bluuebunny/crossref_metadata_2025 huggingface dataset:
Geochemical Anatomy of the Main Magnetitite Layer, Bushveld Complex, South Africa
Authors: Cawthorn Richard Grant , McCarthy Terence Sinclair
Published: August 2023

The mafic layered Bushveld Complex, South Africa, contains numerous examples of monomineralic layers within its succession. The Upper Zone (UZ) contains approximately 24 magnetitite layers, the genesis of which has been extensively debated. The Main Magnetitite Layer (MML) is approximately 2 m thick and is traceable around its edge across >60 000 km2. Its basal contact with underlying anorthosite is planar and sharp, but the top contact grades upward with increasing plagioclase content. Sampling at a vertical spacing of a very few centimetres from seven profiles in the east over many tens of kilometres and one other 300 km to the west reveals concentrations of Cr in magnetite that decrease extremely rapidly upward (typically from >8000 to 1000 ppm within 30–60 cm from the base), punctuated by sharp concentration reversals and rare decreases. Here, we describe an outcrop where the MML splits into three sub-layers, separated by magnetite–plagioclase rocks. Twelve profiles across this zone of splitting have been similarly analysed. Lateral variations in Cr profiles across a few metres are observed at this locality. We offer the suggestion that magnetite formation may have been induced by shock wave nucleation on the bottom of the chamber accounting for the abrupt appearance of magnetitite over such a wide area. Bottom growth of magnetite lowered the density and Cr content of the evolving magma, causing turbulence and convective overturn near the base of the chamber that created inhomogeneities in Cr on various scales, preserved in the ensuing magnetite compositions both vertically and laterally. Intermittent and abrupt (on a scale of 1–2 cm) upward increases in the Cr contents of up to 3000 ppm in magnetite profiles resulted from convective overturn impinging on the floor. The tops of the magnetitite sub-layers grade up into magnetite–plagioclase rocks and continue the upward decrease in Cr content in magnetite, typically at 900 ppm Cr, demonstrating upward continuity of fractionation. In contrast, there are reversals in Cr content between the magnetite–plagioclase rocks and the overlying magnetitite sub-layers that we attribute to convective overturn, with an increase in the Cr content. Two profiles through the MML show abrupt upward discontinuities to lower Cr contents that we attribute to physical erosional events. Anorthosite fragments in magnetitite and magnetitite fragments in anorthosite layers further attest to such processes. The anorthite contents of plagioclase do not change across the MML, suggesting that magma addition was not responsible for the formation of magnetitite layers. Primary topographic variations at the base of the chamber also preclude addition of dense magma for the formation of magnetitite layers. Upward infiltration metasomatism, slightly resetting Cr contents, is limited to <3 cm.
Coronavirus and Culture War: Blunders, Defiance, and Glimmers of Solidarity
Authors: Morone James A
Published: August 2023

The health epidemic of 2020 set off a culture war and, like all national crises, revealed exactly who we Americans are. This essay examines Danielle Allen's Democracy in the Time of Coronavirus, a wise, humane, and indispensable guide for negotiating a health pandemic—if not this one, the inevitable next one. It reflects on her five-point guide to handling pandemics, comparing her ideals to the national experience. This essay places Allen's monograph in the context of the larger literature on the coronavirus in America. The essay traces how and why public health fell into the American culture wars, notes the brief glimmer of a genuine social welfare safety net that briefly emerged during the crisis, and summarizes the epidemic's dismal toll on American lives, suggesting why even much poorer nations did a better job of protecting their citizens.
Cognitive-Behavioral Social Skills Training: Outcome of a Randomized Controlled Trial for Youth at Risk of Psychosis
Authors: Addington Jean , Liu Lu , Braun Amy , Brummitt Kali , Cadenhead Kristin S , Cornblatt Barbara A , Holden Jason L , Granholm Eric
Published: August 2023

Aim

Difficulties in social functioning have been observed in youth at clinical high-risk (CHR) of psychosis even in those who do not go on to develop a psychotic illness. Few treatment studies have attempted to improve social functioning in this population. The aim of this study was to conduct a randomized trial comparing the effects of Cognitive-Behavioral Social Skills Training (CBSST) with a supportive therapy (ST).

Methods

Both CBSST and ST were weekly group therapies, delivered over 18 weeks. This was a 2-arm trial with single-blinded ratings and intention-to-treat analyses. Assessments occurred at baseline, end-of-treatment, and 12 months after the baseline assessment. The primary outcome was social and role functioning and defeatist performance attitudes were the secondary outcome. Attenuated positive and negative symptoms, anxiety, depression, self-efficacy, and beliefs about self and others were examined as exploratory outcomes.

Results

There were no significant differences between the 2 groups at baseline or either of the 2 follow-ups. However, at follow-ups, in each group there were significant improvements in clinical symptoms. These could not be attributed to group treatment since there was no control or wait-list group.

Conclusions

Since poor social functioning is one of the most observed difficulties in CHR individuals, and a decline in social functioning may be a significant predictor of later transition to psychosis, future work will be needed to find effective treatments for this decline in functioning for CHR youth.
Platelet-rich plasma for the treatment of erectile dysfunction: a systematic review of preclinical and clinical studies
Authors: Poulios Evangelos , Mykoniatis Ioannis , Pyrgidis Nikolaos , Kalyvianakis Dimitrios , Hatzichristou Dimitrios
Published: August 2023

Introduction

There has been tremendous growth in regenerative medicine during the last decade. For erectile dysfunction (ED), after the inclusion of low-intensity shockwave therapy as a treatment modality for ED management by the European Association of Urology sexual health guidelines, intracavernosal injection of platelet-rich plasma (PRP) has gained popularity between urologists and patients as a novel ED therapeutic modality with initial promising results. However, limited clinical data exist regarding efficacy and safety in patients with ED. Furthermore, despite numerous preclinical studies in other tissues and organs, the mechanism of action for restoring erectile function remains undetermined.

