bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyto-architecture of Byblis glands and leaf cells based on freeze-substitution and conventional TEM
Authors: Płachno Bartosz J , Lancelle Sue , Świątek Piotr , Hepler Peter K , Weidinger Marieluise , Lichtscheidl Irene
Published: September 2024

Background and Aims

Byblis liniflora (Byblidaceae) is a carnivorous plant that has developed sticky flypaper traps with two types of glandular trichomes producing digestive enzymes and sticky mucilage. This study aimed to analyse the ultrastructure of these glandular leaf trichomes based on rapid freeze-fixation and conventional chemical fixation in the attempt to understand their functional contribution to the carnivorous performance of the plants.

Methods

The Byblis cells were studied in transmission electron microscopy, scanning electron microscopy and scanning transmission electron microscopy using cryo-techniques for fixation and substitution in addition to conventional chemical fixation.

Key Results

We show in detail the architecture of both the digestive glands and the mucilage glands with their relevant sets of organelles. Both mitochondria and plastids have a conspicuous plasticity, with branches and constrictions, and they associate to form clusters. The glandular cells appear to be transfer cells with cell wall ingrowths. Digestive glands occur in different states of development. Their cuticle forms discontinuities that are unique among glands of carnivorous plants. They look like cuticular holes – the cuticle separates from the cell wall in only one spot and then ruptures. Cuticular discontinuities thus differ from the cuticular gaps and cuticular pores so far described in carnivorous plants. We therefore propose for them the term ‘cuticular holes’.

Conclusions

Application of cryo-techniques made it possible to show the true structure of the cell wall and the relationship between cell wall ingrowths and organelles, as well as the morphology and structure of organelles and their associations.
Protein language models are performant in structure-free virtual screening
Authors: Lam Hilbert Yuen In , Guan Jia Sheng , Ong Xing Er , Pincket Robbe , Mu Yuguang
Published: September 2024

Hitherto virtual screening (VS) has been typically performed using a structure-based drug design paradigm. Such methods typically require the use of molecular docking on high-resolution three-dimensional structures of a target protein—a computationally-intensive and time-consuming exercise. This work demonstrates that by employing protein language models and molecular graphs as inputs to a novel graph-to-transformer cross-attention mechanism, a screening power comparable to state-of-the-art structure-based models can be achieved. The implications thereof include highly expedited VS due to the greatly reduced compute required to run this model, and the ability to perform early stages of computer-aided drug design in the complete absence of 3D protein structures.
LEAP: the latent exchangeability prior for borrowing information from historical data
Authors: Alt Ethan M , Chang Xiuya , Jiang Xun , Liu Qing , Mo May , Xia Hong Amy , Ibrahim Joseph G
Published: September 2024

It is becoming increasingly popular to elicit informative priors on the basis of historical data. Popular existing priors, including the power prior, commensurate prior, and robust meta-analytic predictive prior, provide blanket discounting. Thus, if only a subset of participants in the historical data are exchangeable with the current data, these priors may not be appropriate. In order to combat this issue, propensity score approaches have been proposed. However, these approaches are only concerned with the covariate distribution, whereas exchangeability is typically assessed with parameters pertaining to the outcome. In this paper, we introduce the latent exchangeability prior (LEAP), where observations in the historical data are classified into exchangeable and non-exchangeable groups. The LEAP discounts the historical data by identifying the most relevant subjects from the historical data. We compare our proposed approach against alternative approaches in simulations and present a case study using our proposed prior to augment a control arm in a phase 3 clinical trial in plaque psoriasis with an unbalanced randomization scheme.
Rejoinder to the discussion on “LEAP: the latent exchangeability prior for borrowing information from historical data”
Authors: Alt Ethan M , Chang Xiuya , Jiang Xun , Liu Qing , Mo May , Xia Hong Amy , Ibrahim Joseph G
Published: September 2024

The discussions of our paper provide insights into the practical considerations of the latent exchangeability prior while also highlighting further extensions. In this rejoinder, we briefly summarize the discussions and provide comments.
Separation of earthquake and hydrology signals from GRACE satellites data via independent component analysis: a case study in the Sumatra region
Authors: Xiong Yuhao , Feng Wei , Zhou Xin , Kusche Jürgen , Shen Yingchun , Yang Meng , Wang Changqing , Zhong Min
Published: September 2024

