bluuebunny/crossref_metadata_2025 huggingface dataset:
An investigation of the effect of the universal model of family-centered care on patient and family outcomes in patients under home invasive mechanical ventilation
Authors: Kavand Babak , Asgari Parvaneh
Published: May 2024

Background

The number of patients under home mechanical ventilation is increasing worldwide. The unique nature of these patients and their complex health needs exposes home caregivers to various needs and challenges regarding different dimensions of care.

Objective

The present study was conducted to investigate the effect of the universal model of family-centered care on the clinical outcomes of the patient and the family.

Methods

This clinical trial was conducted between 2020 and 2021. A total of 60 patients under invasive mechanical ventilation was selected and divided into control (routine training that is usually given by hospital staff to families to care for patients) and intervention (comprehensive pre-discharge training program to post-discharge follow-up using the universal model of family-centered care) groups using random block design and universal model of family-centered care. Home caregivers’ functional skills and burden, as well as patients’ readmission and mortality rates, were compared in the two groups.

Results

Implementing the intervention 1 and 3 months later effectively increased home caregivers’ functional skills. Moreover, a statistically significant difference was observed between the two groups in terms of the psychological burden of caregiving (P < .001); the implementation of the intervention could highly reduce the psychological burden of caregiving in the intervention group (EF = 0.94). The hospital readmission and mortality rate in the intervention group was significantly lower than in the control group (P = .02 and P = .03, respectively).

Conclusions

Given the significant impact of the universal model of family-centered care on the clinical outcomes of the patient and the family, pre-discharge training and its post-discharge follow-up and continuity of education with an active presence of nurses, as one of the main pillars of the treatment, seems essential.
Sensitivity of Salmonella Typhimurium to nisin in vitro and in orange juice under refrigeration
Authors: Fernandes da Silva Carla Gabriela , Santos Lopes Flávio , Cardoso Vieira Valois Álissy Fernanda , Vieira Prudêncio Cláudia
Published: May 2024

The influence of environmental factors on Salmonella sensitivity to nisin in vitro and in refrigerated orange juice were investigated. Nisin activity was observed in the different conditions, but the highest efficiency was achieved at lower pH (4.0) and with higher bacteriocin concentration (174 µM). Moreover, the bactericidal action was directly proportional to the incubation period. When tested in orange juice, nisin caused a reduction of up to 4.05 logarithm cycles in the Salmonella population. So, environmental factors such as low pH and low temperature favored the sensitization of Salmonella cells to the bactericidal action of nisin. Therefore, this may represent an alternative to control Salmonella in refrigerated foods.
Colonization of vancomycin-resistant Enterococcus faecium in human-derived colonic epithelium: unraveling the transcriptional dynamics of host–enterococcal interactions
Authors: Stege Paul B , Beekman Jeffrey M , Hendrickx Antoni P A , van Eijk Laura , Rogers Malbert R C , Suen Sylvia W F , Vonk Annelotte M , Willems Rob J L , Paganelli Fernanda L
Published: May 2024

Enterococcus faecium is an opportunistic pathogen able to colonize the intestines of hospitalized patients. This initial colonization is an important step in the downstream pathogenesis, which includes outgrowth of the intestinal microbiota and potential infection of the host. The impact of intestinal overgrowth on host–enterococcal interactions is not well understood. We therefore applied a RNAseq approach in order to unravel the transcriptional dynamics of E. faecium upon co-culturing with human derived colonic epithelium. Co-cultures of colonic epithelium with a hospital-associated vancomycin resistant (vanA-type) E. faecium (VRE) showed that VRE resided on top of the colonic epithelium when analyzed by microscopy. RNAseq revealed that exposure to the colonic epithelium resulted in upregulation of 238 VRE genes compared to the control condition, including genes implicated in pili expression, conjugation (plasmid_2), genes related to sugar uptake, and biofilm formation (chromosome). In total, 260 were downregulated, including the vanA operon located on plasmid_3. Pathway analysis revealed an overall switch in metabolism to amino acid scavenging and reduction. In summary, our study demonstrates that co-culturing of VRE with human colonic epithelium promotes an elaborate gene response in VRE, enhancing our insight in host–E. faecium interactions, which might facilitate the design of novel anti-infectivity strategies.
Prevalence of human respiratory pathogens and associated mucosal cytokine levels in young children and adults: a cross-sectional observational study in the Netherlands during the winter of 2012/2013
Authors: van Kasteren Puck B , Gelderloos Anne T , Nicolaie Mioara Alina , den Hartog Gerco , Vissers Marloes , Luytjes Willem , Rots Nynke Y , van Beek Josine
Published: May 2024

Respiratory pathogens can cause severe disease and even death, especially in the very young and very old. Studies investigating their prevalence often focus on individuals presenting to healthcare providers with symptoms. However, the design of prevention strategies, e.g. which target groups to vaccinate, will benefit from knowledge on the prevalence of, risk factors for and host response to these pathogens in the general population. In this study, upper respiratory samples (n = 1311) were collected cross-sectionally during winter from 11- and 24-month old children, their parents, and adults ≥60 years of age that were recruited irrespective of seeking medical care. Almost all children, approximately two-thirds of parents and a quarter of older adults tested positive for at least one pathogen, often in the absence of symptoms. Viral interference was evident for the combination of rhinovirus and respiratory syncytial virus. Attending childcare facilities and having siblings associated with increased pathogen counts in children. On average, children showed increased levels of mucosal cytokines compared to parents and especially proinflammatory molecules associated with the presence of symptoms. These findings may guide further research into transmission patterns of respiratory pathogens and assist in determining the most appropriate strategies for the prediction and prevention of disease.
siRNA that participates in Drosophila dosage compensation is produced by many 1.688X and 359 bp repeats
Authors: Biswas Sudeshna , Gurdziel Katherine , Meller Victoria H
Published: May 2024