Objectives

This systematic review aims to present the current status of preclinical and clinical evidence regarding the use of PRP as treatment option for ED.

Methods

A systematic literature search was conducted using PubMed, Cochrane, and ScienceDirect databases, until February 2023 for studies exploring the effect of PRP on ED.

Results

We identified 517 articles, 23 of which were included in this review. These were 7 preclinical (of which 1 was a comparative trial and 6 were placebo-controlled randomized controlled trials) and 16 clinical studies (of which 1 was a comparative trial, 5 were randomized trials, and 2 were placebo-controlled randomized controlled trials). Preclinical data support the regenerative role of PRP in erectile tissue, in accordance with existing evidence in other tissues. Randomized clinical studies, as well as the first 2 available randomized, placebo-controlled clinical trials, showed promising efficacy and a lack of any adverse events.

Conclusion

As PRP for ED is widely used worldwide, there is an urgent need for high-quality studies with long-term follow-up. Standardization of research protocols, especially on the quality of PRP preparation, is also needed.
Comparison of nickel oxide nano and microparticles toxicity in rat liver: molecular, biochemical, and histopathological study
Authors: Adiguzel Caglar , Karaboduk Hatice , Apaydin Fatma Gokce , Kalender Suna , Kalender Yusuf
Published: August 2023

The unique properties of nickel oxide nanoparticles distinguish it from classical nickel compounds, increasing its use in agriculture, industry, and many industrial areas. The aim of this study is to investigate the possible toxicity of nickel oxide and nickel oxide nanoparticles in the liver. For this purpose, Wistar rats were given nickel oxide and nickel oxide nanoparticles orally, intraperitoneally, and intravenously for 21 days. Liver organ weight, biochemical and hematological parameters, oxidative stress (malondialdehyde, catalase, superoxide dismutase, glutathione peroxidase, and glutathione S transferase), acetylcholinesterase activities, inflammation levels, apoptotic markers, and histopathological changes were evaluated comparatively. When the data obtained were examined in general, it was observed that nickel oxide nanoparticles caused more hepatotoxicity in liver tissue than nickel oxide in terms of oxidative stress parameters, apoptotic markers, inflammation indicators, and other parameters examined. The results suggest that toxicity induced by both nickel oxide and nickel oxide nanoparticles plays an important role in hepatocyte apoptosis.
Evolutionary potential of the monkeypox genome arising from interactions with human APOBEC3 enzymes
Authors: Delamonica Brenda , Davalos Liliana , Larijani Mani , Anthony Simon J , Liu Jia , MacCarthy Thomas
Published: August 2023

APOBEC3, an enzyme subfamily that plays a role in virus restriction by generating mutations at particular DNA motifs or mutational ‘hotspots’, can drive viral mutagenesis with host-specific preferential hotspot mutations contributing to pathogen variation. While previous analysis of viral genomes from the 2022 Mpox (formerly Monkeypox) disease outbreak has shown a high frequency of C>T mutations at TC motifs, suggesting recent mutations are human APOBEC3-mediated, how emerging monkeypox virus (MPXV) strains will evolve as a consequence of APOBEC3-mediated mutations remains unknown. By measuring hotspot under-representation, depletion at synonymous sites, and a combination of the two, we analyzed APOBEC3-driven evolution in human poxvirus genomes, finding varying hotspot under-representation patterns. While the native poxvirus molluscum contagiosum exhibits a signature consistent with extensive coevolution with human APOBEC3, including depletion of TC hotspots, variola virus shows an intermediate effect consistent with ongoing evolution at the time of eradication. MPXV, likely the result of recent zoonosis, showed many genes with more TC hotspots than expected by chance (over-representation) and fewer GC hotspots than expected (under-representation). These results suggest the MPXV genome: (1) may have evolved in a host with a particular APOBEC GC hotspot preference, (2) has inverted terminal repeat (ITR) regions—which may be exposed to APOBEC3 for longer during viral replication—and longer genes likely to evolve faster, and therefore (3) has a heightened potential for future human APOBEC3-meditated evolution as the virus spreads in the human population. Our predictions of MPXV mutational potential can both help guide future vaccine development and identification of putative drug targets and add urgency to the task of containing human Mpox disease transmission and uncovering the ecology of the virus in its reservoir host.
A Survey of Xylella fastidiosa in the U.S. State of Virginia Reveals Wide Distribution of Both Subspecies fastidiosa and multiplex in Grapevine
Authors: Abdelrazek Sahar , Bush Elizabeth , Oliver Charlotte , Liu Haijie , Sharma Parul , Johnson Marcela A. , Donegan Monica A. , Almeida Rodrigo P. P. , Nita Mizuho , Vinatzer Boris A.
Published: August 2023