The Gravity Recovery and Climate Experiment (GRACE) satellites have observed mass migrations caused by megathrust earthquakes. Extracting earthquake-related signals from GRACE data is still a challenge due to the interference from non-earthquake sources such as terrestrial hydrology. Instead of reducing hydrological signals by potentially biased hydrological models, in this study we apply a model-free technique of independent component analysis (ICA), to separate earthquake and non-earthquake signals from non-Gaussian GRACE data. We elucidate the principles and mechanisms of ICA for the separation of earthquake and hydrology signals, employing simulated data to demonstrate the process. Our findings demonstrate that both spatial ICA and temporal ICA are highly effective in discerning earthquake related to 2004 Mw 9.2 event and hydrological signals from GRACE data in the Sumatra region. This stands in stark contrast to principal component analysis, which often encounters challenges with signal intermingling. The utility of ICA is evident in its ability to distinctly delineate coseismic and post-seismic behaviours associated with megathrust events, including the 2004 Sumatra, the 2010 Maule, and the 2011 Tohoku earthquakes. ICA effectively mitigates the potential for misestimation of earthquake signals, an issue that can carry substantial implications. Therefore, employing ICA facilitates the accurate extraction of earthquake-related data from satellite gravity observations—a critical process for refining earthquake source parameters and understanding Earth's rheological properties, especially when non-earthquake signals are significant and cannot be disregarded.
Rare Genetic Variants of NLRP12 in Admixed Latino-American Children With SARS-CoV-2–Related Multisystem Inflammatory Syndrome
Authors: Barreto Thaís M M , Souza Roberta S , São Pedro Raquel B , Paiva Isadora M , Silva Andréia S , Nogueira Ana L , Bellinat Ana P N , Dias Nathália L S , Nunes Sara , Britto Gabriela S G , Amaral Edson H B , Rocha Gabriela D , Silva-Carvalho Carolina , Lyra Ricardo , Kehdy Fernanda S G , Campos Túlio L , Moura Patrícia M M F , Tarazona-Santos Eduardo , Cunha Thiago M , Tavares Natália M , Oliveira-Sá Marcus V B , Ramos Regina C F , Carmo Rodrigo F , Vasconcelos Luydson R S , Oliveira Pablo R S
Published: September 2024

Multisystem inflammatory syndrome in children (MIS-C) is a rare, potentially fatal complication of SARS-CoV-2 infection. Genetic defects in inflammation-related pathways have been linked to MIS-C, but additional research is needed, especially in diverse ethnic groups. The present study aimed to identify genetic variants underlying MIS-C in Brazilian patients. Whole exome sequencing was performed, focusing on genes involved in the host immune response to SARS-CoV-2. Functional assays assessed the impact of selected variants on nuclear factor–κB signaling. Nine rare, potentially deleterious variants were found in 8 of 21 patients, located in the IL17RC, IFNA10, or NLRP12 gene. Unlike the wild type NLRP12 protein, which inhibits nuclear factor–κB activation in HEK 293T cells, the mutant NLRP12 proteins have significantly reduced inhibitory properties. In conclusion, our results indicate that rare autosomal variants in immune-related genes may underlie MIS-C, highlighting the potential role of NLRP12 in its predisposition. These findings provide new insights for the appropriate management of MIS-C.
Intravenous iron staining: real-world incidence, preventability, and mitigation tools from a long-term quality improvement project
Authors: Canning Martin L , Hillen Jodie B , Kashiwagi Maya , Alizadeh Negin , Freeman Christopher R
Published: September 2024

Background

Iron deficiency is the leading cause of anaemia worldwide and is increasingly treated with intravenous (IV) iron therapy. Staining from IV iron therapy is a rare but significant and preventable adverse event. To mitigate patient harm, a health-service-wide quality improvement project was implemented. This study aimed to determine the real-world impact of a quality improvement project on IV iron staining incidents and preventability.

Methods

A retrospective chart audit was undertaken for all IV iron staining episodes reported in a directorate-wide clinical incident reporting database (RiskMan) between 2016 and 2022. Incidence rates of IV iron staining, preventability, and stain severity were compared pre- and post-implementation of a standardized IV iron procedure.

Results

Over 7 years, 103 IV iron stains were identified, resulting in a staining rate of 0.31 stains per 100 infusions (pre 0.27% and post 0.34%, P = .25). Implementation of the standardized IV iron procedure resulted in improvements in pharmacist review of the medication order (61.8% versus 89.7%, P < .01), use of the statewide IV iron infusion consent form (27.3% versus 76.9%, P < .01), and appropriate cannula site (14.3% versus 52.5%, P < .01). Smaller stain sizes were associated with cessation of the infusion at identification of extravasation (312 cm2 versus 35 cm2) (P = .04). Preventability was assigned to 86% of stains.

Conclusion

The incidence rate of IV iron staining in a real-world clinical setting is 0.31%. There was increased compliance with several best practice principles and 86% of stains were preventable. Early identification and intervention of potential staining incidents results in smaller iron stains for patients. Quality improvement tools developed for this project can contribute to patient outcomes internationally.
Microbiological quality of vegan alternatives to dairy and meat products in England during 2022–3
Authors: Willis Caroline , Startin Catherine , Jorgensen Frieda , Sadler-Reeves Lorraine , Aird Heather , Lai Sandra , Amar Corinne
Published: September 2024

Aims

Plant-based alternatives to meat and dairy products have become increasingly popular in the UK. Despite a public perception that they have a relatively low microbiological risk, outbreaks of illness have been linked with these foods. This study aimed to assess the microbiological safety and quality of vegan alternatives to dairy and meat products available in England.

Methods and results

Samples were collected between September 2022 and March 2023 from retail, production, and catering premises, and tested for a range of bacterial pathogens and hygiene indicators using standard procedures. A total of 937 samples were tested, of which 92% were of a satisfactory microbiological quality, 3% were borderline, and 5% were unsatisfactory. Those interpreted as unsatisfactory were due to elevated counts of Enterobacteriaceae and Escherichia coli (indicators of poor hygiene) rather than pathogenic microorganisms. Listeria monocytogenes was present in five samples of tofu, all from the same producer (all at counts of <100 CFU g–1), while other Listeria species were detected at counts of <20 CFU g–1 in two burgers and two ‘vegan chicken’ products. The majority of samples did not have pH and water activity values that would significantly contribute to preventing microbial growth: 62.4% had pH > 5.0 and 82.4% had Aw > 0.94.

