bluuebunny/crossref_metadata_2025 huggingface dataset:
Appropriate Surgical Timing of Salter Innominate Osteotomy for Residual Acetabular Dysplasia in Children
Authors: Sawamura Kenta , Kitoh Hiroshi , Kaneko Hiroshi , Kitamura Akiko , Hattori Tadashi
Published: August 2022

Background:

Salter innominate osteotomy (SIO) provides favorable results for treating residual acetabular dysplasia in young children. In this study, we examined the midterm results of SIO according to the age at surgery to determine the optimal timing of this procedure.

Methods:

We retrospectively examined 50 hips of 42 patients (8 boys and 34 girls) with acetabular dysplasia who underwent SIO and were followed up until skeletal maturity. The center-edge angle (CEA) was measured based on the anteroposterior radiographs of the hip obtained before surgery, 5 weeks after surgery, and at the latest follow-up. Severin classification was evaluated at the latest follow-up. Patients were categorized into 3 groups according to age at surgery: younger than 7 years of age (group A), 7 to 8 years of age (group B), and 9 years of age or older (group C).

Results:

The mean preoperative CEA level of 0.9 degrees improved to 17.1 degrees postoperatively, which was increased to 28.1 degrees at the latest examination. Overall, 45 hips (90%) were classified as Severin I or II, with 96% in group A, 94% in group B, and 57% in group C. In group C, postoperative acetabular coverage was similar to that in the other groups (16.6 degrees in group A, 14.8 degrees in group B, and 18.1 degrees in group C), although the final outcome was unsatisfactory. The average improvement in CEA from postoperative to skeletal maturity was significantly smaller in group C than in the other groups (12.7 degrees in group A, 11.3 degrees in group B, and 3.0 degrees in group C).

Conclusions:

SIO showed favorable outcomes with satisfactory acetabular coverage at skeletal maturity. However, satisfactory acetabular coverage could not be obtained in some older patients because of limited postoperative remodeling capacity and smaller secondary improvement of CEA. We recommend that SIO should be performed in patients aged 8 years or younger.

Level of Evidence:

Level III—retrospective comparative study.
Optimizing Recognition and Management of Patients at Risk for Infection-Related Decompensation Through Team-Based Decision Making
Authors: Martinez Elizabeth M. , Sepanski Robert J. , Jennings A. Dawn , Schmidt James M. , Cholis Thomas J. , Dominy Meaghan E. , Devlin Sanaz B. , Eilers Lindsay Floyd , Zaritsky Arno L. , Godambe Sandip A.
Published: August 2022

Introduction:

Pediatric sepsis is a leading cause of death among children. Electronic alert systems may improve early recognition but do not consistently result in timely interventions given the multitude of clinical presentations, lack of treatment consensus, standardized order sets, and inadequate interdisciplinary team-based communication. We conducted a quality improvement project to improve timely critical treatment of patients at risk for infection-related decompensation (IRD) through team-based communication and standardized treatment workflow.

Methods:

We evaluated children at risk for IRD as evidenced by the activation of an electronic alert system (Children at High Risk Alert Tool [CAHR-AT]) in the emergency department. Outcomes were assessed after multiple improvements including CAHR-AT implementation, clinical coassessment, visual cues for situational awareness, huddles, and standardized order sets.

Results:

With visual cue activation, initial huddle compliance increased from 7.8% to 65.3% (p < .001). Children receiving antibiotics by 3 hours postactivation increased from 37.9% pre–CAHR-AT to 50.7% posthuddle implementation (p < .0001); patients who received a fluid bolus by 3 hours post-CAHR activation increased from 49.0% to 55.2% (p = .001).

Conclusions:

Implementing a well-validated electronic alert tool did not improve quality measures of timely treatment for high-risk patients until combined with team-based communication, standardized reassessment, and treatment workflow.
Is Idiopathic Sudden Sensorineural Hearing Loss Seasonal?
Authors: Simani Liam , Oron Yahav , Shapira Udi , Handzel Ophir , Abu Eta Rani , Warshavsky Anton , Horowitz Gilad , Muhanna Nidal , Shilo Shahaf , Ungar Omer J.
Published: August 2022

Objective

To investigate the circannual rhythm (seasonal incidence) of idiopathic sudden sensorineural hearing loss (ISSNHL).

Methods

Data were retrieved from the medical files of an original cohort of all consecutive patients with ISSNHL in a tertiary medical center between 2012 and 2020. A systematic literature search of “MEDLINE” via “PubMed,” “Embase,” and “Web of Science” on comparable published cases was performed. A Google Trends analysis of the term [sudden hearing loss] and related terms between 2014 and 2020 was also performed.

Results

Most of the published series (9/12) reported the highest ISSNHL incidence in the spring and the lowest in the winter (8/12). In our local series, the incidence during the winter was significantly lower than that for the other seasons by a factor of 0.69 (95% confidence interval, 0.65–0.77; p = 0.041; r = 0.36). Google Trends data showed no significant correlation between the calendric month and the incidence of ISSNHL in any of the analyzed countries (p = 0.873, r
2 = 0.029).

Conclusion

The ISSNHL incidence was lowest during the winter season in our cohort and reported for other cohorts worldwide. Google Trends–based model analysis did not determine any circannual rhythm.
Meta-analysis of the association between new hypoglycemic agents and digestive diseases
Authors: Wang Yu-Wen , Lin Jin-Hao , Yang Cui-Shan
Published: August 2022

Background:

New hypoglycemic agents include sodium-glucose cotransporter-2 inhibitors (SGLT2is), glucagon-like peptide 1 receptor agonists (GLP1RAs), and dipeptidyl peptidase-4 inhibitors (DPP4is). The association between each class of these new hypoglycemic drugs and the risks of various digestive system diseases is unknown. We aimed to explore this relationship by performing a meta-analysis.

