bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychologic Distress and Quality of Life After ICU Treatment for Coronavirus Disease 2019: A Multicenter, Observational Cohort Study
Authors: Vlake Johan H. , Van Bommel Jasper , Hellemons Merel E. , Wils Evert-Jan , Bienvenu O. Joseph , Schut Anna F. C. , Klijn Eva , Van Bavel Marten P. , Gommers Diederik , Van Genderen Michel E.
Published: February 2022

OBJECTIVES:

To quantify short- and long-term psychologic distress, that is, symptoms of posttraumatic stress disorder, anxiety, and depression, and the health-related quality of life in coronavirus disease 2019 ICU survivors.

DESIGN:

A prospective, observational cohort study.

SETTING:

Postcoronavirus disease 2019 clinics of three hospitals in Rotterdam, the Netherlands.

PATIENTS:

Adult patients admitted for coronavirus disease 2019 to the ICU, who visited the postcoronavirus disease 2019 follow-up clinic.

MEASURES AND MAIN RESULTS:

The primary outcomes were psychologic distress and overall and mental health-related quality of life, assessed using the Impact of Event Scale-Revised, Hospital Anxiety and Depression Scale, Short-Form 36, and European Quality of Life 5D, 6 weeks, 3 months, and 6 months post hospital discharge. Second, we compared 3-month psychologic and mental health-related quality of life outcomes with a historical critical illness survivor cohort and overall and mental health-related quality of life with the Dutch population. We included 118 patients with a median age of 61 years (95% range, 36–77 yr) of whom 79 (68%) were male. At 6 weeks, 13 patients (23%) reported psychologic distress, copresence of probable psychiatric disorders was common, and no decline in psychologic distress was observed throughout follow-up. Coronavirus disease 2019 patients tend to suffer less from posttraumatic stress disorder and reported less severe symptoms of anxiety (Hospital Anxiety and Depression Scale Anxiety Score: 3 [0–17] vs 5 [0–16]; estimated mean difference 2.3 [95% CI, 0.0–4.7]; p = 0.05) and depression (Hospital Anxiety and Depression Scale Depression Score: 3 [0–15] vs 5 [0–16]; estimated mean difference 2.4 [95% CI, 0.1–2.4]; p = 0.04) than the historical critical illness cohort. Overall and mental health-related quality of life increased over time. Coronavirus disease 2019 ICU survivors reported better mental health-related quality of life than our historical cohort, but overall and mental health-related quality of life was still poorer than the Dutch population.

CONCLUSIONS:

Psychologic distress was common in coronavirus disease 2019 ICU survivors and remained similar until 6 months after hospital discharge. Health-related quality of life increased over time and was higher than in a historical cohort, but was lower than in the Dutch population. Our findings highlight that coronavirus disease 2019 ICU survivors should be monitored after ICU treatment to detect possible psychologic distress.
Improved oral health knowledge in a primary care pediatric nurse practitioner program
Authors: Pike Nancy A. , Kinsler Janni J. , Peterson Jennifer K. , Verzemnieks Inese , Lauridsen Lauren , Love-Bibbero Laurie , Ramos-Gomez Francisco
Published: February 2022

Pediatric nurse practitioners (PNPs) are a significant workforce in primary care and are uniquely positioned to improve oral health in children through ongoing surveillance in the well-child visit. The purpose of this study was to evaluate PNP student satisfaction and knowledge gained with the integration of the Strategic Partnership for Interprofessional Collaborative Education in Pediatric Dentistry (SPICE-PD) oral health education program into the first-year primary care curriculum. A descriptive, comparative design examined dental test scores across the pre-SPICE-PD (2013–2014; n = 26) and post-SPICE-PD (2015–2020; n = 55) cohorts. An electronic survey was completed (n = 47; 67%), and focus group (n = 12) audio-recordings were analyzed using Atlas.ti 8.0. Chi-square test and independent samples t-test were used to assess differences between groups. The SPICE-PD students reported improved knowledge and skill in clinical practice. Focus group themes were oral health education was beneficial, impact of coronavirus disease 2019, and suggestions for improvement. Mean dental test scores improved pre- and post-SPICE-PD (83 vs. 93; p < .001). The SPICE-PD oral health education improved knowledge and was highly satisfying for students. Pediatric nurse practitioners are ideally positioned to integrate oral health into primary care services, thereby improving access to care and ultimately reducing or mitigating early childhood caries. Evaluation of PNP postgraduation practices in the primary care setting is needed to assess whether improved knowledge results in practice change.
Ex-vivo lung perfusion therapies: do they add value to organ donation?
Authors: Lyengar Amit , Schiazza Alexis , Cantu Edward
Published: February 2022

Purpose of review

Significant limitations in organ availability and postoperative graft dysfunction plague lung transplantation and there is continual need for innovation. Ex-vivo lung perfusion (EVLP) has emerged over the last decade as an alternative and/or complementary allograft storage and assessment tool, however logistical hurdles have limited its widespread dissemination. As such, the overall current and potential value of EVLP on modern-day lung transplantation should be considered as innovation moves forward.

Recent findings

Since inception, EVLP has made important safety strides in conclusively showing noninferiority to cold storage in several trials. Recent advances have highlighted potential mechanisms by which EVLP in its current form may reduce the pathogenic origins of primary graft dysfunction. Exciting work on organ reconditioning with EVLP via reduction in intermediaries of acute inflammation and oxidative stress have been performed in animal models. In addition, cross-circulation during EVLP has emerged as a method to achieve more prolonged ex situ storage. The impending translation of these to clinical use will markedly improve the overall value of EVLP.

