bluuebunny/crossref_metadata_2025 huggingface dataset:
Pheniqs 2.0: accurate, high-performance Bayesian decoding and confidence estimation for combinatorial barcode indexing
Authors: Galanti Lior , Shasha Dennis , Gunsalus Kristin C.
Published: July 2021

Background

Systems biology increasingly relies on deep sequencing with combinatorial index tags to associate biological sequences with their sample, cell, or molecule of origin. Accurate data interpretation depends on the ability to classify sequences based on correct decoding of these combinatorial barcodes. The probability of correct decoding is influenced by both sequence quality and the number and arrangement of barcodes. The rising complexity of experimental designs calls for a probability model that accounts for both sequencing errors and random noise, generalizes to multiple combinatorial tags, and can handle any barcoding scheme. The needs for reproducibility and community benchmark standards demand a peer-reviewed tool that preserves decoding quality scores and provides tunable control over classification confidence that balances precision and recall. Moreover, continuous improvements in sequencing throughput require a fast, parallelized and scalable implementation.

Results and discussion

We developed a flexible, robustly engineered software that performs probabilistic decoding and supports arbitrarily complex barcoding designs. Pheniqs computes the full posterior decoding error probability of observed barcodes by consulting basecalling quality scores and prior distributions, and reports sequences and confidence scores in Sequence Alignment/Map (SAM) fields. The product of posteriors for multiple independent barcodes provides an overall confidence score for each read. Pheniqs achieves greater accuracy than minimum edit distance or simple maximum likelihood estimation, and it scales linearly with core count to enable the classification of > 11 billion reads in 1 h 15 m using < 50 megabytes of memory. Pheniqs has been in production use for seven years in our genomics core facility.

Conclusion

We introduce a computationally efficient software that implements both probabilistic and minimum distance decoders and show that decoding barcodes using posterior probabilities is more accurate than available methods. Pheniqs allows fine-tuning of decoding sensitivity using intuitive confidence thresholds and is extensible with alternative decoders and new error models. Any arbitrary arrangement of barcodes is easily configured, enabling computation of combinatorial confidence scores for any barcoding strategy. An optimized multithreaded implementation assures that Pheniqs is faster and scales better with complex barcode sets than existing tools. Support for POSIX streams and multiple sequencing formats enables easy integration with automated analysis pipelines.
De novo transcriptome analysis of white teak (Gmelina arborea Roxb) wood reveals critical genes involved in xylem development and secondary metabolism
Authors: Yaya Lancheros Mary Luz , Rai Krishan Mohan , Balasubramanian Vimal Kumar , Dampanaboina Lavanya , Mendu Venugopal , Terán Wilson
Published: July 2021

Background

Gmelina arborea Roxb is a fast-growing tree species of commercial importance for tropical countries due to multiple industrial uses of its wood. Wood is primarily composed of thick secondary cell walls of xylem cells which imparts the strength to the wood. Identification of the genes involved in the secondary cell wall biosynthesis as well as their cognate regulators is crucial to understand how the production of wood occurs and serves as a starting point for developing breeding strategies to produce varieties with improved wood quality, better paper pulping or new potential uses such as biofuel production.

In order to gain knowledge on the molecular mechanisms and gene regulation related with wood development in white teak, a de novo sequencing and transcriptome assembly approach was used employing secondary cell wall synthesizing cells from young white teak trees.

Results

For generation of transcriptome, RNA-seq reads were assembled into 110,992 transcripts and 49,364 genes were functionally annotated using plant databases; 5071 GO terms and 25,460 SSR markers were identified within xylem transcripts and 10,256 unigenes were assigned to KEGG database in 130 pathways. Among transcription factor families, C2H2, C3H, bLHLH and MYB were the most represented in xylem. Differential gene expression analysis using leaves as a reference was carried out and a total of 20,954 differentially expressed genes were identified including monolignol biosynthetic pathway genes. The differential expression of selected genes (4CL, COMT, CCoAOMT, CCR and NST1) was validated using qPCR.

Conclusions

We report the very first de novo transcriptome of xylem-related genes in this tropical timber species of commercial importance and constitutes a valuable extension of the publicly available transcriptomic resource aimed at fostering both basic and breeding studies.
Modelling segmental duplications in the human genome
Authors: Abdullaev Eldar T. , Umarova Iren R. , Arndt Peter F.
Published: July 2021

Background

Segmental duplications (SDs) are long DNA sequences that are repeated in a genome and have high sequence identity. In contrast to repetitive elements they are often unique and only sometimes have multiple copies in a genome. There are several well-studied mechanisms responsible for segmental duplications: non-allelic homologous recombination, non-homologous end joining and replication slippage. Such duplications play an important role in evolution, however, we do not have a full understanding of the dynamic properties of the duplication process.

Results

We study segmental duplications through a graph representation where nodes represent genomic regions and edges represent duplications between them. The resulting network (the SD network) is quite complex and has distinct features which allow us to make inference on the evolution of segmantal duplications. We come up with the network growth model that explains features of the SD network thus giving us insights on dynamics of segmental duplications in the human genome. Based on our analysis of genomes of other species the network growth model seems to be applicable for multiple mammalian genomes.

