bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Application of Intrasite™ Hydrogel Dressing for the Management of Facial Gunshot Wounds With a Complex Soft Tissue Avulsion Defect
Authors: Fournier Maxime Y. , Cutbirth Caroline K. , Lam Duc N. , Marchena Jose M. , Pearl Craig B.
Published: July 2022

Study Design

Case report

Objective

To present an alternative method to traditional iodoform gauze packing for the management of soft tissue defects. Hydrogel dressings are modern packing materials that can be used to hold negative space, provide moisture to the wound, and absorb wound exudates.

Methods

This report describes the case of a 28-year-old patient who suffered facial gunshot injuries, including an approximately 3-centimeter diameter avulsion of soft tissue at the posterior right cheek. After wound debridement and irrigation, Intrasite™ hydrogel was used as a wound dressing to fill the soft tissue defect. The injectable and slowly resorbable material was added as needed by the patient for eight weeks until wound healing.

Results

Wound healing by secondary intention was achieved with acceptable esthetic outcomes while avoiding traditional dressing changes.

Conclusions

Facial gunshot wounds present a multitude of challenges particularly when complex soft tissue avulsions are involved. The surgeon must adequately debride these wounds and manage soft tissue healing to prevent infection and ensure satisfactory aesthetic and functional outcomes. Long-term patient compliance is equally important; however, dressing changes are often difficult and uncomfortable for the patient. The use of an injectable hydrogel dressing facilitated soft tissue healing while affording greater comfort to the patient compared with traditional dressing changes, thus likely improving compliance during the crucial healing period.
Families in transition: Living arrangements and intergenerational support in 21st century China
Authors: Huang Youqin , Li Yuyao , Clark William A.V.
Published: July 2022

As China continues the profound socioeconomic transformations set in motion by market reforms, it is important to understand how these changes are impacting Chinese families. The central question examined in this article is whether, and to what extent, the Chinese family is undergoing a Western process of modernization and an associated reduction in the previously very high rate of parent-adult child co-residence. Using recent national survey data, this study reveals that only two decades into the 21st century, co-residence in China is as low as, if not lower than, that in the West, and instead, living apart but in proximity in the same city/county has replaced co-residence as the most prevalent living arrangement. We show that the shift to proximity is a result of the negotiations between traditional and modernizing tendencies, and is further enabled by significantly improved housing and household financial conditions.
Intraosseous delivery of platelet-targeted factor VIII lentiviral vector in humanized NBSGW mice
Authors: Joo Julia H. , Wang Xuefeng , Singh Swati , Chen Chun-Yu , Li Chong , Adair Jennifer E. , Kiem Hans-Peter , Rawlings David J. , Miao Carol H.
Published: July 2022

We previously showed that intraosseous (IO) delivery of factor VIII (FVIII, gene F8) lentiviral vector (LV) driven by the megakaryocyte-specific promoter Gp1bα (G-F8-LV) partially corrected the bleeding phenotype in hemophilia A (HemA) mice for up to 5 months. In this study, we further characterized and confirmed the successful transduction of self-regenerating hematopoietic stem and progenitor cells (HSPCs) in treated mice. In addition, secondary transplant of HSPCs isolated from G-F8-LV–treated mice corrected the bleeding phenotype of the recipient HemA mice, indicating the potential of long-term transgene expression following IO-LV therapy. To facilitate the translation of this technology to human applications, we evaluated the safety and efficacy of this gene transfer therapy into human HSPCs. In vitro transduction of human HSPCs by the platelet-targeted G-F8-LV confirmed megakaryocyte-specific gene expression after preferential differentiation of HSPCs to megakaryocyte lineages. Lentiviral integration analysis detected a polyclonal integration pattern in G-F8-LV–transduced human cells, profiling the clinical safety of hemophilia treatment. Most importantly, IO delivery of G-F8-LV to humanized NBSGW mice produced persistent FVIII expression in human platelets after gene therapy, and the megakaryocytes differentiated from human CD34+ HSPCs isolated from LV-treated humanized mice showed up to 10.2% FVIII expression, indicating efficient transduction of self-regenerating human HSPCs. Collectively, these results indicate the long-term safety and efficacy of the IO-LV gene therapy strategy for HemA in a humanized model, adding further evidence to the feasibility of translating this method for clinical applications.
TMT-based proteomic analysis of liquorice root in response to drought stress
Authors: Zhang Dong , Yang Zhongren , Song Xiaoqing , Zhang Fenglan , Liu Yan
Published: July 2022

Background

Drought stress is a serious threat to land use efficiency and crop yields worldwide. Understanding the mechanisms that plants use to withstand drought stress will help breeders to develop drought-tolerant medicinal crops. Liquorice (Glycyrrhiza uralensis Fisch.) is an important medicinal crop in the legume family and is currently grown mostly in northwest China, it is highly tolerant to drought. Given this, it is considered an ideal crop to study plant stress tolerance and can be used to identify drought-resistant proteins. Therefore, to understand the effects of drought stress on protein levels of liquorice, we undertook a comparative proteomic analysis of liquorice seedlings grown for 10 days in soil with different relative water content (SRWC of 80%, 65%, 50% and 35%, respectively). We used an integrated approach of Tandem Mass Tag labeling in conjunction with LC–MS/MS.