This review will highlight the current status of EVLP as it pertains to overall value in lung transplantation, focusing on historical and recent preclinical work and how innovation therein will improve lung transplantation as a field.
Association between temporal summation and conditioned pain modulation in chronic low back pain: baseline results from 2 clinical trials
Authors: Kong Jiang-Ti , You Dokyong Sophia , Law Christine Sze Wan , Darnall Beth D. , Gross James J. , Manber Rachel , Mackey Sean
Published: February 2022

Introduction:

Temporal summation (TS) and conditioned pain modulation (CPM) represent different aspects of central pain processing. Their relationship and differential performance within distinct body locations are not well understood.

Objectives:

To examine the association between TS and CPM in chronic low back pain and the influence of testing location on this relationship.

Methods:

We analyzed baseline data from 2 clinical trials on participants with chronic low back pain (n = 264; 47.3% female; mean age = 41 years, SD = 12; mean pain = 5.3/10, SD = 1.4). Measures used included questionnaires assessing pain and negative affect, phasic thermal TS at the hand (thenar) and the lower back (lumbar), followed by CPM that included a thermal testing stimulus (Heat-6, the temperature where pain rating is 6/10) and a cold-pressor conditioning stimulus. Nonparametric, proportional odds logistic regression was used to model thenar, and separately, lumbar TS, using CPM, Heat-6, negative affect, and demographics.

Results:

Our models revealed a small association (βs = 0.17, P = 0.01) between reduced CPM and heightened TS at both testing sites, regardless of demographics or negative affect.

Conclusion:

Results suggest a modest association between TS and CPM, irrespective of anatomical testing location, demographics, and negative affect. These findings will help improve the methodology and interpretation of TS and CPM measurement in clinical pain populations.
Creating a Biological Breast Implant with an Omental Fat-Augmented Free Flap
Authors: Nguyen Dung H. , Ma Irene T. , Choi Youna K. , Zak Yulia , Dua Monica M. , Wapnir Irene L.
Published: February 2022

Women with inadequate myocutaneous or fasciocutaneous soft-tissue donor sites for breast reconstruction after mastectomy are mostly limited to implants. Alternative substitutes are needed for those who do not want—or in whom there are contraindications for—implant-based reconstruction. The authors report a novel technique using an omental fat-augmented free flap to create an autologous breast mound that has comparable shape and projection to a breast implant. Three patients with breast cancer who desired unilateral reconstruction were identified in the period 2019 to 2020. All had insufficient traditional autologous sites and were averse to the use of implants. A nipple-sparing mastectomy was performed, and the omentum was laparoscopically harvested and fat-grafted ex vivo and then encased in acellular dermal matrix for microvascular anastomoses. The body mass indexes of the three patients were 17.6, 25, and 28.3 kg/m2. Each individual’s mastectomy specimens and corresponding omentum plus fat-grafting weights were 113.7/228, 271/293, and 270/360 g. No postoperative complications occurred. The reconstructed breast remains soft, with stable breast volume at 6 months and without evidence of fat necrosis. This novel use of fat grafting into an omental flap enveloped in acellular dermal matrix, the omental fat-augmented free flap, provides a viable and successful autologous alternative for patients who are not candidates for traditional autologous breast reconstruction options because of body habitus or personal preference.
Postoperative Sedation Duration as an Independent Risk Factor for Postoperative Pneumonia in Head and Neck Cancer Patients Undergoing Free Flap Reconstruction
Authors: Chuang Chih-Chao , Chen Mei-Chun , Perng Cherng-Kang , Liao Wen-Chieh , Wang Tien-Shiang , Wu Szu-Hsien , Shih Yu-Chung , Lin Chih-Hsun , Hsiao Fu-Yin , Feng Chin-Jung , Ma Hsu
Published: February 2022

Objective

Patients who had reconstruction for head and neck cancer usually have long duration of postoperative sedation and intensive care. This is due to the complex nature of large-area soft tissue defect surgeries and upper respiratory tract infections associated with them. Postoperative pulmonary complications are common in these patients. In this study, we analyzed the risk factors and the relationship between postoperative complications and the duration of sedation to improve the patients' recovery process after free flap reconstruction for head and neck surgery.

Materials and Methods

This was a retrospective study that included 188 patients who had head and neck surgery with free flap reconstruction in 2011 (traditional recovery group) and 2018 (early recovery group). Postoperative recovery events were compared between the 2 groups. Complications such as pneumonia, wound infection, vascular thrombosis, and bleeding were also analyzed.

Results

The results showed that the early recovery group had a shorter duration of sedation (P < 0.001), shorter duration of intensive care unit stay (P = 0.05), more rapid ventilator weaning (P < 0.001), and fewer pneumonia events (8.8% vs 39.1%) than the traditional recovery group. Wound- and vessel-related complications were not affected by the duration of sedation.

