bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic modifier alpha-ketoglutarate modulates aberrant gene body methylation and hydroxymethylation marks in diabetic heart
Authors: Dhat Rohini , Mongad Dattatray , Raji Sivarupa , Arkat Silpa , Mahapatra Nitish R. , Singhal Nishant , Sitasawad Sandhya L.
Published: April 2023

Background

Diabetic cardiomyopathy (DCM) is a leading cause of death in diabetic patients. Hyperglycemic myocardial microenvironment significantly alters chromatin architecture and the transcriptome, resulting in aberrant activation of signaling pathways in a diabetic heart. Epigenetic marks play vital roles in transcriptional reprogramming during the development of DCM. The current study is aimed to profile genome-wide DNA (hydroxy)methylation patterns in the hearts of control and streptozotocin (STZ)-induced diabetic rats and decipher the effect of modulation of DNA methylation by alpha-ketoglutarate (AKG), a TET enzyme cofactor, on the progression of DCM.

Methods

Diabetes was induced in male adult Wistar rats with an intraperitoneal injection of STZ. Diabetic and vehicle control animals were randomly divided into groups with/without AKG treatment. Cardiac function was monitored by performing cardiac catheterization. Global methylation (5mC) and hydroxymethylation (5hmC) patterns were mapped in the Left ventricular tissue of control and diabetic rats with the help of an enrichment-based (h)MEDIP-sequencing technique by using antibodies specific for 5mC and 5hmC. Sequencing data were validated by performing (h)MEDIP-qPCR analysis at the gene-specific level, and gene expression was analyzed by qPCR. The mRNA and protein expression of enzymes involved in the DNA methylation and demethylation cycle were analyzed by qPCR and western blotting. Global 5mC and 5hmC levels were also assessed in high glucose-treated DNMT3B knockdown H9c2 cells.

Results

We found the increased expression of DNMT3B, MBD2, and MeCP2 with a concomitant accumulation of 5mC and 5hmC, specifically in gene body regions of diabetic rat hearts compared to the control. Calcium signaling was the most significantly affected pathway by cytosine modifications in the diabetic heart. Additionally, hypermethylated gene body regions were associated with Rap1, apelin, and phosphatidyl inositol signaling, while metabolic pathways were most affected by hyperhydroxymethylation. AKG supplementation in diabetic rats reversed aberrant methylation patterns and restored cardiac function. Hyperglycemia also increased 5mC and 5hmC levels in H9c2 cells, which was normalized by DNMT3B knockdown or AKG supplementation.

Conclusion

This study demonstrates that reverting hyperglycemic damage to cardiac tissue might be possible by erasing adverse epigenetic signatures by supplementing epigenetic modulators such as AKG along with an existing antidiabetic treatment regimen.
COVID-19 cases reported in Colorado following screening at selected US airports, January – July 2020
Authors: Shaum Anna , Harlow Tye , Gulati Reena K. , Berro Andre , House Jennifer
Published: April 2023

Objective

We sought to estimate the proportion of air travelers who may have been infected with SARS-CoV-2 upon arrival to Colorado by comparing data on Colorado residents screened upon entering the US to COVID-19 cases reported in the state. Data on Colorado’s screened passengers arriving into the US between January 17 and July 30, 2020 were compared to Colorado’s Electronic Disease Reporting System. We conducted a descriptive analysis of true matches, including age, gender, case status, symptom status, time from arrival to symptom onset (days), and time from arrival to specimen collection date (days).

Results

Fourteen confirmed COVID-19 cases in travelers who were diagnosed within 14 days after arriving in Colorado were matched to the 8,272 travelers who underwent screening at 15 designated airports with a recorded destination of Colorado, or 0.2%. Most (N = 13/14 or 93%) of these infected travelers arrived in Colorado in March 2020; 12 (86%) of them were symptomatic. Entry screening for COVID-19 and the sharing of traveler information with the Colorado Department of Public Health and Environment appeared to identify few cases early in the pandemic. Symptom-based entry screening and sharing of traveler information was minimally effective at decreasing travel-associated COVID-19 transmission.
Bilateral pneumothorax in a patient with angiosarcoma of the scalp: a case report
Authors: Vaqar Maham , Sharif Ayesha , Iqbal Nousheen , Irfan Muhammad
Published: May 2023

Background

Angiosarcoma is a rare, vascular malignancy that arises from endothelial cells of blood vessels. This case report aims to create the awareness of its existence in the region and its mode of presentation.

Case presentation

A 63-year-old Pakistani man presented to the emergency department with sudden bilateral chest pain and shortness of breath for 2 days. On examination, a scalp lesion was seen which had been increasing in size over the last 6 weeks. The lesion was 8 × 10 cm in size with an irregular border, non-tender, violet and dome-shaped in elevation on the right occipito-parietal lobe of the skull. Chest computed tomography (CT) showed multiple cystic lesions on both lungs, patchy areas of ground-glass opacities, nodules of variable sizes and bilateral pneumothorax. Bilateral tube thoracostomy was performed which provided symptomatic relief for shortness of breath. His bronchoalveolar lavage (BAL) was negative for infection. He underwent biopsy of scalp lesion which was positive for aggressive angiosarcoma.

Conclusion

Bilateral spontaneous pneumothorax can be the initial manifestation of aggressive cutaneous angiosarcoma and frequently leads to respiratory failure. Early recognition is essential to prevent delay in diagnosis and management.
Spinocerebellar ataxia type 14 (SCA14) in an Argentinian family: a case report
Authors: Duggirala Niharika , Ngo Kathie J. , Pagnoni Sabrina M. , Rosa Alberto L. , Fogel Brent L.
Published: April 2023

Background

Hereditary spinocerebellar ataxias are a group of genetic neurological disorders that result in degeneration of the cerebellum and brainstem, leading to difficulty in controlling balance and muscle coordination.

