bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolite Profiling of Clozapine in Patients Switching Versus Maintaining Treatment
Authors: Kyllesø Lennart , Smith Robert Løvsletten , Wollmann Birgit M. , Karlstad Øystein , Andreassen Ole A. , Molden Espen
Published: August 2022

Purpose/Background

Pharmacokinetics may be of relevance for the risk of clozapine discontinuation. We compared metabolite profiles, accounting for smoking habits, in patients switching versus maintaining clozapine treatment at therapeutic concentrations.

Methods/Procedures

Adult patients with clozapine serum levels above 1070 nmol/L (350 ng/mL) were retrospectively included from a Norwegian therapeutic drug monitoring service during 2018–2020. Inclusion criteria were (1) known smoking habits, (2) blood sample drawn within 10 to 30 hours after last clozapine intake, and (3) detectable levels of N-desmethylclozapine, clozapine-N-oxide, clozapine-5N-glucuronide, or clozapine-N+-glucuronide. Patients comedicated with cytochrome P450 enzyme inducers, inhibitors, or valproic acid were excluded. The high-resolution mass spectrometry assay enabled detection of 21 clozapine metabolites. Metabolite profiles were compared between patients switching treatment (switchers), measured as clozapine being replaced by another antipsychotic drug in blood samples, versus maintaining clozapine treatment (nonswitchers) during the study period.

Findings/Results

Of the 84 patients fulfilling the study criteria, 7 patients (8.3%) were identified as clozapine switchers. After correcting for smoking habits, the clozapine-5N-glucuronide/clozapine ratio was 69% lower (P < 0.001), while the clozapine-N+
-glucuronide/clozapine-5N-glucuronide ratio was 143% higher (P = 0.026), respectively, in switchers versus nonswitchers. The other metabolite ratios did not significantly differ between switchers and nonswitchers.

Implications/Conclusions

The present study found a significantly reduced 5N-glucuronidation phenotype in patients switching from clozapine at therapeutic serum concentrations (>1070 nmol/L) to other antipsychotic drugs. This may indicate that glucuronidation, as a potential detoxification mechanism, is related to clozapine tolerability. However, the causality of this observation needs to be investigated in future studies with larger patient populations.
Case Reports
Authors: McInnis Melvin G. , Yocum Anastasia K.
Published: August 2022

Purposes

The aims of the study were to review 3 cases of lithium toxicity among individuals with bipolar disorder who were diagnosed with COVID-19 and to review the literature discussing the implications of COVID-19 and exposure to SARS-CoV-2 relative to medical use of lithium in management of bipolar disorder.

Methods

This is a case review of medical and psychiatric notes of 3 individuals with bipolar disorder, managed with lithium, who developed COVID-19. This study discussed these cases in context of previous case reports and relevant literature pertaining to lithium and exposure to SARS-CoV-2.

Findings

Infection with SARS-CoV-2 along with symptoms of COVID-19 and mental state changes in three individuals were temporally associated with lithium levels in the toxic range.

Implications

Exposure to SARS-CoV-2 or symptoms suggestive of COVID-19 should result in increased clinical monitoring of individuals taking lithium. Those taking lithium and providers are advised to have a low clinical threshold for requesting lithium levels and kidney function estimates for the duration of the COVD-19 pandemic.
Physician Assistant Program Policies to Assess and Address Student Reports of Mistreatment During Clinical Training
Authors: Hudak Nicholas M. , Blazar Melinda , Knudsen Nancy W.
Published: August 2022

Introduction

Many physician assistant (PA) students experience mistreatment in clinical learning environments, and accredited PA programs are required to define, publish, and make readily available policies and procedures for student reports of mistreatment. The purpose of this study is to describe the prevalence, content, and dissemination of program policies to address students’ reports of mistreatment involving preceptors during supervised clinical experiences.

Methods

To conduct a national policy analysis, the investigators included 10 new survey items in the 2019 Physician Assistant Education Association annual program survey. Deidentified data were analyzed by using descriptive statistics.

Results

The program response rate to the survey items was 99% (232). Approximately 76% of PA programs reported having a learner mistreatment policy. Policy content across programs varied widely, and several student reporting mechanisms were available. Program directors, clinical faculty, and institutional leadership were most likely to be involved in the management of reports. A majority programs actively assessed for mistreatment and most did so through clinical course evaluations and at the end of each clinical phase course. Most programs disseminated information about policy to faculty, students, and preceptors at least once a year.

Discussion

The descriptions of policy content, procedures, and dissemination increase educators’ understanding of current policies across PA programs in the context of renewed efforts to write or revise policy that is specific to mistreatment. The authors discuss key policy priorities to define mistreatment, offer a range of confidential reporting mechanisms, review the management of reports, and consider how to optimize dissemination strategies.
Upper gastrointestinal bleeding in coronavirus disease 2019 patients
Authors: Mauro Aurelio , De Grazia Federico , Anderloni Andrea , Di Sabatino Antonio
Published: August 2022

Purpose of review

Upper gastrointestinal bleeding (UGIB) has significant morbidity and UGIB cases have been described in coronavirus disease 2019 (COVID-19) patients. Management of this condition can be challenging considering both the possible severe COVID-19-related pneumonia as well as the risk of the virus spreading from patients to health operators. The aim of this paper is to review the most recent studies available in the literature in order to evaluate the actual incidence of UGIB, its clinical and endoscopic manifestations and its optimal management.