Conclusions

Our study demonstrated that shortening the duration of postoperative sedation can effectively decrease the length of intensive care unit stay and reduce postoperative incidence of pneumonia without increasing wound- and vessel-related complications.
An integrative analysis of clinical and epigenetic biomarkers of mortality
Authors: Huan Tianxiao , Nguyen Steve , Colicino Elena , Ochoa-Rosales Carolina , David Hill W. , Brody Jennifer A. , Soerensen Mette , Zhang Yan , Baldassari Antoine , Elhadad Mohamed Ahmed , Toshiko Tanaka , Zheng Yinan , Domingo-Relloso Arce , Lee Dong Heon , Ma Jiantao , Yao Chen , Liu Chunyu , Hwang Shih-Jen , Joehanes Roby , Fornage Myriam , Bressler Jan , van Meurs Joyce BJ , Debrabant Birgit , Mengel-From Jonas , Hjelmborg Jacob , Christensen Kaare , Vokonas Pantel , Schwartz Joel , Gahrib Sina A. , Sotoodehnia Nona , Sitlani Colleen M. , Kunze Sonja , Gieger Christian , Peters Annette , Waldenberger Melanie , Deary Ian J. , Ferrucci Luigi , Qu Yishu , Greenland Philip , Lloyd-Jones Donald M , Hou Lifang , Bandinelli Stefania , Voortman Trudy , Hermann Brenner , Baccarelli Andrea , Whitsel Eric , Pankow James S. , Levy Daniel
Published: February 2022

DNA methylation (DNAm) has been reported to be associated with many diseases and mortality. We hypothesized that the integration of DNAm with clinical risk factors would improve mortality prediction.We performed an epigenome-wide association study of whole blood DNAm in relation to mortality in 15 cohorts (n=15,013). During a mean follow-up of 10 years, there were 4314 deaths from all-causes including 1235 cardiovascular disease (CVD) deaths and 868 cancer deaths. Ancestry-stratified meta-analysis of all-cause mortality identified 163 CpGs in European ancestry (EA) and 17 in African ancestry (AA) participants at P<1x10-7, of which 41 (EA) and 16 (AA) were also associated with CVD death, and 15 (EA) and 9 (AA) with cancer death. We built DNAm-based prediction models for all-cause mortality that predicted mortality risk independent of clinical risk factors. The mortality prediction model trained by integrating DNAm with clinical risk factors showed a substantial improvement in prediction of cancer death with 11% and 5% increase in the C-index in internal and external replications, compared with the model trained by clinical risk factors alone. Mendelian randomization identified 15 CpGs in relation to longevity, CVD, or cancer risk. For example, cg06885782 (in KCNQ4) was positively associated with risk for prostate cancer (Beta=1.2, PMR=4.1x10-4), and negatively associated with longevity (Beta=-1.9, PMR=0.02). Pathway analysis revealed that genes associated with mortality-related CpGs are enriched for immune and cancer related pathways. We identified replicable DNAm signatures of mortality and demonstrated the potential utility of CpGs as informative biomarkers for prediction of mortality risk.
Indigenous peoples in eastern Brazil: insights from 19th century genomes and metagenomes
Authors: Cruz Dávalos Diana Ivette , Arizmendi Cárdenas Yami Ommar , Bravo-Lopez Miriam Jetzabel , Neuenschwander Samuel , Reis Silvia , Bastos Murilo Q. R. , Stenderup Jesper , Yediay Fulya Eylem , Villa-Islas Viridiana , Reyna-Blanco Carlos S. , Rodrigues-Carvalho Claudia , Hünemeier Tábita , Allentoft Morten E. , Amorim Carlos Eduardo G. , Moreno-Mayar J. Víctor , Ávila-Arcos María C. , Malaspinas Anna-Sapfo
Published: February 2022

Although Brazil was inhabited by more than 3,000 Indigenous populations prior to European colonization, today’s Indigenous peoples represent less than 1% of Brazil’s census population. Some of the decimated communities belonged to the so-called “Botocudos” from central-eastern Brazil. These peoples are thought to represent a case of long-standing genetic continuity bearing a strong craniometric resemblance to that of the oldest Indigenous Americans (“Paleoamericans”). Yet, little is known about their origins and genetic relationship to other Native Americans, as only two “Botocudo” genomes have been sequenced so far and those were surprisingly of Polynesian ancestry. To deepen our knowledge on the genomic history of pre-contact Indigenous Americans and the pathogens they were exposed to, we carbon-dated and sequenced 24 ancient Brazilians (including 22 “Botocudos”) whose remains were hosted at the National Museum of Rio de Janeiro and recovered prior to the tragic 2018 fire. The resulting genomes’ depth of coverage ranged from 0.001× to 24×. Their genetic ancestry was found to be Indigenous American without gene flow from external populations such as Europeans, Africans or Polynesians. Unlike Mesoamericans, the “Botocudos” and Amazonians do not seem to have experienced a population expansion once in the Americas. Moreover, remarkably, their genomes exhibit amongst the lowest levels of heterozygosity worldwide and long runs of homozygosity, which could be explained by unique social practices or a very small effective size. Finally, whole genomes of likely ancient pathogens were recovered, including lineages of Human parvovirus B19 that were possibly introduced after the European contact.

Significance statement

To better understand the genetic relationship among Indigenous populations in Brazil, we sequenced the genomes of 24 ancient individuals (22 of which labelled as “Botocudos”, a term used to describe hunter-gatherer tribes) whose remains were hosted at the Museu Nacional of Rio de Janeiro prior to the tragic fire that consumed it in 2018. Unlike two previously published “Botocudo” genomes, the 22 “Botocudos” from this study have Indigenous American-related ancestry without any Polynesian-related ancestry, and they are similarly related to several Native Brazilian populations. Finally, unlike Eurasian hunter-gatherers, the “Botocudos” exhibit among the lowest heterozygosity and longest runs of homozygosity worldwide – compatible with a very small effective size and suggesting a unique social structure among hunter-gatherers in the Americas.
Genomic characterization of invasive typhoidal and non-typhoidal Salmonella in southwestern Nigeria
Authors: Ikhimiukor Odion O. , Oaikhena Anderson O. , Afolayan Ayorinde O. , Fadeyi Abayomi , Kehinde Aderemi , Ogunleye Veronica O , Aboderin Aaron O. , Oduyebo Oyinlola O. , Elikwu Charles J. , Odih Erkison Ewomazino , Komolafe Ifeoluwa , Argimón Silvia , Egwuenu Abiodun , Adebiyi Ini , Sadare Oluwadamiloa A. , Okwor Tochi , Kekre Mihir , Underwood Anthony , Ihekweazu Chikwe , Aanensen David M. , Okeke Iruka N.
Published: February 2022

Background

Salmonellosis causes significant morbidity and mortality in Africa. Despite being endemic in Nigeria, information on circulating lineages of invasive Salmonella is sparse.

