bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and predictors of vitamin D deficiency in young African children
Authors: Mogire Reagan M. , Morovat Alireza , Muriuki John Muthii , Mentzer Alexander J. , Webb Emily L. , Kimita Wandia , Ndungu Francis M. , Macharia Alex W. , Cutland Clare L. , Sirima Sodiomon B. , Diarra Amidou , Tiono Alfred B. , Lule Swaib A. , Madhi Shabir A. , Sandhu Manjinder S. , Prentice Andrew M. , Bejon Philip , Pettifor John M. , Elliott Alison M. , Adeyemo Adebowale , Williams Thomas N. , Atkinson Sarah H.
Published: May 2021

Background

Children living in sub-Saharan Africa have a high burden of rickets and infectious diseases, conditions that are linked to vitamin D deficiency. However, data on the vitamin D status of young African children and its environmental and genetic predictors are limited. We aimed to examine the prevalence and predictors of vitamin D deficiency in young African children.

Methods

We measured 25-hydroxyvitamin D (25(OH)D) and typed the single nucleotide polymorphisms, rs4588 and rs7041, in the GC gene encoding the vitamin D binding protein (DBP) in 4509 children aged 0–8 years living in Kenya, Uganda, Burkina Faso, The Gambia and South Africa. We evaluated associations between vitamin D status and country, age, sex, season, anthropometric indices, inflammation, malaria and DBP haplotypes in regression analyses.

Results

Median age was 23.9 months (interquartile range [IQR] 12.3, 35.9). Prevalence of vitamin D deficiency using 25(OH)D cut-offs of < 30 nmol/L and < 50 nmol/L was 0.6% (95% CI 0.4, 0.9) and 7.8% (95% CI 7.0, 8.5), respectively. Overall median 25(OH)D level was 77.6 nmol/L (IQR 63.6, 94.2). 25(OH)D levels were lower in South Africa, in older children, during winter or the long rains, and in those with afebrile malaria, and higher in children with inflammation. 25(OH)D levels did not vary by stunting, wasting or underweight in adjusted regression models. The distribution of Gc variants was Gc1f 83.3%, Gc1s 8.5% and Gc2 8.2% overall and varied by country. Individuals carrying the Gc2 variant had lower median 25(OH)D levels (72.4 nmol/L (IQR 59.4, 86.5) than those carrying the Gc1f (77.3 nmol/L (IQR 63.5, 92.8)) or Gc1s (78.9 nmol/L (IQR 63.8, 95.5)) variants.

Conclusions

Approximately 0.6% and 7.8% of young African children were vitamin D deficient as defined by 25(OH)D levels < 30 nmol/L and < 50 nmol/L, respectively. Latitude, age, season, and prevalence of inflammation and malaria should be considered in strategies to assess and manage vitamin D deficiency in young children living in Africa.
Significant contribution of the CmeABC Efflux pump in high-level resistance to ciprofloxacin and tetracycline in Campylobacter jejuni and Campylobacter coli clinical isolates
Authors: Sharifi Saeed , Bakhshi Bita , Najar-peerayeh Shahin
Published: May 2021

Background

Campylobacter resistance to antimicrobial agents is regarded as a major concern worldwide. The aim of this study was to investigate the expression of the CmeABC efflux pump and the RAPD-PCR pattern in drug-resistant Campylobacter isolates.

Methods

A total of 283 stool specimens were collected from children under the age of five with diarrhea. The minimum inhibitory concentration (MIC) of tetracycline and ciprofloxacin was determined by broth microdilution method and E-test, respectively. Detection of tetracycline and ciprofloxacin determinants was done by amplification of tetO gene and PCR-sequencing of the gyrA gene. The cmeABC transcriptional expression was analyzed by Real-time (RT)-PCR. Clonal correlation of resistant strains was determined by RAPD-PCR genotyping.

Results

Out of 283 fecal samples, 20 (7.02%) samples were positive for Campylobacter spp. Analysis of duplex PCR assay of the cadF gene showed that 737 and 461 bp amplicons were corresponding to Campylobacter jejuni and Campylobacter coli, respectively. All of the 17 phenotypically tetracycline-resistant Campylobacter isolates harbored the tetO gene. Also, four phenotypically ciprofloxacin-resistant Campylobacter isolates had a point mutation at codon 257 of the gyrA gene (ACA to ATA; Thr > Ile). High-level expression of the cmeA gene was observed in ciprofloxacin-resistant and high-level tetracycline-resistant Campylobacter isolates, suggesting a positive correlation between the cmeA gene expression level and tetracycline resistance level. Moreover, a statistically significant difference was observed in the cmeA gene expression between ciprofloxacin-resistant and ciprofloxacin-susceptible strains, which signifies the crucial contribution of the efflux pump in conferring multiple drug resistance phenotype among Campylobacter spp. RAPD analysis of Campylobacter isolates exhibited 16 different patterns. Simpsone`s diversity index of RAPD-PCR was calculated as 0.85, showing a high level of homogeneity among the population; however, no clear correlation was detected among tetracycline and/or ciprofloxacin resistant isolates.

