bluuebunny/crossref_metadata_2025 huggingface dataset:
Giant multinodular goiter with Grave’s disease associated with retrosternal extension: a case report of thyroid-related emergency
Authors: Saleem Athary , Albloushi Fatma , Jamal Abdullah , Alajmi Fahed , Aenezi Ali , Al Shdifat Odai , Hassan Maher , Al Kandari Bashayer
Published: September 2024

Introduction and importance:

Although huge multinodular goiter is a common underlying etiology of hyperthyroidism, retrosternal extension occurs only in up to 7% of instances. Giant goiter is an unusual phenomenon that creates surgical challenges.

Case presentation:

A 48-year-old female, with a background history of Graves with toxic multinodular goiter, presented with a two-day history of tachycardia and a new onset of atrial fibrillation. On admission, the patient had an enlarged diffused neck mass associated with dyspnea and hoarseness of voice, with no evidence of other compressive symptoms. The patient has a 7-year history of thyrotoxicosis that was managed by medical treatment. The diagnosis of huge multinodular goiter and Graves’ disease was confirmed by laboratory investigations and both ultrasonography and computed tomography (CT) of the neck. Then, the patient’s recent presentation necessitates the performance of a total thyroidectomy to manage the emergency situation. The resected specimen was sent for histopathology studies, and the postoperative period was uneventful.

Clinical discussion:

Giant goiter with retrosternal extension is rarely reported by physicians. The clinical manifestations of huge goiter include compressive symptoms and/or thyroid dysfunction. Diagnosis of goiter relies on imaging modalities. Neck CT was used to diagnose the majority of cases. Total thyroidectomy provides the definitive treatment of massive multinodular goiter.

Conclusion:

Because long-term huge goiter is a life-threatening condition, the authors highlight a case of a 48-year-old female patient who presented with a massive thyroid goiter and Graves’ disease that was found to require total thyroidectomy to manage the clinical features.
‘Assessment of ultrasound guided peripheral nerve block practice adherence, cross-sectional study’
Authors: Alemu Eniyew A. , Tawuye Hailu Y. , Fentie Demeke Y. , Ferede Yonas Admasu
Published: September 2024

Background:

Peripheral nerve block is a common way of providing anesthesia and analgesia to the intended area of innervation by a single or plexus supply of nerves by a local anesthetic drug in different ways. The aim of this study was to enhance the practice of ultrasound-guided peripheral nerve anesthesia and analgesia in our operation theater accordance with standards.

Method:

This study was cross-sectional descriptive study carried out in a comprehensive specialized hospital in Ethiopia between 1 March 2023 and 30 March 2023. Patients who receive ultra-sounded guided anesthesia and analgesia in surgical and obstetric operation rooms were included. Data were collected by direct observation using a standardized checklist prepared from the recommendations of the New York Society of Regional Anesthesia (NYSORA) and literature. The data were collected prospectively before, during, and after administering ultra-sound-guided regional anesthesia or analgesia. The data was analyzed using SPSS 25.

Result:

The overall adherence to the safe and effective practice of using ultrasound for regional block use was 88.1%, with assessment of parameters such as optimizing sonoanatomy of visualization (98.7%), optimizing needle imaging with ultrasound (76.8%), safe needle guidance with ultrasound practice (76.8%), optimizing the delivery of local anesthetic near the target nerve (100%), and sensory block was (75%) before skin incision, (60%) before PACU transfer, immediately motor block after local anesthesia administration (52.5%) before skin incision and 2.5% immediate PACU transfer.

Conclusion and recommendation:

Ultrasound-guided regional anesthetic has been demonstrated to be helpful in managing pain during and after surgery. Although utilizing ultrasound in conjunction with nerve blocks has been shown to be safe, the authors advise using a peripheral nerve stimulator combination with ultrasound. Hydro-dissection is a more effective way to block a nerve block and provide the greatest anatomical delineation.
Effect of different covering methods of inflatable heating blanket on the incidence of intraoperative hypothermia in patients undergoing photoselective vaporization of the prostate
Authors: Ju Yu , Wang Tao , Zhang Wei , Wang Shuai , Han Xiaohong , Yu Lijuan
Published: September 2024

Background and purpose:

The use of lavage fluid during photoselective vaporization of the prostate (PVP) may result in perioperative hypothermia. Inflatable warming blankets was used to prevent intraoperative hypothermia (IPH). The authors aimed to evaluate the warming blanket placing above or beneath the patients’ body on IPH in PVP.

Method:

Sixty patients undergoing PVP were randomized into two groups (Underneath group or Above group, with the heating blanket placed beneath or above their body). Nasopharyngeal temperature was measured as core body temperature. The patient’s temperature was recorded at the time of anesthesia induction (T0), at 15 (T15), 30 (T30), 45 (T45), 60 (T60), and 75 min (T75) during surgery. The duration of operation, the volume of intraoperative fluid irrigation, occurrence of postoperative hypothermia, and chills were also documented.

Results:

Forty-five minutes after the initiation of warming blanket application, a decrease in body temperature was observed in both groups. The lowest temperature in the Underneath group was 35.81°C±0.17°C at T60. At time points T30, T45, T60, and T75, patients’ body temperature of the Above group was significantly higher than that of the Underneath group (P<0.05). The incidence of IPH was higher in the Underneath group (P<0.05). Postoperative chills were reported in seven patients from the Underneath group and three patients from the Above group (P>0.05).

