bluuebunny/crossref_metadata_2025 huggingface dataset:
Value of ultrasonography in determining the nature of pleural effusion: Analysis of 582 cases
Authors: Wang Ting , Du Ge , Fang Liping , Bai Yang , Liu Zishuang , Wang Li
Published: August 2022

To explore the value of ultrasonography in the auxiliary diagnosis of pleural effusion, we retrospectively analyzed the ultrasonographic findings of 275 exudates and 307 transudates and summarized the ultrasonographic image features of pleural effusion according to patients’ primary diseases. The findings of thoracic ultrasonography performed before the initial thoracentesis in 582 patients with subsequently confirmed exudative/transudative pleural effusion were analyzed with regard to the sonographic features of pleural effusion. In 275 cases with exudates, thoracic ultrasonography showed a complex septate appearance in 19 cases (6.9%), complex nonseptate appearance in 100 cases (36.4%), complex homogenous sign in 46 cases (16.7%), and pleural thickness > 3 mm in 105 cases. In contrast, in 307 patients with transudates, most patients (97.1%) had bilateral pleural effusion. Ultrasonographic images displayed anechoic appearance and absence of pleural thickening in a vast majority of cases (306, 99.7%; 301, 98%). These positive findings in the exudate were statistically higher than those in their counterparts (P < .05). In the empyema subgroup, the proportion of complex septate appearance, complex nonseptate appearance, complex homogenous sign, and pleural thickening was the highest, at 19/41, 12/41, 10/41, and 30/41, respectively. Ultrasonography is valuable in defining the nature of pleural effusion. Some sonographic features of pleural effusion, such as echogenicity, septation, and pleural thickening, may indicate a high risk of exudative pleural effusion.
Analysis of medication and prescription background risk factors contributing to oral medication administration errors by nurses: A case–control study
Authors: Suzuki Ryohei , Sakai Takamasa , Kato Mariyo , Takahashi Masaaki , Inukai Akira , Ohtsu Fumiko
Published: August 2022

Medication errors, including overdose and underdose, have a significant impact on patients and the medical economy. We need to prevent or avoid recurring medication errors. Therefore, we conducted a survey to identify medication and prescription background risk factors contributing to the administration of medication by nurses. This study surveyed cases of medication administration errors. This study was conducted at Higashinagoya National Hospital from April 1, 2018, to October 31, 2019. Patients’ backgrounds and medication and prescription background risk factors were investigated. Three control cases were randomly selected for each medication error case. We defined the group of medication error cases as the medication error group and the group of control cases as the no-medication-error group. A logistic regression analysis was performed for factors related to medication errors. A total of 202 patients were included in the medication error group. The median age and number of medications were 78 years and 7, respectively. A total of 606 cases were included in the no-medication-error group. The median age and number of medications were 77 years and 6, respectively. The factors that exhibited a relationship with the medication error group were the number of administrations per day, dosing frequency on indicated days, prescription and start dates were the same, medications from multiple prescriptions, and continuous use of a medication received prior to admission. This study identified existing medication and prescription background risk factors. Overlapping risk factors from these groups might contribute to medication administration errors. Therefore, reviewing these factors is necessary to avoid recurring medication administration errors.
Alternative splicing signatures of congenital heart disease and induced pluripotent stem cell-derived cardiomyocytes from congenital heart disease patients
Authors: Xu Xiang , Zou Renchao , Liu Xiaoyong , Su Qianqian
Published: August 2022

Congenital heart disease (CHD) is the most serious congenital defect in newborns with higher mortality. Alternative splicing (AS) plays an essential role in numerous heart diseases. However, our understanding of the link between mRNA splicing and CHD in humans is limited. Here, we try to investigate the genome-wide AS events in CHD using bioinformatics methods. We collected available RNA-seq datasets of CHD-induced pluripotent stem cell-cardiomyocytes (iPSC-CMs) (including single ventricle disease [SVD] and tetralogy of Fallot [TOF]) and non-CHD from the Gene Expression Omnibus database. Then, we unprecedentedly performed AS profiles in CHD-iPSC-CMs and non-CHD-iPSC-CMs. The rMAPS was used to generate RNA-maps for the analysis of RNA-binding proteins’ (RBPs) binding sites. We used StringTie to identify and quantify the transcripts from aligned RNA-Seq reads. A quantification matrix was generated with respect to different groups by extracting the transcripts per million values from StringTie outputs. Then, this matrix was used for correlation analysis between the expression level of RBP and AS level. Finally, we validated our AS results using RNA-seq data from CHD and non-CHD patient tissue samples. We identified CHD-related AS events using CHD-iPSC-CMs and CHD samples from patients. The results showed that functional enrichment of abnormal AS in SVD and TOF was transcription factor-related. Using rMAPS, RNA-binding proteins which regulated these AS were also determined, and RBP-AS regulatory network was constructed. Overall, we identified abnormal AS in CHD-iPSC-CMs and CHD samples from patients. We predicted AS regulators in SVD and TOF, respectively. At last, we concluded that AS played a key role in the pathogenesis of CHD.
Nurses' Perceptions of the Management of Acute Pain in Emergency Departments
Authors: Hämäläinen Jenni , Kvist Tarja , Koota Elina , Kankkunen Päivi
Published: August 2022

Aim

This study aimed to describe registered nurses' perceptions of acute pain management in emergency departments.

