bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterisation of the enzyme transport path between shipworms and their bacterial symbionts
Authors: Pesante Giovanna , Sabbadin Federico , Elias Luisa , Steele-King Clare , Shipway J. Reuben , Dowle Adam A. , Li Yi , Busse-Wicher Marta , Dupree Paul , Besser Katrin , Cragg Simon M. , Bruce Neil C. , McQueen-Mason Simon J. 
Published: November 2021

Abstract
Background
Shipworms are marine xylophagus bivalve molluscs, which can live on a diet solely of wood due to their ability to produce plant cell wall-degrading enzymes. Bacterial carbohydrate-active enzymes (CAZymes), synthesised by endosymbionts living in specialised shipworm cells called bacteriocytes and located in the animal’s gills, play an important role in wood digestion in shipworms. However, the main site of lignocellulose digestion within these wood-boring molluscs, which contains both endogenous lignocellulolytic enzymes and prokaryotic enzymes, is the caecum, and the mechanism by which bacterial enzymes reach the distant caecum lumen has remained so far mysterious. Here, we provide a characterisation of the path through which bacterial CAZymes produced in the gills of the shipworm Lyrodus pedicellatus reach the distant caecum to contribute to the digestion of wood.

Results
Through a combination of transcriptomics, proteomics, X-ray microtomography, electron microscopy studies and in vitro biochemical characterisation, we show that wood-digesting enzymes produced by symbiotic bacteria are localised not only in the gills, but also in the lumen of the food groove, a stream of mucus secreted by gill cells that carries food particles trapped by filter feeding to the mouth. Bacterial CAZymes are also present in the crystalline style and in the caecum of their shipworm host, suggesting a unique pathway by which enzymes involved in a symbiotic interaction are transported to their site of action. Finally, we characterise in vitro four new bacterial glycosyl hydrolases and a lytic polysaccharide monooxygenase identified in our transcriptomic and proteomic analyses as some of the major bacterial enzymes involved in this unusual biological system.

Conclusion
Based on our data, we propose that bacteria and their enzymes are transported from the gills along the food groove to the shipworm’s mouth and digestive tract, where they aid in wood digestion.
A KRT6A mutation p.Ile462Asn in a Chinese family with pachyonychia congenita, and identification of maternal mosaicism: a case report
Authors: Li Yue , Wang Yumeng , Ming Yan , Chaolan Pan , Jia Zhang , Cheng Ni , Qiaoyu Cao , Li Ming , Tianyi Xu 
Published: November 2021

AbstractBackgroundPachyonychia congenita (PC, OMIM #167200, #167210, #615726, #615728, and #615735) is a rare autosomal dominant disorder caused by keratin gene mutations inKRT6A,KRT6B,KRT6C,KRT16orKRT17. It is characterized with nail dystrophy and palmoplantar keratoderma (PPK). The most prominent manifestation is plantar pain. This is a further unusual case of parental mosaicism in PC. Although very rare, germ cell mosaicism should be considered when providing genetic counselling for unaffected parents of a child with PC.Case presentationWe report the case of a 5-year-old boy with thickening nails and oral leukokeratosis at birth. He began to develop palmoplantar keratoderma at 2 years old and his sister has similar clinical manifestation characterized with nail discoloration and thickening. A previously reported heterozygous mutation, p.Ile462Asn, was identified in KRT6A in the proband and his affected sister. SNaPshot sequencing revealed mosaicism at a level of 2.5% and 4.7% in DNA from blood and hair bulbs from the unaffected mother. HiSeq deep sequencing demonstrated low-grade mosaicism in the patient’s younger sister and parents.ConclusionThese findings indicate the ability of WES and SNaPshot sequencing to detect low-frequency mosaic mutations. Although very rare, germinal mosaicism should be considered when genetic counseling is given to families with presumed spontaneous cases of PC.
Learning to walk with a wearable robot in 880 simple steps: a pilot study on motor adaptation
Authors: Haufe Florian L. , Kober Alessia M. , Wolf Peter , Riener Robert , Xiloyannis Michele 
Published: November 2021

Abstract
Background
Wearable robots have been shown to improve the efficiency of walking in diverse scenarios. However, it is unclear how much practice is needed to fully adapt to robotic assistance, and which neuromotor processes underly this adaptation. Familiarization strategies for novice users, robotic optimization techniques (e.g. human-in-the-loop), and meaningful comparative assessments depend on this understanding.

