bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluorescent Light Energy and Chronic Lesions: A Winning Association
Authors: Crema Alberto , Scarpa Carlotta , Sonda Regina , Rizzato Sandro , Masciopinto Giuseppe , Bassetto Franco
Published: July 2021

Background:

Chronic ulcers represent a challenge for healthcare professionals and a large expense for national health care systems for their difficulty in achieving complete healing and for their high incidence of recurrence. With the progressive aging of the general population, the incidence of these injuries will only increase, further affecting the public health budget, hence the need to find new strategies for their management. The purpose of this study was to share the experience of the Complex Operational Unit of Plastic Surgery of the University Hospital of Padua with fluorescent light energy therapy, outlining its role in the treatment of chronic ulcers in the daily use outside the previous EUREKA study.

Methods:

In this case series study, we enrolled 15 patients with chronic ulcers of any etiology between January 2018 and July 2019 and we treated them using fluorescence light energy. We evaluated efficacy and safety endpoints reporting data in excel files completed by medical staff during the study.

Results:

The study confirms the effectiveness of fluorescent light energy inducing chronic ulcer healing, regardless of etiology, or at least preparing the lesions for a skin graft closure surgery. The system showed a low rate of complications established by patient adherence to treatment. Patients also reported a reduction in pain both at home and during outpatient dressings.

Conclusion:

Based on our experience, fluorescent light energy shows an excellent safety and efficacy profile in chronic ulcers no more responsive to traditional dressings and/or surgery.
Psychological and Aesthetic Outcomes in Breast Cancer Patients
Authors: Ermoshchenkova Maria V. , Zikiryahodjaev Aziz D. , Reshetov Igor V. , Svyatoslavov Dmitriy S. , Sinelnikov Mikhail Y.
Published: July 2021

Background:

Patients who undergo breast cancer treatment require psychosocial and aesthetic rehabilitation. Advantages of breast reconstruction in-patient rehabilitation are well known. Oncoplastic organ-preserving surgery offers aesthetically better results, yet is often considered less safe than more radical procedures. We compared the aesthetic and psychological outcomes in patients undergoing breast reconstruction and oncoplastic breast cancer treatment.

Methods:

In total, 1130 patients who received either breast reconstruction or oncoplastic breast cancer surgery were included in the study. Patients were classified into two groups. Group 1 included 510 patients who received breast reconstruction surgery. Group 2 included 620 patients who received oncoplastic surgery. The following aspects were compared between the two groups: demographics, tumor progression, and immunohistochemical aspects, complications, hospitalization stay, and psychological and aesthetic outcomes.

Results:

Patients in the oncoplastic group showed statistically significant higher psychosocial and aesthetic outcomes, as well as lower incidence of complications, revision rate, disease progression, and recurrence. The majority of oncoplastic patients were treated in early stages of breast cancer.

Conclusion:

Offering superior treatment results, oncoplastic organ-preserving surgery should be favored in patients with earlier stages of cancer progression.
Neuroplasticity following Nerve Transfer of the Anterior Interosseous Nerve for Proximal Ulnar Nerve Injuries
Authors: Nyman Erika , Nyman Torbjörn , Rubensson Carin , Thordstein Magnus
Published: July 2021

Background:

Injuries to the ulnar nerve at or above proximal forearm level result in poor recovery despite early microsurgical repair, especially concerning the intrinsic motor function of the hand. To augment the numbers of regenerating axons into the targeted muscles, a nerve transfer of the distal branch of the median nerve, the anterior interosseous nerve, to the ulnar motor branch has been described.

Methods:

Two patients with severe atrophy of the intrinsic hand muscles following an initial proximal ulnar nerve repair had surgery with an end-to-side transfer of the anterior interosseous nerve to the ulnar motor branch at the wrist level. Outcome and neuroplasticity were prospectively studied using questionnaires, clinical examinations, electroneurography, electromyography, somatosensory evoked potentials at pre nerve transfer and 3-, 12-, and 24-months post nerve transfer as well as navigated transcranial magnetic stimulation at pre nerve transfer and 3- and 12-months post nerve transfer.

Results:

Successively improved motor function was observed. Complete reinnervation of intrinsic hand muscles was demonstrated at 12- to 24-months follow-up by electroneurography and electromyography. At the cortical level, navigated transcranial magnetic stimulation detected a movement of the hot-spot for the abductor digiti mini muscle, originally innervated by the ulnar nerve and the size of the area from where responses could be elicited in this muscle changed over time, indicating central plastic processes. An almost complete reinnervation of the pronator quadratus muscle was also observed.

Conclusion:

Both central and peripheral plastic mechanisms are involved in muscle reinnervation after anterior interosseous nerve transfer for treatment of proximal ulnar nerve injuries.
Plastic Surgeons Nationwide Share Experience Regarding Telemedicine in Initial Patient Screening and Routine Postoperative Visits
Authors: Calderon Thais , Skibba Kathryn E.H. , Langstein Howard N.
Published: July 2021

