bluuebunny/crossref_metadata_2025 huggingface dataset:
Adherence to Clinical Practice Guidelines for Non-ST Elevation Acute Coronary Syndrome in the Emergency Department: Exploring the Role of Social, Healthcare-system, and Clinical Determinants
Authors: Işik Abdullah Kürşat , Özturan İbrahim Ulaş , Pekdemir Murat , Doğan Nurettin Özgür , Yaka Elif , Yilmaz Serkan
Published: November 2023

Objectives:

The aim of this study was to assess adherence to the European Society of Cardiology 2020 non-ST elevation acute coronary syndrome (NST-ACS) guidelines, identify factors affecting this compliance, and explore the link between adherence and adverse cardiac outcomes.

Methods:

This prospective cohort study was conducted in a tertiary-level academic hospital between January 2022 and January 2023. Patients diagnosed with NST-ACS in the emergency department (ED) were included. The primary outcome measured was the rate of adherence to the guidelines, and secondary outcomes were factors affecting this adherence in the ED and its association with 28-day adverse cardiac outcomes.

Results:

Of the 298 patients included, guideline adherence was achieved in 32.2% in the ED. The highest compliance was observed in performing a 12-lead electrocardiogram (ECG) within 10 minutes (99.7%), while the lowest was found for obtaining additional right and posterior ECG leads when ongoing ischemia was suspected (42.3%). Factors associated with better adherence included the experience level of the treating physician, the presence of cardiac-quality chest pain, initial ischemic ECG findings, higher initial troponin levels, and advanced history, electrocardiogram, age, risk factors, and troponin score and Charlson comorbidity index. Complete guideline adherence over 28 days was achieved in 19.1% of patients and was found to be significantly associated with lower rates of adverse cardiac outcomes.

Conclusions:

Adherence to NST-ACS guidelines was generally low but was associated with improved patient outcomes. This study highlighted the importance of various factors associated with guideline adherence. Future research should explore further barriers to guideline adherence and develop targeted interventions.
Comparison of the Efficacy and Safety of Ranibizumab 0.5 mg versus 1.0 mg with PPV for the Treatment of PDR: A Randomized, Controlled Trial
Authors: Su Tong , Lai Dongwei , Wu Yang , Gu Chufeng , He Shuai , Meng Chunren , Cai Chunyang , Zhang Jingfa , Luo Dawei , Chen Jili , Zheng Zhi , Qiu Qinghua
Published: November 2023

Purpose:

To investigate the effectiveness of two regimens of ranibizumab-assisted pars plana vitrectomy (PPV) in the treatment of patients with proliferative diabetic retinopathy (PDR).

Methods:

This is a prospective, 6-month, randomized, controlled trial. 80 patients with 87 eyes requiring PPV treatment for PDR were included and randomly divided into a 1.0-mg injection group and a 0.5-mg injection group. The ranibizumab was delivered intra-operatively, at the close of surgery. The vitreous hemorrhage (VH) grade, best corrected visual acuity (BCVA), central macular thickness (CMT) and safety data were assessed to Month 6.

Results:

The 1.0-mg injection group had a milder grade and a lower reoccurrence rate of early postoperatively VH than the 0.5-mg injection group (35.0% and 63.4%, respectively, P =0.0195). The mean BCVA of two groups was significantly improved from baseline to 6 months after surgery,1.60 ± 0.72 LogMAR (<20/200) to 0.47 ± 0.49 LogMAR (20/59) for the 1.0-mg injection group, and 1.51 ± 0.69 LogMAR (<20/200) to 0.50 ± 0.31 LogMAR (20/63) for the 0.5-mg injection group, but there was no significant difference between the two groups (P = 0.74). There was no significant difference in the mean decrease in CMT and probability of postoperative adverse events between the two groups.

Conclusion:

Intravitreal injection of 1.0 mg of ranibizumab after PPV compared with the recommended dose of 0.5 mg significantly reduced the recurrence and severity of early postoperative VH in patients with PDR. It also contributed to the early recovery of visual acuity after surgery and did not increase postoperative adverse events.
Ketamine for Traumatic Assault-Induced Depression: A Case Report
Authors: Coffelt Caitlyn B. , Gibson Kyle , VanLandingham Jason
Published: November 2023

BACKGROUND:

This case report describes the use of ketamine as a rapid, effective treatment of depression in a 68-year-old female patient with no significant medical history of psychiatric disorders. Patients who experience intentional or unintentional traumas are at an increased risk for developing depression or posttraumatic stress disorder, and emerging evidence has supported the use of ketamine as an alternative treatment of depression.

CASE PRESENTATION:

This is the case of a 68-year-old female patient who was assaulted, resulting in multiple stab wounds to both hands and the right upper quadrant. She underwent placement of a chest tube and surgical repair of the liver and was subsequently admitted to the intensive care unit. These events led to the development of severe depression symptoms, as evidenced by a Montgomery–Asberg Depression Rating Scale (MADRS) score of 37. As treatment of her acute depression, the patient received a single intravenous dose of ketamine (0.5 mg/kg) infused over 40 min and was monitored for side effects. The MADRS is a 10-item depression screening tool that assesses symptoms and changes over time. Within 4 hr of receiving ketamine, the patient reported a significant improvement in her mood and her MADRS score decreased to 16, classifying this patient as experiencing mild depression. The patient continued to improve, and 24 hr after receiving ketamine, her MADRS score was 4, indicating remission of her depression symptoms.

