bluuebunny/crossref_metadata_2025 huggingface dataset:
D3PM: a comprehensive database for protein motions ranging from residue to domain
Authors: Peng Cheng , Zhang Xinben , Xu Zhijian , Chen Zhaoqiang , Yang Yanqing , Cai Tingting , Zhu Weiliang
Published: February 2022

Background

Knowledge of protein motions is significant to understand its functions. While currently available databases for protein motions are mostly focused on overall domain motions, little attention is paid on local residue motions. Albeit with relatively small scale, the local residue motions, especially those residues in binding pockets, may play crucial roles in protein functioning and ligands binding.

Results

A comprehensive protein motion database, namely D3PM, was constructed in this study to facilitate the analysis of protein motions. The protein motions in the D3PM range from overall structural changes of macromolecule to local flip motions of binding pocket residues. Currently, the D3PM has collected 7679 proteins with overall motions and 3513 proteins with pocket residue motions. The motion patterns are classified into 4 types of overall structural changes and 5 types of pocket residue motions. Impressively, we found that less than 15% of protein pairs have obvious overall conformational adaptations induced by ligand binding, while more than 50% of protein pairs have significant structural changes in ligand binding sites, indicating that ligand-induced conformational changes are drastic and mainly confined around ligand binding sites. Based on the residue preference in binding pocket, we classified amino acids into “pocketphilic” and “pocketphobic” residues, which should be helpful for pocket prediction and drug design.

Conclusion

D3PM is a comprehensive database about protein motions ranging from residue to domain, which should be useful for exploring diverse protein motions and for understanding protein function and drug design. The D3PM is available onwww.d3pharma.com/D3PM/index.php.
Multiallelic models for QTL mapping in diverse polyploid populations
Authors: Thérèse Navarro Alejandro , Tumino Giorgio , Voorrips Roeland E. , Arens Paul , Smulders Marinus J. M. , van de Weg Eric , Maliepaard Chris
Published: February 2022

Quantitative trait locus (QTL) analysis allows to identify regions responsible for a trait and to associate alleles with their effect on phenotypes. When using biallelic markers to find these QTL regions, two alleles per QTL are modelled. This assumption might be close to reality in specific biparental crosses but is unrealistic in situations where broader genetic diversity is studied. Diversity panels used in genome-wide association studies or multi-parental populations can easily harbour multiple QTL alleles at each locus, more so in the case of polyploids that carry more than two alleles per individual. In such situations a multiallelic model would be closer to reality, allowing for different genetic effects for each potential allele in the population. To obtain such multiallelic markers we propose the usage of haplotypes, concatenations of nearby SNPs. We developed “mpQTL” an R package that can perform a QTL analysis at any ploidy level under biallelic and multiallelic models, depending on the marker type given. We tested the effect of genetic diversity on the power and accuracy difference between bi-allelic and multiallelic models using a set of simulated multiparental autotetraploid, outbreeding populations. Multiallelic models had higher detection power and were more precise than biallelic, SNP-based models, particularly when genetic diversity was higher. This confirms that moving to multi-allelic QTL models can lead to improved detection and characterization of QTLs.

Key message

QTL detection in populations with more than two functional QTL alleles (which is likely in multiparental and/or polyploid populations) is more powerful when using multiallelic models, rather than biallelic models.
Liver stiffness for predicting adverse cardiac events in chinese patients with heart failure: a two-year prospective study
Authors: Wang Qian , Song Yuqing , Wu Qiming , Dong Qian , Yang Song
Published: February 2022

Background

To investigate whether liver stiffness (LS) can predict adverse cardiac events in Chinese patients with heart failure (HF).

Methods

A total of 53 hospitalized patients with HF were enrolled, and LS and tricuspid annual plane systolic excursion (TAPSE) were determined with Fibroscan® and echocardiography before discharge. They were divided into two groups: high LS group (LS > 6.9 Kpa, n = 23) and low LS group (LS ≤ 6.9 Kpa, n = 30). Patients were followed up for 24 months at an interval of 3 months. The endpoint of follow-up was death or rehospitalization for HF.

Results

All patients were followed up for 24 months or until the endpoint. Patients in the high LS group had lower platelet count (P = 0.014), lower creatine clear rate (P = 0.014), higher level of B-type natriuretic peptide at discharge (P = 0.012), and lower TAPSE (P < 0.001) than those in the low LS group. During 24 months of follow-up, 3 (5.7%) deaths and 21 (39.6%) hospitalizations for HF were observed. Patients in the high LS group had a higher rate of death/rehospitalization than those in the low LS group (Hazard ratio 4.81; 95% confidence interval 1.69–13.7, P = 0.003) after adjustment for age, sex, platelet count, creatine clear rate, and B-type natriuretic peptide level. Moreover, TAPSE ≤ 16 could predict adverse cardiac events with an HR of 6.63 (95% confidence interval 1.69–13.7, P = 0.004) after adjustment for age, sex, platelet count, creatine clear rate, and B-type natriuretic peptide level.