Conclusion

Significant contribution of the CmeABC efflux pump in conferring high-level resistance to tetracycline and ciprofloxacin was observed in C. jejuni and C. coli clinical isolates. The resistant phenotype is suggested to be mediated by CmeABC efflux pumps, the tetO gene, and point mutation of the gyrA gene. Genotyping revealed no clonal correlation among resistant strains, indicating distinct evolution of tetracycline and ciprofloxacin resistant genotypes among the isolates.
Reducing drug-use harms among higher education students: MyUSE contextual-behaviour change digital intervention development using the Behaviour Change Wheel
Authors: Vasiliou Vasilis S. , Dockray Samantha , Dick Samantha , Davoren Martin P. , Heavin Ciara , Linehan Conor , Byrne Michael
Published: May 2021

Background

Digital harm-reduction interventions typically focus on people with severe drug-use problems, yet these interventions have moderate effectiveness on drug-users with lower levels of risk of harm. The difference in effectiveness may be explained by differences in behavioural patterns between the two groupings. Harnessing behavioural theories to understand what is at the core of drug-use behaviours and mapping the content of new interventions, may improve upon the effectiveness of interventions for lower-risk drug-users. To the best of our knowledge, this is the first study to systematically apply the Behaviour Change Wheel (BCW) approach to understand the components, influencing capabilities, opportunities, and motivations (COM-B) of higher education students to change their drug-use behaviors. It is also the first study which identifies specific patterns of behaviours that are more responsive to harm reduction practices through the use of the Theoretical Domain Framework (TDF).

Methods

We employed an explanatory sequential mix-method design. We first conducted an on-line survey and a Delphi exercise to understand the factors influencing COM-B components of higher education students to change their drug-use. Subsequently, we mapped all evidence onto the COM-B components and the TDF domains to identify clusters of behaviours to target for change, using a pattern-based discourse analysis. Finally, a series of multidisciplinary group meetings identified the intervention functions—the means by which the intervention change targeted behaviours and the Behavioural Change Techniques (BCTs) involved using the behaviour change technique taxonomy (v.1).

Results

Twenty-nine BCTs relevant to harm-reduction practices were identified and mapped across five intervention functions (education, modelling, persuasion, incentivization, and training) and five policy categories (communication/marketing, guidelines, regulation, service provision, and environmental/social planning). These BCTs were distributed across eight identified saturated clusters of behaviours MyUSE intervention attempts to change.

Conclusions

The BCTs, identified, will inform the development of a digitally delivered behaviour change intervention that focuses on increasing mindful decision-making with respect to drug-use and promotes alternatives to drug-use activities. The findings can also inform implementation scientists in applying context-specific harm-reduction practices in higher education. We present examples of how the eight identified clusters of target behaviours are mapped across the COM-B components and the TDF, along with suggestions of implementation practices for harm reduction at student population level.
Global trends in medical education accreditation
Authors: Bedoll Deborah , van Zanten Marta , McKinley Danette
Published: May 2021

Background

Accreditation systems in medical education aim to assure various stakeholders that graduates are ready to further their training or begin practice. The purpose of this paper is to explore the current state of medical education accreditation around the world and describe the incidence and variability of these accreditation agencies worldwide. This paper explores trends in agency age, organization, and scope according to both World Bank region and income group.

Methods

To find information on accreditation agencies, we searched multiple online accreditation and quality assurance databases as well as the University of Michigan Online Library and the Google search engine. All included agencies were recorded on a spreadsheet along with date of formation or first accreditation activity, name changes, scope, level of government independence, accessibility and type of accreditation standards, and status of WFME recognition. Comparisons by country region and income classification were made based on the World Bank’s lists for fiscal year 2021.

Results

As of August 2020, there were 3,323 operating medical schools located in 186 countries or territories listed in the World Directory of Medical Schools. Ninety-two (49%) of these countries currently have access to undergraduate accreditation that uses medical-specific standards. Sixty-four percent (n = 38) of high-income countries have medical-specific accreditation available to their medical schools, compared to only 20% (n = 6) of low-income countries. The majority of World Bank regions experienced the greatest increase in medical education accreditation agency establishment since the year 2000.

Conclusions

Most smaller countries in Europe, South America, and the Pacific only have access to general undergraduate accreditation, and many countries in Africa have no accreditation available. In countries where medical education accreditation exists, the scope and organization of the agencies varies considerably. Regional cooperation and international agencies seem to be a growing trend. The data described in our study can serve as an important resource for further investigations on the effectiveness of accreditation activities worldwide. Our research also highlights regions and countries that may need focused accreditation development support.
hsa_circ_001946 elevates HOXA10 expression and promotes the development of endometrial receptivity via sponging miR-135b
Authors: Zhao Fang , Guo Yihong , Shi Zhanrong , Wu Menglan , Lv Yuzhen , Song Wenyue
Published: May 2021

Background

Impaired endometrial receptivity is a major reason for embryo implantation failure. There’s a paucity of information regarding the role of circRNAs on endometrial receptivity. Here, we investigated the function of hsa_circ_001946 on endometrial receptivity and its mechanisms.

Methods

A total of 50 women composing 25 with recurrent implantation failure and 25 who conceived after their implantation were recruited in this study. Expression of hsa_circ_001946, miR-135b, and HOXA10 was evaluated by quantitative RT-PCR (qRT-PCR) in biopsied endometrial tissue samples. The levels of HOXA10, and cell cycle markers (CCNB1, CDK1, and CCND1) were determined by IHC and western blotting assays. Binding relationship among miR-135b, hsa_circ_001946 and HOXA10 were confirmed by dual luciferase reporter assays and western blotting. MTT assays and cell cycle assays by FACS were employed to evaluate the proliferation and cell cycle of cells. T-HESCs were cultured with 1 µM medroxyprogesterone acetate (MPA) and 0.5 mM 8-bromoadenosine 3’:5’-cyclic monophosphate (8-Br-cAMP) to induce decidualization. The mechanisms and functions of hsa_circ_001946 on decidualization were further assessed by qRT-PCR evaluating the expression of hsa_circ_001946, miR-135b, HOXA10 and decidual markers (PRL and IGFBP1) in T-HESCs.