Methods

Salmonella enterica isolated from blood (n=60) and cerebrospinal fluid (CSF, n=3) between 2016 and 2020 from five tertiary hospitals in southwest Nigeria were antimicrobial susceptibility-tested and Illumina-sequenced. Genomes were analysed using publicly-available bioinformatic tools.

Results

Isolates and sequence types (STs) from blood were S. Typhi [ST1, n =1 and ST2, n =43] and invasive non-typhoidal Salmonella (iNTS) (S. Enteritidis [ST11, n=7], S. Durham [ST10, n=2], S. Rissen [ST8756, n=2], S. Chester [ST2063, n=1], S. Dublin [ST10, n=1], S. Infantis [ST603, n=1], S. Telelkebir [ST8757, n=1] and S. Typhimurium [ST313, n=1], S. Typhi ST2 (n=2) and S. Adabraka ST8757 (n=1) were recovered from CSF. Most S. Typhi belonged to genotype 3.1.1 (n=44), carried an IncY plasmid and had several antibiotic resistance genes (ARGs) including blaTEM-1 (n=38), aph(6)-Id (n=32), tet(A) (n=33), sul2 (n=32), dfrA14 (n=30) as well as quinolone resistance-conferring gyrA_S83Y SNPs (n=37). All S. Enteritidis harboured aph(3’’)-Ib, blaTEM-1, catA1, dfrA7, sul1, sul2, tet(B) genes, and a single ARG, qnrB19, was detected in S. Telelkebir.. Typhoidal toxins cdtB, pltA and pltB were detected in S. Typhi, Rissen, Chester, and Telelkebir.

Conclusion

Most invasive salmonelloses in south west Nigeria are vaccine-preventable infections due to multidrug-resistant, West African dominant Typhi lineage 3.1.1.. Invasive NTS serovars, including some harbouring typhoidal toxin or resistance genes represented a third of the isolates emphasizing the need for better diagnosis and surveillance.

Author Summary

Whole genome sequencing of 63 invasive Salmonella from 5 tertiary hospitals in Nigeria revealed multiple serovars including a dominant antibiotic-resistance-gene harbouring S. Typhi 3.1.1 genotype comprising a gyrA_S83Y and IncY plasmid. We also report invasive non-typhoidal Salmonella harbouring typhoidal toxins.
Mucins form a nanoscale material barrier against immune cell attack
Authors: Park Sangwoo , Colville Marshall J. , Shurer Carolyn R. , Huang Ling-Ting , Kuo Joe Chin-Hun , Paek Justin H. , Goudge Marc C. , Su Jin , DeLisa Matthew P. , Lammerding Jan , Zipfel Warren R. , Fischbach Claudia , Reesink Heidi L. , Paszek Matthew J.
Published: February 2022

The cancer cell glycocalyx serves as a major line of defense against immune surveillance. However, how specific physical properties of the glycocalyx contribute to immune evasion and how these properties are regulated are not well understood. Here, we uncover how the surface density, glycosylation, and crosslinking of cancer-associated mucins contribute to the nanoscale material thickness of the glycocalyx, and further analyze the effect of the glycocalyx thickness on resistance to effector cell attack. Natural Killer (NK) cell-mediated cytotoxicity exhibits a near perfect inverse correlation with the glycocalyx thickness of target cells regardless of the specific glycan structures present. NK cells expressing a chimeric antigen receptor (CAR) have an enhanced ability to breach the glycocalyx and kill target cells. Equipping the NK cell surface with a mucin-digesting enzyme also improves killing with a performance enhancement that rivals or exceeds CARs in some cases. Together, our results provide new considerations for improving cancer immunotherapies.
The predictive value of double-stranded RNA for A-to-I editing detection
Authors: Shur Guy , Tamir Yuval , Eran Alal
Published: February 2022

Structured Abstract

Motivation

Adenosine-to-inosine (A-to-I) RNA editing, a crucial reaction for many processes that contribute to transcriptome plasticity, is both widely common across the transcriptome and difficult to predict due to a lack of distinctive genomic characteristics that can be obtained and analyzed computationally. An exception to this is the secondary structure of RNA molecules, which has been shown to have a major impact on the selectivity and specificity of the enzymes responsible for A-to-I editing. Yet, this information is rarely used for the task of editing site prediction.

Results

Here, we demonstrated the value of using base-pairing probabilities of RNA nucleotides to classify genomic sites as A-to-I RNA editing sites, using large-scale truth data which we compiled and make available for use in training future models. Our analysis suggests that the span of four bases from –2 (upstream) to +1 (downstream) of a putative editing site is most informative in this regard. A classifier trained on base-pairing probabilities alone performed with a positive predictive value (PPV) of 0.68, a negative predictive value (NPV) of 0.64, and an area under the receiver operating characteristic curve (AUC) of 0.71. By identifying structure-related features that are informative for detecting A-to-I RNA editing sites and quantifying their predictive value, this work advances our understanding of A-to-I editing determinants.

