bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of prone positioning in awake ventilation for COVID-19: Umbrella review
Authors: Guo Dan-yang , Zhang Qin , Wang Li , Pu Zai-chun , Jia Ping
Published: February 2025

Background:

Awake-prone positioning was widely used in COVID-19, combined with high-flow nasal oxygen therapy or noninvasive ventilation, effectively reducing intubation, and the effect on mortality is controversial. We aim to reevaluate the efficacy of awake-prone positioning in COVID-19 and summarize the protocol for awake-prone positioning.

Methods:

We gathered data on the treatment of COVID-19 using awake-prone positioning from Web of Science, Cochrane Library, Embase, PubMed, and CNKI. All the included studies were published between 2019 and 2023. Two researchers used the Assessment of Multiple Systematic Reviews tool to assess the methodological quality of the literature. The evidence was assessed using the Grading of Recommendations Assessment and Evaluation system.

Results:

Thirteen articles were included. The quality assessment using AMSTAR2 revealed that 3 articles were high quality, and 4 were moderate quality. The evidence quality assessment of 41 primary outcomes by the Grading of Recommendations Assessment, Development and Evaluation indicates that 9 indicators were of moderate quality, 21 were of low quality, and 6 were of very low quality.

Conclusions:

The review demonstrates high methodological quality, but the evidence quality of its outcome indicators is low. Awake-prone position has been shown to decrease intubation and improve oxygenation in COVID-19 patients. It is recommended to consult the latest quality assessment standards to develop more rigorous experimental protocols, improve research quality, and facilitate the translation of research findings.
Anti-dipeptidyl-peptidase-like protein-6 encephalitis with late-onset gastric cancer: A case report and 2-year follow-up
Authors: Wu Guolu , Shi Yanhui , Sun Jialan , Wu Feifei , Jiang Mei , Li Qiang
Published: February 2025

Rationale:

Anti-dipeptidyl-peptidase-like-protein 6 (DPPX) encephalitis is a rare form of autoimmune encephalitis, with no more than 80 cases reported to date. Cases of anti-DPPX encephalitis comorbid malignancy are exceedingly rare. Limited cases and diverse clinical presentations bring difficulties in the understanding of this disease, including the etiology, diagnosis, treatment, and prognosis. Herein, we report a case of insidious-onset anti-DPPX encephalitis in a patient with a prior history of Epstein-Barr Virus (EBV) meningitis diagnosed with gastric cancer after 2 years of follow-up.

Patient concerns:

A 72-year-old emaciated male presented with recurrent seizures over the last 20 years, personality changes over 10 years, and memory loss lasting 2 years.

Diagnoses:

The patient was diagnosed with epilepsy, psychiatric symptoms (agitation and irritability), and mild cognitive impairment. Anti-DPPX encephalitis and prior EBV infection were ultimately diagnosed based on the combination of his symptoms and positive DPPX antibody in serum (titer 1:10) and positive EBV-IgG antibody in cerebrospinal fluid.

Interventions:

The patient received a course of intravenous methylprednisolone and oral sodium valproate to treat the seizures.

Outcomes:

After 10 days of treatment, no seizures reoccurred, although the psychiatric symptoms persisted, and his serum antibody against DPPX was still positive (titer 1:10). Unfortunately, the family members asked for the patient to be discharged automatically and refused oral steroids after discharge. Through regular telephone follow-ups for 2 years after discharge, we learned that the patient did not experience any similar convulsions but still showed irritability when administered perphenazine. Unfortunately, the patient had gastric cancer with multiple metastases and was receiving palliative care.

Lessons:

This report illustrates a rare case of EBV meningitis in childhood, resulting in a long-standing, stable course of anti-DPPX encephalitis, and subsequent gastric cancer. This case broadens the atypical presentation spectrum of anti-DPPX encephalitis and emphasizes the need for screening for malignant tumors, including lymphoma, nasopharyngeal carcinoma, and gastric cancer, particularly in patients with latent EBV infection.
PHOX2B-associated Congenital Central Hypoventilation Syndrome Revealed Upon Treatment With Dinutuximab-beta
Authors: Chupin Alix , Dudoignon Benjamin , Couque Nathalie , Bokov Plamen , Mayer Sophie , Simaga Fatoumata , Gauthier-Villars Marion , Masserot Caroline , Benkaddouss Sakina , Philippe-Chomette Pascale , Jouglar Emmanuel , Masliah-Planchon Julien , Aerts Isabelle , Valteau-Couanet Dominique , Bourdeaut Franck , Schleiermacher Gudrun , Bouchoucha Yassine
Published: February 2025

Alterations of PHOX2B function is associated with a wide range of diseases, including congenital central hypoventilation syndrome (CCHS) and neural crest-derived tumors, from low-grade (ganglioneuromas) to malignant forms (neuroblastomas). We report a case bearing a novel nonpolyalanine repeat PHOX2B pathogenic variant presenting both as high-risk neuroblastoma and late-onset CCHS. CCHS was revealed upon severe respiratory decompensation while the patient was administered the anti-GD2 antibody dinutuximab-beta, as part of neuroblastoma treatment. From this experience, we make propositions for the management of patients with high-risk neuroblastoma and a constitutional pathogenic variant of PHOX2B.
Comparison of Diagnostic Accuracies of Commonly Used Trial of Void Parameters
Authors: Shinnick Julia K. , Raker Christina A. , Geller Elizabeth J. , Rardin Charles R. , Cooper Anne C.
Published: February 2025

