bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of Daoyin and massage for lumbar disc herniation
Authors: Shi Mingpeng , Zhang Xianshuai , Wang Siyi , Li Shaojun , Zhao Changwei , Li Zhenhua , Li Jianan
Published: February 2022

Background:

Lumbar disc herniation (LDH) is a common disease, which can cause low back pain, sciatica, and even disability. The treatment of LDH is a global challenge. Conservative therapy with non-drugs is considered to be the first choice for patients with LDH. In recent years, an increasing number of systematic reviews and meta analyses on Daoyin and massage interventions in lumbar disc herniation have been implemented. However, the evidence quality and methodological quality of these systematic reviews/meta analyses are unknown and need to be systematically evaluated. This overview aims to systematically summarize and critically appraise the current evidence on Daoyin and massage for LDH.

Methods:

Eight electronic data will be retrieved, including China National Knowledge Infrastructure (CNKI), Wanfang database (WF), China Biomedical database (CBM), Chinese Scientific Journals Database (VIP), PubMed, Cochrane Library, Web of Science (WOS), and EMBASE from their inception to March 1, 2022. The reporting quality, methodological quality, risk of bias, quality of evidence will be assessed by using The Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 (PRISMA 2020), the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic Review (ROBIS), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Two independent researchers conducted literature screening, data extraction, and quality evaluation process. In addition, we will establish an overlap matrix and calculate the corrected covered area to evaluate the impact of overlapping areas on conclusions.

Results:

The results will be published in a peer-reviewed journal.

Conclusion:

This overview will provide comprehensive evidence of Daoyin and massage for treating lumbar disc herniation.

Systematic review registration:

INPLASY202210019.
Cerebellum/liver index in pretherapeutic 18F-FDG PET/CT as a predictive marker of progression-free survival in follicular lymphoma treated by immunochemotherapy and rituximab maintenance
Authors: Godard François , Durot Eric , Durot Carole , Hoeffel Christine , Delmer Alain , Morland David
Published: February 2022

The purpose of this study was to investigate the value of the “cerebellum/ liver index for prognosis” (CLIP) as a new prognostic marker in pretherapeutic 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG PET) in patients with follicular lymphoma treated by immunochemotherapy and rituximab maintenance, focusing on progression-free survival (PFS).

Clinicobiological and imaging data from patients with follicular lymphoma between March 2010 and September 2015 were retrospectively collected and 5-year PFS was determined. The conventional PET parameters (maximum standardized uptake value and total metabolic tumor volume) and the CLIP, corresponding to the ratio of the cerebellum maximum standardized uptake value over the liver SUVmean, were extracted from the pretherapeutic 18F-FDG PET.

Forty-six patients were included. Eighteen patients (39%) progressed within the 5 years after treatment initiation. Five-year PFS was 78.6% when CLIP was >4.0 and 42.0% when CLIP was <4.0 (P = .04). CLIP was a significant predictor of PFS on univariate analysis (hazard ratio 3.1, P = .049) and was near-significant on multivariate analysis (hazard ratio 2.8, P = .07) with ECOG PS as a cofactor.

The CLIP derived from pretherapeutic 18F-FDG PET seems to be an interesting predictive marker of PFS in follicular lymphoma treated by immunochemotherapy and rituximab maintenance. These results should be evaluated prospectively in a larger cohort.
Acute paraparesis syndrome after ruptured anterior communicating artery aneurysm
Authors: Lee Jong-Myong
Published: February 2022

Here, we describe a series of 7 patients who presented with acute paraparesis due to anterior communicating artery aneurysm rupture. This study aimed to assess the clinical and radiological factors associated with acute paraparesis syndrome caused by subarachnoid hemorrhage (SAH).

Between June 2005 and December 2012, our institution consecutively treated 210 patients with anterior communicating aneurysm rupture within 24 hours after ictus. We divided the patients into 2 groups based on the presence (n = 7) and absence (n = 203) of acute paraparesis after anterior communicating aneurysm rupture.

Diffusion-weighted magnetic resonance imaging revealed high intensity in the medial aspects of the bilateral frontal lobes in 3 patients. The mean third ventricular distance at the time of admission was 9.2 mm (range, 8–12.5 mm), and the mean bicaudate distance was 33.9 mm (range, 24–39 mm). There was a significant difference in the bicaudate distance (P = .001) and third ventricle distance (P = .001) between the 2 groups. Acute hydrocephalus and global cerebral edema (GCE) were confirmed radiologically in all patients in the acute paraparesis group. The presence of acute hydrocephalus (P = .001) and GCE (P = .003) were significantly different between the groups.

Acute paraparesis syndrome after SAH is transient and gradually improves if the patient does not develop severe vasospasm. The present study demonstrates that acute paraparesis after SAH is associated with acute hydrocephalus and GCE.
Willingness to take and ever use of pre-exposure prophylaxis among female sex workers in Ghana
Authors: Guure Chris , Afagbedzi Seth , Torpey Kwasi
Published: February 2022

Pre-exposure prophylaxis (PrEP) is a drug taken by people who are human immunodeficiency virus (HIV) negative and at increased risk of acquiring HIV. It's an effective intervention for HIV prevention. This study seeks to report on the prevalence and determinants of willingness to take and ever use of PrEP among female sex workers (FSW) in Ghana.