Methods
To better understand the process of motor adaptation to robotic assistance, we analyzed the energy expenditure, gait kinematics, stride times, and muscle activities of eight naïve unimpaired participants across three 20-min sessions of robot-assisted walking. Experimental outcomes were analyzed with linear mixed effect models and statistical parametric mapping techniques.

Results
Most of the participants’ kinematic and muscular adaptation occurred within the first minute of assisted walking. After ten minutes, or 880 steps, the energetic benefits of assistance were realized (an average of 5.1% (SD 2.4%) reduction in energy expenditure compared to unassisted walking). Motor adaptation was likely driven by the formation of an internal model for feedforward motor control as evidenced by the reduction of burst-like muscle activity at the cyclic end of robotic assistance and an increase in arm-swing asymmetry previously associated with increased cognitive load.

Conclusion
Humans appear to adapt to walking assistance from a wearable robot over 880 steps by forming an internal model for feedforward control. The observed adaptation to the wearable robot is well-described by existing three-stage models that start from a cognitive stage, continue with an associative stage, and end in autonomous task execution.
Trial registration Not applicable.
Enhanced chromatin accessibility contributes to X chromosome dosage compensation in mammals
Authors: Talon Irene , Janiszewski Adrian , Theeuwes Bart , Lefevre Thomas , Song Juan , Bervoets Greet , Vanheer Lotte , De Geest Natalie , Poovathingal Suresh , Allsop Ryan , Marine Jean-Christophe , Rambow Florian , Voet Thierry , Pasque Vincent 
Published: November 2021

Abstract
Background
Precise gene dosage of the X chromosomes is critical for normal development and cellular function. In mice, XX female somatic cells show transcriptional X chromosome upregulation of their single active X chromosome, while the other X chromosome is inactive. Moreover, the inactive X chromosome is reactivated during development in the inner cell mass and in germ cells through X chromosome reactivation, which can be studied in vitro by reprogramming of somatic cells to pluripotency. How chromatin processes and gene regulatory networks evolved to regulate X chromosome dosage in the somatic state and during X chromosome reactivation remains unclear.

Results
Using genome-wide approaches, allele-specific ATAC-seq and single-cell RNA-seq, in female embryonic fibroblasts and during reprogramming to pluripotency, we show that chromatin accessibility on the upregulated mammalian active X chromosome is increased compared to autosomes. We further show that increased accessibility on the active X chromosome is erased by reprogramming, accompanied by erasure of transcriptional X chromosome upregulation and the loss of increased transcriptional burst frequency. In addition, we characterize gene regulatory networks during reprogramming and X chromosome reactivation, revealing changes in regulatory states. Our data show that ZFP42/REX1, a pluripotency-associated gene that evolved specifically in placental mammals, targets multiple X-linked genes, suggesting an evolutionary link between ZFP42/REX1, X chromosome reactivation, and pluripotency.

