bluuebunny/crossref_metadata_2025 huggingface dataset:
General Anxiety Disorder and Primary Hypertension
Authors: Seifaei Asal , Askarinejad Amir , Bazrafshan Drissi Hamed , Keshtvarz Hesam Abadi Alimohammad , Sasannia Sarvin , Moghadami Mana , Izadpanah Peyman , Bazrafshan Hanieh
Published: May 2023

Chronic forms of morbidity, including mental disorders and hypertension, play a dominant role in determining a disease load in the developing world. This article investigates the associations between the diagnoses of primary hypertension and generalized anxiety disorder (GAD) and the severity of GAD in individuals with primary hypertension. The association of GAD and age, sex, marriage, education level, income, chronic medical conditions, family history of mental disorders, adverse life events, and hypertension was assessed in 470 patients with the diagnosis of primary hypertension. Data analysis was performed with IBM SPSS Statistics software version 16. A significant relationship was found between the prevalence of GAD and the following variables: history of mental disorders (p < 0.0001), chronic medical conditions (p < 0.0001), and adverse life events (p < 0.0001). The mean anxiety score was higher among patients with uncontrolled blood pressure, and a significant relationship was observed between the prevalence of GAD and blood pressure (p < 0.0001). Because of the significant association between GAD and primary hypertension, it is recommended that anxiety disorders be considered in patients in whom primary hypertension is not controlled easily. This may lead to more proper control of hypertension while taking fewer antihypertensive medications.
Whole genome sequence of a Treponema pallidum strain from a formalin-fixed paraffin-embedded fine needle aspirate of a cervical lymph node
Authors: Aldrete Sol , Kroft Steven H. , Romeis Emily , Lieberman Nicole A.P. , Greninger Alexander L. , Giacani Lorenzo , Kron Michael A.
Published: May 2023

A patient with unilateral cervical lymphadenopathy suspicious for malignancy underwent a fine needle aspiration. Histology demonstrated mixed inflammatory infiltrates with abundant spirochetes. Sufficient spirochete DNA was extracted from paraffin-embedded tissue sections to obtain the near-complete genome sequence of a macrolide resistant strain belonging to the SS14 omega strain of Treponema pallidum.
Application of botulinum toxin at the Yonsei point for the treatment of gummy smile: A randomized controlled trial
Authors: Gong Xi , Tang Hao-Nan , Zhang An-Ran , Wang Zhi , Tang Zhi-Hui , Han Xue-Feng , Su Jia-Zeng
Published: May 2023

Background:

Over the years, demand for less invasive procedures for treating gummy smile, such as botulinum toxin A injections, has substantially increased. Meanwhile, the optimal injection site for botulinum toxin A injection is still debatable.

Objective:

To investigate the efficacy of botulinum toxin A injection at the Yonsei point for treating gummy smile.

Methods:

In this double-blind single-site randomized clinical trial, healthy participants with a gummy smile (anterior gingival exposure of ≥3.0 mm) were enrolled and randomized (1:1 ratio) into two groups. The experimental group was administered with 6 units (U)(a single-site injection of 3 U was given to the right Yonsei point and 3 U to the left Yonsei point), while the control group received the same dose in the bilateral levtor labii superioris alaeque nasi (LLSAN) muscle sites. The patients were assessed at baseline and 4, 12, 24, and 48 weeks after the first injection by a digital vernier caliper.

Results:

A total of 49 participants were enrolled. Anterior and bilateral posterior gingival exposure were reduced at 4, 12, and 24 weeks (P ≤ 0.05) and returned to baseline at 48 weeks in both groups; there was no difference between the groups at these time points. The increase in satisfaction among patients was significant, and few adverse events were observed in both groups.

Conclusions:

Both the Yonsei point and the LLSAN muscle site could be used as botulinum toxin A injection sites for treating gummy smiles.
The Impact of a Patient Participating in Evaluating Patient Safety by Using the Patient Measure of Safety in Saudi Arabia: A Cross-Sectional Study
Authors: Al Zahrani Amani K. , Alaska Yasser A. , Alqahtani Nawaf M. , Alotaibi Faisal , Majrashi Mecciya , Alhazani Lamya , Binkheder Samar , Alghadheeb Fatemah , Alkhaldi Ghadah , Hamdan Abdullah B. , Alkutbe Rabab B.
Published: May 2023

Background

Patient safety is an essential element for delivering quality of healthcare. Many studies focus on measuring patient safety from the healthcare provider’s perspective to improve patient safety in healthcare facilities. However, patient participation may reduce medical errors and improve patient safety by providing information regarding the safety of their care. This study aimed to evaluate patient safety from the inpatients’ perspective and the extent of the influence of the sociodemographic factors on their assessment.

Methods

A cross-sectional study was conducted at hospitals in different Saudi Arabian regions with 1569 inpatient adults 18 years of older who voluntarily completed an online questionnaire using the Patient Measure of Safety tool (Arabic translated). Two questions were added to assess patient feedback about the overall perception of safety and witnessing patient safety events. COVID-19 patients and those with a mental disorder or incapable of providing informed consent were excluded.

