bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of ivermectin on COVID-19 outcomes: a systematic review and meta-analysis
Authors: Sai Yengu Nithin , Raheem Abdul , Pons Andrea Gómez , Ho Wing Lam , Ali Syed Muhammad Sinaan , Haseeb Abdul , Fadlalla Ahmad Tagwa Kalool , Mustafa Muhammad Saqlain
Published: December 2024

Background:

The COVID-19 pandemic, resulting in approximately seven million deaths globally, underscores the urgency for effective treatments. Ivermectin, among several repurposed drugs, garnered interest due to its antiviral properties. However, conflicting evidence from observational studies and randomized controlled trials raised questions about its efficacy and safety.

Method:

This systematic review and meta-analysis followed MOOSE and PRISMA guidelines. Comprehensive searches were conducted in databases including Scopus, Embase, PubMed, and Web of Science up to April 2024. Data were extracted independently by two reviewers and analyzed using Comprehensive Meta-Analysis V3 software.

Results:

Across 33 studies encompassing 15,376 participants, ivermectin showed no significant impact on critical outcomes such as mortality [risk ratio (RR) 0.911, 95% confidence intervals (CI) 0.732–1.135], mechanical ventilation (RR 0.727, 95% CI 0.521–1.016), polymerase chain reaction conversion (RR 1.024, 95% CI 0.936–1.120), ICU admissions (RR 0.712, 95% CI 0.274–1.850), or hospitalization rates (RR 0.735, 95% CI 0.464–1.165) compared to controls. However, it significantly reduced time to symptom alleviation (standardized mean difference −0.302, 95% CI −0.587 to −0.018) and sustained symptom relief (RR 0.897, 95% CI 0.873–0.921). Adverse event (AE) rates were similar between the ivermectin and control groups (RR 0.896, 95% CI 0.797–1.007). Meta-regression indicated older age and diabetes as predictors of AEs.

Conclusion:

Despite its observed benefits in symptom management, ivermectin did not significantly influence critical clinical outcomes in COVID-19 patients. These findings highlight the importance of continued research to identify effective treatments for COVID-19, emphasizing the need for high-quality studies with robust methodology to inform clinical practice and public health policy effectively.
Management of Sprengel deformity by modified Woodward approach and outcome: a case series and literature review
Authors: Pandey Abhishek , Kayastha Sabik R. , Pande Prasamsa , Silwal Prabhat , Upadhyaya Prashant , Pandey Archana , Keshari Suraj , Dhungana Sanjay , Singh Yadvinder
Published: December 2024

Introduction:

Sprengel deformity (SD) is a rare congenital deformity consisting of elevation of the scapula, leading to limited range of motion and a visible lump in severe cases. Klippel-Feil syndrome is a rare congenital abnormality characterized by the triad of cervical synostosis, low posterior hairline, and short neck. It is often associated with SD.

Case presentation:

We present two cases of SD of a 7-year-old boy and a 10-year-old boy. They were both born with the abnormality and complained of limited range of motion in the affected shoulder.

Clinical discussion:

Patients with less severe forms of SD can lead a normal life with supportive treatment, and it is not connected with cognitive impairment; however, there may be a limited range of motion and cosmetic concerns. In severe cases, treatment entails operative therapy with corrective placement of the scapula and resection of the omovertebral band.

Conclusion:

Patients with SD require supportive physiotherapy from a young age. Severe cases need operative treatment at a young age. The modified Woodward approach may be an excellent surgical option to correct the deformity.
Surgical strategies for hemorrhagic vestibular schwannoma with acute neurological decline: a case report with a literature review
Authors: Almahariq Fadi , Budimir Krunoslav , Kastelancic Andelo , Lakic Marin , Oreskovic Darko , Blazevic Andrea , Chaurasia Bipin
Published: December 2024

Introduction and importance:

Vestibular schwannomas (VSs) are benign tumors of cranial nerve VIII, comprising 8% of primary intracranial neoplasms. Hemorrhagic VSs, though rare, present unique clinical challenges due to their potential for rapid neurological decline.

Case presentation:

We present a case of a 68-year-old male with sudden severe headache, nausea, vomiting, and balance issues, initially diagnosed with a hematoma at the right cerebellopontine angle until an magnetic resonance imaging (MRI) scan verified a bleeding schwannoma. Due to deteriorating neurological status and signs of obstructive hydrocephalus on computed tomography (CT), urgent neurosurgical neuromonitoring, successfully managed the hemorrhagic VS, with postoperative recovery intervention required. Neurosurgical treatment, guided by intraoperative outcomes, restoring normal life. Urgent transfer to a medical center with a neurosurgical showing favorable outcomes.

Clinical discussion:

Cerebellopontine hematoma verified by CT mandates MRI to exclude tumorous bleeding, which is crucial in cases lacking prior MRI.

