bluuebunny/crossref_metadata_2025 huggingface dataset:
Global trends of targeted therapy for hepatocellular carcinoma: A bibliometric and visualized study from 2008 to 2022
Authors: Yang Xuan-Ang , Jin Rong , Zhang Lei-Ming , Ying Dong-Jian
Published: August 2023

Background:

Hepatocellular carcinoma (HCC) is an exceedingly prevalent malignancy with an exceptionally poor prognosis. Targeted therapy is an effective treatment option for patients with advanced HCC. However, there have been no bibliometric analyses of targeted therapies for HCC.

Methods:

This study aimed to assess the current status and future directions of targeted therapy for HCC to provide future scholars with clearer research contents and popular themes. Methods: Literature on targeted therapy for HCC from 2008 to 2022 was obtained from the Web of Science (WoS) and assessed using bibliometric methodology. Additionally, the VOS viewer was applied in the visualization study to conduct bibliographic coupling, co-authorship, co-citation, and co-occurrence analyses of publications.

Results:

A total of 10,779 papers were subsequently selected. Over the past 15 years, there has been a progressive increase in the number of publications on an annualized basis. China released the most publications in the field, whereas the United States had the highest H-index. Cancers published the most papers. Fudan University had the greatest sway in this area. Studies could be divided into 5 clusters: “Gene and expression research,” “Mechanism study,” “Nanoparticle study,” “Targeted drug research,” and “Clinical study.”

Conclusions:

In the upcoming years, more papers on targeted therapy for HCC are expected to be released, demonstrating the potential for this topic to flourish. Particularly, “Clinical study” is the following trendy topic in this field. Other research subfields may likewise exhibit a continuous tendency towards balanced development.
FIB-4 is closer to FibroScan screen results to detecting advanced liver fibrosis and maybe facilitates NAFLD warning
Authors: Ding Yuping , Wang Zuoyu , Niu Haiyan , Deng Quanjun , Wang Yanan , Xia Shihai
Published: August 2023

To assess the relationship between clinical biochemical characteristics and steatosis or fibrosis by Fibroscan in non-alcoholic fatty liver disease (NAFLD) patients in order to seek the simple effective screening method closed to the results of the fibroScan measurement. A cross-sectional study was conducted on 188 patients with NAFLD who underwent FibroScan examinations. Demographic data and clinical biochemical characteristics were collected and analyzed. The result showed elevated serum uric acid (SUA) (P = .023, odds ratio [OR = 1.005, 95% CI (1.001–1.009) and metabolic syndrome (MetS) (P = .000, OR = 4.549, 95%CI (1.974–10.484) were associated with severe steatosis (controlled attenuation parameter, CAP ≥ 300 dB/m). The magnitude of liver stiffness measured using FibroScan was positively correlated with aspartate transaminase/alanine aminotransferase (AST/ALT) ratio (R = 0.419, P = .000), AST to platelet ratio index (APRI) score (R = 0.309, P = .000), and Fibrosis-4 score (FIB-4) (R = 0.507, P = .000). The areas under the receiver operating curve (ROC) of AST/ALT, APRI, and FIB-4 for mild or severe fibrosis were 0.563, 0.696, and 0.728, respectively, and those for advanced fibrosis were 0.648, 0.750, and 0.821, respectively. The FIB-4 index cutoff value was 1.65 with a sensitivity of 68.3% and specificity of 89.8% during the diagnosis of advanced fibrosis. MetS and elevated SUA are associated with severe steatosis according to the CAP value screen, whereas FIB-4, as the fibrosis score method, is closer to the liver stiffness measurement results from FibroScan, which may facilitate early warning of NAFLD in the community or in remote areas.
Mobile schwannoma of the lumbar spine: A case report and literature review
Authors: Song Shaowen , Li Xiaojing , Lyu Wanqiu , Chen Liyuan , Zhang Binqing
Published: August 2023

Background:

Schwannoma is a benign tumor that originates from the cells of nerve sheaths. The occurrence of mobile schwannoma of the lumbar spine is extremely rare, and when clinicians perform spinal explorations in the expected locations, the results are often negative. This report presents a case of mobile schwannoma in the lumbar spine, aiming to remind doctors to consider the possibility of tumor migration during preoperative planning, thereby avoiding secondary harm to the patient.

Case report:

A 48-year-old male patient presented with a 2-year history of lower back pain and numbness in both lower extremities, which has progressively worsened over the past 3 months. An Magnetic resonance imaging scan revealed an oval-shaped lesion located in the L2/3 vertebral segment, which migrated to the L3/4 vertebral segment following contrast enhancement. The patient underwent tumor resection surgery, and the diagnosis of schwannoma was confirmed through pathological examination.

Conclusion:

Clinical physicians should increase their understanding of mobile schwannoma of the lumbar spine and utilize imaging techniques to accurately locate the tumor before surgery, in order to avoid unnecessary surgical scope and the risks of additional surgery.
Median arcuate ligament syndrome in an old male: a case report with 3-year follow-up
Authors: Hannouneh Zein Alabdin , Alahdab Gieth , Hijazi Amjad , Harfoush Ghaith , Alsayed Chaza , Kanaan Samir , Jamouz Rafah
Published: August 2023

Introduction and importance:

Median arcuate ligament syndrome (MALS) or Dunbar syndrome is a rare compression syndrome that poses a challenge to many clinicians due to its ambiguous symptoms. It is predominantly common in females in their 30s to 50s.

