bluuebunny/crossref_metadata_2025 huggingface dataset:
Peace Pragmatism and the Women, Peace, and Security Agenda
Authors: True Jacqui
Published: September 2022

Jane Addams’s writings and peace activism contribute an early feminist perspective on the ethics of war and peace. This chapter explores the theory and practice of Jane Addams, and its import for contemporary feminist international relations theory and practice. It analyzes the feminist tradition of theorizing war/peace through the pragmatist approach developed by Jane Addams. It critically reflects on Addams’s settlement approach to peacebuilding in her work at Hull House with immigrant women. Revealing Addams’s lasting influence, the chapter explores the peace pragmatism in the evolution of the international women, peace, and security (WPS) agenda. Lastly, the chapter considers the relevance of Addams’s thought and action in light of current global conflicts, notably in Afghanistan and Ukraine. Jane Addams’s rejection of antagonism and her embrace of people-to-people cooperation are helpful in understanding and responding to both conflicts and their implications for women’s rights and security.
The Tantric Temple
Authors: Mills Libbie
Published: September 2022

This chapter explores the characteristics of tantric temples. It will work from the account of the temple built for tantric practice given in the Piṅgalāmata, a Śaiva pratiṣṭhā tantra from the north of India, attested in the tenth century. Pratiṣṭhā tantra materials are specifically concerned with the construction, installation, and consecration of the tantric temple and the image within it. In order to place this singular account within Śaiva tantra as a whole, the study will look across from this early and northern Śaiva text to later ones, and also to those that come from the south and from the Vaiṣṇava stream. The Piṅgalāmata will be followed to learn the temple’s purpose, its design and construction, and the ensuing ritual practices and management that concern the temple structure. In particular, a close watch will be placed on what it is that is given in pratiṣṭhā tantra material of this kind that is not treated in building manuals outside the tantric traditions: what it is about the tantric temple that makes it more than just a building.
Singing Tantra
Authors: Lorea Carola Erika
Published: September 2022

From congregational singing to reenactments of the ḍamburu drumming of Shiva, tantric auditory practices reflect a complex religious acoustemology. Sounds and songs in a variety of vernaculars have represented an important component of lived religion in tantric communities. This is especially relevant when dealing with Bengali esoteric lineages. This chapter employs “tantric” as a “post-emic” category, to ensure that heterodox and esoteric Bengali lineages, who do not define themselves as tāntrikas, can fit into interdisciplinary and comparative discussions on tantra. The chapter questions a scholarly paradigm that has constructed music-making as the domain of emotional bhakti and text-based ritualism, violence, and transgression as the domain of tantra and discusses how singing features ubiquitously in the history of tantric communities, urging us to take aural media into consideration for a fuller anthrohistorical understanding of tantra. The focus is also on the Matua community to address practices of sonic liberation that are embedded in tantric ideology. Transformative songs and soundful sādhana thus emerge as co-constitutive of numerous tantric traditions.
It’s Only Words? Analysing the Roots of the Irish Party System Using Historical Parliamentary Debates
Authors: Weeks Liam , Jankin Mikhaylov Slava , Herzog Alex , Ó Fathartaigh Mícheál , Bechara Hannah
Published: September 2022

While the public image of legislative debates is often less than favourable, parliamentary deliberations can be an important indicator of policy preferences, issue saliency and cohesion within political parties. We consider the case of a parliamentary debate that had a considerable long-term political legacy, forging a party system that endured for almost a century. The debates in the Irish parliament over the 1921 Anglo-Irish Treaty were a critical juncture that split a dominant party, resulting in, first, a civil war and, later, a new mode of party competition. We analyse the text of the debates from this period to see if they contribute to a greater understanding of the ensuing split. Few differences between the two sides in parliament are found, which might explain why few were the differences between the key actors in the party system that evolved.
The Efficiency-Equity Trade-off in a Federal System: Local Financing of Schools and Student Achievement
Authors: Lastra-Anadón Carlos X , Peterson Paul E
Published: September 2022

Federalism theorists debate the desirability of funding local services from local revenues or inter-governmental grants. Tiebout expects efficiency gains from local funding, but Oates says it perpetuates inequalities. Research using data from national probability samples has yet to show whether efficiency-equity trade-offs are associated with funding sources. We describe the trade-off in education by estimating the effect of revenue share from local sources on math and reading achievement. Data come from national probability samples of student performances on tests administered between 1990 and 2017. Relationships are estimated with OLS descriptive models, event study models of school finance reforms, and geographic discontinuity models that exploit differences in state funding policies. For every ten-percentage point increase in local revenue share, mean achievement rises by 0.05 standard deviations (sd) and socio-economic achievement gaps widen by 0.03sd. Voice and exit channels moderate the size of the efficiency-equity trade-off. Implications for inter-governmental grant policy are discussed.
Nos Quieren Sacar para Fuera:Older Undocumented Immigrants’ Perceptions of Living in the United States
Authors: Ayón Cecilia , Kiehne Elizabeth
Published: September 2022

