bluuebunny/crossref_metadata_2025 huggingface dataset:
Milrinone Versus Sildenafil in Treatment of Neonatal Persistent Pulmonary Hypertension: A Randomized Control Trial
Authors: Imam Safaa S. , El-Farrash Rania A. , Taha Amr S. , Saleh Ghada A.
Published: July 2022

Persistent pulmonary hypertension of the newborn (PPHN) is a condition caused by failure of pulmonary vascular adaptation at birth, resulting in severe hypoxia. Several therapeutic modalities are being tried in developing countries where established therapies (inhaled nitric oxide and extracorporeal membrane oxygenation) are widely unavailable. This study aimed to assess the efficacy of milrinone versus sildenafil as available alternative therapeutics in treating PPHN. Forty neonates (>34 weeks) admitted to neonatal intensive care units with evidence of PPHN were randomly allocated to receive either oral sildenafil (0.5–2 mg/kg/6 hours) or intravenous milrinone (0.25–0.75 mic/kg/min). Primary outcomes included improvements in systolic pulmonary artery pressure and oxygen saturation index (OSI) at 24 and 48 hours after treatment. Secondary outcomes included the duration of hospitalization and mechanical ventilation. The ClinicalTrials identifier is NCT04391478. Both groups showed significant improvement in the post-treatment hemodynamic variables compared with pretreatment levels (P < 0.05 for all parameters). Systolic pulmonary artery pressure and OSI values significantly improved in both study groups compared with baseline (P < 0.001). The 24-hour and 48-hour post-treatment OSI values were much lower in the milrinone group than those in the sildenafil group (P < 0.05). The length of hospital stay was significantly shorter in the milrinone group than that in the sildenafil group (P < 0.05). There were no significant differences in the duration of mechanical ventilation, incidence of intracranial hemorrhage and pulmonary hemorrhage, or mortality between the 2 groups (P > 0.05). In conclusion, milrinone and sildenafil are effective and well-tolerated in neonates with PPHN, particularly when inhaled nitric oxide and extracorporeal membrane oxygenation are not available. Milrinone is superior to sildenafil in improving oxygenation without lowering blood pressure parameters.
Adverse Childhood Experiences and Neurocognition in Borderline Personality Disorder: A Call-to-Action Perspective Review
Authors: Estric Clémentine , Calati Raffaella , Lopez-Castroman Jorge
Published: July 2022

Adverse childhood experiences (ACEs) contribute to the development of personality traits leading to adult borderline personality disorder (BPD). Neurocognitive changes could partly mediate the association between ACEs and BPD. We discuss how exposure to ACEs could induce alterations in neurocognition, which, in turn, would contribute to the development of BPD. We conducted a review of MEDLINE articles through 2021, documenting a link between ACEs, neurocognitive impairments, and BPD, and also focusing on the pairwise associations. ACEs appear to have a strong impact on neurocognition and are a predictive factor for BPD. Maltreated, abused, and emotionally invalidated children are more likely to present BPD traits. Neurocognitive impairments in adults exposed to ACEs and in patients with BPD arise from similar brain alterations in the amygdala, hippocampus, and prefrontal cortex. These impairments seem to be linked with clinical dimensions of BPD: increased impulsivity to altered inhibitory control; dissociative experiences to nonspecific autobiographical memory; and emotionally biased facial recognition to unstable interpersonal relationships. This perspective review highlights the contributory role of neurocognition in the association between ACEs and BPD. Additional research is needed, however, on the interconnections among ACEs, neurocognition, and BPD. Future studies could also focus on developing tools to assess early adversity in BPD specifically and on psychotherapeutic approaches to promptly remedy neurocognitive impairments.
Incontinentia pigmenti and the eye
Authors: Islam Yasmin Florence Khodeja , Khurshid Syed Gibran
Published: July 2022

Purpose of Review:

Incontinentia pigmenti (IP) is a rare X-linked dominant phakomatosis that predominately presents with dermatologic manifestations but can also cause central nervous system and ocular abnormalities. Awareness of the ocular complications of IP is crucial to identify ocular abnormalities early and prevent permanent vision loss.

Recent Findings:

There have been significant recent advances in ocular diagnostic imaging in IP. Optical coherence tomography (OCT) has helped characterize outer plexiform layer abnormalities in the macula, which can help explain central vision loss in IP patients. OCT angiography (OCT-A) also identifies macular vascular changes that induce these foveal structural abnormalities and may supplement fluorescein angiography, the current standard of care to identify peripheral retinal ischemia and neovascularization for infants with IP. Additionally, recent studies have presented excellent anatomic outcomes years after laser photocoagulation to ischemic retina. Early data indicates that antivascular endothelial growth factor therapy can induce retinal revascularization, but runs the risk of late recurrent neovascularization and requires long-term monitoring.

Ophthalmic imaging is evolving in the evaluation of IP and is increasingly guiding treatment modalities. A particular focus on the ocular manifestations of IP has been the ideal treatment for retinopathy in this disorder.
Artificial intelligence and corneal diseases
Authors: Kang Linda , Ballouz Dena , Woodward Maria A.
Published: July 2022

Purpose of review

Artificial intelligence has advanced rapidly in recent years and has provided powerful tools to aid with the diagnosis, management, and treatment of ophthalmic diseases. This article aims to review the most current clinical artificial intelligence applications in anterior segment diseases, with an emphasis on microbial keratitis, keratoconus, dry eye syndrome, and Fuchs endothelial dystrophy.

Recent findings

Most current artificial intelligence approaches have focused on developing deep learning algorithms based on various imaging modalities. Algorithms have been developed to detect and differentiate microbial keratitis classes and quantify microbial keratitis features. Artificial intelligence may aid with early detection and staging of keratoconus. Many advances have been made to detect, segment, and quantify features of dry eye syndrome and Fuchs. There is significant variability in the reporting of methodology, patient population, and outcome metrics.

