bluuebunny/crossref_metadata_2025 huggingface dataset:
Iterative Design and Pilot Implementation of a Tiered Coaching Model to Support Socio-Emotional Teaching Practices
Authors: Artman-Meeker Kathleen , Fettig Angel , Cunningham Jennifer E. , Chang Huan-Ching , Choi Gounah , Harbin Shawna
Published: October 2021

We used an iterative process to design the Tiered Coaching Model (TCM) to support preschool teachers’ implementation of the Pyramid Model. In the TCM, teachers are matched to one of three coaching tiers based on their observed classroom practices, individual characteristics, and preferences. Those tiers were self-guided coaching, small group coaching, and individual coaching. We describe TCM model development and two field tests exploring its potential usability and effectiveness. In Field Test 1, the model was tested with 16 lead preschool teachers. Focus groups and teacher feedback informed systematic model revisions. In Field Test 2, we gathered preliminary findings from an additional 24 teachers. All teachers across coaching tiers and field tests increased their use of Pyramid Model practices while engaging in the TCM, providing promising evidence for wider demonstrations and future rigorous evaluations of the model.
The Impact of Online Reviews on the Information Flows and Outcomes of Marketing Systems
Authors: Watson Forrest , Wu Yinglu
Published: October 2021

Online reviews are changing the way that consumers shop and firms respond to consumer feedback. Viewed more broadly, online reviews are a type of information flow altering the functioning of marketing systems at the micro, meso, and macro levels. A systematic review of the past two decades of research shows great attention to the impact of online reviews on information flows, as well as the nuances of micro-and meso-level efficiency outcomes. However, there is scant consideration for the effectiveness related outcomes of online reviews (such as customer well-being, distributive justice, and externalities). Through a macromarketing lens, online reviews are an information flow with the potential to change well-being outcomes for all stakeholders, rather than just a tool to be exploited by firms or consumers. A theoretical framework and a series of questions are presented for future research on how online reviews and more generally information flows between actors may impact the efficiency and effectiveness of a marketing system.
Lung metastasectomy for osteosarcoma in children, adolescents, and young adults: proof of permanent cure
Authors: Pastorino Ugo , Palmerini Emanuela , Porcu Luca , Luksch Roberto , Scanagatta Paolo , Meazza Cristina , Leuzzi Giovanni , Massimino Maura , Picci Piero
Published: October 2021

Introduction

Surgical resection of pulmonary metastases has been associated with increased survival at 5 years for osteosarcoma, but limited information is available on long-term outcome, role of repeated metastasectomies, and surgical sequelae in a pediatric population. We analyzed a consecutive series of children, adolescents, and young adults (AYA) treated by repeated lung metastasectomies during a period >40 years to estimate the clinical benefit and potential cure rate of salvage surgery.

Methods

All patients who underwent lung metastasectomy for osteosarcoma at the IRCCS Istituto Ortopedico Rizzoli of Bologna, University of Modena, and IRCCS Istituto Nazionale Tumori of Milan from May 1973 to January 2014 were included. Overall survival (OS) at 20 years from the first metastasectomy was calculated.

Results

A total of 463 consecutive children and AYA were analyzed. Median age was 15.9 years (range 0.2–23.2 years) and median follow-up 18.6 years. The 5- and 20-year OS were 34.0% and 29.7% (95% CI 25.5–34.0%). Among the 138 (29.8%) alive patients, 42 (30.4%) had disease recurrence cured by repeated metastasectomies. Disease-free interval from primary tumor, number of metastases, and complete resection were the most relevant survival predictors at multivariable model analysis.

Discussion

The extended follow-up of this consecutive series shows that repeated lung metastasectomy can achieve a permanent cure when offered to properly selected patients with metastases from osteosarcoma.
Cytokine release syndrome after CAR infusion in pediatric patients with refractory/relapsed B-ALL: is there a role for diclofenac?
Authors: Napolitano Sara , Ottaviano Giorgio , Bettini Laura , Russotto Vincenzo , Bonanomi Sonia , Rovelli Attilio , Biondi Andrea , Rona Roberto , Balduzzi Adriana
Published: October 2021

Background:

Cytokine release syndrome (CRS) is a major complication after chimeric-antigen receptor T-cell treatment, characterized by an uncontrolled systemic inflammatory reaction. We investigated the potential role of diclofenac in the management of CRS in five pediatric patients treated for relapsed/refractory B-lineage acute lymphoblastic leukemia.

Methods

In case of persistent fever with fever-free intervals shorter than 3 hours, diclofenac continuous infusion was initiated, at the starting dose of 0.5 mg/Kg/day, the lowest effective pediatric dose in our experience, possibly escalated up to 1 mg/Kg/day, as per institutional guidelines.

Results:

CRS occurred at a median of 20 hours (range 8–27) after tisagenlecleucel infusion. Diclofenac was started at a median of 20 hours (range 13–33) after fever onset. A mean of 3.07 febrile peaks without diclofenac and 0.95 with diclofenac were reported ( p = 0.02). Clinical benefit was achieved by hampering the progression of tachypnea and tachycardia. Despite fever control, CRS progressed in four of the five patients, and hypotension requiring vasopressors and fluid retention, as well as hypoxia, occurred. Vasopressors were followed by 1–2 doses of tocilizumab (one in patient 2 and two in patients 3, 4, and 5), plus steroids in patients 4 and 5.