Informed by the ecological perspective, this study explored the ways in which macrosystemic influences interact with other systems and influence Latinx undocumented older adults—specifically, the obstacles and barriers they have faced while living in the United States. Thirty Latinx undocumented older adults (between 55 and 73 years old) participated in in-depth interviews. Four main themes captured participants’ experiences: (1) unfulfilled aspirations; (2) social inequities; (3) fear, uncertainty, and threat of deportation; and (4) good immigrant ideology. Participants migrated to the United States in search of better opportunities; while they may have been able to secure jobs, they were limited by their status to achieve other dreams and aspirations. Participants reported that they lack the rights and privileges granted by citizenship. Their precarious status and the policy climates preclude them from feeling safe in the United States, and they fear detection and deportation. They shared that they hope to adjust their status and engage in best behavior as a sign of respect and to safeguard their future in this country. Several participants remarked that it is clear they are not welcomed. These are critical issues that demand attention at a policy and practice level.
Pre-Conceptional Exposure to Glyphosate Affects the Maternal Hepatic and Ovarian Proteome
Authors: Novbatova Gulnara , Timme Kelsey , Severin Andrew , Sayadi Maryam , Keating Aileen F
Published: September 2022

Exposure to glyphosate (GLY), a commonly used herbicide, is supported by urinary detection and associated with shortened gestation in women. This study tested the hypothesis that chronic low-dose pre-conceptional GLY exposure would affect maternal ovarian function mid- and post-gestation. Mice (C57BL/6; n = 40) were exposed per os to saline vehicle control (CT; n = 20) or GLY (2 mg/kg; n = 20) daily for 10 weeks starting at 7 weeks of age. Post-exposure, females were impregnated and euthanized at gestation day 14 (GD14) or post-weaning (PW). Pregnancy success was reduced from 75% to 55% by GLY exposure. No treatment effect (p > .05) on body weight, maternal serum 17β-estradiol, or litter size was noted. Ovarian weight was unaffected or reduced (p < .05) by GLY in GD14 and PW dams, respectively. Exposure to GLY decreased (p < .05) PW ovarian secondary follicle number with no other follicle composition impacts. Protein abundance analysis by LC-MS/MS identified that GLY altered (p < .05) 26 ovarian and 41 hepatic proteins in GD14 dams and 39 hepatic proteins in PW dams. In GD14 dams, GLY increased ovarian protein abundance of SEC16A (p < .05; 29-fold) and hepatic RPS27L and GM4952 (p < .05; ∼4-fold). In both GD14 and PW dams, GLY exposure increased (p < .05) hepatic RPS4 and decreased (p < .05) ECHDC3. Pathway analysis using DAVID identified 10 GLY hepatic pathway targets with FDR ≤ 0.07 in GD14 dams.
Integrated Transcriptome and Proteome Analysis Reveals that the Antimicrobial Griseofulvin TargetsDidymella segeticolaBeta-Tubulin to Control Tea Leaf Spot
Authors: Huang Hongke , Li Dongxue , Jiang Shilong , Yang Rui , Yang Yuqing , Xia Zhongqiu , Jiang Xinyue , Zhao Yongtian , Wang Delu , Song Baoan , Chen Zhuo
Published: September 2022

Because effective control measures are lacking, tea leaf spot caused by Didymella segeticola results in huge tea ( Camellia sinensis) production losses on tea plantations in Guizhou Province, southwestern China. Screening for natural antimicrobial agents with higher control effects against this pathogen and studying their modes of action may contribute to disease management. Here, Penicillium griseofulvum-derived antimicrobial griseofulvin (GSF) can inhibit the hyphal growth of D. segeticola strain GZSQ-4, with a half-maximal effective concentration of 0.37 μg/ml in vitro and a higher curative efficacy at a lower dose of 25 μg/ml for detached tea twigs. GSF induces deformed and slightly curly hyphae with enlarged ends, with protoplasts agglutinated in the hyphae, and higher numbers of hyphal protuberances. GSF alters hyphal morphology and the subcellular structure's order. The integrated transcriptome and proteome data revealed that the transport of materials in cells, cellular movement, and mitosis were modulated by GSF. Molecular docking indicated that beta-tubulin was the most potent target of GSF, with a binding free energy of −13.59 kcal/mol, and microscale thermophoresis indicated that the dissociation constant (Kd) value of GSF binding to beta-tubulin 1, compared with beta-tubulin 2, was significantly lower. Thus, GSF potentially targets beta-tubulin 1 to disturb the chromosomal separation and fungal mitosis, thereby inhibiting hyphal growth.
Longitudinal Effects of Simultaneous and Sequential Bilateral Cochlear Implantation on Cortical Auditory-Evoked Potentials Recorded at Cz in a Large Cohort of Children
Authors: Polonenko Melissa J. , Vicente Leticia C. , Papsin Blake C. , Gordon Karen A.
Published: September 2022

Objectives:

Auditory development after bilateral cochlear implantation in children has been measured using source localization of multi-channel late latency responses. It is not clear, however, whether this development can be tracked using a more clinically feasible method of recording from one active recording electrode placed at mid-line center of the head (Cz).

Design:

In this prospective cohort study, cortical auditory-evoked potential responses (CAEPs) were recorded from Cz referenced to each earlobe (Cz-CAEP) from 222 children with bilateral cochlear implant (CI); 128 (mean ± SD age: 2.78 ± 3.30 years) received both CIs in the same surgery (simultaneous group) and 94 (aged 7.72 ± 4.45 years) received a second CI after 4.21 ± 2.98 years of unilateral CI use. We sought to (1) identify cortical development over the first couple of years of bilateral CI use; (2) measure known asymmetries in auditory development between the CIs; and (3) detect the effects of bilateral rather than unilateral CI use. 4556 Cz-CAEPs were recorded across the cohort over 33.50 ± 7.67 months duration of bilateral CI use. Given concerns related to peak picking, amplitude areas were measured across two response time windows (50 to 199 ms and 200 to 400 ms).