Methods:

We included large randomized trials of SGLT2is, GLP1RAs, and DPP4is. Outcomes of interest were 91 kinds of digestive diseases including 75 kinds of gastrointestinal disorders and 16 kinds of hepatobiliary disorders. Meta-analysis was done to generate pooled risk ratio (RR) and 95% confidence interval (CI). Subgroup analysis was conducted according to 3 different drug classes.

Results:

We included 21 large trials in this meta-analysis. Compared with placebo, GLP1RAs were associated with the higher risks of gastric ulcer hemorrhage (RR 2.68, 95% CI 1.07–6.68; P
drug = .035; I
2 = 0), pancreatitis (RR 1.48, 95% CI 1.02–2.15; P
drug = .041; I
2 = 0), cholangitis acute (RR 5.96, 95% CI 1.04–34.08; P
drug = .045; I
2 = 0), and cholecystitis acute (RR 1.52, 95% CI 1.08–2.15; P
drug = .017; I
2 = 1.5%), but were not significantly associated with the occurrences of the other 87 kinds of digestive diseases (P
drug ranged from .064 to .999). SGLT2is versus placebo were not significantly associated with the occurrences of 91 kinds of digestive diseases (P
drug ranged from .077 to .995). DPP4is versus placebo were not significantly associated with the occurrences of 91 kinds of digestive diseases (P
drug ranged from .085 to .999).

Conclusions:

Neither SGLT2is nor DPP4is are associated with the occurrences of various kinds of digestive diseases, whereas GLP1RAs are associated with the higher risks of 4 kinds of digestive diseases, namely, gastric ulcer hemorrhage, pancreatitis, cholangitis acute, and cholecystitis acute. These findings seem to suggest that GLP1RAs are not applicable for patients at high risk of 4 specific digestive diseases, whereas SGLT2is and DPP4is are safe for patients susceptible to digestive diseases. However, our findings require to be further verified by future studies with sufficient statistical power.
Prevalence and prognostic significance of malnutrition in patients with acute coronary syndrome treated with percutaneous coronary intervention
Authors: Kang Se Hun , Song Han Na , Moon Jae Youn , Kim Sang-Hoon , Sung Jung-Hoon , Kim In Jai , Lim Sang-Wook , Cha Dong-Hun , Kim Won-Jang
Published: August 2022

The incidence and impact of malnutrition on acute coronary syndrome (ACS) remain unclear. This study aimed to evaluate the prevalence, clinical relevance, and prognostic outcomes of malnutrition in patients with ACS treated with percutaneous coronary intervention. This retrospective study included 1930 consecutive patients with ACS undergoing percutaneous coronary intervention and assessed their nutritional status using 3 scoring systems: Controlling Nutritional Status score, nutritional risk index (NRI), and prognostic nutritional index (PNI). The primary endpoint was all-cause mortality. The Controlling Nutritional Status, NRI, and PNI scores showed that 5.2%, 17.5%, and 3.9% of patients were moderately or severely malnourished, respectively. During a median follow-up of 67.2 months (interquartile range: 46.8–88.5 months), 74 (3.8%) patients died. Malnutrition was associated with a significantly increased risk for all-cause mortality compared with good nutrition (adjusted hazard ratios for moderate and severe malnutrition, respectively: 5.65 [95% confidence interval: 3.27–9.78] and 15.26 [7.50–31.05] for the NRI score, 5.53 [2.10–14.49] and 11.08 [5.69–21.59] for the PNI; P < .001). The current findings demonstrated that malnutrition is prevalent among patients with ACS and is closely associated with increased mortality. Further study is needed to evaluate the effects of nutritional interventions on the outcomes of patients with ACS.
Benign optic nerve gliomas in an adult: A case report
Authors: Cao Yarong , Tang Xinpu , Zan Xin , Li Shuangqing
Published: August 2022

Rationale:

Benign optic nerve gliomas were rarely found in adults, and total resection of these lesions seems impossible. We aimed to share a rare clinical case with an unusual and instructive treatment process.

Patient concerns:

A 52-year-old woman complained of a 4-month history of visual disturbance. Automated perimetry revealed visual field defect in her both eyes.

Diagnosis:

This patient was diagnosed with optic nerve glioma. We found its pathological features consistent with the pilocytic astrocytomas (WHO grade I).

Interventions:

A total resection of the tumor was smoothly performed.

Outcomes:

Repeat MRI 3 months after the surgery demonstrated no recurrence of the lesion. Two years of postoperative telephone follow-up showed a stable status of improved vision.

Lessons:

We reported this interesting case to show a rare kind of condition regarding optic nerve gliomas in adults, which might help neurosurgeons like us to diagnose and treat these “invisible” tumors.
Research hotspots and trends of multimodality MRI on vascular cognitive impairment in recent 12 years: A bibliometric analysis
Authors: Xia Mei-Hui , Li Ang , Gao Rui-Xue , Li Xiao-Ling , Zhang Qinhong , Tong Xin , Zhao Wei-Wei , Cao Dan-Na , Wei Ze-Yi , Yue Jinhuan
Published: August 2022

Background:

Multimodality magnetic resonance imaging (MRI) is widely used to detect vascular cognitive impairment (VCI). However, a bibliometric analysis of this issue remains unknown. Therefore, this study aimed to explore the research hotspots and trends of multimodality MRI on VCI over the past 12 years based on the Web of Science core collection using CiteSpace Software (6.1R2).

