bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistence of SARS-CoV-2 RNA in the nasopharyngeal, blood, urine, and stool samples of patients with COVID-19: a hospital-based longitudinal study
Authors: Joukar Farahnaz , Yaghubi Kalurazi Tofigh , Khoshsorour Mahmoud , Taramian Sonbol , Mahfoozi Lida , Balou Heydar Ali , Jafarinezhad Alireza , Pourkazemi Aydin , Hesni Ezat , Asgharnezhad Mehrnaz , Shenagari Mohammad , Jahanzad Issa , Naghipour Mohammadreza , Maroufizadeh Saman , Mansour-Ghanaei Fariborz
Published: July 2021

Background

The persistence of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) RNA in the body fluids of patients with the novel coronavirus disease 2019 (COVID-19) may increase the potential risk of viral transmission. There is still uncertainty on whether the recommended quarantine duration is sufficient to reduce the risk of transmission. This study aimed to investigate the persistence of SARS-CoV-2 RNA in the nasopharyngeal, blood, urine, and stool samples of patients with COVID-19.

Methods

In this hospital-based longitudinal study, 100 confirmed cases of COVID-19 were recruited between March 2020 and August 2020 in Guilan Province, north of Iran. Nasopharyngeal, blood, urine, and stool samples were obtained from each participant at the time of hospital admission, upon discharge, 1 week after discharge, and every 2 weeks until all samples were negative for SARS-CoV-2 RNA by reverse transcription-polymerase chain reaction (RT-PCR) assay. A survival analysis was also performed to identify the duration of viral persistence.

Results

The median duration of viral RNA persistence in the nasopharyngeal samples was 8 days from the first positive RT-PCR result upon admission (95% CI 6.91–9.09); the maximum duration of viral shedding was 25 days from admission. Positive blood, urine, and stool RT-PCR results were detected in 24%, 7%, and 6% of the patients, respectively. The median duration of viral persistence in the blood, urine, and stool samples was 7 days (95% CI 6.07–7.93), 6 days (95% CI 4.16–8.41), and 13 days (95% CI 6.96–19.4), respectively. Also, the maximum duration of viral persistence in the blood, urine, and stool samples was 17, 11, and 42 days from admission, respectively.

Conclusion

According to the present results, immediately after the hospitalized patients were discharged, no evidence of viral genetic materials was found. Therefore, appropriate treatments were selected for the patients at this hospital. However, we recommend further investigations on a larger sample size in multi-center and prospective randomized controlled trials (RCTs) to evaluate the effects of different drugs on the shedding of the virus through body secretions.
Research on the move: exploring WhatsApp as a tool for understanding the intersections between migration, mobility, health and gender in South Africa
Authors: de Gruchy Thea , Vearey Jo , Opiti Calvin , Mlotshwa Langelihle , Manji Karima , Hanefeld Johanna
Published: July 2021

Background

Reflecting global norms, South Africa is associated with high levels of cross-border and internal population mobility, yet migration-aware health system responses are lacking. Existing literature highlights three methodological challenges limiting the development of evidence-informed responses to migration and health: (1) lack of engagement with the process of migration; (2) exclusion of internal migrants; and (3) lack of methodologies that are able to capture ‘real-time’ data about health needs and healthcare seeking experiences over both time and place. In this paper, we reflect on a four-month pilot project which explored the use of WhatsApp Messenger - a popular mobile phone application used widely in sub-Saharan Africa – and assessed its feasibility as a research tool with migrant and mobile populations in order to inform a larger study that would address these challenges.

Method

A four-month pilot was undertaken with eleven participants between October 2019 and January 2020. Using Survey Node, an online platform that allows for the automatic administration of surveys through WhatsApp, monthly surveys were administered. The GPS coordinates of participants were also obtained. Recruited through civil society partners in Gauteng, participants were over the age of 18, comfortable engaging in English, and owned WhatsApp compatible cell phones. Enrolment involved an administered survey and training participants in the study protocol. Participants received reimbursement for their travel costs and monthly cell phone data.

Results

Out of a possible eighty eight survey and location responses, sixty one were received. In general, participants responded consistently to the monthly surveys and shared their location when prompted. Survey Node proved an efficient and effective way to administer surveys through WhatsApp. Location sharing via WhatsApp proved cumbersome and led to the development of a secure platform through which participants could share their location. Ethical concerns about data sharing over WhatsApp were addressed.

Conclusions

The success of the pilot indicates that WhatsApp can be used as a tool for data collection with migrant and mobile populations, and has informed the finalisation of the main study. Key lessons learnt included the importance of research design and processes for participant enrolment, and ensuring that the ethical concerns associated with WhatsApp are addressed.
CLIMB-COVID: continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance
Authors: Nicholls Samuel M. , Poplawski Radoslaw , Bull Matthew J. , Underwood Anthony , Chapman Michael , Abu-Dahab Khalil , Taylor Ben , Colquhoun Rachel M. , Rowe Will P. M. , Jackson Ben , Hill Verity , O’Toole Áine , Rey Sara , Southgate Joel , Amato Roberto , Livett Rich , Gonçalves Sónia , Harrison Ewan M. , Peacock Sharon J. , Aanensen David M. , Rambaut Andrew , Connor Thomas R. , Loman Nicholas J. ,   The COVID-19 Genomics UK (COG-UK) Consortium
Published: July 2021