Organisms with differentiated sex chromosomes must accommodate unequal gene dosage in males and females. Male fruit flies increase X-linked gene expression to compensate for hemizygosity of their single X chromosome. Full compensation requires localization of the Male-Specific Lethal (MSL) complex to active genes on the male X, where it modulates chromatin to elevate expression. The mechanisms that identify X chromatin are poorly understood. The euchromatic X is enriched for AT-rich, ∼359 bp satellites termed the 1.688X repeats. Autosomal insertions of 1.688X DNA enable MSL recruitment to nearby genes. Ectopic expression of dsRNA from one of these repeats produces siRNA and partially restores X-localization of MSLs in males with defective X recognition. Surprisingly, expression of double-stranded RNA from three other 1.688X repeats failed to rescue males. We reconstructed dsRNA-expressing transgenes with sequence from two of these repeats and identified phasing of repeat DNA, rather than sequence or orientation, as the factor that determines rescue of males with defective X recognition. Small RNA sequencing revealed that siRNA was produced in flies with a transgene that rescues, but not in those carrying a transgene with the same repeat but different phasing. We demonstrate that pericentromeric X heterochromatin promotes X recognition through a maternal effect, potentially mediated by small RNA from closely related heterochromatic repeats. This suggests that the sources of siRNAs promoting X recognition are highly redundant. We propose that enrichment of satellite repeats on Drosophilid X chromosomes facilitates the rapid evolution of differentiated sex chromosomes by marking the X for compensation.
Notch signaling without the APH-2/nicastrin subunit of gamma secretase in Caenorhabditis elegans germline stem cells
Authors: Brinkley David M , Smith Karen C , Fink Emma C , Kwen Woohyun , Yoo Nina H , West Zachary , Sullivan Nora L , Farthing Alex S , Hale Valerie A , Goutte Caroline
Published: May 2024

The final step in Notch signaling activation is the transmembrane cleavage of Notch receptor by γ secretase. Thus far, genetic and biochemical evidence indicates that four subunits are essential for γ secretase activity in vivo: presenilin (the catalytic core), APH-1, PEN-2, and APH-2/nicastrin. Although some γ secretase activity has been detected in APH-2/nicastrin-deficient mammalian cell lines, the lack of biological relevance for this activity has left the quaternary γ secretase model unchallenged. Here, we provide the first example of in vivo Notch signal transduction without APH-2/nicastrin. The surprising dispensability of APH-2/nicastrin is observed in Caenorhabditis elegans germline stem cells (GSCs) and contrasts with its essential role in previously described C. elegans Notch signaling events. Depletion of GLP-1/Notch, presenilin, APH-1, or PEN-2 causes a striking loss of GSCs. In contrast, aph-2/nicastrin mutants maintain GSCs and exhibit robust and localized expression of the downstream Notch target sygl-1. Interestingly, APH-2/nicastrin is normally expressed in GSCs and becomes essential under conditions of compromised Notch function. Further insight is provided by reconstituting the C. elegans γ secretase complex in yeast, where we find that APH-2/nicastrin increases but is not essential for γ secretase activity. Together, our results are most consistent with a revised model of γ secretase in which the APH-2/nicastrin subunit has a modulatory, rather than obligatory role. We propose that a trimeric presenilin-APH-1-PEN-2 γ secretase complex can provide a low level of γ secretase activity, and that cellular context determines whether or not APH-2/nicastrin is essential for effective Notch signal transduction.
A theory of optimal convex regularization for low-dimensional recovery
Authors: Traonmilin Yann , Gribonval Rémi , Vaiter Samuel
Published: May 2024

We consider the problem of recovering elements of a low-dimensional model from under-determined linear measurements. To perform recovery, we consider the minimization of a convex regularizer subject to a data fit constraint. Given a model, we ask ourselves what is the ‘best’ convex regularizer to perform its recovery. To answer this question, we define an optimal regularizer as a function that maximizes a compliance measure with respect to the model. We introduce and study several notions of compliance. We give analytical expressions for compliance measures based on the best-known recovery guarantees with the restricted isometry property. These expressions permit to show the optimality of the $\ell ^{1}$-norm for sparse recovery and of the nuclear norm for low-rank matrix recovery for these compliance measures. We also investigate the construction of an optimal convex regularizer using the examples of sparsity in levels and of sparse plus low-rank models.
Microbiome processing of organic nitrogen input supports growth and cyanotoxin production of Microcystis aeruginosa cultures
Authors: Li Wei , Baliu-Rodriguez David , Premathilaka Sanduni H , Thenuwara Sharmila I , Kimbrel Jeffrey A , Samo Ty J , Ramon Christina , Kiledal Erik Anders , Rivera Sara R , Kharbush Jenan , Isailovic Dragan , Weber Peter K , Dick Gregory J , Mayali Xavier
Published: May 2024

