bluuebunny/crossref_metadata_2025 huggingface dataset:
Infraorbital Subcutaneous Intravascular Lobular Capillary Hemangioma After Rhinoplasty
Authors: Kaiser Benedict , Chijioke Obinna , Bruder Elisabeth , Takes Martin , Haug Martin , Mende Konrad
Published: July 2021

Background

Lobular capillary hemangioma (LCH; also referred to as pyogenic granuloma) is a common benign vascular tumor that is characterized by proliferation of capillaries with a lobular architecture. Lobular capillary hemangioma can involve superficial cutaneous, mucosal, or subcutaneous structures; the subcutaneous and intravascular variant is very rare.

Methods

A 26-year-old female patient presented with a small infraorbital mass that was slowly growing within the last 6 months. She reported no pain but an uncomfortable feeling of pressure in this area. Six months before symptom onset, the patient had undergone a closed rhinoplasty with osteotomies without any reported complication.

Results

An excisional biopsy was performed via a transconjunctival approach, and the histopathological findings were characteristic for a subcutaneous intravascular LCH. At the 3-month follow-up, the patient was asymptomatic with no evidence of a recurrent lesion.

Conclusion

To our knowledge, this is the first report of a subcutaneous intravascular LCH after rhinoplasty. We would like to draw the attention of stakeholders to this rare condition and raise awareness among clinicians to what seems to be a late finding after rhinosurgery.
The Ideal Nasal Tip Projection and Rotation Angles in Chinese: A Preference Analysis of the General Population
Authors: Sun Sijie , Liang Xuebing , Wang Chunhu , Li Jie , Ma Jiguang , Wang Keming
Published: July 2021

Rhinoplasty to reshape the nasal tip is increasingly popular among Chinese women. Aesthetic standards vary across different ethnic groups and it is key to identify preferences for the ideal nasal tip in China to set surgical goals. Therefore, we administered an online survey to plastic surgeons and the public through social media to rank nasal tip images by aesthetic preference. Images were created from a single photograph to show various dimensions of nasal tip projection to nasal dorsum length ratio (NTP/NDL) and nasal labial angle (NLA). Preferences were compared by age, sex, living area, ethnic background, occupation, and history of plastic procedures on respondents’ preferences. Overall, there were 703 respondents, including 441 (63%) women and 50 plastic surgeons. Nasal tip projection to nasal dorsum length ratio of 0.63 was ranked highest by all demographic groups, including women (47%), men (50%), and plastic surgeons (66%). Nasal labial angle of 106° was first choice overall and preferred by 34%, 34%, and 52%, respectively. Preferences followed a bell curve for NTP/NDL and NLA, with lower rates of preference as parameters diverged further from the first choice. The preference for NTP/NDL of 0.63 and NLA of 106° was conserved across surgeons, lay people, and all demographic groups. The authors suggest that these proportions could be used as reference for preoperative design in rhinoplasty.
Botulinum Toxin for a Better Scar in Cleft Lip Surgery: A Prospective Randomized Control Trial
Authors: Sonane Jubin , Sharma Ramesh K. , John Jerry R. , Sharma Raman
Published: July 2021

Introduction:

An unsightly scar following cleft repair can undo the good work of even an experienced surgeon. A functioning orbicularis oris muscle beneath the lip scar maintains a zone of dynamic tension resulting in a stretched scar. Botulinum toxin type A (BTA) can be used to create a temporary paralysis of the orbicularis muscle during the healing phase. This may lead to better scar formation after a cleft lip repair.

Method:

The present prospective randomized control trial enrolled 28 infants with unilateral cleft lip undergoing primary lip repair. They were randomized to receive injection of either BTA (botox group) or normal saline (control group) intraoperatively into adjacent orbicularis oris muscle immediately after completion of cleft lip repair. Blinded experts reassessed the scar after 6 months. Objective assessment was undertaken employing Visual Analogue Scale (VAS), Vancouver Scar Scale (VSS), and photographic scar width measurements.

Results:

Twenty-two subjects were able to complete a follow-up duration of 6 months. Children in the BTA (Botox Group) had a statistically significantly better VAS score and lesser scar width compared to the control group. However, the difference in the VSS score between both groups was not statistically significant. On comparing patients with cleft lip alone with cleft lip and palate, no statistically significant difference was found in VAS, VSS, and scar width. There were no complications associated with the use of botulinum toxin A.

Conclusions:

Botulinum toxin type A injection is a safe and effective addition to improve scar appearance following cleft lip repair. There was improvement in appearance of the scar in terms of width, but no improvement was seen in the scar pigmentation. The scar outcome is independent of cleft lip classification.
Craniofacial Evolution: From Australopithecus to Modern Man
Authors: Sambataro Sergio , Fiorillo Luca , Bocchieri Salvatore , Stumpo Chiara , Cervino Gabriele , Herford Alan Scott , Cicciù Marco
Published: July 2021