Conclusion:

Though rare, hemorrhagic VS must be considered in neurologically decompensated patients, especially with risk factors. Timely surgical intervention, despite precipitating a comatose state, can yield satisfactory results.
Revolutionizing electrocardiography: the role of artificial intelligence in modern cardiac diagnostics
Authors: Qayyum Sardar N. , Iftikhar Muhammad , Rehan Muhammad , Aziz Khan Gulmeena , Khan Maleeka , Naeem Risha , Ansari Rafay S. , Ullah Irfan , Noori Samim
Published: December 2024

Electrocardiography (ECG) remains a cornerstone of non-invasive cardiac diagnostics, yet manual interpretation poses challenges due to its complexity and time consumption. The integration of Artificial Intelligence (AI), particularly through Deep Learning (DL) models, has revolutionized ECG analysis by enabling automated, high-precision diagnostics. This review highlights the recent advancements in AI-driven ECG applications, focusing on arrhythmia detection, abnormal beat classification, and the prediction of structural heart diseases. AI algorithms, especially convolutional neural networks (CNNs), have demonstrated superior accuracy compared to human experts in several studies, achieving precise classification of ECG patterns across multiple diagnostic categories. Despite the promise, real-world implementation faces challenges, including model interpretability, data privacy concerns, and the need for diversified training datasets. Addressing these challenges through ongoing research will be crucial to fully realize AI’s potential in enhancing clinical workflows and personalizing cardiac care. AI-driven ECG systems are poised to significantly advance the accuracy, efficiency, and scalability of cardiac diagnostics.
A young female patient with severe traumatic hemifacial degloving avulsion injury successfully managed with reconstruction and full thickness skin graft: case report
Authors: Mohamed Hassan Muhumed , Hassan Ibrahim Ali , Ahmed Abdirisak Abdikarin , Sidow Nor Osman , Ali Abdullahi Yusuf
Published: December 2024

Introduction and importance:

Road traffic accidents can result in severe ocular injuries, jeopardizing vision. High-speed collisions may lead to facial avulsion and degloving injuries, which pose risks such as airway compromise, bleeding, soft tissue loss, disfigurement, and post-traumatic impairments that necessitate prompt reconstruction.

Case presentation:

A 24-year-old woman sustained injuries in a motorcycle accident, which resulted in a left hemifacial avulsion, a degloving injury, and the loss of her left brow. Additionally, she lost the lower eyelid on the left side and a portion of the left maxilla near the medial canthus. Despite these injuries, the movements of her left eye remained normal.

Clinical discussion:

The primary objectives of periorbital reconstruction are to restore the patient’s vision with minimal discomfort while ensuring stable coverage for orbital protection and achieving functional reconstruction of the defect. Although there are various surgical reconstruction techniques available, skin grafting and regional flap reconstruction methods are the most commonly employed.

Conclusion:

The patient expressed satisfaction with the outcome and reported improved social comfort. After a one-year follow-up, both the patient’s facial functions and vision were found to be normal.
Artificial intelligence and its use in spine surgery and preparation of predictive models: a systematic review
Authors: Khan Muhammad Mohsin , Chaurasia Bipin
Published: December 2024

During the last decade, artificial intelligence (AI) has witnessed phenomenal growth, accompanied by unparalleled opportunities in health. The integration of machine learning at the heart of health systems has shaped a revolution that helps to reduce health, social, and economic inequities while improving global health outcomes. The use of AI for spine surgery, in particular, serves to enhance the accuracy of predicted algorithms and can be used to improve surgical accuracy and reduce operative time, thereby enhancing efficiency and productivity. This review outlines the current literature on the use of AI in spine surgery and identifies its established evidence to provide positive surgical outcomes. With all these promises, AI in spine surgery remains in its infancy; it is anticipated that further development will yield much greater benefits in the immediate future.
Acute renal infarction as an unusual presentation of hypertensive crisis in an elder female patient: a case report and literature review
Authors: Osman Ubah Mumin Ali , Iyow Sowdo Nur , Gedi Ismail Ibrahim , Farah Yusuf Mohamud Mohamed
Published: December 2024

Introduction and importance:

Acute renal infarction is a rare condition characterized by the obstruction of renal arteries, leading to ischemia and infarction of the renal tissue. It is often underdiagnosed and can present with acute abdominal pain.

Case presentation:

A 70-year-old female with a 1-year history of hypertension presented to the emergency room with severe sharp flank pain and vomiting of 8 hours duration. She had no comorbidities and was taking Amlodipine 10 mg for hypertension. Vital signs revealed severely elevated blood pressure (230/180 mmHg) and a pulse rate of 98 bpm. Clinical examination showed tenderness over the right kidney without signs of abdominal guarding. Renal function was normal, and there were no signs of systemic inflammation. Imaging studies, including abdominal ultrasound and contrast-enhanced CT, confirmed the diagnosis of unilateral renal infarction.

Clinical discussion:

A multidisciplinary team, including Internal Medicine, Cardiovascular Surgery, Urology, and Interventional Radiology, convened to discuss the treatment approach. Considering the duration of symptoms and the preserved renal parenchyma, revascularization was not pursued. The patient was admitted and started on therapeutic dose low molecular heparin for anticoagulation. Blood pressure was controlled using intravenous Labetalol. The patient showed significant clinical improvement and was discharged on apixaban and Amlodipine. Follow-up lab tests after 1 month demonstrated normal kidney function.

Conclusion:

This case highlights the importance of considering renal infarction in the differential diagnosis of acute abdominal pain, especially in hypertensive patients. Early recognition and appropriate management are crucial for preventing complications and preserving renal function.
Microplastics and nanoplastics: emerging threats to cardiovascular health – a comprehensive review
Authors: Irfan Hamza , Irfan Haider , Khan Muhammad Ahtesham , Inanc Oyku , Hasibuzzaman Md. Al
Published: December 2024

Background:

Global plastic production surged to 400.3 million metric tons in 2022, contributing significantly to environmental pollution. Projections estimate that 13.2 billion tons of plastic waste will be present in ecosystems by 2050. This increase in plastic production has led to substantial human exposure to microplastics (MPs) and nanoplastics (NPs). While their environmental and general health impacts are well-documented, the specific effects on cardiovascular health remain underexplored.