CONCLUSION:

This case report aims to provide an account of the potential benefits of ketamine as a rapid treatment of depression in an adult trauma patient.
Improving care practices of the patient with type 2 diabetes in community health centers
Authors: Slade Deloris , Carr Kayla , Karimi Masoumeh , Stewart Mary W.
Published: November 2023

Background:

Diabetes ranks seventh in morbidity and mortality in the United States. In addition, more than 25 million Americans living with diabetes depend on community health centers (CHCs) for primary care.

Local problem:

Preimplementation data in a group of CHCs indicated poor adherence to standards of care practices as recommended by the American Diabetes Association (ADA) with quarterly A1c (33.1%), annual serum laboratory tests (66.6%), and annual urine microalbumin (26.5%).

Methods:

Using a pre- and postimplementation comparison method, a NP-led practice improvement project was conducted in a group of CHCs, which sought to (1) identify adherence to ADA care standards; (2) determine whether an intervention could affect adherence to ADA standards; and (3) compare pre- and postimplementation occurrences of hemoglobin A1c greater than 7.1% and greater than 9%.

Intervention:

Intervention composed of an educational component, standing orders to facilitate care practice changes, and electronic health record utilization changes.

Results:

Postimplementation data reveal statistically significant improvements in quarterly hemoglobin A1c (93.6%), annual serum laboratory tests (96.5%), and annual urine microalbumin screening (85.5%).

Conclusions:

Improvements in translation to care for standardized guidelines facilitate improvements in health outcomes for patients. This project demonstrated improvements that can decrease the morbidity and mortality experienced by persons living with diabetes and being seen within a CHC. In addition, this project demonstrated that advanced practice nurses have the training and occupy a unique position within health care to spearhead initiatives for translation of evidence into care practices.
Extreme Reticulocytosis After Splenectomy in a Patient With Hemoglobin Mizuho
Authors: Narvestad-Bøttger Helene , Winther-Larsen Anne , Haugbølle Bjerre Jens , Dziegiel Morten Hanefeld , Hansen Anne Todsen , Hasle Henrik
Published: November 2023

Background:

Patients with Hb Mizuho may be splenectomized at a young age to decrease their need for blood transfusions.

Observations:

Transfusion-dependency decreased dramatically in a 4-year-old white boy with Hb Mizuho after splenectomy. Surprisingly, he developed reticulocytosis (>1000×109/L) with a peak reticulocyte percentage of 49%, and erythrocyte abnormalities, including Heinz bodies, Howell-Jolly bodies, and basophilic stippling. Manual reticulocyte counting and flow cytometric measurement with anti-CD71 antibodies supported a truly elevated reticulocyte count.

Conclusions:

We propose possible explanations for the extreme reticulocytosis that arose postsplenectomy and compare the reticulocyte count in the present case with previously published cases.
Pediatric acute hydrocephalus developing after tubercular meningitis: a case report study
Authors: Kachuei Maryam , Zare Ramin , Sadr Zahra , Eghdami Shayan
Published: November 2023

Background:

Tuberculosis ranks second as the most common cause of death among infectious diseases, preceded only by COVID-19, which can involve multiple organs. Tuberculous meningitis (TBM) is known to have serious and atypical complications affecting the central nervous system, especially in more vulnerable populations such as children and adolescents.

Case presentation:

The 15-year-old female patient was admitted to the hospital with altered mental status after complaining of nausea, weakness, and cough for 3 weeks. A chest computed tomography (CT) scan showed cavitary lesions, a lumbar puncture sample had a glucose level of 15 mg/dl, and the brain CT scan revealed acute hydrocephalus. While the patient was treated with anti-tubercular medications, an external ventricular drain was placed and the patient was monitored.

Conclusion:

This report presents acute hydrocephalus as a rare and atypical consequence of disseminated tubercular infection resulting in meningitis.
First case of congenital methemoglobinemia in Nepalese population: a case report
Authors: Bista Prashu Ram , Shrestha Anjila , Shrestha Saloni
Published: November 2023

Introduction and importance:

Congenital methemoglobinemia is a rare hereditary disorder that leads to decreased oxygen delivery to the tissues. The severity of symptoms is directly proportional to the methemoglobin levels in the blood. Furthermore, this is the first case of congenital methemoglobinemia reported in the Nepalese population.

Case presentation:

We herein present a case of a 33-year-old male with congenital methemoglobinemia, the first reported case among the Nepalese population. His peripheral oxygen saturation level did not improve despite increasing the oxygen supplementation, and a saturation gap of more than 5% was present. The dark brown color of the blood was noted on the blood sample. On investigations, the methemoglobin level was 9%.

Clinical discussion:

Congenital methemoglobinemia can occur due to a deficiency of an enzyme known as cytochrome b5 reductase, which primarily converts methemoglobin to hemoglobin. There are two types of congenital methemoglobinemia, type I and type II which can be distinguished clinically by the presence of neurological impairment and mental retardation, which can be seen in type II congenital methemoglobinemia.

Conclusion:

Congenital methemoglobinemia is a rare syndrome and has not been previously reported in the Nepalese population. Although there are various diagnostic clues including relevant medical history, saturation gap of more than 5%, dark brown coloration of blood, and investigations such as methemoglobin level, healthcare services like cytochrome b5 reductase enzymatic activity and molecular genetic testing regarding congenital methemoglobinemia is recommended.
Tranexamic acid for the prevention and treatment of postpartum hemorrhage in resource-limited settings: a literature review
Authors: Gedeno Gelebo Kanbiro , Mulugeta Hailemariam , Mossie Addisu , Geremu Kuchulo , Darma Bahiru
Published: November 2023

Introduction:

Postpartum haemorrhage is a major cause of maternal morbidity and mortality worldwide. Early recognition and appropriate treatment are crucial for managing postpartum haemorrhage.