Discussion and conclusion:

In patients receiving PVP placing the heating warming blanket above patients seems to be a more effective approach to decrease the occurrence of postoperative hypothermia.
Handoff Education Interventions: A Scoping Review Focused on Sustaining Improvements
Authors: Riesenberg Lee Ann , Davis Joshua J. , Kaplan Elle , Ernstberger Grace C. , O’Hagan Emma C.
Published: September 2024

Handoffs involve the transfer of patient information and responsibility for care between health care professionals. The purpose of the current scoping review was (1) to describe handoff studies with education as part of the intervention and (2) to explore the role of handoff educational interventions in sustaining handoff improvements. This scoping review utilized previously published systematic reviews and a structured, systematic search of 5 databases (January 2006–June 2020). Articles were identified, and data were extracted by pairs of trained, independent reviewers. The search identified 74 relevant articles, most published after 2015 (70%) and conducted in the United States (76%). Almost all of the studies (99%) utilized instruction, 66% utilized skills practice, 89% utilized a memory aid, and 43% utilized reinforcement. However, few studies reported using education theory or followed accepted tenets of curriculum development. There has been a substantial increase over time in reporting actual handoff behavior change (17%–68%) and a smaller but important increase in reporting patient outcomes (11%–18%). Thirty-five percent of studies (26/74) had follow-up for 6 months or more. Twelve studies met the criteria for sustained change, which were follow-up for 6 months or more and achieving statistically significant improvements in either handoff skills/processes or patient outcomes at the conclusion of the study. All 12 studies with sustained change used multi-modal educational interventions, and reinforcement was more likely to be used in these studies than all others (75%, 9/12) versus (37%, 23/62), P = 0.015. Future handoff intervention efforts that include education should use education theory to guide development and include needs assessment and goals and measurable objectives. Educational interventions should be multi-modal and include reinforcement. Future research studies should measure actual handoff behavior change (skills/process) and patient outcomes, include follow-up for more than 6 months, and use education reporting guidelines.
Visual assessments of 11C-Pittsburgh compound-B PET vs. 18F-flutemetamol PET across the age spectrum
Authors: Zeydan Burcu , Johnson Derek R. , Schwarz Christopher G. , Przybelski Scott A. , Lesnick Timothy G. , Senjem Matthew L. , Kantarci Orhun H. , Min Paul H. , Kemp Bradley J. , Jack Clifford R. , Kantarci Kejal , Lowe Val J.
Published: September 2024

Objective

Visual assessments of amyloid-β PET, used for Alzheimer’s disease (AD) diagnosis and treatment evaluation, require a careful approach when different PET ligands are utilized. Because the gray matter (GM) and white matter (WM) ligand bindings vary with age, the objective was to investigate the agreement between visual reads of 11C- and 18F-PET scans.

Methods

Cognitively unimpaired (CU) younger adults (N = 30; 39.5 ± 6.0 years), CU older adults (N = 30; 68.6 ± 5.9 years), and adults with AD (N = 22; 67.0 ± 8.5 years) underwent brain MRI, 11C-Pittsburgh compound-B (PiB)-PET, and 18F-flutemetamol-PET. Amyloid-β deposition was assessed visually by two nuclear medicine specialists on 11C-PiB-PET and 18F-flutemetamol-PET, and quantitatively by PET centiloids.

Results

Seventy-two 11C-PiB-PET and 18F-flutemetamol-PET visual reads were concordant. However, 1 18F-flutemetamol-PET and 9 11C-PiB-PET were discordant with quantitative values. In four additional cases, while 11C-PiB-PET and 18F-flutemetamol-PET visual reads were concordant, they were discordant with quantitative values. Disagreements in CU younger adults were only with 11C-PiB-PET visual reads. The remaining disagreements were with CU older adults.

Conclusion

Age, GM/WM binding, amyloid-β load, and disease severity may affect visual assessments of PET ligands. Increase in WM binding with age causes a loss of contrast between GM and WM on 11C-PiB-PET, particularly in CU younger adults, leading to false positivity. In CU older adults, increased WM signal may bleed more into cortical regions, hiding subtle cortical uptake, especially with 18F-flutemetamol, whereas 11C-PiB can detect true regional positivity. Understanding these differences will improve patient care and treatment evaluation in clinic and clinical trials.
How Can Nursing Faculty Create Case Studies Using AI and Educational Technology?
Authors: Silvestri-Elmore Angela , Burton Candace
Published: September 2024

Background:

Applying artificial intelligence (AI) technology to the development of unfolding case studies in nursing education can reduce barriers to implementation of this educational strategy.

Problem:

Unfolding case studies are effective for improving nursing student outcomes related to clinical judgment skills, but these are often time consuming and difficult to develop.

Approach:

This article describes the use of AI in developing case studies for nursing education.

Outcomes:

Both students and faculty found case studies developed using an AI platform to be effective learning tools, and faculty especially found that using this platform greatly reduced the time required to develop cases.