Results

A total of 7409 proteins were identified in this study, of which 7305 total proteins could be quantified. There were 837 differentially expressed proteins (DEPs) identified after different drought stresses. Compared with CK, 123 DEPs (80 up-regulated and 43 down-regulated) were found in LS; 353 DEPs (254 up-regulated and 99 down-regulated) in MS; and 564 DEPs (312 up-regulated and 252 down-regulated) in SS.The number of differentially expressed proteins increased with increasing water stress, and the number of up-regulated proteins was higher than that of down-regulated proteins in the different drought stress treatments compared with the CK. Used systematic bioinformatics analysis of these data to identify informative proteins we showed that osmolytes such as cottonseed sugars and proline accumulated under light drought stress and improved resistance. Under moderate and severe drought stress, oxidation of unsaturated fatty acids and accumulation of glucose and galactose increased in response to drought stress. Under moderate and severe drought stress synthesis of the terpene precursors, pentacene 2,3-epoxide and β-coumarin, was inhibited and accumulation of triterpenoids (glycyrrhetinic acid) was also affected.

Conclusions

These data provide a baseline reference for further study of the downstream liquorice proteome in response to drought stress. Our data show that liquorice roots exhibit specific response mechanisms to different drought stresses.
Genomic surveillance of Rift Valley fever virus: from sequencing to lineage assignment
Authors: Juma John , Fonseca Vagner , Konongoi Samson L. , van Heusden Peter , Roesel Kristina , Sang Rosemary , Bett Bernard , Christoffels Alan , de Oliveira Tulio , Oyola Samuel O.
Published: July 2022

Genetic evolution of Rift Valley fever virus (RVFV) in Africa has been shaped mainly by environmental changes such as abnormal rainfall patterns and climate change that has occurred over the last few decades. These gradual environmental changes are believed to have effected gene migration from macro (geographical) to micro (reassortment) levels. Presently, 15 lineages of RVFV have been identified to be circulating within the Sub-Saharan Africa. International trade in livestock and movement of mosquitoes are thought to be responsible for the outbreaks occurring outside endemic or enzootic regions. Virus spillover events contribute to outbreaks as was demonstrated by the largest epidemic of 1977 in Egypt. Genomic surveillance of the virus evolution is crucial in developing intervention strategies. Therefore, we have developed a computational tool for rapidly classifying and assigning lineages of the RVFV isolates. The computational method is presented both as a command line tool and a web application hosted at https://www.genomedetective.com/app/typingtool/rvfv/. Validation of the tool has been performed on a large dataset using glycoprotein gene (Gn) and whole genome sequences of the Large (L), Medium (M) and Small (S) segments of the RVFV retrieved from the National Center for Biotechnology Information (NCBI) GenBank database. Using the Gn nucleotide sequences, the RVFV typing tool was able to correctly classify all 234 RVFV sequences at species level with 100% specificity, sensitivity and accuracy. All the sequences in lineages A (n = 10), B (n = 1), C (n = 88), D (n = 1), E (n = 3), F (n = 2), G (n = 2), H (n = 105), I (n = 2), J (n = 1), K (n = 4), L (n = 8), M (n = 1), N (n = 5) and O (n = 1) were also correctly classified at phylogenetic level. Lineage assignment using whole RVFV genome sequences (L, M and S-segments) did not achieve 100% specificity, sensitivity and accuracy for all the sequences analyzed. We further tested our tool using genomic data that we generated by sequencing 5 samples collected following a recent RVF outbreak in Kenya. All the 5 samples were assigned lineage C by both the partial (Gn) and whole genome sequence classifiers. The tool is useful in tracing the origin of outbreaks and supporting surveillance efforts.

Availability: https://github.com/ajodeh-juma/rvfvtyping
Toripalimab combined with concurrent platinum-based Chemoradiotherapy in patients with locally advanced cervical Cancer: an open-label, single-arm, phase II trial
Authors: Chen Jie , Li Chen , Cao Yuanjie , Zhu Li , Zhang Bailin , You Jinqiang , Hou Hailing , Wang Jing , Yuan Zhiyong
Published: July 2022

Background

Concurrent chemoradiotherapy is currently the standard of care for patients with locally advanced cervical cancer. However, even with the application of modern radiotherapy techniques, a considerable number of patients still develop distant metastases. PD-L1 inhibitors show good efficacy in cervical cancer. This single-arm phase II study aims to explore the efficacy and tolerability of combining PD-L1 inhibitor with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer.

