bluuebunny/crossref_metadata_2025 huggingface dataset:
Pattern of Visual-Motor Integration, Visual Perception, and Fine Motor Coordination Abilities in Children Being Assessed for Fetal Alcohol Spectrum Disorder
Authors: Johnston Danielle , Pritchard Lesley , Branton Erin , Gross Douglas P. , Thompson-Hodgetts Sandy
Published: July 2023

Objective:

Motor skill assessment is part of the fetal alcohol spectrum disorder (FASD) multidisciplinary assessment. Some clinicians opt to exclude assessment of the subcomponents of visual-motor integration (visual perception and motor coordination), on the assumption that challenges will be revealed based on the assessment of visual-motor integration. The objective is to describe the visual-motor integration, visual perception, and fine motor coordination pattern of abilities in children with confirmed prenatal alcohol exposure being assessed for fetal alcohol spectrum disorder.

Methods:

This cross-sectional study included 91 children (65 males; mean age: 10 years, 6 months SD = 2 years, 10 months) undergoing assessment for FASD. Friedman and Wilcoxon statistics were used to compare mean visual-motor integration, visual perception, and fine motor coordination percentiles from the Beery-Buktenica Developmental Test of Visual-Motor Integration, Sixth Edition (Beery-6).

Results:

Children being assessed for FASD (n = 91) had the highest normative scores in visual perception, followed by visual-motor integration and fine motor coordination (mean percentiles (SD): 35.9 (24.9), 20.6 (18.3), and 13.8 (15.5), respectively) (χ2 distribution = 46.909, p ≤ 0.001).

Conclusion:

Children being assessed for FASD experience more challenges with fine motor coordination compared with visual-motor integration and visual perception tasks. This pattern differs from the pattern established for the general population in which tasks that require visual-motor integration are more challenging than tasks that isolate visual perception and fine motor coordination. These results suggest that fine motor coordination should be included in FASD diagnostic assessments and considered as an area for intervention.
Effect of permissive hypercarbia on lung oxygenation during one-lung ventilation and postoperative pulmonary complications in patients undergoing thoracic surgery
Authors: Joe Young-Eun , Lee Chang Yeong , Kim Namo , Lee Kyuho , Kang Su Jeong , Oh Young Jun
Published: July 2023

BACKGROUND

The effect of hypercarbia on lung oxygenation during thoracic surgery remains unclear.

OBJECTIVE

To investigate the effect of hypercarbia on lung oxygenation during one-lung ventilation in patients undergoing thoracic surgery and evaluate the incidence of postoperative pulmonary complications.

DESIGN

Prospective randomised controlled trial.

SETTING

A tertiary university hospital in the Republic of Korea from November 2019 to December 2020.

PATIENTS

Two hundred and ninety-seven patients with American Society of Anaesthesiologists physical status II to III, scheduled to undergo elective lung resection surgery.

INTERVENTION

Patients were randomly assigned to Group 40, 50, or 60. An autoflow ventilation mode with a lung protective ventilation strategy was applied to all patients. Respiratory rate was adjusted to maintain a partial pressure of arterial carbon dioxide of 40 ± 5 mmHg in Group 40, 50 ± 5 mmHg in Group 50 and 60 ± 5 mmHg in Group 60 during one-lung ventilation and at the end of surgery.

MAIN OUTCOME MEASURES

The primary outcome was the arterial oxygen partial pressure/fractional inspired oxygen ratio after 60 min of one-lung ventilation.

RESULTS

Data from 262 patients were analysed. The partial pressure/fractional inspired oxygen ratio was significantly higher in Group 50 and Group 60 than in Group 40 (269.4 vs. 262.9 vs. 214.4; P < 0.001) but was not significantly different between Group 50 and Group 60. The incidence of postoperative pulmonary complications was comparable among the three groups.

CONCLUSION

Permissive hypercarbia improved lung oxygenation during one-lung ventilation without increasing the risk of postoperative pulmonary complications or the length of hospital stay.

TRIAL REGISTRATION

NCT 04175379.
Recent evidence of economic evaluation of artificial intelligence in ophthalmology
Authors: Ruamviboonsuk Paisan , Ruamviboonsuk Varis , Tiwari Richa
Published: July 2023

Purpose of review

Health economic evaluation (HEE) is essential for assessing value of health interventions, including artificial intelligence. Recent approaches, current challenges, and future directions of HEE of artificial intelligence in ophthalmology are reviewed.

Recent findings

Majority of recent HEEs of artificial intelligence in ophthalmology were for diabetic retinopathy screening. Two models, one conducted in the rural USA (5-year period) and another in China (35-year period), found artificial intelligence to be more cost-effective than without screening for diabetic retinopathy. Two additional models, which compared artificial intelligence with human screeners in Brazil and Thailand for the lifetime of patients, found artificial intelligence to be more expensive from a healthcare system perspective. In the Thailand analysis, however, artificial intelligence was less expensive when opportunity loss from blindness was included. An artificial intelligence model for screening retinopathy of prematurity was cost-effective in the USA. A model for screening age-related macular degeneration in Japan and another for primary angle close in China did not find artificial intelligence to be cost-effective, compared with no screening. The costs of artificial intelligence varied widely in these models.

