bluuebunny/crossref_metadata_2025 huggingface dataset:
Antispike monoclonal antibodies for prevention and treatment of coronavirus disease-2019 in solid organ transplant recipients
Authors: Yetmar Zachary A. , Bhaimia Eric , Razonable Raymund R.
Published: November 2022

Purpose of review

Coronavirus disease-2019 (COVID-19) disproportionately causes severe outcomes in solid organ transplant recipients (SOTR). Antispike monoclonal antibodies have been authorized for therapy and prophylaxis for COVID-19. Here, we review the current state of antispike monoclonal antibodies and their role for SOTRs.

Recent findings

Bamlanivimab with or without etesevimab, casirivimab-imdevimab and sotrovimab have reduced the rates of hospitalization and severe disease in high-risk patients with mild-to-moderate COVID-19. Multiple retrospective studies have also demonstrated monoclonal antibodies are effective in SOTR populations. However, the evolution of resistant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concerns has resulted in revocation of the authorization of bamlanivimab with or without etesevimab, and casirivimab-imdevimab as treatment and postexposure prophylaxis (PEP). Sotrovimab and bebtelovimab are currently authorized for treatment of the predominant circulating SARS-CoV-2 B.1.1.529 (Omicron), but not as pre or PEP. Tixagevimab–cilgavimab, a long-acting antibody combination preparation, is authorized for preexposure prophylaxis in high-risk immunocompromised populations, including SOTRs, who are less likely to mount an effective immune response following vaccination series and booster.

Antispike monoclonal antibodies are useful for the prevention and treatment of mild-to-moderate COVID-19 in SOTRs. However, their clinical use should be determined by the evolving epidemiology of SARS-CoV-2 variants in the community.
Ischemia-free organ transplantation − a review
Authors: Guo Zhiyong , Luo Tao , Mo Runbing , Zhao Qiang , He Xiaoshun
Published: November 2022

Purpose of review

Organ transplantation is one of the miracles in medicine in the 20th century. However, in the current practice, all the donor organs suffer from ischemia/reperfusion injury (IRI), which compromise transplant outcomes and limits organ availability. Continuous efforts have been made in organ machine perfusion to ameliorate IRI. In 2017, ischemia-free organ transplantation (IFOT) was first proposed with the aim of complete avoidance of IRI in organ transplantation. The purpose of this review is to highlight the latest progresses in IFOT.

Recent findings

The feasibility of IFOT has been validated in liver, kidney, and heart transplantation. The results of the first nonrandomized controlled study demonstrate that ischemia-free liver transplantation (IFLT) may improve transplant outcomes and increase organ availability. Furthermore, laboratory results, including the absence of the characteristic pathological changes, gene transcription and metabolic reprogramming, as well as sterile inflammation activation in IFLT grafts, suggest the virtual avoidance of graft IRI in IFLT.

IFOT might change the current practice by abrogating graft IRI. IFOT also provides a unique model to investigate the interaction between allograft IRI and rejection. The next steps will be to simplify the technique, make long-distance transportation possible and evaluate cost-effectiveness.
Charles Bonnet Syndrome Associated With Recurrent Hypertensive Crisis
Authors: Balsara Charmi , Shahin Alexander , Baviriseaty Niharika , Czuma Richard , Sullivan Gregory A.
Published: November 2022

Charles Bonnet syndrome (CBS) is a disorder of visual hallucinations in psychologically normal patients with ocular disease or damage to visual pathways. The etiology of CBS is not fully understood. It is associated with various triggers, with age-related macular degeneration the most common; other triggers are systemic diseases such as stroke, multiple sclerosis, and anemia as well as lighting issues, fatigue, and medical or surgical eye treatments. Visual disturbances such as decreased visual acuity, visual field deficits, or visual hallucinations are common in association with hypertensive encephalopathy. We describe a patient with episodic CBS triggered by recurrent hypertensive crises, which resolved with blood pressure management in the hospital setting.
Comparative Pharmacology of the 3 Marketed Dual Orexin Antagonists—Daridorexant, Lemborexant, and Suvorexant: Part 1: Pharmacokinetic Profiles
Authors: Preskorn Sheldon H.
Published: November 2022

This first column in a 2-part series focuses on the pharmacokinetics of the 3 Food and Drug Administration-approved dual orexin receptor antagonists, daridorexant, lemborexant, and suvorexant, specifically as they relate to their use as sleep medications. Although other classes of sleep medications are not discussed, the same pharmacokinetic principles also apply to them.
Abdominoplasty and Breast Augmentation with Outpatient Cosmetic Deep Inferior Epigastric Perforator Flaps
Authors: Martinez Carlos A. , Boutros Sean G.
Published: November 2022

Background:

The authors describe the use of deep inferior epigastric perforator (DIEP) flaps in outpatient cosmetic breast augmentation.

Methods:

The authors reviewed patients who had undergone cosmetic breast augmentation with DIEP flaps over a 12-month period. Any patient who desired breast augmentation, implant exchange, or augmentation mastopexy with concomitant abdominoplasty was considered a candidate for the procedure. All patients underwent an early recovery protocol including microfascial incisions to harvest the DIEP flaps and rib preservation in addition to early recovery after surgery protocols with intraoperative anesthetic blocks.