Result

The total number of participants was 1569 inpatients from 17 hospitals. Sixty-one percent of the participants were female, and 41.62% were from the 18- to 35-year age group. Less than half (38.69%) of patients stayed at the hospital between 3 and 5 days. Percentages of positive responses were more than 90% observed in dignity and respect, communication and teamworking, and organization and care planning domains. Percentages of negative responses were more than 20% found in organization and care planning, access to resources, and ward type and layout domains. Among the respondents, 57.3% (n = 899) rated the safety of their wards as excellent as opposed to 2.9% (n = 46) who rated it as poor. Approximately 5% (n = 79) have noticed 1 event, and 2.3% (n = 36) have noticed 2 or 3 events. Unemployed participants had a significantly lower rate of positive responses in domains of communication, access to resources, and ward type. In contrast, the no-schooling group had a significantly greater rate of negative responses in care planning and ward-type domains.

Conclusions

The patient plays a key role in enhancing the quality of care and has the potential to detect adverse events. The study highlighted the need to focus on better communication processes for patients with low education levels to enhance their engagement in their care. Further steps should be taken to understand the extent of the patient’s involvement in the improvement that could be tackled from feedback on the safety of care.
Frontline Worker Safety in the Age of COVID-19: A Global Perspective
Authors: Kavanagh Kevin T. , Maiwald Matthias , Pontus Christine , Cimiotti Jeannie P. , Palmieri Patrick A. , Cormier Lindsay E.
Published: May 2023

The third annual Health Watch USAsm webinar conference assembled 16 speakers from 4 continents who shared information regarding frontline worker safety in the age of COVID-19. The U.S. Bureau of Labor Statistics reported a nearly 4000% increase in workplace illness in 2020 compared with 2019. It is estimated that 2% of the U.S. workforce is not working because of long COVID. In addition, the impact is growing with each surge. After the acute illness, patients are often described as recovered, when in fact many have only survived and are coping with the multisystem impacts of long COVID. Long COVID, including its late cognitive, cardiovascular, embolic, and diabetic complications, disproportionately impacts frontline workers, many of whom are of lower socioeconomic status and represented by ethnic minorities.

Natural infection and current vaccines do not provide durable protection for reinfection. Herd immunity is not possible at this time. Although SARS-CoV-2 is unlikely to be eliminated, decreasing spread is imperative to slow the rate of mutations, decrease the number of reinfections, and lower the chances of developing long COVID. The primary mode of spread is through aerosolization. Both routine breathing and talking aerosolizes the virus. With the extremely high infectivity of SARS-CoV-2, it is unlikely that central building ventilation alone will be enough to satisfactorily mitigate spread. Additional safe active air cleaning technology, such as upper-room germicidal UV-C lighting, needs to be deployed.

Misinformation and disinformation have inhibited response effectiveness. Examples include downplaying the benefit of well-fitted masks and the risks that COVID-19 and long COVID pose to children, along with believing children cannot spread the disease. The engagement of local community leaders is essential to educate the community and drive social change to accept vaccinations and other public health interventions. Vaccinations and natural immunity alone are unlikely to adequately prevent community spread and do not provide durable protection against the risk of long COVID.

Frontline workers must keep their immunity as high as possible and work in settings with clean air, along with wearing N95 masks when they are in contact with the public. Finally, there needs to be a financial safety net for frontline workers and their families in the event of incapacitation or death from COVID-19.
Radioguided Occult Lesion Localization for Gynecologic Tumor Relapses
Authors: Bebia Vicente , Mast Richard , Villasboas-Rosciolesi Diego , Franco-Camps Silvia , Pérez-Benavente María Asunción , Gil-Moreno Antonio , Cabrera Silvia
Published: May 2023

Purpose of the Report

Excision of peritoneal or nodal isolated recurrences frequently involves performing a surgery on a previously operated area, which is more difficult to achieve with minimally invasive approaches. Our aim was to describe the technical aspects, feasibility, and complications derived from the application of the radioguided occult lesions localization (ROLL) in gynecologic oncology recurrence excision.

Patients and Methods

All consecutive patients bearing localized relapses of a gynecologic tumor that were considered candidates for surgical excision were assessed to undergo a ROLL procedure. Radiotracer (99mTc-albumin macroaggregate) injection of the lesions was performed by ultrasonography or CT guidance. Relapses were localized using a gamma probe by minimally invasive surgery when located in the abdomen, or percutaneously when located in the groin. Intraoperative and early (up to postoperative day 30) complications were prospectively recorded.

Results

A total of 8 patients underwent the procedure. The median age was 59 years (range, 35–87 years). Four patients had abdominal relapses, whereas 4 patients presented groin relapses. The mean operative time was 120 minutes (range, 30–190 minutes), whereas the median estimated blood loss was 5 mL (range, 0–150 mL). All the targeted lesions were successfully removed. No intraoperative complications were reported. One postoperative complication (inguinal lymphocele) was recorded.