Conclusion

LS and TAPSE could be used to predict worse outcomes in patients with HF.
Students’ observations of hand hygiene adherence in 20 nursing home wards, during the COVID-19 pandemic
Authors: Sandbekken Ida Hellum , Hermansen Åsmund , Utne Inger , Grov Ellen Karine , Løyland Borghild
Published: February 2022

Background

Healthcare-associated infections are a major threat to patient safety, particularly vulnerable elderly living in nursing homes, who have an increased risk of infections and mortality. Although good hand hygiene is the most effective preventive measure against infections, few studies of hand hygiene adherence have been conducted in nursing homes. The aim of this study is to investigate hand hygiene adherence in nursing homes with students as observers using a validated observation tool. In addition, to examine when healthcare workers perform hand hygiene and when they do not.

Methods

This observational study used the World Health Organization’s observation tool for studying hand hygiene indication and adherence: “My five moments for hand hygiene.” For 1 week each in February and March 2021, 105 first-year nursing students conducted 7316 hand hygiene observations at 20 nursing home wards in one large municipality in Norway.

Results

The overall adherence rate found in this study was 58.3%. Hand hygiene adherence decreased from 65.8% in February to 51.4% in March. The adherence varied largely between the different wards, from 26.4 to 83.1%, and by occupation status, indications of hand hygiene, and use of gloves. Nursing students were found to have the greatest adherence, followed by nurses. The use of gloves reduced adherence. Healthcare workers to a larger degree conduct hand hygiene after contact with patients than before approaching them.

Conclusions

Hand hygiene adherence is too low to protect all residents against healthcare-associated infections, and the findings from this study indicate that there are many factors that influence hand hygiene adherence, eg., education, occupation status and glove use Increasing healthcare workers’ knowledge and skills of hand hygiene is needed to reduce healthcare-associated infections and reminders of the importance of hand hygiene adherence must be an ongoing activity. Interventions to improve hand hygiene adherence in healthcare workers is needed to reduce infections and antibiotic use in nursing homes.
Profiling of exosomal microRNAs expression in umbilical cord blood from normal and preeclampsia patients
Authors: Pan Hai-Tao , Shi Xiao-Liang , Fang Min , Sun Xiang-Mei , Chen Pan-Pan , Ding Jin-Long , Xia Gui-Yu , Yu Bin , Zhang Tao , Zhu Hong-Dan
Published: February 2022

Background

Epidemiological and experimental studies suggest that preeclampsia has a negative impact on maternity and offspring health. Previous studies report that dysregulation in utero-environment increases risk for elderly disease such as cardiovascular disease. However, the underlying mechanisms remain elusive. Specific microRNAs (miRNAs) are packaged in exosomes may regulate microvascular dysfunction in offspring of mothers with preeclampsia. The present study aimed to identify the differential expression profiles of microRNAs in the serum exosomes between patients with preeclampsia and normal pregnancies.

Methods

A comprehensive miRNA sequence-based approach was performed to compare exosomes carry miRNAs (Exo-miRNAs) expression levels in umbilical serum between normal and preeclampsia patients. Exosomes were isolated using the ExoQuick precipitation kit. Serum exosomes were then viewed under electron microscopy, and their characteristics determined by western blotting and nanoparticle-tracking analysis. Illumina platform was used to perform sequencing. Bioinformatics analysis was used to explore differentially expressed Exo-miRNAs in umbilical serum.

Results

Based on sequence similarity, 1733 known miRNAs were retrieved. Furthermore, 157 mature miRNAs in serum exosomes were significantly differential expressed between PE and those control groups (P<0.05, log2|FC| > 1). Out, of the 157 miRNAs, 96 were upregulated miRNAs whereas 61 miRNAs were downregulated. The 157 differentially expressed miRNAs targeted 51,424 differentially expressed genes. Functional analysis through KEGG pathway and Gene Ontology results uncovered that target genes of miRNAs with differential expression were significantly linked to several pathways and biological processes.

Conclusion

The findings of this study showed differential expression of umbilical serum Exo-miRNAs in normal compared with PE patients, implying that these Exo-miRNAs may associate with microvascular dysfunction in offspring of mothers with preeclampsia.
Weight gain and comorbidities associated with oral second-generation antipsychotics: analysis of real-world data for patients with schizophrenia or bipolar I disorder
Authors: Doane Michael J. , Bessonova Leona , Friedler Haley S. , Mortimer Kathleen M. , Cheng Harry , Brecht Thomas , O’Sullivan Amy K. , Cummings Hannah , McDonnell David , Meyer Jonathan M.
Published: February 2022

Background

Many second-generation antipsychotics (SGAs) are associated with weight gain and cardiometabolic effects. Antipsychotic-associated weight gain is linked to treatment interruptions, potentially increasing risk of relapse and hospitalization. This retrospective study assessed clinically significant weight gain (CSWG), treatment interruptions, and development of cardiometabolic conditions in patients with schizophrenia (SZ) or bipolar I disorder (BD-I) following initiation of oral SGAs with moderate to high weight gain risk.

Methods

Patients with no prior use of moderate to high weight gain risk oral SGAs were identified from patient-level medical/pharmacy claims and electronic medical records (January 2013–February 2020; OM1 Real-World Data Cloud). Those with ≥ 1 weight measurement in both the 12 months preceding and 3 months after SGA initiation (index date) were analyzed for continuous changes in weight, CSWG (≥ 7% and ≥ 10% increases from baseline), treatment interruptions (switches/discontinuations), and development of cardiometabolic conditions.