Case presentation:

A 74-year-old male presented with generalized chronic postprandial abdominal pain, anorexia, and weight loss of 6 kg for the past 2 months. Physical examination, abdominal ultrasound, endoscopy, and colonoscopy were all unremarkable. His laboratory workup and tumor marker tests were within normal ranges. Finally, a multi-slice computed tomography (MSCT), an advanced computed tomography with multiple detectors resulting in faster and higher resolution imaging, outlined external compression on the celiac artery (CA) by the median arcuate ligament (MAL). The release of the CA from the MAL was done laparoscopically. Symptoms improved significantly postoperatively. During the follow-up period of 3 years, the patient did not regain his lost weight but had no other complaints.

Clinical discussion:

Due to its vague manifestations, MALS is diagnosed only after extensive evaluation and exclusion. This challenging diagnosis outlines the need for refined diagnostic guidelines. An MSCT plays a crucial role in confirming the diagnosis. Currently, more physicians prefer laparoscopic release of the MAL compared to an open approach.

Conclusion:

Despite MALS predominance in females, the diagnosis of MALS should be considered in males with postprandial abdominal pain and unexplained weight loss. An MSCT, along with other imaging modalities, can provide a comprehensive view of celiac compression. Laparoscopic decompression of the CA is an ideal treatment option.
Thrombosis of sigmoid sinus, transverse sinus, and internal jugular vein in chronic otitis media in 9-year-old girl: a case report
Authors: Shah Ujjwal K. , Shah Bipesh K. , Muskan Vitasta , Bhusal Amrit , Shah Neha
Published: August 2023

Introduction and importance:

Chronic otitis media can lead to dreadful intracranial complications, the most common being meningitis. A concomitant finding of thrombosis in more than one sinus with a cerebral vein is extremely rare. Septic sigmoid sinus thrombosis has an infectious origin and the treatment is debatable between antibiotics and surgery.

Case presentation:

A case of 9-year-old female with prolonged symptoms of right sided ear discharge, fever, right sided neck pain, and vomiting. Examination revealed tachycardia and neck rigidity suggesting meningitis. The child developed shock, generalized seizure, and a persistent high grade fever in the course of hospital stay. Brain imaging revealed sigmoid, transverse, and internal jugular thrombosis. Blood culture grew both gram-positive and gram-negative bacteria, suggesting the infectious origin of the thrombus. The authors treated meningitis with cephalosporin and vancomycin at first, and then additional antibiotics to treat the septic sigmoid sinus thrombosis.

Clinical discussion:

Sigmoid sinus thrombosis is a rare condition caused by infections, thrombophilia, head trauma, some types of cancer, and intravenous drug use. Cerebral vein or sinus thrombosis can lead to raised intracranial pressure and can cause fever, otalgia, headache, vomiting, cranial nerve palsies, papilledema altered mental status and may cause seizures, stupor, and coma. Prompt diagnosis by CT scan or MRI and prompt treatment with antibiotics are crucial.

Conclusion:

Sigmoid sinus thrombosis with involvement of the transverse sinus and internal jugular vein is a rare complication of chronic otitis media, and should be suspected if a recurring fever with features of raised intracranial pressure is present in a child with chronic otitis media.
Practice to Perform
Authors: Kuehn Jo , Zehrung Trisha
Published: August 2023

Background:

In previous years, students expressed their concerns regarding the high-stress nature of the summative skills checkoff, and pass rates were not as high as expected.

Purpose:

To evaluate the impact of mini-skills checkoff assessments and the use of standardized patients (SPs) on summative skills pass rates and nursing students’ perceptions of this teaching approach.

Methods:

A mixed-methods approach was used with a convenience sample of 46 sophomore nursing students.

Results:

There was a significant difference in the summative skills checkoff pass rates after including mini-skills checkoffs and SPs (P < .01). Four dominant themes emerged: emotional impact, preparation and learning, confidence and competence, and readiness.

Conclusions:

Evidence from this pilot study suggests the inclusion of continuous, low-stakes assessments over time, with learner feedback bridges the gap between clinical practice, simulation, and classroom learning.
Extreme Limb Salvage: The Thin SCIP Flap for Distal Amputation Coverage in Highly Comorbid Patients
Authors: Salibian Ara A. , Swerdlow Mark A. , Kondra Katelyn , Patel Ketan M.
Published: August 2023

Background:

Limb length preservation is correlated with overall survival. Successful free flap coverage of forefoot, midfoot, and hindfoot amputations can prevent more proximal below-knee amputations but is challenging in patients with multiple comorbidities. The thin superficial circumflex iliac artery perforator (SCIP) flap is well-suited for these patients, as it provides thin, pliable tissue from a favorable donor site.

Methods:

A retrospective review of all patients with distal amputations requiring coverage with a thin SCIP flap between 2016 to 2022 was performed. Patient demographics, amputation levels, and wound characteristics in addition to flap and microsurgery details were analyzed. The primary outcome was limb salvage. Secondary outcomes included partial flap necrosis, flap revision rate, and additional postoperative complications.