Methods/design

The primary endpoint of the study was the objective response rate assessed according to RECIST v1.1 criteria. The inclusion criteria were previously untreated patients aged 18–75 years with stage III-IVA (FIGO 2018 staging system) locally advanced cervical cancer. During concurrent chemoradiotherapy and consolidation chemotherapy, the enrolled patients will receive toripalimab (240 mg) every 3 weeks. After consolidation chemotherapy, the enrolled patients will be treated with toripalimab (240 mg) once every 6 weeks until the whole treatment cycle reaches 1 year. Intensity modulated radiotherapy was used for external beam radiation, and high-dose rate brachytherapy was delivered under image-guidance. Weekly DDP (40 mg/m2) was given concurrently with radiotherapy while 6 cycles of consolidated chemotherapy (paclitaxel plus DDP) were given after radiotherapy every three weeks. ﻿Secondary objectives included safety and tolerability, toxicity profile, progression-free survival, and overall survival.

Discussion

PD-L1 inhibitor has shown good efficacy in recurrent/metastatic cervical cancer. However, there is still a lack of evidence about its combination with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer. The purpose of this study is to explore the efficacy and tolerance of this combination therapy, so as to lay the foundation for the future phase III randomized study.

Trial registration

﻿clinicaltrials.govNCT05084677. ﻿Retrospectively registered on Octorber 07, 2021.
Impact of a health educational interventional program on reducing the head lice infestation among pupils in an elementary school of a sub-tropical region: a quasi-experimental study
Authors: Najjari Mohsen , Gorouhi Mohammad Amin , Zarrinfar Hossein , Hosseini Farash Bibi Razieh , Jamali Jamshid , Moghaddas Elham , Ebrahimipuor Mohammad
Published: July 2022

Background

Pediculosis is an important social challenge that can be caused by human head louse,Pediculus humanus capitis.This infestation is cosmopolitan, especially in countries with low hygiene and sanitation. Regular health education classes for students and their parents are required to reduce this infestation in schools and families. This study aimed to evaluate the impact of a health education intervention program on reducing head lice among pupils of an elementary school.

Methods

In a quasi-experimental study, a total of 880 elementary school girls were screened for pediculosis in (2017–2018). The prevalence of pediculosis follow-up continued monthly until the end of the school year after a two months educational intervention course. Visual inspection was applied for initial diagnosis of infection. The suspected cases were confirmed by wood lamp and potassium hydroxide (KOH) microscopic examination. Also eight questions about diagnostic, epidemiology, treatment and prevention were answered in a questionnaire by 50 volunteer parents before and after the training intervention course, to evaluate their general knowledge and measure the effectiveness of learning. All data were statistically analyzed using SPSS software (version 20.0, SPSS, Inc., Chicago, IL, USA). McNemar’s test was also applied to investigate the prevalence rate before and after the intervention. Ap-value of less than 0.05 was considered as statistically significant.

Results

At the beginning of study, pre-intervention prevalence of pediculosis among pupils was 8.4% (49/594). The mean age in all pupils was 9.86 ± 1.83 years old and the most infestation was shown in fourth-grade students with 10 years old. Analysis of statistics demonstrated a significant difference between having infestation and the number of members in the families. Post-intervention phase led to a decreased prevalence of pediculosis in pupils to 3% (8/594) (p-value < 0.05). Based on statistical analysis of questions before and after the training in the questionnaire, a significant increase of parental knowledge was observed on the prevention program of pediculosis (p-value < 0.001).

Conclusion

The prevalence of pediculosis was significantly reduced following the educational interventions in the school. The applied interventions may be implemented in other residual centers to get rid of this important infestation.
Magnitude of birth asphyxia and its associated factors among live birth in north Central Ethiopia 2021: an institutional-based cross-sectional study
Authors: Tibebu Nigusie Selomon , Emiru Tigabu Desie , Tiruneh Chalie Marew , Getu Bisrat Dessie , Abate Moges Wubneh , Nigat Adane Birhanu , Bantie Berihun , Legas Getasew , Walle Belete Gelaw , Feleke Mulualem Gete , Birrie Endalk
Published: July 2022

Background

The leading cause of neonatal death worldwide is birth asphyxia. Yearly, in the first month of life, 2.5 million children died around the world. Birth asphyxia is a major problem, particularly in developing nations like Ethiopia. The goal of this study was to determine the magnitude of birth asphyxia and the factors that contributed to it among neonates delivered at the Aykel Primary Hospital in north-central Ethiopia.

Methods

From August 1 to August 31, 2021, a hospital-based cross-sectional study was conducted on 144 live births. An Apgar score less than 7 in the fifth minute of birth authorized the diagnosis of birth asphyxia. Variable contention (P < 0.250) for multivariable analysis was determined after data examination and cleaning. Then, to identify important factors of birth asphyxia, a multivariable logistic regression model with a p-value of 0.05 was developed. Finally, a significant relationship between a dependent variable and independent factors was defined as a p-value less than 0.05 with a 95% confidence interval.