Results:

Results indicated that small response amplitudes occur at initial CI use and amplitudes increase in the negative or positive direction rapidly over the first months of CI use in both time windows. Asymmetries between Cz-CAEPs evoked by each CI were found in the sequential group and reduced with bilateral CI use, particularly in the first time window; these differences increased with longer inter-implant delay. Bilaterally evoked Cz-CAEPs were larger in amplitude than unilateral responses from either CI in the simultaneous group. In the sequential group, bilateral responses were similar to responses from the first implanted side but increased in relative amplitude with bilateral CI use. The Cz-CAEP measures were not able to predict asymmetries or bilateral benefits in speech perception measures.

Conclusions:

The Cz-CAEP was able to indicate cortical detection of CI input and showed gross morphological changes with bilateral CI use. Findings indicate Cz-CAEPs can be used to identify gross changes in auditory development in children with bilateral CIs, but they are less sensitive to tracking the remaining abnormalities that are measured by multi-channel CAEPs and speech perception testing.
The Impact of Type of Acute Myocardial Infarction on Cardiac Patient Self-efficacy After Hospitalization
Authors: Shajrawi Abedalmajeed Methqal , Al-Smadi Ahmed Mohammad , Ashour Ala , Momani Aaliyah , Al-Akash Hekmat Yousef , Granat Malcolm , Jones Ian
Published: September 2022

Background

Self-efficacy is an important psychological construct associated with patient adherence with healthy lifestyle choices. Few studies have focused on the impacts of the type of acute myocardial infarction (AMI), non–ST-elevation myocardial infarction (STEMI) and STEMI, and the different treatment modalities of AMI on changes in cardiac self-efficacy after hospitalization.

Objective

This study examined the changes in cardiac self-efficacy based on the type of AMI and aimed to investigate the impact of different treatment modalities on changes in cardiac self-efficacy among post-AMI patients during hospitalization and at the 3- and 6-month follow-ups subsequent to hospitalization.

Methods

A repeated-measures design was used with a convenient sample of 210 patients diagnosed with first AMI. Patients completed the Cardiac Self-efficacy Questionnaire at the 3 time points. The study was implemented in 3 major hospitals in Jordan. Patients did not have access to cardiac rehabilitation.

Results

There was a statistically significant impact of AMI type on changes in cardiac self-efficacy measured between T1 and T2, between T2 and T3, and subsequently between T1 and T3. Nevertheless, there was no statistically significant impact of treatment modalities of AMI on changes in cardiac self-efficacy measured at the 3 time points.

Conclusions

Assessment of self-efficacy for post-AMI patients is recommended. Moreover, post–non-STEMI patients need more attention when implementing an intervention to enhance self-efficacy after hospitalization. Health decision makers have to consider establishing cardiac rehabilitation to improve self-efficacy in Jordan. Further research is needed to confirm the study results and to investigate other contributing factors that could influence self-efficacy after hospitalization.
Sleep of Intensive Care Patients
Authors: Koçak Ayyüce Tuba , Arslan Selda
Published: September 2022

Background

Intensive care patients experience a high rate of poor sleep quality. As the sleep quality is improved with nursing practices, patients' recovery and the length of stay in the intensive care unit (ICU) may be positively influenced, and patients may benefit from treatment and care at the highest level. Therefore, it is important to explore the experiences and evaluation of nurses working in ICUs.

Objectives

This study was carried out to explore the experiences and evaluations of ICU nurses about patients' sleep.

Methods

The study is a qualitative study conducted in a descriptive phenomenological design. The data were collected using the individual in-depth interview method with the semistructured interview form. Thematic analysis was performed to analyze the data. The Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist was used.

Results

The analysis revealed 4 main themes, which are (1) importance of sleep, (2) evaluation of sleep, (3) reasons for poor sleep, and (4) sleep promotion interventions.

Conclusions

This study revealed that nurses are aware of the importance of sleep; however, they do not evaluate sleep and try to improve sleep quality only based on their own knowledge and experience rather than on evidence-based approaches. However, their interventions are not sufficient and they are restricted because of physical conditions and intensive care procedures.
Advancing the Practice of Family Presence During Resuscitation
Authors: Cornell Rhonda , Powers Kelly
Published: September 2022

Background

After 3 decades of research, much is understood about the benefits of family presence during resuscitation (FPDR), yet translation into clinical practice has been lagging. This article provides guidance for nurse leaders seeking to advance FPDR by sharing the experience of establishing a multifaceted, hospital-wide program of education and policy development.

Objectives

This quality improvement project aimed to (1) implement a hospital-wide FPDR program guided by policy, (2) evaluate classroom and simulation educational interventions, (3) examine chart review data for evidence of FPDR practice change, and (4) act on information learned to further improve the FPDR program and increase practice implementation.

Methods

The Plan-Do-Study-Act (PDSA) cycle provided the model for cyclic evaluation of the FPDR program at a rural Midwestern United States hospital. Interventions were classroom education for existing nursing staff, simulation for new nurses, and implementation of a hospital-wide policy. Outcome measures included nurses' perceptions of FPDR risks and benefits, self-confidence with FPDR, and evidence of practice change via retrospective chart review.