The data analyzed was obtained from the Integrated Bio-behavioral Surveillance Survey conducted across the 16 regions of Ghana in 2020. Analysis was only performed on FSW who were tested negative to HIV and were sexually active. All included variables were described using medians, percentages, and graphs. Bayesian adjusted odds ratios and 95% credible intervals were estimated using a Bayesian generalized linear model via the binomial family of distributions under the logit link function.

Of the 5107 FSW with complete data on willingness to use PrEP, 2737 (53.59%) reported their willingness to take PrEP. Out of the 998 respondents who have ever heard of PrEP only 64 (6.39%) have ever used PrEP. The median age of the respondents was 25 years. People with no comprehensive knowledge of HIV and acquired immunodeficiency syndrome as well as those who entered into the FSW business at age less than 25 years; 946 (34.56%) and 2181 (79.65%) respectively were more willing to take PrEP. FSW from 6 out of the 16 regions of Ghana have never used PrEP. A statistically significant difference between those who entered the sex work at age less than 25 years and those within 25 to 34 years was observed. About 23% of FSWs who had been screened for Sexually Transmitted Infections were more likely to take PrEP.

Respondents with lesser age and no comprehensive knowledge of HIV were more willing to take PrEP. The willingness to accept PrEP among FSWs in Ghana is modest. However, utilization is low. Advocacy or intervention programs are required to improve uptake of PrEP.
Dedicator of cytokinesis 8 deficiency and hyperimmunoglobulin E syndrome
Authors: Wang Zhaojun , Zhang Yanan , Li Gang , Huang Lingyan , Chen Juan
Published: February 2022

Rationale:

Hyperimmunoglobulin E syndrome (HIES) is a rare and complex immunoregulatory multisystem disorder characterized by recurrent eczema, skin and sinopulmonary infections, elevated serum immunoglobulin E levels, and eosinophilia. Onset is most likely in childhood, although infrequent adult cases have been reported. Early diagnosis is important. The use of the National Institutes of Health scoring system and the HIES signal transducer and activation of transcription 3 score can standardize the diagnosis of HIES.

Patient concerns:

A 19-year-old woman presented with complaints of dry cough, pyrexia, dyspnea, and recurrent pneumonia. She had a history of milk allergy, recurrent eczema, suppurative otitis media, chalazia, and aphthous ulcers. Her parents had a consanguineous marriage.

Diagnosis:

HIES; severe pneumonia.

Interventions:

Voriconazole (200 mg iv 2 times/d) and flucytosine (1 g orally 4 times/d) for 3 weeks were administered, followed by oral administration of fluconazole for 3 weeks.

Outcomes:

The patient experienced near-complete remission of her respiratory symptoms. The patient was followed-up for one and a half years. During the follow-up, the patient presented again with cough and dyspnea and was again admitted to hospital. After being hospitalized for 3 weeks of antibiotic treatment, the patient experienced near-complete relief of her respiratory symptoms.

Lessons:

Regardless of patient age, it is important to consider the possibility of HIES when a patient has recurrent eczema, skin and sinopulmonary infections, elevated serum immunoglobulin E levels, and eosinophilia. Early diagnosis and intervention are essential to improve prognosis.
A Meta-Analysis of the Effectiveness of Cognitive Rehabilitation in Improving Memory Function in Patients With Posttraumatic Stress Disorder
Authors: Zare Somayeh , Zare Hossein , Farzad Valiollah , Alipoor Ahmad
Published: February 2022

Posttraumatic stress disorder (PTSD) may have a detrimental effect on a patient's memory function. Memory problems are common after PTSD and can cause problems with a patient's day-to-day life. Cognitive rehabilitation is considered an effective treatment for patients with PTSD who want to improve cognitive memory. We searched keywords in electronic databases to find studies that looked into the effect of cognitive rehabilitation on memory function in patients with PTSD. This report is based on data from four studies with double-blind and placebo-controlled experiments totaling 198 participants. Effect size estimates were calculated using a mixed-effects meta-analysis for memory function. During cognitive rehabilitation, patients with PTSD demonstrated gains in memory in a variety of ways. Our results pointed to the need for further research into the most promising interventions for improving memory function in patients with PTSD. Furthermore, well-designed studies with large sample sizes are needed to confirm our results and determine the magnitude of the problem.
Clinicopathological Analysis of 907 Major and Minor Salivary Gland Tumors
Authors: Dimitrijevic Milovan V. , Boricic Ivan V. , Tomanović Nada R. , Dimitrijevic Ana M. , Bjelogrlić Goran M. , Krstić Aleksandar M. , Stojkovic Goran M. , Rajovic Nina Z. , Djordjevic Ivana P. Mitrovic , Djurkovic Petar M.
Published: February 2022

Purpose:

The frequency and types of salivary gland tumors show significant geographical variations. The most common are primary epithelial tumors, with pleomorphic adenoma and mucoepidermoid carcinoma being the most frequent. This study aims to analyze the clinicopathological data of patients with major and minor salivary gland (MiSG) tumors.

Methods:

The retrospective study included all patients with major and MiSG tumors diagnosed and treated between January 2000 and January 2019. Files of 907 patients were reviewed and investigated for clinicopathologic features of major and MiSG tumors in Serbia.

Results:

The majority of tumors were of epithelial origin. Pleomorphic adenoma was the predominant type of tumor, with 35.1% among all tumors on all sites. Adenoid cystic carcinoma and mucoepider-moid carcinoma (with 7.1% and 2.7%, respectively) were the most common malignant ones. The most common localization was the parotid gland. Minor salivary gland tumors comprised 16.43% of all salivary gland tumors in our series, the most common localization being the oral cavity. The results of our study are mostly consistent with the results of other previously published studies.