Conclusions

Our analysis suggests that duplication rates of genomic loci grow linearly with the number of copies of a duplicated region. Several scenarios explaining such a preferential duplication rates were suggested.
Female-specific genomic regions and molecular sex identification of the clearhead icefish (Protosalanx hyalocranius)
Authors: Xing Teng-Fei , Li Yu-Long , Liu Jin-Xian
Published: July 2021

Background

The clearhead icefish,Protosalanx hyalocranius, is an economically important fishery species in China. Since 1980s,P. hyalocraniuswas widely introduced into lakes and reservoirs of northern China for aquaculture. However, the lack of a rapid and cost-effective sex identification method based on sex specific genetic markers has hindered study on sex determination mechanisms and breeding applications.

Results

Female-specific genomic regions were discovered by comparing whole genome re-sequencing data of both males and females. Two female-specific genomic regions larger than 50 bp were identified, and one (598 bp) contained a putative FOXI gene, which was paralogous to another FOXI gene with sex-associated SNPs. The two FOXI sequences displayed significant length difference with nine deletions of total length of 230 bp. This deletion-type structural variation could be easily and efficiently detected by traditional PCR and agarose gel electrophoresis with one 569 bp band for males and two bands (569 and 339 bp) for females, which were validated in 50 females and 40 males with known phenotypic sexes.

Conclusions

The results provided structural genomic evidence for the ZZ/ZW sex determination system inP. hyalocraniusdiscovered in our previous study with association analysis of SNPs. Moreover, the female-specific markers and rapid and cost-effective PCR-based genetic sex identification method should have applications in further studies of sex determination mechanism for this species.
Natural variation in wild tomato trichomes; selecting metabolites that contribute to insect resistance using a random forest approach
Authors: Kortbeek Ruy W. J. , Galland Marc D. , Muras Aleksandra , van der Kloet Frans M. , André Bart , Heilijgers Maurice , van Hijum Sacha A. F. T. , Haring Michel A. , Schuurink Robert C. , Bleeker Petra M.
Published: July 2021

Background

Plant-produced specialised metabolites are a powerful part of a plant’s first line of defence against herbivorous insects, bacteria and fungi. Wild ancestors of present-day cultivated tomato produce a plethora of acylsugars in their type-I/IV trichomes and volatiles in their type-VI trichomes that have a potential role in plant resistance against insects. However, metabolic profiles are often complex mixtures making identification of the functionally interesting metabolites challenging. Here, we aimed to identify specialised metabolites from a wide range of wild tomato genotypes that could explain resistance to vector insects whitefly (Bemisia tabaci) and Western flower thrips (Frankliniella occidentalis). We evaluated plant resistance,determined trichome density and obtained metabolite profiles of the glandular trichomes by LC-MS (acylsugars) and GC-MS (volatiles). Using a customised Random Forest learning algorithm, we determined the contribution of specific specialised metabolites to the resistance phenotypes observed.

Results

The selected wild tomato accessions showed different levels of resistance to both whiteflies and thrips. Accessions resistant to one insect can be susceptible to another. Glandular trichome density is not necessarily a good predictor for plant resistance although the density of type-I/IV trichomes, related to the production of acylsugars, appears to correlate with whitefly resistance. For type VI-trichomes, however, it seems resistance is determined by the specific content of the glands. There is a strong qualitative and quantitative variation in the metabolite profiles between different accessions, even when they are from the same species. Out of 76 acylsugars found, the random forest algorithm linked two acylsugars (S3:15 and S3:21) to whitefly resistance, but none to thrips resistance. Out of 86 volatiles detected, the sesquiterpene α-humulene was linked to whitefly susceptible accessions instead. The algorithm did not link any specific metabolite to resistance against thrips, but monoterpenes α-phellandrene, α-terpinene and β-phellandrene/D-limonene were significantly associated with susceptible tomato accessions.

Conclusions

Whiteflies and thrips are distinctly targeted by certain specialised metabolites found in wild tomatoes. The machine learning approach presented helped to identify features with efficacy toward the insect species studied. These acylsugar metabolites can be targets for breeding efforts towards the selection of insect-resistant cultivars.
Reprogramming of the wheat transcriptome in response to infection with Claviceps purpurea, the causal agent of ergot
Authors: Tente Eleni , Ereful Nelzo , Rodriguez Anyela Camargo , Grant Paul , O’Sullivan Donal M. , Boyd Lesley A. , Gordon Anna
Published: July 2021

Background

Ergot, caused by the fungal pathogenClaviceps purpurea, infects the female flowers of a range of cereal crops, including wheat. To understand the interaction betweenC. purpureaand hexaploid wheat we undertook an extensive examination of the reprogramming of the wheat transcriptome in response toC. purpureainfection through floral tissues (i.e. the stigma, transmitting and base ovule tissues of the ovary) and over time.

