bluuebunny/crossref_metadata_2025 huggingface dataset:
Trichodysplasia spinulosa in a renal transplant patient: A case report of successful treatment
Authors: Pennou Camille , Javidi Eileen , Lecours Julie , Bélisle Annie , Davar Sandra
Published: September 2020

Trichodysplasia spinulosa is a rare cutaneous disease caused by the trichodysplasia spinulosa–associated polyomavirus. It occurs more frequently in immunocompromised patients, particularly in solid organ transplants. A few successful treatments have been described in the literature. In our report, we present a biopsy-proven trichodysplasia spinulosa case in a kidney transplant recipient who rapidly responded to a reduction of his immunosuppressive therapy.
Port-site implantation of parasitic leiomyoma after laparoscopic myomectomy and its histopathology
Authors: Kai Kentaro , Aoyagi Yoko , Nishida Masakazu , Arakane Motoki , Kawano Yasushi , Narahara Hisashi
Published: September 2020

Although parasitic leiomyoma could be spontaneous or iatrogenic in origin, port-site implantation of parasitic leiomyoma is an iatrogenic benign sequela of laparoscopic surgery. A 30-year-old, primigravida Japanese woman was referred after unresponsiveness to preoperative gonadotropin-releasing hormone for intramural fibroids. Magnetic resonance imaging showed multiple intramural fibroids and left ovarian endometrioma with no malignant features. Laparoscopic myomectomy with power morcellation and ovarian cystectomy were performed, followed by treatment with a combined oral contraceptive. Seven years after the primary surgery, she underwent abdominal myomectomy for a port-site, and peritoneal recurrence of the leiomyoma and intramural leiomyomas was detected. Microscopic examination revealed that resected specimens from the port-site demonstrated leiomyoma with lesser cell density and more prominent hyalinization than those from the uterus. Therefore, clinicians should counsel patients regarding the risks and benefits of laparoscopy with morcellation versus laparotomy. Further development of techniques for uterine tissues extraction is warranted.
Self-Tracking Health Over Time: From the Use of Instagram to Perform Optimal Health to the Protective Shield of the Digital Detox
Authors: Kent Rachael
Published: September 2020

Instagram and self-tracking technologies enable multiple ways to perform and represent the body and health. No research has yet explored how self-tracking technologies and self-representations of health identity on social media, in particular Instagram, influence health “sharing” online and individual health management offline. To enable a thorough investigation of how self-tracking mediations of identity construction work in practice, through a textual and thematic analysis of empirical ethnographic data from online content, reflexive diaries and semi-structured interviews with 14 participants, this research examines the use of these converged technologies to share health-related data on Instagram in the performance of optimal health identities. Participants identified pressures that arose from this continual performative identity of being a healthy role model under persistent self- and community surveillance, which also led to the development of powerful compulsions to use these technologies to document and share many aspects of health and lifestyle. Over time, the participants attempted to disengage and detox either temporarily or permanently from Instagram, to enable a protective shield from the pervasive, normalized surveillance and community practices. Most interestingly, even when they removed these technologies and platforms from their daily lives, participants still felt neglectful to their devices, to themselves, and to their communities online in their abstinence and resistance to perform optimal health practices.
An Optimality Theoretic Description on the Characteristics of Postpositions in Mandarin Chinese
Authors: Tseng Yu-Ching
Published: September 2020

In this paper, we adopt optimality theory to describe some important properties of postpositions. First, they follow the complement in their own projections. Second, they select either an NP or a PrepP as the complement, but they do not select another PostP as the complement to avoid the adjacency of two postpositions. Third, when occurring in a VP, they precede the head verb if they are complements of verbs and follow the verb if they are adjuncts. Fourth, the insertion of de between a postposition and its complement is prohibited. Fifth, postpositional stranding is disallowed. As will be shown in this paper, by using OT as the theoretical framework, we establish a theoretical model that is able to account for the syntactic properties, configurations, and restrictions involving the category of postpositions. Finally, this paper provided a brief cross-linguistic generalization of syntactic properties related to postposition between Mandarin Chinese and English from the perspective of OT.
Delayed Adulthood, Delayed Desistance? A Brief Report on Changing Age Schedules of Risky Behaviors
Authors: Hays Jake J. , Hayford Sarah R. , Furstenberg Frank F.
Published: September 2020

Desistance from the risky behaviors associated with adolescence is linked to entry into adult roles like marriage and employment. Increases in the age of these transitions may delay desistance from risky behaviors. Using population data from the Bureau of Justice Statistics and the National Center for Health Statistics, and tabulated data from Monitoring the Future, we chart trends in six problem behaviors—arrests, marijuana use, binge drinking, suicides, homicides, and motor vehicle deaths—between 1975 and 2017. We find delays in desistance from some behaviors. For instance, binge drinking peaked at ages 19–22 in earlier birth cohorts but at ages 23–26 in later birth cohorts. However, other behaviors showed no change in the timing of desistance. Women’s rates approached men’s in binge drinking and suicide, but gender gaps persist across behaviors. Delayed transitions to adult roles have not produced a singular pattern of delayed desistance from problem behaviors.
Rapid extraction of total lipids and lipophilic POPs from all EU-regulated foods of animal origin: Smedes’ method revisited and enhanced
Authors: Haedrich Johannes , Stumpf Claudia , Denison Michael S.
Published: September 2020

Background

Persistent organic pollutants (POPs) such as dioxins, dioxin-like chemicals and non-dioxin-like PCBs causing adverse effects to human health bio-accumulate through the food web due to their affinity for adipose tissues. Foods of animal origin are therefore the main contributors to human dietary exposure. The European Union’s (EU) food safety policy requires checking of a wide range of samples for compliance with legal limits on a regular basis. Several methods of varying efficiency are applied by official control laboratories for extraction of the different classes of lipids and associated POPs, bound to animal tissue and animal products in varying degrees, sometimes leading to discrepancies especially in fresh weight based analytical results.