Conclusions:

The most important finding, worth emphasizing, is that the most common malignant major and MiSG tumor in our population is adenoid cystic carcinoma, rather than mucoepidermoid carcinoma, in all investigated localizations. In addition, the nasal cavity is the most common localization among malignant MiSG tumors.
Prosthetic Materials Protrusion After Surgical Wall Reconstruction of Temporomandibular Joint Herniation
Authors: Baeg Moon Seung , Moon Seong Kyu , Cho Hyun Sang
Published: February 2022

Herniation of the temporomandibular joint (TMJ) into the external auditory canal (EAC) is rare. The TMJ and EAC are separated by the anterior bony wall of the EAC. Such a defect can be caused by trauma, infection, neoplasm, inflammation, and in rare cases, congenital bony defects. If asymptomatic or mildly symptomatic, supplemental treatment is primarily given, but if the symptoms are severe enough that the patient regularly feels discomfort, surgical procedure is considered. To our knowledge there are no reports about surgery-related complications and recurrence during the postoperative follow-up period for TMJ herniation in English literature. Here, the authors report the first case of implant protrusion after TMJ herniation surgery along with a literature review.
Anthropometric Periocular Soft Tissue Analysis From Preadolescence to Young Adulthood: Photogrammetric Measurements
Authors: Ozdemir Fikri , Golpinar Murat , Nahir Mert , Sahin Bunyamin
Published: February 2022

The periocular region has a central role in the prediction of ethnicity, understanding emotional expression, age, and sex. The aim of this study was to determine the sex-related growth changes in the periocular region of Turkish preadolescents, adolescents, and young adults. The study included a total of 234 individuals (preadolescents: 34 females and 40 males; adolescents: 40 females, 40 males, and young adults: 40 males and 40 females). A total of 7 periocular parameters (3 bilateral, 3 unilateral linear, and 1 angular measurement) were analyzed statistically to determine sex-related differences. The palpebral fissure and canthal indexes were also calculated. Of the 14 periocular measurements, 9 were found to be sexually dimorphic in certain age groups (P <0.05). Right-left palpebral fissure width and left palpebral fissure height were significantly different between young adult males and females (P= 0.018,P= 0.013, andP= 0.027, respectively). A significant sexual dimorphism was observed for outercanthal distance and canthal index in 3 age groups (P< 0.05). The data collected in this study may serve as a sex-dependent database source for the Turkish population during normal growth from preadolescence to young adulthood. The present study results would be useful for planning and designing aesthetic and post-traumatic surgical interventions in the periocular region as well as personal identification in this population.
Complications According to the Handling of the Pterygoid Plate During Bimaxillary Surgery
Authors: Moon Chiho , Park Jin-Young , Choi Na-Rae , Kang Young-Hoon , Jaiswal M. Shriya , Jang Hun , Hwang Dae Seok
Published: February 2022

Background:

During bimaxillary surgery, manipulation of the pterygoid plate is required to facilitate movement of the maxilla. This study examined the complications that occurred after handling the pterygoid plate during a Le Fort I osteotomy.

Patients and Methods:

This study compared and analyzed complications according to the pterygoid plate handling method in 80 patients who underwent bimaxillary surgery at Pusan National University Dental Hospital from December 2015 to July 2020. The pterygoid plate was fractured or removed intentionally only if it interfered with the maxilla. Otherwise, it was not treated. The complications during surgery and the follow-up period were investigated.

Results:

Fourteen patients experienced complications, of which excessive bleeding, hearing problems, and nonunion were encountered in 10, 2, and 2 patients, respectively. Of the 10 patients with excessive bleeding patients, the pterygoid plate was manipulated in 8 patients, which was controlled during surgery. Two patients complained of hearing loss with ear congestion immediately after surgery; both patients improved spontaneously within 1 month. Two nonunion patients underwent plate refixation at least 6 months postoperatively, and normal healing was achieved afterward.

Conclusions:

Fracture and removal of the pterygoid plate during orthognathic surgery did not significantly affect the occurrence of complications during and after surgery.
Rapid, high throughput, automated detection of SARS-CoV-2 neutralizing antibodies against native-like vaccine and delta variant spike trimers
Authors: Cheedarla Narayanaiah , Verkerke Hans P. , Potlapalli Sindhu , McLendon Kaleb Benjamin , Patel Anamika , Frank Filipp , Damhorst Gregory L. , Wu Huixia , O’Sick William Henry , Graciaa Daniel , Hudaib Fuad , Alter David N , Bryksin Jeannette , Ortlund Eric A. , Guarner Jeanette , Auld Sara , Shah Sarita , Lam Wilbur , Mattoon Dawn , Johnson Joseph M , Wilson David H , Dhodapkar Madhav V. , Stowell Sean R. , Neish Andrew S. , Roback John D.
Published: February 2022