Through the analysis and evaluation of the size and morphology of teeth and jaws, it is possible to differentiate animal species including man, allowing the theory of human evolution to be established. Hominin evolution is characterized by two main features, the transition to bipedality and the increase in brain size. This had an important impact on the structure and function of the hominine skull. The aim of this article is to retrace the evolutionary steps that led to Homo Sapiens, the direct ancestor of modern man. For the following paper, scientific articles from Medline (PubMed) and Google Scholar database were used from 1929 to 2018. Hominid evolution is characterized by 2 main features, the transition to bipedality and the increase in brain size. The fossils found show that both trends have had an important impact on the morphology and function of the skull of modern man. The basicranial flexion and growth have led to the facial modifications typical of modern man. The main changes concern the mandibular evolution with the appearance of the chin, the formation of the Spee curve due to mandibular arch growth, the formation of the temporomandibular joint as a hinge joint with a sliding socket as the condyle and a better function and maximum efficiency than its predecessors thanks to respect for the divine proportions of the face. Knowledge of ontogenesis allows us to know the factors underlying human form and function, analyze and evaluate them in the clinical context.
Reconstruction of Severe Neck Scar Contracture After Electrical Injury
Authors: Xiao Haitao , Liu Ruolin , Liu Xiaoxue , Wang Huaisheng , Cen Ying , Xu Xuewen
Published: July 2021

High-voltage (≥1000 V) electrical injury is always related to high mortality and poor prognosis. The incidence rates of the high-voltage electrical injuries of the neck are lower than those of the other parts of the body. This article reports a case of the reconstruction of severe neck scar contracture after electrical injury. Compared with cases of scar contractures caused by nonelectrical injuries, this case had the following remarkable characteristics: extremely severe difficult airway, contracture scars involving whole layers of tissue, muscle and nerve damage, mandibular retraction, and poor occlusal relationship. The chief complaints of the patient upon admission, including forced position and continuous salivation, were greatly relieved through several operations by using different kinds of flaps and offering support to the flap from the palmar tendon and relocated mandible. However, the problem of salivation was incompletely solved. This problem might be caused by damage to related nerves and masticatory muscle function caused by high-voltage electrical injury. The patient was satisfied with the recovery of his appearance and movement function.
Cancer care disparities in the LGBT community
Authors: Wakefield Donna
Published: July 2021

Purpose of review

A review of the recent literature (2019–2021) around the current disparities in care for LGBT individuals with cancer.

Recent findings

Recent studies highlight that there continue to be multiple barriers to LGBT individuals with cancer receiving equity of care. These include healthcare professionals (HCPs) lack of knowledge of LGBT-specific issues and an under appreciation of the importance of sexuality and gender in order to provide holistic, person-centred care. Suggestions are made of how embedding training, updating guidelines, and improving communication skills could help to address this care disparity.

Lesbian, gay, bisexual and/or trans (LGBT) individuals have an increased risk of certain illnesses, including certain types of cancer. They belong to a minority group, who may be subjected to discrimination and so are less likely to present for screening or engage with healthcare professionals. This review of recent studies highlights that LGBT individuals still fear discrimination from HCPs, and that many HCPs themselves admit to poor knowledge of LGBT specific issues and the importance of sexuality and gender identity when providing cancer care. Advances in education programmes, including enhanced communication skills and creating LGBT safe spaces are all vital in reducing the disparity in LGBT cancer care.
Clinical-Community Connections
Authors: Schrodt Lori A. , Sledge Rachel A. , Hergott Colleen , Rohrer Beth , Sidelinker Jennifer , Brach Jennifer S. , Vincenzo Jennifer , Shirley Kathleen D. , Shubert Tiffany E.
Published: July 2021

Incorporating evidence-based community programs into clinical care recommendations and goals may help bridge the clinic-to-community transition for older adults. Engagement in evidence-based programs can help older adults manage chronic conditions and reduce fall risk through behavior change and self-management following a clinical episode of care. This article describes evidence-based fall prevention and physical activity programs, provides resources to locate programs, and strategies to match older adults to the right programs.
Atypical chronic inflammatory demyelinating polyradiculoneuropathy: recent advances on classification, diagnosis, and pathogenesis
Authors: Doneddu Pietro Emiliano , Dentoni Marta , Nobile-Orazio Eduardo
Published: July 2021

Purpose of review

In recent years, there has been an intense debate in literature regarding the definition of the individual variants of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), their possible pathogenetic mechanisms, and impact in the diagnosis of CIDP.

Recent findings

The 2021 European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) guidelines revised the definition of the individual CIDP variants and implemented their diagnostic criteria. Diagnosis of atypical CIDP is challenging and misdiagnosis is frequent, leading to diagnostic delay and consequent greater accumulation of disability and treatment dependency. Recent studies suggest that patients with typical CIDP have an antibody-mediated mechanism of neuropathy whereas in those with Lewis--Sumner syndrome (LSS) neuropathy is preferentially mediated by macrophages and T cells.

Although the validity of the 2021 EFNS/PNS diagnostic criteria for atypical CIDP is unknown, they will hopefully lead to greater uniformity in the selection of patients to be enrolled in future studies and to a greater diagnostic accuracy. New data are emerging on the possible pathological mechanisms of individual variants and this could result in the discovery of specific diagnostic biomarkers and new therapies.
Type I interferon receptor-independent interferon-α induction upon infection with a variety of negative-strand RNA viruses
Authors: Anzaghe Martina , Kronhart Stefanie , Niles Marc A. , Höcker Lena , Dominguez Monica , Kochs Georg , Waibler Zoe
Published: July 2021