Artificial intelligence shows great promise in detecting, diagnosing, grading, and measuring diseases. There is a need for standardization of reporting to improve the transparency, validity, and comparability of algorithms.
A novel diagnostic tool for hyaline vascular Castleman disease versus lymphoma based on contrast-enhanced computed tomography in neck mass
Authors: Lin Huan-Yu , Liao Pei-Shao , Shih Liang-Chun , Hua Chun-Hung , Tsai Ming-Hsui , Lin Chia-Der
Published: July 2022

Background:

Castleman disease and lymphoma each have a distinct treatment plan; however, they share the same features on contrast-enhanced computed tomography.

Methods:

To assess the quantitative outcomes of Castleman disease versus lymphoma using contrast-enhanced computed tomography based on Hounsfield units (HU). We retrospectively reviewed eight patients with unicentric Castleman disease and 30 patients with lymphoma based on pathological diagnosis at China Medical University Hospital between 2015 and 2020. Preoperative computed tomography with contrast scans was reviewed, and the HU of each tumor were measured.

Results:

This study included eight patients with unicentric Castleman disease (four men and four women; mean age, 33 years) and 25 patients with lymphoma (11 men and 14 women; mean age, 53 years). There was no significant difference in heterogeneity between the two diseases (0.161 ± 0.052 vs 0.239 ± 0.063, p = 0.22); however, enhancement in Castleman disease was higher than that in lymphoma (126.40 ± 31.90 vs 74.19 ± 7.11, p < 0.001), providing a very good diagnostic tool (cutoff point at 88.5–91.3, sensitivity 0.86/specificity 0.88). Furthermore, we found a highly linear relationship in Castleman disease, which was not noted in lymphoma.

Conclusion:

The value of HU provides a good diagnostic tool for the differential diagnosis of Castleman disease versus lymphoma in the neck lymph nodes. Considering the linear relationship in Castleman disease, an increasingly accurate differential diagnosis can be made.
Keeping Patients Safer: Reviewing Predictors of Success and Failure of Short Peripheral Intravenous Catheters
Authors: DeVries Michelle , Scott Nancy
Published: July 2022

In 2014, a large urban community hospital adopted protected clinical indication practices as a quality improvement project. It then undertook a research study to examine bedside practices with short peripheral catheters, which included direct observation at the bedside once weekly for 6 months. A total of 4305 catheters were observed and remained in place for a total of 23 423 days. Fifty six percent of devices remained in place beyond 96 hours. The overall rate of peripheral bloodstream infection in patients enrolled in the study was 0.12/1000 peripheral intravenous days. Significant differences were noted based on which department placed the catheter, as well as which department cared for the patient during hospitalization. Patients admitted to step-down critical care units had the highest completion of therapy rates; however, those being cared for in medical/surgical units had the best outcomes. Devices placed in the emergency department had a higher successful dwell rate than those placed in critical care units. Twenty-gauge catheters were found to have the highest successful dwell rate, as well as insertion sites that were observed to be within normal limits during the weekly observation. Dressings that were noted to be clean, dry, and intact had a stronger association with completion of therapy than those that were not fully intact. Emphasis was placed on ensuring consistent practices with insertion, care, and maintenance, which contributed to more consistent outcomes between settings that insert, care for, and maintain devices. Nonmodifiable risk factors may remain.
Antimicrobial Stewardship for the Infusion Nurse
Authors: Linn Becky S. , Jensen Jada
Published: July 2022

The consequences of antimicrobial overuse are complex. Censoring overuse requires strategic efforts directed at tailoring antimicrobial prescribing habits. Antimicrobial stewardship combats the negative consequences for patients and society. All members of the health care team can influence stewardship efforts in the patient treated for infectious diseases. Many of the potent antimicrobials used today are given by infusion, providing an exceptional opportunity for the infusion nurse to become a crucial part of the antimicrobial stewardship team. The goal of this article is to explain why antimicrobials are worth caring for and preserving, as well as to define the role of the infusion nurse in the antimicrobial stewardship team.
Impact of the Virtual Format on Plastic Surgery Residency and Fellowship Interviews: A National Cross-Sectional Study
Authors: Ferry Andrew M. , Asaad Malke , Elmorsi Rami , Rajesh Aashish , Williams Elizabeth M. , Wolf Steven E. , Rohrich Rod J. , Pederson William C. , Maricevich Renata S.
Published: July 2022

Background:

The 2020-2021 residency and fellowship application cycles were profoundly affected by the introduction of virtual interviews (VIs). The authors investigate the impact that the virtual format (VF) had on plastic surgery residency and fellowship interviews from the perspectives of program directors (PDs).

Methods:

Surveys were sent to PDs of integrated plastic surgery residency (RPD) and fellowship (FPD) programs to ascertain their perspectives regarding the VF’s impact on residency and fellowship interviews. PDs were stratified into residency and fellowship cohorts, and comparative analysis was performed.

Results:

A total of 92 PDs, 28 RPDs and 64 FPDs, completed our survey (35%). When compared to in-person interviews, VIs were reported to be more economical and time efficient by RPDs (100% and 46%, respectively) and FPDs (97% and 48%, respectively). Consequentially, 36% and 47% of residency and fellowship programs were able to interview more applicants, respectively. RPDs and FPDs reported that VIs hindered their ability to assess applicants’ fit with the program (75% and 63%, respectively), personality and communication skills (75% and 64%, respectively), and commitment to the field along with their ability to function as a trainee (57% and 50%, respectively). Overall, 71% of RPDs and 58% of FPDs preferred in-person interviews. The majority of residency (71%) and fellowship (56%) programs intend to conduct both in-person and VIs in future application cycles (p=0.12).

