bluuebunny/crossref_metadata_2025 huggingface dataset:
Caring for Patients With Malignant Fungating Wounds
Authors: Yasmara Deni , Tam Sin-Hang , Fang Su-Ying
Published: January 2024

PURPOSE:

The aim of this scoping literature review was to identify current knowledge related to management of malignant fungating wounds (MFWs), gaps in this knowledge, and areas for future research.

METHODS:

This was a scoping literature review.

SEARCH STRATEGY:

Six electronic databases (Embase, MEDLINE, Cochrane (CENTRAL), CINAHL, Scopus, and Web of Science) were searched spanning the years 1987 and 2022. The initial electronic database search retrieved 6041 studies. The search is based on 60 articles published between 1987 and 2022, along with 14 additional studies were based on search of reference lists of key articles.

FINDINGS:

Studies were divided into 2 main domains; the vast majority (65 of 72, 87.8%) focused on symptom impact, measurement, and management. The remaining articles (n = 9, 12.2%) focused on caring for patients with MFW; these studies focused on nursing care experiences and competencies, along with lay caregiver experiences. Findings indicated that instruments have been developed to evaluate symptoms of MFW but only a few have been validated. Most of the studies reviewed evaluated the influence of MFW on physical and psychosocial function. Local and systematic symptom managements such as modern dressings, wound care strategies, surgery, and radiotherapy as well as chemotherapy were found to be effective in alleviating symptoms. Findings also indicated that families and nurses encounter obstacles and burdens when caring for patients with MFW; limited studies were retrieved that investigated the competence and needs of nurses in their caring journey.

IMPLICATIONS:

Future studies should focus on: (1) using better designs to evaluate and compare topical agents and dressings to control odor, (2) validating assessment tools specific to MFW, (3) qualitative studies designed to enhance understanding family and nurses' experiences, and (4) improving the nurse's ability to care for patients with MFWs and their responses to managing these challenging patients.
Health Inequity in Likelihood and Time to Renal Recovery after Living Kidney Donation: Implications for Kidney Health in Black Americans
Authors: Rabbani Muhammad Umaid , Reed Rhiannon D , McLeod Marshall C , MacLennan Paul A , Kumar Vineeta , Locke Jayme E
Published: January 2024

BACKGROUND:

Live donor kidney transplantation has been popularized to help mitigate the organ shortage crisis. At the time of living donor nephrectomy, living donors lose 50% of their kidney function or glomerular filtration rate (GFR). Studies have shown that in healthy living donors, the remaining kidney is able to adapt and recover 10% to 25% of postdonation lost GFR. GFR recovery is critical to long-term kidney health, particularly for Black Americans who disproportionately suffer from kidney disease with an incidence 2.5 times White Americans. To date, no study has examined whether health inequities in renal recovery postdonation exist.

STUDY DESIGN:

We retrospectively analyzed 100,121 living kidney donors reported to the Scientific Registry of Transplant Recipients between 1999 and 2021. We estimated GFR (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration 2021 equation and predicted the likelihood (logistic regression) and time (Cox regression) to recovery of 60% and 75% predonation eGFR. Models adjusted for age, sex, race, BMI, and predonation eGFR.

RESULTS:

Black patients were 47% (adjusted odds ratio 0.53, 95% CI 0.50 to 0.56, p < 0.001) and 43% (adjusted odds ratio 0.57, 95% CI 0.54 to 0.60, p < 0.001) less likely to recover 60% and 75% of predonation eGFR, respectively, compared with their White counterparts. The hazard ratio for time to renal recovery of 60% and 75% of predonation eGFR was 22% (adjusted hazard ratio 0.78, 95% CI 0.76 to 0.80, p < 0.001) and 38% (adjusted hazard ratio 0.62, 95% CI 0.60 to 0.65, p < 0.001) lower, respectively, than White patients.

CONCLUSIONS:

Black living kidney donors were less likely to recover predonation eGFR, and time to renal recovery was significantly longer than their White counterparts. These data highlight the need for enhanced living kidney donor follow-up, particularly for Black living kidney donors who are at greatest future risk of end-stage kidney disease.
The interplay of facilitation and competition drives the emergence of multistability in dryland plant communities
Authors: Pichon Benôıt , Gounand Isabelle , Donnet Sophie , Kéfi Sonia
Published: January 2024

Species are wrapped in a set of feedbacks within communities and with their abiotic environment, which can can generate alternative stable states. So far, research on alternative stable states has mostly focused on systems with a small number of species and a limited diversity of interaction types. Here, we analyze a spatial model of plant community dynamics in drylands, where each species is characterized by a strategy, and interact through facilitation and competition. Our work identifies three different types of multistability emerging from the interplay of competition and facilitation. Under low-stress levels, the community organizes in small groups of coexisting species maintained by space and facilitation, while under higher stress levels, positive feedbacks from competition and facilitation lead to the dominance of a single species before desertification happens. Our study paves the way for bridging community ecology and alternative states theory in a common framework.
The medial entorhinal cortex encodes multisensory spatial information
Authors: Nguyen Duc , Wang Garret , Gu Yi
Published: January 2024