Objectives:

This review aims to examine the presence of MPs and NPs in the environment, their routes of human exposure, and their toxicological implications for the cardiovascular system (CVS), focusing on oxidative stress, apoptosis, cardiac fibrosis, and major adverse cardiovascular events (MACE).

Methods:

A comprehensive literature review was conducted using PubMed, Scopus, and Google Scholar. Relevant studies from the past 10 years were selected based on keywords like “microplastics,” “nanoplastics,” and “cardiovascular health.”

Results:

MPs and NPs are found in air, water, and food, entering the human body primarily through inhalation, ingestion, and dermal contact. These particles induce oxidative stress, mitochondrial dysfunction, and apoptosis, which impair cardiovascular health. MPs have been detected in arterial tissues, particularly in atherosclerotic plaques, correlating with increased MACE risk. MP exposure is linked to VC, reduced vessel flexibility, and increased thrombosis severity. Additionally, MPs contribute to inflammation and lipid metabolism disruption, which further exacerbate heart disease.

Conclusion:

The evidence suggests a concerning link between plastic exposure and cardiovascular health, highlighting the urgent need for further research to understand the long-term effects of MPs and NPs on CVSs.
Risk and pattern analysis of distant metastases in colon cancer: protocol for a systematic review and meta-analysis
Authors: Hu Yonghua , Wei Qinglin , Yu Yang , Li Haiyuan , Chen Hao
Published: December 2024

Background:

Understanding the metastatic risks and patterns of colon cancer is crucial for patient evaluation and decision-making. However, high-quality evidence on colon cancer metastases is lacking. This study aims to conduct a systematic review and meta-analysis to determine the risk of site-specific metastasis and provide a complete profiling of distant metastasis in colon cancer.

Methods:

This review will include studies reporting the proportion of different-site metastases among colon cancer patients. Clinical trials, follow-up studies, and cross-sectional surveys with English publications are eligible for inclusion. We will search Medline, Embase, Web of Science, and the Cochrane Library from inception to June 2023. Two reviewers will independently screen the title/abstract and full texts of identified records according to the eligibility criteria. Data from eligible studies will be extracted and used for meta-analysis. Meta-analyses will be conducted to estimate the overall proportion of site-specific metastasis. During meta-analyses, two proportions will be analyzed, i.e., the incidence of metastasis and component proportion. We will select the appropriate tools to assess the risk of biases based on the study design of included studies.

Results:

This study is still in preparation for launch. Once all analyses are complete, the results will be submitted for publication in a peer-reviewed journal.

Conclusion:

This review will provide a clear and systematic metastatic pattern of colon cancer and evidence-based recommendations for the management of distant metastasis.
The potential of mitochondrially-targeted tetrapeptide in protecting against noise-induced hearing impairment
Authors: Kumar Niranj A. , Marouf Azmi , Alagramam Kumar N. , Stepanyan Ruben
Published: December 2024

Noise-induced hearing loss (NIHL) constitutes a significant global health issue for which there is no effective treatment. The loss of cochlear hair cells and associated synaptopathy are common causes of hearing impairment. One primary mechanism implicated in NIHL is the accumulation of reactive oxygen species (ROS), which ultimately overwhelms cochlear cells. ROS are detected in the cochlea immediately after noise exposure and persist for at least a week. Within cells, ROS are primarily generated in mitochondria as byproducts of cellular metabolism. Elamipretide is a synthetic tetrapeptide known to concentrate in mitochondria, improving mitochondrial function and reducing ROS production. To test the hypothesis that elamipretide treatment mitigates NIHL, 16-week-old male and female CBA/J mice were exposed to 8–16 kHz octave-band noise (OBN) at 98 dB SPL for 2 hours. Elamipretide was administered intraperitoneally immediately after noise exposure and continued for 2 weeks. Efficacy was evaluated based on auditory brainstem response (ABR) thresholds, wave amplitudes, and wave latencies in treated and control groups. Results showed that OBN-exposed mice exhibited an elevation in ABR thresholds at 16 and 32 kHz and a reduction in ABR wave-I amplitude at 32 kHz, although wave-I latencies were not affected at 16 or 32 kHz. Elamipretide treatment prevented the OBN-induced elevation of ABR thresholds and the attenuation of wave-I amplitude. These findings provide proof of concept that mitochondrial-targeted elamipretide can prevent NIHL in a mammalian model and highlight its potential to protect against NIHL in humans.
The spatiotemporal distribution of Mesozoic dinosaur diversity
Authors: Mannion Philip D.
Published: December 2024