Conclusion:

Based on a limited number of patients, diclofenac leads to better fever control, which translates into symptom relief and improvement of tachycardia, but could not prevent the progression of CRS.
Current demand and supply of impact investments across different geographic regions, sectors, and stages of business: Match or mismatch?
Authors: Islam Syrus M , Scott Tom
Published: October 2021

We examine the match/mismatch between the demand and supply of impact investments. We show that some geographic regions display an upward match, while others exhibit a downward match. We explain how regions with well-developed (or less-developed) economies are not necessarily equal to regions with well-developed (or less-developed) impact investment markets. We also highlight the sectors exhibiting a match or mismatch between the demand and supply of investments, and explain the potential reasons. Regarding both geographic and sector concentration, the demand for investments is much more concentrated than their supply. Finally, early-stage companies suffer from an undersupply of investments, while growth-stage companies display an upward match and mature companies have an oversupply of investments. These findings have implications for impact investing theory and practice, including the attainment of Sustainable Development Goals.

JEL Classification: D53; E41; E51; G15; G23
Constructability Reviews Utilization Practices for Traditional and Alternative Project Delivery Methods Across State Transportation Agencies
Authors: Smadi Adi , Tran Dan , Minchin Edward
Published: October 2021

State Transportation Agencies (STAs) recognized that to enhance the quality of construction documents, a review process must be incorporated into project planning, design, and procurement to evaluate projects for constructability. The benefits promised by constructability reviews (CRs) encouraged STAs to adopt it as part of their operations. This approach soon evolved into a structured process, recognized by researchers and practitioners as, the constructability review process (CRP). A significant component to the CRP success is to involve experienced construction personnel in CRs during the design phase; a major limitation of the traditional design-bid-build (DBB) delivery method. To overcome this limitation, more emphasis is being placed towards alternative project delivery methods (APDMs). As such, design–build (DB) and construction manager/general contractor (CM/GC) are among the APDMs most utilized by STAs to deliver transportation projects. Although extensive research has investigated CRs under DBB projects, research on CRs implementation under APDMs is remarkably absent. This study examines CRs utilization and staffing practices adopted by STAs across DBB, DB, and CM/GC projects. The results of this study were drawn utilizing data collected through a national survey questionnaire and interviews with selected STAs. The study found that CRs are initiated and implemented at proportionally similar phases across DBB, DB, and CM/GC projects. Investigation of staffing needs revealed that although the agency holds the executive role in implementation of CRs on DBB projects, their role shifts on DB projects to become more administrative. The agency continues to be involved in CRs under CM/GC projects, along with their allocated design consultant, in conjunction with the GC. The results of this study are anticipated to provide STAs with guidance for CRs utilization on DBB, DB and CM/GC projects.
Health Profile of Preterm Males With Duchenne Muscular Dystrophy
Authors: Soim Aida , Wallace Bailey , Whitehead Nedra , Smith Michael G. , Mann Joshua R. , Thomas Shiny , Ciafaloni Emma ,   the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet)
Published: October 2021

In this retrospective cohort study, we characterize the health profile of preterm males with Duchenne muscular dystrophy. Major clinical milestones (ambulation cessation, assisted ventilation use, and onset of left ventricular dysfunction) and corticosteroids use in males with Duchenne muscular dystrophy identified through a population-based surveillance system were analyzed using Kaplan-Meier survival curves and Cox proportional hazards modeling. The adjusted risk of receiving any respiratory intervention among preterm males with Duchenne muscular dystrophy was 87% higher than among the corresponding full-term males with Duchenne muscular dystrophy. The adjusted risks for ambulation cessation and left ventricular dysfunction were modestly elevated among preterm compared to full-term males, but the 95% confidence intervals contained the null. No difference in the start of corticosteroid use between preterm and full-term Duchenne muscular dystrophy males was observed. Overall, the disease course seems to be similar between preterm and full-term males with Duchenne muscular dystrophy; however, pulmonary function seems to be affected earlier among preterm males with Duchenne muscular dystrophy.
I am a scientist . . . Ask Me Anything: Examining differences between male and female scientists participating in a Reddit AMA session
Authors: Hubner Austin Y. , Bond Robert
Published: October 2021

This article investigates interactions between scientists and the online community Reddit. Given that past research on computer-mediated communication between scientists and the public found that male scientists are typically more popular in online spaces than female scientists, we examined differences in popularity as well as potential gendered differences in communication style. Specifically, we examined 269 Reddit “Ask Me Anything” sessions as well as the comments linked with each session ( n = 125,580). Overall, we find that male scientists receive more comments on their sessions, but the score an individual comment receives does not differ by gender. Similarly, we find that the message complexity of the comments does not differ by gender. Taken together, these suggest that Reddit AMA sessions might be an effective platform for both male and female scientists to engage with the public.
Preparation of n-type polyaniline/hexagonal boron nitride composites with a large thermoelectric power factor
Authors: Ugraskan Volkan , Ceran Ebubekir , Yazici Ozlem
Published: October 2021