Objectives:

This literature review aimed to evaluate the efficacy of tranexamic acid in the prevention and treatment of postpartum haemorrhage in resource-limited settings.

Search methods:

This literature review was conducted based on the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines. A computerized systematic search of the MEDLINE (PubMed), Google Scholar, and Cochrane databases using a combination of the following Medical Subject Headings (MeSH) terms for PubMed: [(obstetric haemorrhage OR postpartum haemorrhage OR massive obstetric haemorrhage) AND (tranexamic acid OR antifibrinolytic drugs) AND (prophylaxis OR prevention) AND (management OR treatment) AND (resource-limited settings OR resource-limited area OR developing countries)] to find articles published in English since 2010.

Selection criteria:

Studies on the obstetric population who underwent vaginal or caesarean delivery, comparing the use of tranexamic acid versus placebo (or no treatment) for treatment (or prevention) of postpartum haemorrhage with the outcome of postpartum haemorrhage rate, blood transfusion requirements, uterotonics requirements, hysterectomy, or mortality were included.

Result:

In total, 5315 articles were identified. Following the elimination of duplicates, the methodological quality of 15 studies was evaluated independently, with eligibility determined based on the inclusion and exclusion criteria, as well as outcome variables. Finally, eight articles were included in the review.

Conclusion:

This review provides evidence that the administration of tranexamic acid has the potential to decrease the need for blood transfusion, incidence of postpartum haemorrhage, demand for supplementary uterotonics, and maternal morbidity and mortality with marginal adverse effects. Healthcare systems must develop and implement interventions that involve the use of tranexamic acid for the treatment of postpartum haemorrhage in resource-limited settings.
Changes in Volume and Bone Density of Calvarial Grafts After Two Years of Orbital Reconstruction
Authors: Flores Hernández José Gabriel , Magaña Fernando González , Hidalgo Héctor Omar Malagón , Cano Eugenio García , Enríquez Benjamín García , Arciniega Fabiola Alejandra Becerra , Rodríguez Marte Erika María , Figueroa González Aneth Itzel
Published: November 2023

One of the greatest challenges in orbital reconstruction is to obtain adequate orbital volume and globe projection after traumatic injury. Autologous bone graft has been considered the gold standard for orbital floor reconstruction, but the harvesting yields many possible complications, such as donor site morbidity. Bone resorption is a frequent problem that can lead to insufficient volume after graft placement. There is a theoretically lower resorption rate of skull bone grafts, even though the exact amount is not known yet. This study is the first to evaluate bone volume and density changes of calvarial split bone grafts after orbital floor reconstruction with a 2-year follow-up. Bone volume and density of calvarial split grafts were determined using computed tomography scans and the software program RadiAnt Dicom Viewer in a total of 10 patients with orbital floor fracture reconstruction. Computed tomography scans taken immediately after surgery (T0) and after a postoperative period of 2 years (T1) were evaluated. The authors found a mean bone volume reduction of 34.25% after 2 years. Bone density was still high after 2 years (over 850 HU), with a mean reduction of 8%. Based on these findings, calvarial split bone grafts represent the ideal reconstruction material for orbital floor fractures.
CIRC-MARC2 SILENCING PROTECTS HUMAN CARDIOMYOCYTES FROM HYPOXIA/REOXYGENATION–INDUCED INJURY BY MODULATING MIR-335-5P/TRPM7 AXIS
Authors: Deng Huazhao , Cui Meihong , Liu Ling , Yang Fei
Published: November 2023

Myocardial ischemia-reperfusion injury (MIRI) is a vital risk factor for cardiovascular diseases. Some circular RNAs have been identified as modulators of MIRI. However, the effects of circ-mitochondrial amidoxime reducing component 2 (circ-MARC2) in MIRI are unclear. Our results showed that circ-MARC2 was overexpressed in hypoxia/reoxygenation (H/R)–treated AC16 cells. Circ-MARC2 silencing reversed the inhibitory effect of H/R treatment on cell proliferation and promoting effects on lactate dehydrogenase activity, creatine kinase activity, and cell apoptosis in AC16 cells. Moreover, circ-MARC2 served as the sponge for miR-335-5p and ameliorated H/R-induced AC16 cell damage by decoying miR-335-5p. In addition, transient receptor potential cation channel subfamily M member 7 (TRPM7) was identified as the target gene of miR-335-5p. Overexpression of miR-335-5p relieved H/R-induced AC16 cell damage, whereas TRPM7 elevation abolished the effect. Circ-MARC2 knockdown was able to relieve H/R-induced AC16 cell injury through miR-335-5p/TRPM7 axis.
Assessment of abnormal skeletal muscle perfusion by contrast-enhanced ultrasound with parametric imaging in rats after severe injury, hemorrhagic shock, and whole blood resuscitation
Authors: St. John Alexander , Wang Xu , Ringgold Kristyn , Lindner Jonathan , White Nathan , Stern Susan , López José
Published: November 2023

Background

After severe injury, optical measures of microvascular blood flow (MBF) decrease and do not normalize with resuscitation to normal blood pressure. These changes are associated with organ dysfunction, coagulopathy, and death. However, the pathophysiology is not well understood. Several possible pathways could also contribute to the development of trauma-induced coagulopathy (TIC). A small-animal model of trauma-related MBF derangement that persists after resuscitation and includes TIC would facilitate further study. Parametric contrast-enhanced ultrasound (CEUS) is particularly advantageous in this setting, because it noninvasively assesses MBF in large, deep vascular beds. We sought to develop such a model, measuring MBF with CEUS.

