bluuebunny/crossref_metadata_2025 huggingface dataset:
Large-scale genomic analysis reveals the genetic cost of chicken domestication
Authors: Wang Ming-Shan , Zhang Jin-Jin , Guo Xing , Li Ming , Meyer Rachel , Ashari Hidayat , Zheng Zhu-Qing , Wang Sheng , Peng Min-Sheng , Jiang Yu , Thakur Mukesh , Suwannapoom Chatmongkon , Esmailizadeh Ali , Hirimuthugoda Nalini Yasoda , Zein Moch Syamsul Arifin , Kusza Szilvia , Kharrati-Koopaee Hamed , Zeng Lin , Wang Yun-Mei , Yin Ting-Ting , Yang Min-Min , Li Ming-Li , Lu Xue-Mei , Lasagna Emiliano , Ceccobelli Simone , Gunwardana Humpita Gamaralalage Thilini Nisank , Senasig Thilina Madusanka , Feng Shao-Hong , Zhang Hao , Bhuiyan Abul Kashem Fazlul Haque , Khan Muhammad Sajjad , Silva Gamamada Liyanage Lalanie Pradeepa , Thuy Le Thi , Mwai Okeyo A. , Ibrahim Mohamed Nawaz Mohamed , Zhang Guojie , Qu Kai-Xing , Hanotte Olivier , Shapiro Beth , Bosse Mirte , Wu Dong-Dong , Han Jian-Lin , Zhang Ya-Ping
Published: June 2021

Background

Species domestication is generally characterized by the exploitation of high-impact mutations through processes that involve complex shifting demographics of domesticated species. These include not only inbreeding and artificial selection that may lead to the emergence of evolutionary bottlenecks, but also post-divergence gene flow and introgression. Although domestication potentially affects the occurrence of both desired and undesired mutations, the way wild relatives of domesticated species evolve and how expensive the genetic cost underlying domestication is remain poorly understood. Here, we investigated the demographic history and genetic load of chicken domestication.

Results

We analyzed a dataset comprising over 800 whole genomes from both indigenous chickens and wild jungle fowls. We show that despite having a higher genetic diversity than their wild counterparts (average π, 0.00326 vs. 0.00316), the red jungle fowls, the present-day domestic chickens experienced a dramatic population size decline during their early domestication. Our analyses suggest that the concomitant bottleneck induced 2.95% more deleterious mutations across chicken genomes compared with red jungle fowls, supporting the “cost of domestication” hypothesis. Particularly, we find that 62.4% of deleterious SNPs in domestic chickens are maintained in heterozygous states and masked as recessive alleles, challenging the power of modern breeding programs to effectively eliminate these genetic loads. Finally, we suggest that positive selection decreases the incidence but increases the frequency of deleterious SNPs in domestic chicken genomes.

Conclusion

This study reveals a new landscape of demographic history and genomic changes associated with chicken domestication and provides insight into the evolutionary genomic profiles of domesticated animals managed under modern human selection.
A method for cryopreservation and single nucleus RNA-sequencing of normal adult human interventricular septum heart tissue reveals cellular diversity and function
Authors: Larson Amy , Chin Michael T.
Published: June 2021

Background

Single cell sequencing of human heart tissue is technically challenging and methods to cryopreserve heart tissue for obtaining single cell information have not been standardized. Studies published to date have used varying methods to preserve and process human heart tissue, and have generated interesting datasets, but development of a biobanking standard has not yet been achieved. Heart transcription patterns are known to be regionally diverse, and there are few single cell datasets for normal human heart tissue.

Methods

Using pig tissue, we developed a rigorous and reproducible method for tissue mincing and cryopreservation that allowed recovery of high quality single nuclei RNA. We subsequently tested this protocol on normal human heart tissue obtained from organ donors and were able to recover high quality nuclei for generation of single nuclei RNA-seq datasets, using a commercially available platform from 10× Genomics. We analyzed these datasets using standard software packages such as CellRanger and Seurat.

Results

Human heart tissue preserved with our method consistently yielded nuclear RNA with RNA Integrity Numbers of greater than 8.5. We demonstrate the utility of this method for single nuclei RNA-sequencing of the normal human interventricular septum and delineating its cellular diversity. The human IVS showed unexpected diversity with detection of 23 distinct cell clusters that were subsequently categorized into different cell types. Cardiomyocytes and fibroblasts were the most commonly identified cell types and could be further subdivided into 5 different cardiomyocyte subtypes and 6 different fibroblast subtypes that differed by gene expression patterns. Ingenuity Pathway analysis of these gene expression patterns suggested functional diversity in these cell subtypes.