Results:

Eleven consecutive patients underwent bilateral cosmetic breast augmentation with DIEP flaps and mastopexy. Overall, all patients reported preoperative dissatisfaction with their abdomen and breasts. Microfascial incisions for single perforator abdominal flaps (n = 17) averaged 1.7 cm (range, 1.3 to 2.4 cm) and flaps with multiple perforators (n = 5) averaged 2.4 cm (range, 2 to 2.5 cm). Dissection of recipient internal mammary artery vessels was performed without disruption of the rib. No fascia or muscle tissue was taken during flap dissection. All patients had strong Doppler signals before discharge within 23 hours. No partial or total flap losses, major complications, or take-backs were reported.

Conclusions:

Patients who desire abdominoplasty and augmentation are ideal candidates for this procedure. Breast augmentation with autologous tissue, particularly the DIEP flap, is an attractive option inherent to the additional abdominal tissue available to harvest. The early recovery protocol allows the surgeon to perform microsurgical breast reconstructions and augmentations in an outpatient setting, with excellent results and no total or partial flap losses, offsetting the high costs associated with the DIEP flap.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Mendelian randomization study on the effect of tumor necrosis factor on schizophrenia
Authors: Ma Ning , Wang Renxi
Published: November 2022

Objective

Previous observational studies have shown that the levels of tumor necrosis factor (TNF) increased in patients with schizophrenia. The present two-sample Mendelian randomization (MR) study aims to identify the causal link between TNF and schizophrenia.

Methods

To date, the largest genome-wide association study (GWAS) for TNF (n = 23 141) and for schizophrenia (53 386 cases and 77 258 controls) was used. All participants were of European ancestry. The MR-egger_intercept test and Cochran’s Q statistic were used to determine the pleiotropy and heterogeneity, respectively. Weighted median and inverse variance weighted (IVW) were used to evaluate the causal association of TNF with schizophrenia.

Results

We found no significant pleiotropy or heterogeneity of all three selected plasma TNF genetic instrumental variants in breast cancer GWAS. Interestingly, the odds ratio (OR) = 1.517 with 95% confidence interval (CI), 1.006–2.288 and P = 0.047 of schizophrenia correspond to one unit increase in natural log-transformed TNF levels using IVW method. The increased trend was further proven using weighted median (OR = 1.585; 95% CI, 1.017–2.469; P = 0.042). Reverse MR analysis shows no causal effect of schizophrenia on plasma TNF levels.

Conclusions

Our analysis suggested a causal association between genetically increased TNF signaling and increased risk of schizophrenia in the European population. Thus, TNF may be a potential risk for schizophrenia.
Shinella lacus sp. nov., a novel microcystin-degrading alphaproteobacterium containing the bla carbapenemase gene
Authors: Gong Zhi-Lian , Deng Yang , Jiang Zhu-Ming , Liu Lu-Qing , Yu Li-Yan , Su Jing , Zhang Yu-Qin
Published: November 2022

A Gram-stain-negative, rod-shaped, microcystin-degrading bacterium, designated as CPCC 100929T, was isolated from a fresh water reservoir in Sichuan Province, PR China. This isolate grew well at 4–37 °C and pH 6.0–8.0, with optimal growth at 28–32 °C and pH 7.0, respectively. The major cellular fatty acids were C18:1 ω7c/C18:1 ω6c, C16:0, C18:1 ω7c 11-methyl and C19:0 cyclo ω8c. The predominant respiratory quinone was Q-10. Diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine and phosphatidylcholine were detected in the polar lipids extraction. The 16S rRNA gene sequence of strain CPCC 100929T was closely related to those of members of the genus

Shinella

, with the highest similarity of 98.6 % to

Shinella zoogloeoides

DSM 287T and 97.4–98.4 % with other identified

Shinella

members. In the phylogenetic trees based on 16S rRNA gene sequences and the core-genes analysis, strain CPCC 100929T was included within the clade of the genus

Shinella

. The values of average nucleotide identity (81.4–86.7 %) and digital DNA–DNA hybridization (25.4–44.6 %) between strain CPCC 100929T and other

Shinella

species were all below the thresholds for bacterial species delineation, respectively. The genomic DNA G+C content of strain CPCC 100929T was 63.6 %. The genomic sequence analysis indicated that this species contained genes encoding peroxidase, bla carbapenemase and the key enzyme for microcystin bio degradation, as well as rich carbohydrate-active enzyme coding genes, which might endow the micro-organism with properties to adapt to diverse environments. Based on its phenotypic and genetic properties, we propose that strain CPCC 100929T (=T1A350T=KCTC 72957T) is the type strain of a novel species with the name Shinella lacus sp. nov.
Antimicrobial activity of Latilactobacillus sakei
isolated from virgin coconut oil under pH and temperature stress
Authors: Miranti Mia , Iwahashi Hitoshi , Syaputri Yolani
Published: November 2022

This study aimed to elucidate whether lactic acid bacteria (LAB) can be used as a
bio-preservative and a natural antimicrobial agent to extend coconut oil
shelf-life, even under stress conditions. Lactiplantibacillus
plantarum and Latilactobacillus sakei were
isolated from virgin coconut oil which was subjected to strong environmental
stresses. L. sakei was sequenced by a universal primer of 16S
rRNA for LAB and included as L. sakei subsp.
sakei. The growth analysis was influenced by pH and the
optimum rate was pH 9.0. Furthermore, there was no growth at pH 3.0. In
addition, the antibacterial activities were estimated using the wells diffusion
method and the results were evaluated based on the presence of a clear halo
surrounding the wells. The antibacterial activities were optimum at pH 4.5-7.0
against Escherichia coli K12 JM109, Bacillus
subtilis, and Staphylococcus aureus JCM 20624. The
antimicrobial activity was evaluated under high temperatures of 60, 70, 80, 90,
and 100°C. The results revealed that even at high temperatures, the
cell-free supernatant of L. sakei still gave antimicrobial
activity. Therefore, it was concluded that L. sakei has
antimicrobial activities under environmental stresses and can be used as a
bio-preservative for coconut oil.
A comparison of physicochemical properties of hamburger steaks made
with pork, beef and venison
Authors: Lee Nan-Hee , Choi Ung-Kyu
Published: November 2022