Animals employ spatial information in multisensory modalities to navigate their natural environments. However, it is unclear whether the brain encodes such information in separate cognitive maps or integrates all into a single, universal map. We addressed this question in the microcircuit of the medial entorhinal cortex (MEC), a cognitive map of space. Using cellular-resolution calcium imaging, we examined the MEC of mice navigating virtual reality tracks, where visual and auditory cues provided comparable spatial information. We uncovered two cell types: “unimodality cells” and “multimodality cells”. The unimodality cells specifically represent either auditory or visual spatial information. They are anatomically intermingled and maintain sensory preferences across multiple tracks and behavioral states. The multimodality cells respond to both sensory modalities with their responses shaped differentially by auditory and visual information. Thus, the MEC enables accurate spatial encoding during multisensory navigation by computing spatial information in different sensory modalities and generating distinct maps.
The 22q11.2 deletion syndrome from a biopsychosocial perspective: an ICF-based approach
Authors: Corrêa Cabral Ana Paula , Gandelman Horovitz Dafne Dain , Santos Lidiane Nogueira , de Carvalho Carvalho Amanda Oliveira , Wing Cristina Maria Duarte , Castaneda Luciana , Simon Liane , Ribeiro Carla Trevisan M.
Published: January 2024

Purpose

To describe children with 22q11.2 deletion syndrome functioning from a biopsychosocial perspective, focusing on the impact of children’s health condition from domains to the International Classification of Functioning, Disability and Health (ICF).

Methods

A descriptive, cross-sectional case series study with 22q11.2del children. A questionnaire with an ICF checklist for 22q11.2del was completed using a structured interview. The Test of Childhood Language ABFW was used to fill in vocabulary, fluency and language pragmatics questions. The Wechsler Abbreviated Scale of Intelligence (WASI) was used to determine Intelligence Quotient (IQ).

Results

Seven participants from 7 to 12 years old, presented some level of IQ impairment. Observed that 22q11.2del children experience significant intellectual, cognitive and speech impairment across ICF Body Function domains. Impairment related to nose and pharynx were found in only one patient. The most relevant categories considered limitations in Activity and Participation component were pertained to producing nonverbal messages, communication, handling stress and social interaction. Family, health professionals and acquaintances were perceived as facilitators in the component Environmental Factors.

Conclusion

Children with 22q11.2del have their functioning affected by aspects that go beyond medical diagnosis. A checklist base on ICF for functional profile can contribute to incorporate a biopsychosocial approach.
Anxiety appraisal in mothers of preterm neonates admitted in critical care unit
Authors: Gul Rafia , Fatima Samer , Khurshid Samina , Niamat Sidra , Anwar Zahid , Ahdi Saher Gul
Published: January 2024

Background

Mothers of premature neonates often confront various psychological challenges including postpartum depression, anxiety, and elevated stress levels. However, anxiety has not received the necessary emphasis in routine clinical practice and research, often going unnoticed. There is insufficient data regarding the utilization of specific tools for screening maternal anxiety in hospitalized preterm infants. The study aimed to determine the prevalence of maternal anxiety and its risk factors among mothers of premature neonates admitted to the intensive care unit.

Methods

Following Institutional Review Board (IRB) approval, a descriptive cross-sectional study was conducted at level-III Neonatal Unit, Fatima Memorial Hospital Shadman, Lahore over duration of 30 months, (January 2021-July 2023). Mothers werescreened for anxiety using Perinatal Anxiety Screening Scale (PASS) having 31 items. Comparative descriptive statistics and multiple logistic regression were applied to identify all risk factor while taking p <0.05 as significant.

Results

Out of 430 mothers, 28.1% experienced anxiety. Statistically significant factors for maternal anxiety include young age, urban residence, higher education, smoking, diabetes, depression/anxiety diagnosis, primiparity, delivery complications, maternal involvement in neonatal care, breastfeeding, fear of handling preterm infants at home, and prematurity-related concerns, as well as gestational age, birth weight, and weight for gestational age (p < 0.05). Among all these, however, prematurity <28 weeks (p < 0.001, AOR 496, 95% CI 22.5–10951) and 28-31+6 weeks (p < 0.001, AOR 265, 95% CI 14– 5010), alongwith primiparity (p = 0.001, AOR 16.483, 95% CI 3.287–82.648), and SGA (p = 0.025, AOR 8.9, 95% CI 1.3–60.6) increase while extended family system protects from maternal anxiety (p = 0.002, AOR 0.25, 95% CI 0.106–0.595).

Conclusion

Every third mother in our study population who delivered prematurely experienced anxiety. The younger gestational age, first-time motherhood, SGA neonate increase while the extended family system serves as a protective factor against maternal anxiety.
Annexin- and calcium-regulated priming of legume root cells for endosymbiotic infection
Authors: Guillory Ambre , Fournier Joëlle , Kelner Audrey , Hobecker Karen , Auriac Marie-Christine , Frances Lisa , Delers Anaïs , Pedinotti Léa , Ru Aurélie Le , Keller Jean , Delaux Pierre-Marc , Gutjahr Caroline , Frei Dit Frey Nicolas , de Carvalho-Niebel Fernanda
Published: January 2024

Legumes establish endosymbioses with arbuscular mycorrhizal (AM) fungi or rhizobia bacteria to improve mineral nutrition. Symbionts are hosted in privileged habitats, root cortex (for AM fungi) or nodules (for rhizobia) for efficient nutrient exchange. To reach these habitats, plants form cytoplasmic bridges, which are key to predicting and guiding the cellular route of entry of fungal hyphae or rhizobia-filled infection threads (ITs). However, the underlying mechanisms are poorly studied. Here we show that unique ultrastructural changes and Ca2+spiking signatures, closely linked to MtAnn1 annexin accumulation, accompany rhizobia-associated bridge formation. Loss ofMtAnn1function inM. truncatulaaffects Ca2+spike amplitude, cytoplasmic configuration and rhizobia infection efficiency, consistent with a role of MtAnn1 in regulating infection priming.MtAnn1,which evolved in species establishing intracellular symbioses, is also AM-symbiosis-induced and required for proper arbuscule formation. Together, we propose that MtAnn1 is part of an ancient Ca2+-regulatory module for transcellular endosymbiotic infection.
Rgf1 GEF activity toward Rho1 defines a new actin-dependent signal to determine growth sites independently of microtubules and Tea1
Authors: Garcia Patricia , Celador Ruben , Edreira Tomas , Sanchez Yolanda
Published: January 2024