Global travel and trade in combination with climate change are expanding the geographic distribution of plant pathogens. The bacterium Xylella fastidiosa is a prime example. Native to the Americas, it has spread to Europe, Asia, and the Middle East. To assess the risk that pathogen introductions pose to crops in newly invaded areas, it is key to survey their diversity, host range, and disease incidence in relation to climatic conditions where they are already present. We performed a survey of X. fastidiosa in grapevine in Virginia using a combination of quantitative PCR, multilocus sequencing, and metagenomics. We also analyzed samples from deciduous trees with leaf scorch symptoms. X. fastidiosa subspecies fastidiosa was identified in grapevines in all regions of the state, even in Northern Virginia, where the temperature was below −9°C for 10 days per year on average in the years preceding sampling. Unexpectedly, we also found for the first time grapevine samples infected with X. fastidiosa subspecies multiplex ( Xfm). The Xfm lineage found in grapevines had been previously isolated from blueberries in the Southeastern United States and was distinct from that found in deciduous trees in Virginia. The obtained results will be important for risk assessment of X. fastidiosa introductions in other parts of the world.
LncRNA PVT1 promotes strong stemness and endothelial progenitor cell characteristics in renal carcinoma stem cells
Authors: Wang Lu , Yang Guang , Guo Pengyu , Lv Yulin , Fu Bo , Bai Yang , Xiong Feng , Zhao Danfeng , Li Cong , Zhang Jianji , Bai Shiyu , Zeng Fanshu , Xu Wanhai
Published: August 2023

Renal cancer stem cells (RCSCs) derived from clear cell renal cell carcinoma (ccRCC) tissues with higher microvessel density (MVD) have strong stemness and endothelial progenitor cells‐like (EPCs‐like) characteristics. A high level of lncRNA PVT1 expression is essential for simultaneously retaining strong RCSC stemness and EPCs‐like characteristics. PVT1 binds with TAZ protein and prevents its phosphorylation, which promotes RCSC stemness. Moreover, RCSCs support endothelial differentiation and angiogenesis, which are mediated via the PVT1/miR‐15b/KDR axis. This report provides insight into the determinants of RCSC impact on stemness and highlights the critical role of RCSC in angiogenesis. The presented findings suggest that targeting RCSC through PVT1 expression may be a new treatment strategy for ccRCC.
Chromatin accessibility memory of donor cells disrupts bovine somatic cell nuclear transfer blastocysts development
Authors: Huang Yuemeng , Zhang Jingcheng , Li Xinmei , Wu Zhipei , Xie Guoxiang , Wang Yong , Liu Zhengqing , Jiao Mei , Zhang Hexu , Shi Binqiang , Wang Yu , Zhang Yong
Published: August 2023

The post‐transfer developmental capacity of bovine somatic cell nuclear transfer (SCNT) blastocysts is reduced, implying that abnormalities in gene expression regulation are present at blastocyst stage. Chromatin accessibility, as an indicator for transcriptional regulatory elements mediating gene transcription activity, has heretofore been largely unexplored in SCNT embryos, especially at blastocyst stage. In the present study, single‐cell sequencing assay for transposase‐accessible chromatin (scATAC‐seq) of in vivo and SCNT blastocysts were conducted to segregate lineages and demonstrate the aberrant chromatin accessibility of transcription factors (TFs) related to inner cell mass (ICM) development in SCNT blastocysts. Pseudotime analysis of lineage segregation further reflected dysregulated chromatin accessibility dynamics of TFs in the ICM of SCNT blastocysts compared to their in vivo counterparts. ATAC‐ and ChIP‐seq results of SCNT donor cells revealed that the aberrant chromatin accessibility in the ICM of SCNT blastocysts was due to the persistence of chromatin accessibility memory at corresponding loci in the donor cells, with strong enrichment of trimethylation of histone H3 at lysine 4 (H3K4me3) at these loci. Correction of the aberrant chromatin accessibility through demethylation of H3K4me3 by KDM5B diminished the expression of related genes (e.g., BCL11B) and significantly improved the ICM proliferation in SCNT blastocysts. This effect was confirmed by knocking down BCL11B in SCNT embryos to down‐regulate p21 and alleviate the inhibition of ICM proliferation. These findings expand our understanding of the chromatin accessibility abnormalities in SCNT blastocysts and BCL11B may be a potential target to improve SCNT efficiency.
Measure It: Proper Wheelchair Fit Is Key to Ensuring Function while Protecting Skin Integrity
Authors: Sprigle Stephen
Published: August 2023

A variety of problems can arise from sitting persons in poorly fitted wheelchairs, including contractures, pain, and pressure injuries. These complications can result in functional consequences for the patient, such as reduced independence and activity. This article focuses specifically on proper wheelchair fit, describing the impact of proper wheelchair fit on the posture and function of wheelchair users. The author aims to help clinicians better recognize the basic biomechanics of posture, describe the appropriate means to configure a wheelchair to permit proper postural support, and identify common problems arising from improper wheelchair fit.

GENERAL PURPOSE

To review the biomechanics of posture, appropriate means to configure a wheelchair to permit proper postural support, and common problems arising from improper wheelchair fit.

TARGET AUDIENCE

This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care.

LEARNING OBJECTIVES/OUTCOMES

After participating in this educational activity, the participant will:

1. Synthesize the concepts influencing proper wheelchair fit.

2. Identify the biomechanics of posture as they apply to wheelchair fit.

3. Summarize the appropriate assessment guidelines for determining and preparing to adjust wheelchair fit.
Decreasing Pressure Injuries on an Adult Inpatient Unit through Implementation of a Nutrition Assessment and Management Process
Authors: Hamidi Lida
Published: August 2023

OBJECTIVE

To lower the rate of hospital-acquired pressure injuries (HAPIs) by identifying at-risk patients based on the Braden Scale score, evaluating nutrition using a Mini Nutrition Assessment (MNA) tool, and implementing nutrition improvement measures.