Like other medical fields, there is limited evidence in assessing the value of artificial intelligence in ophthalmology and more appropriate HEE models are needed.
Computational simulation of the optical performance of an EDOF intraocular lens in post-LASIK eyes
Authors: Lago Carmen M. , de Castro Alberto , Marcos Susana
Published: July 2023

Purpose:

To evaluate computationally the optical performance of AcrySof IQ Vivity extended depth-of-focus (EDOF) intraocular lenses (IOLs) in post–laser in situ keratomileusis (LASIK) eyes.

Setting:

Visual Optics and Biophotonics Laboratory, Madrid, Spain.

Design:

Experimental study.

Methods:

Computer pseudophakic eye models were implemented using reported post-LASIK corneal aberrations (refractive corrections from −7.5 to +4.5 diopters [D]) and virtually implanted with monofocal (AcrySof IQ) or EDOF (AcrySof IQ Vivity) IOLs. Retinal image quality was quantified through visual Strehl (VS). The depth of focus (DOF) was calculated from the through-focus VS curves. Halos were estimated from the light spread in the image of a pinhole. Those quantitative parameters were obtained for 5.0 and 3.0 mm pupil diameters.

Results:

Simulated virgin eyes showed VS of 0.89/0.99 with monofocal IOLs and 0.74/0.52 with EDOF IOLs for 5.0/3.0 mm pupils at best focus. VS decreased with induced spherical aberration (SA) by 25% and with induced SA + coma by 61% on average (3.0 mm pupils). The DOF was 2.50 D in virgin eyes with EDOF IOLs, 1.66 ± 0.30 and 2.54 ± 0.31 D (P < .05) on average in post-LASIK eyes for 3.0 mm pupils, monofocal and EDOF IOLs, respectively. Halos were more sensitive to SA induction for 5.0 mm pupils, and induction of positive SA (myopic LASIK) resulted in reduced halos with the EDOF when compared with the monofocal IOLs, by 1.62 (SA) and 1.86 arc min (SA + coma), on average.

Conclusions:

Computer post-LASIK pseudophakic eye models showed that the DOF was less dependent on the presence of SA and coma with EDOF IOLs and that halos were reduced with EDOF IOLs compared with the monofocal IOL for a range of SA.
Prebrief Time for Immersive Virtual and Augmented Reality Simulation
Authors: Cieslowski Bethany J. , Craig Sarah , Gummadi Sai Deepthi , Butler Kathleen
Published: July 2023

Background:

Virtual reality and augmented technology are rapidly advancing and hold the potential to transform nursing education by offering a convenient, efficient, learner-centered way to educate students. A comprehensive and time-oriented prebrief is essential to the process.

Purpose:

This review analyzes the status of scientific exploration regarding the prebrief and time allotments for virtual and augmented reality simulation.

Methods:

Whittemore and Knafl's 5-stage method guided this integrative review. The authors searched 6 databases and selected 7 articles based on inclusion criteria.

Results:

The findings from this review demonstrated objectives, a safe learning environment, orientation, preparation materials, and time in the prebrief; yet, inconsistencies persist in the virtual and augmented reality prebrief.

Conclusions:

Defining a comprehensive and consistent prebrief is essential for high-quality simulation. A more standardized process, including time allotments, must be established for virtual and augmented reality.
Impact of Simulation Training on the Management of Shoulder Dystocia and Incidence of Permanent Brachial Plexus Birth Injury: An Observational Study
Authors: Kaijomaa Marja , Gissler Mika , Äyräs Outi , Sten Assi , Grahn Petra
Published: July 2023

(Abstracted from BJOG 2023;130:70–77)

The incidence of brachial plexus birth injury (BPBI) varies from 0.4 to 3.8 per 1000 vaginal births. It is a complication caused by traction to the cervical and thoracic nerve roots that can lead to decreased strength, complete paralysis, or limited range of motion in the affected limb in the first year of life.
Disfigured Faces Depicted in Modern Visual Media
Authors: Kim Young Suk , Hwang Kun
Published: July 2023

According to the German sociologist Georg Simmel, of all the parts of the body, the face has the highest degree of inner unity. This study aimed to analyze the depictions of disfigured faces in modern visual media (movie films). The keywords “disfigured-face” and “disfigured-face character” were searched on Google. Based on that information, 57 films were searched on IMDB and TMDB, as movie databases. Six films where the IMDB and TMDB overlapped were omitted, and 6 films not directly related to the concept of “disfigured face” were excluded. All animated movies were replaced with the original movies. Then, 45 valid films were finally selected, and 48 characters with disfigured faces were analyzed. Among 48 disfigured faces, 26 were in male characters and 22 were in female characters. Among the 48 disfigured faces, 30 (62.5%) did not improve and 18 (37.5%) improved. Characters who underwent facial deformity correction surgery were 56 times more likely to improve than those who did not. Characters whose facial disfiguration improved were 7.85 times more likely to have a happy ending than those who did not. Among the methods that the characters with disfigured faces used in attempts to overcome their deformity, surgery had the highest success rate. Although surgery is not perfect, the reality is that there are no other alternatives. The results of our film analysis study, which showed plastic surgery can improve the face and improve quality of life, can be seen as realistic and statistically significant.
Intraoperative Gentamicin Intravesical Instillation for Prevention of Urinary Tract Infection After Urogynecologic Surgery: A Randomized Controlled Trial
Authors: Rieger Mary M. , Shah Nemi M. , Ferrante Kimberly L. , Tan-Kim Jasmine , Jacobs Marni B. , Brubaker Linda , Alperin Marianna
Published: July 2023

Importance

Currently available evidence for efficacy of postoperative antibiotics to prevent postoperative urinary tract infection (UTI) conflicts. Oral antibiotics rely on patient adherence and can cause unwanted systemic effects. Gentamicin is a broad-spectrum antibiotic with rapid bactericidal activity and, when administered intravesically, has no systemic absorption through intact urothelium.