Results

Pilot data demonstrated a statistically significant improvement in nurses' perceptions of FPDR benefits and self-confidence post education, and the rate of FPDR practiced in the facility tripled. The PDSA cycle provided a useful paradigm for ongoing process improvement and program sustainability.

Discussion

After the delivery of an FPDR policy along with classroom and simulation education, an increase in the clinical implementation of FPDR occurred. The use of the PDSA cycle resulted in expanded approaches including the addition of FPDR to in situ mock codes.
EpiSmart Crosslinking for Keratoconus: A Phase 2 Study
Authors: Epstein Randy J. , Belin Michael W. , Gravemann Deborah , Littner Roxanne , Rubinfeld Roy S.
Published: September 2022

Purpose:

The aim of this study was to assess changes in visual acuity after epithelium-on (“epi-on”) corneal crosslinking after a diagnosis of keratoconus.

Methods:

Subjects with corneal ectatic diseases were enrolled in a prospective, randomized, controlled, open-label, multicenter trial. Subjects were randomized to 1 of 3 treatment groups and treated with an epi-on crosslinking system including riboflavin/sodium iodide and pulsed UVA exposure (EpiSmart, CXL Ophthalmics, Encinitas, CA). The UVA treatment groups were 2.4 J/cm2 over 20 minutes, 3.6 J/cm2 over 20 minutes, and 3.6 J/cm2 over 30 minutes. The primary end point was logarithm of the minimum angle of resolution corrected distance visual acuity (CDVA). Secondary end points were logarithm of the minimum angle of resolution uncorrected distance visual acuity (UCVA), maximum corneal curvature (Kmax), and minimum corneal thickness. Data were assessed 6 and 12 months post-operatively, using t-tests for differences from baseline.

Results:

Two thousand two hundred twenty-eight subjects were treated with epi-on crosslinking. One thousand nine hundred twenty-two subjects had a diagnosis of keratoconus; other treated eyes had postsurgical and other ectasias. At 6 and 12 months, the subjects with keratoconus demonstrated significant improvements in CDVA, UCVA, and Kmax; minimum corneal thickness was unchanged. One hundred ninety-five subjects (8.7%) reported at least 1 adverse event (AE). A mild corneal epithelial defect was reported in 31 cases (1.4%) and was the only AE reported in >1% of subjects. There were no serious AEs related to the treatment.

Conclusions:

EpiSmart epi-on crosslinking resulted in mean improvements in CDVA, UCVA, and Kmax at both 6 and 12 months and an excellent safety and efficacy profile in subjects with keratoconus, with few significant side effects. Differences between UVA treatment groups were not significant.
A programmatic taxonomy to define, differentiate, and classify nurse practitioner postgraduate training
Authors: Rettie Candice S. , Huynh DoQuyen
Published: September 2022

Postgraduate residencies and fellowships have become a growing foundational element in the early career path for new nurse practitioners (NPs) and for NPs changing areas of specialization. The proposed programmatic taxonomy provides a straightforward method to recognize and classify NP postgraduate training programs with differing missions, structures, and outcome objectives. Models of postgraduate training for NPs are identified, defined, and differentiated. Each model can serve as an essential and specific purpose for the sponsoring organization. The programmatic models for NP postgraduate training programs are residency, fellowship, and “additional programs.” Differences between residency and fellowship are described. The taxonomy then compares and contrasts the three models on five overarching programmatic characteristics, namely, mission, goals, environment, evaluation, and duration. The potential impact of adopting the NP postgraduate training taxonomy on the NP profession, the public, funding, accreditation, and the early career development of NPs is explored. Recommendations for next steps are suggested.
Qualitative plasma viral load determination as a tool for screening of viral reservoir size in PWH
Authors: Laeremans Thessa , D’haese Sigrid , Aernout Jonathan , Barbé Kurt , Pannus Pieter , Rutsaert Sofie , Vancutsem Ellen , Vanham Guido , Necsoi Coca , Spiegelaere Ward De , Couttenye Marie , Herssens Natacha , Scheerder Marie-Angélique De , Wit Stéphane De , Vandekerckhove Linos , Florence Eric , Aerts Joeri L. , Allard Sabine D.
Published: September 2022

Objective(s):

Suppression of viral replication in patients on antiretroviral therapy (ART) is determined by plasma viral load (pVL) measurement. Whenever pVL reaches values below the limit of quantification, the qualitative parameter ’target detected’ or ’target not detected’ is available but often not reported to the clinician. We investigated whether qualitative pVL measurements can be used to estimate the viral reservoir size.

Design:

The study recruited 114 people with HIV (PWH) who are stable on ART between 2016 and 2018. The percentage of pVL measurements qualitatively reported as ’target detected’ (PTD) within a 2-year period was calculated.

Methods:

t-DNA and US-RNA were used to estimate viral reservoir size and were quantified on peripheral blood mononuclear cells (PBMCs) using droplet digital PCR.

Results:

A median of 6.5 pVL measurements over a 2-year period was evaluated for each participant to calculate PTD. A positive correlation was found between t-DNA and PTD (r = 0.24; P = 0.011) but not between US-RNA and PTD (r = 0.1; P = 0.3). A significantly lower PTD was observed in PWH with a small viral reservoir, as estimated by t-DNA less than 66 copies/106 PBMCs and US-RNA less than 10 copies/106 PBMCs, compared with PWH with a larger viral reservoir (P = 0.001). We also show that t-DNA is detectable whenever PTD is higher than 56% and that ART regimen does not affect PTD.