Results

Median follow-up times in the SZ (n = 8174) and BD-I (n = 9142) cohorts were 153.4 and 159.4 weeks, respectively; 45.5% and 50.7% were obese at baseline. Mean (SD) percent weight increase during treatment was 3.3% (7.2) and 3.7% (7.0) for patients with SZ and BD-I, respectively, and was highest for underweight/normal weight patients (SZ: 4.8% [8.1]; BD-I: 5.5% [8.7]). More than 96% had treatment interruptions during follow-up, primarily discontinuations. CSWG and treatment interruptions occurred within a median of 13 and 14 weeks after treatment initiation, respectively. Of patients with CSWG and treatment interruptions, approximately 75% did not return to baseline weight during follow-up. Among those without baseline cardiometabolic conditions, 14.7% and 11.3% of patients with SZ or BD-I, respectively, developed ≥ 1 condition over 12 months post-index. Incidence was generally highest among those who were overweight/obese at baseline and those who experienced CSWG.

Conclusions

In this analysis of real-world data, both weight gain and treatment interruptions occurred early in treatment for patients with SZ or BD-I. Treatment-associated weight gain persisted despite switching or discontinuing index treatment. Additionally, cardiometabolic morbidity increased within 12 months of treatment initiation. Patients with SZ or BD-I are at greater risk than the general population for cardiometabolic conditions; weight gain associated with SGAs may exacerbate these health risks.
Mean kinetic temperature evaluations through simulated temperature excursions and risk assessment with oral dosage usage for health programs
Authors: Jenkins David , Cancel Aida , Layloff Thomas
Published: February 2022

Background

Temperature excursions occur during the transport and storage of pharmaceuticals, and often result in considerable losses for public health programs operating in countries with limited resources. After a temperature excursion has been identified, often products are discarded without any additional risk assessments. Consulting the manufacturer is the preferred approach but can be challenging depending on the responsiveness of the manufacturer. However, decisions are often required quickly depending on program needs and available stock in country.

Methods

To provide further guidance, simulations have been conducted based on mean kinetic temperature evaluations using accepted default kinetic parameters to assess loss of shelf-life for scenarios involving various levels of temperature excursions on a model pharmaceutical at different recommended storage conditions, shelf-life, and long-term storage conditions.

Results

Although an immediate loss to shelf-life occurred with excursions when the product was stored at the maximum allowed temperature, more extended excursion could be withstood before loss of shelf-life was detected when long-term storage was maintained at temperatures below the maximum storage condition for the product. With the assumption that a shelf-life loss of 2 weeks was negligible when managing program stock, a risk assessment was conducted to outline the various times that excursions at different temperatures could be considered low risk to the program.

Conclusions

Depending on the level of the temperature excursion and the guidance provided by the manufacturer, public health programs will have further information with this assessment to guide decisions that impact safety to the end user and resource management due to temperature excursions that can occur.
The health consequences of child marriage: a systematic review of the evidence
Authors: Fan Suiqiong , Koski Alissa
Published: February 2022

Background

Child marriage, defined as marriage before 18 years of age, is a violation of human rights and a marker of gender inequality. Growing attention to this issue on the global development agenda also reflects concerns that it may negatively impact health. We conducted a systematic review to synthesize existing research on the consequences of child marriage on health and to assess the risk of bias in this body of literature.

Methods and findings

We searched databases focused on biomedicine and global health for studies that estimated the effect of marrying before the age of 18 on any physical or mental health outcome or health behaviour. We identified 58 eligible articles, nearly all of which relied on cross-sectional data sources from sub-Saharan Africa or South Asia. The most studied health outcomes were indicators of fertility and fertility control, maternal health care, and intimate partner violence. All studies were at serious to critical risk of bias. Research consistently found that women who marry before the age of 18 begin having children at earlier ages and give birth to a larger number of children when compared to those who marry at 18 or later, but whether these outcomes were desired was not considered. Across studies, women who married as children were also consistently less likely to give birth in health care facilities or with assistance from skilled providers. Studies also uniformly concluded that child marriage increases the likelihood of experiencing physical violence from an intimate partner. However, research in many other domains, including use of contraception, unwanted pregnancy, and sexual violence came to divergent conclusions and challenge some common narratives regarding child marriage.

Conclusions

There are many reasons to be concerned about child marriage. However, evidence that child marriage causes the health outcomes described in this review is severely limited. There is more heterogeneity in the results of these studies than is often recognized. For these reasons, greater caution is warranted when discussing the potential impact of child marriage on health. We provide suggestions for avoiding common biases and improving the strength of the evidence on this subject.

Trial registration

The protocol of this systematic review was
registered with PROSPERO (CRD42020182652) in May 2020.
COPD profiles and treatable traits using minimal resources: identification, decision tree and stability over time
Authors: Marques Alda , Souto-Miranda Sara , Machado Ana , Oliveira Ana , Jácome Cristina , Cruz Joana , Enes Vera , Afreixo Vera , Martins Vitória , Andrade Lília , Valente Carla , Ferreira Diva , Simão Paula , Brooks Dina , Tavares Ana Helena
Published: February 2022

Background and objective

Profiles of people with chronic obstructive pulmonary disease (COPD) often do not describe treatable traits, lack validation and/or their stability over time is unknown. We aimed to identify COPD profiles and their treatable traits based on simple and meaningful measures; to develop and validate a decision tree and to explore profile stability over time.