Physicians attempted to continue providing patient care through the SARS-CoV2 (COVID-19) pandemic. Surgeons embraced telemedicine as patient evaluation transitioned from physical encounters to virtual appointments. However, there is a paucity in the literature on the utility of telemedicine within plastic surgery or how it can meet patients’ needs. A survey study was created to assess surgeons’ involvement and experience with telemedicine. Subjective experience was assessed on a five-point Likert scale (1 = strongly disagree, 2 = disagree, 3 = neutral, 4 = agree, 5 = strongly agree). This survey was distributed to the members of the American Society of Plastic Surgeons. Data were collected and analyzed via RedCap. Of the total 177 plastic surgeons who responded, 139 (78.5%) surgeons reported the implementation of telemedicine during the pandemic. Plastic surgeons felt that they were able to establish rapport (3.9 ± 0.9), meet the goals of the encounter (3.6 ± 1.0), and efficiently evaluate patients (3.5 ± 1.2). Plastic surgeons reported their overall experience was between helpful and neutral (3.2 ± 1.3). Most plastic surgeons have implemented telemedicine in their practice. The majority of telemedicine use was for breast, cosmetic, and reconstructive patient care. Telemedicine was most frequently used for initial patient screening and routine postoperative visits. Surgeons plan to continue using telemedicine when appropriate for patient screening and routine or unexpected postoperative visits in the future. Many have found utility of telemedicine in providing patient care and it is likely that telemedicine will be a part of routine practice moving forward.
Late-onset haze associated with chikungunya infection
Authors: Souza de Oliveira Renato Correa , Klejnberg Tatiana , Klejnberg Celso , Campos Mauro
Published: July 2021

A 42-year-old woman, who had undergone photorefractive keratectomy (PRK) 12 years earlier, complained of blurring of vision within 2 weeks of chikungunya infection. A central corneal stromal haze was observed in the left eye. Her corrected distance visual acuity was 20/200. The haze did not improve despite the use of topical corticosteroids; however, corneal clarity was restored, and vision improved with phototherapeutic keratectomy (PTK) and treatment with mitomycin-C (MMC) 0.02%. Late-onset stromal scarring can be triggered by systemic infection even years after PRK. PTK with MMC may be an effective treatment option for late-onset scars.
Breast Implants
Authors: Powell Lauren E. , Andersen Emily S. , Nigro Lauren C. , Pozez Andrea L. , Shah Priti A.
Published: July 2021

Modern breast surgery was first introduced in the United States in 1962 with the use of silicone gel-filled breast implants. Over the past 6 decades, development of breast implants has been challenged by a variety of influencers including aesthetic appeal in shape, texture, and material; challenges in managing outcomes such as contracture, disease, and rupture; and public perception of risks associated with implants. In 1992, silicone breast prostheses were banned by the US Food and Drug Administration with exception for use in breast reconstruction, congenital deformities, or to replace existing implants.

The ban led to heightened concerns about implants and possible disease manifestations. Knowledge of the historical evolution of breast prostheses is useful for understanding the associated risks and outcomes unique to each breast implant era. This article aimed to explore characteristics of breast implants by generation, with implications for diagnosis and assistance to modern surgical planning for novice plastic surgeons.
Duodenal ulcer perforation: A systematic literature review and narrative description of surgical techniques used to treat large duodenal defects
Authors: Clinch Darja , Damaskos Dimitrios , Di Marzo Fransesco , Di Saverio Salomone
Published: July 2021

BACKGROUND

There is no consensus on optimal surgical treatment of large duodenal defects arising from perforated ulcers, even though such defects are challenging to repair and inadequate repair is associated with high morbidity and mortality. The aim of this study was to carry out a systematic literature review of different surgical techniques used to treat large duodenal perforations, provide a narrative description of these techniques, and propose a framework for approaching this pathology.

METHODS

PubMed/MEDLINE database was searched for articles published in English between January 1, 1970, and December 1, 2020. Studies describing surgical techniques used to treat giant duodenal ulcer perforation and their outcomes in adult patients were included. No quantitative analysis was planned because of the heterogeneity across studies.

RESULTS

Out of 960 identified records, 25 studies were eligible for inclusion. Two randomized controlled trials, one case-control trial, three cohort studies, 14 case series, and 5 case reports were included. Eight main surgical approaches are described, ranging from simple damage-control operations, such as the omental plug and triple-tube techniques, all the way to complex resections, such as gastrectomy.

CONCLUSION

Evidence on surgical treatment of large duodenal defects is of poor quality, with the majority of studies corresponding to Oxford levels 3b-4. Current evidence does not support any single surgical technique as superior in terms of morbidity or mortality, but choice of technique should be guided by several factors including location of the perforation, degree of duodenal tissue loss, hemodynamic stability of the patient, as well as expertise of the operating surgeon.

LEVEL OF EVIDENCE

SR with more than two negative criteria, Level IV.
Integrated vaccination and non-pharmaceutical interventions based strategies in Ontario, Canada, as a case study: a mathematical modelling study
Authors: Betti Matthew , Bragazzi Nicola Luigi , Heffernan Jane M. , Kong Jude , Raad Angie
Published: July 2021