Cellular asymmetry begins with the selection of a discrete point on the cell surface that triggers Rho-GTPases activation and localized assembly of the cytoskeleton to establish new growth zones. The cylindrical shape of fission yeast is organized by microtubules that deliver the landmark Tea1–Tea4 complex at the cell tips to define the growth poles. However, only a fewtea1Δ cells mistaken the direction of growth, indicating that they manage to detect their growth sites. Here we show that Rgf1 (Rho1-GEF) and Tea4 are components of the same complex and that Rgf1 activity toward Rho1 is required for strengthen Tea4 at the cell tips. Moreover, in cells lacking Tea1, selection of the correct growth site depends on Rgf1 and on a correctly polarized actin cytoskeleton, both necessary for Rho1 activation at the pole. We propose an actin-dependent mechanism driven by Rgf1–Rho1 that marks the poles independently of microtubules and the Tea1–Tea4 complex.
Mechanism and regulation of cargo entry into the Commander recycling pathway
Authors: Butkovič Rebeka , Walker Alexander P. , Healy Michael D. , McNally Kerrie E. , Liu Meihan , Kato Kohji , Collins Brett M. , Cullen Peter J.
Published: January 2024

Commander is a multiprotein complex that orchestrates endosomal recycling of diverse integral cargo proteins and in humans is required for normal skeletal, brain, kidney, and cardiovascular development. While the structure of this complex has recently been described, the central question of how cargo proteins are selected for entry into the Commander recycling pathway remains unclear. Here using recombinant protein reconstitution andin silicopredictions we identify the evolutionary conserved mechanism through which the unstructured carboxy-terminal tail of the integral protein adaptor sorting nexin-17 (SNX17) directly binds to the Retriever sub-complex of Commander. SNX17 adopts an autoinhibited conformation where its carboxy-terminal tail occupies the cargo binding groove. Competitive cargo binding overcomes this autoinhibition, promoting SNX17 endosomal residency and the release of the carboxy tail for Retriever association. Using molecular cell biology and high-resolution microscopy, we establish the central importance of SNX17-Retriever association in the handover of integrin and lipoprotein receptor cargoes into pre-existing endosomal retrieval sub-domains for entry into the recycling pathway. In describing the principal mechanism of cargo entry into the Commander recycling pathway we provide key insight into the function and regulation of this evolutionary conserved sorting complex.
Growth phase-dependent reorganization of cryptophyte photosystem I antennae
Authors: Zhang Shumeng , Si Long , Su Xiaodong , Li Mei
Published: January 2024

Photosynthetic cryptophytes are eukaryotic algae that utilize membrane-embedded chlorophyll a/c binding proteins (CACs) and lumen-localized phycobiliproteins (PBPs) as their light-harvesting antennae. Cryptophytes go through logarithmic and stationary growth phases, and may adjust their light-harvesting capability according to their particular growth state. How cryptophytes change the type/arrangement of the photosynthetic antenna proteins to regulate their light-harvesting remains unknown. Here we solved four structures of cryptophyte photosystem I (PSI) bound with CACs that show the rearrangement of CACs at different growth phases. We identified a cryptophyte-unique protein, PsaQ, which harbors three chlorophyll molecules. PsaQ specifically binds to the lumenal region of PSI during logarithmic growth phase and may assist the association of PBPs with photosystems and energy transfer from PBPs to photosystems.
High-throughput formulation of reproducible 3D cancer microenvironments for drug testing in myelogenous leukemia
Authors: Rudzinska-Radecka M. , Turos-Korgul L. , Mukherjee D. , Podszywalow-Bartnicka P. , Piwocka K. , Guzowski J.
Published: January 2024

Targeting cancer microenvironment is currently one of the major directions in drug development and preclinical studies in leukemia. Despite the variety of available chronic myelogenous leukemia 3D culture models, the reproducible generation of miniaturized leukemia microenvironments, suitable for high-throughput drug testing, has remained a challenge. Here, we use microfluidics to generate over ten thousand highly monodisperse leukemic-bone marrow hydrogel microbeads per minute. We employ gelatin methacrylate (GelMA) as a model extracellular matrix (ECM) and tune the concentration of the biopolymer, as well as other possible components of the ECM (fibrin, hyaluronic acid), cell concentration and the ratio of leukemic cells to bone marrow cells within the microbeads. This allows to achieve optimal cell viability and the propensity of the encapsulated cells to microtissue formation, while also warranting long-term stability of the microbeads in culture. We administer model kinase inhibitor, imatinib, at various concentrations to the microbeads and, via comparing mono-and co-culture conditions (cancer alone vs cancer-stroma), we find that the stroma-leukemia crosstalk systematically protects the encapsulated cells against the drug-induced cytotoxicity, confirming therefore that our system mimics the physiological stroma-dependent protection. We finally discuss applicability of our model to (i) studying the role of direct-or close-contact interactions between leukemia and bone marrow cells embedded in 3D ECM on the stroma-mediated protection, and (ii) high-throughput screening of anti-cancer therapeutics in personalized therapies.
Meta-metabolome ecology reveals that geochemistry and microbial functional potential are linked to organic matter development across seven rivers
Authors: Danczak Robert E. , Goldman Amy E. , Borton Mikayla A. , Chu Rosalie K. , Toyoda Jason G. , Garayburu-Caruso Vanessa A. , Graham Emily B. , Morad Joseph W. , Renteria Lupita , Hager Jacqueline R. , Arnon Shai , Brooks Scott , Bar-Zeev Edo , Jones Michael , Jones Nikki , Lewandowski Jorg , Meile Christof , Mueller Birgit M. , Schalles John , Schulz Hanna , Ward Adam , Stegen James C.
Published: January 2024