Case presentation

A family affected by spinocerebellar ataxia was identified in Argentina and investigated using whole exome sequencing to determine the genetic etiology. The proband, a female white Hispanic aged 48, was noted to have slowly progressive gait ataxia, dysarthria, nystagmus, and moderate cerebellar atrophy. Whole exome sequencing was performed on three affected and two unaffected family members and revealed a dominant pathogenic variant, p.Gln127Arg (19:54392986 A>G), in the protein kinase C gamma gene, and the family was diagnosed with spinocerebellar ataxia type 14.

Conclusions

To our knowledge, no previous cases of spinocerebellar ataxia type 14 have been reported in Argentina, expanding the global presence of this neurological disorder. This diagnosis supports whole exome sequencing as a high-yield method for identifying coding variants causing cerebellar ataxias and emphasizes the importance of broadening the clinical availability of whole exome sequencing for undiagnosed patients and families.
The pluripotent factor OCT4A enhances the self-renewal of human dental pulp stem cells by targeting lncRNA FTX in an LPS-induced inflammatory microenvironment
Authors: Hong Hong , Zeng Kai , Zhou Can , Chen Xiaochuan , Xu Zhezhen , Li Mengjie , Liu Lu , Zeng Qian , Tao Qian , Wei Xi
Published: April 2023

Background

Regulating the pluripotency of human dental pulp stem cells (hDPSCs) is key for the self-repair of injured dental pulp. We previously found that OCT4A promotes the proliferation and odontogenic differentiation of human dental pulp cells (hDPCs). Recent studies have shown the interaction between OCT4A and lncRNAs in pluripotency maintenance of various stem cells. The aim of this study was to explore the underlying roles and mechanisms of OCT4A and its related lncRNAs in the proliferation and multidirectional differentiation of hDPSCs in an inflammatory microenvironment.

Methods

Human lncRNA microarrays were applied to screen out the differentially expressed lncRNAs in hDPSCs between the OCT4A-overexpressing and vector groups. Lipopolysaccharide (LPS) was used to simulate the inflammatory microenvironment. The effects of OCT4A and the lncRNA FTX on the proliferation and multidifferentiation of hDPSCs were observed by the CCK-8 assay, EdU staining, real-time PCR, western blotting, and Alizarin red and oil red O staining. Bioinformatics analysis and chromatin immunoprecipitation (ChIP) assays were performed to clarify the targeted mechanism of OCT4A on FTX. The regulation by FTX of the expression of OCT4A and its downstream pluripotent transcription factors SOX2 and c-MYC was further detected by real-time PCR and western blotting.

Results

The microarray results showed that 978 lncRNAs (250 of which were upregulated and 728 downregulated) were potentially differentially expressed genes (fold change ≥ 2, P < 0.05). LPS stimulation attenuated the self-renewal of hDPSCs. OCT4A enhanced the cell proliferation and multidifferentiation capacities of hDPSCs in an inflammatory microenvironment, while FTX exhibited the opposite effects. OCT4A negatively regulated FTX function by binding to specific regions on the FTX promoter, thereby inhibiting the transcription of FTX. Moreover, overexpression of FTX downregulated the expression of OCT4A, SOX2 and c-MYC, whereas knockdown of FTX facilitated their expression.

Conclusions

OCT4A was found to be a crucial factor maintaining the self-renewal of hDPSCs by transcriptionally targeting FTX in an inflammatory microenvironment. Moreover, we proposed a novel function of FTX in negatively regulating the pluripotency and multilineage differentiation capacity of hDPSCs. The hierarchical organization between OCT4A and FTX expanded the understanding of the network between transcription factors and lncRNAs in fine-tuning the pluripotency/differentiation balance of adult stem cells, and provided prospective targets for optimizing dental-derived stem cell sources for regenerative endodontics.
Semi-automated optimized method to isolate CRISPR/Cas9 edited human pluripotent stem cell clones
Authors: Frank Elie , Cailleret Michel , Nelep Constantin , Fragner Pascal , Polentes Jérome , Herardot Elise , El Kassar Lina , Giraud-Triboult Karine , Monville Christelle , Ben M’Barek Karim
Published: April 2023

Background

CRISPR/Cas9 editing systems are currently used to generate mutations in a particular gene to mimic a genetic disorder in vitro. Such “disease in a dish” models based on human pluripotent stem cells (hPSCs) offer the opportunity to have access to virtually all cell types of the human body. However, the generation of mutated hPSCs remains fastidious. Current CRISPR/Cas9 editing approaches lead to a mixed cell population containing simultaneously non-edited and a variety of edited cells. These edited hPSCs need therefore to be isolated through manual dilution cloning, which is time-consuming, labor intensive and tedious.

Methods

Following CRISPR/Cas9 edition, we obtained a mixed cell population with various edited cells. We then used a semi-automated robotic platform to isolate single cell-derived clones.

Results

We optimized CRISPR/Cas9 editing to knock out a representative gene and developed a semi-automated method for the clonal isolation of edited hPSCs. This method is faster and more reliable than current manual approaches.

Conclusions

This novel method of hPSC clonal isolation will greatly improve and upscale the generation of edited hPSCs required for downstream applications including disease modeling and drug screening.