Nutrient-induced blooms of the globally abundant freshwater toxic cyanobacterium Microcystis cause worldwide public and ecosystem health concerns. The response of Microcystis growth and toxin production to new and recycled nitrogen (N) inputs and the impact of heterotrophic bacteria in the Microcystis phycosphere on these processes are not well understood. Here, using microbiome transplant experiments, cyanotoxin analysis, and nanometer-scale stable isotope probing to measure N incorporation and exchange at single cell resolution, we monitored the growth, cyanotoxin production, and microbiome community structure of several Microcystis strains grown on amino acids or proteins as the sole N source. We demonstrate that the type of organic N available shaped the microbial community associated with Microcystis, and external organic N input led to decreased bacterial colonization of Microcystis colonies. Our data also suggest that certain Microcystis strains could directly uptake amino acids, but with lower rates than heterotrophic bacteria. Toxin analysis showed that biomass-specific microcystin production was not impacted by N source (i.e. nitrate, amino acids, or protein) but rather by total N availability. Single-cell isotope incorporation revealed that some bacterial communities competed with Microcystis for organic N, but other communities promoted increased N uptake by Microcystis, likely through ammonification or organic N modification. Our laboratory culture data suggest that organic N input could support Microcystis blooms and toxin production in nature, and Microcystis-associated microbial communities likely play critical roles in this process by influencing cyanobacterial succession through either decreasing (via competition) or increasing (via biotransformation) N availability, especially under inorganic N scarcity.
Effects of high doses of zearalenone on some antioxidant enzymes and locomotion of Tenebrio molitor larvae (Coleoptera: Tenebrionidae)
Authors: Janković-Tomanić Milena , Petković Branka , Vranković Jelena S , Perić-Mataruga Vesna
Published: May 2024

The mealworm Tenebrio molitor L. (Coleoptera: Tenebrionidae) feeds on wheat bran and is considered both a pest and an edible insect. Its larvae contain proteins and essential amino acids, fats, and minerals, making them suitable for animal and human consumption. Zearalenone (ZEA) is the mycotoxin most commonly associated with Fusarium spp. It is found in cereals and cereal products, so their consumption is a major risk for mycotoxin contamination. One of the most important effects of ZEA is the induction of oxidative stress, which leads to physiological and behavioral changes. This study deals with the effects of high doses of ZEA (10 and 20 mg/kg) on survival, molting, growth, weight gain, activity of antioxidant enzymes superoxide dismutase (SOD) and glutathione S-transferase (GST), and locomotion of mealworm larvae. Both doses of ZEA were found to (i) have no effect on survival, (ii) increase molting frequency, SOD, and GST activity, and (iii) decrease body weight and locomotion, with more pronounced changes at 20 mg/kg. These results indicated the susceptibility of T. molitor larvae to high doses of ZEA in feed.
RE: Expert range maps of global mammal distributions harmonised to three taxonomic authorities
Authors: Arbogast Brian S , Kerhoulas Nicholas J
Published: May 2024

In a recent paper titled Expert range maps of global mammal distributions harmonised to three taxonomic authorities, Marsh et al. (2022) introduced a series of new geographic range maps for all extant species of mammals and made these maps available on the Map of Life (MoL) website (www.mol.org). The title of the paper and inclusion of over 140 prominent mammalogists and biogeographers as coauthors strongly suggested that these new range maps were carefully vetted. However, when examining the maps of Marsh et al. (2022) on the MoL web platform, we found a variety of serious problems, including, but not limited to: range exaggerations (inclusion of substantial geographic areas not represented by specimen records or verified observations); range maps that are geographically shifted so that species are shown as occurring in areas in which they do not, and not occurring in areas in which they do (and in some cases, these new maps do not even encompass the type locality of a species); range maps that simply omit peripheral populations of conservation concern; and range maps for fully marine mammals (i.e., those that do not spend any time on land) that include large swaths of both insular and continental landmasses. Overall, we evaluated the new “expert” mammal range maps on the MoL platform for 78 species (retrieved between 31 March 2022 and 1 April 2023) and show that there are serious, systemic problems with these maps, and that these problems are both geographically and taxonomically widespread. As such, we caution researchers to carefully review and evaluate the range maps of Marsh et al. (2022) on the MoL before using them for any research purpose—including conservation, biogeographical, and macroecological analyses of mammals.
Response to Arbogast and Kerhoulas
Authors: Marsh Charles J , Sica Yanina V , Upham Nathan S , Jetz Walter
Published: May 2024

We welcome feedback on the range maps published in Marsh et al. (2022) where it constructively improves our knowledge on species distributions. Unfortunately, we are concerned that criticisms raised by Arbogast and Kerhoulas are steps backward, not forward, particularly as they did not access the original range map data of Marsh et al. (2022). We stress that evaluating range maps using Global Biodiversity Information Facility data without the necessary quality control and filtering will lead to flawed interpretations—using the same approach, an even greater proportion, >99.5%, of IUCN mammal range maps would fail to meet their expectations. We take this opportunity to highlight the fine-scale inaccuracies, scale limitations, and range map variance that are expected across all expert range map sources and that any researcher should consider during any analysis. Finally, we again announce the availability of an online tool for providing annotations and proposing adjustments to range maps, and suggest this as a more appropriate forum for constructively and transparently improving range maps.
Mosquitoes do not influence Cotton Mouse (Peromyscus gossypinus) giving-up densities
Authors: Morris Gail , Conner L Mike
Published: May 2024