Conclusions:

Despite preferring in-person interviews, PDs intend on hosting both in-person and VIs in future application cycles. It remains to be seen how VIs will be employed moving forward.
Is It Really Safe to Discontinue Anticoagulant Treatment Before Ptosis Surgery From Serious Bleeding?
Authors: Lee Kangmin , Chang Minwook
Published: July 2022

Purpose:

To evaluate the effects of discontinuing anticoagulants (ACs)/antiplatelets (APs) preoperatively on surgery for blepharoptosis.

Method:

A retrospective analysis included patients with acquired blepharoptosis who underwent surgical correction, and were followed for more than 1 month. Patients were classified into 2 groups depending on AC/AP treatment or otherwise. All patients taking AC/AP discontinued with the treatment 1 week prior to surgery in accordance with our clinical guidelines. Preoperative and postoperative marginal reflex distance 1 (MRD1) and ecchymosis grade were evaluated and compared.

Results:

Group 1 (AC/AP treatment cessation) included 47 patients with 93 eyelids, and group 2 (control) included 51 patients with 98 eyelids. The preoperative MRD1 showed no significant difference between groups. Group 1 showed a significantly higher rate of severe ecchymosis (41.8 versus 22.4%, P = 0.004) at 1 week of surgery as well as persistent ecchymosis (58.8 versus 7.3%, P = 0.000) compared with group 2 postoperatively at 1 month. Postoperative MRD1 was significantly lower in group 1 at 1 week (P = 0.019). However, the MRD1 and degree of improvement in lid height (postoperative MRD1 “preoperative MRD1) was not significantly different between the 2 groups (P = 0.499, P = 0.058) at 1 month postoperatively.

Conclusions:

Postoperative ecchymosis was more severe in group 1 at 1 month after ptosis surgery even though the ACs/APs were discontinued. Surgeons should be careful about this before operation.

The Synopsis:

Significant ecchymosis could occur even after discontinuation of antithrombotic agents in patients with a history of taking medication in ptosis surgery. Surgeons should be careful about this before operation.
Glue Embolization Without Surgical Resection for Orbital Venolymphatic Malformation
Authors: Saffari Persiana S. , Rootman Daniel B. , Karlin Justin N.
Published: July 2022

A 59-year-old man presented with worsening left-sided eye pain and headache from a left orbital venous-dominant venolymphatic malformation. He reported a history of sclerotherapy, experiencing only transient relief with this procedure. Oral analgesia had not helped alleviate the pain. He described the pain as dull and intermittent, and noted worsening with physical exertion. Physical examination revealed dense left optic neuropathy, motility restriction, enophthalmos, and Valsalva-induced proptosis. Given baseline enophthalmos and poor vision affecting the left eye, glue embolization without surgical resection was offered. He underwent 2 rounds of percutaneous n-Butyl cyanoacrylate embolization performed 11 months apart. Following these procedures, he reported sustained pain relief, as compared with prior sclerotherapy procedures. Glue embolization without surgical resection may provide a novel approach to orbital venolymphatic malformations in selected patients.
Neck Pain Caused by Giant Dorsal Lipoma
Authors: Choi Jong Yun , Choi Young Jae , Seo Bommie Florence
Published: July 2022

Giant lipomas are uncommon in the neck or craniofacial region. A 55-year-old male presented with a large pendulous mass arising from the dorsal aspect of his neck, which he had known about for 20 years. Discomfort during sleeping, frequent headaches, and chronic neck pain were his chief complaints. Computed topography revealed a well-circumscribed lipomatous lesion. A decrease in cervical spine lordosis was noted on sagittal x-rays. Surgical excision with local flap coverage was performed. The specimen weighed 2800 g. The patient reported immediate resolution of neck pain, and complete resolution of headaches following surgery. An increase in the degree of lordosis was seen in sagittal x-rays. Histopathological results confirmed the diagnosis of lipoma. Although most giant dorsal neck lipomas are benign, they may be a cause for neck pain, headaches and degenerative changes in the cervical spine, undermining the quality of life. Such symptoms should be assessed, and removal recommended.
Pedobacter mucosus sp. nov., isolated from a soil sample of glacier foreland in Austre Lovénbreen, Arctic
Authors: Huang Jun , Peng Xiaoya , Qin Kun , Liu Yixuan , Niu Jingjing , Liu Jia , Dong Jielin , Zhang Yongping , Peng Fang
Published: July 2022

A rod-shaped, Gram-stain-negative, non-motile and aerobic bacterium, designated Q8-18T, was isolated from soil of glacier foreland in Austre Lovénbreen, Arctic, and subjected to a polyphasic taxonomic study. Strain Q8-18T grew optimally at 20 °C, pH 5.0–8.0 and in the presence of 0–1.0 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain Q8-18T belonged to the family

Sphingobacteriaceae

. Strain Q8-18T showed the highest sequence similarity to

Pedobacter mendelii

CCM 8685T (96.8%),

Pedobacter lithocola

CCM 8691T (96.8%),

Pedobacter roseus

CL-GP80T (96.7%),

Pedobacter changchengzhani

E01020T (96.7%),

Pedobacter alluvionis

DSM 19624T (96.6%),

Pedobacter jejuensis

THG-DR3T (96.3%),

Pedobacter ginsengiterrae

DCY49T (95.9%) and

Pedobacter jamesrossensis

CCM 8689T (95.9%). A whole genome-level comparison of strain Q8-18T with

P. roseus

CL-GP80T,

P. changchengzhani

E01020T,

P. alluvionis

DSM 19624T and

Pedobacter heparinus

LMG 10339T revealed average nucleotide identity values of 77.0, 76.0, 77.0 and 70.4%, respectively. The only respiratory isoprenoid quinone was menaquinone-7. The polar lipid profile of strain Q8-18T was found to contain one phosphatidylethanolamine, eight unidentified aminolipids, one aminophospholipids and five unidentified lipids. The G+C content of the genomic DNA was determined to be 35.4 mol%. The main fatty acids were summed feature 3 (comprising C16 : 1
 ω7c and/or C16 : 1
 ω6c), iso-C15 : 0 and anteiso-C15 : 0. On the basis of the evidence presented in this study, a novel species of the genus