Design

The study design was a cross-sectional survey carried out in accordance with Strengthening the Reporting of Observational Studies in Epidemiology guidelines. One hundred one nurses from 5 different emergency departments participated in the survey.

Methods

Data were analyzed using descriptive methods, nonparametric tests, and principal component analysis.

Results

Continuing education was significantly related to pain management. Nurses who had received continuing pain management education thought more often that challenges in pain management impact patients' acute pain management than those who had not received education. Nurses reported that patients received inadequate pain medication. The most used nonpharmacological methods were ice therapy and postural care. The nurses reported that music and conversation with the patient ameliorated the patients' acute pain. Nurses stated that their lack of knowledge concerning pain management and workload affected their acute pain management.

Conclusion

Study results emphasize the need to develop ongoing pain management education for registered nurses and in addition to further research of nonpharmacological alleviation method in emergency departments.
Use of MRI in Patients With Breast Tissue Expanders
Authors: Nahabedian Maurice Y. , Hammer Jason
Published: August 2022

Background:

There are no guidelines on the safety of magnetic resonance imaging (MRI) in patients with breast tissue expanders with metallic/magnetic components. This narrative review was conducted to better understand what is currently known and to identify gaps in knowledge.

Methods:

A literature search was performed using PubMed and Embase and the following terms: breast AND (imaging OR MRI OR resonance) AND expander with no date limitations. We identified 153 citations in PubMed and 154 citations in Embase.

Results:

Nineteen publications were relevant for analysis: 2 retrospective studies, 10 case reports, 6 nonclinical studies, and 1 physician survey. All studies acknowledged the risks of using MRI in patients with tissue expanders. Complications reported included breast/chest pain, discomfort, or burning sensation (46.2 percent); expander or infusion port displacement (38.5 percent); and MR signal loss (23.1 percent). Increases in expander/tissue temperature and torque occurred with MRI, causing pain or expander displacement. In some cases, no complications were reported. The retrospective studies and nonclinical analyses suggested that MRI may not create serious problems if special precautions are taken. The case reports varied in their recommendations, with some recommending avoiding MRI and others recommending exercising caution. The survey indicated that surgeons are uncertain about performing MRI in patients with tissue expanders.

Conclusions:

The evidence on whether to perform MRI in patients with tissue expanders with magnetic ports varies but underscores proceeding with caution. The risk-benefit profile for each patient must be weighed in each situation.
“Lower Nose Arterial Plexus and Implications for Safe Filler Injections”
Authors: Tansatit Tanvaa , Jitaree Benrita , Uruwan Sukanya , Rungsawang Chalermquan
Published: August 2022

Background:

The lower nose has abundant blood supply; however, nasal tip necrosis still occurs following filler injections. This study revealed the complicated pattern of the arterial supply of the lower nose.

Methods:

The arterial pattern of the lower nose was studied in 40 cadavers using conventional dissections and translucent modified Sihler’s staining.

Results:

Two arterial rings were connected in a figure of eight. The upper ring: nasal arterial circle (NAC) consisted of the lateral nasal and the subalar arteries encircling the nasal tip and alae. The lower ring: arterial plexus of the upper lip (ULP) was more important because of the contribution of the facial and superior labial arteries. This specific feature had not been mentioned elsewhere.

Conclusion:

Understanding this specific feature of the blood supply of the lower nose would be essential for aesthetic physicians to be aware and perform the appropriate techniques during the filler injection procedures in the nasal and perioral regions.
“Breast Implant-Associated Anaplastic Large Cell Lymphoma in Brazil: What Are We Missing?”
Authors: Groth Anne K , Clemens Mark W , Graf Ruth , Sebastião Ana P , Azambuja Ana P , Louveira Maria H , Urban Linei A B D , Batista Bernardo N
Published: August 2022

Background:

Breast implant-associated anaplastic large cell lymphomas (BIA-ALCL) have been diagnosed in more than 1,000 patients over thirty countries, though only a few cases have been reported in Latin America and the Caribbean to date. As the second-largest global market for breast implants with a predominance of textured-surface implants, Brazil is a major global market for cosmetic augmentations, making it unlikely that cases of BIA-ALCL are actually scarce.

Methods:

A local and voluntary registry of BIA-ALCL patients was initiated in 2018. All diagnosed BIA-ALCL patients were confirmed by the World Health Organization (WHO) criteria. Implant characteristics, disease symptoms, treatment, and oncologic outcomes were assessed.

Results:

Fourteen cases of BIA-ALCL in a Brazilian population were identified in the Paraná state. Disease-specific diagnostic tests were omitted prior to surgical intervention in 50% of patients. With additional cases from a literature review, the treatment and outcomes of 29 cases of BIA-ALCL in Brazil were assessed.

Conclusions:

Compared to other populations, our initial observations suggest that awareness of the disease by the local breast surgery community remains low and that a number of cases may still be undiagnosed. Lack of preoperative diagnostic testing compromises disease treatment, oncological outcomes, and both short- and long-term surveillance.
‘Comparison of Cromolyn Sodium, Montelukast, and Zafirlukast Prophylaxis for Capsular Contracture’
Authors: MENKÜ ÖZDEMİR Fethiye Damla , ÜSTÜN Galip Gencay , KÖSEMEHMETOĞLU Kemal , İSPİRLİ Mukaddes , BOYNUYOĞUN Etkin , UZUN Hakan
Published: August 2022

Background:

Capsular contracture is the most common complication following breast augmentation. Recently, prophylaxis studies aiming to inhibit the release of profibrotic substances to prevent capsular contracture have gained in importance. This study investigated the effects of cromolyn sodium, montelukast, and zafirlukast on capsular contracture in a rat model.