Conclusions

The majority of vegan products examined were of a satisfactory quality, but results demonstrate that microbiological control must be maintained using appropriate processing and storage temperatures, and application of a safe length of shelf life.
COVID-19 extracellular vesicles display heterogeneity based on viral and host RNA expression: implications for host immune response
Authors: Juárez Esmeralda , Vázquez-Pérez Joel A , Carreto-Binaghi Laura E , Martínez-Sanabria Claudia A , Salgado-Cantú Manuel G , Sarabia Carmen , Herrera María Teresa , Guzmán-Beltrán Silvia , Gutiérrez-González Luis H , González Yolanda
Published: September 2024

Viral RNA and miRNAs released by immune cells contribute to inflammation in COVID-19 patients. Here, we investigated the role of SARS-CoV2 RNA and host miRNAs carried within extracellular vesicles (EVs) in modulating inflammation. EVs were classified as positive or negative depending on their viral RNA cargo. To assess the function of viral RNA, EVs, and lipopolysaccharide (LPS) were used to stimulate whole blood samples from healthy subjects, and the secretion of 27 serum analytes was measured. EVs alone did not induce cytokines, chemokines, or growth factors. However, under LPS stimulation, (SARS-CoV2+) EVs increased IL-12 and decreased IL-13 secretion, while (SARS-CoV2−) EVs increased MIP-1α and IL-1β secretion. Host miR-19a-3p, -192-5p, -let-7c-5p, and -92b-3a were differentially expressed in association with viral RNA. EVs from COVID-19 patients exhibited differences in viral RNA and miRNA expression profiles that modulate LPS responses. This knowledge sheds light on the immunopathology of COVID-19.
A candidate coherent radio flash following a neutron star merger
Authors: Rowlinson A , de Ruiter I , Starling R L C , Rajwade K M , Hennessy A , Wijers R A M J , Anderson G E , Mevius M , Ruhe D , Gourdji K , van der Horst A J , ter Veen S , Wiersema K
Published: September 2024

In this paper, we present rapid follow-up observations of the short GRB 201006A, consistent with being a compact binary merger, using the LOw Frequency ARray (LOFAR). We have detected a candidate 5.6$\sigma$, short, coherent radio flash at 144 MHz at 76.6 min post-GRB with a 3$\sigma$ duration of 38 s. This radio flash is 27 arcsec offset from the GRB location, which has a probability of being co-located with the GRB of $\sim$0.05 per cent (3.8$\sigma$) when accounting for measurement uncertainties. Despite the offset, we show that the probability of finding an unrelated transient within 40 arcsec of the GRB location is $\lt 10^{-6}$ and conclude that this is a candidate radio counterpart to GRB 201006A. We performed image plane dedispersion and the radio flash is tentatively (2.4$\sigma$) shown to be highly dispersed, allowing a distance estimate, corresponding to a redshift of $0.58\pm 0.06$. The corresponding luminosity of the event at this distance is $6.7^{+6.6}_{-4.4} \times 10^{32}$ erg s$^{-1}$ Hz$^{-1}$. If associated with GRB 201006A, this emission would indicate prolonged activity from the central engine that is consistent with being a newborn, supramassive, likely highly magnetized, millisecond spin neutron star (a magnetar).
The expected kinematic matter dipole is robust against source evolution
Authors: von Hausegger Sebastian
Published: September 2024

Recent measurements using catalogues of quasars and radio galaxies have shown that the dipole anisotropy in the large-scale distribution of matter is about twice as large as is expected in the standard lambda cold dark matter ($\Lambda$CDM) model, indeed in any cosmology based on the Friedman–Lemaître–Robertson–Walker (FLRW) metric. This expectation is based on the kinematic interpretation of the dipole anisotropy of the cosmic microwave background, i.e. as arising due to our local peculiar velocity. The effect of aberration and Doppler boosting on the projected number counts on the sky of cosmologically distant objects in a flux-limited catalogue can then be calculated and confronted with observations. This fundamental consistency test of FLRW models proposed by Ellis & Baldwin in 1984 was revisited recently arguing that redshift evolution of the sources can significantly affect the expected matter dipole. In this note, we demonstrate that the Ellis & Baldwin test is in fact robust to such effects, hence the $\gt 5\sigma$ dipole anomaly uncovered recently remains an outstanding challenge to the $\Lambda$CDM model.
Closing the gap: proposing a socio-ecological framework to make cancer clinical trials more accessible, equitable, and acceptable to adolescents and young adults
Authors: Ahmad Zeba , Venkataraman Vinayak , Markwart Michaela , Abrams Annah N , Temel Jennifer S , Perez Giselle K
Published: September 2024

This commentary focuses on what would make cancer clinical trials more accessible, equitable, and acceptable to adolescents and young adults.
Intelligent Borders: Exploring the Suitability of Artificial Intelligence Systems in Refugee Status Determination Under International Law
Authors: Amoroso Mario Pasquale
Published: September 2024

