bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Variability of Palm Lethal Decline Phytoplasmas in the Caribbean Basin and Florida, U.S.A., Based on a Multilocus Analysis
Authors: Soto Noemi , Helmick Ericka E. , Harrison Nigel A. , Bahder Brian W.
Published: November 2021

Palm lethal decline phytoplasmas are an important group of plant pathogens that cause death in a variety of palm species throughout the Caribbean basin and the southeastern United States. The 16SrIV-D phytoplasma was introduced to the state of Florida, United States; it has since caused severe economic losses to the green industries of Florida and is threating natural ecosystems because of its ability to infect the native palm Sabal palmetto. In this study, the genetic variability of the 16SrIV-D phytoplasma was assessed over a 10-year period to determine if multiple introductions had occurred or if natural mutations were occurring. Furthermore, the genetic variability of the palm lethal decline phytoplasma group (16SrIV) was assessed with a multiple locus analysis using the 16S ribosomal RNA gene, the 16S-23S intergenic spacer region, and secA and groEL genes. Overall, no variability of the 16SrIV-D phytoplasma was documented in Florida over a 10-year period. The multilocus analysis showed support for three distinct species of the phytoplasma in the Caribbean basin that infect palms and further support that the 16SrIV-C from Tanzania is not closely related. Furthermore, 16SrIV-B and 16SrIV-D were found to be the same phytoplasma based on 100% identity between the two based on intergenic spacer region, secA, and groEL analysis. This study represents the first robust, multilocus analysis of palm-infecting phytoplasmas from the Caribbean and sheds light on the phylogeny and evolution of the group.
Vagal Tone and Proinflammatory Cytokines Predict Feeding Intolerance and Necrotizing Enterocolitis Risk
Authors: Meister Alissa L. , Gardner Fumiyuki C. , Browning Kirsteen N. , Travagli R. Alberto , Palmer Charles , Doheny Kim Kopenhaver
Published: November 2021

Background:

Necrotizing enterocolitis (NEC) is the leading cause of death due to gastrointestinal disease in preterm neonates; yet, clinicians lack reliable and noninvasive predictive tools.

Purpose:

We aimed to test that diminished high-frequency heart rate variability (HF-HRV) and elevated levels of proinflammatory cytokines would have utility in NEC prediction.

Methods:

In this multisite prospective study, we enrolled 250 preterm (26-34 weeks' postmenstrual age [PMA]) neonates with physiological stability at 72 hours of life. HRV was measured noninvasively using electrocardiograhic data from standardized cardiorespiratory monitors at postnatal week 1 of life and weekly thereafter until 35 weeks' PMA or discharge; blood was collected for cytokines at postnatal weeks 1 and 3. NEC was diagnosed via Modified Bell's Staging Criteria.

Results:

HF-HRV was decreased at weeks 1 and 2 in neonates (47% females) who developed feeding intolerance or stage 2+ NEC. In addition, these neonates displayed elevated levels of IL-8 at week 1 and increased levels of IL-1β, IL-6, TNF-α, and IL-8 at week 3 of life. Low HF-HRV was associated with elevated IL-6 or IL-8 levels at weeks 1 and 3 of life. Logistic regression indicated that only HF-HRV was a significant predictor of feeding intolerance or NEC development.

Implications for Practice and Research:

HRV is a promising noninvasive modality for NEC risk detection. The association of low HF-HRV with elevated proinflammatory cytokines provides evidence for a putative role of the vagal cholinergic pathway in NEC pathogenesis. Future studies should focus on application of these techniques to test clinical therapeutics.

Video Abstract available at https://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx?autoPlay=false&videoId=54.
Tubulin alpha 1c promotes aerobic glycolysis and cell growth through upregulation of yes association protein expression in breast cancer
Authors: Wu Zhu , Sun Shengrong , Fan Rong , Wang Zhuo
Published: November 2021

Tubulin alpha 1c (TUBA1C) as a member of α-tubulin was identified to take part in the occurrence and development of hepatocellular carcinoma and pancreatic cancer. Using the bioinformatics, we noticed that TUBA1C level was also increased in breast cancer was also demonstrated. Here, we explored TUBA1 role in modulation of breast cancer cell aerobic glycolysis, growth and migration and explored whether yes association protein (YAP) was involved. Fifty-five matched breast cancer tissues and the para-carcinoma normal tissues were included in this study and used to verify TUBA1C expression using quantitative reverse transcription-PCR and western blotting. ATP level, lactate secretion and glucose consumption were used to assess aerobic glycolysis. Cell growth, invasion, migration and tumorigenesis were detected using cell count kit-8, transwell, wound healing and animal assays. TUBA1 was upregulated in breast cancer, which associated with advanced primary tumor, lymph node, metastasis stage and tumor size. Silencing of TUBA1C with sh-TUBA1C infection led to significant inhibitions in ATP level, lactate secretion, glucose consumption, cell growth, migration, invasion and tumorigenesis, as well as declined YAP expression, while TUBA1C overexpression induced a opposite result. And, the above tendencies induced by TUBA1C downregulation were reversed by YAP overexpression. This study revealed that TUBA1C was overexpressed in breast cancer and promoted aerobic glycolysis and cell growth through upregulation of YAP expression.
Stewart-Treves syndrome in an older woman successfully treated by metronomic chemotherapy: case report and literature survey
Authors: Maréchal Stephanie , Reginster Pierre , de Muylder Antoine , Servais Arvne , Mutijima Eugene , Focan Christian
Published: November 2021

The authors present the case of a 94-year-old woman suffering from a right arm angiosarcoma developed after primary breast cancer and treated with success by oral metronomic chemotherapy based on daily low doses of cyclophosphamide and prednisone. The case description is followed by a short review of actual knowledge on the subject.
Cellular aging and telomere dynamics in pregnancy
Authors: Panelli Danielle M. , Bianco Katherine
Published: November 2021

Purpose of review

Telomere biology is an emerging area of scientific interest. Telomeres are deoxynucleic acid caps at the ends of chromosomes that naturally shorten over one's lifespan; because of this, short telomeres have been studied as a marker of cellular aging. Given the association between short telomeres and genetic and environmental factors, their role in pregnancy has become an intriguing area of research.