In the present study, it was aimed to investigate the thermoelectric (TE) properties of polyaniline/hexagonal boron nitride (PANI/h-BN) composites. First, h-BN was synthesized from boric acid and urea. Then, PANI-HCl was synthesized by oxidative chemical polymerization. Finally, the composites were prepared using different weight ratios of h-BN. The composites were characterized using attenuated total reflection accessory attached Fourier-transform infrared spectroscopy, UV-vis spectroscopy, X-ray diffraction, and scanning electron microscopy/energy dispersive X-ray analyzer. TE investigation of the composites showed that the addition of h-BN significantly contributes to the TE properties of PANI-HCl. The addition of h-BN increased the power factor of PANI-HCl from 0.07 μWm−1K−2 to 143.05 μWm−1K−2. Furthermore, all the composites showed negative Seebeck coefficients which are the characteristics of n-type semiconductors.
Consanguineous Marriages in India: Prevalence and Determinants
Authors: Acharya Sumana , Sahoo Harihar
Published: October 2021

Consanguineous marriage is the legal union of male and female of a common ancestor related by blood. The most common prevailing form of consanguineous marriages is between first cousins. Middle East Asian countries and southern states in India show high prevalence. A comparative analysis between the two rounds of National Family Health Survey 1 and 4 have shown a declining trend for the practice of consanguineous marriages. The highest percentage of consanguineous marriages is seen among the first cousins from both father’s and mother’s side, most commonly practice in the southern states of Andhra Pradesh, Telangana, Tamil Nadu, and Karnataka except Kerala. Importantly, the practice of consanguineous marriage is higher among the Muslims of North India and Hindus of Southern India, among the Other Backward Classes and the less educated population of the middle and richer wealth index. A significant relationship can be noticed among consanguineous marriages and socio-economic variables.
Investigation of monotherapy and combined anticoronaviral therapies against feline coronavirus serotype II in vitro
Authors: Cook Sarah E , Vogel Helena , Castillo Diego , Olsen Mark , Pedersen Niels , Murphy Brian G
Published: October 2021

Objectives

Feline infectious peritonitis (FIP), caused by genetic mutants of feline enteric coronavirus known as FIPV, is a highly fatal disease of cats with no currently available vaccine or US Food and Drug Administration-approved cure. Dissemination of FIPV in affected cats results in a range of clinical signs, including cavitary effusions, anorexia, fever and lesions of pyogranulomatous vasculitis and perivasculitis, with or without central nervous system or ocular involvement. The objectives of this study were to screen an array of antiviral compounds for anti-FIPV (serotype II) activity, determine cytotoxicity safety profiles of identified compounds with anti-FIPV activity and strategically combine identified monotherapies to assess compound synergy against FIPV in vitro. Based upon clinically successful combination treatment strategies for human patients with HIV and hepatitis C virus infections, we hypothesized that a combined anticoronaviral therapy approach featuring concurrent multiple mechanisms of drug action would result in an additive or synergistic antiviral effect.

Methods

This study screened 90 putative antiviral compounds for efficacy and cytotoxicity using a multimodal in vitro strategy, including plaque bioassays, real-time RT-PCR viral inhibition and cytotoxicity assays.

Results

Through this process, we identified 26 compounds with effective antiviral activity against FIPV, representing a variety of drug classes and mechanisms of antiviral action. The most effective compounds include GC376, GS-441524, EIDD2801 and EIDD1931. We documented antiviral efficacy for combinations of antiviral agents, with a few examined drug combinations demonstrating evidence of limited synergistic antiviral activity.

Conclusions and relevance

Although evidence of compound synergy was identified for several combinations of antiviral agents, monotherapies were ultimately determined to be the most effective in the inhibition of viral transcription.
Racial Differences in the Prognosis and Survival of Cutaneous Melanoma From 1990 to 2020 in North America: A Systematic Review and Meta-Analysis
Authors: Lam Megan , Zhu Jie Wei , Hu Angie , Beecker Jennifer
Published: October 2021

Background

Factors influencing the difference in the diagnosis and treatment of melanoma in racial minority groups are well-described in the literature and include atypical presentations and socioeconomic factors that impede access to care.

Objective

To characterize the differences in melanoma survival outcomes between non-Hispanic white patients and ethnic minority patients in North America.

Methods

We conducted searches of Embase via Ovid and MEDLINE via Ovid of studies published from 1989 to August 5, 2020. We included observational studies in North America which reported crude or effect estimate data on patient survival with cutaneous melanoma stratified by race.

Results

Forty-four studies met our inclusion criteria and were included in this systematic review. Pooled analysis revealed that black patients were at a significantly increased risk for overall mortality (HR 1.42, 95% CI, 1.25-1.60), as well as for melanoma-specific mortality (HR 1.27, 95% CI, 1.03-1.56). Pooled analyses using a representative study for each database yielded similar trends. Other ethnic minorities were also more likely report lower melanoma-specific survival compared to non-Hispanic white patients.