Much of our view on Mesozoic dinosaur diversity is obscured by biases in the fossil record. In particular, spatiotemporal sampling heterogeneity affects identification of the timing and geographical location of radiations, the recognition of the latitudinal diversity gradient, as well as interpretation of purported extinctions, faunal turnovers and their drivers, including the Early Jurassic Jenkyns Event and across the Jurassic/Cretaceous boundary. The current distribution of sampling means it is impossible to robustly determine whether these ‘events’ were globally synchronous and geologically instantaneous or spatiotemporally staggered. Accounting for sampling heterogeneity is also paramount to reconciling notable differences in results based on sampling-standardized dinosaur species richness versus reconstructions of diversification rates, particularly with regards to the lead-up to the Cretaceous/Paleogene mass extinction. Incorporation of a greater proportion of stratigraphically well-resolved dinosaurs into analyses is also imperative and must include the substantial Mesozoic radiation of birds. Given the relative rarity of temporally successive, well-sampled spatial windows, it remains possible that dinosaur species richness and diversification rate showed little change after the clade’s initial radiation until the Cretaceous/Paleogene boundary. However, better understanding of underlying sampling, combined with a holistic approach to reconstructing dinosaur diversity and diversification, is an important step in testing this hypothesis.
Ligand enhanced mode selective photocatalytic CO
2
reduction by quantum dots
Authors: Naz Bushra , Mubeen Muhammad , Mukhtar Maria , Khalid Muhammad Adnan , Huma Zil e , Waseem Sanila , Rashid Zahid , Iqbal Azhar
Published: December 2024

Photocatalytic CO
2
reduction has sparked significant interest in the generation of chemical fuels through solar energy harvesting. However, the activity, stability and selectivity of products are heavily dependent upon the efficiencies of light harvesting ability, charge migration and surface reactions. Herein, colloidal CdS quantum dots (QDs) have been interfacially engineered with four different capping ligands viz. mercaptoacetic acid (MAA), 3-mercaptopropanoic acid (MPA),
l
-cysteine (LC) and oleic acid (OA). Compared to other ligands, MAA functionalization introduces deep trap states by developing interactions with the surface Cd atoms. These states enhance the lifetime of photogenerated electrons for substantial CO
2
reduction with an activity of approximately 2120 mol g
−1
h
−1
. Computational analysis suggests the rate of electron transfer to CO
2
from CdS QDs is much faster as compared to the nuclear degrees of freedom, and the bending angle of CO
2
enhances electron transfer. The maximum electron transfer efficiency was observed at the bent angle of 130°. The bent geometry is supported by the surface proton shutter provided by the acid group of the thiol/acid bifunctional ligand. This work tries to comprehend the crucial effect of ligand-induced deep trap states and change in the bending angle of CO
2
, which makes the C-Cd distance shorter and significantly promotes the photocatalytic reduction of CO
2
to formaldehyde.
Benefits of extended maternal care in a mass-provisioning bee at the cusp of sociality
Authors: Friedel Anna , Soro Antonella , Shafiey Hassan , Tragust Simon , Boff Samuel , Ballote Johannson Victoria Ruth Elisabeth , Quezada-Euán José Javier G. , Paxton Robert John
Published: December 2024

Many invertebrates exhibit parental care, posited as a precursor to sociality. For example, solitary foundresses of the facultative social orchid bee
Euglossa viridissima
guard their brood for 6+ weeks before offspring emerge, when the nest may become social. Guarding comes at the fitness cost of foregoing the production of additional offspring. Yet it is unclear whether guarding (extended maternal care) can enhance offspring survival such that it outweighs those fitness costs, or if it is a consequence of the selective benefits of sociality, including extended female longevity. Experimental removal of solitary foundresses from nests of
E. viridissima
revealed an immediate fitness loss: decreased offspring survival. A mathematical model exploring the trade-off between extended maternal care versus non-guarding revealed that extended maternal care is immediately advantageous to a solitary mother if nest establishment takes longer than a threshold 1.7–12.5 days. Below this threshold, our model suggests that social fitness gains (acquiring helper daughters) need to be invoked to explain the evolution of extended maternal care. Enhanced survival of offspring through guarding and nest inheritance may nevertheless ease conditions for the evolution of sociality by favouring extended adult longevity and brood care in incipient social species like
E. viridissima
.
Ecological drivers of jaw morphological evolution in lepidosaurs
Authors: Ballell Antonio , Dutel Hugo , Fabbri Matteo , Martin-Silverstone Elizabeth , Kersley Aleksandra , Hammond Chrissy L. , Herrel Anthony , Rayfield Emily J.
Published: December 2024

Ecology is a key driver of morphological evolution during adaptive radiations, but alternative factors like phylogeny and allometry can have a strong influence on morphology. Lepidosaurs, the most diverse clade of tetrapods, including lizards and snakes, have evolved a remarkable variety of forms and adapted to disparate ecological niches, representing an ideal case study to understand drivers of morphological evolution. Here, we quantify morphological variation in the lower jaw using three-dimensional geometric morphometrics on a broad sample of 153 lepidosaur species. Our results suggest that phylogeny has significantly influenced mandibular shape evolution, and snakes have diverged from a lizard-like jaw morphology during their evolution. Allometry and ecological factors like diet, foraging mode and substrate also appear to drive the diversification of mandibular forms. Ecological groups differ in patterns of disparity, convergence and rates of evolution, indicating that divergent evolutionary mechanisms are responsible for the acquisition of different diets and habitats. Our analyses support that lepidosaurs ancestrally use their jaws to capture prey, contrary to the traditional view favouring lingual prehension as ancestral. Specialized or ecologically diverse lineages show high rates of jaw shape evolution, suggesting that morphological innovation in the mandible has contributed to the spectacular ecomorphological diversification of lepidosaurs.
What is a unit of nature? Measurement challenges in the emerging biodiversity credit market
Authors: Wauchope Hannah S. , zu Ermgassen Sophus O. S. E. , Jones Julia P. G. , Carter Harrison , Schulte to Bühne Henrike , Milner-Gulland E. J.
Published: December 2024