METHODS

There were three steps in this intervention. First, patients with a Braden Scale score of 18 or lower were identified as being at risk for HAPI. Next, the MNA screening tool was implemented to identify nutrition deficiencies. The MNA screening tool can predict malnutrition, HAPI development, and/or additional complications. It is validated, cost-effective, and easy to administer to patients who are hospitalized with HAPI complications. In the final step, the author implemented a multicomponent nutrition intervention to improve the nutrition status of patients at risk for developing HAPI.

RESULTS

Included patients (N = 205) were hospitalized in the intermediate ICU, had a Braden Scale score of 18 or lower, and had poor nutrition status. There was a 74% decrease in HAPI rate following the MNA nutrition screening and management, with HAPI incidence decreasing from 1.9% preintervention to 0.5% postintervention.

CONCLUSIONS

Categorizing patients who are at risk for developing HAPI, assessing for nutrition deficiency, and then implementing a multicomponent nutrition intervention considerably reduced the rate of HAPIs per number of patients admitted to the unit.
Jet Lavage Irrigation Resolves Stage 4 Pelvic Pressure Injury Undermining
Authors: Stiehl James B.
Published: August 2023

OBJECTIVE

Patients with stage 4 pelvic pressure injuries that have large, undermined cavities are at high risk for treatment failure and often fall into the category of palliative care. This case series identified five cases where treatment had stalled, and surgical reconstructive options were limited. Jet lavage irrigation in the outpatient setting was assessed as a treatment alternative.

METHODS

From an investigational review board study assessing the use of low-pressure jet lavage irrigation in the outpatient setting for chronic wounds, five patients were identified where the wound dimension increased at least 50% resulting from undermined cavities. All were considered high risk with Charlson Comorbidity Index scores of 5 or greater, and their wound healing had stalled with extended treatments of topicals and medicated dressings. A team of physical therapists irrigated these patients’ wounds at the bedside with 3 L of saline 3 to 5 days per week using a special long irrigation tip to reach the depth of the undermined cavity. Digital planimetry was used to assess healing with wound size as the outcome.

RESULTS

Reduction of the undermined cavities was seen early within the first 3 weeks. No patient developed wound sepsis, and bacterial contamination was determined by use of autofluorescence digital imaging. Undermining resolution occurred in four patients, and one patient with an improving wound died of COVID-19.

CONCLUSIONS

This simple method offered clear benefits in each patient, but only one patient survived to complete wound healing. Patient and family satisfaction were high regarding the treatment, which created a painless, odor-free wound.
Plasma exchange for acute and acute-on-chronic liver failure: A systematic review and meta-analysis
Authors: Beran Azizullah , Mohamed Mouhand F.H. , Shaear Mohammad , Nayfeh Tarek , Mhanna Mohammed , Srour Omar , Nawras Mohamad , Mentrose Jonathan A. , Assaly Ragheb , Kubal Chandrashekhar A. , Ghabril Marwan S. , Hernaez Ruben , Patidar Kavish R.
Published: August 2023

Plasma exchange (PE) is a promising therapeutic option in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). However, the impact of PE on patient survival in these syndromes is unclear. We aimed to systematically investigate the use of PE in patients with ALF and ACLF compared with standard medical therapy (SMT). We searched PubMed/Embase/Cochrane databases to include all studies comparing PE versus SMT for patients ≥ 18 years of age with ALF and ACLF. Pooled risk ratios (RR) with corresponding 95% CIs were calculated by the Mantel-Haenszel method within a random-effect model. The primary outcome was 30-day survival for ACLF and ALF. Secondary outcomes were overall and 90-day survival for ALF and ACLF, respectively. Five studies, including 343 ALF patients (n = 174 PE vs. n = 169 SMT), and 20 studies, including 5,705 ACLF patients (n = 2,856 PE vs. n = 2,849 SMT), were analyzed. Compared with SMT, PE was significantly associated with higher 30-day (RR 1.41, 95% CI 1.06–1.87, p = 0.02) and overall (RR 1.35, 95% CI 1.12–1.63, p = 0.002) survival in ALF patients. In ACLF, PE was also significantly associated with higher 30-day (RR 1.36, 95% CI 1.22–1.52, p < 0.001) and 90-day (RR 1.21, 95% CI 1.10–1.34, p < 0.001) survival. On subgroup analysis of randomized controlled trials, results remained unchanged in ALF, but no differences in survival were found between PE and SMT in ACLF. In conclusion, PE is associated with improved survival in ALF and could improve survival in ACLF. PE may be considered in managing ALF and ACLF patients who are not liver transplant (LT) candidates or as a bridge to LT in otherwise eligible patients. Further randomized controlled trials are needed to confirm the survival benefit of PE in ACLF.
The role of nuclear medicine tracers for prostate cancer surgery: from preoperative to intraoperative setting
Authors: Barletta Francesco , Ceci Francesco , van den Bergh Roderick C.N. , Rajwa Pawel , Montorsi Francesco , Briganti Alberto , Gandaglia Giorgio
Published: August 2023

Purpose of review

There has been a growing interest in the use of novel molecular imaging modalities for the management of prostate cancer (PCa), spanning from diagnostic to therapeutic settings. The aim of this review is to provide a comprehensive overview of recently published studies investigating the use of novel nuclear medicine tracers across different stages of PCa management.