Methods

Sixteen male Sprague-Dawley rats were anesthetized, ventilated, and cannulated. Rats were subjected to either no injury (Sham group) or a standardized polytrauma and pressure-targeted arterial catheter hemorrhage with subsequent whole blood resuscitation (Trauma group). At prespecified timepoints, CEUS measurements of uninjured quadriceps muscle, viscoelastic blood clot strength, and complete blood counts were taken.

Results

After resuscitation, blood pressure normalized, but MBF decreased and remained low for the rest of the protocol. This was primarily driven by a decrease in blood volume with a relative sparing of blood velocity. Viscoelastic blood clot strength and platelet count also decreased and remained low throughout the protocol.

Conclusions

We present a rat model of MBF derangement in uninjured skeletal muscle and coagulopathy after polytrauma that persists after resuscitation with whole blood to normal macrohemodynamics. Parametric CEUS analysis shows this change is primarily due to microvascular obstruction. This platform can be used to develop a deeper understanding of this important process.
HYDROGEN PREVENTS LIPOPOLYSACCHARIDE-INDUCED PULMONARY MICROVASCULAR ENDOTHELIAL CELL INJURY BY INHIBITING STORE-OPERATED Ca2+ ENTRY REGULATED BY STIM1/ORAI1
Authors: Li Yuan , Chen Hongguang , Shu Ruichen , Zhang Xuan , Wang Guiyue , Yin Yiqing
Published: November 2023

Background:Sepsis is a type of life-threatening organ dysfunction that is caused by a dysregulated host response to infection. The lung is the most vulnerable target organ under septic conditions. Pulmonary microvascular endothelial cells (PMVECs) play a critical role in acute lung injury (ALI) caused by severe sepsis. The impairment of PMVECs during sepsis is a complex regulatory process involving multiple mechanisms, in which the imbalance of calcium (Ca2+) homeostasis of endothelial cells is a key factor in its functional impairment. Our preliminary results indicated that hydrogen gas (H2) treatment significantly alleviates lung injury in sepsis, protects PMVECs from hyperpermeability, and decreases the expression of plasma membrane stromal interaction molecule 1 (STIM1), but the underlying mechanism by which H2maintains Ca2+homeostasis in endothelial cells in septic models remains unclear. Thus, the purpose of the present study was to investigate the molecular mechanism of STIM1 and Ca2+release–activated Ca2+channel protein1 (Orai1) regulation by H2treatment and explore the effect of H2treatment on Ca2+homeostasis in lipopolysaccharide (LPS)-induced PMVECs and LPS-challenged mice.Methods:We observed the role of H2on LPS-induced ALI of micein vivo. The lung wet/dry weight ratio, total protein in the bronchoalveolar lavage fluid, and Evans blue dye assay were used to evaluate the pulmonary endothelial barrier damage of LPS-challenged mice. The expression of STIM1 and Orai1 was also detected using epifluorescence microscopy. Moreover, we also investigated the role of H2-rich medium in regulating PMVECs under LPS treatment, which induced injury similar to sepsisin vitro. The expression of STIM1 and Orai1 as well as the Ca2+concentration in PMVECs was examined.Results:In vivo, we found that H2alleviated ALI of mice through decreasing lung wet/dry weight ratio, total protein in the bronchoalveolar lavage fluid and permeability of lung. In addition, H2also decreased the expression of STIM1 and Orai1 in pulmonary microvascular endothelium.In vitro, LPS treatment increased the expression levels of STIM1 and Orai1 in PMVECs, while H2reversed these changes. Furthermore, H2ameliorated Ca2+influx under sepsis-mimicking conditions. Treatment with the sarco/endoplasmic reticulum Ca2+adenosine triphosphatase inhibitor, thapsigargin, resulted in a significant reduction in cell viability as well as a reduction in the expression of junctional proteins, including vascular endothelial-cadherin and occludin. Treatment with the store-operated Ca2+entry inhibitor, YM-58483 (BTP2), increased the cell viability and expression of junctional proteins.Conclusions:The present study suggested that H2treatment alleviates LPS-induced PMVEC dysfunction by inhibiting store-operated Ca2+entry mediated by STIM1 and Orai1in vitroandin vivo.
Psychometric Properties of the Chinese Version of the ElectroConvulsive Therapy Cognitive Assessment
Authors: Liu Xinyu , Liang Sixiang , Liu Jun , Sha Sha , Zhang Ling , Jiang Wei , Jiang Changqing , Hermida Adriana P. , Tang Yilang , McDonald William M. , Ren Yanping , Wang Gang
Published: November 2023

Objectives

Electroconvulsive therapy (ECT) is an effective somatic treatment, but it may be limited by cognitive adverse effects. The existing cognitive screening instruments often lack specificity to ECT-associated cognitive deficits. The ElectroConvulsive Therapy Cognitive Assessment was developed and validated in a clinical setting, but the reliability and validity of the Chinese version of ElectroConvulsive Therapy Cognitive Assessment (ECCA-C) have not been studied in a large clinical sample.

Methods

The ECCA-C and the Montreal Cognitive Assessment (MoCA) were administered to patients with major depressive disorder (MDD) undergoing ECT at 3 time points: pretreatment (baseline), before the fifth treatment, and 1 week posttreatment. The instruments were also administered to a sample of healthy subjects.

