bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison of double single suture-button fixation, suture-button fixation, and screw fixation for ankle syndesmosis injury
Authors: Kurtoglu Alper , Kochai Alauddin , Inanmaz Mustafa Erkan , Sukur Erhan , Keskin Dogan , Türker Mehmet , Uysal Mustafa , Sen Zafer , Daldal Ismail
Published: March 2021

Different methods have been used throughout the years for syndesmotic injury but there is no consensus on the ideal treatment. Some methods are expensive and some have more complications. The aim of this study is to compare single suture endobutton with double suture endobutton and screw fixation for syndesmotic injury.

Sixty nine patients with syndesmotic injury with fibular fractures whom were treated with a single interosseous suture endobutton system (ZipTightTM, Zimmer Biomet), a double interosseous suture endobutton system (ZipTightTM, Zimmer Biomet) and 1 syndesmotic screw (TST, Istanbul, Turkey) were included in this study. Functional and radiological results from patient records between 2015 and 2018 were retrospectively evaluated.

Twenty patients were treated with the double interosseous suture endobutton, 23 were treated with the single interosseous suture endobutton, and 26 were treated with traditional AO screw fixation. Three patients from the screw fixation group (11.5%) required revision surgery (P < .05). All the radiologic and clinical outcomes were statistical similar in all 3 groups.

Our findings showed that the interosseous suture endobutton system is at least as safe as the screw fixation technique for treatment of syndesmosis joint injuries and can be used as an alternative to the screw method. The interosseous suture endobutton system eliminates the need for a second surgery to remove the hardware, which minimizes the probability of re-diastasis. Since our results showed no statistical difference between single and double interosseous suture endobutton systems, the less costly single endobutton system may be the better alternative.
High L1CAM expression predicts poor prognosis of patients with endometrial cancer
Authors: Guo Min , Gong Han , Nie Dan , Li Zhengyu
Published: March 2021

Backgroud:

Previous studies have reported that the levels of L1 cell adhesion molecule (L1CAM) indicate poor prognosis of patients with various solid tumors. However, the prognostic significance of L1CAM in endometrial cancer has remained controversial. Herein, we conducted a systematic review and meta-analysis to evaluate the prognostic value of L1CAM in endometrial cancer.

Methods:

All studies related to the association between L1CAM expression and clinical characteristics of endometrial cancer were identified by searching the PubMed, MEDLINE, EMBASE, and Web of Science databases. Primary outcomes of the meta-analysis were the hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS). Secondary outcomes were odds ratios (ORs) for clinicopathological characteristics. Publication bias and sensitivity analysis were conducted to ensure reliability of the results.

Results:

Overall, 17 studies encompassing 7146 patients were eligible for the meta-analysis. Results showed L1CAM overexpression to be significantly associated with decreased overall survival (HR = 2.87, 95% CI; 1.81–4.55, P < .001) and disease-free survival (HR = 3.32, 95% CI; 1.99–5.55, P < .001) in patients with endometrial cancer. High L1CAM expression was also related to adverse clinicopathological characteristics.

Conclusion:

This systematic review demonstrated that high L1CAM expression is correlated with poor survival outcomes and adverse clinicopathological parameters in patients with endometrial cancer.
Conservative treatment and outcome of upper cervical spine fractures in young children
Authors: Tomaszewski Ryszard , Sesia Sergio B. , Studer Daniel , Rutz Erich , Mayr Johannes M.
Published: March 2021

Cervical spine (C-spine) fractures in young children are very rare, and little information on treatment modalities and functional, radiographic, and patient-reported outcome exists. In this 2-center, retrospective case series, we assessed subjective and functional mid-term outcomes in children aged ≤5 years whose C-spine fractures were treated nonoperatively.

Between 2000 and 2018, 6 children (median age at injury: 23.5 months; range: 16–31 months) with C1 or C2 injuries were treated with Minerva cast/brace or soft collar brace at 1 of the 2 study centers. Two patients suffered C1 fractures, and 4 patients had lysis of the odontoid synchondrosis. Overall, 3 children had sustained polytrauma. One child died due to the consequences of massive head injury.

For the primary outcome parameter, we recorded subjective symptoms such as pain and functional restrictions due to the sequelae of C-spine injuries at follow-up.

Based on medical records, we also assessed the causes of injury, diagnostic procedures, treatments and complications, and time to fracture consolidation.

Median follow-up of the 5 surviving children was 51 months (range: 36–160 months). At the latest follow-up, 4 of 5 children did not complain of any pain. One child who sustained an open head injury in combination with a subluxation of the odontoid and undisplaced fracture of the massa lateralis reported occasional headache. All patients experienced complete fracture healing and normal range of motion of the cervical spine.

Median duration of cast/brace treatment was 8.5 weeks. Fracture healing was confirmed by computed tomography in all patients.

All C-spine injuries were managed with either Minerva cast/Halo brace or soft collar brace without complications.