Recent findings

Emerging evidence supports the use of molecular imaging for preoperative staging of PCa, where prostate-specific membrane antigen (PSMA) PET has shown superior accuracy compared to conventional imaging for the detection of nodal and distant metastases, which needs to be translated to new risk stratification. A role for PSMA PET has been proposed for PCa diagnosis, with local activity associated with histology. Surgical guidance, using either visual feedback or gamma-ray detectors to identify tissues with accumulated radio-labeled tracers, may improve the ability to resect locoregional diseases and thus maximize oncological control. PSMA targeted therapy (Lu-PSMA) has been mainly investigated in the castration-resistant setting, but might have a role in earlier settings such as neoadjuvant treatment.

Novel molecular imaging using PSMA-based tracers could significantly improve PCa management in the diagnosis, staging, and intraoperative guidance settings, potentially leading to personalized and effective treatment decisions.
p53 Immunohistochemical Staining and TP53 Gene Mutations in Endometrial Cancer
Authors: Sakamoto Ikuko , Kagami Keiko , Nozaki Takahiro , Hirotsu Yosuke , Amemiya Kenji , Oyama Toshio , Omata Masao
Published: August 2023

Whether immunohistochemistry (IHC) of p53 accurately reflects the TP53 mutational status of endometrial carcinoma (EC) has not yet been established. This study aimed to clarify the relationship between p53 IHC and TP53 mutations in EC and to examine whether p53 IHC can be a more convenient prognostic marker than TP53 mutation in EC. We performed p53 IHC staining of EC samples obtained via surgery and genetic analyses using next-generation sequencing. p53 IHC results showed that of the 101 cases, 71 (70%) were wild-type (WT), 12 (12%) were overexpression (OE), and 18 (18%) were in the null group. Missense mutations were found in 9 cases (47.4%) in OE, 2 (10.5%) in null, and 8 (42.1%) in the WT group. Truncating mutations were found in 1 case (8.3%) in OE, 6 (50%) in null, and 5 (41.7%) in the WT group. The 5-year progression-free survival was 0% in OE, 74.8% in null, and 79.0% in the WT group. In the prognosis for each type of TP53 mutation, the 5-year progression-free survival was missense (32.2%), truncating (65.6%), and WT (79.7%). These survival comparisons showed that the p53 IHC OE had the poorest prognosis. These results suggest that the p53 IHC OE is an independent poor prognostic factor for EC and can be used as a simple and rapid surrogate marker for TP53 mutations. Contrastingly, the complete absence of p53 IHC—the null staining pattern—may not accurately predict a TP53 mutation in EC, and it is necessary to be more careful in making the diagnosis of “abnormal.”
Predictive Ability of Frontal Assessment Battery for Cognitive Improvement After Shunt Surgery in Individuals With Idiopathic Normal Pressure Hydrocephalus
Authors: Asahara Yuki , Suda Machiko , Omoto Shusaku , Kobayashi Kazushige , Atsuchi Masamichi , Nagashima Hiroyasu , Suzuki Masahiko
Published: August 2023

Background:

The predictive ability of the Frontal Assessment Battery (FAB) for postoperative cognitive improvement in idiopathic normal pressure hydrocephalus (iNPH) is unstudied.

Objective:

To compare the predictive ability of the FAB and the Mini-Mental State Examination (MMSE) for postoperative cognitive improvement in individuals with iNPH after shunt surgery.

Method:

We retrospectively reviewed the medical records of individuals with iNPH who had shunt surgery between January 2016 and October 2018. Individuals had completed the tap test and clinical evaluations (FAB, MMSE, Timed Up and Go [TUG]) both before and 24–48 hours after CSF tapping and after surgery. We excluded individuals without complete clinical evaluations and those with shunt surgery performed >6 months after CSF tapping. Factors associated with postoperative FAB and MMSE improvement as per the 2011 iNPH guidelines were extracted using univariate and multivariate logistic regression analyses. Independent variables were baseline FAB and MMSE scores, FAB and MMSE score changes and TUG amelioration rate after CSF tapping, Evans index, age, and days from CSF tapping to surgery and from surgery to postoperative assessment.

Results:

The mean number of days from CSF tapping to surgery and from surgery to postoperative assessment were 77.5 (SD = 36.0) and 42.0 (SD = 14.5), respectively. Logistic regression analyses showed significant associations in the univariate analyses of postoperative FAB improvement with baseline FAB scores (P = 0.043) and with FAB score changes after CSF tapping (P = 0.047).

Conclusion:

The FAB may help predict postoperative cognitive improvement after shunt surgery better than the MMSE.
Cumulative Sum Chart as Complement to Objective Assessment of Graduating Surgical Resident Competency: An Exploratory Study
Authors: Chen Xiaodong (Phoenix) , Harzman Alan , Go Michael , Arnold Mark , Ellison E Christopher
Published: August 2023

Introduction:

Rater-based assessment and objective assessment play an important role in evaluating residents’ clinical competencies. We hypothesize that a cumulative sum (CUSUM) chart of operative time is a complement to the assessment of chief general surgery residents’ competencies with ACGME Milestones, aiding residency programs’ determination of graduating residents’ practice readiness.

Study Design:

We extracted ACGME milestone evaluations of performance of operations and procedures (POP) and three objective metrics (operative time, case type, and case complexity) from three procedures (cholecystectomy, colectomy, and inguinal hernia) performed by three cohorts of residents (N=15) during their PGY4-5. CUSUM charts were computed for each resident on each procedure type. A learning plateau was defined as at least four cases consistently locating around the centerline (target performance) at the end of a CUSUM chart with minimal deviations (range 0-1).