Recent findings

This review describes recent data on telomeres in pregnancy. Specifically, we discuss the association between short maternal leukocyte telomeres and poor nutritional status, between short neonatal telomeres and greater maternal psychosocial stress, and between shorter fetal amniotic membrane telomeres and the spontaneous onset of parturition. We also review recent studies suggesting that events during pregnancy can impact telomeres in the offspring years into the future.

Telomere length varies in maternal, placental, and neonatal cells, but within each of these compartments telomeres may play their own distinct role during pregnancy. Whether telomeres are reflective of the cumulative impact of stressors, or part of an as-yet unknown fetal programming mechanism is an area of interest. With future research, we may work toward a better understanding of gestational biology which could have far reaching intergenerational impacts.
Chatbot-Assisted Care Management
Authors: Schario Mark E. , Bahner Carol A. , Widenhofer Theresa V. , Rajaballey Joan I. , Thatcher Esther J.
Published: November 2021

Purpose/Objectives:

Chatbots are automated conversation pathways that users can access through text message or email on smartphones or other connected devices. In care management, they can be used to monitor patients' health conditions or recovery from procedures. This article describes nurse care managers' experiences using chatbots in patient care, illustrated through two patient case reviews. Considerations for planning and implementing chatbot technology in care management settings are discussed.

Primary Practice Setting:

This care management service is part of an accountable care organization that serves 582,000 patients in University Hospitals of Cleveland, Ohio. Care management focuses on patients with chronic conditions, recent hospital discharges, and other needs. Care managers comprise a centralized team as well as embedded staff in select primary care practices.

Findings/Conclusions:

The two patient cases are exemplars from the care management program serving patients recently discharged from the hospital with ongoing chronic conditions that increase risk for readmission. Use of chatbots helped overcome obstacles to conventional care management outreach and resulted in improved outcomes and strong trusting relationships with the care managers.

Implications for Care Management Practice:

Patients who typically do not respond to other types of care manager outreach may respond to text message–based, asynchronous chatbot communication. Interpersonal relationships between care managers and patients can be strengthened by chatbot support. Chatbot technology tracks patients' progress and offers insights to patients and clinicians to facilitate earlier interventions when problems occur. Chatbots make frequent patient contact to collect and provide routine information, allowing care managers to spend more time on high-value interactions that require clinical judgment. Potential concerns about chatbots include effect on labor force, information security, health equity, and oversight of content.
Postpartum Depressive Symptoms and Experiences During COVID-19
Authors: Goyal Deepika , Beck Cheryl Tatano , Webb Rebecca , Ayers Susan
Published: November 2021

Purpose:

To identify postpartum depression risk and describe experiences of women in the first 6 weeks after giving birth during the COVID-19 pandemic.

Study Design and Methods:

Using a convergent mixed-methods approach, we recruited a convenience sample of women living in the United States who gave birth March 1, 2020 or later from social media Web sites. Participants completed the Postpartum Depression Screening Scale-Short Form and provided written answers to open-ended questions regarding their experiences at home with their new infant.

Results:

Our 262 participants were on average 32.6 years of age, the majority were White (82%), married or partnered (91.9%), and college educated (87.4%). Mean postpartum depression score was 17.7 (SD = 5.9) with 75% scoring ≥14, indicating significant postpartum depressive symptoms. Qualitative content analysis revealed five themes: Isolation and seclusion continue; Fear, anxiety, and stress filled the days; Grieving the loss of normal: It's just so sad; Complicated by postpartum depression: A dark time; and There is a silver lining. Quantitative and qualitative findings provided a holistic view of women's depressive symptoms and experiences at home with their infants during the COVID-19 pandemic.

Clinical Implications:

Although policies that reduce risk of COVID-19 exposure and infection for patients and the health care team must continue to be implemented, the adverse effects of depressive symptoms on maternal–infant wellbeing within the context of increased isolation due to the pandemic need to be kept at the forefront. Nurses need to be aware of the consequences of women sheltering in place and social distancing on maternal–infant outcomes, particularly on depression and likelihood of breastfeeding.
Refining Orthognathic Surgery Results by Synchronous Cheek Fat Compartment Augmentation with Fat Grafting in Adult Females with Class III Skeletal Profiles
Authors: Denadai Rafael , Wallace Christopher Glenn , Chou Pang-Yun , Lo Lun-Jou , Chen Yu-Ray , Chang Chun-Shin
Published: November 2021