In our retrospective case series, nonoperative treatment of atlas fractures and dislocations or subluxations of the odontoid in young children using Minerva casts or prefabricated Halo braces resulted in good subjective and functional outcomes at mid-term. We observed no complications of conservative treatment of C1 and C2 injuries in young children.
Arterial only anastomosis associated with modified Baudet technique in ear replantation
Authors: Pertea Mihaela , Ciobanu Petru , Poroch Vladimir , Velenciuc Natalia , Lunca Sorinel , Anghelina Florin , Palade Dragos Octavian
Published: March 2021

Background:

Total ear amputation is a relatively rare trauma with an absolute indication for surgical treatment. Numerous techniques for auricular reconstruction have been described. When local and general conditions allow microsurgical replantation, this must be the first choice. We propose the association of microsurgical techniques with some modification (modified Baudet technique) to obtain higher survival rate of the reimplanted stump.

Methods:

This study included cases of 3 male patients with total ear amputation, the injuries and their mechanism (workplace accident) being identical. Chief complaints were pain, bleeding, important emotional impact due by an unaesthetic appearance. The established diagnosis was traumatic complete ear amputation (grade IV auricular injury according to Weerda classification). Microsurgical replantation was performed only with arteriorraphy, and no vein anastomosis. Cartilage incisions and skin excisions were made to enlarge the cartilage-recipient site contact area. Medicinal leeches were used to treat venous congestion, to which systemic anticoagulant therapy was added.

Results:

The results showed the survival of the entire replanted segment in all cases, with good function and esthetical appearance. Patients were fully satisfied with the final outcome.

Conclusion:

Microsurgical replantation is the gold standard, for the surgical treatment of total ear amputation. We believe that cartilage incisions and the increased surface of contact between cartilage and recipient site has an adjuvant role in revascularization of the amputated stump (with only arterial anastomosis) and the use of hirudotherapy helps to relieve early venous congestion.
Recurrent and metastatic female adnexal tumor of probable Wolffian origin
Authors: Chen Qiuhe , Shen Yangmei , Xie Chuan
Published: March 2021

Rationale:

Female adnexal tumors of probable Wolffian origin (FATWOs) are rare gynecologic neoplasms arising from the mesonephric duct remnants. Less than 90 cases have been reported in the English literature. Although most cases of FATWO are considered benign, recurrence and metastasis may occur in very few cases during the course of the disease. Due to the small number of recurrent and metastatic FATWO cases, there are no clear recommendations regarding optimal treatment.

Patient concerns:

A 75-year-old postmenopausal woman, who underwent a mass excision of the right broad ligament three years ago, was found to have a right adnexal mass during a regular postoperative physical examination.

Diagnoses:

Vaginal ultrasound examination revealed a cystic and solid mass approximately 3.6 × 4.4 × 3.8 cm on the right side of the uterus. Three years ago, the mass of the right broad ligament was diagnosed with FATWO in the local hospital. Following extensive immunohistochemistry analysis and after reviewing the histology slides from the primary tumor, the final diagnosis of the mass on the right side of the uterus was recurrent and metastatic FATWO.

Interventions:

The patient underwent laparoscopic mass excision, hysterectomy and resection of the metastatic lesion in the small intestine, and then she received 6 cycles of docetaxel and carboplatin-based chemotherapy.

Outcomes:

The disease has recurred three years after the first surgery in the local hospital. After the second surgery followed by systemic chemotherapy, there is no evidence of recurrence with 24 months of follow-up till now.

Lessons:

FATWO is considered a benign entity. However, a few FATWOs have been shown to behave aggressively. Due to only a few reported cases, there are no comprehensive recommendations regarding the optimal clinical management of recurrent and metastatic FATWOs. Complete surgical resection followed by combination chemotherapy is considered to be the most effective therapy for recurrent and metastatic FATWOs. Chemotherapy with docetaxel plus carboplatin, which is most commonly used in malignant cases, may be effective in the treatment of recurrent and metastatic FATWOs.
Use of the Griffiths mental development scale-Chinese in the assessment of children with autism spectrum disorder and global developmental delay/intellectual disability
Authors: Wang Hui , Du Yu , Mao Zhenghuan , Che Yueping , Li Haifeng , Ding Li , Jin Huiying
Published: March 2021

The Griffiths Mental Development Scale-Chinese (GDS-C) is used in China to assess the development of children from birth to 8 years of age. Language disorders are a common symptom of autism spectrum disorder (ASD) and global developmental delay (GDD)/intellectual disability (ID). There is a need to identify distinct clinical characteristics in children suspected of having these 2 disorders, mainly presenting as language disorders. Here, we aimed to use the GDS-C to evaluate children presenting with language problems to identify characteristics that distinguish ASD and GDD/ID. Children with language problems were recruited between August 2018 and December 2019. A total of 150 children aged 25 to 95.2 months were enrolled (50 in the ASD group, 50 in the GDD/ID group, and 50 in the typical group). Each group was subdivided by age as follows: 24–36 months, >36–60 months, and >60–96 months. Developmental characteristics assessed using the GDS-C were analyzed and compared. Both, children with ASD and GDD/ID presented with a lower developmental level than typical children in all six subscales of the GDS-C. No significant differences were observed in the six subscale scores between the ASD and GDD/ID groups, except for the practical reasoning subscale score in the >36 to 60 months subgroups, which was significantly lower in the GDD/ID group than in the ASD group. The developmental imbalance of subscales within the ASD and GDD/ID groups identified troughs in the personal-social, language, and practical reasoning areas in children with ASD and in the language and practical reasoning areas in children with GDD/ID relative to typical children. The GDS-C is a useful, comprehensive tool for the assessment of the developmental state of children with ASD and GDD/ID. Characteristics of practical reasoning subscale help diagnose autism in >36 to 60 months old children.
Comparison of the sensitizing effects of cocaine and ethanol on histone deacetylase isoforms in the rat brain
Authors: Xu Shijie , Koo Ja Wook , Kang Ung Gu
Published: March 2021