Results:

All residents reached the ACGME graduation targets for the overall POP by the end of chief year. A total of 2446 cases were included (cholecystectomy N=1234, colectomy N=507, and inguinal hernia N=705). Three CUSUM chart patterns emerged: skewed distribution, bimodal distribution, and peaks-and-valleys distribution. Analysis of CUSUM charts reveal surgery residents’ development process in the OR towards a learning plateau vary and only 46.7% residents reach a learning plateau in all three procedures upon graduation.

Conclusions:

CUSUM charts of operative time is a complement to the ACGME Milestones evaluations. The use of both may enable residency programs to holistically determine graduating residents’ practice readiness and provide recommendations for their upcoming career/practice transition.
Genomic mining and diversity of assembly line polyketide synthases
Authors: Kishore Shreya , Khosla Chaitan
Published: August 2023

Assembly line polyketide synthases (PKSs) are a large family of multifunctional enzymes responsible for synthesizing many medicinally relevant natural products with remarkable structural variety and biological activity. The decrease in cost of genomic sequencing paired with development of computational tools like antiSMASH presents an opportunity to survey the vast diversity of assembly line PKS. Mining the genomic data in the National Center for Biotechnology Information database, our updated catalogue (https://orphanpkscatalog2022.stanford.edu/catalog) presented in this article revealed 8799 non-redundant assembly line polyketide synthase clusters across 4083 species, representing a threefold increase over the past 4 years. Additionally, 95% of the clusters are ‘orphan clusters' for which natural products are neither chemically nor biologically characterized. Our analysis indicates that the diversity of assembly line PKSs remains vastly under-explored and also highlights the promise of a genomics-driven approach to natural product discovery.
Assessing motile cilia coverage and beat frequency in mammalian
in vitro
cell culture tissues
Authors: Fradique Ricardo , Causa Erika , Delahousse Clara , Kotar Jurij , Pinte Laetitia , Vallier Ludovic , Vila-Gonzalez Marta , Cicuta Pietro
Published: August 2023

Cilia density, distribution and beating frequency are important properties of airway epithelial tissues. These parameters are critical in diagnosing primary ciliary dyskinesia and examining
in vitro
models, including those derived from induced pluripotent stem cells. Video microscopy can be used to characterize these parameters, but most tools available at the moment are limited in the type of information they can provide, usually only describing the ciliary beat frequency of very small areas, while requiring human intervention and training for their use. We propose a novel and open-source method to fully characterize cilia beating frequency and motile cilia coverage in an automated fashion without user intervention. We demonstrate the ability to differentiate between different coverage densities, identifying even small patches of cilia in a larger field of view, and to fully characterize the cilia beating frequency of all moving areas. We also show that the method can be used to combine multiple fields of view to better describe a sample without relying on small pre-selected regions of interest. This is released with a simple graphical user interface for file handling, enabling a full analysis of individual fields of view in a few minutes on a typical personal computer.
A vicissicaudatan arthropod from the Silurian Herefordshire Lagerstätte, UK
Authors: Briggs Derek E. G. , Siveter David J. , Siveter Derek J. , Sutton Mark D. , Legg David , Lamsdell James C.
Published: August 2023

A new arthropod,Carimersa neptunigen. et sp. nov., is described from the Silurian (Wenlock Series) Herefordshire Konservat-Lagerstätte, UK. The head bears pedunculate eyes and five pairs of appendages. Triflagellate antennae are followed by two pairs of uniramous limbs each with an endopod bearing a pronounced gnathobasic basipod. The posterior two pairs of head limbs and all trunk limbs bear an endopod, exopod and filamentous exite. The trunk consists of 10 appendage-bearing segments followed by an apodous abdomen of four segments. The arthropod resolves as sister taxon toKodymirusandEozetetes+ Aglaspidida. It is the first representative of Vicissicaudata reported from the Herefordshire Lagerstätte and the first Silurian example with well-preserved appendages. The preservation of a cluster of radiolarians apparently captured by the trunk appendages is the first direct association of predator and prey discovered in the Herefordshire fauna, and suggests thatCarimersawas a nektobenthic form that used its gnathobasic basipods in microdurophagy.
Extending the analysis on the best solar activity proxy for long-term ionospheric investigations
Authors: Zossi Bruno S. , Medina Franco D. , Tan Jun Gloria , Lastovicka Jan , Duran Trinidad , Fagre Mariano , de Haro Barbas Blas F. , Elias Ana G.
Published: August 2023

Based on a previous study to select the best solar activity proxy for foF2 modelling, we expand the analysis to include 24 h time span, increase the spatial coverage by considering additional ionospheric stations, and update the analysis to 2021. Annual means of foF2 are analysed for 12 selected stations from Europe, Asia and Oceania, with high-quality data covering the period 1978–2021 in most of the cases, including two of the three European stations of the previous study. The same four solar proxies were used: F10.7, F30, MgII and HeII, which, based on the high linear correlation between each of them and foF2, serve to model this ionospheric parameter through a linear regression. The results of our comparative analysis, extended to more stations, all the hours and updated time series, agree with previous works, with MgII and F30 being the best solar proxies for foF2 modelling, while HeII is found to be the least effective for this purpose. The importance of the solar proxy selection to model foF2 for filtering purposes to later estimate long-term trends is highlighted considering that different solar proxies applied might result in somewhat different foF2 long-term trend values.
Characterization of a sperm motility signalling pathway in a gonochoric coral suggests conservation across cnidarian sexual systems
Authors: Glass Benjamin H. , Ashey Jill , Okongwu Amarachukwu R. , Putnam Hollie M. , Barott Katie L.
Published: August 2023