Recent findings

UGIB has an incidence between 0.5% and 1.9% among COVID-19 patients, and it typically presents with melena or hematemesis. Peptic ulcers are the most common endoscopic findings. High Charlson Comorbidity Index (CCI), dialysis, acute kidney injury and advanced oncological disease increase the risk for UGIB. Although anticoagulants are commonly used in COVID-19 patients they are not associated with an increased incidence of UGIB. Conservative management is a common approach that results in similar outcomes compared to upper GI endoscopic treatment. Apparently, UGIB in COVID-19 seems not have a detrimental effect and only one study showed an increased mortality in those who developed UGIB during hospitalization.

Incidence of UGIB in COVID-19 patients is similar to that of the general population. Despite the widespread use of anticoagulants in these patients, they are not associated with an increased risk of UGIB. Conservative management could be an effective option, especially for patients that are at risk of intubation.
Fibrin structure, viscoelasticity and lysis face the interplay of biorelevant polyions
Authors: Komorowicz Erzsébet , Kolev Krasimir
Published: August 2022

Purpose of review

In the past 5 decades, heparins have been widely used as anticoagulants in the prevention and treatment of thrombosis. Subsequent development of heparin variants of various size and charge facilitated the discovery of their multiple biological actions and nonanticoagulant benefits. Platelet-derived or microbial polyphosphates, as well as DNA released in the course of neutrophil extracellular trap-formation are additional polyanions, which can modulate the development and stability of thrombi associated with cancer or inflammation. In this review, we focus on the size-dependent and electric charge-dependent modulatory effects of the three polyanions of different chemical structure.

Recent findings

The polycationic histones have been recognized as potential biomarkers and therapeutic targets in several diseases related to inflammation and thrombosis. Since combating histones with activated protein C or heparin could cause unwanted bleeding, the quest for nonanticoagulant histone-neutralizing agents is ongoing. Polyanions may neutralize or exaggerate certain histone-mediated effects depending on their electric charge, size and histone effects under investigation. Several prothrombotic effects of polyphosphates and DNA are also size-dependent.

The efficiency of future therapeutics targeting prothrombotic polyanions or histones is not a simple matter of electric charge, but may rely on a delicate combination of size, charge and chemical composition.
Immunomodulatory roles of red blood cells
Authors: Dobkin Jane , Mangalmurti Nilam S.
Published: August 2022

Purpose of the Review

To discuss recent advances supporting the role of red blood cells (RBCs) in the host immune response

Recent Findings

Over the last century, research has demonstrated that red blood cells exhibit functions beyond oxygen transport, including immune function. Recent work indicates that the nucleic acid sensing receptor, toll-like receptor 9 (TLR9), is expressed on the RBC surface and implicated in innate immune activation and red cell clearance during inflammatory states. In addition to this DNA-sensing role of RBCs, there is growing evidence that RBCs may influence immune function by inducing vascular dysfunction. RBC proteomics and metabolomics have provided additional insight into RBC immune function, with several studies indicating changes to RBC membrane structure and metabolism in response to severe acute respiratory syndrome coronavirus 2 infection. These structural RBC changes may even provide insight into the pathophysiology of the ‘long-coronavirus disease 2019’ phenomenon. Finally, evidence suggests that RBCs may influence host immune responses via complement regulation. Taken together, these recent findings indicate RBCs possess immune function. Further studies will be required to elucidate better how RBC immune function contributes to the heterogeneous host response during inflammatory states.

The appreciation for nongas exchanging, red blood cell immune functions is rapidly growing. A better understanding of these RBC functions may provide insight into the heterogeneity observed in the host immune response to infection and inflammation.
Radical cystectomy and women's sexual health – can we do better?
Authors: Escott Megan , Avulova Svetlana , Bree Kelly K. , Westerman Mary E.
Published: August 2022

Purpose of review

Female sexual function after radical cystectomy is a crucial, but historically overlooked component of bladder cancer survivorship. This review focuses on recent studies, which have investigated pelvic health and sexual function after radical cystectomy. We discuss modifiable factors, which may contribute to decreased sexual function after radical cystectomy and techniques, which may lead to improved outcomes.

Recent findings

Sexual function is important to women and there is a significant desire (and unmet need) for more perioperative counseling and discussion regarding sexual function changes and quality of life impacts. Sexual function may be altered due to a combination of hormonal changes from ovarian removal, anatomic changes from vaginal alteration, and sensation changes due to damage to the neurovascular bundle. Techniques to preserve these structures have been developed.

Sexual function is an important component of survivorship and increasing attention is being focused on this area. Long term studies with objective measures are needed for to compare various techniques and ensure oncologic safety. Ovarian preservation, anterior vaginal wall preservation, and vaginal estrogen replacement should be carefully considered for most patients.
Surgeons’ Leadership Style and Team Behavior in the Hybrid Operating Room
Authors: Soenens Gilles , Marchand Benoit , Doyen Bart , Grantcharov Teodor , Van Herzeele Isabelle , Vlerick Peter
Published: July 2022

Objective:

This study aimed to assess the relationship between surgeons’ leadership style and team behavior in the hybrid operating room through video coding. Secondly, possible fluctuations possible fluctuations in leadership styles and team behavior during operative phases were studied.

Background:

Leadership is recognized as a key component to successful team functioning in high-risk industries. The ‘full range of leadership’ theory is commonly used to evaluate leadership, marking transformational, transactional, and passive. Few studies have examined the effects of these leadership styles on team behavior in surgery and/or their fluctuations during surgery.