Results

Endometrial tissues from patients with recurrent implantation failure had lower hsa_circ_001946 expression, higher miR-135b expression, and lower HOXA10 expression. Hsa_circ_001946 promoted HOXA10 expression by sponging miR-135b in T-HESCs. Overexpression of hsa_circ_001946 restored cell proliferation and cell cycle that were disrupted by miR-135b overexpression in T-HESCs. Decidualized T-HESCs had higher hsa_circ_001946 expression, lower miR-135b expression, and higher HOXA10 expression. Overexpression of hsa_circ_001946 reversed the expression of decidual markers (PRL and IGFBP1) that were suppressed by miR-135b overexpression in T-HESCs.

Conclusions

In conclusion, our findings suggest that hsa_circ_001946 promotes cell proliferation and cell cycle process and increases expression of decidualization markers to enhance endometrial receptivity progression via sponging miR-135b and elevating HOXA10.
Needle tract seeding in renal tumor biopsies: experience from a single institution
Authors: Zhou Yan , Murugan Paari , Li Faqian , Bu Lihong
Published: May 2021

Background

Percutaneous needle biopsy of renal masses has been increasingly utilized to aid the diagnosis and guide management. It is generally considered as a safe procedure. However, tumor seeding along the needle tract, one of the complications, theoretically poses potential risk of tumor spread by seeded malignant cells. Prior studies on the frequency of needle tract seeding in renal tumor biopsies are limited and clinical significance of biopsy-associated tumor seeding remains largely controversial.

Methods

Here we investigated the frequencies of biopsy needle tract tumor seeding at our institution by reviewing the histology of renal cell carcinoma nephrectomy specimens with a prior biopsy within the last seventeen years. Biopsy site changes were recognized as a combination of foreign body reaction, hemosiderin deposition, fibrosis and fat necrosis. The histologic evidence of needle tract tumor seeding was identified as clusters of tumor cells embedded in perinephric tissue spatially associated with the biopsy site. In addition, association between parameters of biopsy techniques and tumor seeding were investigated.

Results

We observed needle tract tumor seeding to perinephric tissue in six out of ninety-eight (6 %) renal cell carcinoma cases including clear cell renal cell carcinoma, papillary renal cell carcinoma, chromophobe, and clear cell papillary renal cell carcinoma. The needle tract tumor seeding was exclusively observed in papillary renal cell carcinomas (6/28, 21 %) that were unifocal, small-sized (≤ 4 cm), confined to the kidney and had type 1 features. No recurrence or metastasis was observed in the papillary renal cell carcinoma cases with tumor seeding or the stage-matched cases without tumor seeding.

Conclusions

Our study demonstrated a higher than reported frequency of needle tract tumor seeding. Effective communication between pathologists and clinicians as well as documentation of tumor seeding is recommended. Further studies with a larger patient cohort and longer follow up to evaluate the impact of needle tract tumor seeding on long term prognosis are needed. This may also help reach a consensus on appropriate pathologic staging of renal cell carcinoma when the only site of perinephric fat invasion is within a biopsy needle tract.
A new prediction model for patient satisfaction after total knee arthroplasty and the roles of different scoring systems: a retrospective cohort study
Authors: Liu Jinyu , Yang Yi , Wan Shengcheng , Yao Zhenjun , Zhang Ying , Zhang Yueqi , Shi Peng , Zhang Chi
Published: May 2021

Background

Although total knee arthroplasty (TKA) is an efficacious treatment for end-stage osteoarthritis, ~20% of patients are dissatisfied with the results. We determined which factors contribute to patient satisfaction and compared the various scoring systems before and after surgery.

Methods

In this retrospective cohort study, 545 patients were enrolled and evaluated preoperatively and 1 year postoperatively. Patient demographics, as well as scores for the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Short Form (SF)-12, and 1989 Knee Society Clinical Rating System (1989 KSS), were recorded preoperatively and postoperatively. The possible predictors were introduced into a prediction model. Scores for overall satisfaction and the 2011 Knee Society Score (2011 KSS) were also assessed after TKA to identify the accuracy and agreement of the systems.

Results

There were 134 male patients and 411 female patients, with an overall prevalence of satisfaction of 83.7% 1 year after surgery. A history of surgery (p < 0.001) and the 1989 KSS and SF-12 were of the utmost importance in the prediction model, whereas the WOMAC score had a vital role postoperatively (change in WOMAC pain score, p < 0.001; change in WOMAC physical function score, p < 0.001; postoperative WOMAC pain score, p = 0.004). C-index of model was 0.898 > 0.70 (95% confidence interval (CI): 0.86-0.94). The Hosmer-Lemeshow test showed a p value of 0.586, and the AUC of external cohort was 0.953 (sensitivity=0.87, specificity=0.97). The agreement between the assessment of overall satisfaction and the 2011 KSS satisfaction assessment was general (Kappa=0.437 > 0.4, p < 0.001).