(Abstracted from Urogynecology (Phila) 2024;30:888–895)

Standard care after pelvic surgical procedures often includes assessing for postoperative urinary retention, which is evaluated using postoperative trials of void (TOV). Accuracy of TOV findings is needed to limit both excess catheterization and health care utilization.
Fetal Fraction of Cell-Free DNA in Noninvasive Prenatal Testing and Adverse Pregnancy Outcomes: A Nationwide Retrospective Cohort Study of 56,110 Pregnant Women
Authors: Becking Ellis C. , Scheffer Peter G. , Henrichs Jens , Bax Caroline J. , Crombag Neeltje M.T.H. , Weiss Marjan M. , Macville Merryn V.E. , Van Opstal Diane , Boon Elles M.J. , Sistermans Erik A. , Henneman Lidewij , Schuit Ewoud , Bekker Mireille N.
Published: February 2025

(Abstracted from Am J Obstet Gynecol 2024;231:244.e1–244.e18)

Noninvasive prenatal testing (NIPT) for Down, Edwards, and Patau syndromes is widely available. Its accuracy depends on a sufficient amount of fetal cell-free DNA (cfDNA) in maternal plasma.
MiR-340-5p affects the proliferation and transfer of gastric cancer cells by targeting lncRNA HCG11 and NRF2 expression
Authors: Su Rina , Luan Wei , Zhang Kai , Liu Shuai , Zhang Xiaoqing , Gao Yanwei
Published: February 2025

Objective

The aim of the study was to investigate the expression and biological role of nuclear factor erythroid–related factor 2 (NRF2) in gastric cancer cells.

Methods

Western blotting (WB) and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect the expression of NRF2 in the tumor tissues of patients with gastric cancer and MKN45 cells. NRF2 was transfected into MKN45 gastric cancer cells, and apoptosis was detected using flow cytometry. The 3-(4,5-dimethylthiazole-2-yl)-2.5-dipheny-tetrazolium bromide (MTT) assay was performed to detect cell proliferation. Transwell and scratch experiments were performed to detect cell invasion and migration rates. WB blotting was performed to detect Bcl-2, COX-2, PEG2, Bax, and Cyt-C protein expression. RT-PCR was used to detect Bcl-2, COX-2, PEG2, Bax, Cyt-C, miR-340-5p, lncRNA HCG11, and NRF2 mRNA expression.

Results

NRF2 expression increased in gastric cancer tissues and in the MKN45 gastric cancer cell model. Compared with the blank group, the shNRF2 knockdown group showed a significant increase in the MKN45 gastric cancer cell apoptosis rate (p < 0.05) and a significant decrease in invasion and migration rates (p < 0.05). WB and RT-PCR showed that, in the shNRF2 knockdown group, Bcl-2 protein and mRNA, miR-340-5p, and lncRNA HCG11 expression was significantly increased, whereas COX-2, PEG2, Bax, and Cyt-C protein and mRNA expression was significantly reduced (p < 0.05). In the NRF2 overexpression group, Bcl-2 protein and mRNA expression was significantly reduced, whereas COX-2, PEG2, Bax, and Cyt-C protein and mRNA expression was significantly increased (p < 0.05). The opposite was observed for the NRF2 overexpression group. When miR-340-5p mimics were transfected into MKN45 gastric cancer cells, NRF2 and HCG11 expression significantly reduced (p < 0.05). When the miR-340-5p inhibitor was transfected into MKN45 gastric cancer cells, NRF2 and HCG11 expression significantly increased (p < 0.05).

Conclusions

The invasion, migration, abnormal proliferation, and apoptosis of MKN45 gastric cancer cells are closely related to an imbalance in NRF2 expression, suggesting that MiR-340-5p may target and regulate the lncRNA HCG11, thereby inhibiting NRF2 expression.
Scintigraphic Improvement of Primary Intestinal Lymphangiectasia in a Patient Treated With Alpelisib for a PIK3CA-Related Overgrowth Spectrum
Authors: Dubois Julien , Vauchot Fabien
Published: February 2025

A 33-year-old man with primary intestinal lymphangiectasia (Waldmann disease) associated with PIK3CA-related overgrowth spectrum was explored using 99mTc serum albumin scintigraphy before and during treatment by alpelisib, a specific PIK3CA inhibitor. Before treatment, scintigraphic images evidenced a focal uptake on the right colonic angle 4 hours postinjection (p.i.), diffusing to the transverse and left colon 24 hours p.i., compatible with a diffuse colonic exudation. Significant scintigraphic improvement was observed with a disappearing of the right colonic angle uptake 4 hours p.i. and later images 14 months after alpelisib introduction.
Primary iliac bone tuberculosis: A case report
Authors: Dahou Hajar , Saley Younoussa Fataou , Aragon Imane , El Aouadi Salma , El Harras Yahya , Benaissa Elmostafa , Ben Lahlou Yassine , Bahadi Abdelaali , El Fenni Jamal , Maleb Adil , Chadli Mariama , Elouennass Mostafa
Published: February 2025