Methods:

A single-center study included patients planned for routine endovascular procedures. A medical data capture system was used to allow post hoc video coding through Behavior Anchored Rating Scales. Multilevel statistical analysis was performed to assess possible correlations between leadership style and 3 team behavior indicators (speaking up, knowledge sharing, and collaboration) on an operative phase level.

Results:

Twenty-two cases were analyzed (47 hours recording). Transformational leadership is positively related to the extent to which team members work together (γ=0.20, P<0.001), share knowledge (γ=0.45, P<0.001), and speak up (γ=0.64, P<0.001). Passive leadership is significantly positively correlated with speaking up (γ=0.29, P=0.004). Leadership style and team behavior clearly fluctuate during a procedure, with similar patterns across different types of endovascular procedures.

Conclusions:

Consistent with other professional fields, surgeons’ transformational leadership enhances team behavior, especially during the most complex operative phases. This suggests that encouraging surgeons to learn and actively implement a transformational leadership style is meaningful to enhance patient safety and team performance.
A Breakthrough Improvement Collaborative Significantly Reduces Hospital Stay After Elective Colectomy for Cancer Across a Healthcare System
Authors: Coeckelberghs Ellen , Vanhaecht Kris , Seys Deborah , Cox Bianca , Bislenghi Gabriele , Wolthuis Albert M. , D’Hoore André ,   on behalf of BIC4CRC Research group
Published: August 2022

Objective:

This multicenter study aimed to assess (1) the effect of an improvement collaborative on enhanced recovery after surgery (ERAS) protocol adherence after elective colectomy and (2) the association between adherence and patient outcomes.

Background:

ERAS pathways provide a framework to standardize care processes and improve postoperative outcomes in patients after colon surgery. Despite growing evidence of its effectiveness, adherence to these guidelines remains a challenge.

Methods:

This prospective, multicenter collaborative was initiated throughout 11 hospitals in Flanders, Belgium. A structured audit tool was used to study patient outcomes and adherence to 12 ERAS components, defined by the collaborative. Three retrospective audits (based on patient record analysis) were conducted in 2017, 2019, and 2021, respectively.

Results:

Overall, 740 patients were included (45.4% female; mean±SD age, 71±12 years). The overall adherence increased from 42.8% in 2017 to 58.4% in 2019 and 69.2% in 2021. Compared with low adherence, length of stay was increasingly reduced by 1.3 days for medium [95% confidence interval (95% CI): −2.5; 0.0], 3.6 days for high (95% CI: −4.9; −2.2), and up to 4.4 days for very high adherence (95% CI: −6.1; −2.7). Corresponding odds ratios for postoperative complications were 0.62 (95% CI: 0.33; 1.17), 0.19 (95% CI: 0.09; 0.43), and 0.14 (95% CI: 0.05; 0.39), respectively. No increase in 30-day readmissions was observed.

Conclusions:

A peer-constructed improvement collaborative effectively increases adherence to an ERAS protocol in individual hospitals. Across time, length of stay and postoperative complications decreased significantly, and a dose-response relationship was observed.
Treatment of penetrating cardiac wounds for the general surgeon on call
Authors: Khaitan Puja Gaur , Feliciano David V. , Rozycki Grace F. , Symbas Panagiotis , O’Connor James V. , Scalea Thomas M.
Published: August 2022

“Scoop and run” approaches for severely injured patients have been adopted by emergency medical services over the past 40 years. This has resulted in more patients with severe injuries including penetrating cardiac wounds arriving at trauma centers and other acute care hospitals. General surgery trauma teams and general surgeons taking trauma call are the first responders for diagnosis, resuscitation, and operative management of injured patients. By natural selection, 96% to 98% of patients with signs of life on arrival to the trauma center after sustaining a penetrating cardiac wound have injuries that are amenable to repair by a general surgeon, fellow, or senior surgical resident without the need for a cardiothoracic surgeon or cardiopulmonary bypass.

This literature and experience-based review summarizes the diagnostic and operative approaches that should be known by all trauma teams and general surgeons taking trauma call. In addition, it describes when a cardiothoracic surgeon should be consulted and briefly reviews how complex penetrating cardiac injuries are repaired.
Pseudovibrio flavus sp. nov. isolated from the sea sponge Verongula gigantea
Authors: Goldberg Stacey R. , Haltli Brad A. , Correa Hebelin , Kerr Russell G.
Published: August 2022

A Gram-negative, motile, rod-shaped marine bacterium, designated RKSG542T, was isolated from the sea sponge Verongula gigantea collected at a depth of 20 m off the west coast of San Salvador, The Bahamas. Phylogenetic analyses based on 16S rRNA gene and genome sequences place RKSG542T in a monophyletic clade with members of the genus

Pseudovibrio

. Strain RKSG542T shared <96.7 % 16S rRNA gene sequence similarity,<72.2 % average nucleotide identity,<66.7 % average amino acid identity, and <24.8 % digital DNA–DNA hybridization with type strains of the family

Stappiaceae

. Growth occurred at 22–37 °C (22–30 °C optimum), at pH 7–9 (pH 7 optimum), and with 0.5–5 % (w/v) NaCl (2 % optimum). The predominant fatty acids (>10 %) were summed feature 8 (C18 : 1
 ω6c and/or C18 : 1
 ω7c), C18 : 0 and C16 : 0, and the respiratory lipoquinone was Q-10. The polar lipid composition comprised phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, three unknown aminolipids, six unknown phospholipids and four unknown lipids. The DNA G+C content of the genome sequence was 52.5 mol%. Based on the results of biochemical, phylogenetic and genomic analyses, RKSG542T (=TSD-76T=LMG 29867T) is presented here as the type strain of a novel species within the genus