Traditional cellular and live-virus methods for detection of SARS-CoV-2 neutralizing antibodies (nAbs) are labor- and time-intensive, and thus not suited for routine use in the clinical lab to predict vaccine efficacy and natural immune protection. Here, we report the development and validation of a rapid, high throughput method for measuring SARS-CoV-2 nAbs against native-like trimeric spike proteins. This assay uses a blockade of hACE-2 binding (BoAb) approach in an automated digital immunoassay on the Quanterix HD-X platform. BoAb assays using vaccine and delta variant viral strains showed strong correlation with cell-based pseudovirus and live-virus neutralization activity. Importantly, we were able to detect similar patterns of delta variant resistance to neutralization in samples with paired vaccine and delta variant BoAb measurements. Finally, we screened clinical samples from patients with or without evidence of SARS-CoV-2 exposure by a single-dilution screening version of our assays, finding significant nAb activity only in exposed individuals. In principle, these assays offer a rapid, robust, and scalable alternative to time-, skill-, and cost-intensive standard methods for measuring SARS-CoV-2 nAb levels.
Discovery of a new but established population of the guppy in Germany
Authors: Bierbach David , Schutz Christopher , Weimar Nils , Alegre Alessandra Escurra , Francisco Fritz A. , Wersing Serafina , O’Connor Olivia L. , Kempkes Michael , Rose Udo , Miesen Friedrich Wilhelm , Habedank Marie , Jourdan Jonas , Kabus Jana , Hof Delia , Hornung Simon , Emde Sebastian , Rüffert Leon , Lukas Juliane
Published: February 2022

Feral populations of tropical fish species in temperate climates like Central Europe are a rare but repeatedly observed phenomenon. Due to the influence of industrial or geothermal heated water, released tropical fish may be able to survive harsh winter conditions. Here we characterize a newly discovered thermally polluted river, with an established population of the guppy (Poecilia reticulata) co-occurring with native species. Through a mark-recapture approach, we estimated the population size of the guppies close to the warm water inflow to be around 2000 individuals during summer and we further provide descriptive demographics of this population which allow us to assume it is well established in that river. Further, we found some of the sampled specimen being parasitized by Camallanus roundworms, thus showing the guppies’ host potential for this genus of internal parasites. The popularity and widespread distribution of guppies as ornamental fish often leads to their intentional or unintentional release into the wild where they are often pioneer species in anthropogenically heavily modified habitats. Guppies threaten native species through niche competition and transmission of diseases. Accordingly, early awareness and knowledge on the status of non-native populations is crucial for effective management strategies.
Describing Chemical Kinetics in the Time Dimension with Mean Reaction Time
Authors: Park Chiwook
Published: February 2022

The chemical kinetics is such a fundamental topic in chemistry. By analyzing how the experimental conditions and parameters influence the reaction rate, chemists have deciphered the molecular details on how the chemical reactions occur. The quantitative analysis of the reaction rate requires the formulation of the rate equation, which describes the dependence of the reaction rate on the concentrations of the reactants and also the rate constants of the elementary steps. Though the methods to derive the rate equation from the kinetic model have been known for a century, it is still mathematically challenging to derive the rate equation for complex reactions with multiple steps, which requires a solution for simultaneous differential equations. Therefore, chemists frequently resort to the steady-state approximation or the numerical simulation. One way to avoid the mathematical difficulty is to describe the chemical kinetics in the time dimension. Describing the mean reaction time, the average of the time required for the completion of the chemical reaction, using the elementary rate constants of the kinetic model is much simpler mathematically than deriving the rate equation for the kinetic model. Here, we describe the basic rules for the derivation of the formula of the mean reaction time, derive the generalized equation for the mean reaction time, and analyze the components of the formula to determine how the individual steps in the complex reaction contribute to the mean reaction time. Being the ensemble-averaged value, the mean reaction time does not provide the information on the actual distribution of the reaction time of individual chemical entity. However, the formula of the mean reaction time reveals invaluable insights on how the energy levels of the ground state and the transition states affect the kinetics of the complex reaction and offers a way to identify the most time-consuming process of the complex reaction in a straightforward manner. We also apply the mean reaction time to enzyme kinetics and demonstrate that one can derive the expressions of the kinetic parameters (kcat/KM and kcat) in a surprisingly simple way even without resorting to the steady-state application.
Novel plasma exosome biomarkers for prostate cancer progression in co-morbid metabolic disease
Authors: Jafari Naser , Chen Andrew , Kolla Manohar , Pompa Isabella R. , Qiu Yuhan , Yu Rebecca , Llevenes Pablo , Ennis Christina S. , Mori Joakin , Mahdaviani Kiana , Halpin Meredith , Gignac Gretchen A. , Heaphy Christopher M. , Monti Stefano , Denis Gerald V.
Published: February 2022

Comorbid Type 2 diabetes (T2D), a metabolic complication of obesity, associates with worse cancer outcomes for prostate, breast, head and neck, colorectal and several other solid tumors. However, the molecular mechanisms remain poorly understood. Emerging evidence shows that exosomes carry miRNAs in blood that encode the metabolic status of originating tissues and deliver their cargo to target tissues to modulate expression of critical genes. Exosomal communication potentially connects abnormal metabolism to cancer progression. Here, we hypothesized that T2D plasma exosomes induce epithelial-mesenchymal transition (EMT) and immune checkpoints in prostate cancer cells. We demonstrate that plasma exosomes from subjects with T2D induce EMT features in prostate cancer cells and upregulate the checkpoint genesCD274andCD155. We demonstrate that specific exosomal miRNAs that are differentially abundant in plasma of T2D adults compared to nondiabetic controls (miR374a-5p, miR-93-5p and let-7b-3p) are delivered to cancer cells, thereby regulating critical target genes. We build on our previous reports showing BRD4 controls migration and dissemination of castration-resistant prostate cancer, and transcription of key EMT genes, to show that T2D exosomes require BRD4 to drive EMT and immune ligand expression. We validate our findings with gene set enrichment analysis of human prostate tumor tissue in TGCA genomic data. These results suggest novel, non-invasive approaches to evaluate and potentially block progression of prostate and other cancers in patients with comorbid T2D.
Platinum-Induced Mitochondrial OXPHOS Contributes to Cancer Stem Cell Enrichment in Ovarian Cancer
Authors: Sriramkumar Shruthi , Sood Riddhi , Huntington Thomas D. , Ghobashi Ahmed H. , Wang Weini , Nephew Kenneth P. , O’Hagan Heather M.
Published: February 2022