Patients with maxillomandibular disharmony may present with a flat to concave midface. The effects of orthognathic surgery concomitant with midface fat grafting on facial appearance and midface volumetric and positional change have not formally been assessed to date. The authors’ approach for synchronous orthognathic surgery and fat grafting is described and evaluated. Adult female patients (n = 20) who underwent synchronous two-jaw orthognathic surgery and cheek-specific fat grafting (1.9 ± 0.6 cm3 per side) for correction of skeletal class III deformity and anteromedial cheek deficiency were prospectively included. Preoperative and postoperative photographs were appraised by 42 blinded raters using facial appearance scales for beauty, attractiveness, and pleasantness parameters. The three-dimensional midface soft-tissue volume change and postoperative cheek mass position were computed. Facial imaging data from gender-, ethnic-, and facial pattern–matched adult patients (n = 20) who underwent isolated two-jaw orthognathic surgery (n = 20) were included for comparison. The three-dimensional facial norms database–derived cheek mass position information (2.19 ± 1.31mm) was also adopted for analysis. Patients treated with the synchronous procedure had significantly (p < 0.001) increased facial appearance–related perception change for beauty (2.9 ± 1.6), attractiveness (2.8 ± 1.8), and pleasantness (3.0 ± 1.5) parameters, three-dimensional midface volume change (1.8 ± 0.5 cm3), and postoperative cheek mass position (2.16 ± 0.47 mm) in comparison with those treated with the isolated procedure (2.0 ± 1.5, 1.9 ± 1.6, 2.3 ± 1.6, 0.6 ± 0.2 cm3, and 1.84 ± 0.43 mm, respectively). Healthy female individuals had similar and larger cheek mass position than patients treated with synchronous (p > 0.05) and isolated (p < 0.001) procedures, respectively. Synchronous orthognathic surgery and check-specific fat grafting resulted in superior enhancement of facial appearance and midface volume and position compared with isolated orthognathic surgery.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Gingivosupraperiosteoplasty following Presurgical Maxillary Orthopedics Is Associated with Normal Midface Growth in Complete Unilateral and Bilateral Cleft Patients at Mixed Dentition
Authors: Mejia Martha , Wolfe Erin M. , Murphy Blake D. , Rothenberg Leonard , Tejero Ana , Bauer Mislen , Wolfe S. Anthony
Published: November 2021

Background:

Passive orthodontic appliances and gingivosupraperiosteoplasty are adjuncts that can be used by surgeons at the time of primary cleft lip repair. These treatments, along with the surgical technique of cleft lip and palate repair, may impact midface growth. The objective of this study was to describe the authors’ protocol for unilateral and bilateral cleft lip repair and to evaluate midfacial growth in a cohort of patients at mixed dentition who had undergone presurgical passive orthodontic appliance therapy and gingivosupraperiosteoplasty at the time of unilateral and bilateral cleft lip repair.

Methods:

Fifteen complete unilateral and 15 complete bilateral cleft lip and palate patients underwent passive orthodontic appliance treatment and primary lip repair with gingivosupraperiosteoplasty. Lateral cephalograms were analyzed by three blinded reviewers. Mean cephalometric measurements at mixed dentition were compared to cephalometric values for noncleft patients, unilateral cleft lip and palate patients who did not undergo gingivoperiosteoplasty or presurgical treatment, and unilateral cleft lip and palate patients who underwent gingivoperiosteoplasty/nasoalveolar molding with independent samples t tests.

Results:

Mean cephalometric values were within age-specific normal values for sella-nasion–A point, sella-nasion–B point, A point–nasion–B point, and facial axis. Eighty-seven (13/15) percent of unilateral cleft lip and palate patients and 93 percent (14/15) of bilateral cleft lip and palate patients did not exhibit skeletal class III malocclusion. There was no significant difference between cephalometric values for our patients and patients who did not receive gingivosupraperiosteoplasty or presurgical treatment or who underwent the gingivoperiosteoplasty/nasoalveolar molding protocol.

Conclusions:

Presurgical passive orthodontic appliances, combined with gingivosupraperiosteoplasty at the time of lip repair, leads to normal maxillary development in most patients at mixed dentition. Assessment of midface growth at skeletal maturity is required.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Costal Cartilage Spring Graft for Late Correction of Cleft Lip Nose Deformity: New Technique
Authors: Erol Onur O. , Agaoglu Galip
Published: November 2021

Background:

Late correction of cleft lip nose deformity continues to be a challenge because of the weakness of cartilages and the collapsing forces of tight contracted soft tissues. The authors describe the new technique of costal cartilage spring graft for columella and lower lateral cartilage as a block to achieve symmetric, aesthetically more durable, and acceptable results for the late correction of cleft lip nose deformity.

Methods:

Late cleft lip nose repair with simultaneous rhinoplasty was performed in 92 patients with unilateral cleft lip nose deformity. For correction of cleft lip nose deformity, a strut graft 2 to 3 mm in width, 0.5 to 1 mm in thickness, and 5 to 7 cm in length was prepared from costal cartilage (autograft or allograft). The strut graft was curved and bowed with fingers to simulate the medial and lateral crura of the alar cartilage. A crescent-shaped skin excision from the alar rim and a vertical incision in the columella were made. The intercrural and alar areas were dissected to create sufficient space for the insertion of a bow-shaped spring cartilage graft. After insertion of the cartilage graft, the alar rim was closed with continuous 6-0 Monocryl and the columella was closed with 5-0 Vicryl.

Results:

Correction of depressed alar cartilage and webbing, lengthening the columella using spring costal cartilage, and symmetric nostrils were achieved in all cases. The mean follow-up period was 5 years (range, 2 to 15 years).