Type I interferons (IFNs) are a first line of defence against viral infections. Upon infection, a first small wave of early type I IFN, mainly IFN-β and particularly IFN-α4, are induced and bind to the type I IFN receptor (IFNAR) to amplify the IFN response. It was shown for several viruses that robust type I IFN responses require this positive feedback loop via the IFNAR. Recently, we showed that infection of IFNAR knockout mice with the orthomyxovirus Thogoto virus lacking the ML open reading frame (THOV(ML-)) results in the expression of unexpected high amounts of type I IFN. To investigate if IFNAR-independent IFN responses are unique for THOV(ML-), we performed infection experiments with several negative-strand RNA viruses using different routes and dosages for infection. A variety of these viruses induced type I IFN responses IFNAR-independently when using the intraperitoneal (i.p.) route for infection. In vitro studies demonstrated that myeloid dendritic cells (mDC) are capable of producing IFNAR-independent IFN-α responses that are dependent on the expression of the adaptor protein mitochondrial antiviral-signalling protein (MAVS) whereas pDC where entirely depending on the IFNAR feedback loop in vitro. Thus, depending on dose and route of infection, the IFNAR feedback loop is not strictly necessary for robust type I IFN expression and an IFNAR-independent type I IFN production might be the rule rather than the exception for infections with numerous negative-strand RNA viruses.
Evaluation of lymphocyte subtypes in COVID-19 patients
Authors: Rezaei Mitra , Marjani Majid , Tabarsi Payam , Moniri Afshin , purabdollah Mihan , Abtahian Zahra , Dizaji Mehdi Kazempour , Roofchayee Neda Dalil , Dezfuli Neda K. , Mansouri Davood , Hossein-Khannazer Nikoo , Varahram Mohamad , Mortaz Esmaeil , Velayati Ali Akbar
Published: July 2021

Background

Although the many aspects of COVID-19 have not been yet recognized, it seems that the dysregulation of the immune system has a very important role in the progression of the disease. In this study the lymphocyte subsets were evaluated in COVID-19 patients with different severity.

Methods

In this prospective study, the levels of peripheral lymphocyte subsets (CD3+, CD4+, CD8+T cells; CD19+and CD20+B cells; CD16+/CD56+NK cells, and CD4+/CD25+/FOXP3+regulatory T cells) were measured in 67 confirmed patients with COVID-19 on the first day of admission.

Results

The mean age of cases was 51.3 ± 14.8 years. Thirty-two patients (47.8%) were classified as severe cases and 11 (16.4%) patients were categorized as critical. The frequency of blood lymphocytes, CD3+cells, CD25+FOXP3+T cells; and absolute count of CD3+T cells, CD25+FOXP3+T cells, CD4+T cells, CD8+T cells, CD16+56+lymphocytes were lower in more severe cases in comparison to milder cases. Percentages of lymphocytes, T cells, and NK cells were significantly lower inthe patients who died (p= 0.002 and P= 0.042, p=0.006, respectively).

Conclusion

Findings of this cohort study suggests that the frequency of CD4+, CD8+, CD25+FOXP3+T cells, and NK cells were difference in the severe COVID-19 patients. Moreover, lower frequency of, T cells, and NK cells are predictors of mortality of these patients.
EVALUATION OF THE PANBIO SARS-COV-2 RAPID ANTIGEN DETECTION TEST IN THE BAHAMAS
Authors: Johnson Christoph , Ferguson Kirvina , Smith Tavion , Wallace Dashaunette , McConnell Keith , Conserve Donaldson , Martin Indira
Published: July 2021

Identification and isolation of persons infected with SARS-COV-2 are key mitigation strategies in the current pandemic, and rapid antigen detection tests (RADTs) offer the promise of decreased turnaround time to diagnosis when compared with gold standard RT-PCR testing. We evaluated the analytical performance of the Abbott® Panbio™ RADT on nasopharyngeal samples stored at the Ministry of Health National Reference Lab in Nassau, Bahamas. The Panbio™ demonstrated a test sensitivity of 94% and a specificity of 100% on 50 PCR negative samples and 50 samples presumed to be infectious based on having PCR cycle threshold values below 30. Additionally, in our examination of operator results there was low interpersonal variation (1%) among three blind operators and significant correlation between sample Ct value and perceived signal strength on the RADT device. However, three PCR positive samples below Ct 30 were misdiagnosed by RADT, including one sample with Ct value less than 20. These results support the use of the Panbio™ in symptomatic persons to detect active SARS-COV-2 infections, with the caveat that RADT-negative samples should be confirmed by RT-PCR.
Clinical outcomes in vaccinated individuals hospitalized with Delta variant of SARS-CoV-2
Authors: Jagadeesh Kumar V , Sowpati Divya Tej , Munigela Apoorva , Banu Sofia , Siva Archana Bharadwaj , Sasikala M , Nutalapati Chandrasekhar , Kulkarni Anand , Mukherjee Payel , Zaveri Lamuk ,   CCMB COVID-19 Team,   AIG Hospitals COVID-19 Vaccine study Team, Tallapaka Karthik Bharadwaj , Reddy D Nageshwar
Published: July 2021