This study aimed to pave the way for the industrialization of deer-based meat
products. Hamburger steak prepared using deer meat as an alternative to pork as
a raw material was evaluated for yield after heat treatment, water-holding
capacity, shear force, color, and texture. The pH of all test groups was found
to be within the range of pH 5.7-5.8, with no significant differences based on
the raw meat. The yield of venison hamburger steak after heat treatment was
significantly higher than pork. Adding deer meat reduced the water-holding
capacity. Shear force ranged from 1.79 to 1.82%, with no statistically
significant differences among any stakes. The venison imparted a rich brown hue
to the hamburger steak. The venison steak had a darker red shade compared to the
pork. Hardness, elasticity, cohesiveness, and chewiness were all significantly
higher in HVV, HPV, and HPB than in HPP. HVV had the highest adhesiveness,
followed by HPP, HPB, and HPV. The promising results suggested that deer
meat-based hamburger steaks may have a high utility as a meat product.
Outcome Of Total Surgical Debridement Of Covid Associated Skull base Mucormycosis Based on a New Surgical Staging System: Evidence From A Cohort Study
Authors: Kurup Lekshmy R , Singh Harshita , Sharma Shilpee Bhatia , Dehgani-Mobaraki Puya , Zaidi Asiya Kamber , Janakiram Narayanan
Published: November 2022

Purpose

To propose a surgical staging system with management protocol for post-covid Rhino-Orbito-Cerebral Mucormycosis (ROCM) with central skull base osteomyelitis.

Methods

A prospective cohort study of post-covid ROCM patients between May 2021 and January 2022. Patients were assessed radiologically and staged from I to V. Follow up period was 6 to 18 months and the surgical outcome was assessed.

Results

Total of 193 patients (129 primary and 64 revision). Maxilla was found to be the epicenter of anterior disease (69.3%) and pterygoid wedge, the epicenter of posterior disease (85.6%). More than 65% of our patients, at the time of presentation, presented with ROCM with involvement of the central skull base. Intracranial disease was noted in 13.9% of patients and the mortality rate was 6.2 %.

Conclusion

This staging system provides a systematic step-by-step protocol for the management of ROCM, with emphasis on meticulous disease clearance at the central skull base.
Destin2: integrative and cross-modality analysis of single-cell chromatin accessibility data
Authors: Guan Peter Y. , Lee Jin Seok , Wang Lihao , Lin Kevin Z. , Mei Wenwen , Jiang Yuchao
Published: November 2022

We propose Destin2, a novel statistical and computational method for cross-modality dimension reduction, clustering, and trajectory reconstruction for single-cell ATAC-seq data. The framework integrates cellular-level epigenomic profiles from peak accessibility, motif deviation score, and pseudo-gene activity and learns a shared manifold using the multimodal input, followed by clustering and/or trajectory inference. We apply Destin2 to real scATAC-seq datasets with both discretized cell types and transient cell states and carry out benchmarking studies against existing methods based on unimodal analyses. Using cell-type labels transferred with high confidence from unmatched single-cell RNA sequencing data, we adopt four performance assessment metrics and demonstrate how Destin2 corroborates and improves upon existing methods. Using single-cell RNA and ATAC multiomic data, we further exemplify how Destin’s cross-modality integrative analyses preserve true cell-cell similarities using the matched cell pairs as ground truths. Destin2 is compiled as a freely available R package available athttps://github.com/yuchaojiang/Destin2.
Virtual Home Visits Reduce Asthma Burden in Low-Income, Black Communities amidst the COVID-19 Pandemic
Authors: Bakshi Arundhati , Apantaku Elora , Marquette Tracy , Jacob Colette , Dumas S. Amanda , Friedman Kate , Aubin Kathleen , Soileau Shannon , Kemmerly Shaun
Published: November 2022

Objectives

Pilot an asthma virtual home visits program, and evaluate its reach and ability to promote asthma self-management strategies in underserved communities.

Methods

Participants were continuously recruited into the 3-month-long program starting March 2021 and provided with materials related to asthma education. Participants reporting poorly-controlled asthma and home-based triggers were also offered three virtual home visits with a respiratory therapist. All participants were asked to complete a pre- and post-intervention knowledge test and Asthma Control Test (ACT), and a final survey assessing perceptions regarding asthma management and environmental trigger reduction.

Results

As of October 2022, 147 participants were enrolled, and 52 had consented and received at least one virtual home visit. Approximately 77% of virtual visit recipients were children, 76% were non-Hispanic Black persons, and 90% were from ‘extremely low’ or ‘low’ income families. Asthma symptoms improved across the whole group, with a median increase of 2.39 points on the ACT score. Knowledge tests revealed that 86% of participants learned about at least one new asthma trigger, with a larger fraction of virtual visit recipients (68% vs. 36% non-recipients) showing an improved score post-intervention. About 75% of participants reported feeling more empowered to self-manage their asthma after participating in the program, and reported a significant improvement in their quality of life due to asthma.