Conclusions

ROLL surgery constitutes a new approach for isolated recurrences in gynecological tumors.
Testicular Metastasis From Prostate Cancer Demonstrated on PSMA PET/CT
Authors: Mamaliga Tatiana , Obando Jose Antonio , Liu Yiyan
Published: May 2023

Testicular metastasis from prostate cancer is rarely reported in radiology literature. We present the case of an 84-year old man with history of prostate cancer, who obtained an 18F-Pylarify PET/CT for biochemical recurrence, with an incidentally detected prostate-specific membrane antigen–avid large right testicular mass. The 18F-Pylarify PET/CT showed no evidence of local prostate tumor recurrence in the prostate bed, but demonstrated small right common and external lymph node metastases in addition to the incidentally noted large right testicular mass. The patient underwent orchiectomy with subsequent histopathologic examination confirming metastasis from prostate cancer.
In patients with combined clavicle and multiple rib fractures, does fracture fixation of the clavicle improve clinical outcomes? A multicenter prospective cohort study of 232 patients
Authors: Hoepelman Ruben J. , van der Linde Rens A. , Beeres Frank J.P. , Beks Reinier B. , Sweet Arthur A.R. , Lansink Koen W.W. , van Wageningen Bas , Tromp Tjarda N. , Minervini Fabrizio , Link Björn-Christian , van Veelen Nicole M. , Hoogendoorn Jochem M. , de Jong Mirjam B. , van Baal Mark C.P. , Leenen Luke P.H. , Groenwold Rolf H.H. , Houwert Roderick M. , IJpma Frank F.
Published: May 2023

BACKGROUND

Clavicle and rib fractures are often sustained concomitantly. The combination of injuries may result in decreased stability of the chest wall, making these patients prone to (respiratory) complications and prolonged hospitalization. This study aimed to assess whether adding chest wall stability by performing clavicle fixation improves clinical outcomes in patients with concurrent clavicle and rib fractures.

METHODS

A prospective multicenter study was performed including all adult patients admitted between January 2018 and March 2021 with concurrent ipsilateral clavicle and rib fractures. Patients treated operatively versus nonoperatively for their clavicle fracture were matched using propensity score matching. The primary outcome was hospital length of stay (HLOS). Secondary outcomes were intensive care unit length of stay, duration of mechanical ventilation, pain, complications, and quality of life at 6 weeks and 12 months of follow-up.

RESULTS

In total, 232 patients with concomitant ipsilateral clavicle and rib fractures were included. Fifty-two patients (22%) underwent operative treatment of which 39 could be adequately matched to 39 nonoperatively treated patients. No association was observed between clavicle plate fixation and HLOS (mean difference, 2.3 days; 95% confidence interval, −2.1 to 6.8; p = 0.301) or any secondary endpoint. Eight of the 180 nonoperatively treated patients (4%) had a symptomatic nonunion, for which 5 underwent secondary clavicle fixation.

CONCLUSION

We found no evidence that, in patients with combined clavicle and multiple rib fractures, plate fixation of the clavicle reduces HLOS, pain, or (pulmonary) complications, nor that it improves quality of life.

STUDY TYPE

Therapeutic/Care Management; Level III.
Promoting post discharge telephone follow-up of patients with transurethral resection for bladder cancer: a best practice implementation project
Authors: Hajebrahimi Sakineh , Talebpour Amin , Kabiri Neda , Ahmadian Niloufar , Soleimanzadeh Farzin , Behbahani Zahereh , Salehi-Pourmehr Hanieh
Published: May 2023

Introduction and objectives:

Telephone follow-up (TFU) is a method that can be recommended for patients with chronic disease, including patients with nonmuscle-invasive bladder cancer (NMIBC) after transurethral resection of the bladder (TURB). This project aimed to improve postdischarge TFU of patients with TURB in a tertiary care system and referral system in Tabriz, Iran.

Methods:

This evidence implementation project used the JBI evidence implementation framework. Two audit criteria were used. A baseline audit was conducted, followed by the implementation of multiple strategies. The project was finalized with a follow-up audit to evaluate changes in practice.

Results:

The aggregated data collated from the urology ward demonstrated that all criteria had achieved 0% compliance in the baseline audit round. Strategies such as patient education about TFU, educational pamphlets developed according to the latest validated guidelines, and a mobile app for education material about bladder cancer, diagnosis, management, and follow-up were implemented. The Phase 3 follow-up showed an 88% increase in compliance with staff education about the postdischarge TFU as a component of comprehensive discharge planning and a 22% achievement of timely patient follow-up by telephone.

Conclusions:

A clinical audit is an effective approach to promoting postdischarge TFU in bladder cancer cases following TURB. TFU for bladder cancer patients who underwent TURB is an optimal goal that is easily achieved through patient, nursing staff, and residents’ education using the latest guidelines.
Prevalence and determinants of not testing for HIV among young adult women in Papua New Guinea: findings from the 2016–2018 Demographic and Health Survey
Authors: Maviso McKenzie K. , Kalembo Fatch Welcome
Published: May 2023

Objective

The study investigated the factors associated with not ever testing for HIV among women aged 15–29 years in Papua New Guinea (PNG).

Design and setting

The study used secondary data from the 2016–2018 Demographic and Health Survey (DHS) of PNG, a nationally representative cross-sectional survey that used a two-stage stratified sampling.

Participants

A total weighed sample of 5,164 young adult women aged 15–29 years were included in the study.

Primary outcome measure

Ever been tested for HIV was the primary outcome of the study. All analyses were adjusted using survey weights to account for unequal sampling probabilities.

Results

The prevalence of not testing for HIV was 58.8% (95% CI: 57.4%, 60.1%). The mean age was 21.65 (SD ± 4.23) years. The majority (62.9%) of young adult women in rural areas were not tested for HIV. In the multivariable analysis, those who were never married (AOR: 4.9, 95% CI: 3.6–6.6), had poor wealth index (AOR: 1.8, 95% CI: 1.3–2.5), from rural areas (AOR: 2.0, 95% CI: 1.5–2.6), from the Momase region (AOR: 1.3, 95% CI: 1.0–1.7, did not read newspaper or magazine (AOR: 1.7, 95% CI: 1.3–2.1), did not listen to radio (AOR: 1.5, 95% CI: 1.1–2.0), experienced early sexual debut (AOR: 1.5, 95% CI: 1.1–1.9), had one sexual partner (AOR: 1.5, 95% CI: 1.2–2.0), and reported no STI in the past 12 months (AOR: 1.8, 95% CI: 1.1–3.1) had higher odds of not testing for HIV.