Results:

Thirty-two patients (mean age, 57.3 years) underwent reconstruction of forefoot, midfoot, and hindfoot amputations with thin SCIP flaps (mean follow-up, 36 months). Twenty-eight patients (87.5%) had diabetes, 27 (84.4%) had peripheral artery disease, and 15 (46.9%) were dialysis-dependent. Average flap size was 59.5 cm2 and average flap thickness was 5.7 mm. Successful limb salvage was achieved in 27 patients (84.3%). Three cases (9.4%) had total flap loss. Twenty-one flaps (65.6%) had partial necrosis, of which 12 (57.1%) healed with conservative management and 7 (33.3 %) healed after late revision.

Conclusions:

The thin SCIP flap is a useful option for coverage of distal pedal amputations in patients with significant comorbidities. Despite higher rates of partial flap necrosis, free flap reconstruction allowed for high rates of limb salvage in a challenging patient population.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Can Craniosynostosis be Diagnosed on Physical Examination? A Retrospective Review
Authors: Zavala Carmen A. , Zima Laura A. , Greives Matthew R. , Fletcher Stephen A. , Shah Manish N. , Miller Brandon A. , Sandberg David I. , Nguyen Phuong D.
Published: August 2023

Craniosynostosis is a developmental craniofacial defect in which one or more sutures of the skull fuse together prematurely. Uncorrected craniosynostosis may have serious complications including elevated intracranial pressure, developmental delay, and blindness. Proper diagnosis of craniosynostosis requires a physical examination of the head with assessment for symmetry and palpation of sutures for prominence. Often, if craniosynostosis is suspected, computed tomography (CT) imaging will be obtained. Recent literature has posited that this is unnecessary. This study aims to address whether physical examination alone is sufficient for the diagnosis and treatment planning of single suture craniosynostosis. Between 2015 and 2022, the Divisions of Pediatric Neurosurgery and Pediatric Plastic Surgery at UTHealth Houston evaluated 140 children under 36 months of age with suspected craniosynostosis by physical examination and subsequently ordered CT imaging for preoperative planning. Twenty-three patients received a clinical diagnosis of multi-sutural or syndromic craniosynostosis that was confirmed by CT. One hundred seventeen patients were diagnosed with single suture craniosynostosis on clinical examination and follow-up CT confirmed suture fusion in 109 (93.2%) patients and identified intracranial anomalies in 7 (6.0%) patients. These patients underwent surgical correction. Eight (6.8%) patients showed no evidence of craniosynostosis on CT imaging. Treatment for patients without fused sutures included molding helmets and observation alone. This evidence suggests that physical examination alone may be inadequate to accurately diagnose single suture synostosis, and surgery without preoperative CT evaluation could lead to unindicated procedures.
It’s Hip to Go Home: An Evaluation of Outpatient Alveolar Bone Grafting in Patients With Cleft Palate
Authors: Mitchell David T. , Obinero Chioma , Ekeoduru Rhashedah A. , Nye Jessica , Green Jackson C. , Talanker Michael , Nguyen Phuong D. , Greives Matthew R.
Published: August 2023

Introduction:

Secondary alveolar bone grafting (ABG) is a common procedure performed at cleft care centers used to fill the alveolar cleft. The advent of techniques such as minimally invasive trephine drill harvest and placement of continuous-infusion pain pumps at the donor site has made outpatient ABG an increasingly feasible and cost-effective procedure. However, enhanced recovery after surgery protocols to maximize pain control and recovery times for this patient population have not been well established.

Methods:

A retrospective single-institution review was conducted of pediatric patients with cleft palate who underwent iliac crest bone graft ABG at a large urban academic children’s hospital from 2017 to 2022. Patient age, alveolar cleft repair laterality, pain scores, surgery duration, hospital LOS, readmissions, and re-operations within 30 days were examined.

Results:

Fifty-four patients met our inclusion criteria. Fifty patients (92.6%) received a pain pump during the operation. The median duration of surgery and LOS in the post-anesthesia care unit were 1.28 and 1.75 hours, respectively. Fifty-two patients (96.3%) were discharged on the same day as their surgery whereas 2 patients (3.7%) stayed in the hospital overnight. The median pain score at the time of discharge was 0 (interquartile range 0, 0). There were 6 (11.1%) minor complications including 5 pain pump malfunctions and 1 recipient site wound breakdown. There was 1 readmission (1.9%) for development of a surgical site infection at the hip and no re-operations within 30 days of surgery.

Conclusion:

The described outpatient ABG protocol demonstrates effective postoperative pain control, short hospital LOS, and few complications requiring hospital readmission or reoperation.
Direct or Indirect Surgical Approach of Zygomatic Complex Fracture: A Comparative Study
Authors: Alshalah Muamer E. , Enezei Hamid H. , Aldaghir Osamah M. , Khalil Afrah A. , Aldelaimi Tahrir N. , Al-Ani Raid M.
Published: August 2023