Pseudovibrio

(family

Stappiaceae

, order

Hyphomicrobiales

, class

Alphaproteobacteria

), for which the name Pseudovibrio flavus sp. nov. is proposed.
Transcriptional regulation of the mtrCDE efflux pump operon: importance for Neisseria gonorrhoeae antimicrobial resistance
Authors: Ayala Julio C. , Balthazar Jacqueline T. , Shafer William M.
Published: August 2022

This review focuses on the mechanisms of transcriptional control of an important multidrug efflux pump system (MtrCDE) possessed by

Neisseria gonorrhoeae

, the aetiological agent of the sexually transmitted infection termed gonorrhoea. The mtrCDE operon that encodes this tripartite protein efflux pump is subject to both cis- and trans-acting transcriptional factors that negatively or positively influence expression. Critically, levels of MtrCDE can influence levels of gonococcal susceptibility to classical antibiotics, host-derived antimicrobials and various biocides. The regulatory systems that control mtrCDE can have profound influences on the capacity of gonococci to resist current and past antibiotic therapy regimens as well as virulence. The emergence, mechanisms of action and clinical significance of the transcriptional regulatory systems that impact mtrCDE expression in gonococci are reviewed here with the aim of linking bacterial antimicrobial resistance with multidrug efflux capability.
Synthetic modified vaccinia Ankara vaccines confer potent monkeypox immunity in non-human primates and healthy adults
Authors: Chiuppesi Flavia , Zaia John A. , Francisco Sandra Ortega , Ly Minh , Wussow Felix , Diamond Don J.
Published: July 2022

The recent outbreak of monkeypox (MPXV) outside its endemic boundaries has attracted global attention and prompted world leaders to reserve millions of doses of the only approved third-generation smallpox/MPXV vaccine, Jynneos, which is based on the highly attenuated modified vaccinia Ankara (MVA) vector. We previously developed COH04S1, a multiantigen SARS-CoV-2 vaccine built on a synthetic MVA (sMVA) platform. COH04S1 was extensively tested for efficacy and immunogenicity in animal models, including non-human primates (NHP), and was found to be safe and to induce SARS-CoV-2-specific immunity in a Phase 1 clinical trial in healthy adults. Here we demonstrate that one or two vaccinations of NHP with either COH04S1 or sMVA elicit robust othopoxvirus-specific binding and neutralizing antibody responses. Furthermore, healthy adults vaccinated with COH04S1 at different dose levels develop robust othopoxvirus-specific humoral and cellular immune responses that are durable for over six months post-vaccination. Importantly, both COH04S1 and sMVA vaccinations induce elevated and sustained antibody responses to MPXV-proteins that are major targets of protective neutralizing antibodies. These results demonstrate that COH04S1 and sMVA are valuable vaccine candidates to stimulate robust orthopox/MPXV-specific humoral and cellular immunity.
Level of Compliance and Predictors with Personal COVID-19-preventive measures Among Office Government Employees Returning to work in the post-epidemic period in Western Ethiopia: A Multicenter Cross-sectional Study
Authors: Kabito Gebisa Guyasa , Abreham Meskele , Tesfaye Amensisa Hailu , Guadu Tadesse
Published: July 2022

Background

The contemporary global issues, COVID-19 pandemic continued causing unprecedented impact on the public health, occupational health and the global economy. Keeping compliance with personal preventive measures is a vital tool for managing COVID-19 pandemic control and returning to work as no pharmaceutical treatments are currently available in Ethiopia. Although compliance with COVID -19 personal preventive measures (CPPMs) and predictors is well addressed in healthcare settings, data on the level of CPPMs and its determinants among government employees working in offices worldwide, including Ethiopia, is limited. This paper is aimed to fill this gaps.

Methods

We applied a cross-sectional study design from February to March, 2021. The participants were government workers working in offices who had resumed work. Stratified followed by simple random sampling technique was used to select 422 study participants from 30 government offices that had resumed work. Data were collected using a pre-tested and structured interviewer-administered questionnaires and analyzed by STATA 14 software. The significance of associations was established at p< 0.05 and adjusted odds ratio (AOR) with 95% confidence intervals (CI) in the multivariable model.

Results

Response rate 95.44% (N=394). The study found 22.3% (88) of study participants (95% CI = 18.5, 26.6) had high compliance with COVID -19 personal preventive measures during past month. Female workers were 2.80 times more likely than males to comply with COVID-19 personal preventive measures (AOR: 2.80, 95%CI (1.10, 7.12), favorable attitude towards COVID-19 prevention measures (AOR: 13.73, 95% CI (4.85, 38.83), high-risk perception of COVID-19 infections (AOR: 2.34; 95% CI (1.24, 4.41), and high misconception about COVID-19 (AOR : 3.92, 95% CI (1.45, 10.62) were predicted better compliance with COVID-19 PPMs (P < 0.05).