Conclusion:

Our study shows that PTD provides an efficient parameter to preselect participants with a small viral reservoir based on already available pVL data for future HIV cure trials.
Cancer in patients with and without HIV infection in the national cancer registry of Rwanda
Authors: Hagenimana Marc , Kodan Asha E. , George Nivya , Businge Lydia , Francois Uwikindi , Nsanzimana Sabin , Riedel David J.
Published: September 2022

Objective:

As antiretroviral therapy (ART) has been widely scaled up in Rwanda, life expectancies among people with HIV (PWH) have increased. With increasing viral suppression, AIDS-defining cancers (ADCs) typically decrease; however, as the PWH population ages, non-AIDS-defining cancers (NADCs) will be expected to increase. The aim of this study was to compare cancer diagnoses between PWH and patients without HIV in Rwanda and to describe the changes in the number and types of cancer over time.

Design:

Retrospective cohort study.

Methods:

Rwanda National Cancer Registry (RNCR) recorded the HIV status, primary site, and morphological description for cancer diagnoses from 2007 to 2018. Descriptive analyses were carried out by cancer group (HIV+ and HIV–). A portion of patients whose HIV status was unknown (63%) were excluded from the present analysis.

Results:

Among the 20 258 cases registered in the Registry, there were 1048 PWH and 6359 HIV– individuals. The proportion of ADCs were significantly higher in the PWH group compared to those without HIV (P < 0.001). Among PWH, there was a longitudinal increase in NADCs and a decrease in ADCs (P < 0.001) over time. Among the ADCs in the PWH group, there was a significant decline in Kaposi sarcoma cases over time.

Conclusions:

The study demonstrates a decreasing frequency of ADCs driven by declines in Kaposi sarcoma diagnoses and an increased frequency of NADCs among PWH in Rwanda over time. These findings support a need for focusing early detection and management efforts on NADCs, as they begin to play a larger role in the disease processes that affect the aging PWH population.
Amplitude of Somatosensory Evoked Potentials (SEPs) Recorded in Short-Latency SEP Condition Is 80% of That in Giant SEP Condition
Authors: Demura Ai , Demura Yutaka , Sato Kazuaki , Kinoshita Masako
Published: September 2022

Purpose:

Giant somatosensory evoked potentials (SEPs) with enhanced long-loop reflex (C-reflex) are useful to detect cortical motor hyperexcitability in patients with myoclonic epilepsy. The recording conditions of giant SEPs are different from those of short-latency SEPs (SSEPs). We investigated the waveform characteristics obtained for each condition.

Methods:

Forty-eight upper limbs of 24 adult normal subjects (12 men, age 35.5 ± 9.7 years [mean ± SD]) were investigated. Somatosensory evoked potentials of each subject were recorded in both conditions on the same day. The main differences in recording conditions were reference electrodes (SSEP: Fz vs. giant SEP: the earlobe electrode ipsilateral to the stimulated limb), stimulus rate (5 vs. 1 Hz), and bandpass filter (20 Hz–3 kHz vs. 1 Hz–1 kHz). Somatosensory evoked potentials were elicited by unilateral percutaneous electrical stimulation of the median nerve at the wrist with intensity of 110% of the movement threshold and recoded at C3'/C4'.

Results:

The amplitudes of N20 onset–N20 and N20–P25 were significantly larger in giant SEP condition than in SSEP condition (p < 0.001). The mean + 3SD of N20–P25 amplitude was 10.0 μV in giant SEP condition and 7.8 μV in SSEP condition. The N20–P25 amplitude was significantly correlated between giant SEP condition and SSEP condition (R = 0.64, p < 0.001). C-reflex was not elicited.

Conclusions:

The amplitude of SEPs in SSEP condition is equivalent to 80% of that in giant SEP condition. The information is useful for detecting cortical hyperexcitability in various neurological disorders including myoclonic epilepsy.
Effectiveness of Digital Delivery of Diabetes-Related Lifestyle Interventions in Decreasing A1c: A Systematic Review
Authors: Rapoport Hannah
Published: September 2022

Background

Digital delivery of lifestyle interventions offers a potentially effective, affordable, and convenient option for patients to prevent and monitor type 2 diabetes (T2D) (Khan et al., 2019). Hemoglobin A1c (A1c) is a measure used to monitor T2D progression. Standard of care- based approaches to encourage lifestyle modification have been shown to decrease A1c, yet high healthcare costs and travel-related barriers limit the accessibility of these strategies. Rising T2D rates globally underscore the immediate need to identify the most comparably effective options that decrease A1c and address disease prevention and management.

Objectives

This systematic review examines the effectiveness of digital delivery of lifestyle interventions in decreasing A1c among adults globally both overall and compared to standard ofcare and monitoring only based approaches.

Methods

Based on application of the Navigation Guide systematic review methodology, 10 studies conducted in eight countries met the inclusion criteria and were evaluated for bias, quality, and strength of evidence. Conclusions were drawn from evaluating quantitative results.

Results

A systematic review of the literature demonstrated sufficient evidence of an association between digital delivery of lifestyle interventions and decreased A1c trends. Research did not show significant differences in A1c changes among the intervention groups when compared to the standard of care and monitoring only based control groups.