Conclusions

Here we report a simple technical method for cryopreservation and subsequent nuclear isolation of human interventricular septum tissue that can be done with common laboratory equipment. We show how this method can be used to generate single nuclei transcriptomic datasets that rival those already published by larger groups in terms of cell diversity and complexity and suggest that this simple method can provide guidance for biobanking of human myocardial tissue for complex genomic analysis.
miR-181a-regulated pathways in T-cell differentiation and aging
Authors: Kim Chulwoo , Ye Zhongde , Weyand Cornelia M. , Goronzy Jörg J.
Published: June 2021

MicroRNAs (miRNAs) are regulatory noncoding RNAs important for many aspects of cellular processes including cell differentiation and proliferation. Functions of numerous miRNAs have been identified in T cells, with miR-181a regulating T cell activation thresholds during thymic T cell development and during activation of peripheral T cells. Intriguingly, miR-181a is implicated in defective antiviral and vaccine responses in older individuals, as its expression declines in naïve T cells with increasing age. Here, we review the pathways that are regulated by miR-181a and that explain the unique role of miR-181a in T cell development, T cell activation and antiviral T cell responses. These studies provide a framework for understanding how a decline in miR-181a expression in T cells could contribute to age-related defects in adaptive immunity. We furthermore review the mechanisms that cause the age-related decline in miR-181a expression and discuss the potential of restoring miR-181a expression or targeting miR-181a-regulated pathways to improve impaired T cell responses in older individuals.
Serious games for upper limb rehabilitation after stroke: a meta-analysis
Authors: Doumas Ioannis , Everard Gauthier , Dehem Stéphanie , Lejeune Thierry
Published: June 2021

Background

Approximately two thirds of stroke survivors maintain upper limb (UL) impairments and few among them attain complete UL recovery 6 months after stroke. Technological progress and gamification of interventions aim for better outcomes and constitute opportunities in self- and tele-rehabilitation.

Objectives

Our objective was to assess the efficacy of serious games, implemented on diverse technological systems, targeting UL recovery after stroke. In addition, we investigated whether adherence to neurorehabilitation principles influenced efficacy of games specifically designed for rehabilitation, regardless of the device used.

Method

This systematic review was conducted according to PRISMA guidelines (PROSPERO registration number: 156589). Two independent reviewers searched PubMed, EMBASE, SCOPUS and Cochrane Central Register of Controlled Trials for eligible randomized controlled trials (PEDro score ≥ 5). Meta-analysis, using a random effects model, was performed to compare effects of interventions using serious games, to conventional treatment, for UL rehabilitation in adult stroke patients. In addition, we conducted subgroup analysis, according to adherence of included studies to a consolidated set of 11 neurorehabilitation principles.

Results

Meta-analysis of 42 trials, including 1760 participants, showed better improvements in favor of interventions using serious games when compared to conventional therapies, regarding UL function (SMD = 0.47; 95% CI = 0.24 to 0.70;P < 0.0001), activity (SMD = 0.25; 95% CI = 0.05 to 0.46;P = 0.02) and participation (SMD = 0.66; 95% CI = 0.29 to 1.03;P = 0.0005). Additionally, long term effect retention was observed for UL function (SMD = 0.42; 95% CI = 0.05 to 0.79;P = 0.03). Interventions using serious games that complied with at least 8 neurorehabilitation principles showed better overall effects. Although heterogeneity levels remained moderate, results were little affected by changes in methods or outliers indicating robustness.

Conclusion

This meta-analysis showed that rehabilitation through serious games, targeting UL recovery after stroke, leads to better improvements, compared to conventional treatment, in three ICF-WHO components. Irrespective of the technological device used, higher adherence to a consolidated set of neurorehabilitation principles enhances efficacy of serious games. Future development of stroke-specific rehabilitation interventions should further take into consideration the consolidated set of neurorehabilitation principles.
Full-length transcriptome sequences by a combination of sequencing platforms applied to isoflavonoid and triterpenoid saponin biosynthesis of Astragalus mongholicus Bunge
Authors: Yin Minzhen , Chu Shanshan , Shan Tingyu , Zha Liangping , Peng Huasheng
Published: June 2021

Background

Astragalus mongholicus Bunge is an important medicinal plant used in traditional Chinese medicine. It is rich in isoflavonoids and triterpenoid saponins. Although these active constituents of A. mongholicus have been discovered for a long time, the genetic basis of isoflavonoid and triterpenoid saponin biosynthesis in this plant is virtually unknown because of the lack of a reference genome. Here, we used a combination of next-generation sequencing (NGS) and single-molecule real-time (SMRT) sequencing to identify genes involved in the biosynthetic pathway of secondary metabolites in A. mongholicus.

Results

In this study, NGS, SMRT sequencing, and targeted compound analysis were combined to investigate the association between isoflavonoid and triterpenoid saponin content, and specific gene expression in the root, stem, and leaves of A. mongholicus. Overall, 643,812 CCS reads were generated, yielding 121,107 non-redundant transcript isoforms with an N50 value of 2124 bp. Based on these highly accurate transcripts, 104,756 (86.50%) transcripts were successfully annotated by any of the seven databases (NR, NT, Swissprot, KEGG, KOG, Pfam and GO). Levels of four isoflavonoids and four astragalosides (triterpenoid saponins) were determined. Forty-four differentially expressed genes (DEGs) involved in isoflavonoid biosynthesis and 44 DEGs from 16 gene families that encode enzymes involved in triterpenoid saponin biosynthesis were identified. Transcription factors (TFs) associated with isoflavonoid and triterpenoid saponin biosynthesis, including 72 MYBs, 53 bHLHs, 64 AP2-EREBPs, and 11 bZIPs, were also identified. The above transcripts showed different expression trends in different plant organs.

