiences on the psychosocial health of obstetric healthcare professionals. METHODS: A cross-sectional study using validated measurement tools (Impact of Event Scale Revised IES-R, Copenhagen Burnout Inventory CBI) and assessing post-traumatic growth (PGI-SF) through an online survey of midwives and obstetricians in German-speaking areas. RESULTS: The study included 700 participants with peripartum and/or personal traumas. Of the 528 participants who completed the IES-R, 33 (6.3%) with post-traumatic stress disorder (PTSD) received less support from colleagues (p = 0.007) and were more likely to experience workplace consequences (p < 0.001) than participants without PTSD. A moderate to high level of burnout was found in 66.2% of the 542 participants who completed the CBI. Personal growth through experiencing trauma was reported by 75.9% of the 528 participants who completed the PGI-SF. CONCLUSION: The psychosocial health of midwives and obstetricians is at risk due to traumatic birth experiences. Screening tests and the provision of collegial and professional debriefings to strengthen resilience are essential preventive interventions.

Reconsidering the usefulness of long-term high-dose buprenorphine.

Buprenorphine has been successfully used for decades in the treatment of opioid use disorder, yet there are complexities to its use that warrant attention to maximize its utility. While the package insert of the combination product buprenorphine\naloxone continues to recommend a maximum dose of 16 mg daily for maintenance, the emergence of fentanyl and synthetic analogs in the current drug supply may be limiting the effectiveness of this standard dose. Many practitioners have embraced and appropriately implemented novel practices to mitigate the sequelae of our current crisis. It has become common clinical practice to stabilize patients with 24 - 32 mg of buprenorphine daily at treatment initiation. Many of these patients, however, are maintained on these high doses (>16 mg/d) indefinitely, even after prolonged stability. Although this may be a necessary strategy in the short term, there is little evidence to support its safety and efficacy, and these high doses may be exposing patients to more complications and side effects than standard doses. Commonly known side effects of buprenorphine that are likely dose-related include hyperhidrosis, sedation, decreased libido, constipation, and hypogonadism. There are also complications related to the active metabolite of buprenorphine (norbuprenorphine) which is a full agonist at the mu opioid receptor and does not have a ceiling on respiratory suppression. Such side effects can lead to medical morbidity as well as decreased medication adherence, and we, therefore, recommend that after a period of stabilization, practitioners consider a trial of decreasing the dose of buprenorphine toward standard dose recommendations. Some patients' path of recovery may never reach this stabilization phase (i.e., several months of adherence to medications, opioid abstinence, and other clinical indicators of stability). Side effects of buprenorphine may not have much salience when patients are struggling for survival and safety, but for those who are fortunate enough to advance in their recovery, the side effects become more problematic and can limit quality of life and adherence.

Assessment of genetic diversity and population structure of U.S. Polypay sheep from breed origins to future genomic selection.

Knowledge of past and present genetic diversity within a breed is critical for the design and optimization of breeding programs as well as the development of strategies for the conservation of genetic resources. The Polypay sheep breed was developed at the U.S. Sheep Experiment Station (USSES) in 1968 with the goal of improving productivity in Western U.S. range flocks. It has since flourished in the more intensively managed production systems throughout the U.S. The genetic diversity of the breed has yet to be documented. Therefore, the primary objective of this study was to perform a comprehensive evaluation of the genetic diversity and population structure of U.S. Polypay sheep using both pedigree- and genomic-based methods. Pedigree data from 193 Polypay flocks participating in the National Sheep Improvement Program (NSIP) were combined with pedigree records from USSES (n = 162,997), tracing back to the breed's origin. A subset of these pedigreed sheep from 32 flocks born from 2011 to 2023 were genotyped with the GGP Ovine 50K BeadChip containing 51,867 single nucleotide polymorphisms (SNPs). Four subgroups were used for the pedigree-based analyses: 1) the current generation of animals born in 2020-2022 (n = 20,701), 2) the current generation with a minimum of four generations of known ancestors (n = 12,685), 3) only genotyped animals (n = 1,856), and 4) the sires of the current generation (n = 509). Pedigree-based inbreeding for the full population was 2.2%, with a rate of inbreeding of 0.22% per generation. Pedigree-based inbreeding, Wright's inbreeding, and genomic inbreeding based on runs of homozygosity were 2.9%, 1.3%, and 5.1%, respectively, for the genotyped population. The effective population size ranged from 41 to 249 for the pedigree-based methods and 118 for the genomic-based estimate. Expected and observed heterozygosity levels were 0.409 and 0.403, respectively. Population substructure was evident based on the fixation index (FST), principal component analysis, and model-based population structure. These analyses provided evidence of differentiation from the foundation flock (USSES). Overall, the Polypay breed exhibited substantial genetic diversity and the presence of a population substructure that provides a basis for the implementation of genomic selection in the breed.