Tuberculosis remains one of the world's leading causes of morbidity and mortality. It occurs in both pulmonary and extra-pulmonary forms. Primary iliac bone tuberculosis remains a rare clinical entity, even in endemic areas. The diagnosis of the disease can be challenging due to its similarity to other bone diseases. We report a rare case of primary iliac bone tuberculosis in a 63-year-old patient who was on peritoneal dialysis, and had a medical history of hypertension, and type II diabetes, which was complicated by diabetic retinopathy and diabetic kidney disease. Magnetic resonance imaging (MRI) revealed osteomyelitis in the iliac bone, while real-time polymerase chain reaction (PCR) using the GeneXpert® system on a gluteal collection sample confirmed the diagnosis of tuberculosis (TB). The integration of advanced molecular tools, such as GeneXpert®, represents a significant progress, enabling rapid and accurate diagnosis of TB and facilitating early initiation of treatment.
Study of Clostridioides difficile associated diarrheain Acute care areas of atertiary care centre in Western Rajasthan-a prospective study
Authors: Roy Nithya S , Kombade Sarika Prabhakar , Abhishek Kumar S , Singh Kuldeep , Kothari Nikhil , Khera Daisy , Kumar Deepak
Published: February 2025

Purpose
The aim of this study is to identify Clostridioides difficile associated diarrhoea (CDAD) in patients admitted to acute care units of the hospital. It also examines different detection methods, including anaerobic culture, GDH assay, and Toxin A/B ELISA, while exploring how the infection relates to patient risk factors and clinical features.
Materials and Method
Cross sectional study conducted in the Department of microbiology over 2 years. Patients >1 year of age, who were admitted and passing atleast 3 unformed stool over 24 hours, with history of taking antibiotics were included in the study. Stool samples from the included patients were collected, with one part used for anaerobic culture and another part for serological testing using Glutamate Dehydrogenase (GDH) ELISA and Toxin A/B ELISA for C. difficile. Identification of isolates was performed using MALDI-TOF MS. The results were analysed using statistical methods.
Result
Out of 180 suspected cases of Antibiotic Associated Diarrheal (AAD), 95(52.8%) were males. Maximum cases were in age group, above 60 years (27.8%) & 51 to 60 years (15.6%). Out of the 180 samples, GDH ELISA was positive in 29 (16%) cases, however Toxin A/B ELISA was positive in 5 (2.8%) samples. Thus, the prevalence of CDAD was found to be 2.8%. Isolation of Clostridioides difficile from culture was in 3 (1.7%) cases. 80% of confirmed CDAD cases were received more than one antibiotics. The median antibiotic duration among CDAD cases was 14 days (IQR = 9). All CDAD cases had a history of consumption of BL-BLI antibiotics, while 40% were on Meropenem, and 20% were on Ceftriaxone and Levofloxacin antibiotics. A possible association between abdominal surgery and CDAD was also noted in the study. Mortality rate in confirmed CDAD cases was 60%.
Conclusion
This study in Western Rajasthan underscores the paramount importance of early CDAD detection and management to forestall fatal complications and mortality in critically ill patients, while fostering prudent antibiotic utilization and fortifying antimicrobial stewardship practices in hospital setting.
Declining juvenile survival of Adelie penguins in Antarctica
Authors: Barracho Teo , Bardon Gael , Choquet Remi , Houstin Aymeric , Winterl Alexander , Beaulieu Michael , Blanchard Pierrick , Cornet Cindy C , Cristofari Robin , Raclot Thierry , Richter Sebastian , Chatelain Nicolas , Courtecuisse Julien , Brucker Matthieu , Zitterbart Daniel P , Lecomte Nicolas , Le Bohec Celine
Published: February 2025

As summer sea ice around Antarctica reaches historical lows, quantifying the demographic response of polar species to such environmental changes becomes critical. To achieve this, synthesizing results from across species' ranges and elucidating the environmental factors driving population dynamics are key. Adelie penguins are considered reliable indicators of changes in Antarctica but the pathways through which sea ice and other environmental factors shape their population dynamics are still unclear, especially for the juvenile stage. Using a 17-year dataset of electronically tagged Adelie penguins from Adelie Land (Antarctica), we found that juvenile survival probability was most impacted by sea ice concentration near their natal colony right after fledging, with lower ice concentrations detrimental to survival. Importantly, we found that juvenile survival declined by 32% from 2007 to 2020, mirroring trends at other distant colonies. The emergence of similar patterns at opposite ends of the continent may be an early signal for shifts in population trends expected from climate change.
The relationship of glutamate and glutamine and metabolic profiling in focal epilepsy using 7T CRT-FID-MRSI
Authors: Chambers Stefanie , Lazen Philipp , Shayeste Haniye , Tomschik Matthias , Wais Jonathan , Hingerl Lukas , Strasser Bernhard , Haider Lukas , Traub-Weidinger Tatjana , Baumgartner Christoph , Koren Johannes , Mayer Florian , Feucht Martha , Dorfer Christian , Pataraia Ekaterina , Bogner Wolfgang , Trattnig Siegfried , Kasprian Gregor , Rössler Karl , Hangel Gilbert
Published: February 2025

Approximately one-third of people with epilepsy (PWE) remain drug-resistant. In these cases, surgical resection of the epileptogenic zone may significantly reduce or eliminate seizures. Surgery necessitates precise delineation of the epileptogenic zone which proves especially challenging in the 20% of PWE that remain MRI-negative. To this end, the purpose of this study was to analyze the feasibility and robustness of ultra-high-field MRSI in identifying and characterizing pathologies in focal epilepsy. In addition, the relationship of glutamate and glutamine was evaluated in the epileptogenic zone (EZ)

Fifty-six people with focal epilepsy were prospectively measured using 7T concentric ring trajectory direct acquisition of free-induction-decay MRSI which generated whole-brain metabolic maps with an isotropic resolution of 3.4mm3. After exclusion criteria were applied, we assessed metabolite ratios in 29 lesional- and MRI-negative PWE.