Conclusion

Our results support findings that melanoma patients of ethnic minorities, particularly black patients, experience worse health outcomes with regards to mortality. Overall survival and melanoma-specific survival are significantly decreased in black patients compared to non-Hispanic white patients. With the advent of more effective, contemporary treatments such as immunotherapy, our review identifies a gap in the literature investigating present-day or prospective data on melanoma outcomes, in order to characterize how current racial differences compare to findings from previous decades.
Participatory photography and undocumented migration through Mexico at the intersection of social work and anthropology
Authors: Doering-White John
Published: October 2021

This article reflects on participatory photography in the context of ethnographic fieldwork at a humanitarian migrant shelter in Central Mexico to consider broader intersections between social work and anthropology. I describe how shifting immigration enforcement trends across Mexico reconfigured my original plan for integrating participatory photography into my work as a researcher and shelter worker. Tracing these changes through three cases examples, I highlight tensions between photography as a reflection of social experience and photography as a mechanism for enacting social change. In light of recent critiques surrounding formulaic and cursory discussions of empowerment in participatory photography, I argue that unexpected shifts in research and practice strategies are themselves meaningful data, especially in uncertain policy environments.
Social Transformative Learning in Human Rights Delegations: Critical Research on the Maritimes-Guatemala Breaking the Silence Network
Authors: Rankin Lisa , English Leona M.
Published: October 2021

This article examines the experience of six participants in the Maritimes-Guatemala Breaking the Silence Network (BTS) delegation program. Human rights education is central to this program that operates between Canada and Guatemala. Key findings from this research include participants’ rethinking of their own power and privilege upon returning to Canada and making connections with the struggle of Indigenous peoples in both countries. Another finding concerns how specific communal aspects of the BTS delegation (communitas) lead to social transformation and the development of solidarity relationships that are transformative to all. The research affirms the need for experiential learning experiences which use transformative learning approaches to support human rights and social change.
Renewable energy and energy storage to offset diesel generators at expeditionary contingency bases
Authors: Katalenich Scott M , Jacobson Mark Z
Published: October 2021

Expeditionary contingency bases (non-permanent, rapidly built, and often remote outposts) for military and non-military applications represent a unique opportunity for renewable energy. Conventional applications rely upon diesel generators to provide electricity. However, the potential exists for renewable energy, improved efficiency, and energy storage to largely offset the diesel consumed by generators. This paper introduces a new methodology for planners to incorporate meteorological data for any location worldwide into a planning tool in order to minimize air pollution and carbon emissions while simultaneously improving the energy security and energy resilience of contingency bases. Benefits of the model apply not just to the military, but also to any organization building an expeditionary base—whether for humanitarian assistance, disaster relief, scientific research, or remote community development. Modeling results demonstrate that contingency bases using energy efficient buildings with batteries, rooftop solar photovoltaics, and vertical axis wind turbines can decrease annual generator diesel consumption by upward of 75% in all major climate zones worldwide, while simultaneously reducing air pollution, carbon emissions, and the risk of combat casualties from resupply missions.
Myanmar's Foreign Policy: Shifting Legitimacy, Shifting Strategic Culture
Authors: Shang Po P.
Published: October 2021

Since 2011, while the principles of foreign policy “independent, active, and non-aligned” under the respective governments under the Union Solidarity and Development Party and the National League for Democracy have remained the same, the foreign policy approaches – including the concept of non-alignment – of the two leaders of these governments have been quite different. This article describes the survival and foreign policy of the small country of Myanmar beyond the great power lens, arguing that the impact of strategic culture on the two governments since 2011 has differed because of the different levels of legitimacy enjoyed by the two leaders. The cornerstones of Myanmar's strategic culture are (1) that it shall never tolerate foreign interference, (2) that it shall always pursue self-reliance in its diplomacy, and (3) that the very nature of Myanmar is to be independent.
Internet Use and Cognitive Engagement in Older Adulthood
Authors: Schwaba Ted , Bleidorn Wiebke
Published: October 2021

Internet use is increasingly ubiquitous among older adults and may buffer against declines in cognitive engagement. We examined longitudinal associations between three types of internet use (media, social, and instrumental) and two indicators of cognitive engagement (Openness to Experience and Need for Cognition) in a nationally representative sample of Dutch older adults ( N = 2,922 adults aged 65–99) assessed annually from 2008 to 2017. Preregistered analyses indicated that older adults who were more cognitively engaged used the internet more frequently, especially for instrumental purposes like search and email. Those who increased in their use of online media declined less in Need for Cognition than their peers. These associations remained constant over time even as internet use became more common. We benchmarked our findings against null associations between cognitive engagement and TV/radio use and tested associations in younger comparison samples. Findings bolster our understanding of the role that technology use plays in personality development and aging.
Sex and survival following pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension: a Scandinavian observational cohort study
Authors: Kallonen Janica , Korsholm Kasper , Bredin Fredrik , Corbascio Matthias , Andersen Mads Jønsson , Ilkjær Lars Bo , Mellemkjær Søren , Sartipy Ulrik
Published: October 2021