Background

Platinum based agents – cisplatin and carboplatin in combination with taxanes are used for the treatment of ovarian cancer (OC) patients. However, the majority of OC patients develop recurrent, platinum resistant disease that is uniformly fatal. Acute platinum treatment enriches for chemoresistant aldehyde dehydrogenase (ALDH) + ovarian cancer stem cells (OCSCs), which contribute to tumor recurrence and disease relapse. Acquired platinum resistance includes metabolic reprograming and switching to oxidative phosphorylation (OXPHOS). Chemosensitive cells rely on glycolysis while chemoresistant cells have the ability to switch between glycolysis and OXPHOS, depending on which pathway drives a selective advantage for growth and chemoresistance. High expression of genes involved in OXPHOS and high production of mitochondrial ROS are characteristics of OCSCs, suggesting that OCSCs favor OXPHOS over glycolysis. Based on connections between OCSCs, chemoresistance and OXPHOS, we hypothesize that platinum treatment induces changes in metabolism that contribute to platinum-induced enrichment of OCSCs.

Methods

The effect of cisplatin on mitochondrial activity was assessed by JC1 staining and expression of OXPHOS genes by quantitative RTPCR. Cisplatin-induced changes in Sirtuin 1 (SIRT1) levels and activity were assessed by Western blot. Small molecule inhibitors of mitochondrial complex I and SIRT1 were used to determine if their enzymatic activity contributes to the platinum-induced enrichment of OCSCs. The percentage of ALDH+ OCSCs in OC cells and tumor tissue from xenograft models across different treatment conditions was analyzed using ALDEFLUOR assay and flow cytometry.

Results

We demonstrate that acute platinum treatment increases mitochondrial activity. Combined treatment of platinum agents and OXPHOS inhibitors blocks the platinum-induced enrichment of ALDH+ OCSCs in vitro and in vivo. Furthermore, platinum treatment increases SIRT1 levels and subsequent deacetylase activity, which likely contributes to the increase in platinum-induced mitochondrial activity.

Conclusions

These findings on metabolic pathways altered by platinum-based chemotherapy have uncovered key targets that can be exploited therapeutically to block the platinum-induced enrichment of OCSCs, ultimately improving the survival of OC patients.
The Longitudinal Aging Study Amsterdam COVID-19 exposure index: a cross-sectional analysis of the impact of the pandemic on daily functioning of older adults
Authors: Hoogendijk Emiel O. , Schuster Noah A. , van Tilburg Theo G. , Schaap Laura A. , Suanet Bianca , de Breij Sascha , Kok Almar A.L. , van Schoor Natasja M. , Timmermans Erik J. , de Jongh Renate T. , Visser Marjolein , Huisman Martijn
Published: February 2022

Objectives

The aim of this study was to develop an index to measure older adults’ exposure to the COVID-19 pandemic, and to study its association with various domains of functioning.

Design

Cross-sectional study.

Setting

The Longitudinal Aging Study Amsterdam (LASA), a cohort study in the Netherlands.

Participants

Community dwelling older adults aged 62-102 years (n=1089) who participated in the LASA COVID-19 study (June-September 2020), just after the first wave of the pandemic.

Primary outcome measures

A 35-item COVID-19 exposure index with a score ranging between 0 and 1 was developed, including items that assess the extent to which the COVID-19 situation affected daily lives of older adults. Descriptive characteristics of the index were studied, stratified by several socio-demographic factors. Logistic regression analyses were performed to study associations between the exposure index and several indicators of functioning (functional limitations, anxiety, depression, and loneliness).

Results

The mean COVID-19 exposure index score was 0.20 (SD 0.10). Scores were relatively high among women and in the southern region of the Netherlands. In models adjusted for socio-demographic factors and pre-pandemic functioning (2018-2019), those with scores in the highest tertile of the exposure index were more likely to report functional limitations (OR: 2.23; 95% CI: 1.48 to 3.38), anxiety symptoms (OR: 3.87; 95% CI: 2.27 to 6.61), depressive symptoms (OR: 2.45; 95% CI: 1.53 to 3.93) and loneliness (OR: 2.97; 95% CI: 2.08-4.26) than those in the lowest tertile.

Conclusions

Among older adults in the Netherlands, those with higher scores on a COVID-19 exposure index reported worse functioning in the physical, mental and social domain. The index may be used to identify persons for whom targeted interventions are needed to maintain or improve functioning during the pandemic or post-pandemic.

Strengths and limitations of this study

This study was based on a representative sample of older adults from three culturally different regions in the Netherlands.

The Longitudinal Aging Study Amsterdam COVID-19 study provides unique data on functioning of older adults in various life domains during the COVID-19 pandemic.

The items of the COVID-19 exposure index that was developed were based on self-report, more objective sources such as medical records were lacking.