Pedobacter

, Pedobacter mucosus sp. nov., is proposed, with the type strain Q8-18T (=CCTCC AB 2020009T=KCTC 82636T).
Sinomicrobium kalidii sp. nov., an indole-3-acetic acid-producing endophyte from a shoot of halophyte Kalidium cuspidatum
Authors: Li Lu-Fan , Xu Lian , Li Wen-Hao , Sun Ji-Quan
Published: July 2022

To better understand the effects of endophytic bacteria on halophytes, a bacteria that produced indole-3-acetic acid and 1-aminocyclopropane-1-carboxylic acid deaminase, designated HD2P242T, was isolated from a shoot of Kalidium cuspidatum collected in Tumd Right Banner, Inner Mongolia, PR China. The cells of strain HD2P242T were Gram-stain-negative, strictly aerobic, motile by gliding, non-spore-forming and rod-shaped. Strain HD2P242T grew at pH 6.0–9.0 (optimum, pH 7.0) and 10–45 °C (optimum 37 °C), in the presence of 0–8 % (w/v) NaCl (optimum, 4 %). The strain was positive for oxidase and catalase. The phylogenetic trees based on the 16S rRNA gene sequences and the whole genome sequences both showed that strain HD2P242T clustered with

Sinomicrobium pectinilyticum

5DNS001T and

S. oceani

SCSIO 03483T, and had 95.6, 94.3 and <94.3 % 16S rRNA gene similarities to

S. pectinilyticum

5DNS001T,

S. oceani

SCSIO 03483T and all the other current type strains. Strain HD2P242T contained menaquinone 6 as its sole respiratory quinone. Its major polar lipids were phosphatidylethanolamine, two unidentified aminolipids, two unidentified phospholipids and an unidentified lipid. The major fatty acids were iso-C17 : 0, iso-C16 : 0 3-OH, anteiso-C17 : 0 and summed feature 6 (C19 : 1
 ω9c and/or C19 : 1
 ω11c). The genome consisted of a 5 364 211 bp circular chromosome, with a G+C content of 45.1 mol%, predicting 4391 coding sequence genes, 47 tRNA genes and two rRNA operons. The average nucleotide identity based on blast and the digital DNA–DNA hybridization values of strain HD2P242T with

S. oceani

SCSIO 03483T and

S. pectinilyticum

5DNS001T were 73.8 and 77.0%, and 22.3 and 22.2%, respectively. The comparative genome analysis showed that the pan-genomes of strain HD2P242T and three

Sinomicrobium

type strains possessed 4236 clusters, whereas the core genome possessed 2162 clusters, which accounted for 52.3 % of all the clusters. The genomic analysis revealed that all four

Sinomicrobium

members could utilize d-glucose by the glycolysis–gluconeogenesis pathway or the pentose phosphate pathway. The tricarboxylic acid cycle was utilized as a metabolic centre. The phylogenetic, physiological and phenotypic characteristics allowed the discrimination of strain HD2P242T from its phylogenetic relatives. Therefore, Sinomicrobium kalidii sp. nov. is proposed, and the type strain is HD2P242T (=CGMCC 1.19025T=KCTC 92136T).
The quality characteristics of plant-based garlic mayonnaise using
chickpea aquafaba with different ultrasonic treatment time
Authors: Kim Jungsoo , Kim Jiyoon , Jeong Saeul , Kim Minhyun , Park Sanghyeok , Kim Insun , Nam Inju , Park Junyeong , Moon Kwang-Deog
Published: July 2022

Recently, there has been a growing trend to replace animal ingredients used in
food with plant-based alternatives for health, environment, and animal welfare.
In this study, chickpea aquafaba was used as emulsifier for mayonnaise, and the
effect of ultrasound on aquafaba and plant-based mayonnaise was investigated.
Aquafaba with chickpea [1:2 (w/w)] was treated by ultrasound in 40 kHz and 200 W
for 0, 30, 60, and 90 min. The emulsion property and quality of aquafaba with
ultrasonic treatment time (UTT) and plant-based mayonnaise (UTT0, UTT30, UTT60,
and UTT90) were analyzed, and compared with mayonnaise using egg yolk (CONT). As
the UTT of aquafaba, the protein solubility increased, but emulsion activity
index was highest in sample treated for 30 min (p<0.05). These results
affected plant-based mayonnaise. The microstructure was confirmed that oil
droplet of plant-based mayonnaises were larger than CONT, and size of oil
droplet decreased by UTT. The emulsion stability of plant-based mayonnaises were
about 7-11% lower than CONT, and among plant-based mayonnaises, UTT30 was the
highest at 81.30%, and UTT60 and UTT90 were the lowest. Plant-based mayonnaise
had higher viscosity and overall acceptability than CONT, and viscosity
decreased by UTT. Optimal UTT had a beneficial effect on the emulsion property
of aquafaba and mayonnaise, and a positive role can be expected as plant-based
alternative emulsifier.
The specificity of different-distance connections in human structural connectomes
Authors: Yang Yaqian , Zheng Yi , Zhen Yi , Tang Shaoting , Zheng Hongwei , Zheng Zhiming
Published: July 2022