In the lesional group, metabolic alterations in the suspected EZ were present in 86.7% of maps normalized to NAA, whereas this was reduced to 80% in creatine ratios. Metabolites with the highest stability in the lesional group included myo-inositol and choline, increased in 92.3%. In MRI-negative patients, changes were heterogeneous and less circumscribed, with a detection rate of 57.1%. We also observed a tendency towards an inverse relationship of glutamate to glutamine in the EZ, with relative increases of glutamine in PWE with lower seizure frequencies, contrasting relative glutamate increases in higher seizure frequencies.

Our preliminary analysis suggests that 7T CRT-FID MRSI shows promise not only in identifying metabolic alterations in focal epilepsy but may also provide insights into disease pathomechanisms.
Peripheral heterochromatin tethering is required for chromatin-based nuclear mechanical response
Authors: Attar A. Goktug , Paturej Jaroslaw , Sariyer Ozan S. , Banigan Edward J. , Erbas Aykut
Published: February 2025

The cell nucleus is a mechanically responsive structure that governs how external forces affect chromosomes. Chromatin, particularly transcriptionally inactive heterochromatin, resists nuclear deformations through its mechanical response. However, chromatin also exhibits liquid-like properties, casting ambiguity on the physical mechanisms of chromatin-based nuclear elasticity. To determine how heterochromatin strengthens nuclear mechanical response, we performed polymer physics simulations of a nucleus model validated by micromechanical measurements and chromosome conformation capture data. The attachment of peripheral heterochromatin to the lamina is required to transmit forces directly to the chromatin and elicit its elastic response. Thus, increases in heterochromatin levels increase nuclear rigidity by increasing the linkages between chromatin and the lamina. Crosslinks within heterochromatin, such as HP1αproteins, can also stiffen nuclei, but only if chromatin is peripherally tethered. In contrast, heterochromatin affinity interactions that may drive liquid-liquid phase separation do not contribute to nuclear rigidity. When the nucleus is stretched, gel-like peripheral heterochromatin can bear stresses and deform, while the more fluid-like interior euchromatin is less perturbed. Thus, heterochromatin’s internal structure and stiffness may regulate nuclear mechanics via peripheral attachment to the lamina, while also enabling nuclear mechanosensing of external forces and external measurement of the nucleus’ internal architecture.
Targeting Colorectal Cancer Liver Metastasis Through Repurposing Metabolic and Immune Inhibitors : A Theoretical Study
Authors: Mondal Madhurima , Lahiri Aditya , Datta Aniruddha
Published: February 2025

Liver metastasis from colorectal cancer is a major cause of death in patients with advanced colorectal cancer (CRC) and remains a difficult challenge in oncology. Inspite of commnedable developments in medical inventions, the complexity and poor prognosis of metastatic stage, alliterative strategies are required to address Colorectal cancer liver metastasis (CRLM). This paper presents a computational study on drug repurposing for CRLM using a Boolean Network model. We comprehensively analyze CRLM signaling pathways such as WNT, PI3K/AKT/mTOR, MAPK, Hedgehog, TGF-β, NF-kB, NOTCH and HGF and target them with metabolic and immune inhibitors. This study utilizes a computational analysis to evaluate single and multi-agent treatments across scenarios involving single and multiple genetic mutations. Our findings highlights the efficacy of metabolic inhibitors such as Simvastatin, Metformin, and predict compatible partner drugs to enhance their effiacy. Additionaly, we predict possible improvements for CRLM treatment using an immunotherapy drug like Pembrolizumab. Overall, this paper provides new insights into drug repurposing to improve CRLM treatment outcomes.
Comparative pangenome and mobilome analysis of clostridial species clusters reveals different levels of host adaptation and novel conserved biosynthetic potential
Authors: De Vrieze Lucas , Aerts Jan , Masschelein Joleen
Published: February 2025

Background

The classClostridiacomprises a diverse and industrially relevant group of anaerobes, ranging from free-living soil inhabitants to beneficial human gut symbionts. Analysing their genomic history and ecological adaptation dynamics beyond the species level allows us to gain deeper insights into their evolutionary traits and understand the impact of host adaptation on their innate functional capabilities.

Results

We constructed pangenomes and built core genome phylogenies for four ecologically distinct clostridial species clusters (rRNA clusters I, IV, XIVa and XIVb), analysing 492 clostridial genomes in total. All pangenomes were functionally annotated and fitted into a genomic divergence rate model, revealing a striking contrast in metabolic versatility and evolutionary dynamics among the host-associated clusters, IV and XIVa. Based on these findings, we hypothesized that cluster XIVa species are in the earlier stages of a host adaptation process compared to their cluster IV relatives. Targeted follow-up analyses confirmed this and yielded two additional key findings. First, cluster XIVa species are comparably less dependent on their host metabolically, and possess a more extensive secondary metabolism than anticipated for a host-associated clade. Second, a remarkable conservation of ranthipeptide biosynthetic gene clusters reveals underexplored biosynthetic potential with significant evolutionary advantages.