Methods:

Literature related to multimodality MRI for VCI from 2010 to 2021 was identified and analyzed from the Web of Science core collection database. We analyzed the countries, institutions, authors, cited journals, references, keyword bursts, and clusters using CiteSpace.

Results:

In total, 587 peer-reviewed documents were retrieved, and the annual number of publications showed an exponential growth trend over the past 12 years. The most productive country was the USA, with 182 articles, followed by China with 134 papers. The top 3 active academic institutions were Capital Medical University, Radboud UNIV Nijmegen, and UNIV Toronto. The most productive journal was the Journal of Alzheimer’s Disease (33 articles). The most co-cited journal was Neurology, with the highest citations (492) and the highest intermediary centrality (0.14). The top-ranked publishing author was De Leeuw FE (17 articles) with the highest intermediary centrality of 0.04. Ward Law JM was the most cited author (123 citations) and Salat Dh was the most centrally cited author (0.24). The research hotspots of multimodal MRI for VCI include Alzheimer disease, vascular cognitive impairment, white matter intensity, cerebrovascular disease, dementia, mild cognitive impairment, neurovascular coupling, acute ischemic stroke, depression, and cerebral ischemic stroke. The main frontiers in the keywords are fMRI, vascular coupling, and cerebral ischemic stroke, and current research trends include impact, decline, and classification.

Conclusions:

The findings from this bibliometric study provide research hotspots and trends for multimodality MRI for VCI over the past 12 years, which may help researchers identify hotspots and explore cutting-edge trends in this field.
Using Sankey diagrams to explore the trend of article citations in the field of bladder cancer: Research achievements in China higher than those in the United States
Authors: Lee Yen-Ling , Chien Tsair-Wei , Wang Jhih-Cheng
Published: August 2022

Background:

Urology authors are required to evaluate research achievements (RAs) in the field of bladder cancer (BC). However, no such bibliometric indices were appropriately applied to quantify the contributions to BC in research. In this study, we examined 3 questions: whether RAs in China are higher than those in the United States, how the Sankey-based temporal bar graph (STBG) may be applied to the analysis of the trend of article citations in the BC field, and what subthemes were reflected in China’s and the United States’ proportional counts in BC articles.

Methods:

Using the PubMed search engine to download data, we conducted citation analyses of BC articles authored by urology scholars since 2012. A total of 9885 articles were collected and analyzed using the relative citations ratios (RCRs) and the STBG. The 3 research goals were verified using the RCRs, the STBG, and medical subject headings (MesH terms). The choropleth map and the forest plot were used to 1 highlight the geographical distributions of publications and RCRs for countries/regions and 2 compare the differences in themes (denoted by major MeSH terms on proportional counts using social network analysis to cluster topics) between China and the United States.

Results:

There was a significant rise over the years in RCRs within the 9885 BC articles. We found that the RCRs in China were substantially higher than those in the United States since 2017, the STBG successfully explored the RCR trend of BC articles and was easier and simpler than the traditional line charts, area plots, and TBGs, and the subtheme of genetics in China has a significantly higher proportion of articles than the United States. The most productive and influential countries/regions (denoted by RCRs) were {Japan, Germany, and Italy} and {Japan, Germany, New York}, respectively, when the US states and provinces/metropolitan cities/areas in China were separately compared to other countries/regions.

Conclusions:

With an overall increase in publications and RCRs on BC articles, research contributions assessed by the RCRs and visualized by the STBGs are suggested for use in future bibliographical studies.
Key pathways and genes in hepatitis B virus-related liver inflammation: Expression profiling and bioinformatics analysis
Authors: Zhao Jing-Yuan , Zhong Zhao-Zhong , Zhao Li-Yun , Li Wen
Published: August 2022

Chronic hepatitis B virus infection has become a major public health issue worldwide, which can lead to liver inflammation, fibrosis, and hepatocellular carcinoma. According to the inflammation activity, liver tissues can be divided into 5 grades (G0–G4). However, the mechanism of the development of liver inflammation remains unclear. In our study, expression profiling by microarray and bioinformatics technology was used to systemically identify differentially expressed genes (DEGs) between low grades (G0–G1) and high (G2–G4) grades of liver inflammation. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and protein–protein interaction network construction were performed for further identification of the key functions, pathways, and hub genes that might play important roles in the inflammation development. A total of 1982 DEGs were identified, consisting of 1220 downregulated genes and 762 upregulated genes. GO analysis revealed the DEGs were mainly enriched in GO terms that related to neutrophil activation and degranulation. MAPK1, ITGA2, CDK2, TGFB1, CDKN2A, MTOR, IL6, PCNA, OAS2, and EP300 were hub genes that had the highest centricity and might be potential markers for inflammation development. This study identified the differentially expressed genes between different grades of inflammation, which would enlighten the study that focuses on the mechanism of liver inflammation development.
Case report: Biallelic variants in POLR3B gene lead to 4H leukodystrophy from the study of brother and sister
Authors: Bai Hengzhou , Li Dingming , Zheng Yi , Jiang XiaoHui
Published: August 2022

Introduction:

4H leukodystrophy, one of POLR3-related leukodystrophy, is a rare hereditary brain white matter disease caused by the pathogenic biallelic variations in POLR3A, POLR3B, or POLR1C. Hypomyelination, hypodontia, and hypogonadotropic hypogonadism is mainly presented in patients with 4H leukodystrophy.