Conclusion:

These procedures, septoplasty, and simultaneous rhinoplasty provided long-term satisfactory results in the late correction of cleft lip nose deformity.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Safety Comparison of Abdominoplasty and Brazilian Butt Lift: What the Literature Tells Us
Authors: Del Vecchio Daniel A. , Wall Simeon J. , Mendieta Constantino G. , Aslani Alexander A. , Hoyos Alfredo E. , Mallucci Patrick L. , Whitaker Iain S.
Published: November 2021

Background:

Although abdominoplasty is a mainstay of the plastic surgeon, the safety of the Brazilian butt lift (BBL) has been questioned, effectively being prohibited in some countries. The central rationale for the safety concern over the BBL stems from a publication stating a mortality rate of one in 3000. The question remains: What is the real safety of these procedures?

Methods:

Focusing on mortality, literature searches were performed for BBL and for abdominoplasty. The 2017 Aesthetic Surgery Education and Research Foundation survey data and publication were examined and analyzed. Additional data from the American Association for Accreditation of Ambulatory Surgical Facilities were obtained independently.

Results:

Abdominoplasty and BBL appear to have similar safety based on mortality; however, the nature of their mortalities is different. Although most abdominoplasty deaths are secondary to deep venous thrombosis/pulmonary embolism—inherent circulatory thrombotic abnormality—BBL mortality is associated with iatrogenic pulmonary fat embolism. BBL mortality rates from more recent surveys on BBL safety demonstrate a mortality of one in 15,000.

Conclusions:

Although deep venous thrombosis/pulmonary embolism will always remain an abdominoplasty risk, intraoperative BBL pulmonary fat embolism has the potential to be reduced dramatically with a better understanding of dynamic anatomy, surgical instrumentation, and technique. The authors are now presented with a better lens with which to view a more accurate safety profile of BBL surgery, including its place among other commonly performed aesthetic procedures.
Advanced imaging in acute ischemic stroke: an updated guide to the hub-and-spoke hospitals
Authors: Sharobeam Angelos , Yan Bernard
Published: November 2021

Purpose of review

The purpose of this review is to summarize the role of the hub-and-spoke system in acute stroke care, highlight the role of advanced imaging and discuss emerging concepts and trials relevant to the hub-and-spoke model.

Recent findings

The advent of advanced stroke multimodal imaging has provided increased treatment options for patients, particularly in rural and regional areas. When used in the hub-and-spoke model, advanced imaging can help facilitate and triage transfers, appropriately select patients for acute therapy and treat patients who may otherwise be ineligible based on traditional time metrics.

Recent, ongoing trials in this area may lead to an even greater range of patients being eligible for acute reperfusion therapy, including mild strokes and patients with large core infarct volumes.

Integration of advanced imaging into a hub-and-spoke system, when complemented with other systems including telemedicine, improves access to acute stroke care for patients in regional and rural areas.
Atorvastatin does not display an antimicrobial activity on its own nor potentiates the activity of other antibiotics against Acinetobacter baumannii ATCC17978 or A. baumannii AB030
Authors: Kornelsen Vanessa , Unger Mark , Kumar Ayush
Published: November 2021

With the current arsenal of antibiotics increasingly becoming ineffective against bacteria, there is an increasing interest in the possibility of using previously approved non-antibiotic drugs as antimicrobials. Statins have recently been investigated for their antimicrobial activity and their ability to potentially synergize with current treatment options. Atorvastatin had been shown previously to be the most promising candidate for effectivity against

Acinetobacter baumannii

ATCC17978. In this study, we tested atorvastatin for its activity against an extensively drug-resistant (XDR) strain

A. baumannii

AB030. However, our data show that atorvastatin has no effect

A. baumannii

AB030. Intriguingly, atorvastatin was also ineffective against our laboratory’s

A. baumannii

ATCC17978. This lack of atorvastatin activity against

A. baumannii

ATCC17978 cannot be attributed to RND efflux pumps as a strain deficient in the three most clinically relevant RND efflux systems in

A. baumannii

showed no change in susceptibility compared to its parent strain ATCC17978. Further, atorvastatin failed to potentiate the activity of tobramycin and ciprofloxacin. While it is not clear to us why atorvastatin is not active against

A. baumannii

ATCC17978 used in our study, our study shows that evaluation of compounds for their antibacterial activity should involve multiple strains to account for strain-to-strain variation.
Effect of COVID-19 on vaccination coverage in Brazil
Authors: Silveira Marcelle Moura , Conrad Neida Lucia , Leivas Leite Fábio Pereira
Published: November 2021

During the COVID-19 pandemic, recommendations for maintaining physical distance, restricted mobility measures, as well as fear of mass transmission by going to health centers have significantly contributed to the general vaccination coverage, which by and large is decreasing worldwide; thus, favoring the potential re-emergence of vaccine-preventable diseases. In this study, we have used the existing data on vaccination coverage during the pre-pandemic (2019) as well as the pandemic (2020) period to evaluate the impact of coronavirus outbreaks during the vaccination drive in Brazil. Furthermore, we have accumulated data since 2015 among the different regions of the country to acquire more consistent information. The various vaccines analyzed in our study were meningococcal C conjugate, Triple antigen vaccine, 10-valent pneumococcal conjugate, and BCG; subsequently, the data were obtained from the National Disease Notification System. This study revealed that the ongoing immunization drive saw a steep decline of around 10 to 20% during the (2019–2020) pandemic period in Brazil. These results provide strong evidence towards the decreasing trends following the vaccination programs during the COVID-19 pandemic period in Brazil. Furthermore, our results also highlight the importance of adopting widespread multi-component interventions to improve vaccination uptake rates.
Shared components of heritability across genetically correlated traits
Authors: Ballard Jenna Lee , O’Connor Luke Jen
Published: November 2021