Studies have suggested sex‐related survival differences in chronic thromboembolic pulmonary hypertension (CTEPH). Whether long‐term prognosis differs between men and women following pulmonary endarterectomy for CTEPH remains unclear. We investigated sex‐specific survival after pulmonary endarterectomy for CTEPH. We included all patients who underwent pulmonary endarterectomy for CTEPH at two Scandinavian centers and obtained baseline characteristics and vital statuses from patient charts and national health‐data registers. Propensity scores and weighting were used to account for baseline differences. Flexible parametric survival models were employed to estimate the association between sex and all‐cause mortality and the absolute survival differences. The expected survival in an age‐, sex‐, and year of surgery matched general population was obtained from the Human Mortality Database, and the relative survival was used to estimate cause‐specific mortality. A total of 444 patients were included, comprising 260 (59%) men and 184 (41%) women. Unadjusted 30‐day mortality was 4.2% in men versus 9.8% in women (p = 0.020). In weighted analyses, long‐term survival did not differ significantly in women compared with men (hazard ratio: 1.36; 95% confidence interval: 0.89–2.06). Relative survival at 15 years conditional on 30‐day survival was 94% (79%–107%) in men versus 75% (59%–88%) in women. In patients who underwent pulmonary endarterectomy for CTEPH, early mortality was higher in women compared with men. After adjustment for differences in baseline characteristics, female sex was not associated with long‐term survival. However, relative survival analyses suggested that the observed survival in men was close to the expected survival in the matched general population, whereas survival in women deviated notably from the matched general population.
Pain Medication Prescribing Patterns in Augmentation Mammoplasty
Authors: Winter Jessica , Cruise Braden , Peters Blair R. , Islur Avi
Published: October 2021

Background:

The rate of opioid prescribing after low-risk surgical procedures has increased over the past decade, and surgeons are responsible for prescribing approximately one-third of all opioid medications. There is additional supporting evidence that patients only consume about half of the opioids prescribed to them after outpatient plastic surgery. Currently, there is no literature to provide surgeons with reference ranges for how much opioid medication will adequately provide analgesia for patients after undergoing bilateral breast augmentation (BBA) surgery.

Objective:

To quantify the amount of opioid medication required to adequately control pain for patients after undergoing BBA and use these data to provide recommendations on opioid prescribing practices.

Methods:

Cross-sectional prospective data were obtained through a take-home medication and pain tracking questionnaire for 56 patients after they underwent either subpectoral or subglandular BBA. Patients documented their pain scores on a 0 to 10 analogue scale and documented the type and amount of pain medication they took for a 7-day period.

Results:

Our study demonstrated that patients in the subglandular BBA group required an average of either 25 ± 1.2 Tylenol #3 or 19.3 ± 2.3 Tramacet tablets, and the subpectoral group required 27.7 ± 1.7 Tylenol #3 or 25.6 ± 0.9 Tramacet tablets over a 7-day period. There was no statistically significant difference between the 2 surgical groups.

Conclusion:

We propose a reference range of medication required on average for patients undergoing BBA to obtain adequate pain control in the initial postoperative period that falls within the most recent Canadian guidelines for safe opioid prescribing practices.
Newborn With Vaginal Cyst
Authors: Willborg Brooke E. , Carroll Vanessa G. , Meltzer Julie
Published: October 2021

A full-term newborn female was born with a 0.5 × 0.5 cm golden-colored fluid filled sac at the posterior aspect of the vaginal introitus. Physical examination revealed a patent introitus without additional cysts, a normal positioned urethral meatus, and a patent anus. Stool and voiding occurred in the first 24 hours of life. Hymenal cysts are rare and spontaneously resolve in the first few weeks of life without intervention. Physical examination is important to distinguish hymenal cysts from other interlabial cysts that may require treatment.
Dissemination and Cultural Change as an Alternative Business Value Proposition in the Construction Industry: Manni Group Case Study
Authors: Tinazzi Umberto
Published: October 2021

There is a gap of knowledge between practitioners about the off-site construction. For this reason, the Manni Group case study presented in this article highlights the positive role of dissemination as business value proposition support in the context of off-site construction industry. The Manni Group involved opinion leaders, professionals, universities and industrial partners in a network of dissemination that, going beyond the concept of advertising, it generated a multiple effect of value creation between the direct and indirect involved stakeholders. Dissemination emerges as a model of action that creates impacts on cultural change. It is scalable and applicable in many areas where actors have the right competences to manage the dissemination. Wherever there is a knowledge gap or friction towards new techniques and methodologies, the model is able to create value for companies and stakeholders involved in the emerging network.
Therapeutic options for relapsed/refractory mantle cell lymphoma
Authors: Eyre Toby A. , Cheah Chan Y. , Wang Michael L.
Published: October 2021