In response to the ongoing SARS-CoV-2 pandemic in the UK, the COVID-19 Genomics UK (COG-UK) consortium was formed to rapidly sequence SARS-CoV-2 genomes as part of a national-scale genomic surveillance strategy. The network consists of universities, academic institutes, regional sequencing centres and the four UK Public Health Agencies. We describe the development and deployment of CLIMB-COVID, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and sample-associated metadata produced across the COG-UK network.
Long-term study of Borrelia and Babesia prevalence and co-infection in Ixodes ricinus and Dermacentor recticulatus ticks removed from humans in Poland, 2016–2019
Authors: Pawełczyk Agnieszka , Bednarska Małgorzata , Hamera Adrianna , Religa Emilia , Poryszewska Milena , Mierzejewska Ewa J. , Welc-Falęciak Renata
Published: July 2021

Background

Lyme borreliosis (LB) is the most common vector-borne disease in Europe. Monitoring changes in the prevalence of different Borrelia species in ticks may be an important indicator of risk assessment and of differences in pathogenicity in humans. The objective of our study was to assess the prevalence, co-infection and distribution of Borrelia and Babesia species in ticks removed from humans in a large sample collected during a study period of 4 years.

Methods

The ticks were collected throughout Poland from March to November over 4-year period from 2016 to 2019. All ticks (n = 1953) were morphologically identified in terms of species and developmental stage. Molecular screening for Borrelia and Babesia by amplification of the flagellin gene (flaB) or 18S rRNA marker was performed. Pathogen identity was confirmed by Sanger sequencing or PCR–restriction fragment length polymorphism analysis.

Results

The ticks removed from humans in Poland during this study belonged to two species: Ixodes ricinus (97%) and Dermacentor reticulatus (3%). High Borrelia prevalence (25.3%), including B. miyamotoi (8.4%), was confirmed in Ixodes ricinus ticks removed from humans, as was the change in frequency of occurrence of Borrelia species during the 4-year study. Despite Babesia prevalence being relatively low (1.3%), the majority of tested isolates are considered to be pathogenic to humans. Babesia infection was observed more frequently among Borrelia-positive ticks (2.7%) than among ticks uninfected with Borrelia (0.8%). The most frequent dual co-infections were between Borrelia afzelii and Babesia microti. The presence of Borrelia was also confirmed in D. reticulatus (12.7%); however the role of these ticks in spirochete transmission to susceptible hosts is still unclear.

Conclusions

Although the overall risk of developing LB after a tick bite is low in Europe, knowledge of the prevalence and distribution of Borrelia and Babesia species in ticks might be an important indicator of the risk of both these tick-borne diseases.

Graphical abstract
Exploring sources of engineering teaching self-efficacy for pre-service elementary teachers
Authors: Yesilyurt Ezgi , Deniz Hasan , Kaya Erdogan
Published: July 2021

Background

The Next Generation Science Standards (2013) put a special emphasis on engineering for K-12 science education. However, a significant number of elementary teachers still feel unprepared to integrate engineering into their science programs. It is, therefore, incumbent upon science educators to update their elementary science methods courses to accommodate engineering especially in the states which adopted the NGSS. In this study, we taught an engineering unit in an elementary science teaching methods course to examine what instructional components and learning experiences provided in the engineering unit enhance teachers’ engineering teaching self-efficacy beliefs.

Our research questions addressed to what extent the engineering education intervention improved pre-service teachers’ engineering teaching efficacy beliefs and what instructional components and learning experiences served as sources of self-efficacy contributing to the improvement of pre-service elementary teachers’ engineering teaching efficacy beliefs. We also explored how pre-service teachers viewed the relative importance of the sources of teaching efficacy stemming from the engineering unit.

Results

The participants comprised 84 pre-service teachers enrolled in an elementary education program at a public university in the Southwestern United States. Data obtained from the Engineering Teaching Efficacy Beliefs Instrument (ETEBI) indicated that the pre-service teachers’ personal teaching efficacy beliefs significantly improved after the engineering intervention; however, the engineering intervention had a small impact on teachers’ engineering teaching outcome expectancy beliefs. Written reflections used to explore the sources of engineering teaching efficacy and the relative importance of each source showed that cognitive content mastery and cognitive pedagogical mastery were the major sources of engineering teaching self-efficacy among the pre-service elementary teachers.

Conclusion

Our study illustrated that integrating engineering design activities with explicit-reflective instruction on the nature of engineering concepts could enhance pre-service teachers’ personal engineering teaching efficacy beliefs even though a relatively small impact was observed in their engineering teaching outcome expectancy beliefs. Also, the study indicated cognitive content mastery and cognitive pedagogical mastery were the most important sources of engineering teaching efficacy. Therefore, the study suggests that it is vital to integrate a variety of mastery and vicarious experiences in methods courses to support the development of teachers’ engineering teaching efficacy beliefs. Besides, the current study could provide an example for integrating engineering education in methods courses.
Digoxin absorption decreased independently of P-gp activity in rats with irinotecan-induced gastrointestinal damage
Authors: Tsuchitani Toshiaki , Akiyoshi Takeshi , Imaoka Ayuko , Ohtani Hisakazu
Published: July 2021

Background

Irinotecan (CPT-11) is clinically known to cause severe diarrhea and gastrointestinal damage. Recently, we have reported that CPT-11-induced gastrointestinal damage is associated with the upregulation of intestinal P-glycoprotein (P-gp) expression and decreased absorption of its substrate, dabigatran etexilate (DABE), using a rat model. However, the P-gp activity or its contribution to the decreased absorption remains unclear. The aim of this study was to quantitatively evaluate how P-gp activity changes in rats with CPT-11-induced gastrointestinal damage, as assessed by the absorption of digoxin (DGX), a typical P-gp substrate.