Conclusions
Our data reveal the existence of intrinsic compensatory mechanisms that involve modulation of chromatin accessibility to counteract X-to-Autosome gene dosage imbalances caused by evolutionary or in vitro X chromosome loss and X chromosome inactivation in mammalian cells.
Retinal organoids as models for development and diseases
Authors: Zhang Xiao , Wang Wen , Jin Zi-Bing 
Published: November 2021

AbstractThe evolution of pluripotent stem cell-derived retinal organoids (ROs) has brought remarkable opportunities for developmental studies while also presenting new therapeutic avenues for retinal diseases. With a clear understanding of how well these models mimic native retinas, such preclinical models may be crucial tools that are widely used for the more efficient translation of studies into novel treatment strategies for retinal diseases. Genetic modifications or patient-derived ROs can allow these models to simulate the physical microenvironments of the actual disease process. However, we are currently at the beginning of the three-dimensional (3D) RO era, and a general quantitative technology for analyzing ROs derived from numerous differentiation protocols is still missing. Continued efforts to improve the efficiency and stability of differentiation, as well as understanding the disparity between the artificial retina and the native retina and advancing the current treatment strategies, will be essential in ensuring that these scientific advances can benefit patients with retinal disease. Herein, we briefly discuss RO differentiation protocols, the current applications of RO as a disease model and the treatments for retinal diseases by using RO modeling, to have a clear view of the role of current ROs in retinal development and diseases.
Patient-important outcomes reported in randomized controlled trials of pharmacologic treatments for COVID-19: a protocol of a META-epidemiological study
Authors: Jimenez-Mora Mario A. , Varela Andrea Ramírez , Meneses-Echavez Jose F. , Bidonde Julia , Angarita-Fonseca Adriana , Siemieniuk Reed A. C. , Zeraatkar Dena , Bartoszko Jessica J. , Brignardello-Petersen Romina , Honarmand Kimia , Rochwerg Bram , Guyatt Gordon , Yepes-Nuñez Juan José 
Published: November 2021

AbstractBackgroundThe coronavirus disease 19 (covid-19) pandemic has underscored the need to expedite clinical research, which may lead investigators to shift away from measuring patient-important outcomes (PIO), limiting research applicability. We aim to investigate if randomized controlled trials (RCTs) of covid-19 pharmacological therapies include PIOs.MethodsWe will perform a meta-epidemiological study of RCTs that included people at risk for, or with suspected, probable, or confirmed covid-19, examining any pharmacological treatment or blood product aimed at prophylaxis or treatment. We will obtain data from all RCTs identified in a living network metanalysis (NMA). The main data sources are the living WHO covid-19 database up to 1 March 2021 and six additional Chinese databases up to 20 February 2021. Two reviewers independently will review each citation, full-text article, and abstract data. To categorize the outcomes according to their importance to patients, we will adapt a previously defined hierarchy: a) mortality, b) quality of life/ functional status/symptoms, c) morbidity, and d) surrogate outcomes. Outcomes within the category a) and b) will be considered critically important to patients, and outcomes within the category c) will be regarded as important. We will use descriptive statistics to assess the proportion of studies that report each category of outcomes. We will perform univariable and multivariable analysis to explore associations between trial characteristics and the likelihood of reporting PIOs.DiscussionThe findings from this meta-epidemiological study will help health care professionals and researchers understand if the current covid-19 trials are effectively assessing and reporting the outcomes that are important to patients. If a deficiency in capturing PIOs is identified, this information may help inform the development of future RCTs in covid-19.Systematic review registrationsOpen Science Framework registration:osf.io/6xgjz.
Legal environment and corporate finance: evidence from the Italian manufacturing industry
Authors: Falavigna Greta , Ippoliti Roberto 
Published: November 2021

AbstractConsidering the Italian manufacturing industry between 2014 and 2016 (more than 250,000 observations), this technical note analyzes the relation between the courts’ ability to enforce credit rights and the opportunity to finance business activities with trade credits instead of financial debts, delaying payments and decreasing the financial costs. According to our results, and considering mortgage foreclosure, if the time necessary to settle an insolvency case increases by 1000 days, we can expect an increase in operating debt between 3 and 11%, and a decrease of financial expenses between 3000 and 7000 Euro.
Introduction to this special section: Geomechanics
Authors: Finkbeiner Thomas , Bathija Arpita P. 
Published: November 2021