Conclusion

A history of surgery, the preoperative 1989 KSS, and the preoperative SF-12 influenced patient satisfaction after primary TKA. We recommend the WOMAC (particularly the pain subscale score) to reflect overall patient satisfaction postoperatively.
Case report: surgical resection of right ventricular cardiac fibroma in an adult patient
Authors: Ikegami Hirohisa , Lemaire Anthony , Gowda Subhashini , Fyfe Billie , Ali Mahmoud , Russo Mark J. , Lee Leonard Y.
Published: May 2021

Background

Cardiac fibromas are rare benign cardiac neoplasms, most frequently occurring in the pediatric population; with very rare cases identified in adults. The tumors are comprised of spindled cells with myofibroblastic ultrastructural features embedded in generally collagenous and elastic stroma. The tumors are intramural in the ventricles, most commonly the left ventricle. Clinical symptoms vary by location and size of tumor and some are asymptomatic. Surgical resection is curative, but rare cases require cardiac transplantation.

Case presentation

We report an asymptomatic, large, right ventricular fibroma in a 64-year-old woman. The patient underwent open incisional tumor biopsy via lower hemi-sternotomy, followed by complete tumor resection via full sternotomy a week later after confirming the tumor is benign. The tumor was resected using cardiopulmonary bypass, and the defect of right ventricular free wall was repaired using a prosthetic double-patch technique. The postoperative course was uneventful. The patient was discharged to home on day 4 post-complete tumor resection.

Conclusion

This report expands the existing literature for better comprehension and detection of cardiac fibroma patients and also highlights the various imaging modalities, surgical management, and histological analysis.
Family care for persons with severe mental illness: experiences and perspectives of caregivers in Uganda
Authors: Verity F. , Turiho A. , Mutamba B. B. , Cappo D.
Published: May 2021

Background

In low-income settings with limited social protection supports, by necessity, families are a key resource for care and support. Paradoxically, the quality of family care for people living with Severe Mental Illness (PLSMI) has been linked to support for recovery, hospital overstay and preventable hospital readmissions. This study explored the care experiences of family members of PLSMI with patients at the national mental hospital in Kampala, Uganda, a low income country. This study was undertaken to inform the development of YouBelongHome (YBH), a community mental health intervention implemented by YouBelong Uganda (YBU), a registered NGO in Uganda.

Methods

Qualitative data was analysed from 10 focus groups with carers of ready to discharge patients on convalescent wards in Butabika National Referral Mental Hospital (BNRMH), Kampala. This is a subset of data from a mixed methods baseline study for YouBelong Uganda, undertaken in 2017 to explore hospital readmissions and community supports for PLSMI from the Wakiso and Kampala districts, Uganda.

Results

Three interrelated themes emerge in the qualitative analysis: a range of direct, practical care provided by the caregiver of the PLSMI, emotional family dynamics, and the social and cultural context of care. The family care giving role is multidimensional, challenging, and changing. It includes protection of the PLSMI from harm and abuse, in the context of stigma and discrimination, and challenging behaviours that may result from poor access to and use of evidence-based medicines. There is reliance on traditional healers and faith healers reflecting alternative belief systems and health seeking behaviour rather than medicalised care. Transport to attend health facilities impedes access to help outside the family care system. Underpinning these experiences is the impact of low economic resources.

Conclusions

Family support can be a key resource and an active agent in mental health recovery for PLSMI in Uganda. Implementing practical family-oriented mental health interventions necessitates a culturally aware practice. This should be based in understandings of dynamic family relationships, cultural understanding of severe mental illness that places it in a spiritual context, different family forms, caregiving practices and challenges as well as community attitudes. In the Ugandan context, limited (mental) health system infrastructure and access to medications and service access impediments, such as economic and transport barriers, accentuate these complexities.
Molecular investigation of bacterial and protozoal pathogens in ticks collected from different hosts in Turkey
Authors: Köseoğlu Ahmet Efe , Can Hüseyin , Güvendi Mervenur , Erkunt Alak Sedef , Kandemir Çağrı , Taşkın Turğay , Demir Samiye , Akgül Gülşah , Değirmenci Döşkaya Aysu , Karakavuk Muhammet , Döşkaya Mert , Gürüz Adnan Yüksel , Ün Cemal
Published: May 2021

Background

The emergence of tick-borne disease is increasing because of the effects of the temperature rise driven by global warming. In Turkey, 19 pathogens transmitted by ticks to humans and animals have been reported. Based on this, this study aimed to investigate tick-borne pathogens including Hepatozoon spp., Theileria spp., Babesia spp., Anaplasma spp., Borrelia spp., and Bartonella spp. in tick samples (n = 110) collected from different hosts (dogs, cats, cattle, goats, sheep, and turtles) by molecular methods.

Methods

To meet this objective, ticks were identified morphologically at the genus level by microscopy; after DNA isolation, each tick sample was identified at the species level using the molecular method. Involved pathogens were then investigated by PCR method.

Results

Seven different tick species were identified including Rhipicephalus sanguineus, R. turanicus, R. bursa, Hyalomma marginatum, H. anatolicum, H. aegyptium, and Haemaphysalis erinacei. Among the analyzed ticks, Hepatozoon spp., Theileria spp., Babesia spp., and Anaplasma spp. were detected at rates of 6.36%, 16.3%, 1.81%, and 6.36%, respectively while Borrelia spp. and Bartonella spp. were not detected. Hepatozoon spp. was detected in R. sanguineus ticks while Theileria spp., Babesia spp., and Anaplasma spp. were detected in R. turanicus and H. marginatum. According to the results of sequence analyses applied for pathogen positive samples, Hepatozoon canis, Theileria ovis, Babesia caballi, and Anaplasma ovis were identified.