Conclusion:

The use of AI to support development of unfolding case studies is an innovation that allows flexibility for faculty as well as improving student outcomes in practice domains that may otherwise be difficult to target.
Moderate-severe peripheral neuropathy in diabetes associated with an increased risk of dry eye disease
Authors: Tummanapalli Shyam Sunder , Wang Leiao Leon , Dhanapalaratnam Roshan , Poynten Ann , Papas Eric B. , Krishnan Arun Vishwanathan , Markoulli Maria
Published: September 2024

SIGNIFICANCE

This study establishes an increased risk of developing dry eye disease (DED) in patients with diabetic peripheral neuropathy using validated diagnostic criteria for both conditions.

PURPOSE

The disruption of ocular surface homeostasis has been associated with diabetes. However, it remains unclear if this association is independently influenced by peripheral neuropathy secondary to diabetes. This study aimed to investigate the clinical signs and symptoms of DED and their association with the severity of peripheral neuropathy in participants with type 2 diabetes.

METHODS

This prospective cross-sectional study recruited 63 participants with type 2 diabetes. All participants underwent a detailed assessment of DED using dry eye questionnaires (Ocular Surface Disease Index, Dry Eye Questionnaire-5), tear osmolarity, lipid layer thickness, noninvasive keratographic tear breakup time, phenol red thread test (PRT), and ocular surface staining. Corneal nerve morphology was imaged using corneal confocal microscopy. Based on the Total Neuropathy Scale, participants were stratified into no/mild (n = 48) and moderate/severe (n = 15) neuropathy groups.

RESULTS

Dry eye disease was diagnosed in 31 participants (50%) of the total cohort, and the odds of developing DED in the moderate/severe neuropathy group were four times (95% confidence interval, 1.10 to 13.80; p=0.030) higher compared with the no/mild neuropathy group. The Dry Eye Questionnaire-5 scores were significantly higher (p=0.020), and PRT values (p=0.048) and corneal nerve fiber length (p<0.001) were significantly reduced in the moderate/severe neuropathy group compared with the no/mild neuropathy group. In regression analysis, neuropathy scores were independently associated with PRT measurements (β = −0.333, p=0.023) and nerve fiber length (β = −0.219, p=0.012) while adjusting for age, gender, hemoglobin A1c, and duration of diabetes.

CONCLUSIONS

Type 2 diabetic patients with peripheral neuropathy have a risk of developing DED, which increases with the severity of neuropathy. The observation that worsening peripheral neuropathy is associated with reduced tear secretion suggests that it may contribute to aqueous insufficiency.
Detection of Pulmonary Nodules on Ultra-low Dose Chest Computed Tomography With Deep-learning Image Reconstruction Algorithm
Authors: Bocquet Wesley , Bouzerar Roger , François Géraldine , Leleu Antoine , Renard Cédric
Published: September 2024

Purpose:

To evaluate the accuracy of ultra-low dose (ULD) chest computed tomography (CT), with a radiation exposure equivalent to a 2-view chest x-ray, for pulmonary nodule detection using deep learning image reconstruction (DLIR).

Material and Methods:

This prospective cross-sectional study included 60 patients referred to our institution for assessment or follow-up of solid pulmonary nodules. All patients underwent low-dose (LD) and ULD chest CT within the same examination session. LD CT data were reconstructed using Adaptive Statistical Iterative Reconstruction-V (ASIR-V), whereas ULD CT data were reconstructed using DLIR and ASIR-V. ULD CT images were reviewed by 2 readers and LD CT images were reviewed by an experienced thoracic radiologist as the reference standard. Quantitative image quality analysis was performed, and the detectability of pulmonary nodules was assessed according to their size and location.

Results:

The effective radiation dose for ULD CT and LD CT were 0.13±0.01 and 1.16±0.6 mSv, respectively. Over the whole population, LD CT revealed 733 nodules. At ULD, DLIR images significantly exhibited better image quality than ASIR-V images. The overall sensitivity of DLIR reconstruction for the detection of solid pulmonary nodules from the ULD CT series was 93% and 82% for the 2 readers, with a good to excellent agreement with LD CT (ICC=0.82 and 0.66, respectively). The best sensitivities were observed in the middle lobe (97% and 85%, respectively).

Conclusions:

At ULD, DLIR reconstructions, with minimal radiation exposure that could facilitate large-scale screening, allow the detection of pulmonary nodules with high sensitivity in an unrestricted BMI population.
Improvement of myocardial fibrosis injury by Shengmai injection in ischemia-induced heart failure in a rat model
Authors: Ding Yurong , Wei Junying , Ji Enhui , Wang Menglan , Wu Yue , Chang Mengli , Zhang Yi , Xu Jing
Published: September 2024

Background

Heart failure (HF) is the leading cause of death worldwide. Myocardial infarction (MI) is a major contributor to HF. Shengmai injection (SMI) has exhibited protective efficacy in preventing HF. However, the advantages of SMI in the progression of MI-induced HF remain unclear.

Objective

To reveal the advantages of SMI in the progression of MI-induced HF.