Rivers receive substantial dissolved organic matter (DOM) input from the land and transport it to the ocean. As DOM travels through watersheds, it undergoes biotic and abiotic transformations that impact biogeochemical cycles and any subsequent CO2release into the atmosphere. While recent research has increased our mechanistic knowledge of DOM composition within watersheds, DOM development across broad spatial distances and within divergent biomes is under investigated. Here, we combined DOM characterization, geochemical analyses, and shotgun metagenomics to analyze samples from seven rivers ranging from the U.S. Pacific Northwest to Berlin, Germany. Initial analyses revealed that many DOM properties were distinguished by river type (e.g., wastewater, headwater) and that geochemistry often explained variation across rivers. At a global scale, analyses rooted in meta-metabolome ecology indicated that DOM was structured overwhelmingly by deterministic selection. When controlling for scale, however, analyses indicated that ecological assembly dynamics were again partially structured by river type. Finally, microbial analyses revealed that many riverine microbes from our systems shared core metabolic functional potential while differing in peripheral capabilities in across the rivers. Further analysis of the carbon degradation potential for recovered metagenomically assembled genomes indicated that the sampled rivers had strong taxonomically conserved niche differentiation and that carbon degradation potential diversity was significantly related to organic matter diversity. Together, these results help us uncover interconnections between the development of DOM, riverine geochemistry, and microbial functional potential.
Negative Synergistic Effects of Drought and Heat During Flowering and Seed Setting in Soybean
Authors: Poudel Sadikshya , Vennam Ranadheer Reddy , Sankarapillai Lekshmy V. , Liu Jinbo , Reddy K. Raja , Wijewardane Nuwan K. , Mukhtar M. Shahid , Bheemanahalli Raju
Published: January 2024

Rising temperatures and intense heatwaves combined with lower precipitations are the new norms of current global scenarios. These altered climatic conditions negatively impact soybean yield potential and quality. Ten soybean cultivars were subjected to four different growing conditions: control, drought, heat, and combined heat and drought to understand the physiological, yield, and molecular changes. Stomatal conductance was reduced by 62% and 10% under drought and heat, respectively. This reduction was further exacerbated to 93% when exposed to both stresses simultaneously. The highest canopy temperature was recorded at +8 °C with combinatorial treatments, whereas heat and drought exhibited +5.4 °C and +2 °C, respectively. Furthermore, combined stress displayed a more pronounced negative impact on greenness-associated vegetative index; the gene expression analysis further corroborated these findings. Particularly, each °C increase in temperature during flowering-seed filling reduced seed weight by ∼7% and ∼4% with and without drought, respectively. The seed protein increased under drought, whereas the oil showed a converse trend under drought and combined stresses. Most physiology and yield traits showed no significant correlations between control or individual and combined stress. This suggests that selection for combinatorial stress may not be appropriate based on nonstress or individual stress performance. Thus, incorporating stress-resilient traits into elite soybean cultivars could significantly boost soybean production under hot and dry climatic conditions.
Evaluation of the efficacy of a full-spectrum medicinal cannabis plant extract with less than 0.3% Δ9-tetrahydrocannabinol inin vitromodels of inflammation and excitotoxicity
Authors: Ross-Munro Emily , Isikgel Esra , Fleiss Bobbi
Published: January 2024

The rapid development of research on the therapeutic benefits of medicinal cannabis, in parallel with an increased understanding of the endocannabinoid system, has driven research ofCannabis sativaconstituents for managing neurological conditions. While most studies have focused on the therapeutic potential of the major components of cannabis plant extract isolated or combined, limited research has explored the pharmacological benefits of whole cannabis plant extract. In this study, we investigated the potential anti-inflammatory and neuroprotective effects of NTI-164, a novel full-spectrum cannabis extract with negligible Δ9-tetrahydrocannabinol (THC), compared with cannabidiol (CBD) alone in BV-2 microglial and SHSY-5Y neuronal cells. The inflammation-induced upregulation of microglial inflammatory mediators, being tumour necrosis factor α (TNFα), granulocyte-macrophage colony-stimulating factor (GM-CSF), inducible nitric oxide synthase (iNOS), and Arginase-1 (Arg-1), were significantly attenuated by NTI-164. This immunomodulatory effect was not observed upon treatment with isolated CBD. Compared to CBD alone, NTI-164 prevented elevated mitochondrial activity while normalising cell numbers in immune-activated microglia cells. NTI-164 also promoted the proliferation of undifferentiated neurons and the survival of differentiated neurons under excitotoxic conditions. Overall, our work shows that the anti-inflammatory and neuroprotective effects of NTI-164 as a full-spectrum cannabis extract are enhanced relative to that of CBD alone, highlighting the potential therapeutic efficacy of NTI-164 for the treatment of neuropathologies such as autism spectrum disorder (ASD) and related neuropathologies. This study has further shown that understanding the synergistic effect of phytocannabinoids is integral to realising the therapeutic potential of full-spectrum cannabis extract to inform the design of botanical-derived treatments for managing neurological disorders.
Early detection and treatment of postpartum haemorrhage: a cost-effectiveness analysis of the E-MOTIVE trial
Authors: Williams E.V. , Goranitis I. , Oppong R. , Perry S.J. , Devall A. , Martin J.T. , Mammoliti K-M. , Beeson L. , Sindhu K.N. , Galadanci H. , Alwy Al‑beity F. , Qureshi Z. , Hofmeyr G.J. , Moran N. , Fawcus S. , Mandondo S. , Middleton L. , Hemming K. , Oladapo O. , Gallos I. , Coomarasamy A. , Roberts T.E.
Published: January 2024