This article assesses the potential use of Artificial Intelligence (AI) in Refugee Status Determination, exploring how AI systems, including biometrics, predictive analytics, and emotion recognition, could support or replace human decision-making in determining refugee status. While AI could speed up and improve the objectivity of Refugee Status Determination procedures, the article raises concerns about its limitations in assessing the subjective fear of persecution, a critical element of refugee claims. The inability of AI systems to fully account for emotional and personal nuances leads to the possibility of discriminatory practices, particularly when AI is used without human oversight. The study highlights how AI could exacerbate power imbalances between asylum-seekers and States, transforming these technologies into tools for anti-immigration policies. It therefore calls for caution in the use of AI in Refugee Status Determination procedures and stresses that human interaction remains essential for the fair assessment of refugee claims. This article concludes that while AI can assist in certain aspects of the Refugee Status Determination procedures, its full implementation without careful legal and human rights considerations poses significant risks.
Challenges of Creating a Peer Support Online Community for Patients With Diabetes—A Case Study
Authors: Bujanda-Sainz de Murieta Arantxa , Isomursu Minna , Escalada-Hernández Paula , San Martín-Rodríguez Leticia , García-Vivar Cristina , Soto-Ruiz Nelia
Published: September 2024

This study aims to explore the challenges and strategies in creating online communities for individuals with diabetes, emphasizing their role in fostering connections among individuals facing similar health conditions. Using a single-case approach, we investigated the design process of a diabetes online community using the classic waterfall model. Participants were recruited from a diabetes local association, and usability was assessed using the System Usability Scale and the think-aloud method. Subsequently, semistructured interviews were conducted to evaluate functionality and user experience. Data collection was conducted from August until December 2023. The development of the community unveiled significant usability challenges, highlighting the need for user feedback and improvement. Ethical considerations, including anonymity, usage conditions, privacy terms, and health information sharing, emerged as critical areas requiring meticulous attention. Furthermore, healthcare professional moderation was deemed essential to ensure a secure environment. Users expressed strong interest in enhanced interaction features and personalized notifications. Although online diabetes communities hold potential for peer support, addressing usability challenges, ethical considerations, and moderation issues is essential. This study emphasizes the ongoing necessity for research to enhance the development of patient communities, ensuring accessibility, mitigating ethical risks, and leveraging nurses as moderators.
Cardiovascular Manifestations of Pseudoxanthoma Elasticum: Pathophysiology, Management, and Research
Authors: Desai Dev , Maheta Darshilkumar , Agrawal Siddharth Pravin , Soni Zeal , Frishman William H. , Aronow Wilbert S.
Published: September 2024

Pseudoxanthoma elasticum is a rare genetic disorder characterized by calcification of elastic fibers in the connective tissue. The abundance of elastic tissues at these sites: skin, eyes, and heart make them the most affected systems. It has multifactorial pathogenesis, meaning, it manifests due to both environmental and genetic factors, but ABCC6 gene mutation plays an important role. This gene is responsible for causing defective MRP6 protein which in return is required for cell transport in the connective tissue. The clinical features range from minor skin lesions to fatal cardiovascular complications. Thus, it is important to diagnose it early and give appropriate treatment. This article provides insight into the cardiovascular manifestations of pseudoxanthoma elasticum, its diagnosis and management plans.
Evaluation of a New Diabetes Mellitus Index Based on Measurements Using the Scheimpflug Analyzer Corvis ST
Authors: Ramm Lisa , Herber Robert , Patzner Maria Magdalena , Pillunat Lutz E.
Published: September 2024

Purpose:

Chronic hyperglycemia causes changes in corneal biomechanics that can be measured with the Scheimpflug Analyzer Corvis ST. The diagnostic reliability of the new diabetes mellitus (DM) index developed based on this should be evaluated.

Methods:

In a prospective cross-sectional study, the index was initially developed using data from 81 patients with DM and 75 healthy subjects based on logistic regression analysis. The reliability of the DM index was subsequently assessed using data from another 61 patients and 37 healthy individuals. In addition, the dependence of the DM index on indicators of disease severity was analyzed.

Results:

The index initially achieved a sensitivity of 79% and specificity of 80% with a cutoff value of 0.58. The evaluation showed a sensitivity of 67% and specificity of 76% with an optimized cutoff of 0.51 (area under the curve = 0.737, P < 0.001). The DM index correlated weakly with the severity of diabetic retinopathy (r = 0.209, P = 0.014). It was increased in the presence of diabetic maculopathy (P = 0.037) and in type 1 DM compared with patients with type 2 disease (P = 0.039).

Conclusions:

In this first evaluation, the new DM index achieved sufficiently good sensitivity and specificity and was weakly associated with disease-specific factors. With further improvements, it could complement the diagnostic options in DM with a simple, rapid, and noninvasive assessment method.
Foundation models in ophthalmology: opportunities and challenges
Authors: Sevgi Mertcan , Ruffell Eden , Antaki Fares , Chia Mark A. , Keane Pearse A.
Published: September 2024

Purpose of review

Last year marked the development of the first foundation model in ophthalmology, RETFound, setting the stage for generalizable medical artificial intelligence (GMAI) that can adapt to novel tasks. Additionally, rapid advancements in large language model (LLM) technology, including models such as GPT-4 and Gemini, have been tailored for medical specialization and evaluated on clinical scenarios with promising results. This review explores the opportunities and challenges for further advancements in these technologies.

Recent findings

RETFound outperforms traditional deep learning models in specific tasks, even when only fine-tuned on small datasets. Additionally, LMMs like Med-Gemini and Medprompt GPT-4 perform better than out-of-the-box models for ophthalmology tasks. However, there is still a significant deficiency in ophthalmology-specific multimodal models. This gap is primarily due to the substantial computational resources required to train these models and the limitations of high-quality ophthalmology datasets.