Most stony corals liberate their gametes into the water column via broadcast spawning, where fertilization hinges upon the activation of directional sperm motility. Sperm from gonochoric and hermaphroditic corals display distinct morphological and molecular phenotypes, yet it is unknown whether the signalling pathways controlling sperm motility are also distinct between these sexual systems. Here, we addressed this knowledge gap using the gonochoric, broadcast spawning coral
Astrangia poculata
. We found that cytosolic alkalinization of sperm activates the pH-sensing enzyme soluble adenylyl cyclase (sAC), which is required for motility. Additionally, we demonstrate for the first time in any cnidarian that sAC activity leads to protein kinase A (PKA) activation, and that PKA activity contributes to sperm motility activation. Ultrastructures of
A. poculata
sperm displayed morphological homology with other gonochoric cnidarians, and sAC exhibited broad structural and functional conservation across this phylum. These results indicate a conserved role for pH-dependent sAC-cAMP-PKA signalling in sperm motility across coral sexual systems, and suggest that the role of this pathway in sperm motility may be ancestral in metazoans. Finally, the dynamics of this pH-sensitive pathway may play a critical role in determining the sensitivity of marine invertebrate reproduction to anthropogenic ocean acidification.
Pathogenicity, genomic analysis and structure of abalone asfa-like virus: evidence for classification in the family Asfarviridae
Authors: Matsuyama Tomomasa , Kiryu Ikunari , Mekata Tohru , Takano Tomokazu , Umeda Kousuke , Matsuura Yuta
Published: August 2023

This paper presents the rationale for classifying abalone asfa-like virus (AbALV) in the family Asfarviridae based on analyses of the host, whole genome and electron microscopic observations. AbALV caused >80 % cumulative mortality in an experimentally infected mollusc, Haliotis madaka. The AbALV genome was found to be linear, approximately 281 kb in length, with a G+C content of 31.32 %. Of the 309 predicted ORFs, 48 of the top hits with African swine fever virus (ASFV) genes in homology analysis were found to be in the central region of the genome. Synteny in the central region of the genome was conserved with ASFV. Similar to ASFV, paralogous genes were present at both ends of the genome. The pairwise average amino acid identity (AAI) between the AbALV and ASFV genomes was 33.97 %, within the range of intra-family AAI values for Nucleocytoviricota. Electron microscopy analysis of the gills revealed ~200 nm icosahedral virus particles in the cytoplasm of epithelial cells, and the size and morphology resembled ASFV. In addition to swine, ASFV also infects ticks, which are protostomes like abalone. The overall genome structure and virion morphology of AbALV and ASFV are similar, and both viruses infect protostomes, suggesting that AbALV is a new member of the family Asfarviridae.
RNA-sequencing-based detection of human viral pathogens in cerebrospinal fluid and serum samples from children with meningitis and encephalitis
Authors: Fan Guohao , Li Sai , Tian Fengyu , Yang Longgui , Yi Suwu , Chen Sitian , Li Chengyi , Zhang Ruiqing , He Xiaozhou , Ma Xuejun
Published: August 2023

Encephalitis and meningitis are notable global public health concerns, especially among infants or children. Metagenomic next-generation sequencing (mNGS) has greatly advanced our understanding of the viruses responsible for these diseases. However, the detection rate of the aetiology remains low. We conducted RNA sequencing and virome analysis on cerebrospinal fluid (CSF) and serum samples commonly used in the clinical diagnosis to detect viral pathogens. In total, 226 paired CSF and serum samples from 113 children with encephalitis and meningitis were enrolled. The results showed that the diversity of viruses was higher in CSF, with a total of 12 viral taxa detected, including one case each of herpesvirus, coronavirus and enterovirus, and six cases of adenovirus related to human diseases. In contrast, the Anelloviridae was the most abundant viral family detected in serum, and only a few samples contained human viral pathogens, including one case of enterovirus and two cases of adenovirus. The detection rate for human viral pathogens increases to 10.6 %(12/113) when both types of samples are used simultaneously, compared to CSF along 7.9 % (9/113) or serum alone 2.6 % (3/113). However, we did not detect these viruses simultaneously in paired samples from the same case. These results suggest that CSF samples still have irreplaceable advantages for using mNGS to detect viruses in patients with meningitis and encephalitis, and serum can supplement to improve the detection rate of viral encephalitis and meningitis. The findings of this study could help improve the etiological diagnosis, clinical management and prognosis of patients with meningitis and encephalitis in children.
Epigenetic liquid biopsies reveal elevated vascular endothelial cell turnover and erythropoiesis in asymptomatic COVID-19 patients
Authors: Ben-Ami Roni , Loyfer Netanel , Cohen Eden , Fialkoff Gavriel , Sharkia Israa , Bogot Naama , Kochan Danit , Kalak George , Jarjoui Amir , Chen-Shuali Chen , Azulai Hava , Barhoum Hezi , Arish Nissim , Greenberger Moshe M , Vellema David , Kurd Ramzi , Chetrit Eli Ben , Bohm Davina , Wolak Talya , Quteineh Ahmad , Cann Gordon , Glaser Benjamin , Friedman Nir , Kaplan Tommy , Shemer Ruth , Rokach Ariel , Dor Yuval
Published: August 2023