Methods

Male Sprague-Dawley rats were intravenously administered CPT-11 at a dose of 60 mg/kg/day for 4 days to induce gastrointestinal damage. Then, the rats were administered DGX orally (40 μg/kg), after some of them were orally administered clarithromycin (CAM; 10 mg/kg), a P-gp inhibitor. DGX (30 μg/kg) was administered intravenously to determine the bioavailability (BA). The rats’ DGX plasma concentration profiles were determined using LC-MS/MS.

Results

CPT-11 treatment decreased the maximum concentration (Cmax) and area under the plasma concentration-time curve (AUCpo) of DGX, which does not contradict to the DABE study. Although in the CPT-11-treated group the BA of DGX was significantly decreased to 40% of the control value, CAM did not affect the BA of DGX in the CPT-11-treated group.

Conclusions

Increased P-gp expression in rats with CPT-11-induced gastrointestinal damage is not necessarily associated with increased P-gp activity or contribution to the drug absorption in vivo. The decreased DGX absorption observed in this study might be attributable to other factors, such as a reduction in the absorptive surface area of the gastrointestinal tract.
Potentially harmful excipients in neonatal medications: a multicenter nationwide observational study in Japan
Authors: Saito Jumpei , Nadatani Naomi , Setoguchi Makoto , Nakao Masahiko , Kimura Hitomi , Sameshima Mayuri , Kobayashi Keiko , Matsumoto Hiroaki , Yoshikawa Naoki , Yokoyama Toshihiro , Takahashi Hitomi , Suenaga Mei , Watanabe Ran , Imai Kinuko , Obara Mami , Hashimoto Mari , Yamamoto Kazuhiro , Fujiwara Naoko , Sakata Wakako , Nagai Hiroaki , Enokihara Takeshi , Katayama Sayaka , Takahashi Yuta , Araki Mariko , Iino Kanako , Akiyama Naoko , Katsu Hiroki , Fushimi Kumiko , Takeda Tomoya , Torimoto Mayumi , Kishi Rina , Mitsuya Naoki , Kihara Rie , Hasegawa Yuki , Hamada Yukihiro , Kimura Toshimi , Wada Masaki , Tanzawa Ayano , Yamatani Akimasa
Published: July 2021

Background

A multicenter investigation of neonate exposure to potentially harmful excipients (PHEs) in neonatal intensive care units (NICUs) in Japan has not been conducted.

Methods

A multicenter nationwide observational study was conducted. Neonate patient demographic data and information on all medicines prescribed and administered during hospitalization on 1 day between November 2019 and March 2021 were extracted from the medical records. Nine PHEs, paraben, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol, benzalkonium chloride, and aspartame, were selected. PHEs were identified from the package insert and the Interview Form. The quantitative daily exposure was calculated if quantitative data were available for each product containing the PHE.

Results

Prescription data was collected from 22 NICUs in Japan. In total, 343 neonates received 2360 prescriptions for 426 products containing 228 active pharmaceutical ingredients. PHEs were found in 52 (12.2%) products in 646 (27.4%) prescriptions for 282 (82.2%) neonates. Benzyl alcohol, sodium benzoates, and parabens were the most common PHEs in parenteral, enteral, and topical formulations, respectively. Quantitative analysis showed that 10 (10%), 38 (42.2%), 37 (94.9%), and 9 (39.1%) neonates received doses exceeding the acceptable daily intake of benzyl alcohol, polysorbate 80, propylene glycol, and sorbitol, respectively. However, due to the lack of quantitative information for all enteral and topical products, accurate daily PHE exposure could not be quantified.

Conclusions

Neonates admitted to NICUs in Japan were exposed to PHEs, and several of the most commonly prescribed medicines in daily clinical practice in NICUs contained PHEs. Neonate PHE exposure could be reduced by replacing these medicines with available PHE-free alternatives.
Physical activity, confidence and quality of life among cancer patient-carer dyads
Authors: Ng Siu-man , Fung Melody H. Y. , Chan Jessie S. M. , Chan Celia H. Y. , Chan Cecilia L. W.
Published: July 2021

Background

Physical activity (PA) has been positively associated with health-related quality of life (HRQoL) among cancer patients and family caregivers. However, there has been no relevant research for patient-caregiver dyads.

Methods

Path analysis, based on the actor–partner interdependence model (APIM), was used to examine the relationship between physical activity and health-related quality of life and explore the mediating role of emotional distress in 233 dyads.

Results

In both patients and caregivers, physical activity had a direct positive effect on physical quality of life (QoL) but not on mental. There was a significant indirect effect of physical activity on health-related quality of life via emotional distress for both dyad members. Patients’ and caregivers’ confidence in fighting cancer was negatively associated with their own emotional distress. Caregivers’ confidence in fighting cancer was positively associated with their physical activity and also negatively associated with patients’ emotional distress.