Methods:

Thirty female Wistar albino rats were randomly divided into five groups: control, sham, cromolyn sodium, montelukast, and zafirlukast. Intraperitoneal injections were administered daily to the sham (1 ml per day), cromolyn sodium (10 mg/kg per day), montelukast (10 mg/kg per day), and zafirlukast (1.25 mg/kg per day) groups one month before surgery. Mini-breast implants were then placed on the backs of the rats in each group. Injections were continued for the next 3 months. The rats were subsequently euthanized, and the capsules were harvested and assessed histopathologically. The histopathological outcomes were acute inflammation status, inflammation severity, synovial metaplasia, foreign body reaction, mast cell count, and capsular thickness.

Results:

The cromolyn sodium, montelukast, and zafirlukast groups had less acute inflammation as well as lower mean inflammation severity scores, foreign body reaction occurrence, mast cell counts, and capsular thickness than the C and S groups (p < 0.05). These parameters were better in the cromolyn sodium group than in the montelukast and zafirlukast groups (p < 0.05).

Conclusion:

Cromolyn sodium appears to inhibit capsular contracture more efficiently than montelukast and zafirlukast. This report may be a pioneer study for the prophylactic use of cromolyn sodium in capsular contracture.
Large Volume Fat Grafting: Identifying Risk Factors for Fat Necrosis
Authors: Chang Catherine S. , Lanni Michael A. , Mirzabeigi Michael N. , Bucky Louis P.
Published: August 2022

Purpose:

Fat necrosis is a well-recognized complication following autologous fat grafting. The purpose of this study is to evaluate the incidence of fat necrosis after large volume fat grafting (LVFG) and identify risk factors for fat necrosis.

Methods:

A retrospective review was performed on 83 consecutive patients who underwent LVFG (>100ccs) to the breast performed by the senior author between September 2011-May 2016. Fat necrosis was defined as palpable nodules or nodules seen on imaging.

Results:

A total of 148 breasts underwent 170 autologous fat transplantations. Indications included: 72 reconstructions after surgical therapy and 98 cosmetic augmentations. Mean age was 48 years, median graft volume of 300ccs and median length of follow-up 423 days. Overall incidence of necrosis was 32.9%, with 47.8% in previously irradiated patients. Increased incidence of necrosis was associated with increasing fat graft volumes(p=0.032, OR=1.002), increasing BMI(p=0.04, OR=1.13), and simultaneous implant exchange with fat(p=0.003). Fat grafting volumes greater than 450ccs in a single breast was also associated with an increase in fat necrosis(p=0.04). Within a group of six patients that had bilateral fat grafting with unilateral radiation, there was a significant increase in necrosis on the radiated side(p=0.015). In a cohort of non-BRAVA patients, reconstruction (compared to augmentation) was associated with fat necrosis(p=0.039).

Conclusion:

Increased rates of fat necrosis were associated with volumes greater than 450ccs, patients undergoing concurrent implant exchange with fat grafting, and fat grafting after a history of lumpectomy or mastectomy without preexpansion. Additionally, radiation may be associated with a higher rate of complications.
The Role of Social Biases, Race, and Condom Use in Willingness to Prescribe HIV Pre-exposure Prophylaxis to MSM: An Experimental, Vignette-Based Study
Authors: Bunting Samuel R. , Feinstein Brian A. , Calabrese Sarah K. , Hazra Aniruddha , Sheth Neeral K. , Wang Gary , Garber Sarah S.
Published: August 2022

Introduction:

Daily antiretroviral pre-exposure prophylaxis (PrEP) is a safe and effective method of preventing HIV. Clinicians' assumptions, biases, and judgments may impede access to PrEP. Specifically, concern that patients will engage in more condomless sex (“risk compensation”) has been cited by clinicians as a reason for not prescribing PrEP.

Methods:

In this experimental study among medical students, we systematically varied race (White or Black) and condom-use behaviors (continued-use, planned-discontinuation, or continued-nonuse) of a fictional patient (all men with multiple male sex partners). Participants indicated the patients' assumed adherence to PrEP, patients' overall HIV risk, and willingness to prescribe PrEP. Participants completed an implicit association test to detect implicit racism and measures of heterosexism and attitudes toward nonmonogamy, which were examined as moderators of patient race and condom-use effects on participants' assumptions and ultimate willingness to prescribe PrEP.

Results:

Participants (N = 600) were most willing to prescribe PrEP to the continued-nonuse patient and least willing to prescribe to the planned-discontinuation patient. No differences were identified based on patient race. The continued-nonuse (vs. continued-use) patient was perceived as less likely to adhere to PrEP, which was associated with lower willingness to prescribe. Negative attitudes toward nonmonogamy exacerbated this effect. No effects of implicit racism or explicit heterosexism were identified.