Methods

An observational, prospective study was conducted. Clinical characteristics, lung function, symptoms, impact of the disease (COPD Assessment Test—CAT), health-related quality of life, physical activity, lower-limb muscle strength and functional status were collected cross-sectionally and a subsample was followed-up monthly over six months. A principal component analysis and a clustering procedure with k-medoids were applied to identify profiles. A decision tree was developed and validated cross-sectionally. Stability was explored over time with the ratio between the number of timepoints that a participant was classified in the same profile and the total number of timepoints (i.e., 6).

Results

352 people with COPD (67.4 ± 9.9 years; 78.1% male; FEV1 = 56.2 ± 20.6% predicted) participated and 90 (67.6 ± 8.9 years; 85.6% male; FEV1 = 52.1 ± 19.9% predicted) were followed-up. Four profiles were identified with distinct treatable traits. The decision tree included CAT (< 18 or ≥ 18 points); age (< 65 or ≥ 65 years) and FEV1 (< 48 or ≥ 48% predicted) and had an agreement of 71.7% (Cohen’s Kappa = 0.62, p < 0.001) with the actual profiles. 48.9% of participants remained in the same profile whilst 51.1% moved between two (47.8%) or three (3.3%) profiles over time. Overall stability was 86.8 ± 15%.

Conclusion

Four profiles and treatable traits were identified with simple and meaningful measures possibly available in low-resource settings. A decision tree with three commonly used variables in the routine assessment of people with COPD is now available for quick allocation to the identified profiles in clinical practice. Profiles and treatable traits may change over time in people with COPD hence, regular assessments to deliver goal-targeted personalised treatments are needed.
The evolution of clot strength in critically ill COVID-19 patients: a prospective observational thromboelastography study
Authors: Muzaffar Syed Nabeel , Siddiqui Suhail Sarwar , Chakraborty Nilanchal , Azim Afzal
Published: February 2022

The authors have done commendable work in exploring the utility of a comprehensive viscoelastic test for assessment of the coagulation cascade in Coronavirus disease 2019 (COVID-19) patients. This article published in your esteemed journal in November 2021 “The evolution of clot strength in critically-ill COVID-19 patients: a prospective observational thromboelastography study” found hypercoagulability in most of the patients at Intensive Care Unit (ICU) admission and also noted a persistently increased fibrin contribution to clot strength. However, we would like to comment upon a few points which may be of importance to the readers.
A web-based prediction model for overall survival of elderly patients with early renal cell carcinoma: a population-based study
Authors: Wang Jinkui , Tang Jie , Chen Tiaoyao , Yue Song , Fu Wanting , Xie Zulong , Liu Xiaozhu
Published: February 2022

Background

The number of elderly patients with early renal cell carcinoma (RCC) is on the rise. However, there is still a lack of accurate prediction models for the prognosis of early RCC in elderly patients. It is necessary to establish a new nomogram to predict the prognosis of elderly patients with early RCC.

Methods

The data of patients aged above 65 years old with TNM stage I and II RCC were downloaded from the SEER database between 2010 and 2018. The patients from 2010 to 2017 were randomly assigned to the training cohort (n = 7233) and validation cohort (n = 3024). Patient data in 2018(n = 1360) was used for external validation. We used univariable and multivariable Cox regression model to evaluate independent prognostic factors and constructed a nomogram to predict the 1-, 3-, and 5-year overall survival (OS) rates of patients with early-stage RCC. Multiple parameters were used to validate the nomogram, including the consistency index (C-index), the calibration plots, the area under the receiver operator characteristics (ROC) curve, and the decision curve analysis (DCA).

Results

The study included a total of 11,617 elderly patients with early RCC. univariable and multivariable Cox regression analysis based on predictive variables such as age, sex, histologic type, Fuhrman grade, T stage, surgery type, tumors number, tumor size, and marriage were included to establish a nomogram. The C-index of the training cohort and validation cohort were 0.748 (95% CI: 0.760–0.736) and 0.744 (95% CI: 0.762–0.726), respectively. In the external validation cohort, C-index was 0.893 (95% CI: 0.928–0.858). The calibration plots basically coincides with the diagonal, indicating that the observed OS was almost equal to the predicted OS. It was shown in DCA that the nomogram has more important clinical significance than the traditional TNM stage.

Conclusion

A novel nomogram was developed to assess the prognosis of an elderly patient with early RCC and to predict prognosis and formulate treatment and follow-up strategies.
Breastfeeding practices among Syrian refugees in Turkey
Authors: Yalçin Siddika Songul , Erat Nergiz Meryem , Elci Ömur Cinar , Zikusooka Monica , Yalçin Suzan , Sucakli Mustafa Bahadir , Keklik Kanuni
Published: February 2022

Background

We evaluated (a) opinion of Syrian and Turkish healthcare workers (HCWs), and perceptions and attitudes of Syrian refugee mothers, pregnant women, fathers and grandmothers on age-appropriate breastfeeding, (b) the effect of cultural characteristics, migration and pandemics on Syrian’s infant nutrition, and (c) the suggestions of HCWs and Syrian family members to improve breastfeeding practices in the Syrian refugee society in a qualitative study.