Objective

We aimed to determine whether a single intravesical instillation of gentamicin at the conclusion of urogynecologic surgery would reduce the proportion of women treated for UTI within 6 weeks postoperatively compared with sham instillation.

Study Design

This was a multicenter, randomized (stratified by study site, route of prolapse repair ±suburethral sling, with balanced 1:1 randomization), participant-masked, sham-controlled, study. The primary outcome was the proportion of participants treated with antibiotics for UTI within 6 weeks postoperatively. An adjusted multivariable logistic regression model was constructed to determine predictors of postoperative UTI treatment.

Results

Three hundred seventy participants were randomized (gentamicin, 185; sham, 185), and data from 363 participants were analyzed (gentamicin, 183; sham, 180). Nineteen women in the gentamicin group and 20 women in the sham group were treated for UTI within 6 weeks postoperatively (10.4% vs 11.1%, P = 0.87). There were no adverse events related to the instillations. Increasing age (odds ratio, 1.028 [1.000–1.057]) and number of intraoperative transurethral instrumentations (odds ratio, 1.342 [1.080–1.668]) were independent predictors of postoperative UTI treatment.

Conclusions

In women undergoing urogynecologic surgery, postoperative intravesical gentamicin did not reduce the incidence of postoperative UTI. The number of intraoperative transurethral instrumentations is an important, potentially modifiable risk factor for postoperative UTI treatment.
“I’m Not Going Home With a Catheter”: Patient-Perceived Outcomes Associated With Perioperative Intermittent Catheterization
Authors: Shinnick Julia K. , Raker Christina A. , Geller Elizabeth J. , Rardin Charles R. , Cooper Anne C.
Published: July 2023

Importance

Indwelling catheters are a known source of dissatisfaction for postoperative patients. There is a paucity of data describing patient-perceived outcomes associated with the alternative of intermittent self-catheterization (ISC).

Objectives

The aim of this study was to describe patient satisfaction and outcomes associated with ISC after outpatient female pelvic reconstructive surgery.

Study Design

This was a secondary analysis of a prospective cohort study at an academic tertiary referral center from September 2018 to June 2021. Participants completed preoperative ISC instruction that included an instructional video, 1:1 demonstration with a health care provider, and provision of ISC supplies. Participants were instructed to perform ISC postoperatively until they had 2 consecutive outpatient PVRs less than one-half the voided volume. Participant satisfaction was assessed 2 weeks postprocedure, with adverse events evaluated at 6 weeks.

Results

One hundred sixty participants completed preoperative ISC instruction and were included in this analysis. Mean age was 52.1 (SD +/− 11.4) years, mean body mass index was 28.9 (SD +/− 5.8), and mean time from ISC instruction to surgery was 16.4 (SD +/− 15.7) days. Most participants reported no difficulty with ISC (124/160 [78%]) and had high levels of satisfaction (148/151 [98%]). Difficulty performing ISC was not associated with time since ISC instruction (P = 0.32), difficulty noted at ISC instruction by the health care provider (P = 0.24), or the duration of ISC instruction (P = 0.16). On multiple logistic regression, age, body mass index, and prolapse beyond the hymen did not predict difficulty learning or performing ISC. At 6 weeks postprocedure, 22 of 155 participants (14%) endorsed symptoms of a urinary tract infection, and 15 of 160 (9%) had a culture-proven urinary tract infection.

Conclusions

Women undergoing outpatient pelvic reconstructive surgery report ease and satisfaction with ISC.
Role of humanities in modern medical education
Authors: Isaac Mohan
Published: July 2023

Purpose of review

The role and importance of integrating humanities into medical education has been recognized for a long time. However, to what extent humanities are included in the medical curricula and how and when they are taught during the medical training in medical schools across the world is unclear. The review was undertaken to study the current status and role of humanities in medical education

Recent findings

Humanities content in the medical curriculum and the teaching of humanities continue to remain unstandardized. What constitutes medical humanities is unclear as there are several understandings of medical humanities. The benefits and value – both short term and long term - of including humanities in training of doctors and other health professionals remain unresolved and continue to be debated. Although some surveys have shown that exposure to the humanities was significantly correlated with positive personal qualities, including empathy, tolerance for ambiguity, wisdom, emotional appraisal, self-efficacy, and spatial skills, and inversely correlated with some components of burnout, robust evidence from well conducted studies to support the benefits of integrating humanities into medical training is very limited. An overreaching conceptual or theoretical framework for the health humanities in health professionals’ education continue to be elusive.