Emerging variants of SARS-CoV-2 with increased transmissibility or immune escape have been causing large outbreaks of COVID-19 infections across the world. As most of the vaccines currently in use have been derived from viral strains circulating in the early part of the pandemic, it becomes imperative to constantly assess the efficacy of these vaccines against emerging variants. In this hospital-based cohort study, we analysed clinical profiles and outcomes of 1161 COVID-19 hospitalized patients (vaccinated with COVISHIELD (ChAdOx1) or COVAXIN (BBV-152), n = 495 and unvaccinated n = 666) in Hyderabad, India between April 24th and May 31st 2021. Viral genome sequencing revealed that >90% of patients in both groups were harbouring the Delta variant (Pango lineage B.1.617.2) of SARS-CoV-2. Vaccinated individuals showed higher neutralizing antibodies (545±1256 AU/ml Vs 51.1±296 AU/ml; p<0.001) and significantly decreased Ferritin (392.26 ± 448.4 ng/mL Vs 544.82 ± 641.41 ng/mL; p<0.001) and LDH (559.45 ± 324.05 U/L Vs 644.99 ± 294.03 U/L; p<0.001), when compared to the unvaccinated group. Severity of the disease (3.2% Vs 7.2%; p=0.0039) and requirement of ventilatory support (2.8% Vs 5.9%; p=0.0154) were significantly low in the vaccinated group despite the fact that these individuals had significantly higher age and risk factors. The rate of mortality was about 50% lower (2/132=1.51%) in the completely vaccinated breakthrough infections although mortality in individuals who had received a single dose was similar to the unvaccinated group (9/269=3.35% vs 23/666= 3.45%). Our results demonstrate that both COVISHIELD and COVAXIN are effective in preventing disease severity and mortality against the Delta variant in completely vaccinated hospitalized patients.
The age-stratified analytical model for the spread of the COVID-19 epidemic
Authors: Mairanowski F. , Below
Published: July 2021

The previously developed ASILV model for calculating epidemic spread under conditions of lockdown and mass vaccination was modified to analyse the intensity of COVID-19 infection growth in the allocated age groups.

Comparison of the results of calculations of the epidemic spread, as well as the values of the seven-day incidence values with the corresponding observation data, shows their good correspondence for each of the selected age groups.

The greatest influence on the overall spread of the epidemic is in the 20-40 age groups. The relatively low level of vaccination and the high intensity of contact in these age groups contributes to the emergence of new waves of the epidemic, which is especially active when the virus mutates and the lockdown conditions are relaxed.

The intensity of the epidemic in the 90+ age group has some peculiarities compared to other groups, which may be explained by differences in contact patterns among individuals in this age group compared to others.

Approximate ratios for estimating mortality as a function of the intensity of infection for individual age groups are provided.

The proposed stratified ASILV model by age group will allow more detailed and accurate prediction of the spread of the COVID-19 epidemic, including when new, more transmissible versions of the virus mutate and emerge.
Estimating the basic reproduction number at the beginning of an outbreak under incomplete data
Authors: Boonpatcharanon Sawitree , Heffernan Jane , Jankowski Hanna
Published: July 2021

We compare different methods of estimating the basic reproduction number,R0, focusing on the early stages of an epidemic, and considering weekly reports of new infecteds. We study three standard epidemiological models: SIR, SEIR, and SEAIR and examine the sensitivity of the estimators to the model structure. As some methods are developed assuming specific epidemiological models, our work adds a study of their performance in both the well- and miss-specified settings. We focus on parameters matching various types of respiratory viruses, although the general approach is easily extendable to other scenarios.
Hemodilution in High Risk Cardiac Surgery: Laboratory Values, Physiological Parameters and Outcomes
Authors: Mladinov Domagoj , Padilla Luz A , Leahy Benjamin , Norman Joseph B , Enslin Jacob , Camp Riley S , Eudailey Kyle W , Tanaka Kenichi , Davies James E
Published: July 2021

Background

Acute normovolemic hemodilution (ANH) is a blood conservation strategy in cardiac surgery, predominantly used in coronary artery bypass graft (CABG) and/or valve procedures. Although higher complexity cardiac procedures may benefit from ANH, concerns for hemodynamic instability and organ injury during hemodilution hinder its wider acceptance. Laboratory and physiological parameters during hemodilution in complex cardiac surgeries have not been described.

Study Design and Methods

This observational cohort (2019-2021) study included 169 patients who underwent thoracic aortic repair, multiple valve procedure, concomitant CABG with the aforementioned procedure, and/or redo sternotomies. Patients who received allogeneic blood were excluded. Statistical comparisons were performed between ANH (N=66) and non ANH controls (N=103). ANH consisted of removal of blood at the beginning of surgery and its return after cardiopulmonary bypass (CPB).

Results

Intraoperatively, the ANH group received more albumin (p=0.04) and vasopressor medications (p=0.01); while urine output was no different between ANH and controls. Bilateral cerebral oximetry (rSO2) values were similar before and after hemodilution. During bypass rSO2were discretely lower in the ANH vs. control group (right rSO2p=0.03, left rSO2(p=0.05). No differences in lactic acid values were detected across the procedural continuum. Postoperatively, no differences in extubation times, ICU length of stay, kidney injury, stroke or infection were demonstrated.

Discussion

This study suggests hemodilution to be a safe and comparable blood conservation technique, even without accounting for potential benefits of reduced allogenic blood administration. The study may contribute to better understanding and wider acceptance of ANH protocols in high risk cardiac surgeries.
Upper airway gene expression reveals a more robust innate and adaptive immune response to SARS-CoV-2 in children compared with older adults
Authors: Mick Eran , Tsitsiklis Alexandra , Spottiswoode Natasha , Caldera Saharai , Serpa Paula Hayakawa , Detweiler Angela M. , Neff Norma , Pisco Angela Oliveira , Li Lucy M. , Retallack Hanna , Ratnasiri Kalani , Williamson Kayla M. , Soesanto Victoria , Simões Eric A. F. , Kistler Amy , Wagner Brandie D. , DeRisi Joseph L. , Ambroggio Lilliam , Mourani Peter M. , Langelier Charles R.
Published: July 2021