Conclusions

Physical activity may be considered as a possible behavioral and rehabilitation strategy for improving health-related quality of life in patient-caregiver dyads and reducing negative symptoms. Future research and intervention may consider cancer patient-family caregiver dyad as a unit of care.
Innovative trial approaches in immune-mediated inflammatory diseases: current use and future potential
Authors: Grayling Michael J. , Bigirumurame Theophile , Cherlin Svetlana , Ouma Luke , Zheng Haiyan , Wason James M. S.
Published: July 2021

Background

Despite progress that has been made in the treatment of many immune-mediated inflammatory diseases (IMIDs), there remains a need for improved treatments. Randomised controlled trials (RCTs) provide the highest form of evidence on the effectiveness of a potential new treatment regimen, but they are extremely expensive and time consuming to conduct. Consequently, much focus has been given in recent years to innovative design and analysis methods that could improve the efficiency of RCTs. In this article, we review the current use and future potential of these methods within the context of IMID trials.

Methods

We provide a review of several innovative methods that would provide utility in IMID research. These include novel study designs (adaptive trials, Sequential Multi-Assignment Randomised Trials, basket, and umbrella trials) and data analysis methodologies (augmented analyses of composite responder endpoints, using high-dimensional biomarker information to stratify patients, and emulation of RCTs from routinely collected data). IMID trials are now well-placed to embrace innovative methods. For example, well-developed statistical frameworks for adaptive trial design are ready for implementation, whilst the growing availability of historical datasets makes the use of Bayesian methods particularly applicable.

To assess whether and how these innovative methods have been used in practice, we conducted a review via PubMed of clinical trials pertaining to any of 51 IMIDs that were published between 2018 and 20 in five high impact factor clinical journals.

Results

Amongst 97 articles included in the review, 19 (19.6%) used an innovative design method, but most of these were relatively straightforward examples of innovative approaches. Only two (2.1%) reported the use of evidence from routinely collected data, cohorts, or biobanks. Eight (9.2%) collected high-dimensional data.

Conclusions

Application of innovative statistical methodology to IMID trials has the potential to greatly improve efficiency, to generalise and extrapolate trial results, and to further personalise treatment strategies. Currently, such methods are infrequently utilised in practice. New research is required to ensure that IMID trials can benefit from the most suitable methods.
Thoracoscopic T2-T3 versus T4 sympathectomy for primary palmar hyperhidrosis in children and adolescents: a randomized comparative study
Authors: Elhalaby Ismael Essam , Mansour Mohamed Awad , Tawfik Ahmed Mohamed Ismail , Aly Hisham Fayad
Published: July 2021

Background

Controversy exists regarding the appropriate level of sympathectomy for primary palmar hyperhidrosis (PH) as different levels are associated with variable postoperative patients’ satisfaction and potential complications. The aim of this study was to investigate the safety, efficacy, and outcome of T2-T3 thoracoscopic sympathectomy (TS) versus T4 TS in this age group.

Results

This prospective study included 32 patients (17 males and 15 females) with primary PH treated at the department of pediatric surgery, in our institution during the period from February 2019 to February 2020. Inclusion criteria included moderate and/or severe degrees of PH not responding to conservative measures. The patients were divided randomly into two groups: group I treated by T2-T3 TS and group II underwent only T4 TS. All patients were evaluated regarding operative details and postoperative outcome. Follow-up ranged from 6 to 24 months. Group I included 18 patients (14 operated on both sides and 4 operated on one side), and group II included 14 patients (11 operated on both sides and 3 operated on one side). The ages ranged between 5 and 18 years (mean 14.25 ± 3.14 years). The difference in mean age among both groups (14.5 versus 13.9 years) was not statistically significant. The mean operative time was significantly longer in group I (22.4 versus 17.2 min, p value 0.046). The hospital stay (1 day) was similar for both groups. Postoperative compensatory hyperhidrosis (CH) was more frequent in group I (n=7, 50% versus n=5, 45.5%), but the difference was not statistically significant. Postoperative over dryness occurred in 5 patients in group I (28.6%) and temporary Horner’s syndrome in one patient (7.14%). No over dryness or Horner’s syndrome occurred in any patient in group II. The QOL score has improved in both groups; the degree of improvements was better in group II.

Conclusion

Both T2-T3 TS and T4 TS are effective in treating primary palmar hyperhidrosis in children and adolescents. T4 TS is preferred than T2-3 TS due to less frequent postoperative complications and better patients’ satisfaction.
Can the botanical azadirachtin replace phased-out soil insecticides in suppressing the soil insect pest Diabrotica virgifera virgifera?
Authors: Toepfer Stefan , Toth Szabolcs , Szalai Mark
Published: July 2021

Background

Due to recent bans on the use of several soil insecticides and insecticidal seed coatings, soil-dwelling insect pests are increasingly difficult to manage. One example is the western corn rootworm (Diabrotica virgifera virgifera, Coleoptera: Chrysomelidae), a serious root-feeder of maize (Zea mays). We investigated whether the less problematic botanical azadirachtin, widely used against above-ground insects, could become an option for the control of this soil insect pest.