Recently, two coronavirus disease 2019 (COVID-19) vaccine products have been authorized in Canada. It is of crucial importance to model an integrated/combined package of non-pharmaceutical (physical/social distancing) and pharmaceutical (immunization) public health control measures. A modified epidemiological, compartmental SIR model was used and fit to the cumulative COVID-19 case data for the province of Ontario, Canada, from 8 September 2020 to 8 December 2020. Different vaccine roll-out strategies were simulated until 75% of the population was vaccinated, including a no-vaccination scenario. We compete these vaccination strategies with relaxation of non-pharmaceutical interventions. Non-pharmaceutical interventions were supposed to remain enforced and began to be relaxed on 31 January, 31 March or 1 May 2021. Based on projections from the data and long-term extrapolation of scenarios, relaxing the public health measures implemented by re-opening too early would cause any benefits of vaccination to be lost by increasing case numbers, increasing the effective reproduction number above 1 and thus increasing the risk of localized outbreaks. If relaxation is, instead, delayed and 75% of the Ontarian population gets vaccinated by the end of the year, re-opening can occur with very little risk. Relaxing non-pharmaceutical interventions by re-opening and vaccine deployment is a careful balancing act. Our combination of model projections from data and simulation of different strategies and scenarios, can equip local public health decision- and policy-makers with projections concerning the COVID-19 epidemiological trend, helping them in the decision-making process.
Seismic localization of elephant rumbles as a monitoring approach
Authors: Reinwald Michael , Moseley Ben , Szenicer Alexandre , Nissen-Meyer Tarje , Oduor Sandy , Vollrath Fritz , Markham Andrew , Mortimer Beth
Published: July 2021

African elephants (Loxodonta africana) are sentient and intelligent animals that use a variety of vocalizations to greet, warn or communicate with each other. Their low-frequency rumbles propagate through the air as well as through the ground and the physical properties of both media cause differences in frequency filtering and propagation distances of the respective wave. However, it is not well understood how each mode contributes to the animals’ abilities to detect these rumbles and extract behavioural or spatial information. In this study, we recorded seismic and co-generated acoustic rumbles in Kenya and compared their potential use to localize the vocalizing animal using the same multi-lateration algorithms. For our experimental set-up, seismic localization has higher accuracy than acoustic, and bimodal localization does not improve results. We conclude that seismic rumbles can be used to remotely monitor and even decipher elephant social interactions, presenting us with a tool for far-reaching, non-intrusive and surprisingly informative wildlife monitoring.
Parallel evolution of trehalose production machinery in anhydrobiotic animals via recurrent gene loss and horizontal transfer
Authors: Hara Yuichiro , Shibahara Reira , Kondo Koyuki , Abe Wataru , Kunieda Takekazu
Published: July 2021

Trehalose is a versatile non-reducing sugar. In some animal groups possessing its intrinsic production machinery, it is used as a potent protectant against environmental stresses, as well as blood sugar. However, the trehalose biosynthesis genes remain unidentified in the large majority of metazoan phyla, including vertebrates. To uncover the evolutionary history of trehalose production machinery in metazoans, we scrutinized the available genome resources and identified bifunctional trehalose-6-phosphate synthase-trehalose-6-phosphate phosphatase (TPS–TPP) genes in various taxa. The scan included our newly sequenced genome assembly of a desiccation-tolerant tardigrade
Paramacrobiotus
sp. TYO, revealing that this species retains TPS–TPP genes activated upon desiccation. Phylogenetic analyses identified a monophyletic group of the many of the metazoan TPS–TPP genes, namely ‘pan-metazoan’ genes, that were acquired in the early ancestors of metazoans. Furthermore, coordination of our results with the previous horizontal gene transfer studies illuminated that the two tardigrade lineages, nematodes and bdelloid rotifers, all of which include desiccation-tolerant species, independently acquired the TPS–TPP homologues via horizontal transfer accompanied with loss of the ‘pan-metazoan’ genes. Our results indicate that the parallel evolution of trehalose synthesis via recurrent loss and horizontal transfer of the biosynthesis genes resulted in the acquisition and/or augmentation of anhydrobiotic lives in animals.
Early detection of wildlife morbidity and mortality through an event-based surveillance system
Authors: Kelly Terra R. , Pandit Pranav S. , Carion Nicole , Dombrowski Devin F. , Rogers Krysta H. , McMillin Stella C. , Clifford Deana L. , Riberi Anthony , Ziccardi Michael H. , Donnelly-Greenan Erica L. , Johnson Christine K.
Published: July 2021

The ability to rapidly detect and respond to wildlife morbidity and mortality events is critical for reducing threats to wildlife populations. Surveillance systems that use pre-diagnostic clinical data can contribute to the early detection of wildlife morbidities caused by a multitude of threats, including disease and anthropogenic disturbances. Here, we demonstrate proof of concept for use of a wildlife disease surveillance system, the ‘Wildlife Morbidity and Mortality Event Alert System’, that integrates pre-diagnostic clinical data in near real-time from a network of wildlife rehabilitation organizations, for early and enhanced detection of unusual wildlife morbidity and mortality events. The system classifies clinical pre-diagnostic data into relevant clinical classifications based on a natural language processing algorithm, generating alerts when more than the expected number of cases is recorded across the rehabilitation network. We demonstrated the effectiveness and efficiency of the system in alerting to events associated with both common and emerging diseases. Tapping into this readily available unconventional general surveillance data stream offers added value to existing wildlife disease surveillance programmes through a relatively efficient, low-cost strategy for the early detection of threats.
Transmission of SARS-CoV-2 into and within immigrant households. Nation-wide registry-study from Norway
Authors: Methi Fredrik , Hart Rannveig , Godøy Anna , Jørgensen Silje , Kacelnik Oliver , Telle Kjetil
Published: July 2021

Background

Minority ethnic groups and immigrants have been hit disproportionally hard by COVID-19 in many developed countries, including Norway. Most transmissions of SARS-CoV-2 occur in households.