Conclusions

This study provides important genetic information on the A. mongholicus genes that are essential for isoflavonoid and triterpenoid saponin biosynthesis, and provides a basis for developing the medicinal value of this plant.
Handoffs and transitions in critical care—understanding scalability: study protocol for a multicenter stepped wedge type 2 hybrid effectiveness-implementation trial
Authors: Lane-Fall Meghan B. , Christakos Athena , Russell Gina C. , Hose Bat-Zion , Dauer Elizabeth D. , Greilich Philip E. , Hong Mershon Bommy , Potestio Christopher P. , Pukenas Erin W. , Kimberly John R. , Stephens-Shields Alisa J. , Trotta Rebecca L. , Beidas Rinad S. , Bass Ellen J.
Published: June 2021

Background

The implementation of evidence-based practices in critical care faces specific challenges, including intense time pressure and patient acuity. These challenges result in evidence-to-practice gaps that diminish the impact of proven-effective interventions for patients requiring intensive care unit support. Research is needed to understand and address implementation determinants in critical care settings.

Methods

The Handoffs and Transitions in Critical Care—Understanding Scalability (HATRICC-US) study is a Type 2 hybrid effectiveness-implementation trial of standardized operating room (OR) to intensive care unit (ICU) handoffs. This mixed methods study will use a stepped wedge design with randomized roll out to test the effectiveness of a customized protocol for structuring communication between clinicians in the OR and the ICU. The study will be conducted in twelve ICUs (10 adult, 2 pediatric) based in five United States academic health systems. Contextual inquiry incorporating implementation science, systems engineering, and human factors engineering approaches will guide both protocol customization and identification of protocol implementation determinants. Implementation mapping will be used to select appropriate implementation strategies for each setting. Human-centered design will be used to create a digital toolkit for dissemination of study findings. The primary implementation outcome will be fidelity to the customized handoff protocol (unit of analysis: handoff). The primary effectiveness outcome will be a composite measure of new-onset organ failure cases (unit of analysis: ICU).

Discussion

The HATRICC-US study will customize, implement, and evaluate standardized procedures for OR to ICU handoffs in a heterogenous group of United States academic medical center intensive care units. Findings from this study have the potential to improve postsurgical communication, decrease adverse clinical outcomes, and inform the implementation of other evidence-based practices in critical care settings.

Trial registration

ClinicalTrials.gov identifier: NCT04571749. Date of registration: October 1, 2020.
Programmed suppression of oxidative phosphorylation and mitochondrial function by gestational alcohol exposure correlate with widespread increases in H3K9me2 that do not suppress transcription
Authors: Chang Richard C. , Thomas Kara N. , Mehta Nicole A. , Veazey Kylee J. , Parnell Scott E. , Golding Michael C.
Published: June 2021

Background

A critical question emerging in the field of developmental toxicology is whether alterations in chromatin structure induced by toxicant exposure control patterns of gene expression or, instead, are structural changes that are part of a nuclear stress response. Previously, we used a mouse model to conduct a three-way comparison between control offspring, alcohol-exposed but phenotypically normal animals, and alcohol-exposed offspring exhibiting craniofacial and central nervous system structural defects. In the cerebral cortex of animals exhibiting alcohol-induced dysgenesis, we identified a dramatic increase in the enrichment of dimethylated histone H3, lysine 9 (H3K9me2) within the regulatory regions of key developmental factors driving histogenesis in the brain. However, whether this change in chromatin structure is causally involved in the development of structural defects remains unknown.

Results

Deep-sequencing analysis of the cortex transcriptome reveals that the emergence of alcohol-induced structural defects correlates with disruptions in the genetic pathways controlling oxidative phosphorylation and mitochondrial function. The majority of the affected pathways are downstream targets of the mammalian target of rapamycin complex 2 (mTORC2), indicating that this stress-responsive complex plays a role in propagating the epigenetic memory of alcohol exposure through gestation. Importantly, transcriptional disruptions of the pathways regulating oxidative homeostasis correlate with the emergence of increased H3K9me2 across genic, repetitive, and non-transcribed regions of the genome. However, although associated with gene silencing, none of the candidate genes displaying increased H3K9me2 become transcriptionally repressed, nor do they exhibit increased markers of canonical heterochromatin. Similar to studies in C. elegans, disruptions in oxidative homeostasis induce the chromatin looping factor SATB2, but in mammals, this protein does not appear to drive increased H3K9me2 or altered patterns of gene expression.

Conclusions

Our studies demonstrate that changes in H3K9me2 associate with alcohol-induced congenital defects, but that this epigenetic change does not correlate with transcriptional suppression. We speculate that the mobilization of SATB2 and increased enrichment of H3K9me2 may be components of a nuclear stress response that preserve chromatin integrity and interactions under prolonged oxidative stress. Further, we postulate that while this response may stabilize chromatin structure, it compromises the nuclear plasticity required for normal differentiation.
SARS-COV-2 infection outcomes in patients with congenital generalized lipodystrophy
Authors: Madeira Mayara Ponte , Freire Erika Bastos Lima , Fernandes Virginia Oliveira , Lima Grayce Ellen da Cruz Paiva , Melo Ivana da Ponte , Montenegro Ana Paula Dias Rangel , Freire José Ednésio da Cruz , Moreira-Nunes Caroline de Fátima Aquino , Montenegro Raquel Carvalho , Colares Jeová Keny Baima , Montenegro Junior Renan Magalhães ,   Brazilian Group for the Study of Inherited and Acquired Lipodystrophies (BRAZLIPO)
Published: June 2021

Background

A new strain of human coronavirus (HCoV) spread rapidly around the world. Diabetes and obesity are associated with a worse prognosis in these patients. Congenital Generalized Lipodystrophy (CGL) patients generally have poorly controlled diabetes and require extremely high doses of insulin. There is no documentation in the literature of cases of COVID in CGL patients. Thus, we aimed to evaluate the prevalence of SARS-CoV-2 infection in CGL patients, and the association of their clinical and metabolic characteristics and outcomes.