Brain structural connectomes underpin complex cognitive processes. To date, abundant organizational features have been distilled by network-based tools, including hubs, modules, and small-worldness. However, these features are often devoid of spatial characteristics which directly shape connection formation. By considering the spatial embedding of brain networks, we reveal the connection specificity, that is, the similarity of similar-distance connections and the dissimilarity of different-distance connections. It is induced by the whole-brain connection length distribution, allowing areas to send and receive diverse signals through different-distance connections. Based on it, areas’ functional repertoires are associated with their connection length profiles, and meanwhile, length dispersion and clustering coefficients can be integrated into a hierarchy whose age-related degeneration may be related to cognitive decline. These results construct a putative bridge between brain spatial, topological, and functional features, expanding our understanding of how different architectures complement and reinforce each other to achieve complicated brain functions.
Human iPSC-derived neuron of 16p11.2 deletion reveals haplotype-specific expression of MAPK3 and its contribution to variable NDD phenotypes
Authors: Liu Fang , Liang Chen , Li Zhengchang , Zhao Sen , Shangguan Shaofang , Yuan Haiming , Yao Ruen , Qin Zailong , Zhang Shujie , Zou Liping , Gao Zhijie , Chen Qian , Wen Suiwen , Peng Jing , Yin Fei , Chen Fei , Qiu Xiaoxia , Luo Jinsi , Xie Yingjun , Lu Dian , Zhang Yu , Xie Hua , Wang Hongying , Cui Xiaodai , Wang Jian , Huang Hailiang , Liu Ruize , Sun Xiaofang , Chen Chao , Wu Nan , Liu Chunyu , Shen Yiping , Gusella James F. , Chen Xiaoli
Published: July 2022

Recurrent proximal 16p11.2 deletion (16p11.2del) is risk factor of diverse neurodevelopmental disorders (NDDs) with variable penetrance. Although previous human induced pluripotent stem cell (hiPSC) models of 16p11.2del confirmed disrupted neuron development, it is not known which gene(s) at this interval are mainly responsible for the abnormal cellular phenotypes and how the NDD penetrance is regulated. After haplotype phasing of 16p11.2 region, we generated hiPSCs for two 16p11.2del families with distinct residual haplotypes and variable NDD phenotypes. We also differentiated the hiPSCs to cortical neural cells and demonstrated MAPK3 as a driver signal of 16p11.2 region contributing to the dysfunctions in multiple pathways related to neuron development, which leads to altered morphological or electrophysiological properties in neuron cells. Furthermore, residual haplotype-specific MAPK3 expression was identified in 16p11.2del neuron cells, associating MAPK3 down-expression with the minor allele of the residual haplotype. Ten SNPs of the residual haplotype are mapped as enhancer SNPs (enSNPs) of MAPK3, eight enSNPs were functionally validated by luciferase assays, implying enSNPs contribute to residual haplotype-specific MAPK3 expression via cis-regulation. Finally, the analyses of three different patient cohorts showed that the residual haplotype of 16p11.2del is associated with variable NDD phenotypes.
Layer-specific, retinotopically-diffuse modulation in human visual cortex by emotional faces
Authors: Liu Tina T. , Fu Jason Z , Chai Yuhui , Japee Shruti , Chen Gang , Ungerleider Leslie G. , Merriam Elisha P.
Published: July 2022

Emotionally expressive faces evoke enhanced neural responses in multiple brain regions, a phenomenon thought to depend critically on the amygdala. This emotion-related modulation is evident even in primary visual cortex (V1), providing a potential neural substrate by which emotionally salient stimuli can affect perception. How does emotional valence information, computed in the amygdala, reach V1? Here we use high-resolution functional MRI to investigate the layer profile and retinotopic distribution of neural activity specific to emotional facial expressions. Across three experiments, human participants viewed centrally presented face stimuli varying in emotional expression and performed a gender judgment task. We found that facial valence sensitivity was evident only in superficial cortical layers and was not restricted to the retinotopic location of the stimuli, consistent with diffuse feedback-like projections from the amygdala. Together, our results provide a feedback mechanism by which the amygdala directly modulates activity at the earliest stage of visual processing.
Parallel processing relies on a distributed, low-dimensional cortico-cerebellar architecture
Authors: Müller Eli J. , Hou Kevin Y. , Palesi Fulvia , Tan Joshua , Close Thomas , Gandini Wheeler-Kingschott Claudia A.M. , D’Angelo Egidio , Calamante Fernando , Shine James M.
Published: July 2022

A characteristic feature of human cognition is our ability to ‘multi-task’ – performing two or more tasks in parallel – particularly when one task is well-learned. How the brain supports this capacity remains poorly understood. Most past studies have focussed on identifying the areas of the brain – typically the dorsolateral prefrontal cortex – that are required to navigate information processing bottlenecks. In contrast, we take a systems neuroscience approach to test the hypothesis that the capacity to conduct effective parallel processing relies on a distributed architecture that interconnects the cerebral cortex with the cerebellum. The latter structure contains over half of the neurons in the adult human brain, and is well-suited to support the fast, effective, dynamic sequences required to perform tasks relatively automatically. By delegating stereotyped within-task computations to the cerebellum, the cerebral cortex can be freed up to focus on the more challenging aspects of performing the tasks in parallel. To test this hypothesis, we analysed task-based fMRI data from 50 participants who performed a task in which they either balanced an avatar on a screen (‘Balance’), performed serial-7 subtractions (‘Calculation’) or performed both in parallel (‘Dual-Task’). Using a set of approaches that include dimensionality reduction, structure-function coupling and time-varying functional connectivity, we provide robust evidence in support of our hypothesis. We conclude that distributed interactions between the cerebral cortex and cerebellum are crucially involved in parallel processing in the human brain.
Structural epitope profiling identifies antibodies associated with critical COVID-19 and long COVID
Authors: Kearns Patrick K.A. , Dixon Charles , Badonyi Mihaly , Lee Kim , Czapiewski Rafal , Fleming Olivia , Nadukkandy Prajitha , Gerasimivicius Lukas , Sahputra Rinal , Potts Bethany , Benton Sam , Guy Jacky , Neilson Scott , Wise Helen , Jenks Sara , Templeton Kate ,   CIRCO, Dold Christina , Lambe Teresa , Pollard Andrew , Mentzer Alexander J , Knight Julian C ,   COMBAT, Dunachie Susanna , Klenerman Paul , Barnes Eleanor , Carson Alan , McWhirter Laura , Hussell Tracy , Fragkoudis Rennos , Rosser Susan , Cavanagh David , Cowan Graeme , Menon Madhvi , Marsh Joseph A. , Kleinjan Dirk A. , Gilbert Nick
Published: July 2022