Conclusions

These results show that comparing genomic patterns beyond the species level can uncover distinct ecological trends, such as host and niche adaptation, across entire species groups. Understanding these trends provides valuable insights into the metabolic versatility and biosynthetic potential of these groups.
3BTRON: A Blood-Brain Barrier Recognition Network
Authors: Fletcher-Lloyd Nan , Bravo-Ferrer Isabel , Gaasdal-Bech Katrine , Díaz Castro Blanca , Barnaghi Payam
Published: February 2025

The blood-brain barrier (BBB) plays a crucial role in maintaining brain homeostasis. During ageing, the BBB undergoes structural alterations. Electron microscopy (EM) is the gold standard for studying the structural alterations of the brain vasculature. However, analysis of EM images is time-intensive and can be prone to selection bias, limiting our understanding of the structural effect of ageing on the BBB. Here, we introduce 3BTRON, a deep learning framework for the automated analysis of the BBB architecture (the morphology, structure, and texture of its various components) in EM images. Using age as a readout, we trained and validated our model on a unique dataset (n = 359). We show that the proposed model could confidently identify the BBB architecture of aged mouse brains from young mouse brains across three different brain regions, achieving a sensitivity of 77.8% and specificity of 80.0% post-stratification when predicting on unseen data. Additionally, feature importance methods revealed the spatial features of each image that contributed most to the predictions. These findings demonstrate a new data-driven approach to analysing age-related changes in the architecture of the BBB.
Facial video photoplethysmography for measuring average and instantaneous heart rate: a pilot validation study
Authors: Pstras Leszek , Okupnik Tymoteusz , Ponikowska Beata , Paleczny Bartlomiej
Published: February 2025

Introduction

Video photoplethysmography (vPPG) is a contactless optical technique of recording blood pulsations in the skin vasculature using a digital camera, which is increasingly used to measure or estimate various physiological parameters. Here, we evaluate the accuracy of heart rate (HR) measurements performed using facial vPPG technology Shen.AI Vitals and a smartphone camera.

Methods

We studied 35 healthy volunteers in a sitting position (median age 25 years, 17 females). Video recordings of participants’ faces were obtained using the front camera of a smartphone mounted on a tripod. In parallel, a 1-lead chest electrocardiogram (ECG) was recorded to obtain reference HR values (average value from the entire 60-second measurement and multiple values averaged over 10-second or 4-second periods during the measurement).

Results

The mean absolute errors were 0.1, 0.2, and 0.4 beats per minute (bpm) for HR averaged over 60-second, 10-second, and 4-second periods, respectively. The errors did not exceed 1 bpm in 100.0%, 99.8%, and 94.5% of cases, respectively. Regardless of the HR averaging time, the correlation between the vPPG-based and reference values was very strong (r > 0.99, P < 0.001).

Conclusions

In predominantly young, white, sitting subjects, the tested vPPG technology provided highly accurate HR values, both when averaging over 60 seconds as well as in the case of short-term averages over 10 seconds or instantaneous HR values averaged over 4 seconds. The results should be confirmed in a larger study with greater diversity in age, skin tone, and lighting conditions.
A subset of conserved phagocytic genes are likely used for the intracellular theft of cnidarian stinging organelles in nudibranch gastropods
Authors: Goodheart Jessica A. , Fiorenza Rose , Rio Robin , Lopez-Anido Rebecca N. , Martin Noah J. , Herrlinger Timothy J. , Tarvin Rebecca D. , Lyons Deirdre C.
Published: February 2025

Background

Phagocytosis is a universal physiological process in eukaryotes with many important biological functions. In nudibranch gastropods, a novel form of phagocytosis called nematocyst sequestration is specialized for the uptake of venomous stinging organelles stolen from their cnidarian prey. This process is highly selective. Here we use the emerging model nudibranch speciesBerghia stephanieaeandHermissenda opalescensto identify genes enriched within the body regions where nematocyst sequestration occurs, and investigate how the expression profile of phagocytosis, immune, and digestive genes differs between nematocyst sequestering regions relative to those where other phagocytic functions occur.

Results

We identified 166 genes with significantly higher expression in sequestering regions inB. stephanieae, including genes associated with development, membrane transport, and metabolism. Of these, 41 overlap with transcripts upregulated inH. opalescenssequestering tissues. Using Hybridization Chain Reactionin situs, we show that at least two of these genes were localized to sequestering cells inB. stephanieae, including a putative C-type lectin receptor and a collagen. Genes annotated with phagocytosis, digestion, or immunity GO terms were often expressed in both sequestering and non-sequestering tissues, suggesting that they may also play a role in sequestration processes.

Conclusion

Our results suggest that phagocytosis genes likely play a role in the sequestration phenotype, and that a small subset of genes (e.g., collagen) may play unique functions yet to be uncovered. However, we also show that genes categorized in GO terms related to endocytosis, immunity, and digestion show a clear decrease in overall expression in sequestering tissues. This study lays the foundation for further inquiry into mechanisms of organelle sequestration in nudibranchs and other organisms.
Hip stabilization in an australopithecine-like hip: the influence of shape on muscle activation
Authors: Kramer Patricia Ann , Sylvester Adam D.
Published: February 2025

Hip stabilization through muscular activation of the gluteals is a key feature of hominin walking, but the role of pelvic shape on muscular activation remains uncertain. Coupled with this is the uncertainty regarding whether or not the kinematics and kinetics of modern humans are appropriate proxies for the patterns in extinct hominins. In this work we treat modern human kinematics and kinetics as a null hypothesis by applying them to musculoskeletal models with modern human-like and australopithecine-like hips and examine the resulting joint reaction and muscle forces. We test the prediction that the hip functional complex that includes biacetabular breadth, femoral neck length, and iliac blade flare produces hip abductor muscle activations and hip joint reactions that are similar in the modern human- and australopithecine-like forms.