Results

Starting fromSmedes’lipid extraction from marine tissue, we optimized the extraction efficiency for both lipids and lipophilic pollutants, abandoning the time-consuming centrifugation step. The resulting modifiedSmedesextraction (MSE) method was validated based on multiple analyses of a large number of real-world samples, matrix calibration and performance assessment in proficiency testing utilizing both instrumental and bioanalytical methodologies. Intermediate precision in 12 different foods was below 3% in chicken eggs, egg powder, animal fat, fish, fish oil, poultry, whole milk, milk fat and milk powder, and below 5% in bovine meat, liver, and infant food. In comparison toTwisselmannhot extraction, results presented here show an increased efficiency of MSE by + 25% for bovine liver, + 14% for chicken eggs, + 13% for poultry meat, + 12% for fish, 8% for bovine meat, and 6% for infant food.

Conclusions

For the first time, a fast and reliable routine method is available that enables the analyst to reproducibly extract "total" lipids from any EU-regulated food sample of animal origin within 6 to 8 min. Increased efficiency translates into a considerable increase in both lipid and wet weight-based analytical results measured for associated POPs, reducing the risk of false non-compliant results. Compared to a 4 hTwisselmannextraction, the extraction of 1000 samples using MSE would result in annual savings of about 250 h or 32 working days. Our MSE procedure contributes to the European Commission's objective of harmonizing analytical results across the EU generated according to Commission Regulation (EU) 2017/644.
Systems pharmacology-based approach to investigate the mechanisms of Danggui-Shaoyao-san prescription for treatment of Alzheimer’s disease
Authors: Wu Qihui , Chen Yunbo , Gu Yong , Fang Shuhuan , Li Weirong , Wang Qi , Fang Jiansong , Cai Chuipu
Published: September 2020

Background

Alzheimer’s disease (AD) is the most common cause of dementia in the elderly, characterized by a progressive and irreversible loss of memory and cognitive abilities. Currently, the prevention and treatment of AD still remains a huge challenge. As a traditional Chinese medicine (TCM) prescription, Danggui-Shaoyao-san decoction (DSS) has been demonstrated to be effective for alleviating AD symptoms in animal experiments and clinical applications. However, due to the complex components and biological actions, its underlying molecular mechanism and effective substances are not yet fully elucidated.

Methods

In this study, we firstly systematically reviewed and summarized the molecular effects of DSS against AD based on current literatures of in vivo studies. Furthermore, an integrated systems pharmacology framework was proposed to explore the novel anti-AD mechanisms of DSS and identify the main active components. We further developed a network-based predictive model for identifying the active anti-AD components of DSS by mapping the high-quality AD disease genes into the global drug-target network.

Results

We constructed a global drug-target network of DSS consisting 937 unique compounds and 490 targets by incorporating experimental and computationally predicted drug–target interactions (DTIs). Multi-level systems pharmacology analyses revealed that DSS may regulate multiple biological pathways related to AD pathogenesis, such as the oxidative stress and inflammatory reaction processes. We further conducted a network-based statistical model, drug-likeness analysis, human intestinal absorption (HIA) and blood-brain barrier (BBB) penetration prediction to uncover the key ani-AD ingredients in DSS. Finally, we highlighted 9 key ingredients and validated their synergistic role against AD through a subnetwork.

Conclusion

Overall, this study proposed an integrative systems pharmacology approach to disclose the therapeutic mechanisms of DSS against AD, which also provides novel in silico paradigm for investigating the effective substances of complex TCM prescription.
Positive association between triglyceride glucose index and arterial stiffness in hypertensive patients: the China H-type Hypertension Registry Study
Authors: Li Minghui , Zhan Aihua , Huang Xiao , Hu Lihua , Zhou Wei , Wang Tao , Zhu Lingjuan , Bao Huihui , Cheng Xiaoshu
Published: September 2020

Background

Data are limited on whether TyG index is an independent predictor of arterial stiffness in hypertensive patients. The purpose of this study was to assess the association between the TyG index and arterial stiffness, and examined whether there were effect modifiers, in hypertensive patients.

Methods

This study included 4718 hypertensive adults, a subset of the China H-type Hypertension Registry Study. The TyG index was calculated as ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Arterial stiffness was determined by measuring brachial-ankle pulse wave velocity (baPWV).