Mantle cell lymphoma (MCL) is an uncommon subtype of non-Hodgkin lymphoma in which immunochemotherapy, with or without high-dose therapy, and autologous stem cell transplantation remain standard frontline therapies. Despite their clear efficacy, patients inevitably relapse and require subsequent therapy. In this review, we discuss the key therapeutic approaches in the management of relapsed MCL, covering in depth the data supporting the use of covalent Bruton tyrosine kinase (BTK) inhibitors at first or subsequent relapse. We describe the outcomes of patients progressing through BTK inhibitors and discuss the mechanisms of covalent BTKi resistance and treatment options after covalent treatment with BTKi. Options in this setting may depend on treatment availability, patient’s and physician’s preference, and the patient’s age and comorbidity status. We discuss the rapid recent development of anti-CD19 chimeric antigen receptor T-cell therapy, as well as the utility of allogenic stem cell transplantation and novel therapies, such as noncovalent, reversible BTK inhibitors; ROR1 antibody drug conjugates; and bispecific antibodies.
A SISCAPA-based approach for detection of SARS-CoV-2 viral antigens from clinical samples
Authors: Mangalaparthi Kiran K. , Chavan Sandip , Madugundu Anil K. , Renuse Santosh , Vanderboom Patrick M. , Maus Anthony D. , Kemp Jennifer , Kipp Benjamin R. , Grebe Stefan K. , Singh Ravinder J. , Pandey Akhilesh
Published: October 2021

SARS-CoV-2, a novel human coronavirus, has created a global disease burden infecting > 100 million humans in just over a year. RT-PCR is currently the predominant method of diagnosing this viral infection although a variety of tests to detect viral antigens have also been developed. In this study, we adopted a SISCAPA-based enrichment approach using anti-peptide antibodies generated against peptides from the nucleocapsid protein of SARS-CoV-2. We developed a targeted workflow in which nasopharyngeal swab samples were digested followed by enrichment of viral peptides using the anti-peptide antibodies and targeted parallel reaction monitoring (PRM) analysis using a high-resolution mass spectrometer. This workflow was applied to 41 RT-PCR-confirmed clinical SARS-CoV-2 positive nasopharyngeal swab samples and 30 negative samples. The workflow employed was highly specific as none of the target peptides were detected in negative samples. Further, the detected peptides showed a positive correlation with the viral loads as measured by RT-PCR Ct values. The SISCAPA-based platform described in the current study can serve as an alternative method for SARS-CoV-2 viral detection and can also be applied for detecting other microbial pathogens directly from clinical samples.
Transcriptome dynamics during metamorphosis of imaginal discs into wings and thoracic dorsum in Apis mellifera castes
Authors: Soares Michelle Prioli Miranda , Pinheiro Daniel Guariz , de Paula Freitas Flávia Cristina , Simões Zilá Luz Paulino , Bitondi Márcia Maria Gentile
Published: October 2021

Background

Much of the complex anatomy of a holometabolous insect is built from disc-shaped epithelial structures found inside the larva, i.e., the imaginal discs, which undergo a rapid differentiation during metamorphosis. Imaginal discs-derived structures, like wings, are built through the action of genes under precise regulation.

Results

We analyzed 30 honeybee transcriptomes in the search for the gene expression needed for wings and thoracic dorsum construction from the larval wing discs primordia. Analyses were carried out before, during, and after the metamorphic molt and using worker and queen castes. Our RNA-seq libraries revealed 13,202 genes, representing 86.2% of the honeybee annotated genes. Gene Ontology analysis revealed functional terms that were caste-specific or shared by workers and queens. Genes expressed in wing discs and descendant structures showed differential expression profiles dynamics in premetamorphic, metamorphic and postmetamorphic developmental phases, and also between castes. At the metamorphic molt, when ecdysteroids peak, the wing buds of workers showed maximal gene upregulation comparatively to queens, thus underscoring differences in gene expression between castes at the height of the larval-pupal transition. Analysis of small RNA libraries of wing buds allowed us to build miRNA-mRNA interaction networks to predict the regulation of genes expressed during wing discs development.

Conclusion

Together, these data reveal gene expression dynamics leading to wings and thoracic dorsum formation from the wing discs, besides highlighting caste-specific differences during wing discs metamorphosis.
Genome wide association mapping for agronomic, fruit quality, and root architectural traits in tomato under organic farming conditions
Authors: Tripodi Pasquale , Soler Salvador , Campanelli Gabriele , Díez María José , Esposito Salvatore , Sestili Sara , Figàs Maria R. , Leteo Fabrizio , Casanova Cristina , Platani Cristiano , Soler Elena , Bertone Aldo , Pereira-Dias Leandro , Palma Daniela , Burguet Resurrección , Pepe Andrea , Rosa-Martínez Elena , Prohens Jaime , Cardi Teodoro
Published: October 2021

Background

Opportunity and challenges of the agriculture scenario of the next decades will face increasing demand for secure food through approaches able to minimize the input to cultivations. Large panels of tomato varieties represent a valuable resource of traits of interest under sustainable cultivation systems and for genome-wide association studies (GWAS). For mapping loci controlling the variation of agronomic, fruit quality, and root architecture traits, we used a heterogeneous set of 244 traditional and improved tomato accessions grown under organic field trials. Here we report comprehensive phenotyping and GWAS using over 37,300 SNPs obtained through double digest restriction-site associated DNA (dd-RADseq).