Methods

Artificial diet-based bioassays were implemented under standard laboratory conditions to establish dose response curves for the pest larvae. Then, potted-plant experiments were implemented in greenhouse to assess feasibility and efficacy of a novel granular formulation of azadirachtin under more natural conditions and in relation to standard insecticides.

Results

Bioassays in three repetitions revealed a 3-day LD50of 22.3 µg azadirachtin/ml which corresponded to 0.45 µg/neonate ofD. v. virgiferaand a 5-day LD50of 19.3 µg/ml or 0.39 µg/first to second instar larva. No sublethal effects were observed. The three greenhouse experiments revealed that the currently proposed standard dose of a granular formulation of 38 g azadirachtin/hectare for in-furrow application at sowing is not enough to controlD. v. virgiferaor to prevent root damage. At 10× standard-dose total pest control was achieved as well as the prevention of most root damage. This was better than the efficacy achieved by cypermethrin-based granules and comparable to tefluthrin-granules, or thiamethoxam seed coatings. The ED50for suppressing larval populations were estimated at 92 g azadirachtin/ha, for preventing heavy root damage 52 g/ha and for preventing general root damage 220 g/ha.

Conclusions

There seems clear potential for the development of neem-based botanical soil insecticides for arable crops such as maize. They might become, if doses are increased and more soil insecticides phased out, a promising, safer solution as part of the integrated pest management toolkit against soil insects.
President's Page: Synergy is today's superpower: Thoughts on mergers, meetings, and other matters
Authors: Nessim Maurice
Published: July 2021

As we enter the third quarter of the year, we are deep in planning for our Annual Meeting in Denver this September. This is IMAGE '21, our first joint annual meeting with the American Association of Petroleum Geologists (AAPG) since 1955, and it is shaping up to be an extraordinary event.
Memorial
Authors: Witherly Ken , Teskey Dennis
Published: July 2021

Peter Jonathan Hood, 1929–2020
Seismic Soundoff
Authors: Geary Andrew
Published: July 2021

In this episode, Andrew Geary speaks with Michal Ruder about continuing education and her new course, Gravity and Magnetics for Explorationists. Ruder shares the most important thing for explorationists to focus on right now, what she would say to the CEO of an oil and gas company, the future of GIS data for exploration, and the importance of nonseismic work in geophysics. Hear the full episode at https://seg.org/podcast/post/12455 .
Aging, Cardiovascular Risk, and SHBG Levels in Men and Women From the General Population
Authors: Aribas Elif , Kavousi Maryam , Laven Joop S E , Ikram M Arfan , Roeters van Lennep Jeanine E
Published: July 2021

Aims

Prior studies have reported inconsistent results for the association between sex hormone-binding globulin (SHBG) and cardiovascular disease among men and women. Although it is suggested that SHBG levels change with aging, the exact trend of SHBG across age and cardiovascular risk and the underlying mechanisms of these changes remain to be elucidated.

Methods

Using data of 3264 men and women from a large population-based cohort study, we first visualized the distribution of serum SHBG levels across age. Second, we computed a cardiovascular risk factor sum score and investigated the mean SHBG levels across categories of the risk factor sum score and stratified per age-category. Next, linear regression models were used to investigate the associations between serum SHBG levels and age and potential regulators of SHBG, including body mass index (BMI), fasting insulin, sex steroids, thyroxine, and triglycerides.

Results

Among men, a linear increase in SHBG levels with age and among women a U-shaped pattern was observed. Participants with larger number of cardiovascular risk factors had lower SHBG levels. When stratified by age, older participants had higher SHBG levels. A multivariate model including total testosterone and triglyceride levels in men and total testosterone, triglycerides, BMI, and fasting insulin in women explained, respectively, 46.2% and 31.8% of the variance in SHBG levels.

Conclusion

We observed a clear sex-specific pattern for SHBG levels with age. Our findings highlight the importance of taking into account the age-related changes in SHBG levels to avoid controversial results in the assessment of the cardiovascular risk associated with SHBG.
Growing Up in the Shadow of Confederate Monuments
Authors: Bynum Caroline Walker
Published: July 2021

Drawing on her memories of growing up in a racially segregated South, the author argues not so much for the removal and erasure of Confederate memorials as for mutilating them or retaining a version of their presence glossed with an explanation for their rejection. Connecting the southern anti-Semitism and anti-Black racism of her youth, she explains the parallels and differences between German efforts to come to terms with the Holocaust and American efforts, southern and northern, to move beyond and make reparation for both slavery and continuing twentieth- and twenty-first-century racism.
Jan van Eyck at London in 1428
Authors: Richmond Colin
Published: July 2021