Bending the curve of biodiversity loss requires the business and financial sectors to disclose and reduce their biodiversity impacts and help fund nature recovery. This has sparked interest in developing generalizable, standardized measurements of biodiversity—essentially a ‘unit of nature’. We examine how such units are defined in the rapidly growing voluntary biodiversity credits market and present a framework exploring how biodiversity is quantified, how delivery of positive outcomes is detected and attributed to the investment and how the number of credits issued is adjusted to account for uncertainties. We demonstrate that there are deep uncertainties throughout the process and question if the benefits of biodiversity credits, and other efforts to abstract nature to a single unit, outweigh the harms. Credits can only be positive for biodiversity if they are used with unprecedentedly strict regulation that ensures businesses mostly avoid negative impacts and if they are purchased to quantify positive contributions rather than as direct offsets. While there may be a role for markets in attracting conservation funding, they will only ever be part of the solution, especially for the many aspects of nature that cannot be reduced to a unit.
Mitochondrial remodelling supports migration in white-crowned sparrows (
Zonotrichia leucophrys
)
Authors: Mesquita Paulo H. C. , Rhodes Emma M. , Yap Kang Nian , Mueller Breanna J. , Hill Geoffrey E. , Hood Wendy R. , Kavazis Andreas N.
Published: December 2024

The migratory movements undertaken by birds are among the most energetically demanding behaviours observed in nature. Mitochondria are the source of aerobic energy production on which migration depends, but a key component of mitochondrial function, mitochondrial remodelling, has not been investigated in the context of bird migration. We measured markers of mitochondrial remodelling in the skeletal muscles of the Gambel’s (migratory) and Nuttall’s (non-migratory) white-crowned sparrows within and outside migratory periods. Gambel’s were collected in (i) a non-migration period (baseline), (ii) preparation to depart for spring migration (pre-migration) and (iii) active autumn migration (mid-migration). Nuttall’s were collected at timepoints corresponding to baseline and mid-migration in Gambel’s. Across all sampling periods, we found that migratory birds had greater mitochondrial remodelling compared with non-migratory birds. Furthermore, birds from the migratory population also displayed flexibility, increasing several markers of mitochondrial remodelling (e.g. NRF1, OPA1 and Drp1) pre- and during migration. Further, the greater levels of mitochondrial remodelling and its upregulation during migration were specific to the pectoralis muscle used in flapping flight. Our study is the first to show that mitochondrial remodelling supports migration in Gambel’s white-crowned sparrows, indicating a highly specific and efficient phenotype supporting the increased energetic demands of migration.
The Ratchet Model of Synovial Flares in Palindromic Rheumatism
Authors: Chakraborty S. , Phatak S. , Rath S. , Goel P.
Published: December 2024

Synovial flares in palindromic rheumatism (PR) are aperiodic bursts of inflammation in the joints, which usually self-resolve in a timescale hours or days. PR patients are believed to transit to a chronic auto-immune disease called rheumatoid arthritis (RA) in most cases, however, many patients remain palindromic indefinitely. We utilize and adapt a minimal ODE model of rheumatoid arthritis (RA) developed by Baker et al. to study PR in greater detail. We address questions characterizing the incidence, decay and sustenance of synovial flares in palindromic patients. A key question is to describe the nature of the transition from palindromic to full RA. We show that PR flares ordinarily resolve spontaneously, however, there is a secondary equilibrium in the model into which the trajectory can sometimes get trapped. When this “meta-stable locking” occurs, it initiates an adaptation that helps rescue the flare. Furthermore, this adaptation in turn activates a secondary adaptation in response to fluctuations in the healthy steady state. Finally, we show that if metastable locking occurs frequently enough these adaptation sequences turn maladaptive and the system slowly progresses into fully developed RA.
Sorting the mob: using geometric morphometrics and machine learning to differentiate kangaroo postcrania for zooarchaeological applications
Authors: Mein Erin , Manne Tiina , Veth Peter , Weisbecker Vera
Published: December 2024

Taxonomic identification of bone is one of the building blocks of zooarchaeological research into human foraging behaviour. However, it can prove difficult in regions, such as Australia, that have biodiverse taxa that are difficult to differentiate using bone morphology. One such case are the kangaroos and wallabies (macropods), one of the most speciose groups of marsupials whose remains are frequently recovered from Australian archaeological sites. Despite their clear importance to Indigenous economies, little research has been undertaken on how to reliably differentiate the postcranial remains of extant macropods. Here we address this gap by applying three-dimensional geometric morphometrics to describe how the astragalus and calcaneus differs between several large macropod genera. We describe taxonomically diagnostic anatomical attributes between genera and identify the size related (allometric) shape variation that could be mistaken for taxonomic differences. We then compare several machine learning models to demonstrate how these can be applied to geometric morphometric data to statistically classify unknown specimens from palaeozoological contexts with a high degree of accuracy. Our results show that non-linear methods of supervised machine learning outperform classical discriminant function analysis when used on our geometric morphometric data. Statistical classification of palaeozoological specimens has the potential to be a valuable tool, where differentiating skeletal remains of closely related taxa continues to prove challenging.
Transgenic augmentation of erythroferrone in mice ameliorates anemia in adenine-induced chronic kidney disease
Authors: Czaya Brian , Olivera Joseph D. , Zhang Moya , Lundin Amber , Castro Christian D. , Jung Grace , Nemeth Elizabeta , Ganz Tomas
Published: December 2024