Conclusions

Our study found a very high unmet need for HIV testing among young adult women in PNG. Health promotion programmes should be designed to increase HIV knowledge and access to HIV testing services. Furthermore, efforts to optimise HIV testing services should target women who are disadvantaged and from rural areas.

Strengths and limitations of this study

This study used a nationally representative large sample of young adult women aged 15–29 years from the 2016–2018 PNGDHS; thus, the findings are generalisable to the entire population of this age group.

The study provides much-needed data for strategic planning and programming to improve the health outcomes of young adult women in the country.

This is a cross-sectional study, and as such, it is not possible to make causal inferences.

The level of knowledge or awareness of where to get tested for HIV was not included in the analysis, and it remains unknown whether this variable contributes to the high proportion of respondents who remain unaware of their HIV status.

Responses to the questions from respondents were self-reported, and this could have resulted in behavioural desirability bias.
Cohort Profile: Post-hospitalisation COVID-19 study (PHOSP-COVID)
Authors: Elneima Omer , McAuley Hamish J C , Leavy Olivia C , Chalmers James D , Horsley Alex , Ho Ling-Pei , Marks Michael , Poinasamy Krisnah , Raman Betty , Shikotra Aarti , Singapuri Amisha , Sereno Marco , Harris Victoria C , Houchen-Wolloff Linzy , Saunders Ruth M , Greening Neil J , Richardson Matthew , Quint Jennifer K , Briggs Andrew , Docherty Annemarie B , Kerr Steven , Harrison Ewen M , Lone Nazir I , Thorpe Mathew , Heaney Liam G , Lewis Keir E , Aul Raminder , Beirne Paul , Bolton Charlotte E , Brown Jeremy S , Choudhury Gourab , Diar Bakerly Nawar , Easom Nicholas , Echevarria Carlos , Fuld Jonathan , Hart Nick , Hurst John R , Jones Mark G , Parekh Dhruv , Pfeffer Paul , Rahman Najib M , Rowland-Jones Sarah L , Thompson AA Roger , Jolley Caroline , Shah Ajay M , Wootton Dan G , Chalder Trudie , Davies Melanie J , De Soyza Anthony , Geddes John R , Greenhalf William , Heller Simon , Howard Luke S , Jacob Joseph , Jenkins R Gisli , Lord Janet M , Man William D-C , McCann Gerry P , Neubauer Stefan , Openshaw Peter JM , Porter Joanna C , Rowland Matthew J , Scott Janet T , Semple Malcolm G , Singh Sally J , Thomas David C , Toshner Mark , Sheikh Aziz , Brightling Christopher E , Wain Louise V , Evans Rachael A
Published: May 2023

PHOSP-COVID is a national UK multi-centre cohort study of patients who were hospitalised for COVID-19 and subsequently discharged.

PHOSP-COVID was established to investigate the medium- and long-term sequelae of severe COVID-19 requiring hospitalisation, understand the underlying mechanisms of these sequelae, evaluate the medium- and long-term effects of COVID-19 treatments, and to serve as a platform to enable future studies, including clinical trials.

Data collected covered a wide range of physical measures, biological samples, and Patient Reported Outcome Measures (PROMs).

Participants could join the cohort either in Tier 1 only with remote data collection using hospital records, a PROMs app and postal saliva sample for DNA, or in Tier 2 where they were invited to attend two specific research visits for further data collection and biological research sampling. These research visits occurred at five (range 2-7) months and 12 (range 10-14) months post-discharge. Participants could also participate in specific nested studies (Tier 3) at selected sites.

All participants were asked to consent to further follow-up for 25 years via linkage to their electronic healthcare records and to be re-contacted for further research.

In total, 7935 participants were recruited from 83 UK sites: 5238 to Tier 1 and 2697 to Tier 2, between August 2020 and March 2022.

Cohort data are held in a Trusted Research Environment and samples stored in a central biobank. Data and samples can be accessed upon request and subject to approvals.
Immunogenicity of NVX-CoV2373 in PREVENT-19: A Phase 3, Randomized, Placebo-Controlled Trial in Adults in the United States and Mexico
Authors: Áñez Germán , Kotloff Karen L. , Gay Cynthia L. , Nelson Joy , Dunbar Haoua , Cloney-Clark Shane , McGarry Alice , Woo Wayne , Cho Iksung , Plested Joyce S. , Glenn Gregory M. , Dunkle Lisa M.
Published: May 2023

Background

NVX-CoV2373, an adjuvanted, recombinant SARS-CoV-2 spike (rS) protein vaccine, consistently demonstrated protective efficacy against COVID-19 in clinical trials and has received regulatory authorizations or approvals worldwide.

Methods

PREVENT-19 (NCT04611802) is a phase 3, randomized, observer-blinded, placebo-controlled trial evaluating safety, immunogenicity, and efficacy of NVX-CoV2373 in ≈30 000 participants ≥18 years in the United States and Mexico. Vaccine humoral immune response (ie, serum immunoglobulin [IgG] antibodies, hACE2 receptor binding inhibition antibodies, and neutralizing antibodies to SARS-CoV-2) (ancestral strain) was assessed in 1200 participants randomly selected and equally divided between participants 18–64 and ≥65 years.