Conclusion

Theileria ovis and Anaplasma ovis were detected for the first time to our knowledge in H. marginatum and R. turanicus collected from Turkey, respectively. Also, B. caballi was detected for the first time to our knowledge in ticks in Turkey.

Graphical Abstract
Prospective and detailed behavioral phenotyping in DDX3X syndrome
Authors: Tang Lara , Levy Tess , Guillory Sylvia , Halpern Danielle , Zweifach Jessica , Giserman-Kiss Ivy , Foss-Feig Jennifer H. , Frank Yitzchak , Lozano Reymundo , Belani Puneet , Layton Christina , Lerman Bonnie , Frowner Emanuel , Breen Michael S. , De Rubeis Silvia , Kostic Ana , Kolevzon Alexander , Buxbaum Joseph D. , Siper Paige M. , Grice Dorothy E.
Published: May 2021

Background

DDX3X syndrome is a recently identified genetic disorder that accounts for 1–3% of cases of unexplained developmental delay and/or intellectual disability (ID) in females, and is associated with motor and language delays, and autism spectrum disorder (ASD). To date, the published phenotypic characterization of this syndrome has primarily relied on medical record review; in addition, the behavioral dimensions of the syndrome have not been fully explored.

Methods

We carried out multi-day, prospective, detailed phenotyping of DDX3X syndrome in 14 females and 1 male, focusing on behavioral, psychological, and neurological measures. Three participants in this cohort were previously reported with limited phenotype information and were re-evaluated for this study. We compared results against population norms and contrasted phenotypes between individuals harboring either (1) protein-truncating variants or (2) missense variants or in-frame deletions.

Results

Eighty percent (80%) of individuals met criteria for ID, 60% for ASD and 53% for attention-deficit/hyperactivity disorder (ADHD). Motor and language delays were common as were sensory processing abnormalities. The cohort included 5 missense, 3 intronic/splice-site, 2 nonsense, 2 frameshift, 2 in-frame deletions, and one initiation codon variant. Genotype–phenotype correlations indicated that, on average, missense variants/in-frame deletions were associated with more severe language, motor, and adaptive deficits in comparison to protein-truncating variants.

Limitations

Sample size is modest, however, DDX3X syndrome is a rare and underdiagnosed disorder.

Conclusion

This study, representing a first, prospective, detailed characterization of DDX3X syndrome, extends our understanding of the neurobehavioral phenotype. Gold-standard diagnostic approaches demonstrated high rates of ID, ASD, and ADHD. In addition, sensory deficits were observed to be a key part of the syndrome. Even with a modest sample, we observe evidence for genotype–phenotype correlations with missense variants/in-frame deletions generally associated with more severe phenotypes.
Variation in the vulnerability of mice expressing human superoxide dismutase 1 to prion-like seeding: a study of the influence of primary amino acid sequence
Authors: Ayers Jacob I. , Xu Guilian , Dillon Kristy , Lu Qing , Chen Zhijuan , Beckman John , Moreno-Romero Alma K. , Zamora Diana L. , Galaleldeen Ahmad , Borchelt David R.
Published: May 2021

Misfolded forms of superoxide dismutase 1 (SOD1) with mutations associated with familial amyotrophic lateral sclerosis (fALS) exhibit prion characteristics, including the ability to act as seeds to accelerate motor neuron disease in mouse models. A key feature of infectious prion seeding is that the efficiency of transmission is governed by the primary sequence of prion protein (PrP). Isologous seeding, where the sequence of the PrP in the seed matches that of the host, is generally much more efficient than when there is a sequence mis-match. Here, we used paradigms in which mutant SOD1 seeding homogenates were injected intraspinally in newborn mice or into the sciatic nerve of adult mice, to assess the influence of SOD1 primary sequence on seeding efficiency. We observed a spectrum of seeding efficiencies depending upon both the SOD1 expressed by mice injected with seeds and the origin of the seed preparations. Mice expressing WT human SOD1 or the disease variant G37R were resistant to isologous seeding. Mice expressing G93A SOD1 were also largely resistant to isologous seeding, with limited success in one line of mice that express at low levels. By contrast, mice expressing human G85R-SOD1 were highly susceptible to isologous seeding but resistant to heterologous seeding by homogenates from paralyzed mice over-expressing mouse SOD1-G86R. In other seeding experiments with G85R SOD1:YFP mice, we observed that homogenates from paralyzed animals expressing the H46R or G37R variants of human SOD1 were less effective than seeds prepared from mice expressing the human G93A variant. These sequence mis-match effects were less pronounced when we used purified recombinant SOD1 that had been fibrilized in vitro as the seeding preparation. Collectively, our findings demonstrate diversity in the abilities of ALS variants of SOD1 to initiate or sustain prion-like propagation of misfolded conformations that produce motor neuron disease.
Technical features of a ninth-century silver vessel of southern China uncovered from Famen Monastery, Shaanxi province
Authors: Tan Panpan , Yang Junchang , Ren Xinlai
Published: May 2021