Anemia is a common and disabling complication of chronic kidney disease (CKD). Current therapies can be burdensome, and full correction of anemia is limited by cardiovascular side effects. New approaches that may offer additional therapeutic options are needed. We explored the anti-anemic effects of erythroferrone, an erythroid hormone that induces iron mobilization by suppressing the master iron-regulatory hormone hepcidin. In a preclinical murine model of adenine-induced CKD, transgenic augmentation of erythroferrone mobilized iron, increased hemoglobin concentrations by approximately 2 g/dl, and modestly improved renal function without affecting systemic or renal inflammation, fibrosis, or markers of mineral metabolism. This study supports the concept that therapeutic augmentation of erythroferrone is a promising approach for alleviating CKD-associated anemia.
Anti-obesity compounds, Semaglutide and LiPR, do not change the proportion of human and mouse POMC+ neurons
Authors: Jörgensen Sara K.M. , Surridge-Smith May , Jones Kimberley , Maletínská Lenka , Allen Nicholas D. , Petrik David
Published: December 2024

Anti-obesity medications (AOMs) have become one of the most prescribed drugs in human medicine. While AOMs are known to impact adult neurogenesis in the hypothalamus, their effects on the functional maturation of hypothalamic neurons remain unexplored. Given that AOMs target neurons in the Medial Basal Hypothalamus (MBH), which play a crucial role in regulating energy homeostasis, we hypothesized that AOMs might influence the functional maturation of these neurons, potentially rewiring the MBH. To investigate this, we exposed hypothalamic neurons derived from human induced pluripotent stem cells (hiPSCs) to Semaglutide and lipidized prolactin-releasing peptide (LiPR), two anti-obesity compounds. Contrary to our expectations, treatment with Semaglutide or LiPR during neuronal maturation did not affect the proportion of anorexigenic, Pro-opiomelanocortin-expressing (POMC+) neurons. Additionally, LiPR did not alter the morphology of POMC+ neurons or the expression of selected genes critical for the metabolism or development of anorexigenic neurons. Furthermore, LiPR did not impact the proportion of adult-generated POMC+ neurons in the mouse MBH. Taken together, these results suggest that AOMs do not influence the functional maturation of anorexigenic hypothalamic neurons.
Collablots: Quantification of collagen VI levels and its structural disorganisation in cell cultures from patients with collagen VI-related dystrophies
Authors: Osegui-Barcenilla Nadia , Sendino Maria , Martín-González Sergio , Gómez-Moro Itziar , Benito-Agustino Ainhoa , Torres-Conde Noemi , López-Martínez Andrea , Jiménez-Mallebrera Cecilia , López-Márquez Arístides , Arechavala-Gomeza Virginia
Published: December 2024

Aims

This study aims to develop a quantitative method for assessing collagen VI expression in cell cultures, which is crucial for the diagnosis and treatment of collagen VI-related dystrophies.

Methods

We developed a combined in-cell western (ICW) and on-cell western (OCW) assay, that we have called ‘collablot’ to quantify collagen VI and its organisation in the extracellular matrix of cell cultures from patients and healthy controls. To optimise it, we optimised cell density and the protocols to induce collagen expression in cultures, as well as the cell fixation and permeabilisation methods. This was completed with a thorough selection of collagen antibodies and a collagen hybridising peptide (CHP). We then used collablots to compare cultures from patients and controls and evaluate therapeutic interventions in the cultures.

Results

Collablots enabled the quantification of collagen VI expression in both control and patient cells, aligning with immunocytochemistry findings and detecting variations in collagen VI expression following treatment of the cultures. Additionally, CHP analysis revealed a marked increase in collagen network disruption in patients compared to the controls.

Conclusions

The collablot assay represents an optimal method for quantifying collagen VI expression and its organisation in culture and assessing the effect of therapies.

Key Points

- Evaluating therapies for collagen VI-related dystrophies (COL6-RD) requires the quantification of collagen VI levels.

- Collablot assays are a novel method for quantifying collagen VI expression and its structural organisation in cell culture.

- Due to the significant role of phenotype heterogeneity in this complex disease, quantifying collagen alone might not be adequate for diagnosing COL6-RD, but the addition of a peptide to quantify collagen disorganisation could help in the characterisation of patient cultures.
Deep predictive coding networks partly capture neural signatures of short-term temporal adaptation in human visual cortex
Authors: Brands Amber Marijn , Ortiz Paulo , Groen Iris Isabelle Anna
Published: December 2024