The full spectrum of tissues affected by SARS-CoV-2 infection is crucial for deciphering the heterogenous clinical course of COVID-19. Here, we analyzed DNA methylation and histone modification patterns in circulating chromatin to assess cell type-specific turnover in severe and asymptomatic COVID-19 patients, in relation to clinical outcome. Patients with severe COVID-19 had a massive elevation of circulating cell-free DNA (cfDNA) levels, which originated in lung epithelial cells, cardiomyocytes, vascular endothelial cells and erythroblasts, suggesting increased cell death or turnover in these tissues. The immune response to infection was reflected by elevated B cell and monocyte/macrophage cfDNA levels, and by evidence of an interferon response in cells prior to cfDNA release. Strikingly, monocyte/macrophage cfDNA levels (but not monocyte counts), as well as lung epithelium cfDNA and vascular endothelial cfDNA, predicted clinical deterioration and duration of hospitalization. Asymptomatic patients had elevated levels of immune-derived cfDNA but did not show evidence of pulmonary or cardiac damage. Surprisingly, these patients showed elevated levels of vascular endothelial cell and erythroblast cfDNA, suggesting that sub-clinical vascular and erythrocyte turnover are universal features of COVID-19, independent of disease severity. Epigenetic liquid biopsies provide non-invasive means of monitoring COVID-19 patients, and reveal sub-clinical vascular damage and red blood cell turnover.
Induced pluripotent stem cell-derived human macrophages as an infection model forLeishmania donovani
Authors: Baert Lore , Rudy Serena , Pellisson Mélanie , Doll Thierry , Rocchetti Romina , Kaiser Marcel , Mäser Pascal , Müller Matthias
Published: August 2023

The parasiteLeishmania donovaniis one of the species causing visceral leishmaniasis in humans, a deadly infection claiming up to 40,000 lives each year. The current drugs for leishmaniasis treatment have severe drawbacks and there is an urgent need to find new anti-leishmanial compounds. However, the search for drug candidates is complicated by the intracellular lifestyle ofLeishmania. Here, we investigate the use of human induced pluripotent stem cell (iPS)-derived macrophages (iMACs) as host cells forL. donovani. iMACs obtained through embryoid body differentiation were infected withL. donovanipromastigotes, and high-content imaging techniques were used to optimise the iMACs seeding density and multiplicity of infection, allowing us to reach infection rates up to 70% five days after infection. IC50values obtained for miltefosine and amphotericin B using the infected iMACs or mouse peritoneal macrophages as host cells were comparable and in agreement with the literature, showing the potential of iMACs as an infection model for drug screening.

Author Summary

Yearly, up two million people in poverty-stricken areas contract leishmaniasis, a disease caused by parasites of the genusLeishmania. When an infected sandfly takes a blood meal,Leishmaniaparasites enter the host where they are taken up by macrophages. Inside the macrophage,Leishmaniaparasites establish a niche where they can proliferate. Although this infection often leads to disability or death, the drugs currently available are lacking due to toxic side effects, high expenses or difficulties in usage. Drug screening assays that are currently used for compound screening often rely on mouse peritoneal macrophages. We have generated human induced pluripotent stem cell derived macrophages and used these as new host cells forLeishmania donovaniin the testing of anti-leishmanial compounds. This model has many advantages. For one, it allows us to work with human cells, mimicking the natural infection more closely than possible with murine cells. Secondly, it allows to obtain bigger batches of uniform cells for screening campaigns. Finally, this approach aligns with the principle of 3R, replacing the use of animals for cultivation ofLeishmaniaand drug screening purposes.
Novel automaticity index reveals a cognitive ability-related decline in gait automaticity during dual-task walking
Authors: Liu Shuqi , Rosso Andrea L. , Baillargeon Emma M. , Weinstein Andrea M. , Rosano Caterina , Torres-Oviedo Gelsy
Published: August 2023

Gait automaticity refers to the ability to walk with minimal recruitment of attentional networks typically mediated through the prefrontal cortex (PFC). Reduced gait automaticity is common with aging, contributing to an increased risk of falls and reduced quality of life. A common assessment of gait automaticity involves examining PFC activation using near-infrared spectroscopy (fNIRS) during dual-task (DT) paradigms, such as walking while performing a cognitive task. However, neither PFC activity nor task performance in isolation measures automaticity accurately. For example, greater PFC activation could be interpreted as worse gait automaticity when accompanied by poorer DT performance, but when accompanied by better DT performance, it could be seen as successful compensation. Thus, there is a need to incorporate behavioral performance and PFC measurements for a more comprehensive evaluation of gait automaticity. To address this need, we propose a novel automaticity index as an analytical approach that combines changes in PFC activity with changes in DT performance to quantify gait automaticity. We validated the index in 173 participants (≥65 y/o) who completed DTs with two levels of difficulty while PFC activation was recorded with fNIRS. The two DTs consisted of reciting every other letter of the alphabet while walking over either an even or uneven surface. We found that as DT difficulty increases, more participants showed the anticipated decrease in automaticity as measured by the novel index compared to PFC activation. Furthermore, when comparing across individuals, lower cognitive function related to worse automaticity index, but not PFC activation or DT performance. In sum, the proposed index better quantified the differences in automaticity between tasks and individuals by providing a unified measure of gait automaticity that includes both brain activation and performance. This new approach opens exciting possibilities to assess participant-specific deficits and compare rehabilitation outcomes from gait automaticity interventions.