The study covered the first months of the pandemic in the Netherlands, longitudinal data is needed to monitor functioning of older adults in later stages of the pandemic.
Enhancing high-temperature degradation of polyethylene terephthalate through a synergistic division of enzyme labour between a solid-degrading thermostable cutinase and a reaction intermediate-degrading thermostable carboxylesterase
Authors: Mrigwani Arpita , Thakur Bhishem , Guptasarma Purnananda
Published: February 2022

Cutinases degrade PET (polyethylene terephthalate) into various degradation intermediates (DIs) such as OET (oligoethylene terephthalate), BHET (bis-hydroxyethyl terephthalate), and MHET (mono-hydroxyethyl terephthalate), and eventually into TPA (terephthalic acid), which is the terminal product of degradation. Unlike PET, which is insoluble, TPA and the DIs are sparingly soluble in water. This causes both DIs and TPA to be partitioned into aqueous solution, where DIs accumulate without undergoing significant further degradation, despite being better substrates of cutinase than solid PET. This frustrates the creation of a circular economy involving PET and TPA (since TPA must be separated from DIs before re-condensation into PET). We argue that the non-degradation of DIs owes to cutinase becoming progressively depleted from solution, through binding to solid PET. This creates a conundrum, in that degradation of PET is anticipated to be inversely correlated with degradation of DIs (at least while solid PET remains available to deplete cutinase from solution), causing any improvement of the cutinase’s PET-binding efficiency to only further ensure non-degradation of released DIs. Here, we propose the deployment of a second DI-degrading enzyme; one that remains in solution, and acts as an ‘assistant’ to the ‘master’ PET-invading cutinase acting upon PET’s surface. We demonstrate that one such dual-enzyme system, consisting of a thermostable Thermus thermophilus carboxylesterase (TTCE), characterized here for the first time, and the already-used thermostable leaf-branch compost cutinase (LCC), allows complete degradation of all products of PET hydrolysis into TPA in solution, at 60 °C, even in the presence of residual solid PET.
Chromatin sequesters pioneer transcription factor Sox2 from exerting force on DNA
Authors: Nguyen Tuan , Li Sai , Chang Jeremy , Watters John , Ng Htet , Osunsade Adewola , David Yael , Liu Shixin
Published: February 2022

Formation of biomolecular condensates constitutes an emerging mechanism for transcriptional regulation. Recent studies suggest that the co-condensation between transcription factors (TFs) and DNA can generate mechanical forces driving genome rearrangements. However, the reported forces generated by such protein-DNA co-condensation are typically below one piconewton (pN), questioning its physiological significance. Moreover, the force-generating capacity of these condensates in the chromatin context remains unknown. Using single-molecule biophysical techniques, we show that Sox2, a nucleosome-binding pioneer TF, forms co-condensates with DNA, thereby exerting considerable mechanical tension on DNA strands both in cis and trans. Sox2 can generate forces up to 7 pN—similar in magnitude to other cellular forces. Sox2:DNA condensates are highly stable, withstanding disruptive forces high enough to melt DNA. We find that the disordered domains of Sox2 are required for maximum force generation but not condensate formation per se. Finally, we show that nucleosomes dramatically attenuate the mechanical stress exerted by Sox2 via sequestering it from coalescing on bare DNA. Our findings reveal that TF-mediated DNA condensation can exert significant mechanical stress which can nonetheless be alleviated by the chromatin organization, suggesting a new function of eukaryotic chromatin in protecting the genome from potentially deleterious nuclear forces.
Extinction Risk of Sonoran Desert Annuals Following Potential Changes in Precipitation Regimes
Authors: Cuello William S. , Schreiber Sebastian J. , Gremer Jennifer R. , Venable D. Lawrence , Trimmer Pete C. , Sih Andrew
Published: February 2022

Rapid environmental change can affect both the mean and variability in environmental conditions. Natural selection tends to favour those organisms that best respond to such changes. Here, we consider delayed germination as bet hedging strategies for 10 Sonoran Desert annuals. We use a germination model parameterized with long-term demographic and climate data to explore potential effects of changes in the mean and variance in precipitation on the evolution of germination strategies, as well as the risk of extinction. We then explored the potential for evolutionary rescue in response to these changes. As expected, results indicate that as rainfall declines, or uncertainty in rainfall increases, all species have higher extinction risk (the former being more detrimental). These shifts also increased the benefit of delayed germination. Results also indicate that evolutionary rescue can often occur for small shifts, especially for more variable rainfall regimes, but would not likely save populations experiencing larger environmental changes. Finally, we identified life history traits and functional responses to precipitation that were most strongly correlated to the ability to cope with changes in rainfall and with potential for evolutionary rescue: dormant seed survivorship and, to a smaller degree, chance of reproduction and seed yield sensitivity to precipitation.
Primary macrophages exhibit a modest inflammatory response early in SARS-CoV-2 infection
Authors: Zhang Ziyun , Penn Rebecca , Barclay Wendy S , Giotis Efstathios S
Published: February 2022