Methods

The qualitative study consisting of structured focus group discussions (FGDs) was held in four provinces in Turkey where Syrian refugees live intensely in September and October 2020. Seven different types of online FGDs were held with Turkish HCWs working in maternity hospitals, Syrian HCWs working in Refugee Health Centers (RHCs), Syrian pregnant women, mothers, fathers, and grandmothers. In total, we carried out 46 FGDs with 335 individuals. Thematic analysis of the transcripts in a deductive-inductive fashion was carried out with MAXQDA 11.

Results

Most Syrian HCWs did not get any training on breastfeeding counseling. The short duration of breastfeeding in Syrian refugees was seen to be related to the cultural characteristics, and migration. Some cultural characteristics can be summarized as “believing that breastfeeding harms mother’s health”, “adolescent marriages”, “wanting to have as many children as possible”, “giving anise to infants and not breastfeeding at night”, “prelacteal feeding”, “believing that milk is not enough”, “over controlling mother–child interaction by grandmothers, which limits the interaction”, “short pregnancy intervals”, and “not using modern family planning techniques”. We found out that migration increased the tendency for adolescent pregnancies, deepened the poverty, and decreased family social support. We did not observe any change in breastfeeding practices during pandemics.

Conclusions

Breastfeeding counseling programs should be designed in consideration of cultural characteristics of Syrian HCWs and family members. Continuing health education programs for family members with socially appropriate interventions to prevent adolescent marriages are important.
Clinical disease characteristics of patients with Niemann-Pick Disease Type C: findings from the International Niemann-Pick Disease Registry (INPDR)
Authors: Bolton Shaun C. , Soran Vina , Marfa Mercedes Pineda , Imrie Jackie , Gissen Paul , Jahnova Helena , Sharma Reena , Jones Simon , Santra Saikat , Crushell Ellen , Stampfer Miriam , Coll Maria Jose , Dawson Charlotte , Mathieson Toni , Green James , Dardis Andrea , Bembi Bruno , Patterson Marc C. , Vanier Marie T. , Geberhiwot Tarekegn
Published: February 2022

Background

Niemann-Pick Disease Type C (NPC) is an autosomal recessive rare disease characterised by progressive neurovisceral manifestations. The collection of on-going large-scale NPC clinical data may generate better understandings of the natural history of the disease. Here we report NPC patient data from the International Niemann-Pick Disease Registry (INPDR).

Method

The INPDR is a web-based, patient-led independent registry for the collection of prospective and retrospective clinical data from Niemann-Pick Disease patients. Baseline data from NPC patients enrolled into the INPDR from September 2014 to December 2019 was extracted to analyse the demographic, genetic and clinical features of the disease.

Results

A total of 203 NPC patients from six European countries were included in this study. The mean age (SD) at diagnosis was 11.2 years (14.2). Among enrolled patients, 168 had known neurological manifestations: 43 (24.2%) had early-infantile onset, 47 (26.4%) had late-infantile onset, 41 (23.0%) had juvenile onset, and 37 (20.8%) had adult onset. 10 (5.6%) patients had the neonatal rapidly fatal systemic form. Among the 97 patients with identified NPC1 variants, the most common variant was the c. 3182T > C variant responsible for the p.lle1061Thr protein change, reported in 35.1% (N = 34) of patients. The frequencies of hepatomegaly and neonatal jaundice were greatest in patients with early-infantile and late-infantile neurological onset. Splenomegaly was the most commonly reported observation, including 80% of adult-onset patients. The most commonly reported neurological manifestations were cognitive impairment (78.5%), dysarthria (75.9%), ataxia (75.9%), vertical supranuclear gaze palsy (70.9%) and dysphagia (69.6%). A 6-domain composite disability scale was used to calculate the overall disability score for each neurological form. Across all with neurological onset, the majority of patients showed moderate to severe impairments in all domains, except for ‘swallowing’ and ‘seizure’. The age at diagnosis and death increased with increased age of neurological symptom onset. Miglustat use was recorded in 62.4% of patients and the most common symptomatic therapies used by patients were antiepileptics (32.9%), antidepressants (11.8%) and antacids (9.4%).

Conclusion

The proportion of participants at each age of neurological onset was relatively equal across the cohort. Neurological manifestations, such as ataxia, dysphagia, and dysarthria, were frequently observed across all age categories.
Assessing gender responsiveness of COVID-19 response plans for populations in conflict-affected humanitarian emergencies
Authors: Asi Yara M. , Bebasari Priliantina , Hardy Emily , Lokot Michelle , Meagher Kristen , Ogbe Emilomo , Parray Ateeb Ahmad , Sharma Vandana , Standley Claire J. , Vahedi Luissa
Published: February 2022

Background

The COVID-19 pandemic has necessitated rapid development of preparedness and response plans to quell transmission and prevent illness across the world. Increasingly, there is an appreciation of the need to consider equity issues in the development and implementation of these plans, not least with respect to gender, given the demonstrated differences in the impacts both of the disease and of control measures on men, women, and non-binary individuals. Humanitarian crises, and particularly those resulting from conflict or violence, exacerbate pre-existing gender inequality and discrimination. To this end, there is a particularly urgent need to assess the extent to which COVID-19 response plans, as developed for conflict-affected states and forcibly displaced populations, are gender responsive.