Methods

This is a cross-sectional study carried out between July and October 2020. Clinical data collected were respiratory or other flu-like symptoms, need of hospitalization in the last three months, CGL comorbidities, and medications in use. Cholesterol, triglycerides, glycohemoglobin A1c levels, anti-SARS-CoV-2 antibodies and nasopharyngeal swab for RT-qPCR were also obtained in all CGL patients. Mann-Whitney U test was used to analyze the characteristics of the participants, verifying the non-adherence of the data to the Gaussian distribution. In investigating the association between categorical variables, we used Pearson's chi-square test and Fisher's exact test. A significance level of 5% was adopted.

Results

Twenty-two CGL patients were assessed. Eight subjects (36.4%) had reactive anti-SARS-CoV-2 antibodies. Only one of these, also presented detectable RT-qPCR. Five individuals (62.5%) were women, median age of 13.5 years (1 to 37). Symptoms like fever, malaise, nausea, diarrhea and chest pain were present, and all asymptomatic patients were children. All subjects had inadequate metabolic control, with no difference between groups. Among positive individuals there was no difference between those with AGPAT2 (75%) and BSCL2 gene mutations (25%) (p > 0.05). No patient needed hospitalization or died.

Conclusions

We described a high prevalence of SARS-CoV-2 infection in CGL patients with a good outcome in all of them. These findings suggest that at least young CGL patients infected by SARS-COV-2 are not at higher risk of poor outcome, despite known severe metabolic comorbidities.
On a class of difference equations with interlacing indices
Authors: Stević Stevo , Ahmed A. El-Sayed , Kosmala Witold , Šmarda Zdeněk
Published: June 2021

Some results on the long-term behavior of solutions to a class of difference equations, which includes numerous nonlinear difference equations of various orders that attracted some attention in the last 15 years, are presented. We also present a natural connection among these difference equations, compare some results on the equations with some other ones in the literature, and give a list of a considerable number of difference equations which can be treated in a similar way.
A pilot study of the functionality and clinician acceptance of a clinical decision support tool to improve primary care of opioid use disorder
Authors: Rossom Rebecca C. , Sperl-Hillen JoAnn M. , O’Connor Patrick J. , Crain A. Lauren , Nightingale Laurel , Pylkas Anne , Huntley Kristen V. , Bart Gavin
Published: June 2021

Objective

Most Americans with opioid use disorder (OUD) do not receive indicated medical care. A clinical decision support (CDS) tool for primary care providers (PCPs) could address this treatment gap. Our primary objective was to build OUD-CDS tool and demonstrate its functionality and accuracy. Secondary objectives were to achieve high use and approval rates and improve PCP confidence in diagnosing and treating OUD.

Methods

A convenience sample of 55 PCPs participated. Buprenorphine-waivered PCPs (n = 8) were assigned to the intervention. Non-waivered PCPs (n = 47) were randomized to intervention (n = 24) or control (n = 23). Intervention PCPs received access to the OUD-CDS, which alerted them to patients at potentially increased risk for OUD or overdose and guided diagnosis and treatment. Control PCPs provided care as usual.

Results

The OUD-CDS was functional and accurate following extensive multi-phased testing. PCPs used the OUD-CDS in 5% of encounters with at-risk patients, far less than the goal of 60%. OUD screening confidence increased for all intervention PCPs and OUD diagnosis increased for non-waivered intervention PCPs. Most PCPs (65%) would recommend the OUD-CDS and found it helpful with screening for OUD and discussing and prescribing OUD medications.

Discussion

PCPs generally liked the OUD-CDS, but use rates were low, suggesting the need to modify CDS design, implementation strategies and integration with existing primary care workflows.

Conclusion

The OUD-CDS tool was functional and accurate, but PCP use rates were low. Despite low use, the OUD-CDS improved confidence in OUD screening, diagnosis and use of buprenorphine.

NIH Trial registration NCT03559179. Date of registration: 06/18/2018. URL: https://clinicaltrials.gov/ct2/show/NCT03559179
What do clinicians want? Understanding frontline addiction treatment clinicians’ preferences and priorities to improve the design of measurement-based care technology
Authors: Tauscher Justin S. , Cohn Eliza B. , Johnson Tascha R. , Diteman Kaylie D. , Ries Richard K. , Atkins David C. , Hallgren Kevin A.
Published: June 2021

Background

Measurement-based care (MBC) is the practice of routinely administering standardized measures to support clinical decision-making and monitor treatment progress. Despite evidence of its effectiveness, MBC is rarely adopted in routine substance use disorder (SUD) treatment settings and little is known about the factors that may improve its adoptability in these settings. The current study gathered qualitative data from SUD treatment clinicians about their perceptions of MBC, the clinical outcomes they would most like to monitor in MBC, and suggestions for the design and implementation of MBC systems in their settings.