Conclusions

The program successfully provided virtual asthma education to underserved, at-risk communities, and improved asthma outcomes for participants. Similar virtual models can be used to promote health equity, especially in areas with limited access to healthcare.

Summary Box

What is the current understanding on this subject?

Home-based interventions are known to be beneficial for improving asthma outcomes, especially among children; however, in-person visits have been a challenge during the COVID-19 pandemic.

What does this report add to the literature?

This report suggests that virtual, home-based models for asthma education are a viable alternative to in-person visits. As such, they can be an important tool for promoting health equity, especially in areas with limited access to healthcare.

What are the implications for public health practice?

Public health practitioners should be educated regarding the benefits of home-based asthma interventions, including virtual programs, as an adjuvant to standard clinical practices.
Reduced glymphatic function after traumatic brain injury measured using diffusion MRI
Authors: Butler Tracy , Zhou Liangdong , Ozhasin Ilker , Wang Xiuyuan Hugh , Garretti Jacob , Zetterberg Henrik , Blennow Kai , Jamison Keith , de Leon Mony J. , Li Yi , Kuceyeski Amy , Shah Sudhin A.
Published: November 2022

The glymphatic system is a perivascular fluid clearance system, most active during sleep, considered important for clearing the brain of waste products and toxins. Glymphatic failure is hypothesized to underlie brain protein deposition in neurodegenerative disorders like Alzheimer’s Disease. Preclinical evidence suggests that a functioning glymphatic system is also essential for recovery from traumatic brain injury (TBI), which involves release of debris and toxic proteins that need to be cleared from the brain.

We estimated glymphatic clearance using Diffusion Tensor Imaging Along Perivascular Spaces (DTI-ALPS), an MRI-derived measure of water diffusivity surrounding veins, in 13 non-injured controls and 37 subjects with TBI (∼5 months post). We additionally measured plasma concentrations of Neurofilament light chain (NfL), a biomarker of injury severity, in a subset of subjects.

DTI-ALPS was significantly lower in TBI subjects compared to controls, after controlling for age, and significantly, negatively correlated with NfL.

Glymphatic impairment after TBI could be due to mechanisms such as mis-localization of glymphatic water channels, inflammation, proteinopathy and/or sleep disruption. Additional work, including longitudinal studies, are needed to confirm results and assess glymphatic associations with outcome. Understanding post-TBI glymphatic functioning could inform novel therapies to improve short-term recovery and reduce later risk of neurodegeneration.
Impact ofAPOEgenotype on cognition in idiopathic and genetic forms of Parkinson’s disease
Authors: Koros Christos , Brockmann Kathrin , Simitsi Athina-Maria , Bougea Anastasia , Liu Hui , Hauser Ann-Kathrin , Schulte Claudia , Lerche Stefanie , Pachi Ioanna , Papagiannakis Nikolaos , Antonelou Roubina , Zahou Athina , Wurster Isabel , Efthymiopoulou Efthymia , Beratis Ion , Maniati Matina , Moraitou Marina , Michelakakis Helen , Paraskevas Georgios , Papageorgiou Sokratis G. , Potagas Constantin , Papadimitriou Dimitra , Bozi Maria , Stamelou Maria , Gasser Thomas , Stefanis Leonidas
Published: November 2022

Background

Apolipoprotein E-ε4 (APOEε4) genotype may be associated with the development of cognitive decline in idiopathic Parkinson’s disease i(PD), however its effect in genetic PD is understudied.

Objectives

In the current work we aimed to assess the impact ofAPOEgenotype on cognition in iPD as well as in genetic PD with mutations in theAlpha-synuclein(SNCA) andGlycocerebrosidase(GBA1) genes.

Methods

Two independent PD cohorts were analyzed: The first cohort (Athens) included 50 iPD patients, 35 patients with the p.A53TSNCAmutation and 59 patients withGBA1mutations (13 mild /46 severe). The second cohort (Tübingen) included 292 patients withGBA1mutations (170 risk/ 52 mild/ 70 severe). All patients underwent cognitive testing and were genotyped forAPOE.

Results

In the iPD subgroup, carriers of at least oneAPOEε4 exhibited lower Montreal Cognitive Assessment test (MoCA) score as compared to non-carriers (p=0.044). Notably, in the p.A53TSNCAsubgroup,APOEε4 carriers also had lower MoCA scores compared to non-carriers (p=0.039). There were noAPOEε4-related differences in the twoGBA1subgroups (Athens, p=0.729; Tübingen p=0.585).

Conclusions

We confirm the impact ofAPOEε4 on cognitive decline in iPD and for the first time report a similar effect in p.A53TSNCAmutation carriers, who represent the prototypical genetic synucleinopathy. Contrary, the lack of such an effect in two independent cohorts ofGBA1mutation carriers, who are thought to also manifest a predominant alpha-synuclein-driven cognitive decline, suggests differences in factors associated with cognitive dysfunction between different genetic forms of synucleinopathies.
Exploration of the gut microbiome in Thai patients with major depressive disorder uncovered a specific bacterial profile with depletion of theRuminococcusgenus as a putative biomarker
Authors: Maes Michael , Vasupanrajit Asara , Jirakran Ketsupar , Klomkliew Pavit , Chanchaem Prangwalai , Tunvirachaisakul Chavit , Payungporn Sunchai
Published: November 2022