On the basis of reports that Jan van Eyck visited England (he was well traveled in the service of Philip the Good, duke of Burgundy), this essay speculates freely on what the diplomat and painter actually did in and around London for three weeks in 1428. The essay claims, for example, that van Eyck went to the village of Foots Cray to buy watercresses to use as models when painting greenery on the Ghent Altarpiece of the Mystic Lamb (which he completed in 1432). The recently erected gateway to the palace at Greenwich is said likewise to be the model for a towered gateway depicted on the altarpiece. After providing local detail about relevant parts of England in 1428, the essay closes with speculation (although the author writes, “The facts are known”) about the origin of a harp, of a purportedly Welsh variety, appearing on the altarpiece in the hands of an angel. The author argues that it was the instrument of an itinerant Breton musician whom van Eyck had heard in recital at the Poor Clares convent of the Holy Trinity at the Minories in Aldgate. The harpist subsequently murdered his Stepney landlady and was himself killed by enraged local housewives. Van Eyck is said to have purchased the man's harp when his worldly goods were posthumously sold.
scRNA sequencing uncovers a TCF4-dependent transcription factor network regulating commissure development in mouse
Authors: Wittmann Marie-Theres , Katada Sayako , Sock Elisabeth , Kirchner Philipp , Ekici Arif B. , Wegner Michael , Nakashima Kinichi , Lie Dieter Chichung , Reis André
Published: July 2021

Transcription factor 4 (TCF4) is a crucial regulator of neurodevelopment and has been linked to the pathogenesis of autism, intellectual disability and schizophrenia. As a class I bHLH transcription factor (TF), it is assumed that TCF4 exerts its neurodevelopmental functions through dimerization with proneural class II bHLH TFs. Here, we aim to identify TF partners of TCF4 in the control of interhemispheric connectivity formation. Using a new bioinformatic strategy integrating TF expression levels and regulon activities from single cell RNA-sequencing data, we find evidence that TCF4 interacts with non-bHLH TFs and modulates their transcriptional activity in Satb2+ intercortical projection neurons. Notably, this network comprises regulators linked to the pathogenesis of neurodevelopmental disorders, e.g. FOXG1, SOX11 and BRG1. In support of the functional interaction of TCF4 with non-bHLH TFs, we find that TCF4 and SOX11 biochemically interact and cooperatively control commissure formation in vivo, and regulate the transcription of genes implicated in this process. In addition to identifying new candidate interactors of TCF4 in neurodevelopment, this study illustrates how scRNA-Seq data can be leveraged to predict TF networks in neurodevelopmental processes.
Srsf3 mediates alternative RNA splicing downstream of PDGFRα signaling in the facial mesenchyme
Authors: Dennison Brenna J. C. , Larson Eric D. , Fu Rui , Mo Julia , Fantauzzo Katherine A.
Published: July 2021

Signaling through the platelet-derived growth factor receptor alpha (PDGFRα) is crucial for mammalian craniofacial development, although the mechanisms by which the activity of downstream intracellular effectors is regulated to mediate gene expression changes have not been defined. We find that the RNA-binding protein Srsf3 is phosphorylated at Akt consensus sites downstream of PI3K-mediated PDGFRα signaling in mouse palatal mesenchyme cells, leading to its nuclear translocation. We further demonstrate that ablation of Srsf3 in the mouse neural crest lineage leads to facial clefting due to defective cranial neural crest cell proliferation and survival. Finally, we show that Srsf3 regulates the alternative RNA splicing of transcripts encoding protein kinases in the mouse facial process mesenchyme to regulate PDGFRα-dependent intracellular signaling. Collectively, our findings reveal that alternative RNA splicing is an important mechanism of gene expression regulation downstream of PI3K/Akt-mediated PDGFRα signaling in the facial mesenchyme and identify Srsf3 as a critical regulator of craniofacial development.
The initial expansion of the C. elegans syncytial germ line is coupled to incomplete primordial germ cell cytokinesis
Authors: Bauer Jack , Poupart Vincent , Goupil Eugénie , Nguyen Ken C. Q. , Hall David H. , Labbé Jean-Claude
Published: July 2021

The C. elegans germline is organized as a syncytium in which each germ cell possesses an intercellular bridge that is maintained by a stable actomyosin ring and connected to a common pool of cytoplasm, termed the rachis. How germ cells undergo cytokinesis while maintaining this syncytial architecture is not completely understood. Here, we use live imaging to characterize primordial germ cell (PGC) division in C. elegans first-stage larvae. We show that each PGC possesses a stable intercellular bridge that connects it to a common pool of cytoplasm, which we term the proto-rachis. We further show that the first PGC cytokinesis is incomplete and that the stabilized cytokinetic ring progressively moves towards the proto-rachis and eventually integrates with it. Our results support a model in which the initial expansion of the C. elegans syncytial germline occurs by incomplete cytokinesis, where one daughter germ cell inherits the actomyosin ring that was newly formed by stabilization of the cytokinetic ring, while the other inherits the pre-existing stable actomyosin ring. We propose that such a mechanism of iterative cytokinesis incompletion underpins C. elegans germline expansion and maintenance.
Vacuolar H+-ATPase dysfunction rescues intralumenal vesicle cargo sorting in yeast lacking PI(3,5)P2 or Doa4
Authors: Wilson Zachary N. , Buysse Dalton , West Matt , Ahrens Daniel , Odorizzi Greg
Published: July 2021

Endosomes undergo a maturation process highlighted by a reduction in lumenal pH, a conversion of surface markers that prime endosome–lysosome fusion and the sequestration of ubiquitylated transmembrane protein cargos within intralumenal vesicles (ILVs). We investigated ILV cargo sorting in mutant strains of the budding yeast Saccharomyces cerevisiae that are deficient for either the lysosomal/vacuolar signaling lipid PI(3,5)P2 or the Doa4 ubiquitin hydrolase that deubiquitylates ILV cargos. Disruption of PI(3,5)P2 synthesis or Doa4 function causes a defect in sorting of a subset of ILV cargos. We show that these cargo-sorting defects are suppressed by mutations that disrupt Vph1, a subunit of vacuolar H+-ATPase (V-ATPase) complexes that acidify late endosomes and vacuoles. We further show that Vph1 dysfunction increases endosome abundance, and disrupts vacuolar localization of Ypt7 and Vps41, two crucial mediators of endosome–vacuole fusion. Because V-ATPase inhibition attenuates this fusion and rescues the ILV cargo-sorting defects in yeast that lack PI(3,5)P2 or Doa4 activity, our results suggest that the V-ATPase has a role in coordinating ILV cargo sorting with the membrane fusion machinery.