Conclusions

In sum, little proportion of sampled study participants complied with COVID -19 personal preventive measures. Sex, attitudes, risk perception, and misconception have all been identified as significant risk factors. Actions are needed to strengthen COVID -19 personal preventive measures among government employees to maintain COVID -19 control following work resumption. In the future, it’s vital to work on government employees’ attitudes and perceptions in order to improve compliance.
Post-traumatic Stress Disorder symptom sub-cluster severity predicts gray matter volume changes better than overall symptom severity
Authors: Azma Sheeva , Thompson Rachel , Bermudez Diana , Renton Rachael , Adeyemo Adebanke , Meyerhoff James , Amdur Richard , Green Bonnie , Dutton Mary Ann , VanMeter John W.
Published: July 2022

Meta-analysis shows that sub-clusters defined by affected domains of psychosocial functioning capture PTSD subtypes better than symptom clusters defined in the DSM-IV. This pilot study investigated the association between symptom sub-clusters and brain volume in twelve persons with PTSD (females, mean age 40.9 years). Structural magnetic resonance imaging (MRI) images were acquired, and voxel-based morphometry (VBM) was used to estimate local gray matter volume throughout the brain. Participants’ gray matter volume was correlated with both overall PTSD severity and sub-cluster severities. In this preliminary study examining sub-clusters and brain morphometry, we found that neuronal changes associated with sub-clusters may provide a more complete understanding of the neuroanatomical changes that occur in PTSD beyond what can be ascertained using overall disorder severity or comparisons with control subjects. The results of our study suggest that the neurobiological changes resulting from severe trauma depend on the specific sub-clusters of symptoms experienced by individuals with PTSD.
Evoked midfrontal activity predicts cognitive dysfunction in Parkinson’s disease
Authors: Singh Arun , Cole Rachel C , Espinoza Arturo I , Wessel Jan R. , Cavanagh James F. , Narayanan Nandakumar S
Published: July 2022

Cognitive dysfunction is a major feature of Parkinson’s disease (PD), but the pathophysiology remains unknown. One potential mechanism is abnormal low-frequency cortical rhythms which engage cognitive functions and are deficient in PD. We tested the hypothesis that midfrontal delta/theta rhythms predict cognitive dysfunction in PD. We recruited 100 PD patients and 49 demographically-similar control participants who completed a series of cognitive control tasks, including the Simon, oddball, and interval timing tasks. We focused on cue-evoked delta (1-4 Hz) and theta (4-7 Hz) rhythms from a single midfrontal EEG electrode (Cz) in PD patients who were either cognitively normal, with mild-cognitive impairments (PDMCI), or had dementia (PDD). We found that PD-related cognitive dysfunction was associated with increased response latencies and decreased midfrontal delta power across all tasks. Within PD patients, the first principal component of evoked EEG features from a single electrode (Cz) strongly correlated with clinical metrics such as the Montreal Cognitive Assessment (MOCA; rho=0.36) and with NIH-toolbox Executive Function scores (rho=0.46). These data demonstrate that cue-evoked midfrontal delta/theta rhythms directly relate to cognition in PD. Our results provide insight into the nature of low-frequency frontal rhythms and suggest that PD-related cognitive dysfunction results from decreased delta/theta activity. These findings could facilitate the development of new biomarkers and targeted therapies for cognitive symptoms of PD.
High seroprevalence of Immunoglobulin G (IgG) and IgM antibodies to SARS-CoV-2 in asymptomatic and symptomatic individuals amidst vaccination roll-out in western Kenya
Authors: Awandu Shehu Shagari , Ochieng Alfred , Onyango Benson , Magwanga Richard Odongo , Were Pamella , Ochung Angeline , Okumu Fredrick , Oloo Marceline Adhiambo , Katieno Jim Seth , Lidechi Shirley , Ogutu Fredrick , Awuor Dorothy , Kirungu Joy Nyangasi , Omoto Francis Orata , Midega Justine , Oure Bonface , Nyunja Regina , Muok Eric M O , Munga Steven , Estambale Benson
Published: July 2022

Background

The population’s antibody response is a key factor in comprehending SARS-CoV-2 epidemiology. This is especially important in African settings where COVID-19 impact, and vaccination rates are relatively low. This study aimed at characterizing the Immunoglobulin G (IgG) and Immunoglobulin M (IgM) in both SARS-CoV-2 asymptomatic and symptomatic individuals in Kisumu and Siaya counties in Western Kenya using enzyme linked immunosorbent assays.

Results

The IgG and IgM overall seroprevalence in 98 symptomatic and asymptomatic individuals in western Kenya between December 2021-March 2022 was 76.5% (95% CI =66.9-84.5) and 31.6% (95% CI =22.6-41.8) respectively. In terms of gender, males had slightly higher IgG positivity 87.8% (36/41) than females 68.4% (39/57). Amidst the ongoing vaccination roll-out during the study period, over half of the study participants (55.1%, 95% CI= 44.7-65.2) had not received any vaccine. About one third, (30.6%, 95% CI= 21.7-40.7) of the study participants had been fully vaccinated, with close to a quarter (14.3% 95% CI=8.04-22.8) partially vaccinated. When considering the vaccination status and seroprevalence, out of the 30 fully vaccinated individuals, IgG seropositivity was 86.7% (95% CI =69.3-96.2) and IgM seropositivity was 40% (95% CI =22.7-59.4). Out of the participants that had not been vaccinated at all, IgG seroprevalence was 70.3% (95% CI 56.4-82.0) with 20.4% (95% CI 10.6-33.5) seropositivity of IgM antibodies. SARs-CoV-2 PCR positivity did not significantly predict IgG (p = 0.457 [95% CI 0.514-4.371]) and IgM (p = 0.858 [95% CI 0.350-2.395]) positivity.