Methods

Fifteen clinicians from one publicly-funded and two privately-funded outpatient SUD treatment clinics participated in one-on-one research interviews. Interviews focused on clinicians’ perceived benefits, drawbacks, and ideas related to implementing MBC technology into their clinical workflows. Interviews were audio recorded, transcribed, and coded to allow for thematic analysis using a mixed deductive and inductive approach. Clinicians also completed a card sorting task to rate the perceived helpfulness of routinely measuring and monitoring different treatment outcomes.

Results

Clinicians reported several potential benefits of MBC, including improved patient-provider communication, client empowerment, and improved communication between clinicians. Clinicians also expressed potential drawbacks, including concerns about subjectivity in patient self-reports, limits to personalization, increased time burdens, and needing to learn to use new technologies. Clinicians generated several ideas and preferences aimed at minimizing burden of MBC, illustrating clinical changes over time, improving ease of use, and improving personalization. Numerous patient outcomes were identified as “very helpful” to track, including coping skills, social support, and motivation for change.

Conclusions

MBC may be a beneficial tool for improving clinical care in SUD treatment settings. MBC tools may be particularly adoptable if they are compatible with existing workflows, help illustrate gradual and nonlinear progress in SUD treatment, measure outcomes perceived as clinically useful, accommodate multiple use cases and stakeholder groups, and are framed as an additional source of information meant to augment, rather than replace, existing practices and information sources.
A Health Technician-delivered Brief Intervention linked to AUDIT for reduction of alcohol use in Chilean primary care: a randomized controlled trial
Authors: Barticevic Nicolas A. , Poblete Fernando , Zuzulich Soledad M. , Rodriguez Victoria , Quevedo Diego , Sena Brena F. , Bradshaw Laura
Published: June 2021

Background

Because of the shortage of health professionals in Chilean primary care, Health Technicians (HT) are providing Brief Interventions (BI) for risky alcohol consumption. We compared the efficacy of two AUDIT-linked interventions provided by HTs: an informative leaflet and a BI plus leaflet.

Methods

This is a parallel-group randomized controlled trial with 1:1 randomization. Participants were identified through screening with the Alcohol Use Disorders Identification Test (AUDIT) at five primary care centers between March 2016 and July 2017. People older than 18 years at intermediate-risk (AUDIT score 8 to 15, inclusive) were randomized to receive either an HT-delivered BI (n = 174) or an informative leaflet (n = 168). Only data from participants (n = 294) who completed the 6-month assessment were analyzed. The leaflet was delivered without further advice. It contains alcohol consumption limits, a change planner, and strategies to decrease drinking. The BI was a 5-min discussion on the leaflet´s content plus normative feedback, tailored information on alcohol and health, and a change plan. The change in the AUDIT risk category six months after randomization (primary outcome) was compared among groups with a Chi-squared test. Changes in the secondary outcomes, which were scores on the AUDIT and the AUDIT´s consumption items (AUDIT-C), were compared with T-tests. Mixed-effects linear models adjusted for potential confounders. Outcome adjudicators were blinded to group assignment.

Results

At 6-month follow-up, low-risk alcohol consumption was observed in 119 (80%) participants in the BI group, and in 103 (71%) in the leaflet group, with no difference among groups ($$\chi 2$$

χ
2

[1, N = 294] = 2.6, p = 0.1; adjusted odds ratio 0.6; 95% confidence interval [CI] 0.34, 1.05). The mean AUDIT score decreased by 5.76 points in the BI group, and by 5.07 in the leaflet group, which represents a 0.86 AUDIT point reduction attributable to the BI (secondary outcome) (T = 2.03, p = 0.043; adjusted mean difference 0.86 CI 0.06, 1.66).

Conclusions

The AUDIT-linked BI delivered by HTs was not associated with a greater reduction of risky alcohol consumption than an informative leaflet. Delivering a leaflet could be more efficient than a BI when provided by HTs; however, more research on the effectiveness of the leaflet is needed.

Trial registration ClinicalTrials.gov NCT02642757 (December 30, 2015) https://clinicaltrials.gov/ct2/show/NCT02642757.
Effect of perioperative use of parecoxib on chronic post-surgical pain in elderly patients after hepatectomy: a prospective randomized controlled study
Authors: Ge Xiaodong , Pan Yan , Jin Danfeng , Wang Ying , Ge Shengjin
Published: June 2021

Background

Chronic post-surgical pain (CPSP) has a negative impact on the recovery, quality of life, and physical functioning of elderly patients. This study aimed to test the superiority of parecoxib vs. placebo in preventing chronic post-hepatectomy pain in elderly patients under combined general-epidural anesthesia.

Methods

A total of 105 elderly patients undergoing hepatectomy under combined general-epidural anesthesia were randomized into the parecoxib or placebo group. The primary outcome was the proportion of patients with CPSP 3 months postoperatively. The secondary outcomes included the Short-Form McGill Pain Questionnaire score in CPSP-positive responders, acute pain intensity, postoperative analgesic demand, inflammatory markers change, and postoperative complications within 28 days.