Silver art is an important feature of the Tang dynasty in China and the manufacturing center for silver shifted from north to south after the mid-eighth century CE. The typology, stylistics, and iconography of silver vessels from both regions have been studied in detail. However, their technical characteristics have rarely been discussed, in particular, those of the southern ones. The current study presents a non-invasive scientific analysis on a partially-gilded silver box from Jiangnanxidao of Tang (southern China), uncovered from the pagoda crypt of the Famen Monastery, Shaanxi province. The results reveal that the box was made of refined silver from cupellation, and composed of five pieces, brazed together with hard solder. Ag–Cu alloy was identified to braze the ring foot and the box bottom. Brazing, hammering, engraving, repoussé, chasing, punching, and partial fire-gilding were employed to shape and decorate the box. More strikingly, the comparative analysis of technical details between this southern box and the previously reported northern silver vessels demonstrates that the former is more precise. Moreover, the similarities in motif expressions of southern-origin silver vessels after the mid-eighth century CE and northern-origin silver vessels before the mid-eighth century CE reflect the inheritance of decorative style. These differences and inheritance indicate that southern artisans after the mid-eighth century CE inherited the decorative technology of the northern-origin silver vessels before the mid-eighth century CE and developed them to greater perfection. The current study presents novel insights into the silver technology of southern China during the late Tang dynasty.
Double-thin-shell approach to deriving total electron content from GNSS signals and implications for ionospheric dynamics near the magnetic equator
Authors: Maruyama Takashi , Hozumi Kornyanat , Ma Guanyi , Supnithi Pornchai , Tongkasem Napat , Wan Qingtao
Published: May 2021

A new technique was developed to estimate the ionospheric total electron content (TEC) from Global Navigation Satellite System (GNSS) satellite signals. The vertically distributed electron density was parameterized by two thin-shell layers (double-shell approach). The spatiotemporal variation of TEC (strictly speaking, partial electron content) associated with each shell was approximated by the functional fitting of spherical surface harmonics. The major improvements over the conventional single-shell approach were as follows: (1) the precise estimation of TEC was achieved; (2) the estimated TEC was less dependent on the choice of shell heights; and (3) the equatorial anomaly was captured more correctly. Furthermore, higher and lower shells exhibited a different pattern of local time vs latitude variation, providing information on the ionosphere–thermosphere dynamics.
The effect of targeting Tie2 on hemorrhagic shock-induced renal perfusion disturbances in rats
Authors: van Leeuwen Anoek L. I. , Dekker Nicole A. M. , Van Slyke Paul , de Groot Esther , Vervloet Marc G. , Roelofs Joris J. T. H. , van Meurs Matijs , van den Brom Charissa E.
Published: May 2021

Background

Hemorrhagic shock is associated with acute kidney injury and increased mortality. Targeting the endothelial angiopoietin/Tie2 system, which regulates endothelial permeability, previously reduced hemorrhagic shock-induced vascular leakage. We hypothesized that as a consequence of vascular leakage, renal perfusion and function is impaired and that activating Tie2 restores renal perfusion and function.

Methods

Rats underwent 1 h of hemorrhagic shock and were treated with either vasculotide or PBS as control, followed by fluid resuscitation for 4 h. Microcirculatory perfusion was measured in the renal cortex and cremaster muscle using contrast echography and intravital microscopy, respectively. Changes in the angiopoietin/Tie2 system and renal injury markers were measured in plasma and on protein and mRNA level in renal tissue. Renal edema formation was determined by wet/dry weight ratios and renal structure by histological analysis.

Results

Hemorrhagic shock significantly decreased renal perfusion (240 ± 138 to 51 ± 40, p < 0.0001) and cremaster perfusion (12 ± 2 to 5 ± 2 perfused vessels, p < 0.0001) compared to baseline values. Fluid resuscitation partially restored both perfusion parameters, but both remained below baseline values (renal perfusion 120 ± 58, p = 0.08, cremaster perfusion 7 ± 2 perfused vessels, p < 0.0001 compared to baseline). Hemorrhagic shock increased circulating angiopoietin-1 (p < 0.0001), angiopoietin-2 (p < 0.0001) and soluble Tie2 (p = 0.05), of which angiopoietin-2 elevation was associated with renal edema formation (r = 0.81, p < 0.0001). Hemorrhagic shock induced renal injury, as assessed by increased levels of plasma neutrophil gelatinase-associated lipocalin (NGAL: p < 0.05), kidney injury marker-1 (KIM-1; p < 0.01) and creatinine (p < 0.05). Vasculotide did not improve renal perfusion (p > 0.9 at all time points) or reduce renal injury (NGAL p = 0.26, KIM-1 p = 0.78, creatinine p > 0.9, renal edema p = 0.08), but temporarily improved cremaster perfusion at 3 h following start of fluid resuscitation compared to untreated rats (resuscitation + 3 h: 11 ± 3 vs 8 ± 3 perfused vessels, p < 0.05).

Conclusion

Hemorrhagic shock-induced renal impairment cannot be restored by standard fluid resuscitation, nor by activation of Tie2. Future treatment strategies should focus on reducing angiopoietin-2 levels or on activating Tie2 via an alternative strategy.
The survival rate of transcrestal sinus floor elevation combined with short implants: a systematic review and meta-analysis of observational studies
Authors: Lin Zhe-Zhen , Jiao Yan-Qing , Ye Zhang-Yan , Wang Ge-Ge , Ding Xi
Published: May 2021

Background

Currently, insufficient bone volume always occurs in the posterior maxilla which makes implantation difficult. Short implants combined with transcrestal sinus floor elevation (TSFE) may be an option to address insufficient bone volume.