Patient concerns:

Here, we reported the brother and the sister with new compound heterozygous (c.1615G>T and c.165-167del) with various degrees of phenotypes including dysbasia, myopia, dental abnormal, and hypogonadotropic hypogonadism.

Diagnosis:

The brother and sister were diagnosed with 4H leukodystrophy.

Interventions:

Gonadotrophins treatment of the brother could significantly improve the development of secondary sexual characteristics and genitalia.

Outcomes:

This study showed that the same genotype of POLR3B may have variable clinical phenotypes in the brother and sister.

Conclusion:

The exploration of molecular functions and genetic counseling are crucial for further diagnosis and treatment of POLR3-related leukodystrophy.
Depressive Symptoms and Caregiving Intensity Before and After Onset of Dementia in Partners
Authors: Harris Melissa L. , Errickson Josh , Ha Jinkyung , Hoffman Geoffrey J.
Published: August 2022

Background:

Caring for a partner with dementia poses significant emotional burden and high care demands, but changes in impacts before and after dementia onset is unclear.

Objective:

Examine changes in depressive symptoms and hours of care provided by caregivers through the course of their partners’ cognitive decline.

Methods:

Retrospective, observational study using household survey data from 2000–2016 Health and Retirement Study and count models to evaluate older individuals’ (ages ≥51 y) depressive symptoms (measured using the shortened Center for Epidemiologic Studies Depression Scale) and weekly caregiving in the 10 years before and after their partners’ dementia onset (identified using Telephone Interview Cognitive Status screening). Relationships were examined overall and by sex and race.

Results:

We identified 8298 observations for 1836 older caregivers whose partners developed dementia. From before to after partners’ dementia onset, caregivers’ mean (SD) depressive symptoms increased from 1.4 (1.9) to 1.9 (2.1) (P<0.001) and weekly caregiving increased from 4.4 (19.7) to 20.8 (44.1) (P<0.001) hours. Depressive symptoms and caregiving hours were higher for women compared with men. Depressive symptoms were higher for Blacks compared with Whites, while caregiving hours were higher for Whites. The expected count of caregivers’ depressive symptoms and caregiving hours increased by 3% (P<0.001) and 9% (P=0.001) before partners’ dementia onset and decreased by 2% (P<0.001) and 1% (P=0.63) following partners’ dementia onset. No differences observed by sex or race.

Discussion:

Depressive symptoms and instrumental burdens for caregivers increase substantially before the onset of dementia in partners. Early referral to specialty services is critical.
NUTM1-rearranged Carcinoma of the Thyroid
Authors: Barletta Justine A. , Gilday Steven D. , Afkhami Michelle , Bell Diana , Bocklage Theresa , Boisselier Pierre , Chau Nicole G. , Cipriani Nicole A. , Costes-Martineau Valerie , Ghossein Ronald A. , Hertzler Hans J. , Kramer Alan M. , Limaye Sewanti , Lopez Carlos A. , Ng Tony L. , Weissferdt Annikka , Xu Bin , Zhang Songlin , French Christopher A.
Published: August 2022

NUT carcinoma (NC) is a rare subtype of squamous cell carcinoma defined by NUTM1 rearrangements encoding NUT fusion oncoproteins (the most frequent fusion partner being BRD4) that carries a very poor prognosis, with most patients dying in under 1 year. Only rare primary thyroid NCs have been reported. Here, we evaluated a series of 14 cases. The median patient age at diagnosis was 38 years (range: 17 to 72 y). Eight of 13 cases with slides available for review (62%) showed a morphology typical of NC, whereas 5 (38%) had a non–NC-like morphology, some of which had areas of cribriform or fused follicular architecture resembling a follicular cell–derived thyroid carcinoma. For cases with immunohistochemistry results, 85% (11/13) were positive for NUT on biopsy or resection, though staining was significantly decreased on resection specimens due to fixation; 55% (6/11) were positive for PAX8, and 54% (7/13) for TTF-1. Tumors with a non–NC-like morphology were all positive for PAX8 and TTF-1. The fusion partner was known in 12 cases: 9 (75%) cases had a NSD3-NUTM1 fusion, and 3 (25%) had a BRD4-NUTM1 fusion. For our cohort, the 2-year overall survival (OS) was 69%, and the 5-year OS was 58%. Patients with NC-like tumors had a significantly worse OS compared with that of patients with tumors with a non–NC-like morphology (P=0.0462). Our study shows that NC of the thyroid can mimic other thyroid primaries, has a high rate of NSD3-NUTM1 fusions, and an overall more protracted clinical course compared with nonthyroid primary NC.
Effect of Pranayama on Perceived Stress, Well Being and Quality of Life of Frontline Healthcare Professionals on Covid-19 Duty: A Quasi-Randomized Clinical Trial
Authors: Sarwal Rakesh , Dhamija Rajinder K. , Jain Khushbu , Basavaraddi Ishwar V.
Published: August 2022

Background

The COVID-19 pandemic has brought unparalleled challenges for health systems worldwide, the impact of which has also been borne by the Healthcare Professionals (HCPs). Numerous studies have revealed the positive effects of Pranayama and Meditation on mental health. The effect of Pranayama in improving mental health of frontline HCP exposed to Covid-19 patients has not been studied.