The status, stature, profile, and role of humanities in medical education remain varied across medical schools and universities. There is a need for standardized curricula, uniform criteria and guidelines for teaching medical humanities, training modules / materials, methods of assessment and better integration of humanities in medical education.
A glimpse into the dark – The bacterial and archaeal diversity of tropical anchialine cave sediments
Authors: Meland Kenneth , Iliffe Thomas M. , Thiele Stefan
Published: July 2023

Using Ion Torrent sequencing of the V4 region of the 16S rRNA gene, we investigated the sediment from four anchialine caves on Eleuthera (Bahamas). Anchialine caves are secluded, landlocked marine ecosystems, with high degrees of endemism. In the cave sediments, the bacterial and archaeal communities differ from marine communities and between caves, while often resembling those from low oxygen or anaerobic marine sediments. The waters of all caves investigated here were mostly saline and oxygenated, with Windermere Abyss differing from the other caves. This was mirrored by the bacterial and archaeal communities, with members of the wb1-A12 clade, Nitrosopumilaceae, members of the NB1-j phylum, and Actinomarinales being dominant in Preacher’s Blue Hole, Valentine’s Cave, and Bung Hole while Desulfatiglans, Bathyarchaeia, and members of the GIF3 and Sva0485 clades were dominant in Windermere Abyss. All communities showed taxa found in oxygenated and anoxic sediments, thus indicating a variety of chemoautotrophic lifestyles, including methane-, nitrogen-, and sulfur cycling. The communities were different from other caves and included understudied or otherwise rare taxa, partially from deep sea sediments, implying that the isolation mightdrive the evolution of the communities , and indicating that anchialine caves could be a window into the deep sea.
Serological status for TORCH in women of childbearing age: a decade-long surveillance (2012–2022) in Italy
Authors: Palazzotto Emilia , Bonura Floriana , Calà Cinzia , Capra Giuseppina , Pistoia Daniela , Mangione Donatella , Mascarella Chiara , Minì Giuseppe , Enea Marco , Giammanco Giovanni M. , Ferraro Donatella , De Grazia Simona
Published: July 2023

Introduction. Serological screening and seroprevalence data for TORCH infections represent a key instrument to estimate immunity and vaccination levels and exposure rates to prevent and treat TORCH congenital infections.

Hypothesis. Serology allows us to identify women susceptible to primary infection.

Aim. Assess the prevalence of women at risk of primary infections by TORCH pathogens in Palermo, Sicily, Italy, in the decade 2012–2022.

Methodology. A retrospective study was performed to evaluate the serological status (IgG and/or IgM) of 2359 women of childbearing age (WCBA), ranging from 16 to 46 years, attending the AOUP ‘P. Giaccone’ University Hospital of Palermo.

Results. The results showed an overall prevalence of anti-TORCH IgG of 90.5 % for herpesvirus (HSV), 81.2 % for rubella virus (RV), 72.1 % for cytomegalovirus (CMV), 20.9 % for Toxoplasma gondii (TOX) and 4.8 % for

Treponema pallidum

(TP). IgM positivity was 16.9 % for HSV2, 10.3 % for TOX, 4 % for CMV and, 2 % for RV. A recent/active infection by TP was confirmed in 28.3 % of the seropositive women. Our results indicate that only a small percentage of WCBA were subjected to a comprehensive TORCH serological screening, while most WCBA were only tested for a single pathogen. In addition, no significant differences were found in terms of the overall TORCH IgG seroprevalence among different age groups (P>0.05).

Conclusion. Identifying WCBA at risk of exposure during pregnancy allows us to prevent and reduce possible congenital infections, providing detailed guidelines and instructions. The results of this study showed that in Italy the risk of acquiring a primary infection by a TORCH agent is still high, therefore effective prevention strategies, including serological screening, should be implemented.
Implementation of routine genomic surveillance provided insights into a locally acquired outbreak caused by a rare clade of Salmonella enterica serovar Enteritidis in Queensland, Australia
Authors: Rathnayake Irani U. , Graham Rikki M. A. , Bayliss Jo , Staples Megan , Micalizzi Gino , Ariotti Lawrence , Cover Leonie , Heron Brett , Graham Trudy , Stafford Russell , Rubenach Sally , D'Addona Andrew , Jennison Amy V.
Published: July 2023

Salmonellosis is a significant public health problem globally. In Australia,

Salmonella enterica

serovar Enteritidis is one of the main causes of salmonellosis. This study reports how the implementation of routine genetic surveillance of isolates from human S. Enteritidis cases enabled identification of the likely source of an outbreak that occurred in a remote town in Far North Queensland, Australia. This study included patient, food and water samples collected during an outbreak investigation. S. Enteritidis of the novel sequence type 5438 was isolated from all seven patient samples and one bore water sample but not any of the food samples. Both whole-genome single nucleotide polymorphism (SNP) and core-genome multilocus sequence typing analysis revealed that S. Enteritidis isolated from outbreak-related patient samples and the bore water isolates clustered together with fewer than five SNP differences and ten allelic differences. This genetic relatedness informed the outbreak response team around public health interventions and no further cases were identified post-treatment of the bore water. This disease cluster was identified through the routine sequencing of S. Enteritidis performed by the state public health laboratory in an actionable time frame. Additionally, genomic surveillance captured a case with unknown epidemiological links to the affected community, ruled out a simultaneous outbreak in an adjacent state as the source and provided evidence for the likely source preventing further transmission. Therefore, this report provides compelling support for the implementation of whole-genome sequencing based genotyping methods in public health microbiology laboratories for better outbreak detection and management.
Liebig’s law of the minimum in the TGF-β/SMAD pathway
Authors: Li Yuchao , Deng Difan , Höfer Chris Tina , Kim Jihye , Heo Won Do , Xu Quanbin , Liu Xuedong , Zi Zhike
Published: July 2023