Zygoma is considered the main support of the midface. Zygoma is frequently fractured owing to its prominent site on the face. Treatment of zygomaticomaxillary complex fractures can be performed through either conservative or surgical measures (closed or open reduction). The study was a cross-sectional retrospective observational investigation done at 4 hospitals in Ramadi and Baghdad cities, Iraq. This investigation covered a duration of 6 years (2016–2021). We reviewed the medical records of patients with ZCFs. The participants were divided into 2 groups according to the approach used for their management (direct versus indirect approach). Data regarding the demographic and clinical characteristics were recorded for each subject. Of 265 patients with ZCFs, 209 (78.9%) were males. The highest age group affected was 18 to 40 years (51.7%). The majority of the ZCFs were caused by road traffic accidents (31.7%). Most of the cases belong to single fractures (72.1%). Cheek flattening (73.6%) was the commonest sign of the ZCFs. The majority of the fractures were treated by direct approach, 65.4% of the isolated fractures and 62.2% for multiple fractures. Excellent patient satisfaction was seen in the majority of the cases. There were no statistically significant differences between the 2 approaches regarding the abovementioned variables (P-value > 0.05). The majority of the cases were with excellent patient satisfaction (n = 149) while only 7 patients with poor satisfaction. The age groups below 18 years and 18 to 40 years were associated with excellent patient satisfaction than good and poor satisfaction. All (n = 7) of the cases with poor satisfaction belong to the age group above 40 years. The majority of male (n = 113) and female (n = 36) patients were with excellent satisfaction, while all patients with poor results were males (n = 7). There were statistically significant differences between the results of the patient satisfaction and age group and complications (P-value < 0.05). The ophthalmic complications were the most complications seen after ZCF surgical treatment (2.56%). Direct and indirect approaches can be used safely in the treatment of ZCFs owing to excellent patient satisfaction in the majority of the cases and a low complication rate. This study aims to evaluate the demographic and clinical characteristics and to compare different surgical procedures to treat patients with zygomaticomaxillary complex fractures in a country overwhelmed by violence.
miR-379-5p inhibition enhances intestinal epithelial proliferation and barrier function recovery after ischemia/reperfusion by targeting EIF4G2
Authors: Jia Zirui , Wang Yuhang , Gao Jiacheng , Zheng Mingcan , Wang Puxu , Zu Guo
Published: August 2023

Gut barrier dysfunction caused by intestinal ischemia/reperfusion (I/R) injury is associated with substantial death and morbidity. In this research, the role of microRNAs (miRNAs) in regulating intestinal I/R injury was investigated. We used miRNA sequencing to analyze clinical ischemic and normal intestinal samples. Through bioinformatics analysis based on sequencing results, we found that upregulated miRNAs inhibited epithelial barrier function and cell proliferation, with miR-379-5p being the most significantly upregulated in the ischemic intestine. Further studies confirmed the role of miR-379-5p through experiments in the human ischemic intestine, the mouse I/R injury model in vivo, and cell H/R models in vitro. Inhibiting miR-379-5p increased epithelial cell proliferation and improved barrier function after I/R injury. We also identified eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) as a downstream target gene of miR-379-5p through bioinformatics prediction and experimental verification. The findings suggest that inhibiting miR-379-5p could improve intestinal epithelial cell proliferation and barrier function by targeting EIF4G2. The goal of this study was to find a potential target for treating I/R injury in the intestine, as well as to prevent and mitigate the damage caused.
Dexmedetomidine ameliorates acute brain injury induced by myocardial ischemia-reperfusion via upregulating the HIF-1 pathway
Authors: Yang Xue , Wu Jianjiang , Cheng Hu , Chen Siyu , Wang Jiang
Published: August 2023

Objective

Neurological complications after myocardial ischemia/reperfusion (IR) injury remain high and seriously burden patients and their families. Dexmedetomidine (Dex), an α2 agonist, is endowed with analgesic-sedative and anti-inflammatory effects. Therefore, our study aims to explore the mechanism and effect of Dex on brain damage following myocardial IR injury.

Methods

C57BL/6 mice were randomly divided into Sham, IR, and IR + Dex groups, and myocardial IR models were established. The impact of Dex on brain injury elicited by myocardial IR was assessed via enzyme-linked immunosorbent assay (ELISA) for inflammatory factors in serum and brain; Evans blue for blood-brain barrier (BBB) permeability; Hematoxylin-eosin (H&E) staining for pathological injury in brain; Immunofluorescence for microglia activation in brain; Morris water maze for cognitive dysfunction; Western blot for the expression level of HIF-1α, Occludin, Cleaved caspase-3, NF-κB p65 and p-NF-κB p65 in brain. In addition, HIF-1α knockout mice were used to verify whether the neuroprotective function of Dex is associated with the HIF-1 pathway.

Results

Dex was capable of reducing myocardial IR-induced brain damage including inflammatory factor secretion, BBB disruption, neuronal edema, microglial activation, and acute cognitive dysfunction. However, the protective role of Dex was attenuated in HIF-1α knockout mice.

Conclusions

Dex protects against myocardial IR-induced brain injury, and the neuroprotection of Dex is at least partially dependent on the activation of the HIF-1 pathway.
Comparison of 2 Immunosuppression Minimization Strategies in Kidney Transplantation: The ALLEGRO Trial
Authors: van den Born Joost C. , Meziyerh Soufian , Vart Priya , Bakker Stephan J.L. , Berger Stefan P. , Florquin Sandrine , de Fijter Johan W. , Gomes-Neto António W. , Idu Mirza M. , Pol Robert A. , Roelen Dave L. , van Sandwijk Marit S. , de Vries Dorottya K. , de Vries Aiko P.J. , Bemelman Frederike J. , Sanders Jan Stephan F.
Published: August 2023

Background.

Evidence on the optimal maintenance of immunosuppressive regimen in kidney transplantation recipients is limited.

Methods.

The Amsterdam, LEiden, GROningen trial is a randomized, multicenter, investigator-driven, noninferiority, open-label trial in de novo kidney transplant recipients, in which 2 immunosuppression minimization strategies were compared with standard immunosuppression with basiliximab, corticosteroids, tacrolimus, and mycophenolic acid. In the minimization groups, either steroids were withdrawn from day 3, or tacrolimus exposure was reduced from 6 mo after transplantation. The primary endpoint was kidney transplant function at 24 mo.