Results

The majority of the mothers, 71.53%, received at least one Antenatal care visit, and more than half of the newborns were male (62.50%). The percentage of neonates that had asphyxia at delivery was 11.11% (95% CI: 6.3 -16.9%). Male newborns were 5.02 times more probable than female newborns to asphyxiate [AOR: 5.02, 95% CI (1.11–22.61)]. Mothers who have not had at least one Antenatal Care visit were 3.72 times more likely to have an asphyxiated newborn than those who have at least one Antenatal Care visit [AOR: 3.72, 95%CI (1.11–12.42)]. Similarly, mothers who had an adverse pregnancy outcome were 7.03 times more likely to have an asphyxiated newborn than mothers who had no such history [AOR: 7.03, 95% CI (2.17–22.70)].

Conclusion

Birth asphyxia in newborn has come to a standstill as a major public health issue. The sexual identity of the newborn, Antenatal Care visits, and a history of poor pregnancy outcomes were all found to be significant risk factors for birth asphyxia. These findings have great importance for various stakeholders who are responsible for reducing birth asphyxia; in addition, policymakers should establish and revise guidelines associated to newborn activities and workshops.
Impact of a peer-led, community-based parenting programme delivered at a national scale: an uncontrolled cohort design with benchmarking
Authors: Day Crispin , Harwood Joshua , Kendall Nadine , Nicoll Jo
Published: July 2022

Background

Childhood behavioural problems are the most common mental health disorder worldwide and represent a major public health concern, particularly in socially disadvantaged communities. Treatment barriers mean that up to 70% of children do not receive recommended parenting interventions. Innovative approaches, including evidence-based peer-led models, such as Empowering Parents Empowering Communities’ (EPEC) Being a Parent (BAP) programme, have the potential to reduce childhood difficulties and improve parenting if replicable and successfully delivered at scale.

Method

This real-world quasi-experimental study, with embedded RCT benchmarking, examined the population reach, attendance, acceptability and outcomes of 128 BAP groups (n = 930 parents) delivered by 15 newly established sites participating in a UK EPEC scaling programme.

Results

Scaling programme (SP) sites successfully reached parents living in areas of greater social deprivation (n = 476, 75.3%), experiencing significant disadvantage (45.0% left school by 16; 39.9% lived in rental accommodation; 36.9% lone parents). The only benchmarked demographic difference was ethnicity, reflecting the greater proportion of White British parents living in scaling site areas (SP 67.9%; RCT 22.4%). Benchmark comparisons showed scaling sites’ parent group leaders achieved similar levels of satisfaction. Scaling site parent participants reported substantial levels of improvement in child concerns (ES 0.6), parenting (ES 0.9), parenting goals (ES 1.2) and parent wellbeing (ES 0.6) that were of similar magnitude to RCT benchmarked results. Though large, parents reported lower levels of parenting knowledge and confidence acquisition compared with the RCT benchmark.

Conclusion

Despite common methodological limitations associated with real-world scaling evaluations, findings suggest that this peer-led, community-based, parenting approach may be capable of successful replication at scale and may have considerable potential to improve child and parenting difficulties, particularly for socially disadvantaged populations.
The effect of video-based multimedia training on knowledge, attitude, and performance in breast self-examination
Authors: Karimian Zahra , Zare Roya , Zarifsanaiey Nahid , Salehi Nasim
Published: July 2022

Background/Objectives

Breast neoplasm is one of the most common cancers in Iranian women due to the late diagnosis. Awareness of breast neoplasm and using Breast Self-Examination (BSE) assist in the early detection and treatment of cancer. This study examined the effectiveness of video-based multimedia training versus face-to-face training in awareness of breast neoplasm and BSE and possible factors affecting their effectiveness.

Methods

This research was a pre-test, a post-test experimental study comparing the knowledge, attitude, and performance of women about BSE across two training intervention groups (face-to-face versus video-based multimedia). The study was conducted at Shiraz University of Medical Sciences (SUMS), and 100 women between 20 to 60 years old were allocated to each intervention group via multi-stage cluster sampling (n:110). Three valid and reliable researcher-made questioners were used. Data were analyzed using SPSS 24 with independent t-test, paired t-test, and ANOVA.

Results

Both video-based multimedia and face-to-face training methods significantly increased the participant's knowledge, attitude, and skills about breast self-examination (P < 0.001). In the sub-categories, the results showed that the face-to-face training improved negligence and forgetfulness in applying BSE (P = 0.03) and correcting or modifying the previous knowledge around the issue (P = 0.02). The effect of the video-based method on participants with university education was more than on non-university (P = 0.04).