Conclusions:

Participants were least willing to prescribe PrEP to patients who planned to discontinue condom use. Patients seeking PrEP are exhibiting agency over their sexual health, and clinicians should fulfill their role in ensuring access to this primary preventative therapy. Training and curricular reform regarding PrEP are needed.
Congenital cytomegalovirus infection diagnostics and management
Authors: Pinninti Swetha , Boppana Suresh
Published: August 2022

Purpose of the review

Congenital cytomegalovirus infection (cCMV) is the most frequent congenital infection and a leading nongenetic cause of sensorineural hearing loss (SNHL) and brain disease. The purpose of this review is to highlight recent developments in the diagnosis and management of children with cCMV.

Recent Findings

Progress is being made in the efforts to identify more infants with cCMV, especially those with asymptomatic infection. Largely due to efforts by various advocacy/parent groups, a number of states in the United States and many hospital systems have implemented hearing targeted CMV screening and mandated education of pregnant women about CMV.

cCMV is an important cause of SNHL and neurologic morbidity worldwide. Early identification of infected children is critical to improve outcomes by providing timely interventions and guidance for long-term follow up. The fact that most infants with cCMV have no abnormal clinical findings, and the need to obtain samples for diagnosis within the first 2–3 weeks of life, makes it challenging to identify a majority of infants with cCMV without universal newborn CMV screening.
Critical Importance of the First Postoperative Days After Head and Neck Free Flap Reconstruction
Authors: Elmer Nicholas A. , Baltodano Pablo A. , Webster Theresa , Deng Mengying , Egleston Brian , Massada Karen , Kaplunov Briana , Brebion Rohan , Araya Sthefano , Patel Sameer A.
Published: August 2022

Background

Head and neck free flaps remain associated with considerable rates of take-back and prolonged hospital length of stay. However, there have been no studies on a national level benchmarking the timeline and predictors of head and neck free flap take-back.

Methods

Patients undergoing head and neck free flap reconstruction from the American College of Surgeons National Surgical Quality Improvement Program 2012–2019 database were analyzed to determine the rates of take-back. Timing and rates of unplanned head and neck free flap take-backs were stratified by tissue type and postoperative day (POD) over the first month. Weibull survival models were used to compare rates of take-backs among time intervals. Multivariable logistic regression was used to identify the independent predictors of take-back.

Results

Three thousand nine hundred six head and neck free flaps were analyzed. The mean daily proportion of patients experiencing take-back during PODs 0 to 1 was 0.95%; this dropped significantly to a mean daily proportion of 0.54% during POD 2 (P < 0.01). In addition, there were significant drops in take-back when comparing POD 2 (0.54%) to POD 3 (0.26%) and also when comparing POD 4 (0.20%) with PODs 5 to 30 (0.032% per day) (P < 0.05). The soft tissue and osseous flap populations demonstrated a similar trend in unplanned take-back.

Conclusion

This is the first national study to specifically analyze the timing of take-back in the head and neck reconstruction population. These data highlight the importance of flap monitoring during the first 5 PODs, with ERAS pathway optimization aiming for discharge by the end of the first postoperative week.
Dorsal Augmentation With the Dorsal Extension Spreader Graft
Authors: Phillips Sarah J. , Carney Martin J. , Jazayeri Hossein E. , Reategui Alvaro , Moores Craig , Prassinos Alexandre J. , Lopez Joseph , Steinbacher Derek M.
Published: August 2022

Spreader grafts traditionally are used to improve airflow through opening the internal nasal valve, as well as enhance the cosmetic appearance of the nose. The graft’s versatility proves useful in surgical correction of several nasal profiles by enhancing dorsal aesthetic lines and by maintenance of the nasal pyramid at midline. The authors describe a modified spreader graft that adds an additional benefit of dorsal augmentation in patients with underprojected or saddle noses. This technique utilizes harvested septal cartilage and fixation of the graft that extends beyond the septal and upper lateral cartilage dorsal border to improve nasal dorsum height. Patients who received this operative technique by the senior author were identified and their operative courses and surgical outcomes were analyzed. Case examples are provided to illustrate indications and outcomes. This grafting technique allows for improved functionality, defined dorsal aesthetic lines, changes in nasal width, and a more balanced profile in patients with underprojected noses.
Development of the Sm14/GLA-SE - schistosomiasis vaccine candidate: An open, not placebo-controlled, standardized dose immunization phase Ib clinical trial targeting healthy young women
Authors: Santini-Oliveira Marilia , Pinto Patrícia Machado , dos Santos Tatiane , Vilar Monica Magno , Grinsztejn Beatriz , Veloso Valdilea , Paes-de-Almeida Elan C. , Amaral Maria A. Z. , Ramos Celso R. , Marroquin-Quelopana Miryam , Coler Rhea , Reed Steven , Ciol Marcia , Savino Wilson , de Carvalho Parra Juçara , dos Santos Almeida Marília Sirianni , Tendler Miriam
Published: August 2022