Conclusion

Our data indicate a high seroprevalence of antibodies to SARS-CoV-2 in western Kenya. This suggests larger fraction of the population were infected with SARS-CoV-2 within the defined period than what PCR testing could cover.
Evolution of SARS-CoV-2 Shedding in Exhaled Breath Aerosols
Authors: Lai Jianyu , Coleman Kristen K. , Sheldon Tai S.-H. , German Jennifer , Hong Filbert , Albert Barbara , Esparza Yi , Srikakulapu Aditya K. , Schanz Maria , Maldonado Isabel Sierra , Oertel Molly , Fadul Naja , Gold T. Louie , Weston Stuart , Mullins Kristin , McPhaul Kathleen M. , Frieman Matthew , Milton Donald K.
Published: July 2022

Aerosol inhalation is increasingly well recognized as a major if not primary mode of transmission of SARS-CoV-21,2. Over the course of the COVID-19 pandemic, three highly transmissible lineages evolved and became globally dominant3. One hypothesis to explain increased transmissibility is that natural selection favours variants with higher rates of viral aerosol shedding. However, the extent of aerosol shedding of successive SARS-CoV-2 variants is unknown. Here, we demonstrate that viral shedding (measured as RNA copies) into exhaled breath aerosol was significantly greater during infections with Alpha, Delta, and Omicron than with ancestral strains and variants not associated with increased transmissibility. The three highly transmissible variants independently evolved a high viral aerosol shedding phenotype, demonstrating convergent evolution. We did not observe statistically significant differences in rates of shedding between Alpha, Delta, and Omicron infections. The highest shedder in our study, however, had an Omicron infection and shed three orders of magnitude more viral RNA copies than the maximum observed for Delta and Alpha4. Our results also show that fully vaccinated and boosted individuals, when infected, can shed infectious SARS-CoV-2 via exhaled breath aerosols. These findings provide additional evidence that inhalation of infectious aerosols is the dominant mode of transmission and emphasize the importance of ventilation, filtration, and air disinfection to mitigate the pandemic and protect vulnerable populations. We anticipate that monitoring aerosol shedding from new SARS-CoV-2 variants and emerging pathogens will be an important component of future threat assessments and will help guide interventions to prevent transmission via inhalation exposure.
The Association of Fear of Movement and Postural Sway in People with Low Back Pain
Authors: Meinke Anita , Maschio Cinzia , Meier Michael , Karlen Walter , Swanenburg Jaap
Published: July 2022

Background

Fear of movement is thought to interfere with the recovery from low back pain (LBP). To date, the relationship between fear of movement and postural balance has not been adequately elucidated. Recent findings suggest that more specific fears need to be assessed and put in relation to a specific movement task. We propose that the fear to bend the trunk in a certain direction is distinctly related to the amount of postural sway in different directions. Therefore, our aim was to investigate whether fear of movement in general and fear of bending the trunk in a certain plane is related to postural sway.

Methods

Data was collected from participants with LBP during two assessments approximately three weeks apart. Postural sway was measured with a force-platform during quiet standing with the eyes closed. Fear of movement was assessed with an abbreviated version of the Tampa Scale of Kinesiophobia (TSK-11) and custom items referring to fear of bending the trunk in the sagittal and the frontal plane.

Results

Based on data from 25 participants, fear of bending the trunk in the frontal plane was positively related to displacement in the sagittal and frontal plane and to velocity in the frontal plane (X2=4.35, P=.04; X2=8.15, P=.004; X2=9.79, P=.002). Fear of bending the trunk in the sagittal plane was not associated with any direction specific measure of sway. A positive relation of the TSK-11 with velocity of the frontal plane (X2=7.14, P=.008) was found, but no association with undirected measures of sway.

Discussion

Fear of bending the trunk in the frontal plane may be especially relevant to postural sway under the investigated stance conditions. It is possible that fear of bending the trunk in the frontal plane could interfere with balance control at the hip, shifting the weight from side to side to control balance.

Conclusion

For the first time the directional relationship of fear of movement and postural sway was studied. Fear of bending the trunk in the frontal plane was positively associated with several measures of postural sway.
Chromatin accessibility profiling in tissue sections by spatial ATAC
Authors: Llorens-Bobadilla Enric , Zamboni Margherita , Marklund Maja , Bhalla Nayanika , Chen Xinsong , Hartman Johan , Frisén Jonas , Ståhl Patrik L
Published: July 2022

Current methods for epigenomic profiling are limited in the ability to obtain genome wide information with spatial resolution. Here we introduce spatial ATAC, a method that integrates transposase-accessible chromatin profiling in tissue sections with barcoded solid-phase capture to perform spatially resolved epigenomics. We show that spatial ATAC enables the discovery of the regulatory programs underlying spatial gene expression during mouse organogenesis, lineage differentiation and in human pathological samples.
Physiological traits and their relationships vary along an elevational gradient within and among Fijian bee species
Authors: da Silva Carmen Rose Burke , Beaman Julian Edward , Tuiwawa Marika , Stevens Mark I , Schwarz Michael P. , Gloag Rosalyn , Kellermann Vanessa , Alton Lesley A.
Published: July 2022