Methods

The differently expressed proteins in rat models with ischemia at the 7th, 14th, 21st, and 28th days were obtained from PubMed. The “compound-target” network of SMI was constructed via the Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine database. The protein-protein interaction relationship was constructed, and biological function was applied to evaluate the advantage effect of SMI in the progression of MI-induced HF. In addition, the prediction results were validated in rats with left anterior descending coronary artery ligation. The cardiac function and heart performance were observed via echocardiography, hematoxylin-eosin staining, and Masson staining, and the levels of procollagen type I carboxy-terminal propeptide, recombinant versican (VCAN), and collagen 1A1 (COL1A1) were measured via enzyme-linked immunosorbent assay in rat plasma. In vitro, H9c2 cells were treated with Angiotensin II (Ang II), and the cell viability, the level of reactive oxygen species (ROS) and Ca2+, and the expression of ANP and connective tissue growth factor were evaluated. Furthermore, the schizandrin A was identified as one of the possible key compounds. After schizandrin A treatment, the level of ROS and Ca2+ and the expression of COL1A1 and VCAN were evaluated.

Results

There were 189 compounds and 1612 targets involved in the “compound-target” network, and an interaction relationship was constructed. According to the top subnetwork, the Gene Ontology annotation revealed that SMI may have an antifibrotic and cardiac protective effect against MI-induced HF. In rats, SMI increased ejection fraction, left ventricular fractional shortening, and cardiac output and decreased fibrosis injury; moreover, SMI decreased the levels of procollagen type I carboxy-terminal propeptide, VCAN, and COL1A1 within 35 days. When compared with the Ang II treatment group, SMI increased cell viability and decreased cellular calcium concentration, ROS generation, and the expression of ANP and connective tissue growth factor in vitro. Furthermore, schizandrin A was discovered to be a possible compound in myocardial protection. Schizandrin A increased cell viability after Ang II treatment while decreasing COL1A1 and VCAN levels.

Conclusions

This method demonstrates that SMI has an antifibrotic effect. This study provides a promising perspective on translating omics data to clinical applications, as well as an appealing approach to investigating the precise intervention of a multicomponent drug.
Analysis of the distribution of Astragalus membranaceus var. mongholicus in Inner Mongolia under climate change using the GEE platform
Authors: Guo Jingxia , Zhang Chunhong , Zhang Mingxu , Bi Yaqiong , Wang Mengchao , Li Minhui
Published: September 2024

Objective

Astragali Radix, commonly used in traditional Chinese medicine, is subjected to an analysis of the habitat distribution of Astragalus membranaceus var. mongholicus in the Inner Mongolia Autonomous Region of China under climate change. This analysis is crucial for the conservation of medicinal plants, the assessment of their adaptability to climate change, and the promotion of sustainable development in the ecological environment.

Methods

This study explores the currently suitable habitats for A. membranaceus var. mongholicus using a random forest species distribution model on the Google earth engine platform. Based on future climate data, the study predicts distribution dynamics for 4 time periods (2021–2040, 2041–2060, 2061–2080, and 2081–2100) under three climate change scenarios (SSP126, SSP245, and SSP585).

Results

The results indicate that under current climatic conditions, the suitable habitat distribution of A. membranaceus var. mongholicus is mainly concentrated in the southwestern region of Inner Mongolia. Under future climate change scenarios, there is a varying degree of contraction in suitable habitats, with notable reductions. Particularly, under the SSP126 scenario (2081–2100), there is a significant decrease of 22.77% in suitable habitat. The SSP245 scenario (2041–2060) exhibits the most pronounced habitat loss, with a reduction of 36.38%. Additionally, with climate change, the overall suitable range of A. membranaceus var. mongholicus is expected to shift toward higher latitudes and contract.

Conclusion

This study can be used to improve conservation efforts for wild A. membranaceus var. mongholicus. It also provides a scientific basis for the cultivation of this medicinal plant in the context of climate change. This, in turn, can encourage more industries to achieve both sustainable development and economic benefits, providing valuable insights for building a low-carbon economy.
A computationally guided approach to improve expression of VHH binders
Authors: OZDEMIR EMINE SILA , Tolley Jessica , Goncalves Florian , Gomes Michelle , Wagnell Eli , Branchaud Bruce , Ranganathan Srivathsan
Published: September 2024

The variable heavy chain fragments derived from camelid antibodies, called VHHs or nanobodies, have recently shown promise as high-affinity reagents. They offer higher stability compared to conventional antibodies and fragments thereof. Furthermore, their smaller size (~15-20 kDa) allows better targeting of molecules localized inside the cell and in crowded environments, like tissues and protein aggregates. Despite these advantages, nanobody clones screened using phage display can suffer from poor soluble expression, which we hypothesized, is due to the presence of hydrophobic hotspots on their surface. In this work, we propose a novel computationally guided workflow for screening and production of nanobody binders for optimized expression. After an initial round of phage display screens against our target (K-Ras), we modeled the lead candidates to generate Spatial Aggregation Propensity (SAP) maps to highlight the hydrophobic hotspots with single amino acid resolution, which were subsequently used to guide mutagenesis of the binders for soluble expression. We followed two approaches to perform point hydrophilic mutations: i) performing point hydrophilic mutations in the hydrophobic hotspots; ii) combining point mutation resulting from a round of random mutagenesis that show favorable SAP scores. Both approaches led a remarkable increase in soluble expression which allowed production and characterization of their binding to their target (K-Ras) on soluble ELISA, and biolayer interferometry. We observed that the latter approach resulted in clones with stronger binding affinity compared to the former approach. Our results emphasize the need to perform a round of random mutagenesis to identify point mutations, which can then be used in an in-silico guided pipeline to identify the right combination of mutations for high soluble expression.
Comparative cell free salivary miRNA profile in Bubalus bubalis between diestrus and estrus stages
Authors: CHANDEL RAJEEV , Singh Dheer , Onteru Suneel Kumar
Published: September 2024