It is commonly recognized that predation and the risk of predation can have profound effects on behaviors and population ecology of prey. Comparatively, little attention has been paid to the trade-offs hosts make to manage the risk of parasitism, but there is evidence that hosts make behavioral trade-offs to avoid parasitism in ways that resemble those made by prey animals under the risk of predation. Mosquitoes are common hematophagous ectoparasites which parasitize a wide range of vertebrates, resulting in blood loss, distraction, and disease transmission. Many hosts engage in defensive behaviors to repel or kill mosquitoes and these behaviors likely come at the expense of activities such as foraging and vigilance for predators. We placed a mosquito attractant (BG-Sweetscent) and repellant (allethrin) near artificial foraging patches in areas where mosquitoes were common and measured the amount of grain left after a night of foraging (giving-up density) to investigate whether mosquitoes influenced Cotton Mouse (Peromyscus gossypinus) foraging. We predicted that in patches with mosquito attractants, mosquito harassment would cause mice to engage in defensive behaviors which would distract or deter them from foraging, resulting in less grain consumption relative to control patches. Conversely, we predicted that in mosquito-repellent patches, mice would experience less harassment, resulting in more grain consumption. Indoor arena trials found no evidence that the mosquito treatments influenced cotton mouse behavior in the absence of mosquitoes. However, we found no evidence that mosquito treatments affected giving-up densities.
Macromolecular tool box to elucidate CLAVATA3/EMBRYO SURROUNDING REGION-RELATED–RLK binding, signaling, and downstream effects
Authors: Narasimhan Madhumitha , Jahnke Nina , Kallert Felix , Bahafid Elmehdi , Böhmer Franziska , Hartmann Laura , Simon Rüdiger
Published: May 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 the CLAVATA3/EMBRYO SURROUNDING REGION-RELATED peptide family in Arabidopsis, we have developed a novel set of CLAVATA3 (CLV3)-based peptide tools. After carefully evaluating the CLE peptide binding characteristics, using solid phase synthesis process, we modified the CLV3 peptide and attached a fluorophore and a photoactivable side group. We observed that the labeled CLV3 shows binding specificity within the 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 is trafficked to the vacuole via ARA7 (a Rab GTPase)-labeled endosomes. Additionally, modifying CLV3 for light-controlled activation enabled spatial and temporal control over CLE signaling. 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.
Polycomb proteins RING1A/B promote H2A monoubiquitination to regulate female gametophyte development in Arabidopsis
Authors: Lv Yanfang , Li Jian , Wang Zheng , Liu Yue , Jiang Yili , Li Yanzhuo , Lv Zhaopeng , Huang Xiaoyi , Peng Xiongbo , Cao Ying , Yang Hongchun
Published: May 2024

A functional female gametophyte is the basis of successful sexual reproduction in flowering plants. During female gametophyte development, the megaspore mother cell (MMC), which differentiates from a single subepidermal somatic cell in the nucellus, undergoes meiosis to produce four megaspores; only the one at the chalazal end, referred to as the functional megaspore (FM), then undergoes three rounds of mitosis and develops into a mature embryo sac. Here, we report that RING1A and RING1B (RING1A/B), two functionally redundant Polycomb proteins in Arabidopsis, are critical for female gametophyte development. Mutations of RING1A/B resulted in defects in the specification of the MMC and the FM, and in the subsequent mitosis of the FM, thereby leading to aborted ovules. Detailed analysis revealed that several genes essential for female gametophyte development were ectopically expressed in the ring1a ring1b mutant, including Argonaute (AGO) family genes and critical transcription factors. Furthermore, RING1A/B bound to some of these genes to promote H2A monoubiquitination (H2Aub). Taken together, our study shows that RING1A/B promote H2Aub modification at key genes for female gametophyte development, suppressing their expression to ensure that the development progresses correctly.
Identification and in vitro characterization of UDP-GlcNAc-RNA cap-modifying and decapping enzymes
Authors: Weber Frederik , Motzkus Nikolas Alexander , Brandl Leona , Möhler Marvin , Alempijevic Andrijana , Jäschke Andres
Published: May 2024

In recent years, several noncanonical RNA caps derived from cofactors and metabolites have been identified. Purine-containing RNA caps have been extensively studied, with multiple decapping enzymes identified and efficient capture and sequencing protocols developed for nicotinamide adenine dinucleotide (NAD)-RNA, which allowed for a stepwise elucidation of capping functions. Despite being identified as an abundant noncanonical RNA-cap, UDP-sugar-capped RNA remains poorly understood, which is partly due to its complex in vitro preparation. Here, we describe a scalable synthesis of sugar-capped uridine-guanosine dinucleotides from readily available protected building blocks and their enzymatic conversion into several cell wall precursor-capped dinucleotides. We employed these capped dinucleotides in T7 RNA polymerase-catalyzed in vitro transcription reactions to efficiently generate RNAs capped with uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), its N-azidoacetyl derivative UDP-GlcNAz, and various cell wall precursors. We furthermore identified four enzymes capable of processing UDP-GlcNAc-capped RNA in vitro: MurA, MurB and MurC from Escherichia coli can sequentially modify the sugar-cap structure and were used to introduce a bioorthogonal, clickable moiety, and the human Nudix hydrolase Nudt5 was shown to efficiently decap UDP-GlcNAc-RNA. Our findings underscore the importance of efficient synthetic methods for capped model RNAs. Additionally, we provide useful enzymatic tools that could be utilized in the development and application of UDP-GlcNAc capture and sequencing protocols. Such protocols are essential for deepening our understanding of the widespread yet enigmatic GlcNAc modification of RNA and its physiological significance.
A neural tract-inspired conduit for facile, on-demand biopsy of glioblastoma
Authors: Betancur Martha I , Case Ayden , Ilich Ekaterina , Mehta Nalini , Meehan Sean , Pogrebivsky Sabrina , Keir Stephen T , Stevenson Kevin , Brahma Barun , Gregory Simon , Chen Wei , Ashley David M , Bellamkonda Ravi , Mokarram Nassir
Published: May 2024

Background

A major hurdle to effectively treating glioblastoma (GBM) patients is the lack of longitudinal information about tumor progression, evolution, and treatment response.