Results

A wide range of phenotypic diversity was observed in the studied collection, with highly significant differences encountered for most traits. A variable level of heritability was observed with values up to 69% for morphological traits while, among agronomic ones, fruit weight showed values above 80%. Genotype by environment analysis highlighted the strongest genotypic effect for aboveground traits compared to root architecture, suggesting that the hypogeal part of tomato plants has been a minor objective for breeding activities. GWAS was performed by a compressed mixed linear model leading to 59 significantly associated loci, allowing the identification of novel genes related to flower and fruit characteristics. Most genomic associations fell into the region surrounding SUN, OVATE, and MYB gene families. Six flower and fruit traits were associated with a single member of the SUN family (SLSUN31) on chromosome 11, in a region involved in the increase of fruit weight, locules number, and fruit fasciation. Furthermore, additional candidate genes for soluble solids content, fruit colour and shape were found near previously reported chromosomal regions, indicating the presence of synergic and multiple linked genes underlying the variation of these traits.

Conclusions

Results of this study give new hints on the genetic basis of traits in underexplored germplasm grown under organic conditions, providing a framework for the development of markers linked to candidate genes of interest to be used in genomics-assisted breeding in tomato, in particular under low-input and organic cultivation conditions.
The liver steatosis severity and lipid characteristics in primary biliary cholangitis
Authors: Zhang Yuan , Hu Xing , Chang Jing , Chen Jie , Han Xue , Zhang Tieying , Shen Jianjun , Shang Ning , Han Jing , Wang Hui , Kang Weiwei , Meng Fankun
Published: October 2021

Background

Patients with primary biliary cholangitis (PBC) often have comorbid dyslipidemia, and determining the degree of hepatic steatosis can help predict the risk of cardiovascular events in PBC patients. The aim of our study was to analyze the characteristics of lipid distribution and the degree of hepatic steatosis in PBC.

Methods

We retrospectively analyzed 479 cases of PBC, chronic hepatitis B (CHB), chronic hepatitis C (CHC), non-alcoholic fatty liver disease (NAFLD), and healthy subjects (Normal) diagnosed by liver biopsy or definitive clinical diagnosis. Controlled attenuation parameter (CAP) values were applied to assess the degree of steatosis of the liver, and lipid levels were also compared in the five cohorts.

Results

We found that among the five groups of subjects, the PBC group had the lowest CAP values (P < 0.001), and the high-density lipoprotein cholesterol (HDL-C) level in the PBC group was higher than normal, CHC and CHB group (P = 0.004,P = 0.033,P < 0.001, respectively).In the multivariate linear analysis, only BMI (β = 1.280,P = 0.028), ALP (β = − 0.064,P = 0.012), TBA (β = − 0.126,P = 0.020), TG (β = 12.520,P = 0.000), HDL-C (β = − 11.338,P = 0.001) and LDL-C (β = 7.012,P = 0.002) were independent predictors of CAP.

Conclusions

Among PBC, CHB, CHC, NAFLD and healthy subjects, PBC had the lowest degree of hepatic steatosis and higher HDL-C levels, all of which were found to be protective factors against atherosclerosis and cardiovascular risk and would provide a valuable reference for the risk of developing cardiovascular events in PBC patients.
Comparison of sampling methods in assessing the microbiome from patients with ulcerative colitis
Authors: Kim Dan , Jung Jun-Young , Oh Hyun-Seok , Jee Sam-Ryong , Park Sung Jae , Lee Sang-Heon , Yoon Jun-Sik , Yu Seung Jung , Yoon In-Cheol , Lee Hong Sub
Published: October 2021

Background

Dysbiosis of ulcerative colitis (UC) has been frequently investigated using readily accessible stool samples. However, stool samples might insufficiently represent the mucosa-associated microbiome status. We hypothesized that luminal contents including loosely adherent luminal bacteria after bowel preparation may be suitable for diagnosing the dysbiosis of UC.

Methods

This study included 16 patients with UC (9 men and 7 women, mean age: 52.13 ± 14.09 years) and 15 sex- and age-matched healthy individuals (8 men and 7 women, mean age: 50.93 ± 14.11 years). They donated stool samples before colonoscopy and underwent luminal content aspiration and endoscopic biopsy during the colonoscopy. Then, the composition of each microbiome sample was analyzed by 16S rRNA-based next-generation sequencing.

Results

The microbiome between stool, luminal contents, and biopsy was significantly different in alpha and beta diversities. However, a correlation existed between stool and luminal contents in the Procrustes test (p = 0.001) and Mantel test (p = 0.0001). The stool microbiome was different between patients with UC and the healthy controls. Conversely, no difference was found in the microbiome of luminal content and biopsy samples between the two subject groups. The microbiome of stool and lavage predicted UC, with AUC values of 0.85 and 0.81, respectively.

Conclusion

The microbiome of stool, luminal contents, and biopsy was significantly different. However, the microbiome of luminal contents during colonoscopy can predict UC, with AUC values of 0.81. Colonoscopic luminal content aspiration analysis could determine microbiome differences between patients with UC and the healthy control, thereby beneficial in screening dysbiosis via endoscopy.