Unlike other respiratory viruses, SARS-CoV-2 disproportionately causes severe disease in older adults and only rarely in children. To investigate whether differences in the upper airway immune response could contribute to this disparity, we compared nasopharyngeal gene expression in 83 children (<19-years-old; 38 with SARS-CoV-2, 11 with other respiratory viruses, 34 with no virus) and 154 adults (>40-years-old; 45 with SARS-CoV-2, 28 with other respiratory viruses, 81 with no virus). Expression of interferon-stimulated genes (ISGs) was robustly activated in both children and adults with SARS-CoV-2 compared to the respective non-viral groups, with only relatively subtle distinctions. Children, however, demonstrated markedly greater upregulation of pathways related to B cell and T cell activation and proinflammatory cytokine signaling, including TNF, IFNγ, IL-2 and IL-4 production. Cell type deconvolution confirmed greater recruitment of B cells, and to a lesser degree macrophages, to the upper airway of children. Only children exhibited a decrease in proportions of ciliated cells, the primary target of SARS-CoV-2, upon infection with the virus. These findings demonstrate that children elicit a more robust innate and adaptive immune response to SARS-CoV-2 infection in the upper airway that likely contributes to their protection from severe disease in the lower airway.
Elderly acceptance of telemedicine use in Hong Kong during and after the COVID-19 pandemic: a cross-sectional cohort survey
Authors: Yin Choi Maxwell Chun , Chu Shing Him , Siu Lok Lam , Tse Anakin Gajy , Yuen Wu Justin Che , Fung Hong , Fai Chiu Billy Chi , Tong Mok Vincent Chung
Published: July 2021

Background

Telemedicine services worldwide have experienced an unprecedented boom since the beginning of the COVID-19 pandemic. Multiple studies have noted telemedicine as an effective alternative to traditional face-to-face management of patients. This study provides insight into public perception and impression of telemedicine in Hong Kong, specifically among the elderly who are the most vulnerable to COVID-19.

Methods

Face-to-face surveys were conducted on elderly relatives of current medical students at the Chinese University of Hong Kong who were aged ≥ 60 years. The survey included socio-demographic details; past medical history; and concerns towards telemedicine use. Univariate and multivariable regression analyses were conducted to examine statistically significant associations. The primary outcomes are consideration of telemedicine use during: (1) a severe outbreak; and (2) after the COVID-19 pandemic.

Results

109 surveys were conducted. Multivariable regression analyses revealed that expectation of government subsidies for telemedicine services was the strongest common driver, and also the only positive independent predictors of telemedicine use for both during a severe outbreak, as well as after the COVID-19 pandemic. No negative independent predictors of telemedicine use during severe outbreak were found. Negative independent predictors of telemedicine use after the COVID-19 pandemic included old age, and living in the New Territories.

Conclusions

Government support such as telemedicine-specific subsidies will be crucial in promoting telemedicine use in Hong Kong both during a severe outbreak and after the current COVID-19 pandemic. Robust dissemination of information regarding the pros and cons of telemedicine towards the public, especially towards the elderly population, is warranted.
“If somebody had told me I’d feel like I do now, I wouldn’t have believed them…” Older adults’ experiences of the BELL trial: a qualitative study
Authors: Meigh Neil J. , Davidson Alexandra R. , Keogh Justin W.L. , Hing Wayne
Published: July 2021

Objectives

This study examined older adults’ experiences of participating in the BELL trial, involving 12-weeks of group-based hardstyle kettlebell training.

Methods

In the BELL trial, 28 insufficiently active older adults (15 women, 13 men, 59-79 years) completed 6 weeks of face-to-face group training, and 6 weeks of home-based training. In-depth semi-structured interviews were audio recorded and transcribed, inductively coded, with themes constructed thematically from patterns of shared meaning.

Results

Four higher-order themes were developed that reflect older adults’ experiences participating in a group-exercise program of hardstyle kettlebell training. These included: (1) “It’s one of the best things we’ve done” - enjoying the physical and psychosocial benefits, (2) “It’s improved it tremendously!” - change in a long-term health condition, (3) “It put me on a better course” - overcoming challenges, (4) “I wasn’t just a number” - feeling part of a group/community.

Discussion

Findings highlight the perceived physical and psychological benefits of participating in hardstyle group kettlebell training, the value attributed to being part of an age-matched community of like-minded people engaged in group-exercise, as well as the challenges participants faced, and the sense of achievement in overcoming them. Implications for program design and delivery, and future research are discussed.
Characterising within-hospital SARS-CoV-2 transmission events: a retrospective analysis integrating epidemiological and viral genomic data from a UK tertiary care setting across two pandemic waves
Authors: Lindsey Benjamin B. , Villabona-Arenas Ch. Julián , Campbell Finlay , Keeley Alexander J. , Parker Matthew D. , Shah Dhruv R , Parsons Helena , Zhang Peijun , Kakkar Nishchay , Gallis Marta , Foulkes Benjamin H. , Wolverson Paige , Louka Stavroula F , Christou Stella , State Amy , Johnson Katie , Raza Mohammad , Hsu Sharon , Jombart Thibaut , Cori Anne ,   Sheffield COVID-19 Genomics Group,   The COVID-19 Genomics UK (COG-UK) consortium,   CMMID COVID-19 working group, Evans Cariad M. , Partridge David G. , Atkins Katherine E. , Hué Stéphane , de Silva Thushan I.
Published: July 2021

Structured abstract

Objectives

To characterise within-hospital SARS-CoV-2 transmission across two waves of the COVID-19 pandemic.