Results

The parecoxib group provided a non-significant absolute 9.1% reduction in the rate of CPSP compared to the placebo group (P = 0.34). The average chronic pain visual analog scale in the parecoxib group was lower than that in the placebo group (P = 0.04). Significantly less moderate-to-severe acute pain at rest (P = 0.04) and with coughing (P < 0.001), less patient-controlled epidural analgesia (PCEA) consumption (P = 0.01), and less rescue analgesia (P < 0.001) were observed in the parecoxib group compared to the placebo group. Furthermore, no between-group difference was observed in inflammatory markers (P > 0.05) and postoperative complications (P = 0.65).

Conclusions

Parecoxib reduced the prevalence of CPSP in elderly patients after hepatectomy under combined general-epidural anesthesia from 44.4 to 35.3% with no statistical significance. Moreover, significantly alleviated CPSP intensity and improved acute pain management were observed.

Trial registration

This study was retrospectively registered in the Chinese Clinical Trial Registry (URL: http://www.chictr.org.cn/edit.aspx?pid=56961&htm=4) on August 3, 2020 (ChiCTR-2,000,035,198).
Effectiveness of modified cutting and suture technique for endonasal caudal septoplasty in correcting nasal obstruction and preventing nasal tip projection loss
Authors: Hosokawa Yu , Miyawaki Takeshi , Akutsu Taisuke , Omura Kazuhiro , Tsumiyama Shinya , Iimura Jiro , Otori Nobuyoshi , Kojima Hiromi
Published: June 2021

Purpose

Caudal septoplasty is a difficult procedure. The cutting and suture technique is suitable for caudal septoplasty, but a batten graft is always necessary and bears the risk of nasal tip projection loss. We established a modified cutting and suture technique (MCAST), without using a batten graft, and investigated its effectiveness in correcting nasal obstruction and preventing nasal tip projection loss.

Methods

We retrospectively reviewed the medical records of 22 patients who underwent caudal septoplasty using MCAST. Subjective assessment by Nasal Obstruction Symptom Evaluation (NOSE) score and objective assessment by computed tomography (CT) were performed before and after the surgery. For evaluating nasal tip projection, we asked patients about their awareness of external nasal deformity. Additionally, the nasal tip projection was measured by CT and compared before and after surgery.

Results

The median preoperative NOSE score reduced significantly after MCAST ( P < 0.001). On CT, the ratio of the area of the convex side to that of the concave side in the anterior portion of the nasal cavity increased significantly after MCAST ( P < 0.001). All patients were unaware of external nasal deformity. There were no significant differences in the mean preoperative and postoperative nasal tip height and nasolabial angle. The mean supra tip height was significantly greater postoperatively than preoperatively ( P = 0.02).

Conclusions

The MCAST was useful for correcting nasal obstruction with caudal septal deviation. There was no postoperative loss of nasal tip projection. The MCAST can be suitable for correcting C-shaped caudal deviations without dislocating the caudal septum from the anterior nasal septum.
Reactive arthritis in the right hip following COVID-19 infection: a case report
Authors: Shokraee Kamyar , Moradi Soroush , Eftekhari Tahereh , Shajari Rasoul , Masoumi Maryam
Published: June 2021

Background

SARS-COV-2 usually presents with respiratory symptoms but can have various other manifestations and sequelae. One of the rare complications of COVID-19 infection is Reactive Arthritis. While this complication is more likely to occur following sexually transmitted or gastrointestinal infections, other infections such as COVID-19 can lead to reactive arthritis as well.

Case presentation

Herein, we report a 58 year old woman hospitalized following COVID-19 infection and was discharged after a week. She consequently presented to the clinic ten days after her discharge, complaining of walking difficulties and radiating pain in her right hip. After ultrasound and MRI, she was diagnosed with reactive arthritis inflammation in the hip’s neck. Other known microorganisms responsible for reactive arthritis were ruled out before attributing it to the earlier COVID-19 infection. Clinical symptoms were resolved after being treated using a combination of indomethacin and depot methyl-prednisolone for 14 days.

Conclusion

Latest evidence shows that COVID-19 can lead to autoimmune reactions, including reactive arthritis. Further attention should be paid to symptoms occurring after an episode of infection with COVID-19 to expand our understanding of the disease and the symptoms with which it can manifest.
Dynamic assessing silica particle-induced pulmonary fibrosis and associated regulation of long non-coding RNA expression in Wistar rats
Authors: Sai Linlin , Qi Xuejie , Yu Gongchang , Zhang Juan , Zheng Yuxin , Jia Qiang , Peng Cheng
Published: June 2021

Background

Exposure to respirable crystalline silica (RCS) can induce accelerated silicosis (AS), a form of silicosis that is more progressive and severe form of silicosis. In this project we aimed to assess processes of silicosis in rats exposed to RCS with focus on the regulation of long noncoding RNAs (lncRNAs).

Results

The results showed that RCS induced acute inflammatory response as indicated by the appearance of inflammatory cells in the lung from the first day and peaked on day 7 of exposure. The fibroblasts appeared along with the inflammatory cells decreasing gradually on day 14. Extensive fibrosis appeared in the lung tissue, and silicon nodules were getting larger on day 28. Interestingly, the number of altered lncRNAs increased with the exposure time with 193, 424, 455, 421 and 682 lncRNAs on day 1, 7, 14, 21, and 28 after exposure, respectively. We obtained 285 lncRNAs with five significant temporal expression patterns whose expressions might correlate with severity of silicosis. KEGG analysis showed that lncRNAs from short time-series expression miner (STEM)-derived data mainly involved in 17 pathways such as complement and coagulation cascades.