Results

The overall mean TyG index was 8.84. Multivariate linear regression analyses showed that TyG index was independently and positively associated with baPWV (β, 1.02; 95% confidence interval [CI] 0.83, 1.20). Consistently, Multiple logistic analyses showed a positive association between TyG index risk of elevated baPWV (> 75th percentile) (odds ratio [OR], 2.12; 95% CI 1.80, 2.50). Analyses using restricted cubic spline confirmed that the associations of TyG index with baPWV and elevated baPWV were linear. Subgroup analyses showed that stronger associations between TyG index and baPWV were detected in men (all P for interaction < 0.05).

Conclusion

TyG index was independently and positively associated with baPWV and elevated baPWV among hypertensive patients, especially in men. The data suggest that TyG index may serve as a simple and effective tool for arterial stiffness risk assessment in daily clinical practice.
Rabies virus phosphoprotein P5 binding to BECN1 regulates self-replication by BECN1-mediated autophagy signaling pathway
Authors: Liu Juan , Liao Min , Yan Yan , Yang Hui , Wang Hailong , Zhou Jiyong
Published: September 2020

Background

Rabies virus (RABV) is reported to encode five phosphoproteins (P), which are involved in viral genomic replication, axonal transport, oxidative stress, interferon antagonism, and autophagy induction. However, the functions of the different P proteins are poorly understood.

Methods

Immunofluorescence staining and western blot were performed to detect the autophagy activity, the form of ring-like structure, and the colocalization of BECN1 and P. Co-immunoprecipitation was performed to detect the interaction between P and BECN1. QRT-PCR and TCID50 assay were performed to detect the replication level of RABV. Small interfering RNA was used to detect the autophagy signaling pathway.

Results

We found that P5 attaches to N-terminal residues 1–139 of BECN1 (beclin1) on the BECN1 ring-like structure through amino acid residues 173–222 of P5. Subsequently, we found that P5-induced autophagosomes did not fuse with lysosomes. Becn1 silencing did not recover P5 overexpression-induced promotion of RABV replication. Mechanistically, RABV protein PΔN82 (P5) induced incomplete autophagy via the BECN1-mediated signaling pathway.

Conclusions

Our data indicate that P5 binding to the BECN1 ring benefits RABV replication by inducing BECN1 signaling pathway-dependent incomplete autophagy, which provides a potential target for antiviral drugs against RABV.

Graphical abstract
National physical activity and sedentary behaviour policies in 76 countries: availability, comprehensiveness, implementation, and effectiveness
Authors: Klepac Pogrmilovic Bojana , Ramirez Varela Andrea , Pratt Michael , Milton Karen , Bauman Adrian , Biddle Stuart J. H. , Pedisic Zeljko
Published: September 2020

Background

Evidence on current, national physical activity (PA) and sedentary behaviour (SB) policies is limited. We, therefore, analysed availability, comprehensiveness, implementation, and effectiveness of PA and SB policies internationally.

Methods

In this cross-sectional study, Global Observatory for Physical Activity (GoPA!) Country Contacts from 173 countries were asked to provide data on their national PA and SB policies by completing GoPA! Policy Inventory. Data were collected for 76 countries (response rate = 44%).

Results

Formal written policies for PA and SB were found in 92% (95% confidence interval [CI]: 86, 98) and 62% (95% CI: 50, 75) of countries, respectively. Sixty-two percent (95% CI: 51, 73) of countries have national PA guidelines, while 40% (95% CI: 29, 52) have SB guidelines. Fifty-two (95% CI: 40, 64) and 11% (95% CI: 3, 19) of countries have quantifiable national targets for PA and SB, respectively. The most represented ministries/departments involved in the promotion of more PA and/or less SB were in the sport (reported by 99% countries; 95% CI: 96, 100), health (97%; 95% CI: 94, 100), education (94%; 95% CI: 88, 100), and recreation and leisure (85%; 95% CI: 71, 99) sectors. The median score (0–10) for the comprehensiveness of PA and SB policies was 4 (95% CI: 4, 5) and 2 (95% CI: 2, 3), respectively. For PA and SB policy implementation it was 6 (95% CI: 5, 6). For the effectiveness of PA and SB policies it was 4 (95% CI: 3, 5) and 3 (95% CI: 2, 4), respectively. PA and SB policies were generally best developed in high-income countries and countries of European and Western-Pacific regions.

Conclusions

Most of the included countries have PA policies, but their comprehensiveness, implementation, and effectiveness are generally low-to-moderate. SB policies are less available, comprehensive, implemented, and effective than PA policies. PA and SB policies are better developed in high-income countries, compared with low- and lower-middle-income countries, and in countries of European and Western-Pacific regions, compared with other world regions. More investment is needed in development and implementation of comprehensive and effective PA and SB policies, particularly in low- and lower-middle-income countries.
Development of a CD19 PET tracer for detecting B cells in a mouse model of multiple sclerosis
Authors: Stevens Marc Y. , Cropper Haley C. , Lucot Katherine L. , Chaney Aisling M. , Lechtenberg Kendra J. , Jackson Isaac M. , Buckwalter Marion S. , James Michelle L.
Published: September 2020

Background

B cells play a central role in multiple sclerosis (MS) through production of injurious antibodies, secretion of pro-inflammatory cytokines, and antigen presentation. The therapeutic success of monoclonal antibodies (mAbs) targeting B cells in some but not all individuals suffering from MS highlights the need for a method to stratify patients and monitor response to treatments in real-time. Herein, we describe the development of the first CD19 positron emission tomography (PET) tracer, and its evaluation in a rodent model of MS, experimental autoimmune encephalomyelitis (EAE).