Comparative genome analysis and the genome-shaping role of long terminal repeat retrotransposons in the evolutionary divergence of fungal pathogens Blastomyces dermatitidis and Blastomyces gilchristii.

Blastomyces dermatitidis and Blastomyces gilchristii are cryptic species of fungi that cause blastomycosis, an often severe disease involving pulmonary infection capable of systemic dissemination. While these species appear morphologically identical, differences exist in the genetic makeup, geographical range, and possibly the clinical presentation of infection. Here, we show genetic divergence between the cryptic species through both a Blastomyces species tree constructed from orthologous protein sequences and whole genome single nucleotide variant phylogenomic analysis. Following linked-read sequencing and de novo genome assembly, we characterized and compared the genomes of 3 B. dermatitidis and 3 B. gilchristii isolates. The B. gilchristii genomes (73.25-75.4 Mb), were ∼8 Mb larger than the B. dermatitidis genomes (64.88-66.61 Mb). Average nucleotide identity was lower between genomes of different species than genomes of the same species, yet functional classification of genes suggested similar proteomes. The most striking difference involved long terminal repeat retrotransposons. Although the same retrotransposon elements were detected in the genomes, the quantity of elements differed between the two species. Gypsy retrotransposon content was significantly higher in B. gilchristii (38.04-39.26 Mb) than in B. dermatitidis (30.85-32.40 Mb), accounting for the majority of genome size difference between species. Age estimation and phylogenetic analysis of the reverse transcriptase domains suggested that these retrotransposons are relatively ancient, with genome insertion predating the speciation of B. dermatitidis and B. gilchristii. We postulate that different trajectories of genome contraction led to genetic incompatibility, reproductive isolation and speciation, highlighting the role of transposable elements in fungal evolution.

Flow cytometry assay modifications: Recommendations for method validation based on CLSI H62 guidelines.

The Clinical and Laboratory Standards Institute (CLSI) H62-Validation of Assays Performed by Flow Cytometry guideline, released in 2021, provides recommendations for platform workflow and quality system essentials, instrument setup and standardization, assay development and optimization and fit-for-purpose analytical method validation. In addition, CLSI H62 includes some recommendations for the validation strategies after a validated flow cytometric method has been modified. This manuscript builds on those recommendations and discusses the impact of different types of assay modifications on assay performance. Recommendations regarding which validation parameters to evaluate depending on the type of modification are provided. The impact of assay modification on the assay's intended use is discussed. When recommending minor deviations from the CLSI H62 process for a laboratory-initiated assay revision (e.g., specimen numbers for sensitivity, specificity, or precision studies), a rationale based on expert opinion is provided with the understanding that not every laboratory, assay type, and circumstance can be comprehensively addressed in this paper. These recommendations are meant as a practical recommendation and are not intended to be restrictive, prescriptive, or understood as necessarily sufficient to meet every specific requirement from regulatory bodies (e.g., FDA or New York State Department of Health).

The genus Cortinarius should not (yet) be split.

The genus Cortinarius (Agaricales, Basidiomycota) is one of the most species-rich fungal genera, with thousands of species reported. Cortinarius species are important ectomycorrhizal fungi and form associations with many vascular plants globally. Until recently Cortinarius was the single genus of the family Cortinariaceae, despite several attempts to provide a workable, lower-rank hierarchical structure based on subgenera and sections. The first phylogenomic study for this group elevated the old genus Cortinarius to family level and the family was split into ten genera, of which seven were described as new. Here, by careful re-examination of the recently published phylogenomic dataset, we detected extensive gene-tree/species-tree conflicts using both concatenation and multispecies coalescent approaches. Our analyses demonstrate that the Cortinarius phylogeny remains unresolved and the resulting phylogenomic hypotheses suffer from very short and unsupported branches in the backbone. We can confirm monophyly of only four out of ten suggested new genera, leaving uncertain the relationships between each other and the general branching order. Thorough exploration of the tree space demonstrated that the topology on which Cortinarius revised classification relies on does not represent the best phylogenetic hypothesis and should not be used as constrained topology to include additional species. For this reason, we argue that based on available evidence the genus Cortinarius should not (yet) be split. Moreover, considering that phylogenetic uncertainty translates to taxonomic uncertainty, we advise for careful evaluation of phylogenomic datasets before proposing radical taxonomic and nomenclatural changes.