Graphical Abstract
Immunomodulatory amnion-derived mesenchymal stromal cells preserve muscle function in a mouse model of Duchenne muscular dystrophy
Authors: Nitahara-Kasahara Yuko , Nakayama Soya , Kimura Koichi , Yamaguchi Sho , Kakiuchi Yuko , Nito Chikako , Hayashi Masahiro , Nakaishi Tomoyuki , Ueda Yasuyoshi , Okada Takashi
Published: April 2023

Background

Duchenne muscular dystrophy (DMD) is an incurable genetic disease characterized by degeneration and necrosis of myofibers, chronic inflammation, and progressive muscle weakness resulting in premature mortality. Immunosuppressive multipotent mesenchymal stromal cell (MSC) therapy could be an option for DMD patients. We focused on amnion-derived mesenchymal stromal cells (AMSCs), a clinically viable cell source owing to their unique characteristics, such as non-invasive isolation, mitotic stability, ethical acceptability, and minimal risk of immune reaction and cancer. We aimed to identify novel immunomodulatory effects of AMSCs on macrophage polarization and their transplantation strategies for the functional recovery of skeletal and cardiac muscles.

Methods

We used flow cytometry to analyze the expression of anti-inflammatory M2 macrophage markers on peripheral blood mononuclear cells (PBMCs) co-cultured with human AMSCs (hAMSCs). hAMSCs were intravenously injected into DMD model mice (mdxmice) to assess the safety and efficacy of therapeutic interventions. hAMSC-treated and untreatedmdxmice were monitored using blood tests, histological examinations, spontaneous wheel-running activities, grip strength, and echocardiography.

Results

hAMSCs induced M2 macrophage polarization in PBMCs via prostaglandin E2production. After repeated systemic hAMSC injections,mdxmice exhibited a transient downregulation of serum creatin kinase. Limited mononuclear cell infiltration and a decreased number of centrally nucleated fibers were indicative of regenerated myofibers following degeneration, suggesting an improved histological appearance of the skeletal muscle of hAMSC-treatedmdxmice. Upregulated M2 macrophages and altered cytokine/chemokine expressions were observed in the muscles of hAMSC-treatedmdxmice. During long-term experiments, a significant decrease in the grip strength in controlmdxmice significantly improved in the hAMSC-treatedmdxmice. hAMSC-treatedmdxmice maintained running activity and enhanced daily running distance. Notably, the treated mice could run longer distances per minute, indicating high running endurance. Left ventricular function in DMD mice improved in hAMSC-treatedmdxmice.

Conclusions

Early systemic hAMSC administration inmdxmice ameliorated progressive phenotypes, including pathological inflammation and motor dysfunction, resulting in the long-term improvement of skeletal and cardiac muscle function. The therapeutic effects might be associated with the immunosuppressive properties of hAMSCs via M2 macrophage polarization. This treatment strategy could provide therapeutic benefits to DMD patients.
The preclinical and clinical progress of cell sheet engineering in regenerative medicine
Authors: Hu Danping , Li Xinyu , Li Jie , Tong Pei , Li Zhe , Lin Ge , Sun Yi , Wang Juan
Published: April 2023

Cell therapy is an accessible method for curing damaged organs or tissues. Yet, this approach is limited by the delivery efficiency of cell suspension injection. Over recent years, biological scaffolds have emerged as carriers of delivering therapeutic cells to the target sites. Although they can be regarded as revolutionary research output and promote the development of tissue engineering, the defect of biological scaffolds in repairing cell-dense tissues is apparent. Cell sheet engineering (CSE) is a novel technique that supports enzyme-free cell detachment in the shape of a sheet-like structure. Compared with the traditional method of enzymatic digestion, products harvested by this technique retain extracellular matrix (ECM) secreted by cells as well as cell-matrix and intercellular junctions established during in vitro culture. Herein, we discussed the current status and recent progress of CSE in basic research and clinical application by reviewing relevant articles that have been published, hoping to provide a reference for the development of CSE in the field of stem cells and regenerative medicine.
Disposition to pediatric intensive care unit post supraglottoplasty repair: A systematic review
Authors: Kang Esther ShinHyun , Turkdogan Sena , Yeung Jeffrey C.
Published: April 2023

Background

Patients undergoing supraglottoplasty are often routinely admitted post-operatively to the pediatric intensive care unit (PICU) due to rare but potentially fatal complications such as airway compromise. A systematic review was performed to determine the rate of post-operative PICU-level respiratory support required by pediatric patients following supraglottoplasty, to identify risk factors for patients who may benefit from post-operative PICU admission and limit unnecessary use of intensivist resources.

Review methods

Key search terms ‘supraglottoplasty’ OR ‘supraglottoplasties’ were queried on three databases: CINHAL, Medline and Embase. Inclusion criteria were pediatric patients under 18 years of age who underwent a supraglottoplasty procedure with either an admission to PICU or requirement for PICU-level respiratory support. Risk of bias was assessed by two independent reviewers using QUADAS-2. Findings were critically appraised by three independent reviewers and pooled proportions of criteria meeting PICU admission were calculated for meta-analysis.

Results

Nine studies met inclusion criteria, totaling 922 patients. Age at time of surgery ranged from 19 days to 15.7 years with mean age of 5.65 months. A weighted pooled estimate suggested that 19% (95% CI 14–24%) of patients who underwent supraglottoplasty required PICU-admission. The included studies revealed several patient and surgical factors have been linked to postoperative respiratory issues requiring PICU admission, including: neurological disease, perioperative oxygen saturation < 95%, prolonged surgical time and age < 2 months.