Using previously developed musculoskeletal models that approximate gluteus maximus with twelve muscle elements, gluteus medius with twelve, and gluteus minimus with three, we calculated joint reaction and muscle forces using inverse dynamics analyses and a muscle redundancy algorithm. We used data from ten individuals who walked at their normal velocity. We found that the shape of the australopithecine-like pelvis produces absolutely higher muscle activations in gluteus medius and gluteus minimus, but lower muscle activations across a long period of stance in gluteus maximus compared to the modern human-like pelvis when kinematics and size are held constant. Hip joint reaction forces are similarly heterogeneous: the australopithecine-like hip exhibits lower forces in the direction of travel but higher in the vertical. These results suggest that, while the australopithecine-like pelvis is compatible with human walking patterns, influences on pelvic shape other than accommodating muscle and joint reaction forces during walking are present.
H2S is a potential universal reducing agent for Prx6-type peroxiredoxins
Authors: Lang Lukas , Leiskau Laura , Thullen Lea , Deponte Marcel
Published: February 2025

The absence of a universal reducing agent distinguishes the Prx6-type subfamily of peroxiredoxins from the structurally similar Prx1-type subfamily. A likely explanation for the lack of reactivity of Prx6-type enzymes with common reducing agents is that a Prx6-specific histidyl residue at the bottom of the active-site pocket traps the oxidized enzyme with a potentially hypervalent cysteinyl sulfur atom in an inaccessible fully-folded protein conformation. Here, we analyzed the reduction of oxidized PfPrx6 from the human malaria parasitePlasmodium falciparumand human PrxVI by the hydrosulfide ion, HS−, as the smallest possible sulfur-containing universal electron donor using stopped-flow kinetic measurements. We show that HS−rapidly reacts with oxidized wild-type PfPrx6 or human PrxVI (but not the histidyl mutant PfPrx6H39Y) with a second-order rate constant of >108M−1s−1at pH 7.4. The potential protein-persulfide species of PfPrx6 is neither reduced by thioredoxin nor glutaredoxin and glutathione, but further reacts with an excess of HS−with a second-order rate constant of 6.3×103M−1s−1, yielding the reduced enzyme. In summary, we identified HS−as a highly reactive, potential universal electron donor for Prx6-type enzymes in eukaryotes, bacteria, and archaea. Our study marks the starting point for the characterization of the complex reduction pathway of Prx6-type enzymes with potential implications for H2S detoxification, redox signaling, and iron-sulfur metabolism.
Construction of a register-based severity index for anorexia nervosa in Denmark: Association with overall and cause-specific mortality
Authors: Larsen Janne Tidselbak , Chatwin Hannah , Zhang Ziping , Clausen Loa , Bulik Cynthia Marie , Thornton Laura Marie , Micali Nadia , Petersen Liselotte Vogdrup , Yilmaz Zeynep
Published: February 2025

Background

Considering the high likelihood of chronicity, it is imperative to understand the risk factors and outcomes associated with severe anorexia nervosa (AN), for which Danish registers provide a unique opportunity. We developed a measure of AN severity adapted from clinical literature for use in register-based research.

Methods

The study population included all Danish individuals born between 1963 and 2007 who were diagnosed with AN from 1969 to 2013. Using register data, we constructed the Anorexia Nervosa Register-based Severity Index (AN-RSI), incorporating early or late illness onset, number of inpatient admissions and outpatient treatments, cumulative treatment length, and illness duration, each weighted based on clinical importance. Associations between AN-RSI scores, evaluated five years after first AN diagnosis, and mortality were estimated using survival analysis.

Results

Among 9,167 individuals diagnosed with AN, 132 died during follow-up: 17 from AN; 30 from suicide; and 85 from other causes. Higher AN-RSI scores were associated with increased rates of mortality from AN, somatic anorexia diagnosis, suicide, alcohol-related causes, and any cause. AN cases who scored in the top 20% of AN-RSI had especially high mortality rates. Furthermore, severe AN cases were also more likely to be in treatment in the next five years after severity was established.

Conclusions

AN-RSI effectively captures mortality and long-term treatment in the absence of detailed patient records and is associated with later mortality in AN patients. AN-RSI could serve as a tool to examine epidemiological and genetic risk factors associated with AN course and outcomes.
Structural and Thermodynamic Impact of Oncogenic Mutations on the Nucleosome Core Particle
Authors: Onyema Augustine C. , DiForte Christopher , Patel Rutika , Poget Sébastien F. , Loverde Sharon M.
Published: February 2025

The nucleosome core particle (NCP) is essential for chromatin structure and function, serving as the fundamental unit of eukaryotic chromatin. Oncogenic mutations in core histones disrupt chromatin dynamics, altering DNA repair and transcription processes. Here, we investigate the molecular consequences of two mutations—H2BE76K and H4R92T—using 36 µs of all-atom molecular dynamics simulations and experimental biophysical assays. These mutations destabilize the H2B-H4 interface by disrupting critical salt bridges and hydrogen bonds, reducing binding free energy at this interface. Principal component analysis reveals altered helix conformations and increased interhelical distances in mutant systems. Thermal stability assays (TSA) and differential scanning calorimetry (DSC) confirm that these mutations lower the dimer dissociation temperature and reduce enthalpy compared to the wild type. Taken together, our results elucidate how these mutations compromise nucleosome stability and propose mechanisms through which they could modulate chromatin accessibility and gene dysregulation in cancer.