Methods

Female C57BL/6 J mice were induced with EAE through immunization with myelin oligodendrocyte glycoprotein (MOG1–125). PET imaging of naïve and EAE mice was performed 19 h after administration of [64Cu]CD19-mAb. Thereafter, radioactivity in organs of interest was determined by gamma counting, followed by ex vivo autoradiography of central nervous system (CNS) tissues. Anti-CD45R (B220) immunostaining of brain tissue from EAE and naïve mice was also conducted.

Results

Radiolabelling of DOTA-conjugated CD19-mAb with 64Cu was achieved with a radiochemical purity of 99% and molar activity of 2 GBq/μmol. Quantitation of CD19 PET images revealed significantly higher tracer binding in whole brain of EAE compared to naïve mice (2.02 ± 0.092 vs. 1.68 ± 0.06 percentage of injected dose per gram, % ID/g, p = 0.0173). PET findings were confirmed by ex vivo gamma counting of perfused brain tissue (0.22 ± 0.020 vs. 0.12 ± 0.003 % ID/g, p = 0.0010). Moreover, ex vivo autoradiography of brain sections corresponded with PET imaging results and the spatial distribution of B cells observed in B220 immunohistochemistry—providing further evidence that [64Cu]CD19-mAb enables visualization of B cell infiltration into the CNS of EAE mice.

Conclusion

CD19-PET imaging can be used to detect elevated levels of B cells in the CNS of EAE mice, and has the potential to impact the way we study, monitor, and treat clinical MS.
NanoPASS: an easy-to-use user interface for nanoparticle dosimetry with the 3DSDD model
Authors: Frenzel Falko , König-Mattern Laura , Stock Valerie , Voss Linn , Paul Maxi B. , Sieg Holger , Braeuning Albert , Voigt Andreas , Böhmert Linda
Published: September 2020

Nanoparticles exhibit a specific diffusion and sedimentation behavior under cell culture conditions as used in nantoxicological in vitro testing. How a particular particle suspension behaves depends on the particular physicochemical characteristics of the particles and the cell culture system. Only a fraction of the nanoparticles applied to a cell culture will thus reach the cells within a given time frame. Therefore, dosimetric calculations are essential not only to determine the exact fraction of nanoparticles that has come into contact with the cells, but also to ensure experimental comparability and correct interpretation of results, respectively. Yet, the use of published dosimetry models is limited. Not the least because the correct application of these in silico tools usually requires bioinformatics knowledge, which often is perceived a hurdle. Moreover, not all models are freely available and accessible. In order to overcome this obstacle, we have now developed an easy-to-use interface for our recently published 3DSDD dosimetry model, called NanoPASS (NanoParticle Administration Sedimentation Simulator). The interface is freely available to all researchers. It will facilitate the use of in silico dosimetry in nanotoxicology and thus improve interpretation and comparability of in vitro results in the field.
Cost-utility analysis of extensile lateral approach versus sinus tarsi approach in Sanders type II/III calcaneus fractures
Authors: Li Zihua , Wu Xinbo , Zhou Haichao , Xu Shaochen , Xiao Fajiao , Huang Hui , Yang Yunfeng
Published: September 2020

Background

Extensile lateral approach had been recognized as the gold standard technique for displaced intra-articular calcaneus fractures (DIACFs) while sinus tarsi approach had been increasingly valued by surgeons and comparative clinical outcome was shown in both techniques. Appropriate decisions could be made by the clinicians with the help of cost-utility analysis (CUA) about optimal healthcare for type II/III calcaneus fracture.

Method

A single-center, retrospective study was conducted in which basic characteristics, clinical outcomes, and health care costs of 109 patients had been obtained and analyzed. Changes in health-related quality of life (HRQoL) scores, validated by EuroQol five-dimensional-three levels (EQ-5D-3L), were used to enumerate quality-adjusted life years (QALYs). Cost-effectiveness was determined by the incremental cost per QALY.

Results

One hundred nine patients were enrolled in our study including 62 in the ELA group and 47 in the STA group. There were no significant differences between these two groups in mean total cost, laboratory, and radiographic evaluation expense, surgery, anesthesia, and antibiotic expense. The expense of internal fixation materials ($3289.0 ± 543.9) versus ($2630.6 ± 763.7) and analgesia ($145.8 ± 85.6) versus ($102.9 ± 62.7) in ELA group were significantly higher than in the STA group (P < .001, P = .008, respectively). Visual Analogue Scale (VAS) scores showed significant difference at postoperative 3 and 5 days (P < .001). American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores and the Bohlers’ and Gissane angle showed no significant differences between the two groups before and after the operation. The cost-effectiveness ratios of ELA and STA were $8766.8 ± 2835.2/QALY and $7914.9 ± 1822.0/QALY respectively, and incremental cost-effectiveness ratio (ICERs) of ELA over STA was $32110.00/QALY, but both showed no significant difference.