Results

In the per protocol analysis, NVX-CoV2373 induced vigorous serum antibody responses among the 1063 analyzed participants who were SARS-CoV-2 seronegative at baseline, received both doses of study treatment, and had serology results available 2 weeks after dose 2. Geometric mean (GM) responses in both younger and older adults were higher among recipients of vaccine versus placebo for IgG (64 259 vs 121 and 37 750 vs 133 ELISA units, respectively), hACE2 receptor binding inhibition GM titers (GMTs) (222 vs 5 and 136 vs 5, respectively), and neutralizing antibody GMTs (1303 vs 11 and 900 vs 11, respectively). Humoral responses were 30–40% lower in participants ≥65 years or HIV-positive; however, seroconversion rates were high and comparable between the age cohorts, regardless of HIV serostatus.

Conclusions

NVX-CoV2373 elicited robust humoral immune responses against ancestral SARS-CoV-2 virus 2 weeks following the second vaccination in adult PREVENT-19 participants, consistent with previously reported high vaccine efficacy.

PREVENT-19ClinicalTrials.govnumber,NCT04611802
Comparison of prehospital assessment by paramedics and in-hospital assessment by physicians in suspected stroke patients
Authors: Dekker Luuk , Daems Jasper D. , Duvekot Martijne H.C. , Nguyen T. Truc My , Venema Esmee , van Es Adriaan C.G.M. , Rozeman Anouk D. , Moudrous Walid , Dorresteijn Kirsten R.I.S. , Hensen Jan-Hein J. , Bosch Jan , van Zwet Erik W. , de Schryver Els L.L.M. , Kloos Loet M.H. , de Laat Karlijn F. , Aerden Leo A.M. , van den Wijngaard Ido R. , Dippel Diederik W.J. , Kerkhoff Henk , Wermer Marieke J.H. , Roozenbeek Bob , Kruyt Nyika D.
Published: May 2023

Background

It is unknown if ambulance paramedics adequately assess neurological deficits used for prehospital stroke scales to detect anterior large-vessel occlusions. We aimed to compare prehospital assessment of these stroke-related deficits by paramedics with in-hospital assessment by physicians.

Methods

We used data from two prospective cohort studies: the Leiden Prehospital Stroke Study (LPSS) and PREhospital triage of patients with suspected STrOke (PRESTO) study. In both studies, paramedics scored 9 neurological deficits in stroke code patients in the field. Trained physicians scored the National Institutes of Health Stroke Scale (NIHSS) at hospital presentation. Patients with transient ischemic attack were excluded because of the transient nature of symptoms. Spearman’s rank correlation coefficient (rs) was used to assess correlation between the total prehospital assessment score, defined as the sum of all prehospital items, and the total NIHSS score. Correlation, sensitivity and specificity were calculated for each prehospital item with the corresponding NIHSS item as reference.

Results

We included 2850 stroke code patients. Of these, 1528 had ischemic stroke, 243 intracranial hemorrhage, and 1079 stroke mimics. Correlation between the total prehospital assessment score and NIHSS score was strong (rs=0.70; 95%CI: 0.68-0.72). Concerning individual items, prehospital assessment of arm (rs=0.68) and leg (rs=0.64) motor function correlated strongest with corresponding NIHSS items, and had highest sensitivity (arm 95%, leg 93%) and moderate specificity (arm 71%, leg 70%). Neglect (rs=0.31), abnormal speech (rs=0.50) and gaze deviation (rs=0.51) had weakest correlations. Neglect and gaze deviation had lowest sensitivity (52% and 66%) but high specificity (84% and 89%), whilst abnormal speech had high sensitivity (85%) but lowest specificity (65%).

Conclusions

The overall prehospital assessment of stroke code patients correlates strongly with in-hospital assessment. Prehospital assessment of neglect, abnormal speech and gaze deviation differed most from in-hospital assessment. Focused training on these deficits may improve prehospital triage.
Contact patterns of older adults with and without frailty in the Netherlands during the COVID-19 pandemic
Authors: Backer Jantien A , van de Kassteele Jan , Fakiri Fatima El , Hens Niel , Wallinga Jacco
Published: May 2023

Background

During the COVID-19 pandemic, social distancing measures were imposed to protect the population from exposure, especially older adults and people with frailty, who have the highest risk for severe outcomes. These restrictions greatly reduced contacts in the general population, but little was known about behaviour changes among older adults and people with frailty themselves. Our aim was to quantify how COVID-19 measures affected the contact behaviour of older adults and how this differed between older adults with and without frailty.

Methods

In 2021, a contact survey was carried out among people aged 70 years and older in the Netherlands. A random sample of persons per age group (70–74, 75–79, 80–84, 85–89, and 90+) and gender was invited to participate, either during a period with stringent (April 2021) or moderate (October 2021) measures. Participants provided general information on themselves, including their frailty, and they reported characteristics of all persons with whom they had face-to-face contact on a given day over the course of a full week.