Results

Sixty-five patients with MDD and 50 age- and sex-matched healthy controls were recruited in this study. Overall, the patient group had statistically significantly lower MoCA and ECCA-C scores than the control group (both P values <0.001). The Cronbach α of the ECCA-C was 0.88 at baseline. Statistically significant decreases over time were observed in ECCA-C: pre-ECT (23.9 ± 4.0) > mid-ECT (21.3 ± 3.4) > post-ECT (18.7 ± 4.8) (all P values <0.001), whereas no statistically significant changes in MoCA scores were found at these 3 time points (F = 1.86, P = 0.165). A cutoff score of 26.5 on the ECCA-C was found to best differentiate between MDD patients and healthy controls.

Conclusions

The ECCA-C showed satisfactory psychometric properties and may be a more sensitive instrument than the MoCA to assess cognitive impairment associated with ECT.
Progress towards the implementation of control programmes for strongyloidiasis in endemic areas: estimation of number of adults in need of ivermectin for strongyloidiasis
Authors: Buonfrate Dora , Montresor Antonio , Bisoffi Zeno , Tamarozzi Francesca , Bisanzio Donal
Published: November 2023

The World Health Organization has started a process to issue guidelines for the control of strongyloidiasis. The guidelines might recommend to implement preventive chemotherapy (PC) at community level (i.e. to all individuals above 5 years of age), over a defined prevalence threshold. We previously estimated the number of school-age children (SAC) who would need PC. Here we estimate the number of people above 15 years of age who might be included in PC for strongyloidiasis. Based on previous
Strongyloides
prevalence estimates and on countries' age distribution, we retrieved the number of adults in need of PC. We then subtracted the number of people already involved in ivermectin mass distribution for the elimination of onchocerciasis and lymphatic filariasis and people living in countries where
Loa loa
is endemic. The number of adults to be involved in PC was estimated at 905.4 (95% confidence interval (CI): 520.6–1177.2), 660.2 (95% CI: 512.7-1214.9), and 512.1 (95% CI: 276–719.4) million people, when the strongyloidiasis prevalence threshold for implementing PC was set to 10%, 15% and 20%, respectively. Estimates at country level are also provided.These estimates might help endemic countries wishing to implement PC for strongyloidiasis to allocate resources to include adults in addition to SAC in control programmes.

This article is part of the Theo Murphy meeting issue ‘
Strongyloides
: omics to worm-free populations’.
Invade or die: behaviours and biochemical mechanisms that drive skin penetration in
Strongyloides
and other skin-penetrating nematodes
Authors: McClure Courtney R. , Patel Ruhi , Hallem Elissa A.
Published: November 2023

Skin-penetrating nematodes, including the human threadworm
Strongyloides stercoralis
and hookworms in the genera
Necator
and
Ancylostoma
, are gastrointestinal parasites that are a major cause of neglected tropical disease in low-resource settings worldwide. These parasites infect hosts as soil-dwelling infective larvae that navigate towards hosts using host-emitted sensory cues such as odorants and body heat. Upon host contact, they invade the host by penetrating through the skin. The process of skin penetration is critical for successful parasitism but remains poorly understood and understudied. Here, we review current knowledge of skin-penetration behaviour and its underlying mechanisms in the human parasite
S. stercoralis
, the closely related rat parasite
Strongyloides ratti,
and other skin-penetrating nematodes such as hookworms. We also highlight important directions for future investigations into this underexplored process and discuss how recent advances in molecular genetic and genomic tools for
Strongyloides
species will enable mechanistic investigations of skin penetration and other essential parasitic behaviours in future studies.

This article is part of the Theo Murphy meeting issue ‘
Strongyloides
: omics to worm-free populations’.
Locally acquired strongyloidiasis in remote Australia: why are there still cases?
Authors: Ross Kirstin
Published: November 2023

In Australia, strongyloidiasis primarily affects returned travellers, Vietnam veterans and refugees or asylum seekers, and First Nations people. Non-overseas acquired cases are seen almost exclusively in Australian First Nations remote communities. Australian First Nations communities have one of the highest rates of strongyloidiasis in the world. Our work has shown that strongyloidiasis is a disease of poverty. Acknowledging this is important—we need to shift the lens to socioeconomic factors, particularly environmental health hardware such as working toilets and sewerage systems, showers and laundries, and effective wastewater and rubbish removal. The rates of strongyloidiasis in First Nations communities is a result of decades of inadequate, poorly constructed and/or poorly maintained housing, and poor environmental health hardware (hereafter hardware). The solution lies in adequate funding, resulting in well designed and maintained housing and appropriate hardware. Governments need to allow First Nations communities themselves to take the lead role in funding allocation, and design, construction and maintenance of their housing and hardware. This will ensure housing and hardware fulfils cultural and physical needs and desires, and protects health. Improving housing and hardware will also improve other health outcomes.