Overall, foundation models in ophthalmology present promising opportunities but face challenges, particularly the need for high-quality, standardized datasets for training and specialization. Although development has primarily focused on large language and vision models, the greatest opportunities lie in advancing large multimodal models, which can more closely mimic the capabilities of clinicians.
Is Orbital Lobe of the Lacrimal Gland Dispensable? Tear Volume, Ocular Surface, and MRI Volumetric Analysis
Authors: Singh Swati , Ali Mohammad Javed
Published: September 2024

Purpose:

To investigate the effects of lacrimal gland reduction surgeries on the tear volume and ocular surface.

Methods:

This is a cohort study of patients post 2 lacrimal gland reduction surgeries: partial orbital lobe dacryoadenectomy for refractory epiphora (4 patients, mean age: 31 ± 13.6 years, 3 males) and complete orbital lobe dacryoadenectomy for lacrimal gland pleomorphic adenoma (15 patients, mean age: 41 ± 12 years, 7 females). Changes in Schirmer I, ocular surface staining, symptomatology, and lacrimal gland volumetrics (MRI) were assessed before and after the surgical procedure.

Results:

The median Schirmer value reduction following partial orbital lobe dacryoadenectomy was 5 mm at a mean follow-up of 18 ± 4.9 months. None of them developed dry eye disease or positive ocular staining. The gland volume was reduced by 45.9% to 53.5% in 3 patients and 13.3% in 1 patient. The epiphora improved moderately in 93% of patients. Of 15 patients with lacrimal gland pleomorphic adenoma excision, the median reduction in Schirmer I was 4 mm at a mean follow-up of 12.8 months.

Conclusion:

Partial or complete removal of the orbital lobe of the lacrimal gland does not induce dry eye disease in otherwise healthy individuals. However, gland volume does not recover following partial reduction, and it seems unlikely that the lacrimal gland regenerates following partial removal.
DRESS syndrome and tuberculosis: Implementation of a desensitization and re-desensitization protocol to recover antituberculosis drugs in a case series at a specialized TB Unit in Lima, Peru
Authors: Morán-Mariños Cristian , Llanos-Tejada Felix , Salas-Lopez Juan , Villanueva-Villegas Renzo , Chavez-Huamani Antonella , Vidal-Ruiz María , Rodriguez-Calienes Aaron , Casanova-Mendoza Renato
Published: September 2024

Rationale:

Antituberculosis drugs (ATDs) could cause severe and rare reactions, such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome. Recovering ATDs might guarantee a higher cure rate for tuberculosis patients. Our aim was to evaluate the results of desensitization and re-desensitization to recover ATDs in a case series of patients with DRESS syndrome.

Patient concerns and diagnoses:

A retrospective case series study was conducted on patients with DRESS syndrome due to therapy with ATDs from 2021 to 2023. Desensitization and re-desensitization protocols, designed with an algorithm proposed by the Tuberculosis Specialized Unit of the Dos de Mayo National Hospital in Lima, Peru, were implemented.

Interventions and outcomes:

A total of 18 patients underwent desensitization or re-desensitization protocols, achieving an overall success rate of 72.2%. The average time for the development of DRESS syndrome due to ATDs was 19 days. Rifampicin (84.2%), isoniazid (68.4%), and pyrazinamide (26.3%) were identified as the main drugs responsible for this adverse reaction. All patients presented with fever and skin rash, with an average eosinophil percentage of 16.7% (interquartile range: 4.5–28.8). Organ involvement (liver, kidney, and heart) was observed in 8 patients, but only 2 patients experienced severe complications due to DRESS syndrome. A significant association was found between the number of ATDs used and eosinophil levels (P=.03).

Lessons:

The study introduced a desensitization and re-desensitization algorithm for the treatment of DRESS syndrome, notable for its safety, adaptability, and high success rate. This advancement provided healthcare professionals with safer and more effective therapeutic approaches for managing this complex condition.
Administration of the Postpartum Glucose Tolerance Test During the Delivery Hospitalization Compared With 4–12 Weeks Postpartum
Authors: Ciomperlik Hailie , Harper Megan , Hossain Md Faruk , Turrentine Mark A.
Published: September 2024

OBJECTIVE:

To estimate the rate of noncompletion of testing for type 2 diabetes in individuals with gestational diabetes mellitus (GDM) with a fasting 75-g, 2-hour oral glucose tolerance test in the immediate postpartum period before hospital discharge compared with 4–12 weeks postpartum by performing a systematic review and meta-analysis.

DATA SOURCES:

We explored EMBASE, MEDLINE, Web of Science, CINAHL, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials for studies comparing the rate of type 2 diabetes screening in individuals with GDM in the immediate postpartum period before hospital discharge with 4–12 weeks postpartum.

METHODS OF STUDY SELECTION:

Two reviewers separately identified studies, obtained data, and gauged study quality. The rate of type 2 diabetes screening was compared, and odds ratios (ORs) with 95% CIs were estimated.

TABULATION, INTEGRATION, AND RESULTS:

Five prospective and two retrospective cohort studies were identified with 2,254 individuals with GDM at 13 hospitals. Studies evaluated individuals with GDM who delivered and underwent screening for type 2 diabetes in the immediate postpartum period from May 1994 through October 2021. Four studies were from the United States, and one was from Korea, Brazil, and Iran. In these studies, testing was offered in both periods: A pooled proportion of 6.6% (95% CI, 0.23–20.5%) did not complete immediate postpartum testing before hospital discharge, and 53.0% (95% CI, 37.1–68.6%) did not complete testing at 4–12 weeks postpartum. The overall rate of noncompletion of screening in the immediate postpartum period was lower compared with individuals who had screening in the 4–12 week follow-up (pooled OR 0.21, 95% CI, 0.05–0.79, I
2=93%).