Despite buffaloes being primary farm animals, their reproductive performance remains poor mainly due to inaccurate estrus detection methods that ultimately has an economic impact on dairy industry as well as farmers. Recently, numerous studies showed potential of miRNAs as estrus biomarker. However, a miRNA profile of buffalo cell free saliva, a non-invasive fluid, at estrus and diestrus stages is missing. Hence, the present study was planned to identify differential levels of salivary cell free miRNAs in estrus as compared to the diestrus phase of buffalo oestrous cycle (n=3) in order to discover a possible estrus specific miRNAs as biomarkers. miRNA-Seq data analysis showed that in total 10 miRNAs i.e bta-miR-375, bta-miR-200c, bta-miR-30d, bta-let-7f, bta-miR-200a, bta-miR-12034, bta-let-7b, bta-miR-142-5p, bta-miR-2467-3p, bta-miR-30a-5p are significantly altered (log2foldchange >3 and p<0.05) during estrus in comparison to the diestrus phase in buffaloes, suggesting their estrus biomarker potential. Overall, 8 miRNAs i.e bta-miR-375 (6.87 Fold; p-value 0.003), bta-miR-200c (5.98 Fold; p-value 0.003), bta-miR-30d (4.17 Fold; p-value 0.015), bta-let-7f (3.34 Fold; p-value 0.022), bta-miR-200a (4.92 Fold; p-value 0.024), bta-miR-12034 (3.58 Fold; p-value 0.0025), bta-let-7b (3.06 Fold; p-value 0.031), bta-miR-30a-5p (4.7 Fold; p-value 0.036) were upregulated, whereas bta-miR-142-5p (-3.4 Fold; p-value 0.032) and bta-miR-2467-3p (-5.24 Fold; p-value 0.035) were downregulated during estrus. However, further validation study using qPCR is required in a large sample size in order to determine their estrus biomarker potential. In summary, our results revealed differential salivary cell free miRNAs profile during the oestrous cycle that may lead to the development of estrus specific miRNAs based point-of-care test applicable for the reproductive management of buffaloes in the field condition in the near future.
A scalable approach to absolute quantitation in metabolomics
Authors: Ferro Luke S , Wong Alan Y. L. , Howland Jack , Costa Ana S. H. , Pruyne Jefferson G. , Shah Devesh , Lauterbach Joshua D. , Hooper Steven B. , Delmar Mimoun Cadosch , Geremia Jack , Kassis Timothy , Kanarek Naama , Campbell Jennifer M.
Published: September 2024

Mass spectrometry-based metabolomics allows for the quantitation of metabolite levels in diverse biological samples. The traditional method of converting peak areas to absolute concentrations involves the use of matched heavy isotopologues. However, this approach is laborious and limited to a small number of metabolites. We addressed these limitations by developing PyxisTM, a machine learning-based technology which converts raw mass spectrometry data to absolute concentration measurements without the need for per-analyte standards. Here, we demonstrate Pyxis performance by quantifying metabolome concentration dynamics in murine blood plasma. Pyxis performed equivalently to traditional quantitation workflows used by research institutions, with a fraction of the time needed for analysis. We show that absolute quantitation by Pyxis can be expanded to include concentrations for additional metabolites, without the need to acquire new data. Furthermore, Pyxis allows for absolute quantitation as part of an untargeted metabolomics workflow. By removing the bottleneck of per-analyte standards, Pyxis allows for absolute quantitation in metabolomics that is scalable to large numbers of metabolites. The ability of Pyxis to make concentration-based measurements across the metabolome has the potential to deepen our understanding of diverse metabolic perturbations.
The neurotrophic factor artemin and its receptor GFRα3 mediate migraine-like pain via the ion channel TRPM8
Authors: Yang Chenyu , Wei Chao , Alam Sanaa , Chen Xunyang , McKemy David D.
Published: September 2024

Background

Migraine has a strong genetic foundation, including both monogenic and polygenic types. The former are rare, with most migraine considered polygenic, supported by genome-wide association studies (GWAS) identifying numerous genetic variants associated with migraine risk. Surprisingly, some of the most common mutations are associated with TRPM8, a non-selective cation channel that is the primary sensor of cold temperatures in primary afferent neurons of the somatosensory system. However, it is unlikely that the temperature sensitivity of TRPM8 underlies its role in migraine pathogenesis. To define the basis of the channel’s involvement, we reasoned that cellular processes that increase cold sensitivity in the skin, such as the neurotrophic factor artemin, via its receptor GFRα3, also mediate TRPM8-associated migraine-like pain in the meninges.

Methods

To investigate the role of artemin and GFRα3 in preclinical rodent migraine models, we infused nitroglycerin acutely and chronically, and measured changes in periorbital and hind paw mechanical sensitivity in male and female mice lacking GFRα3, after neutralization of free artemin with specific monoclonal antibodies, or by systemic treatment with a TRPM8-specific antagonist. Further, in wildtypes and mice lacking either GFRα3 or TRPM8, we tested the effects of supradural infusions of a mix of inflammatory mediators, artemin, and a TRPM8-specific agonist on migraine-related pain in mice.