Purpose

The clinical performance of short implants combined with TSFE was compared with that of conventional implants combined with TSFE according to the survival rate.

Method

In this systematic review and meta-analysis, we followed the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Articles were identified through PubMed, Embase, the Cochrane Library, and manual searching. Eligibility criteria included clinical human studies. The quality assessment was performed according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. The odds ratio (OR) with its confidence interval (CI) was considered the essential outcome for estimating the effect of short implants combined with TSFE.

Results

The registration number is INPLASY202050092. Eleven studies met the inclusion criteria, including 1 cohort study and 10 cross-sectional studies. With respect to the 1-year survival rate, no significant effect was observed between short implants (length ≤ 8 mm) and conventional implants combined with TSFE (I2=0%, OR=1.04, 95% CI: 0.55-1.96). Similarly, no difference was seen between the two groups regarding the survival rate during the healing period (I2=10%, OR=0.74, 95% CI: 0.28-1.97) and 3-year loading (OR=1.76, 95% CI: 0.65-4.74).

Conclusion

There was no evidence that the survival rate of short implants combined with TSFE was lower or higher than that of conventional implants combined with TSFE when the residual bone height was poor and the implant protrusion length of short implants was less than or similar to conventional implants. Nevertheless, the results should be interpreted cautiously due to the lack of random controlled trials in our meta-analysis.
Oxidative DNA damage and subclinical hypothyroidism in children with obesity
Authors: Ahmad Inass Hassan , Elwahab Marwa khairy Abd , El Wakeel Mervat El Shahat , Kamal Mohamed A. M. , Elhady Marwa
Published: May 2021

Background

Obesity-related oxidation stress plays a key role in obesity complications; however, its relation to thyroid status is an area for further research. The study aimed to assess thyroid function in obese children and its relation to oxidative deoxyribonucleic acid (DNA) damage.

Results

Fifty obese and 40 normal weight children were included. Anthropometric measurement, lipid profile, thyroid function, anti-thyroglobulin antibody, thyroid peroxidase antibody, and 8-hydroxydeoxyguanosine serum level as marker of oxidative DNA damage were measured. Thirty-six percent of children with obesity have subclinical hypothyroidism. Central obesity but not oxidative DNA damage and lipid profile was significantly associated with subclinical hypothyroidism. Waist circumference > 97th centile increases the risk for subclinical hypothyroidism (odd ratio 10.82; confidence interval 95% 2.75–42.409; p-value<0.001).

Conclusion

Central obesity represents a risk factor for subclinical hypothyroidism in obese children. Oxidation DNA damage did not show significant association with subclinical hypothyroidism.
Zeta potentials of fluoride anion result in the instability of DNA hairpin
Authors: Jing Yang , Han Zhengwei , Luo Di , Chen Hu , Liu Yanhui
Published: May 2021

High dose intake of fluoride results in fluorosis and our previous experiments at single-molecule level using magnetic tweezers have proved that fluoride anions destabilize DNA hairpin and its equilibrium critical force decreases with increasing concentration of fluoride anions. One possible mechanism is that a fluoride anion competes with a DNA base and forms a hydrogen bond with its complementary base. The Isothermal Titration Calorimetry experiments suggest that the fluoride anion does not form a hydrogen bond with a DNA base. With increasing concentration of fluoride anions, decreasing Zeta potentials for different oligonucleotides enhance the electrostatic repulsion between complementary oligonucleotides, which accounts for the decreasing association constant and destabilization of DNA hairpin. Molecule dynamics simulation was further performed to determine the ion distribution around the oligonucleotide, radial distribution functions (RDFs) indicate that the fluoride anion distributes far from the oligonucleotide in comparison with the chloride anion, which is the possible mechanism that decreases Zeta potentials with the increasing concentration of fluoride anions.
Carbon Vitalism
Authors: Pasek Anne
Published: May 2021

This article names and examines carbon vitalism, a strain of climate denial centered on the moral recuperation of carbon dioxide—and thus fossil fuels. Drawing on interconnections between CO2, plant life, and human breath, carbon vitalists argue that carbon dioxide is not pollution but the stuff of life itself and thus possesses ethical and ecological standing. This philosophy contains a poetics of denial that is too often overlooked by studies of climate skepticism focusing narrowly on industry funding. Accordingly, this article develops a reparative theory of climate denial, asking what values and relations are gathered together within carbon vitalist speech and how speakers work to sustain these connections. Through close readings of carbon vitalist media and interviews with key figures in its network, the article demonstrates how the body is central to carbon vitalism’s rhetorical and emotional framing of ecological interdependence and epistemological populism. As such, carbon vitalism in effect reenacts long-established feminist appeals to the body (though to decidedly different political purposes). The article concludes by evaluating how the climate movement could both challenge and remobilize these logics, exploring what this corporeal turn in climate denial means for feminist and antiracist theories of environmental justice and the body.
Anxieties of Access
Authors: Smith James L.
Published: May 2021