Methods

Using a multi-step selection process, we identified and analyzed 30 plans from states affected by conflict and those hosting forcibly displaced refugees and utilized an adapted version of the World Health Organization’s Gender Responsive Assessment Scale (WHO-GRAS) to determine whether existing COVID-19 response plans were gender-negative, gender-blind, gender-sensitive, or gender-transformative.

Results

We find that although few plans were gender-blind and none were gender-negative, no plans were gender-transformative. Most gender-sensitive plans only discuss issues specifically related to women (such as gender-based violence and reproductive health) rather than mainstream gender considerations throughout all sectors of policy planning.

Conclusions

Despite overwhelming evidence about the importance of intentionally embedding gender considerations into the COVID-19 planning and response, none of the plans reviewed in this study were classified as ‘gender transformative.’ We use these results to make specific recommendations for how infectious disease control efforts, for COVID-19 and beyond, can better integrate gender considerations in humanitarian settings, and particularly those affected by violence or conflict.
Identification of an SRY-negative 46,XX infertility male with a heterozygous deletion downstream of SOX3 gene
Authors: Qin Shengfang , Wang Xueyan , Wang Jin
Published: February 2022

Background

A male individual with a karyotype of 46,XX is very rare. We explored the genetic aetiology of an infertility male with a kayrotype of 46,XX andSRYnegative.

Methods

The peripheral blood sample was collected from the patient and subjected to a few genetic testing, including chromosomal karyotyping, azoospermia factor (AZF) deletion, short tandem repeat (STR) analysis forAMELX, AMELYandSRY, fluorescence in situ hybridization (FISH) with specific probes for CSP 18/CSP X/CSP Y/SRY, chromosomal microarray analysis (CMA) for genomic copy number variations(CNVs), whole-genome analysis(WGA) for genomic SNV&InDel mutation, and X chromosome inactivation (XCI) analysis.

Results

The patient had a karyotype of 46,XX.AZFanalysis showed that he missed theAZFregion (including a, b and c) andSRYgene. STR assay revealed he possessed theAMELXin the X chromosome, but he had no theAMELYandSRYin the Y chromosome. FISH analysis with CSP X/CSP Y/SRYshowed only two X centromeric signals, but none Y chromosome andSRY. The above results of the karyotype, FISH and STR analysis did not suggest a Y chromosome chimerism existed in the patient's peripheral blood. The result of the CMA indicated a heterozygous deletion with an approximate size of 867 kb in Xq27.1 (hg19: chrX: 138,612,879–139,480,163 bp), located at 104 kb downstream ofSOX3gene, includingF9,CXorf66,MCF2andATP11C. WGA also displayed the above deletion fragment but did not present known pathogenic or likely pathogenic SNV&InDel mutation responsible for sex determination and development. XCI assay showed that he had about 75% of the X chromosome inactivated.

Conclusions

Although the pathogenicity of 46,XX male patients withSRYnegative remains unclear,SOX3expression of the acquired function may be associated with partial testis differentiation of these patients. Therefore, the CNVs analysis of theSOX3gene and its regulatory region should be performed routinely for these patients.
Sunset Without AIDS: protocol for a randomized controlled trial of a brief video-based intervention to improve the ability of AIDS prevention in elderly men
Authors: Ren Jianlan , Li Mei , Luo Yue , Zheng Yu , Tang Jian , Wang Ying , Chen Yanhua
Published: February 2022

Background

Although progress has been made in the prevention and treatment of HIV in China, there are still a considerable number of new infections annually, especially in older men. HIV health education for older men is urgently needed. Evidence-based, acceptable, and scalable interventions are urgently needed to increase their capacity to prevent HIV. We describe a trial protocol to evaluate the effectiveness of a brief video-based intervention targeting older men's knowledge of HIV prevention.

Design

This study is a randomized controlled trial. The trial will be held in the residents’ activity centers of three communities.

Methods

A total of 450 older men will be randomly divided into three groups (Sunset Without AIDS intervention group and two control groups) for 2 weeks. We will assess the feasibility and acceptability of intervention through interviews. The primary outcome includes changes in participants’ knowledge related to AIDS after 2 weeks intervention and 1, 3, and 6 months of follow-up. The secondary outcomes, e.g., changes in participants’ stigma attitude, risk behaviors attitude, and risk behaviors related to AIDS, will be respectively assessed 2 weeks, 1 month, 3 months, and 6 months after the second intervention.

Discussion

Sunset Without AIDS may be an innovative way to help older men improve HIV prevention knowledge, fill the gap in video-based HIV prevention education for the older men in China, and gain experience of HIV education. This project will innovate the HIV education ideas of older men and enrich the theoretical research content of AIDS-related education of older men. The findings may also provide the basis for the research and formulation of more reasonable AIDS education strategies, prevention, and control policies for the elderly.