Most disease-associated genetic variants are pleiotropic, affecting multiple genetically correlated traits. Their pleiotropic associations can be mechanistically informative: if many variants have similar patterns of association, they may act via similar pleiotropic mechanisms, forming a shared component of heritability. We developed Pleiotropic Decomposition Regression (PDR) to identify shared components and their underlying genetic variants. We validated PDR on simulated data and identified limitations of existing methods in recovering the true components. We applied PDR to three clusters of 5-6 traits genetically correlated with coronary disease, asthma, and type II diabetes respectively, producing biologically interpretable components. For CAD, PDR identified components related to BMI, hypertension and cholesterol, and it clarified the relationship among these highly correlated risk factors. We assigned variants to components, calculated their posterior-mean effect sizes, and performed out-of-sample validation. Our posterior-mean effect sizes pool statistical power across traits and substantially boost the correlation (r2) between true and estimated effect sizes compared with the original summary statistics: by 94% and 70% for asthma and T2D out of sample, and by a predicted 300% for CAD.
Representation of Drosophila larval behaviors by muscle activity patterns
Authors: Zhou Jinrun , Huang Zenan , Li Xinhang , Song Zhiying , Sun Yixuan , Ping Junyu , Chen Xiaopeng , Fei Peng , Zheng Nenggan , Gong Zhefeng
Published: November 2021

How muscle actions are coordinated to realize animal movement is a fundamental question in behavioral study. To obtain the overall muscular activity patterns accompanying behaviors at high spatiotemporal resolution is technically difficult. In this work, we used light sheet microscopy to simultaneously image and analyze the activity, length and orientation of Drosophila larval muscles across body segments at single muscle resolution in nearly free behaviors. For typical behavioral modes such as peristalsis, head cast and turning, larval muscles showed behavioral mode specific activity patterns. Unexpectedly, reorientation of larval head involves muscle tone in the apparently motionless posterior segments. With a STGCN(spatial temporal graph convolution neural network)-Generator model, sequence of larval behavioral poses outlined by morphological patterns of muscles could be accurately predicted based on the time series of ventral but not dorsal muscle activities, and vice versa. Laser ablation of ventral but not dorsal muscles interrupted peristaltic wave and undermined head cast in both frequency and amplitude. Our results provide a simplified muscle activity representation of soft body motion that can be used for probing the key components of animal motor control.
The online delivery of exercise oncology classes supported with health coaching: A pilot randomized controlled trial
Authors: Eisele Maximilian , Twomey Rosie , Pohl Andrew J. , McDonough Meghan H. , McNeely Margaret L. , Ester Manuel , Daun Julia T. , Culos-Reed S. Nicole
Published: November 2021

Purpose

The primary objective was to investigate the feasibility of a synchronous, online delivered, group-based, supervised, exercise oncology maintenance program supported with health coaching.

Methods

All participants had previously completed a 12-week group-based exercise study. In the current study, participants were randomized to a 12-week exercise oncology maintenance class with or without health coaching. The primary outcome was feasibility, assessed as intervention attendance, safety and fidelity, study recruitment, attrition and outcome assessment completion. Additionally, semi-structured interviews at the end of the intervention provided participants’ perspectives on intervention feasibility.

Results

Forty participants (n8WK=25; n12WK=15) enrolled in the study. Feasibility was confirmed for recruitment rate (42.6%), attrition rate (2.5%), safety (no adverse events), health coaching attendance (97%), health coaching fidelity (96.7%), class attendance (91.2%), class fidelity (92.6%), and assessment completion (questionnaire=98.8%; physical functioning=97.5%). Based on the qualitative feedback, feasibility was facilitated by the convenience, while the diminished ability to connect with other participants online was a drawback compared to in-person delivery.

Conclusion

The synchronous online delivery of an exercise oncology maintenance class, the additional health coaching support, and the tools used to measure the intervention effectiveness were feasible for individuals living with and beyond cancer.
The immunogenicity and reactogenicity of four COVID-19 booster vaccinations against SARS-CoV-2 variants of concerns (Delta, Beta, and Omicron) following CoronaVac or ChAdOx1 nCoV-19 primary series
Authors: Angkasekwinai Nasikarn , Niyomnaitham Suvimol , Sewatanon Jaturong , Phumiamorn Supaporn , Sukapirom Kasama , Senawong Sansnee , Toh Zheng Quan , Umrod Pinklow , Somporn Thitiporn , Chumpol Supaporn , Ritthitham Kanokphon , Jantraphakorn Yuparat , Srisutthisamphan Kanjana , Chokephaibulkit Kulkanya
Published: November 2021