Results

We find that mechanical allodynia induced by systemic nitroglycerin, or supradural infusion of inflammatory mediators, involves GFRα3. In addition, neutralization of circulating artemin reduces the nitroglycerin phenotype, demonstrating the importance of this neurotrophic pathway. Further, we show TRPM8 expression in the meninges and that direct supradural infusion of either a TRPM8-specific agonist or artemin itself produces mechanical allodynia, the latter dependent on TRPM8 and ameliorated by concurrent treatment with sumatriptan.

Conclusions

These results indicate that neuroinflammatory events in the meninges can produce migraine-like pain in mice via artemin and GFRα3, likely acting upstream of TRPM8, providing a novel pathway that may contribute to migraine pathogenesis.
Inkjet-printed graphene multielectrode arrays: an accessible platform forin vitrocardiac electrophysiology
Authors: Lumpuy-Castillo Jairo , Fu Yujie , Ávila Alan , Solodka Kateryna , Li Jiantong , Lorenzo Oscar , Zeglio Erica , Garma Leonardo D.
Published: September 2024

In vitromodels have now become a realistic alternative to animal models for cardiotoxicity assessment. However, the cost and expertise required to implementin vitroelectrophysiology systems to study cardiac cells poses a strong obstacle to their widespread use. This study presents a novel, cost-effective approach forin vitrocardiac electrophysiology using fully-printed graphene-based microelectrode arrays (pGMEAs) coupled with an open-source signal acquisition system. We characterized the pGMEAs’ electrical properties and biocompatibility, observing low impedance values and cell viability. We demonstrated the platform’s capability to record spontaneous electrophysiological activity from HL-1 cell cultures, and we monitored and quantified their responses to chemical stimulation with noradrenaline. This study demonstrates the feasibility of producing fully-printed, graphene-based devices forin vitroelectrophysiology. The accessible and versatile platform we present here represents a step further in the development of alternative methods for cardiac safety screening.
Molecular basis of the urate transporter URAT1 inhibition by gout drugs
Authors: Suo Yang , Fedor Justin G. , Zhang Han , Tsolova Kalina , Shi Xiaoyu , Sharma Kedar , Kumari Shweta , Borgnia Mario , Zhan Peng , Im Wonpil , Lee Seok-Yong
Published: September 2024

Hyperuricemia is a condition when uric acid, a waste product of purine metabolism, accumulates in the blood1. Untreated hyperuricemia can lead to crystal formation of monosodium urate in the joints, causing a painful inflammatory disease known as gout. These conditions are associated with many other diseases and affect a significant and increasing proportion of the population2–4. The human urate transporter 1 (URAT1) is responsible for the reabsorption of ∼90% of uric acid in the kidneys back into the blood, making it a primary target for treating hyperuricemia and gout5. Despite decades of research and development, clinically available URAT1 inhibitors have limitations because the molecular basis of URAT1 inhibition by gout drugs remains unknown5. Here we present cryo-electron microscopy structures of URAT1 alone and in complex with three clinically relevant inhibitors: benzbromarone, lesinurad, and the novel compound TD-3. Together with functional experiments and molecular dynamics simulations, we reveal that these inhibitors bind selectively to URAT1 in inward-open states. Furthermore, we discover differences in the inhibitor dependent URAT1 conformations as well as interaction networks, which contribute to drug specificity. Our findings illuminate a general theme for URAT1 inhibition, paving the way for the design of next-generation URAT1 inhibitors in the treatment of gout and hyperuricemia.
A Framework to Assess Clinical Safety and Hallucination Rates of LLMs for Medical Text Summarisation
Authors: Asgari Elham , Montaña-Brown Nina , Dubois Magda , Khalil Saleh , Balloch Jasmine , Pimenta Dominic
Published: September 2024

The integration of large language models (LLMs) into healthcare settings holds great promise for improving clinical workflow efficiency and enhancing patient care, with the potential to automate tasks such as text summarisation during consultations. The fidelity between LLM outputs and ground truth information is therefore paramount in healthcare, as errors in medical summary generation can lead to miscommunication between patients and clinicians, leading to incorrect diagnosis and treatment decisions and compromising patient safety. LLMs are well-known to produce a variety of errors. Currently, there is no established clinical framework for assessing the safety and accuracy of LLM-generated medical text.

We have developed a new approach to: a) categorise LLM errors within the clinical documentation context, b) establish clinical safety metrics for the live usage phase, and c) suggest a framework named CREOLA for assessing the safety risk for errors. We present clinical error metrics over 18 different LLM experimental configurations for the clinical note generation task, consisting of 12,999 clinician-annotated sentences. We illustrate the utility of using our platform CREOLA for iteration over LLM architectures with two experiments. Overall, we find our best- performing experiments outperform previously reported model error rates in the note generation literature, and additionally outperform human annotators. Our suggested framework can be used to assess the accuracy and safety of LLM output in the clinical context.
Association of Parental Prenatal Mental Health on Offspring Neurodevelopmental Disorders: A Systematic Review and Meta-Analysis
Authors: Kepinska Adrianna P , Smout Shelby , Robakis Thalia , Cohen Lily , Gustavsson Mahjani Ingrid Christina , Skalkidou Alkistis , Bergink Veerle , Mahjani Behrang
Published: September 2024