Maes et al. (2008) published the first paper demonstrating that major depressive disorder (MDD) is accompanied by abnormalities in the microbiota-gut-brain axis, as evidenced by elevated serum IgM/IgA to lipopolysaccharides (LPS) of Gram-negative bacteria, such asMorganella morganiiandKlebsiella Pneumoniae. The latter aberrations, which point to increased gut permeability (leaky gut), are linked to activated neuro-immune and oxidative pathways in MDD. To delineate the profile and composition of the gut microbiome in Thai patients with MDD, we examined fecal samples of 32 MDD patients and 37 controls using 16S rDNA sequencing and analyzed α-(Chao and Shannon indices) and β-diversity (Bray-Curtis dissimilarity) and conducted Linear discriminant analysis (LDA) Effect Size (LEfSe) analysis. Neither α-nor β-diversity differed significantly between MDD and controls.Rhodospirillaceae, Hungatella, Clostridium bolteae, Hungatella hathewayi, andClostridium propionicumwere significantly enriched in MDD, while Gracillibacteraceae family,Lutispora, and Ruminococcus genus, Ruminococcus callidus, Desulfovibrio piger, Coprococcus comes, andGemmiger, were enriched in controls. Contradictory results have been reported for all these taxa, with the exception ofRuminococcuswhich is depleted in 6 different MDD studies (one study showed increased abundance), many medical disorders that show comorbidities with MDD, and animal MDD models. Our results may suggest a specific profile of compositional gut dysbiosis in Thai MDD patients with increases in some pathobionts and depletion of some beneficial microbiota. The results suggest that depletion ofRuminococcusmay be a more universal biomarker of MDD that maybe contributes to increased enteral LPS load, LPS translocation, and gut-brain axis abnormalities.
The Desire to Avoid Pregnancy Scale: clinical considerations and comparison with other questions about pregnancy preferences
Authors: Hall Jennifer A , Barrett Geraldine , Stephenson Judith , Edelman Natalie , Rocca Corinne H
Published: November 2022

Background

Clinicians and people of reproductive age would benefit from a reliable way to identify who is, or is not, likely to become pregnant in the next year, to direct health advice. The 14-item Desire to Avoid Pregnancy (DAP) Scale is predictive of pregnancy; this paper compares it with other ways of assessing pregnancy preferences to shortlist options for clinical implementation.

Methods

A cohort of 994 UK women of reproductive age completed the DAP and other questions about pregnancy preferences, including the Attitude towards Potential Pregnancy Scale (APPS), at baseline, and reported on pregnancies quarterly for a year. For each question, DAP item, and combinations of DAP items, we examined the predictive ability, sensitivity, specificity, area under the receiver operating curve (AUROC), and positive and negative predictive values.

Results

The AUROCs and predictive ability of the APPS and DAP single items were weaker than the full DAP, though all except one had acceptable AUROCs (>0.7). The most predictive individual DAP item was ‘It would be a good thing for me if I became pregnant in the next three months’, where women who strongly agreed had a 66.7% chance of pregnancy within 12months and the AUROC was acceptable (0.77).

Conclusion

We recommend exploring the acceptability to women and healthcare professionals of asking a single DAP item (‘I wouldn’t mind if I became pregnant in the next three months’), possibly in combination with additional DAP items. This will help to guide the provision of information and services to support reproductive preferences.

Key messages

Clinicians do not currently have a valid and reliable way of asking people about their pregnancy preferences.

A single item from the Desire to Avoid Pregnancy Scale is effective at identifying who is likely to become pregnant in the next year; other questions, including the APPS, are less discriminative but may be more acceptable.

The acceptability to women and health professionals of different ways of asking people about their pregnancy preferences in health care settings should be explored.
Genomic Characterization of Dengue Virus Outbreak in 2022 from Pakistan
Authors: Umair Massab , Rehman Zaira , Haider Syed Adnan , Ali Qasim , Jamal Zunera , Ammar Muhammad , Hakim Rabia , Bibi Shaheen , Sagheer Rida , Salman Muhammad , Ikram Aamer
Published: November 2022

Pakistan, a dengue endemic country has encountered several outbreaks during the past decade. The current study aimed to explore the serotype and genomic diversity of dengue virus responsible for the 2022 outbreak in Pakistan. During August-October 2022, blood samples (n=436) were collected from dengue patients, among which 64.4% (n=281) were positive based on RT-PCR. A subset of DENV-2 and DENV-1 samples were further subjected to whole-genome sequencing. In terms of gender and age, dengue infection was more prevalent in male patients (62.9%) with more adults (77.5%) being infected. Moreover, serotyping revealed DENV-2 to be most predominant serotype (64%; n=180), followed by DENV-1 (35.2%; n=99) and DENV-3 (0.35%; n=1). Phylogenetic analysis of sequenced samples indicates that all the samples (n=8) belong to the DENV-2 Cosmopolitan genotype, falling within a single monophyletic clade that is closely related to sequences from China and Singapore in 2018. Dengue virus dynamics reported in the current study warrants large scale genomic surveillance in order to better respond to future outbreaks.
Neurologic sequalae of COVID-19 are determined by immunologic imprinting from previous Coronaviruses
Authors: Spatola Marianna , Nziza Nadège , Jung Wonyeong , Deng Yixiang , Yuan Dansu , Dinoto Alessandro , Bozzetti Silvia , Chiodega Vanessa , Ferrari Sergio , Lauffenburger Douglas A , Mariotto Sara , Alter Galit
Published: November 2022

Coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global public health emergency. Although SARS-CoV-2 is primarily a respiratory pathogen, extra-respiratory organs, including the central nervous system (CNS), can also be affected. Neurologic symptoms have been observed not only during acute SARS-CoV-2 infection, but also at distance from respiratory disease, also known as long-COVID or neurological post-acute sequelae of COVID-19 (neuroPASC). The pathogenesis of neuroPASC is not well understood, but hypotheses include SARS-CoV-2-induced immune dysfunctions, hormonal dysregulations, and persistence of SARS-CoV-2 reservoirs. In this study, we used a high throughput systems serology approach to dissect the humoral response to SARS-CoV-2 (and other common Coronaviruses - 229E, HKU1, NL63, OC43) in the serum and cerebrospinal fluid (CSF) from 112 infected individuals who developed or did not develop neuroPASC. Unique SARS-CoV-2 humoral profiles were observed in the CSF of neuroPASC. All antibody isotypes (IgA, IgM, IgA) and subclasses (IgA1-2; IgG1-4) were detected in serum, whereas CSF was characterized by focused IgG1 (and absence of IgM). These data argue in favor of compartmentalized brain-specific responses against SARS-CoV-2 through selective transfer of antibodies from the serum to the CSF across the blood-brain-barrier, rather than intrathecal synthesis, where more diversity in antibody classes/subclasses would be expected. Moreover, compared to individuals who did not develop post-acute neurological complications following infection (n=94), those with neuroPASC (n=18) exhibited attenuated systemic antibody responses against SARS-CoV-2, characterized by decreased capacity to activate antibody-dependent complement deposition (ADCD), NK cell activation (ADNKA) and to bind Fcγ receptors. However, surprisingly, neuroPASC showed significantly expanded antibody responses to other common Coronaviruses, including 229E, HKU1, NL63, and OC43. This biased humoral activation across coronaviruses was particularly enriched in neuroPASC individuals with poor outcome, suggesting anoriginal antigenic sin(or immunologic imprinting), where pre-existing immune responses against related viruses shape the response to current infection, as a key prognostic marker of neuroPASC disease. Overall, these findings point to a pathogenic role for compromised anti-SARS-CoV-2 responses in the CSF, likely resulting in incomplete virus clearance from the brain and persistent neuroinflammation, in the development of post-acute neurologic complications of SARS-CoV-2 infection.
Mapping the electrophysiological structure of dystonic Globus Pallidus pars interna through intraoperative microelectrode recordings
Authors: Kaymak Ahmet , Vissani Matteo , Rinaldo Sara , Eleopra Roberto , Romito Luigi , Mazzoni Alberto
Published: November 2022

Objective

The Globus Pallidus pars interna (GPi) is one of the main targets for Deep Brain Stimulation (DBS) therapies for dystonia and other movement disorders. Still, a complete picture of the spiking dynamics of the nucleus is far from being achieved. Microelectrode recordings (MER) provide a unique brain window opportunity to shed light on GPi organization, which might support intraoperative DBS target localization, as previously done for the Subthalamic nucleus (STN).

Approach

Here we propose a novel procedure to analyze explorative MERs from DBS implants in dystonic patients. The procedure identifies the neural activity markers discriminating neurons in the GPi from those in the neighbouring structures, as well as the markers discriminating neurons located in different regions within the GPi.

Main results

The identification of the borders of the GPi based on neural markers was a difficult task, due to internal inhomogeneities in GPi firing dynamics. However, the procedure was able to exploit these inhomogeneities to characterize the internal electrophysiological structure of the GPi. In particular, we found a reliable dorsolateral gradient in firing activity and regularity.

Significance

Overall, we characterized the spatial distribution of neural activity markers in the dystonic GPi, paving the way for the use of these markers for DBS target localization. The procedure we developed to achieve this result could be easily extended to MER performed for other disorders and in other areas.
Assessing the accuracy of California county level COVID-19 hospitalization forecasts to inform public policy decision making
Authors: White Lauren A. , McCorvie Ryan , Crow David , Jain Seema , León Tomás M.
Published: November 2022

Background

The COVID-19 pandemic has highlighted the role of infectious disease forecasting in informing public policy. However, significant barriers remain for effectively linking infectious disease forecasts to public health decision making, including a lack of model validation. Forecasting model performance and accuracy should be evaluated retrospectively to understand under which conditions models were reliable and could be improved in the future.

Methods

Using archived forecasts from the California Department of Public Health’s California COVID Assessment Tool(https://calcat.covid19.ca.gov/cacovidmodels/), we compared how well different forecasting models predicted COVID-19 hospitalization census across California counties and regions during periods of Alpha, Delta, and Omicron variant predominance.

Results

Based on mean absolute error estimates, forecasting models had variable performance across counties and through time. When accounting for model availability across counties and dates, some individual models performed consistently better than the ensemble model, but model rankings still differed across counties. Local transmission trends, variant prevalence, and county population size were informative predictors for determining which model performed best for a given county based on a random forest classification analysis. Overall, the ensemble model performed worse in less populous counties, in part because of fewer model contributors in these locations.

Conclusions

Ensemble model predictions could be improved by incorporating geographic heterogeneity in model coverage and performance. Consistency in model reporting and improved model validation can strengthen the role of infectious disease forecasting in real-time public health decision making.
Physical inactivity among corporate bank workers in Accra, Ghana: Implications for health promotion
Authors: Nketiah George B. , Odoi-Agyarko Kwasi , Ndanu Tom A , Hayford Frank E. A. , Amoh Gordon , Lawson Henry J.
Published: November 2022

Introduction

It is common knowledge that any activity that results in caloric expenditure has the potential to prevent cardiovascular diseases, nonetheless, most people are physically inactive, especially office workers. This study sort to evaluate at baseline, the extent of physical inactivity and its determinants among staff of selected banks in Accra, Ghana.