Results.

A total of 295 participants were included in the intention-to-treat analysis. Noninferiority was shown for the primary endpoint; estimated glomerular filtration rate at 24 mo was 45.3 mL/min/1.73 m2 in the early steroid withdrawal group, 49.0 mL/min/1.73 m2 in the standard immunosuppression group, and 44.7 mL/min/1.73 m2 in the tacrolimus minimization group. Participants in the early steroid withdrawal group were significantly more often treated for rejection (P = 0.04). However, in this group, the number of participants with diabetes mellitus during follow-up and total cholesterol at 24 mo were significantly lower.

Conclusions.

Tacrolimus minimization can be considered in kidney transplant recipients who do not have an increased immunological risk. Before withdrawing steroids the risk of rejection should be weighed against the potential metabolic advantages.
BelNet: basis enhanced learning, a mesh-free neural operator
Authors: Zhang Zecheng , Wing Tat Leung , Schaeffer Hayden
Published: August 2023

Operator learning trains a neural network to map functions to functions. An ideal operator learning framework should be mesh-free in the sense that the training does not require a particular choice of discretization for the input functions, allows for the input and output functions to be on different domains, and is able to have different grids between samples. We propose a mesh-free neural operator for solving parametric partial differential equations. The basis enhanced learning network (BelNet) projects the input function into a latent space and reconstructs the output functions. In particular, we construct part of the network to learn the ‘basis’ functions in the training process. This generalized the networks proposed in Chen & Chen (Chen and Chen 1995
IEEE Trans. Neural Netw.
49
, 911–917. (
doi:10.1109/72.392253
) and
6
, 904–910. (
doi:10.1109/IJCNN.1993.716815
)) to account for differences in input and output meshes. Through several challenging high-contrast and multiscale problems, we show that our approach outperforms other operator learning methods for these tasks and allows for more freedom in the sampling and/or discretization process.
Discovering governing equations from partial measurements with deep delay autoencoders
Authors: Bakarji Joseph , Champion Kathleen , Nathan Kutz J. , Brunton Steven L.
Published: August 2023

A central challenge in data-driven model discovery is the presence of hidden, or latent, variables that are not directly measured but are dynamically important. Takens’ theorem provides conditions for when it is possible to augment partial measurements with time delayed information, resulting in an attractor that is diffeomorphic to that of the original full-state system. This diffeomorphism is typically unknown, and learning the dynamics in the embedding space has remained an open challenge for decades. Here, we design a deep autoencoder network to learn a coordinate transformation from the delay embedded space into a new space, where it is possible to represent the dynamics in a sparse, closed form. We demonstrate this approach on the Lorenz, Rössler and Lotka–Volterra systems, as well as a Lorenz analogue from a video of a chaotic waterwheel experiment. This framework combines deep learning and the sparse identification of nonlinear dynamics methods to uncover interpretable models within effective coordinates.
Trapped DNA fragments in marine sponge specimens unveil North Atlantic deep-sea fish diversity
Authors: Neave Erika F. , Cai Wang , Arias Maria Belén , Harper Lynsey R. , Riesgo Ana , Mariani Stefano
Published: August 2023

Sponges pump water to filter feed and for diffusive oxygen uptake. In doing so, trace DNA fragments from a multitude of organisms living around them are trapped in their tissues. Here we show that the environmental DNA retrieved from archived marine sponge specimens can reconstruct the fish communities at the place of sampling and discriminate North Atlantic assemblages according to biogeographic region (from Western Greenland to Svalbard), depth habitat (80–1600 m), and even the level of protection in place. Given the cost associated with ocean biodiversity surveys, we argue that targeted and opportunistic sponge samples – as well as the specimens already stored in museums and other research collections – represent an invaluable trove of biodiversity information that can significantly extend the reach of ocean monitoring.
Accelerometer-based detection of African swine fever infection in wild boar
Authors: Morelle Kevin , Barasona Jose Angel , Bosch Jaime , Heine Georg , Daim Andreas , Arnold Janosch , Bauch Toralf , Kosowska Aleksandra , Cadenas-Fernández Estefanía , Aviles Marta Martinez , Zuñiga Daniel , Wikelski Martin , Vizcaino-Sanchez Jose Manuel , Safi Kamran
Published: August 2023

Infectious wildlife diseases that circulate at the interface with domestic animals pose significant threats worldwide and require early detection and warning. Although animal tracking technologies are used to discern behavioural changes, they are rarely used to monitor wildlife diseases. Common disease-induced behavioural changes include reduced activity and lethargy (‘sickness behaviour’). Here, we investigated whether accelerometer sensors could detect the onset of African swine fever (ASF), a viral infection that induces high mortality in suids for which no vaccine is currently available. Taking advantage of an experiment designed to test an oral ASF vaccine, we equipped 12 wild boars with an accelerometer tag and quantified how ASF affects their activity pattern and behavioural fingerprint, using overall dynamic body acceleration. Wild boars showed a daily reduction in activity of 10–20% from the healthy to the viremia phase. Using change point statistics and comparing healthy individuals living in semi-free and free-ranging conditions, we show how the onset of disease-induced sickness can be detected and how such early detection could work in natural settings. Timely detection of infection in animals is crucial for disease surveillance and control, and accelerometer technology on sentinel animals provides a viable complementary tool to existing disease management approaches.
COVID-19 vaccine coverage targets to inform reopening plans in a low incidence setting
Authors: Conway Eamon , Walker Camelia R. , Baker Christopher , Lydeamore Michael J. , Ryan Gerard E. , Campbell Trish , Miller Joel C. , Rebuli Nic , Yeung Max , Kabashima Greg , Geard Nicholas , Wood James , McCaw James M. , McVernon Jodie , Golding Nick , Price David J. , Shearer Freya M.
Published: August 2023