This article is part of the Theo Murphy meeting issue ‘
Strongyloides
: omics to worm-free populations’.
Advancing
Strongyloides
omics data: bridging the gap with
Caenorhabditis elegans
Authors: Al-Jawabreh Reem , Lastik Dominika , McKenzie Darrin , Reynolds Kieran , Suleiman Mona , Mousley Angela , Atkinson Louise , Hunt Vicky
Published: November 2023

Among nematodes, the free-living model organism
Caenorhabditis elegans
boasts the most advanced portfolio of high-quality omics data. The resources available for parasitic nematodes, including
Strongyloides
spp., however, are lagging behind. While
C. elegans
remains the most tractable nematode and has significantly advanced our understanding of many facets of nematode biology,
C. elegans
is not suitable as a surrogate system for the study of parasitism and it is important that we improve the omics resources available for parasitic nematode species. Here, we review the omics data available for
Strongyloides
spp
.
and compare the available resources to those for
C. elegans
and other parasitic nematodes. The advancements in
C. elegans
omics offer a blueprint for improving omics-led research in
Strongyloides
. We suggest areas of priority for future research that will pave the way for expansions in omics resources and technologies.

This article is part of the Theo Murphy meeting issue ‘
Strongyloides
: omics to worm-free populations’.
Is strongyloidiasis a zoonosis from dogs?
Authors: Bradbury Richard S. , Streit Adrian
Published: November 2023

Strongyloides stercoralis
infection remains a major veterinary and public health challenge globally. This chronic and potentially lifelong disease has fatal outcomes in immunosuppressed people and dogs. Currently, the role of dogs in the transmission cycle of human strongyloidiasis remains enigmatic. While zoonotic transmission to humans from companion animals has been proposed, this has not been confirmed. Modern molecular methods have allowed greater opportunity to explore the genotypes of
S. stercoralis
in dogs and humans. Work thus far has demonstrated that at least two distinct lineages exist, one apparently confined to canine hosts and one found in canine, feline, human and non-human primate hosts. Although genotyping of dog and human isolates from the same village has demonstrated identical genotypes in both species, coprophagia of human waste by dogs confounds interpretation. It remains unclear if dogs act as a zoonotic reservoir for human infection, or vice versa, or if this occurs only in some regions of the world and not in others. These questions must be answered before effective control strategies for strongyloidiasis can be instituted. This review explores the evidence for and against cross-species transmission of
S. stercoralis
between dogs and humans and summarizes future directions for research in this area.

This article is part of the Theo Murphy meeting Issue ‘
Strongyloides
: omics to worm-free populations’.
Strongyloides
in non-human primates: significance for public health control
Authors: Nosková Eva , Sambucci Kelly M. , Petrželková Klára J. , Červená Barbora , Modrý David , Pafčo Barbora
Published: November 2023

Primates are an important source of infectious disease in humans. Strongyloidiasis affects an estimated 600 million people worldwide, with a global distribution and hotspots of infection in tropical and subtropical regions. Recently added to the list of neglected tropical diseases, global attention has been demanded in the drive for its control. Through a literature review of
Strongyloides
in humans and non-human primates (NHP), we analysed the most common identification methods and gaps in knowledge about this nematode genus. The rise of molecular-based methods for
Strongyloides
detection is evident in both humans and NHP and provides an opportunity to analyse all data available from primates. Dogs were also included as an important host species of
Strongyloides
and a potential bridge host between humans and NHP. This review highlights the lack of molecular data across all hosts—humans, NHP and dogs—with the latter highly underrepresented in the database. Despite the cosmopolitan nature of
Strongyloides
, there are still large gaps in our knowledge for certain species when considering transmission and pathogenicity. We suggest that a unified approach to
Strongyloides
detection be taken, with an optimized, repeatable molecular-based method to improve our understanding of this parasitic infection.

This article is part of the Theo Murphy meeting issue ‘
Strongyloides
: omics to worm-free populations’.
Language Uncovers Visuospatial Dysfunction in Posterior Cortical Atrophy: A Natural Language Processing Approach
Authors: Rezaii Neguine , Hochberg Daisy , Quimby Megan , Wong Bonnie , McGinnis Scott , Dickerson Bradford C , Putcha Deepti
Published: November 2023

Introduction

Posterior Cortical Atrophy (PCA) is a syndrome characterized by a progressive decline in higher-order visuospatial processing, leading to symptoms such as space perception deficit, simultanagnosia, and object perception impairment. While PCA is primarily known for its impact on visuospatial abilities, recent studies have documented language abnormalities in PCA patients. This study aims to delineate the nature and origin of language impairments in PCA, hypothesizing that language deficits reflect the visuospatial processing impairments of the disease.

Methods

We compared the language samples of 25 patients with PCA with age-matched cognitively normal (CN) individuals across two distinct tasks: a visually-dependent picture description and a visually-independent job description task. We extracted word frequency, word utterance latency, and spatial relational words for this comparison. We then conducted an in-depth analysis of the language used in the picture description task to identify specific linguistic indicators that reflect the visuospatial processing deficits of PCA.

Results

Patients with PCA showed significant language deficits in the visually-dependent task, characterized by higher word frequency, prolonged utterance latency, and fewer spatial relational words, but not in the visually-independent task. An in-depth analysis of the picture description task further showed that PCA patients struggled to identify certain visual elements as well as the overall theme of the picture. A predictive model based on these language features distinguished PCA patients from CN individuals with high classification accuracy.

Discussion

The findings indicate that language is a sensitive behavioral construct to detect visuospatial processing abnormalities of PCA. These insights offer theoretical and clinical avenues for understanding and managing PCA, underscoring language as a crucial marker for the visuospatial deficits of this atypical variant of Alzheimer’s disease.
The Impact of Group II Pulmonary Hypertension on Congestive Heart Failure Patients Admitted with ST Elevation Myocardial Infarction, A Nationwide Study
Authors: Labban Mohamad El , Mir Mikael R , Abruzzo Alexandra , Boike Sydney , Niaz Fayreal A , Vo Natasha T , Rauf Ibtisam , Khan Syed Anjum
Published: November 2023

Objective

To study the impact of group II pulmonary hypertension (PH) on the outcomes of patients admitted with ST-elevation Myocardial Infarction (STEMI), we conducted a nationwide retrospective cohort study.