Objective: Parental prenatal mood and anxiety disorders (PMAD) are linked to child neurodevelopmental disorders (NDDs), but evaluations of the magnitude and mechanisms of this association are limited. This study estimates the strength of the association and whether it is impacted by genetic and environmental factors. Method: A systematic search of PubMed, CENTRAL, PsycINFO, OVID, and Google Scholar was performed for articles published from January 1988 to January 2024. Of 2,170 articles screened, 64 met the inclusion criteria. Meta-analyses were conducted on 20 studies, and 44 were included in the narrative synthesis. We conducted random-effects meta-analyses, along with tests for heterogeneity (I^2) and publication bias (Egger's test). The review followed PRISMA and MOOSE guidelines. Results: Maternal PMADs were associated with a significantly increased risk of ADHD (OR 1.91, 95% CI 1.45-2.52) and ASD (OR 1.57, 95% CI 1.37-1.81) in children. Paternal PMADs were also associated with the risk of NDDs, with combined odds for ASD and ADHD (OR 1.24, 95% CI 1.15-1.34). Several studies suggested that the link between parental PMADs and offspring NDDs might be impacted by both genetic and environmental factors, including the impact of ongoing parental depression on child behavior. Conclusions and Relevance: Parental PMADs are significantly associated with an increased risk of NDDs in children. These associations may be influenced by both genetic predispositions and environmental factors. Understanding these pathways is important for informing interventions aimed at mitigating mental health risks in families and supporting child development.
IFT and BBSome proteins are required for Leishmania mexicana pathogenicity, but flagellar motility is dispensable
Authors: Beneke Tom , Neish Rachel , Catta-Preta Carolina M C , Smith James , Valli Jessica , McCoy Ciaran J , Albuquerque-Wendt Andreia , Mottram Jeremy C , Gluenz Eva
Published: September 2024

Protists of the order Kinetoplastida possess a single multifunctional flagellum, which powers cellular displacement and mediates attachment to tissues of the arthropod vector. The kinetoplastid flagellar cytoskeleton consists of a nine-microtubule doublet axoneme; further structural elaborations, which can vary between species and life cycle stages, include the assembly of axonemal dynein complexes, a pair of singlet microtubules and the extra-axonemal paraflagellar rod. The intracellular amastigote forms of Leishmania spp. build a short, non-motile cilium whose function has remained enigmatic. Here we used a panel of 25 barcoded promastigote cell lines, including mutants lacking genes encoding flagellar assembly proteins, cytoskeletal proteins required for normal motility, or flagellar membrane proteins to examine how these defects impact on their virulence in macrophages and mice. Mutants lacking intraflagellar transport (IFT) protein 88 were severely attenuated indicating that assembly of a flagellum is necessary to allow for Leishmania survival in a mammalian host. A similarly severe loss of virulence was observed upon deletion of BBS2, a core component of the BBSome complex, which may act as a cargo adapter for IFT. By contrast, promastigotes that were unable to beat their flagella due to loss of PF16 could establish an infection and only showed a small reduction of parasite burden in vivo compared to the parental cell lines. These results confirm that flagellar motility is not necessary for mammalian infection but flagellum assembly and the integrity of the BBSome are essential for pathogenicity.
Study of
B→PP
decays in the modified perturbative QCD approach
Authors: Lü Sheng , Wang Ru-Xuan , Yang Mao-Zhi
Published: September 2024

We study the nonleptonic decays of B→PP in the modified perturbative QCD approach, where P stands for pseudoscalar mesons. Transverse momenta of partons and the Sudakov factor are included, which help to suppress the contributions of soft interactions. The wave function of the B meson obtained from the relativistic potential model is used, and then the contributions in the infrared region cannot be suppressed completely. So a soft cutoff scale and soft form factors are introduced. The contributions with the scale higher than the soft cutoff scale are calculated with perturbative QCD, while the contributions lower than the cutoff scale are replaced by the soft form factors. To explain experimental data, we find that contributions of color-octet operators for the quark-antiquarks in the mesons in the final state need to be considered. The contributions of the color-octet operators are parametrized by a few parameters with the help of SU(3) flavor symmetry and symmetry breaking. These parameters for color-octet contributions are universal for all the nonleptonic decay modes of the B meson, where the mesons in the final state belong to the same flavor SU(3) nonet. Both the branching ratios and CP violations are studied. We find that the theoretical calculation can well explain the experimental data of B factories.

Published by the American Physical Society
2024
Radiative decay and axial-vector decay behaviors of octet pentaquark states
Authors: Lei Ya-Ding , Li Hao-Song
Published: September 2024

In this work, we systematically calculate transition magnetic moments, radiative decay widths, and axial-vector coupling constants of octet hidden-charm molecular pentaquark states with different flavor representations in constituent quark model. We discuss the relations between transition magnetic moments and decay widths for pentaquark states. For octet pentaquark states with the 81f and 82f flavor representations, decay widths of the processes Pψ|32−⟩(12+⊗1−)→Pψ|12−⟩(12+⊗0−)γ and Pψ|12−⟩(12+⊗1−)→Pψ|12−⟩(12+⊗0−)γ are quite close, and decay widths of the Pψ|32−⟩(12+⊗1−)→Pψ|12−⟩(12+⊗1−)γ process are close to zero, and we notice that the axial-vector coupling constants of the pentaquark states are generally smaller than that of the nucleon.