Temperature and water availability are hypothesised to be important abiotic drivers of the evolution of metabolic rates and gas exchange patterns, respectively. Specifically, the metabolic cold adaptation hypothesis (MCA) predicts that cold environments select for faster metabolic rates to counter the thermodynamics of biochemical reactions while the hygric hypothesis predicts that dry environments select for discontinuous gas exchange to reduce water loss. Although these two hypotheses consider different physiological traits and how they vary along different abiotic gradients, metabolic rate drives frequency of gas exchange patterns in insects meaning these two traits are inherently linked. Despite this link, the MCA and hygric hypotheses are rarely considered together and the extent to which metabolic rates and frequency of gas exchange vary and co-vary across climatic gradients remains unclear. We tested the MCA and hygric hypotheses within a species of endemic Fijian bee, Homalictus fijiensis, across an altitudinal gradient of 1100 m, and among four Fijian bee species, including H. fijiensis, that inhabit different altitudinal bands. In Fiji, environmental temperature is ~5C lower in the central highlands than in the coastal lowlands with the highlands receiving ~100 mm of additional precipitation than the lowlands each month. We found an MCA like pattern within H. fijiensis and among Fijian bee species, where metabolic rate decreased with increasing temperature, but precipitation also explained variation in metabolic rate. However, we did not find support for the hygric hypothesis within H. fijiensis or among species (frequency of gas exchange was not negatively correlated with precipitation). The relationship between metabolic rate and frequency of gas exchange was steeper for species that occupied lower elevations on average, suggesting it is possible that these two traits can evolve independently of each other despite being positively correlated.
Regulation of cell size and Wee1 by elevated levels of Cdr2
Authors: Berg Rachel A. , Moseley James B.
Published: July 2022

Many cell cycle regulatory proteins catalyze cell cycle progression in a concentration-dependent manner. In fission yeast S. pombe, the protein kinase Cdr2 promotes mitotic entry by organizing cortical oligomeric nodes that lead to inhibition of Wee1, which itself inhibits Cdk1. cdr2Δ cells lack nodes and divide at increased size due to overactive Wee1, but it has not been known how increased Cdr2 levels might impact Wee1 and cell size. Using a Tetracycline-inducible expression system, we found that a 6X increase in Cdr2 expression caused hyperphosphorylation of Wee1 and reduction in cell size. This overexpressed Cdr2 formed clusters that sequestered Wee1 adjacent to the nuclear envelope. Cdr2 mutants that disrupt either kinase activity or clustering ability failed to sequester Wee1 and to reduce cell size. We propose that Cdr2 acts as a dosage-dependent regulator of cell size by sequestering its substrate Wee1 away from Cdk1 in the nucleus. This mechanism has implications for other clustered kinases, which may act similarly by sequestering substrates.
Hierarchical cell-type identifier accurately distinguishes immune-cell subtypes enabling precise profiling of tissue microenvironment with single-cell RNA-sequencing
Authors: Lee Joongho , Kim Minsoo , Kang Keunsoo , Yang Chul-Su , Yoon Seokhyun
Published: July 2022

Abstract

Single-cell RNA-seq enabled in-depth study on tissue micro-environment and immune-profiling, where a crucial step is to annotate cell identity. Immune cells play key roles in many diseases while their activities are hard to track due to diverse and highly variable nature. Existing cell-type identifiers had limited performance for this purpose. We present HiCAT, a hierarchical, marker-based cell-type identifier utilizing gene set analysis for statistical scoring for given markers. It features successive identification of major-type, minor-type and subsets utilizing subset markers structured in a three-level taxonomy tree. Comparison with manual annotation and pairwise match test showed HiCAT outperforms others in major- and minor-type identification. For subsets, we qualitatively evaluated marker expression profile demonstrating that HiCAT provide most clear immune cell landscape. HiCAT was also used for immune cell profiling in ulcerative colitis and discovered distinct features of the disease in macrophage and T cell subsets that could not be identified previously.
Combined SPT and FCS methods reveal a mechanism of RNAP II oversampling in cell nuclei
Authors: Fournier Marie , Leclerc Pierre , Leray Aymeric , Champelovier Dorian , Agbazahou Florence , Bidaux Gabriel , Furlan Alessandro , Héliot Laurent
Published: July 2022

Gene expression orchestration is a key question in fundamental and applied research. Different models for transcription regulation were proposed, yet the dynamic regulation of RNA polymerase II (RNAP II) activity remains a matter of debate. To improve our knowledge of this topic, we investigated RNAP II motility in eukaryotic cells by combining Single Particle Tracking (SPT) and Fluorescence Correlation Spectroscopy (FCS) techniques, to take advantage of their different sensitivities in order to analyze together slow and fast molecular movements. Thanks to calibrated samples, we developed a benchmark for quantitative analysis of molecular dynamics, to eliminate the main potential instrumental biases. We applied this workflow to study the diffusion of RPB1, the catalytic subunit of RNAP II. By a cross-analysis of FCS and SPT, we could highlight different RPB1 motility states and identifyed a stationary state, a slow diffusion state, and two different modes of subdiffusion. Interestingly, our analysis also unveiled the oversampling by RPB1 of nuclear subdomains. Based on these data, we propose a novel model of spatio-temporal transcription regulation. Altogether, our results highlight the importance of combining microscopy approaches at different time scales to get a full insight into the real complexity of molecular diffusion kinetics in cells.
Retromer oligomerization drives SNX-BAR coat assembly and membrane constriction
Authors: Gopaldass Navin , De Leo Maria Giovanna , Courtellemont Thibault , Mercier Vincent , Bissig Christin , Roux Aurélien , Mayer Andreas
Published: July 2022