Design

A retrospective Bayesian modelling study to reconstruct transmission chains amongst 2181 patients and healthcare workers using combined viral genomic and epidemiological data.

Setting

A large UK NHS Trust with over 1400 beds and employing approximately 17,000 staff.

Participants

780 patients and 522 staff testing SARS-CoV-2 positive between 1st March 2020 and 25th July 2020 (Wave 1); and 580 patients and 299 staff testing SARS-CoV-2 positive between 30th November 2020 and 24th January 2021 (Wave 2).

Main outcome measures

Transmission pairs including who-infected-whom; location of transmission events in hospital; number of secondary cases from each individual, including differences in onward transmission from community and hospital onset patient cases.

Results

Staff-to-staff transmission was estimated to be the most frequent transmission type during Wave 1 (31.6% of observed hospital-acquired infections; 95% CI 26.9 to 35.8%), decreasing to 12.9% (95% CI 9.5 to 15.9%) in Wave 2. Patient-to-patient transmissions increased from 27.1% in Wave 1 (95% CI 23.3 to 31.4%) to 52.1% (95% CI 48.0 to 57.1%) in Wave 2, to become the predominant transmission type. Over 50% of hospital-acquired infections were concentrated in 8/120 locations in Wave 1 and 10/93 locations in Wave 2. Approximately 40% to 50% of hospital-onset patient cases resulted in onward transmission compared to less than 4% of definite community-acquired cases.

Conclusions

Prevention and control measures that evolved during the COVID-19 pandemic may have had a significant impact on reducing infections between healthcare workers, but were insufficient during the second wave to prevent a high number of patient-to-patient transmissions. As hospital-acquired cases appeared to drive most onward transmissions, more frequent and rapid identification and isolation of these cases will be required to break hospital transmission chains in subsequent pandemic waves.
Viral Load of SARS-CoV-2 in Respiratory Aerosols Emitted by COVID-19 Patients while Breathing, Talking, and Singing
Authors: Coleman Kristen K. , Wen Tay Douglas Jie , Tan Kai Sen , Xiang Ong Sean Wei , Son Than The , Koh Ming Hui , Chin Yi Qing , Nasir Haziq , Mak Tze Minn , Hann Chu Justin Jang , Milton Donald K. , Chow Vincent T. K. , Tambyah Paul Anantharajah , Chen Mark , Wai Tham Kwok
Published: July 2021

Background

Multiple SARS-CoV-2 superspreading events suggest that aerosols play an important role in driving the COVID-19 pandemic. However, the detailed roles of coarse (>5μm) and fine (≤5μm) respiratory aerosols produced when breathing, talking, and singing are not well-understood.

Methods

Using a G-II exhaled breath collector, we measured viral RNA in coarse and fine respiratory aerosols emitted by COVID-19 patients during 30 minutes of breathing, 15 minutes of talking, and 15 minutes of singing.

Results

Among the 22 study participants, 13 (59%) emitted detectable levels of SARS-CoV-2 RNA in respiratory aerosols, including 3 asymptomatic patients and 1 presymptomatic patient. Viral loads ranged from 63–5,821 N gene copies per expiratory activity per patient. Patients earlier in illness were more likely to emit detectable RNA, and loads differed significantly between breathing, talking, and singing. The largest proportion of SARS-CoV-2 RNA copies was emitted by singing (53%), followed by talking (41%) and breathing (6%). Overall, fine aerosols constituted 85% of the viral load detected in our study. Virus cultures were negative.

Conclusions

Fine aerosols produced by talking and singing contain more SARS-CoV-2 copies than coarse aerosols and may play a significant role in the transmission of SARS-CoV-2. Exposure to fine aerosols should be mitigated, especially in indoor environments where airborne transmission of SARS-CoV-2 is likely to occur. Isolating viable SARS-CoV-2 from respiratory aerosol samples remains challenging, and whether this can be more easily accomplished for emerging SARS-CoV-2 variants is an important enquiry for future studies.

Key Points

We sampled respiratory aerosols emitted by COVID-19 patients and discovered that fine aerosols (≤5μm) generated during talking and singing contain more SARS-CoV-2 copies than coarse aerosols (>5μm) and may play a significant role in the transmission of SARS-CoV-2.
COVID-19 Chest X-Ray Image Classification Using Deep Learning
Authors: Bacellar Gunther Correia , Chandrappa Mallikarjuna , Kulkarni Rajlakshman , Dey Soumava
Published: July 2021