Patients and Methods

Using the National Inpatient Sample (NIS) Database from 2017 to 2020, a retrospective study of adult patients with a principal diagnosis of STEMI with a secondary diagnosis with or without group II PH according to ICD-10 codes. Several demographics, including age, race, and gender, were analyzed. The primary endpoint was mortality, while the secondary endpoints included cardiogenic shock, mechanical intubation, length of stay in days, and patient charge in dollars. Multivariate logistic regression model analysis was used to adjust for confounders, with a p-value less than 0.05 considered statistically significant.

Results

The study included 27,020 patients admitted with a STEMI, 95 of whom had group II PH. The mean age for patients with and without PH was 66 and 67, respectively. In the PH group, 37% were females compared to 34% in the non-PH group. The in-hospital mortality rate was higher in the PH group (31.5% vs. 9.5%,P <.001, aOR 3.25,P <.023). The rates and adjusted odds of cardiogenic shock and mechanical ventilation were higher in the PH groups (aOR 1.12 aOR 2.16, respectively) but not statistically significant. Patients with PH had a longer length of stay and a higher total charge.

Conclusion

Group II PH was associated with worse clinical and economic outcomes in heart failure patients admitted with STEMI.
Locally low-rank denoising in transform domains
Authors: Moeller Steen , Buko Erick O. , Parvaze Suhail P. , Dowdle Logan , Ugurbil Kamil , Johnson Casey P. , Akcakaya Mehmet
Published: November 2023

Purpose

To develop an extension to locally low rank (LLR) denoising techniques based on transform domain processing that reduces the number of images required in the MR image series for high-quality denoising.

Theory and Methods

LLR methods with random matrix theory-based thresholds are successfully used in the denoising of MR image series in a number of applications. The performance of these methods depend on how well the LLR assumption is satisfied, which deteriorates with few numbers of images, as is commonly encountered in quantitative MRI applications. We propose a transform-domain approach for denoising of MR image series to represent the underlying signal with higher fidelity when using a locally low rank approximation. The efficacy of the method is demonstrated for fully-sampled k-space, undersampled k-space, DICOM images, and complex-valued SENSE-1 images in quantitative MRI applications with as few as 4 images.

Results

For both MSK and brain applications, the transform domain denoising preserves local subtle variability, whereas the quantitative maps based on image domain LLR methods tend to be locally more homogeneous.

Conclusion

A transform domain extension to LLR denoising produces high quality images and is compatible with both raw k-space data and vendor reconstructed data. This allows for improved imaging and more accurate quantitative analyses and parameters obtained therefrom.
A validated heart-specific model for splice-disrupting variants in childhood heart disease
Authors: Lesurf Robert , Breckpot Jeroen , Bouwmeester Jade , Hanafi Nour , Jain Anjali , Liang Yijing , Papaz Tanya , Lougheed Jane , Mondal Tapas , Alsalehi Mahmoud , Altamirano-Diaz Luis , Oechslin Erwin , Audain Enrique , Dombrowsky Gregor , Postma Alex V , Woudstra Odilia I , Bouma Berto J , Hitz Marc-Phillip , Bezzina Connie R , Blue Gillian , Winlaw David S , Mital Seema
Published: November 2023

Congenital heart disease (CHD) is the most common congenital anomaly. Non-canonical splice-disrupting variants are not routinely evaluated by clinical tests. Algorithms including SpliceAI predict such variants, but are not specific to cardiac-expressed genes. Whole genome (WGS) (n=1083) and myocardial RNA-Sequencing (RNA-Seq) (n=114) of CHD cases was used to identify splice-disrupting variants. Using features of variants confirmed to affect splicing in myocardial RNA, we trained a machine learning model that outperformed SpliceAI for predicting cardiac-specific splice-disrupting variants (AUC 0.92 vs 0.66), and was independently validated in 43 cardiomyopathy probands (AUC 0.88 vs 0.64). Application of this model to 971 CHD WGS samples identified 9% patients with splice-disrupting variants in CHD genes. Forty-one% of predicted splice-disrupting variants were deeply intronic. The burden of variants in CHD genes was higher in cases compared with 2,570 controls. Our model improved genetic yield by identifying splice-disrupting variants that are not evaluated by routine tests.
Repeat mediated excision of gene drive elements for restoring wild-type populations
Authors: Chennuri Pratima R , Zapletal Josef , Monfardini Raquel D , Ndeffo-Mbah Martial Loth , Adelman Zach N , Myles Kevin M
Published: November 2023

We demonstrate here that single strand annealing (SSA) repair can be co-opted for the precise autocatalytic excision of a drive element. Although SSA is not the predominant form of DNA repair in eukaryotic organisms, we increased the likelihood of its use by engineering direct repeats at sites flanking the drive allele, and then introducing a double-strand DNA break (DSB) at a second endonuclease target site encoded within the drive allele. We have termed this technologyRepeatMediatedExcision of aDriveElement (ReMEDE). Incorporation of ReMEDE into the previously described mutagenic chain reaction (MCR) gene drive, targeting theyellowgene ofDrosophila melanogaster, replaced drive alleles with wild-type alleles demonstrating proof-of-principle. Although the ReMEDE system requires further research and development, the technology has a number of attractive features as a gene drive mitigation strategy, chief among these the potential to restore a wild-type population without releasing additional transgenic organisms or large-scale environmental engineering efforts.
VirusImmu: a novel ensemble machine learning approach for viral immunogenicity prediction
Authors: Li Jing , Zhao Zhongpeng , Tai ChengZheng , Sun Ting , Tan Lingyun , Li Xinyu , He Wei , Li HongJun , Zhang Jing
Published: November 2023

Background

The viruses threats provoke concerns regarding their sustained epidemic transmission, making the development of vaccines particularly important. In the prolonged and costly process of vaccine development, the most important initial step is to identify protective immunogens. Machine learning (ML) approaches are productive in analyzing big data such as microbial proteomes, and can remarkably reduce the cost of experimental work in developing novel vaccine candidates.