Results

C. purpureahyphae were observed to have grown into and down the stigma at 24 h (H) after inoculation. By 48H hyphae had grown through the transmitting tissue into the base, while by 72H hyphae had surrounded the ovule. By 5 days (D) the ovule had been replaced by fungal tissue. Differential gene expression was first observed at 1H in the stigma tissue. Many of the wheat genes differentially transcribed in response toC. purpureainfection were associated with plant hormones and included the ethylene (ET), auxin, cytokinin, gibberellic acid (GA), salicylic acid and jasmonic acid (JA) biosynthetic and signaling pathways. Hormone-associated genes were first detected in the stigma and base tissues at 24H, but not in the transmitting tissue. Genes associated with GA and JA pathways were seen in the stigma at 24H, while JA and ET-associated genes were identified in the base at 24H. In addition, several defence-related genes were differential expressed in response toC. purpureainfection, including antifungal proteins, endocytosis/exocytosis-related proteins, NBS-LRR class proteins, genes involved in programmed cell death, receptor protein kinases and transcription factors. Of particular interest was the identification of differential expression of wheat genes in the base tissue well before the appearance of fungal hyphae, suggesting that a mobile signal, either pathogen or plant-derived, is delivered to the base prior to colonisation.

Conclusions

Multiple host hormone biosynthesis and signalling pathways were significantly perturbed from an early stage in the wheat –C. purpureainteraction. Differential gene expression at the base of the ovary, ahead of arrival of the pathogen, indicated the potential presence of a long-distance signal modifying host gene expression.
Mucormycosis causing massive lower gastrointestinal bleeding: a case report
Authors: Chiang Ting-Hsuan , Lee Yi-Wei , Tan Jui-Hsiang , Kao Chih-Chin , Chang Chun-Chao , Fang Kuan-Chieh
Published: July 2021

Background

Lower gastrointestinal bleeding (LGIB) is very common in the hospital setting. Most bleedings stop spontaneously, but rare infectious causes of LGIB may lead to rapid and serious complications if left untreated and are sometimes very difficult to diagnose preoperatively.

Case presentation

We described a young man with poorly controlled Type I diabetes mellitus and chronic alcohol abuse who presented with acute altered mental status. During his hospitalization for treatment of diabetic ketoacidosis, acute renal failure, and sepsis, he suddenly developed massive hematochezia of 1500 mL. Colonoscopy was performed and a deep ulcer covered with mucus with peripheral elevation was noted at the transverse colon. Biopsy of the ulcer later revealed nonpigmented, wide (5–20 µm in diameter), thin-walled, ribbon-like hyphae with few septations and right-angle branching suggestive of mucormycosis demonstrated by Periodic acid–Schiff stain. He received 2 months of antifungal treatment. Follow up colonoscopy post-treatment was normal with no ulcer visualized.

Conclusions

Early diagnosis and treatment of gastrointestinal (GI) mucormycosis infection is critical but can be challenging, especially in the setting of massive hematochezia. Therefore, clinical awareness for immunocompromised patients and prompt antifungal prophylaxis in cases with high suspicion of infection are essential.
Systematic geriatric assessment for older patients with frailty in the emergency department: a randomised controlled trial
Authors: Alakare Janne , Kemp Kirsi , Strandberg Timo , Castrén Maaret , Jakovljević Dimitrije , Tolonen Jukka , Harjola Veli-Pekka
Published: July 2021

Background

Comprehensive geriatric assessment provided in hospital wards in frail patients admitted to hospital has been shown to reduce mortality and increase the likelihood of living at home later. Systematic geriatric assessment provided in emergency departments (ED) may be effective for reducing days in hospital and unnecessary hospital admissions, but this has not yet been proven in randomised trials.

Methods

We conducted a single-centre, randomised controlled trial with a parallel-group, superiority design in an academic hospital ED.

ED patients aged ≥ 75 years who were frail, or at risk of frailty, as defined by the Clinical Frailty Scale, were included in the trial. Patients were recruited during the period between December 11, 2018 and June 7, 2019, and followed up for 365 days.

For the intervention group, systematic geriatric assessment was added to their standard care in the ED, whereas the control group received standard care only.

The primary outcome was cumulative hospital stay during 365-day follow-up. The secondary outcomes included: admission rate from the index visit, total hospital admissions, ED-readmissions, proportion of patients living at home at 365 days, 365-day mortality, and fall-related ED-visits.

Results

A total of 432 patients, 63 % female, with median age of 85 years, formed the analytic sample of 213 patients in the intervention group and 219 patients in the control group.

Cumulative hospital stay during one-year follow-up as rate per 100 person-years for the intervention and control groups were: 3470 and 3149 days, respectively, with rate ratio of 1.10 (95 % confidence interval, 0.55–2.19, P = .78). Admission rates to hospital wards from the index ED visit for the intervention and control groups were: 62 and 70 %, respectively (P = .10). No significant differences were observed between the groups for any outcomes.

Conclusion

Systematic geriatric assessment for older adults with frailty in the ED did not reduce hospital stay during one-year follow-up. No statistically significant difference was observed for any secondary outcomes. More coordinated, continuous interventions should be tested for potential benefits in long-term outcomes.