Behavioral sensitization, an animal model of drug addiction, persists for a prolonged period after repeated exposure to drugs of abuse. The persistence of an addiction behavioral phenotype suggests long-lasting changes in gene regulation at the epigenetic level. We measured the expression of histone deacetylases (HDACs) isoforms in the prefrontal cortex and dorsal striatum following the development of sensitization to cocaine (15 mg/kg, administered five times) and ethanol (0.5 g/kg, administered 15 times) to investigate the epigenetic changes that mediate sensitization. Animals sensitized to ethanol exhibited augmented locomotor activity in response to the cocaine challenge. Similarly, those sensitized to cocaine exhibited increased locomotor activity in response to an ethanol challenge. These findings indicate cross-sensitization between ethanol and cocaine and suggest that a common molecular mechanism underlying the cross-sensitization. In animals sensitized to cocaine or ethanol, mRNA levels of class II HDACs (HDAC4 and HDAC5) were decreased in the prefrontal cortex and dorsal striatum, whereas acute treatments with either drug had no effect on the expression of class II HDACs. By contrast, class I HDACs (HDAC1 and HDAC2) responded to the acute cocaine challenge, whereas sensitization itself did not have a consistent effect on class I HDAC levels. These findings support the hypothesis of a common epigenetic mechanism underlying persistent behavioral sensitization induced by different drugs, which may be mediated by the altered expression of class II HDACs.
COVID-19 policy analysis: labour structure dictates lockdown mobility behaviour
Authors: Heroy Samuel , Loaiza Isabella , Pentland Alex , O’Clery Neave
Published: March 2021

Countries and cities around the world have resorted to unprecedented mobility restrictions to combat COVID-19 transmission. Here we exploit a natural experiment whereby Colombian cities implemented varied lockdown policies based on ID number and gender to analyse the impact of these policies on urban mobility. Using mobile phone data, we find that the restrictiveness of cities’ mobility quotas (the share of residents allowed out daily according to policy advice) does not correlate with mobility reduction. Instead, we find that larger, wealthier cities with more formalized and complex industrial structure experienced greater reductions in mobility. Within cities, wealthier residents are more likely to reduce mobility, and commuters are especially more likely to stay at home when their work is located in wealthy or commercially/industrially formalized neighbourhoods. Hence, our results indicate that cities’ employment characteristics and work-from-home capabilities are the primary determinants of mobility reduction. This finding underscores the need for mitigations aimed at lower income/informal workers, and sheds light on critical dependencies between socio-economic classes in Latin American cities.
Protein-assisted scalable mechanochemical exfoliation of few-layer biocompatible graphene nanosheets
Authors: Thomas Deepak-George , De-Alwis Steven , Gupta Shalabh , Pecharsky Vitalij K. , Mendivelso-Perez Deyny , Montazami Reza , Smith Emily A. , Hashemi Nicole N.
Published: March 2021

A facile method to produce few-layer graphene (FLG) nanosheets is developed using protein-assisted mechanical exfoliation. The predominant shear forces that are generated in a planetary ball mill facilitate the exfoliation of graphene layers from graphite flakes. The process employs a commonly known protein, bovine serum albumin (BSA), which not only acts as an effective exfoliation agent but also provides stability by preventing restacking of the graphene layers. The latter is demonstrated by the excellent long-term dispersibility of exfoliated graphene in an aqueous BSA solution, which exemplifies a common biological medium. The development of such potentially scalable and toxin-free methods is critical for producing cost-effective biocompatible graphene, enabling numerous possible biomedical and biological applications. A methodical study was performed to identify the effect of time and varying concentrations of BSA towards graphene exfoliation. The fabricated product has been characterized using Raman spectroscopy, powder X-ray diffraction, transmission electron microscopy and scanning electron microscopy. The BSA-FLG dispersion was then placed in media containing Astrocyte cells to check for cytotoxicity. It was found that lower concentrations of BSA-FLG dispersion had only minute cytotoxic effects on the Astrocyte cells.
Predicting potential future reduction in shark bites on people
Authors: Bradshaw Corey J. A. , Meagher Phoebe , Thiele Madeline J. , Harcourt Robert G. , Huveneers Charlie
Published: March 2021

Despite the low chance of a person being bitten by a shark, there are serious associated costs. Electronic deterrents are currently the only types of personal deterrent with empirical evidence of a substantial reduction in the probability of being bitten by a shark. We aimed to predict the number of people who could potentially avoid being bitten by sharks in Australia if they wear personal electronic deterrents. We used the Australian Shark Attack File from 1900 to 2020 to develop sinusoidal time-series models ofper capitaincidents, and then stochastically projected these to 2066. We predicted that up to 1063 people (range: 185–2118) could potentially avoid being bitten across Australia by 2066 if all people used the devices. Avoiding death and injury of people over the next half-century is of course highly desirable, especially when considering the additional costs associated with the loss of recreational, commercial and tourism revenue potentially in the tens to hundreds of millions of dollars following clusters of shark-bite events.
Deep eutectic solvent-based emulsification liquid–liquid microextraction for the analysis of phenoxy acid herbicides in paddy field water samples
Authors: Mohamad Yusoff Nur ‘An Nisaa , Rahim Nurul Yani , Mohammad Rania Edrees Adam , Yahaya Noorfatimah , Miskam Mazidatulakmam
Published: March 2021