Aim & Objective

This quasi-randomized clinical trial was done to study the effect of especially designed Pranayama protocol on perceived stress, wellbeing and quality of life of frontline health care professionals who were exposed to COVID-19 patients in hospital settings.

Methodology

This study was done with 280 frontline healthcare professionals (HCP) assigned duties with COVID-19 patients during September-November, 2020 in 5 government hospitals and COVID-19 quarantine/isolation centres in New Delhi, India. The HCPs were first assessed for COVID-19 infection in the past using antibody test, and only those found negative were recruited. The enrolled respondents were randomly assigned to two arms – an intervention arm where there were to practice 28-day Pranayama module (morning and evening sessions) under supervision of a trainer, and a Control arm where the HCPs continued routine physical activity (walking, jogging etc.). Baseline and end-line (total: 250 HCPs) Psychological parameters of Perceived Stress, Well Being and Quality of Life were collected through self-reported questionnaires.

Results

The intervention (HCPs: 123) and control (HCPs: 127) groups (Total: 250) were comparable in their demographic profile and baseline characteristics. Intervention with Pranayama module led to a significant reduction (Mean diff: -2.46; P-value: 0.028) in perceived stress score in the intervention group compared to the control group. The wellbeing index in Interventional group intervention showed a non-significant increase. The WHO Quality-of-life score increased in the intervention group as compared to the controls (mean difference 2.78, p-value: 0.17). Of its four components, the one for Psychological domain increased significantly (mean diff: 1.52, P-value: 0.019), while those for Physical domain and Environmental domains increased (mean diff: 0.64, P-value: 0.29 and mean diff: 0.68, p-value: 0.48) though not statistical significantly.

Cconclusion

The intervention of twice daily practice of the Pranayama module for 28 days in frontline HCPs performing COVID-19 duties had a noteworthy effect in lowering Perceived Stress, improving perceived Quality of life, especially its Psychological domains as measured through standardized questionnaires.

CTRI Number

CTRI/2020/07/026667
Grid Cell Percolation
Authors: Dabaghian Yuri
Published: August 2022

Grid cells play a principal role in enabling mammalian cognitive representations of ambient environments. The key property of these cells—the regular arrangement of their firing fields—is commonly viewed as means for establishing spatial scales or encoding specific locations. However, using grid cells’ spiking outputs for deducing spatial orderliness proves to be a strenuous task, due to fairly irregular activation patterns triggered by the animal’s sporadic visits to the grid fields. The following discussion addresses statistical mechanisms enabling emergent regularity of grid cell firing activity, from the perspective of percolation theory. In particular, it is shown that the range of neurophysiological parameters required for spiking percolation phenomena matches experimental data, which points at biological viability of the percolation approach and casts a new light on the role of grid cells in organizing the hippocampal map.
MOLECULAR INSIGHTS INTO BINDING BEHAVIOUR OF LAMOTRIGINE WITH INITIATION FACTOR 2 PROTEIN: AN INTEGRATED COMPUTATIONAL STUDIES
Authors: Arora Smriti , Patra Jeevan
Published: August 2022

CONSPECTUS

Aims

The ribosomal protein (r-protein) of bacteria is composed of 2.6 MDa ribonucleoproteins of the 30S and 50S subunits, which are essential elements for protein translation. The translational initiation step is an intensive regulated multi-step reaction in protein biosynthesis. During bacterial protein synthesis, the correct reading frame of the mRNA defines when the initiator fMet-tRNAiMet binds to the start codon AUG at the P-site of the 30S subunit. The formation of the P-site of the 30S subunit initiation complex (30S-IC) is governed by three ubiquitous initiation factors (IFs) such as IF1, IF2, and IF3. IF2 protein is an essential player that plays during the last stage of the initiation process. Earlier, Stokes and his co-workers studied chemicals probes using 30K diverse drugs that induced cold-sensitive growth inhibition in the bacterium. The assay studies revealed, Lamotrigine (LTG) effectively binds at domain II of IF2 protein. In our research, we took an attempt in identifying promising active residues that could responsible for anti-bacterial bioactivity with help of computational studies.

Computational Methods

In the present study, initially, we performed C-α backbone alignment with the retrieved IF2 chain from AlphaFold. Further, we utilized SiteMap and CastP for the identification of plausible active binding sites. Further, we bound LTG with the designated domain(s) of IF2 protein and studied its binding affinity potential with help of adaptive molecular dynamics simulations at atomic levels using Desmond.

Key Findings

Our research findings have shown accurate results and we could able to prove the assertion in contrast with the findings of Stokes and his co-workers where the LTG bind at domain II of IF2 protein. The key interacting residue Glu179 was revealed to have strong hydrogen bonding contacts with LTG at the sub-nanomolar range. In addition, we predicted the alternative promising site I Further, we gained in-depth analysis for studying multiple sites, to understand the synergism inhibitory activity. Promisingly, LTG could be able to bound with at Site 1 showing better affinity over the proposed domain II and other predicted sites. The adaptive molecular dynamics studies confirmed the promising active residues

Significance

The binding site predictions approach provides an insight for further development of anti-bacterial therapeutics that might helpful for bacteria disease management and exhibiting inhibitory activity against various strains.
Utah Array Characterization and Histological Analysis of a Multi-Year Implant in Non-Human Primate Motor and Sensory Cortices
Authors: Patel Paras R. , Welle Elissa J. , Letner Joseph G. , Shen Hao , Bullard Autumn J. , Caldwell Ciara M. , Vega-Medina Alexis , Richie Julianna M. , Thayer Hope E. , Patil Parag G. , Cai Dawen , Chestek Cynthia A.
Published: August 2022