Availability

All source codes and data are available at https://github.com/Ally-s-Lab/P-BEP
SARS-CoV-2 leverages airway epithelial protective mechanism for viral infection
Authors: Greaney Allison M. , Raredon Micha S.B. , Kochugaeva Maria P. , Niklason Laura E. , Levchenko Andre
Published: February 2022

Despite much concerted effort to better understand SARS-CoV-2 viral infection, relatively little is known about the dynamics of early viral entry and infection in the airway. Here we analyzed a single-cell RNA sequencing dataset of early SARS-CoV-2 infection in a humanized in vitro model, to elucidate key mechanisms by which the virus triggers a cell-systems-level response in the bronchial epithelium. We find that SARS-CoV-2 virus preferentially enters the tissue via ciliated cell precursors, giving rise to a population of infected mature ciliated cells, which signal to basal cells, inducing further rapid differentiation. This feed-forward loop of infection is mitigated by further cell-cell communication, before interferon signaling begins at three days post-infection. These findings suggest hijacking by the virus of potentially beneficial tissue repair mechanisms, possibly exacerbating the outcome. This work both elucidates the interplay between barrier tissues and viral infections, and may suggest alternative therapeutic approaches targeting non-immune response mechanisms.
Highly efficient, all-organic bioluminescence-photosensitizer conjugate eradicates early-stage tumors and prevents metastasis in mice
Authors: Yan Hao , Forwad Sarah , Kim Kwon-Hyeon , Wu Yue , Hui Jie , Kashiparekh Anokhi , Yun Seok-Hyun
Published: February 2022

Photodynamic therapy (PDT) is an established treatment modality using light-activatable drugs. Despite its unique cytotoxic mechanism, the shallow penetration of light has been a serious drawback limiting the applications of PDT. Here, we report bioluminescence-activated PDT (BL-PDT) using efficient bioluminescence resonance energy transfer (BRET) conjugates of clinically approved photosensitizers, Ce6, and luciferase proteins. A high photon-to-Ce6 conversion efficiency (80%), along with intracellular delivery by membrane-fusion liposomes, enabled effective cancer cell killingin vitro. In a syngeneic mouse model of aggressive 4T1 triple-negative breast cancer, as well as a xenograft model of MDA-MB-231 tumors, BL-PDT resulted in complete tumor remission and prevention of metastasis, as well as neo-adjuvant effects. Our result shows the promise of molecularly activable, clinically viable, depth-unlimited phototherapy.
Quantitative risk assessment of COVID-19 and serious illness among spectators at mass gathering events with vaccine-testing package implementation
Authors: Murakami Michio , Fujita Tsukasa , Iwasaki Yuichi , Onishi Masaki , Naito Wataru , Imoto Seiya , Yasutaka Tetsuo
Published: February 2022

While mass gathering events have resumed in conjunction with vaccine-testing (VT) packages, their effects on reducing COVID-19 risk remain unclear. Here, we used an environmental exposure model to analyze the effects of vaccinations and proof of negative test results on reducing infection risk and serious illness among spectators at mass gathering events. We then analyzed the difference in risk with and without VT and regular seat zoning. Risk of infection and serious illness were quantified using a model incorporating parameters such as vaccination coverage, vaccine prevention effectiveness, and sensitivity of polymerase chain reaction (PCR) or qualitative antigen tests. When vaccine prevention effectiveness was 50% (corresponding to 4 months for the delta variant and 1–2 months for the omicron variant after the second vaccine dose), the risk of infection and serious illness among vaccinated spectators were 0.32–0.40 and 0.13–0.16 times of those who tested negative, respectively. In contrast, the risks of infection and serious illness among vaccinated spectators without measures such as mask wearing were 4.0 and 1.6 times higher than those among unvaccinated spectators with such measures, respectively. The risk of infection with an 80% vaccination coverage and a vaccine prevention effectiveness of 20% (corresponding to 5–6 months for the delta variant or 3–4 months for the omicron variant after the second vaccine dose) was comparable to that of a 20% vaccine coverage and a vaccine prevention effectiveness of 80% (corresponding to 1–3 months for delta variant after the second vaccine dose). Regarding zoning, there was little difference in risk with a vaccination coverage of ≥80%. Adherence to individual measures after vaccination and maintenance of high vaccine effectiveness among spectators at stadiums are important for reducing risk of infection and serious illness. Furthermore, seat zoning did not affect overall infection risk reduction.
Remote Intensive Parent-Implemented Intervention for Young Children on the Autism Spectrum During Covid-19: The Experience of Parents and Therapists
Authors: Wood de Wilde Hilary , Kojovic Nada , Robertson Celine , Karr Catherine , Akman Leyla , Caccia Florence , Costes Astrid , Etienne Morgane , Franchini Martina , Gentaz Edouard , Schaer Marie
Published: February 2022

In response to a Covid-19 period of home-confinement, autism early intervention programs in Geneva, Switzerland, converted their in-person services to a telehealth format. Forty-five families received daily videoconferencing sessions of primarily parent-implemented intervention. Questionnaires were completed at three time points. Child progress was monitored using the Early Start Denver Model Curriculum Checklist. Parents maintained high levels of participation and satisfaction, regardless of socio-economic or cultural background, with the majority reporting an improvement in their use of intervention techniques. Child progress followed a pattern of continued significant improvement across most developmental domains. Findings suggest that a more frequent dosage of parent-implemented intervention than typically studied is not only feasible, but appreciated by caregivers, especially when delivered via the time-saving videoconferencing format.
The impact of retracted randomised controlled trials on systematic reviews and clinical practice guidelines: a meta-epidemiological study
Authors: Kataoka Yuki , Banno Masahiro , Tsujimoto Yasushi , Ariie Takashi , Taito Shunsuke , Suzuki Tomoharu , Oide Shiho , Furukawa Toshi A.
Published: February 2022

Objectives

To investigate whether and when the correction is done in Systematic Reviews (SRs) and Clinical Practice Guidelines (CPGs) when their included Randomised Controlled Trials (RCTs) have been retracted.