Cells use signaling pathways to sense and respond to their environments. The transforming growth factor-β (TGF-β) pathway produces context-specific responses. Here, we combined modeling and experimental analysis to study the dependence of the output of the TGF-β pathway on the abundance of signaling molecules in the pathway. We showed that the TGF-β pathway processes the variation of TGF-β receptor abundance using Liebig’s law of the minimum, meaning that the output-modifying factor is the signaling protein that is most limited, to determine signaling responses across cell types and in single cells. We found that the abundance of either the type I (TGFBR1) or type II (TGFBR2) TGF-β receptor determined the responses of cancer cell lines, such that the receptor with relatively low abundance dictates the response. Furthermore, nuclear SMAD2 signaling correlated with the abundance of TGF-β receptor in single cells depending on the relative expression levels of TGFBR1 and TGFBR2. A similar control principle could govern the heterogeneity of signaling responses in other signaling pathways.

One-sentence summary

Heterogeneous TGF-β signaling responses are dictated by the low abundance TGF-β receptor in different cell types and in single cells, resembling Liebig’s law of the minimum.
Indigenous probioticsLactobacillus reuteriandEnterococcus faeciumexhibit positive growth performance and disease prevention against extended-spectrum cephalosporin and fluoroquinolones resistantSalmonella entericain broiler chicks
Authors: Siddique Abubakar , Ali Roomana , Ali Amjad , Andleeb Saadia , Nimatullah  , Mohiuddin Mudassar , Akbar Samina , Imran Muhammad , Syoc Emily Van , Yue Min , Rahman Abdur , Ganda Erika
Published: July 2023

ABSTRACT

The rapid increase in antibiotic resistance poses a global threat to public health, necessitating the development of effective antimicrobial alternatives. This study compared an indigenous probiotic mix containingLactobacillus reuteriand two strains ofEnterococcus faeciumto a commercial probiotic blend ProtexinRon the growth performance, mortality rate, histomorphology, serum immunoglobulins, and intestinal microflora of broiler chickens challenged with two multi drug resistantSalmonellaserovars, Typhimurium and Enteritidis. Two hundred and forty day-old broiler chicks were randomly assigned to six treatment groups for 4 weeks: the treatment groups were; birds continuously supplemented with only indigenous probiotic strains (108CFU/mL) (IPRO-); birds challenged withSalmonellaserovars 106(CFU/mL) (PC+); birds continuously supplemented with indigenous probiotic strains and challenged withSalmonellaserovars (IPRO+); birds supplemented with ProtexinRand challenged withSalmonellaserovars (CM+); birds supplemented with only ProtexinR(CM-); and birds with noSalmonellachallenge or probiotics (negative control; PC-). The results revealed that IPRO- diets significantly improved feed conversion ratio (FCR) and increased body weight (BW) (P≤ 0.05). No effect of probiotic treatments was observed on IPRO- and CM- on relative organ weights as compared to the negative control (PC-). TheSalmonella- challenged group PC+ had the highest (20%) mortality rate and lowest BW. The IPRO- had significantly lower FCR (1.55) compared to PC- (1.86) and PC+ (1.95). The broilers in the IPRO- group showed significantly increased serum concentrations of IgA and IgG relative to both control groups (P≤ 0.05). Morphological analysis of the ileum revealed significant increases (P≤ 0.05) in the villus height and villus height/crypt depth in birds fed IPRO- compared with the PC+. CecalLactobacillusandEnterococcuscounts were the highest (P≤ 0.05) andSalmonellacounts were the lowest (P≤ 0.05) in the IPRO- group compared to theSalmonellainfected group PC+. These results indicated that indigenous probiotic strainsLactobacillus reuteriandEnterococcus faeciumcan be an effective and low-cost alternative compared to commercial probiotics in the Pakistan poultry industry.
Chimeric oncolytic adenovirus evades neutralizing antibodies from human patients and exhibits enhanced anti-glioma efficacy in immunized mice
Authors: Shin Dong Ho , Jiang Hong , Gillard Andrew , Kim Debora , Fan Xuejun , Singh Sanjay , Nguyen Teresa T , Sohoni Sagar , Lopez-Rivas Andres , Parthasarathy Akhila , Ene Chibawanye I. , Gumin Joy , Lang Frederick , Alonso Marta M , Gomez-Manzano Candelaria , Fueyo Juan
Published: July 2023

BACKGROUND

Oncolytic adenoviruses, such as Delta-24-RGD, show promise as a potential breakthrough in treating patients with high-grade gliomas. However, their effectiveness against gliomas can be hindered by the presence of neutralizing antibodies.

METHODS

Production of human neutralizing antibodies against adenoviruses was assessed in two cohorts of patients with malignant gliomas treated with Delta-24-RGD in a phase 1 clinical trial. Sera containing neutralizing antibodies were also obtained from mice immunized with intramuscular injections of wild-type Ad5. Chimeric adenovirus was constructed using molecular cloning, and its activity was assessed in vitro using quantitative PCR, western blot, and transmission electron microscopy. The therapeutic efficacy of the chimeric virus was tested in vivo using sera from patients previously treated with Delta-24-RGD and immunocompetent murine models of glioma.