We report the successful closure of Phase I clinical trials of the Schistosoma mansoni 14 kDa fatty acid-binding protein (Sm14) + glucopyranosyl lipid A in squalene emulsion (GLA-SE) vaccine candidate against human Schistosomiasis, comprising Phases Ia and Ib. Shown here are the results of Phase Ib, an open, not placebo-controlled, standardized-dose immunization trial, involving 10 healthy 18-49 years old women submitted to the same clinical protocol and the same batch of cGMP Sm14+GLA-SE used in Phase Ia, which was one on men. Fifty µg Sm14 protein plus 10 µg GLA-SE per dose were given intramuscularly thrice at 30-day intervals. Participants were assessed clinically, biochemically, and immunologically for up to 120 days. In preambular experiments involving vaccinated pregnant female rabbits, we did not find any toxicological feature either in offspring or mothers, as ascertained by histopathology and biochemical parameters. The vaccine induced adaptive immunity in the animals, as defined by the detection of anti-Sm14 antibodies in the sera. In women, neither serious nor light adverse events were observed. Sm14+GLA-SE vaccination induced high titers of anti-Sm14 serum IgG antibody production. Total anti-IgG serum levels remained high 120 days after the first vaccination dose. Significant increases in Sm14-specific total IgG, IgG1, and IgG3 were observed 30 days after the first vaccination, with specific IgG2 and IgG4 after 60 days. Sm14+GLA-SE vaccination also elicited robust cytokine responses with increased TNFα, IFNγ, and IL-2 profiles in all female vaccinees on days 90 and 120.

As in Phase Ia, the Sm14+GLA-SE vaccine was shown to be strongly immunogenic and well tolerated. The completion of Phase I clinical trials performed to the highest standards set by the Good Clinical Research Practice (GCP) standards and pre-clinical data in pregnant rabbits enabled the vaccine candidate to proceed to Phase II clinical trials in endemic areas.

Study registration ID

NCT01154049 at http://www.clinicaltrials.gov. Brazilian Registry of Clinical Trials UTN: U1111-1135-6815
Myosin-X recruits lamellipodin to filopodia tips
Authors: Miihkinen Mitro , Popović Ana , Ghimire Sujan , Saup Rafael , Grönloh Max L.B. , Ball Neil J. , Goult Benjamin T. , Ivaska Johanna , Jacquemet Guillaume
Published: August 2022

Myosin-X (MYO10), a molecular motor localizing to filopodia, is thought to transport various cargo to filopodia tips, modulating filopodia function. Yet, only a few MYO10 cargoes have been described. Here, using GFP-Trap and BioID approaches combined with mass spectrometry, we identified lamellipodin (RAPH1) as a novel MYO10 cargo. We report that the FERM domain of MYO10 is required for RAPH1 localization and accumulation at filopodia tips. Previous studies have mapped RAPH1 interaction with adhesome components to its talinbinding and Ras-association domains. Surprisingly, we find that the RAPH1 MYO10-binding site is not within these domains. Instead, it comprises an area with previously unknown functions. Functionally, RAPH1 supports MYO10 filopodia formation and stability but is not involved in regulating integrin activity in filopodia tips. Taken together, our data indicate a feed-forward mechanism whereby MYO10 filopodia are positively regulated by MYO10-mediated transport of RAPH1 to the filopodium tip.
Uptake of health insurance in Malawi in 2019-2020: Evidence from the Multiple Indicator Cluster Survey
Authors: Ng’ambi Wingston Felix , Chigaru Farai , Mwase Takondwa , Banda Agnes Jack , Mfutso-Bengo Joseph
Published: August 2022

Introduction

Although countries in sub-Sahara Africa (SSA) show progress in implementing various forms of health insurance, there is a dearth of information regarding health insurance in settings like Malawi. Therefore, we conducted this study to determine the uptake of health insurance and describe some of the factors associated with the prevailing uptake of health insurance in Malawi using the 2019-20 Multiple Indicator Cluster Survey (MICS).

Methods

This was a secondary analysis of the 2019-20 MICS data. Data were analysed using frequencies and weighted percentages in Stata v.17. Furthermore, since the number of persons with health insurance is very small, we were unable to perform multivariate analysis.

Results

A total of 205 (1%) of the 31259 had health insurance in Malawi in 2019-20. Of the 205 individuals that owned health insurance, 118 (47%) had health insurance through their employers while 39 (16%) had health insurance through mutual health organization or ccommunity-based. Men had higher uptake of health insurance than the women. The residents from urban areas were more likely to have a health insurance than those in the rural areas. Persons with media exposure were more likely to own health insurance as compared to their counterparts. There was increasing trend in the uptake of health insurance by wealth of the individual with the poorest being less likely to have health insurance compared to the richest. The persons with no education being least likely to have a health insurance while those with tertiary education were most likely to have health insurance.

Conclusion

The uptake of health insurance in Malawi was extremely low. In order to increase the uptake of health insurance, there is need to increase insurance coverage amongst those in formal employment, consider minimizing the geographic, economic and demographic barriers in accessing the health insurance.
Relative contributions of vaccination and previous infection to population-level SARS-CoV-2 immunity over time: a simulation modelling study
Authors: Szanyi Joshua , Wilson Tim , Andrabi Hassan , Blakely Tony
Published: August 2022