An emulsification liquid–liquid microextraction (ELLME) method was successfully developed using phenolic-based deep eutectic solvent (DES) as an extraction solvent for the determination of phenoxy acid herbicides, 3,6-dichloro-2-methoxybenzoic acid (dicamba) and 2-methyl-4-chlorophenoxyacetic acid (MCPA) in environmental water samples. Five different phenolics-based DESs were successfully synthesized by using phenol (DES 1), 2-chlorophenol (DES 2), 3-chlorophenol (DES 3), 4-chlorophenol (DES 4) and 3,4-dichlorophenol (DES 6) as the hydrogen-bond donor (HBD) and choline chloride as the hydrogen-bond acceptor (HBA). The DESs were mixed at 1 : 2 ratio. A homogeneous solution (clear solution) was observed upon the completion of successful synthesis. The synthesized DESs were characterized by using Fourier transform infrared and nuclear magnetic resonance (NMR). Under optimum ELLME conditions (50 µl of DES 2 as extraction solvent; 100 µl of THF as emulsifier solvent; pH 2; extraction time 5 min), enrichment factor obtained for dicamba and MCPA were 43.1 and 59.7, respectively. The limit of detection and limit of quantification obtained for dicamba were 1.66 and 5.03 µg l
−1
, respectively, meanwhile for MCPA were 1.69 and 5.12 µg l
−1
, respectively. The developed ELLME-DES method was applied on paddy field water samples, with extraction recoveries in the range of 79–91% for dicamba and 82–96% for MCPA.
Study of crystallization behaviour of electron beam irradiated polypropylene and high-density polyethylene
Authors: Svoboda Petr , Trivedi Krunal , Stoklasa Karel , Svobodova Dagmar , Ougizawa Toshiaki
Published: March 2021

The influence of electron-beam irradiation on polypropylene (PP) and high-density polyethylene (HDPE) was investigated with a focus on crystallization. A high-temperature (200°C) creep test revealed that the HDPE gradually increased cross-linking density in the range 30–120 kGy, while the PP underwent a chain scission which was quantitatively evaluated by gel permeation chromatography. The mechanical properties were measured in the range -150 to 200°C by a dynamic mechanical analysis. A small presence of C=C and C=O bonds was found in the irradiated PP by a Fourier transform infrared spectroscopy. Crystallization kinetics measured by differential scanning calorimetry and hot-stage optical microscopy results were influenced tremendously by irradiation for HDPE and to a lesser extent for PP. Irradiation caused a decrease in both the number of nucleation centres and the growth rate of individual spherulites. Crystallization was analysed in detail with the help of Hoffman–Lauritzen, Avrami and Arrhenius equations. Interestingly an increasing
β
-crystal formation with an increasing irradiation level was discovered for PP by X-ray diffraction. A generation of defects in the crystalline structure owing to irradiation was discussed.
Predators, prey or temperature? Mechanisms driving niche use of a foundation plant species by specialist lizards
Authors: Bell Kristian J. , Doherty Tim S. , Driscoll Don A.
Published: March 2021

Foundation species interact strongly with other species to profoundly influence communities, such as by providing food, refuge from predators or beneficial microclimates. We tested relative support for these mechanisms using spinifex grass (Triodiaspp.), which is a foundation species of arid Australia that provides habitat for diverse lizard communities. We first compared the attributes of live and dead spinifex, bare ground and a structurally similar plant (Lomandra effusa), and then tested the relative strength of association of two spinifex specialist lizard species (Ctenophorus spinodomusandCtenotus atlas) with spinifex using a mesocosm experiment. Temperatures were coolest within spinifex compared to bare ground andLomandra.Invertebrate abundance and the threat of predation were indistinguishable between treatments, suggesting temperature attenuation may be a more important driver. Overall, the dragonC. spinodomuspreferred live over dead spinifex, while the skinkC. atlaspreferred dead spinifex, particularly at warmer air temperatures. However, both species displayed individual variability in their use of available microhabitats, with some individuals rarely using spinifex. Our results provide an example of temperature attenuation by a foundation species driving niche use by ectothermic animals.
Characteristics of urban environments and novel problem-solving performance in Eurasian red squirrels
Authors: Chow Pizza Ka Yee , Uchida Kenta , von Bayern Auguste M. P. , Koizumi Itsuro
Published: March 2021

Urban environments can be deemed ‘harsh’ for some wildlife species, but individuals frequently show behavioural flexibility to cope with challenges and demands posed by life in the city. For example, urban animals often show better performance in solving novel problems than rural conspecifics, which helps when using novel resources under human-modified environments. However, which characteristics of urban environments fine-tune novel problem-solving performance, and their relative importance, remain unclear. Here, we examined how four urban environmental characteristics (direct human disturbance, indirect human disturbance, size of green coverage and squirrel population size) may potentially influence novel problem-solving performance of a successful ‘urban dweller’, the Eurasian red squirrel, by presenting them with a novel food-extraction problem. We found that increased direct human disturbance, indirect human disturbance and a higher squirrel population size decreased the proportion of solving success at the population level. At the individual level, an increase in squirrel population size decreased the latency to successfully solve the novel problem the first time. More importantly, increased direct human disturbance, squirrel population size and experience with the novel problem decreased problem-solving time over time. These findings highlight that some urban environmental characteristics shape two phenotypic extremes in the behaviour-flexibility spectrum: individuals either demonstrated enhanced learning or they failed to solve the novel problem.
Negative resistance and resilience: biotic mechanisms underpin delayed biological recovery in stream restoration
Authors: Barrett Isabelle C. , McIntosh Angus R. , Febria Catherine M. , Warburton Helen J.
Published: March 2021