Trial registration

Chinese Clinical Trial Registry ChiCTR2100045708. Registered on 23 April 2021
CPR63 promotes pyrethroid resistance by increasing cuticle thickness in Culex pipiens pallens
Authors: Xu Yang , Xu Jingwei , Zhou Yang , Li Xixi , Meng Yufen , Ma Lei , Zhou Dan , Shen Bo , Sun Yan , Zhu Changliang
Published: February 2022

The cuticle protein (CP) encoded by CPR63 plays a role in deltamethrin resistance in Culex pipiens pallens. Herein, we investigated the distribution of CPR63 transcripts in this organism and observed high expression levels in legs and wings. Furthermore, expression of CPR63 in the legs of deltamethrin-resistant (DR) strains was 2.17-fold higher than in deltamethrin-susceptible (DS) strains. Cuticle analysis of small interfering RNA (siRNA) groups by scanning electron microscopy (SEM) revealed a significantly thinner cuticle of the tarsi in the siCPR63 group than in the siNC (negative control siRNA) group. Transmission electron microscopy (TEM) revealed that the exocuticle and endocuticle thickness of the tarsi were significantly thinner, which contributes the thinner procuticle of tarsi in the siCPR63 group than in the siNC group. Our results suggested that CPR63 might contribute to the resistance phenotype by thickening the cuticle and thereby possibly increasing the tolerance of mosquitoes to deltamethrin.
Determining the optimal strategies to achieve elimination of transmission for Schistosoma mansoni
Authors: Kura Klodeta , Ayabina Diepreye , Hollingsworth T. Deirdre , Anderson Roy M.
Published: February 2022

Background

In January 2021, the World Health Organization published the 2021–2030 roadmap for the control of neglected tropical diseases (NTDs). The goal for schistosomiasis is to achieve elimination as a public health problem (EPHP) and elimination of transmission (EOT) in 78 and 25 countries (by 2030), respectively. Mass drug administration (MDA) of praziquantel continues to be the main strategy for control and elimination. However, as there is limited availability of praziquantel, it is important to determine what volume of treatments are required, who should be targeted and how frequently treatment must be administered to eliminate either transmission or morbidity caused by infection in different endemic settings with varied transmission intensities.

Methods and Results

In this paper, we employ two individual-based stochastic models of schistosomiasis transmission developed independently by the Imperial College London (ICL) and University of Oxford (SCHISTOX) to determine the optimal treatment strategies to achieve EOT. We find that treating school-age children (SAC) only is not sufficient to achieve EOT within a feasible time frame, regardless of the transmission setting and observed age–intensity of infection profile. Both models show that community-wide treatment is necessary to interrupt transmission in all endemic settings with low, medium and high pristine transmission intensities.

Conclusions

The required MDA coverage level to achieve either transmission or morbidity elimination depends on the prevalence prior to the start of treatment and the burden of infection in adults. The higher the worm burden in adults, the higher the coverage levels required for this age category through community-wide treatment programmes. Therefore, it is important that intensity and prevalence data are collected in each age category, particularly from SAC and adults, so that the correct coverage level can be calculated and administered.

Graphical Abstract
Chondrocyte-derived exosomes promote cartilage calcification in temporomandibular joint osteoarthritis
Authors: Liu Qian , Wang Ruoxin , Hou Shujie , He Feng , Ma Yuanjun , Ye Tao , Yu Shibin , Chen Hongwei , Wang Helin , Zhang Mian
Published: February 2022

Backgrounds

Abnormal cartilage calcification is one of the pathological changes of temporomandibular joint (TMJ) osteoarthritis (OA). Recent studies have reported that exosomes can regulate the formation of abnormal calcified nodules in diseases including atherosclerosis and chronic kidney disease. However, the influences of chondrocyte-derived exosomes on abnormal cartilage calcification in TMJ OA are still unclear.

Methods

TMJ OA was induced by unilateral anterior crossbite (UAC) for 4, 8, or 12 weeks in rats to observe abnormal calcification in TMJ condylar cartilage and exosome formation. Concomitantly, GW4869, the inhibitor of exosome formation, was locally injected to the TMJ of rats under stimulation of UAC, while the exosomes extracted from primary condylar chondrocytes stimulated with fluid flow shear stress (FFSS) were locally injected to rats TMJ.

Results

Abnormal calcification was enhanced in the degenerative cartilage of TMJ OA in UAC rats, and a large number of exosome-like structures with diameters of 50-150 nm were found in the calcified cartilage together with decreased expression of matrix Gla protein (MGP) and increased expression of CD63, tissue-nonspecific alkaline phosphatase (TNAP) and nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1). After FFSS stimulation, the number of exosomes secreted by chondrocytes and the numbers of calcified nodules were increased in cultured cells, and the protein levels of MGP, TNAP, and NPP1 in exosomes were changed. Inhibition of exosome formation, TNAP, and NPP1 or supplementation with exogenous MGP effectively alleviated FFSS-induced chondrocyte calcification. Local injection of GW4869, the exosome inhibitor, alleviated TMJ OA-related cartilage degeneration and calcification in UAC rats. Local injection of exosomes obtained from chondrocytes stimulated by FFSS to the TMJs of normal rats induced cartilage degeneration and calcification similar to that in TMJ OA.