Trial registration: This trial was registered athttp://cris.nih.go.kr. Registration No.: KCT0003352), Date: 2018–11-13.
Systematic review of invasive meningococcal disease epidemiology in the Eastern Mediterranean and North Africa region
Authors: Dogu Alp Giray , Oordt-Speets Anouk M. , van Kessel-de Bruijn Femke , Ceyhan Mehmet , Amiche Amine
Published: October 2021

Background

Invasive meningococcal disease (IMD) represents a global health burden. However, its epidemiology in the Eastern Mediterranean (EM) and North Africa (NA) regions is currently not well understood. This review had four key objectives: to describe asymptomatic meningococcal carriage, IMD epidemiology (e.g. serogroup prevalence, case-fatality rates [CFRs]), IMD presentation and management (e.g. clinical diagnosis, antibiotic treatments) and economic impact and evaluation (including health technology assessment [HTA] recommendations) in EM and NA.

Methods

A systematic literature search (MEDLINE and EMBASE) was conducted (January 2000 to February 2021). Search strings included meningococcal disease and the regions/countries of interest. Identified publications were screened sequentially by title/abstract, followed by screening of the full-text article; articles were also assessed on methodological quality. Literature reviews, genetic sequencing or diagnostic accuracy studies, or other non-pertinent publication type were excluded. An additional grey literature search (non-peer-reviewed sources; start date January 2000) was conducted to the end of April 2019.

Results

Of the 1745 publications identified, 79 were eligible for the final analysis (n = 61 for EM and n = 19 for NA; one study was relevant to both). Asymptomatic meningococcal carriage rates were 0–33% in risk groups (e.g. military personnel, pilgrims) in EM (no data in NA). In terms of epidemiology, serogroups A, B and W were most prevalent in EM compared with serogroups B and C in NA. IMD incidence was 0–20.5/100,000 in EM and 0.1–3.75/100,000 in NA (reported by 7/15 countries in EM and 3/5 countries in NA). CFRs were heterogenous across the EM, ranging from 0 to 57.9%, but were generally lower than 50%. Limited NA data showed a CFR of 0–50%. Data were also limited in terms of IMD presentation and management, particularly relating to clinical diagnosis/antibiotic treatment. No economic evaluation or HTA studies were found.

Conclusions

High-risk groups remain a significant reservoir of asymptomatic meningococcal carriage. It is probable that inadequacies in national surveillance systems have contributed to the gaps identified. There is consequently a pressing need to improve national surveillance systems in order to estimate the true burden of IMD and guide appropriate prevention and control programmes in these regions.
Prevalence and factors associated with skin-to-skin contact (SSC) practice: findings from a population-based cross-sectional survey in 10 selected districts of Bangladesh
Authors: Ali Nazia Binte , Priyanka Sabrina Sharmin , Bhui Bal Ram , Herrera Samantha , Azad Md. Rashidul , Karim Afsana , Shams Zubair , Rahman Mahmoodur , Rokonuzzaman S M , Meena Umme Salma Jahan , El Arifeen Shams , Billah Sk Masum
Published: October 2021

Background

Skin-to-skin contact (SSC) practice improves newborn survival and child development through preventing hypothermia in newborns, improving early initiation of breastfeeding practice, and strengthening mother-child bonding. Despite having numerous benefits, it is one of the least practiced interventions in low and middle-income countries (1 to 74%). In Bangladesh, the prevalence of SSC was 26% in 2014. In this study, we aimed to estimate the prevalence of SSC in the study districts and identify factors that facilitate or inhibit SSC practice so that context-specific recommendations can be made to advance the use of this intervention.

Methods

We used baseline household survey data of USAID’s MaMoni MNCSP project conducted in 10 districts of Bangladesh in 2019. Our analysis included 13,695 recently delivered women (RDW) with a live birth outcome. Our primary outcome was the mother’s reported practice of SSC. We examined various antepartum, intrapartum, newborn, and sociodemographic factors associated with SSC using a multivariable generalized linear model. Our findings were reported using adjusted Prevalence Risk Ratios (aPRRs) and 95% Confidence Intervals (CIs).

Results

Overall, 28% of RDW reported practicing SSC across the 10 surveyed districts. Our multivariable analysis showed that public facility delivery (aPRR 2.01; 95%CI: 1.80, 2.26), private facility delivery (aPRR 1.23; 95%CI: 1.06, 1.42) and ≥ 4 antenatal care (ANC) visits at least one from a medically trained provider (MTP) (aPRR 1.17; 95%CI: 1.03, 1.26) had a significant positive association with SSC practice. Caesarean section (aPRR 0.64; 95%CI: 0.56, 0.73) had a significant negative association with SSC practice compared to vaginal births. We also found a significant positive association of SSC practice with mothers’ who perceived the birth size of their baby to be small, mothers with a higher education level (≥10 years), and mothers from households in the highest wealth quintile.

Conclusions

The prevalence of SSC is very low in the surveyed districts of Bangladesh. Considering the factors associated with SSC, relevant stakeholders need to increase their efforts on improving ANC and facility delivery coverages as well as improving SSC practice in the facilities especially after caesarean deliveries. Countries with a high burden of home deliveries, also need to emphasize community-based interventions and increasing coverage of skilled birth attendance for improving this life-saving intervention.