Conclusions

These results indicate that while the digital delivery of lifestyle interventions is effective in lowering A1c levels in T2D patients, these interventions do not outperform standard of care and monitoring only based approaches to prevent and manage T2D.
Clinical testing panels for ALS: global distribution, consistency, and challenges
Authors: Dilliott Allison A. , Al Nasser Ahmad , Elnageeb Marwa , Fifita Jennifer , Henden Lyndal , Keseler Ingrid M. , Lenz Steven , Marriott Heather , McCann Emily , Mesaros Maysen , Opie-Martin Sarah , Owens Emma , Palus Brooke , Ross Justyne , Wang Zhanjun , White Hannah , Al-Chalabi Ammar , Andersen Peter M. , Benatar Michael , Blair Ian , Cooper-Knock Johnathan , Drury Luke , Harrington Elizabeth , Heckmann Jeannine , Landers John , Moreno Cristiane , Nel Melissa , Rampersaud Evadnie , Roggenbuck Jennifer , Rouleau Guy , Traynor Bryan , van Blitterswijk Marka , van Rheenen Wouter , Veldink Jan , Weishaupt Jochen , Harms Matthew B. , Farhan Sali M.K.
Published: September 2022

Objective

In 2021, the Clinical Genome Resource (ClinGen) amyotrophic lateral sclerosis (ALS) spectrum disorders Gene Curation Expert Panel (GCEP) was established to evaluate the strength of evidence for genes previously reported to be associated with ALS. Through this endeavor, we will provide standardized guidance to laboratories on which genes should be included in clinical genetic testing panels for ALS. In this manuscript, we aimed to assess the heterogeneity in the current global landscape of clinical genetic testing for ALS.

Methods

We reviewed the National Institutes of Health (NIH) Genetic Testing Registry (GTR) and members of the ALS GCEP to source frequently used testing panels and compare the genes included on the tests.

Results

14 clinical panels specific to ALS from 14 laboratories covered 4 to 54 genes. All panels report on ANG, SOD1, TARDBP, and VAPB; 50% included or offered the option of including C9orf72 hexanucleotide repeat expansion (HRE) analysis. Of the 91 genes included in at least one of the panels, 40 (44.0%) were included on only a single panel. We could not find a direct link to ALS in the literature for 14 (15.4%) included genes.

Conclusions

The variability across the surveyed clinical genetic panels is concerning due to the possibility of reduced diagnostic yields in clinical practice and risk of a missed diagnoses for patients. Our results highlight the necessity for consensus regarding the appropriateness of gene inclusions in clinical genetic ALS tests to improve its application for patients living with ALS and their families.
Plasma multi-omics analysis reveals very long chain ceramides as validated biomarkers of Friedreich’s ataxia
Authors: Wang Dezhen , Cotticelli M. Grazia , Himes Blanca E. , Lynch David R. , Mesaros Clementina
Published: September 2022

Friedreich’s Ataxia (FRDA) is an autosomal neurodegenerative disease caused by the deficiency of the protein frataxin. Frataxin is a critical enzyme in the assembly of iron-sulfur clusters that are cofactors for several metabolic enzymes. To identify metabolic features that could be used as potential biomarkers for FRDA in plasma, we performed a multi-omics analysis using a discovery-validation cohort design. We combined metabolomics, lipidomics and proteomics from several liquid chromatography-high resolution mass spectrometry platforms. The analyses revealed that FRDA patients compared to healthy controls and unaffected carriers had dysregulated sphingolipids metabolism, phospholipid metabolism, citric acid cycle, amino acid metabolism, and apolipoprotein metabolism. Using an ROC, the decreased very long chain ceramides can distinguished FRDA patients from healthy controls with AUC from 0.75 to 0.85. Using induced pluripotent stem cell differentiated cardiomyocytes (iPSC-CMs), we demonstrated that frataxin deficiency preferentially affected ceramide synthase (CerS2), enriching long chain ceramides, and depleting very long chain ceramides. The ceramide metabolism was differentially regulated in two of the affected tissues in FRDA: heart and muscles. A machine-learning model improved the prediction of FRDA using the combination of three plasma metabolites (AUC > 0.9). In conclusion, decreased very long chain ceramides are reliable plasma biomarkers for FRDA patients.

One Sentence Summary

New plasma lipids biomarkers of Friedreich’s Ataxia (FRDA) were validated using a discovery-validation design with two independent cohorts.
Effects of more natural housing conditions on the muscular and skeletal characteristics of female C57BL/6J mice
Authors: Mieske Paul , Scheinpflug Julia , Yorgan Timur Alexander , Brylka Laura , Palme Rupert , Hobbiesiefken Ute , Preikschat Juliane , Diederich Kai , Lewejohann Lars
Published: September 2022

Background

Enrichment of home cages in laboratory experiments offers clear advantages, but has been criticized in some respects. First, there is a lack of definition, which makes methodological uniformity difficult. Second, there is concern that the enrichment of home cages may increase the variance of results in experiments. Here, the influence of more natural housing conditions on physiological parameters of female C57BL/6J mice was investigated from an animal welfare point of view. For this purpose, the animals were kept in three different housing conditions: conventional cage housing, enriched housing and the semi-naturalistic environment. The focus was on musculoskeletal changes after long-term environmental enrichment.