Methods

In this study, we report the use of a neural tract-inspired conduit containing aligned polymeric nanofibers (i.e., an aligned nanofiber device) to enable on-demand access to GBM tumors in 2 rodent models. Depending on the experiment, a humanized U87MG xenograft and/or F98-GFP+ syngeneic rat tumor model was chosen to test the safety and functionality of the device in providing continuous sampling access to the tumor and its microenvironment.

Results

The aligned nanofiber device was safe and provided a high quantity of quality genomic materials suitable for omics analyses and yielded a sufficient number of live cells for in vitro expansion and screening. Transcriptomic and genomic analyses demonstrated continuity between material extracted from the device and that of the primary, intracortical tumor (in the in vivo model).

Conclusions

The results establish the potential of this neural tract-inspired, aligned nanofiber device as an on-demand, safe, and minimally invasive access point, thus enabling rapid, high-throughput, longitudinal assessment of tumor and its microenvironment, ultimately leading to more informed clinical treatment strategies.
Trimethoprim-Sulfamethoxazole Plus Azithromycin to Prevent Malaria and Sexually Transmitted Infections in Pregnant Women With HIV (PREMISE): A Randomized, Double-Masked, Placebo-Controlled, Phase IIB Clinical Trial
Authors: Dionne Jodie A , Anchang-Kimbi Judith , Hao Jiaying , Long Dustin , Apinjoh Tobias , Tih Pius , Mbah Rahel , Ngah Edward Ndze , Juliano Jonathan J , Kahn Mauricio , Bruxvoort Katia , Van Der Pol Barbara , Tita Alan T N , Marrazzo Jeanne , Achidi Eric
Published: May 2024

Background

This trial tested the effectiveness of a novel regimen to prevent malaria and sexually transmitted infections (STIs) among pregnant women with HIV in Cameroon. Our hypothesis was that the addition of azithromycin (AZ) to standard daily trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis would reduce malaria and STI infection rates at delivery.

Methods

Pregnant women with HIV at gestational age <28 weeks were randomized to adjunctive monthly oral AZ 1 g daily or placebo for 3 days and both groups received daily standard oral TMP-SMX through delivery. Primary outcomes were (1) positive peripheral malaria infection by microscopy or polymerase chain reaction and (2) composite bacterial genital STI (Chlamydia trachomatis, Neisseria gonorrhoeae, or syphilis) at delivery. Relative risk and 95% confidence intervals were estimated using 2 × 2 tables with significance as P < .05.

Results

Pregnant women with HIV (n = 308) were enrolled between March 2018 and August 2020: 155 women were randomized to TMP-SMX-AZ and 153 women to TMP-SMX-placebo. Groups were similar at baseline and loss to follow up was 3.2%. There was no difference in the proportion with malaria (16.3% in TMP-SMX-AZ vs 13.2% in TMP-SMX; relative risk, 1.24 [95% confidence interval, .71-2.16]) or STI at delivery (4.2% in TMP-SMX-AZ vs 5.8% in TMP-SMX; relative risk, 0.72 [95% confidence interval, .26-2.03]). Adverse birth outcomes were not significantly different, albeit lower in the TMP-SMX-AZ arm (preterm delivery 6.7% vs 10.7% [P = .3]; low birthweight 3.4% vs 5.4% [P = .6]).

Conclusions

The addition of monthly azithromycin to daily TMP-SMX prophylaxis in pregnant women living with HIV in Cameroon did not reduce the risk of malaria or bacterial STI at delivery.
Policy variation in the external evaluation of research for tenure at U.S. universities
Authors: Hannon Lance , Bergey Meredith
Published: May 2024

There is a robust literature documenting differences in peer review processes for scholarly outlets. Knowledge of this variability has provoked thoughtful debate about the best approach for promoting rigor and innovation in scientific research (e.g. single-blind vs. double-blind review, or more recently, double-blind vs. open review). We aim to expand this conversation to external peer review processes specified in rank and tenure guidelines. We qualitatively analyze a corpus of publicly available rank and tenure procedures at research-intensive universities in the United States. Results indicate significant variation in (1) the required minimum and maximum number of external reviews, (2) the candidate’s role in the reviewer selection process, (3) the level of ensured anonymity for reviewers, and (4) attention to potential conflict of interest scenarios. We argue that many of the debates about best practices in research evaluation for journals and funding agencies are also relevant for rank and tenure procedures. Moreover, rank and tenure policies may be subject to unique tensions, such as cases where external reviews are formally cast as disinterested assessments by referees but informally understood as letters of recommendation by sponsors. We discuss the relevance of our findings for existing work on the perceived clarity of evaluation criteria—especially how guideline ambiguity can be linked to inequality and how labor issues can conflict with idealized assessment principles.
Tibetan mesenchymal stem cell-derived exosomes alleviate pulmonary vascular remodeling in hypoxic pulmonary hypertension rats
Authors: Zhang Qingqing , Liu Hong , Liu Chuanchuan , Wang Yuxiang , Huang Pan , Wang Xiaobo , Ma Yougang , Ma Lan , Ge Rili
Published: May 2024