Conclusions

The differential expression profiles of lncRNAs may be potential biomarkers in silicosis through modulating expressions of their relevant genes in lungs of rat and thus warrant further investigation.
Prediction of gene expression regulation by human microRNAs in Plasmodium falciparum
Authors: Grinev Alexandr , Fokina Natalya , Bogomolov Denis , Berechikidze Iza , Lazareva Yuliya
Published: June 2021

Background

Malaria is a disease annually causing over 400,000 deaths. Deep understanding of molecular and genetic processes underlying its life cycle and pathogenicity is required to efficiently resist it. RNA interference is a mechanism of the gene expression regulation typical for a wide variety of species. Even though the existence of this phenomenon in Plasmodium falciparum has long been rejected, several recent works pose hypotheses and provide direct and indirect evidence of the existence of mechanisms similar to RNA interference in this organism. In particular, the possibility of regulation of P. falciparum gene expression through human microRNAs is of great importance both for fundamental biology and for medicine. In the present work we address the problem of possibility of the existence in the P. falciparum genome of the nucleotide sequences such that mRNAs transcribed from genes containing these sequences could form duplexes with human microRNAs. Using bioinformatics methods we have analysed genomes of 15 P. falciparum isolates for sequences homological to these microRNAs.

Results

The analysis has demonstrated the existence of a vast number of genes that could potentially be regulated by the human microRNAs in the plasmodial genome.

Conclusions

Despite the fact that the numbers of homological intervals vary significantly between isolates, the hsa-miR-451a and hsa-miR-223-3p microRNAs are expected to make the most notable contribution to the pathogenesis of P. falciparum malaria. The majority of homological intervals occur in genes encoding cell adhesion proteins.
Antibacterial, antioxidant, and sun protection potential of selected ethno medicinal plants used for skin infections in Uganda
Authors: Namukobe Jane , Sekandi Peter , Byamukama Robert , Murungi Moses , Nambooze Jennifer , Ekyibetenga Yeremiah , Nagawa Christine Betty , Asiimwe Savina
Published: June 2021

Background

Rural populations in Uganda rely heavily on medicinal plants for the treatment of bacterial skin infections. However, the efficacy of these medicinal plants for their pharmacological action is not known. The study aimed at evaluating the antibacterial, antioxidant, and sun protection potential of Spermacoce princeae, Psorospermum febrifugum, Plectranthus caespitosus, and Erlangea tomentosa extracts.

Methods

The plant samples were extracted by maceration sequentially using hexane, dichloromethane, ethyl acetate, methanol, and distilled water. Antibacterial activity of each extract was carried out using an agar well diffusion assay against Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Klebsiella pneumonie, Streptococcus pyogenes, and Salmonella typhi. Acute dermal toxicity of the aqueous extract of S. princeae and P. febrifugum, and E. tomentosa was assessed in young adult healthy Wistar albino rats at a dose of 8000 and 10,000 mg/kg body weight. The antioxidant activity of each extract was carried out using a 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging assay. The sun protection factor was determined using Shimadzu UltraViolet-Visible double beam spectrophotometer between 290 and 320 nm.

Results

The plant extracts showed good antibacterial activity against the tested bacterial strains with minimum inhibitory concentration (MIC) ranging between 3.12 and 12.5 mg/ml. There was no significant change in the levels of creatinine, alanine aminotransferase, and aspartate aminotransferase in the rats even at a higher dose of 10,000 mg/kg, which was related to the results of biochemical analysis of the blood samples from the treated and control groups. The aqueous and methanol extracts of S. princeae showed potential antioxidant properties, with half maximal inhibitory concentration (IC50) values of 59.82 and 61.20 μg/ml respectively. The organic and aqueous extracts of P. caespitosus showed high levels of protection against Ultraviolet light with sun protection potential values ranging between 30.67 and 37.84.

Conclusions

The study demonstrated that the selected medicinal plants possessed good antibacterial, antioxidant, and sun protection properties. Therefore, the plants are alternative sources of antibacterial, antioxidant, and sun protection agents in managing bacterial skin infections.
Updates on genetics in systemic sclerosis
Authors: Ota Yuko , Kuwana Masataka
Published: June 2021

Systemic sclerosis (SSc) is a complex disease, in which an interaction of genetic and environmental factors plays an important role in its development and pathogenesis. A number of genetic studies, including candidate gene analysis and genome-wide association study, have found that the associated genetic variants are mainly localized in noncoding regions in the expression quantitative trait locus and influence corresponding gene expression. The gene variants identified as a risk for SSc susceptibility include those associated with innate immunity, adaptive immune response, and cell death, while there are only few SSc-associated genes involved in the fibrotic process or vascular homeostasis. Human leukocyte antigen class II genes are associated with SSc-related autoantibodies rather than SSc itself. Since the pathways between the associated genotype and phenotype are still poorly understood, further investigations using multi-omics technologies are necessary to characterize the complex molecular architecture of SSc, identify biomarkers useful to predict future outcomes and treatment responses, and discover effective drug targets.
Impact of sedimentary facies on machine learning of acoustic impedance from seismic data: Lessons from a geologically realistic 3D model
Authors: Zeng Hongliu , He Yawen , Zeng Leo
Published: June 2021