Conclusions

This study found that the majority of supraglottoplasty patients do not require significant postoperative respiratory support and suggests that routine PICU admission of these patients may be avoided by careful patient selection. Given the wide heterogeneity of outcome measures, further studies are needed to determine the ideal PICU admission criteria following supraglottoplasty.

Graphical Abstract
Surgical strategies for localized colorectal amyloidosis
Authors: Tahara Shunya , Kohyama Mohei , Nakamitsu Atsushi , Sugiyama Yoichi , Tazaki Tatsuya , Taogoshi Hiroyuki , Komo Toshiaki , Yamaguchi Takuro , Ueda Mitsuharu , Ishikawa Akira , Takahashi Shinya , Sasaki Masaru
Published: April 2023

Background

Localized colorectal amyloidosis has a good prognosis, but cases involving bleeding or perforation may require surgery. However, there are few case reports discussing the differences in the surgical strategy between the segmental and pan-colon types.

Case presentation

A 69-year-old woman with a history of abdominal pain and melena was diagnosed with amyloidosis localized in the sigmoid colon by colonoscopy. Since preoperative imaging and intraoperative findings could not rule out malignancy, we performed laparoscopic sigmoid colectomy with lymph-node dissection. Histopathological examination and immunohistochemical staining revealed a diagnosis of AL amyloidosis (λ type). We diagnosed localized segmental gastrointestinal amyloidosis, because there was no amyloid protein in the margins, and the tumor was localized. There were no malignant findings.

Conclusions

Unlike systemic amyloidosis, localized amyloidosis has a favorable prognosis. Localized colorectal amyloidosis can be classified into the segmental type, in which amyloid protein is deposited locally, and the pan-colon type, in which amyloid protein is deposited extensively in the colon. Amyloid protein causes ischemia due to vascular deposition, weakening of the intestinal wall due to muscle layer deposition, and decreased peristalsis due to nerve plexus deposition. No amyloid protein should remain outside the resection area. The pan-colon type is often reported to cause complications such as anastomotic leakage, and primary anastomosis should be avoided. On the other hand, if there is no contamination or tumor remnants in the margin, the segmental type may be considered for primary anastomosis.
Genome-wide expression analysis reveals different heat shock responses in indigenous (Bos indicus) and crossbred (Bos indicus X Bos taurus) cattle
Authors: Sajjanar Basavaraj , Aalam Mohd Tanzeel , Khan Owais , Tanuj Gunturu Narasimha , Sahoo Aditya Prasad , Manjunathareddy Gundallahalli B. , Gandham Ravi Kumar , Dhara Sujoy K. , Gupta Praveen K. , Mishra Bishnu Prasad , Dutt Triveni , Singh Gyanendra
Published: May 2023

Environmental heat stress in dairy cattle leads to poor health, reduced milk production and decreased reproductive efficiency. Multiple genes interact and coordinate the response to overcome the impact of heat stress. The present study identified heat shock regulated genes in the peripheral blood mononuclear cells (PBMC). Genome-wide expression patterns for cellular stress response were compared between two genetically distinct groups of cattle viz., Hariana (B. indicus) and Vrindavani (B. indicus X B. taurus). In addition to major heat shock response genes, oxidative stress and immune response genes were also found to be affected by heat stress. Heat shock proteins such as HSPH1, HSPB8, FKB4, DNAJ4 and SERPINH1 were up-regulated at higher fold change in Vrindavani compared to Hariana cattle. The oxidative stress response genes (HMOX1, BNIP3, RHOB and VEGFA) and immune response genes (FSOB, GADD45B and JUN) were up-regulated in Vrindavani whereas the same were down-regulated in Hariana cattle. The enrichment analysis of dysregulated genes revealed the biological functions and signaling pathways that were affected by heat stress. Overall, these results show distinct cellular responses to heat stress in two different genetic groups of cattle. This also highlight the long-term adaptation of B. indicus (Hariana) to tropical climate as compared to the crossbred (Vrindavani) with mixed genetic makeup (B. indicus X B. taurus).
Cueing natural event boundaries improves memory in people with post-traumatic stress disorder
Authors: Pitts Barbara L. , Eisenberg Michelle L. , Bailey Heather R. , Zacks Jeffrey M.
Published: April 2023

People with post-traumatic stress disorder (PTSD) often report difficulty remembering information in their everyday lives. Recent findings suggest that such difficulties may be due to PTSD-related deficits in parsing ongoing activity into discrete events, a process called event segmentation. Here, we investigated the causal relationship between event segmentation and memory by cueing event boundaries and evaluating its effect on subsequent memory in people with PTSD. People with PTSD (n = 38) and trauma-matched controls (n = 36) watched and remembered videos of everyday activities that were either unedited, contained visual and auditory cues at event boundaries, or contained visual and auditory cues at event middles. PTSD symptom severity varied substantial within both the group with a PTSD diagnosis and the control group. Memory performance did not differ significantly between groups, but people with high symptoms of PTSD remembered fewer details from the videos than those with lower symptoms of PTSD. Both those with PTSD and controls remembered more information from the videos in the event boundary cue condition than the middle cue or unedited conditions. This finding has important implications for translational work focusing on addressing everyday memory complaints in people with PTSD.
Lessons learnt during COVID-19: making sense of Australian and Swedish university lecturers’ experience
Authors: Turner Kristina , O’Brien Siobhan , Wallström Helena , Samuelsson Katarina , Uusimäki Sirkka-Liisa Marjatta
Published: April 2023