Results

We intensively evaluated the immunogenicity prediction power of eight commonly-used ML methods by random sampling cross validation on a large dataset consisting of known viral immunogens and non-immunogens we manually curated from the public domain. XGBoost, kNN and RF showed the strongest predictive power. We then proposed a novel soft-voting based ensemble approach (VirusImmu), which demonstrated a powerful and stable capability for viral immunogenicity prediction across the test set and external test set irrespective of protein sequence length. VirusImmu was successfully applied to facilitate identifying linear B cell epitopes against African Swine Fever Virus as confirmed by indirect ELISA in vitro.

Conclusions

VirusImmu exhibited tremendous potentials in predicting immunogenicity of viral protein segments. It is freely accessible athttps://github.com/zhangjbig/VirusImmu.
An In-Depth Evaluation of Federated Learning on Biomedical Natural Language Processing
Authors: Peng Le , Luo Gaoxiang , Zhou Sicheng , Chen Jiandong , Xu Ziyue , Zhang Rui , Sun Ju
Published: November 2023

Language models (LMs) such as BERT and GPT have revolutionized natural language processing (NLP). However, the medical field faces challenges in training LMs due to limited data access and privacy constraints imposed by regulations like the Health Insurance Portability and Accountability Act (HIPPA) and the General Data Protection Regulation (GDPR). Federated learning (FL) offers a decentralized solution that enables collaborative learning while ensuring data privacy. In this study, we evaluated FL on 2 biomedical NLP tasks encompassing 8 corpora using 6 LMs. Our results show that: 1) FL models consistently outperformed models trained on individual clients’ data and sometimes performed comparably with models trained with polled data; 2) with the fixed number of total data, FL models training with more clients produced inferior performance but pre-trained transformer-based models exhibited great resilience. 3) FL models significantly outperformed large language models using zero-/one-shot learning and offered lightning inference speed.
Multi-omics features-based machine learning method improve immunotherapy response in clear cell renal cell carcinoma
Authors: Zhang Yiqun , Pei Zhihua
Published: November 2023

Programmed cell death 1 (PD-1) or PD-ligand 1 (PD-L1) blocker-based strategies have improved the survival outcomes of clear cell renal cell carcinomas (ccRCCs) in recent years, but only a small number of patients have benefited from them. In this study, we identified three inflammatory features through over 1900 autoimmune nephropathy patients-related bulk RNA sequencing, single-cell RNA sequencing analysis, and three immunogenic signatures using genomics (TIs), both of which are associated with response to immune checkpoint blocks (ICBs) and the survival of ccRCC patients. Here, we developed a framework with a TIs-based machine learning approach to accurately predict ICB efficacy. We enrolled more than 1000 ccRCC patients with ICB treatment from five cohorts to apply the model and demonstrated its excellent specificity and robustness. Moreover, our model outperforms well-known ICB predictive biomarkers such as tumor mutational burden (TMB), PD-L1 expression, and tumor immune microenvironment (TME). Overall, the TIs-ML model provides a novel method for guiding precise immunotherapy in ccRCC.
Introducing multifactorial electroculturomics: Alternating Current Electric Pulses, combined with mild thermal treatment, exhibit antimicrobial or stimulatory effects on bacterial pathogens and enteroviruses, implying prospects for targeted microbiomics applications
Authors: Spanou Grigoria , Daskou Maria , Kambouris Manousos E. , Mitsagga Chrysanthi , Mossialos Dimitris , Velegraki Aristea , Patrinos George P. , Giavasis Ioannis
Published: November 2023

AIMS

To surrogate chemical and high-energy microbicidals, Electroceuticals may be used as a stand-alone or combined treatment under the guise of Electroculturomics.

METHODS AND RESULTS

Using high and low settings of Intensity and Frequency of a medical-rated instrument (TENS) of alternating current the viability and propagation of seven pathogenic bacteria and one enterovirus of environmental and medical importance were testedin vitro, in order to establish the interaction of electroceuticals and mild pasteurization protocols and identify potential synergies and/or antagonism of these treatments. The combined regimen showed synergy, following the prerogatives of the Bioelectric Effect, and antagonism. High frequency (800Hz) rather than low (2 Hz) seems detrimental, while intensity (10 or 1 mA) seems almost inconsequential, while longer sessions enhance detrimental effects but short exposure may be beneficial.

CONCLUSIONS

No single treatment seems optimal for all tested bacteria. High frequency can be effective against low titers of Enterovirus, but at higher titers, the effect may be reversed. Case-specific effects on microbial growth patterns seem to be the norm.

SIGNIFICANCE AND IMPACT OF STUDY

Diverse mechanisms of microbicidal or stimulatory activity are implied, allowing individualized uses and targeted applications in food and environmental safety, therapeutics and industrial bioprocessing.