Hypoxic pulmonary hypertension (HPH) is characterized by progressive pulmonary vasoconstriction, vascular remodeling, and right ventricular hypertrophy, causing right heart failure. This study aimed to investigate the therapeutic effects of exosomes from Tibetan umbilical cord mesenchymal stem cells on HPH via the TGF-β1/Smad2/3 pathway, comparing them with exosomes from Han Chinese individuals. An HPH rat model was established in vivo, and a hypoxia-induced injury in the rat pulmonary artery smooth muscle cells (rPASMCs) was simulated in vitro. Exosomes from human umbilical cord mesenchymal stem cells were administered to HPH model rats or added to cultured rPASMCs. The therapeutic effects of Tibetan-mesenchymal stem cell-derived exosomes (Tibetan-MSC-exo) and Han-mesenchymal stem cell-derived exosomes (Han-MSC-exo) on HPH were investigated through immunohistochemistry, western blotting, EdU, and Transwell assays. The results showed that Tibetan-MSC-exo significantly attenuated pulmonary vascular remodeling and right ventricular hypertrophy in HPH rats compared with Han-MSC-exo. Tibetan-MSC-exo demonstrated better inhibition of hypoxia-induced rPASMCs proliferation and migration. Transcriptome sequencing revealed upregulated genes (Nbl1, Id2, Smad6, and Ltbp1) related to the TGFβ pathway. Nbl1 knockdown enhanced hypoxia-induced rPASMCs proliferation and migration, reversing Tibetan-MSC-exo-induced downregulation of TGFβ1 and p-Smad2/3. Furthermore, TGFβ1 overexpression hindered the therapeutic effects of Tibetan-MSC-exo and Han-MSC-exo on hypoxic injury. These findings suggest that Tibetan-MSC-exo favors HPH treatment better than Han-MSC-exo, possibly through the modulation of the TGFβ1/Smad2/3 pathway via Nbl1.
Arp2/3 mediated dynamic lamellipodia of the hPSC colony edges promote liposome-based DNA delivery
Authors: Surma Michelle , Anbarasu Kavitha , Das Arupratan
Published: May 2024

Cationic liposome-mediated delivery of drugs, DNA, or RNA plays a pivotal role in small molecule therapy, gene editing, and immunization. However, our current knowledge regarding the cellular structures that facilitate this process remains limited. Here, we used human pluripotent stem cells (hPSCs), which form compact colonies consisting of dynamically active cells at the periphery and epithelial-like cells at the core. We discovered that cells at the colony edges selectively got transfected by cationic liposomes through actin-related protein 2/3 (Arp2/3) dependent dynamic lamellipodia, which is augmented by myosin II inhibition. Conversely, cells at the core establish tight junctions at their apical surfaces, impeding liposomal access to the basal lamellipodia and thereby inhibiting transfection. In contrast, liposomes incorporating mannosylated lipids are internalized throughout the entire colony via receptor-mediated endocytosis. These findings contribute a novel mechanistic insight into enhancing therapeutic delivery via liposomes, particularly in cell types characterized by dynamic lamellipodia, such as immune cells or those comprising the epithelial layer.
Gene expression regulation of the effect of shading on chlorophyll content in Fuding White Tea (Camellia sinensis L.)
Authors: Li Guangzheng , Chen Xi , Zhao Yichen , Zhao Degang
Published: May 2024

Shading is an important practical method to improve the quality of green tea. Previous research of our group found that because the biosynthesis and distribution of theanine in tea plants were affected by down regulation of gene encoding amino acid permeases, theanine content in tea leaves which grown under shading condition was significantly higher than those under natural light. In this study, our group analyzed the changes of tea leaf area, free amino acid content and photosynthetic parameters under natural light and shading conditions, to ensure that moderate shading did not reduce but improve the quality of tea. Transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted to reveal the expression levels of genes related to chlorophyll content and chlorophyll a/b ratio under natural light and shading conditions. Experimental results revealed the presence of the following differentially expressed genes (DEGs) in the porphyrin and chlorophyll metabolism pathway of tea under natural light and shading conditions: the up regulation of CPOX expression may lead to an increase in the accumulation of raw materials of chlorophyll synthesis, while the down regulation of SGR expression may lead to a decrease in chlorophyll degradation. The combined effect of these two genes may lead to an increase in the total chlorophyll content of tea. The down regulation of NOL expression may lead to the obstruction of chlorophyll b transform to chlorophyll a, that is, the decrease of the chlorophyll a/b ratio. This study investigated the molecular mechanism of chlorophyll content and component alteration in Fuding white tea under natural light and shading conditions, and elucidated the effects of different light intensities on the porphyrin and chlorophyll metabolism pathway of tea. Thus provided deep understanding of chlorophyll regulation under shading condition in tea cultivation, which could contribute to high-quality matcha production.
Electroencephalographic Indices for Clinical Endpoints during Propofol Anesthesia in Infants: An Early-phase Propofol Biomarker-finding Study
Authors: Yuan Ian , Garcia-Marcinkiewicz Annery G. , Zhang Bingqing , Ulrich Allison M. , Georgostathi Georgia , Missett Richard M. , Lang Shih-Shan , Bruton James L. , Kurth C. Dean
Published: May 2024

Background

Unlike expired sevoflurane concentration, propofol lacks a biomarker for its brain effect site concentration, leading to dosing imprecision particularly in infants. Electroencephalography monitoring can serve as a biomarker for propofol effect site concentration, yet proprietary electroencephalography indices are not validated in infants. The authors evaluated spectral edge frequency (SEF95) as a propofol anesthesia biomarker in infants. It was hypothesized that the SEF95 targets will vary for different clinical stimuli and an inverse relationship existed between SEF95 and propofol plasma concentration.