Results

The housing conditions had a long-term effect on the body weight of the test animals. The more complex and natural the home cage, the heavier the animals. This was associated with increased adipose deposits in the animals. There were no significant changes in muscle and bone characteristics except for single clues (femur diameter, bone resorption marker CTX-1). Additionally, the animals in the semi naturalistic environment (SNE) were found to have the fewest bone anomalies. Housing in the SNE appears to have the least effect on stress hormone concentrations. The lowest oxygen uptake was observed in enriched cage housing.

Conclusions

Despite increasing values, observed body weights were in the normal and strain-typical range. Overall, musculoskeletal parameters were slightly improved and age-related effects appear to have been attenuated. The variances in the results were not increased by more natural housing. This confirms the suitability of the applied housing conditions to ensure and increase animal welfare in laboratory experiments.
Cell type-independent profiling of interactions between intracellular pathogens and the human phosphoproteome
Authors: Mohler Kyle , Moen Jack , Rogulina Svetlana , Rinehart Jesse
Published: September 2022

Interactions between proteins from intracellular pathogens and host proteins in an infected cell are often mediated by post-translational modifications encoded in the host proteome. Identifying protein modifications, such as phosphorylation, that dictate these interactions remains a defining challenge in unraveling the molecular mechanisms of pathogenesis. We have developed a platform in engineered bacteria that displays over 110,000 phosphorylated human proteins coupled to a fluorescent reporter system capable of identifying the host-pathogen interactome of phosphoproteins (H-PIP). This resource broadly enables cell-type independent interrogation and discovery of proteins from intracellular pathogens capable of binding phosphorylated human proteins. As an example of the H-PIP platform, we generated a unique, high-resolution SARS-CoV-2 interaction network which expanded our knowledge of viral protein function and identified understudied areas of host pathology.
POPULATION PHARMACOKINETICS OF BENZNIDAZOLE IN NEONATES, INFANTS AND CHILDREN USING A NEW PEDIATRIC FORMULATION
Authors: Altcheh Jaime , Moscatelli Guillermo , Caruso Martin , Moroni Samanta , Bisio Margarita , Miranda Maria Rosa , Monla Celia , Vaina Maria , Valdez Maria , Moran Lucrecia , Ramirez Teresa , Patiño Oscar Ledesma , Riarte Adelina , Gonzalez Nicolas , Fernandes Jayme , Alves Fabiana , Ribeiro Isabela , Garcia-Bournissen Facundo
Published: September 2022

Background

There is a major need for information on pharmacokinetics (PK) of benznidazole in children with Chagas disease (CD). We present herein the results of a multicentre population PK, safety and efficacy study in children, infants and neonates with CD treated with BZN (100 mg and the 12.5 mg dispersible tablet, developed in a collaboration of DNDi and LAFEPE).

Methods

81 children 0-12 years of age were enrolled at 5 pediatric centers in Argentina. Diagnosis of T. cruzi infection was confirmed by direct microscopic examination or at least two positive conventional serologies. Subject enrolment was stratified by age: newborns to 2 years (minimum of 10 newborns) and >2-12 years. BNZ 7.5 mg/kg/d was administered in two daily doses for 60 days. Five blood samples per child were obtained at random times: at Day 0, at 2 – 5 h post-dose; during steady state, one sample at Day 7 and at Day 30; and two samples at 12 – 24 h after final BNZ dose at Day 60. The primary efficacy endpoint was parasitological clearance by qualitative PCR at the end of treatment.

Results

Forty-one (51%) patients were under 2 years of age (including 14 newborns <1 month of age). Median age at enrolment was 22 months (mean: 43.2; interquartile range (IQR) 7-72 months). The median measured BNZ Cmax was 8.32 mg/L (IQR 5.95 – 11.8; range 1.79 – 19.38). Median observed BNZ Cmin (trough) concentration was 2 mg/L (IQR 1.25 – 3.77; range 0.14 – 7.08). Overall median simulated Css was 6.3 mg/L (IQR 4.7 – 8.5 mg/L). CL/F increased quickly during the first month of postnatal life and reached adult levels after approximately 10 years of age. Negative qPCR was observed at the end of treatment in all 76 patients who completed the treatment. Five patients discontinued treatment (3 due to AEs and 2 due to lack of compliance).

Conclusion

We observed lower BNZ plasma concentrations in infants and children than those previously reported in adults treated with comparable mg/kg doses. Despite these lower concentrations, pediatric treatment was well tolerated and universally effective, with a high response rate and infrequent, mild AEs.
Populational analysis of the immunoglobulin G response to different COVID-19 vaccines in Brazil
Authors: Paula Nigella M. , Conzentino Marcelo S. , Gonçalves Ana C.A. , da Silva Renata , Weissheimer Karin V. , Kluge Carlos H.S. , Marins Paulo H.S.A. , Camargo Haxley S.C. , Farias Lucas R.P. , Sant’Ana Thamyres P. , Vargas Letícia R. , Aldrighi Juliane D. , Lima Ênio S. , Jacotenski Guiomar T. , Pedrosa Fabio O. , Gonçalves Alan G. , Joucoski Emerson , Huergo Luciano F.
Published: September 2022