The rise of the coronavirus disease 2019 (COVID-19) pandemic has made it necessary to improve existing medical screening and clinical management of this disease. While COVID-19 patients are known to exhibit a variety of symptoms, the major symptoms include fever, cough, and fatigue. Since these symptoms also appear in pneumonia patients, this creates complications in COVID-19 detection especially during the flu season. Early studies identified abnormalities in chest X-ray images of COVID-19 infected patients that could be beneficial for disease diagnosis. Therefore, chest X-ray image-based disease classification has emerged as an alternative to aid medical diagnosis. However, manual detection of COVID-19 from a set of chest X-ray images comprising both COVID-19 and pneumonia cases is cumbersome and prone to human error. Thus, artificial intelligence techniques powered by deep learning algorithms, which learn from radiography images and predict presence of COVID-19 have potential to enhance current diagnosis process. Towards this purpose, here we implemented a set of deep learning pre-trained models such as ResNet, VGG, Inception and EfficientNet in conjunction with developing a computer vision AI system based on our own convolutional neural network (CNN) model: Deep Learning in Healthcare (DLH)-COVID. All these CNN models cater to image classification exercise. We used publicly available resources of 6,432 images and further strengthened our model by tuning hyperparameters to provide better generalization during the model validation phase. Our final DLH-COVID model yielded the highest accuracy of 96% in detection of COVID-19 from chest X-ray images when compared to images of both pneumonia-affected and healthy individuals. Given the practicality of acquiring chest X-ray images by patients, we also developed a web application (link: https://toad.li/xray) based on our model to directly enable users to upload chest X-ray images and detect the presence of COVID-19 within a few seconds. Taken together, here we introduce a state-of-the-art artificial intelligence-based system for efficient COVID-19 detection and a user-friendly application that has the capacity to become a rapid COVID-19 diagnosis method in the near future.
Neutralization of recombinant RBD-subunit vaccine ZF2001-elicited antisera to SARS-CoV-2 variants including Delta
Authors: Zhao Xin , Zheng Anqi , Li Dedong , Zhang Rong , Sun Huan , Wang Qihui , Gao George F. , Han Pengcheng , Dai Lianpan
Published: July 2021

SARS-CoV-2 variants brought new waves of infection worldwide. In particular, Delta variant (B.1.617.2 lineage) has become predominant in many countries. These variants raised the concern for their potential immune escape to the currently approved vaccines. ZF2001 is a subunit vaccine received emergency use authorization (EUA) in both China and Uzbekistan, with more than 100-million doses administrated with a three-dose regimen. The tandem-repeat dimer of SARS-CoV-2 spike protein receptor binding domain (RBD) was used as the antigen. In this work, we evaluated the neutralization of ZF2001-elicited antisera to SARS-CoV-2 variants including all four variants of concern (Alpha, Beta, Gamma and Delta) and other three variants of interest (Epsilon, Eta and Kappa) by pseudovirus-based assay. We found antisera preserved majority of the neutralizing activity against these variants. E484K/Q substitution is the key mutation to reduce the RBD-elicited sera neutralization. Moreover, ZF2001-elicited sera with a prolonged intervals between the second and third dose enhanced the neutralizing titers and resilience to SARS-CoV-2 variants.
Understanding Mechanisms of Chamber-Specific Differentiation Through Combination of Lineage Tracing and Single Cell Transcriptomics
Authors: Gonzalez David M. , Schrode Nadine , Ebrahim Tasneem , Beaumont Kristin G. , Sebra Robert , Dubois Nicole C.
Published: July 2021

The specification and differentiation of atrial and ventricular myocardial cell types during development is incompletely understood. We have previously shown that Foxa2 expression during gastrulation identifies a population of ventricular fated progenitors, allowing for labeling of these cells prior to the morphogenetic events that lead to chamber formation and acquisition of bona fide atrial or ventricular identity. In this study, we performed single cell RNA sequencing of Foxa2Cre;mTmG embryos at the cardiac crescent (E8.25), primitive heart tube (E8.75) and heart tube (E9.25) stage in order to understand the transcriptional mechanisms underlying formation of atrial and ventricular cell types at the earliest stages of cardiac development. We find that progression towards differentiated myocardial cell types occurs primarily based on heart field progenitor identity, and that different progenitor populations contribute to ventricular or atrial identity through separate differentiation mechanisms. We identified a number of candidate markers that define such differentiation processes, as well as differential regulation of metabolic processes that distinguish atrial and ventricular fated cells at the earliest stages of development. We further show that exogenous injection with retinoic acid during formation of the cardiac primordia causes defects in ventricular chamber size and is associated with dysregulation in FGF signaling in anterior second heart field cells and a shunt in differentiation towards orthogonal lineages. Retinoic acid also causes defects in cell-cycle exit in myocardial committed progenitors that result in formation of hypomorphic ventricles with decreased expression of important metabolic processes and sarcomere assembly. Collectively, our data identify, at a single cell level, distinct lineage trajectories during cardiac progenitor cell specification and differentiation, and the precise effects of manipulating cardiac progenitor field patterning via exogenous retinoic acid signaling.
Network-based pathogenicity prediction for variants of uncertain significance
Authors: Kamada Mayumi , Takagi Atsuko , Kojima Ryosuke , Tanaka Yoshihisa , Nakatsui Masahiko , Tanabe Noriko , Hirata Makoto , Yoshida Teruhiko , Okuno Yasushi
Published: July 2021

While the number of genome sequences continues to increase, the functions of many detected gene variants remain to be identified. These variants of uncertain significance constitute a major barrier to precision medicine 1–3. Although many computational methods have been developed to predict the function of these variants, they all rely on individual gene features and do not consider complex molecular relationships. Here we develop PathoGN, a molecular network-based approach for predicting variant pathogenicity. PathoGN significantly outperforms existing methods using benchmark datasets. Moreover, PathoGN successfully predicts the pathogenicity of 3,994 variants of uncertain significance in the real-world database ClinVar and designates potential pathogenicity. This is the first computational method for the clinical interpretation of variants using biomolecular networks, and we anticipate our method to be broadly useful for the clinical interpretation of variants and for assigning biological function to unknown variants at the genomic scale.
A rapid F0 CRISPR screen in zebrafish to identify regulators of neuronal development in the enteric nervous system
Authors: Davidson Ann E , Straquadine Nora RW , Cook Sara A , Liu Christina G , Ganz Julia
Published: July 2021