Results

In total, 720 community-dwelling older adults were included (overall response rate of 15%), who reported 16,505 contacts. During the survey period with moderate measures, participants without frailty had significantly more contacts outside their household than participants with frailty. Especially for females, frailty was a more informative predictor of the number of contacts than age. During the survey period with stringent measures, participants with and without frailty had significantly lower numbers of contacts compared to the survey period with moderate measures. The reduction of the number of contacts was largest for the eldest participants without frailty. As they interact mostly with adults of a similar high age who are likely frail, this reduction of the number of contacts indirectly protects older adults with frailty from SARS-CoV-2 exposure.

Conclusions

The results of this study reveal that social distancing measures during the COVID-19 pandemic differentially affected the contact patterns of older adults with and without frailty. The reduction of contacts may have led to the direct protection of older adults in general but also to the indirect protection of older adults with frailty.
Yes, it matters: in contrast to blood plasma, serum metabolomics is confounded by platelets
Authors: Hagn Gerhard , Meier-Menches Samuel M. , Plessl-Walder Günter , Mitra Gaurav , Mohr Thomas , Preindl Karin , Schlatter Andreas , Schmidl Doreen , Gerner Christopher , Garhöfer Gerhard , Bileck Andrea
Published: May 2023

Metabolomics is an emerging and powerful molecular profiling method supporting clinical investigations. For clinical metabolomics studies, serum is commonly used. Serum is collected after blood coagulation, a complex biochemical process involving active platelet metabolism. This may proof relevant as platelet counts and function may vary substantially in individuals. Applying a multi-omics analysis strategy comprising proteins and metabolites with a focus on lipid mediators, we systematically investigated serum and plasma obtained from the same healthy donors. While Biocrates MxP Quant 500 results correlated well (n=461, R2=0.991), lipid mediators (n=77, R2=0.906) and proteins (n=322, R2=0.860) differed substantially between serum and plasma. Actually, secretome analysis of activated platelets identified all proteins and most lipid mediators significantly enriched in serum when compared to plasma. Furthermore, a prospective, randomized, controlled parallel group metabolomics trial was performed, monitored by serum and plasma analyses. Healthy individuals received either acetylsalicylic acid, affecting platelets, or omega-3 fatty acids, hardly affecting platelets, for a period of seven days. In the acetylsalicylic acid group, serum analysis apparently demonstrated a significant drug-induced downregulation of the lipid mediators TXB2 and 12-HETE. The absence of these observation in plasma analyses suggested that these drug effects took place only during blood coagulation. Other effects of acetylsalicylic acid on alpha-linolenic acid and the fatty acid composition of triglycerides were detected both in serum and plasma. In the omega-3 fatty acid group, serum and plasma analysis results did not differ. These data strongly support the hypothesis that the serum metabolome is substantially confounded by platelets.

Key points

Serum metabolomics data are confounded by platelets

Clinical evaluation of drug effects should be based on plasma metabolomics
Quantitative modeling of EGF receptor ligand discrimination via internalization proofreading
Authors: Leblanc Jaleesa A , Sugiyama Michael G , Antonescu Costin N , Brown Aidan I
Published: May 2023

The epidermal growth factor receptor (EGFR) is a central regulator of cell physiology that is stimulated by multiple distinct ligands. Although ligands bind to EGFR while the receptor is exposed on the plasma membrane, EGFR incorporation into endosomes following receptor internalization is an important aspect of EGFR signaling, with EGFR internalization behavior dependent upon the type of ligand bound. We develop quantitative modeling, both kinetic and with spatial details, for EGFR recruitment to and internalization from clathrin domains and competition with ligand unbinding from EGFR. We find that a combination of spatial and kinetic proofreading leads to enhanced EGFR internalization ratios in comparison to unbinding differences between ligand types. Various stages of the EGFR internalization process, including recruitment to and internalization from clathrin domains, modulate the internalization differences between receptors bound to different ligands. Our results indicate that following ligand binding, EGFR may encounter multiple clathrin domains before successful recruitment and internalization. The quantitative modeling we have developed describes competition between EGFR internalization and ligand unbinding and the resulting proofreading.
Revealing global stoichiometry conservation architecture in cells from Raman spectral patterns
Authors: Kamei Ken-ichiro F. , Kobayashi-Kirschvink Koseki J. , Nozoe Takashi , Nakaoka Hidenori , Umetani Miki , Wakamoto Yuichi
Published: May 2023

Cells can adapt to various environments by changing their biomolecular profiles while maintaining physiological homeostasis. What organizational principles in cells enable the simultaneous realization of adaptability and homeostasis? To address this question, we measure Raman scattering light fromEscherichia colicells under diverse conditions, whose spectral patterns convey their comprehensive molecular composition. We reveal that dimension-reduced Raman spectra can predict condition-dependent proteome profiles. Quantitative analysis of the Raman-proteome correspondence characterizes a low-dimensional hierarchical stoichiometry-conserving proteome structure. The network centrality of each gene in the stoichiometry conservation relations correlates with its essentiality and evolutionary conservation, and these correlations are preserved from bacteria to human cells. Furthermore, stoichiometry-conserving core components obey growth law and ensure homeostasis across conditions, whereas peripheral stoichiometry-conserving components enable adaptation to specific conditions. Mathematical analysis reveals that the stoichiometrically constrained architecture is reflected in major changes in Raman spectral patterns. These results uncover coordination of global stoichiometric balance in cells and demonstrate that vibrational spectroscopy can decipher such biological constraints beyond statistical or machine-learning inference of cellular states.
Identification of cytokine-predominant immunosuppressive class and prognostic risk signatures in glioma
Authors: Tian Ziyue , Yang Zhongyi , Jin Meng , Ding Ran , Wang Yuhan , Chai Yuying , Wu Jinpu , Yang Miao , Zhao Weimin
Published: May 2023

Purpose

The advent of immune checkpoint blockade (ICB) therapies this year has changed the way glioblastoma (GBM) is treated. Meanwhile, some patients with strong PD-L1 expression remain immune checkpoint resistant. To better understand the molecular processes that influence the immune environment, there is an urgent need to characterize the immunosuppressive tumor microenvironment and identify biomarkers to predict patient survival outcomes.