Methods

Using individual-level registry data of all Norwegian residents we compared infections across all multi-person households. A household with at least one member born abroad was defined as an immigrant household. For the subset of households where at least one person tested positive for SARS-CoV-2 from August 1st 2020 to May 1st 2021, we calculated secondary attack rates (SARs) as the percent of other household members testing positive within 14 days after the first household member tested positive. Logistic regression model was used to adjust for sex, age, household composition and geography.

Results

Among all multi-person households in Norway (n=1 421 642), immigrant households (n=341 604) comprised more members on average (3.2) than households with only Norwegian-born members (2.8). The share of immigrant households where at least one member had been tested, was 56% (vs 49% in the households with only Norwegian-born members), and the share where at least one member was infected was 3.7% (vs 1.4% in households with only Norwegian-born members). Secondary attack rates were higher in immigrant (32%) than Norwegian-born households (20%). Results differed considerably by country of birth, with secondary attack rates particularly high in households from Syria, Iraq, Turkey, and Pakistan, also after adjustment for sex, age, household composition and geography.

Conclusion

SARS-CoV-2 is more frequently introduced into multi-person immigrant households than into households with only Norwegian-born members, and transmission within the household occurs more frequently in immigrant households. The results are likely related to living conditions, family composition or differences in social interaction, emphasizing the need to prevent introduction of SARS-CoV-2 into these vulnerable households.
Lentiviral vector optimization enhances the expression and cytotoxicity of chimeric antigen receptors
Authors: Guo Changjiang , Chen Han , Yu Jie , Lu Hui , Guo Xiali , Li Xiaojuan , Wang Tong , Zhi Lingtong , Niu Zhiyuan , Zhu Wuling
Published: July 2021

Adoptive chimeric antigen receptor (CAR)-modified T or NK cells (CAR-T/NK) have emerged as a novel form of disease treatment. Lentiviral vectors (LVs) are commonly employed to engineer T/NK cells for the efficient expression of CARs. This study reported for the first time the influence of single-promoter and dual-promoter LVs on the CAR expression and cytotoxicity of engineered NK cells. Our results demonstrated that the selected CAR exhibits both a higher expression level and a higher coexpression concordance with the GFP reporter in HEK-293T or NK92 cells by utilizing the optimized single-promoter pCDHsp rather than the original dual-promoter pCDHdp. After puromycin selection, the pCDHsp produces robust CAR expression and enhancedin vitrocytotoxicity of engineered NK cells. Therefore, infection with a single-promoter pCDHsp lentivector is recommended to prepare CAR-engineered cells. This research will help to optimize the production of CAR-NK cells and improve their functional activity, to provide CAR-NK cell products with better and more uniform quality.
Nitrous Oxide Enhances Focused Ultrasound Mediated Delivery of Viral Gene Therapy
Authors: Shah Bhavya R. , Bailey Rachel M. , Youssef Ibrahim , Holmes Sydni K. , Marckx Austin , Estill-Terpac Sandi Jo , Diamond Marc , Chopra Rajiv
Published: July 2021

Transcranial Magnetic Resonance Guided Focused Ultrasound (MRgFUS) can be used in conjunction with intravenous microbubbles to open the blood brain barrier (BBB) in discrete brain regions. This method is limited by the microbubble dose, the amount of energy that can be safely delivered across an intact skull, and the inability to target areas of the brain outside of central brain regions. We find that N2O administration substantially decreases the required dose of microbubbles and/or focused ultrasound pressure while still reliably opening the blood brain barrier. Additionally, we observe that the use of nitrous oxide improves the delivery of adeno-associated virus (AAV9) vector when compared to medical air. Our findings may help overcome focused ultrasound limitations and improve targeted delivery of therapeutics in humans.

One Sentence Summary

Nitrous Oxide potentiates Blood Brain Barrier opening with Focused Ultrasound and enhances viral vector delivery.
Variation in root system architecture among the founder parents of two 8-way MAGIC wheat populations for selection in breeding
Authors: Pariyar Shree R. , Nagel Kerstin A. , Lentz Jonas , Galinski Anna , Wilhelm Jens , Putz Alexander , Adels Sascha , Heinz Kathrin , Frohberg Claus , Watt Michelle
Published: July 2021

Root system architecture (RSA) is a target for breeding because of the interest to develop crops with roots that use nutrients and water more effectively. Breeding for RSA requires phenotypic diversity in populations amenable to QTL identification to provide markers for large breeding programs. This study examined the variation for root traits across the parents of two multi-parent advanced generation inter-cross (MAGIC) wheat populations from NIAB and CSIRO for 16 days in an upgraded version of the non-invasive, germination paper-based phenotyping platform, GrowScreen-PaGe. Across all parents, total root length varied up to 1.90 fold, root biomass 2.25 fold and seminal root angle 1.16 fold. The CSIRO parents grew faster, exhibited slightly wider seminal root angle and produced larger root systems compared to NIAB parents. Lateral root lengths, leaf lengths and biomass contrasted most between fastest (Robigus - NIAB and AC Barrie - CSIRO) and slowest growing parents (Rialto - NIAB and G204 Xiaoyan54 - CSIRO). Lengths of lateral and total root, and leaf number and length had moderate to high heritability (0.30-0.67) and repeatability. Lengths of lateral roots and leaves are good targets for enhancing wheat crop establishment, a critical stage for crop productivity.
Rapid shifts in mitochondrial tRNA import in a plant lineage with extensive mitochondrial tRNA gene loss
Authors: Warren Jessica M. , Salinas-Giegé Thalia , Triant Deborah A. , Taylor Douglas R. , Drouard Laurence , Sloan Daniel B.
Published: July 2021