Background

Timely detection and treatment of postpartum haemorrhage (PPH) are crucial to prevent complications or death. A calibrated blood-collection drape can help provide objective, accurate, and early diagnosis of PPH and a treatment bundle can address delays or inconsistencies in the use of effective interventions.

Methods

We conducted an incremental cost-effectiveness analysis alongside the E-MOTIVE trial, an international, parallel cluster-randomised trial with a baseline control phase, designed to assess a multi-component intervention for PPH in patients having vaginal delivery. We compared the E-MOTIVE intervention, which included a calibrated blood-collection drape for early detection of PPH and a bundle of first-response treatments (uterine massage, oxytocic drugs, tranexamic acid, intravenous fluids, examination, and escalation), with usual care. We used multilevel modelling to estimate incremental cost-effectiveness ratios from the perspective of the public healthcare system for outcomes of cost per case of severe PPH (blood loss ≥1000 mL) prevented and cost per disability-adjusted life-year (DALY) averted.

Results

A total of 80 secondary-level hospitals across Kenya, Nigeria, South Africa, and Tanzania, in which 210,132 patients underwent vaginal delivery, were randomly assigned to the E-MOTIVE group or the usual-care group. Among hospitals and patients with data, severe PPH was diagnosed in 1.6% of patients in the E-MOTIVE group and 4.3% of patients in the usual-care group (risk difference, -2.6%; 95% CI -3.1% to -2.1%). Mean DALYs per patient were lower for the E-MOTIVE group (-0.0027; 95% CI -0.0081 to 0.0029) whilst mean costs per patient were slightly higher compared with the usual-care group (0.30 USD; 95% CI -2.31 to 2.78). The E-MOTIVE intervention was deemed cost-effective at contemporary willingness-to-pay thresholds and remained cost-effective across the full range of sensitivity and country-level analyses.

Interpretation

Use of a calibrated blood-collection drape for early detection of PPH and bundled first-response treatment is cost-effective and should be perceived by decision makers as a worthwhile use of healthcare budgets.

Funding

Bill & Melinda Gates Foundation (NCT04341662).
The pandemic, COVID-19 disease and perinatal health
Authors: Jung Shelley , Liu Emily F , Goin Dana E , Rudolph Kara E , Mujahid Mahasin S , Dow William H , Ahern Jennifer
Published: January 2024

Adverse effects of COVID-19 on perinatal health have been documented, however there is a lack of research that separates individual disease from other changing risks during the pandemic period. We linked California statewide birth and hospital discharge data for 2019-2020, and compared health indicators among 3 groups of pregnancies: [a] 2020 delivery with COVID-19, [b] 2020 delivery with no documented COVID-19, and [c] 2019 pre-pandemic delivery. We aimed to quantify the links between COVID-19 and perinatal health, separating individual COVID-19 disease (a vs b) from the pandemic period (b vs c). We examined the following health indicators: preterm birth, hypertensive disorders of pregnancy, gestational diabetes mellitus and severe maternal morbidity. We applied model based standardization to estimate “average effect of treatment on the treated” risk differences (RD), and adjusted for individual and community-level confounders. Among pregnancies in 2020, those with COVID-19 disease had higher burdens of preterm birth (RD[95% confidence interval (CI)]=2.8%[2.1,3.5]), hypertension (RD[95% CI]=3.3%[2.4,4.1]), and severe maternal morbidity (RD[95% CI]=2.3%[1.9,2.7]) compared with pregnancies without COVID-19 (a vs b) adjusted for confounders. Pregnancies in 2020 without COVID-19 had a lower burden of preterm birth (RD[95% CI]=-0.4%[-0.6,-0.3]), particularly spontaneous preterm, and a higher burden of hypertension (RD[95% CI]=1.0%[0.9,1.2]) and diabetes RD[95%CI]=0.9%[0.8,1.1] compared with pregnancies in 2019 (b vs c) adjusted for confounders. Protective associations of the pandemic period for spontaneous preterm birth may be explained by socioenvironmental and behavioral modifications, while increased maternal conditions may be due to stress and other behavioral changes. To our knowledge, our study is the first to distinguish between individual COVID-19 disease and the pandemic period in connection with perinatal outcomes.
Metabolomic and Immunologic Discriminators of MIS-C at Emergency Room Presentation
Authors: Vella Laura A. , Berna Amalia Z. , Blatz Allison M. , Logan Joey , Sharma Priya , Liu Yang , Tedesco Jonathan , Toland Cara , Babiker Leena , Hafertepe Kathryn , Kammerman Shane , Novacek Josef , Akaho Elikplim , Gonzalez Alexander K. , Taylor Deanne , Diorio Caroline , Balamuth Fran , Bassiri Hamid , Odom John Audrey R.
Published: January 2024