Vaccination is a strategy that confers protection against symptomatic infections and/or development of severe COVID-19. In Brazil, COVID-19 vaccination began in January 2021 and has been performed using vaccines from different manufactures including CoronaVac (Sinovac), ChAdOx1 (Oxford/AstraZeneca) and BNT162b2 (Pfizer/BioNTech). One of the main protective mechanisms triggered by vaccination involves the production of IgG antibodies reactive to the Spike antigen of SARS-CoV-2, the levels of which correlates with vaccine efficacy. Although phase III clinical studies confirmed the efficacy of the vaccines used in Brazil, there are just few studies comparing vaccine immunogenicity in a real-world scenario. This study aimed to depict the IgG response to natural infections and to vaccination using different types of vaccines at population scale in Matinhos, a city located in south of Brazil. Nucleocapsid seroconversion rates indicated that more than a quarter of the cohort has been subjected to natural infections by SARS-CoV-2 by the first trimester of 2022. Spike seroconversion rates achieved >95% by February 2022 and maintained stable as far as June 2022 confirming the effectiveness of the vaccination program. Immunogenicity concerning IgG reactive to Spike was higher using the BNT162b2 vaccine, followed by ChAdOx1 and CoronaVac. Natural infections boosted IgG levels reactive to Spike in those individuals that completed primary vaccination with ChAdOx1 and CoronaVac but not with BNT162b2. The levels of IgG reactive to Spike increased with the number of vaccine doses administered. The application of BNT162b2 as booster dose resulted in high levels of IgG reactive to Spike which were similar despite the type of the vaccine used during primary vaccination.
A novel map of human p53 response elements uncovers evidence of selection pressures and variants similar to Li-Fraumeni Syndrome mutations
Authors: Zhang Ping , Brown Katherine , Barnes David , Kitchen-Smith Isaac , Sims David , Flanagan Adrienne , De Noon Solange , Van Loo Peter , Hargreaves Steven , Cross Will , Pillay Nischalan , Jafri Mariam , Wallis Yvonne , Ucanok Deniz , Ntaoulas Sotirios , Manz Markus G , Tebaldi Toma , Inga Alberto ,   Genomics England Research Consortium, Grochola Lukasz F. , Bond Gareth
Published: September 2022

Background

The advent of functional genomic techniques and next generation sequencing has improved the characterization of the non-protein coding regions of the genome. However, the integration of these data into clinical practice is still in its infancy. Fifty percent of cancers mutate TP53, which promotes tumorigenesis, in part, by inhibiting its ability to bind to non-coding regions of the genome and function as a sequence-specific transcription factor. P53 is a tumour suppressor that inhibits cell survival through regulating transcription of anti-survival genes. However, p53 also regulates transcription of pro-survival genes and the target gene(s) responsible for p53 tumour suppression remains an open topic of research.

Methods

In this study, we integrate detailed genome-wide maps of p53 responsive elements (p53-RE), p53 occupancy, recently defined candidate cis-Regulatory Elements (cCREs) and whole genome sequencing for cancers to better define the regions of the genome that harbour functional p53 enhancers.

Results

We determine that p53-REs are more likely to be closer to the consensus binding site, to be evolutionarily conserved and to be occupied by p53 in cellulo, when they reside in regions of the genome that have been noted to have accessible DNA and a regulatory epigenomic mark in at least one human cell even without obvious p53 activation signals (cCRE p53-REs). We offer evidence that it is only in cCRE p53-REs, where multiple signs of differential natural selection between pro-survival and anti-survival target genes can be noted. Using whole genome sequences of 38,377 individuals, we go on to demonstrate that carriers of rare germline mutations in cCRE p53-REs can have similar traits to carriers of rare p53 coding mutations that cause the Li-Fraumeni cancer predisposition syndrome.

Conclusions

Together, these observations suggest that functional p53 enhancers are enriched in cCREs and that germline mutations in them have the potential to improve current cancer risk management and screening strategies.
Seasonal Dynamics of Anopheles stephensi and its Implications for Mosquito Detection and Emergent Malaria Control in the Horn of Africa
Authors: Whittaker Charles , Hamlet Arran , Sherrard-Smith Ellie , Winskill Peter , Cuomo-Dannenburg Gina , Walker Patrick G.T. , Sinka Marianne , Pironon Samuel , Kumar Ashwani , Ghani Azra , Bhatt Samir , Churcher Thomas S.
Published: September 2022

Invasion of the malaria vector Anopheles stephensi across the Horn of Africa threatens control efforts across the continent, particularly in urban settings where the vector is able to proliferate. Malaria transmission across Africa is primarily determined by the abundance of dominant vectors, which often varies seasonally with rainfall. However, it remains unclear how An.stephensi abundance changes throughout the year, despite this being a crucial input to surveillance and control activities. We collate longitudinal catch-data from across its endemic range to better understand the vector’s seasonal dynamics and explore the implications of this seasonality for malaria surveillance and control across the Horn of Africa. Our analyses reveal pronounced variation in seasonal dynamics, the timing and nature of which are poorly predicted by rainfall patterns. Instead, they are associated with temperature and patterns of land-use, with seasonality frequently differing between rural and urban settings. Our results show that timing entomological surveys to coincide with rainy periods is unlikely to improve the likelihood of detecting An.stephensi. Integrating these results into a model of malaria transmission, we show that timing indoor residual spraying campaigns to coincide with peak rainfall offers little improvement in reducing disease burden compared to starting in a random month. Our results suggest that unlike other major malaria vectors in Africa, rainfall may be a poor guide to predicting the timing of peaks in An.stephensi-driven malaria transmission. This highlights the urgent need for longitudinal entomological monitoring of the vector in its new environments given recent invasion and potential spread across the continent.