In most eukaryotes, transfer RNAs (tRNAs) are one of the very few classes of genes remaining in the mitochondrial genome, but some mitochondria have lost these vestiges of their prokaryotic ancestry. Sequencing of mitogenomes from the flowering plant genus Silene previously revealed a large range in tRNA gene content, suggesting rapid and ongoing gene loss/replacement. Here, we use this system to test longstanding hypotheses about how mitochondrial tRNA genes are replaced by importing nuclear-encoded tRNAs. We traced the evolutionary history of these gene loss events by sequencing mitochondrial genomes from key outgroups (Agrostemma githago and Silene [=Lychnis] chalcedonica). We then performed the first global sequencing of purified plant mitochondrial tRNA populations to characterize the expression of mitochondrial-encoded tRNAs and the identity of imported nuclear-encoded tRNAs. We also confirmed the utility of high-throughput sequencing methods for the detection of tRNA import by sequencing mitochondrial tRNA populations in a species (Solanum tuberosum) with known tRNA trafficking patterns. Mitochondrial tRNA sequencing in Silene revealed substantial shifts in the abundance of some nuclear-encoded tRNAs in conjunction with their recent history of mt-tRNA gene loss and surprising cases where tRNAs with anticodons still encoded in the mitochondrial genome also appeared to be imported. These data suggest that nuclear-encoded counterparts are likely replacing mitochondrial tRNAs even in systems with recent mitochondrial tRNA gene loss, and the redundant import of a nuclear-encoded tRNA may provide a mechanism for functional replacement between translation systems separated by billions of years of evolutionary divergence.
Double nicking by RNA-directed Cascade-nCas3 for high-efficiency large-scale genome engineering
Authors: Hao Yile , Wang Qinhua , Li Jie , Yang Shihui , Ma Lixin , Zheng Yanli , Peng Wenfang
Published: July 2021

New CRISPR-based genome editing technologies are developed to continuedly drive advances in life sciences, which, however, are predominantly derived from systems of Type II CRISPR-Cas9 and Type V CRISPR-Cas12a for eukaryotes. Here we report a novel CRISPR-n(nickase)Cas3 genome editing tool established upon an endogenous Type I system of Zymomonas mobilis. We demonstrate that nCas3 variants can be created by alanine-substituting any catalytic residue of the Cas3 helicase domain. While nCas3 overproduction via plasmid shows severe cytotoxicity; an in situ nCas3 introduces targeted double-strand breaks, facilitating genome editing, without visible cell killing. By harnessing this CRISPR-nCas3, deletion of genes or genomic DNA stretches can be consistently accomplished with near-100% efficiencies, including simultaneous removal of two large genomic fragments. Our work describes the first establishment of a CRISPR-nCas3-based genome editing technology, thereby offering a simple, easy, yet useful approach to convert many endogenous Type I systems into advanced genome editing tools. We envision that many CRISPR-nCas3-based toolkits would be soon available for various industrially important non-model bacteria that carry active Type I systems to facilitate high-throughput prokaryotic engineering.
Immunogenicity and pre-clinical efficacy of an OMV-based SARS-CoV-2 vaccine
Authors: Grandi Alberto , Tomasi Michele , Bertelli Cinzia , Vanzo Teresa , Gagliardi Assunta , Caproni Elena , Tamburini Silvia , Fantappiè Laura , Di Lascio Gabriele , Bisoffi Zeno , Piubelli Chiara , Valenti Maria Teresa , Carbonare Luca Dalle , Zipeto Donato , Ravà Micol , Fumagalli Valeria , Di Lucia Pietro , Marotta Davide , Sala Eleonora , Iannacone Matteo , Cherepanov Peter , Bolognesi Martino , Pizzato Massimo , Grandi Guido
Published: July 2021

The vaccination campaign against SARS-CoV-2 relies on the world-wide availability of effective vaccines, with a potential need of 20 billion vaccine doses to fully vaccinate the world population. To reach this goal, the manufacturing and logistic processes should be affordable to all countries, irrespectively of economical and climatic conditions.