Conclusion

Incorporating video-based multimedia training in awareness of breast neoplasm and breast self-examination provides an easy, flexible, and affordable way for detection, particularly considering crisis restrictions. This can be of particular attention in more populated, developing/low-income countries and rural and remote areas to enhance equitable access to training and facilitation diagnosis and treatment if applicable.
(Re)Conceptualising ‘good’ proxy decision-making for research: the implications for proxy consent decision quality
Authors: Shepherd Victoria
Published: July 2022

People who are unable to make decisions about participating in research rely on proxies to make a decision based on their wishes and preferences. However, patients rarely discuss their preferences about research and proxies find it challenging to determine what their wishes would be. While the process of informed consent has traditionally been the focus of research to improve consent decisions, the more conceptually complex area of what constitutes ‘good’ proxy decision-making for research has remained unexplored. Interventions are needed to improve and support proxy decision-making for research but are hampered by a lack of understanding about what constitutes decision quality in this context. A global increase in conditions associated with cognitive impairment such as dementia has led to an urgent need for more research into these conditions. The COVID-19 pandemic and subsequent necessity to conduct research with large numbers of critically ill patients has made this need even more pressing. Much of the empirical research centres on the desire to improve decision accuracy, despite growing evidence that authenticity is more reflective of the aim of proxy decisions and concerns about the methodological flaws in authenticity-focused studies. Such studies also fail to take account of the impact of decision-making on proxies, or the considerable body of research on improving the quality of healthcare decisions. This paper reports a concept synthesis of the literature that was conducted to develop the first conceptualisation of ‘good’ proxy decisions about research participation. Elements of decision quality were identified across three stages of decision-making: proxy preparedness for decision-making which includes knowledge and understanding, and values clarification and preference elicitation; the role of uncertainty, decisional conflict, satisfaction and regret in the decision-making process; and preference linked outcomes and their effect. This conceptualisation provides an essential first step towards the future development of interventions to enhance the quality of proxy decision-making and ensure proxy decisions represent patients’ values and preferences.
Combined Dusp4 and p53 loss with Dbf4 amplification drives tumorigenesis via cell cycle restriction and replication stress escape in breast cancer
Authors: Hanna Ann , Nixon Mellissa J. , Estrada M. Valeria , Sanchez Violeta , Sheng Quanhu , Opalenik Susan R. , Toren Abigail L. , Bauer Joshua , Owens Phillip , Mason Frank M. , Cook Rebecca S. , Sanders Melinda E. , Arteaga Carlos L. , Balko Justin M.
Published: July 2022

Aim

Deregulated signaling pathways are a hallmark feature of oncogenesis and driver of tumor progression. Dual specificity protein phosphatase 4 (DUSP4) is a critical negative regulator of the mitogen-activated protein kinase (MAPK) pathway and is often deleted or epigenetically silenced in tumors. DUSP4 alterations lead to hyperactivation of MAPK signaling in many cancers, including breast cancer, which often harbor mutations in cell cycle checkpoint genes, particularly in TP53.

Methods

Using a genetically engineered mouse model, we generated mammary-specific Dusp4-deleted primary epithelial cells to investigate the necessary conditions in which DUSP4 loss may drive breast cancer oncogenesis.

Results

We found that Dusp4 loss alone is insufficient in mediating tumorigenesis, but alternatively converges with loss in Trp53 and MYC amplification to induce tumorigenesis primarily through chromosome 5 amplification, which specifically upregulates Dbf4, a cell cycle gene that promotes cellular replication by mediating cell cycle checkpoint escape.

Conclusions

This study identifies a novel mechanism for breast tumorigenesis implicating Dusp4 loss and p53 mutations in cellular acquisition of Dbf4 upregulation as a driver of cellular replication and cell cycle checkpoint escape.
High-throughput techniques enable advances in the roles of DNA and RNA secondary structures in transcriptional and post-transcriptional gene regulation
Authors: Georgakopoulos-Soares Ilias , Chan Candace S. Y. , Ahituv Nadav , Hemberg Martin
Published: July 2022

The most stable structure of DNA is the canonical right-handed double helix termed B DNA. However, certain environments and sequence motifs favor alternative conformations, termed non-canonical secondary structures. The roles of DNA and RNA secondary structures in transcriptional regulation remain incompletely understood. However, advances in high-throughput assays have enabled genome wide characterization of some secondary structures. Here, we describe their regulatory functions in promoters and 3’UTRs, providing insights into key mechanisms through which they regulate gene expression. We discuss their implication in human disease, and how advances in molecular technologies and emerging high-throughput experimental methods could provide additional insights.
Recommendations for clinical interpretation of variants found in non-coding regions of the genome
Authors: Ellingford Jamie M. , Ahn Joo Wook , Bagnall Richard D. , Baralle Diana , Barton Stephanie , Campbell Chris , Downes Kate , Ellard Sian , Duff-Farrier Celia , FitzPatrick David R. , Greally John M. , Ingles Jodie , Krishnan Neesha , Lord Jenny , Martin Hilary C. , Newman William G. , O’Donnell-Luria Anne , Ramsden Simon C. , Rehm Heidi L. , Richardson Ebony , Singer-Berk Moriel , Taylor Jenny C. , Williams Maggie , Wood Jordan C. , Wright Caroline F. , Harrison Steven M. , Whiffin Nicola
Published: July 2022

Background

The majority of clinical genetic testing focuses almost exclusively on regions of the genome that directly encode proteins. The important role of variants in non-coding regions in penetrant disease is, however, increasingly being demonstrated, and the use of whole genome sequencing in clinical diagnostic settings is rising across a large range of genetic disorders. Despite this, there is no existing guidance on how current guidelines designed primarily for variants in protein-coding regions should be adapted for variants identified in other genomic contexts.