The CoronaVac (Sinovac Biotech) and ChAdOx1(Oxford-AstraZeneca) are two widely used COVID-19 vaccines. We examined the immunogenicity of four COVID-19 booster vaccine: BBIBP-CorV (Sinopharm Biotech), ChAdOx1, 30μg-BNT162b2 and 15μg-BNT162b2 (Pfizer-BioNTech), in healthy adults who received a two-dose CoronaVac or ChAdOx1 8-12 weeks earlier. Among the 352 participants (179 CoronaVac and 173 ChAdOx1 participants), 285 (81%) were female, and median age was 39(IQR: 31-47) years. 98%(175/179) and 99%(172/173) of Coronavac and ChAdOx1 participants remained seropositive at baseline. Two weeks post-booster, both 30μg- and 15μg-BNT162b2 induced the highest anti-RBD IgG concentration (BAU/mL); Coronavac-prime: 30μg-BNT162b2, 5152.2(95%CI 4491.7-5909.8); 15μg-BNT162b2, 3981.1(3397.2-4665.4); ChAdOx1, 1358.0(1141.8-1615.1); BBIBP-CorV, 154.6(92.11-259.47); ChAdOx1-prime: 30μg-BNT162b2, 2363.8(2005.6-2786.1; 15μg-BNT162b2, 1961.9(1624.6-2369.1); ChAdOx1, 246.4(199.6-304.2); BBIBP-CorV, 128.1(93.5-175.4). Similarly, both 30μg- and 15μg-BNT162b2 boosting induced the highest neutralizing antibodies (nAb) titres against all variants and highest T-cell response evaluated by interferon gamma released asssays. While all BNT162b2 or heterologous ChAdOx1-boosted participants had nAb against Omicron, these were <50% for BBIBP-CorV and 75% for homologous ChAdOx1-boosted participants. There was significant decrease in nAb (>4-fold) 16-20 weeks post booster. Heterologous boosting with BNT162b2 following CoronaVac or ChAdOx1 primary series is most immunogenic. A lower dose BNT162b2 may be considered as booster in settings with limited vaccine supply.
Transdiagnostic Profiles of Behaviour and Communication Relate to Academic and Socioemotional Functioning and Neural White Matter Organisation
Authors: Mareva Silvana , Akarca Danyal ,   The CALM team, Holmes Joni
Published: November 2021

Background

Behavioural and language difficulties co-occur in multiple neurodevelopmental conditions. Our understanding of these problems has arguably been slowed by an overreliance on study designs that compare deficit/diagnostic groups and fail to capture the overlap across different neurodevelopmental disorders and the heterogeneity within them.

Methods

We recruited a large transdiagnostic cohort of children with complex needs (N = 805) to identify distinct subgroups of children with common profiles of behavioural and language strengths and difficulties. We then investigated whether and how these data-driven groupings could be distinguished from a comparison sample (N = 158) on measures of academic and socioemotional functioning and patterns of global and local white matter connectome organisation. Academic skills were assessed via standardised measures of reading and maths. Socioemotional functioning was captured by the parent-rated version of the Strengths and Difficulties Questionnaire.

Results

We identified three distinct subgroups of children, each with different levels of difficulties in structural language, pragmatic communication, and hot and cool executive functions. All three subgroups struggled with academic and socioemotional skills relative to the comparison sample, potentially representing three alternative but related developmental pathways to difficulties in these areas. The children with the weakest language skills had the most widespread difficulties with learning, whereas those with more pronounced difficulties with hot executive skills experienced the most severe difficulties in the socioemotional domain. Each data-driven subgroup could be distinguished from the comparison sample based on both shared and subgroup-unique patterns of neural white matter organisation. Children with the most pronounced deficits in language, cool executive, or hot executive function were differentiated from the comparison sample by altered connectivity in predominately thalamocortical, temporal-parietal-occipital, and frontostriatal circuits, respectively.

Conclusion

These findings advance our understanding of commonly co-morbid behavioural and language problems and their relationship to behavioural outcomes and neurobiological substrates. Transdiagnostic Profiles of Behaviour and Communication Relate to Academic and Socioemotional Functioning and Neural White Matter Organisation
Favipiravir for the Treatment of Coronavirus Disease 2019; a propensity score-matched cohort study
Authors: Alattar Rand A. , Abdalla Shiema , Abdallah Tasneem A.K. , Kazman Rashid , Qadmour Aseelah , Ibrahim Tawheeda B. H. , Alhariri Bassem , Shaar Shahd H. , Bajwa Abeer , Alimam Abeir B. , Qazi Rabia , Ben Abid Fatma , Daghfal Joanne , Eldeeb Ali M. , Shukri Kinda , Elsayed Ahmed , Rustom Fatima , Alsamawi Musaed , Abdelmajid Alaaeldin , Basulto Miguel A. P. , Cobian Armando A. R. , Abukhattab Mohamed , Almaslamani Muna A. , Alkhal Abdullatif , Omrani Ali S.
Published: November 2021

Background

We investigated clinical outcomes of favipiravir in patients with COVID-19 pneumonia.

Methods

Patients who between 23 May 2020 and 18 July 2020 received ≥24 hours of favipiravir were assigned to the favipiravir group, while those who did not formed the non-favipiravir group. The primary outcome was 28-day clinical improvement, defined as two-category improvement from baseline on an 8-point ordinal scale. Propensity scores (PS) for favipiravir therapy were used for 1:1 matching. Cox regression was used to examine associations with the primary endpoint.