Since the emergence of SARS-CoV-2 in 2019 through to mid-2021, much of the Australian population lived in a COVID-19-free environment. This followed the broadly successful implementation of a strong suppression strategy, including international border closures. With the availability of COVID-19 vaccines in early 2021, the national government sought to transition from a state of minimal incidence and strong suppression activities to one of high vaccine coverage and reduced restrictions but with still-manageable transmission. This transition is articulated in the national ‘re-opening’ plan released in July 2021. Here, we report on the dynamic modelling study that directly informed policies within the national re-opening plan including the identification of priority age groups for vaccination, target vaccine coverage thresholds and the anticipated requirements for continued public health measures—assuming circulation of the Delta SARS-CoV-2 variant. Our findings demonstrated that adult vaccine coverage needed to be at least 60% to minimize public health and clinical impacts following the establishment of community transmission. They also supported the need for continued application of test–trace–isolate–quarantine and social measures during the vaccine roll-out phase and beyond.
Fractional dosing to improve vaccination coverage, vaccine hesitancy, and cost-effectiveness in Africa: a systematic review
Authors: Yacouba Abdourahamane , Brah Souleymane , Daou Maman , Andia Abdoul-Kader , Ibrahim Alkassoum , Moustapha Lamine Mahaman , Alhousseini Daouda , Doutchi Mahamadou , Guindo Ousmane , Soumana Issaka , Coldiron Matthew E. , Mamadou Saidou , Adehossi Eric , Grais Rebecca F.
Published: August 2023

Background

The major challenges of vaccination programs are notably coverage in the target population, vaccine hesitancy, and cost-effectiveness. A vaccination strategy with fractional doses is a dose-saving strategy to address current vaccine shortages. Herein, we aimed to review the literature on administering fractional vaccine doses in Africa.

Methods

A methodical search of PubMed was conducted to identify articles published up till March 31, 2023. Peer-reviewed studies were selected for inclusion if they focused on studies that described the use of fractional doses of vaccines and were conducted in any of the 54 African countries.

Results

Findings from eleven eligible studies were analyzed. Studies were from the Democratic Republic of the Congo, Gambia, Ghana, Kenya, South Africa, and Uganda. They covered five vaccines including the yellow fever vaccine (n=3; 27.3%), inactivated poliovirus vaccine (n=3; 27.3%), meningococcal A/C/Y/W135 vaccine (n=2; 18.2%),Haemophilus influenzaetype b vaccine (n=2; 18.2%), and malaria vaccine (n=1; 9.1%). Fractionated doses used most often consist of one-fifth of the standard dose (n=8; 72.7%). Regarding immunogenicity/efficacity, eight of ten studies that addressed immunogenicity suggest that immune responses to the fractional dose vaccines were comparable to that of the standard dose vaccines and resulted in higher antibody titers. Regarding safety, all of the eight studies that addressed the safety of fractional doses in Africa, suggest that safety and tolerability data of fractional dosing were favorable compared to full dose regimen.

Conclusion

Fractional dosing may be considered to address the availability and acceptability of certain vaccines while maintaining protection. This strategy also has the potential advantage of reducing the cost of vaccination programs, vaccine antigen overload, and vaccine side effects.
WITHDRAWN: Influences of Formalin Gas on Gene Expression Level of Tumor Protein TP53 in the Liver and Kidney of the Quail (Coturnix coturnix)
Authors: Albaghdady Eman F. , Al hacham Iman Ibrahim , Baqer kadhim Abdulrazzaq
Published: August 2023

Withdrawal Statement

The authors have withdrawn their manuscript due to [doubt about the validity of the results]. Therefore, the authors do not wish to cite this work as a reference for the project. If you have any questions, please contact the corresponding author.
Building the bioeconomy: A targeted assessment approach to identifying biobased technologies, challenges and opportunities in the UK
Authors: Holland Claire , Shapira Philip
Published: August 2023

We explore opportunities, challenges, and strategies to translate and responsibly scale innovative biobased technologies to build more sustainable bioeconomies. The pandemic and other recent disruptions have increased exposure to issues of resilience and regional imbalance and raised attention to pathways that could shift production and consumption regimes based more on local biobased resources and dispersed production. The paper reviews potential biobased technologies strategies and then identifies promising and feasible options with a focus on the United Kingdom. Initial landscape and bibliometric analyses identified 50 potential existing and emerging potential biobased technologies. These technologies were assessed for their ability to fulfil requirements related to biobased production, national applicability, and economic, societal, and environmental benefits, leading to identification of 18 promising biobased production technologies. Through further analysis and focus group discussion with industrial, governmental, academic, agricultural, and social stakeholders, three technology clusters were identified for targeted assessment, drawing on cellulose-, lignin-, and seaweed-feedstocks. Case studies for each of these clusters were developed, addressing conversations around sustainable management and the use of biomass feedstocks, and associated environmental, social, and economic challenges. These cases are presented with discussion of insights and implications for policy. The approach presented in the paper is put forward as a scalable assessment method which can be useful in prompting, informing, and advancing discussion and deliberation on opportunities and challenges for biobased transformations.
HDAC6 inhibition as a mechanism to prevent axon degeneration in the mSOD1G93Amouse model of ALS
Authors: Phipps Andrew J , Dwyer Samuel , Collins Jessica M , Kabir Fariha , Atkinson Rachel AK , Chowdhury Md Anisuzzaman , Matthews Lyzette , Dixit Deepika , Terry Rhiannon S , Smith Jason , Gueven Nuri , Bennett William , Cook Anthony L , King Anna E , Perry Sharn
Published: August 2023