Even within a single protein, antibody binding can have beneficial, neutral, or harmful effects during the response to infection. Resolving a polyclonal antibody repertoire across a pathogen’s proteome to specific epitopes may therefore explain much of the heterogeneity in susceptibility to infectious disease. However, the three-dimensional nature of antibody-epitope interactions makes the discovery of non-obvious targets challenging. We implemented a novel computational method and synthetic biology pipeline for identifying epitopes that are functionally important in the SARS-CoV-2 proteome and identified an IgM-dominant response to an exposed Membrane protein epitope which to our knowledge is the strongest correlate of severe disease identified to date (adjusted OR 72.14, 95% CI: 9.71 – 1300.15), stronger even than the exponential association of severe disease with age. We also identify persistence (> 2 years) of this IgM response in individuals with longCOVID, and a correlation with fatigue and depression symptom burden. The repetitive arrangement of this epitope and the pattern of isotype class switching is consistent with this being a previously unrecognized T independent antigen. These findings point to a coronavirus host-pathogen interaction characteristic of severe virus driven immune pathology. This epitope is a promising vaccine and therapeutic target as it is highly conserved through SARS-CoV-2 variant evolution in humans to date and in related coronaviruses (e.g. SARS-CoV), showing far less evolutionary plasticity than targets on the Spike protein. This provides a promising biomarker for longCOVID and a target to complement Spike-directed vaccination which could broaden humoral protection from severe or persistent disease or novel coronavirus spillovers.

One-Sentence Summary

Using a novel protein-structure-based B cell epitope discovery method with a wide range of possible applications, we have identified a simple to measure host-pathogen antibody signature associated with severe COVID-19 and longCOVID and suggest the viral Membrane protein contains an epitope that acts as a T independent antigen during infection triggering extrafollicular B cell activation.
Systems-level patterns in biological processes are changed under prolongevity interventions and across biological age
Authors: Watanabe Kengo , Wilmanski Tomasz , Baloni Priyanka , Robinson Max , Garcia Gonzalo G. , Hoopmann Michael R. , Midha Mukul K. , Baxter David H. , Maes Michal , Morrone Seamus R. , Crebs Kelly M. , Kapil Charu , Kusebauch Ulrike , Wiedrick Jack , Lapidus Jodi , Lovejoy Jennifer C. , Magis Andrew T. , Lausted Christopher , Roach Jared C. , Glusman Gustavo , Cummings Steven R. , Schork Nicholas J. , Price Nathan D. , Hood Leroy , Miller Richard A. , Moritz Robert L. , Rappaport Noa
Published: July 2022

Aging manifests as progressive deterioration in cellular and systemic homeostasis, requiring systems-level perspectives to understand the gradual molecular dysregulation of underlying biological processes. Here, we report systems-level changes in the molecular regulation of biological processes under multiple lifespan-extending interventions in mice and across age in humans. In mouse cohorts, Differential Rank Conservation (DIRAC) analyses of liver proteomics and transcriptomics show that mechanistically distinct prolongevity interventions tighten the regulation of aging-related biological modules, including fatty acid metabolism and inflammation processes. An integrated analysis of liver transcriptomics with mouse genome-scale metabolic model supports the shifts in fatty acid metabolism. Additionally, the difference in DIRAC patterns between proteins and transcripts suggests biological modules which may be tightly regulated via cap-independent translation. In a human cohort spanning the majority of the adult lifespan, DIRAC analyses of blood proteomics and metabolomics demonstrate that regulation of biological modules does not monotonically loosen with age; instead, the regulatory patterns shift according to both chronological and biological ages. Our findings highlight the power of systems-level approaches to identifying and characterizing the biological processes involved in aging and longevity.
Type 1 and type 2 diabetes mellitus: Clinical outcomes due to COVID-19. Protocol of a systematic literature review
Authors: Pérez Bedoya Juan Pablo , Muñoz Alejandro Mejía , Barengo Noël Christopher , Diaz Valencia Paula Andrea
Published: July 2022

Introduction

Diabetes has been associated with an increased risk of complications in patients with COVID-19. Most studies do not differentiate between patients with type 1 and type 2 diabetes, which correspond to two pathophysiological distinct diseases that could represent different degrees of clinical compromise.

Objective

To identify if there are differences in the clinical outcomes of patients with COVID-19 and diabetes (type 1 and type 2) compared to patients with COVID-19 without diabetes.

Methods

Observational studies of patients with COVID-19 and diabetes (both type 1 and type 2) will be included without restriction of geographic region, gender or age, whose outcome is hospitalization, admission to intensive care unit or mortality compared to patients without diabetes. Two authors will independently perform selection, data extraction, and quality assessment, and a third reviewer will resolve discrepancies. The data will be synthesized regarding the sociodemographic and clinical characteristics of patients with diabetes and without diabetes accompanied by the measure of association for the outcomes. The data will be synthesized regarding the sociodemographic and clinical characteristics of patients with diabetes and without diabetes accompanied by the measure of association for the outcomes.