Patients and methods

Our study analyzed RNA-sequencing data from 178 GBM samples. Their unique gene expression patterns in the tumor microenvironment were analyzed by an unsupervised clustering algorithm. Through these expression patterns, a panel of T-cell exhaustion signatures, immunosuppressive cells, and clinical features correlates with immunotherapy response. The presence or absence of immune status and prognostic signatures was then validated with the test dataset.

Results

38.2% of GBM patients showed increased expression of anti-inflammatory cytokines, significant enrichment of T cell exhaustion signals, higher proportion of immunosuppressive cells (macrophages and CD4 regulatory T cells) and nine inhibitory checkpoints (CTLA4, PDCD1, LAG3, BTLA, TIGIT, HAVCR2, IDO1, SIGLEC7, and VISTA). The immunodepleted class (IDC) was used to classify these immunocompromised individuals. Despite the high density of tumor-infiltrating lymphocytes shown by IDC, such patients have a poor prognosis. Although PD-L1 was highly expressed in IDC, it suggested that there might be ICB resistance. There are many IDC predictive signatures to discover.

Conclusion

PD-1 is strongly expressed in a novel immunosuppressive class of GBM, but this cluster may be resistant to ICB therapy. A comprehensive description of this drug-resistant tumor microenvironment could provide new insights into drug resistance mechanisms and improved immunotherapy techniques.
QUALITATIVE ANALYSIS OF CRUCIFEROUS VEGETABLE EXTRACTS USEFUL FOR ESTROGEN METABOLISM FOR DIINDOLYLMETHANE (DIM)
Authors: Odimegwu Joy Ifunanya , Oyinkansola Omotuyi Elizabeth
Published: May 2023

3,3′-Diindolylmethane (DIM) is a compound derived from the digestion of indole-3-carbinol, found in Cruciferous vegetables (Broccoli, Cabbage, Cauliflower,) which promotes Estrogen metabolism in females. It has been known to help in reduction of heavy blood flow during menstruation especially in females with uterine fibroids. Dim-plus a herbal supplement contains Vitamin E, DIM, Phosphatidlycholine, Spinach, Cabbage, and Broccoli powder. The purpose of this research is to extract and identify the compounds present in Broccoli, Spinach and Cabbage obtained in local markets in Lagos, Nigeria and compare it with the reference standard DIM-plus. Identification of compounds qualitatively by TLC showed different Rf values which were compared with the reference to identify compounds with similar Rf values. Extract was also subjected to HPLC analysis to confirm the presence of DIM in the Cruciferous vegetables using Dim-plus® as standard. Based on the TLC and HPLC analysis it was discovered that the common peak which the crude extracts of the vegetables has is DIM. Thus, the vegetable extracts have Diindolylmethane.
Songbirds avoid the oxidative stress costs of high blood glucose levels
Authors: Vágási Csongor I. , Vincze Orsolya , Adámková Marie , Kauzálová Tereza , Lendvai Ádám Z. , Pătra□ Laura , Pénzes Janka , Pap Péter L. , Albrecht Tomáš , Tomášek Oldřich
Published: May 2023

Chronically high blood glucose levels (hyperglycaemia) can compromise healthy ageing and lifespan at the individual level. Elevated oxidative stress can play a central role in hyperglycaemia-induced pathologies. Nevertheless, the lifespan of birds shows no species-level association with blood glucose. This suggests that the potential pathologies of high blood glucose levels can be avoided by adaptations in oxidative physiology at the macroevolutionary scale. However, this hypothesis remains unexplored. Here, we examined this hypothesis using comparative analyses controlled for phylogeny, allometry and fecundity based on data from 51 songbird species (681 individuals with blood glucose and 1021 individuals with oxidative state data). We measured blood glucose at baseline and after stress stimulus and computed glucose stress reactivity as the magnitude of change between the two time points. We also measured three parameters of non-enzymatic antioxidants (uric acid, total antioxidants and glutathione) and a marker of oxidative lipid damage (malondialdehyde). We found no clear evidence for blood glucose concentration being correlated with either antioxidant or lipid damage levels at the macroevolutionary scale, as opposed to the hypothesis postulating that high blood glucose levels entail oxidative costs. The only exception was the moderate evidence for species with a stronger stress-induced increase in blood glucose concentration evolving moderately lower investment into antioxidant defence (uric acid and glutathione). Neither baseline nor stress-induced glucose levels were associated with oxidative physiology. Our findings support the hypothesis that birds evolved adaptations preventing the (glyc)oxidative costs of high blood glucose observed at the within-species level. Such adaptations may explain the decoupled evolution of glycaemia and lifespan in birds and possibly the paradoxical combination of long lifespan and high blood glucose levels relative to mammals.