Design

A meta-epidemiological study.

Data sources

The Retraction Watch Database.

Eligibility criteria for selecting studies

SRs and CPGs citing the retracted RCTs on Web of Science.

Review methods

We investigated how often the retracted RCTs were cited in SRs and CPGs. We also investigated whether and when such SRs and CPGs corrected themselves by visually inspecting their current web pages. We summarized the proportion of correction and the time from retraction to correction.

Results

We identified 98 retracted RCTs as well as 360 articles (335 SRs and 25 CPGs) citing them. Among the 360 articles, 157 (44%) were published after the retraction, 203 (56%) were published before retraction. Among 77 articles published citing already retracted RCTs in their evidence synthesis without caution, none corrected themselves after publication. Of 203 articles published before retraction, 149 included RCTs that were later retracted in their evidence synthesis. Among them, one SR was retracted due to plagiarism. Only 5% of SRs (6/130) and 11% of CPGs (2/18) corrected their results.

Conclusions

A large number of SRs and CPGs included already retracted RCTs without caution and never corrected themselves. When SRs and CPGs had included RCTs which were later retracted, only a small minority corrected their evidence syntheses. The scientific community, including publishers and researchers, should make systematic and concerted efforts to remove the impact of retracted RCTs.

What is already known on this topic

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Systematic Reviews (SRs) and Clinical Practice Guidelines (CPGs) aggregating randomised controlled trials (RCTs) are important sources of information for clinical decision making.

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There are anecdotal reports of publications citing retracted RCTs and point to the problem of their continued citation after retraction.

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However, there are no studies that comprehensively examined the fate of retracted RCTs on SRs and CPGs in their evidence synthesis.

What this study adds

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A considerable number of SRs and CPGs cited already retracted RCTs and none corrected themselves later.

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Only a small minority of SRs (5%, 6/130) and CPGs (11%, 2/18) which cited RCTs that were later retracted corrected their findings after the retraction was announced.

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The results indicate that publishers and researchers should make efforts to remove the impact of retracted RCT.
Presentation and Short-term Course of New Onset Cannabis Induced Psychotic Disorder in Males
Authors: D’Souza Deepak Cyril , Raj Justin , Ganesh Suhas , Goyal Nishant , KL Vidya , Tikka Sai Krishna , Shreekantiah Umesh , Murthy Pratima , Ram Daya , Sharma Priyamvada , Sinha Vinod K , Cortes-Briones Jose
Published: February 2022

Introduction

Cannabis use has been associated with several psychosis outcomes including acute and persistent psychosis termed Cannabis Induced Psychotic Disorder (CIPD). The clinical and cognitive profile, course of CIPD, and the extent to which it is different from psychosis unrelated to cannabis exposure (PsyNoCan) is not clear.

Methods

The acute presentation and short-term (∼4 weeks) course of hospitalized male patients with new onset CIPD were compared prospectively to PsyNoCan using measures of psychosis, depression, mania, memory and other cognitive processes at admission, and after 4 weeks of inpatient hospitalization. A subsample of CIPD patients were followed up after 4-6 months of discharge. Cognitive test performance was benchmarked for comparison in healthy controls and individuals with Cannabis Use Disorder.

Results

Compared to PsyNoCan (n=53), CIPD (n=66) had a significantly lower severity of psychotic symptoms at admission but no differences in mood symptoms. After 4 weeks of hospitalization, the CIPD group had less psychosis. While both groups had significant cognitive deficits at baseline compared to healthy controls, cognitive test performance improved to a greater extent in CIPD. Amongst 16 CIPD cases with longitudinal follow-up data, 10 relapsed with psychosis within 6 months after resuming cannabis use.

Conclusion

CIPD in males has a distinct presentation and short-term course, characterized by less severe psychosis, and greater resolution of psychopathology and cognitive deficits relative to PsyNoCan. Relapse of cannabis use may predict poorer long-term outcomes with greater psychotic relapses. The longer-term course, prognosis and biology of CIPD, and its presentation in females needs further study.
Composite branch construction by dual autozooidal budding modes in hornerids (Bryozoa: Cyclostomatida)
Authors: Batson Peter B. , Tamberg Yuta , Taylor Paul D.
Published: February 2022