Conclusions

Abnormal biomechanical loading leads to enhanced formation of chondrocyte-derived exosomes, in which promoters of calcification increased and inhibitors decreased, resulting in accelerating abnormal cartilage calcification in TMJ OA. The inhibition of degenerative chondrocyte-derived exosomes is expected to be a new way to prevent and treat TMJ OA.
The long-term cost-effectiveness of oral semaglutide versus empagliflozin and dulaglutide in Portugal
Authors: Malkin Samuel J. P. , Carvalho Davide , Costa Catarina , Conde Vasco , Hunt Barnaby
Published: February 2022

Background

Oral semaglutide is a novel glucagon-like peptide-1 (GLP-1) analog that has been associated with improvements in glycated hemoglobin (HbA1c) and body weight versus sodium-glucose cotransporter-2 inhibitor empagliflozin and injectable GLP-1 receptor agonist dulaglutide in the PIONEER 2 clinical trial and in a recent network meta-analysis (NMA), respectively. The aim of the present study was to evaluate the long-term cost-effectiveness of oral semaglutide 14 mg versus empagliflozin 25 mg and dulaglutide 1.5 mg for the treatment of type 2 diabetes from a healthcare payer perspective in Portugal.

Methods

In two separate analyses, outcomes were projected over patients’ lifetimes using the IQVIA CORE Diabetes Model (v9.0), discounted at 4% per annum. Clinical data were sourced from the PIONEER 2 trial and the NMA for the comparisons versus empagliflozin and dulaglutide, respectively. Patients were assumed to receive initial therapies until HbA1c exceeded 7.5%, then treatment-intensified to solely basal insulin therapy. Costs were accounted from a National Healthcare Service perspective in Portugal and expressed in 2021 euros (EUR). Utilities were taken from published sources.

Results

Oral semaglutide 14 mg was associated with improvements in life expectancy of 0.10 and 0.03 years, and quality-adjusted life expectancy of 0.11 and 0.03 quality-adjusted life years (QALYs), versus empagliflozin 25 mg and dulaglutide 1.5 mg, respectively. Improved clinical outcomes were due to a reduced cumulative incidence and increased time to onset of diabetes-related complications with oral semaglutide. Total costs were projected to be EUR 2548 and EUR 814 higher with oral semaglutide versus empagliflozin and dulaglutide, with higher acquisition costs partially offset by cost savings from avoidance of diabetes-related complications. Oral semaglutide 14 mg was therefore associated with incremental cost-effectiveness ratios of EUR 23,571 and EUR 23,927 per QALY gained versus empagliflozin 25 mg and dulaglutide 1.5 mg, respectively.

Conclusions

Based on a willingness-to-pay threshold of EUR 30,000 per QALY gained, oral semaglutide 14 mg was considered cost-effective versus empagliflozin 25 mg and dulaglutide 1.5 mg for the treatment of type 2 diabetes in Portugal.
Survival capability of Campylobacter upsaliensis under environmental stresses
Authors: Elmonir Walid , Vetchapitak Torrung , Amano Tomoko , Taniguchi Takako , Misawa Naoaki
Published: February 2022

Objective

Campylobacter upsaliensis has been recognized as an emerging pathogen. However, little is known about its survival in the environment. To evaluate its survival capability, we estimated the reduction in viable counts of C. upsaliensis after aerobic exposure to starvation in phosphate-buffered saline (PBS), acidity (pH = 4.3), high osmolarity (4% NaCl), and dryness in wet pulp disks at different temperatures. Also, survival in dog feces and dog food at variable temperate was assessed.

Results

Campylobacter upsaliensis remained culturable under starvation for 4 days at 25 °C and for 10 weeks at 4 °C. C. upsaliensis was also recoverable after exposure to high osmolality for 9 days, dryness for 5 days, and acidity for 2 days, respectively. Similarly, C. upsaliensis survived in dog feces and dog food for several days at 25 °C and weeks at 4 °C. The survival capability of the organism was dependent on the water content, and also temperature. Notably, the tested C. upsaliensis strain was less resilient under all tested conditions than a C. jejuni strain used as a control. The findings showed that C. upsaliensis is able to survive under various environmental stresses, suggesting that it could pose a potential threat to public health.
The impacts of faecal subsampling on microbial compositional profiling
Authors: Cox Amanda J. , Hughes Lily , Nelson Tiffanie M. , Hatton-Jones Kyle M. , Ramsey Rebecca , Cripps Allan W. , West Nicholas P.
Published: February 2022

Objective

Despite the move to at-home, small-volume collection kits to facilitate large population-based studies of faecal microbial compositional profiling, there remains limited reporting on potential impacts of faecal subsampling approaches on compositional profiles. This study aimed to compare the microbial composition from faecal subsamples (< 5 g) collected from the beginning and end of a single bowel movement in ten otherwise healthy adults (6 female, 4 male; age: 24–55 years). Microbial composition was determined by V3–V4 16s rRNA sequencing and compared between subsamples.

Results

There were no significant differences in OTU count (p = 0.32) or Shannon diversity index (p = 0.29) between the subsamples. Comparison of relative abundance for identified taxa revealed very few differences between subsamples. At the lower levels of taxonomic classification differences in abundance of the Bacillales (p = 0.02) and the Eubacteriaceae family (p = 0.03), and the Eubacterium genera (p = 0.03) were noted. The observation of consistent microbial compositional profiles between faecal subsamples from the beginning and end of a single bowel movement is an important outcome for study designs employing this approach to faecal sample collection. These findings provide assurance that use of a faecal subsample for microbial composition profiling is generally representative of the gut luminal contents more broadly.