Statement of Significance

The nucleosome is the essential packaging unit of DNA. ‘Oncohistones’ which are histone mutations that are associated with cancer, are known to compromise the stability of the nucleosome and affect nucleosome sliding. Here we perform long-time molecular dynamics simulations of two buried histone core mutations, demonstrating that these mutations reduce the stability of the histone core at the H2B-H4 interface. Next, we demonstrate that these same mutations lower the dimer dissociation temperature and shift the nucleosome dissociation pathway.
DDX5 and DDX17 RNA helicases regulate hepatitis B virus RNA splicing
Authors: Giraud Guillaume , Grand Xavier , Huchon Pélagie , Rodà Mélanie , Diederichs Audrey , Chapus Fleur , De Nicola Francesca , Parent Romain , Rivoire Michel , Bourgeois Cyril F. , Zoulim Fabien , Testoni Barbara
Published: February 2025

Chronic HBV infection remains a major health burden worldwide and is the main driver of severe liver diseases. Liver pathogenesis is associated with the increased proportion of HBV spliced variants that encode viral proteins involved in liver disease progression. However, how HBV RNA splicing is regulated is poorly understood. Here, we focused on DDX5 and DDX17 RNA helicases, known to regulate HBV RNA metabolism and alternative splicing of host genes. By performing 5’RACE-PCR combined with single molecule sequencing, we demonstrated that silencing both proteins increased the usage of a specific splicing donor site and the expression of the derived HBV spliced variants. Polysome fractionation highlighted the ability of these RNA species to encode new viral proteins potentially contributing to liver pathogenesis. Overall, our data established DDX5 and DDX17 helicases as master regulators of HBV RNA metabolism, by fine-tuning viral splicing, which is linked to HBV-induced liver pathogenesis and disease progression.
Viral-mediated delivery of morphogenic regulators enables leaf transformation inSorghum bicolor(L.)
Authors: Butler Nathaniel M. , Carlson Aidan T. , Starker Colby , Voytas Daniel F.
Published: February 2025

Recent advancements in monocot transformation, using leaf tissue as explant material, have expanded the number of grass species capable of transgenesis. However, the complexity of vectors and reliance on inducible excision of essential morphogenic regulators have so far limited widespread application. Plant RNA viruses, such as Foxtail Mosaic Virus (FoMV), present a unique opportunity to express morphogenic regulator genes, such asBabyboom(Bbm),Wuschel2(Wus2),Wuschel-like homeobox protein 2a(Wox2a), and the GROWTH-REGULATING FACTOR 4 (GRF4) GRF-INTERACTING FACTOR 1 (GIF1) fusion protein transiently in leaf explant tissues. Furthermore, altruistic delivery of conventional and viral vectors could provide opportunities to simplify vectors used for leaf transformation— facilitating vector optimization and reducing reliance on morphogenic regulator gene integration. In this study, both viral and conventional T-DNA vectors were tested for their ability to promote the formation of embryonic calli, a critical step in leaf transformation protocols, usingSorghum bicolorleaf explants. Although conventional leaf transformation vectors yielded viable embryonic calli (43.2 ± 2.9%: GRF4-GIF1, 50.2± 3%:Bbm/Wus2), altruistic conventional vectors employing the GRF4-GIF1 morphogenic regulator resulted in improved efficiencies (61.3 ± 4.7%). Altruistic delivery was further enhanced with the use of viral vectors employing both GRF4-GIF1 andBbm/Wus2regulators, resulting in 75.1 ± 2.3% and 79.2 ± 2.5% embryonic calli formation, respectively. Embryonic calli generated from both conventional and viral vectors produced shoots expressing fluorescent reporters, which were confirmed using molecular analysis. This work provides an important proof-of-concept for use of both altruistic vectors and viral-expressed morphogenic regulators for improving plant transformation.
Maternal age and genome-wide failure of meiotic recombination are associated with triploid conceptions in humans
Authors: Picchetta Ludovica , Ottolini Christian Simon , Tao Xin , Zhan Yiping , Jobanputra Vaidehi , Marin Vallejo Carlos , Mulas Francesca , Paraboschi Elvezia Maria , Escribá Pérez Maria José , Molinaro Thomas , Whitehead Christine , Gill Pavan , Mounts Emily , Babariya Dhruti , Rienzi Laura Francesca , Ubaldi Filippo Maria , Garcia-Velasco Juan Antonio , Pellicer Antonio , Carmi Shai , Hoffmann Eva R , Capalbo Antonio
Published: February 2025

Triploid and haploid conceptions are not viable and are a common occurrence in humans, where they account for 10% of all pregnancy losses. Despite the parent-of-origin being important in the etiology of the pregnancy, our knowledge of their causes is limited, especially at the point of conception. Using a dataset of 96,660 biopsies and a validation dataset of 44,324 from human blastocysts embryos generated by intra-cytoplasmic sperm injection (ICSI), we estimate that 1.1% of human conceptions (n=1,063) contain extra or missing chromosome sets in zygotes. We identify a maternal age effect, with a 1.059 per year increased risk in triploidy/haploidy (p=0.0008). In 0.03% of couples, we identified three or more triploid/haploid embryos, suggesting a personal risk effect (p=0.03). Genotype analysis of 55 triploid embryo biopsies and their parents show that one third of maternal triploid conceptions originate in meiosis I and two thirds in meiosis II. Seven of these embryos are inferred to have entirely failed to initiate meiotic recombination genome-wide, suggesting that human oocytes with pervasive meiotic recombination failure that are formed during fetal development are capable of ovulation in adult life. Finally, we identify a new type of genome-wide maternal isodiploidy (two maternal chromosome sets) in 0.05% of embryos (41 of 74,009). Collectively, our findings shed light on the biology of meiosis and the formation of human oocytes with the number of chromosome sets.
Fluoroscopic-Guided Magnetic Soft Millirobot for Atraumatic Endovascular Drug Delivery
Authors: Le Tuan-Anh , Alabay Husnu Halid , Singh Prabh G. , Austin Melissa Gioia , Misra Sanjay , Ceylan Hakan
Published: February 2025