Expected results

Update the evidence regarding the risk of complications in diabetic patients with COVID-19 and in turn synthesize the information available regarding type 1 and type 2 diabetes mellitus, to provide keys to a better understanding of the pathophysiology of diabetics.

Systematic review registry

This study was registered at the International Prospective Registry for Systematic Reviews (PROSPERO) - CRD42021231942.
Maternal immunisation against Group B Streptococcus: a global analysis of health impact and cost-effectiveness
Authors: Procter Simon R. , Gonçalves Bronner P. , Paul Proma , Chandna Jaya , Seedat Farah , Koukounari Artemis , Hutubessy Raymond , Trotter Caroline , Lawn Joy E , Jit Mark
Published: July 2022

Background

Group B Streptococcus (GBS) can cause invasive disease (iGBS) in young infants, typically presenting as sepsis or meningitis, and is also associated with stillbirth and preterm birth. GBS vaccines are under development, but their potential health impact and cost-effectiveness have not been assessed globally.

Methods

We assessed the health impact and value (using net monetary benefit, NMB, which measures both health and economic effects of vaccination into monetary units), of GBS maternal vaccination across 183 countries in 2020. Our analysis uses a decision-tree model, combining risks of GBS-related outcomes from a Bayesian disease burden model with estimates of GBS related costs and Quality-Adjusted Life Years (QALYs) lost. We assumed 80% vaccine efficacy against iGBS and stillbirth, following the WHO Preferred Product Characteristics, and coverage based on the proportion of pregnant women receiving at least four antenatal visits. One dose was assumed to cost $50 in high-income countries, $15 in upper-middle income countries, and $3.50 in low-/lower-middle income countries. We estimated NMB using alternative normative assumptions that may be adopted by policy makers.

Findings

Vaccinating pregnant women could avert 214,000 (95% uncertainty range 151,000 – 457,000) infant iGBS cases, 31,000 deaths (14,000 – 67,000), 21,000 (9,000 – 52,000) cases of neurodevelopmental impairment, and 23,000 (10,000 – 58,000) stillbirths. A vaccine effective against GBS-associated prematurity might also avert 172,000 (13,000 – 378,000) preterm births. Globally, a 1-dose vaccine programme could cost $1.7 billion but save $385 million in healthcare costs. Estimated global NMB ranged from $1.1 billion ($-0.2 – 3.8 billion) to $17 billion ($9.1 – 31 billion).

Interpretation

Maternal GBS vaccination could have a large impact on infant morbidity and mortality globally and at reasonable prices is likely to be cost-effective.
Tuberculosis knowledge gaps and associated factors among suspects of tuberculosis in a peripheral emerging region of northwest Ethiopia: a case of Benishangul Gumuz
Authors: Lobie Tekle Airgecho , Roba Aklilu Abrham
Published: July 2022

Good Knowledge about tuberculosis (TB) is a key element to have a favourable attitude and practice in the control of TB. However, in the resources limited peripheral emerging region of Ethiopia, there is a limited knowledge about it. Therefore, this study aimed to investigate the knowledge about TB symptoms, transmission, and prevention methods and identify the associated factors in Northwest Ethiopia.

Methods

A facility-based cross-sectional study was conducted among 391 TB suspects in two hospitals and seven health centres in the Benishangul Gumuz region. Composite scales were generated for knowledge about TB symptoms, route of transmission, and prevention methods. Data were analysed by Statistical Package for Social Sciences (SPSS) Version 25. Multivariate logistic regression was conducted to identify associated factors. A P-value less than 0.05 was considered statistically significant.

Results

From a total of 391 approached TB suspects, 383 (98%) participated in the study with the mean age of 33.34 ±14.10 years ranging from 11-89 years. There was very poor knowledge about TB symptoms (12%) but fair knowledge about TB transmission (61.6%), and prevention (57.4%). The previous history of treatment was significantly associated with the participants’ overall poor knowledge about TB symptoms (AOR 2.787, 95% CI=1.148-6.765), route of transmission (AOR=4.03, 95% CI=1.82-8.92), and prevention methods (AOR=4.89, 95% CI=2.18-10.99). Also, being illiterate was associated with poor knowledge about the route of TB transmission (AOR 11.39, 95% CI 2.15 - 60.33) prevention methods (AOR 13.28, 95% CI 2.69-65.73).

Conclusion

There was little knowledge about TB symptoms while fair knowledge about the mode of transmission and means of prevention in the Benishangul Gumuz region. Health education intervention particularly targeting TB symptoms, transmission, and prevention methods should be initiated through easily accessible media supported by effective strategies.
COVID-19 Vaccination Uptake and Self-Reported Side Effects among Healthcare Workers in Mbale City Eastern Uganda
Authors: Akech Gabriel Madut , Kanyike Andrew Marvin , Nassozi Ashah Galabuzi , Aguti Beatrice , Nakawuki Ashley Winfred , Kimbugwe Denis , Kiggundu Josen , Maiteki Robert , Mukyala Dorothy , Bongomin Felix , Obakiro Samuel Baker , Rebecca Nekaka , Iramiot Jacob Stanley
Published: July 2022

Background

Fear of anticipated side effects has hindered the COVID-19 vaccination program globally. We report the uptake and the self-reported side effects (SEs) of the COVID-19 vaccine among Healthcare workers (HCWs) in Mbale City Eastern Uganda.

Methods

A cross-sectional survey of HCWs at seven different level health facilities was conducted from 6th September to 7th October 2021 using a structured self-administered questionnaire.