Methods

This was a cross-sectional study involving 219 banking staff randomly selected from five commercial banking institutions in Accra, Ghana. Demographic data was collected with a structured questionnaire. Physical inactivity was assessed using the Global Physical Activity Questionnaire. Study associations were determined using univariate analysis, and multivariate logistic regression models with adjusted odds ratio (AOR) and 95% confidence intervals (CI) estimated.

Results

Of the 219 participants studied, the male to female ratio was 1.3:1.0 and the mean age (± SD) was 40.0±7.9 years. Overall, 165 (75.3%) of the study participants indulged in some form of physical activity, however, only 40 (18.3%) achieved the recommended levels. Physical inactivity was observed in 179 (81.7%) participants. The following were independently associated with physical inactivity: travel-related activities (AOR, 0.151; 95% CI, 0.059-0.384; p<0.001); working in the bank for 6-10 years (AOR, 4.617; 95% CI, 1.590-13.405; p=0.005); and working in the bank for 11 years and above (AOR, 2.816; 95% CI, 1.076-7.368; p=0.035).

Conclusion

Physical inactivity was very high among bankers. Travel-related activities and working at the bank for more than six years were associated with physical inactivity. Thus, promoting regular physical activity, frequent monitoring, and implementation of other appropriate healthy lifestyle intervention strategies are vital to reduce risk of early onset disease conditions associated with physical inactivity in this population.
The interface between SARS-CoV-2 and non-communicable diseases (NCDs) in a high HIV/TB burden district level hospital setting, Cape Town, South Africa
Authors: Mnguni Ayanda Trevor , Schietekat Denzil , Ebrahim Nabilah , Sonday Nawhaal , Boliter Nicholas , Schrueder Neshaad , Gabriels Shiraaz , Cois Annibale , Tamuzi Jacques L. , Tembo Yamanya , Davies Mary-Ann , English Rene , Nyasulu Peter S. ,   the COVID-19 Research Response Collaboration.
Published: November 2022

Background

COVID-19 experiences on noncommunicable diseases (NCDs) from district-level hospital settings during waves I and II are scarcely documented. The aim of this study is to investigate the NCDs associated with COVID-19 severity and mortality in a district-level hospital with a high HIV/TB burden.

Methods

This was a retrospective observational study that compared COVID-19 waves I and II at Khayelitsha District Hospital in Cape Town, South Africa. COVID-19 adult patients with a confirmed SARS-CoV-2 polymerase chain reaction (PCR) or positive antigen test were included. In order to compare the inter wave period, clinical and laboratory parameters on hospital admission of noncommunicable diseases, the Student t-test or Mann-Whitney U for continuous data and the X2 test or Fishers’ Exact test for categorical data were used. The role of the NCD subpopulation on COVID-19 mortality was determined using latent class analysis (LCA).

Findings

Among 560 patients admitted with COVID-19, patients admitted during wave II were significantly older than those admitted during wave I. The most prevalent comorbidity patterns were hypertension (87%), diabetes mellitus (65%), HIV/AIDS (30%), obesity (19%), Chronic Kidney Disease (CKD) (13%), Congestive Cardiac Failure (CCF) (8.8%), Chronic Obstructive Pulmonary Disease (COPD) (3%), cerebrovascular accidents (CVA)/stroke (3%), with similar prevalence in both waves except HIV status [(23% vs 34% waves II and I, respectively), p = 0.022], obesity [(52% vs 2.5%, waves II and I, respectively), p <0.001], previous stroke [(1% vs 4.1%, waves II and I, respectively), p = 0.046]. In terms of clinical and laboratory findings, our study found that wave I patients had higher haemoglobin and HIV viral loads. Wave II, on the other hand, had statistically significant higher chest radiography abnormalities, fraction of inspired oxygen (FiO2), and uraemia. The adjusted odds ratio for death vs discharge between waves I and II was similar (0.94, 95%CI: 0.84-1.05). Wave I had a longer average survival time (8.0 vs 6.1 days) and a shorter average length of stay among patients discharged alive (9.2 vs 10.7 days). LCA revealed that the cardiovascular phenotype had the highest mortality, followed by diabetes and CKD phenotypes. Only Diabetes and hypertension phenotypes had the lowest mortality.

Conclusion

Even though clinical and laboratory characteristics differed significantly between the two waves, mortality remained constant. According to LCA, the cardiovascular, diabetes, and CKD phenotypes had the highest death probability.
An image cryptography method in highly error-prone DNA storage channel
Authors: Zan Xiangzhen , Xie Ranze , Chu Ling , Su Yanqing , Yao Xiangyu , Xu Peng , Liu Wenbin
Published: November 2022

Rapid development in synthetic technologies has boosted DNA as a potential medium for large-scale data storage. Meanwhile, how to implement data security in DNA storage system is still an unsolved problem. In this paper, we propose an image encryption method based on the modulation-based storage architecture. The key idea is to take advantage of the unpredictable modulation signals to encrypt image in highly error-prone DNA storage channel. Numerical results demonstrate that our image encryption method is feasible and effective with excellent security against various attacks (statistical, differential, noise and data loss, etc.). Compared with other methods by DNA molecules hybridization reaction, the proposed method is more reliable and feasible for large-scale applications.
Demographic Reporting and Phenotypic Exclusion in fNIRS
Authors: Kwasa Jasmine , Peterson Hannah M , Jones Lietsel , Karrobi Kavon , Parker Termara , Nickerson Nia , Wood Sossena
Published: November 2022

1.