CONCLUSION:

Improved compliance with screening for type 2 diabetes in individuals diagnosed with GDM can be achieved after delivery before hospital discharge compared with screening at 4–12 weeks postpartum.

SYSTEMATIC REVIEW REGISTRATION:

PROSPERO, CRD42024530659.
PM&R Connections: A pilot study evaluating the adoptability and impact of a serious educational game on trainees at a Physical Medicine and Rehabilitation program
Authors: Stone Shane N. , Kirshblum Steven
Published: September 2024

To enhance engagement and educational outcomes, game-based learning has been introduced into undergraduate and graduate medical education programs. Using a free website, “PM&R Connections”, a serious game, was created to provide trainees with an alternative method of reviewing content to identify knowledge gaps to direct studying. The game was used by 19/33 trainees and 92.3% of users required <10 minutes to complete a puzzle. 76.9% of users found the tool helpful, 69.2% recommended the game, and 92.3% desired more puzzles to be developed. Confusion on how to play and intimidation were the most reported barriers to play, and only 46% of users changed their study habits. The positive feedback and desire for more puzzles to be developed provide a foundation to further develop the game.
Optimizing Intraflap Anastomosis of Conjoined Bilateral DIEP Flap for Breast Reconstruction: Planning, Execution and Outcomes in 201 patients
Authors: Kim Ju Hee , Lee Kyeong-Tae , Mun Goo-Hyun
Published: September 2024

BACKGROUND

Conjoined bilateral deep inferior epigastric perforator (DIEP) flap with intraflap anastomosis is an efficient approach for breast reconstruction, enabling the use of almost the entire abdominal tissue. Variations in bilateral DIEA anatomy may make it challenging to apply this technique consistently. This study aimed to derive optimal strategies for achieving reliable conjoined bilateral DIEP flap with intraflap anastomosis universally.

METHODS:

For all consecutive patients undergoing conjoined bilateral DIEP flap-based breast reconstruction from 2009 to 2023, preoperative planning and intraoperative execution for the pedicle configurations were reviewed. Their postoperative outcomes were evaluated.

RESULTS:

In total 201 patients were included, with no cases requiring conversion to extraflap anastomosis. In preoperative planning, candidates for recipient vessels for intraflap anastomosis were typically selected based on DIEA branching patterns, identified through computed tomographic angiography; Type I (single trunk) prioritizing the superior continuation, type II (two main trunks) considering a side branch, and type III (three main trunks) favoring the first bifurcating branch. Comparing candidates from bilateral DIEA, the primary pedicle was determined, providing larger recipient vessels. Most cases followed the planned approach smoothly, however 28 required intraoperative changes, mostly aimed at securing larger recipients by changing the primary pedicle or harvesting more caudally located perforators to obtain larger superior continuations. Four perfusion-related complications developed, which were resolved successfully without flap failure.

CONCLUSIONS:

Our results suggest an efficient strategy for securing a reliable recipient vessel, tailored to patient anatomy, in conjoined bilateral DIEP flap breast reconstruction with intraflap anastomosis, leading to achieving optimal outcomes.
Drug-induced Acute Lung Injury
Authors: Hamishegi Fatemeh Saber , Singh Ria , Baruah Dhiraj , Chamberlin Jordan , Hamouda Mohamed , Akkaya Selcuk , Kabakus Ismail
Published: September 2024

Drug-induced acute lung injury is a significant yet often underrecognized clinical challenge, associated with a wide range of therapeutic agents, including chemotherapy drugs, antibiotics, anti-inflammatory drugs, and immunotherapies. This comprehensive review examines the pathophysiology, clinical manifestations, and radiologic findings of drug-induced acute lung injury across different drug categories. Common imaging findings are highlighted to aid radiologists and clinicians in early recognition and diagnosis. The review emphasizes the importance of immediate cessation of the offending drug and supportive care, which may include corticosteroids. Understanding these patterns is crucial for prompt diagnosis and management, potentially improving patient outcomes.
Effect of Preoperative Autologous Blood Storage in Major Hepatectomy for Perihilar Malignancy
Authors: Onoe Shunsuke , Yokoyama Yukihiro , Igami Tsuyoshi , Yamaguchi Junpei , Mizuno Takashi , Sunagawa Masaki , Watanabe Nobuyuki , Kawakatsu Shoji , Ando Masahiko , Nagino Masato , Ebata Tomoki
Published: September 2024

Objective:

To reappraise whether preoperative autologous blood donation reduces post-hepatectomy liver failure (PHLF) in major hepatectomy for perihilar malignancy.

Summary Background Data:

Autologous blood storage and transfusion are carried out to reduce the use of allogeneic blood transfusion during hepatectomy and prevent postoperative complications. However, the clinical benefit in major hepatectomy has been controversial.

Methods:

This randomized clinical trial included patients who underwent major hepatectomy with extrahepatic bile duct resection for perihilar malignancy. Eligible patients were randomly assigned (1:1) to undergo surgery with or without the use of autologous blood transfusion. The primary outcome was the incidence of clinically relevant PHLF (grade B/C according to the International Study Group of Liver Surgery definition).