Trial registration

The trial was registered in the ClinicalTrials.gov (registration number and date NCT03751319 23/11/2018).
Regional citrate anticoagulation “non-shock” protocol with pre-calculated flow settings for patients with at least 6 L/hour liver citrate clearance
Authors: Yessayan Lenar , Sohaney Ryann , Puri Vidhit , Wagner Benjamin , Riddle Amy , Dickinson Sharon , Napolitano Lena , Heung Michael , Humes David , Szamosfalvi Balazs
Published: July 2021

Background

Regional citrate anticoagulation (RCA) for the prevention of clotting of the extracorporeal blood circuit during continuous kidney replacement therapy (CKRT) has been employed in limited fashion because of the complexity and complications associated with certain protocols. Hypertonic citrate infusion to achieve circuit anticoagulation results in variable systemic citrate- and sodium load and increases the risk of citrate accumulation and hypernatremia. The practice of “single starting calcium infusion rate for all patients” puts patients at risk for clinically significant hypocalcemia if filter effluent calcium losses exceed replacement. A fixed citrate to blood flow ratio, personalized effluent and pre-calculated calcium infusion dosing based on tables derived through kinetic analysis enable providers to use continuous veno-venous hemo-diafiltration (CVVHDF)-RCA in patients with liver citrate clearance of at least 6 L/h.

Methods

This was a single-center prospective observational study conducted in intensive care unit patients triaged to be treated with the novel pre-calculated CVVHDF-RCA “Non-shock” protocol. RCA efficacy outcomes were time to first hemofilter loss and circuit ionized calcium (iCa) levels. Safety outcomes were surrogate of citrate accumulation (TCa/iCa ratio) and the incidence of acid-base and electrolyte complications.

Results

Of 53 patients included in the study, 31 (59%) had acute kidney injury and 12 (22.6%) had the diagnosis of cirrhosis at the start of CVVHDF-RCA. The median first hemofilter life censored for causes other than clotting exceeded 70 h. The cumulative incidence of hypernatremia (Na > 148 mM), metabolic alkalosis (HCO3- > 30 mM), hypocalcemia (iCa < 0.9 mM) and hypercalcemia (iCa > 1.5 mM) were 1/47 (1%), 0/50 (0%), 1/53 (2%), 1/53 (2%) respectively and were not clinically significant. The median (25th–75th percentile) of the highest TCa/iCa ratio for every 24-h interval on CKRT was 1.99 (1.91–2.13).

Conclusions

The fixed citrate to blood flow ratio, as opposed to a titration approach, achieves adequate circuit iCa (< 0.4 mm/L) for any hematocrit level and plasma flow. The personalized dosing approach for calcium supplementation based on pre-calculated effluent calcium losses as opposed to the practice of “one starting dose for all” reduces the risk of clinically significant hypocalcemia. The fixed flow settings achieve clinically desirable steady state systemic electrolyte levels.
Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study
Authors: Liebert Ann , Bicknell Brian , Laakso E-Liisa , Heller Gillian , Jalilitabaei Parastoo , Tilley Sharon , Mitrofanis John , Kiat Hosen
Published: July 2021

Background

Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons.

Objective

To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT).

Methods

Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12 weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14 weeks before commencing the same treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4 weeks of treatment, after 12 weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%.

Results

Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved (p < 0.05) with PBM treatment for 12 weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed.

Conclusions

PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted.

Trial registration

Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p, registered on 12/01/2018.
The significance of the oxidative stress markers in the one-year prognosis of patients with acute ischemic stroke: a case-control study
Authors: Shaafi Sheida , Hadisi Fina , Mahmoudinezhad Mahsa , Razmi Hamidreza , Nejadghaderi Seyed Aria , Khalili Mohammad
Published: July 2021

Background

Stroke is a major cause of mortality and morbidity. Also, free radicals and oxidative stress are deleterious factor in the stroke progression. We aimed to evaluate the association between oxidative stress markers and odds of having risk factor for stroke or developing stroke.

Methods

The present case-control study was conducted on 556 participants in Imam-Reza hospital, Tabriz, Iran. Subjects were divided into three group, including individuals with acute ischemic stroke, those who were at risk of stroke, and healthy controls. All enrolled participants except for controls underwent neurological examinations and brain magnetic resonance imaging (MRI). Stroke-related disability and stroke severity were evaluated by modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS), respectively. Serum malondialdehyde (MDA) level and total antioxidant capacity (TAC) were measured within 48 h of the initiation of stroke. One-way ANOVA and Chi-square tests were used for comparing characteristics between groups. Multivariable logistic regression was implemented for odds of stroke based on MDA and TAC quartiles. Also, Spearman’s correlation was utilized.

Results

Serum MDA, systolic and diastolic blood pressure, cholesterol, and triglyceride were significantly higher in the stroke group than controls. High levels of MDA were associated with increased development of stroke (P-value < 0.001), however TAC and MDA were not associated with having risk factors for stroke (P-value = 1.00 and 0.27, respectively). Also, TAC level was negatively associated with baseline (ρ = − 0.28;P-value = 0.04) and follow-up (ρ = − 0.31;P-value = 0.03) NIHSS scores. Moreover, MDA was correlated with mRS score at follow-up (ρ = − 0.26;P-value = 0.04).