RESULTS

Examination of sera from patients with malignant gliomas treated with Delta-24-RGD revealed that in the cohort treated with multiple injections of this oncolytic adenovirus, a higher percentage of patients developed neutralizing antibodies when compared to the patients treated with a single injection of Delta-24-RGD. Of note, long-term survival was only observed in patients who received a single injection. Delta-24-RGD-H43m, a chimeric oncolytic adenovirus engineered to overcome virus neutralization, demonstrated a potent anti-glioma effect both in vitro and in vivo. This chimeric virus showed resilience against anti-Ad5 neutralizing antibodies and conferred better therapeutic efficacy compared to Delta-24-RGD in mice with immunity against Ad5. Of further clinical relevance, Delta-24-RGD-H43m also evaded the inhibitory effects of sera from human patients treated with Delta-24-RGD.

CONCLUSIONS

The development of neutralizing antibodies due to multiple virus injections was associated with lower frequency of long-term survivors in a clinical trial. The new chimeric virus shows increased resilience to inactivation by the sera of human patients compared to the parental virus. These findings lay the foundation for a novel oncolytic virus treatment approach targeting a significant percentage of glioma patients with prior exposure to adenovirus.
Absence of CD47 in the tumor microenvironment modulates tumor metabolism and immunosuppressive signatures limiting breast cancer progression
Authors: Stirling Elizabeth R. , Tsai Yu-Ting , Bronson Steven M. , Wilson Adam , Westwood Brian , Thomas Alexandra , Triozzi Pierre L. , Furdui Cristina M. , Lesser Glenn J. , Cook Katherine L. , Soto-Pantoja David R.
Published: July 2023

The majority of breast cancers are generally considered immune-deprived tumors. This lack of immunogenicity severely hinders effectiveness of current immunotherapy approaches limiting therapeutic options to control disease. Therefore, we need new biomarkers to determine and enhance immune responses to improve the outcome of cancer patients experiencing invasive disease. Our data in matched human patient biopsies show that CD47 expression increases from primary to metastatic tumors. CD47 is an integral membrane protein that impairs antitumor immunosurveillance and influences normal tissue metabolism. However, whether CD47 plays a role in regulating tumor bioenergetics is unknown. A carcinogen-induced mouse mammary carcinogenesis model demonstrates that the absence of CD47 reduces tumor burden, which is associated with a distinct metabolic signature compared to WT tumors. Depletion of several lipid metabolites was observed in the absence of CD47, and metabolic dependency experiments suggest that anti-sense blockade of CD47 limits reliance on fatty acid oxidation as a fuel supporting cellular respiration on cancer cells. Our global metabolomics analysis also implicated the absence of CD47 in downregulation of immunosuppressive metabolites of the tryptophan and prostaglandin pathways. Spatial proteomic analysis revealed increased immune infiltrate and substantial reduction in immunosuppressive immune checkpoint proteins in the absence of CD47 with the highest reduction in intra-tumoral PD-L1 expression. Since anti-PD-L1 therapy is used in the current strategy to treat triple-negative breast cancer (TNBC), we targeted CD47 in an EMT-6 syngeneic TNBC model. Thein vivoknockdown of CD47 sensitized tumors to anti-PD-L1 therapy to decrease tumor burden and increase intratumoral cytotoxic T cells. Therefore, targeting CD47 may be a suitable immunotherapeutic option to limit immunosuppression and enhance the efficacy of immune checkpoint blockade.
Tutorial on MUedit: An open-source software for identifying and analysing the discharge timing of motor units from electromyographic signals
Authors: Avrillon Simon , Hug François , Gibbs Ciara , Farina Dario
Published: July 2023

We introduce the open-source software MUedit and we describe its use for identifying the discharge timing of motor units from all types of electromyographic (EMG) signals recorded with multi-channel systems. MUedit performs EMG decomposition using a blind-source separation approach. Following this, users can display the estimated motor unit pulse trains and inspect the accuracy of the automatic detection of discharge times. When necessary, users can correct the automatic detection of discharge times and recalculate the motor unit pulse train with an updated separation vector. Here, we provide an open-source software and a tutorial that guides the user through i) the parameters and steps of the decomposition algorithm, and ii) the manual editing of motor unit pulse trains. Further, we provide simulated and experimental EMG signals recorded with grids of surface electrodes and intramuscular electrode arrays to benchmark the performance of MUedit. Finally, we discuss advantages and limitations of the blind-source separation approach for the study of motor unit behaviour during muscle contractions in humans.
Single Cell Portal: an interactive home for single-cell genomics data
Authors: Tarhan Leyla , Bistline Jon , Chang Jean , Galloway Bryan , Hanna Emily , Weitz Eric
Published: July 2023

Single-cell omics research has the power to leave a deep impact on modern healthcare. Sharing data widely and freely advances this progress in both the academic and clinical spheres. We developed the Single Cell Portal (SCP) to maximize the impact of this work. SCP enables data sharing, supports dynamic results visualization, and facilitates scientific exploration across a large repository of single-cell datasets. SCP’s data contributors maintain full control over how their data are shared and presented, without requiring web development expertise. Finally, SCP supports the entire lifecycle of a research project, from sparking an idea, to fine-tuning the data with collaborators, to sharing results in an accessible and interactive way. This paper highlights the most valuable ways in which SCP helps to advance single-cell research.
Development and Assessment of a Sustainable PhD Internship Program Supporting Diverse Biomedical Career Outcomes
Authors: Brandt Patrick D. , Whittington Dawayne , Wood Kimberley D. , Holmquist Chris , Nogueira Ana T. , Gaines Christiann H. , Brennwald Patrick J. , Layton Rebekah L.
Published: July 2023