This article reports on a study analysing changes in the use of digital technologies and working from home during the COVID-19 crisis and the impact of these changes on the wellbeing of five female university lecturers from Australia and Sweden. Applying collaborative autoethnographical methods, this study employed Weick’s sensemaking framework to explore how the academics made sense of these sudden changes. The Positive emotion, Engagement, Relationships, Meaning, and Accomplishment (PERMA) wellbeing framework was also employed to explore the effect of these changes on the academics’ wellbeing. Findings from the reflective narratives show that after the initial experiences of stress, each university lecturer was able to adapt and navigate the online teaching environment during the pandemic. However, the time constraints in preparing and adapting to online teaching, and working from home, were experienced by some of the university lecturers as highly stressful and isolating which impacted their sense of wellbeing. Even so, working from home was recognized as a positive experience, providing time for research, hobbies, and time with family. This study addresses a gap in current knowledge by examining the impact of the sudden transition to online teaching and learning had on academic wellbeing as conceptualised through the PERMA framework. In addition, by applying Weick’s sensemaking framework, this study provides a unique perspective around how academics made sense of the sudden switch to online teaching and learning during COVID-19.
Changes in canopy cover and forest structure following dormant season and early growing season prescribed burns in the Southern Appalachians, USA
Authors: Melcher Allison L. , Hagan Donald , Barrett Kyle , Ross Beth , Lorber Jean
Published: April 2023

Background

Fire seasonality is important for forest managers to consider when restoring historical disturbance regimes and recovering native ecosystem structure and composition, but it is less understood and less frequently studied than other aspects of fire ecology. In the Southern Appalachians, historical fires likely occurred most often in late spring and early summer when fuels were dry and canopy conditions were conducive to fire; however, most prescribed fires today occur during the dormant season (January–March). Because fire behavior can vary seasonally, it is important for forest managers to understand the practical applications of fire season in order to burn at a time that meets management objectives. Therefore, we investigated the effect of fire seasonality on forest structure and land cover diversity in the Southern Appalachians.

Results

Using a complete randomized block design, we analyzed leaf-on canopy cover imagery with ArcGIS Pro to compare canopy cover and forest structure between growing and dormant season burns. We compared imagery between three blocks, each with an unburned control unit, dormant season burn, and growing season burn, and found an average of 8.84% (SE = ± 1.46) reduction in canopy cover in growing season treatment units from pre-burn (2017) to post-burn (2019) compared to 5.21% (SE = ± 1.51) reduction in dormant season treatment units and 0.01% (SE = ± 0.009) reduction in unburned controls. Canopy cover reductions corresponded with substantial increases in early- and mid-successional habitat, edge length, and land cover diversity — especially in growing season burn treatment units.

Conclusions

Our results indicate that early growing season burns are more effective than dormant season burns at enhancing forest structural heterogeneity. Early growing season burns, therefore, may be a viable option for forest managers looking to expand their burn season and achieve restoration and management goals faster than traditional dormant season burns.
A look at the field response of MEMS sensors compared to analog geophones
Authors: Criss Jason , Selvakumar Arjun
Published: May 2023

Commercial sensors for seismic data collection have changed little in the previous 20 years. The sensors that are available today have exceptional dynamic range and sensitivity. This paper explores and compares the field response of analog geophones and all-digital microelectrical-mechanical-sensors-based accelerometers from the perspective of the dynamic range of the recorded data. Also discussed are other characteristics of each sensor type and the potential impact on seismic data quality.
Geophysics Bright Spots
Authors: Behura Jyoti
Published: May 2023

Welcome to the latest installment of Geophysics Bright Spots. There are a number of interesting research articles in the recent issue of Geophysics. Here is an article that piqued the editors’ interests.
Dose-Escalated Radiation Alone or in Combination With Short-Term Total Androgen Suppression for Intermediate-Risk Prostate Cancer: Patient-Reported Outcomes From NRG/Radiation Therapy Oncology Group 0815 Randomized Trial
Authors: Movsas Benjamin , Rodgers Joseph P. , Elshaikh Mohamed A. , Martinez Alvaro A. , Morton Gerard C. , Krauss Daniel J. , Yan Di , Citrin Deborah E. , Hershatter Bruce W. , Michalski Jeff M. , Ellis Rodney J. , Kavadi Vivek S. , Gore Elizabeth M. , Gustafson Gary S. , Schulz Craig A. , Velker Vikram M. , Olson Adam C. , Cury Fabio L. , Papagikos Michael A. , Karrison Theodore G. , Sandler Howard M. , Bruner Deborah W.
Published: April 2023

PURPOSE

To report patient-reported outcomes (PROs) of a phase III trial evaluating total androgen suppression (TAS) combined with dose-escalated radiation therapy (RT) for patients with intermediate-risk prostate cancer.

METHODS

Patients with intermediate-risk prostate cancer were randomly assigned to dose-escalated RT alone (arm 1) or RT plus TAS (arm 2) consisting of luteinizing hormone-releasing hormone agonist/antagonist with oral antiandrogen for 6 months. The primary PRO was the validated Expanded Prostate Cancer Index Composite (EPIC-50). Secondary PROs included Patient-Reported Outcome Measurement Information System (PROMIS)-fatigue and EuroQOL five-dimensions scale questionnaire (EQ-5D). PRO change scores, calculated for each patient as the follow-up score minus baseline score (at the end of RT and at 6, 12, and 60 months), were compared between treatment arms using a two-sample t test. An effect size of 0.50 standard deviation was considered clinically meaningful.