Conclusions

The balance between antioxidants and oxidants markers might reveal a new approach in this context. Further studies are warranted to identify the source of oxidative stress as well as cessation of the production of oxygen radicals in stroke.
Facilitating better postnatal care with women-held documents in The Gambia: a mixed-methods study
Authors: Gooden Tiffany , Gustafsson Lotta , Lu Fides , Rickard Faith , Sitch Alice , Cummins Carole , Manneh Kebba , Wilson Amie , MacArthur Christine , Manaseki-Holland Semira
Published: July 2021

Background

Women-held documents are a basic component of continuity of maternity care. The use and completion of women-held documents following discharge could improve treatment and care for postnatal women. Using a mixed-methods study design, we aimed to assess the number, type, quality and completeness of women-held discharge documents, identify factors contributing to document completeness and facilitators or barriers for effective use of the documents.

Methods

Documents given to women at discharge from three hospitals in the Greater Banjul Area, The Gambia, were reviewed for content and quality. All women completed a questionnaire on the use of the documents. Poisson regression was used to estimate factors predicting document completion. Semi-structured interviews (n = 21) and focus groups (n = 2) were carried out with healthcare professionals (HCPs).

Results

Nearly all (n = 211/212; 99%) women were given a document to take home. The most complete document (maternal record) had on average 17/26 (65%) items completed and 10% of women held an illegible document. None of the women’s sociodemographic or clinical characteristics predicted document completeness. The following facilitators for effective use of documents were identified from the women’s responses to the questionnaire and interviews with HCPs: 94% of women thought written information is important, 99% plan to have postnatal check-ups and 67% plan to use their documents, HCPs understand the importance of the documents and were familiar with the document’s use and content. The following barriers for effective use of documents were identified: HCPs had too many women-held documents to complete at discharge, there is no national protocol and HCPs think women do not understand the documents due to a lack of education and that women often lose or forget their documents.

Conclusions

Women-held documents are well established in The Gambia; though quality and completeness needs improving. Future research should determine the impact of using only one document at discharge, protocols and training on completeness, among other outcomes, and on ways to ensure all women are using the documents for their postnatal care.
Perinatal health care access, childbirth concerns, and birthing decision-making among pregnant people in California during COVID-19
Authors: Whipps Mackenzie D. M. , Phipps Jennifer E. , Simmons Leigh Ann
Published: July 2021

Background

During public health emergencies, including the COVID-19 pandemic, access to adequate healthcare is crucial for providing for the health and wellbeing of families. Pregnant and postpartum people are a particularly vulnerable subgroup to consider when studying healthcare access. Not only are perinatal people likely at higher risk for illness, mortality, and morbidity from COVID-19 infection, they are also at higher risk for negative outcomes due to delayed or inadequate access to routine care.

Methods

We surveyed 820 pregnant people in California over two waves of the COVID-19 pandemic: (1) a ‘non-surge’ wave (June 2020, n = 433), and (2) during a ‘surge’ in cases (December 2020, n = 387) to describe current access to perinatal healthcare, as well as concerns and decision-making regarding childbirth, over time. We also examined whether existing structural vulnerabilities – including acute financial insecurity and racial/ethnic minoritization – are associated with access, concerns, and decision-making over these two waves.

Results

Pregnant Californians generally enjoyed more access to, and fewer concerns about, perinatal healthcare during the winter of 2020–2021, despite surging COVID-19 cases and hospitalizations, as compared to those surveyed during the COVID-19 ‘lull’ in the summer of 2020. However, across ‘surge’ and ‘non-surge’ pandemic circumstances, marginalized pregnant people continued to fare worse – especially those facing acute financial difficulty, and racially minoritized individuals identifying as Black or Indigenous.

Conclusions

It is important for clinicians, researchers, and policymakers to understand whether and how shifting community transmission and infection rates may impact access to perinatal healthcare. Targeting minoritized and financially insecure communities for increased upstream perinatal healthcare supports are promising avenues to blunt the negative impacts of the COVID-19 pandemic on pregnant people in California.
Risk assessment of paternal depression in relation to partner delivery during COVID-19 pandemic in Wuhan, China
Authors: Sun Guo-qiang , Wang Qi , Wang Shan-shan , Cheng Yao
Published: July 2021

Background

The COVID-19 pandemic and relevant prevention and control measures may affect the mental health and induce depressive symptoms in fathers with concurrent partner delivery exposure. This study aims to investigate the prevalence of depression in fathers with simultaneous exposure to COVID-19 pandemic and the effects of family functions on paternal perinatal depression (PPD) risk.

Methods

A cross-sectional study was conducted among the perinatal fathers recruited in a large tertiary hospital in Wuhan across the whole pandemic period from 31 December 2019 to 11 April 2020. Edinburgh Postnatal Depression Scale (EPDS) and APGAR family function scale were used to evaluate PPD and family function, respectively. Chi-square test and multivariable-adjusted logistic regression model were applied for data analysis.