Predictive coding is a leading theory of cortical function which posits that the brain continually makes predictions of incoming sensory stimuli using a hierarchical network of top-down and bottom-up connections. This theory is supported by prior work showing that PredNet, a deep learning network designed according to predictive coding principles, exhibits several characteristics of neural responses commonly observed in primate visual cortex. However, one ubiquitous neural phenomenon that has not yet been investigated is short-term visual adaptation: the adjustment of neural responses over time when exposed to static visual inputs that are either prolonged or directly repeated. Here, we examine whether PredNet exhibits two neural signatures of temporal adaptation previously observed in intracranial recordings of human participants viewing prolonged and repeated stimuli (Brands et al., 2024). We find that, like human visual cortex, PredNet adapts to static images, evidenced by subadditive temporal response summation: a non-linear accumulation of response magnitudes when prolonging stimulus durations, which results from neurally plausible transient-sustained dynamics in the unit activation time courses. However, PredNet activations also show a systematic response to stimulus offsets, which is absent in the human neural data. For repeated stimuli, PredNet shows slight response suppression for any two images presented in quick succession, but no repetition suppression, a comparatively stronger response reduction for identical than for non-identical image pairs that is robustly observed throughout human visual cortex. We show that these results are stable across multiple training datasets and two different types of loss computation. Lastly, in both PredNet and the neural data, we find a relationship between temporal adaptation and visual input properties, showing that temporally sustained activity is enhanced for more complex scenes containing clutter. All together, these results suggest that the emergent temporal dynamics in the PredNet only partly align with neural data and are linked to low-level properties of the visual input rather than high-level predictions arising from top-down processes.
Donor HLA-DQ reactive B cells clonally expand under chronic immunosuppression and include atypical CD21lowCD27−B cells with high-avidity germline B-cell receptors
Authors: Russum Steven , Sayin Ismail , Shwetar Jasmine , Baughan Eleonore , Jeong Jong Cheol , Kim Andrea , Reyentovich Alex , Moazami Nader , Zeevi Adriana , Chong Anita S , Habal Marlena
Published: December 2024

Long-term allograft survival is limited by humoral-associated chronic allograft rejection, suggesting inadequate constraint of humoral alloimmunity by contemporary immunosuppression. Heterogeneity in alloreactive B cells and the incomplete definition of which B cells participate in chronic rejection in immunosuppressed transplant recipients limits our ability to develop effective therapies. Using a double-fluorochrome single-HLA tetramer approach combined with single-cellin vitroculture, we investigated the B-cell receptor (BCR) repertoire characteristics, avidity, and phenotype of donor HLA-DQ reactive B cells in a transplant recipient with end-stage donor specific antibody (DSA)-associated cardiac allograft vasculopathy while receiving maintenance immunosuppression (tacrolimus, mycophenolate mofetil, prednisone). Donor DQB1*03:02/DQA1*03:01 (DQ8)-reactive IgG+ B cells were enriched for minimally mutated and germline encoded high avidity BCRs (median KD4.26×10-09) with an atypical, antigen-experienced and proliferative phenotype (CD27-CD21lowCD71+CD11c+/-). These B cells coexisted with a smaller subset of more highly mutated, affinity matured IgG+CD27+ B cells. Circulating donor-reactive B cells and DSA remained detectable after rituximab, contrasting with the marked reduction in DSA after allograft explant and retransplant. Together, these findings define the persistence of germline high-avidity HLA-DQ alloreactive B cells and their co-existence with affinity matured clones that were both driven by the allograft despite conventional immunosuppression.
Scouter: Predicting Transcriptional Responses to Genetic Perturbations with LLM embeddings
Authors: Zhu Ouyang , Li Jun
Published: December 2024

This paper addresses the challenging problem of predicting transcriptional outcomes— the expression levels of all genes—in gene perturbation experiments and introduces a novel method called Scouter. By leveraging the capabilities of large language models and employing a neural network that facilitates easy training, Scouter overcomes key limitations of current approaches and accurately predicts the outcomes of single-gene and two-gene perturbations, reducing the error of state-of-the-art methods by half or more.
QUANTIFYING EXPLAINABLE AI METHODS IN MEDICAL DIAGNOSIS: A STUDY IN SKIN CANCER
Authors: Sangwan Hardik
Published: December 2024

Deep learning models have shown substantial promise in assisting medical diagnosis, offering the potential to improve patient outcomes and reduce clinician workloads. However, the widespread adoption of these models in clinical practice has been hindered by concerns surrounding their trustworthiness, transparency, and interpretability. Addressing these challenges requires not only the development of explainable AI (xAI) techniques but also quantitative metrics to evaluate their effectiveness.

This study presents a comprehensive framework for training, explaining, and quantitatively assessing deep learning models for skin cancer diagnosis. Leveraging the HAM10000 dataset of seven diagnostic skin lesion categories, multiple convolutional neural network architectures—including custom CNNs, DenseNet, MobileNet, and ResNet—were trained and optimized using augmentation, oversampling, and hyperparameter tuning. Following model training, explainability techniques such as SHAP, LIME, and Integrated Gradients were deployed to generate post hoc explanations. Critically, the primary contribution of this work is the quantitative evaluation of these explanation methods using metrics related to faithfulness, robustness, and complexity. All code, models, and results are publicly available, providing a reproducible pathway toward more trustworthy, explainable diagnostic tools.
Cross-Field Strength and Multi-Vendor Validation of MagDensity for MRI-based Quantitative Breast Density Analysis
Authors: Ying Jia , Cattell Renee , Huang Chuan
Published: December 2024

Purpose

Breast density (BD) is a significant risk factor for breast cancer, yet current assessment methods lack automation, quantification, and cross-platform consistency. This study aims to evaluate MagDensity, a novel magnetic resonance imaging (MRI)-based quantitative BD measure, for its validity and reliability across different imaging platforms.