A doctoral-level internship program was developed at the University of North Carolina at Chapel Hill with the intent to create customizable experiential learning opportunities for biomedical trainees to support career exploration, preparation, and transition into their post-graduate professional roles. We report the outcomes of this program over a five-year period. During that 5-year period, 123 internships took place at over 70 partner sites, representing at least 20 academic, for-profit, and non-profit career paths in the life sciences. A major goal of the program was to enhance trainees’ skill development and expertise in careers of interest. The benefits of the internship program for interns, host/employer, and supervisor/principal investigator were assessed using a mixed-methods approach, including surveys with closed- and open-ended responses as well as focus group interviews. Balancing stakeholder interests is key to creating a sustainable program with widespread support; hence, the level of support from internship hosts and faculty members were key metrics analyzed throughout. We hypothesized that once a successful internship program was implemented, faculty culture might shift to be more accepting of internships; indeed, the data quantifying faculty attitudes support this. Furthermore, host motivation and performance expectations of interns were compared with results achieved, and this data revealed both expected and surprising benefits to hosts. Data suggests a myriad of benefits for each stakeholder group, and themes are cataloged and discussed. Program outcomes, evaluation data, policies, resources, and best practices developed through the implementation of this program are shared to provide resources that facilitate the creation of similar internship programs at other institutions. Program development was initially spurred by National Institutes of Health pilot funding, thereafter, successfully transitioning from a grant-supported model, to an institutionally supported funding model to achieve long-term programmatic sustainability.
A Burst-dependent Thalamocortical Substrate for Perceptual Awareness
Authors: Whyte Christopher J. , Müller Eli J. , Aru Jaan , Larkum Matthew , John Yohan , Munn Brandon R. , Shine James M.
Published: July 2023

Contemporary models of perceptual awareness lack tractable neurobiological constraints. Inspired by recent cellular recordings in a mouse model of tactile threshold detection, we constructed a biophysical model of perceptual awareness that incorporated essential features of thalamocortical anatomy and cellular physiology. Our model reproduced, and mechanistically explains, the keyin vivoneural and behavioural signatures of perceptual awareness in the mouse model, as well as the response to a set of causal perturbations. We generalised the same model (with identical parameters) to a more complex task – visual rivalry – and found that the same thalamic-mediated mechanism of perceptual awareness determined perceptual dominance. This led to the generation of a set of novel, and directly testable, electrophysiological predictions. Analyses of the model based on dynamical systems theory show that perceptual awareness in simulations of both threshold detection and visual rivalry arises from the emergent systems-level dynamics of thalamocortical loops.
RNA Strain-Match: A tool for matching single-nucleus, single-cell, or bulk RNA-sequencing alignment data to its corresponding genotype
Authors: Willcox Jon A. L. , Telpoukhovskaia Maria A. , Hadad Niran , Boas Stephanie M. , Dunn Amy , Saul Michael C. , Ashbrook David G. , Williams Robert W. , O’Connell Kristen M. S. , Kaczorowski Catherine C.
Published: July 2023

When next generation sequencing is performed in large batches, there are several stages at which samples can be swapped or mislabeled. It is therefore helpful, when possible, to integrate measures into analysis pipelines to confirm that samples match their assigned metadata. Here, we introduce RNA Strain-Match (GitHub:https://github.com/jon-willcox/RNA-strain-match), a quality control tool developed to match RNA data in the form of sequence alignment files (i.e. SAM or BAM files) to their corresponding genotype without the use of an RNA variant call format file. We successfully used RNA Strain-Match in tandem with assessment of markers for sex and transgene status to identify and correct sample mismatches in 50/379 samples (13%) from two distinct recombinant inbred mouse models (BXD and Collaborative Cross). We believe this tool will be beneficial to any research group working with similar data.
Fully automated and integrated proteomics sample preparation platform for high-throughput drug target identification
Authors: Wu Qiong , Zheng Jiangnan , Sui Xintong , Fu Changying , Cui Xiaozhen , Liao Bin , Ji Hongchao , Luo Yang , He An , Lu Xue , Tan Chris Soon Heng , Tian Ruijun
Published: July 2023

With the increased demand of large-cohort proteomic analysis, fast and reproducible sample preparation has become the critical issue that needs to be solved. Herein, we developed a fully automated and integrated proteomics sample preparation workflow (autoSISPROT), enabling the simultaneous processing of 96 samples in less than 2.5 hours. Benefiting from its 96-channel all-in-tip operation, protein digestion, peptide desalting, and TMT labeling could be achieved in a fully automated manner. The autoSISPROT demonstrated good sample preparation performances, including >94% of digestion efficiency, nearly 100% of alkylation efficiency, >98% of TMT labeling efficiency, and >0.9 of intra- and inter-batch Pearson correlation coefficients. Furthermore, by combining with cellular thermal shift assay-coupled to mass spectrometry (CETSA-MS), the autoSISPROT was able to process and TMT-label 40 samples automatically and accurately identify the known target of methotrexate. Importantly, taking advantage of the data independent acquisition and isothermal CETSA-MS, the autoSISPROT was well applied for identifying known targets and potential off-targets of 20 kinase inhibitors by automatedly processing 87 samples, affording over a 10-fold improvement in throughput when compared to classical CETSA-MS. Collectively, we developed a fully automated and integrated workflow for high-throughput proteomics sample preparation and drug target identification.
Short and Long-term Mortality of Pneumococcal Pneumonia in Adults and Children- A Detailed Scoping Review
Authors: Vijayan Rupalakshmi , Nagpal Shavy , Dissanayake Manthi , Masthan Shameera Shaik , Fatima Aiman , Ramirez Julio , Karkera Sahana , Dutta Ipshita , Karani Pavani , Chao Andrea Galecio
Published: July 2023