Population-level immunity to SARS-CoV-2 directly impacts the incidence of COVID-19 morbidity and mortality. Understanding how this immunity is likely to change over time in the context of future vaccination schedules and emerging SARS-CoV-2 variants is critical to inform pandemic policy. This study simulates population-level COVID-19 immunity (including relative contributions of vaccination and previous infection) in Victoria, Australia over 18 months using an agent-based model and logistic regression equations that predict immunity and waning following vaccination and/or infection. Previous infection was found to drive most immunity against infection even with ongoing regular vaccination, however a greater proportion of overall immunity against mortality was accounted for by vaccination. Although previous infection appears to be driving a substantial component of population-level COVID-19 immunity currently, improved vaccines providing longer lasting (and better sterilizing) immunity are likely to be a critical component of the future pandemic response given the risks associated with SARS-CoV-2 infection.
The Vitality Project: A Randomized Control Trial Comparing Effects of Qigong and Exercise/Nutrition Training on Fatigue, Emotional Health, and Stress in Fatigued Female Cancer Survivors
Authors: Zimmerman Chloe S. , Temereanca Simona , Daniels Dylan , Penner Cooper , Cannonier Tariq , Jones Stephanie R. , Kerr Catherine
Published: August 2022

Cancer-related fatigue (CRF) is a common and burdensome, often long term side effect of cancer and its treatment. Many non-pharmacological treatments have been investigated as possible CRF therapies, including exercise, nutrition, health/psycho-education, and mind-body therapies. However, studies directly comparing the efficacy of these treatments are lacking. To fill this gap, we conducted a parallel single blind randomized control trial with women with CRF to directly compare the effects of Qigong (a form of mind-body intervention) (n=11) to an intervention that combined strength and aerobic exercise, plant-based nutrition and health/psycho-education (n=13). This design was chosen to determine the comparative efficacy of two non-pharmacologic interventions, with different physical demand intensity, in reducing the primary outcome measure of self-reported fatigue (FACIT ‘Additional Concerns’ subscale). Both interventions showed a mean fatigue improvement of more than double the pre-established minimal clinically important difference of three (Qigong: 7.068 +/- 10.30, Exercise/Nutrition: 8.846 +/- 12.001). Mixed effects ANOVA analysis of group x time interactions revealed a significant main effect of time, such that both groups significantly improved fatigue from pre- to post treatment (F(1,22)=11.898, p=.002, generalized eta squared effect size=.116) There was no significant difference between fatigue improvement between groups (independent samples t-test: p=.70), suggesting a potential equivalence or non-inferiority of interventions, which we could not definitively establish due to our small sample size. This study provides evidence from a small sample that Qigong improves fatigue similarly to standard exercise-nutrition. Qigong additionally significantly improved secondary measures of mood, emotion regulation, and stress, while exercise/nutrition significantly improved secondary measures of sleep/fatigue. These findings provide preliminary evidence for divergent mechanisms of fatigue improvement across interventions, with Qigong providing a gentler and lower-intensity alternative to exercise/nutrition. This clinical trial was registered with clinicaltrials.gov.
Genetic analysis of protein efficiency and its association with performance and meat quality traits under a protein-restricted diet
Authors: Ewaoluwagbemiga Esther Oluwada , Bee Giuseppe , Kasper Claudia
Published: August 2022

Background

An essential component in the development of a sustainable pig production is the reduction of nitrogen excretion in fattening pigs. Pig feeds typically contain high levels of dietary crude protein, and due to incomplete conversion to muscle tissue, excess nitrogen is excreted, resulting in environmental problems such as nitrate pollution and greenhouse gas emissions. Therefore, improving protein efficiency (PE), i.e., the proportion of dietary protein that remains in the carcass, is desirable. This study aimed to estimate the heritability (h2) of PE and its genetic correlations with phosphorus efficiency, three performance, seven meat quality and two carcass quality traits when pigs were fed a 20% protein-restricted diet, using a total of 1,071 Swiss Large White pigs. To determine PE, the intake of feed with known nutrient content was accurately recorded for each pig and the nitrogen and phosphorus content of the carcass was determined using dual-energy X-ray absorptiometry.

Results

We found an average PE of 0.39 ± 0.04 and a heritability of 0.60 ± 0.08. PE showed a high genetic correlation with phosphorus efficiency (0.68 ± 0.08), moderate genetic correlations with feed conversion ratio (−0.53 ± 0.13) and average daily feed intake (−0.42 ± 0.13), and very little to no genetic correlation with average daily gain (−0.06 ± 0.16). While PE has favourable genetic correlations with the performance traits and some meat quality traits, there is a potentially unfavourable relationship of PE with meat colour (redness [rg= −0.26 ± 0.17]; yellowness [rg= −0.30 ± 0.18]) and intra-muscular fat (IMF; rg= −0.39 ± 0.15). Feed conversion ratio (FCR) also showed unfavourable genetic correlations with meat lightness, redness yellowness, IMF and cooking loss.

Conclusions

PE is heritable and can be considered in breeding to reduce the environmental impact of pig production. We found no strong negative influence on meat quality traits (except for meat color and IMF), and there is the potential for indirectly selecting for improved phosphorus efficiency. Selecting nutrient efficiencies might be a more suitable strategy to reduce nitrogen pollution from manure than focusing on FCR because the latter also shows genetic antagonism with some meat quality traits in our population.
Characterization of three-dimensional bone-like tissue growth and organization under influence of curvature and directional fluid flow
Authors: de Wildt Bregje W.M. , Zhao Feihu , Lauwers Iris , van Rietbergen Bert , Ito Keita , Hofmann Sandra
Published: August 2022