Outer membrane vesicles (OMVs) are bacterial-derived vesicles that can be engineered to incorporate heterologous antigens. Given the inherent adjuvanticity, such modified OMVs can be used as vaccine to induce potent immune responses against the associated protein. Here we show that OMVs engineered to incorporate peptides derived from the receptor binding motif (RBM) of the spike protein from SARS-CoV-2 elicit an effective immune response in immunized mice, resulting in the production of neutralizing antibodies. The immunity induced by the vaccine is sufficient to protect K18-hACE2 transgenic mice from intranasal challenge with SARS-CoV-2, preventing both virus replication in the lungs and the pathology associated with virus infection. Furthermore, we show that OMVs can be effectively decorated with RBM peptides derived from a different genetic variant of SARS-CoV-2, inducing a similarly potent neutralization activity in vaccinated mice. Altogether, given the convenience associated with ease of engineering, production and distribution, our results demonstrate that OMV-based SARS-CoV-2 vaccines can be a crucial addition to the vaccines currently available.
Complete genomic and epigenetic maps of human centromeres
Authors: Altemose Nicolas , Logsdon Glennis A. , Bzikadze Andrey V. , Sidhwani Pragya , Langley Sasha A. , Caldas Gina V. , Hoyt Savannah J. , Uralsky Lev , Ryabov Fedor D. , Shew Colin J. , Sauria Michael E.G. , Borchers Matthew , Gershman Ariel , Mikheenko Alla , Shepelev Valery A. , Dvorkina Tatiana , Kunyavskaya Olga , Vollger Mitchell R. , Rhie Arang , McCartney Ann M. , Asri Mobin , Lorig-Roach Ryan , Shafin Kishwar , Aganezov Sergey , Olson Daniel , de Lima Leonardo Gomes , Potapova Tamara , Hartley Gabrielle A. , Haukness Marina , Kerpedjiev Peter , Gusev Fedor , Tigyi Kristof , Brooks Shelise , Young Alice , Nurk Sergey , Koren Sergey , Salama Sofie R. , Paten Benedict , Rogaev Evgeny I. , Streets Aaron , Karpen Gary H. , Dernburg Abby F. , Sullivan Beth A. , Straight Aaron F. , Wheeler Travis J. , Gerton Jennifer L. , Eichler Evan E. , Phillippy Adam M. , Timp Winston , Dennis Megan Y. , O’Neill Rachel J. , Zook Justin M. , Schatz Michael C. , Pevzner Pavel A. , Diekhans Mark , Langley Charles H. , Alexandrov Ivan A. , Miga Karen H.
Published: July 2021

Existing human genome assemblies have almost entirely excluded highly repetitive sequences within and near centromeres, limiting our understanding of their sequence, evolution, and essential role in chromosome segregation. Here, we present an extensive study of newly assembled peri/centromeric sequences representing 6.2% (189.9 Mb) of the first complete, telomere-to-telomere human genome assembly (T2T-CHM13). We discovered novel patterns of peri/centromeric repeat organization, variation, and evolution at both large and small length scales. We also found that inner kinetochore proteins tend to overlap the most recently duplicated subregions within centromeres. Finally, we compared chromosome X centromeres across a diverse panel of individuals and uncovered structural, epigenetic, and sequence variation at single-base resolution across these regions. In total, this work provides an unprecedented atlas of human centromeres to guide future studies of their complex and critical functions as well as their unique evolutionary dynamics.

One-sentence summary

Deep characterization of fully assembled human centromeres reveals their architecture and fine-scale organization, variation, and evolution.
How drugs modulate the performance of the human heart
Authors: Peirlinck Mathias , Yao Jiang , Costabal Francisco Sahli , Kuhl Ellen
Published: July 2021

Many drugs interact with ion channels in the cells of the heart and trigger heart rhythm disorders with potentially fatal consequences. Computational modeling can provide mechanistic insight into the onset and propagation of drug-induced arrhythmias, but the effect of drugs on the mechanical behavior of the heart remains poorly understood. Here we establish a multiphysics framework that integrates the biochemical, electrical, and mechanical effects of drugs from single cardiac cells to the overall response of the whole heart. For the example of the drug dofetilide, we show that drug concentrations of 3.0x and 4.8x increase the heart rate to 122 and 114 beats per minute, increase the myofiber stretches up to 10%, and decrease tissue relaxation by 6%. Strikingly, the drug-induced interventricular and atrial-ventricular dyssynchrony results in a 2.5% decreased and 7% increased cardiac output, respectively. Our results demonstrate the potential for multiphysics, multiscale modeling towards understanding the mechanical implications of drug-induced arrhythmias. Knowing how differing drug concentrations affect the performance of the heart has important clinical implications in drug safety evaluation and personalized medicine.
Prolonged morphological expansion of spiny-rayed fishes following the end-Cretaceous
Authors: Ghezelayagh Ava , Harrington Richard C. , Burress Edward D. , Campbell Matthew A. , Buckner Janet C. , Chakrabarty Prosanta , Glass Jessica R. , Tyler McCraney W. , Unmack Peter J. , Thacker Christine E. , Alfaro Michael E. , Friedman Sarah T. , Ludt William B. , Cowman Peter F. , Friedman Matt , Price Samantha A. , Dornburg Alex , Faircloth Brant C. , Wainwright Peter C. , Near Thomas J.
Published: July 2021

Spiny-rayed fishes (Acanthomorpha) dominate modern marine habitats and comprise more than a quarter of all living vertebrate species1–3. It is believed that this dominance resulted from explosive lineage and phenotypic diversification coincident with the Cretaceous-Paleogene (K-Pg) mass-extinction event4. It remains unclear, however, if living acanthomorph diversity is the result of a punctuated burst or gradual accumulation of diversity following the K-Pg. We assess these hypotheses with a time-calibrated phylogeny inferred using ultraconserved elements from a sampling of species that represent over 91% of all acanthomorph families, as well as an extensive body shape dataset of extant species. Our results indicate that several million years after the end-Cretaceous, acanthomorphs underwent a prolonged and significant expansion of morphological disparity primarily driven by changes in body elongation, and that acanthomorph lineages containing the bulk of the living species diversity originated throughout the Cenozoic. These acanthomorph lineages radiated into distinct regions of morphospace and retained their iconic phenotypes, including a large group of laterally compressed reef fishes, fast-swimming open-ocean predators, bottom-dwelling flatfishes, seahorses, and pufferfishes. The evolutionary success of spiny-rayed fishes is the culmination of a post K-Pg adaptive radiation in which rates of lineage diversification were decoupled from periods of high phenotypic disparity.
An atlas of the Norway spruce needle seasonal transcriptome
Authors: Bag Pushan , Lihavainen Jenna , Delhomme Nicolas , Riquelme Thomas , Robinson Kathryn M , Jansson Stefan
Published: July 2021