We have developed a new machine-learning (ML) workflow that uses random forest (RF) regression to predict sedimentary-rock properties from stacked and migrated 3D seismic data. The training, validation, and testing are performed with 40 features extracted from a geologically realistic 46 × 66-trace model built in the Miocene Powderhorn Field in South Texas. We focus on the responses of the RF model to sedimentary facies and the strategies adopted to achieve better prediction with various data conditions. We apply explained variation (R2) and root-mean-square (rms) prediction errors to map the relationship between the quality of prediction and the sedimentary facies. In the single-well model, R2 and rms error maps highly resemble sand-percentage maps, or lithofacies maps, showing the facies control on the quality of the ML model. We observe that training with a small well data set (1–10 wells) leads to low and unstable test scores (R2 = 0.2–0.7). The R2 score increases and stabilizes with more (as many as 1000) training wells (R2 = 0.7–0.9), realizing the effective correction of facies bias. The stratigraphic and spatial features are useful and should be used. Weak to moderate random noise (−20 to −15 dB) slightly lowers the training score (R2 < 0.05) and should not be a major concern. Sparse well-supported models can outperform linear regression and model-based inversion and can be useful if caution is exercised. In the best-case scenario (500 wells), the predicted model largely duplicates the true model with a significant improvement in accuracy (R2 = 0.85) and stability. Such results can be applied in most, if not all, exploration and production practices.
Strengthening Pathology Capacity to Deliver Quality Cancer Care in Cities in LMICs
Authors: Frech Silvina , Bravo Luis Eduardo , Rodriguez Ingrid , Pomata Alicia , Aung Khin Thida , Soe Aung Naing , Hornburg Beatriz , Guarner Jeannette , Brock Jane , Camacho Rolando , Milner Dan
Published: June 2021

Diagnostic pathology services for oncology health systems are essential; yet, surveys, observations, and hard data from across low- and middle-income countries have revealed that these services are almost always lacking adequate quality and often missing completely. The City Cancer Challenge Foundation (C/Can), the American Society for Clinical Pathology, and C/Can partner cities undertook intense analysis of their existing pathology services as part of a year-long assessment process including the specific formation of a pathology-focused team. Internal and external expert assessments identified sustainable solutions adapted to the local context and level of resources and created specific local implementation projects. Through local leadership, capacity development, and collaboration, services were improved city-wide in three cities: Cali, Colombia; Asunción, Paraguay; and Yangon, Myanmar. Common problems identified across cities included deficiencies in personnel training, equipment, reagents, processes, quality, and coordination. Specific solutions included quality training, standard process development and regulation, implementation of new services, and public-private collaboration. As the first cities joining the C/Can initiative, Cali, Asunción, and Yangon demonstrate the success of the approach and the value of local expertise in identifying problems and solutions. The additional value of international partners' expertise created opportunities for growth through mentorship and technical support. Importantly, the power of healthcare programs with strong political support is emphasized.
Mortgage Lending Bias and Breast Cancer Survival Among Older Women in the United States
Authors: Beyer Kirsten M. M. , Zhou Yuhong , Laud Purushottam W. , McGinley Emily L. , Yen Tina W. F. , Jankowski Courtney , Rademacher Nicole , Namin Sima , Kwarteng Jamila , Beltrán Ponce Sara , Nattinger Ann B.
Published: June 2021

PURPOSE

The objective was to examine the relationship between contemporary redlining (mortgage lending bias on the basis of property location) and survival among older women with breast cancer in the United States.

METHODS

A redlining index using Home Mortgage Disclosure Act data (2007-2013) was linked by census tract with a SEER-Medicare cohort of 27,516 women age 66-90 years with an initial diagnosis of stage I-IV breast cancer in 2007-2009 and follow-up through 2015. Cox proportional hazards models were used to examine the relationship between redlining and both all-cause and breast cancer–specific mortality, accounting for covariates.

RESULTS

Overall, 34% of non-Hispanic White, 57% of Hispanic, and 79% of non-Hispanic Black individuals lived in redlined tracts. As the redlining index increased, women experienced poorer survival. This effect was strongest for women with no comorbid conditions, who comprised 54% of the sample. For redlining index values of 1 (low), 2 (moderate), and 3 (high), as compared with 0.5 (least), hazard ratios (HRs) (and 95% CIs) for all-cause mortality were HR = 1.10 (1.06 to 1.14), HR = 1.27 (1.17 to 1.38), and HR = 1.39 (1.25 to 1.55), respectively, among women with no comorbidities. A similar pattern was found for breast cancer–specific mortality.

CONCLUSION

Contemporary redlining is associated with poorer breast cancer survival. The impact of this bias is emphasized by the pronounced effect even among women with health insurance (Medicare) and no comorbid conditions. The magnitude of this neighborhood level effect demands an increased focus on upstream determinants of health to support comprehensive patient care. The housing sector actively reveals structural racism and economic disinvestment and is an actionable policy target to mitigate adverse upstream health determinants for the benefit of patients with cancer.