Results:

Between February 6, 2019, and May 12, 2023, 138 consecutive patients were enrolled in the study (blood storage group n=68, non-storage group n=70). Twenty-five patients who did not undergo resection were excluded; the remaining 113 patients were investigated as the full analysis set (blood storage group n=60, non-storage group n=53). Surgical procedures, operative time, and blood loss were not significantly different between the two groups. The incidence of PHLF was comparable (blood storage group n=10 [17%], non-storage group n=10 [19%]; P=0.760). There were also no between-group differences in other postoperative outcomes, including the incidence of Clavien-Dindo Grade Ⅲ or higher (72% vs. 72%, P=0.997) and median duration of hospital stay (25 vs. 29 d, P=0.277).

Conclusions:

Autologous blood storage did not contribute to reducing the incidence of PHLF in patients undergoing major hepatectomy.
Characterization of gut symbionts from wild-caught Drosophila and other Diptera: description of Utexia brackfieldae gen. nov., sp. nov., Orbus sturtevantii sp. nov., Orbus wheelerorum sp. nov, and Orbus mooreae sp. nov.
Authors: Phillips Laila E. , Sotelo Kathleen L. , Moran Nancy A.
Published: September 2024

Non-culture based surveys show that the bacterial family Orbaceae is widespread in guts of insects, including wild Drosophila. Relatively few isolates have been described, and none has been described from Drosophila. We present the isolation and characterization of five strains of Orbaceae from wild-caught flies of the genera Drosophila (Diptera: Drosophilidae) and Neogriphoneura (Diptera: Lauxaniidae). Cells are generally rod-shaped, mesophilic, and measure 0.8–2.0 µm long by 0.3–0.5 µm wide. Optimal growth was observed under ambient atmosphere. Reconstruction of phylogenies from the 16S rRNA gene and from single-copy orthologs verify placement of these strains within Orbaceae. Cells exhibited similar fatty acid profiles to those of other Orbaceae. Strain lpD01T shared 74% average nucleotide identity (ANI) with its closest relatives Ca. Schmidhempelia bombi Bimp and Zophobihabitans entericus IPMB12T. Results from multiple genome-wide similarity comparisons indicate lpD01T should be classified as a novel species within a novel genus. The major respiratory quinone for lpD01T is ubiquinone Q-8. lpD02T, lpD03, lpD04T, and BiBT are more closely related to Orbus hercynius CN3T (76, 77, 76, and 77% ANI, respectively) than to other described Orbaceae. Genomic and phylogenetic analyses suggest that lpD03 and lpD04T belong to the same species and that lpD02T, lpD03/lpD04T, and BiBT are each novel species of the genus Orbus. The proposed names of these strains are Utexia brackfieldae gen. nov., sp. nov. (type strain lpD01T =NCIMB 15517T =ATCC TSD-399T), Orbus sturtevantii sp. nov (type strain lpD02T =NCIMB 15518T =ATCC TSD-400T), Orbus wheelerorum sp. nov. (type strain lpD04T =NCIMB 15520T =ATCC TSD-401T), and Orbus mooreae sp. nov (type strain BiBT=NCIMB 15516T =ATCC TSD-402T). The isolation and characterization of these strains expands the repertoire of culturable bacteria naturally associated with insects, including the model organism D. melanogaster.
Machine Learning-Enhanced Drug Discovery for BACE1: A Novel Approach to Alzheimer's Therapeutics
Authors: Sangeet Satyam
Published: September 2024

Alzheimer's disease (AD) remains a significant global health challenge, with BACE1, a critical therapeutic target due to its role in the amyloidogenic pathway. This study presents an innovative approach to drug development by integrating machine learning (ML) techniques to identify the potential BACE1 inhibitors. Utilizing a comprehensive dataset of protein-ligand interactions, the current study employed a machine learning model to generate novel ligands with high binding affinity and specificity for the BACE1 active site. The model's efficacy was validated through molecular docking studies, which demonstrated superior binding affinities compared to existing FDA-approved inhibitors such as Atabecestat and Lanabecestat. The findings reveal that the top candidate, MLC10, exhibits a unique mechanism of action by promoting controlled flexibility in BACE1, contrasting with the rigid conformations induced by traditional inhibitors. This dynamic modulation enhances the enzyme's inhibition, suggesting a promising avenue for therapeutic intervention. Furthermore, solvent-accessible surface area analyses indicate that MLC10 facilitates a more favourable protein conformation, potentially altering catalytic behaviour through increased solvent interactions. This work underscores the transformative potential of machine learning in drug discovery, paving the way for the development of next-generation BACE1 inhibitors. By harnessing computational techniques, the present work aims to address the limitations of current therapies and contribute to more effective treatments for Alzheimer's disease, ultimately improving patient outcomes and quality of life.
A Biological Signature of Quantum Gravity?
Authors: Lone Irfan
Published: September 2024