The enteric nervous system (ENS) provides the intrinsic innervation of the gastrointestinal (GI) tract with millions of neurons and diverse neuronal subtypes and glial cells. The ENS regulates essential gut functions such as motility, nutrient uptake, and immune response, but basic information about the genes that control ENS neuronal specification and differentiation remains largely unknown. Deficits in ENS neuron numbers and composition cause gut dysfunction with debilitating GI symptoms, and are associated with e.g. Hirschsprung disease, inflammatory gut diseases, autism spectrum disorder, and neurodegenerative diseases such as Parkinson’s disease. The genetic basis of most of these ENS disorders remains unknown. Recent transcriptomic analyses have identified many candidate genes for regulating ENS neurogenesis. However, functional evaluation of these candidate genes significantly lags because experimental testing of their role in ENS neurogenesis is time-consuming and expensive. Here, we have developed a rapid, scalable F0 CRISPR genome editing screen in zebrafish to functionally determine which candidate genes control neuronal development in the ENS. Proof-of-concept experiments targeting the known ENS regulators sox10 and ret phenocopy stable mutants with high efficiency and precision showing that our approach is reliable to identify regulators ENS neurogenesis using F0 guide RNA-injected larvae (F0 crispants). We then evaluate the role of 10 transcription factor genes for regulating ENS neurogenesis and function. Pools of guide RNAs targeting 2-3 candidate genes are co-injected with Cas9 protein into one-cell stage phox2bb:GFP transgenic zebrafish embryos to directly assess qualitative change in ENS neuron numbers compared to controls in 6-day old F0 crispants. Target genes from crispant pools exhibiting reduced ENS neuronal numbers were then tested individually to identify the responsible gene(s). We identify five transcription factors that show a reduction in ENS neurons indicating an influence on enteric progenitor cell differentiation into ENS neurons. Adding a simple and efficient test to further assess crispant gut motility, we find that loss-of-function of two of the transcription factor genes reduced intestinal transit of fluorescently labeled food through the gut. In summary, our novel, multistep, yet straight-forward CRISPR screening approach in zebrafish enables testing the genetic basis of ENS developmental and disease gene functions that will facilitate high-throughput evaluation of the manifold candidate genes emerging from transcriptomic, genome-wide association or other ENS-omics studies. Such in vivo ENS crispant screens will contribute to a better understanding of ENS neuronal development regulation in vertebrates and what goes awry in ENS disorders.
Structural Characterization of the PawL-Derived Peptide Family, an Ancient Subfamily of Orbitides
Authors: Payne Colton D. , Fisher Mark F. , Mylne Joshua S. , Rosengren K. Johan
Published: July 2021

Plants are an excellent source of bioactive peptides, often with disulfide bonds and/or a cyclic backbone. While focus has predominantly been directed at disulfide-rich peptides, a large family of small, cyclic but non-disulfide bonded plant peptides, known as orbitides, has been relatively ignored. A recently discovered subfamily of orbitides is the PawL-Derived Peptides (PLPs), produced during the maturation of precursors for seed storage albumins. Although their evolutionary origins have been dated, in-depth exploration of the family’s structural characteristics and potential bioactivities remains to be conducted. Here we present an extensive and systematic characterization of the PLP family. Nine PLPs were chosen and prepared by solid phase peptide synthesis. Their structural features were studied using solution NMR spectroscopy and seven were found to possess regions of backbone order. Ordered regions consist of β-turns, with some PLPs adopting two well-defined β-turns within sequences as short as seven residues, which are largely the result of side chain interactions. Our data highlight that the sequence diversity within this family results in equally diverse molecular scaffolds. None of these nine PLPs showed antibacterial or antifungal activity.
High-accuracy measurement of mass attenuation coefficients and the imaginary component of the atomic form factor of zinc from 8.51 keV to 11.59 keV, and X-ray absorption fine structure with investigation of zinc theory and nanostructure
Authors: Ekanayake Ruwini S. K. , Chantler Christopher T. , Sier Daniel , Schalken Martin J. , Illig Alexis J. , de Jonge Martin D. , Johannessen Bernt , Kappen Peter , Tran Chanh Q.
Published: July 2021

High-accuracy X-ray mass attenuation coefficients were measured from the first X-ray Extended Range Technique (XERT)-like experiment at the Australian Synchrotron. Experimentally measured mass attenuation coefficients deviate by ∼50% from the theoretical values near the zinc absorption edge, suggesting that improvements in theoretical tabulations of mass attenuation coefficients are required to bring them into better agreement with experiment. Using these values the imaginary component of the atomic form factor of zinc was determined for all the measured photon energies. The zinc K-edge jump ratio and jump factor are determined and results raise significant questions regarding the definitions of quantities used and best practice for background subtraction prior to X-ray absorption fine-structure (XAFS) analysis. The XAFS analysis shows excellent agreement between the measured and tabulated values and yields bond lengths and nanostructure of zinc with uncertainties of from 0.1% to 0.3% or 0.003 Å to 0.008 Å. Significant variation from the reported crystal structure was observed, suggesting local dynamic motion of the standard crystal lattice. XAFS is sensitive to dynamic correlated motion and in principle is capable of observing local dynamic motion beyond the reach of conventional crystallography. These results for the zinc absorption coefficient, XAFS and structure are the most accurate structural refinements of zinc at room temperature.