Methods

Ten healthy volunteers participated in this prospective study, undergoing fat-water MRI scans on three scanners: 3T Siemens Prisma, 3T Siemens Biograph mMR, and 1.5T GE Signa. Great effort was made to schedule all scans within a narrow three-hour window on the same day to minimize any potential intraday variations, highlighting the logistical challenges involved. BD was assessed using the MagDensity technique, which included combining magnitude and phase images, applying a fat-water separation technique, employing an automated whole-breast segmentation algorithm, and quantifying the volumetric water fraction. The agreement between measures was analyzed using mean differences, two-tailed t-tests, Pearson’s correlation coefficients, and Bland-Altman plots.

Results

No statistically significant differences in BD measurements by MagDensity within the same field strength and vendor (3T Siemens), with high correlation (Pearson’s r > 0.99) and negligible mean differences (< 0.2%). Cross-platform comparison between the 3T Siemens and the 1.5T GE scanners showed mean differences of < 5%. After linear calibration, these variations were reduced to insignificant levels, yielding a strong correlation (Pearson’s r > 0.97) and mean differences within ±0.2%.

Conclusion

MagDensity, an MRI-based BD measure, exhibits robustness and reliability across diverse scanner models, vendors, and field strengths, marking a promising advancement towards standardizing BD measurements across multiple MRI platforms. It provides a valuable tool for monitoring subtle longitudinal changes in BD, which is vital for breast cancer prevention and personalized treatment strategies.
Long-Term Carotid Plaque Progression and the Role of Intraplaque Hemorrhage: A Deep Learning-Based Analysis of Longitudinal Vessel Wall Imaging
Authors: Guo Yin , Akcicek Ebru Yaman , Hippe Daniel S. , HashemizadehKolowri SeyyedKazem , Wang Xin , Akcicek Halit , Canton Gador , Balu Niranjan , Geleri Duygu Baylam , Kim Taewon , Shibata Dean , Zhang Kaiyu , Ma Xiaodong , Ferguson Marina S. , Mossa-Basha Mahmud , Hatsukami Thomas S. , Yuan Chun
Published: December 2024

Background

Carotid atherosclerosis is a major contributor in the etiology of ischemic stroke. Although intraplaque hemorrhage (IPH) is known to increase stroke risk and plaque burden, its long-term effects on plaque dynamics remain unclear. This study aimed to evaluate the long-term impact of IPH on carotid plaque burden progression using deep learning-based segmentation on multi-contrast magnetic resonance vessel wall imaging (VWI).

Methods

Twenty-eight asymptomatic subjects with carotid atherosclerosis underwent an average of 4.7 ± 0.6 VWI scans over 5.8 ± 1.1 years. Deep learning pipelines were developed and validated to segment the carotid vessel walls and IPH. Bilateral plaque progression was analyzed using generalized estimating equations, and linear mixed-effects models evaluated long-term associations between IPH occurrence, IPH volume, and plaque burden (%WV) progression.

Results

IPH was detected in 23/50 of arteries. Of arteries without IPH at baseline, 11/39 developed new IPH that persisted, while 5/11 arteries with baseline IPH exhibited it throughout the study. Bilateral plaque growth was significantly correlated (r = 0.54, p < 0.001), but this symmetry was weakened with IPH presence. The progression rate for arteries without IPH was -0.001 %/year (p = 0.90). However, IPH presence or development at any point was associated with a 2.3% absolute increase in %WV on average (p < 0.001). The volume of IPH was also positively associated with increased %WV (p = 0.005).

Conclusions

Deep learning-based segmentation pipelines were utilized to identify IPH, quantify IPH volume, and measure their effects on carotid plaque burden during long-term follow-up. Findings demonstrated that IPH may persist for extended periods. While arteries without IPH demonstrated minimal progression under contemporary treatment, presence of IPH and greater IPH volume significantly accelerated long-term plaque growth.
Optimizing long-term prevention of cardiovascular disease with reinforcement learning
Authors: Zhou Yekai , Luo Ruibang , Blais Joseph Edgar , Tan Kathryn , Lui David , Yiu Kai Hang , Tsun Lai Francisco Tsz , Fai Wan Eric Yuk , Cheung CL , Wong Ian CK , Chui Celine SL
Published: December 2024

The prevention of chronic disease is a long-term combat with continual fine-tuning to adapt to the course of disease. Without comprehensive insights, prescriptions may prioritize short-term gains but deviate from trajectories toward long-term survival. Here we introduce Duramax, a fully evidence-based framework to optimize the dynamic preventive strategy in the long-term. This framework synchronizes reinforcement learning with real-world data modeling, leveraging the diverse treatment trajectories in electronic health records (EHR). In our study, Duramax learned from millions of treatment decisions of lipid-modifying drugs, becoming specialized in cardiovascular disease (CVD) prevention. The extensive volume of implicit knowledge Duramax harnessed far exceeded that of individual clinicians, resulting in superior performance. Specifically, when clinicians’ treatment decisions aligned with those suggested by Duramax, a reduction in CVD risk was observed. Moreover, post hoc analysis confirmed that Duramax’s decisions were transparent and reasonable. Our research showcases how tailored computational analysis on well-curated EHR can achieve high nuance in personalized disease prevention.