Results

Among the 1187 participants, the prevalence of PPD was 13.82% throughout the COVID-19 pandemic. Compared with that in the time period before the announcement of human-to-human transmission on 19 January 2020, the depression risk was significantly lower during the traffic restriction (OR = 0.54, 95% CI: 0.34, 0.86) and public transportation reopening periods (OR = 0.29, 95% CI: 0.14, 0.59). Poor/fair family functions was associated with elevated depression risk (OR = 2.93, 95% CI: 1.90, 4.52). Individuals reporting a low family income and smoking had high depression risks.

Conclusions

A declined risk of PPD was observed over the traffic restriction period of the COVID-19 pandemic. An improved family function may help alleviate the risk of PPD during the pandemic. Health authorities are recommended to formulate targeted prevention and control strategies to handle PPD.
Does social support matter? The mediating links with coping strategy and anxiety among Chinese college students in a cross-sectional study of COVID-19 pandemic
Authors: Li Yue , Peng Jun
Published: July 2021

Background

The provision of public adaptive coping strategies to reduce psychological tension during the ongoing COVID-19 pandemic is critical. We sought to provide evidence-based guidance for psychological intervention, exploring the potential mediating roles of three sources of social support (i.e., subjective support, family support and counselor support) between coping strategies (i.e., cognitive coping, emotional coping and behavioral coping), and anxiety among college students at the height of the pandemic in China.

Methods

Using the Coping Strategy Questionnaire, Social Support Questionnaire, and Self-Rating Anxiety Scale, this large-scale online study analyzed the levels of social support, coping, and anxiety among 2640 college students in China from February 21st to 24th, 2020, when the students had been isolated at home for 1 month since the lockdown of Wuhan city.

Results

Students reported high levels of cognitive coping, behavioral coping, and social support. They also experienced low levels of anxiety and emotional coping. Anxiety was significantly and negatively related to coping and social support. The mediating roles of three sources of social support were found between cognitive coping, behavioral coping, and anxiety, respectively. However, the effect of emotional coping on anxiety was not found to be mediated by social support.

Conclusions

Adopting positive coping strategies may enhance social support that in turn relieves anxiety. The effect of social support, especially family and counselor support, should arouse greater awareness in coping with the pandemic cognitively and behaviorally.
Combined use of low T3 syndrome and NT-proBNP as predictors for death in patients with acute decompensated heart failure
Authors: Zhao Xinke , Zhang Rongcheng , Jiang Hugang , Liu Kai , Ma Chengxu , Bai Ming , An Tao , Yao Younan , Wang Xinqiang , Wang Ming , Li Yingdong , Zhang Yuhui , Zhang Jian
Published: July 2021

Background

In patients with established HF, low triiodothyronine syndrome (LT3S) is commonly present, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a useful marker for predicting death. This study was aimed to evaluate the prognostic value of LT3S in combination with NT-proBNP for risk of death in patients with heart failure (HF).

Methods

A total of 594 euthyroid patients hospitalized with acute decompensated HF were enrolled by design. Of these patients, 27 patients died during hospitalization and 100 deaths were identified in patients discharged alive during one year follow-up. Patients were divided into 2 groups on the base of the reference ranges of free T3 (FT3) levels: LT3S group (FT3 < 2.3pg/mL, n = 168) and non-LT3S group (FT3 ≥ 2.3pg/mL, n = 426).

Results

In multivariable Cox regression, LT3S was significantly associated with 1 year all-cause mortality (adjusted hazard ratio, 1.85; 95 % confidence interval [CI], 1.21 to 2.82; P = 0.005), but not significant for in-hospital mortality (adjusted hazard ratio, 1.58; 95 % CI, 1.58 to 2.82; P = 0.290) after adjustment for clinical variables and NT-proBNP.

Addition of LT3S and NT-proBNP to the prediction model with clinical variables significantly improved the C statistic for predicting 1 year all-cause mortality.

Conclusions

In patients with acute decompensated HF, the combination of LT3S and NT-proBNP improved prediction for 1 year all-cause mortality beyond established risk factors, but was not strong enough for in-hospital mortality.
Breast cancer cell line toxicity of a flavonoid isolated from Baccharis densiflora
Authors: Sotillo Wendy Soria , Tarqui Santiago , Huang Xiaoli , Almanza Giovanna , Oredsson Stina
Published: July 2021

Background

Flavonoids are compounds of interest in the search for new anti-cancer therapies. We have previously isolated the methoxyflavones 5,4′-dihydroxy-6,7,8,3′-tetramethoxyflavone (8-methoxycirsilineol), 5,4′-dihydroxy-6,7,8-trimethoxyflavone (xanthomicrol), and 5,4,'3′-trihydroxy-6,7,8-trimethoxyflavone (sideritoflavone) from Baccharis densiflora. Herein, we investigate the toxicity of these methoxyflavones in human breast-derived cell line. Our main aim was to focus on the cancer stem cell (CSC) sub-population of JIMT-1 breast cancer cells.