Boreal conifers possess a tremendous ability to survive and remain evergreen during harsh winter conditions and resume growth during summer. This is enabled by coordinated regulation of major cellular functions at the level of gene expression, metabolism, and physiology. Here we present a comprehensive characterization of the annual changes in the global transcriptome of Norway spruce needles as a resource to understand needle development and acclimation processes throughout the year. In young, growing needles (May 15 – June 30), cell walls, organelles etc. were formed, and this developmental program heavily influenced the transcriptome, explained by over represented Gene Ontology (GO) categories. Later changes in gene expression were smaller but four phases were recognized: summer (July-August), autumn (September-October), winter (November-February) and spring (March-April), where over represented GO categories demonstrated how the needles acclimated to the various seasons. Changes in the seasonal global transcriptome profile were accompanied by differential expression of members of the major transcription factor families. We present a tentative model of how cellular activities are regulated over the year in needles of Norway spruce, which demonstrates the value of mining this dataset, accessible in ConGenIE together with advanced visualization tools.

Significance statement

The development of Norway spruce needles and their annual cycle of biochemical activities (photosynthesis in the summer, adaptation and survival of the harsh boreal winter) is not well understood. We use deep RNA sequencing to profile the transcriptome over the season, and show how the dataset could be used to give information about “what needles do” over the year, and are here making the dataset available for the scientific community.

Graphical abstract
A drug candidate for treating adverse reactions caused by pathogenic antibodies inducible by COVID-19 virus and vaccines
Authors: Wang Huiru , Wu Xiancong , Zhang Yuekai , Chen Qiuchi , Dai Lin , Chen Yuxing , Liu Xiaoling
Published: July 2021

In a recent study, we reported that certain anti-spike antibodies of COVID-19 and SARS-CoV viruses can have a pathogenic effect through binding to sick lung epithelium cells and misleading immune responses to attack self-cells. We termed this new pathogenic mechanism “Antibody Dependent Auto-Attack” (ADAA). This study explores a drug candidate for prevention and treatment of such ADAA-based diseases. The drug candidate is a formulation comprising N-acetylneuraminic acid methyl ester (NANA-Me), an analog of N-acetylneuraminic acid. NANA-Me acts through a unique mechanism of action (MOA) which is repairment of the missing sialic acid on sick lung epithelium cells. This MOA can block the antibodies’ binding to sick cells, which are vulnerable to pathogenic antibodies. Our in vivo data showed that the formulation significantly reduced the sickness and deaths caused by pathogenic anti-spike antibodies. Therefore, the formulation has the potential to prevent and treat the serious conditions caused by pathogenic antibodies during a COVID-19 infection. In addition, the formulation has potential to prevent and treat the adverse reactions of COVID-19 vaccines because the vaccines can induce similar antibodies, including pathogenic antibodies. The formulation will be helpful in increasing the safety of the vaccines without reducing the vaccine’s efficacy. Compared to existing antiviral drugs, the formulation has a unique MOA of targeting receptors, broad spectrum of indications, excellent safety profile, resistance to mutations, and can be easily produced.
Crystal structure of 2-oxo-2-phenylethyl diisopropylcarbamate
Authors: Martens Viktor , Görls Helmar , Imhof Wolfgang
Published: July 2021

In the molecular structure of the title compound, C15H21NO3, the urethane function and the benzoyl group are almost perpendicular to each other [dihedral angle 88.97 (5)°]. In the crystal structure, infinite supramolecular layers in the bc plane are formed by weak C—H...O hydrogen bonds.
Practical expedients and theoretical flaws: the IASB's legitimacy strategy during the COVID-19 pandemic
Authors: Moscariello Nicola , Pizzo Michele
Published: July 2021

Purpose

Grounded in the legitimacy theory and framed within the context of European Union’s (EU's) endorsement process, this paper analyses the International Accounting Standards Board’s (IASB's) response to the COVID-19 crisis and the impact of its practical expedient COVID-19-Related Rent Concession on the IASB's output legitimacy.

Design/methodology/approach

This study uses a qualitative process-tracing approach and combines inductive historical narratives and deductive reasoning to draw theoretical implications concerning the COVID-19 crisis' impact on the standard-setting process.

Findings

The paper shows a growing reliance on practical expedients in International Financial Reporting Standards (IFRS) to maintain the IASB's output legitimacy. While introducing some theoretical flaws, practical expedients increase the standards' flexibility and strengthen the IASB's ability to respond to the European political bodies' concerns. Indeed, an analysis of the IASB's response to the COVID-19 outbreak reveals the role practical expedients might play not only in reducing (ex ante) new IFRS transition costs but also in dealing (ex-post) with the broader economic impact of unexpected systemic crises to limit criticisms and controversies surrounding IFRS.