Functional near-infrared spectroscopy (fNIRS) promises to be a leading non-invasive neuroimaging method due to its portability and low cost. However, concerns are rising over its inclusivity of all skin tones and hair types (Parker and Ricard 2022, Webb et al 2022). Functional NIRS relies on direct contact of light-emitting optodes to the scalp, which can be blocked more by longer, darker, and especially curlier hair. Additionally, NIR light can be attenuated by melanin, which is accounted for in neither fNIRS hardware nor analysis methods. Recent work has shown that overlooking these considerations in other modalities like EEG leads to the disproportionate exclusion of individuals with these phenotypes – especially Black people – in both clinical and research literature (Bradford et al 2022, Choy 2020). In this article, we sought to determine if (1) biomedical optics developers and researchers report fNIRS performance variability between skin tones and hair textures, (2a) fNIRS neuroscience practitioners report phenotypic and demographic details in their articles, and thus, (2b) is a similar pattern of participant exclusion found in EEG also present in the fNIRS literature. We present a literature review of top Biomedical Optics and Human Neuroscience journals, showing that demographic and phenotypic reporting is unpopular in both fNIRS development and neuroscience applications. We conclude with a list of recommendations to the fNIRS community including examples of Black researchers addressing these issues head-on, inclusive best practices for fNIRS researchers, and recommendations to funding and regulatory bodies to achieve an inclusive neuroscience enterprise in fNIRS and beyond.
Single-molecule long-read methylation profiling reveals regional DNA methylation regulated by Elongator Complex Subunit 2 in Arabidopsis roots experiencing spaceflight
Authors: Zhou Mingqi , Riva Alberto , Gauthier Marie-Pierre L. , Kladde Michael P. , Ferl Robert J. , Paul Anna-Lisa
Published: November 2022

The Advanced Plant Experiment-04 - Epigenetic Expression (APEX04-EpEx) experiment onboard the International Space Station examined the spaceflight-altered cytosine methylation in two genetic lines ofArabidopsis thaliana, wild-type Col-0 and the mutantelp2-5,which is deficient in an epigenetic regulator Elongator Complex Subunit 2 (ELP2). Whole-genome bisulfite sequencing (WGBS) revealed distinct spaceflight associated methylation differences, presenting the need to examine specific space- altered methylation at single molecule resolution to associate specific changes over large regions of spaceflight related genes. Therefore flap-enabled next-generation capture (FENGC), a novel targeted multiplexed DNA capture and enrichment technique allowing cleavage at any specified sites, was applied to survey spaceflight-altered DNA methylation at the single-molecule level. The FENGC capture panel contained 108 targets ranging from 509 to 704 nt within the promoter or gene body regions of gene targets derived from spaceflight whole-genome data sets. In addition to genes with significant changes in expression and average methylation levels between spaceflight and ground control, targets without differentially methylated WGBS but with space- altered distributions of the proportion of methylated cytosines per molecule were further identified. Moreover, trends of co-methylation of different cytosine contexts were exhibited in the same DNA molecules. We further identified significant DNA methylation changes in three previously biological process-unknown genes, and two of them showed enhanced root growth rate in loss-of-function mutants (named asELP2- regulated Methylation in Orbit 1and2). FENGC makes multiplexed targeted single- molecule profiling of methylation simple and cost-effective, which provides an additional power to population-based data for methylation analysis and identification of epigenetically modified substrates in plants. This case study has revealed regional spaceflight-altered methylation in selected targets, which were not identified by short- read methods in spaceflight plants. The newly identifiedEMO1andEMO2are root growth regulators, which can be epigenetically involved in plant adaptation to spaceflight.
The structural, dynamical and biochemical characterizations ofVerticillium dahliaepectate lyase, VdPelB, highlight its specificities
Authors: Safran Josip , Ung Vanessa , Bouckaert Julie , Habrylo Olivier , Molinié Roland , Fontaine Jean-Xavier , Lemaire Adrien , Voxeur Aline , Pilard Serge , Pau-Roblot Corinne , Mercadante Davide , Pelloux Jérôme , Sénéchal Fabien
Published: November 2022

Pectins, complex polysaccharides and major components of the plant primary cell wall, can be degraded by pectate lyases (PLs). PLs cleave glycosidic bonds of homogalacturonans (HG), the main pectic domain, by β-elimination, releasing unsaturated oligogalacturonides (OGs). To understand the catalytic mechanism and structure/function of these enzymes, we characterized VdPelB fromVerticillium dahliae, a plant pathogen. We first solved the crystal structure of VdPelB at 1.2Å resolution showing that it is a right-handed parallel β-helix structure. Molecular dynamics (MD) simulations further highlighted the dynamics of the enzyme in complex with substrates that vary in their degree of methylesterification, identifying amino acids involved in substrate binding and cleavage of non-methylesterified pectins. We then biochemically characterized wild type and mutated forms of VdPelB. VdPelB was most active on non-methylesterified pectins, at pH 8 in presence of Ca2+ions. VdPelB-G125R mutant was most active at pH 9 and showed higher relative activity compared to native enzyme. The OGs released by VdPelB differed to that of previously characterized PLs, showing its peculiar specificity in relation to its structure. OGs released fromVerticillium-partially tolerant and sensitive flax cultivars differed which could facilitate the identification VdPelB-mediated elicitors of defence responses.