Methods

We convened a panel of nine clinical and research scientists with wide-ranging expertise in clinical variant interpretation, with specific experience in variants within non-coding regions. This panel discussed and refined an initial draft of the guidelines which were then extensively tested and reviewed by external groups.

Results

We discuss considerations specifically for variants in non-coding regions of the genome. We outline how to define candidate regulatory elements, highlight examples of mechanisms through which non-coding region variants can lead to penetrant monogenic disease, and outline how existing guidelines can be adapted for the interpretation of these variants.

Conclusions

These recommendations aim to increase the number and range of non-coding region variants that can be clinically interpreted, which, together with a compatible phenotype, can lead to new diagnoses and catalyse the discovery of novel disease mechanisms.
Shifts in the immunoepigenomic landscape of monocytes in response to a diabetes-specific social support intervention: a pilot study among Native Hawaiian adults with diabetes
Authors: Dye Christian K. , Corley Michael J. , Ing Claire , Lum-Jones Annette , Li Dongmei , Mau Marjorie K. L. M. , Maunakea Alika K.
Published: July 2022

Background

Native Hawaiians are disproportionately affected by type 2 diabetes mellitus (DM), a chronic metabolic, non-communicable disease characterized by hyperglycemia and systemic inflammation. Unrelenting systemic inflammation  frequently leads to a cascade of multiple comorbidities associated with DM, including cardiovascular disease, microvascular complications, and renal dysfunction. Yet few studies have examined the link between chronic inflammation at a cellular level and its relationship to standard DM therapies such as diabetes-specific lifestyle and social support education, well recognized as the cornerstone of clinical standards of diabetes care. This pilot study was initiated to explore the association of monocyte inflammation using epigenetic, immunologic, and clinical measures following a 3-month diabetes-specific social support program among high-risk Native Hawaiian adults with DM.

Results

From a sample of 16 Native Hawaiian adults with DM, monocytes enriched from peripheral blood mononuclear cells (PBMCs) of 8 individuals were randomly selected for epigenomic analysis. Using the Illumina HumanMethylation450 BeadChip microarray, 1,061 differentially methylated loci (DML) were identified in monocytes of participants at baseline and 3 months following a DM-specific social support program (DM-SSP). Gene ontology analysis showed that these DML were enriched within genes involved in immune, metabolic, and cardiometabolic pathways, a subset of which were also significantly differentially expressed. Ex vivo analysis of immune function showed improvement post-DM-SSP compared with baseline, characterized by attenuated interleukin 1β and IL-6 secretion from monocytes. Altered cytokine secretion in response to the DM-SSP was significantly associated with changes in the methylation and gene expression states of immune-related genes in monocytes between intervention time points.

Conclusions

Our pilot study provides preliminary evidence of changes to inflammatory monocyte activity, potentially driven by epigenetic modifications, 3 months following a DM-specific SSP intervention. These novel alterations in the trajectory of monocyte inflammatory states were identified at loci that regulate transcription of immune and metabolic genes in high-risk Native Hawaiians with DM, suggesting a relationship between improvements in psychosocial behaviors and shifts in the immunoepigenetic patterns following a diabetes-specific SSP. Further research is warranted to investigate how social support influences systemic inflammation via immunoepigenetic modifications in chronic inflammatory diseases such as DM.
Attentional influences on neural processing of biological motion in typically developing children and those on the autism spectrum
Authors: Knight Emily J. , Krakowski Aaron I. , Freedman Edward G. , Butler John S. , Molholm Sophie , Foxe John J.
Published: July 2022

Background

Biological motion imparts rich information related to the movement, actions, intentions and affective state of others, which can provide foundational support for various aspects of social cognition and behavior. Given that atypical social communication and cognition are hallmark symptoms of autism spectrum disorder (ASD), many have theorized that a potential source of this deficit may lie in dysfunctional neural mechanisms of biological motion processing. Synthesis of existing literature provides some support for biological motion processing deficits in autism spectrum disorder, although high study heterogeneity and inconsistent findings complicate interpretation. Here, we attempted to reconcile some of this residual controversy by investigating a possible modulating role for attention in biological motion processing in ASD.

Methods

We employed high-density electroencephalographic recordings while participants observed point-light displays of upright, inverted and scrambled biological motion under two task conditions to explore spatiotemporal dynamics of intentional and unintentional biological motion processing in children and adolescents with ASD (n = 27), comparing them to a control cohort of neurotypical (NT) participants (n = 35).

Results

Behaviorally, ASD participants were able to discriminate biological motion with similar accuracy to NT controls. However, electrophysiologic investigation revealed reduced automatic selective processing of upright biologic versus scrambled motion stimuli in ASD relative to NT individuals, which was ameliorated when task demands required explicit attention to biological motion. Additionally, we observed distinctive patterns of covariance between visual potentials evoked by biological motion and functional social ability, such that Vineland Adaptive Behavior Scale-Socialization domain scores were differentially associated with biological motion processing in the N1 period in the ASD but not the NT group.