Traditionally, resistance and resilience are associated with good ecological health, often underpinning restoration goals. However, degraded ecosystems can also be highly resistant and resilient, making restoration difficult: degraded communities often become dominated by hyper-tolerant species, preventing recolonization and resulting in low biodiversity and poor ecosystem function. Using streams as a model, we undertook a mesocosm experiment to test if degraded community presence hindered biological recovery. We established 12 mesocosms, simulating physically healthy streams. Degraded invertebrate communities were established in half, mimicking the post-restoration scenario of physical recovery without biological recovery. We then introduced a healthy colonist community to all mesocosms, testing if degraded community presence influenced healthy community establishment. Colonists established less readily in degraded community mesocosms, with larger decreases in abundance of sensitive taxa, likely driven by biotic interactions rather than abiotic constraints. Resource depletion by the degraded community likely increased competition, driving priority effects. Colonists left by drifting, but also by accelerating development, reducing time to emergence but sacrificing larger body size. Since degraded community presence prevented colonist establishment, our experiment suggests successful restoration must address both abiotic and biotic factors, especially those that reinforce the ‘negative’ resistance and resilience which perpetuate degraded communities and are typically overlooked.
Cerebral Small Vessel Disease Burden and Longitudinal Cognitive Decline from age 73 to 82: the Lothian Birth Cohort 1936
Authors: Hamilton OKL , Cox SR , Okely JA , Conte F , Ballerini L , Bastin ME , Corley J , Taylor AM , Page D , Gow AJ , Muñoz Maniega S , Redmond P , Valdés-Hernández M del C , Wardlaw JM , Deary IJ
Published: March 2021

Slowed processing speed is considered a hallmark feature of cognitive decline in cerebral small vessel disease (SVD), however, it is unclear whether SVD’s association with slowed processing might be due to its association with overall declining general cognitive ability. We quantified the total MRI-visible SVD burden of 540 members of the Lothian Birth Cohort 1936 (age:72.6□0.7 years; 47% female). Using latent growth curve modelling, we tested associations between total SVD burden at mean age 73 and changes in general cognitive ability, processing speed, verbal memory, and visuospatial ability, measured at age 73, 76, 79 and 82. Covariates included age, sex, vascular risk, and childhood cognitive ability. In the fully-adjusted models, greater SVD burden was associated with greater declines in general cognitive ability (standardised β: -0.201; 95%CI: [-0.36, -0.04]; pFDR=0.022) and processing speed (−0.222; [-0.40, -0.04]; pFDR=0.022). SVD burden accounted for between 4 and 5% of variance in declines of general cognitive ability and processing speed. After accounting for the covariance between tests of processing speed and general cognitive ability, only SVD’s association with greater decline in general cognitive ability remained significant, prior to FDR correction (−0.222; [-0.39, -0.06]; p=0.008; pFDR=0.085). Our findings do not support the notion that SVD has a specific association with declining processing speed, independent of decline in general cognitive ability (which captures the variance shared across domains of cognitive ability). The association between SVD burden and declining general cognitive ability supports the notion of SVD as a diffuse, whole-brain disease and suggests that trials monitoring SVD-related cognitive changes should consider domain-specific changes in the context of overall, general cognitive decline.
Prevalence of childhood cough in epidemiological studies: does it matter which question we use?
Authors: Mallet Maria Christina , Mozun Rebeca , Ardura-Garcia Cristina , Latzin Philipp , Moeller Alexander , Kuehni Claudia E.
Published: March 2021

We assessed how prevalence estimates of cough in 6-17-year-olds vary depending on the question asked in the population-based Luftibus in the school (LUIS) study. 3427 parents answered three different questions on cough. The prevalence of parent-reported cough varied substantially depending on the question: 25% of parents reported cough without a cold, 11% dry night cough and 5% that their child coughs more than other children. There was only partial overlap with 3% answering yes to all questions. This suggests that the exact question used to assess cough strongly affects prevalence estimates and must be taken into account when comparing studies.
Shared and disease-specific host gene-microbiome interactions across human diseases
Authors: Priya Sambhawa , Burns Michael B. , Ward Tonya , Mars Ruben A. T. , Adamowicz Beth , Lock Eric F. , Kashyap Purna C. , Knights Dan , Blekhman Ran
Published: March 2021