The retromer coat mediates protein exit from endosomes and impacts many signaling pathways, lysosomal biogenesis, and diseases such as Parkinson’s, Alzheimer’s and COVID-19. Retromer complexes (CSC in yeast) form coats by interconnecting sorting nexins (SNX). The dynamics of this process is poorly explored. Here, we analyze the oligomerization of CSC/SNX-BAR retromer coats on oriented synthetic lipid tubules. SNX-BARs and CSC assemble a static tubular coat that does not exchange subunits. Coat formation proceeds bidirectionally, adding new subunits at both ends of the coat. High concentrations of SNX-BARs alone suffice to constrict membrane tubes to an invariant radius of 19 nm. At lower concentrations, CSC-complexes must drive constriction, which requires their oligomerization. CSCs populate the SNX-BAR layer at densities that increase with the starting radius of the membrane tube. We hence propose that retromer-mediated crosslinking of SNX-BARs at variable densities tunes the coat according to the energy required to deform the membrane. This model is supported by the effects of mutations interfering with retromer oligomerization, which impair retromer function in yeast and human cells.
Csf1 from marrow adipogenic precursors is required for osteoclast formation and hematopoiesis in bone
Authors: Zhong Leilei , Lu Jiawei , Fang Jiankang , Yao Lutian , Yu Wei , Gui Tao , Holdreith Nicholas , Bautista Catherine , Choi Yongwon , Jiang Jean X. , Yang Shuying , Tong Wei , Dyment Nathaniel , Qin Ling
Published: July 2022

Colony stimulating factor 1 (Csf1) is an essential growth factor for osteoclast progenitors and thus an important regulator for bone resorption. It remains elusive which mesenchymal cells synthesizeCsf1stimulating osteoclastogenesis. We recently identified a novel mesenchymal cell population, marrow adipogenic lineage precursors (MALPs), in bone. Single cell RNA- sequencing indicated specific expression ofCsf1in MALPs, which is further increased during aging. To investigate its role, we constructedCsf1 CKOmice usingAdipoq-Cre. These mice showed increased femoral trabecular bone over time, but their cortical bone appeared normal. In comparison, depletion of Csf1 in the entire mesenchymal lineage usingPrx1-Creled to a more striking high bone mass phenotype, suggesting that additional mesenchymal subpopulations secrete Csf1. TRAP staining revealed diminished osteoclasts in the femoral secondary spongiosa region ofCsf1 CKOAdipoqmice, but not at the chondral-osseous junction nor at the endosteal surface of cortical bone. Moreover,Csf1 CKOAdipoqmice were resistant to LPS-induced calvarial osteolysis. Bone marrow cellularity, hematopoietic progenitors, and macrophages were also reduced in these mice. Taken together, our studies demonstrate that MALPs are a critical player in controlling bone remodeling and hematopoiesis.
Metagenomic profiling pipelines improve taxonomic classification for 16S amplicon sequencing data
Authors: Faits Tyler , Odom-Mabey Aubrey R. , Castro-Nallar Eduardo , Crandall Keith A. , Johnson W. Evan
Published: July 2022

Most experiments studying bacterial microbiomes rely on the PCR amplification of all or part of the gene for the 16S rRNA subunit, which serves as a biomarker for identifying and quantifying the various taxa present in a microbiome sample. Several computational methods exist for analyzing 16S amplicon-based metagenomics. However, the most-used bioinformatics tools cannot produce quality genus-level or species-level taxonomic calls and may underestimate the degree to which these calls are possible. We used 16S sequencing data from mock bacterial communities to evaluate the sensitivity and specificity of several bioinformatics pipelines and genomic reference libraries used for microbiome analyses, concentrating on measuring the accuracy of species-level taxonomic assignments of 16S amplicon reads. We evaluated the tools Qiime 2, Mothur, PathoScope 2, and Kraken 2 in conjunction with reference libraries from Greengenes, Silva, Kraken, and RefSeq. Profiling tools were compared using publicly available mock community data from several sources, comprising 136 samples with varied species richness and evenness, several different amplified regions within the 16S gene, and both DNA spike-ins and cDNA from collections of plated cells. PathoScope 2 and Kraken 2, both tools designed for whole-genome metagenomics, outperformed Qiime 2 using the DADA2 plugin and Mothur, both of which are theoretically specialized for 16S analyses.
Hoverfly (Eristalis tenax) pursuit of artificial targets
Authors: Thyselius Malin , Ogawa Yuri , Leibbrandt Richard , Wardill Trevor J. , Gonzalez-Bellido Paloma T. , Nordström Karin
Published: July 2022

The ability to visualize small moving objects is vital for the survival of many animals, as these could represent predators or prey. For example, predatory insects, including dragonflies, robber flies and killer flies, perform elegant, high-speed pursuits of both biological and artificial targets. Many non-predatory insects, including male hoverflies and blowflies, also pursue targets during territorial or courtship interactions. To date, most hoverfly pursuits were studied outdoors. To investigate naturalistic hoverfly (Eristalis tenax) pursuits under more controlled settings, we constructed an indoor arena that was large enough to encourage naturalistic behavior. We presented artificial beads of different sizes, moving at different speeds, and filmed pursuits with two cameras, allowing subsequent 3D reconstruction of the hoverfly and bead position as a function of time. We show that maleE. tenaxhoverflies are unlikely to use strict heuristic rules based on angular size or speed to determine when to start pursuit, at least in our indoor setting. We found that hoverflies pursued faster beads when the trajectory involved flying downwards towards the bead. Furthermore, we show that target pursuit behavior can be broken down into two stages. In the first stage the hoverfly attempts to rapidly decreases the distance to the target by intercepting it at high speed. During the second stage the hoverfly’s forward speed is correlated with the speed of the bead, so that the hoverfly remains close, but without catching it. This may be similar to dragonfly shadowing behavior, previously coined ‘motion camouflage’.