Involvement of macrophages in the SARS-CoV-2-associated cytokine storm, the excessive secretion of inflammatory/anti-viral factors leading to the acute respiratory distress syndrome (ARDS) in COVID-19 patients, is unclear. In this study, we sought to characterize the interplay between the virus and primary human monocyte-derived macrophages (MDM). MDM were stimulated with recombinant IFN-α and/or infected with either live or UV-inactivated SARS-CoV-2 or with two reassortant influenza viruses containing external genes from the H1N1 PR8 strain and heterologous internal genes from a highly pathogenic avian H5N1 or a low pathogenic human seasonal H1N1 strain. Virus replication was monitored by qRT-PCR for theEviral gene for SARS-CoV-2 orMgene for influenza and TCID50or plaque assay, and cytokine levels were assessed semiquantitatively with qRT-PCR and a proteome cytokine array. We report that MDM are not susceptible to SARS-CoV-2 whereas both influenza viruses replicated in MDM, albeit abortively. We observed a modest cytokine response in SARS-CoV-2 infected MDM with notable absence of IFN-β induction, which was instead strongly induced by the influenza viruses. Pre-treatment of MDM with IFN-α enhanced proinflammatory cytokine expression upon infection. Together, the findings concur that the hyperinflammation observed in SARS-CoV-2 infection is not driven by macrophages.
In silico structure-based analysis of the predicted protein-protein interaction of Syntaxin-18, a putative receptor of Peregrinus maidis Ashmead (Hemiptera: Delphacidae) with Maize mosaic virus glycoprotein
Authors: Castrosanto Melvin A. , Clemente Apel Jae N. , Whitfield Anna E. , Alviar Karen B.
Published: February 2022

The corn planthopper, Peregrinus maidis, is a widely distributed insect pest which serves as a vector of two phytopathogenic viruses, Maize mosaic virus (MMV) and Maize stripe virus (MStV). It transmits the viruses in a persistent and propagative manner. MMV is an alphanucleorhabdovirus with a negative-sense, single-stranded (ss) RNA unsegmented genome. One identified insect vector protein that may serve as receptor to MMV is Syntaxin-18 (PmStx18) which belongs to the SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors). SNAREs play major roles in the final stage of docking and subsequent fusion of diverse vesicle-mediated transport events. In this work, in silico analysis of the interaction of MMV glycoprotein (MMV G) and PmStx18 was performed. Various freely available protein-protein docking web servers were used to predict the 3D complex of MMV G and PmStx18. Analysis and protein-protein interaction (PPI) count showed that the complex predicted by the ZDOCK server has the highest number of interaction and highest affinity, as suggested by the calculated solvation free energy gain upon formation of the interface (ΔiG = −31 kcal/mol). Molecular dynamics simulation of the complex revealed important interactions at the interface over the course of 50 ns. This is the first in silico analysis performed for the interaction on a putative receptor of P. maidis and MMV G. The results of the protein-protein interaction prediction provide novel information for studying the role of STX18 in the transport, docking and fusion events involved in virus particle transport in the insect vector cells and its release.
Rapid aggregation of Staphylococcus aureus in synovial fluid is influenced by synovial fluid concentration, viscosity, and fluid dynamics-with evidence of polymer bridging
Authors: Staats Amelia , Burback Peter W. , Schwieters Andrew , Li Daniel , Sullivan Anne , Horswill Alexander R. , Stoodley Paul
Published: February 2022

Early bacterial survival in the post-surgical joint is still a mystery. Recently, synovial fluid-induced aggregation was proposed as a potential mechanism of bacterial protection upon entry into the joint. As synovial fluid is secreted back into the joint cavity following surgery, rapid fluctuations in synovial fluid concentration, composition, and viscosity occur. These changes, along with fluid movement from post-operative joint motion, will modify the environment and potentially affect the kinetics of aggregate formation. Through this work, we sought to evaluate the influence of exposure time, synovial fluid concentration, viscosity, and fluid dynamics on aggregation. Furthermore, we aimed to elucidate the primary mechanism of aggregate formation by assessing the interaction of bacterial adhesins with synovial fluid polymer, fibrinogen. Following incubation in each simulated post-operative joint condition, the aggregates were imaged using confocal microscopy. Our analysis revealed the formation of two distinct aggregate phenotypes dependent on whether the incubation was conducted under static or dynamic conditions. Using a surface adhesin mutant, we have narrowed down the genetic determinants for synovial fluid aggregate formation and identified essential host polymers required. We report here that synovial fluid-induced aggregation is influenced by various changes specific to the post-surgical joint environment. While we now have evidence that select synovial fluid polymers facilitate bridging aggregation through essential bacterial adhesins, we suspect that their utility is limited by the increasing viscosity under static conditions. Furthermore, dynamic fluid movement recovers the ability of the bacteria with present surface proteins to aggregate under high viscosity conditions, yielding large, globular aggregates.

Importance

Infection is a major complication of knee and hip joint replacement surgery which is used to treat arthritis or joint damage. We have shown that Staphylococcus aureus, a common bacterial pathogen, aggregates upon contact with synovial fluid. Within seconds, the bacterial cells will interact with synovial fluid polymers in the joint fluid through their cell wall adhesins. The rapid formation of these aggregates likely aids in early bacterial survival in the joint-potentially contributing to the likelihood of developing an infection. By strengthening our basic understanding of the mechanics of synovial fluid aggregate formation under clinically relevant conditions, we hope to expand the knowledge of how to prevent or disrupt aggregation and reduce and more successfully treat these joint infections.
BNT162b2, mRNA-1273, and Sputnik V vaccines induce comparable immune responses on a par with severe course of COVID-19
Authors: Kaznadzey Anna , Tutukina Maria , Bessonova Tatiana , Kireeva Maria , Mazo Ilya
Published: February 2022