Conclusion

Both ELA and STA techniques are effective operative procedures for the patients with calcaneus fracture. Moreover, STA seems to be more reasonable for its merits including less postoperative pain, and less expense of analgesia as well as internal fixation materials.

Level of evidence

5
Prevalence of coat colour traits and congenital disorders of South American camelids in Austria, Germany and Switzerland
Authors: Jost Stéphanie Mali , Knoll Andrea , Lühken Gesine , Drögemüller Cord , Zanolari Patrik
Published: September 2020

Background

The increasing popularity of alpacas and llamas outside of South America is undeniable. The associated limited genetic diversity raises questions about health and other genetically determined traits like coat colour. Therefore, a survey studying the prevalence of congenital disorders and coat colours and patterns in South American camelids was performed in Austria, Germany and Switzerland. Moreover, the motivation for keeping these animals, the herd size and breeds was assessed.

Results

A total of 146 questionnaires were returned corresponding to 16 farms from Austria, 69 farms from Germany, and 61 farms from Switzerland. In total, the returned surveys reported data on 2770 animals including ~ 85% alpacas and ~ 15% llamas. The most common alpaca breed was Huacaya (87.7%), the most common llama breed was Wooly (15.6%). Breeding (69.4%), wool production (63.3%) and keeping them as pets (53.7%) were the most common motivations to keep these animals, although this varied among countries. The three coat colour groups, solid white (24.8%), brown and black (64.8%) and grey (10.4%), occurred at different frequencies. About 7% of the South American camelids with solid white coat showed blue-pigmented eyes, corresponding to the known blue-eyed white phenotype, of which more than every second animal was apparently deaf. Uniform solid coloured animals occurred predominantly (81.4%), whereas pinto (8.8%), speckled (6.4%) and spotted (3.4%), also known as appaloosa, were comparably less prevalent. In total 161 observations of congenital disorders occurring during a 5-year-period were reported. The most prevalent disorders were in the group of musculoskeletal disorders such as spiral toe growth (16.4%), hyperextension of the fetlock joint (12.3%), angular limb deformities (11.0%) and axial rotation of the limbs (8.2%).

Conclusions

This survey revealed first insights into the occurrence of different traits and disorders in the current South American camelid population of Austria, Germany, and Switzerland. The identification of the most common musculoskeletal disorders might encourage the breeders to eliminate affected animals from their breeding program to decrease the incidence although traits such as spiral toe growth might also represent phenocopies.
Implementation of external quality assessment of microscopy for improved parasite detection and confirmatory diagnosis of malaria in Tanzanian Military health facilities
Authors: Kalinga Akili K. , Mgata Saidi , Kavishe Reginald A. , Mahikwano Lucas , Temu Lucky , Mswanya Christopher , Mwanziva Charles , Amoo George , Kamau Edwin , Vesely Brian , Ishengoma Deus S.
Published: September 2020

Objective

Good quality microscopy is critical for accurate detection and confirmation of malaria parasite infections. Microscopy relies on the skills of technicians to prepare and read slides, high quality reagents, and a good program of internal and external quality control (EQA), which are lacking in most malaria endemic settings. This study was undertaken between January 2016 and December 2018 to pilot an EQA of microscopy for improved diagnosis of malaria and patient care in Tanzanian Military health facilities.

Results

Of all blood smears crosschecked (n = 4000) at baseline, only 38.5% were incorrectly diagnosed by laboratory staff with false positive and negative rates of 46.7% and 16.4%, respectively. During the implementation of EQA, false positive and negative results decreased due to increased quality index of slide preparation and reading through supportive supervision, and retraining of laboratory personnel. There was a gradual increase of quarterly and annual total quality index for all laboratories, from 60% in 2016 to 78% in 2017 and 90% in 2018. The mean proficiency testing performance scores also increased from 75% in 2016 to 82% in 2017 and to 90% in 2018. Poor blood smear preparation and staining contributed to high false positive and negative rates while EQA helped in improvement of diagnostics.
Early-stage bilayer tissue-engineered skin substitute formed by adult skin progenitor cells produces an improved skin structure in vivo
Authors: Zhang Qun , Wen Jie , Liu Chang , Ma Chuan , Bai Fuxiang , Leng Xue , Chen Zhihong , Xie Zhiwei , Mi Jun , Wu Xunwei
Published: September 2020

Background

In recent years, significant progress has been made in developing highly complex tissue-engineered skin substitutes (TESSs) for wound healing. However, the lack of skin appendages, such as hair follicles and sweat glands, and the time required, are two major limitations that hinder its broad application in the clinic. Therefore, it is necessary to develop a competent TESS in a short time to meet the needs for clinical applications.

Methods

Adult scalp dermal progenitor cells and epidermal stem cells together with type I collagen as a scaffold material were used to reconstitute bilayer TESSs in vitro. TESSs at 4 different culture times (5, 9, 14, and 21 days) were collected and then grafted onto full-thickness wounds created in the dorsal skin of athymic nude/nude mice. The skin specimens formed from grafted TESSs were collected 4 and 8 weeks later and then evaluated for their structure, cell organization, differentiation status, vascularization, and formation of appendages by histological analysis, immunohistochemistry, and immunofluorescent staining.