Published by the American Physical Society
2024
Solar chameleons: Novel channels
Authors: O’Shea Tomás , Davis Anne-Christine , Giannotti Maurizio , Vagnozzi Sunny , Visinelli Luca , Vogel Julia K.
Published: September 2024

We revisit the flux of chameleons (light scalar particles which could play a role in the dark energy phenomenon) produced in the interior of the Sun. Our novel analysis incorporates various important details and new processes that have previously been overlooked, including the impact of the bulk magnetic field profile, as well as Primakoff production of chameleons in the electric fields of electrons and ions. In this paper we consider only the contributions of transverse photons. The production of chameleons from longitudinal electromagnetic excitations will be presented in a dedicated follow-up work. Demanding that the total flux of chameleons does not exceed 3% of the solar luminosity leads to the stringent upper limit on the chameleon-photon conformal coupling βγ≲1010, assuming that the height of the chameleon potential is set to the dark energy scale Λ=2.4  meV, and independently of other couplings to matter. Although this bound is tighter than current upper limits on βγ from the CAST helioscope, these limits will have to be reassessed in terms of the updated solar chameleon flux we have computed. We argue that solar chameleons, potentially detectable in next-generation helioscopes such as IAXO, can be used to probe a region of chameleon parameter space that has yet to be covered.

Published by the American Physical Society
2024
Local quenches in fracton field theory: Lieb-Robinson bound, noncausal dynamics and fractal excitation patterns
Authors: Ageev Dmitry S. , Bagrov Andrey A. , Belokon Aleksandr I. , Iliasov Askar , Pushkarev Vasilii V. , Verheijen Femke
Published: September 2024

We study the out-of-equilibrium dynamics induced by a local perturbation in fracton field theory. For the Z4- and Z8-symmetric free fractonic theories, we compute the time dynamics of several observables such as the two-point Green’s function, ⟨ϕ2⟩ condensate, energy density, and the dipole momentum. The time-dependent considerations highlight that the free fractonic theory breaks causality and exhibits instantaneous signal propagation, even if an additional relativistic term is included to enforce a speed limit in the system. We show that it is related to the fact that the Lieb-Robinson bound does not hold in the continuum limit of the fracton field theory, and the effective bounded speed of light does not emerge. For the theory in finite volume, we show that the fracton wave front acquires fractal shape with nontrivial Hausdorff dimension and argue that this phenomenon cannot be explained by a simple self-interference effect.

Published by the American Physical Society
2024
Bank performance – what are the main roles of the human capital and asset diversification? Evidence from France
Authors: Hemrit Wael , Kasraoui Naziha , Feidi Amira
Published: September 2024

Purpose

The aim of this paper is to determine whether the efficiency of banks’ human capital (HC) has moderating effects on the relationship between asset diversification and bank performance over the 2008–2020 period.

Design/methodology/approach

Our study considers generalized least squares estimation in fixed effects panel.

Findings

Results show that banks with higher levels of HC and higher degree of diversification reduce bank profitability and efficiency. The results also depict that the financial stability-reducing effects of Income diversification decrease as bank HC efficiency increases. At the same time, the effects of income and asset diversity on financial stability change depending on the performance aspect.

Originality/value

Previous research on banks’ performance is concentrated on asset diversification. This article broadens to the HC, Asset diversification and the moderating effects of the profitability, stability and efficiency of French Banks.
Syrian refugees in Canada: a qualitative report of the impact of the COVID-19 pandemic on psychosocial adaptation
Authors: Devereux Chloe , Yohani Sophie , Tremblay Melissa , Nour Eddin Joud
Published: September 2024

Purpose

Since March 2020, the global COVID-19 pandemic has disproportionately impacted refugees by compounding preexisting and systemic health, social and economic inequities. In Canada, approximately 50,000 Syrian refugees arrived between 2015 and 2020 and were in the process of rebuilding their lives when the pandemic started. This study aims to explore the impact of the COVID-19 pandemic for Syrian refugees in Canada and identify supports needed.

Design/methodology/approach

Drawing on frameworks for refugee psychosocial adaptation and social integration and a qualitative descriptive design, the study used thematic analysis to examine semi-structured interviews with 10 Syrians.

Findings

Findings indicated four themes that provide a snapshot of impacts relatively early in the pandemic: facing ongoing development, inequity and insecurity during integration; disruption of settlement, integration and adaptation due to the pandemic; ongoing adaptation and resilience during integration in Canada; and ongoing needs and solutions for integration and adaptation.

Originality/value

This study builds upon growing research concerning Syrian refugees and psychosocial adaptation, particularly during the pandemic. The findings highlight the impacts of the pandemic on a population already facing inequities in a resettlement country. While the findings emphasize the resilience of the Syrian refugee community, the study also demonstrates the need for ongoing supports and justice-oriented action to fulfill resettlement commitments, especially in the face of additional stressors like the COVID-19 pandemic. Implications for policy, practice and future research are discussed.