The Utah array is widely used in both clinical studies and neuroscience. It has a strong track record of safety. However, it is also known that implanted electrodes promote the formation of scar tissue in the immediate vicinity of the electrodes, which negatively impacts the ability to record neural waveforms. This scarring response has been primarily studied in rats and mice, which may have a very different response than primate brain. Here, we present a rare nonhuman primate histological dataset (n=1 rhesus macaque) obtained 848 and 590 days after implantation in two brain hemispheres. For 2 of 4 arrays that remained within the cortex, NeuN was used to stain for neuron somata at 3 different electrode depths. Images were filtered and denoised, with neurons then counted in the vicinity of the arrays as well as a nearby section of control tissue. Additionally, 3 of 4 arrays were imaged with a scanning electrode microscope (SEM) to evaluate any materials damage that might be present. Overall, we found a 63% percent reduction in the number of neurons surrounding the electrode compared to control areas. In terms of materials, the arrays remained largely intact with metal and Parylene C present, though tip breakage and cracks were observed on many electrodes. Overall, these results suggest that the tissue response in the nonhuman primate brain shows similar neuron loss to previous studies using rodents. Electrode improvements, for example using smaller or softer probes, may therefore substantially increase the neuronal recording yield in primate cortex.
Auditory accessory stimulus boosts pupil-linked arousal and reduces choice bias
Authors: Bruel B.M. , Katopodis V.G. , de Vries R. , Donner T.H. , McGinley M.J. , de Gee J.W.
Published: August 2022

Abstract

Recent work indicates that pupil-linked phasic arousal signals reduce the impact of prior expectations and biases on decision formation. It has remained unclear whether phasic arousal (i) causes the bias reduction, if (ii) choosing against one’s bias causes phasic arousal, or if (iii) a third variable is driving both. Here, using an auditory accessory stimulus, we found evidence for the first scenario: on accessory stimulus vs normal trials, pupil-linked phasic arousal was robustly elevated and choice bias was reduced. With computational modeling of behavior, we established that the bias reduction was not due to a change in response caution (i.e., speed-accuracy tradeoff), but due to a change in a bias in the accumulation of evidence leading up to a choice. Thus, pupil-linked phasic arousal shapes choice behavior.
An educated guess: how coral reef fish make decisions under uncertainty
Authors: Newport Cait , Sibeaux Adelaide , Wallis Guy , Wilkins Lucas , de Perera Theresa Burt
Published: August 2022

Making informed decisions is fundamental to intelligent life and is crucial to survival. The problem many organisms face, is how to make optimal decisions in the face of incomplete, unreliable, or conflicting information. In many aquatic environments, fish use visual information to guide key behaviours, but the environment itself can alter or mask the very signals they rely on. Here, we asked how a highly visual species,Rhinecanthus aculeatus, responds to a learned discrimination task as signal reliability decreases, and whether probabilistic information gained during previous experience can be incorporated into their decision strategy. Fish were first trained to select a target (dark grey circle) from three distractors (light grey circles). In the first experiment, the target was more likely to appear in one of four possible stimulus positions. In the second experiment, the target appeared in all positions equally. In a series of trials, the difference in brightness between the target and distractors was reduced until all four stimuli were identical. We found that target selection accuracy decreased with decreasing target and distractor disparity. However, in Experiment 1 where the target was more likely to be in one position, fish increasingly selected stimuli in the biased position as target selection accuracy decreased, but not in Experiment 2. These results demonstrate 1) that fish learned more than a simple select/avoid rule based on stimulus brightness, but also integrated information (stimulus position) that could be considered ancillary to the primary task. 2) Fish can learn probability distributions and apply this knowledge as uncertainty increases, ultimately increasing the overall frequency of correct choices. Our results reveal that probabilistic decision rules can be used by fish when visual information is unreliable, indicating a possible mechanism for decision making given the inherent noise in incoming sensory information.
Cryptic functional diversity in ant tandem runs
Authors: Mizumoto Nobuaki , Tanaka Yasunari , Valentini Gabriele , Richardson Thomas O. , Annagiri Sumana , Pratt Stephen C , Shimoji Hiroyuki
Published: August 2022

Ants have evolved diverse recruitment methods to guide colony members to valuable resources, such as food or nest sites. One of these methods, tandem running, consists of an informed leader directly guiding a naive follower every step of the way from nest to resource. Although this behavior appears superficially similar in the different ant taxa in which it has independently evolved, this similarity could conceal underlying functional and mechanistic differences. Here we present a combined network and information-theoretic analysis, which reveals fundamental differences in the tandem recruitment between two distantly related ant genera, Temnothorax and Diacamma. Temnothorax uses tandem running to recruit additional recruiters, whereas Diacamma uses it principally to move the passive majority of the colony, a task that Temnothorax accomplishes with a different behavior, social carrying. Accordingly, the structure of the tandem run recruitment networks of Diacamma was different from those of Temnothorax, with Diacamma networks more closely resembling the social carrying networks of Temnothorax. Furthermore, an information-theoretic analysis of the spatial trajectories of leaders and followers revealed that Diacamma tandem runs lack bidirectional information flow, the signature of route-learning in Temnothorax tandem runs. These results suggest that Diacamma uses tandem runs not to share information, but to transport nestmates. By quantifying the cryptic diversity of communication behavior, this study increases the resolution of our understanding of animal societies.
Estimating Treatment Effects for Time-to-Treatment Antibiotic Stewardship in Sepsis
Authors: Liu Ruoqi , Buck Katherine H. , Caterino Jeffrey M. , Zhang Ping
Published: August 2022