The loss of upper and lower motor neurons, and their axons is central to the loss of motor function and death in amyotrophic lateral sclerosis (ALS). Due to the diverse range of genetic and environmental factors that contribute to the pathogenesis of ALS, there have been difficulties in developing effective therapies for ALS. One dichotomy emerging in the field is that protection of the neuronal cell soma itself does not prevent axonal vulnerability and degeneration, suggesting the need for targeted therapeutics to prevent axon degeneration. Post-translational modifications of protein acetylation can alter the function, stability and half-life of individual proteins, and can be enzymatically modified by histone acetyltransferases (HATs) and histone deacetyltransferases (HDACs), which add, or remove acetyl groups, respectively. Maintenance of post-translational microtubule acetylation has been suggested as a potential mechanism to stabilise axons and prevent axonal loss and neurodegeneration in ALS. This study has utilized an orally dosed HDAC6 specific inhibitor, ACY-738, prevent deacetylation and stabilize microtubules in the mSOD1G93Amouse model of ALS. Furthermore, co-treatment with riluzole was performed to determine any effects or drug interactions and potentially enhance preclinical research translation. This study shows ACY-738 treatment increased acetylation of microtubules in the spinal cord of mSOD1G93Amice, reduced lower motor neuron degeneration in the lumbar spinal cord of female mice, ameliorated reduction in peripheral nerve axon puncta size, but did not prevent overt motor function decline. The current study also shows peripheral nerve axon puncta size to be partially restored after treatment with riluzole and highlights the importance of co-treatment to measure the potential effects of therapeutics in ALS.

Highlights

ACY-738 inhibits HDAC6 and leads to increased microtubule acetylation in spinal cord of mSOD1G93Amice.

ACY-738 treatment reduces lower motor neuron degeneration in the lumbar spinal cord of mSOD1G93Amice.

ACY-738 treatment restores peripheral nerve axon puncta size of mSOD1G93Amice.

ACY-738 treatment does not prevent overt motor function decline mSOD1G93Amice.

Riluzole treatment partially restores peripheral nerve axon puncta size in mSOD1G93Amice.
Discovery of 2-amide-3-methylester thiophenes that target SARS-CoV-2 Mac1 and repress coronavirus replication, validating Mac1 as an anti-viral target
Authors: Wazir Sarah , Parviainen Tomi A. O. , Pfannenstiel Jessica J. , Duong Men Thi Hoai , Cluff Daniel , Sowa Sven T. , Galera-Prat Albert , Ferraris Dana , Maksimainen Mirko M. , Fehr Anthony R. , Heiskanen Juha P. , Lehtiö Lari
Published: August 2023

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has made it clear that further development of antiviral therapies will be needed to combat additional SARS-CoV-2 variants or novel CoVs. Here, we describe small molecule inhibitors for SARS-CoV-2 Mac1, which counters ADP-ribosylation mediated innate immune responses. The compounds inhibiting Mac1 were discovered through high-throughput screening (HTS) using a protein FRET-based competition assay and the best hit compound had an IC50of 14 µM. Three validated HTS hits have the same 2-amide-3-methylester thiophene scaffold and the scaffold was selected for structure-activity relationship (SAR) studies through commercial and synthesized analogs. We studied the compound binding mode in detail using X-ray crystallography and this allowed us to focus on specific features of the compound and design analogs. Compound27(MDOLL-0229) had an IC50of 2.1 µM and was generally selective for CoV Mac1 proteins after profiling for activity against a panel of viral and human ADP-ribose binding proteins. The improved potency allowed testing of its effect on virus replication and indeed,27inhibited replication of both MHVa prototype CoV, and SARS-CoV-2. Furthermore, sequencing of a drug-resistant MHV identified mutations in Mac1, further demonstrating the specificity of27.Compound27is the first Mac1 targeted small molecule demonstrated to inhibit coronavirus replication in a cell model. This, together with its well-defined binding mode, makes27a good candidate for further hit/lead-optimization efforts.
Microbiome transfer from native to invasive species may increase invasion risk and shorten invasion lag
Authors: Martignoni Maria M. , Kolodny Oren
Published: August 2023