Outcomes following Humeral Head Autograft Glenoid Reconstruction in Primary Reverse Total Shoulder Arthroplasty.

BACKGROUND: Patients with severe glenoid bone loss are at increased risk for poor implant fixation, scapular notching, dislocation, joint kinematic disturbances, and prosthetic failure following reverse total shoulder arthroplasty (rTSA). Glenoid bone grafting has proven useful when performing rTSA in patients with inadequate glenoid bone stock, although the current literature is limited. The purpose of this study is to evaluate clinical outcomes in patients with significant glenoid deformity undergoing primary rTSA with one-stage glenoid reconstruction using a humeral head autograft. METHODS: A database of prospectively enrolled patients was reviewed to identify patients who underwent primary rTSA with humeral head autograft (n=40) between 2008 and 2020 by six high-volume shoulder arthroplasty surgeons with minimum two-year follow-up. Variables studied included demographics, medical comorbidities, range of motion (ROM), Constant score, American Shoulder and Elbow Surgeons (ASES) score, pain score, patient satisfaction, glenoid deformity, revisions and complications. Preoperative glenoid deformity was characterized using glenoid version and beta-angles, measured on computed tomography (CT). Improvement at final follow-up was compared to a matched control group of 120 standard primary rTSA patients. Following the post hoc Bonferroni correction, an adjusted alpha value of 0.004 was used to define statistical significance. RESULTS: Forty patients were included with a mean follow-up of 5.3 (range, 2.0-13.2) years. Patients exhibited a mean preoperative glenoid retroversion and beta-angle of 29° and 80°, respectively. At final follow-up, patients who received a graft exhibited lower mean scores for active external rotation (25° vs. 39°; p = 0.001) in comparison to those who did not receive a graft. No differences were observed in active abduction (p = 0.029), active forward elevation (p = 0.009), active internal rotation (p = 0.147), passive external rotation (p = 0.082), Global Shoulder Function score (p = 0.157), Constant score (p = 0.036), ASES score (p = 0.009), or pain score (p = 0.186) between groups. Seven patients (17.5%) exhibited complications of which the most common being aseptic glenoid loosening (15%). CONCLUSION: This study demonstrates that patients undergoing primary rTSA with autogenous humeral head autograft for severe glenoid deficiency experience postoperative improvements in ROM and functional outcome scores that exceeded the minimal clinically important difference and substantial clinical benefit but inferior to matched controls. This suggests that glenoid reconstruction using a resected humeral head autograft is an effective strategy when conducting primary rTSA in patients with significant glenoid deformity.

IMSIS: An instrumented microphysiological system with integrated sensors for monitoring cellular metabolic activities.

Well plates are widely used in biological experiments, particularly in pharmaceutical sciences and cell biology. Its popularity stems from its versatility to support a variety of fluorescent markers for high throughput monitoring of cellular activities. However, using fluorescent markers in traditional well plates has its own challenges, namely, they can be potentially toxic to cells, and thus, may perturb their biological functions; and it is difficult to monitor multiple analytes concurrently and in real-time inside each well. This paper presents a fully instrumented microphysiological system with integrated sensors (IMSIS) with a similar well format. Each well in the microphysiological system has a set of sensors for monitoring multiple metabolic analytes in real-time. The IMSIS platform is supported by integrated bioelectronic circuits and a graphical user interface for easy user configuration and monitoring. The system has integrated microfluidics to maintain its microphysiological environment within each well. The IMSIS platform currently incorporates O2, H2O2, and pH sensors inside each well, allowing up to six wells to perform concurrent measurements in real-time. Furthermore, the architecture is scalable to achieve an even higher level of throughput. The miniaturized design ensures portability, suitable for small offices and field applications. The IMSIS platform was successfully used to monitor in real-time the mitochondrial functions of live bovine embryos in O2 consumption, H2O2 release as an indication of ROS production, and extracellular acidity changes before and after the introduction of external substrates.

Mapping safe drinking water use in low- and middle-income countries.

Safe drinking water access is a human right, but data on safely managed drinking water services (SMDWS) is lacking for more than half of the global population. We estimate SMDWS use in 135 low- and middle-income countries (LMICs) at subnational levels with a geospatial modeling approach, combining existing household survey data with available global geospatial datasets. We estimate that only one in three people used SMDWS in LMICs in 2020 and identified fecal contamination as the primary limiting factor affecting almost half of the population of LMICs. Our results are relevant for raising awareness about the challenges and limitations of current global monitoring approaches and demonstrating how globally available geospatial data can be leveraged to fill data gaps and identify priority areas in LMICs.