This article has an associated First Person interview with the first author of the paper.
Cyclic AMP is dispensable for allorecognition in Dictyostelium cells overexpressing PKA-C
Authors: Hirose Shigenori , Katoh-Kurasawa Mariko , Shaulsky Gad
Published: July 2021

Allorecognition and tissue formation are interconnected processes that require signaling between matching pairs of the polymorphic transmembrane proteins TgrB1 and TgrC1 in Dictyostelium. Extracellular and intracellular cAMP signaling are essential to many developmental processes. The three adenylate cyclase genes, acaA, acrA and acgA are required for aggregation, culmination and spore dormancy, respectively, and some of their functions can be suppressed by activation of the cAMP-dependent protein kinase PKA. Previous studies have suggested that cAMP signaling might be dispensable for allorecognition and tissue formation, while others have argued that it is essential throughout development. Here, we show that allorecognition and tissue formation do not require cAMP production as long as PKA is active. We eliminated cAMP production by deleting the three adenylate cyclases and overexpressed PKA-C to enable aggregation. The cells exhibited cell polarization, tissue formation and cooperation with allotype-compatible wild-type cells, but not with incompatible cells. Therefore, TgrB1-TgrC1 signaling controls allorecognition and tissue formation, while cAMP is dispensable as long as PKA-C is overexpressed.
Genomic evidence for the parallel regression of melatonin synthesis and signaling pathways in placental mammals
Authors: Emerling Christopher A. , Springer Mark S. , Gatesy John , Jones Zachary , Hamilton Deana , Xia-Zhu David , Collin Matt , Delsuc Frédéric
Published: July 2021

Background: The study of regressive evolution has yielded a wealth of examples where the underlying genes bear molecular signatures of trait degradation, such as pseudogenization or deletion. Typically, it appears that such disrupted genes are limited to the function of the regressed trait, whereas pleiotropic genes tend to be maintained by natural selection to support their myriad purposes. One such set of genes is involved in the synthesis (AANAT, ASMT) and signaling (MTNR1A, MTNR1B) of melatonin, a hormone secreted by the vertebrate pineal gland. Melatonin provides a signal of environmental darkness, thereby influencing the circadian and circannual rhythmicity of numerous physiological traits. Therefore, the complete loss of a pineal gland and the underlying melatonin pathway genes seems likely to be maladaptive, unless compensated by extrapineal sources of melatonin.

Methods: We examined AANAT, ASMT, MTNR1A and MTNR1B in 123 vertebrate species, including pineal-less placental mammals and crocodylians. We searched for inactivating mutations and modelled selective pressures (dN/dS) to test whether the genes remain functionally intact.

Results: We report that crocodylians retain intact melatonin genes and express AANAT and ASMT in their eyes, whereas all four genes have been repeatedly inactivated in the pineal-less xenarthrans, pangolins, sirenians, and whales. Furthermore, colugos have lost these genes, and several lineages of subterranean mammals have partial melatonin pathway dysfunction. These results are supported by the presence of shared inactivating mutations across clades and analyses of selection pressure based on the ratio of non-synonymous to synonymous substitutions (dN/dS), suggesting extended periods of relaxed selection on these genes.

Conclusions: The losses of melatonin synthesis and signaling dates to tens of millions of years ago in several lineages of placental mammals, raising questions about the evolutionary resilience of pleiotropic genes, and the causes and consequences of losing melatonin pathways in these species.
What’s Worth Knowing? Research and Instructional Impacts of Books on Working-Class Academics
Authors: Vander Putten Jim
Published: July 2021

What are the research impacts and instructional impacts of books of essays on the perspectives of faculty from working-class backgrounds? To what extent are these books used in undergraduate or graduate courses? Previous research on the content of these edited volumes has been limited to manual constant comparative analyses that described book content. This study employed data analysis methods in the emerging field of altmetric sciences to investigate the impacts of books of personal essays about faculty from working-class backgrounds (N=11). Book-level and chapter-level analyses were conducted to measure research impact using the Altmetric Explorer online tool and instructional impact using the Open Syllabus Project Explorer online tool. Data analysis results on research impacts for books on working-class academics produced extremely low impact levels. Few books (N=4) generated patterns of attention and these patterns were limited in scope. Data analysis results on instructional impacts identified that each of the 11 books generated a Teaching Score, but all scores were minimal and indicated low impact levels. The results suggest that scholarship on faculty from working-class social origins is not being widely included in undergraduate or graduate course syllabi. Further, a large proportion of the book-level scholarship in the subject area of ‘faculty diversity’ has been limited to the constructs of race and gender. Issues involving faculty social origins have been largely omitted from curricula in this area and raises the important question: What is worth knowing?
Neodymium (III) and Samarium (III) Complexes of 2, 2′- ((1E, 1′E) - (1, 2- Phenylenebis(Azanlylidene) bis(Methanylylidene)) DiphenolLigand: Synthesis, Characterization and Biological Activity
Authors: Jimmyuwanta Emaime , Ukoha Pius Oziri , Ukpong Emmanuel Jimmy , Johnson Andatim Sunday
Published: July 2021