Results

The unmatched cohort included 1,493 patients, of which 51.7% were in the favipiravir group, and 48.3% were not receiving supplemental oxygen at baseline. Favipiravir was started within a median of 5 days from symptoms onset. Significant baseline differences between the two unmatched groups existed, but not between the PS-matched groups (N = 774). After PS-matching, there were no significant differences between the two groups in the proportion with 28-day clinical improvement (93.3% versus 92.8%, P 0.780), or 28-day all-cause mortality (2.1% versus 3.1%, P 0.360). Favipiravir was associated with more viral clearance by day 28 (79.8% versus 64.1%, P <0.001). In the adjusted Cox proportional hazards model, favipiravir therapy was not associated 28-day clinical improvement (adjusted hazard ratio 0.978, 95% confidence interval 0.862 –1.109, P 0.726). Adverse events were common in both groups, but the 93.9% were Grades 1–3.

Conclusion

Favipiravir therapy for COVID-19 pneumonia is well tolerated but is not associated with an increased likelihood of clinical improvement or reduced all-cause mortality by 28 days.
Increased Brain Volumetric Measurement Precision from Multi-Site 3D T1-weighted 3T Magnetic Resonance Imaging by Correcting Geometric Distortions
Authors: Nanayakkara Nuwan D. , Arnott Stephen R. , Scott Christopher J.M. , Solovey Igor , Liang Shuai , Fonov Vladimir S. , Gee Tom , Broberg Dana N. , Haddad Seyyed M.H. , Ramirez Joel , Berezuk Courtney , Holmes Melissa , Adamo Sabrina , Ozzoude Miracle , Theyers Athena , Sujanthan Sujeevini , Zamyadi Mojdeh , Casaubon Leanne , Dowlatshahi Dar , Mandzia Jennifer , Sahlas Demetrios , Saposnik Gustavo , Hassan Ayman , Swartz Richard H. , Strother Stephen C. , Szilagyi Gregory M. , Black Sandra E. , Symons Sean ,   ONDRI Investigators, Bartha Robert
Published: November 2021

Magnetic resonance imaging (MRI) scanner-specific geometric distortions may contribute to scanner induced variability and decrease volumetric measurement precision for multi-site studies. The purpose of this study was to determine whether geometric distortion correction increases the precision of brain volumetric measurements in a multi-site multi-scanner study. Geometric distortion variation was quantified over a one-year period at 10 sites using the distortion fields estimated from monthly 3D T1-weighted MRI geometrical phantom scans. The variability of volume and distance measurements were quantified using synthetic volumes and a standard quantitative MRI (qMRI) phantom. The effects of geometric distortion corrections on MRI derived volumetric measurements of the human brain were assessed in two subjects scanned on each of the 10 MRI scanners and in 150 subjects with cerebrovascaular disease (CVD) acquired across imaging sites.

Geometric distortions were found to vary substantially between different MRI scanners but were relatively stable on each scanner over a one-year interval. Geometric distortions varied spatially, increasing in severity with distance from the magnet isocenter. In measurements made with the qMRI phantom, the geometric distortion correction decreased the standard deviation of volumetric assessments by 35% and distance measurements by 42%. The average coefficient of variance decreased by 16% in gray matter and white matter volume estimates in the two subjects scanned on the 10 MRI scanners. Geometric distortion correction using an up-to-date correction field is recommended to increase precision in volumetric measurements made from MRI images.
Mammalian octopus cells are direction selective to frequency sweeps by synaptic sequence detection
Authors: Lu Hsin-Wei , Smith Philip , Joris Philip
Published: November 2021

Octopus cells are remarkable projection neurons of the mammalian cochlear nucleus, with extremely fast membranes and wide frequency tuning. They are considered prime examples of coincidence detectors but are poorly characterized in vivo. We discover that octopus cells are selective to frequency sweep direction, a feature that is absent in their auditory nerve inputs. In vivo intracellular recordings reveal that direction selectivity does not derive from cross-channel coincidence detection but hinges on the amplitudes and activation sequence of auditory nerve inputs tuned to clusters of “hotspot” frequencies. A simple biophysical model of octopus cell excited with real nerve spike trains recreates direction selectivity through interaction of intrinsic membrane conductances with activation sequence of clustered inputs. We conclude that octopus cells are sequence detectors, sensitive to temporal patterns across cochlear frequency channels. The detection of sequences rather than coincidences is a much simpler but powerful operation to extract temporal information.
Fast maturation of splenic dendritic cells upon TBI is associated with FLT3/FLT3L signaling
Authors: Zhang Jin , Li Zhenghui , Chandrasekar Akila , Li Shun , Ludolph Albert , Boeckers Tobias , Huber-Lang Markus , Roselli Francesco , Heuvel Florian olde
Published: November 2021

Systemic inflammatory consequences remain a significant burden after traumatic brain injury (TBI), with almost all organs affected. The spleen is connected with the brain by autonomic innervation and by soluble mediators, and the cross-talk between brain and spleen may be important to establish the systemic inflammatory response to TBI. Ethanol intoxication, the most common comorbidity of TBI, is posited to influence the peripheral inflammatory response either directly or through the brain-spleen cross-talk. Here we show that TBI causes a substantial change in transcription of genes associated with dendritic cells activation in the spleen, in particular a FLT3/FLT3L induction 3h after TBI, which was enhanced by EI. The FLT3L induction was associated with the phosphorylation of FLT3 receptor in CD11c+ dendritic cells, which enhanced the protein synthesis of a subset of mRNAs, as shown by the increase in pS6, peIF2A levels in dendritic cells. This corresponded to the upregulation of proteins associated with maturation process and immunostimulatory properties such MHC-II, LAMP1 and CD68, and of pro-inflammatory cytokines such as TNFα. Notably, EI enhanced the maturation of dendritic cells. However, whereas TBI decreases expression of the adrenergic 2b receptors on dendritic cells, EI increased it, thus augmenting the chances of cross-talk regulation of immune function by the autonomic system. In conclusion, this data indicates that TBI induces a fast maturation of the immunomodulatory functions of dendritic cells which is associated by FLT3/FLT3L signaling and which is enhanced by EI prior to TBI.
Increased expression of viral sensor MDA5 in pancreatic islets and in hormone-negative endocrine cells in recent onset type 1 diabetic donors
Authors: Nigi Laura , Brusco Noemi , Grieco Giuseppina E. , Fignani Daniela , Licata Giada , Formichi Caterina , Aiello Elena , Marselli Lorella , Marchetti Piero , Krogvold Lars , Jorgensen Knut Dahl , Sebastiani Guido , Dotta Francesco
Published: November 2021