In a recent proposal on the experimental tests of quantum gravity creation of non-Gaussianity in a Bose-Einstein condensate (BEC) has been suggested as a decisive confirmation of quantum gravity. In a related proposal, a gas of ultracold Rb or Cs atoms has previously been suggested as a possible platform for tests of quantum gravity. Since a practical demonstration of above proposals is a very challenging and costly affair, exploring cost-effective alternatives to these technologically demanding experimental protocols becomes very important. We here show that the phenomenon of Bicoid (Bcd) gradient formation in the early fruit fly embryo, considered basically here as a multipartite quantum system with an ensemble of initial states and a unitary evolutionUthat implements a quantum Newtonian Hamiltonian over this gravitationally interacting system, naturally combines the essential features of above proposals in a single system giving a viable signature of quantum gravity through the creation of non-Gaussianity. We conclude that although the phenomenon of Bcd gradient formation in the early Drosophila embryo is accompanied by quantum gravitational effects, it might need further experiments to verify such a noval claim.
FishCODE: a web-based information platform for comprehensive omics data exploration in fish research
Authors: Li Heng , Zhang Wanting , Ren Keyi , Yang Hong , Zhang Lei , Younas Waqar , Cheng Yingyin , Wang Yaping , Shi Mijuan , Xia Xiao-Qin
Published: September 2024

In terms of the utilization of omics data, the current fish database analysis functions are primarily relatively simple tools at the transcriptional level, aimed at obtaining the co-expression levels of specified genes or the data visualization of multiple genes, and do not enable users to perform comprehensive omics data analysis. Furthermore, the gene-level information currently provided by these multispecies fish genomics databases is incomplete, and there is a lack of a comprehensive portal that can offer multidimensional genetic information. To address these challenges, we collected extensive multi-omics information on 35 fishes and established the primary comprehensive multi-omics data information platform for fish, FishCODE (http://bioinfo.ihb.ac.cn/fishcode). We have collected experimental background of dataset which pertaining to the target fishes, selected a range of datasets that encompass a broad spectrum of research areas, and downloaded the corresponding raw omics data from public repositories such as the Sequence Read Archive (SRA). Through a unified pipeline analysis, FishCODE contains 11,216 samples from 540 sets of genomic, transcriptomic, and methylomic datasets. These data encompass transcript structure and expression, gene methylation levels, protein domains, protein subcellular localization, protein interactions, best matched protein (Swiss-Prot), associated SNP site information (47,111,018), orthologous genes, phylogenetic tree and GO/KEGG annotations. To facilitate comparison, we annotated the experimental background data sets of the FishCODE, FishGET, PhyloFish, FishSED and FishSCT databases using the Fish Experimental Condition Ontology. Currently, the FishCODE database omics dataset includes 146 unique experimental condition words, 654 cumulative experimental condition words, and 13 species with rich experimental background (more than 20 unique FECO words). These data are 3.5 times (42), 8.3 times (74), and 6.5 times (2) those of the second-ranked databases respectively. We generated word cloud maps for the experimental condition vocabularies of FishCODE and FishGET, illustrating the superior richness of FishCODE’s experimental background.
Betacoronaviruses Differentially Activate the Integrated Stress Response to Optimize Viral Replication in Lung Derived Cell Lines
Authors: Renner David M. , Parenti Nicholas A. , Weiss Susan R.
Published: September 2024

The betacoronavirus genus contains five of the seven human viruses, making it a particularly critical area of research to prepare for future viral emergence. We utilized three human betacoronaviruses, one from each subgenus-HCoV-OC43 (embecovirus), SARS-CoV-2 (sarbecovirus) and MERS-CoV (merbecovirus)- to study betacoronavirus interaction with the PKR-like ER kinase (PERK) pathway of the integrated stress response (ISR)/unfolded protein response (UPR). The PERK pathway becomes activated by an abundance of unfolded proteins within the endoplasmic reticulum (ER), leading to phosphorylation of eIF2α and translational attenuation in lung derived cell lines. We demonstrate that MERS-CoV, HCoV-OC43, and SARS-CoV-2 all activate PERK and induce responses downstream of p-eIF2α, while only SARS-CoV-2 induces detectable p-eIF2α during infection. Using a small molecule inhibitor of eIF2α dephosphorylation, we provide evidence that MERS-CoV and HCoV-OC43 maximize replication through p-eIF2α dephosphorylation. Interestingly, genetic ablation of GADD34 expression, an inducible phosphatase 1 (PP1)-interacting partner targeting eIF2α for dephosphorylation, did not significantly alter HCoV-OC43 or SARS-CoV-2 replication, while siRNA knockdown of the constitutive PP1 partner, CReP, dramatically reduced HCoV-OC43 replication. Combining growth arrest and DNA damage-inducible protein (GADD34) knockout with peripheral ER membrane–targeted protein (CReP) knockdown had the maximum impact on HCoV-OC43 replication, while SARS-CoV-2 replication was unaffected. Overall, we conclude that eIF2α dephosphorylation is critical for efficient protein production and replication during MERS-CoV and HCoV-OC43 infection. SARS-CoV-2, however, appears to be insensitive to p-eIF2α and, during infection, may even downregulate dephosphorylation to limit host translation.

IMPORTANCE

Lethal human betacoronaviruses have emerged three times in the last two decades, causing two epidemics and a pandemic. Here, we demonstrate differences in how these viruses interact with cellular translational control mechanisms. Utilizing inhibitory compounds and genetic ablation, we demonstrate that MERS-CoV and HCoV-OC43 benefit from keeping p-eIF2α levels low to maintain high rates of virus translation while SARS-CoV-2 tolerates high levels of p-eIF2α. We utilized a PP1:GADD34/CReP inhibitor, GADD34 KO cells, and CReP-targeting siRNA to investigate the therapeutic potential of these pathways. While ineffective for SARS-CoV-2, we found that HCoV-OC43 seems to primarily utilize CReP to limit p-eIF2a accumulation. This work highlights the need to consider differences amongst these viruses, which may inform the development of host-directed pan-coronavirus therapeutics.