Results

Early-stage bilayer TESSs after transplantation had a better efficiency of grafting. A normal structure of stratified epidermis containing multiple differentiated layers of keratinocytes was formed in all grafts from both early-stage and late-stage TESSs, but higher levels of the proliferation marker Ki-67 and the epidermal progenitor marker p63 were found in the epidermis formed from early-stage TESSs. Interestingly, the transplantation of early-stage TESSs produced a thicker dermis that contained more vimentin- and CD31-positive cells, and importantly, hair follicle formation was only observed in the skin grafted from early-stage TESSs. Finally, early-stage TESSs expressed high levels of p63 but had low expression levels of genes involved in the activation of the apoptotic pathway compared to the late-stage TESSs in vitro.

Conclusions

Early-stage bilayer TESSs reconstituted from skin progenitor cells contained more competent cells with less activation of the apoptotic pathway and produced a better skin structure, including hair follicles associated with sebaceous glands, after transplantation, which should potentially provide better wound healing when applied in the clinic in the future.
Sex differences in severity and mortality from COVID-19: are males more vulnerable?
Authors: Pradhan Ajay , Olsson Per-Erik
Published: September 2020

Coronavirus disease 2019 (COVID-19) has shown high infection and mortality rates all over the world, and despite the global efforts, there is so far no specific therapy available for COVID-19. Interestingly, while the severity and mortality of COVID-19 are higher in males than in females, the underlying molecular mechanisms are unclear. In this review, we explore sex-related differences that may be contributing factors to the observed male-biased mortality from COVID-19. Males are considered the weaker sex in aspects related to endurance and infection control. Studies show that viral RNA clearance is delayed in males with COVID-19. A recent study has indicated that the testis can harbor coronavirus, and consequently, males show delayed viral clearance. However, the role of testis involvement in COVID-19 severity and mortality needs further research. Males and females show a distinct difference in immune system responses with females eliciting stronger immune responses to pathogens. This difference in immune system responses may be a major contributing factor to viral load, disease severity, and mortality. In addition, differences in sex hormone milieus could also be a determinant of viral infections as estrogen has immunoenhancing effects while testosterone has immunosuppressive effects. The sex-specific severity of COVID-19 infections indicates that further research on understanding the sex differences is needed. Inclusion of both males and females in basic research and clinical trials is required to provide critical information on sex-related differences that may help to better understand disease outcome and therapy.
High-throughput screening identifies modulators of sarcospan that stabilize muscle cells and exhibit activity in the mouse model of Duchenne muscular dystrophy
Authors: Shu Cynthia , Parfenova Liubov , Mokhonova Ekaterina , Collado Judd R. , Damoiseaux Robert , Campagna Jesus , John Varghese , Crosbie Rachelle H.
Published: September 2020

Background

Duchenne muscular dystrophy (DMD) is a degenerative muscle disease caused by mutations in the dystrophin gene. Loss of dystrophin prevents the formation of a critical connection between the muscle cell membrane and the extracellular matrix. Overexpression of sarcospan (SSPN) in the mouse model of DMD restores the membrane connection and reduces disease severity, making SSPN a promising therapeutic target for pharmacological upregulation.

Methods

Using a previously described cell-based promoter reporter assay of SSPN gene expression (hSSPN-EGFP), we conducted high-throughput screening on libraries of over 200,000 curated small molecules to identify SSPN modulators. The hits were validated in both hSSPN-EGFP and hSSPN-luciferase reporter cells. Hit selection was conducted on dystrophin-deficient mouse and human myotubes with assessments of (1) SSPN gene expression using quantitative PCR and (2) SSPN protein expression using immunoblotting and an ELISA. A membrane stability assay using osmotic shock was used to validate the functional effects of treatment followed by cell surface biotinylation to label cell surface proteins. Dystrophin-deficient mdx mice were treated with compound, and muscle was subjected to quantitative PCR to assess SSPN gene expression.

Results

We identified and validated lead compounds that increased SSPN gene and protein expression in dystrophin-deficient mouse and human muscle cells. The lead compound OT-9 increased cell membrane localization of compensatory laminin-binding adhesion complexes and improved membrane stability in DMD myotubes. We demonstrated that the membrane stabilizing benefit is dependent on SSPN. Intramuscular injection of OT-9 in the mouse model of DMD increased SSPN gene expression.