In a fast-changing world, understanding how organisms adapt to their environment is a pressing necessity. Research has focused on genetic adaptation, while our understanding of non-genetic modes is still in its infancy. Particularly, the host-associated microbiome may strongly influence an organism’s ability to cope with its environment. The presence of certain microbes in the gut, for example, can facilitate the utilization of dietary resources, provide protection from pathogens, and increase resilience to diverse abiotic conditions. However, the role that the microbiome may play in species’ adaptation to novel challenges is largely unexplored, experimentally as well as theoretically. Here, we study the possibility of such adaptation in invasive species. We present and explore a new hypothesis: Invasive species may rapidly adapt to local conditions by adopting beneficial microbes of similar co-occurring native species. Ironically, due to competition, these native species are also those most likely to suffer from the invaders’ spread. We formulate a mathematical framework to investigate how the transfer of beneficial microbes between a native and an introduced species can alter their competitive dynamics. We suggest that, non-intuitively, the presence of a related native species mayfacilitatethe success of an invasive species’ establishment. This occurs when the invader’s fitness is strongly influenced by adaptation to local conditions that is provided by microbes acquired from the natives’ microbiomes. Further, we show that in such cases a delayed acquisition of native microbes may explain the occurrence of an invasion lag, and we discuss biological systems that could lend themselves for the testing of our hypotheses. Overall, our results contribute to broadening the conceptualization of rapid adaptation via microbiome transfer and offer possible insights for designing early intervention strategies for invasive species management during their lag phase.
Developmental pyrethroid exposure disrupts molecular pathways for MAP kinase and circadian rhythms in mouse brain
Authors: Nguyen Jennifer H. , Curtis Melissa A. , Imami Ali S. , Ryan William G. , Alganem Khaled , Neifer Kari L. , Saferin Nilanjana , Nawor Charlotte N. , Kistler Brian P. , Miller Gary W. , Shukla Rammohan , McCullumsmith Robert E. , Burkett James P.
Published: August 2023

Neurodevelopmental disorders (NDDs) are a category of pervasive disorders of the developing nervous system with few or no recognized biomarkers. A significant portion of the risk for NDDs, including attention deficit hyperactivity disorder (ADHD), is contributed by the environment, and exposure to pyrethroid pesticides during pregnancy has been identified as a potential risk factor for NDD in the unborn child. We recently showed that low-dose developmental exposure to the pyrethroid pesticide deltamethrin in mice causes male-biased changes to ADHD- and NDD-relevant behaviors as well as the striatal dopamine system. Here, we used an integrated multiomics approach to determine the broadest possible set of biological changes in the mouse brain caused by developmental pyrethroid exposure (DPE). Using a litter-based, split-sample design, we exposed mouse dams during pregnancy and lactation to deltamethrin (3 mg/kg or vehicle every 3 days) at a concentration well below the EPA-determined benchmark dose used for regulatory guidance. We raised male offspring to adulthood, euthanized them, and pulverized and divided whole brain samples for split-sample transcriptomics, kinomics and multiomics integration. Transcriptome analysis revealed alterations to multiple canonical clock genes, and kinome analysis revealed changes in the activity of multiple kinases involved in synaptic plasticity, including the mitogen-activated protein (MAP) kinase ERK. Multiomics integration revealed a dysregulated protein-protein interaction network containing primary clusters for MAP kinase cascades, regulation of apoptosis, and synaptic function. These results demonstrate that DPE causes a multi-modal biophenotype in the brain relevant to ADHD and identifies new potential mechanisms of action.

NEW & NOTEWORTHY

Here, we provide the first evidence that low-dose developmental exposure to the pyrethroid pesticide, deltamethrin, results in molecular disruptions in the adult mouse brain in pathways regulating circadian rhythms and neuronal growth (MAP kinase). This same exposure causes a neurodevelopmental disorder (NDD) relevant behavioral changes in adult mice, making these findings relevant to the prevention of NDDs.
Tumor-Specific CD8+T Cells from the Bone Marrow Resist Exhaustion and Exhibit Increased Persistence in Tumor-Bearing Hosts as Compared to Tumor Infiltrating Lymphocytes
Authors: Zawidzka Elizabeth M. , Biavati Luca , Thomas Amy , Zanettini Claudio , Marchionni Luigi , Leone Robert , Borrello Ivan
Published: August 2023

Immunotherapy is now an integral aspect of cancer therapy. Strategies employing adoptive cell therapy (ACT) have seen the establishment of chimeric antigen receptor (CAR)-T cells using peripheral blood lymphocytes as well as tumor infiltrating lymphocytes (TILs) with significant clinical results. Despite these successes, the limitations of the current strategies are also emerging and novel approaches are needed. The bone marrow (BM) is an immunological niche that houses T cells with specificity for previously encountered antigens, including tumor-associated antigens from certain solid cancers. This study sought to improve our understanding of tumor-specific BM T cells in the context of solid tumors by comparing them with TILs, and to assess whether there is a rationale for using the BM as a source of T cells for ACT against solid malignancies. Herein, we demonstrate that T cells from the BM appear superior to TILs as a source of cells for cellular therapy. Specifically, they possess a memory-enriched phenotype and exhibit improved effector function, greater persistence within a tumor-bearing host, and the capacity for increased tumor infiltration. Taken together, these data provide a foundation for further exploring the BM as a source of tumor-specific T cells for ACT in solid malignancies.

Key Messages

What is already known on this topic

TIL therapy shows efficacy but significant limitations. T cell quality is an important determinant of responses to cellular immunotherapy.

What this study adds

T cells from the BM appear superior to TILs in phenotype, transcriptional profile, and function. These differences appear driven by tissue (e.g., bone marrow as compared to tumor).

How this study might affect research, practice or policy

The BM could serve as an alternative source of cells for adoptive cellular therapy for solid tumors.