This article explores the nature of remembering as a lake, with a lake, or through a lake; the differential relationships, knowledge, and perspectives contained within; and the potentially troubling implications found at the intersection of scientific and humanistic perspectives on lake being. It also reflects on the totalizing nature of assuming a single form of memory, of archiving, or of trauma in a world of lakes riven with partially occluded, subsumed, ever-present, and retrieved stories expressed through water. Memory for whom? Recollection for whom? Archiving is never simple, never complete, and never without ingrained and intersecting structures of suppressed and channeled violence. Waters leave a trail of their own, writ on and in water. It contains stories that are recorded and relived. It has ontologies that are plural, overlapping, and multiple modes of memory captured in a hydrocommons where perspectives pool. Rather than asserting that a lake is an archive, this article concludes by proposing that it is a counterarchive where archival modes and anxieties can be exposed and explored. This is true of all waters, but lakes offer an ideal case study.
Coordination of mitochondrial and cellular dynamics by the actin-based motor Myo19
Authors: Majstrowicz Katarzyna , Honnert Ulrike , Nikolaus Petra , Schwarz Vera , Oeding Stefanie J. , Hemkemeyer Sandra A. , Bähler Martin
Published: May 2021

Myosin XIX (Myo19) is an actin-based motor that competes with adaptors of microtubule-based motors for binding to the outer mitochondrial transmembrane proteins Miro1 and Miro2 (collectively Miro, also known as RhoT1 and RhoT2, respectively). Here, we investigate which mitochondrial and cellular processes depend on the coordination of Myo19 and microtubule-based motor activities. To this end, we created Myo19-deficient HEK293T cells. Mitochondria in these cells were not properly fragmented at mitosis and were partitioned asymmetrically to daughter cells. Respiratory functions of mitochondria were impaired and ROS generation was enhanced. On a cellular level, cell proliferation, cytokinesis and cell–matrix adhesion were negatively affected. On a molecular level, Myo19 regulates focal adhesions in interphase, and mitochondrial fusion and mitochondrially associated levels of fission protein Drp1 and adaptor proteins dynactin and TRAK1 at prometaphase. These alterations were due to a disturbed coordination of Myo19 and microtubule-based motor activities by Miro.
­­­­­­­A type I IFN, prothrombotic hyperinflammatory neutrophil signature is distinct for COVID-19 ARDS­­­
Authors: Reyes Leila , A. Sanchez-Garcia Manuel , Morrison Tyler , Howden Andy J. M. , Watts Emily R. , Arienti Simone , Sadiku Pranvera , Coelho Patricia , Mirchandani Ananda S. , Zhang Ailiang , Hope David , Clark Sarah K. , Singleton Jo , Johnston Shonna , Grecian Robert , Poon Azin , McNamara Sarah , Harper Isla , Fourman Max Head , Brenes Alejandro J. , Pathak Shalini , Lloyd Amy , Blanco Giovanny Rodriguez , von Kriegsheim Alex , Ghesquiere Bart , Vermaelen Wesley , Cologna Camila T. , Dhaliwal Kevin , Hirani Nik , Dockrell David H. , Whyte Moira K. B. , Griffith David , Cantrell Doreen A. , Walmsley Sarah R.
Published: May 2021

Background: Acute respiratory distress syndrome (ARDS) is a severe critical condition with a high mortality that is currently in focus given that it is associated with mortality caused by coronavirus disease 2019 (COVID-19). Neutrophils play a key role in the lung injury characteristic of non-COVID-19 ARDS and there is also accumulating evidence of neutrophil mediated lung injury in patients who succumb to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods: We undertook a functional proteomic and metabolomic survey of circulating neutrophil populations, comparing patients with COVID-19 ARDS and non-COVID-19 ARDS to understand the molecular basis of neutrophil dysregulation.

Results: Expansion of the circulating neutrophil compartment and the presence of activated low and normal density mature and immature neutrophil populations occurs in ARDS, irrespective of cause. Release of neutrophil granule proteins, neutrophil activation of the clotting cascade and upregulation of the Mac-1 platelet binding complex with formation of neutrophil platelet aggregates is exaggerated in COVID-19 ARDS. Importantly, activation of components of the neutrophil type I interferon responses is seen in ARDS following infection with SARS-CoV-2, with associated rewiring of neutrophil metabolism, and the upregulation of antigen processing and presentation. Whilst dexamethasone treatment constricts the immature low density neutrophil population, it does not impact upon prothrombotic hyperinflammatory neutrophil signatures.

Conclusions: Given the crucial role of neutrophils in ARDS and the evidence of a disordered myeloid response observed in COVID-19 patients, this work maps the molecular basis for neutrophil reprogramming in the distinct clinical entities of COVID-19 and non-COVID-19 ARDS.
The Avon Longitudinal Study of Parents and Children - a resource for COVID-19 research: approaches to the identification of cases November 2020
Authors: Northstone Kate , Mummé Mark , Mitchell Ruth , Timpson Nicholas J.
Published: May 2021

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992 and has followed these women, their partners (Generation 0; G0) and their offspring (Generation 1; G1) ever since. The study reacted rapidly to the coronavirus disease 2019 (COVID-19) pandemic, deploying three online questionnaires in March, May and October 2020. Home-based antibody tests accompanied the third questionnaire. In addition, linkage to Public Health England (PHE) Pillar I and II testing results has been obtained for all participants who have consented or for whom we have NHS Confidentiality approval group permitted Section 251 access.

For the purposes of ongoing study, we have identified likely cases of COVID-19 from available data. To determine likely cases, we have developed a hierarchy depending on the source of the data: self-report, antibody test result and Pillar I and II linkage and a combination thereof; providing more certainty in the case status. This data note describes how we have ascertained case status in ALSPAC. The subsequent case variable will be made available through our COVID release files alongside testing data from PHE.