Conclusions

This study identifies a pharmacological approach to treat DMD and sets the path for the development of SSPN-based therapies.
Harnessing the strategy of metagenomics for exploring the intestinal microecology of sable (Martes zibellina), the national first-level protected animal
Authors: Yan Jiakuo , Wu Xiaoyang , Chen Jun , Chen Yao , Zhang Honghai
Published: September 2020

Sable (Martes zibellina), a member of family Mustelidae, order Carnivora, is primarily distributed in the cold northern zone of Eurasia. The purpose of this study was to explore the intestinal flora of the sable by metagenomic library-based techniques. Libraries were sequenced on an Illumina HiSeq 4000 instrument. The effective sequencing data of each sample was above 6000 M, and the ratio of clean reads to raw reads was over 98%. The total ORF length was approximately 603,031, equivalent to 347.36 Mbp. We investigated gene functions with the KEGG database and identified 7140 KEGG ortholog (KO) groups comprising 129,788 genes across all of the samples. We selected a subset of genes with the highest abundances to construct cluster heat maps. From the results of the KEGG metabolic pathway annotations, we acquired information on gene functions, as represented by the categories of metabolism, environmental information processing, genetic information processing, cellular processes and organismal systems. We then investigated gene function with the CAZy database and identified functional carbohydrate hydrolases corresponding to genes in the intestinal microorganisms of sable. This finding is consistent with the fact that the sable is adapted to cold environments and requires a large amount of energy to maintain its metabolic activity. We also investigated gene functions with the eggNOG database; the main functions of genes included gene duplication, recombination and repair, transport and metabolism of amino acids, and transport and metabolism of carbohydrates. In this study, we attempted to identify the complex structure of the microbial population of sable based on metagenomic sequencing methods, which use whole metagenomic data, and to map the obtained sequences to known genes or pathways in existing databases, such as CAZy, KEGG, and eggNOG. We then explored the genetic composition and functional diversity of the microbial community based on the mapped functional categories.
Effective educational interventions for the promotion of sexual and reproductive health and rights for school-age children in low- and middle-income countries: a systematic review protocol
Authors: Fantaye Arone Wondwossen , Buh Amos Wung , Idriss-Wheeler Dina , Fournier Karine , Yaya Sanni
Published: September 2020

Background

Biological changes underlying the sexual and reproductive maturation of school-age children are linked with various sexual and reproductive health and rights risks. SRHR risks are predictors of poor SRHR outcomes, such as poor knowledge of sexually transmitted diseases and early sexual initiation occurring predominantly among school-age children. The aim of this proposed review, therefore, is to identify educational interventions that have proven to be effective in promoting or supporting the sexual and reproductive health and rights of school-aged children in low- and middle-income countries.

Methods

A systematic review of studies on the strategies promoting the SRHR of school-aged children shall be conducted. Electronic searches will be conducted from January 2000 onwards on the following databases: MEDLINE(R) ALL (Ovid), Embase (Ovid), CINAHL (EBSCOHost), APA PsycInfo (Ovid), ERIC (Ovid), Cochrane Central Register of Controlled Trials (Ovid), Education Source (EBSCOHost), Web of Science (Clarivate Analytics), SciELO Citation Index (Clarivate Analytics), Global Health (Ovid), and Sociological Abstract (Proquest). Studies eligible for inclusion will be randomized control trials (RCTs), non-randomized trials, quasi-experimental studies (e.g., pre-post tests), and observational studies (cross-sectional and cohort studies). Peer-reviewed studies published in English and/or French and involving school-aged children 5–10 years old will be included. The primary outcomes of interest will include knowledge, awareness, or attitudes about SRHR topics. The secondary outcomes of interest will include sexual and reproductive behaviors. Two reviewers will independently screen all citations, abstract data, and full-text articles, and the methodological quality of each study will be appraised using JBI critical appraisal tools. A narrative synthesis of extracted data will be conducted.

Discussion

The systematic review will synthesize the evidence on existing educational interventions targeting SRHR outcomes of school-aged children in low- and middle-income countries. It will identify which interventions have proven to be effective, and which interventions have not proven to be effective in promoting or supporting their SRHR. Review findings will provide a useful reference for policy-makers, program developers, global health leaders, and decision makers who wish to support the SRHR of school-age children.

Systematic review registration

The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO CRD42020173158).
Hermite–Hadamard-type inequalities for the interval-valued approximately h-convex functions via generalized fractional integrals
Authors: Zhao Dafang , Ali Muhammad Aamir , Kashuri Artion , Budak Hüseyin , Sarikaya Mehmet Zeki
Published: September 2020

In this paper, we present a new definition of interval-valued convex functions depending on the given function which is called “interval-valued approximatelyh-convex functions”. We establish some inequalities of Hermite–Hadamard type for a newly defined class of functions by using generalized fractional integrals. Our new inequalities are the extensions of previously obtained results like (D.F. Zhao et al. in J. Inequal. Appl. 2018(1):302, 2018 and H. Budak et al. in Proc. Am. Math. Soc., 2019). We also discussed some special cases from our main results.
Blow-up criterion for the density dependent inviscid Boussinesq equations
Authors: Li Li , Zhou Yanping
Published: September 2020

In this work, we consider the density-dependent incompressible inviscid Boussinesq equations in$\mathbb{R}^{N}\ (N\geq 2)$RN(N≥2). By using the basic energy method, we first give the a priori estimates of smooth solutions and then get a blow-up criterion. This shows that the maximum norm of the gradient velocity field controls the breakdown of smooth solutions of the density-dependent inviscid Boussinesq equations. Our result extends the known blow-up criteria.
Senses of place: architectural design for the multisensory mind
Authors: Spence Charles
Published: September 2020