Methods

Initially, dose response experiments yielding inhibitory concentration 50 (IC50) values were performed using MCF-7, HCC1937, and JIMT-1 breast cancer, and the MCF-10A normal-like breast cell lines to get an understanding of toxic ranges. Due to a clear difference in the toxicity of the flavones, only sideritoflavone was selected for further studies using the JIMT-1 cell line. Effects on the CSC sub-population was investigated using flow cytometry-based methods. A wound healing assay and digital holographic microscopy were used to investigate effects on cell movement. A reporter assay was used to study effects on signal transduction pathways and Western blot for protein expression.

Results

The dose response data showed that 8-methoxycirsilineol was non-toxic at concentrations below 100 μM, that the IC50 of xanthomicrol was between 50 and 100 μM, while sideritoflavone was highly toxic with a single digit μM IC50 in all cell lines. Treatment of the JIMT-1 cells with 2 μM sideritoflavone did not selectively effect the CSC sub-population. Instead, sideritoflavone treatment inhibited the proliferation of both the non-CSC and the CSC sub-populations to the same extent. The inhibition of cell proliferation resulted in an accumulation of cells in the G2 phase of the cell cycle and the treated cells showed an increased level of γ-H2A histone family member X indicating DNA double strand breaks. Analysis of the effect of sideritoflavone treatment on signal transduction pathways showed activation of the Wnt, Myc/Max, and transforming growth factor-β pathways. The level of p65/nuclear factor kappa-light-chain-enhancer of activated Β cells was increased in sideritoflavone-treated cells. Cell movement was decreased by sideritoflavone treatment.

Conclusions

Altogether our data show that the methoxyflavone sideritoflavone has favourable anti-cancer effects that may be exploited for development to be used in combination with CSC specific compounds.
Psychometric evaluation of the perceived access to health care questionnaire
Authors: Hoseini-Esfidarjani Sara-Sadat , Negarandeh Reza , Delavar Farzaneh , Janani Leila
Published: July 2021

Background and objective

Access to health care is a universal concern. Therefore, this study was conducted to develop a questionnaire to assess the Perceived Access to Health care based on Penchansky and Thomas’s definition of access and the assessment of its psychometric properties.

Method

The initial questionnaire contains 31 items developed based on a deductive approach with an extensive review of the related literature. Content validity, face validity, construct validity, internal consistency, and instrument reliability were further examined. Data analysis was conducted using SPSS software version 24, R software version 4, and lavaan package.

Results

The initial questionnaire was examined using qualitative content validity, and the necessary modifications were applied to each item. The content validity ratio (CVR) was approved in 30 items with a value greater than 0.78, and one item with a CVR value lower than 0.78 was removed. In the case of the content validity index (CVI), 29 items were approved with a CVI value of greater than 0.79, and one item with a CVI value between 0.70 and 0.79 was revised. In qualitative face validity, all items were approved by a panel of experts and the participants. All 30 items with an impact score index higher than 1.5 were approved for the next steps. The confirmatory factor analysis results showed that the six-factor model of access to health care has an appropriate fit. Cronbach’s alpha coefficient for the questionnaire was calculated 0.86. The value of Cronbach’s alpha for the dimensions of availability, accessibility, affordability, accommodation, acceptability, and awareness were 0.61, 0.76, 0.66, 0.60, 0.80, and 0.76, respectively. The Intraclass Correlation Index (ICC) value for reliability (test-retest) of the whole instrument was calculated 0.94 using the two-way mixed absolute agreement method.

Conclusion

The success of health programs depends on eliminating barriers to access to provided health care services. One of the most critical barriers to understanding access is a perception of limited access. This questionnaire might be used further to understand perceived health care access in different global contexts.
Longitudinal change in lung function and subsequent risks of cardiovascular events: evidence from four prospective cohort studies
Authors: Cheng Yun-Jiu , Chen Zhen-Guang , Li Zhu-Yu , Mei Wei-Yi , Bi Wen-Tao , Luo Dong-Ling
Published: July 2021

Background

Lung function is constantly changing over the life course. Although the relation of cross-sectional lung function measure and adverse outcomes has been reported, data on longitudinal change and subsequent cardiovascular (CV) events risks are scarce. Therefore, this study is to determine the association of longitudinal change in lung function and subsequent cardiovascular risks.

Methods

This study analyzed the data from four prospective cohorts. Subjects with at least two lung function tests were included. We calculated the rate of forced respiratory volume in 1 s (FEV1) and forced vital capacity (FVC) decline for each subject and categorized them into quartiles. The primary outcome was CV events, defined as a composite of coronary heart disease (CHD), chronic heart failure (CHF), stroke, and any CV death. Cox proportional hazards regression and restricted cubic spline models were applied.