Atraumatic and precise drug delivery to arteries and veins remains an unmet need in interventional medicine, with significant implications for managing vascular diseases and long-term patient outcomes. Conventional endovascular methods, such as drug-coated balloons and drug-eluting stents, often damage vessel endothelium and compromise wall integrity, leading to reduced therapeutic efficacy and severe complications including restenosis and thrombosis. To address these limitations, we introduce EndoBot, an untethered soft millirobot designed for atraumatic vessel navigation and localized drug delivery under physiological blood flow. EndoBot achieves this through magnetically actuated corkscrew propulsion and mechanically adaptive surface crawling, exerting low radial pressure (< 1 kPa) to preserve endothelial integrity. We validated its performance in phantom vessels, ex vivo human umbilical veins under normothermic perfusion, and in vivo rat inferior vena cava under fluoroscopic guidance using a human-scale magnetic manipulation platform. Despite dynamic vessel contractions and compressions along non-uniform cross-sections, mechanically adaptive locomotion strategy ensures safe navigation and protects the inner endothelial lining. EndoBot is deployable and retrievable via clinical vascular sheaths and remains stable even under supra-physiological blood flow conditions (> 155 cm/s). Extensive blood compatibility tests demonstrated minimal hemolysis (<0.01%), low platelet activation on the robot surface, and no increased coagulation tendency. For drug delivery, a hydrophobic transfer coating enables EndoBot to gently deposit a stable, flow-resistant drug layer onto the vessel wall without fragmentation. This novel platform enables safer and more effective targeted endovascular drug delivery, paving the way for transformative approaches to address early-stage vascular pathologies and deliver more effective preventive interventions.
Crystal structure of dihydroorotate dehydrogenase from Helicobacter pylori with bound flavin mononucleotide
Authors: Agarwal Ashna A. , Georgiades John D. , Dranow David M. , Lorimer Donald D. , Edwards Thomas , Barrett Kayleigh F. , Craig Justin K. , Van Voorhis Wesley C. , Myler Peter J. , Smith Craig L.
Published: February 2025

Helicobacter pylori is the primary causative agent of peptic ulcer disease, among other gastrointestinal ailments, and currently affects over half of the global population. Although some treatments exist, growing resistance to these drugs has prompted efforts to develop novel approaches to fighting this pathogen. To generate many of the nucleotides essential to biochemical processes, H. pylori relies exclusively on the de novo biosynthesis of these molecules. Recent drug-discovery efforts have targeted the first committed step of this pathway, catalysed by a class 2 dihydroorotate dehydrogenase (DHODH). However, these initiatives have been limited by the lack of a crystal structure. Here, we detail the crystal structure of H. pylori DHODH (HpDHODH) at 2.25 Å resolution (PDB entry 6b8s). We performed a large-scale bioinformatics search to find evolutionary homologs. Our results indicate that HpDHODH shows high conservation of both sequence and structure in its active site. We identified key polar interactions between the HpDHODH protein and its requisite flavin mononucleotide (FMN) cofactor, identifying amino-acid residues that are critical to its function. Most notably, we found that HpDHODH maintains several structural features that allow it to associate with the inner membrane and utilize ubiquinone to achieve catalytic turnover. We discovered a hydrophobic channel that runs from the putative membrane interface on the N-terminal microdomain to the core of the protein. We predict that this channel establishes a connection between the ubiquinone pool in the membrane and the FMN in the active site. These findings provide a structural explanation for the competitive inhibition of ubiquinone by pyrazole-based compounds that was determined biochemically in other studies. Understanding this mechanism may facilitate the development of new drugs targeting this enzyme and push the effort to find a resistance-free treatment for H. pylori.
Forward guidance and interest rate pass-through: evidence from New Zealand
Authors: Wang Siyi , Liu Ming-Hua , Margaritis Dimitris
Published: February 2025

Purpose

This paper examines the impact of forward guidance in monetary policy on the pass-through of interest rates in New Zealand by analyzing the degree of both the long-term and short-term pass-through.

Design/methodology/approach

We use dynamic OLS to estimate the long-term relationship between the official cash rate and the time-deposit rates and various lending rates of New Zealand banks. We use a standard error correction model to estimate the short-term dynamics.

Findings

The results show that implementing forward guidance improves the degree of long-term pass-through, especially for time-deposit interest rates and longer-term fixed mortgage rates. Furthermore, the markup for various lending rates decreased, and the degree of short-term pass-through increased slightly after the implementation.

Practical implications

Implementing forward guidance enhances the transmission of monetary policy. Commercial banks are able to respond more quickly to changes in monetary policy by adjusting their deposit and loan rates.

Originality/value

New Zealand is the first country to mandate inflation targeting. Since its birth in 1990, the 2% inflation target has become the norm for central banks all over the world, including the FED, European Central Bank, Bank of Japan, Bank of England, etc. To our knowledge, ours is the first paper to examine the impact of forward guidance on the interest rate pass-through.