Complexes of Nd(III) and Sm(III) of a Schiff base ligand derived from the condensation of o-phenylenediamie and 2-hydroxybenzaldehyde were synthesised and characterised by various analytical and spectroscopic techniques. The analytical values revealed a metal to ligand ratio of 1:2 for the Nd(III) complex and a 1:1(ligand: metal) for Sm(III) complex. The complexes were characterised by elemental analysis, molar conductance, UV – Visible and infrared spectral studies. Plausible structures were proposed for Nd(BSOPD)2 and SmBSOPD based on the results obtained. In-vitro antimicrobial activities of both the Schiff base and the synthesised metal complexes were evaluated against six (6) human pathogens. The complexes showed significant activity compared to the free ligand. These complexes may be employed as active ingredients in the development of antibacterial and antifungal agents.
One Pot Synthesis, Characterization of Benzothiazole/ Benzimidazole Tethered Imidazole Derivatives using Clay as Catalyst
Authors: Pandey Himanshu , Shrivastava S.P.
Published: July 2021

A Green approach for benzothiazole / benzimidazole tethered imidazole derivative synthesis utilizing brick derived clay as a catalyst. Brick clay catalyst used in this synthesis has shown excellent catalytic activity by increasing efficiency, reducing the reaction time and most importantly it is reusable for further reaction runs. These derivatives were synthesized by four component condensation reaction that involvebenzil, aldehyde, 2-aminobenzimidazole / 2-amino-6-nitrobenzothiazole and ammonium acetate. The clay catalyst is characterized by FT-IR while the synthesized derivatives were characterized by FT-IR, 1H NMR and 13C NMR.Brick clay is a cheap, non-hazardous catalyst and can be reused up to many reaction runs with good to excellent yields.
Solid-State Synthesis, Characterization, Biological Studies and Theoretical Evaluation of (E)-2-(2-(naphthalene-2-yloxy)-1-phenylethylidene) Hydrazine Thiocarboxamide
Authors: Rajmohan G. , Ravindran G. , Arivazhagan G.
Published: July 2021

The title compound (E)-2-(2-(naphthalene-2-yloxy)-1-phenylethylidene) hydrazine thiocarboxamide (NAPTCAR) is synthesized by condensing 2-(Naphthalen-2-yloxy)-1-phenyl-ethanone (2-NAPETH) with thiosemicarbazide in 1: 1 molar ratio in solid state medium. Purity of compounds has been confirmed by Thin Layer Chromatography. Characterization and structure elucidation of these ligands have been made using 1H NMR, 13C NMR and FTIR spectral studies and DFT calculations. Interestingly, 13C NMR spectrum of thiosemicarbazone ligand exhibits the presence of two conformational structures. The HOMO – LUMO energy gap of conformer A is found to be almost equal to that of conformer B. Conformer A is has relatively a stronger nucleophilic character than conformer B as indicated by the molecular electrostatic potential surface. Van der Waals and the steric interactions play a dominant role in stabilizing the structure of both the conformers. The ligands have been examined for antibacterial and antifungal activities and are quite active in this respect.
Fretting and corrosion of metal liners from modular dual mobility constructs
Authors: Hemmerling Kimberly J. , Weitzler Lydia , Bauer Thomas W. , Padgett Douglas E. , Wright Timothy M.
Published: July 2021

Aims

Dual mobility implants in total hip arthroplasty are designed to increase the functional head size, thus decreasing the potential for dislocation. Modular dual mobility (MDM) implants incorporate a metal liner (e.g. cobalt-chromium alloy) in a metal shell (e.g. titanium alloy), raising concern for mechanically assisted crevice corrosion at the modular liner-shell connection. We sought to examine fretting and corrosion on MDM liners, to analyze the corrosion products, and to examine histologically the periprosthetic tissues.

Methods

A total of 60 retrieved liners were subjectively scored for fretting and corrosion. The corrosion products from the three most severely corroded implants were removed from the implant surface, imaged using scanning electron microscopy, and analyzed using Fourier-transform infrared spectroscopy.

Results

Fretting was present on 88% (53/60) of the retrieved liners, and corrosion was present on 97% (58/60). Fretting was most often found on the lip of the taper at the transition between the lip and the dome regions. Macrophages and particles reflecting an innate inflammatory reaction to corrosion debris were noted in six of the 48 cases for which periprosthetic tissues were examined, and all were associated with retrieved components that had high corrosion scores.

Conclusion

Our results show that corrosion occurs at the interface between MDM liners and shells and that it can be associated with reactions in the local tissues, suggesting continued concern that this problem may become clinically important with longer-term use of these implants. Cite this article: Bone Joint J 2021;103-B(7):1238–1246.