Summary statement

High blood glucose levels can harm organisms by causing oxidative stress. We show that, at the macroevolutionary level, songbirds defy this expectation, as their glucose levels and oxidative physiology are uncoupled.
Activity and abundance of nitrous oxide consuming bacteria inPlatismatia glaucacryptogamic lichen in boreal Finnish spruce forest
Authors: Abagnale Vincenzo , Palacin-Lizarbe Carlos , Paul Dhiraj , Kerttula Johanna , Siljanen Henri M.P.
Published: May 2023

The boreal spruce forest soil can assimilate atmospheric N2O through symbiotic relationships with mycorrhizae or with bacteria, especially during spring and autumn, when aerobic microsites to soil can form. In cold soils with large field capacity (FCD), high humidity and absence of fertilisation, a balance between absorption and emission of nitrous oxide and dinitrogen was observed to be close to zero, and even to assume negative values in some cases, thus suggesting that forest soils absorb more N2O than they emit. Furthermore, in the presence of cryptogamic coverings of mosses and lichens, the absorption value was observed to be greater than in forests with less coverage; although the main role in N2O absorption is played by soil and root system. However, the role played by epiphytic organisms in N2O absorption in the boreal forests has not been uncovered yet. We studied, N2O dynamics of the lichen,Platismatia glauca, showing that N2O is consumed especially at lower incubation temperatures. The quantitative analysis with real-time PCR of nitrous oxide reductase gene fragment nosZ, showed that enzyme is present in the lichen and the gene is more transcribed under lower incubation temperature. The presented results unveil that cryptogamic covers consume nitrous oxide (with values between 0.1 and 0.4 ng N2O-C/g (ww)/h) at the atmospheric concentration via complete dissimilatory denitrification when nitrogen is limited.
Integrating biodiversity assessments into local conservation planning: the importance of assessing suitable data sources
Authors: Ferraille Thibaut , Kerbiriou Christian , Bigard Charlotte , Claireau Fabien , Thompson John D.
Published: May 2023

Strategic Environmental Assessment (SEA) of land-use planning is a fundamental tool to minimize environmental impacts of artificialization. In this context, Systematic Conservation Planning (SCP) tools based on Species Distribution Models (SDM) are frequently used for the elaboration of spatially exhaustive biodiversity diagnostics. Despite the paradigm of “garbage in - garbage out” that emphasises the importance of testing the suitability of data for SDM and priority conservation areas, the assessment of database sources remains relatively rare. In addition, the lack of practical recommendations for the use of open-access databases by SEA stakeholders remains a problem. The aim of this study is to explore the quality of data sources that can be used in SEA to assess priority conservation areas in SEA. The study used data for nine taxonomic groups (commonly used in inventories for environmental impact assessment) and three databases available to SEA stakeholders. Three local administrative entities in very different socio-ecological contexts were used to examine three main issues : (i) the suitability of local versus regional or country databases for assessing conservation priorities, (ii) differences among taxonomic groups or territories in terms of the suitability of databases, (iii) the importance of the quality of databases for the application of SDM to assess priority conservation areas. Our study provides several clear messages for potential users of open- access databases. First, the need for prudence in the interpretation of biodiversity maps. Second, the collection of individual databases at the country scale is necessary to complete local data and ensure the suitability of SDM in a local context. Third, a data driven approach can lead to the use of notably different species communities to identify priority conservation areas when compared to the community in the original database. Finally, we propose a workflow to guide SEA stakeholders through the process of data rationalization and use in conservation planning.
Lipoteichoic acid biosynthesis byStaphylococcus aureusis controlled by the MspA protein through competitive interference
Authors: Bonini Dora , Duggan Seána , Alnahari Alaa , Brignoli Tarcisio , Strahl Henrik , Massey Ruth C.
Published: May 2023

Staphylococcus aureusproduces a plethora of virulence factors critical to its ability to establish an infection and cause disease. We have previously characterised a small membrane protein, MspA, which has pleiotropic affects on virulence and contributes toS. aureuspathogenicityin vivo. Here we report thatmspAinactivation triggers overaccumulation of the essential cell wall component lipoteichoic acid (LTA) which, in turn, decreases autolytic activity and leads to increased cell size due to a delay in cell separation. We show that MspA directly interacts with the LTA synthesis enzymes UgtP, LtaA and LtaS, and competitively interferes with the association between LtaA and LtaS. While complementation of themspAmutant with wild-typemspAreduces the amount of LTA, expression of a mutated version of MspA that does not interfere with the interactions between LtaA and LtaS does not. We suggest that MspA contributes to maintaining a physiological level of LTA in the cell wall by interacting with the LTA synthetic enzymes. In conclusion, this study uncovers the critical role of the MspA protein in regulating cell envelope biosynthesis and pathogenicity.

IMPORTANCE

TheS. aureuscell envelope, comprising of the cytoplasmic membrane, a thick peptidoglycan layer and the anionic polymers lipoteichoic acid and wall teichoic acids, is fundamental for bacterial growth and division, as well as being the main interface between the pathogen and the host. It has become increasingly apparent that the synthesis and turnover of cell envelope components also affect the virulence ofS. aureus. In this study, we show that MspA, a novel effector ofS. aureusvirulence, contributes to the maintenance of normal levels of lipoteichoic acid in the cell wall, with implications on cell cycle and size. These findings further our understanding of the connections between envelope synthesis and pathogenicity and suggests MspA as a novel a target for therapeutic intervention.