While the gut microbiome and host gene regulation separately contribute to gastrointestinal disorders, it is unclear how the two may interact to influence host pathophysiology. Here, we developed a machine learning-based framework to jointly analyze host transcriptomic and microbiome profiles from 416 colonic mucosal samples of patients with colorectal cancer, inflammatory bowel disease, and irritable bowel syndrome. We identified potential interactions between gut microbes and host genes that are disease-specific, as well as interactions that are shared across the three diseases, involving host genes and gut microbes previously implicated in gastrointestinal inflammation, gut barrier protection, energy metabolism, and tumorigenesis. In addition, we found that mucosal gut microbes that have been associated with all three diseases, such asStreptococcus, interact with different host pathways in each disease, suggesting that similar microbes can affect host pathophysiology in a disease-specific manner through regulation of different host genes.
Arf GTPase-Activating proteins SMAP1 and AGFG2 regulate the size of Weibel-Palade bodies and exocytosis of von Willebrand factor
Authors: Watanabe Asano , Hataida Hikari , Inoue Naoya , Kamon Kosuke , Baba Keigo , Sasaki Kuniaki , Kimura Rika , Sasaki Honoka , Eura Yuka , Ni Wei-Fen , Shibasaki Yuji , Waguri Satoshi , Kokame Koichi , Shiba Yoko
Published: March 2021

Arf GTPase-Activating proteins (ArfGAPs) mediate the hydrolysis of GTP bound to ADP-ribosylation factors, which are important for intracellular transport. ArfGAPs have been shown to be critical for cargo sorting in the Golgi-to-ER and post-Golgi traffic. However, their roles in the sorting of secretory proteins remains unclear. Weibel-Palade bodies (WPBs) are cigar-shaped secretory granules in endothelial cells that contain von Willebrand factor (vWF) as their main cargo. WPBs are formed at thetrans-Golgi Network, and this process is thought to be coupled with the sorting of vWF. WPB biogenesis was reported to be regulated by ADP-ribosylation factors and their regulators, but the role of ArfGAPs has been unknown. In this study, we performed siRNA screening of ArfGAPs to investigate the biogenesis of WPBs. We found two ArfGAPs, SMAP1 and AGFG2, to be involved in WPB size and vWF exocytosis, respectively. SMAP1 depletion resulted in small-sized WPBs, and the lysosomal inhibitor leupeptin recovered the size of WPBs. These results indicate that SMAP1 functions in preventing the degradation of cigar-shaped WPBs. However, AGFG2 downregulation resulted in the inhibition of vWF secretion upon Phorbol 12-myristate 13-acetate (PMA)-stimulation, suggesting that AGFG2 plays a role in vWF exocytosis. Our study revealed unexpected processes regulated by ArfGAPs for vWF transport.

Summary Statement

The ArfGAP proteins SMAP1 and AGFG2 were identified as regulating WPB size and vWF exocytosis.
Healthcare workers’ perceptions and attitudes towards the UK’s COVID-19 vaccination programme
Authors: Manby Louisa , Dowrick Anna , Karia Amelia , Maio Laura , Buck Caroline , Singleton Georgina , Lewis-Jackson Sasha , Uddin Inayah , Vanderslott Samantha , Martin Sam , Vindrola-Padros Cecilia
Published: March 2021

Objectives

To explore healthcare workers’ (HCWs) perceptions and attitudes towards the COVID-19 vaccination programme in the UK, including their expectations, concerns and views on whether to promote vaccination to others. To understand the key factors shaping HCWs’ attitudes towards COVID-19 vaccination in the UK.

Design

This study was designed as a rapid qualitative appraisal integrating data from a review of UK policies and guidance on COVID-19 vaccination with data from in-depth semi-structured telephone interviews with frontline HCWs in the UK. Data were analysed using framework analysis.

Participants

Interviews were carried out with a purposive sample of HCWs from two large London-based hospital Trusts (n=24) and 24 government policies and guidelines on the vaccination programme were reviewed.

Results

The level of uncertainty about the vaccines’ long-term safety and efficacy against mutant strains made it difficult for HCWs to balance the benefits against the risks of vaccination. HCWs felt that government decisions on vaccine rollout had not been supported by evidence-based science and this impacted their level of trust and confidence in the programme. The spread of misinformation online also impacted HCWs’ attitudes towards vaccination, particularly among junior level and Black, Asian and Minority Ethnic (BAME) HCWs. Most HCWs felt encouraged to promote vaccination to their patients and the majority said they would advocate vaccination or engage in conversations about vaccination with others when relevant.

Conclusion

In order to improve HCWs’ trust and confidence in the UK’s COVID-19 vaccination programme, there needs to be clarity about what is known and not known about the vaccines and transparency around the evidence-base supporting government decisions on vaccine rollout. Effort is also needed to dispel the spread of vaccine-related misinformation online and to address specific concerns, particularly among BAME and junior level HCWs.

Strengths and limitations of this study

This is the first qualitative study to understand the factors influencing healthcare workers’ (HCWs) attitudes towards COVID-19 vaccination in the UK

This study integrated interview and policy data and captured HCWs’ perceptions and attitudes in real-time as the vaccination programme was being rolled out in the UK

Our interview study sample was limited in its representation of junior level HCWs and areas of the UK

This research may have been impacted by selection bias as those with stronger views on vaccination may have been more likely to participate in the study
COVID-19 vaccine impact on rates of SARS-CoV-2 cases and post vaccination strain sequences among healthcare workers at an urban academic medical center: a prospective cohort study
Authors: Bouton Tara C. , Lodi Sara , Turcinovic Jacquelyn , Weber Sarah E. , Quinn Emily , Korn Cathy , Steiner Jacqueline , Schechter-Perkins Elissa M. , Duffy Elizabeth , Ragan Elizabeth J. , Taylor Bradford P. , Schaeffer Beau , Miller Nancy , Davidoff Ravin , Hanage William P. , Connor John , Pierre Cassandra , Jacobson Karen R.
Published: March 2021

Background

COVID-19 vaccine trials and post-implementation data suggest vaccination decreases SARS-CoV-2 infections. We examine COVID-19 vaccination’s impact on SARS-CoV-2 case rates and viral diversity among healthcare workers (HCW) during a high community prevalence period.