The transition in the field of bone tissue engineering from bone regeneration to three-dimensional in vitro models has come with the challenge of recreating a dense and anisotropic bone-like extracellular matrix with cell culture. The creation of such an organized bone-like extracellular matrix has received little attention thus far. Although the mechanism by which bone extracellular matrix gains its structure is not fully understood, curvature (especially concavities), mechanical loading due to deformations or directional fluid flow, and osteocyte signaling have been identified as potential contributors. Here, guided by computational simulations, we evaluated three-dimensional cell and bone-like tissue growth and organization in a concave channel with and without directional fluid flow stimulation. Human bone-marrow derived mesenchymal stromal cells were seeded on donut-shaped silk fibroin scaffolds and stimulated to undergo osteogenic differentiation for 42 days statically or in a flow perfusion bioreactor. Constructs were investigated for cell distribution, and tissue growth and organization on day 14, 28, and 42. As a result, directional fluid flow was able to improve bone-like tissue growth but not organization. After 28 days of culture, when osteogenic differentiation was likely accomplished, cells tended to have a small preference for orientation in the tangential (i.e., circumferential) direction of the channel. Based on our results, we suggest that three-dimensional bone-like tissue anisotropy might be guided by curvature, while extracellular matrix production can be increased through the application of fluid shear stress. With this study, an initial attempt in three-dimensions was made to improve the resemblance of in vitro produced bone-like extracellular matrix to the physiological bone extracellular matrix.
Rational optimization of a transcription factor activation domain inhibitor
Authors: Basu Shaon , Martínez-Cristóbal Paula , Pesarrodona Mireia , Frigolé-Vivas Marta , Lewis Michael , Szulc Elzbieta , Bañuelos C. Adriana , Sánchez-Zarzalejo Carolina , Bielskutė Stasė , Zhu Jiaqi , Pombo-García Karina , Garcia-Cabau Carla , Batlle Cristina , Mateos Borja , Biesaga Mateusz , Escobedo Albert , Bardia Lídia , Verdaguer Xavier , Ruffoni Alessandro , Mawji Nasrin R. , Wang Jun , Tam Teresa , Brun-Heath Isabelle , Ventura Salvador , Meierhofer David , García Jesús , Robustelli Paul , Stracker Travis H. , Sadar Marianne D. , Riera Antoni , Hnisz Denes , Salvatella Xavier
Published: August 2022

Transcription factors are among the most attractive therapeutic targets but are considered largely undruggable due to the intrinsically disordered nature of their activation domains. Here we show that the aromatic character of the activation domain of the androgen receptor, a therapeutic target for castration resistant prostate cancer, is key for its activity as a transcription factor by allowing it to partition into transcriptional condensates. Based on this knowledge we optimized the structure of a small molecule inhibitor, previously identified by phenotypic screening, that targets a specific transactivation unit within the domain that is partially folded and rich in aromatic residues. The optimized compounds had more affinity for their target, inhibited androgen receptor-dependent transcriptional programs, and had antitumorigenic effect in models of castration-resistant prostate cancer in cells andin vivo. These results establish a generalizable framework to target small molecules to the activation domains of oncogenic transcription factors and other disease-associated proteins with therapeutic intent.
The Rab GTPase Ypt1p governs the activation of Unfolded Protein Response (UPR) in Saccharomyces cerevisiae by promoting the preferential nuclear degradation of pre-HAC1 mRNA
Authors: Paira Sunirmal , Chakraborty Anish , Das Biswadip
Published: August 2022

Induction of unfolded protein response (UPR) involves activation of transcription factor Hac1p that facilitates the transactivation of genes encoding ER-chaperones. Hac1p is encoded by HAC1 pre-mRNA harboring an intron and a bipartite element (BE) at its 3′-UTR. This precursor RNA undergoes a reversible and differential intra-nuclear mRNA decay by the nuclear exosome/CTEXT at various phases of UPR. In this investigation, using a combination of genetic, and biochemical approach, the Rab-GTPase Ypt1p is demonstrated to control UPR signaling dynamics. Regulation of UPR by Ypt1p relies on its characteristic nuclear localization in absence of ER-stress resulting in its strong association with pre-HAC1 mRNA at its 3′-UTR that promotes sequential recruitments of Nrd1-Nab3p-Sen1p (NNS) complex → CTEXT → the nuclear exosome onto the pre-HAC1 mRNA that is accompanied by its rapid and selective nuclear decay. This accelerated 3′→5′ mRNA decay produces a pre-HAC1 mRNA pool lacking the functional BE thus causing its inefficient targeting to Ire1p foci leading to their diminished splicing and translation. ER stress triggers a rapid relocalization of Ypt1p to the cytoplasm with its consequent dissociation from pre-HAC1 mRNA thereby causing a decreased recruitment of NNS/exosome/CTEXT to precursor HAC1 RNA leading to its diminished 3′→5′ degradation by the exosome. This diminished decay produces an increased abundance of pre-HAC1 mRNA population with intact functional BE leading to its enhanced recruitment to Ire1p foci that is followed by its increased splicing and translation. This enhanced translation produces a huge burst of Hac1p that rapidly transactivates the genes encoding ER-chaperones.
Network analysis with either Illumina or MinION reveals that detecting vertebrate species requires metabarcoding of iDNA from a diverse fly community
Authors: Srivathsan Amrita , Ker Rebecca Loh , Ong Elliott James , Lee Leshon , Ang Yuchen , Kutty Sujatha Narayanan , Meier Rudolf
Published: August 2022