Horneridae (Cyclostomata; Cancellata) is a family of marine bryozoans that form tree-like colonies bearing functionally unilaminate branches. Colony development in this clade is not well understood. We used micro-CT and SEM to trace zooidal budding in Hornera from the ancestrula onwards. Results show that hornerid branches are constructed by dual zooidal budding modes occurring synchronously at two separate budding sites at the growing tips. Frontal autozooids bud from a multizooidal budding lamina. Lateral autozooids bud from discrete abfrontal budding loci by 'exomural budding', a previously undescribed form of budding centred on hypostegal pores in interzooidal grooves on the colonial body wall. These two budding modes are integrated during primary branch morphogenesis, forming composite, developmentally bilaminate, branches. Tracing development back to the founding zooids shows that the ancestrula and adventitious periancestrular autozooids are the first-formed lateral autozooids. They grow as a vertical stem onto which new laterals bud exomurally, intercalating with earlier autozooids to form an expanding funnel. The inner wall of this funnel becomes a ring-shaped budding lamina, from which the first frontal autozooids bud centripetally. When the branch crown splits, the ring lamina is subdivided, each fragment becoming a paramedial budding lamina in its own branch, while new laterals continue to be budded exomurally onto the frontal walls of existing laterals. Co-occurrence of two rare cyclostome frontal budding types - adventitious budding on the ancestrula and exomural budding on the branches - suggests they may be homologous. Patterns of exomural budding vary among hornerids. Narrow-branched taxa possess a single medial line of budding sites on the abfrontal wall; wide-branched species have up to six parallel lines of loci. Exomural budding also occurs sporadically in Calvetia osheai, a radial-branching hornerid. Future studies of cancellate taxonomy and phylogeny may benefit from morphological concepts presented here.
Clonal dynamics of SARS-CoV-2-specific T cells in children and adults with COVID-19
Authors: Khoo Weng Hua , Jackson Katherine , Phetsouphanh Chansavath , Zaunders John J. , Alquicira-Hernandez José , Yazar Seyhan , Ruiz-Diaz Stephanie , Singh Mandeep , Dhenni Rama , Kyaw Wunna , Tea Fiona , Merheb Vera , Lee Fiona X. Z. , Burrell Rebecca , Howard-Jones Annaleise , Koirala Archana , Zhou Li , Yuksel Aysen , Catchpoole Daniel R. , Lai Catherine L. , Vitagliano Tennille L. , Rouet Romain , Christ Daniel , Tang Benjamin , West Nicholas P. , George Shane , Gerrard John , Croucher Peter I. , Kelleher Anthony D. , Goodnow Christopher G. , Sprent Jonathan D. , Powell Joseph D. , Brilot Fabienne , Nanan Ralph , Hsu Peter S. , Deenick Elissa K. , Britton Philip N. , Phan Tri Giang
Published: February 2022

Children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop less severe coronavirus disease 2019 (COVID-19) than adults. The mechanisms for the age-specific differences and the implications for infection-induced immunity are beginning to be uncovered. We show by longitudinal multimodal analysis that SARS-CoV-2 leaves a small footprint in the circulating T cell compartment in children with mild/asymptomatic COVID-19 compared to adult household contacts with the same disease severity who had more evidence of systemic T cell interferon activation, cytotoxicity and exhaustion. Children harbored diverse polyclonal SARS-CoV- 2-specific naïve T cells whereas adults harbored clonally expanded SARS-CoV-2-specific memory T cells. More naïve interferon-activated CD4+T cells were recruited into the memory compartment and recovery was associated with the development of robust CD4+memory T cell responses in adults but not children. These data suggest that rapid clearance of SARS-CoV-2 in children may compromise their cellular immunity and ability to resist reinfection.

HIGHLIGHTS

Children have diverse polyclonal SARS-CoV-2-specific naïve T cells

Adults have clonally expanded exhausted SARS-CoV-2-specific memory T cells

Interferon-activated naïve T cells differentiate into memory T cells in adults but not children

Adults but not children develop robust memory T cell responses to SARS-CoV-2
Task-based fMRI in early Multiple Sclerosis: what is the best head motion correction approach?
Authors: Soares Júlia F. , Abreu Rodolfo , Cláudia Lima Ana , Sousa Lívia , Batista Sónia , Castelo-Branco Miguel , Duarte João Valente
Published: February 2022

Functional MRI (fMRI) is one of the most common brain imaging modalities used for understanding brain organization and connectivity abnormalities associated with multiple sclerosis (MS). The fMRI signal is highly perturbed by head motion, which degrades data quality and influences all image-derived metrics. Numerous correction approaches have been proposed over the years to overcome the problems induced by head motion, however, despite a few efforts, there are still current and persistent controversies regarding the best correction strategy. The lack of a systematic comparison between different correction approaches motivates the search for optimal correction models, particularly in studies with clinical populations prone to characterize by higher motion. Moreover, motion correction strategies gain more relevance in task-based designs, which are less explored compared to resting-state and may have a crucial role in describing the functioning of the brain and highlighting specific connectivity changes.

We acquired fMRI data from a group of patients with early MS and matched healthy controls (HC) during performance of a visual task, characterized motion in both groups, and compared the most used motion correction methods. We compared task-activation metrics obtained from models without motion correction, models containing 6 or 24 motion parameters (MPs) as nuisance regressors, models containing 6 or 24 MPs and motion outliers detected with FD or DVARS as nuisance regressors (scrubbing) and models with 6 or 24 MPs where motion outliers were corrected through volume interpolation. To our knowledge, volume interpolation is a frequently used approach but was never compared with other existent methods.

Our results showed that there were no differences in motion between groups, suggesting that recently diagnosed MS patients do not present problematic motion. In general, models with 6 MPs present higher Z-scores than models with 24 MPs, suggesting the 6 MPs as the best trade-off between motion correction and preservation of valuable information. However, correction approaches differ between groups, regarding the combination of MPs with correction of motion outliers. Models with 6 MPs and outliers’ volume interpolation or scrubbing with FD presented higher Z-scores in the MS group, while models with 6 MPs and scrubbing with DVARS or volume interpolation were the best combinations for the HC group. Differences between groups in motion correction strategies draw attention to the intrinsic impact of MS on fMRI analyses, which should be carefully addressed.