Streptococcus pneumoniae is a common infectious agent responsible for pneumonia, which can result in serious complications such as meningitis, sepsis, morbidity, and mortality. The objective of this study is to examine the risk factors and complications associated with mortality caused by community-acquired pneumococcal pneumonia in both adults and children. To conduct this research, a thorough literature review was carried out by researchers between May 1, 2021, and August 1, 2021. Various databases, including PubMed, WHO,clinicaltrials.gov, Embase, Web of Science, Cochrane, and Google Scholar, were searched using specific keywords such as mortality, pneumococcal pneumonia, adults, children, and their combinations. The study encompassed patients of all age groups affected by pneumococcal pneumonia, while systematic reviews focusing on other types of pneumonia and non-pneumonia patients were excluded. After eliminating duplicate studies, the search yielded 1783 relevant articles, which underwent title and abstract screening. Ultimately, 8 studies were included in the final review. In conclusion, pneumococcal pneumonia is a significant contributor to mortality among both adults and children. This research emphasizes the importance of implementing effective management strategies to reduce long-term mortality
Causal association of COVID-19 with brain structure changes: Findings from a non-overlapping 2-sample Mendelian randomization study
Authors: Ding Pingjian , Xu Rong
Published: July 2023

Recent cohort studies suggested that SARS-CoV-2 infection is associated with changes in brain structure. However, the potential causal relationship remains unclear. We performed a two-sample Mendelian randomization analysis to determine whether genetic susceptibility of COVID-19 is causally associated with changes in cortical and subcortical areas of the brain. This 2-sample MR (Mendelian Randomization) study is an instrumental variable analysis of data from the COVID-19 Host Genetics Initiative (HGI) meta-analyses round 5 excluding UK Biobank participants (COVID-19 infection, N=1,348,701; COVID-19 severity, N=1,557,411), the Enhancing NeuroImaging Genetics through Meta Analysis (ENIGMA) Global and regional cortical measures, N=33,709; combined hemispheric subcortical volumes, N=38,851), and UK Biobank (left/right subcortical volumes, N=19,629). A replication analysis was performed on summary statistics from different COVID-19 GWAS study (COVID-19 infection, N=80,932; COVID-19 severity, N=72,733). We found that the genetic susceptibility of COVID-19 was not significantly associated with changes in brain structures, including cortical and subcortical brain structure. Similar results were observed for different (1) MR estimates, (2) COVID-19 GWAS summary statistics, and (3) definitions of COVID-19 infection and severity. This study suggests that the genetic susceptibility of COVID-19 is not causally associated with changes in cortical and subcortical brain structure.
Risk factors for severe complications and mortality among hospitalized children with measles during a major outbreak in Northern Vietnam, 2017 - 2019
Authors: Tran Minh Dien , Pham Nhung T. H. , Vu Hoang Nguyen , Tran Minh-Hung , Ngo Hoang-Anh , Phan Phuc H
Published: July 2023

Introduction

Measles outbreaks increased worldwide during the period of 2017-2019. Similarly, Vietnam experienced one of the largest measles outbreaks in recent decades, with various paediatric patients presenting severe complications. In this study, we aim to identify factors associated with death and severity among children with measles admitted to Vietnam National Children’s Hospital (VNCH) in Hanoi, Vietnam between 2017 and 2019.

Method

This single-center retrospective cohort study included 2, 072 patients with measles admitted to VNCH from 1/1/2017 to 31/12/2019. Data on epidemiological, clinical characteristics, vaccine status, and outcomes were collected and summarised. We conducted both univariable and multivariable logistic regression analyses to examine the correlations between various characteristics of hospitalized children and mortality.

Findings

In total, there were 2, 072 patients, including 1, 297 (62.6%) males and 775 (37.4%) females. The median age was 9 months (interquartile range 7−17). 87.3% of cases had not received any measles-containing vaccine (MCV). 30 (1.4%) patients died, with 40% aged less than 9 months. Only 3 among 30 (10%) who died had received at least 1 dose of MCV. Bronchopneumonia was the most common complication, occurring in 1, 413 (68.2%) patients. The following characteristics were significantly associated with mortality in the multivariable analysis: age under 9 months and age from 9 months to 5 years, residing 20 to 200 kilometres from VNCH, and having co-infection with adenovirus or other hospital acquired infections. Age group was also significantly associated with severity in the multivariable analysis.

Interpretation

Vietnam continues to face the threat of future measles epidemics, given the burden of hospitalization and the high rate of complications observed in hospitalized patients. This highlights the critical need to maintain high measles vaccine coverage, particularly by targeting the unvaccinated population. To prevent future outbreaks and lower measles incidence, routine immunization needs to be strengthened, and earlier scheduling of MCV1 needs to be further evaluated. The comprehensive analysis of the 2017-19 measles outbreak presented in this study will contribute to informed decision-making regarding appropriate measures to counteract future resurgences of measles in Vietnam.

Funding

No specific grant from funding agencies in the public, commercial or not-for-profit sectors supported the submission and publication of this manuscript.