Traditionally, architectural practice has been dominated by the eye/sight. In recent decades, though, architects and designers have increasingly started to consider the other senses, namely sound, touch (including proprioception, kinesthesis, and the vestibular sense), smell, and on rare occasions, even taste in their work. As yet, there has been little recognition of the growing understanding of the multisensory nature of the human mind that has emerged from the field of cognitive neuroscience research. This review therefore provides a summary of the role of the human senses in architectural design practice, both when considered individually and, more importantly, when studied collectively. For it is only by recognizing the fundamentally multisensory nature of perception that one can really hope to explain a number of surprising crossmodal environmental or atmospheric interactions, such as between lighting colour and thermal comfort and between sound and the perceived safety of public space. At the same time, however, the contemporary focus on synaesthetic design needs to be reframed in terms of the crossmodal correspondences and multisensory integration, at least if the most is to be made of multisensory interactions and synergies that have been uncovered in recent years. Looking to the future, the hope is that architectural design practice will increasingly incorporate our growing understanding of the human senses, and how they influence one another. Such a multisensory approach will hopefully lead to the development of buildings and urban spaces that do a better job of promoting our social, cognitive, and emotional development, rather than hindering it, as has too often been the case previously.
A new report on gene expression of three killer toxin genes with antimicrobial activity of two killer toxins in Iraq
Authors: Abu-Mejdad Najwa Mohammed Jameel Ali , Al-Badran Adnan I. , Al-Saadoon Abdullah H. , Minati Mohammed Hussein
Published: September 2020

Background

The K1, K2, and K28 toxins are usually encoded by several cytoplasmically genetic satellite dsRNAs (M1, M2, and M28), which are encapsulated with virus-like particles (VLPs) and reliant on an additional assembly of assistant yeast viruses (L-A) for their reproduction and encapsidation. Ascomycetous yeast species that have these VLPs are especially attractive targets for finding killer toxins like proteins. This is because the organisms are known in producing a large variety of secondary metabolites and extracellular enzymes, which have medical importance as alternative drugs for resistance bacterial strains, particularly multi-resistance drugs (MRD).

Results

For the first time, 31 type strains of yeasts were tested for killer toxin production in Iraq via the measurement of gene expression of three killer toxin genes (M1, M2, and M28) within the mycovirus in yeasts. All the type strains gave an expression for the three killer toxins with variable levels. The highest expression was recorded for the killer toxin genes in Torulaspora delbrueckii followed by Wickerhamomyces anomalus. Determined antibacterial activity of two killer toxins appeared with high inhibition zone against pathogenic strains of bacteria. Cytotoxicity against human blood cells was not found. These results considered the first record of killer toxins isolated from type strains in Iraq.

Conclusion

The two typical strains Torulaspora delbrueckii and Wickerhamomyces anomalus showed the highest level of gene expression for the three killer toxins.
Cause-Specific Mortality Following Initial Chemotherapy in a Population-Based Cohort of Patients With Classical Hodgkin Lymphoma, 2000-2016
Authors: Dores Graça M. , Curtis Rochelle E. , Dalal Nicole H. , Linet Martha S. , Morton Lindsay M.
Published: September 2020

PURPOSE

Mortality for patients with classical Hodgkin lymphoma (cHL) treated during an era characterized in the United States by widespread use of doxorubicin, bleomycin, vinblastine, and dacarbazine and diminishing use of radiotherapy is not well understood.

PATIENTS AND METHODS

We identified 20,007 individuals diagnosed with stage I/II (early) or III/IV (advanced) cHL between age 20 and 74 years treated with initial chemotherapy in US population-based cancer registries during 2000-2015 (follow-up through 2016). We used standardized mortality ratios (SMRs) to compare cause-specific relative mortality risk following cHL to that expected in the general population and estimated excess absolute risks (EARs; per 10,000 patient-years) to quantify disease-specific death burden.

RESULTS

We identified 3,380 deaths in the cHL cohort, including 1,321 (39%) not attributed to lymphoma. Overall, noncancer SMRs were increased 2.4-fold (95% CI, 2.2 to 2.6; observed, 559; EAR, 61.6) and 1.6-fold (95% CI, 1.4 to 1.7; observed, 473; EAR, 18.2) for advanced- and early-stage cHL, respectively, compared with the general US population. SMRs and EARs differed substantially by cause of death and cHL stage. Among the highest EARs for noncancer causes of death were those for heart disease (EAR, 15.1; SMR, 2.1), infections (EAR, 10.6; SMR, 3.9), interstitial lung disease (ILD; EAR, 9.7; SMR, 22.1), and adverse events (AEs) related to medications/drugs (EAR, 7.4; SMR, 5.0) after advanced-stage cHL and heart disease (EAR, 6.6; SMR, 1.7), ILD (EAR, 3.7; SMR, 13.1), and infections (EAR, 3.1; SMR, 2.2) after early-stage cHL. Strikingly elevated SMRs for ILD, infections, and AEs were observed < 1 year after cHL. Individuals age 60-74 years with advanced-stage cHL experienced a disproportionate excess of deaths as a result of heart disease, ILD, infections, AEs, and solid tumors.

CONCLUSION

Despite evolving cHL treatment approaches, patients continue to face increased nonlymphoma mortality risks from multiple, potentially preventable causes. Surveillance, early interventions, and cHL treatment refinements may favorably affect patient longevity, particularly among high-risk subgroups.