Metabarcoding of vertebrate DNA obtained from invertebrates (iDNA) has been used to survey vertebrate communities, but we here show that it can also be used to study species interactions between invertebrates and vertebrates in a spatial context. We sampled the dung and carrion fly community of a swamp forest remnant along a disturbance gradient (10 sites: 80-310m from a road). Approximately, 60% of the baited 407 flies yield 294 vertebrate identifications based on two COI fragments and 16S sequenced with Illumina and/or MinION. A bipartite network analysis finds no specialization in the interaction between flies and vertebrate species, but a spatial analysis revealed that surprisingly 18 of the 20 vertebrate species can be detected within 150m of the road. We show that the fly community sourced for iDNA was unexpectedly rich (24 species, 3 families) and carried DNA for mammals, birds, and reptiles. They included common and rare ground-dwelling (e.g., wild boar, Sunda pangolin), and arboreal species (e.g., long-tailed macaque, Raffles’ banded langur) as well as small bodied vertebrates (skinks, rats). All of our results were obtained with a new, greatly simplified iDNA protocol that eliminates DNA extraction by obtaining template directly through dissolving feces and regurgitates from individual flies with water. Lastly, we show that MinION- and Illumina-based metabarcoding yield similar results. Overall, flies from several families (calliphorids, muscids and sarcophagids) should be used in iDNA surveys because we show that uncommon fly species carry the signal for several vertebrate species that are otherwise difficult to detect with iDNA.
Pan-flavivirus analysis reveals sfRNA-independent, 3’UTR-biased siRNA production from an Insect-Specific Flavivirus
Authors: Besson Benoit , Overheul Gijs J. , Wolfinger Michael T. , Junglen Sandra , van Rij Ronald P.
Published: August 2022

RNA interference (RNAi) plays an essential role in mosquito antiviral immunity, but it is not known whether viral siRNA profiles differ between mosquito-borne and mosquito-specific viruses. A pan-Orthoflavivirus analysis inAedes albopictuscells revealed that viral siRNAs were evenly distributed across the viral genome of most representatives of theFlavivirusgenus. In contrast, siRNA production was biased towards the 3’ untranslated region (UTR) of the genomes of classical insect-specific flaviviruses (cISF), which was most pronounced for Kamiti River virus (KRV), a virus with a unique, 1.2 kb long 3’ UTR. KRV-derived siRNAs were produced in high quantities and almost exclusively mapped to the 3’ UTR. We mapped the 5’ end of KRV subgenomic flavivirus RNAs (sfRNAs), products of the 5’-3’ exoribonuclease XRN1/Pacman stalling on secondary RNA structures in the 3’ UTR of the viral genome. We found that KRV produces high copy numbers of a long, 1017 nt sfRNA1 and a short, 421 nt sfRNA2, corresponding to two predicted XRN1-resistant elements. Expression of both sfRNA1 and sfRNA2 was reduced inPacmandeficientAedes albopictuscells, however, this did not correlate with a shift in viral siRNA profiles. We suggest that cISFs and particularly KRV developed a unique mechanism to produce high amounts of siRNAs as a decoy for the antiviral RNAi response in an sfRNA-independent manner.

IMPORTANCE

TheFlavivirusgenus contains diverse mosquito viruses ranging from insect-specific viruses circulating exclusively in mosquito populations to mosquito-borne viruses that cause disease in humans and animals. Studying the mechanisms of virus replication and antiviral immunity in mosquitoes is important to understand arbovirus transmission and may inform the development of disease control strategies. In insects, RNA interference (RNAi) provides broad antiviral activity and constitutes a major immune response against viruses. Comparing diverse members of theFlavivirusgenus, we found that all flaviviruses are targeted by RNAi. However, the insect-specific Kamiti River virus was unique in that small interfering RNAs are highly skewed towards its uniquely long 3’ untranslated region. These results suggest that mosquito-specific viruses have evolved unique mechanisms for genome replication and immune evasion.
Mental Health and Stress Level of Ukrainians Seeking Psychological Help Online
Authors: Asanov Noha Anastasiya-Mariya , Asanov Igor , Buenstorf Guido
Published: August 2022

We screen the mental well-being and psychological distress of 1165 refugees, migrants, internally displaced, and non-displaced people from Ukraine who seek psychological help online in Ukraine and across 24 countries of the European Union. We see that more than half of the respondents exhibit low levels of mental well-being and high psychological distress, with 81% being at risk of depression and 57% having severe psychological distress. Refugees and internally displaced people in our sample show a particularly high risk of depression and severe psychological distress. Nevertheless, the majority of Ukrainians seeking psychological help still work, study, or volunteer, and those who do have relatively alleviated mental levels of well-being.
Survival of mineral-bound peptides into the Miocene
Authors: Demarchi Beatrice , Mackie Meaghan , Li Ziheng , Deng Tao , Collins Matthew J. , Clarke Julia
Published: August 2022

The oldest authenticated peptide sequences to date were reported in 2016 from 3.8 Ma old ostrich eggshell (OES) from the site of Laetoli, Tanzania (Demarchi et al., 2016). Here we demonstrate survival of the same sequences in 6.5-9 Ma OES recovered from a palaeosteppe setting in northwestern China. The eggshell is thicker than those observed in extant species and consistent with the Liushu Struthio sp. ootaxon. These findings push the preservation of ancient proteins back to the Miocene and highlight their potential for paleontology, paleoecology and evolutionary biology.