The term “geomechanics” means different things to different people. We assert that in the petroleum industry the broad consensus for a definition would probably be something like this: Geomechanics is the discipline that investigates rock mechanical behavior in the subsurface (i.e., at the wellbore wall, the overburden, cap rock, and/or the reservoir) under present-day in-situ stress and pore pressure conditions or those changed through human activity/intervention (e.g., production, injection, stimulation) during the life of a well.
Prediction of biological age by morphological staging of sarcopenia in Caenorhabditis elegans
Authors: Dhondt Ineke , Verschuuren Clara , Zečić Aleksandra , Loier Tim , Braeckman Bart P. , De Vos Winnok H. 
Published: November 2021

ABSTRACT
Sarcopenia encompasses a progressive decline in muscle quantity and quality. Given its close association with ageing, it may represent a valuable healthspan marker. The commonalities with human muscle structure and facile visualization possibilities make Caenorhabditis elegans an attractive model for studying the relationship between sarcopenia and healthspan. However, classical visual assessment of muscle architecture is subjective and has low throughput. To resolve this, we have developed an image analysis pipeline for the quantification of muscle integrity in confocal microscopy images from a cohort of ageing myosin::GFP reporter worms. We extracted a variety of morphological descriptors and found a subset to scale linearly with age. This allowed establishing a linear model that predicts biological age from a morphological muscle signature. To validate the model, we evaluated muscle architecture in long-lived worms that are known to experience delayed sarcopenia by targeted knockdown of the daf-2 gene. We conclude that quantitative microscopy allows for staging sarcopenia in C. elegans and may foster the development of image-based screens in this model organism to identify modulators that mitigate age-related muscle frailty and thus improve healthspan.
The microtubule-associated protein She1 coordinates directional spindle positioning by spatially restricting dynein activity
Authors: Ecklund Kari H. , Bailey Megan E. , Kossen Kelly A. , Dietvorst Carsten K. , Asbury Charles L. , Markus Steven M. 
Published: November 2021

ABSTRACT
Dynein motors move the mitotic spindle to the cell division plane in many cell types, including in budding yeast, in which dynein is assisted by numerous factors including the microtubule-associated protein (MAP) She1. Evidence suggests that She1 plays a role in polarizing dynein-mediated spindle movements toward the daughter cell; however, how She1 performs this function is unknown. We find that She1 assists dynein in maintaining the spindle in close proximity to the bud neck, such that, at anaphase onset, the chromosomes are segregated to mother and daughter cells. She1 does so by attenuating the initiation of dynein-mediated spindle movements within the mother cell, thus ensuring such movements are polarized toward the daughter cell. Our data indicate that this activity relies on She1 binding to the microtubule-bound conformation of the dynein microtubule-binding domain, and to astral microtubules within mother cells. Our findings reveal how an asymmetrically localized MAP directionally tunes dynein activity by attenuating motor activity in a spatially confined manner.
Modifications to the delivery of NHS face-to-face general practice consultations during the COVID-19 pandemic in England
Authors: Duncan Lorna J. , Cheng Kelly F.D. 
Published: November 2021