This work paves the way towards finding an optimal motion correction strategy, which is required to improve the accuracy of fMRI analyses, crucially in clinical studies in MS and other patient populations.
Flagellar energy costs across the Tree of Life
Authors: Schavemaker Paul E , Lynch Michael
Published: February 2022

Flagellar-driven motility grants unicellular organisms the ability to gather more food and avoid predators, but the energetic costs of construction and operation of flagella are considerable. Paths of flagellar evolution depend on the deviations between fitness gains and energy costs. Using structural data available for all three major flagellar types (bacterial, archaeal, and eukaryotic), flagellar construction costs were determined for Escherichia coli, Pyrococcus furiosus, and Chlamydomonas reinhardtii. Estimates of cell volumes, flagella numbers, and flagellum lengths from the literature, yield flagellar costs for another ∼200 species. The benefits of flagellar investment were analysed in terms of swimming speed, nutrient collection, and growth rate; showing, among other things, that the cost-effectiveness of bacterial and eukaryotic flagella follows a common trend. However, a comparison of whole cell costs and flagellum costs across the Tree of Life reveals that only cells with larger cell volumes than the typical bacterium could evolve the more expensive eukaryotic flagellum. These findings provide insight into the unsolved evolutionary question of why the three domains of life each carry their own type of flagellum.
Histone deacetylase inhibitor induces acetyl-CoA depletion leading to lethal metabolic stress in RAS-pathway activated cells
Authors: Basseville Agnes , Violet Pierre-Christian , Safari Maryam , Sourbier Carole , Linehan W. Marston , Robey Robert W. , Levine Mark , Sackett Dan L. , Bates Susan E.
Published: February 2022

RAS-mutant cancers are among the most refractory to treatment. Apart from new G12C genotype targeted therapies, strategies to kill RAS-mutant cells by directly targeting RAS or its downstream effectors have been mostly unsuccessful, mainly due to pathway redundancy and heterogeneities in RAS-induced phenotypes. Here we identified a RAS-phenotype that can be targeted by the histone deacetylase inhibitor (HDACi) romidepsin. We showed that the hyperacetylation induced by romidepsin depleted acetyl-CoA, the cell donor substrate for acetylation, and led to metabolic stress and death in KRAS-activated cells. Elastic net analysis on transcriptomics from a 608-cell panel confirmed that HDACi sensitivity was linked to a difference in profiles in two pathways involved in acetyl-CoA metabolism. The analysis of a clinical dataset confirmed that perturbation of the two acetyl-CoA pathways were correlated with HDACi sensitivity in patients treated with belinostat. Our analysis suggests the potential utility of a RAS-associated acetyl-CoA phenotype to sharpen treatment choices for RAS-activated tumors.
Hybridoma Screening by Antibody Capture: Detection of Cell-Surface Binding by Immunofluorescence
Authors: Greenfield Edward A.
Published: February 2022

If the antigen of interest is a cell-surface protein, immunofluorescence can be used to identify hybridomas secreting monoclonal antibodies to these proteins. They can be stained on microscope chamber slides, flat-bottomed cell culture plates (96, 48, or 24 well), or imaging plates (96 well). This protocol uses 96-well imaging plates.
Cryopreservation of Xenopus Sperm and In Vitro Fertilization Using Frozen Sperm Samples
Authors: Noble Anna , Abu-Daya Anita , Guille Matt
Published: February 2022

The cryopreservation of Xenopus sperm allows for a significant reduction of the number of animals that must be kept, more efficient archiving of genetically altered (GA) lines, and easy exchange of lines with other laboratories, leading to improvements in animal welfare and cost efficiency. In this protocol, sperm from Xenopus laevis or Xenopus tropicalis are frozen using straightforward techniques and standard laboratory equipment. Testes are macerated in Leibovitz's L-15 medium, mixed with a simple cryoprotectant made from egg yolk and sucrose, and frozen slowly overnight in a polystyrene box at −80°C. Unlike mouse sperm, Xenopus sperm can be stored at −80°C rather than in liquid nitrogen, further reducing costs. The frozen sperm are then used for in vitro fertilization.
Short-term cooling load prediction for office buildings based on feature selection scheme and stacking ensemble model
Authors: Gao Wenzhong , Huang Xingzong , Lin Mengya , Jia Jing , Tian Zhen
Published: February 2022

Purpose

The purpose of this paper is to target on designing a short-term load prediction framework that can accurately predict the cooling load of office buildings.

Design/methodology/approach

A feature selection scheme and stacking ensemble model to fulfill cooling load prediction task was proposed. Firstly, the abnormal data were identified by the data density estimation algorithm. Secondly, the crucial input features were clarified from three aspects (i.e. historical load information, time information and meteorological information). Thirdly, the stacking ensemble model combined long short-term memory network and light gradient boosting machine was utilized to predict the cooling load. Finally, the proposed framework performances by predicting cooling load of office buildings were verified with indicators.

Findings

The identified input features can improve the prediction performance. The prediction accuracy of the proposed model is preferable to the existing ones. The stacking ensemble model is robust to weather forecasting errors.

Originality/value

The stacking ensemble model was used to fulfill cooling load prediction task which can overcome the shortcomings of deep learning models. The input features of the model, which are less focused on in most studies, are taken as an important step in this paper.