Sepsis is a life-threatening condition with high in-hospital mortality rate. The timing of antibiotic (ATB) administration poses a critical problem for sepsis management. Existing work studying antibiotic timing either ignores the temporality of the observational data or the heterogeneity of the treatment effects. In this paper, we propose a novel method to estimate TreatmenT effects for Time-to-Treatment antibiotic stewardship in sepsis (T4). T4 estimates individual treatment effects (ITEs) by recurrently encoding temporal and static variables as potential confounders, and then decoding the outcomes under different treatment sequences. We propose a mini-batch balancing matching that mimics the randomized controlled trial process to adjust the confounding. The model achieves interpretability through a global-level attention mechanism and a variable-level importance examination. Meanwhile, we incorporate T4 with uncertainty quantification to help prevent overconfident recommendations. We demonstrate that T4 can identify effective treatment timing with estimated ITEs for antibiotic stewardship on two real-world datasets. Moreover, comprehensive experiments on a synthetic dataset exhibit the outstanding performance of T4 compared to the state-of-the-art models on ITE estimation.
Gli2andGli3Regulate Horizontal Basal Cell-Mediated Regeneration of the Olfactory Epithelium
Authors: Shirazyan Anna , Park Haeyoung , Joiner Ariell M. , Ra Justine , Kim Melissa S. , Kumari Archana , Franks Nicole E. , Peng Tien , Bradley Robert K. , Mistretta Charlotte M. , Dlugosz Andrzej A. , Allen Benjamin L.
Published: August 2022

The olfactory epithelium (OE) is a specialized neuroepithelium that is replenished by two stem cell populations: globose basal cells (GBCs) and horizontal basal cells (HBCs). Previous work indicated that HBCs contain primary cilia, organelles that mediate Hedgehog (HH) pathway activity. However, a role for HH signaling in HBCs has not been investigated. We find that GLI2 and GLI3, transcriptional effectors of the HH pathway, are expressed in HBCs in the adult OE and that their expression expands following injury. Further,Gli2-expressing descendants contribute to all major OE cell types during OE regeneration. HBC-specific expression of constitutively active GLI2 drives inappropriate HBC proliferation, alters HBC identity, and culminates in a failure of HBCs to differentiate into olfactory sensory neurons (OSNs) following injury. HBC- specific deletion of endogenousGli2andGli3results in decreased HBCs and OSNs following OE injury. These data identify GLI2 and GLI3 as key regulators of HBC-mediated OE regeneration.
Evolution within a given virulence phenotype (pathotype) is driven by changes in aggressiveness: a case study of French wheat leaf rust populations
Authors: Fontyn Cécilia , Meyer Kevin JG , Boixel Anne-Lise , Delestre Ghislain , Piaget Emma , Picard Corentin , Suffert Frédéric , Marcel Thierry C , Goyeau Henriette
Published: August 2022

Plant pathogens are constantly evolving and adapting to their environment, including their host. Virulence alleles emerge, and then increase, and sometimes decrease in frequency within pathogen populations in response to the fluctuating selection pressures imposed by the deployment of resistance genes. In some cases, these strong selection pressures cannot fully explain the evolution observed in pathogen populations. A previous study on the French population ofPuccinia triticina, the causal agent of wheat leaf rust, showed that two major pathotypes — groups of isolates with a particular combination of virulences — predominated but then declined over the 2005-2016 period. The relative dynamics and the domination of these two pathotypes — 166 317 0 and 106 314 0 —, relative to the other pathotypes present in the population at a low frequency although compatible, i.e. virulent on several varieties deployed, could not be explained solely by the frequency ofLrgenes in the landscape. Within these two pathotypes, we identified two main genotypes that emerged in succession. We assessed three components of aggressiveness — infection efficiency, latency period and sporulation capacity — for 44 isolates representative of the fourP. triticinapathotype-genotype combinations. We showed, for both pathotypes, that the more recent genotypes were more aggressive than the older ones. Our findings were highly consistent for the various components of aggressiveness for pathotype 166 317 0 grown on Michigan Amber — a ‘naive’ cultivar never grown in the landscape — or on Apache — a ‘neutral’ cultivar, which does not affect the pathotype frequency in the landscape and therefore was postulated to have no or minor selection effect on the population composition. For pathotype 106 314 0, the most recent genotype had a shorter latency period on several of the cultivars most frequently grown in the landscape, but not on ‘neutral’ and ‘naive’ cultivars. We conclude that the quantitative components of aggressiveness can be significant drivers of evolution in pathogen populations. A gain in aggressiveness stopped the decline in frequency of a pathotype, and subsequently allowed an increase in frequency of this pathotype in the pathogen population, providing evidence that adaptation to a changing varietal landscape not only affects virulence but can also lead to changes in aggressiveness.
Regenotyping structural variants through an accurate force-calling method
Authors: Jiang Tao , Cao Shuqi , Liu Yadong , Liu Shiqi , Liu Bo , Wang GuoHua , Wang Yadong
Published: August 2022