Vaccines against the severe acute respiratory syndrome coronavirus 2, which have been in urgent need and development since the beginning of 2020, are aimed to induce a prominent immune system response capable of recognizing and fighting future infection. Here we analyzed the levels of IgG antibodies against the receptor-binding domain (RBD) of the viral spike protein after the administration of three types of popular vaccines, BNT162b2, mRNA-1273, or Sputnik V, using the same ELISA assay to compare their effects. An efficient immune response was observed in the majority of cases. The obtained ranges of signal values were wide, presumably reflecting specific features of the immune system of individuals. At the same time, these ranges were comparable among the three studied vaccines. The anti-RBD IgG levels after vaccination were also similar to those in the patients with moderate/severe course of the COVID-19, and significantly higher than in the individuals with asymptomatic or light symptomatic courses of the disease. No significant correlation was observed between the levels of anti-RBD IgG and sex or age of the vaccinated individuals. The signals measured at different time points for several individuals after full Sputnik V vaccination did not have a significant tendency to lower within many weeks. The rate of neutralization of the interaction of the RBD with the ACE2 receptor after vaccination with Sputnik V was on average slightly higher than in patients with a moderate/severe course of COVID-19. The importance of the second dose administration of the two-dose Sputnik V vaccine was confirmed: while several individuals had not developed detectable levels of the anti-RBD IgG antibodies after the first dose of Sputnik V, after the second dose the antibody signal became positive for all tested individuals and raised on average 5.4 fold. Finally, we showed that people previously infected with SARS-CoV-2 developed high levels of antibodies, efficiently neutralizing interaction of RBD with ACE2 after the first dose of Sputnik V, with almost no change after the second dose.
Proteostasis in ice: The role of heat shock proteins and ubiquitin in the freeze tolerance of the intertidal mussel, Mytilus trossulus
Authors: Gill Lauren T. , Kennedy Jessica R. , Marshall Katie E.
Published: February 2022

The bay mussel, Mytilus trossulus, is one of the few animals that can survive internal ice formation. Freeze tolerant intertidal animals, like M. trossulus, may freeze and thaw many times during the winter, depending on air and ocean temperatures. Freezing can cause protein denaturation, leading to an induction of the heat shock response with expression of proteins like HSP70, and an increase in ubiquitin conjugated proteins. There has been little work on the mechanisms of freeze tolerance in intertidal species, limiting our understanding of this survival strategy. Additionally, this limited research has focused solely on the effects of single freezing events, but the act of repeatedly crossing the freezing threshold may present novel physiological or biochemical stressors that have yet to be discovered. We predicted that repeated freeze exposures would increase mortality, upregulate HSP70 expression, and increase ubiquitin conjugates in mussels, relative to single, prolonged freeze exposures. Mytilus trossulus from Vancouver, Canada were repeatedly frozen for a combination of 1 × 8 hours, 4 × 2 hours, or 2 × 4 hours. We then compared mortality, HSP70 expression, and ubiquitin quantity across experimental groups. We found a single 8-hour freeze caused significantly more mortality than repeated freeze-thaw cycles. We also found that HSP70 and ubiquitin expression was upregulated exclusively after freeze-thaw cycles, suggesting that freeze-thaw cycles offer a period of damage repair between freezes. This indicates that freeze-thaw cycles, which happen naturally in the intertidal, are crucial for M. trossulus survival in sub-zero temperatures.
Synergistic Activity of Repurposed Peptide Drug Glatiramer Acetate with Tobramycin Against Cystic Fibrosis Pseudomonas aeruginosa
Authors: Murphy Ronan A. , Coates Matthew , Thrane Sophia , Sabnis Akshay , Harrison James , Schelenz Silke , Edwards Andrew M. , Vorup-Jensen Thomas , Davies Jane C.
Published: February 2022

Pseudomonas aeruginosa is the most common pathogen infecting the lungs of people with cystic fibrosis (CF), causing both acute and chronic infections. Intrinsic and acquired antibiotic resistance, coupled with the physical barriers resulting from desiccated CF sputum, allow P. aeruginosa to colonise and persist in spite of antibiotic treatment. As well as the specific difficulties in eradicating P. aeruginosa from CF lungs, P. aeruginosa is also subject to the wider, global issue of antimicrobial resistance. Glatiramer acetate (GA) is a peptide drug, used in the treatment of multiple sclerosis (MS), which has been shown to have moderate anti-pseudomonal activity. Other antimicrobial peptides (AMPs) have been shown to be antibiotic resistance breakers; potentiating the activities of antibiotics when given in combination restoring and/or enhancing antibiotic efficacy. Growth, viability, minimum inhibitory concentration (MIC)-determination and synergy analysis showed that GA improved the efficacy of TOB against reference strains of P. aeruginosa, reducing TOB MICs and synergising with the aminoglycoside. This was also the case for clinical strains from people with CF. GA significantly reduced the concentration of TOB required to inhibit 50% (MIC50) of viable cells (from 1.69 [95%CI 0.26-8.97] to 0.62 [95%CI 0.15-3.94] mg/L, p=0.002) and inhibit 90% (MIC90) (from 7.00 [95%CI 1.18-26.50] to 2.20 [95%CI 0.99-15.03] mg/L, p=0.001) compared with TOB-only. Investigating mechanisms of GA activity showed that GA resulted in significant disruption of outer membranes, depolarisation of cytoplasmic membranes and permeabilisation of P. aeruginosa and was the only agent tested (including cationic AMPs) to significantly affect all three.