Background: In order to minimise transmission of SARS-CoV-2, the virus causing COVID-19, delivery of English general practice consultations was modified in March 2020 to enable the separation of patients with diagnosed or suspected COVID-19 from others. Remote triage and consultations became the default, with adapted face-to-face contact used only when clinically necessary. Face-to-face delivery modifications were decided locally and this study aimed to identify the different models used nationwide in spring/summer 2020. Methods: In June 2020, a survey was sent by email to the 135 Clinical Commissioning Groups (CCGs) responsible for planning and commissioning NHS health care services in England to identify the local organisation of face-to-face general practice consultations since March 2020. Results: All CCGs responded. Between March and July 2020, separation of patients with diagnosed or suspected COVID-19 (‘COVID-19 patients’) from others was achieved using the following models: zoned practices (used within 47% of CCGs), where COVID-19 and other patients were separated within their own practice;‘hot’ or ‘cold’ hubs (used within 90% of CCGs), separate sites where COVID-19 or other patients registered at one of several collaborating practices were seen;‘hot’ and ‘cold’ home visits (used within 70% of CCGs). For around half of CCGs, either all their GP practices used zoning, or all used hubs; in other CCGs, both models were used. Demand-led hub availability offered flexibility in some areas. Home visits were mainly used supplementally for patients unable to access other services, but in two CCGs, they were the main/only form of COVID-19 provision. Conclusions: Varied, flexible ways of delivering face-to-face general practice consultations were identified. Analysis of the modified delivery in terms of management of COVID-19 and other conditions, and other impacts on staff and patients, may both aid future pandemic management and identify beneficial elements for practice beyond this.
The legal implications of prenatal diagnosis in Malaysia
Authors: Kuek Chee Ying 
Published: November 2021

Background: Prenatal diagnosis enables detection of any disease or disability of the fetus during the pregnancy of a woman. Parents whose fetus is found to have a serious disorder from antenatal testing may terminate the pregnancy if it is permitted by the law or continue with the pregnancy to term. However, the chance of terminating a pregnancy may be denied if there is prenatal negligence by the medical practitioner in terms of diagnosis or failure to advise on the test results correctly. The purpose of this research is to examine the possible legal implications of prenatal diagnosis in Malaysia. Methods: This study adopts doctrinal legal research in which the researcher examines statutes and decided cases in Malaysia, the United Kingdom (UK) and Singapore relating to abortion, wrongful birth and wrongful life claims, in order to determine the legal implications of prenatal diagnosis in Malaysia. Results: In Malaysia, abortion following a prenatal diagnosis is only legally possible if the statutory criteria in the Penal Code are met. Abortion is illegal if it is not done for therapeutic purposes. A wrongful birth action brought by a woman who claims to be deprived of the opportunity to terminate her pregnancy may be successful in Malaysia, if it can be proven that a legal abortion could have been performed if not because of the prenatal negligence of the medical practitioner. However, a wrongful life action brought in the child’s name for being allowed to be born with a disability may not be viable since the claim could hardly be established and it is against the public policy. Conclusions: Theoretically, it is possible to bring a wrongful birth action resulted from negligence in prenatal diagnosis successfully in Malaysia, but the chance is relatively slim for wrongful life action.
What factors drive polyethylene wear in total knee arthroplasty?
Authors: Currier John H. , Currier Barbara H. , Abdel Matthew P. , Berry Daniel J. , Titus Alexander J. , Van Citters Douglas W. 
Published: November 2021

Aims Wear of the polyethylene (PE) tibial insert of total knee arthroplasty (TKA) increases the risk of revision surgery with a significant cost burden on the healthcare system. This study quantifies wear performance of tibial inserts in a large and diverse series of retrieved TKAs to evaluate the effect of factors related to the patient, knee design, and bearing material on tibial insert wear performance. Methods An institutional review board-approved retrieval archive was surveyed for modular PE tibial inserts over a range of in vivo duration (mean 58 months (0 to 290)). Five knee designs, totalling 1,585 devices, were studied. Insert wear was estimated from measured thickness change using a previously published method. Linear regression statistical analyses were used to test association of 12 patient and implant design variables with calculated wear rate. Results Five patient-specific variables and seven implant-specific variables were evaluated for significant association with lower insert wear rate. Six were significant when controlling for other factors: greater patient age, female sex, shorter duration in vivo, polished tray, highly cross-linked PE (HXLPE), and constrained knee design. Conclusion This study confirmed that knee wear rate increased with duration in vivo. Older patients and females had significantly lower wear rates. Polished modular tibial tray surfaces, HXLPE, and constrained TKA designs were device design factors associated with significantly reduced wear rate. Cite this article: Bone Joint J 2021;103-B(11):1695–1701.