Multisystem Inflammatory Syndrome in Childhood (MIS-C) follows SARS-CoV-2 infection and frequently leads to intensive care unit admission. The inability to rapidly discriminate MIS-C from similar febrile illnesses delays treatment and leads to misdiagnosis. To identify diagnostic discriminators at the time of emergency department presentation, we enrolled 104 children who met MIS-C screening criteria, 14 of whom were eventually diagnosed with MIS-C. Before treatment, we collected breath samples for volatiles and peripheral blood for measurement of plasma proteins and immune cell features. Clinical and laboratory features were used as inputs for a machine learning model to determine diagnostic importance. MIS-C was associated with significant changes in breath volatile organic compound (VOC) composition as well as increased plasma levels of secretory phospholipase A2 (PLA2G2A) and lipopolysaccharide binding protein (LBP). In an integrated model of all analytes, the proportion of TCRVβ21.3+ non-naive CD4 T cells expressing Ki-67 had a high sensitivity and specificity for MIS-C, with diagnostic accuracy further enhanced by low sodium and high PLA2G2A. We anticipate that accurate diagnosis will become increasingly difficult as MIS-C becomes less common. Clinical validation and application of this diagnostic model may improve outcomes in children presenting with multisystem febrile illnesses.
Diagnostic Performance of Radiomics in Prediction of Ki-67 Index Status in Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis
Authors: Shahidi Ramin , Hassannejad Ehsan , Baradaran Mansoureh , Klontzas Michail E. , HajiEsmailPoor Zanyar , Chong Weelic , Broomand Nima , Alizadeh Mohammadreza , Sadeghsalehi Hamidreza , Mozafari Navid , Teimoori Soraya , Farhadi Akram , Nouri Hamed , Shobeiri Parnian , Sotoudeh Houman
Published: January 2024

Background

Lung cancer is a global health concern, in part due to its high prevalence and invasiveness. The Ki-67 index, indicating cellular proliferation, is pivotal for assessing lung cancer aggressiveness. Radiomics is the inference of quantifiable data features from medical images through algorithms and may offer insights into tumor behavior. Here, we perform a systematic review and meta-analysis to assess the performance of radiomics for predicting Ki-67 status in Non-small Cell Lung Cancer (NSCLC) on CT scan.

Methods and materials

A comprehensive search of the current literature was conducted using relevant keywords in PubMed/MEDLINE, Embase, Scopus, and Web of Science databases from inception to November 16, 2023. Original studies discussing the performance of CT-based radiomics for predicting Ki-67 status in NSCLC cohorts were included. The quality assessment involved quality assessment of diagnostic accuracy studies (QUADAS-2) and radiomics quality score (RQS). Quantitative meta-analysis, using R, assessed pooled sensitivity and specificity in NSCLC cohorts.

Results

We identified 10 studies that met the inclusion criteria, involving 2279 participants, with 9 of these studies included in quantitative meta-analysis. The overall quality of the included studies was moderate to high based on QUADAS-2 and RQS assessment. The pooled sensitivity and specificity of radiomics-based models for predicting the Ki-67 status of NSCLC training cohorts were 0.78 (95% CI [0.73; 0.83]) and 0.76 (95% CI [0.70; 0.82]), respectively. The pooled sensitivity and specificity of radiomics-based models for predicting the Ki-67 status of NSCLC validation cohorts were 0.79 (95% CI [0.73; 0.84]) and 0.69 (95% CI [0.61; 0.76]), respectively. Substantial heterogeneity was noted in the pooled sensitivity and specificity of training cohorts and the pooled specificity of validation cohorts (I2> 40%). It was identified that utilizing ITK-SNAP as a segmentation software contributed to a significantly higher pooled sensitivity.

Conclusion

This meta-analysis indicates promising diagnostic accuracy of radiomics in predicting Ki-67 in NSCLC. The study underscores radiomics’ potential in personalized lung cancer management, advocating for prospective studies with standardized methodologies and larger samples.
Macromolecular toolbox to elucidate CLE-RLK binding, signaling and downstream effects
Authors: Narasimhan Madhumitha , Jahnke Nina , Kallert Felix , Bahafid Elmehdi , Böhmer Franziska , Hartmann Laura , Simon Rüdiger
Published: January 2024

Plant peptides communicate by binding to a large family of receptor-like kinases (RLKs) and they share a conserved binding mechanism, which may account for their promiscuous interaction with several RLKs. In order to understand the in vivo binding specificity of CLE peptide family, we have developed a novel set of CLAVATA 3 (CLV3) based peptide tools. After carefully evaluating the CLE peptide binding characteristics, using solid phase synthesis process, we have modified the CLV3 peptide and attached a fluorophore and a photoactivable side group. We observed that the labeled CLV3 shows binding specificity within CLAVATA1 clade of RLKs while avoiding the distantly-related PEP RECEPTOR clade, thus resolving the contradictory results obtained previously by many in vitro methods. Furthermore, we observed that the RLK-bound CLV3 undergoes clathrin-mediated endocytosis and gets trafficked to vacuole via ARA7-labeled endosomes. Additionally, modifying CLV3 for light-controlled activation enabled spatial and temporal control over CLE signalling. Hence our CLV3 macromolecular toolbox can be used to study rapid cell specific down-stream effects. Given the conserved binding properties, in the future our toolbox can also be used as a template to modify other CLE peptides.