Methods

A prospective cohort study from Boston Medical Center (BMC)’s HCW vaccination program, where staff received two doses of BNT162b2 or mRNA-1273. We included PCR-confirmed SARS-CoV-2 cases among HCWs from December 09, 2020 to February 23, 2021. Weekly SARS-CoV-2 rates per 100,000 person-day overall and by time from first injection (1-14 and >14 days) were compared with surrounding community rates. Viral genomes were sequenced from SARS CoV-2 positive samples.

Results

SARS-CoV-2 cases occurred in 1.4% (96/7109) of HCWs given at least a first dose and 0.3% (17/5913) of HCWs given both vaccine doses. Adjusted SARS-CoV-2 infection rate ratios were 0.73 (95% CI 0.53-1.00) 1-14 days and 0.18 (0.10-0.32) >14 days from first dose. HCW SARS-CoV-2 cases >14 days from initial dose compared to within 14 days were more often older (46 versus 38 years, p=0.007), Latinx (10% versus 8%, p=0.03), and asymptomatic (48% versus 11%, p=0.0002). SARS-CoV-2 rates among HCWs fell below those of the surrounding community, with a 18% versus 11% weekly decrease respectively (p=0.14). Comparison of 48 SARS-CoV-2 genomes sequenced from post-first dose cases did not indicate selection pressure towards known spike-antibody escape mutations.

Conclusions

Our results indicate a positive impact of COVID-19 vaccines on SARS-CoV-2 case rates. Post-vaccination isolates did not show unusual genetic diversity or selection for mutations of concern.

Main Point

Cases of SARS-CoV-2 among health care workers dropped rapidly with COVID-19 vaccination. Sequencing 48 breakthrough infections (overwhelmingly in 14 days after 1st dose) showed no clear sign of any differences in spike protein compared with time-matched, unvaccinated control sequences.
Epigenome erosion drives neural crest-like phenotypic mimicry in triple-negative breast cancer and other SOX10+ malignancies
Authors: Saunus Jodi M. , De Luca Xavier M. , Northwood Korinne , Raghavendra Ashwini , Hasson Alexander , McCart Reed Amy E. , Lim Malcolm , Lal Samir , Vargas Ana Cristina , Kutasovic Jamie R. , Dalley Andrew J. , Miranda Mariska , Kalaw Emarene , Kalita-de Croft Priyakshi , Gresshoff Irma , Al-Ejeh Fares , Gee Julia M.W. , Ormandy Chris , Khanna Kum Kum , Beesley Jonathan , Chenevix-Trench Georgia , Green Andrew R. , Rakha Emad A. , Ellis Ian O. , Nicolau Dan V. , Simpson Peter T. , Lakhani Sunil R.
Published: March 2021

Abstract

Background

Intratumoural heterogeneity is a poor prognostic feature in triple-negative breast cancer (TNBC) and other high-grade malignancies. It is caused by genomic instability and phenotypic plasticity, but how these features co-evolve during tumour development remains unclear. SOX10 is a transcription factor, neural crest stem cell (NCSC) specifier and candidate mediator of cancer-associated phenotypic plasticity.

Methods

Using immunophenotyping, we investigated the expression of SOX10 in normal human breast tissue and breast cancer (n=21 cosmetic breast reduction and 1,860 tumour samples with clinical annotation). We then defined the context and evolution of its expression in TNBC compared to 21 other malignancies using systems-level transcriptomics.

Results

SOX10 was detected in nuclei of normal mammary luminal progenitor cells, the histogenic origin of most TNBCs. In breast cancer, nuclear SOX10 predicted poor outcome amongst cross-sectional (log-rank p=0.0015, hazard ratio 2.02, n=224) and metaplastic (log-rank p=0.04, n=66) TNBCs. Systems-level transcriptional network analysis identified a core module in SOX10’s normal mammary epithelial transcription program that is rewired to NCSC genes in TNBC. Reprogramming was proportional to DNA damage and genome-wide promoter hypomethylation, particularly at CpG island shores. Using a novel network analysis pipeline, we found that NCSC-like transcriptional reprogramming is also strongly associated with promoter hypomethylation in other SOX10+ malignancies: glioma and melanoma.