Limitations

The cross-sectional design of this study does not allow us to definitively answer the question of whether developmental differences in attention to biological motion cause disruption in social communication, and the sample was limited to children with average or above cognitive ability.

Conclusions

Together, these data suggest that individuals with ASD are able to discriminate, with explicit attention, biological from non-biological motion but demonstrate diminished automatic neural specificity for biological motion processing, which may have cascading implications for the development of higher-order social cognition.
Andrographolide protects bone marrow mesenchymal stem cells against glucose and serum deprivation under hypoxia via the NRF2 signaling pathway
Authors: Sun Yanting , Xu Hao , Tan Bin , Yi Qin , Liu Huiwen , Chen Tangtian , Xiang Han , Wang Rui , Xie Qiumin , Tian Jie , Zhu Jing
Published: July 2022

Background

Bone marrow mesenchymal stem cell (BMSCs) therapy is an important cell transplantation strategy in the regenerative medicine field. However, a severely ischemic microenvironment, such as nutrient depletion and hypoxia, causes a lower survival rate of transplanted BMSCs, limiting the application of BMSCs. Therefore, improving BMSCs viability in adverse microenvironments is an important means to improve the effectiveness of BMSCs therapy.

Objective

To illustrate the protective effect of andrographolide (AG) against glucose and serum deprivation under hypoxia (1% O2) (GSDH)-induced cell injury in BMSCs and investigate the possible underlying mechanisms.

Methods

An in vitro primary rat BMSCs cell injury model was established by GSDH, and cellular viability, proliferation and apoptosis were observed after AG treatment under GSDH. Reactive oxygen species levels and oxidative stress-related genes and proteins were measured by flow cytometry, RT-qPCR and Western blotting. Mitochondrial morphology, function and number were further assessed by laser confocal microscopy and flow cytometry.

Results

AG protected BMSCs against GSDH-induced cell injury, as indicated by increases in cell viability and proliferation and mitochondrial number and decreases in apoptosis and oxidative stress. The metabolic status of BMSCs was changed from glycolysis to oxidative phosphorylation to increase the ATP supply. We further observed that the NRF2 pathway was activated by AG, and treatment of BMSCs with a specific NRF2 inhibitor (ML385) blocked the protective effect of AG.

Conclusion

Our results suggest that AG is a promising agent to improve the therapeutic effect of BMSCs.
The Campbell Collaboration’s systematic review of school-based anti-bullying interventions does not meet mandatory methodological standards
Authors: Littell Julia H. , Gorman Dennis M.
Published: July 2022

Background

Many published reviews do not meet the widely accepted PRISMA standards for systematic reviews and meta-analysis. Campbell Collaboration and Cochrane reviews are expected to meet even more rigorous standards, but their adherence to these standards is uneven. For example, a newly updated Campbell systematic review of school-based anti-bullying interventions does not appear to meet many of the Campbell Collaboration’s mandatory methodological standards.

Issues

In this commentary, we document methodological problems in the Campbell Collaboration's new school-based anti-bullying interventions review, including (1) unexplained deviations from the protocol; (2) inadequate documentation of search strategies; (3) inconsistent reports on the number of included studies; (4) undocumented risk of bias ratings; (5) assessments of selective outcome reporting bias that are not transparent, not replicable, and appear to systematically underestimate risk of bias; (6) unreliable assessments of risk of publication bias; (7) use of a composite scale that conflates distinct risks of bias; and (8) failure to consider issues related to the strength of the evidence and risks of bias in interpreting results and drawing conclusions. Readers who are unaware of these problems may place more confidence in this review than is warranted. Campbell Collaboration editors declined to publish our comments and declined to issue a public statement of concern about this review.

Conclusions

Systematic reviews are expected to use transparent methods and follow relevant methodological standards. Readers should be concerned when these expectations are not met, because transparency and rigor enhance the trustworthiness of results and conclusions. In the tradition of Donald T. Campbell, there is need for more public debate about the methods and conclusions of systematic reviews, and greater clarity regarding applications of (and adherence to) published standards for systematic reviews.
Benchmarking public policies to create healthy food environments compared to best practice: the Healthy Food Environment Policy Index in Guatemala
Authors: Sánchez-Nóchez Carmen María , Ramirez-Zea Manuel , Vandevijvere Stefanie , Kroker-Lobos María Fernanda
Published: July 2022

Background

Benchmarking the implementation of healthy food environment public policies against international best practices may accelerate the government response to prevent obesity and non-communicable diseases (NCDs) in the countries. The aim of the study was to determine the extent of food environment policy implementation in Guatemala and to identify and prioritize actions for the government to accelerate their implementation.