Highlight

A macromolecular tool box consisting of modified CLE peptide with fluorescent molecule and photoactivable group offers reliable insights into its in vivo binding characteristics, localization and signaling.
Transcriptional responses of brain endothelium toPlasmodium falciparumpatient-derived isolatesin vitro
Authors: Askonas Caroline , Storm Janet , Camarda Grazia , Craig Alister , Pain Arnab
Published: January 2024

A hallmark of cerebral malaria (CM) is sequestration ofPlasmodium falciparuminfected erythrocytes (IE) within the brain microvasculature. Binding of IE to endothelium reduces microvascular flow and combined with an inflammatory response perturbs endothelial barrier function, resulting in breakdown of the blood- brain barrier (BBB). Cytoadherence leads to activation of the endothelium and alters a range of cell processes affecting signalling pathways, receptor expression, coagulation, and disruption of BBB integrity. Here, we investigated whether CM derived parasites elicit differential effects on human brain microvascular endothelial cells (HBMECs), as compared to uncomplicated malaria (UM) derived parasites. Patient-derived IE from UM and CM clinical cases, as well as non-binding skeleton-binding protein 1 knockout parasites, were overlaid onto TNF-activated HBMECs. Gene expression analysis of endothelial responses was performed using probe-based assays of a panel of genes involved in inflammation, apoptosis, endothelial barrier function, and prostacyclin synthesis pathway. We observed a significant effect on endothelial transcriptional responses in the presence of IE, yet there was no significant correlation between HBMEC responses and type of clinical syndrome (UM or CM). Further, there was no correlation between HBMEC gene expression and both binding itself and level of IE binding to HBMEC, as we detected the same change in endothelial responses when employing both binding and non-binding parasites. Our results suggest that interaction of IE with endothelial cells in this co-culture model induce some endothelial responses that are independent of clinical origin and independent of the expression of the major variant antigenPfEMP1 on the IE surface.
Single nuclei multiomics reveals the drought-driven gene regulatory atlas in Arabidopsis
Authors: Liu Jinbao , Majeed Aqsa , Kumar Nilesh , Pajerowska-Mukhtar Karolina M. , Mukhtar M. Shahid
Published: January 2024

The regulation of gene expression in plant responses to drought has been thoroughly investigated in previous studies. Despite this, a detailed understanding of the cell type-specific regulatory mechanisms, encompassing multi-layered biological processes, is lacking. In this study, we report the use of single-nucleus multiomic analysis in Arabidopsis seedlings in response to drought stress. Our single-nuclei RNA (snRNA) analysis delineated 14 distinct clusters representing major root and shoot cell types and discovered new cell type-specific drought markers. Integration of snRNA with single-nuclei ATAC (snATAC) data in leaf epidermis, root endodermis, and guard cells revealed accessible chromatin regions (ACRs)-linked genes predominantly enriched in pathways responsive to drought, heat, and light. Motif enrichment analysis and gene regulatory network (GRN) inference highlighted key transcription factors (TFs) and regulatory networks related to ethylene signaling pathways in endodermis as well as circadian rhythms in both endodermis and guard cells. Pseudotime analysis identified critical transcriptomic progression from metabolic process to stress response within three cell types. Overall, this study elucidates drought-related regulatory mechanisms in Arabidopsis at single-cell resolution, providing valuable insights into the fundamental regulatory events involved in stress responses. It also serves as a reference for future single-cell multiomic investigations in crop plants.

One Sentence Summary

Single cell multiomic analysis under drought stress
Transcriptomic analysis of pubertal and adult virgin mouse mammary epithelial and stromal cell populations
Authors: Heijmans Nika , Wiese Katrin E. , Jonkers Jos , van Amerongen Renée
Published: January 2024

Conflicting data exist as to how mammary epithelial cell proliferation changes during the reproductive cycle. To study the effect of endogenous hormone fluctuations on gene expression in the mouse mammary gland, we performed bulk RNAseq analyses of epithelial and stromal cell populations that were isolated either during puberty or at different stages of the adult virgin estrous cycle. Our data confirm prior findings that proliferative changes do not occur in every mouse in every cycle. We also show that during the estrous cycle the main gene expression changes occur in adipocytes and other stromal cells. Finally, we present a comprehensive overview of theWntgene expression landscape in different mammary gland cell types in pubertal and adult mice. This work contributes to understanding the effects of physiological hormone fluctuations and locally produced signaling molecules on gene expression changes in the mammary gland during the reproductive cycle and should be a useful resource for future studies investigating gene expression patterns in different cell types across different developmental timepoints.
Evaluating Evapotranspiration in a Commercial Greenhouse: A Comparative Study of Microclimatic Factors and Machine-Learning Algorithms
Authors: Averbuch Nir , Moshelion Menachem
Published: January 2024

The FAO-56 Penman-Monteith equation (FPME) is commonly used to calculate evapotranspiration and apply necessary irrigation, based on environmental data usually taken from a single measuring station. In this study, we hypothesized that the accuracy of the FPME is affected by microclimatic changes over time and space within the target area. Therefore, we tested the impact of numerous spatial and temporal environmental measurement points in a commercial greenhouse on the accuracy of the FPME, by comparing its evapotranspiration evaluation to the actual evaporation measured by dozens of weighing lysimeters throughout the year. Additionally, we harnessed the capabilities of machine-learning algorithms to utilize the extensive data acquired for predicting evapotranspiration. Our results revealed that the daily FPME exhibited a -22% to +22% discrepancy in accuracy, as compared to the lysimeters, with overestimation in the winter and underestimation in the summer. Interestingly, using more data points per day led to less accurate FPME evaluation. The conflict between an increased number of data points and a reduction in accuracy was explained by daily hysteresis. Machine-learning algorithms (Decision Tree, Random Forest, XGBoost and Neural Network) showed impressive accuracy in predicting evapotranspiration, when the model dataset contained temporal parameters (R2> 0.918). Furthermore, we demonstrated that spatial sampling had a stronger effect on the accuracy of predictions than the amount of the data collected. Specifically, when we used 10% of the original dataset (3.01e5 entries) with high consideration of spatial measurements, the best-performing models (Random Forest and XGBoost) were highly accurate (R2= 0.913 andR2= 0.935, respectively). The top three most influential features of all models were light, day and hour, underscoring the importance of the temporal dimension. This approach allowed us to explore the potential of leveraging advanced computational methods to improve the estimation of water loss under various environmental conditions.
The Zymoseptoria tritici avirulence factor AvrStb6 accumulates in hyphae close to stomata and triggers a wheat defense response hindering fungal penetration
Authors: Alassimone Julien , Praz Coraline , Lorrain Cécile , Francesco Agustina De , Carrasco-López Cristian , Faino Luigi , Meile Lukas , Sánchez-Vallet Andrea
Published: January 2024