Conclusions

We propose that cancer-associated genome hypomethylation simulates the open chromatin landscape of more primitive cell states, and that on this relatively unrestricted background, SOX10 recreates its ancestral gene regulatory circuits by default. These findings provide new insights about the basis of intratumoural heterogeneity and resurrection of developmental phenotypes in cancer; and highlight the potential for therapeutics that limit chromatin remodelling.
Differential effects of environmental and endogenous 24h rhythms within a deep-coverage spatiotemporal proteome
Authors: Kay Holly , Grünewald Ellen , Feord Helen K. , Gil Sergio , Peak-Chew Sew Y. , Stangherlin Alessandra , O’Neill John S. , van Ooijen Gerben
Published: March 2021

The cellular landscape of most eukaryotic cells changes dramatically over the course of a 24h day. Whilst the proteome responds directly to daily environmental cycles, it is also regulated by a cellular circadian clock that anticipates the differing demands of day and night. To quantify the relative contribution of diurnal versus circadian regulation, we mapped spatiotemporal proteome dynamics under 12h:12h light:dark cycles compared with constant light. UsingOstreococcus tauri, a prototypical eukaryotic cell, we achieved 85% coverage of the theoretical proteome which provided an unprecedented insight into the identity of proteins that drive and facilitate rhythmic cellular functions. Surprisingly, the overlap between diurnally- and circadian-regulated proteins was quite modest (11%). These proteins exhibited different phases of oscillation between the two conditions, consistent with an interaction between intrinsic and extrinsic regulatory factors. The relative amplitude of rhythmic protein abundance was much lower than would be expected from daily variations in transcript abundance. Transcript rhythmicity was poorly predictive of daily variation in abundance of the encoded protein. We observed coordination between the rhythmic regulation of organelle-encoded proteins with the nuclear-encoded proteins that are targeted to organelles. Rhythmic transmembrane proteins showed a remarkably different phase distribution compared with rhythmic soluble proteins, indicating the existence of a novel circadian regulatory process specific to the biogenesis and/or degradation of membrane proteins. Taken together, our observations argue that the daily spatiotemporal regulation of cellular proteome composition is not dictated solely by clock-regulated gene expression. Instead, it also involves extensive rhythmic post-transcriptional, translational, and post-translational regulation that is further modulated by environmental timing cues.
The nuclear receptor DHR3/Hr46 is required in the blood brain barrier of mature males for courtship
Authors: Lama Chamala , Love Cameron R. , Le Hoa Nhu , Lama Jyoti , Dauwalder Brigitte
Published: March 2021

The blood brain barrier (BBB) forms a stringent barrier that protects the brain from components in the circulation that could interfere with neuronal function. At the same time, the BBB enables selective transport of critical nutrients and other chemicals to the brain. Many of these processes are still poorly understood. Beyond these functions, another recently recognized function is even less characterized, specifically the role of the BBB in modulating behavior by affecting neuronal function in a sex dependent manner. Notably, signaling in the adultDrosophilaBBB is required for normal male courtship behavior. Courtship regulation also relies on male-specific molecules in the BBB. Our previous studies have demonstrated that adult feminization of these cells in males significantly lowered courtship. Here, we conducted microarray analysis of BBB cells isolated from males and females. Findings revealed that these cells contain male- and female-enriched transcripts, respectively. Among these transcripts, nuclear receptor DHR3/Hr46 was identified as a male-enriched BBB transcript. DHR3/Hr46 is best known for its essential roles in the ecdysone response during development and metamorphosis. In this study, we demonstrate that DR3/Hr46 is specifically required in the BBB cells of mature males for courtship behavior. The protein is localized in the nuclei of sub-perineurial glial cells (SPG), indicating that it might act as a transcriptional regulator. These data provide a catalogue of sexually dimorphic BBB transcripts and demonstrate a physiological adult role for the nuclear receptor DH3/Hr46 in the regulation of male courtship, a novel function that is independent of its developmental role.

Author summary

The blood brain barrier very tightly regulates which molecules can enter the brain. This is an important protection for the brain, however, it also complicates communication between molecules in the circulating fluid and the brain. In fly courtship, for example, circulating male-specific products are crucially required for normal courtship. But the neuronal circuits that ultimately control the behavior are inside the brain, separated from these molecules by the blood brain barrier. The mechanisms of this communication are not known. Here we show that the blood brain barrier itself contains sex-specific RNAs and we show that one of them, a nuclear receptor called DHR3, is required in adult males for normal courtship. These findings promise new insight into the communication between blood brain barrier and the brain.
Caspase-2 regulates S-phase cell cycle events to protect from DNA damage accumulation independent of apoptosis
Authors: Boice Ashley , Pandita Raj K , Lopez Karla , Parsons Melissa J , Charendoff Chloe I , Charaka Vijay , Carisey Alexandre F. , Pandita Tej K. , Bouchier-Hayes Lisa
Published: March 2021

In addition to its classical role in apoptosis, accumulating evidence suggests that caspase-2 has non-apoptotic functions, including regulation of cell division. Loss of caspase-2 is known to increase proliferation rates but how caspase-2 is regulating this process is currently unclear. We show that caspase-2 is activated in dividing cells in G1- and early S-phase. In the absence of caspase-2, cells exhibit numerous S-phase defects including delayed exit from S-phase, S-phase-associated chromosomal aberrations, and increased DNA damage following S-phase arrest. In addition, caspase-2-deficient cells have a higher frequency of stalled replication forks, decreased DNA fiber length, and impeded progression of DNA replication tracts. This indicates that caspase-2 reduces replication stress and promotes replication fork protection to maintain genomic stability. These functions are independent of the pro-apoptotic function of caspase-2 because blocking caspase-2-induced cell death had no effect on cell division or DNA damage-induced cell cycle arrest. Thus, our data supports a model where caspase-2 regulates cell cycle events to protect from the accumulation of DNA damage independently of its pro-apoptotic function.