Results

The final sample comprised 12,899 participants (mean age 48.58 years; 43.61% male). Following an average of 14.79 (10.69) years, 3950 CV events occurred. Compared with the highest FEV1 quartile (Q4), the multivariable HRs for the lowest (Q1), 2nd (Q2), and 3rd quartiles (Q3) were 1.33 (95%CI 1.19, 1.49), 1.30 (1.16, 1.46), and 1.07 (0.95, 1.21), respectively. Likewise, compared with the reference quartile (Q4), the group that experienced a faster decline in FVC had higher HRs for CV events (1.06 [95%CI 0.94–1.20] for Q3, 1.15 [1.02–1.30] for Q2, and 1.28 [1.14–1.44] for Q1). The association remained robust across a series of sensitivity analyses and nearly all subgroups but was more evident in subjects < 60 years.

Conclusions

We observed a monotonic increase in risks of CV events with a faster decline in FEV1 and FVC. These findings emphasize the value of periodic evaluation of lung function and open new opportunities for disease prevention.
RNA-seq analysis reveals significant transcriptome changes in huntingtin-null human neuroblastoma cells
Authors: Bensalel Johanna , Xu Hongyuan , Lu Michael L. , Capobianco Enrico , Wei Jianning
Published: July 2021

Background

Huntingtin (Htt) protein is the product of the gene mutated in Huntington’s disease (HD), a fatal, autosomal dominant, neurodegenerative disorder. Normal Htt is essential for early embryogenesis and the development of the central nervous system. However, the role of Htt in adult tissues is less defined. Following the recent promising clinical trial in which both normal and mutant Htt mRNA were knocked down in HD patients, there is an urgent need to fully understand the molecular consequences of knocking out/down Htt in adult tissues. Htt has been identified as an important transcriptional regulator. Unbiased investigations of transcriptome changes with RNA-sequencing (RNA-Seq) have been done in multiple cell types in HD, further confirming that transcriptional dysregulation is a central pathogenic mechanism in HD. However, there is lack of direct understanding of the transcriptional regulation by normal Htt.

Methods

To investigate the transcriptional role of normal Htt, we first knocked out Htt in the human neuroblastoma SH-SY5Y cell line using the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9) gene editing approach. We then performed RNA-seq analysis on Htt-null and wild type SH-SY5Y cells to probe the global transcriptome changes induced by Htt deletion.

Results

In general, Htt has a widespread effect on gene transcription. Functional analysis of the differentially expressed genes (DEGs) using various bioinformatic tools revealed irregularities in pathways related to cell communication and signaling, and more specifically those related to neuron development, neurotransmission and synaptic signaling. We further examined the transcription factors that may regulate these DEGs. Consistent with the disrupted pathways associated with cellular development, we showed that Htt-null cells exhibited slower cell proliferation than wild type cells. We finally validated some of the top DEGS with quantitative RT-PCR.

Conclusions

The widespread transcriptome changes in Htt-null cells could be directly caused by the loss of Htt-mediated transcriptional regulation or due to the secondary consequences of disruption in the gene regulatory network. Our study therefore provides valuable information about key genes associated with Htt-mediated transcription and improves our understanding of the molecular mechanisms underlying the cellular functions of normal and mutant Htt.
The impact of empagliflozin on cardiac physiology and fibrosis early after myocardial infarction in non-diabetic rats
Authors: Daud Elias , Ertracht Offir , Bandel Nadav , Moady Gassan , Shehadeh Monah , Reuveni Tali , Atar Shaul
Published: July 2021

Background

Myocardial fibrosis is a multistep process, which results in collagen deposition in the injured muscle. Empagliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), decreases cardiovascular events risk. Little is known on the effects of empagliflozin in non-diabetic patients early post myocardial infarction.

Methods

Fourteen non-diabetic rats underwent myocardial infarction induction, and treated or not (control)immediately after myocardial infarction by daily empagliflozin (30 mg/kg/day). We evaluated cardiac function at baseline, 2 and 4 weeks after myocardial infarction by echocardiography, and prior to sacrifice by Millar pressure–volume system. We performed histological and biochemical evaluation of fibrosis and humoral factors promoting fibrosis.

Results

Baseline ejection fractions were 69.9 ± 5.3% and 76.4 ± 5.4%, and dropped to final values of 40.1 ± 5.8% and 39.4 ± 5.4% in the control and empagliflozin groups, respectively (P < 0.001 vs. baseline, P > 0.05 between groups). Collagen deposition, measured as collagen volume fraction, was higher in both the scar and the remote cardiac areas of the control group 79.1 ± 6.2% and 4.6 ± 2.5% for control, and 53.8 ± 5.4% and 2.5 ± 1.3% for empagliflozin group, respectively (P < 0.05 for each). Remote cardiac muscle collagen, measured by hydroxyproline, was 4.1 ± 0.4 μg/μl and 3.6 ± 0.2 μg/μl (P = 0.07). TGF-β1 and Smad3 expression decreased by empagliflozin—18.73 ± 16.32%, 9.16 ± 5.69% and 16.32 ± 5.4%, 7.00 ± 5.28% in the control and empagliflozin groups, respectively (P < 0.05).

Conclusion/interpretation

Empagliflozin administered early after myocardial infarction reduce myocardial fibrosis and inhibit the TGF-β1/Smad3 fibrotic pathway, probably prior to exerting any hemodynamic or physiological effect.