Originality/value

This study reveals a causal relationship between the rise of the European public good criterion in the EU endorsement process and the wider use of practical expedients in IFRS. An analysis of the latest amendment to IFRS 16 in response to the COVID-19 crisis also confirms the role of practical expedients in strengthening the acceptance of IFRS in an increasingly complex economic reality and sheds some light on the new strategies adopted by the IASB to preserve its legitimacy in the EU.
On copula moment: empirical likelihood based estimation method
Authors: Abdelli Jihane , Brahimi Brahim
Published: July 2021

Purpose

In this paper, the authors applied the empirical likelihood method, which was originally proposed by Owen, to the copula moment based estimation methods to take advantage of its properties, effectiveness, flexibility and reliability of the nonparametric methods, which have limiting chi-square distributions and may be used to obtain tests or confidence intervals. The authors derive an asymptotically normal estimator of the empirical likelihood based on copula moment estimation methods (ELCM). Finally numerical performance with a simulation experiment of ELCM estimator is studied and compared to the CM estimator, with a good result.

Design/methodology/approach

In this paper we applied the empirical likelihood method which originally proposed by Owen, to the copula moment based estimation methods.

Findings

We derive an asymptotically normal estimator of the empirical likelihood based on copula moment estimation methods (ELCM). Finally numerical performance with a simulation experiment of ELCM estimator is studied and compared to the CM estimator, with a good result.

Originality/value

In this paper we applied the empirical likelihood method which originally proposed by Owen 1988, to the copula moment based estimation methods given by Brahimi and Necir 2012. We derive an new estimator of copula parameters and the asymptotic normality of the empirical likelihood based on copula moment estimation methods.
Extension of the unsymmetric 8-node hexahedral solid element US-ATFH8 to geometrically nonlinear analysis
Authors: Li Zhi , Cen Song , Li Chenfeng
Published: July 2021

Purpose

The purpose of this paper is to extend a recent unsymmetric 8-node, 24-DOF hexahedral solid element US-ATFH8 with high distortion tolerance, which uses the analytical solutions of linear elasticity governing equations as the trial functions (analytical trial function) to geometrically nonlinear analysis.

Design/methodology/approach

Based on the assumption that these analytical trial functions can still properly work in each increment step during the nonlinear analysis, the present work concentrates on the construction of incremental nonlinear formulations of the unsymmetric element US-ATFH8 through two different ways: the general updated Lagrangian (UL) approach and the incremental co-rotational (CR) approach. The key innovation is how to update the stresses containing the linear analytical trial functions.

Findings

Several numerical examples for 3D structures show that both resulting nonlinear elements, US-ATFH8-UL and US-ATFH8-CR, perform very well, no matter whether regular or distorted coarse mesh is used, and exhibit much better performances than those conventional symmetric nonlinear solid elements.

Originality/value

The success of the extension of element US-ATFH8 to geometrically nonlinear analysis again shows the merits of the unsymmetric finite element method with analytical trial functions, although these functions are the analytical solutions of linear elasticity governing equations.
A three-dimensional dental model restoration method based on tooth feature contours
Authors: Yang Shuai , Zhao Wenjie , Ke Yongzhen , Liu Jiaying , Xue Yongjiang
Published: July 2021

Purpose

Due to the inability to directly apply an intra-oral image with esthetic restoration to restore tooth shape in the computer-aided design system, this paper aims to propose a method that can use two-dimensional contours obtained from the image for the three-dimensional dental mesh model restoration.

Design/methodology/approach

First, intra-oral image and smiling image are taken from the patient, then teeth shapes of the images are designed based on esthetic restoration concepts and the pixel coordinates of the teeth’s contours are converted into the vertex coordinates in the three-dimensional space. Second, the dental mesh model is divided into three parts – active part, passive part and fixed part – based on the teeth’s contours of the mesh model. Third, the vertices from the teeth’s contours of the dental model are matched with ones from the intra-oral image and with the help of matching operation, the target coordinates of each vertex in the active part can be calculated. Finally, the Laplacian-based deformation algorithm and mesh smoothing algorithm are performed.

Findings

Benefitting from the proposed method, the dental mesh model with esthetic restoration can be quickly obtained based on the intra-oral image that is the result of doctor-patient communication. Experimental results show that the quality of restoration meets clinical needs, and the typical time cost of the method is approximately one second. So the method is both time-saving and user-friendly.

Originality/value

The method provides the possibility to design personalized dental esthetic restoration solutions rapidly.
What effect did the Green Credit Policy have on China's energy or emission intensive firms?
Authors: Zhang Qin , Xu Li , Wang Keying , Shi Xunpeng
Published: July 2021

Purpose

The role of energy or emission intensive firms face contradictory demands from advancing economic development and environmental improvement and protection and thus require appropriate policy interventions to balance the two needs. China's “Green Credit” policy that restricts loans to energy or emission intensive firms provides an example to study the impact of these kinds of policy intervention.

Design/methodology/approach

Using the data of all A-share listed companies in Shanghai and Shenzhen stock exchanges, our paper empirically analyzes the impact of the Green Credit Policy on performance of these energy or emission intensive firms.

Findings

(1) Using difference-in-difference (DID) and propensity score matching (PSM)-DID method and the dynamic effect method, we found that from 2012 to 2015, the Green Credit Policy had an inhibiting effect on the performance of energy or emission intensive firms. This inhibiting effect was gradually weakened in 2016, and it turned into a positive promoting effect in 2017; (2) The performance's change of these firms around 2015 showed that Green Credit promoted the green transformation and upgrading of these firms; (3) Loans were helpful to the performance of energy or emission intensive firms to some extent, but government subsidies were not significant.

Originality/value

The results suggest that the government, banks and other institutions should dynamically assess the implementation results of the Green Credit Policy on energy or emission intensive firms.