RESULTS

For the primary PRO instrument (EPIC), the completion rates were ≥86% through the first year of follow-up and 70%-75% at 5 years. For the EPIC hormonal and sexual domains, there were clinically meaningful ( P < .0001) deficits in the RT + TAS arm. However, there were no clinically meaningful differences by 1 year between arms. There were also no clinically meaningful differences at any time points between arms for PROMIS-fatigue, EQ-5D, and EPIC bowel/urinary scores.

CONCLUSION

Compared with dose-escalated RT alone, adding TAS demonstrated clinically meaningful declines only in EPIC hormonal and sexual domains. However, even these PRO differences were transient, and there were no clinically meaningful differences between arms by 1 year.
Learning run-and-tumble chemotaxis with support vector machines
Authors: Ramakrishnan Rahul O. , Friedrich Benjamin M.
Published: April 2023

To navigate in spatial fields of sensory cues, bacterial cells employ gradient sensing by temporal comparison for run-and-tumble chemotaxis. Sensing and motility noise imply trade-off choices between precision and accuracy. To gain insight into these trade-offs, we learn optimal chemotactic decision filters using supervised machine learning, applying support vector machines to a biologically motivated training dataset. We discuss how the optimal filter depends on the level of sensing and motility noise, and derive an empirical power law for the optimal measurement time

with

as a function of the rotational diffusion coefficient D
rot characterizing motility noise. A weak amount of motility noise slightly increases chemotactic performance.
Allometric Scaling of Testosterone Enanthate Pharmacokinetics to Adolescent Hypogonadal Males (IM and SC Administration)
Authors: Vogiatzi Maria G , Jaffe Jonathan S , Amy Takugo , Rogol Alan D
Published: April 2023

Context

Intramuscular (IM) testosterone enanthate (TE) and testosterone pellets were US Food and Drug Administration approved before 1962 for pediatric use but not studied in controlled trials in adolescents.

Objective

An analysis using nonlinear mixed effect (NLME) modeling was designed to evaluate the adult pharmacokinetics (PK) of subcutaneous (SC) and IM TE. This model was used to simulate SC and IM TE administration in adolescents of different weight groups.

Methods

Data from adult male patients in a phase 2 trial were used to characterize the PK of TE using population PK modeling for SC and IM administration: Allometry was used to scale PK parameters from the adult model to simulate adolescent (aged 12 to < 18 years) serum testosterone levels at body weights of 30, 40, 50, and 60 kg after weekly, every-other-week (EOW), and monthly SC and IM administration of 12.5, 25, 50, 75, and 100 mg TE regimens.

Results

The final data set included 714 samples from 15 patients receiving 100 mg SC TE and 123 samples from 10 patients receiving 200 mg IM TE. In simulated populations, average serum concentration SC:IM ratios were 0.783, 0.776, and 0.757 at steady state for weekly, EOW, and monthly dosing groups, respectively. Simulated regimens of 12.5 mg SC TE monthly produced serum testosterone levels representative of early puberty and simulated pubertal stage progression following multiple subsequent testosterone dose increases.

Conclusion

SC TE administration achieved a testosterone exposure-response relationship similar to IM TE in simulated adolescent hypogonadal males, which may reduce size of fluctuations in serum T and related symptoms.
Elevated temperatures dampen the innate immune capacity of developing lake sturgeon (Acipenser fulvescens)
Authors: Bugg William S. , Yoon Gwangseok R. , Schoen Alexandra N. , Weinrauch Alyssa M. , Jeffries Ken M. , Anderson W. Gary
Published: April 2023

Chronic exposure to high temperatures may leave freshwater fishes vulnerable to opportunistic pathogens, particularly during early life stages. Lake sturgeon, Acipenser fulvescens, populations within the northern expanse of their range in Manitoba, Canada, may be susceptible to high temperature stress and pathogenic infection. We acclimated developing lake sturgeon for 22 days to two ecologically relevant, summer temperatures (16 and 20°C). Individuals from both acclimation treatments were then exposed to 0, 30 and 60 µg ml−1 bacterial lipopolysaccharides (endotoxins), as an immune stimulus, for 48 h and sampled 4 and 48 h during trial exposures and following a 7 day recovery period. We then measured whole-body transcriptional (mRNA) responses involved in the innate immune, stress and fatty acid responses following acute exposure to the bacterial endotoxins. Data revealed that overall levels of mRNA transcript abundance were higher in 20°C-reared sturgeon under control conditions. However, following exposure to a bacterial stimulus, lake sturgeon acclimated to 16°C produced a more robust and persistent transcriptional response with higher mRNA transcript abundance across innate immune, stress and fatty acid responses than their 20°C-acclimated counterparts. Additional whole-animal performance metrics (critical thermal maximum, metabolic rate, cortisol concentration and whole-body and mucosal lysozyme activity) demonstrated acclimation-specific responses, indicating compromised metabolic, stress and enzymatic capacity following the initiation of immune-related responses. Our study showed that acclimation to 20°C during early development impaired the immune capacity of developing lake sturgeon as well as the activation of molecular pathways involved in the immune, stress and fatty acid responses. The present study highlights the effects of ecologically relevant, chronic thermal stress on seasonal pathogen susceptibility in this endangered species.
Image guidance and interfractional anatomical variation in paediatric abdominal radiotherapy
Authors: Taylor Sabrina , Lim Pei , Cantwell Jessica , D’Souza Derek , Moinuddin Syed , Chang Yen-Ching , Gaze Mark N , Gains Jennifer , Veiga Catarina
Published: April 2023

Objectives:

To identify variables predicting interfractional anatomical variations measured with cone-beam CT (CBCT) throughout abdominal paediatric radiotherapy, and to assess the potential of surface-guided radiotherapy (SGRT) to monitor these changes.