Zymoseptoria tritici, the causal agent of septoria tritici blotch, is one of Europe’s most damaging wheat pathogens, causing significant economic losses. Genetic resistance is a common strategy to control the disease,Stb6being a resistance gene used for over 100 years in Europe. This study investigates the molecular mechanisms underlying Stb6-mediated resistance. Utilizing confocal microscopy imaging, we identified thatZ. triticiepiphytic hyphae mainly accumulates the corresponding avirulence factor AvrStb6 in close proximity to stomata. Consequently, the progression of AvrStb6-expressing avirulent strains is hampered during penetration. The fungal growth inhibition co-occurs with a transcriptional reprogramming in wheat characterized by an induction of immune responses, genes involved in stomata regulation, and cell wall-related genes. Overall, we shed light on the gene-for-gene resistance mechanisms in the wheat -Z. triticipathosystem at the cytological and transcriptomic level, and our results highlight that stomata penetration is a critical process for pathogenicity and resistance.
NEUROG2regulates a human-specific neurodevelopmental gene regulatory program
Authors: Chinchalongporn Vorapin , Vasan Lakshmy , Saleh Fermisk , Zinyk Dawn , Ghazale Hussein , Oproescu Ana-Maria , Patel Shruti , Rozak Matthew , Amemiya Yutaka , Han Sisu , Moffat Alexandra , Black Sandra E , McLaurin JoAnne , Near Jamie , Seth Arun , Goubran Maged , Reiner Orly , Okawa Satoshi , Schuurmans Carol
Published: January 2024

Unique hallmarks of human neocortical development include slower rates of neurogenesis and the establishment of an extracellular matrix-rich, outer-subventricular zone that supports basal neural progenitor cell expansion. How gene regulatory networks have evolved to support these human-specific neurodevelopmental features is poorly understood. Mining single cell data from cerebral organoids and human fetal cortices, we found thatNEUROG2expression is enriched in basal neural progenitor cells. To identify and purifyNEUROG2-expressing cells and trace their short-term lineage, we engineered twoNEUROG2-mCherryknock-in human embryonic stem cell lines to produce cerebral organoids. Transcriptomic profiling of mCherry-high organoid cells revealed elevated expression ofPPP1R17, associated with a fast-evolving human-accelerated regulatory region, oligodendrocyte precursor cell and extracellular matrix-associated gene transcripts. Conversely, only neurogenic gene transcripts were enriched in mCherry-high cortical cells fromNeurog2:mCherryknock-in mice. Finally, we show thatNeurog2is sufficient to inducePpp1r17, which slows human neural progenitor cell division, andCol13a1, an extracellular matrix gene, in P19 cells.NEUROG2thus regulates a human neurodevelopmental gene regulatory program implicated in supporting a pro-proliferative basal progenitor cell niche and tempering the neurogenic pace.

SUMMARY STATEMENT

Transcriptomic analyses ofNEUROG2-mCherryknock-in human embryonic stem cell-derived cerebral organoids reveal a link betweenNEUROG2and extracellular matrix remodeling during human cortical development.
Trans2express – de novo transcriptome assembly pipeline optimized for gene expression analysis
Authors: Kasianova Aleksandra M. , Penin Aleksey A. , Schelkunov Mikhail I. , Kasianov Artem S. , Logacheva Maria D. , Klepikova Anna V.
Published: January 2024

Background

As genomes of many eukaryotic species, especially plants, are large and complex, theirde novosequencing and assembly is still a difficult task despite progress in sequencing technologies. An alternative to genome assembly is the assembly of transcriptome, the set of RNA products of the expressed genes. While a bunch ofde novotranscriptome assemblers exists, the challenges of transcriptomes (the existence of isoforms, the uneven expression levels across genes) complicates the generation of high-quality assemblies suitable for downstream analyses.

Results

We developed Trans2express – a web-based tool and a pipeline ofde novohybrid transcriptome assembly and postprocessing based on rnaSPAdes with a set of subsequent filtrations. The pipeline was tested onArabidopsis thalianacDNA sequencing data obtained using Illumina and Oxford Nanopore Technologies platforms. The comparison of structural characteristics of the transcriptome assembly with referenceArabidopsisgenome revealed the high quality of assembled transcriptome with 86.1% ofArabidopsisexpressed genes assembled as a single contig. We tested the applicability of the transcriptome assembly for gene expression analysis and showed high congruence of gene expression levels and sets of differentially expressed genes between analyses based on genome and based on the transcriptome assembly.

Conclusions

We present Trans2express – a protocol forde novohybrid transcriptome assembly aimed at recovering of a single transcript per gene. We expect this protocol to promote the characterization of transcriptomes and gene expression analysis in non-model plants and web-based tool to be of use to a wide range of plant biologists.