The interaction between genetic and environmental factors determines the development of type 1 diabetes (T1D). Some viruses are capable of infecting and damaging pancreatic β-cells, whose antiviral response could be modulated by specific viral RNA receptors and sensors such as Melanoma Differentiation Associated gene 5 (MDA5), encoded by the IFIH1 gene. MDA5 has been shown to be involved in pro-inflammatory and immunoregulatory outcomes, thus determining the response of pancreatic islets to viral infections. Although the function of MDA5 has been previously well explored, a detailed immunohistochemical characterization of MDA5 in pancreatic tissues of non-diabetic and T1D donors is still missing. In the present study we used multiplex immunofluorescence imaging analysis to characterize MDA5 expression and distribution in pancreatic tissues obtained from 22 organ donors (10 non-diabetic autoantibody-negative, 2 autoantibody-positive, 8 recent-onset and 2 long-standing T1D).

In non-diabetic control donors, MDA5 was expressed both in α- and in β-cells. The colocalization rate imaging analysis showed that MDA5 was preferentially expressed in α-cells.

In T1D donors, we observed an increased colocalization rate MDA5-glucagon respect to MDA5-insulin in comparison to non-diabetic controls; such increase was more pronounced in recent onset respect to long standing T1D donors. Of note, an increased colocalization rate MDA5-glucagon was found in insulin-deficient-islets (IDI) respect to insulin containing islets (ICI).

Strikingly, in T1D donors we detected the presence of MDA5-positive/hormones-negative endocrine islet-like clusters, putatively deriving from dedifferentiation or neogenesis phoenomena. These clusters were exclusively identified in recent onset donors and not detected in autoantibody-positive non-diabetic or T1D long-standing ones.

In conclusion, we showed that MDA5 is preferentially expressed in α-cells and its expression is increased in recent onset T1D donors. Finally, we observed that MDA5 may also characterize the phenotype of dedifferentiated or newly forming islet cells, thus opening to novel roles for MDA5 in pancreatic endocrine cells.
Structural and functional organization of visual responses in the inferior olive of larval zebrafish
Authors: Felix Rita , Markov Daniil A , Renninger Sabine L. , Tomás Raquel , Laborde Alexandre , Carey Megan R , Orger Michael B , Portugues Ruben
Published: November 2021

The olivo-cerebellar system plays an important role in vertebrate sensorimotor control. According to a classical theory of cerebellar cortex, the inferior olive (IO) provides Purkinje cells with error information which drives motor learning in the cerebellum. Here we investigate the sensory representations in the IO of larval zebrafish and their spatial organization. Using single-cell labeling of genetically identified IO neurons we find that they can be divided into at least two distinct groups based on their spatial location, dendritic morphology, and axonal projection patterns. In the same genetically targeted population, we recorded calcium activity in response to a set of visual stimuli using 2-photon imaging. We found that most IO neurons showed direction selective and binocular responses to visual stimuli and that functional properties were spatially organized within the IO. Light-sheet functional imaging that allowed for simultaneous activity recordings at the soma and axonal level revealed tight coupling between soma location, axonal projections and functional properties of IO neurons. Taken together, our results suggest that anatomically-defined classes of inferior olive neurons correspond to distinct functional types, and that topographic connections between IO and cerebellum contribute to organization of the cerebellum into distinct functional zones.
Mechanism of FtsZ assembly dynamics revealed by filament structures in different nucleotide states
Authors: Ruiz Federico M. , Huecas Sonia , Santos-Aledo Alicia , Prim Elena A. , Andreu José M. , Fernández-Tornero Carlos
Published: November 2021

Treadmilling protein filaments perform essential cellular functions by growing from one end while shrinking from the other, driven by nucleotide hydrolysis. Bacterial cell division relies on the primitive tubulin homolog FtsZ, a target for antibiotic discovery that assembles into single treadmilling filaments that hydrolyse GTP at an active site formed upon subunit association. We determined high-resolution filament structures of FtsZ from the pathogen Staphylococcus aureus in complex with different nucleotide analogues and cations, including mimetics of the ground and transition states of catalysis. Together with mutational and biochemical analyses, our structures reveal interactions made by the GTP γ-phosphate and Mg2+ at the subunit interface, a K+ ion stabilizing loop T7 for co-catalysis, new roles of key residues at the active site and a nearby crosstalk area, and rearrangements of a dynamic water shell bridging adjacent subunits upon GTP hydrolysis. We propose a mechanistic model that integrates nucleotide hydrolysis signalling with assembly-associated conformational changes and filament treadmilling. Equivalent assembly mechanisms may apply to more complex tubulin and actin cytomotive filaments that share analogous features with FtsZ.