Methods:

Metrics of variation in gastrointestinal (GI) gas volume and separation of the body contour and abdominal wall were calculated from 21 planning CTs and 77 weekly CBCTs for 21 abdominal neuroblastoma patients (median 4 years, range: 2 – 19 years). Age, sex, feeding tubes, and general anaesthesia (GA) were explored as predictive variables for anatomical variation. Furthermore, GI gas variation was correlated with changes in body and abdominal wall separation, as well as simulated SGRT metrics of translational and rotational corrections between CT/CBCT.

Results:

GI gas volumes varied 74 ± 54 ml across all scans, while body and abdominal wall separation varied 2.0 ± 0.7 mm and 4.1 ± 1.5 mm from planning, respectively. Patients < 3.5 years (p = 0.04) and treated under GA (p < 0.01) experienced greater GI gas variation; GA was the strongest predictor in multivariate analysis (p < 0.01). Absence of feeding tubes was linked to greater body contour variation (p = 0.03). GI gas variation correlated with body (R = 0.53) and abdominal wall (R = 0.63) changes. The strongest correlations with SGRT metrics were found for anterior-posterior translation (R = 0.65) and rotation of the left-right axis (R = −0.36).

Conclusions:

Young age, GA, and absence of feeding tubes were linked to stronger interfractional anatomical variation and are likely indicative of patients benefiting from adaptive/robust planning pathways. Our data suggest a role for SGRT to inform the need for CBCT at each treatment fraction in this patient group.

Advances in knowledge:

This is the first study to suggest the potential role of SGRT for the management of internal interfractional anatomical variation in paediatric abdominal radiotherapy.
Effect of eel and tempe composite flour supplementation on the nutritional status biomarkers of rats with a restricted protein diet: Data from a preclinical trial
Authors: Mentang Feny , Taher Nurmeilita , Nurkolis Fahrul , Gunawan William Ben , Yusuf Vincentius Mario , Sabrina Nindy , Qhabibi Faqrizal Ria , Mayulu Nelly , Taslim Nurpudji Astuti , Permatasari Happy Kurnia
Published: April 2023

Incorporating eels and tempe can replace and complement the content of proteins, macronutrients, and micronutrients, which may be related to curative effects for malnutrition. In addition, converting the ingredients into a form of flour can increase their shelf life and nutrient concentration. Therefore, an in vivo approach was undertaken to explore further the nutritional status value of biomarkers in malnourished male rats (Rattus norvegicus) after Eel and Tempe Composite (ETC) flour supplementation. Data was collected from blood samples (both plasma and serum) of rats in all groups, and the appropriate biomarkers were analyzed. The final data presented in this study is openly available and can be further analyzed using statistical means to determine the dose of ETC flour as the basis of clinical trials, which other researchers can reproduce. This data may also be valuable for those interested in using different analytical methods to research the same questions or even new preclinical studies focusing solely on nutritional status biomarker analysis methods, including clinical trial prospects.
Effectiveness of nifedipine, labetalol, and hydralazine as emergency antihypertension in severe preeclampsia: a randomized control trial
Authors: S Donel , Novri Dhini Aiyulie , Hamidy Yulis , Savira Maya
Published: April 2023

Background: Preeclampsia is a highly prevalent disease among pregnant women. In the event of hypertensive emergency, nifedipine, labetalol, and hydralazine are assigned as first-line therapies in preeclampsia. Further studies are needed to compare the effectiveness of these drugs to find the most cost-effective drug with minimal side effects. This study aimed to compare the effectiveness of these drugs in lowering blood pressure during hypertensive emergencies in severe preeclampsia.

Methods: 60 pregnant women with severe preeclampsia were recruited in this multiple centre double-blind randomized clinical trial from May 2021 to April 2022 in Indonesia. The patients were divided equally into three groups and treated with three doses of nifedipine, labetalol, and hydralazine, respectively within one hour with 20 minutes interval. The effectiveness was measured based on systolic and diastolic blood pressures, and mean arterial pressure (MAP). The observation was carried out until five hours post-third dose administration.  

Results: The blood pressure was reduced significantly after the administration of the first to the third dose of each antihypertensive (p<0.05). A single dose administration, four, one, and three patients had 20% MAP reduction in nifedipine, labetalol, and hydralazine group. Three, seven, and one patient had a failure of reaching 20% MAP reduction even after receiving the third dose. The effectiveness of the drugs to achieve 20% reduction of MAP could be ranked as follows: nifedipine>labetalol>hydralazine (57.49%, 42.13%, and 40.87%, respectively) for single dose and hydralazine>nifedipine>labetalol (111.3%, 85.12%, and 90.04%, respectively) for triple dose.

Conclusions: Nifedipine is the most effective drug to reduce the blood pressure when single dose administration is used, but requires more doses to further reduce the blood pressure. Hydralazine is the most effective when the drug administration is maxed up to three doses within 60 minutes with 20 minutes interval.

Thai Clinical Trials Registry (TCTR): TCTR20221014007 (14/10/2022)
Identifying the most effective Traditional Chinese Medicine treatment modalities for premature ovarian insufficiency: a systematic review and network meta-analysis
Authors: Sin Yen Suan , Chen Min , Sng Kim Sia , Zhang Jianwei
Published: April 2023

Background:This study aimed to systematically evaluate and compare the clinical efficacy of different modalities of Traditional Chinese Medicine (TCM) for the treatment of premature ovarian insufficiency (POI) and identify the most effective treatment modality.