Methods

This prospective study enrolled infants (3 to 12 months) to determine the SEF95 ranges for three clinical endpoints of anesthesia (consciousness-pacifier placement, pain-electrical nerve stimulation, and intubation-laryngoscopy) and correlation between SEF95 and propofol plasma concentration at steady state. Dixon’s up–down method was used to determine target SEF95 for each clinical endpoint. Centered isotonic regression determined the dose–response function of SEF95 where 50% and 90% of infants (ED50 and ED90) did not respond to the clinical endpoint. Linear mixed-effect model determined the association of propofol plasma concentration and SEF95.

Results

Of 49 enrolled infants, 44 evaluable (90%) showed distinct SEF95 for endpoints: pacifier (ED50, 21.4 Hz; ED90, 19.3 Hz), electrical stimulation (ED50, 12.6 Hz; ED90, 10.4 Hz), and laryngoscopy (ED50, 8.5 Hz; ED90, 5.2 Hz). From propofol 0.5 to 6 μg/ml, a 1-Hz SEF95 increase was linearly correlated to a 0.24 (95% CI, 0.19 to 0.29; P < 0.001) μg/ml decrease in plasma propofol concentration (marginal R
2 = 0.55).

Conclusions

SEF95 can be a biomarker for propofol anesthesia depth in infants, potentially improving dosing accuracy and utilization of propofol anesthesia in this population.

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Abdominal Aortic Calcification is Associated with Degeneration of The Paraspinal Muscles – A Retrospective cross-sectional Study
Authors: Schömig Friederike , Schönnagel Lukas , Zhu Jiaqi , Suwalski Phillip , Köhli Paul , Caffard Thomas , Guven Ali E. , Chiapparelli Erika , Arzani Artine , Amoroso Krizia , Shue Jennifer , Sama Andrew A. , Cammisa Frank P. , Girardi Federico P. , Hughes Alexander P.
Published: May 2024

Study Design.

Retrospective cohort study.

Objective.

To analyze the relationship of abdominal aortic calcification (AAC) and a reduction in the cross-sectional area (CSA) and the fatty infiltration (FI) of the paravertebral muscles in patients undergoing lumbar fusion surgery.

Background.

Both AAC and paraspinal muscle degeneration have been shown to be associated with poorer outcomes after surgical treatment of degenerative diseases of the lumbar spine. However, there is a lack of data on the association between AAC and paraspinal muscle changes in patients undergoing spine surgery.

Methods.

We retrospectively analyzed patients undergoing lumbar fusion for degenerative spinal pathologies. Muscular and spinal degeneration were measured on magnetic resonance imaging (MRI). AAC was classified on lateral lumbar radiographs. The association of AAC and paraspinal muscle composition was assessed by a multivariate regression analysis adjusted for age, sex, body mass index (BMI), comorbidities, and lumbar degeneration.

Results.

A total of 301 patients was included. Patients with AAC showed significantly higher degrees of intervertebral disc and facet joint degeneration as well as higher total endplate scores at the L3/4 level. The univariable regression analysis showed a significant positive correlation between the degree of AAC and the FI of the erector spinae (b=0.530, P<0.001) and multifidus (b=0.730, P<0.001). The multivariable regression analysis showed a significant positive correlation between the degree of AAC and the FI of the erector spinae (b=0.270, P=0.006) and a significant negative correlation between the degree of AAC and the CSA of the psoas muscle (b=-0.260, P=0.003).

Conclusion.

This study demonstrates a significant and independent association between AAC and degeneration of the erector spinae and the psoas muscles in patients undergoing lumbar fusion. As both AAC and degeneration of paraspinal muscles impact postoperative outcomes negatively, preoperative assessment of AAC may aid in identifying patients at higher risk after lumbar surgery.
The Association Between Cervical Foraminal Stenosis and Adhesive Capsulitis
Authors: Russo Salvatore , Sharma Aadhar , Vardanyan Robert , Thavarajasingam Santhosh Gouthaman , Riew K. Daniel
Published: May 2024

Study Design.

Retrospective single-center imaging-based case-control study.

Objective.

To determine the association between cervical foraminal stenosis and adhesive capsulitis.

Summary of Background Data.

Patients with cervical spondylosis often exhibit shoulder symptoms. Cervical radiculopathies, particularly C5, can cause severe shoulder pain and reduced shoulder mobility, mimicking glenohumeral adhesive capsulitis (frozen shoulder), a common shoulder condition. This is the first study investigating the connection between adhesive capsulitis and cervical radiculopathy.

Methods.