Methods

The INFORMAS Healthy Food Environment Policy Index (Food-EPI from the International Network for Food and Obesity/NCDs Research, Monitoring and Action Support) was used. Evidence of implementation for 50 good practice indicators within the seven food policies and six infrastructure support domains was compiled, and subsequently validated by Guatemalan government officials. A national civil society expert panel on public health and nutrition performed an online assessment of the implementation of healthy food environment policies against best international practices. The level of agreement among evaluators was measured using the Gwet second order agreement coefficient (AC2). The expert panel recommended actions for each indicator during on-site workshops and those actions were prioritized by importance and achievability.

Results

The expert panel rated implementation at zero for 26% of the indicators, very low for 28% of indicators, low for 42%, and medium for 4% of indicators (none were rated high). Indicators at medium implementation were related to the use of evidence for developing policies and ingredient list/nutrition information panels on packaged foods. Seventy-seven actions were recommended prioritizing the top 10 for immediate action. The Gwet AC2 was 0.73 (95% CI 0.67–0.80), indicating a good concordance among experts.

Conclusions

In the Food-EPI of Guatemala, almost all indicators of good practice had a low or less level of implementation. The expert panel proposed 12 priority actions to accelerate policy implementation to tackle obesity and NCDs in the country.
Serum and plasma levels of brain-derived neurotrophic factor in individuals with eating disorders (EDs): a systematic review and meta-analysis
Authors: Shobeiri Parnian , Bagherieh Sara , Mirzayi Parsa , Kalantari Amirali , Mirmosayyeb Omid , Teixeira Antônio L. , Rezaei Nima
Published: July 2022

Background

Brain-derived neurotrophic factor (BDNF) is essential for neuronal survival, differentiation, development, and plasticity. Evidence suggests that fluctuations in peripheral levels (i.e., plasma or serum) of BDNF are associated with eating behaviors. Nevertheless, the findings are inconsistent. The purpose of this study is to determine if serum or plasma levels of BDNF are altered in individuals with eating disorders (EDs) compared to controls.

Methods

We conducted a systematic search of the core electronic medical databases from inception to March 2022 and identified observational studies that compared individuals with EDs to controls without EDs on serum or plasma levels of BDNF. R version 4.0.4 was used for all visualizations and calculations.

Results

The current meta-analysis comprised 15 studies that fulfilled the inclusion criteria. Subjects with EDs (n = 795) showed lower BDNF levels compared to non-EDs controls (n = 552) (SMD: − 0.49, 95% CI [− 0.89; − 0.08], p-value = 0.01). Moreover, subgroup analysis was conducted based on the specimen (plasma and serum), which revealed no statistically significant difference in the levels of BDNF between the two subgroups (p-value = 0.92). Additionally, meta-regression results revealed that publication year, mean age of the individuals with EDs, NOS scores, and the number of individuals with EDs collectively accounted for 25.99% percent of the existing heterogeneity.

Conclusion

Lower BDNF levels are associated with EDs.
Qualitative study of patient experiences of mental distress during TB investigation and treatment in Zambia
Authors: Mainga T. , Gondwe M. , Mactaggart I. , Stewart R. C. , Shanaube K. , Ayles H. , Bond V.
Published: July 2022

Background

The mental health and TB syndemic is a topic that remains under-researched with a significant gap in acknowledging and recognizing patient experiences, particularly in the sub-Saharan African region. In this qualitative study conducted in Zambia, we aimed to explore the lived mental health experiences of TB patients focusing on their multi-layered drivers of distress, and by so doing highlighting contextual factors that influence mental distress in TB patients in this setting.

Methods

The study draws on qualitative data collected in 2018 as part of the Tuberculosis Reduction through Expanded Antiretroviral Treatment and Screening for active TB trial (TREATS) being conducted in Zambia. The data was collected through in-depth interviews with former TB patients (n = 80) from 8 urban communities participating in the TREATS trial. Thematic analysis was conducted. Additional quantitative exploratory analysis mapping mental distress symptoms on demographic, social, economic and TB characteristics of participants was conducted.

Results

Most participants (76%) shared that they had experienced some form of mental distress during their TB investigation and treatment period. The reported symptoms ranged in severity. Some participants reported mild distress that did not disrupt their daily lives or ability to adhere to their TB medication, while other participants reported more severe symptoms of distress, for example, 15% of participants shared that they had suicidal ideation and thoughts of self-harm during their time on treatment. Mental distress was driven by unique interactions between individual, social and health level factors most of which were inextricably linked to poverty. Mental distress caused by individual level drivers such as TB morbidity often abated once participants started feeling better, however social, economic and health system level drivers of distress persisted during and beyond TB treatment.

Conclusion

The findings illustrate that mental distress during TB is driven by multi-layered and intersecting stresses, with the economic stress of poverty often being the most powerful driver. Measures are urgently needed to support TB patients during the investigation and treatment phase, including increased availability of mental health services, better social security safety nets during TB treatment, and interventions targeting TB, HIV and mental health stigma.

Trial registration ClinicalTrials.gov NCT03739736. Trial registration date: November 14, 2018.