Methods:Six electronic databases (PubMed, OVID, Scopus, CNKI, VIP and WanFang) were screened from their inception until 20/01/2022. This network meta-analysis (NMA) incorporated hormone replacement therapy (HRT) as the placebo and six different TCM treatment modalities as interventions.The primary outcome was total effective rate; the secondary outcomes were improvement in serum follicle-stimulating hormone (FSH), estradiol (E2), luteinizing hormone (LH) and anti-Müllerian hormone (AMH) levels. The Cochrane risk of bias tool was used to appraise the quality of the included studies. Random effect model was used for pairwise meta-analysis using RevMan 5.4. NMA was performed in STATA. The surface under the cumulative ranking curves (SUCRA) and mean rank (MR) were used as evaluation indexes.

Results:Overall, 37 randomized clinical trials involving 2,597 subjects that conformed to the inclusion criteria were included.Herbal medicine combined with catgut-embedding therapy was concluded to achieve the highest total effective rate (MD 4.35; 95% CI 1.32, 14.38) and improvement in AMH level (MD 0.74; 95% CI -0.74, 2.22). HRT combined with herbal medicine and acupuncture was determined to be the most effective treatment model for POI in improving their FSH (MD -13.17; 95% CI -18.17, -8.17), E2(MD 34.29; 95% CI 14.41, 54.18) and LH (MD -15.01; 95% CI -19.95, -10.06) levels.

Conclusions:Combination of HRT, herbal medicine and acupuncture was the most effective treatment modality for patients with POI. We also found that combination of herbal medicine with conventional HRT for patients with POI could effectively improve the clinical effectiveness in all aspects. This result may provide guidance for future treatment guideline implementation for POI.

Registration:PROSPERO(CRD42020163873; 28/04/2020).
Knowledge of disease, diagnosis, adherence and impact of research in an Irish cohort of patients with inflammatory arthritis
Authors: Marzaioli Viviana , Canavan Mary , Donnelly Alex , Wade Siobhan , Fraser Alexander , O'Sullivan Tim , Harney Sinead , Ireland Arthritis , Veale Douglas J. , Fearon Ursula
Published: April 2023

Background: Patient engagement with clinicians results in shared decision making and increased adherence to medication. However, in order for strong patient: clinician partnerships to be achieved, communication barriers need to be identified. Therefore, the aim of this study was to examine the level of understanding of inflammatory arthritis patients and the need for strong patient-partnership in research.

Methods: An online anonymous survey was distributed to patients living with inflammatory arthritis which addressed questions about diagnosis, routine tests, medications and how they work, medication adherence, disease flare, heredity, pregnancy, and patient involvement in research.

Results: There were 1,873 respondents, 1416 of which had inflammatory arthritis (IA)- rheumatoid arthritis (RA) (65.8%) and psoriatic arthritis (PsA) (34.2%). They were predominantly female (RA 86%, PsA 85 %), aged 55±13 and 50±12 years. Less than 35% of patients had an understanding of diagnostic tests, what was measured and the implication for disease, with 75.5% also concerned about heredity. There was a high level of understanding of how specific medications treat inflammatory arthritis (72.9%). Adherence was also very high (>87%), with the main reasons for stopping medication without the advice of their clinician,  ‘feeling better’ and ‘side effects’ however  a significant proportion of patients (69.9%) reported a disease-flare following cessation of medication. Patients (31%) were also concerned that inflammatory arthritis reduced their chances of getting pregnant, with only 8% believing arthritis medications were safe to take during pregnancy. Finally, only 9% of patients had ever been asked to participate in a research study.

Conclusions: This study demonstrates a need for the development of stronger patient-partnerships with clinicians and researchers in relation to patient education and engagement with research, to create a platform where patients can have meaningful input and involvement in future research studies.
Treatment-resistant granulomatosis with polyangiitis: An unusual presentation
Authors: Rahesh Jasmin , Mapp Tavien , Gonugunta Anant , Kazi Iqra , Day Sarah , Diab Mousab , Ratheesh Rani , Naguib Tarek
Published: April 2023

Granulomatosis with polyangiitis (GPA) is a rare systemic small-vessel vasculitis. This inflammatory reaction can affect the upper and lower respiratory tract, as well as the kidneys. The expected age of presentation is in the sixth and seventh decades of life, and Caucasians are mostly affected. The cornerstone of treatment is high-dose glucocorticoids in combination with immunosuppressant, steroid-sparing drugs, which leads to remission in almost 80% of patients. We present an unusual case of a 55-year-old Hispanic woman presenting with acute kidney injury secondary to treatment-resistant GPA. The failure of standard treatment is extremely rare. In addition, this patient presented with primarily renal symptoms, even though head and neck and airway symptoms are expected in almost all cases initially.Keywords: Granulomatosis with polyangiitis, renal failure, treatment failure
Hemopericardium in chronic kidney disease: An uncommon manifestation of pericarditis with a bloody pericardial effusion
Authors: Martin Jackson , Williams Brian , Otahbachi Mohammad
Published: April 2023

Patients with end-stage renal disease are at increased risk for the development of uremic pericarditis or dialysis-associated pericarditis, and either comorbidity can be complicated by pericardial effusion. Patients with end-stage renal disease complaining of dyspnea and chest pain demand a robust differential diagnosis, which can delay an appropriate intervention. Here we describe a patient with pericarditis and hemopericardium causing symptomatic pericardial effusion.Keywords: Uremic hemopericardium, uremic pericarditis, pericardiocentesis