438 patients who underwent glenohumeral hydrodistension between 2012 and 2019 were reviewed. Included were individuals with unilateral frozen shoulder investigated using ultrasound and cervical spine MRI to investigate cervical spondylosis. Foraminal stenosis at C3/4, C4/5, C5/6 and C6/7 was graded in axial T2 MRI, ipsilateral and contralateral to the adhesive capsulitis. The presence of foraminal stenosis ipsilateral to the frozen shoulder (cases) was compared with the contralateral side (control). McNemar’s exact test was used to assess the strength of a correlation.

Results.

Among 438 patients, 107 reported frozen shoulder and neck pain (24.5%), with 48 matching the study criteria. A significant association between ipsilateral frozen shoulder and C4/5 foraminal stenosis was observed (P=0.00000008636). Ipsilateral foraminal stenosis was observed in 57.3% of these cases, with bilateral stenosis in 29.1%. Additionally, 78% had neck pain on the same side as their frozen shoulder, and 44% had pain radiating to the shoulder. 48% patients underwent nerve-targeted interventions, with 44% addressing the C5 nerve (25% C5 steroid injection and 19% C4/5 anterior cervical discectomy and fusion).

Conclusion.

A substantial association between C5 foraminal stenosis and ipsilateral frozen shoulder was found. C5 radiculopathy could be a risk factor for “neurogenic frozen shoulder”. Those diagnosing frozen shoulder and cervicobrachialgia should recognize that frozen shoulder and C5 radiculopathy may coexist. A multidisciplinary approach involving both shoulder and spine specialists is recommended for a definitive diagnosis.
Elderly patients with advanced HER2-positive breast cancer with liver metastases benefit from low dose disitamab vedotin (RC48): case series and literature review
Authors: Qu Fan-jie , Kong Yan , Yan Xin , Wang Hai
Published: May 2024

Currently, although some antibody-drug conjugates have been shown to be safe and effective in the treatment of drug-resistant relapsed human epidermal growth factor receptor 2 (HER2)-positive (IHC 3+ or IHC 2+/fluorescence in situ hybridization+) breast cancer, they are already approved for clinical use in China. But the clinical needs of advanced HER2-positive patients cannot be met due to adverse reactions, drug resistance, drug accessibility and other problems, thus affecting the prognosis of patients. In particular, the representation of elderly and frail patients in randomized clinical trials is significantly under-represented. We report on two elderly women with breast cancer who developed recurrent metastatic lesions after breast cancer surgery and were again confirmed HER2-positive by histopathology and immunohistochemistry. They all developed multiple metastases in the liver after second- or third-line anti-HER2 therapy. Subsequent treatment with RC48 produced good responses and tolerable adverse reactions. One patient obtained progression-free survival for more than 7 months. Based on preliminary evidence, this study shows that RC48 in HER2-positive breast cancer with liver metastases can achieve rapid remission, thereby reducing tumor load and improving patients’ quality of life. In particular, RC48 has low side effects and can be well tolerated by elderly patients after dose adjustment, providing them with treatment opportunities. It needs to be further discussed in the future research.
Mapping the Landscape of Continuing Professional Development: A Pilot Gap Map of Systematic Reviews
Authors: Nexoe Mette Andersen , Andersen Tue Helms , Nilsson Sigrid Mørkeberg , Bjerre-Christensen Ulla , Lomborg Kirsten , Norgaard Ole
Published: May 2024

Gap maps graphically represent evidence from systematic reviews. We developed and tested a pilot gap map of systematic reviews examining the impact of continuing professional development (CPD). We conducted a mapping review and charted the content of systematic reviews in a pilot gap map. Directive content analysis helped develop categories in three dimensions: evaluation framework, study characteristics, and number of systematic reviews. Of 389 identified records, 29 systematic reviews were included in the pilot map. We found gaps in evidence evaluating the impact of e-learning and skills training programs on various outcomes (patient, care, and work environment). Most evaluations corresponded to Kirkpatrick's learning model, with few considering other outcomes or how CPD could be mediated or influenced by contextual factors. Rooted in social epidemiological principles, the pilot map framework introduced new ways of understanding evidence from systematic reviews. Although the pilot map illuminated several evidence gaps and perspectives important to future CPD, a complete map is needed to validate the findings.
Cutaneous Perivascular Hemophagocytosis: A Report of 2 Cases With Emphasis on Clinical and Histological Features
Authors: Cazzato Gerardo , Rongioletti Franco
Published: May 2024

Cutaneous perivascular hemophagocytosis (CH) is a histological manifestation that manifests as systemic hemophagocytic syndrome, also known as hemophagocytic lymphohistiocytosis, when accompanied by fever, hepatosplenomegaly, liver dysfunction, and cytopenia, and may rarely manifest independently of hemophagocytic lymphohistiocytosis. CH typically presents as purpuric or brownish macules and patches on the extremities, abdomen, and trunks. Histopathologically, the hallmark of CH includes extravasated erythrocytes and karyorrhectic debris phagocytized by histiocytes, associated with dermal capillary ectasia, perivascular infiltration of neutrophils, nuclear dust, and histiocytes without atypia. In this study, we report 2 cases of CH encountered in routine diagnostic practice and elucidate their significant clinical and histologic features. Our first patient had leukocytoclastic vasculitis with CH in the setting of Yersinia enterocolitis, and the second case represents CH in association with non-Hodgkin lymphoma. This study highlights the importance of considering CH as a potential indicator of underlying systemic pathology, including infectious and hematological disorders, in clinical practice.