Long-read sequencing technologies have great potential for the comprehensive discovery of structural variation (SV). However, accurate genotype assignment for SV is still a challenge due to unavoidable factors, such as specific sequencing errors or limited coverage. Herein, we propose cuteSV2, a fast and accurate long-read-based regenotyping approach that is used to force calling genotypes for given records. In cuteSV2, which is an upgraded version of cuteSV, an improved refinement strategy is applied on the signatures, and the heuristic extracted signatures are purified through spatial and allele similarity estimation. The benchmarking results on several baseline evaluations demonstrate that cuteSV2 outperforms the state-of-the-art methods and is a scalable and robust approach for population studies and clinical practice. cuteSV2 is available athttps://github.com/tjiangHIT/cuteSV.
Synaptic Expression of TAR-DNA-Binding Protein 43 in the Mouse Spinal Cord Determined Using Super-Resolution Microscopy
Authors: Broadhead Matthew J. , Doucet Katherine , Kantelberg Owen , Zhu Fei , Grant Seth GN , Horrocks Mathew H , Miles Gareth B.
Published: August 2022

Cellular inclusions of hyperphosphorylated TAR-DNA-Binding Protein 43 (TDP-43) are a key hallmark of neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS). ALS is characterised by a loss of motor neurons in the brain and spinal cord that is preceded by early-stage changes in synaptic function that may be associated with TDP-43 pathology. However, there has been little characterisation of the synaptic expression of TDP-43 in spinal cord synapses. This study utilises a range of high-resolution and super-resolution microscopy techniques with immunolabelling, as well as an aptamer-based TDP-43 labelling strategy visualised with single-molecule localisation microscopy, to characterise and quantify the presence of phosphorylated TDP-43 (pTDP-43) in spinal cord synapses. We observe that TDP-43 is expressed in the majority of spinal cord synapses as nanoscale clusters as small as 60 nm in diameter. Synaptic TDP-43 expression is more frequently associated with presynaptic terminals than postsynaptic densities, and is more enriched in VGLUT1-associated synapses, compared to VGLUT2-associated synapses. Our nanoscopy techniques showed no difference in the subsynaptic expression of pTDP-43 in the ALS mouse model, SOD1G93a compared to healthy controls. This research characterizes the basic synaptic expression of TDP-43 with nanoscale precision and provides a framework with which to investigate the potential relationship between TDP-43 pathology and synaptic pathology in neurodegenerative diseases.
Small Training Dataset Convolutional Neural Networks for Application Specific Super-Resolution Microscopy
Authors: Mannam Varun , Howard Scott
Published: August 2022

Significance

Machine learning (ML) models based on deep convolutional neural networks have been used to significantly increase microscopy resolution, speed (signal-to-noise ratio), and data interpretation. The bottleneck in developing effective ML systems is often the need to acquire large datasets to train the neural network. This paper demonstrates how adding a “dense encoder-decoder” block can be used to effectively train a neural network that produces super-resolution images from conventional microscopy diffraction-limited images trained using a small dataset (15 field-of-views).

Aim

ML helps to retrieve super-resolution information from a diffraction-limited image when trained with a massive training dataset. The aim of this work is to demonstrate a neural network that estimates super-resolution images from diffraction-limited images using modifications that enable training with a small dataset.

Approach

We employ “Dense Encoder-Decoder” (called DenseED) blocks in existing super-resolution ML network architectures. DenseED blocks use a dense layer that concatenates features from the previous convolutional layer to the next convolutional layer. DenseED blocks in fully convolutional networks (FCNs) estimate the super-resolution images when trained with a small training dataset (15 field-of-views) of human cells from the Widefield2SIM dataset and in fluorescent-labeled fixed bovine pulmonary artery endothelial cells (BPAE samples).

Results

Conventional ML models without DenseED blocks trained on small datasets fail to accurately estimate super-resolution images while models including the DenseED blocks can. The average peak signal-to-noise ratio (PSNR) and resolution improvements achieved by networks containing DenseED blocks are ≈3.2 dB and 2×, respectively. We evaluated various configurations of target image generation methods (e.g, experimentally captured target and computationally generated target) that are used to train FCNs with and without DenseED blocks and showed including DenseED blocks in simple FCNs outperforms compared to simple FCNs without DenseED blocks.

Conclusions

DenseED blocks in neural networks show accurate extraction of super-resolution images even if the ML model is trained with a small training dataset of 15 field-of-views. This approach shows that microscopy applications can use DenseED blocks to train on smaller datasets that are application-specific imaging platforms and there is a promise for applying this to other imaging modalities such as MRI/X-ray, etc.
Dlg1 regulates subcellular distribution of non-muscle myosin II during Drosophila germband extension
Authors: Fuentes Melisa A. , Piper Hayley N. , He Bing
Published: August 2022

Elongation of the body axis through convergent extension is a conserved developmental process that is mediated by cell intercalation. During convergent extension of the germband epithelium in Drosophila embryos, planar polarized activation of non-muscle myosin II (“myosin”) promotes cell intercalation by facilitating patterned remodeling of adherens junctions. Here, we report that loss of the basolateral determinant Dlg1 leads to defects in the subcellular distribution of myosin during germband extension, and consequently, impairs proper junctional remodeling and apical area maintenance during cell intercalation. In dlg1 mutant embryos, ectopic accumulation of myosin is observed at the medioapical domain and along the lateral membrane, whereas junctional myosin is greatly reduced. Analogous myosin mis-localization patterns are observed upon knockdown of other basolateral determinants, Scrib and Lgl, but not the apical determinants. The function of Dlg1 in regulating the spatial distribution of myosin requires its intact SH3 and GUK domains and involves the Rho1 GEF Cyst, active Rho1 and Rok. We propose that Dlg1 facilitates correct junctional remodeling and prevents undesired apical area variation during cell intercalation by regulating the subcellular location of myosin activation.