Results

COVID-19 vaccine had been received by 119 (69%) participants of which 79 (66%) received the two recommended doses of the AstraZeneca vaccine. Getting vaccinated was associated with working in a lower health facility (aOR= 14.1, 95% CI: 4.9 – 39.6, P=0.000), perceived minor risk of contracting COVID-19 (aOR= 12.3, 95% CI: 1.0 – 44.6, p=0.047), and agreeing that COVID-19 vaccine is protective (aOR= 16.7, 95% CI: 5.6 – 50.4, p=0.000). 97 (82%) of participants experienced side effects to at least one dose of which most were mild on both the first (n=362, 51%) and second dose (n=135, 69%). The most frequently reported side effects on the first and second dose were fever (79% and 20%), injection site pain (71% and 25%), and Fatigue (69% and 20%) respectively.

Conclusions

The majority of the HCWs in Mbale City had received at least one dose of the COVID-19 vaccine and experienced a side effect. The side effects were mostly mild on either dose thus the vaccines are generally safe.
High-Intensity Interval Training Improves physical morphology, Cardiopulmonary Fitness and Metabolic Risk Indicators of Cardiovascular Disease in Children and Adolescents: A Systematic Review and Meta-Analysis
Authors: Menjie  , Shuangling Zou , Majia  , chenmin Xiang , Shufeng Li , Junli Wang
Published: July 2022

Objective

To systematically evaluate the safety and efficacy of high-intensity interval training in children and adolescents.

Design

Systematic Review and Meta-Analysis

Methods

Eight databases were searched. Descriptive analysis of the efficacy and safety of high-intensity interval training on body shape, cardiorespiratory fitness, and metabolic risk markers for cardiovascular disease between children and adolescents. Subgroup analysis was performed with age, participants, intervention time, and exercise frequency as covariates.

Results

47 studies included 2995 children and adolescents. Meta-analysis results showed that high-intensity interval training significantly improved cardiorespiratory fitness indicators (VO2max, SBP, DBP and HRmax) and cardiovascular disease metabolic risk indicators (TC, HDL-C). HIIT had no significant effect on body shape indicators (BMI, BF% and WC) and some cardiometabolic indicators (TG and LDL-C).

Conclusion

Current evidence shows insufficient evidence that high-intensity interval training with intermittent running as the main form of exercise improves body shape indicators in children and adolescents. Nevertheless, it deserves to recommend for the purpose of improving cardiorespiratory fitness and reducing the metabolic risk of cardiovascular disease.
Structural basis of human PRPS2 filaments
Authors: Lu Guangming , Hu Huan-Huan , Chang Chia-Chun , Zhong Jiale , Zhou Xian , Guo Chen-Jun , Zhang Tianyi , Li Yi-Lan , Yin Boqi , Liu Ji-Long
Published: July 2022

PRPP synthase (PRPS) transfers the pyrophosphate groups from ATP to ribose-5-phosphate to produce 5-phosphate ribose-1-pyrophosphate (PRPP), a key intermediate in the biosynthesis of several metabolites including nucleotides, dinucleotides and some amino acids. There are three PRPS isoforms encoded in human genome. While hPRPS1 and hPRPS2 are expressed in most tissues, hPRPS3 is exclusively expressed in testis. Although hPRPS1 and hPRPS2 share 95% sequence identity, hPRPS2 has been shown to be less sensitive to allosteric inhibition and specifically upregulated in certain cancers in the translational level. Recent studies demonstrate that PRPS can form a subcellular compartment termed the cytoophidium in multiple organisms across prokaryotes and eukaryotes. Forming the cytoophidium is considered as a distinctive mechanism involving the polymerization of the protein. In order to investigate the function and molecular mechanism of hPRPS2 polymerization, we solve the polymer structure of hPRPS2 at 3.08Å resolution using cryo-Electron Microscopy (cryo-EM). hPRPS2 hexamers stack into polymers in the conditions with the allosteric/competitive inhibitor ADP. The binding modes of ADP at the canonical allosteric site and at the catalytic active site are clearly determined. A point mutation disrupting the inter-hexamer interaction prevents hPRPS2 polymerization and results in significantly reduced catalytic activity. Our findings suggest that the regulation of hPRPS2 polymer is distinct from E. coli PRPS polymer and provide new insights to the regulation of hPRPS2 with structural basis.
Mismatch resolution for repeat-mediated deletions show a polarity that is mediated by MLH1
Authors: Trost Hannah , Merkell Arianna , Lopezcolorado Felicia Wednesday , Stark Jeremy M.
Published: July 2022

Repeat-mediated deletions (RMDs) are a type of chromosomal rearrangement between two homologous sequences that causes loss of the sequence between the repeats, along with one of the repeats. Sequence divergence between repeats suppresses RMDs; the mechanisms of such suppression and of resolution of the mismatched bases remains poorly understood. We identified RMD regulators using a set of reporter assays in mouse cells that test two key parameters: repeat sequence divergence and the distances between one repeat and the initiating chromosomal double-strand break. We found that the mismatch repair factor MLH1 suppresses RMDs with sequence divergence in a manner that is epistatic with the mismatch repair factors MSH2 and MSH6, and which is dependent on residues in MLH1 and its binding partner PMS2 that are important for nuclease activity. Additionally, we found that resolution of mismatches in the RMD product have a specific polarity, where mismatched bases that are proximal to the chromosomal break end are preferentially removed. Moreover, we found that the MLH1 endonuclease domain is important for this polarity of mismatch resolution. Finally, we identified distinctions between MLH1 vs. TOP3α in regulation of RMDs. We suggest that MLH1 suppresses RMDs with sequence divergence, while also promoting directional mismatch resolution.